Ultrasound in Surgery

Focused
Ultrasound Surgery
in Gynecology
Introduction and Application

Felix Wong
Lian Zhang
Zhibiao Wang
123
Focused Ultrasound Surgery in Gynecology
Felix Wong • Lian Zhang • Zhibiao Wang
Focused Ultrasound
Surgery in Gynecology
Introduction and Application
Felix Wong Lian Zhang
School of Women’s and Children’s Health College of Biomedical Engineering
The University of New South Wales Chongqing Medical University
Sydney Chongqing
NSW China
Australia
Zhibiao Wang
College of Biomedical Engineering
Chongqing Medical University
Chongqing
China
ISBN 978-981-16-0938-1 ISBN 978-981-16-0939-8 (eBook)

https://doi.org/10.1007/978-981-16-0939-8
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Foreword
This book is an eye-opening science book blending cutting-edge science and tech-
nology with profound humanity.
The book opens with a description of the Haifu® Focused Ultrasound Tumor
Therapeutic System. In doing so, the author arouses readers’ attention to practical
clinical issues while guiding them on a fascinating science and technology journey.
Tracing the arduous path leads to this hard-won breakthrough in modern science
and technology. The book represents a significant milestone in the acceptance and
popularization of therapeutic HIFU. That is where the value and readability of this
book lie.
According to Hippocrates of Kos, Father of Medicine, in treating diseases, iron
is applied when drugs fail, and fire is applied when the iron fails. Application of iron
can deem to be surgery, while utilization of fire can deem to be the medical applica-
tion of various energies. Haifu® Focused Ultrasound Tumor Therapeutic System is,
in essence, a form of energy.
Hippocrates also cautioned doctors, “First, do no harm!” is a universally appli-
cable maxim. Therefore, we promote and practice minimally invasive and noninva-
sive medicine. Haifu® Focused Ultrasound Tumor Therapeutic system is the
embodiment of minimally invasive and noninvasive medicine.
Mastery of this state-of-the-art minimally invasive and noninvasive technology,
a superior weapon against diseases, marks a great leap forward in our strive towards
the ultimate goal of “protecting patients’ physical organs, tissues, functions, and
mental well-being.”
When it comes to treating diseases, including gynecologic tumor treatment, we
advocate and abide by the principle of standardized, individualized, humane, and
minimally invasive treatment. Furthermore, this rationale conforms to the treatment
with Haifu® Focused Ultrasound Tumor Therapeutic System.
Particular attention must be given to two types of information, i.e., information
on the tumor(s) and information about the patient.
Information on the tumor includes the symptoms, sizes and numbers, the effect,
and the tumor’s characters. Information about the patient consists of her age, mind,
emotion, desires, wishes, marital and fertility status, past health, and family
background.
Therapies and treatment methods based on these two types of information maxi-
mize the benefit of treatment and minimize its harm to patients.
v
vi Foreword
The range of applications of the Haifu® Focused Ultrasound Tumor Therapeutic

Systems is increasingly more extensive now. In addition to uterine fibroids, adeno-
myosis, C-scar pregnancy, it is also used to manage other solid tumors such as liver
cancer, pancreatic cancer, and retroperitoneal sarcoma. Experience in treating uter-
ine fibroids and adenomyosis with Haifu® Focused Ultrasound Tumor therapeutic
system is particularly abundant and fruitful. To date, encouraging long-term treat-
ment outcomes of a 20-center study of HIFU ablation on fibroids have been pub-
lished in a well-known international journal and a monograph on the HIFU ablation
on adenomyoma. The related major project accomplishment release conferences
and international academic exchanges have won intense attention and high acclaims
worldwide.
The experience in treating uterine fibroids with Haifu® Focused Ultrasound
Tumor Therapeutic System has awakened us to realize that humanity or humanistic
ideology ought to be the guiding morality (philosophy) for medical treatment. In her
constant reminder to doctors, Prof. Qiaozhi LIN, pioneer of modern gynecology
and obstetrics in China, delivered a similar message, “There are times when you
have healed the disease, but the patient does not necessarily feel happy, and worse
than that, she/he may become even more anxious and painful, even though HIFU
ablation has cured her/his disease. Therefore, we should have overall considerations
for the patient.” Victor Bonny, an excellent British gynecologist, also said,
“Removing the uterus of a dozen women just because of a benign uterine fibroid is
nothing short of a complete surgical failure.”
Humanity requires doctors to respect people and respect patients. By protecting
their organs, tissues, functions, and mental well-being, we pay our patients the high-
est possible respect. This medical practice answers patients’ needs as a patient, a
woman, and a mother and meets the expectations of the nation, communities, and
individuals. It must, therefore, be our lifelong pursuit.
Resection or preservation of the organ depends, among other factors, on indica-
tions and contraindications. We must avoid rash decisions to resect or preserve an
organ. Any such procedure must be with sound evidence and a comprehensive eval-
uation of the actual situation.
The surgical procedure is a technique, and more importantly, a Philosophy and
an Art. Sir William Osler, a great medical educator, cautioned that we should avoid
the separation of science from humanity and the isolation of technological advance-
ment from humanitarianism.
Readers would be delighted to learn that this “Made in China” Haifu® system has
been exported to more than 26 countries and regions, benefiting people worldwide.
A crown jewel among China’s self-made large medical devices, the Haifu® Focused
Ultrasound Tumor Therapeutic System is exactly “China made” and a spirited
Chinese brand.
Finally, I am happy to introduce Prof. Felix Wong, the lead author of this book,
to our readers. Prof. Wong is a gynecological expert, well-known at home and
abroad. With a great zest for gynecology and obstetrics in mainland China, he has
been actively engaged in academic exchanges, cultivating young doctors and
Foreword vii
promoting good practice in management. We honored him with the Chinese

Obstetricians and Gynecologists Association Award (Lin Qiaozhi Award).
I want to conclude by congratulating Prof. Felix Wong on successfully complet-
ing the first science book introducing high intensity focused ultrasound ablation
surgery and applying Haifu® Focused Ultrasound Tumor Therapeutic Systems.
Jinghe Lang
Chinese Obstetricians and Gynecologists Association
China
Preface
This book is written because of the surprise realization that high intensity focused
ultrasound ablation surgery (HIFU ablation surgery) would significantly impact
operative surgery, especially in Obstetrics and Gynecology. It is an innovative sur-
gery that has been invented and developed in China with recent rapid growth and
recognition. It has greatly benefited women with this noninvasive surgery that had
remained largely unknown in the western world. The technology involves the
destruction of solid tumors, either benign or malignant, by focused ultrasound
energy that can penetrate the human body without even a wound in the skin. Despite
more than 10 years of intensive research and many publications, hardly any text-
book has been written on this topic. Fewer western doctors realize its great potential
in managing women with fibroids and adenomyosis and preserving the reproductive
functions and organs.
After learning from the inventor Professor Zhi Biao Wang, the co-editor of this
book, one gradually realizes that because HIFU ablation surgery is not a traditional
surgical approach introduced to China from western countries, HIFU ablation sur-
gery took a long time to be recognized and endorsed by the majority of doctors in
our O&G fields in China, not to say to doctors in the western countries. Times are
to change now, and it is because more and more doctors recognize this new technol-
ogy, and now up to 26 countries had imported the machine and started treating
patients with this surgical approach. However, compared to the number of patients
with fibroids and adenomyosis, who might benefit from this noninvasive approach,
there are still more patients treated with hysterectomies or myomectomy either by
laparoscopy or open surgery. The popularity and impact of this new technology are
still minimal, as it is just the beginning.
Another major problem of this new technology is the lack of understanding of its
merits among doctors and laypeople. It was similar to the beginning of adopting
minimally invasive surgery (MIS), which had encountered many disbelief and
obstacles among our medical professionals. Only when the demands from patients
who had learned of the minimally invasive surgery, the attitudes of surgeons, the
governments, and the industries change to endorse minimally invasive surgery. Now
MIS becomes a standard approach that benefits women requiring surgery.
Therefore, with the staff’s support at HAIFU Medical Technology Company Ltd.
and with the information provided from their publications, we manage to coordinate
ix
x Preface
the writing of this first introductory book on HIFU ablation surgery in Obstetrics
and Gynecology.
Compared with minimal access surgery, high intensity focused ultrasound abla-
tion surgery is a clean surgery without smoke or radiation, no medical waste, no
blood loss, no leaking of anesthetic gas, and no sharps or chemicals. While patients
do not need general anesthesia, enjoy quick recovery to normal activities, no loss of
working hours, best of all, many will have their problems solved with one or two
hours of noninvasive HIFU ABLATION surgery.
Hopefully, this book can also clarify the differences of HAIFU @knife with
other increasing non-HIFU ablation products in the China market. Many machines
are hyperthermia machines that cannot produce the same therapeutic effects to
ablate effectively many solid tumors. On the contrary, they may produce more harm
like skin burn, nerve, bladder, and bowel injuries. Without proper documentation in
their uses as written in our books, HIFU’s applications and complications might not
be known. HIFU may produce side effects impacting the excellent reputation of this
noninvasive approach.
This book introduces HIFU ablation applications in O&G without too many
details in its technology and procedures. Hopefully, it will enable the laypeople to
understand this new surgical approach in managing fibroids, adenomyosis, and
other gynecological conditions that HIFU can treat. Although this introductory
book may appear to be biased, mainly on the products from Chongqing HAIFU
Medical Technology Co. Ltd., there is scanty information from other similar HIFU
products in the market. We aim to introduce this new HIFU technology without
comparing it with other products, thus our apologies for the incompleteness and
unbalance in our information. Hopefully, this book may arouse the laymen and
young medical professionals interested in this HIFU technology as a noninvasive
HIFU ablation approach in their future career development.
Sydney, NSW, Australia Felix Wong

Chongqing, China Lian Zhang
Chongqing, China Zhi Biao Wang
Declaration of Interest
The experience and knowledge presented in this book was based on the equipment
of CQ HAIFU Medical Technology Company Ltd., which may be different from
how the HIFU ablation is done using equipment from other companies.
Professor Felix Wong is an honorary Professor of the Chongqing Key Laboratory
of Ultrasound in Medicine and Engineering and has no relevant financial interests to
disclose.
Professor Zhibiao Wang is the inventor of the HIFU tumor therapeutic systems
in China and on the board of directors of CQ HAIFU Medical Technology Company.
He receives salary as a member of the board of directors.
Professor Lian Zhang is a Professor at the Chongqing Key Laboratory of
Ultrasound in Medicine and Engineering and receives salary from Medical Director
of CQ HAIFU Medical Technology Company where he is the Medical Director.
xi
Contents
1 An Introduction�� 1

1.1 The HAIFU Knife® �� 2
1.2 The “HAIFU Knife®”�� 3
1.2.1 Other Focused Ultrasound Equipment Systems
in the Market �� 4
1.2.2 Ultrasound-Guided (USg) HIFU Systems�� 4
1.3 MRgHIFU Systems�� 5
1.4 Focused Ultrasound Hyperthermia Therapy and High
Intensity Focused Ultrasound Ablation�� 10
1.5 Conclusion�� 11
References�� 12
2 Sedation and Analgesia for HIFU Ablation �� 13
2.1 The Choice of Drugs for Sedation and Analgesia�� 13
2.2 First-Line Drugs�� 14
2.3 Second-Line Drugs �� 15
2.4 Other Auxiliary Drugs Should Be Available�� 16
2.4.1 Sedation and Analgesia Protocol for HIFU Ablation�� 17
2.5 Midazolam and Fentanyl Sedation Protocol �� 17
2.6 Other Sedation and Analgesic Regimes: Dexmedetomidine
and Remifentanil Sedation Protocol �� 18
2.7 Monitoring During HIFU Surgery Under Sedation�� 18
2.8 Treatment of Complications�� 19
2.8.1 Respiratory Depression�� 19
2.8.2 Muscle Stiffness�� 20
2.9 Factors Affecting the Effects of Sedation and Analgesia�� 20
References�� 21
3 Ultrasound and MRI Imaging of Uterine Fibroids and Adenomyosis�� 23
3.1 Imaging for Uterine Fibroids�� 23
3.1.1 Ultrasound Imaging�� 23
3.2 Locations of Fibroids�� 26
3.2.1 MRI Imaging�� 26
3.3 Uterine Adenomyosis�� 29
xiii
xiv Contents
3.4 Transvaginal Ultrasound Appearances of Adenomyosis�� 30

3.5 MRI Appearances of Adenomyosis�� 31
3.6 Leiomyosarcoma and Endometrial Stromal Sarcoma—MRI
Features �� 34
References�� 34
4 Uterine Fibroids and HIFU Ablation �� 37
4.1 Symptoms of Uterine Fibroids�� 37
4.2 Indications for Treatment�� 38
4.3 Investigative Methods �� 39
4.4 Treatments�� 40
4.5 HIFU Treatment�� 42
4.6 The USgHIFU Ablation Procedure�� 43
4.7 The Indications for HIFU Treatment�� 45
4.8 The Contraindications for HIFU Ablation�� 46
4.9 Preparation Before HIFU Ablation �� 47
4.9.1 Simulation Test �� 47
4.10 Other Preparations�� 48
4.11 HIFU Ablation�� 49
4.12 Factors Influencing HIFU Effectiveness �� 50
4.13 The Types and Locations of Fibroids that Affect HIFU Ablation�� 51
4.14 Assessment of the Effectiveness of the Ablation at the End
of HIFU Ablation Procedure�� 53
4.15 Post-HIFU Ablation Care�� 53
4.16 Postoperative Follow-up �� 54
4.17 Results of HIFU Ablation on Follow-up�� 54
4.17.1 The Non-perfused Volume Ratio�� 54
4.17.2 The Volume Reduction After HIFU Ablation �� 55
4.18 Other Issues of Fibroid Ablation�� 57
4.19 Recurrence of Fibroids�� 59
4.20 Pregnancy After HIFU Ablation �� 59
References�� 60
5 Adenomyosis and HIFU Ablation�� 63
5.1 The Symptoms of Adenomyosis �� 64
5.2 Treatment of Adenomyosis �� 64
5.2.1 Drug Treatment �� 64
5.2.2 Surgical Treatment�� 65
5.2.3 Bilateral Uterine Artery Embolization (UAE)�� 66
5.2.4 High Intensity Focused Ultrasound (HIFU) Therapy �� 66
5.3 Factors Influencing HIFU Effectiveness for Adenomyosis
Treatment are Listed as Follow�� 67
5.4 Advantages of HIFU Treatment for Adenomyosis �� 67
5.5 Pregnancy�� 69
References�� 69
Contents xv
6 Complications of HIFU Ablation�� 71

6.1 Fever�� 72
6.2 Pain �� 72
6.3 Skin Burn Injury �� 73
6.4 Urinary Tract Injury�� 74
6.5 Bowel Injury �� 75
6.6 Vaginal Bleeding or Discharge �� 76
6.7 Other Rare Complications or Those Not Reported�� 76
References�� 78
7 Fertility and Pregnancy After HIFU Ablation�� 81
7.1 The Reproductive Impact After HIFU Ablation
for Uterine Fibroids�� 81
7.1.1 HIFU Impact on Ovarian Functions �� 84
7.1.2 HIFU Impact on Uterine Function�� 84
7.1.3 Risks of Miscarriage After HIFU Ablation�� 84
7.1.4 The Cesarean Section Rate After HIFU Ablation �� 85
7.2 The Reproductive Impact After HIFU Ablation for Adenomyosis�� 85
7.3 Conclusion�� 86
References�� 87
8 Other Issues of HIFU Treatment�� 89
8.1 MRI-Guided and Ultrasound-Guided HIFU Ablation�� 89
8.2 HIFU Ablation and HIFU Hyperthermia�� 90
8.3 Malignant Fibroids�� 90
8.4 Multiple Fibroids�� 91
8.5 The Cost of HIFU Treatment�� 91
References�� 92
9 Other HIFU Ablation Applications in Gynecology and Related
to Obstetrics�� 93
9.1 Abnormal Placenta Attachment—Placenta Accreta�� 93
9.2 Cesarean Scar Pregnancy (CSP) �� 96
9.3 Abdominal Wall Endometriosis�� 98
References�� 100
About the Authors
Felix Wong is at present the Adjunct Professor at the

University of New South Wales. He was the past
Professor and Medical Director of Liverpool Hospital
in Sydney, Australia. He had contributed to medical
education in Asia Pacific Countries over the past
30 years. In recognition of his contributions to teaching,
he received many awards and honors. In 2009, he
received the Endos Award in Medical Science and
Technology, China, for his excellent achievement in
Endoscopic surgery. In 2017, he was granted Lin
Qiaozhi Cup by the Chinese Obstetricians and
Gynecologists Association (COGA) to recognize his
significant contribution to obstetrics and gynecology in
China. In 2017, he was honored with Lifetime
Achievement Award by Asia-Pacific Association for
Gynecologic Endoscopy and Minimally Invasive
Therapy (APAGE). In 2018, he was awarded by the
European Society for Gynecological Endoscopy
(ESGE) for Outstanding Contribution Award. Professor
Wong had edited 14 medical books and had published
more than 200 papers in local and international jour-
nals. He is currently the Chairman of the China-Asia
Pacific Association of Minimally Invasive Gynecologic
Oncologists (CA-AMIGO) and Foundation Chairman
of China-Australia-Asia Pacific Forum of Minimally
Invasive Surgery and Vice President of the World
Association of Chinese Obstetricians and Gynecologists.
Despite his unique endoscopic contributions, he
continues to contribute towards the development of
HIFU education and services in China and Asia
Pacific Areas.
xvii
xviii About the Authors
Lian Zhang graduated from Chongqing Medical

University in 1987, studied in UCSD in 1998, and,
after returning to China in 2004, worked in the
Oncology Center of the Second Hospital Affiliated to
Chongqing Medical University. He was one of the
chief researchers working to develop HIFU (high-
intensity focused ultrasound) system. He was in charge
of (or participated in) multiple scientific research proj-
ects. He was awarded multiple city-level and national-
level scientific awards.
Over the last 10 years, he was at CIRSE, WCIO,
SIUMB, PARIS, and among others, as an invited
speaker. Prof. Lian Zhang’s research areas and inter-
ests extend to anatomy, molecular biology, molecular
genealogy, oncology, etc. He has published more than
80 papers in the peered review journals such as Acta
Obstet Gynecol Scand., BJOG., Int J Gynaecol Obstet.,
Circulation, Journal of Clinical Investigation,
Radiology, European Radiology, European Journal of
Radiology, American Journal of Roentgenology,
Ultrasounics Sonochemistry, International Journal of
Hyperthermia and Medicine.
He is now responsible for training HIFU surgeons
or physicians worldwide. He is currently the Secretary
General of the International Society of Minimally
Invasive and Virtual Surgery, the Secretary General of
the Minimally Invasive and Noninvasive Medical
Committee of Chinese Medical Doctor Association.
He serves as a section editor of the International
Journal of Hyperthermia.
Zhi Biao Wang, MD, PhD Professor of ObGyn and
Biomedical Engineering, PhD student supervisor,
Senior Consultant of ObGyn, Chongqing Medical
University; Director of the National Engineering
Research Center of Ultrasound Medicine (NERCUM),
and the State Key Laboratory of Ultrasound in
Medicine and Engineering, respectively; Council
member of the International Society of Minimally
Invasive and Virtual Surgery (ISMIVS). Professor
Wang is the Principal Investigator of the research grant
awarded by the National Key Basic Research and
Development Program (973 Program) in 2010 and the
special fund for the Development of major Scientific
Research Equipment awarded by the National Natural
About the Authors xix
Science Foundation of China. He was the recipient of

the National Science Fund for Distinguished Young
Scholars, the second prize of the State Technological
Invention Award in 2000, the HLHL (HO LEUNG HO
LEE) Advancement Prize in 2008, the second prize of
the National Science and Technology Progress Award
in 2010, and the National Innovation Award in 2020.
Prof. Wang has devoted for decades to the develop-
ment and clinical implementation of minimally inva-
sive and noninvasive treatment of common
gynecological diseases, such as uterine fibroids, ade-
nomyosis, cervicitis, and non-neoplastic epithelial dis-
orders of the vulva.
Since 1988, adhering to the medical philosophy of
“Treatment-minimize harm to patients,” Professor
Wang has a long track record of innovative and origi-
nal research on the theoretic framework of therapeutic
ultrasound, its clinical translation, and clinical devel-
opment of focused ultrasound therapies. He proposed
for the very first time the concept of “Biological Focal
Region,” laying the theoretic foundation for clinical
application of focused ultrasound ablative therapy. His
team successfully developed the world-first High
Intensity Focused Ultrasound Tumor Therapeutic
System, the JC series with independent intellectual
property rights. It led the clinical development and
global deployment of HIFU technology, realizing the
medical dream of noninvasive extracorporeal treat-
ment of the lesions within the body. At present, a series
of ultrasound therapy devices developed by Prof.
Wang’s team is being used by more than 2800 hospi-
tals worldwide, having treated more than 150,000
patients with benign and malignant diseases, such as
uterine fibroids, liver cancer, breast cancer, and osteo-
sarcoma and more than 2 million patients with non-
tumor diseases.
Abbreviations
CNS Central nervous system

CQ HAIFU Chongqing HAIFU Medical Technology Co. Ltd.
CS Cesarean section
D&C Dilatation and curettage
FIGO International Federation of Gynecology and Obstetrics
FUS Focused ultrasound surgery
GH Growth hormone
GnRH-a Gonadotrophin-releasing hormone analog
HCG Human chorionic gonadotrophin
HIFU High intensity focused ultrasound
HIFUa High intensity focused ultrasound ablation
HPL Human placental lactogen
MIS Minimally invasive surgery
MRI Magnetic resonance imaging
RMB Renminbi
UAE Uterine arterial embolization
xxi
An Introduction
1
When an object vibrates between 20 and 20,000 Hz, it produces an audible sound.

In simple terms, sound is a vibration that can be picked up by our ears. Ultrasound
is a sound wave with a frequency higher than 20,000 Hz (Fig. 1.1), which is higher
than the upper audible limit of hearing. Thus, it cannot be heard by the human ear.
Focused ultrasound is a noninvasive treatment procedure that uses ultrasound waves
emitted from a transducer outside the body using its penetration and focusing ability
to form a focus inside the body. When ultrasound waves fire, a combination of ther-
mal, cavitation, and mechanical effects of the ultrasonic wave produce instanta-
neous high temperature at the focal point to cause coagulation necrosis of the target
tissue. Focused ultrasound is used for the treatment of benign gynecologic diseases
including uterine fibroids [1], adenomyosis [2], cesarean scar pregnancy [3] and
placenta accreta [4] as well as liver cancer [5], breast cancer [6], pancreatic cancer
[7], bone cancer [8], retroperitoneal sarcoma [9], and other solid tumors [10].
At present, surgery has evolved from open to minimally invasive surgery. We
now use minimally invasive surgery to treat many diseases. With the advancement
of medical technology and improved quality of life, many people want to be treated
with less invasive or even noninvasive techniques. Now we are shifting from “mini-
mally invasive surgery” to “noninvasive surgery.” It is the dream of doctors and
patients to minimize harm while achieving therapeutic goals. Therefore, even mini-
mally invasive surgery is not enough to meet all of the treatment requirements for
patients. We need to be able to treat diseases in a less invasive way than even lapa-
roscopy or hysteroscopy. This is the method of HIFU ablation to be introduced in
this book. The book is written based on many of the information from scientific
literature and that of HAIFU knife® surgery produced by Chongqing HAIFU
Medical Technologies Co., Ltd.
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 1
F. Wong et al., Focused Ultrasound Surgery in Gynecology,
https://doi.org/10.1007/978-981-16-0939-8_1
2 1 An Introduction
20 Hz 20,000 Hz (20 kHz)
Range of
human hearing
Ultrasound
Low High
pitch pitch
0 10 100 1000 10000 100000 1000000 10000000

Frequency (Hz)
Fig. 1.1 Ultrasound is a sound wave with a frequency from 20 kHz up to several gigahertz
1.1 The HAIFU Knife®
The “HAIFU knife®,” also known as “focused ultrasound knife,” is the trademark of
high intensity focused ultrasound (HIFU) tumor therapeutic system developed by
Chongqing HAIFU Medical Technologies Co., Ltd. The English abbreviation
“HIFU” used loosely in the book is for any high intensity focused ultrasound treat-
ment, including HAIFU knife® and other HIFU ablation or hyperthermia systems.
The HAIFU knife® system is an ultrasound-guided HIFU ablation system that can
treat liver cancer, pancreatic cancer, bone tumors, soft tissue tumors, and benign
uterine diseases. Other HIFU systems may not have enough experience in these
diseased organs.
The principle of HIFU is similar to focusing sunlight through a convex lens, but
with the ultrasound comes to a focus within the body after safely penetrating the body
tissue (Fig. 1.2). The main mechanisms include thermal, cavitational, and mechanical
effects. A noninvasive treatment, the HIFU ablation produces a temperature above
60 °C at the focused target tissue within a very short timespan. This action results in
coagulation necrosis at the target without inflicting injury to the surrounding tissues.
The necrotic tissue is gradually absorbed or becomes a fibrotic scar.
The HIFU ablation will not wholly replace open surgery or minimally invasive
surgery. Any operation has indications and contraindications, advantages and disad-
vantages. Abdominal hysterectomy is the treatment of choice for malignant uterine
tumors, while uterine fibroids with abundant blood supply and pedunculated subse-
rous fibroids are more suitable for minimally invasive surgery. Since HIFU ablation
is a noninvasive treatment that is less harmful to the body than open surgery or mini-
mally invasive surgery, the recovery time after HIFU is much shorter. Thus, if the
disease is suitable for HIFU treatment, it should be considered a first choice. To
achieve the principle of “minimizing harm to patients,” either HIFU treatment or
endoscopic surgery is our treatment.
1.2 The “HAIFU Knife®” 3
Fig. 1.2 Focusing high-intensity ultrasound through the body for fibroid ablation (Courtesy from
CQ HAIFU Medical Technology Co. Ltd.)
Fig. 1.3 JC Model: high intensity focused ultrasound (HIFU) tumor therapeutic system for all
surgical specialties
1.2 The “HAIFU Knife®”
Several different models of the HAIFU knife® are manufactured by Chongqing

HAIFU Medical Technology Co., Ltd., with different appearances and features.
These two models (Figs. 1.3 and 1.4) are used commonly to treat solid tumors
and organs such as uterine fibroids, uterine adenomyosis, placental accreta, cesar-
ean pregnancy scars, with the larger JC model more suitable for liver tumors, kidney
tumors, bone cancers, breast cancers, pancreatic cancers, and soft tissue tumors of
the solid tumor type.
Over the years, HAIFU knife® has been exported from China to Asia, Europe,
Africa, and South America. It is currently operating in 26 countries, including the
4 1 An Introduction
Fig. 1.4 JC 200 model: high intensity focused ultrasound (HIFU) tumor therapeutic system for
gynecology
United Kingdom, Germany, Italy, Bulgaria, Argentina, Japan, South Korea,

Thailand, Saudi Arabia, Jordan, South Africa, and Egypt. Many studies from these
countries have shown their effectiveness and safety. In Spain, the Minister of Public
Health even declared that the HIFU ablation is the treatment of choice for uterine
fibroids and uterine adenomyosis. Many famous hospitals or institutes, including
Oxford, the European Institute of Oncology in Milan, Bonn University in Germany,
etc., had used HIFU ablation to treat liver cancer, bone metastasis, and pancreatic
cancers. The HIFU ablation technique does offer patients a choice when no other
treatment is available or exhausted.
1.2.1 O
ther Focused Ultrasound Equipment Systems
in the Market
The differences between various HIFU systems depend on (1) the image-guided
models, (2) ultrasound transducers designs, and (3) mounting positions of the ultra-
sound transducer. This variation of image guidance and transducer design results in
various degrees of treatment effectiveness and safety concerns.
1.2.2 Ultrasound-Guided (USg) HIFU Systems
In addition to the above HAIFU knife@ tumor therapeutic systems—JC and JC200
models, which are ultrasound-guided HIFU ablation systems, there are many other
types of ultrasound-guided HIFU systems available in the China market, for
1.3 MRgHIFU Systems 5
Fig. 1.5 Other USgHIFU systems commercially available in China (1) PRO 2008, (2) HIFUNIT
9000, (3) HIFU 2001, and (4) CZ 901
examples, The PRO 2008 HIFU system produced by Shenzhen Promethe Medical
Sci-
tech co Ltd., the HIFUNIT 9000 system produced by Shanghai Aishen
Technology (China) [11], the HIFU-2001 from Shenzhen Wikkon (Huikang Medical
Apparatus Co Ltd), and the CZ 901 HIFU tumor therapeutic system from MainYang
Sonic electric Ltd. (Fig. 1.5).
Due to different designs’ patent issues, and the ultrasound transducer’s location,
the therapeutic focused ultrasound systems are two major types based on whether
the ultrasound transducer is bottom-mounted or top-mounted at the treatment table.
For “HIFU ablation,” patients receiving treatment with models JC, JC200, ExAblate
2000/2100, and Sonalleve HIFU device are required to lie prone, i.e., on their stom-
ach, with the transducer bottom-mounted below the table (Fig. 1.6).
The alternative systems are with a top-mounted ultrasound transducer above the
operating table. The patient will lie on their back during treatment with the thera-
peutic head loaded onto the abdomen from above the table. In general, the top-
mounted HIFU device’s treatment efficiency is low, and it is not easy to obtain the
ablative effect.
1.3 MRgHIFU Systems
There are two Magnetic Resonance Imaging-guided (MRg) HIFU systems com-
mercially available in the market, namely the ExAblate system (Insightec Ltd.,
Haifa, Israel) based on the General Electric MR platform, and the Sonalleve HIFU
6 1 An Introduction
Fig. 1.6 Model JC 200 therapeutic focused ultrasound system with the ultrasound transducer
below the table
Fig. 1.7 The Sonalleve MRgHIFU system from Philips Healthcare
system (Koninklijke Philips Electronics, Eindhoven, the Netherlands) based on the

Phillips MR platform. Both involve a process of volumetric heating of fibroids by
HIFU with MRI feedback. The Sonalleve MRgHIFU is a system (Fig. 1.7) devel-
oped by Philips Healthcare to treat uterine fibroids [11]. At present, it is also under-
way for clinical trials and study for bone metastasis [12], prostate cancer [13], and
breast cancer [14].
The InSightec ExAblate® 2000 MRI-guided FUS system was the first commer-
cial MRg-FUS system (Fig. 1.8) that received the Food and Drug Administration
(FDA) approved FUS device for the treatment of uterine fibroids in America [15].
Since then, it had been utilized in the treatment of uterine fibroids and adenomyosis
[16]. Other reports are also available in oncology, including the brain, bone, thyroid,
and prostate.
Fig. 1.8 The InSightec ExAblate® 2000 MRI-guided FUS system
While USgHIFU was the original image-guided system, MRg-FUS(MR-HIFU)

was developed to incorporate three-dimensional treatment planning and tempera-
ture monitoring at the target zone. These MRgHIFU systems have been demon-
strated promising results in the treatment of both uterine fibroids.
With accumulating practical experience, a comparison of merits of MRg and
USgHIFU systems are tabled as follow:
Features MRgHIFU USgHIFU

Anatomical resolution Good Fair
Target temperature Available Not available
monitoring
Cost of HIFU system Expensive including MRI set up Less expensive without MRI
set up
MRI chamber and noise Noisy and isolated Friendly environment
Machine space Large area Average room area (about
requirement 300–400 square ft)
Transducer motility Fixed Movement needed
Treatment time, e.g., for a 2–3 h (dependent on MRI 1 h (independent of MRI
5 cm fibroid functions) functions)
Treatment efficiency 20–50% 80–90%
Treatment cost Expensive Economical
Operator Interventional radiologist and Surgeon or gynecologist
surgeon together
In China, there are several companies that produce HIFU machines. Of the dif-
ferent types of USgHIFU systems, their effectiveness and safety depend on the
ultrasound transducer design (single-chip vs. phased array) and position (top-
mounted vs. bottom-mounted).
8 1 An Introduction
Single-chip HIFU system has an ultrasonic transducer mediated by a single

ceramic piezoelectric chip, and the focus target has a fixed distance and angle.
During treatment, it needs to move the transducer mechanically while the
B-ultrasound scans the lesion. Multiphased array ultrasound transducer consists of
a combination of multielement phased array ultrasound transducers.
The target focus is not fixed and can be adjusted according to the location of the
lesion. Changing the direction of each probe in the transducer refocuses onto a new
position for treatment. Therefore, the multiphased array transducer does not move
during the HIFU treatment (Fig. 1.9).
However, when the multiphased array is focused, each transducer phase needs to
be adjusted in phase to obtain the maximum focus energy, and out of phase in ultra-
sound wave will deviate and reduce the focused energy at the target (Fig. 1.10).
Therefore, single-chip ultrasound transducers are superior to multiphased array
transducers in terms of efficiency unless the design of the latter transducer synchro-
nization is perfect.
Tumor
Skin
Ultrasound
energy beams
Ultrasound
Move transducer
Single chip ultrasound transducer Multiphase array ultrasound transducer
Fig. 1.9 Movement of single-chip and multiphase array ultrasound transducer in actions
Combined waveform
Wave 1
Wave 2
Synchronous in phase 180° phase difference
Fig. 1.10 The combined waveform at the target area is a combination of waveforms focused in
synchronized phase; a 180° out of phase might negate all the ultrasound energy of each waveform
The transducers’ position, i.e., whether it is top-mounted and bottom-mounted,

is important in terms of skin complications and the frequency of treatment. The top-
mounted transducer projects ultrasound waves through multilayer interfaces: water
bag membrane, membrane to ultrasound media, and ultrasound media to skin. Some
ultrasonic energies will then stay at these interfaces, leading to an increase in the
temperature at the skin level and increase the risk of skin burns. Therefore, multiple
treatment sessions with lower energy are used (thermotherapy) instead of one-off
treatment to avoid skin complications. In contrast, a bottom-mounted transducer
produces an ultrasound wave in a water tank with degassed water. There is only one
interface between the ultrasound transducer and the patient’s skin, i.e., only a single
interface retents penetrating acoustic energy. With cold water in the tank that can
also cool down and reduce skin temperature at the time of treatment (Fig. 1.11), skin
burns’ risk will become minimal. It also allows more energies to be delivered at the
focused target during one treatment.
With a better understanding of the ultrasound transducer design and energy
delivery, in the 1990s, scientists from Chongqing HAIFU Medical Technology Co.,
Ltd. performed experiments using a system with the transducer above the table, i.e.,
top-mounted transducer. They found that the usable power was significantly lower
than that of a system with the ultrasound transducer located below the treatment
table, e.g., bottom-mounted transducer, due to safety issues. Energy from ultra-
sound transducers placed above the table are theoretically inferior for treatment due
to the following reasons:
1. A top-mounted ultrasound transducer requires a sealed water bag to put between

the ultrasound transducer and the skin; this sealed water bag interface results in
energy loss because of the reflection and absorption of energy by the bag and can
also involve burns to the skin.
2. Air bubbles may form between the skin and the sealed water bag during the
HIFU treatment. These reflect ultrasound and energy, requiring higher energy
power levels with the possibility of inducing pain and skin burns.
Ultrasound Skin
transducer
Water layer, enclosed

inside a bag
Ultrasonic media layer

Skin
Water
layer
Ultrasound transducer
Fig. 1.11 The number of interfaces of the top-mounted and bottom-mounted ultrasound transducer
10 1 An Introduction
3. The water in the sealed water bag needs to be degassed as well. If not, energy
traveling through the water will also be absorbed and may produce gas bubbles
which adhere to the ultrasound transducer and surface of the ultrasound monitor-
ing probe. To the former, it hinders ultrasonic wave transmission during treat-
ment. To the latter, it reduces the clarity (quality) of the ultrasonic image.
The bottom-mounted HIFU systems overcome these two potential types of gas
interferences using automatic cycling of degassed water (oxygen content <3 ppm, at
an adjustable temperature 10–40 °C). This measure ensures minimal ultrasonic
energy loss during treatment. Moreover, direct contact of degassed cold water with
the skin produces a cooling effect and further reduces skin burns. The specialized
water degassing device used with the HAIFU knife® also reduces ultrasonic energy
loss and improves ultrasonic energy availability for treatment.
The effect of the HAIFU knife® ablation is under real-time ultrasound scanning.
The extent and dose of ablation can be adjusted according to patients’ responses.
Patients do not require general or spinal anesthesia during treatment. If necessary,
analgesic sedation, if given, is to control any discomfort. Patients are conscious and
can communicate with the medical staff or nurses next to them, closely observing
vital signs and problems. Any problems during the treatment can be dealt with
promptly.
1.4 ocused Ultrasound Hyperthermia Therapy and High

F
Intensity Focused Ultrasound Ablation
In the market, there are two types of therapeutic ultrasound devices. One offers
focused ultrasound hyperthermal therapy at lower energy; the other type provides
enough energy to achieve HIFU ablation. HAIFU knife@ is the type of high inten-
sity focused ultrasound therapy providing higher energy. The differences between
the two treatment HIFU systems are
1. The temperature of the focused ultrasound hyperthermal therapy can only reach
42–50 °C, increasing tumor cell susceptibility to other damaging factors, e.g.,
increasing the sensitivity to radiotherapy and chemotherapy. Even longer, hyper-
thermal heating time does not cause coagulative necrosis of all tumor cells. The
temperature of HIFU ablation, on the other hand, is usually between 60–100 °C,
which induces coagulative necrosis, and causes irreversible thermal damage.
This action results in tissue necrosis in the ablated area.
2. The focus for the focused ultrasound hyperthermal therapy is large, and thus the
precision is poor. On the other hand, the HAIFU knife® ablation’s focal point is
small and precise (Fig. 1.12), with a controllable treatment range.
3. Focused ultrasound hyperthermal therapy often requires multiple treatment ses-
sions. HAIFU knife® ablation usually requires only one ablation session.
4. Hyperthermia is a low-energy technology that essentially equates to the prelimi-
nary stage of focused ultrasound treatment. It is only similar to an ultrasound
1.5 Conclusion 11
80º 3 mm
Focal point
10 mm
3 mm
Sizes of the HIFU focal point
Ultrasound transducer
Fig. 1.12 The small and precise target point of HAIFU knife® ablation (Courtesy from CQ
HAIFU Medical Technology Co. Ltd.)
scanner in energy terms, delivering lower energy that is not suitable for one-off
treatment. Dose adjustment of hyperthermia treatment varies depending on the
patient’s subjective pain level during prolonged treatment at lower energy and
may require several times to complete the treatment. On the other hand, HIFU
ablation is an advanced stage of focused ultrasound treatment technology that
uses higher energy. Its dose adjustment varies according to the treatment effect.
The curative effect’s evaluation is made quantitatively using real-time ultrasound
imaging (US-guided) or enhanced magnetic resonance imaging (MR-guided).
1.5 Conclusion
HIFU ablation for the treatment of solid tumors had begun for more than 20 years.
Many studies with a large number of patients have shown that ultrasound-guided
high intensity focused ultrasound treatment is safe and effective in treating patients
with solid tumors [17–19]. It is now recognized as a noninvasive procedure that is
safe and effective in the treatment of solid tumors with the following advantages:
1. No open surgery, no bleeding, minimal pain or just mild discomfort, and rapid
postoperative recovery requiring only a few hours postoperative bed rest
2. No general anesthesia or spinal anesthesia is required
3. Tumor size and shape do not affect the treatment
4. The targeted organ preserved, and surrounding organs and healthy tissues are
not damaged
5. Usually, just one ablation treatment is required except in exceptional

circumstance
6. The treatment time is short, generally within 1–2 h
12 1 An Introduction
7 . There is no risk of radiation; and

8. The treatment can be repeated for a recurrent tumor. The HIFU effectiveness and
safety for treating fibroids and adenomyosis will be elaborated in subsequent
chapters.
References
1. Marinova M, et al. Novel non-invasive treatment with high-intensity focused ultrasound
(HIFU). Ultraschall Med. 2016;37(1):46–55.
2. Shui L, et al. High-intensity focused ultrasound (HIFU) for adenomyosis: two-year follow-up
results. Ultrason Sonochem. 2015;27:677–81.
3. Huang L, Du Y, Zhao C. High-intensity focused ultrasound combined with dilatation and
curettage for cesarean scar pregnancy. Ultrasound Obstet Gynecol. 2014;43(1):98–101.
4. Lee J-S, et al. High-intensity focused ultrasound combined with hysteroscopic resection to
treat retained placenta accreta. Obstet Gynecol Sci. 2016;59(5):421–5.
5. Aubry J-F, et al. The road to clinical use of high-intensity focused ultrasound for liver cancer:
technical and clinical consensus. J Ther Ultrasound. 2013;1(1):13.
6. Li S, Wu P-H. Magnetic resonance image-guided versus ultrasound-guided high-intensity
focused ultrasound in the treatment of breast cancer. Chin J Cancer. 2013;32(8):441.
7. Dababou S, et al. A meta-analysis of palliative treatment of pancreatic cancer with high inten-
sity focused ultrasound. J Ther Ultrasound. 2017;5(1):9.
8. Li C, et al. Non-invasive treatment of malignant bone tumors using high-intensity focused
ultrasound. Cancer. 2010;116(16):3934–42.
9. Thompson SM, et al. Image-guided thermal ablative therapies in the treatment of sarcoma.
Curr Treat Options Oncol. 2017;18(4):25.
10. Maloney E, Hwang JH. Emerging HIFU applications in cancer therapy. Int J Hyperth.

2015;31(3):302–9.
11. Stewart EA, et al. Sustained relief of leiomyoma symptoms by using focused ultrasound sur-
gery. Obstet Gynecol. 2007;110(2 Part 1):279–87.
12. Schlesinger D, et al. MR-guided focused ultrasound surgery, present and future. Med Phys.
2013;40(8):080901.
13. Zini C, et al. Ultrasound-and MR-guided focused ultrasound surgery for prostate cancer. World
J Radiol. 2012;4(6):247.
14. Merckel LG, et al. MR-guided high-intensity focused ultrasound ablation of breast cancer with
a dedicated breast platform. Cardiovasc Intervent Radiol. 2013;36(2):292–301.
15. Yiallouras C, Damianou C. Review of MRI positioning devices for guiding focused ultrasound
systems. Int J Med Robotics Comput Assist Surg. 2015;11(2):247–55.
16. Hesley GK, et al. A clinical review of focused ultrasound ablation with magnetic resonance
guidance: an option for treating uterine fibroids. Ultrasound Q. 2008;24(2):131–9.
17. Wang W, et al. Safety and efficacy of US-guided high-intensity focused ultrasound for treat-
ment of submucosal fibroids. Eur Radiol. 2012;22(11):2553–8.
18. Chen J, et al. Safety of ultrasound-guided ultrasound ablation for uterine fibroids and adeno-
myosis: a review of 9988 cases. Ultrason Sonochem. 2015;27:671–6.
19. Zhang L, et al. Ultrasound-guided high intensity focused ultrasound for the treatment of gyn-
aecological diseases: a review of safety and efficacy. Int J Hyperth. 2015;31(3):280–4.
Sedation and Analgesia for HIFU
Ablation 2
Sedation reduces irritability or agitation by administering sedative drugs; generally,

it is used in a medical procedure or diagnostic procedure. Sedation can be classified
into four stages: mild sedation (anxiety); moderate sedation (conscious sedation);
deep sedation; and general anesthesia. Table 2.1 showed the Ramsay sedation score
most commonly used to define sedation [1]. Most HIFU ablation of uterine fibroids
and adenomyosis in gynecology is performed under conscious sedation with
analgesia.
A Ramsay score of grade 3–4 is ideal for alleviating anxiety. It allows a patient
to tolerate mild discomfort and pain yet still can make conscious responses to verbal
instructions and light tactile stimuli. Conscious sedation facilitates surgery by
reducing patient movements while maintaining an adequate cardiopulmonary func-
tion. Deeper sedation or general anesthesia is not advisable or necessary for this
type of HIFU surgery. Excessive respiratory movements of a deeply sedated patient
affect the position of the target area for ablation. To avoid heat injury to the skin and
injury to the sacral nerves and their distributions, the patient needs to be sufficiently
awake throughout the procedure to communicate if her skin feels too hot or if she
feels numbness over her lower back and thighs.
2.1 The Choice of Drugs for Sedation and Analgesia
The ideal properties of anesthetic drugs used in HIFU ablation of uterine fibroids
should be rapid onset, rapid recovery, controllable, minimal accumulation, and min-
imal adverse cardiovascular and other side effects.
https://doi.org/10.1007/978-981-16-0939-8_2
14 2 Sedation and Analgesia for HIFU Ablation
Table 2.1 Ramsay sedation score

Score status Description
1 Patient anxiety, restlessness
2 Sober, cooperative, quiet, directional
3 Quiet to sleep and respond to instructions
4 Drowsiness, quick response to light eyebrows or loud auditory
stimuli
5 Drowsiness, unresponsive to light eyelashes or loud acoustic
stimuli
6 Deep sleep, no reaction, loss of consciousness
2.2 First-Line Drugs
The commonly used drugs include midazolam (a benzodiazepine) and other short-
acting opioid analgesics like fentanyl, sufentanil, and remifentanil.
(a) Midazolam (trade name: Dormicum)

Midazolam, also known as imidazolinium, is currently the most commonly
used benzodiazepine sedative-hypnotics for procedural sedation, preoperative
sedation, and the induction of general anesthesia. It has dose-dependent seda-
tion, hypnosis, anxiolytic, anticonvulsant, antiepileptic, and central muscle
relaxation effects with increasing dosages. There is a strong antegrade amnesic
effect. The drug itself can enhance other anesthetics’ analgesic effect and has a
half-life of (2.4 ± 0.8) h after infusion. The cardiovascular side effects are mild,
and the respiratory depression effect is dose-related.
(b) Propofol (Trade name: Diprivan) 2,6- Diisopropylphenol
Propofol is a short-acting intravenous anesthetic. Its rapid onset and rapid
recovery with amnesic effects make it a popular agent for use in sedation and
anesthesia. The drug is highly protein-bound and metabolized in the liver (elim-
ination half-life 2–24 h); however, its clinical effects are much shorter. The
effects are terminated by rapid distribution into the peripheral tissues.
The side effects of Propofol include hypotension and respiratory depression.
Its hemodynamic effect is more pronounced than many intravenous anesthetic
agents and is related to the dose and rate of administration and potentiated by
opioid analgesics.
(c) Fentanyl
Fentanyl is a short-acting potent opioid receptor agonist with 100 times the
potency of morphine. It is commonly used as an adjunct in clinical anesthesia
and to provide intraoperative analgesia. Its onset time is 30 s after intravenous
injection reaching peak effect within 5–10 min, and has a duration of action
between 30 and 60 min. Fentanyl provides pain relief by acting on μ-receptor in
the brain and spinal cord and effectively obtunds nociceptive stimuli. It is a
2.3 Second-Line Drugs 15
powerful respiratory depressant with little effect on the cardiovascular system.

In higher doses, it may cause muscle rigidity.
( d) Pethidine
Pethidine is a synthetic opioid receptor agonist and is one of the most com-
monly used perioperative analgesics. Its action and mechanism are similar to
that of morphine, but its sedative and anesthetic effects are relatively small. It
has 1/10th of the potency of morphine and is indicated to treat moderate to
severe pain with a duration of action of 2–4 h. It works mainly as a centrally
acting opioid agonist and has anticholinergic properties, which can cause relax-
ation of cardiovascular and smooth muscle. Therefore, unlike other opioids, it
does not cause miosis. As is typical of opioids, common side effects are nausea,
vomiting, dizziness, euphoria, and respiratory depression.
2.3 Second-Line Drugs
Due to the availability of drugs in different countries and patients’ condition, e.g.,
drug allergy, second-line drugs are sometimes used to replace the above medica-
tions. These are:
(e) Sufentanil
Sufentanil is a novel opioid analgesic and is a highly selective μ-receptor agonist.
It is an analog of fentanyl used as an adjunct to anesthesia and for intraoperative
analgesia. It has shorter distribution and elimination half-lives and is ten times
more potent analgesic than fentanyl. Sufentanil produces similar respiration
depression, but for a more prolonged period than an equivalent dose of fentanyl.
(f) Remifentanil
Remifentanil is a new synthetic, ultra short-acting potent opioid analgesic from
the Fentanyl family with rapid onset of action, strong efficacy, and rapid recov-
ery. The elimination half-life is less than 10 min as it is metabolized by esterase.
It is best given as a continuous intravenous infusion as an adjunct to anesthesia.
The analgesic effect of remifentanil is dose-dependent with a ceiling effect. Its
most common side effects are hypotension and respiratory depression, stron-
gest within a few minutes after administration, partial recovery in about 6 min,
and complete recovery in about 15 min.
(g) Tramadol
Tramadol is a synthetic nonnarcotic central analgesic used to treat moderate to
moderately severe pain. It is available as injection as well as oral tablets alone
or in combination with paracetamol. Tramadol acts on opioid receptors, alpha
adrenoceptors, serotonin, and both muscarinic and nicotinic acetylcholine
receptors. Although it can bind to opioid receptors, its affinity is very weak. The
drug is metabolized in the liver and excreted by the kidneys. As is typical of
opioids, common side effects include nausea, pruritis, and constipation.
(h) Hydromorphone
Also known as dihydromorphine, hydromorphone is a semisynthetic derivative
of morphine. It is a pure μ-opioid receptor agonist administered by a single
intramuscular injection (2 mg/injection) in patients with severe pain after HIFU
treatment of adenomyosis. Pain relief begins within half an hour and lasts up to
5 h. Adverse effects of hydromorphone are similar to those of other potent opi-
oid analgesics like morphine and pethidine. Dose-related respiratory depression
is a concern, especially if used in conjunction with other sedatives and opioids.
Other common side effects include dizziness, sedation, nausea, and vomiting.
(i) Nonsteroidal anti-inflammatory drugs
Nonsteroidal anti-inflammatory drugs (NSAID) have antipyretic, analgesic,
and anti-inflammatory effects. NSAID exerts their analgesic effects by cyclo-
oxygenase inhibition, reducing peripheral prostaglandin synthesis and a central
mechanism blocking serotonin release (5-HT). There are two forms of cyclo-
oxygenase enzymes (COX-1 and COX-2). Inhibition of COX-2 is the most
likely mechanism of action for NSAIDs’ analgesic effects, while COX-1 inhibi-
tion may be responsible for its adverse effects, the most common being gastro-
intestinal irritation.
Half an hour before ultrasound ablation, an NSAID such as diclofenac
sodium can be taken orally for synergistic analgesia, reducing the use of opioid
drugs, thereby reducing side effects. NSAIDs should be avoided in patients
with a history of peptic ulcer and gastrointestinal bleeding. Routine prescription
of antacids is unnecessary for patients on short-term NSAIDs and not at risk of
peptic ulcers.
2.4 Other Auxiliary Drugs Should Be Available
1. Antagonist
(a) Flumazenil (0.5 mg/ampoule) is a specific benzodiazepine antagonist used
to antagonize the sedative effect of midazolam and other benzodiazepines;
(b) Naloxone (0.4 mg/ampoule) is a competitive opioid antagonist used to
reverse respiratory depression caused by fentanyl and other opioid analgesics.
2. Other Drugs
(a) Ondansetron and granisetron are highly potent selective antagonists at 5HT3
receptors. They are used to reduce or prevent opioid-induced nausea and
vomiting.
(b) Phencyclidine hydrochloride or atropine, which is used to reduce respiratory
secretions.
(c) Dexamethasone should be available for the prevention of allergic reactions
when using hexafluoro-microbubbles (SonoVue).
(d) Standard drugs for cardiopulmonary resuscitation include ephedrine, phen-
ylephrine, norepinephrine, and lidocaine.
2.5 Midazolam and Fentanyl Sedation Protocol 17
2.4.1 Sedation and Analgesia Protocol for HIFU Ablation
Adjuvant medications, like anticholinergic (atropine) and antiemetic drugs (ondan-

setron or granisetron), may be given half an hour before HIFU treatment. When an
anesthetist is available to give sedative and analgesic drugs, the dosage of these
drugs can be given based on their knowledge and experience. The dosages were
titrated according to the patient’s response during HIFU treatment. If the anesthetist
is not available, the following common sedation and analgesic programs can be
used and administrated by the doctor or nurse during the procedure.
2.5 Midazolam and Fentanyl Sedation Protocol
1. Drug Usage: (1) Fentanyl is diluted with 0.9% physiological saline to 10 μg/mL;
Midazolam is diluted with 0.9% normal saline to 0.5 mg/mL. (2) Medication: as
intravenous injection, fentanyl generally takes effect within 3 min; peak respira-
tory depression of midazolam occurs 5–10 min after administration.
2. Medication Principles: Patients’ depth of sedation and respiration are evaluated
during administration and after administration of the drugs. The depth of seda-
tion should be controlled at Grade 3–4 to prevent overdose, causing excessive
sedation and respiratory depression.
3. The combination use of drugs are administered following the protocol below
with the following notes (see Table 2.2).
4. Dosing considerations (1) Both fentanyl and midazolam should be given as a
slow intravenous bolus over at least 1 min. There should be a minimum of 5 min
interval between the administration of the two drugs at each step. Five minutes
after the injection of fentanyl, observe the patient for any respiratory depression
and sedation depth, which should not exceed Ramsay score level 4 before mid-
azolam is added. (2) Fentanyl generally takes effect 3 min after administration.
The patient may experience dizziness and facial pruritus, which are manifesta-
tions of fentanyl’s onset of action. (3) Observe the patient’s breathing during the
infusion of these medicines. The respiratory rate should be greater than 12 times/
min, and the oxygen saturation should be higher than 90% (see the detailed index
below). Otherwise, the infusion should be stopped. (4) The patient’s depth of
sedation should be assessed during drug infusion and preferably maintained is at
levels 3–4.
Table 2.2 ABCD steps of Midazolam and Fentanyl

Step Intervals Fentanyl (ug/kg) Midazolam (mg/kg)
A 1.0 0.03
B 30 min interval from A 1.0 0.02
C 30 min interval from B 0.8 0.02
D 40 min interval from C 0.8 0.015
2.6 ther Sedation and Analgesic Regimes:

O
Dexmedetomidine and Remifentanil Sedation Protocol
1. Drug Usage
(a) Dexmedetomidine is diluted with 0.9% normal saline to a concentration of
4 ug/mL and remifentanil to a concentration of 20 ug/mL. Dexmedetomidine
is contraindicated in patients with hypertension and cardiac arrhythmia.
(b) Method of administration: Dexmedetomidine is effective 10–20 min after
the first loading dose for intravenous injection. Remifentanil generally acts
within 1 min.
2. Medication principles: Patients’ depth of sedation and respiration are assessed
during and after administration. The depth of sedation is controlled at grade 3–4
(Ramsay sedation score), or the awakening score is at grade 2–3. Based on the
above, remifentanil TCI concentration is adjusted at 1.0–1.8 ng/mL. This medi-
cation regime provides a stable sedative effect; the patient’s sedation depth will
be well controlled at Ramsay’s sedation score of grades 3–4 with no respiratory
depression.
3. Dosing steps: Drugs are infused with dedicated drug infusion pumps.
2.7 Monitoring During HIFU Surgery Under Sedation
(a) The degree of consciousness

The patient’s response to verbal and tactile stimuli should be observed closely
throughout the procedure. She should be able to communicate with medical
personnel at all times, either by making verbal responses or, if inconvenient, to
vocalize, be able to move her fingers to indicate that she is aware of the verbal
and tactile stimuli.
(b) Monitoring of pulmonary ventilation
The anesthetist or the surgeon can monitor pulmonary ventilation by physical
observation and observe the arterial oxygen saturation (SaO2) and the end-tidal
carbon dioxide.
1. Physician observations: By following the patient’s spontaneous respiratory
activity, including the respiratory rate displayed by the monitor, judging the
respiratory motion by observing the movements of the patient’s chest and
abdomen, and if necessary by breath sounds.
2. Oxygen saturation monitoring by pulse oximetry: The alarm threshold
should be set so that the presence of oxygen deficiency can be observed in
time (alarm threshold is set to 90% of SaO2).
3. Capnography: Monitoring end-tidal carbon dioxide can directly assess real-time
ventilation, making it easier to diagnose early respiratory depression, apnea, and
airway disorders, especially during sedation leading to serious complications.
Capnography monitoring enhances safety during procedural sedation.
(c) Monitoring oxygenation
Pulse oximetry has the advantage of being a simple, convenient, and noninva-
sive device to measure oxygen saturation during procedures. However, it cannot
2.8 Treatment of Complications 19
be relied on to assess the adequacy of ventilation (PaCO2), especially if the

patient is breathing oxygen-enriched air. The numerical decrease in SaO2 will
lag behind actual hypoxemia. Merely observing the decrease in oxygen satura-
tion can delay the diagnosis of apnoea and respiratory depression.
(d) Hemodynamic monitoring
There should be timely monitoring of blood pressure (automatic measurement
is recommended every 5–10 min), heart rate, and the number of breaths, and
continuous monitoring of ECG (if any) in patients with cardiovascular disease
and arrhythmia.
(e) Monitoring time
After using sedation analgesics, the time should be monitored throughout the
patient’s treatment until she leaves the operating room.
2.8 Treatment of Complications
2.8.1 Respiratory Depression
The most severe possible complication with the analgesic sedation protocol is respi-
ratory depression.
The criteria of respiratory depression are one of the following
1 . The number of breaths per minute is less than 12 times;

2. Over 15 s without spontaneous breathing, it is apnea;
3. Hypoxemia, i.e., oxygen saturation less than 90%, excludes the effects of poor
peripheral blood circulation and poor probe contact;
It is particularly noteworthy that after using fentanyl, a patient may forget to

breathe despite being fully conscious.
The treatment of respiratory depression
1. Encourage or stimulate the patient to take a deep breath (gentle prodding of the
patient’s back);
2. Increase the flow rate of oxygen through the nasal cannula;
3. Oxygen administered via an oro-nasal mask delivers a higher percentage of oxy-
gen to the patient than the nasal cannula or Hudson mask. The anesthetist or the
nurse can also gently hand ventilating the patient with an oro-nasal mask.
4. Administer an opioid antagonist—Naloxone is the drug of choice to antagonize opi-
oid-induced respiratory depression. The first dose of intravenous Naloxone 0.3–0.4 mg,
is effective within 2–3 min after treatment and has a duration of action of about 45 min.
Repeat doses, 0.1–0.2 mg boluses, or a continuous intravenous infusion of 5 ug/g/h of
Naloxone can be given if the respiratory depression relapses or persists.
5. Extend the observation period in the Recovery Area for 2 h, especially after
using antagonist drugs, to ensure that the patient’s vital signs are stable and that
respiratory depression does not reoccur.
2.8.2 Muscle Stiffness
(a) Muscle stiffness in the abdominal and abdominal wall can occur after adminis-
tering large doses of intravenous fentanyl [2]. This complication can cause
breathing difficulties and is potentially life-threatening; therefore, it must be
dealt with promptly. An anesthetist should be notified immediately. Intravenous
Suxamethonium 1.5 mg/kg should be given immediately to allow for rapid
endotracheal intubation and positive pressure ventilation. This complication is
rare for this protocol for HIFU surgery as the dosage of fentanyl used is rela-
tively small.
(b) Bradycardia
After the application of fentanyl, there may be a transient drop in heart rate. If
the heart rate decrease is mild, it will return to normal within 1–2 min without
treatment. If the heart rate decreases significantly (less than 60 beats/min) after
remifentanil [3] or shows a persistent decline, intravenous atropine should be
given immediately to normalize the heart rate.
2.9 Factors Affecting the Effects of Sedation and Analgesia
(a) Communication with patients is the best way to eliminate tension in patients.
The basic principle of conversation is not to increase the patient’s psychological
burden to trust the doctor and the treatment’s technology.
(b) The patient’s psychological burden comes from concerns about safety and effi-
cacy. She will work hard to stay awake to feel the reaction during treatment,
which increases the patient’s anxiety and reduces sedatives’ effect.
(c) Environmental factors: A comfortable environment is essential for the patient to
relax and fall asleep during her treatment. This environment includes lighting,
sounds and conversations with medical personnel. New HIFU theaters have
been specially designed to provide a comfortable and pleasant environment for
patients receiving HIFU ablation [4].
(d) Communication during treatment. The verbal communication between the

medical staff and the patient will inevitably increase the patient’s excitability
and influence sedation. It is recommended that gestures be used for communi-
cation, and verbal communication should be adopted only when the doctor
deems it necessary. When verbal communication between medical staff is
required, the volume should be reduced to a low level to prevent patients from
misunderstanding communication contents and unnecessarily increase their
concerns.
References 21
References
1. Sessler CN, Grap MJ, Ramsay MAE. Evaluating and monitoring analgesia and sedation in the
intensive care unit. Crit Care. 2008;12(3):S2.
2. Ackerman WE, Phero JC, Theodore GT. Ineffective ventilation during conscious sedation due
to chest wall rigidity after intravenous midazolam and fentanyl. Anesth Prog. 1990;37(1):46.
3. DeSouza G, Lewis MC, TerRiet MF. Severe bradycardia after remifentanil. J Am Soc
Anesthesiol. 1997;87(4):1019–20.
4. Zhang L, Wong F. A high-intensity focused ultrasound surgery theater design in a private
clinic. Gynecol Minim Invas Ther. 2020;9(1):1–5.
Ultrasound and MRI Imaging of Uterine
Fibroids and Adenomyosis 3
At present, the commonly used diagnostic examination of fibroids and adenomyosis

are MRI and ultrasound imaging.
3.1 Imaging for Uterine Fibroids
3.1.1 Ultrasound Imaging
Ultrasound imaging for fibroids can be divided into two approaches: (1) trans-
abdominal ultrasound and (2) transvaginal ultrasound. Transabdominal ultra-
sound is used to diagnose fibroids based on the findings of hypoechoic nodules
or lesions. However, with the increasing use of transvaginal ultrasound, it can
give more detailed and comprehensive uterine features to diagnose fibroids
with great certainty. Even in degenerative fibroids, they will have correspond-
ing echoic changes such as cystic changes or calcification. Such an ultrasound
scan will show these lesions as either hypoechoic, isoechoic, or hyper-
echoic images.
In most cases, a fibroid has a clear border due to the pseudo-capsule, which
results in a distinct boundary from the surrounding uterine muscle layer.
However, after the fibroid has grown to a larger size and after multiple fusions,
the well- defined structure disappears. Such fibroids will present with
mixed echos.
With Color Doppler Flow Imaging (CDFI), the fibroid’s blood supply usually
manifests as peripheral annular or semicircular blood flow signals, internal points-
like, rod-like, or cord-like blood flow signals. The vascularity of fibroids can be
classified by the Alder Classification, which categorizes the blood flow of the uter-
ine fibroid as follows
https://doi.org/10.1007/978-981-16-0939-8_3
24 3 Ultrasound and MRI Imaging of Uterine Fibroids and Adenomyosis
• Grade 0: no blood flow signal is seen within the lesion;

• Grade I: A small amount of blood flow within the fibroid. It shows 1–2 punctate
blood flow.
• Grade II: Moderate blood flow within the fibroid, with 1 visible main blood ves-
sel, whose length exceeds the radius of the fibroid or shows 2–3 small blood
vessels.
• Grade III: Rich blood flow within the fibroid, showing more than 4 blood vessels
or interconnected blood vessels;
• Grade IV: Peripheral blood vessels envelop the entire leiomyoma with multiple
dendritic branches extending into the leiomyoma. It can be seen that more than
four blood vessels interweave into a mesh, or blood vessels have a diameter of
more than 3 mm (Fig. 3.1).
The characteristic vascular distribution of a uterine fibroid is either scanty or in

the periphery or semicircular position of a fibroid; thus, it may help distinguish a
benign from adenomyosis or malignant uterine tumor.
Transvaginal ultrasound images of uterine fibroids (Figs. 3.2, 3.3, 3.4, and 3.5)
give more detailed and comprehensive uterine features to diagnose fibroids with
great certainty
Fig. 3.1 Transvaginal ultrasound images of a uterine fibroid, the uterus is retroverted. There is a
hypoechoic lesion visible at the fundus of the uterus, with a regular morphology and clear bound-
ary; Color Doppler Flow Image (CDFI) shows a typical circular blood flow signal around the
uterine lesion
3.1 Imaging for Uterine Fibroids 25
Fig. 3.2 Ultrasound scan showed an anterior fibroid
Fig. 3.3 Ultrasound showed a posterior fibroid

Fig. 3.4 Ultrasound scan showed multiple fibroids
3.2 Locations of Fibroids
Currently, the widely used FIGO (International Federation of Gynecology and

Obstetrics) classification (2011) is used to identify the locations of fibroids, as
shown in Fig. 3.5:
Each fibroid can allocate with one or two numbers. If the fibroid is assigned two
numbers, e.g., 2–5, the first number 2 indicates the relationship with the endome-
trium, and the second number 5 indicates the relationship with the serosa. However,
both have less than 50% towards the endometrium and serosa.
3.2.1 MRI Imaging
The MRI signal can directly reflect the locations, sizes, and characteristics of the
fibroid, to some extent, the fibroid’s pathological nature; T2WI images not only
diagnose the histological subtypes, fibroid degeneration, or sometimes neoplastic
changes of the fibroid. Therefore, MRI imaging is recommended before all HIFU
ablations for fibroids.
3.2 Locations of Fibroids 27
Submucosal 0 Pedunculated intracavity

5
1 <50% intramural
2 => 50% intramural

Intramural 3 Contacts endometrium:100% 4
intramural 6 0
4 100% intramural
1 3
5 =>50% intramural, subserous 7
Subserous 6 Subserous, < 50% intramural 2
7 Subserous, pudunculated
2-5
Other 8 Cervical, parasitic
Hybrid 2-5 Submucosal and subserous, each
with less than half the diameter in
the endometrial and peritoneal
cavities
Fig. 3.5 The FIGO classification showing locations of fibroids in the uterus
1. Since HIFU treatment is a noninvasive procedure, there will not be any patho-
logical diagnosis of the fibroids made before HIFU ablation. MRI is an essential
auxiliary examination to evaluate and determine the nature of the uterine fibroids,
and particularly the possibility of malignancy. In patients with heavy or irregular
vaginal bleeding, an irregularly thickened endometrium (>15 mm) shown in the
MRI scan would suggest the need for endometrial sampling or D&C to exclude
uterine lesions or cancer.
2. MRI is accurate to reveal the number, sizes, location, blood supply, and the
fibroids’ relationship to surrounding tissues. Preoperative MRI T2WI and con-
trast T1WI signals can make a preliminary assessment of the susceptibility of the
fibroids to HIFU ablation and make a reliable prediction on the difficulty and
effectiveness of treatment [1].
MRI shows a clearer picture of uterine fibroids, and according to the locations of
fibroids, MRI images show three categories of fibroids—(1) submucosal fibroids,
(2) intramural fibroids, and (3) subserosal fibroids (Fig. 3.6).
MRI signal intensity depends on the tissue proton density, T1 and T2 relaxation
time, so the MRI signal intensity directly reflects the tissue’s characteristics. Many
uterine fibroids show homogeneous low signal intensity in the MRI T2WI image.
These fibroids consist of closely arranged myomatous cells but lack sufficient inter-
cellular fluid and mucin between cells. Therefore, on the T2WI image, these fibroids
appear darker than the surrounding uterine wall, i.e., hypointense signal.
Based on the MRI signal intensities, T1-weighted images show isointense sig-
nals resembling those of the adjacent myometrium, and T2-weighted images may
show low/equal/high signals. Fibroids usually have low T2WI signal intensity, clear
a b
c d
Fig. 3.6 Locations of fibroids: (a): the white arrow indicates type 2 fibroids; (b): the white arrow
shows type 2–5 fibroids, black arrows show type 5 fibroids; (c): the white arrow indicates type 2
fibroids, white triangle indicates a type 4 fibroid, and black arrows indicate type 5 fibroids; (d):
Multiple fibroids, white arrows show type 0 fibroids
boundaries, and may sometimes have a slightly high signal appearance. However,
fibroids in some conditions can present with different T1 and T2 weighting signal
intensities. These conditions are (1) calcification shows hypointense signals at T1
and T2, (2) cystic changes are hypointense signals at T1 but hyperintense at T2, (3)
mucoid degeneration has slight hyperintense signals at T1 and hyperintense signals
at T2. The above various MRI signal intensities have a tremendous and significant
influence on the HIFU ablation result.
The gold standard for determining benign from malignant tumors is the patho-
logical examination, which has an accuracy reaching 99%. Developments in imag-
ing technology, including color Doppler ultrasound, enhanced MRI and tumor
markers, etc., allow accuracy rates approaching 95% or more [2, 3]. Although mag-
netic resonance imaging features of uterine sarcoma have been described, confusing
appearances between uterine leiomyosarcomas and other atypical leiomyomas can
make it challenging to make an accurate diagnosis. If malignancy is suspected, sur-
gical treatment is recommended to remove it.
3.3 Uterine Adenomyosis 29
3.3 Uterine Adenomyosis
Imaging has an indispensable role in diagnosing adenomyosis, defining its extent,

assisting in planning and evaluating the effect of treatment. Ultrasound, an espe-
cially transvaginal ultrasound, is the first-line imaging method for adenomyosis
because of its advantages of simplicity, no radiation, easy repeatability.
Transabdominal ultrasound is the commonly used ultrasound examination
method, and it can display a full picture of the uterus (Fig. 3.7). The transabdominal
ultrasound features of adenomyosis are shown in Figs. 3.8 and 3.9. However, these
features are susceptible to abdominal wall thickness, degree of bladder distension,
and intestinal flatulence.
The transvaginal ultrasound scan is one of the commonly used ultrasound inves-
tigations in gynecology if it is feasible. Due to the high frequency of transvaginal
probe, its proximity to the pelvic organs, and excellent image resolution, it can
display the structural characteristics of adenomyosis and its blood flow and any
uterine ovarian or pelvic lesions. It is also not affected by bowel gas interference
and abdominal wall thickness. A transvaginal scan is superior to a transabdominal
ultrasound scan in the detailed observation of adenomyosis.
Fig. 3.7 Transabdominal
scan image of diffuse
adenomyosis, showing a
diffusely and uniformly
enlarged uterus in the
uterine fundus, anterior
wall, and posterior wall of
the same thickness. The
cervix was of normal size
ultrasound image showed
that the echo of the
posterior wall adenomyosis
ultrasound image showed
that the anterior uterine
muscle layer was
significantly thickened, and
the echo was uneven.
Multiple small echoless
areas scattered in the lesion
were visible. It was a
diffuse anterior wall
adenomyosis
3.4 Transvaginal Ultrasound Appearances of Adenomyosis
The main ultrasound features of adenomyosis include uterine enlargement, asym-

metry thickening of the anterior and posterior wall of the uterus, uneven echoes,
small cysts, or microcysts in the affected muscular layer. Besides, the increase in
CDFI blood flow signals is a common manifestation. The blood flow signals in the
affected area of the myometrium will present as penetrating vascularity. The ultra-
sound features of adenomyosis can be listed as follows:
1. The uterus is enlarged, with the asymmetry of the anterior and posterior walls of
the uterus. The distribution of adenomyosis lesions can classify into diffuse type,
anterior/posterior wall type, and focal type. Regardless of diffuse or focal adeno-
myosis, the unevenly affected myometrium is the most common ultrasound
appearance of adenomyosis.
2. Another specific ultrasound features of adenomyosis is the small cysts in the
myometrium (Fig. 3.10). A recent study had shown that the most specific ultra-
sound feature of transvaginal ultrasound diagnosis of adenomyosis was myome-
trial cysts (98% specificity), and the most sensitive ultrasound feature is the
uneven myometrial echo (88% sensitivity) [4]. Of course, myometrial cysts may
also be cystic degeneration in uterine fibroids and need to be identified.
3. Other characteristic ultrasound features are the fan-shaped sound shadow in the
myometrium due to the disturbances of echo-enhanced and echo-reduced areas
in the adenomyosis (Fig. 3.11).
4. In adenomyosis, due to myofibrosis and hypertrophy of the uterine myometrium,
blood vessels in the uterine myometrium have also generally increased. Color Doppler
flow imaging (CDFI) showed increased blood flow signals in the uterine myometrial
area (Fig. 3.12). The area of increased blood flow signal can reflect the distribution of
adenomyosis in the myometrium. At the same time, the CDFI appearance of adeno-
myosis can also distinguish between adenomyosis and uterine fibroids [5].
3.5 MRI Appearances of Adenomyosis 31
Fig. 3.10 Transvaginal
ultrasound image of an
anterior wall adenomyosis
showing that the thickened
anterior wall and the echo
are significantly uneven.
There are several small
non-echoic cysts and high
echoes around the
non-echoic area
Fig. 3.11 Transvaginal ultrasound image of adenomyosis shows fan-shaped sound shadows
(white arrows) in the uterus, which are straight and thin by many streaks or pencils like sound
shadows. These sound shadows are arranged in a fan-shaped or jalousie-like arrangement
3.5 MRI Appearances of Adenomyosis
The classic appearance of MRI for adenomyosis is the diffuse enlargement of the
uterus, generally with smooth outer contours, with the lesions more clearly dis-
played on the T2-weighted image. They are low-signal lesions with poorly defined
borders, adjacent to the endometrium, and unclear boundaries. The MRI appearance
Fig. 3.12 A CDFI image shows typical penetrating blood flow signals into the uterine adenomyosis
Fig. 3.13 The MRI

picture of diffuse
adenomyosis in both the
anterior and posterior
uterine walls
of adenomyosis depends on adenomyosis lesions and echo features; this disease can
classify into diffuse type, anterior/posterior wall type, and focal type.
1 . Diffuse type (Fig. 3.13)

2. Anterior/posterior wall type (Fig. 3.14)
3. Focal (adenomyoma) type (Fig. 3.15)
3.5 MRI Appearances of Adenomyosis 33
Fig. 3.14 The MRI

picture of diffuse
adenomyosis in the
posterior uterine wall
Fig. 3.15 The MRI

picture of focal
adenomyoma in both the
anterior and posterior
uterine wall. The
endometrial-myometrial
junction appears normal
Kishi et al. [6] proposed to divide adenomyosis into four subtypes according to
the MRI appearances: Subtype I is called internal adenomyosis, which occurs only
in the inner layer of the uterus. It shows a thickened endometrium-myometrial junc-
tional zone but does not involves the outer uterine layer. Subtype II is called external
adenomyosis, which occurs in the outer uterine layer and does not involve the junc-
tional zone. Subtype III is called intramural adenomyosis, which exists alone in the
myometrial layer, and does not involve other structures. Subtype IV includes adeno-
myosis that has a mixed presentation, including two or three of the above.
The adenomyosis has various presentations due to its involvement of different
parts of the uterus Adenomyoma appears on the T2-weighted image as a low-
signaled focal adenomyosis lesion in the muscle layer with an ill-defined border and
may contain small cystic foci with high signals. Sometimes small cystic foci appear
brighter on the T1-weighted image [7].
With the increasing use of an MRI scan for adenomyosis, there will be more
descriptions of adenomyosis features. The implications of these features may cor-
respond to the histopathological findings well. However, the correlation of these
features to the severity of the lesions and their clinical treatment responses should
be studied.
3.6 eiomyosarcoma and Endometrial Stromal Sarcoma—

L
MRI Features
MRI features of leiomyosarcoma (LMS) include nodular borders, non-perfused

areas, hyperintensity areas on T1WI, and quick enhancement at the early arterial
phase; and shared MRI features with that of uterine sarcomas include heteroge-
neous intermediate signal on T2WI, and hyperintensity on DWI with low ADC
value, associated with intratumoral hemorrhage and necrosis [8, 9]. Both MRI
T2W1 and contrast-enhanced MRI have proven the ability to detect tumor necrosis,
which is a significant finding of the rapidly growing malignant uterine neoplasms.
In their study, Huang et al. [10] reported that central non-enhancement (CNE) and
well-demarcated pocket-like non-enhanced areas have significantly higher diagnos-
tic accuracy than T2WI, T1WI, and T2WI, in the differentiation between leiomyo-
sarcoma and uterine fibroids. Hyperintensity on DWI is also reported to have high
sensitivity in differentiation between LMS and uterine fibroids [11].
Endometrial stromal sarcoma (ESS) is the second most common uterine sar-
coma. ESS tends to show high signal intensity on T2WI and increased and pro-
longed contrast enhancement. MRI feature of ESS includes nodular lesions at the
tumor margin, or marginal nodules, intramyometrial worm-like nodular exten-
sions [12].
References
1. Cheng H, Wang C, Tian J. Correlation between uterine fibroids with various magnetic reso-
nance imaging features and therapeutic effects of high-intensity focused ultrasound ablation.
Pak J Med Sci. 2015;31(4):869.
2. Santos P, Cunha TM. Uterine sarcomas: clinical presentation and MRI features. Diagn Interv
Radiol. 2015;21(1):4.
3. Koyama T, et al. MR imaging of endometrial stromal sarcoma: correlation with pathologic
findings. AJR Am J Roentgenol. 1999;173(3):767–72.
4. Tellum T, et al. Development of a clinical prediction model for diagnosing adenomyosis. Fertil
Steril. 2018;110(5):957–964.e3.
5. Exacoustos C, et al. Adenomyosis: three-dimensional sonographic findings of the junctional
zone and correlation with histology. Ultrasound Obstet Gynecol. 2011;37(4):471–9.
6. Kishi Y, et al. Four subtypes of adenomyosis assessed by magnetic resonance imaging and
their specification. Am J Obstet Gynecol. 2012;207(2):114.e1–7.
References 35
7. Song SE, et al. MR imaging features of uterine adenomyomas. Abdom Imaging.
2011;36(4):483–8.
8. Shah SH, et al. Uterine sarcomas: then and now. Am J Roentgenol. 2012;199(1):213–23.
9. Lakhman Y, et al. Differentiation of uterine leiomyosarcoma from atypical leiomyoma: diag-
nostic accuracy of qualitative MR imaging features and feasibility of texture analysis. Eur
Radiol. 2017;27(7):2903–15.
10. Huang Y-T, et al. Current status of magnetic resonance imaging in patients with malignant
uterine neoplasms: a review. Korean J Radiol. 2019;20(1):18–33.
11. Tirumani SH, et al. Current concepts in the imaging of uterine sarcoma. Abdom Imaging.
2013;38(2):397–411.
12. Ueda M, et al. MR imaging findings of uterine endometrial stromal sarcoma: differentiation
from endometrial carcinoma. Eur Radiol. 2001;11(1):28–33.
Uterine Fibroids and HIFU Ablation
4
Uterine fibroids are common benign uterine tumors in women of childbearing age,
with an incidence ranging from 20 to 40% [1]. They mainly develop from uterine
smooth muscle cell proliferation, including a small amount of fibrous connective
tissues. The medical terminology is “uterine leiomyoma,” but the condition is com-
monly known as uterine fibroids by the lay public.
The etiology of uterine fibroids is still not fully understood. A large number of
clinical observations and experimental research have found that uterine fibroids are
hormone-dependent tumors. Estrogen is a major causative factor in the growth of
fibroids. Growth hormone (GH) and human placental lactogen (HPL) are also
related to fibroids’ growth. Since the upper central nervous system (CNS) controlled
ovarian function and hormone metabolism, CNS activity may play an important role
in fibroids’ pathogenesis. Uterine fibroids are common in women of childbearing
age, widowed, and sexually inactive women. Some studies have also suggested that
long-term sexual imbalances might cause chronic pelvic congestion leading to uter-
ine fibroids. In short, the occurrence and development of uterine fibroids are
multifactorial.
4.1 Symptoms of Uterine Fibroids
Many patients with uterine fibroids are asymptomatic, with the condition often only
identified during routine pelvic examinations or ultrasound examinations. Common
clinical symptoms arising from fibroids include
1. Menstrual disorder—this is the most common presenting symptom of uterine

fibroids and occurs in more than half of patients with this condition. It can mani-
fest as increased menstrual flow, prolonged menstrual periods, or shorter cycles.
Submucosal fibroids and intramural fibroids are the common types of fibroids
https://doi.org/10.1007/978-981-16-0939-8_4
38 4 Uterine Fibroids and HIFU Ablation
that cause such symptoms. Subserosal fibroids rarely cause menstrual

disturbances.
2. Abdominal mass and pressure symptoms—fibroids can grow to such a size they
may mimic a pregnancy. The finding is especially apparent in the early morning
when the bladder is full. Such masses are solid, movable, and free from pain dur-
ing palpation. Fibroids reaching a specific size can cause pressure symptoms to
the surrounding organs. Anterior uterine wall fibroids close to the bladder can
produce urinary frequency and urgency. Large cervical fibroid can compress the
bladder, which can, in turn, block the urine outflow causing urinary retention.
Posterior uterine fibroids, especially at the cervix, can compress the rectum and
cause weak bowel movements and discomfort at defecation. Large, broad liga-
ment fibroid can compress the ureter and even cause hydronephrosis, i.e., swell-
ing of the kidney.
3. Pain—under normal circumstances, uterine fibroids do not cause pain. Some
patients however may have lower abdominal distension and low back pain. When
a pedunculated fibroid undergoes torsion or develops red degeneration, it can
produce acute abdominal pain. Fibroids can often associate with endometriosis
or adenomyosis simultaneously; in such situations, patients can also have pain
during menstruation.
4. Increased vaginal discharge—any submucosal fibroid will cause vaginal dis-
charge. Such fibroids will enlarge the uterine cavity’s sizes, the number of endo-
metrial glands, and pelvic congestion thus causing increased whitish vaginal
discharge—leucorrhea. Endometrial or cervical submucosal fibroids can develop
ulcers, infections, necrosis, bloody, or purulent vaginal discharge.
5. Infertility and miscarriage—large-sized uterine fibroids can cause deformation
of the uterine cavity, impacting embryo implantation, embryo growth, and devel-
opment. Fibroids close to the tubal lumen can compress the tubal openings and
give rise to a closed tubal lumen. Submucosal fibroids can hinder embryo
implantation or delay the entry of sperm into the tubal lumens. These fibroids
may lead to infertility.
6. Anemia—fibroids can cause increased menstrual flow or prolonged irregular
vaginal bleeding. Therefore, severe anemia is more common in patients with
large fibroids and submucosal fibroids.
7. Polycythemia—a small number of patients with large uterine fibroids may

develop increased numbers of red blood cells (polycythemia). It is likely due to
ectopic hormones produced by the fibroid tumor.
8. Hypoglycemia is a low sugar level in the blood, probably related to ectopic hor-
mones, loss of appetite, anemia, and weakness. The patient may feel dizziness
and fainting at work.
4.2 Indications for Treatment
Asymptomatic and small fibroids usually do not need any treatment. However,
patients could have HIFU treatment for the following indications:
4.3 Investigative Methods 39
1. Due to their different positions and sizes, fibroids can cause moderate or severe
clinical symptoms, e.g., heavy bleeding and pressure symptoms, some of which
are sufficiently disturbing or debilitating to require treatment;
2. Fibroids may lead to difficulty in patients to get pregnant. Thus, treatment may
be suitable for patients of reproductive age with infertility or miscarriage
problems;
3. When patients have severe psychological burdens due to fibroids and their asso-
ciated symptoms, they should have treatment to reduce their mental stress.
4. Young patients with multiple small fibroids may wish to consider therapy to
decrease the risk of subsequent problems as they get old.
4.3 Investigative Methods
Before treatment, patients should have investigations for the presence of uterine
fibroids and confirm the need for medical or surgical treatment.
1. Ultrasound: Ultrasound examination is the most commonly used diagnostic

method at present. It is cheap, convenient, quick, and easy to perform. It can
readily display an enlarged uterus with an irregular shape, together with the
number, locations, and sizes of fibroids. It can also show a fibroid’s content,
whether it is wholly solid, liquefied, or cystic. Ultrasound can identify whether
there is degeneration, calcifications, or possibly suspected malignant changes in
the fibroid. It is also helpful in distinguishing fibroids from ovarian tumors or
other pelvic masses. As demonstrated by ultrasound imaging, fibroids’ details
are fully described in Chap. 3 in this book.
2. Hysteroscopy: Hysteroscopy can be used to directly observe the uterine cavity,
with or without abnormal growths thus contributing to the diagnosis of submu-
cosal fibroids. Because of the need to use a distending medium like saline or
dextrose into the uterine cavity through the cervix, some patients may feel pain
and discomfort if diagnostic hysteroscopy is performed without a sedative
analgesic.
3. Laparoscopy: Fibroids should be distinguished from ovarian tumors or other pel-
vic masses, then sometimes laparoscopic examination is performed. This proce-
dure allows direct observation of uterine size, morphology, site of the tumor, and
judgment of the nature of the problem. However, laparoscopy requires general
anesthesia, hospitalization, and is an invasive surgery. It is the last resort in the
list of investigations.
4. Magnetic Resonance Imaging (MRI): MRI allows a high diagnostic accuracy of
uterine fibroids. It can clearly show the size, number, location, and relationship
of fibroids to adjacent tissues and is especially useful for differential diagnosis of
benign and malignant uterine fibroids. However, such imaging is expensive and
takes about 15–30 min for the examination. MRI machines are also noisy and
used in an isolated room. Thus, it is not suitable for patients that have claustro-
phobia. It is also not permitted for patients with metal implants that could be
affected by the strong electromagnetic field of MRI. As demonstrated by MRI

imaging, fibroids’ details are fully described in Chap. 3 in this book.
4.4 Treatments
Treatment can be either by observation or surgery, depending on the patients’ age,

symptoms, sizes, and locations of the fibroid/s.
1. Conservative management by follow-up observation

If the patient has small fibroids, say 5 cm or below, but with no apparent clinical
symptom and no malignant transformation signs, they can be observed regularly
at follow-up visits. If fibroids continue to grow or clinical symptoms develop,
conservative management should cease, and the patient should have treatment.
2. Medical treatment with drugs
The following medications are used to treat symptomatic fibroids:
(a) Gonadotropin-releasing hormone agonist (GnRH-a, e.g., leuprorelin)—
GnRH-a is not suitable for long-term continuous use. It is for preoperative or
postoperative adjuvant treatment. It is usually limited to 3–6 monthly cycles
to avoid producing severe menopausal symptoms or osteoporosis associated
with the low estrogen status.
(b) Mifepristone—Mifepristone is a progesterone antagonist. In recent years, it
has been clinically used to treat uterine fibroids to reduce fibroids’ size.
However, the fibroids tend to regrow again after the drug treatment stops.
(c) Danazol—Danazol is used for the preoperative treatment of unsuitable uter-
ine fibroids to reduce their size. However, uterine fibroids often regrow after
the drug stops. Danazol has many side effects caused by its androgenic
action, e.g., weight gain, acne, hoarseness of voice, etc. It can also some-
times cause severe liver damage [2].
(d) Tamoxifen—Tamoxifen inhibits fibroid growth. However, long-term use in
individual patients may increase some uterine fibroids’ size and may even
induce endometriosis or endometrial cancer [3].
(e) Androgen drugs—Drugs in this category include testosterone (methyltestos-
terone) and testosterone propionate. They can inhibit the growth of fibroids.
However, patients may develop masculinizing features.
3. Surgical treatment
Conventional surgical treatment includes myomectomy and hysterectomy, using
either the abdominal, transvaginal, or endoscopic (hysteroscopic or laparoscopic)
approach. The surgical procedure’s choice depends on the patient’s age, fertility
desire, sizes, number, and locations of fibroids. Other factors to be considered
include the surgeon’s skill, the range of techniques he/she has competence in,
and whether the patient is suffering any other medical conditions.
(a) Myomectomy—Myomectomy is performed by cutting open the uterine
wall, removing the fibroid from its pseudo-capsule, and then suturing the
uterine wound. It is mainly used for younger women under the age of 40
4.4 Treatments 41
because they would like to conserve the uterus and preserve fertility by this
surgical procedure.
These surgical indications are large fibroids, menorrhagia, pressure symptoms,
infertility due to fibroids, large submucosal fibroids, and fast-growing fibroids
without malignancy features. However, there remains a problem of fibroid recur-
rence after this surgery. The recurrence rate is about 50% within 5 years [4].
(b) Hysterectomy—Hysterectomy can be performed for patients with severe
symptoms but without fertility desire. It can also be for fibroids that have
features of malignant transformation. The hysterectomy is to remove the
uterus and the cervix and retain one or both appendices. Bilateral fallopian
tubes and ovaries are removed together in patients of older age, particularly
those after menopause. There are three main approaches to removing the
uterus: laparoscopy, vaginal, or open abdominal surgery.
Hysterectomy includes either total hysterectomy (cervix removed) or subto-
tal hysterectomy (cervix conserved). In older women, total hysterectomy is
more appropriate to reduce the risk of cervical malignancy or repeated sur-
geries. Pap smear before the operation should be performed to exclude cervi-
cal malignancy. Subtotal hysterectomy can be offered to younger women to
avoid sexual dysfunction or genital prolapse after surgery.
(c) Uterine arterial embolization (UAE)—This procedure is performed by
inserting an arterial catheter into the uterine arteries via the femoral artery at
the groin and injecting embolic particles to block the blood supply to the
uterine fibroid. It achieves a reduction in fibroids’ sizes by atrophy or, ide-
ally, even causes fibroids’ disappearance. However, 5% of patients have a
risk of premature ovarian failure after UAE surgery. There are also rare
reports of pelvic infections, bowel obstruction, and accidental thrombosis
threats in other major blood vessels [5].
(d) Laparoscopy—Laparoscopic hysterectomy or myomectomy is a common
surgical technique for treating fibroids today. Laparoscopic surgery refers to
using a cold light source to provide illumination after introducing a laparo-
scope into the abdominal cavity. Through the laparoscope, the operating sur-
geons observe and operate within the abdominal cavity while watching on a
dedicated monitor to perform either myomectomy or hysterectomy to treat
uterine fibroids.
(e) High intensity focused ultrasound(HIFU)or Focused ultrasound surgery
(FUS)—By taking advantage of the ultrasound ability to penetrate tissue and
focusing capacity to create a high temperature over 65 °C within the target
area, HIFU/FUS induces coagulation necrosis of the fibroid. Fibroids after
HIFU ablation can be gradually absorbed and then shrink in size, and then
fibroids-related symptoms would progressively relieve. It applies to patients
with symptomatic uterine fibroids, severe psychological burdens, and fertil-
ity requirements. By keeping uterine integrity, HIFU/FUS has the advan-
tages of noninvasiveness, rapid postoperative recovery, and repeatability.
When HIFU/FUS compares to traditional open surgery and laparoscopy, it has

the following differences as listed in Table 4.1
Table 4.1 Comparisons of surgical treatment vs. HIFU ablation (FUS)

Traditional open Laparoscopic surgery
Approach surgery (MIS) HIFU ablation (FUS)
Nature Cut wound Cut wounds Focused ultrasound
Surrounding Maximal harm Minimal harm Nearly no harm
healthy tissues
Uterus May remove the May remove the uterus Uterus and its
uterus functions conserved
Wound Large wound Small wounds No wound
Treatment time Long Long Short to moderate
General anesthesia General anesthesia General anesthesia with No need for general
with intubation intubation anesthesia
Recovery time 3 months 4–6 weeks <2 days
Adhesions 50–90% 10–30% 0%
Compared to HIFU/FUS, minimally invasive surgery (MIS) skill requirements

such as laparoscopic surgery are relatively high, with the following risks related to
the laparoscopic procedure: (1) General anesthesia. (2) Intraoperative bleeding. (3)
Postoperative infection. (4) Potential intra-abdominal implantations of malignancy
during the removal of fibroids. (5) Poor uterine wound healing. (6) Long-term risk
of uterine rupture during postoperative pregnancy and labor. (7) High recurrent rate
of fibroids (about 30–51%) [4, 6].
Therefore, minimally invasive surgery is not yet an ideal approach for the treat-
ment of uterine fibroids. Regardless of any surgical approach, the treatment that
retains the uterus will raise the possibility of recurrent uterine fibroids or new
fibroids formation. No such treatment can guarantee the complete removal of uter-
ine fibroids apart from a hysterectomy, which is currently the only treatment that
can remove all uterine fibroids. However, after hysterectomy, fertility is lost. It may
cause a series of physical and psychological problems such as vaginal dryness, sex-
ual pain, impaired ovarian function, early menopause, genital prolapse, and person-
ality changes. The decision to remove a uterus due to benign uterine diseases
requires careful consideration by the doctor and the patient.
HIFU ablation had treated uterine fibroids for about 20 years; up to now, many
studies have confirmed its safety and effectiveness. The clinical outcomes are simi-
lar to those of conventional and minimally invasive surgery, but the incidence of
major complications is lower than that of other surgical treatment [7].
4.5 HIFU Treatment
HIFU treatment described here is the treatment using a focused ultrasound tumor
therapeutic system from Chongqing HAIFU Medical Technology Co., Ltd. The pri-
mary mechanism of focused ultrasound treatment is to use the ultrasound beams
generated from an ultrasound transducer placed outside the body to enable rapid
heating of a target lesion while leaving surrounding tissue outside the ultrasound
4.6 The USgHIFU Ablation Procedure 43
Target
Skin
Sound Tumor
pathway
Transducer
Normal tissue
Fig. 4.1 The mechanism of the focused ultrasound ablation
pathway unaffected (Fig. 4.1). The instantaneous high temperature within the
fibroid will result in coagulation necrosis without damage to the surrounding tissue.
The body will gradually absorb the necrotic fibroid, leading to reduced uterine size
and related symptoms. To better understand the HIFU mechanism, it is similar to
using a magnifying glass to focus the sun’s light onto a piece of paper, creating a
burn. However, it is the sound waves that focus on a solid tumor.
4.6 The USgHIFU Ablation Procedure
During the HIFU ablation, the patient lies prone on the HIFU treatment table. She
will be carefully positioned with the anterior abdominal wall in contact with the
degassed water over the ultrasound transducer in a sealed tank. A water balloon, if
necessary, is used to compress or push away the bowel from the acoustic pathway to
achieve a focus on the tumor.
The ultrasound energy power is adjusted to 350–400 W, with energy intermit-
tently applied, each energy exposure lasting from 1 s and a rest period of 3 s. HIFU
sonication continues at a spot when a gray-scale change appears (Fig. 4.2). If not,
the energy exposure can be increased with less resting time. Cautions are taken to
avoid sonication ablation close to the endometrium and serosa of the uterus, usually,
appropriately 1–1.5 cm distance away. This protocol will help minimize the thermal
injury to the endometrium and sounding tissues situated next to the uterus. The
HIFU treatment can be terminated when the hyperechoic area covered the majority
of the ablated lesion. Contrast-enhanced ultrasound with microbubble (SonoVue,
Bracco, Italy) is performed before and after USgHIFU to evaluate the lesions’
response to USgHIFU treatment (Fig. 4.3).
Sacrum
Uterus
Treatment bed
Fibroid
HIFU transducer head Degassed water
Fig. 4.2 HIFU ablation of uterine fibroid with a patient lying prone on the HIFU treatment table,
with the HIFU transducer mounted below the HIFU treatment table
a b
Fig. 4.3 Contrast-enhanced ultrasound scan with microbubble. (a) Before HIFU ablation, uterine
fibroid visualized as bright spots; (b) after HIFU ablation, the fibroid showed a marked reduction
of bright areas representing ablated lesions
All fibroids that are assessed preoperatively to be suitable for HIFU ablation can
be treated. Theoretically, as long as the fibroid can be displayed, i.e., 1 cm in diam-
eter or larger ultrasound image, HIFU ablation for the fibroid is feasible with a safe
acoustic pathway. For fibroids larger than 15 cm in diameter, multiple sessions of
HIFU treatments may need to complete the ablation. HIFU ablation can be used to
treat intramural fibroids, submucosal fibroids, and subserous fibroids. It can also be
used to treat both single and multiple fibroids with one single attempt. The tech-
nique is superior to laparoscopic surgery in treating multiple fibroids when the sizes
of fibroids are small. For recurrent fibroids, the advantages of HIFU ablation are
obvious because of its noninvasiveness and repeatability. In patients with multiple
uterine fibroids, more than 80% of them are clinically suitable for HIFU ablation.
Soon after treatment with HIFU ablation, coagulation necrosis occurs in the
ablated fibroid tissue, somewhat analogous to localized cooking of a meat piece. At
this early stage, the fibroids will remain in their original position, and their size will
4.7 The Indications for HIFU Treatment 45
a b c d e
Fig. 4.4 MRI pictures showed a gradual reduction of uterine fibroid’s sizes at 24 months after
HIFU treatment. (a) Before treatment; (b) 1 week after ablation; (c) 3 months after ablation; (d)
12 months after ablation; (e) 24 months after ablation (Courtesy from CQ HAIFU Medical
Technology Co., Ltd.)
not have changed significantly. Nevertheless, fibroids that are ablated will not con-
tinue to grow. Leukocytes, phagocytes, macrophages, mast cells, etc., from the sur-
rounding healthy tissues will accumulate and remove the dead tissue as foreign
bodies. Eventually, they will remove necrotic cells and tissues in the fibroids. The
necrotic fibroids are then slowly absorbed (Fig. 4.4). Under regular ultrasound mon-
itoring, fibroids would gradually shrink in size over periods of months. In the case
of a submucosal fibroid, it will gradually become absorbed and shrink totally in size
or discharged via the cervix. Occasionally, uterine curettage may be required to
remove the intrauterine necrotic fibroid if the patient complains of pain and continu-
ous bleeding.
During HIFU ablation, the patient’s blood pressure, pulse, respiration rate, and
peripheral oxygenation are monitored continuously. The patient is requested to
inform the doctor of any skin burning sensation, leg pain, or back discomfort during
HIFU treatment.
The ultrasound energy emitted from the therapeutic ultrasound transducer passes
through the lower abdomen’s skin into the body. The entire process does not create
open wound or keyhole wounds, with no bleeding or general anesthesia, and the
patient can mobilize immediately after HIFU treatment.
4.7 The Indications for HIFU Treatment
As a noninvasive treatment, HIFU treatment for fibroids should be the first-line

consideration if surgery is required. Patients with age near menopause and present
with symptoms are most suitable for HIFU ablation. HIFU treatment is also a better
choice for patients who want to conceive soon because the interval from HIFU treat-
ment to pregnancy is short, and pregnancy outcome is good compared to conserva-
tive surgery [8].
Peri-menopausal patients will soon have menopause, after which their fibroids
may not cause any problem. However, they may also be symptomatic at this age.
HIFU treatment in these patients will relieve their fibroid-related symptoms without
surgery and preserve their uterus by this noninvasive treatment.
Treatment options however will also depend on the fibroid size, symptoms, and
specific circumstances of the patients. Patients close to menopause can also opt for
close observation, reserving HIFU treatment only when the fibroids are causing
symptoms. Young patients are likely to experience fibroid growth and increasing
symptoms. Therefore, early intervention with HIFU ablation is acceptable by
patients even when they have small fibroids. HIFU ablation is also suitable for
patients with multiple fibroids because they are expected to grow, increasing the
need for invasive surgery or even hysterectomy. Infertile patients may wish to con-
sider HIFU treatment because even small fibroids, particularly if close to the tubes
or involving the endometrial cavity, can adversely impact fertility [9].
Some patients may experience heavy menstrual flow with severe anemia, often
requiring blood transfusion before surgery. The HIFU ablation does not have intra-
operative bleeding; hence, it may not be necessary to give a blood transfusion to
correct the severe anemia before the operation. In general, the patient’s hemoglobin
needs to be above 7 g/dL for HIFU ablation. Otherwise, the sedative analgesic drugs
used with HIFU ablation may further weaken their hypoxia tolerance due to anemia.
Even severely anemic patients are sometimes not willing to undergo a blood trans-
fusion. Therefore, before HIFU ablation, they should be treated with medication to
reduce the amount of menstrual bleeding and undergo iron therapy to correct the
anemia to meet the basic hemoglobin requirements for HIFU treatment.
Obese patients are usually not appropriate candidates for open surgery, but HIFU
treatment can still be possible. Obesity is neither an absolute contraindication to
HIFU ablation nor a significant factor influencing the efficacy of treatment.
Therefore, the following group of patients is suitable for HIFU ablation: (1)
Patients with symptomatic uterine fibroids and refuse conventional surgical opera-
tions. (2) The subclinical uterine fibroid imposes excessive psychological stress on
the patients. (3) The uterine fibroid has indications for surgery, but the patient is
intolerant of the surgical operation. (4) Patients with small fibroids 2–3 cm, but want
to have a baby shortly after treatment.
4.8 The Contraindications for HIFU Ablation
1. Patients with serious medical illness: They are high-risk patients with uncontrol-
lable hypertension, recent cerebrovascular accident (<6 months), cardiac failure,
renal failure, or hepatic failure.
2. Patients with a history of radiotherapy on the lower abdomen: radiotherapy
induces fibrosis of tissues in the lower abdomen. HIFU ablation may cause heat
injury to the fibrotic tissues in patients with a history of radiotherapy.
3. Suspected uterine sarcoma: Complete removal of the uterus is obligatory for the
surgical management of uterine sarcoma. Bilateral salpingo-oophorectomy
(BSO) may be considered, depending on menopausal status. The HIFU ablation
cannot completely eradicate the sarcoma, but sometimes it can be used to treat
recurrent abdominal sarcoma for palliative purposes.
4.9 Preparation Before HIFU Ablation 47
4. Acute inflammatory disease or suspected cancerous diseases of the genital tract:

the inflammatory disease may increase patients’ pain during HIFU and have an
increased risk for secondary infection to the treated tissue. Treatment of the
underlying diseases should take place prior to the initiation of HIFU ablation.
5. Patients with low back disorders: If these patients cannot lie prone for more than
1 h, they are not suitable for a lengthy HIFU treatment. Because prolonged prone
position >1 h may aggravate the back disorders, the patient may fail to continue
the treatment.
6. There are two major technical problems that HIFU cannot overcome at present,
namely (a) Limitations due to fibroid locations, which may hinder the acoustic
pathway and increase the risk for complications. For example, in ablating a cer-
vical fibroid, the pubic symphysis obstructs the acoustic pathway, resulting in
pelvic tenderness or burns. HIFU sometimes not be safely applied to a small
pedunculated subserosal fibroid because of the risk of bowel injury; (b) Foreign
objects in the acoustic pathway can make HIFU ablation a risky procedure, e.g.,
IUD inside the endometrium, it may cause injury to the endometrium.
4.9 Preparation Before HIFU Ablation
4.9.1 Simulation Test
The day or few days before HIFU treatment, patients should have a HIFU simula-
tion test on the HIFU table to assess whether HIFU ablation can be safely performed
with a distended bladder. Patients need to be tolerable to the bladder distension. For
the simulation test, the patient lies prone on the HIFU table just as she will be during
HIFU treatment. She needs a distended bladder for the ultrasound scan and focused
ultrasound beams targeting the fibroid. We should obtain the following information
from the simulation: (1) the status of the therapeutic ultrasound acoustic pathway to
determine whether any assisting device is needed to improve the acoustic pathway;
(2) whether there is a sound-absorbing structure or foreign objects within the acous-
tic pathway, e.g., an intrauterine device, the symphysis pubis, or a scar; (3) the
patient can tolerate the prone position with a distended bladder without complaints.
After the simulation, if a patient is found not tolerable to a distended bladder,
there is a safety issue when bowels cannot be pushed away from the acoustic path-
way. Then the treatment has to be postponed or canceled.
Proper pre-HIFU preparation is a prerequisite to ensure a safe and effective
HIFU ablation. In addition to a thorough physical examination, pre-HIFU routine
blood test, liver function test, renal function test, bleeding and coagulation test
(including prothrombin time, activated partial thromboplastin time, international
normalized ratio), echocardiogram, and Pap smear should be done.
Proper bowel preparation the day before HIFU treatment is essential. Because
the uterus is adjacent to the intestine, and the respiratory movement will influence
the internal organs’ position, even there is a strict criterion to select the acoustic
pathway. The bowel still has the risk of entering the acoustic pathway during deep
breathing. Strict bowel preparation must be performed before the ablation treatment
to avoid distended and loaded bowel that can push into the acoustic pathway. Bowel
preparations include dietary preparation, oral laxative, and enema. The goal is to
remove food and fecal matter from the intestines and reduce intestinal gas. The key
points of bowel preparation should be on dietary preparation and oral laxative,
which are listed as follows:
Dietary preparation: The time of dietary preparation is determined according to
the patient’s defecation habit. If the patient’s bowel habit is once daily, dietary prep-
aration is 1 day before surgery (within 24 h). If the bowel habits are every 2 days,
dietary preparation time is 2 days, and so on, but the longest dietary preparation
time should not exceed 3 days. The dietary requirement is to eat roughage-free food
and also easily digestible soft food. The recipe in China consists of congee, gruel,
lotus root, corn porridge, cheese, various stews, and water, etc., or 400–600 mL of
gastrointestinal nutrient solution, with added nutrients.
Intestinal catharsis: if the patient has a history of constipation, a laxative is nec-
essary; the time to use laxatives is the same as dietary preparation. The method is to
use paraffin oil or castor oil 30 mL orally three times a day. In severe cases, senna
can be taken. It is to induce diarrhea from 4 to 6 pm of the day before the HIFU
ablation treatment. An oral compound, polyethylene glycol electrolyte flushing with
1000–1500 mL of water, or 50% magnesium sulfate with 50–80 mL of drinking
water orally can also be used. If the catharsis is effective, the use of enemas can be
reduced or omitted; if the patient has signs of dehydration during catharsis, such as
thirst, weakness, etc., she should be encouraged to drink more water or electrolytes
solution.
Last bowel preparation can be repeated on the morning of HIFU ablation for
patients with inadequate diet and catharsis. Per rectal enema is used to stimulate the
rectal contractions, to remove the last residue in the rectum. This however may
cause over-stimulation of the rectum and increase the patient’s discomfort during
treatment thus interfere with the intensity of treatment dose and treatment efficiency.
Therefore, it is used if it is necessary.
4.10 Other Preparations
Some patients need to take mifepristone or GnRH-a after HIFU ablation because of
a fibroid’s large size. More than 95% of patients need no further medication after
treatment. Some patients, particularly with large fibroids, may not notice short-term
symptom improvement for a while, and these medications may then be useful.
Others with large fibroids may benefit from GnRH-a (leuprorelin) for 3 months
before HIFU treatment to reduce the fibroid’s size for easier and quicker HIFU abla-
tion. Whether or not it is to give GnRH-a before surgery depends on the age of
patients, the blood supply, size of the fibroids, and the MRI features of the fibroids.
Therefore, the size of the fibroid is not the only criterion for adjuvant use of GnRH-a.
For patients with uterine fibroids with an abundant blood supply on an ultrasound
4.11 HIFU Ablation 49
scan and a hyperintensity on MRI T2-weighted image, 3–6 cycles of GnRH-a treat-

ment are used before HIFU treatment. GnRH-a’s use is to reduce the blood supply
and sizes of the fibroids to improve HIFU ablation effectiveness. The monthly dose
of leuprorelin per injection is 3.75 mg given subcutaneously. However, the disad-
vantage of GnRH-a treatment is the increased overall cost of treatment and its side
effects during treatment. The side effects however vary a lot in the treated patients.
In many patients, menstruation does not occur after using GnRH-a. Still, a small
number of patients experience small amounts of bleeding or even normal menstrua-
tion at the beginning of treatment. While receiving GnRH-a medication, many
patients suffer from hot flushes, night sweats, and other menopause-like symptoms.
For a short period, such symptoms are usually considered tolerable. Following the
completion of three monthly injections, some patients will resume menstruation
within 1–2 months; other patients will not come to menstruation until after
3–6 months.
HIFU treatment can be performed at any time of the menstrual cycle as long as
it is not actively menstruating. It is to avoid bleeding contamination of the HIFU
therapeutic system, confusion with HIFU induced bleeding, if any, after treatment,
and the risks of ascending infection at the time of menstruation.
Some patients may require bladder training before treatment. During treatment,
the bladder needs to be distended to push the bowels out of the acoustic pathway, to
prevent any bowel injury. Patients with reduced bladder capacity may not have a
safe acoustic pathway to achieve a safe HIFU treatment. These patients are advised
to undergo bladder training to increase the bladder’s capacity.
On the morning of the treatment day, the skin from the umbilicus level to the
pubic symphysis’s upper margin must be shaved, degreased, and degassed
before HIFU.
A urinary catheter is inserted to control the bladder volume through the infusion
of normal saline at the time of HIFU treatment.
4.11 HIFU Ablation
Although HIFU ablation is a noninvasive treatment, patients may experience pain

during the procedure since some tissues and organs in the acoustic pathway are
sensitive to ultrasound energy. Thus, some patients may feel during the HIFU abla-
tion of uterine fibroids, mainly including sacrum/buttock pain, lower abdominal
pain, and sometimes skin burning sensation; a small number may experience leg
pain perineal tingling feeling. In general, patients can tolerate this pain and unpleas-
ant feeling. Intravenous sedation and analgesia used during the treatment will assist.
The small amount of sedation and analgesia can relieve discomfort and allow the
patient to communicate with the doctor.
Through timely communication with the operating HIFU doctor about any prob-
lem, any symptoms related to HIFU ablation complications can be avoided, espe-
cially when the ultrasound energy is increased to maximize the patients’ treatment
benefit. General anesthesia and spinal anesthesia are not used because they block
the patients’ subjective heat sensation to the skin, the abdomen, and the back. It also
masks any radiating pain to the lower limb, which would alert the operating doctors
about any potential nerve injury.
The duration of HIFU ablation will depend on the sizes of fibroids and the treat-
ment condition. Fibroids measuring 5–7 cm typically take about 30–40 min for the
HIFU ablation to complete. For patients with multiple uterine fibroids or large
fibroids with degeneration, which also have an abundant blood supply or fluid con-
tent, ablation time can last for 3 h.
4.12 Factors Influencing HIFU Effectiveness
No fibroids are treated with the same ease, time used, or dosage of ultrasound
energy. Several factors can help to predict the difficulties of the HIFU ablation, and
measures can be adopted to enhance the effectiveness and to improve the success
rate of HIFU treatment:
1. Using color Doppler ultrasonography, it can show the location, the number, the
sizes of fibroids, and the relation between the fibroids and the endometrium.
They also show the blood supply, echogenicity, liquefied necrosis, and calcifica-
tion of fibroids. These ultrasound features have a great impact on the duration
and energy used to ablate the fibroids. A fibroid is hypervascular if transabdomi-
nal color Doppler ultrasound shows grade 3 blood flow (Alder classification:0, 1,
2, 3) in an anterior wall fibroid, or grade 2 or higher in a posterior wall fibroid,
or the vaginal ultrasound shows grade 3 blood flow. These hypervascular fibroids
are difficult to ablate, and require high dose intensity for ablation, and may even
require multiple ablations at different times. Therefore, this information is useful
to decide whether adjuvant treatment with GnRH-a or other medication may be
necessary before HIFU ablation.
2. MRI examination can give accurate and objective information about the fibroids.
It can show the amount of blood supply, identify the degeneration, necrosis, and
calcification of tumors through different sequences. The MRI imaging character-
istics of fibroids can reflect the degree of difficulty in HIFU ablation. The uterine
fibroid and uterus are of similar signal intensity on the T1 weighted image
(T1WI). In contrast, on the T2 weighted image (T2WI), a fibroid often shows
homogeneous low signal intensity with a clear margin. Fibroids with low signal
intensity (hypointense) on the T2WI are easy to ablate in time and low energy.
However, T2WI hyperintense fibroids generally have a rich blood supply and
indicate the difficulty of ablation through this enhanced MRI image. When the
enhancement is markedly enhanced, i.e., the degree of signal intensity is equal to
or higher than the uterine muscle wall, especially in the posterior wall fibroids,
such fibroids are difficult to ablate, and even if the residual fibroids can be
ablated, the recurrence rate is higher. It may be necessary to use a higher dose
intensity and longer time for treatment, and adjuvant treatment may be needed
before HIFU treatment. For T2WI homogeneous hyperintense fibroids, even the
4.13 The Types and Locations of Fibroids that Affect HIFU Ablation 51
use of GnRH-a for 3 months sometimes may not be effective in improving the
ablation; it is recommended that this type of fibroids should be treated by surgery.
3. During the HIFU procedure, 80 units of oxytocin are added in 500 mL of 5%
glucose or 0.9% normal saline running at a rate of 2 mL/min (0.32 U/min) to
reduce the blood supply to the fibroid. Oxytocin induces uterine contraction and
reduces the blood supply to facilitate the HIFU ablation of the fibroid [10].
4. Poor bladder deformability: A small number of patients in the ultrasonic simula-
tion test shows that due to small bladder or high bladder tension, the bladder
cannot be deformed, resulting in the intestine cannot be pushed up into the upper
abdomen. If, at the time of simulation assessment, it has not been able to deter-
mine whether this type of patient is suitable for ultrasound ablation or not. The
patient can be instructed to perform 3–7 days of bladder distension training, i.e.,
more attempts to retain urine longer, increase the bladder volume and elasticity,
and perform an ultrasound simulation test again. Most patients have increased
bladder compliance and can effectively push the intestine away from the acoustic
pathway. The patient will then become suitable for ultrasound ablation.
5. Extremely retroflexed uterus: When an ultrasound simulation test is performed
before ultrasound ablation, it may find that the focal beams cannot be focused
effectively at the target fibroids, and the focal length is not deep enough. The
patient can be placed in a knee-chest position for a while, hopefully displacing
the uterus toward the abdominal wall and target the fibroids to the area covered
by the focal zone. Alternatively, under ultrasound monitoring, try to depress the
buttock to change the uterus’ position so that the ultrasound-focused point can
effectively target and cover the fibroid. When only a part of the retroverted uterus
is ablated, the effect will be limited.
6. During the HIFU procedure, an ultrasound water bag is placed between the
HIFU transducer and the abdomen. By manipulating the HIFU transducer and
scanner, it helps to push the ultrasound water bag against the abdomen and push
the bowels away from the ultrasound acoustic pathway, securing the ease and the
safety of HIFU ablation. The inability to push the bowels away from the ultra-
sound acoustic pathway by the transducer or water bag will affect HIFU ablation
effectiveness or completeness of the HIFU ablation.
7. Provided the patient receiving the HIFU ablation feels comfortable without pain,
increasing the speed of delivering HIFU ablation energy with the short resting
time between firing the ultrasound energy can speed up the ablation process
within a reasonable time. However, if the patient complains of sacral pain, nerve
pain, or skin discomfort, the ablation will be interrupted from time to time,
affecting the treatment’s speed and effectiveness.
4.13 T
he Types and Locations of Fibroids that Affect
HIFU Ablation
The different histological types and uterine fibroids’ positions will influence ultra-
sound ablation effectiveness, such as cellular leiomyomas, vascular leiomyomas,
diffuse leiomyomata, and cervical fibroids.
(a) Cellular leiomyomas consisted mainly of tightly arranged myoma cells with
large cell bodies, with very few interstitial collagen fibers, and high water con-
tent in the lesions. Therefore, cellular fibroids show uniformly high signals in
the MRI T2W1 image. The contrast enhancement image shows uniform hyper-
intense signals after the contrast medium, suggesting an abundant blood supply.
Due to these histological features, and the ablation energy is not conductive in
water, ultrasound ablation will be ineffective. Therefore, cellular leiomyoma is
challenging to ablate. After ultrasound ablation, any residual tumor tissue is
easy to regrow, but the outcome needs further study.
(b) Vascular smooth muscle leiomyoma
Vascular smooth muscle leiomyoma comprises smooth muscle and densely
proliferating blood vessels with a thick blood vessel wall with large lumens.
The color Doppler ultrasound scan will show a colored vascular pool. After
MRI contrast enhancement, the fibroid is hyperintense compatible with high
blood flow. These fibroids are difficult to take up ultrasonic energy and are not
suitable for ultrasound ablation.
(c) Diffuse uterine leiomyomatosis
This is a condition in which the uterine myometrium contains numerous large
and small fibroids replacing most of the myometrium; the main feature is a
significantly enlarged uterus. MRI Imaging can show multiple fibroids of vari-
ous sizes, often diagnosed as multiple fibroids. Different fibroids in the group
have very different responses to the ultrasound ablation. Even if ultrasound
energy can ablate some fibroids, residual untreated fibroids can continue to
grow. Therefore, the recurrence rate is very high.
(d) Cervical fibroids
Some cervical fibroids, especially in the posterior cervix, half or more of the
acoustic pathway are blocked by the pubic symphysis, affecting the ultrasonic
energy to go through and preventing it from reaching the target area. Meanwhile,
the pubic bone will absorb the ultrasound energy on the acoustic pathway and
cause local pain during ablation. It may also damage superficial soft tissues
over the bone. Therefore, cervical fibroids need to be carefully evaluated for the
suitability for ultrasound ablation.
(e) Leiomyosarcoma: the incidence of leiomyosarcoma is approximately 0.1–0.3%.
Early diagnosis is difficult. Clinical diagnosis is based on medical history, lac-
tate dehydrogenase, color Doppler ultrasound, and MRI.
1. The history of the leiomyosarcoma is mainly manifested by the rapid growth
of “fibroids,” but early sarcoma does not necessarily show rapid growth;
2. Color Doppler imaging can reveal a rich blood flow within the “fibroids”
(For example, abdominal ultrasound of anterior wall myoma can show a
grade 3 blood flow, posterior wall fibroids grade 2 or more; vaginal ultra-
sound blood flow grade 3). The maximum systolic peak blood flow velocity
higher than 40 mm/s is suspicious. If higher than 60 mm/s, it is more likely
to be a sarcoma;
4.15 Post-HIFU Ablation Care 53
3. T2WI image on MRI showed hyperintense signals in the “fibroids,” which

are markedly enhanced by contrast enhancement; the margin is not clear,
with multiple nodules;
4. Lactate dehydrogenase (LDH) is significantly elevated; uterine sarcoma
diagnosis is highly suggested [11].
If there are two of the above abnormal investigations, it is recommended to treat

with surgery. To avoid treating the uterine sarcoma by HIFU ablation, we must have
a high index of suspicions. Some uterine fibroids are fast-growing even after meno-
pause, although the reason is not clear. Suppose the patient refuses surgery but has
a relatively heavy psychological burden. In that case, we can first check the tumor
markers (including CEA, CA125, CA199, LDH), perform an MRI examination to
exclude the possibility of malignancy, and evaluate whether ultrasound ablation is
feasibly indicated. After treatment, regular follow-up is necessary to determine
whether a missed malignant tumor can be detected early and appropriately treated,
not to affect the prognosis.
4.14 A
ssessment of the Effectiveness of the Ablation
at the End of HIFU Ablation Procedure
A real-time ultrasound scan can monitor the HIFU ablation process. Meanwhile, the
vascularity within the fibroid can be assessed by the Doppler blood flow scan. At
this time, the oxytocin should be stopped; the absence of oxytocin allows uterine
relaxation to visualize any residual blood flow within the fibroid. The marked reduc-
tion or total disappearance of blood flow inside the fibroid suggests that the ablation
process is nearly completed. The ultrasound contrast agent—the intravenous micro-
bubble (SonoVue) infusion can start 10 min after oxytocin. The microbubble flow
within the fibroid will identify the site and assess the volume of non-ablated parts of
the lesion. A near 85–90% of ablated volume would be considered adequate ablation.
4.15 Post-HIFU Ablation Care
Two hours after HIFU treatment, a light liquid diet is permissible. For the next 24 h,
a semi-liquid diet, such as porridge, green vegetables, and fruits, can be eaten, but
the food needs to be as easy to digest as possible. After 48 h, if the patient does not
feel any discomfort, such as abdominal pain, abdominal distension, fever, nausea,
vomiting, etc., she can resume a regular diet. In general, after HIFU treatment, one
should take more soft food, such as sweet potatoes, mulberries, bananas, leeks,
turnips, spinach, taro, etc. As far as possible, do not eat foods that are hard to digest,
such as japonica rice, deep-fried, pan-fried foods, etc. Since strict bowel preparation
is practiced before the HIFU treatment, for some time postoperatively, if foods that
are not easy to digest are eaten, abdominal distension, abdominal pain, or other
gastrointestinal discomforts may occur. These discomforts are due to the bowel
function not fully recovered after the HIFU procedure. Daily gentle exercises can
help prevent constipation. There is no absolute dietary contraindication after the
treatment. Patients should first wait for the return of normal menstruation after the
surgery before restarting intercourse.
4.16 Postoperative Follow-up
Patients after HIFU treatment usually do not need to stay in the hospital unless they
live far away from the hospital. The average stay in some hospitals in China after
HIFU treatment is 3–4 days, although many hospitals require only 1 day for the
operation and hospitalization. One day after HIFU, most patients, under doctors’
guidance, can generally go back to work and perform non-strenuous exercise and
light physical labor.
Following discharge home, most patients do not require further medications. If
pain is a problem, nonsteroidal anti-inflammatory drugs like Panadol extend or
Arcoxia is usually suffice. Some patients may need antibiotics if they have exces-
sive or odorous vaginal discharge.
Patients should return for follow-up examinations at 1, 3, 6, 12, 18, and 24 months
of post-HIFU treatment. Examination methods can include pelvic ultrasound, pel-
vic MRI (if necessary), and some blood tests. The standardized examination is to
monitor the therapeutic effect, follow up the ablated fibroids’ sizes, detect any size
increases after treatment, and combine with imaging examination; one can decide
whether patients require re-intervention. The importance of follow-up is to assess
the treatment’s effectiveness and identify whether it is a benign or rarely a misdiag-
nosed malignant tumor.
4.17 Results of HIFU Ablation on Follow-up
4.17.1 The Non-perfused Volume Ratio
It is now evident that the reduction of fibroid volume is related to the non-perfused
volume (NPV) ratio. This ratio is evaluated by either microbubble contrast-enhanced
ultrasound at the end of the operation or posttreatment magnetic resonance imaging
(MRI). From the literature, many papers reported the ablation ratio of HIFU abla-
tion ranging from 74 to 100% [12–18]. After many years of HIFU ablation for
fibroids, the NPV ratio of both USgHIFU and MRg-FUS can achieve up to 100%
with an average of about 80%. Table 4.2 lists the studies in which data is collected
for evaluating NPV ratio.
4.17 Results of HIFU Ablation on Follow-up 55
Table 4.2 Studies showed the ablation ratio expressed in NPV%, ranging from 74.2 to 100%
Study
Author, year Guidance Country Study design size NPV (%) SD
Wang (2012) USg China Single center 76 80% ± 12
[12] prospective study
Zhao (2015) USg China Single center study 73 77.1% ± 14.9
[13]
Xu (2015) MRg China Single center 43 84.3% ± 15.7
Peng (2015) USg China Single center 68 83.7% ± 13.6
Wang (2018) MRg vs. China Single center 43/51 10/43 and 22/51
[18] USg prospective study achieved 100%
Fan (2019) USg China Single center 346 74.4% ± 14.7
[16] retrospective study
Lozinski MRg Poland Single center 276 74.2%
(2019) [17] retrospective study
Table 4.3 The fibroid volume reduction rate reported from the literature
Image No. of
Author, year guidance patients Follow-up 3 months 6 months 12 months
Lee (2015) USg 928 12 months 58.08% 66.18% 77.59%
[19]
Wang (2012) USg 76 12 months 46.7% 68.2% 78.9%
[12]
Funaki (2009) MRg 91 24 months NA 36.5% 39.5%
[20]
Ruhnke MRg 21 6 months 28% 45% NA
(2013) [21]
Ren (2009) USg 145 12 months 27.2% 47.9% 50.3%
[22]
4.17.2 The Volume Reduction After HIFU Ablation
The size of fibroids will not change much 1 month after the HIFU treatment.
According to some reports from the literature (Table 4.3), at 3 months’ follow-up
after surgery, fibroids will typically reduce to about 28–58% of the initial volume.
In half a year, absorption will cause fibroids to reduce to about 36.5–68.2% in size,
and in a year, about 39.5–78.8% in size. When the volume of fibroid has decreased
by 70%, its clinical effect is equivalent to surgical myomectomy. More than 70% of
volume reduction is usually considered as the criterion for successful ablation. At
such a time, the need for a repeat for HIFU treatment is generally ruled out.
The rate of absorption of fibroids after HIFU ablation varies from patient to
patient, the sizes, types, and locations of fibroids. The complete absorption takes an
Before HIFU 1 month after HIFU 3 month after HIFU 6 month after HIFU
Fig. 4.5 The MRI images showed the reabsorption rate of an ablated necrotic fibroid over
6 months. (a) Showed a preoperative uterine fibroid of size 60 mm × 63 mm × 70 mm. (b) Showed
the ablated area of the fibroid at 1 month after HAIFU knife® treatment. (c) Showed that fibroid
had a 50% reduction in size 3 months after surgery. (d) Showed that at 6 months after surgery, the
ablated fibroid had reduced in size by 79%. (From the courtesy of CQ HAIFU Medical Technology
Co., Ltd.)
average of 3–6 months for small fibroids, but longer with large fibroids. The larger
the fibroid, the more considerable amount of ablated tissue needs to be adsorbed per
cm. Experience showed that the absorption rate after HIFU surgery reached a peak
at 12 months [23].
In some patients, fibroids can also be wholly absorbed, while others may develop
fibroid scarring that prevents and limits further absorption of ablated necrotic tis-
sues. Therefore, doctors should advise their patients not to worry as fibroids take
time to shrink or reduce in size after HIFU ablation. For example:
(a) Intramural fibroid after HIFU treatment

Clinical follow-up of ablated fibroids revealed that ablated pedunculated
fibroids could also significantly reduce in size after HIFU treatment (Figs. 4.5
and 4.6). The reabsorption rate of ablated fibroid at different locations from fast
to slow are as follows: pedunculated submucosal fibroids (fastest) > non-
pedunculated submucosal fibroids > intramural fibroids > non-pedunculated
subserosal fibroids and pedunculated subserosal fibroids (slowest). The submu-
cosal fibroids, intramural fibroids, and non-pedunculated subserosal fibroids
have a 50–60% volume reduction after 6 months. The submucosal fibroids are
the fastest to shrink because of transvaginal drainage of the entire fibroid.
However, the pedunculated subserosal fibroids can only be absorbed slowly and
even not absorbed. At present, there has been no reported case of pedunculated
subserous fibroid found shed into the abdominal cavity. Therefore, peduncu-
lated submucosal or subserosal fibroids are also suitable for ultrasound ablation.
Still, for patients with pedunculated subserosal fibroids at the fundal location,
ultrasound ablation should be performed with caution because of the surround-
ing bowels or vital tissues.
4.18 Other Issues of Fibroid Ablation 57
a b c
Before HAIFU knife Day 1 after HIFU ablation 8 months after HIFU ablation
@ treatment
Fig. 4.6 The MRI images showed the reabsorption of a submucous fibroid over 8 months. (a)
Showed a type II submucosal fibroid before HIFU ablation; (b) showed the ablated type II submu-
cosal fibroid 1 day after treatment; (c) showed the ablated submucosal fibroid almost disappeared
in 8 months follow-up
Compared to traditional surgical removal, HIFU ablation does not remove

the fibroid, only stopping it from growing and then slowly shrinking it. HIFU
treatment enables maximum ablation of up to 90–95% of uterine fibroids and
relief of associated symptoms. The criteria to determine the effectiveness or
success rate also depend on the extent of clinical symptom relief and the results
of imaging examinations using MRI and ultrasonography. It is important to
assess the likelihood of success of HIFU treatment before operation. There were
reports that a few cases in which the results of treatment were not ideal. As this
ultrasonic ablation involves no wound, no trauma, no bleeding, and minimal
damage to the body, even a treatment failure will not affect the body. It will also
not preclude other treatment options or a repeat of the HIFU ablation from
being undertaken.
4.18 Other Issues of Fibroid Ablation
HIFU ablation has been used to treat patients for more than 20 years. During this
HIFU ablation technique, standardized ablation protocols based on increasing clini-
cal experience have been developed. It is now a very safe treatment with minimal
complication rates. However, a few issues need to be addressed to ensure safety and
success before and after HIFU ablation.
(a) Patients with acute pelvic inflammatory disease, chronic pelvic inflammatory
disease, and recurrent subacute attacks are relatively sensitive to ultrasound’s
mechanical effects. Pain in the treatment area is prone to occur during HIFU
ablation treatment; thus, any reduced dose intensity may affect the therapeutic
effect. The effect of ultrasonic ablation on pelvic inflammatory disease is

unclear, especially whether it will increase the inflammatory response.
Therefore, it is proposed that ultrasound ablation therapy should be performed
after the inflammation is treated and settled. The appropriate dose intensity
should be carefully controlled during the subsequent HIFU treatment. However,
to what extent an anti-inflammatory treatment can be beneficial to HIFU abla-
tion remains unclear.
(b) Patients with surgical scars have scar tissue that has a strong absorption capac-
ity for ultrasonic energy. Current techniques and protocols are acceptable for
the treatment of scar widths of up to 15 mm. However, if the scar width exceeds
15 mm, the ultrasound energy shows diminished behind the scar tissue, espe-
cially after multiple surgical incisions or scars that had infection after surgery.
We do not know how safe and how controllable ultrasound ablation can be at
these scars. It is noteworthy that at this time, the scar within the acoustic path-
way will have strong absorption of therapeutic ultrasound energy, and patients
can easily complain of pain in the abdominal wall or burning skin thus affecting
the ablation dose intensity and increased unsafety factors. Therefore, appropri-
ate therapeutic dose intensity with adequate cooling time and controlled abla-
tion time can be used, then the incidence of burns can be reduced. However,
whether it can be suitably safe and effective for a T2WI hyperintense fibroid
over an obese abdominal wall with a thick layer of fat (big body mass index)
needs further study.
(c) Patients after a history of abdominal liposuction may have extensive scar for-
mation in the subcutaneous tissue, especially in the puncture channel, then the
scar tissue absorption of ultrasound is stronger. While liposuction also exten-
sively damages the cutaneous nerves, it may affect the skin’s sensation, and skin
damage may occur because it cannot experience the pain. Therefore, patients
can only be strongly advised about this problem and willing to bear the risk of
treatment.
(d) Patients with severe anemia: Hemoglobin should be corrected to at least above
7 g/dL, and ultrasound ablation can be performed in patients without any symp-
toms caused by anemia. The main unsafe factors in patients with very severe
anemia are unresponsive and unable to timely and accurately reflect the treat-
ment experience during sedation, leading to severe adverse reactions. However,
if the patient refuses blood transfusion because of the fear of blood contamina-
tion, intravenous iron infusion, and control of menorrhagia may be adopted to
raise the hemoglobin level before HIFU treatment. Due to various clinical con-
ditions, some patients with hemoglobin less than 60 g/L had been subjected to
ultrasound ablation with good results. Nevertheless, care should be taken to
adjust the depth of sedation, establish a reasonable plan, and make a good judg-
ment by experienced HIFU surgeons.
(e) Patients with medical illnesses are to be treated with care. Patients with a his-
tory of hypertension need to control blood pressure to a stable level before
undergoing ultrasound ablation. Those with a history of cardiac disease or con-
genital heart disease should have the cardiac function assessed to be stable and
has no obvious clinical symptoms. Ultrasound ablation can be performed with
4.20 Pregnancy After HIFU Ablation 59
close monitoring of cardiac function during HIFU ablation, and subsequent

hospital stay is necessary to ensure patient safety. Patients with hyperthyroid-
ism should be carefully assessed by a comprehensive physical examination and
laboratory tests before surgery. It is often necessary to check tracheal displace-
ment and compression, electrocardiogram, etc., to check for any abnormal car-
diac function. Under the control of an endocrine specialist, the patient can be
treated with ultrasound ablation after the disease becomes stable.
(f) No shrinkage of fibroids: After the HIFU ablation, some fibroids do not shrink
in size. Usually, fibroids shrink slowly in size. The degree of shrinking however
varies from person to person. Using an MRI image, if fibroids are associated
with tissue necrosis, no blood flow/perfusion in the MRI scan, with symptoms
improvement, such as reduced menstrual flow, improved dysmenorrhea, HIFU
treatment can be considered successful. If the fibroid’s reexamination shows no
shrinkage, that may be due to the following situations. After HIFU ablation,
necrosis of fibroid tissue is complete, but the absorption decreases slowly. If
there are no clinical symptoms, follow-up observations continue to monitor its
progress. In the case of fibroid volume has reduced, but the remaining tumor
edge has increased. In this situation, the fibroid may not shrink further or
increase slowly in size. Further evaluation is needed, and possibly additional
HIFU treatment or surgery may be required because of undiagnosed uterine
sarcoma risks.
4.19 Recurrence of Fibroids
The pathogenesis of uterine fibroids is not yet clear and may relate to the uterine
myometrium’s high sensitivity to estrogen. Proper diet, exercise, sleep, and emo-
tional control are advisable. For young patients with no plan of pregnancy, they
should have strict contraception. They should also take fewer soy products, honey,
and others rich in phytoestrogens. Regular follow-up examinations are necessary to
monitor any recurrence.
The recurrence rate of fibroids evaluated up to 24 months after HIFU treatment
was lower than or comparable to other uterus-preserving operations like the myo-
mectomy. The reported recurrence rate was 7.4% at 12 months, 14–21.7% after
24 months [24]. Follow-up data after 5 years is still not available. The reported
cumulative recurrence rate after 5 years is 32% for uterine artery embolization and
5.7–33% for myomectomy. So far, HIFU ablation showed a lower recurrence and
re-intervention rate (<20%) when the treated volumes were around 70% or more of
the fibroid volume [25].
4.20 Pregnancy After HIFU Ablation
HIFU ablation is a “green” treatment. The ultrasound beam used in the treatment
has no radiation and no harm to the body. Besides, HIFU ablation is a precise
treatment that only destroys the target tumor and does not damage the
surrounding tissues and organs. In general, there should be at least 3 months

interval between HIFU treatment and subsequent pregnancy to be encouraged.
Studies have shown that the HIFU treatment of uterine fibroid is safe for patients
who wish to retain fertility; they can conceive and deliver vaginally after treat-
ment. There are no obvious safety issues to the baby or the mother, and there is
no reduced ovarian reserve. No uterine rupture or teratogenicity has been reported
after HIFU treatment [2, 3].
Although there is currently no systematic study on the effects of pregnancy, there
are already many cases of pregnancy and related reports suggesting that there may
be little effect on pregnancy. The number of cases requiring continued childbirth is
still small, and there is not enough scientific evidence to explain the effects on
mother and child during pregnancy. Further follow-up discussion of this issue is in
Chap. 7.
References
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Surv. 2005;60(2):132–8.
2. Malaguarnera M, et al. Liver damage induced by Danazol. Drug Investig. 1994;8(2):122–5.
3. van Leeuwen FE, et al. Risk of endometrial cancer after tamoxifen treatment of breast cancer.
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4. Fedele L, et al. Recurrence of fibroids after myomectomy: a transvaginal ultrasonographic
study. Hum Reprod. 1995;10(7):1795–6.
5. Payne JF, Haney A. Serious complications of uterine artery embolization for conservative
treatment of fibroids. Fertil Steril. 2003;79(1):128–31.
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ultrasound ablation of uterine fibroids. Int J Gynecol Obstet. 2012;117(3):273–7.
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evidence. Fertil Steril. 2009;91(4):1215–23.
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adenomysis: a prospective study. Eur J Radiol. 2014;83(9):1607–11.
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ment of submucosal fibroids. Eur Radiol. 2012;22(11):2553–8.
13. Zhao W-P, et al. A retrospective comparison of microwave ablation and high intensity focused
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Adenomyosis and HIFU Ablation
5
Adenomyosis is due to the invasion or presence of endometrial glands in the uterine

myometrium accompanied by hyperplasia and hypertrophy of the surrounding mus-
cle cells, forming diffuse or focal lesions. Adenomyosis occurs most often in women
between the ages of 30 and 50, but it can also be in younger women who have not
had children. The incidence of adenomyosis is about 20–30% of reproductive-aged
women, but this varies according to the particular population [1]. Recently, there
appears to have a significant increase in the incidence and younger age patients.
Thirty-five percent of patients are without symptoms, 15–30% associated with pel-
vic endometriosis, and 50% with uterine fibroids. The pathogenesis of adenomyosis
is unknown, but in some patients, there is a belief that any intrauterine manipula-
tions such as surgical termination of pregnancy can damage the endometrium’s
basal layer, causing the endometrial gland to invade into the myometrium thus
increasing the extent and severity of adenomyosis. Adenomyosis can then lead to
dysmenorrhea and increased menstrual flow, infertility, and other related symptoms
[2]. This disease seriously affects women’s physical and mental health.
The imaging appearance of adenomyosis under ultrasound and MRI have been
described in Chap. 3. Adenomyosis classification depends on the distribution of
lesions and echoes features; this disease can be classified into diffuse type, anterior/
posterior wall type, and focal type.
1. Diffuse type
2. Anterior/posterior wall type
3. Focal type
https://doi.org/10.1007/978-981-16-0939-8_5
64 5 Adenomyosis and HIFU Ablation
5.1 The Symptoms of Adenomyosis
Dysmenorrhea is a common presenting symptom of adenomyosis. However, uterine

cramping pain during the menstrual period may be due to backache, lower abdomi-
nal pain, or other discomfort sites. Severe dysmenorrhea can affect a patient’s life
and work. The overall incidence of dysmenorrhea is 33.9%, of which approximately
1 in 10 is severe enough. Dysmenorrhea can be classified into primary and second-
ary types. Primary dysmenorrhea refers to dysmenorrhea without pelvic organic
lesions and is presently unexplainable. Secondary dysmenorrhea is usually a conse-
quence of organic pelvic disease and usually occurs several years after menarche.
The causes of secondary dysmenorrhea may be due to endometriosis, adenomyosis,
pelvic inflammatory disease, etc. [3]. These types of dysmenorrhea require treat-
ment. Either ultrasound or magnetic resonance imaging can confirm the diagnosis
of patients suspected of having adenomyosis.
The risk of malignant transformation of adenomyosis is rare, and adenomyosis is
slow to grow and usually stops developing during pregnancy or after menopause.
5.2 Treatment of Adenomyosis
There are many treatments available for adenomyosis: drugs, surgery, and High
Intensity Focused Ultrasound (HIFU) ablation. Each treatment method has certain
advantages and disadvantages, and individual treatment plans should be employed
according to the patient’s particular conditions.
5.2.1 Drug Treatment
For patients with mild adenomyosis symptoms, especially young patients, conser-
vative treatments such as drug therapy and reassurance are advisable. Several types
of drugs are available for treating adenomyosis.
5.2.1.1 Mirena (LNG-IUS)

This is a birth control device that slowly releases Levonorgestrel (progesterone)
locally in the uterine cavity, causing temporary atrophy of the endometrium and
myometrium, inhibiting endometrial growth. As a result, bleeding from the ectopic
endometrium can be reduced within the myometrium. Thus, it can relieve dysmen-
orrhea. However, the most common undesirable side effect is irregular vaginal
bleeding; this bleeding disorder typically subsides 3–6 months after Mirena inser-
tion. This contraceptive device is more expensive than other birth control devices;
in some patients, the IUD device may shift or fall out when the vaginal blood flow
is heavy at the beginning of the IUD insertion. It is also not suitable for young
patients with an intact hymen.
5.2 Treatment of Adenomyosis 65
5.2.1.2 Gonadotropin-Releasing Hormone Agonist (GnRH-a)

This drug is currently the most effective medication for treating endometriosis.
GnRH-a inhibits the secretion of gonadotropins by the pituitary gland, leading to a
significant reduction in ovarian hormone levels, causing temporary cessation of
menstruation.
GnRH-a can significantly relieve dysmenorrhea because of the absence of men-
struation. After the discontinuation of this drug, dysmenorrhea due to adenomyosis
will recur. GnRH-a also has menopausal side effects such as hot flushes, night
sweating, insomnia, and bone pain due to ovarian suppression with a marked reduc-
tion of estrogen. Generally, GnRH-a has also been used for 3–6 cycles after surgery
for adenomyosis, starting on days 1–5 of menstruation. The subcutaneous injection
will be given on the first day of menstruation, followed by one injection cycle every
28 days. Most patients stop menstruating after the second month of injection.
Prolonged use of GnRH-a for more than 6–8 months is not recommended because
of the side effects of persistent low estrogen status induced by the medication.
5.2.1.3 Oral Contraceptives

Many contraceptive pills contain a low dose of estrogen and progestogen with an
anti-estrogenic effect if taken daily. The impacts of progestogen in the pills can act
directly on the ectopic endometrium, leading to reduced adenomyosis’s glandular
tissue thus relieving bleeding in the myometrium and painful periods.
5.2.2 Surgical Treatment
The surgery of adenomyosis is either conservative surgery or radical surgery. For

those younger with fertility requirements, focal adenomyoma can be treated by sur-
gical adenomyomectomy, i.e., removing the focal adenomyoma. Both laparoscopic
and open abdominal approach can be used. However, the diffuse type of adenomyo-
sis has unclear tumor boundaries. It will be a challenge to remove the entire adeno-
myotic lesion by surgery, unless by a hysterectomy.
For women who have not yet completed childbirth, any surgical approach should
be of cautions because (1) there is no clear boundary between the adenomyosis
lesions and the myometrium. Thus, it is not easy to remove all the entire adenomy-
otic lesions, (2) the uterine elasticity of adenomyosis is typically poor. Therefore,
the uterus’ excised wound is not easy to suture, (3) surgery will likely be associated
with bleeding, infection, abnormal uterine shape after surgery. As a result, there is a
higher risk of pelvic adhesions, (4) a deeply excised uterine wound damaging endo-
metrium or entering the uterine cavity increases the risk of abnormal placenta devel-
opment such as adherent placenta or placenta accreta, (5) uterine scars on the uterus
can be prone to rupture during pregnancy and labor, which is a concern.
Therefore, it is recommended that postoperative contraception should be used
for 2–3 years to allow good healing, preventing the risk of uterine rupture during
any subsequent pregnancy. It is also difficult to expect that limited conservative

surgery can achieve a satisfactory result because of incomplete resection of the ade-
nomyosis. Furthermore, long-term treatment with a combination of drugs or alter-
native therapies may still be needed to relieve its symptoms after surgery.
For patients with no fertility requirements or with diffuse adenomyosis, hyster-
ectomy can be offered when dysmenorrhea does not respond to medical treatment.
Hysterectomy is a major surgery, which may be associated with bleeding, infection,
pain, and a long time to recover. Depending on the patients’ age, one can decide
whether the ovaries should be conserved or not. If both ovaries and tubes are
removed, there will be a loss of ovarian function leading to an adverse impact on
sexual life. Either laparoscopic, vaginal, or open abdominal hysterectomy can be
the approach options. This radical surgical treatment applies only to older patients
with severe symptoms, extensive lesions, and no fertility requirements. Laparoscopic
surgery has the advantage of being minimally invasive and aesthetic and is often
more readily accepted by the patient.
5.2.3 Bilateral Uterine Artery Embolization (UAE)
Bilateral UAE is to use a guidewire to direct an arterial catheter to enter the leg
artery by a direct puncture. The catheter is guided to reach both sides of the uterine
artery supply, releasing embolization drugs that block both sides’ blood vessels.
This treatment helps block the uterine arteries, which provide blood supply to the
adenomyosis. The acute reduction of blood supply causes necrosis and reduced
adenomyosis lesions, with a short-term effect of reduced menstrual flow soon after
UAE treatment. The remission rate of dysmenorrhea is also high. Both the uterus
and the adenomyosis lesions will reduce in size accordingly [4]. However, postop-
erative uterine contractions in response to embolization can cause more severe pel-
vic pain and require a high dose of analgesic drugs to control the pain. Other side
effects may also occur, including vaginal bleeding, fever, and ovarian dysfunction.
Sometimes uterine wall ischemia can traumatize the uterine wall’s integrity, affect-
ing natural pregnancy and delivery [5, 6]. Young patients who have fertility require-
ments must carefully consider this treatment.
5.2.4 High Intensity Focused Ultrasound (HIFU) Therapy
HIFU energy produces a highly localized temperature of 60–100 °C at the adeno-

myotic lesion, causing coagulation necrosis without much damage to the surround-
ing healthy myometrium and endometrium. After the absorption of necrotic
adenomyosis, the uterus gradually shrinks in size, and the symptoms of dysmenor-
rhea and excessive menstrual flow can be improved. The improvement of the uterine
cavity environment after HIFU treatment can also increase pregnancy [7]. The main
advantage of the HIFU treatment is its noninvasive nature because there is no bleed-
ing, no scar, requiring a small amount of sedative analgesics, and importantly, fewer
5.4 Advantages of HIFU Treatment for Adenomyosis 67
major complications compared to traditional surgery. After HIFU treatment, the

patients suffer much less pain, have a rapid recovery, and do not develop postopera-
tive pelvic adhesions. However, there is a possibility of recurrence of symptoms
after HIFU treatment; it can be repeatedly treated with HIFU ablation that is still
acceptable to some patients because of its noninvasive nature. So far, many studies
of HIFU ablation for adenomyosis showed that this treatment is highly effective and
safe [8–12].
HIFU ablation can treat either focal adenomyoma or diffuse adenomyosis in a
large uterus. In some patients, the combined therapy of GnRH-a or/and Mirena with
HIFU treatment can further consolidate the curative effect and reduce the recur-
rence of adenomyosis [13, 14].
Nevertheless, it may not be possible to provide a cure for adenomyosis by HIFU
treatment because of the diffuse distributions of adenomyosis in the uterine wall and
preserving an intact endometrium. The untreated endometrium would be source of
adenomyosis recurrence. The only way to cure adenomyosis is total hysterectomy.
However, in patients with associated pelvic endometriosis, even if we remove the
uterus, this approach will not achieve the results of a “radical” surgical treatment,
i.e., a complete cure. HIFU ablation treatment’s primary purpose is to ablate and
reduce lesions’ sizes, control growth, relieve dysmenorrhea, and improve clinical
symptoms [11]. There are individual differences in the time and recurrence of
symptoms, and many patients do have remission of symptoms for more than 2 years,
then recur.
5.3 actors Influencing HIFU Effectiveness for Adenomyosis

F
Treatment are Listed as Follow
(a) The large size of adenomyosis; (b) the diffuse distribution of lesions in the
uterus; (c) the number of hyperintense regions in MRI T2WI images; (d) increased
abdominal wall thickness with extensive adenomyosis; and (e) the distance from the
skin to the remote part of the adenomyosis [15, 16].
Other adjuvant treatments of adenomyosis can be through various treatment
methods, such as Chinese medicine, GnRH-a [13], hormones, and Mirena [17], to
provide integrative management and improve the quality of life for patients.
5.4 Advantages of HIFU Treatment for Adenomyosis
(a) HIFU treatment is not an open surgery or minimally invasive surgery with no
wound, no bleeding, or radiation. The treatment is safe and reliable, allowing
rapid recovery [18].
(b) HIFU treatment can keep the integrity of the uterus with no scars. It does not
interfere with women’s endocrine and reproductive functions. There might only
be a small number of mild side effects that may affect the patients [12].
(c) HIFU treatment does not require general anesthesia; it only needs sedation and
analgesia. The patient under HIFU treatment can keep awake and communicate
with the doctor throughout the procedure. This treatment thus reduces
anesthesia-related complications.
Eighty percent of patients with adenomyosis can safely receive HIFU ablation,
which results in coagulation necrosis of adenomyosis lesions in the uterine wall.
The body would gradually absorb the ablated necrotic tissues, and then the adeno-
myosis lesion would decrease in size and extent. The uterus with the ablated lesion
then slowly returns to normal or near-normal thus reducing the menstrual flow and
pain relief during periods.
HIFU treatment can sometimes cause pain during the ablation procedure. The
degree of pain is related to the size, activity, and location of the adenomyosis and
the patient’s tolerance to pain [12]. During HIFU treatment with intravenous seda-
tion and analgesia, most patients feel comfortable and painless or experience only a
slight degree of tolerable pain. Postoperatively, patients would have uterine pain
that is less intense than their period pain, and it usually may last for about 2–4 h.
After HIFU ablation, some patients can be prescribed oral analgesics to control their
postoperative pain and dexamethasone to reduce the ablated adenomyosis’ aseptic
inflammation thus reducing the discomfort after treatment.
However, HIFU ablation for adenomyosis is not suitable for the following
situations:
1. Bowel adhesions are found in the acoustic pathway because they will increase
the risk of bowel injury during treatment. Particular attention must be paid to
patients with previous surgical treatment for this condition because of surgical
adhesion.
2. Unlike the uterine fibroid, adenomyoma is without a pseudo-capsule surround-
ing the lesion. Therefore, if the lesion is too small, with the uterine wall thickness
less than 3 cm, ablation heat can spread to the uterine serosa or endometrium and
damage these tissues.
3. Severe abdominal keloid scars or hypertrophic scars can affect ultrasound pene-
tration and lead to skin burn.
4. Situation where the distance from the adenomyosis lesion to the sacrococcygeal
nerve is close to or less than 1 cm. The risk of post-HIFU complications to the
nerve will increase. Then, in some large posterior adenomyosis, HIFU treatment
may not be advisable.
Some patients should have GnRH-a before (or after) HIFU treatment, especially
those with large adenomyosis lesions with rich blood supplies [13]. It is a good idea
to be aware of the challenges of HIFU treatment to large adenomyosis lesions. This
GnRH-a treatment reduces the size and blood supply of the adenomyosis. In turn,
this will reduce the treatment difficulty and improve the effectiveness of treatment.
However, in some patients, experience suggested that GnRH-a before HIFU treat-
ment can allow treatment done effectively. However, a rebound of adenomyosis
References 69
activities after the cessation of GnRH-a and HIFU treatment may lead to early
recurrence.
Instead of using GnRH-a alone with HIFU ablation, Mirena (LNG-IUS) has
been used together after HIFU treatment as long-term management [19]. Mirena is
not suitable for everyone, particularly the virgins. Besides, suppose the size of the
uterine cavity is larger than 8 cm in length Mirena can be ineffective or easily
expelled from the uterine cavity, and thus it is not always appropriate. However,
GnRH-a and Mirena’s combined use is useful to consolidate the HIFU ablation
effectiveness and reduce the recurrence of symptoms [14, 20, 21]. Since any conser-
vative treatment of adenomyosis, including HIFU ablation, may have a chance of
tumor recurrence, the primary purpose of the combination of GnRH-a and Mirena
after HIFU treatment is to lengthen clinical remission and delay disease recurrence.
5.5 Pregnancy
HIFU ablation can improve the uterine cavity environment, the uterine size and pos-
sibly increase pregnancy chances [7, 22]. Our experience is that the possibility of
getting pregnant is encouraging and higher after HIFU treatment compared with
spontaneous pregnancy without any treatment. The chance of getting pregnant is
about 40% for those who want to get pregnant. At present, patients are advised to
use contraception and not conceive within 1 year after HIFU treatment. However,
many patients get unintended pregnancies 3–6 months after HIFU treatment and
have a successful pregnancy outcome without complications [23, 24]. Therefore,
pregnancy timing can be adjusted according to the lesion’s size, treatment, and fol-
low-up. Large studies with many cases were not available in the literature, but
enough experience has been accumulated in China, as presented in Chap. 7.
References
1. Naftalin J, et al. How common is adenomyosis? A prospective study of prevalence using trans-
vaginal ultrasound in a gynaecology clinic. Hum Reprod. 2012;27(12):3432–9.
2. Peric H, Fraser I. The symptomatology of adenomyosis. Best Pract Res Clin Obstet Gynaecol.
2006;20(4):547–55.
3. Bernardi M, et al. Dysmenorrhea and related disorders. F1000 Res. 2017;6:1645.
4. Zhou J, et al. Outcomes in adenomyosis treated with uterine artery embolization are asso-
ciated with lesion vascularity: a long-term follow-up study of 252 cases. PLoS One.
2016;11(11):e0165610.
5. Takeda J, et al. Spontaneous uterine rupture at 32 weeks of gestation after previous uterine
artery embolization. J Obstet Gynaecol Res. 2014;40(1):243–6.
6. Homer H, Saridogan E. Pregnancy outcomes after uterine artery embolisation for fibroids.
Obstet Gynaecol. 2009;11(4):265–70.
7. Zhou C, Xu X, He J. Pregnancy outcomes and symptom improvement of patients with adeno-
myosis treated with high intensity focused ultrasound ablation. Zhonghua Fu Chan Ke Za Zhi.
2016;51(11):845–9.
9. Zhou M, et al. Ultrasound-guided high-intensity focused ultrasound ablation for adenomyosis:

the clinical experience of a single center. Fertil Steril. 2011;95(3):900–5.
10. Zhang X, et al. Effective ablation therapy of adenomyosis with ultrasound-guided high-
intensity focused ultrasound. Int J Gynecol Obstet. 2014;124(3):207–11.
11. Shui L, et al. High-intensity focused ultrasound (HIFU) for adenomyosis: two-year follow-up
results. Ultrason Sonochem. 2015;27:677–81.
12. Feng Y, et al. Safety of ultrasound-guided high-intensity focused ultrasound ablation for dif-
fuse adenomyosis: a retrospective cohort study. Ultrason Sonochem. 2017;36:139–45.
13. Guo Y, et al. Gonadotrophin-releasing hormone agonist combined with high-intensity

focused ultrasound ablation for adenomyosis: a clinical study. BJOG Int J Obstet Gynaecol.
2017;124(S3):7–11.
14. Yang X, et al. Combined therapeutic effects of HIFU, GnRH-a and LNG-IUS for the treatment
of severe adenomyosis. Int J Hyperth. 2019;36(1):485–91.
15. Gong C, et al. Factors influencing the ablative efficiency of high intensity focused ultrasound
(HIFU) treatment for adenomyosis: a retrospective study. Int J Hyperth. 2016;32(5):496–503.
16. Liu X, et al. Clinical predictors of long-term success in ultrasound-guided high-intensity
focused ultrasound ablation treatment for adenomyosis: a retrospective study. Medicine.
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17. Ye M, et al. Clinical study of high intensity focused ultrasound ablation combined with
GnRH-a and LNG-IUS for the treatment of adenomyosis. Zhonghua Fu Chan Ke Za Zhi.
2016;51(9):643–9.
18. Cheung VY. Current status of high-intensity focused ultrasound for the management of uterine
adenomyosis. Ultrasonography. 2017;36(2):95.
19. Wu Ziyu PZ, Xiuping L, Yueyue D, Mingjie J. Clinical observation of high-intensity focused
ultrasound in combination with LNG-IUS treatment of uterine adenomyosis. Shandong Med.
2018;58(3):65–7.
20. Ye Mingzhu DX, Xiaogang Z, Min X. High-intensity focused ultrasound ablation techniques
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Complications of HIFU Ablation
6
Any surgical procedure has potential complications. Abdominal and laparoscopic

surgery may have heavy bleeding at operation, infection, poor wound healing, pel-
vic adhesion, ureter or bladder injury, bowel injury, and many others. HIFU ablation
involves no wound, no bleeding, and is a type of noninvasive treatment. Complications
are extremely low. However, organs and tissues close to the uterus include the
bowel, bladder, nerves, and sacral bone, as well as the skin of the lower abdomen,
may be within the acoustic pathway during the HIFU ablation procedure. Therefore,
there is a potential for thermal injuries to these organs or tissues within the pathway,
causing bowel perforation, bladder injury, nerve injury, bone damage, or skin burn.
However, these are infrequent complications of HIFU treatment. As reported in the
literature, skin burn incidence is about 0.2–0.5% [1], and the nerve injury, though
reported in the early stage of HIFU ablation development, is now even much lower.
Up to 99% of HIFU induced adverse events were mild and not requiring any special
treatment [2]. From the literature, the severity of adverse effects was reported
according to the SIR classification system for complications by outcome: (a) Class
A: no therapy, no consequence; (b) Class B: nominal therapy, no consequence; (c)
Class C: require therapy, minor hospitalization (<48 h); (d) Class D: required major
therapy, unplanned increase in level of care, prolonged hospitalization (>48 h); (e)
Class E: permanent adverse sequelae; (f) Class F: death. Class A and B were con-
sidered minor complications in this classification system; Class C, Class D, Class E,
and Class F were considered major complications [3]. Although there were case
reports of major adverse effects, including skin burn, bowel injury, acute renal fail-
ure, deep vein thrombosis, pubic symphysis injury, in the early literature. From a
multicenter study with large data analysis, the complication rate during and after the
HIFU ablation is mild in Class A and Class B. The complications were also much
lower than laparoscopic surgery and conventional open surgery [4]. The major
adverse events in Class C and D categories were only 0.38% [2].
The following are known and reported complications of HIFU ablation from the
literature:
https://doi.org/10.1007/978-981-16-0939-8_6
72 6 Complications of HIFU Ablation
6.1 Fever
Fever occurred in less than 1% of patients after HIFU treatment of uterine fibroids.
In a study of 27,053 patients, 79 (0.29%) patients had a fever with a temperature
lower than 38 °C, 3 (0.01%) patients had a fever with a temperature higher than
38 °C, and 7 (0.03%) had hyperpyrexia requiring therapy and <48 h hospitalization
after HIFU treatment [2]. HIFU ablation belongs to the class of heat treatment. If
the lesion is large, the heated tumor’s cooling process may disseminate heat for
1–2 days. Low-grade fever therefore is normal. Often, the fever is associated with
the necrotic ablated tumor’s absorption process, so after ruling out other causes of
the fever, generally, no special treatment is required. Patients however should ensure
they take sufficient rest and maintain vulval health to avoid secondary infections.
Antibiotic and antipyretic may be given to those with temperature >38 °C, or there
appears to be suspected infection.
6.2 Pain
During HIFU treatment, high ultrasound energy ablates the fibroids or adenomyo-
sis, and patients may feel lower abdominal pain due to heat treatment. The absorp-
tion of the coagulated and necrotic tissue may also lead to slight abdominal pain or
discomfort postoperatively. This phenomenon is normal. Lower abdominal pain
occurred in 2–9% of all patients with uterine fibroids or adenomyosis within 7 days
of HIFU treatments [5, 6].
If the ultrasound intensity needs to increase to a higher level due to the fibroids
or uterus’ positions, and when the target fibroids are relatively close to the sacrum
or the pelvic sidewall, the risk of leg pain, sacral pain, or sciatic pain may occur
during treatment. The leg or buttock pain happened in less than 1% (76/9988) of all
patients after HIFU treatment [2, 5]. While lumbar and sacrum pain and weakness
in the lower limb were reported in 1–11% of patients, compared to those with myo-
mectomy or hysterectomy surgery [4]. Transient leg pain, sciatic pain, and buttock
pain after the HIFU procedure were more frequent for the retroverted uterus [6].
Other factors influencing the severity and incidence of these pains are sizes of
fibroids, therapeutic dose, and sonication time. Fortunately, many of these adverse
events are Class A and B of the SIR classification.
Among those patients who experienced lower abdominal pain, these pains are
often mild and controllable by NSAID (NonSteroidal Anti-Inflammatory Drug)
analgesic. Sometimes they do not need any special treatment, and the pain usually
disappears entirely after simple treatment. However, in cases the pain is after HIFU
ablation of a submucosal fibroid, it is the process of expulsion of the necrotic fibroid
tissue that can cause uterine contractions and pain symptoms. Such patients can be
temporarily under observation. Depending on the degree of pain or discomfort, mild
anti-inflammatory analgesic medication can be prescribed to control the pain, such
as Panadol extend, diclofenac sodium, etc. If the pain is due to an ablated submu-
cous fibroid, sometimes a dilatation and curettage can speed up removing the
necrotic submucosal fibroid and relieve the pain.
6.3 Skin Burn Injury 73
Lumbar, sacral, and leg pain: During HIFU ablation or shortly after treatment,
heat stimulation of nerve tissue next to the fibroid or adenomyosis may cause some
symptoms such as pain and numbness at the back causing lumbar pain. Sacral pain
may be related to ultrasonic energy stimulating the sacral coccyx and gluteal muscle
fascia during treatment. During or shortly after HIFU ablation of some fibroids or
adenomyosis at the posterior uterine wall, sharp pain may be felt in the sacral coc-
cygeal region. As long as it does not radiate to the lower limbs, it is likely to be
normal. If a sharp needle-like pain or an electric shock-like feeling is felt in both
lower legs during HIFU ablation, the patient should immediately inform the doctor,
and the HIFU ablation dosage or target area should be adjusted to resolute the
symptom.
A few patients may experience occasional leg numbness after surgery, but this
naturally disappears after 1–2 weeks. If this occurs, the patient should immediately
inform the doctor. The doctor can then use different methods to ease the pain or
discomfort, such as ice compress and physical therapy, to the sacral tail tip. This
sacrococcyx distending pain or discomfort may last for several hours or days. Such
pain will be mostly mild, requiring no special treatment and only just for observa-
tion. A small number of patients may require anti-inflammatory analgesic drugs
under the doctor’s guidance to reduce the pain, especially if the patient finds it dif-
ficult to tolerate.
Nerve damage is only likely to occur in unusual situations, such as large fibroids
located at the posterior uterine wall too close to the sacrum or arising from the cer-
vix. In order to avoid these complications, doctor-patient communication during
HIFU ablation is crucial for the doctor to identify any nerve stimulation at any spe-
cific parts of the pelvis. After timely communication with the doctor, the doctor can
adjust the focus position, sonication dosage, or ablation time to ensure the safety of
the nerve or bone.
6.3 Skin Burn Injury
In two retrospective studies of 27,053 patients and 9988 patients, skin burn occurred
in less than 1% of patients (26/17,402) with uterine fibroids or adenomyosis after
USgHIFU treatment [2, 5]. These skin burns were first, or second-degree skin burn.
There are a few situations that may increase the risk of a skin burn. Common
reasons are thick abdomen fat layer, abdominal wall scar, and superficial skin
lesions. Abdominal scars, notably those keloid scars, absorb some of the ultrasonic
energy, which may increase the risk of skin burns or keloid burn. However, adequate
and careful skin preparation before the treatment and timely communication
between patients and the medical staff will reduce skin burn. Prompt communica-
tion of feeling hot or pain at the skin will alert the doctor to stop the treatment tem-
porarily or change the target position thus reducing the risks of skin burn. However,
a “hot” skin sensation was also experienced by 48% of patients during the HIFU
treatment in patients with anteverted uterus compared to 27% of patients with a
retroverted uterus in a study [6]. It is likely due to timely communications, reduced
a b
Fig. 6.1 (a) Model demonstrated the use of infrared monitoring of the skin temperature; (b)
Infrared monitoring of skin temperature during HIFU treatment
treatment time as well as skin protection with cool degassed water that abdominal
skin burn is not commonly reported in the patients with HIFU ablation.
On the other hand, skin burn occurred in 2% of patients at the back or buttock
with the retroverted uterus in this study. Regular cooling down the temperature of
the buttock skin with cool water can also reduce the risk. Recently the application
of an infrared technology to monitor the buttock skin temperature can also reduce
the risk of buttock skin injury (Fig. 6.1).
Abdominal surgical scars have no significant influence on the effectiveness of
HIFU treatment. Although the risk of skin burn is higher in patients with abdominal
scars than without, the incidence rate is still acceptable [7]. Even patients have verti-
cal scars for previous surgery, HIFU treatment can still be performed. HIFU treat-
ment can be conducted 3 weeks after recent abdominal surgery, as long as the
healing of the wound is normal. However, if patients have received previous abdom-
inal surgery, the scar should be evaluated through pretreatment ultrasound screening
to see whether there is any attenuation of ultrasound energy caused by the scar. If no
attenuation is found, HIFU treatment is feasible without interference from the scar.
With adequate skin preparation, intraoperative communication, and skin palpation
to assess the skin temperature, these measures will reduce the risk of skin burns.
First-degree and second-degree skin burn may appear as redness or blisters for-
mation in the skin, which can be treated with a cold pack plus aloe vera gel. The skin
toxicity can resolve over days without skin resection or further medication.
6.4 Urinary Tract Injury
Urinary tract adverse events after HIFU treatment may present with urinary reten-
tion, urinary bladder irritation, or hematuria. Urinary retention was reported in less
than 1% of all patients with uterine fibroids or adenomyosis after HIFU treatment
[4, 5]. Symptoms of bladder irritation, dysuria, or bladder retention occurred in 4%
6.5 Bowel Injury 75
of patients, but much less than after surgical myomectomy [8]. Hematuria was
uncommon, occurring in <1% of HIFU treated patients. It could be a sign of blad-
der injury.
In general, bladder injury from HIFU ablation treatment is rare. Theoretically,
bladder injury could happen in the following situations. Firstly, an air bubble in the
bladder. With the ultrasonic thermal effect, the cavitation effect, and mechanical
effect, small blood vessels, and capillaries in the bladder wall are dilated and rup-
tured, and their permeability may increase, causing exudation of the red blood cells
and then hematuria which is the main manifestations of bladder injury. Secondly,
there is a scar on the bladder wall due to previous surgery; since the scar can absorb
ultrasonic energy and the temperature at the scar increases thus it may lead to coag-
ulation necrosis of the bladder wall. Thirdly, any calcification on the surface of a
subserous fibroid close to the bladder can reflect ultrasonic energy to the bladder
wall and causes bladder injury. In extreme situations, perforation of the bladder wall
and formation of a uterine bladder fistula or peritoneal bladder fistula may happen.
Fortunately, all these kinds of severe theoretical bladder injuries have not been
reported.
It is essential not to have air bubbles inside the bladder to avoid bladder injury. If
air bubbles are found in the bladder before HIFU ablation, they have to be removed
via flushing with cold saline through the urinary catheter. If hematuria happens after
HIFU treatment, this may be treated with cold saline rinsing the bladder. For rare
cases in which the duration of hematuria may be quite long, hemostatic drugs like
oral Transamin 500 mg three times daily can be prescribed for a few days. Generally,
after 1–2 days, the symptoms will disappear, and there will be no sequelae after
recovery.
After the HIFU ablation, a patient may complain of painful urination after the
urinary catheter is removed. If it happens, the patient should inform the doctor or
nurse to have more water intake to promote frequent urination. The doctor will also
prescribe Pyridium oral tablets three times daily for 5–7 days to relieve the
symptoms.
6.5 Bowel Injury
Bowel injury was reported in less than 1% of patients with HIFU treatment for uter-
ine fibroids. It may present as bowel perforation and a rare complication between 15
and 30 days after HIFU treatment [5]. The actual incidence of this severe complica-
tion after HIFU ablation is not known because only case reports of delayed bowel
perforation have been reported [9, 10]
Patients with previous open surgery are more likely to have bowel adhesions,
which increase the risk of bowel injury during HIFU treatment. However, many of
these patients are still suitable and safe for treatment. Preoperative localization
assessment, through ultrasound positioning, can evaluate whether the bowel or
bowel adhesion is inside the acoustic pathway during HIFU treatment. If the bowel
cannot be pushed away from the acoustic pathway by bladder distension or
increasing abdominal pressure by the ultrasound transducer, in this case, HIFU

treatment is not suitable because of the risk of thermal bowel injury with potential
bowel perforation. A strict preoperative diet and adequate bowel preparation can
also reduce the risk of bowel injury due to thermal damage from any bowel con-
tent or gas.
Patients should undergo strict bowel preparation before HIFU treatment. The
patient should only have light diets 1–3 days before HIFU ablation and strict cathar-
sis with cleansing enema the day before. A safe acoustic pathway should be estab-
lished during the treatment by pushing all bowels away from the ultrasonic energy
beam. During the time of HIFU ablations, the patient will have to keep her body still
to avoid thermal bowel injury. The recovery time of bowel function after HIFU abla-
tion will vary from person to person. An increase in the consumption of fruit and
vegetables, maintaining a relaxed mood, and undertaking moderate exercise all help
to improve intestinal peristalsis and lead to functional recovery.
6.6 Vaginal Bleeding or Discharge
Vaginal bleeding was reported in less than 1% of patients after HIFU treatment for
uterine fibroids [2]. Vaginal bleeding and discharge occurred in 5–9% of patients
after HIFU treatment, which is significantly lower than those after surgical myo-
mectomy [2, 6, 8]. Minor bleeding may occur after HIFU ablation of submucosal
fibroids or adenomyosis, particularly when they are close to the endometrium of the
uterus. It is due to the disseminated heat energy passing through and impacting on
the endometrium. This heat energy can result in aseptic inflammation and edema of
the endometrial tissue, which in some patients will present as a small amount of
bleeding. The influence of thermal ultrasound injury on the endometrium, mani-
fested as vaginal drainage or a small amount of bleeding, may last for days to weeks.
Sometimes after HIFU ablation, the menstrual period cycle may change, although
HIFU ablation itself does not affect the menstrual cycle. A women’s menstrual
cycles rely on many factors, especially emotion, stress due to admission to hospital
treatment; therefore, these can cause menstrual irregularities for the first few cycles
after HIFU ablation.
Provided that the amount of vaginal discharge and bleeding is small and no more
than the amount during menstruation, and there is no associated fever, abdominal
pain, and other discomforts, the patient can be kept under observation. Sometimes
antibiotics and hemostatic drugs can be prescribed according to the discretion of
her doctor.
6.7 Other Rare Complications or Those Not Reported
Postoperative aseptic pelvic peritonitis can occur after the HIFU ablation, especially
if the heat from ablation reaches the uterine serosal surface (Fig. 6.2).
6.7 Other Rare Complications or Those Not Reported 77
Fig. 6.2 Aseptic
peritonitis due to thermal
injury after HIFU ablation
for fibroid. (Photo was
provided by Dr. Zhenjiang
Lin, Affiliated Hospital of
Zunyi Medical College)
Fig. 6.3 Hysteroscopic
finding of the endometrial
cavity with endometrial
damage leaving an area of
no endometrial lining
(Photo was provided by Dr.
Hua Guo, Baoan MCH
Hospital, Shenzhen)
The patient can feel severe lower abdominal pain, which may be difficult to con-
trol. Ultrasound examination may show a mild to moderate amount of pelvic fluid.
The abdominal pain will gradually get easier and subside with analgesic and antibi-
otic treatment. Laparoscopy may sometimes be performed because of the fear of
severe complications of HIFU ablation.
On the other hand, the endometrium may also suffer from thermal injury if the
ablation to a fibroid is too close to the endometrial lining. Sometimes, after healing,
either endometrial adhesions or endometrial depletion (Fig. 6.3) can occur. These
complications may only be diagnosed at the hysteroscopic investigation for
infertility.
There are also some unusual but unexplainable complications after HIFU treat-
ment, such as renal failure, deep vein thrombosis, hydronephrosis, pubic symphysis
injury, thrombocytopenia, blurred vision, hernia, respiratory tract infection, dizzi-

ness, and headache. They occurred in less than 1% of patients receiving HIFU abla-
tion for fibroids and adenomyosis [2, 4, 5]. However, the incidence reduces as more
experience has been accumulated and clinical treatment protocols are established.
In conclusion, in the early HIFU fibroid ablation trials before 2011, the incidence
of skin burn had been reported in up to 2% (112/5526 patients); other adverse events
had also occurred like nerve injury, prolonged abdominal pain, and hematuria [11].
Analysis of adverse events showed that the frequency depended on the location of
the lesions and the type of HIFU device. With a better understanding of the side
effects of ultrasound-guided HIFU treatment, stringent HIFU ablation protocols for
fibroid treatment were followed in subsequent clinical trials. As more and more
HIFU centers for fibroid treatment are established in China, they provide more com-
prehensive data to better understand the safety profile of HIFU ablation. In 2018, a
multicenter prospective study of HIFU ablation for uterine fibroids was reported,
comparing the conventional surgeries for uterine fibroids with HIFU ablation [4]. In
this study, 2411 patients with symptomatic uterine fibroids were enrolled from 20
medical centers in China. The results showed that the effectiveness of HIFU abla-
tion of uterine fibroids is comparable to conventional surgical treatment. Its safety
is significantly superior to traditional surgery, with minimal trauma and significant
improvement in symptoms. The quality of life improved, hospital stay shortened,
and medical costs reduced. Currently, many centers in China and overseas have
considered this technology as an alternative treatment for fibroids and other solid
tumors [12, 13].
References
1. Feng Y, et al. Safety of ultrasound-guided high-intensity focused ultrasound ablation for dif-
fuse adenomyosis: a retrospective cohort study. Ultrason Sonochem. 2017;36:139–45.
2. Liu Y, et al. Adverse effect analysis of high-intensity focused ultrasound in the treatment of
benign uterine diseases. Int J Hyperth. 2018;35(1):56–61.
3. Goldberg SN, et al. Image-guided tumor ablation: standardization of terminology and report-
ing criteria. Radiology. 2005;235(3):728–39.
4. Chen J, et al. Evaluation of high-intensity focused ultrasound ablation for uterine fibroids: an
IDEAL prospective exploration study. BJOG Int J Obstet Gynaecol. 2018;125(3):354–64.
6. Zhang W, et al. A comparison of ultrasound-guided high intensity focused ultrasound for the
treatment of uterine fibroids in patients with an anteverted uterus and a retroverted uterus. Int
J Hyperth. 2016;32(6):623–9.
7. Xiong Y, et al. Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for
the treatment of patients with adenomyosis and prior abdominal surgical scars: a retrospective
study. Int J Hyperth. 2015;31(7):777–83.
8. Wang X, et al. Effect of high-intensity focused ultrasound on sexual function in the treat-
ment of uterine fibroids: comparison to conventional myomectomy. Arch Gynecol Obstet.
2013;288(4):851–8.
9. Hwang DW, et al. Delayed intestinal perforation and vertebral osteomyelitis after high-intensity
focused ultrasound treatment for uterine leiomyoma. Obstet Gynecol Sci. 2017;60(5):490–3.
References 79
10. Ko JK, Seto MT, Cheung VY. Thermal bowel injury after ultrasound-guided high-intensity
focused ultrasound treatment of uterine adenomyosis. Ultrasound Obstet Gynecol.
2018;52(2):282–3.
11. Yu T, Luo J. Adverse events of extracorporeal ultrasound-guided high intensity focused ultra-
sound therapy. PLoS One. 2011;6(12):e26110.
12. Zhang L, Wang Z-B. High-intensity focused ultrasound tumor ablation: review of ten years of
clinical experience. Front Med China. 2010;4(3):294–302.
13. Orsi F, et al. High intensity focused ultrasound ablation: a new therapeutic option for solid
tumors. J Cancer Res Ther. 2010;6(4):414.
Fertility and Pregnancy After HIFU
Ablation 7
7.1 he Reproductive Impact After HIFU Ablation

T
for Uterine Fibroids
Some evidence showed that uterine fibroids might adversely affect fertility, causing
1–2.4% of infertility in patients [1]. Uterine fibroids may cause fertility, pregnancy,
and labor complications such as miscarriage, preterm labor, obstructed labor, or
postpartum bleeding. The impact of HIFU ablation on patients’ fertility and preg-
nancy outcome becomes a topic of interest because HIFU ablation is currently used
as a new technology for treating fibroids.
After HIFU treatment, it successfully reduces the sizes of fibroids and improves
the endometrial environment; thus, the pregnancy rate appears to have improved. It
has also been demonstrated that HIFU ablation would not affect the patient’s ovar-
ian reserve after treatment [2, 3]. Regarding the evidence, case reports of pregnan-
cies with vaginal delivery at term had been reported in the early date after MRgHIFU
treatment, and none has complications during pregnancy and labor [4–6]. Some
larger studies, including individual and multicentre collaborative trials, also con-
firmed successful pregnancies after HIFU therapy [7–12]. Table 7.1 showed that
natural pregnancies occur after HIFU treatment, and no reported risks in pregnancy
and labor occurred in patients wishing to have a vaginal delivery.
After early case reports have demonstrated successful pregnancies and deliveries
after MRgHIFU, Chinese authors from 2012 started to present their data of preg-
nancies after USgHIFU in a larger series of patients. They also did not show any
obstetric or labor complications in patients after USgHIFU treatment.
Compared with myomectomy, which is associated with risks of infection, bleed-
ing, adhesion formation, and early recurrence of fibroids or adenomyosis, HIFU
treatment is a comparatively noninvasive method with minimal impairment of fertil-
ity. Furthermore, a report suggested that HIFU may promote fertility in women with
uterine fibroids [4].
https://doi.org/10.1007/978-981-16-0939-8_7
82 7 Fertility and Pregnancy After HIFU Ablation
Table 7.1 The pregnancy outcomes after MRgHIFU/USgHIFU ablation for uterine fibroids
Author, Tumors/ Months to
No. Year Country Treatment pregnancies Outcome
1 Hanstede USA Fibroid/ 1.5 years 1 spontaneous pregnancy;
(2007) [4] MRgHIFU vaginal delivery at 39 weeks
2 Morita Japan Fibroids/ 3 months 1 spontaneous pregnancy;
(2007) [5] MRgHIFU vaginal delivery at 39 weeks
3 Yoon Korea Fibroids/ 4 months 1 spontaneous pregnancy, vaginal
(2010) [6] MRgHIFU delivery at 39 weeks
4 Funaki Japan Fibroids/ Within 4 pregnancies. 1 pregnancy
(2009) MRgHIFU 24 months occurred 3 months after
[13] MRgHIFU, 2 at 12 months, and
1 within 24 months. There were
2 live full-term births and 2
first-trimester miscarriages.
5 Rabinovici Israel, Fibroids/ (Mean) 54 pregnancies in 51 women
(2010) [7] Germany, MRgHIFU 8 months have occurred after MRgHIFU
Japan, treatment of uterine leiomyomas.
USA Live births 41% of pregnancies,
64% vaginal delivery, 28%
spontaneous abortion rate, 11%
termination of pregnancy, and 11
(20%) ongoing pregnancies
beyond 20 weeks
6 Qin (2012) China Fibroids/ <3 months 24 pregnancies. 8 women had
[8] USgHIFU (n = 4), desired pregnancy while the
3–6 months remaining 16 had not. Of the 8
(n = 13), and desiring pregnancy, 7 continued
>7 months to elective cesarean section at
(n = 7) full term with birth weights at
least 2500 g and Apgar scores
within normal ranges (8–9) in all
cases
7 Bohlmann Germany Fibroids/ n.a. One hundred one pregnancy from
(2014) [9] USgHIFU, an analytic study of 40 published
MRgHIFU papers. Miscarriage 17.8%,
premature labor 5.9%, and
Cesarean section rate 33.3%
8 Zou (2017) China Fibroids/ 5.6 ± 2.7 80 pregnancies, including 4 IVF
[10] USgHIFU months pregnancies, 15 vaginal
deliveries, 56 cesarean sections,
3 miscarriages, 1 induced
abortion, 5 ongoing pregnancies,
no uterine rupture or postpartum
complications
7.1 The Reproductive Impact After HIFU Ablation for Uterine Fibroids 83
Table 7.1 (continued)
Author, Tumors/ Months to
No. Year Country Treatment pregnancies Outcome
9 Li (2017) China Fibroids/ 3 years 131 pregnancies out of 189
[11] USgHIFU (69.3%) FUS treated nulliparous,
spontaneous conception rate
95.4%, show 87 reached full
term, Pregnancy complications,
10.8% Cesarean section 67/93
(72%). Labor complications—5
premature birth, 1 fetal distress,
and 6 bleeding at delivery
10 Liu (2018) China Fibroids/ Median of 88 pregnancies, 74 full-term
[12] USgHIFU 76 months deliveries (84%) including 37
cesarean sections, 9 miscarriages
(10%), 5 induced abortions (6%),
none have complications during
pregnancy and labor
n.a. not available
From Felix Wong, J Gynecol 2020, 5(1): 000203
Uterine artery embolization (UAE) treatment, another minimally invasive

approach increasingly used to treat symptomatic fibroids, had also reported success-
ful pregnancies after its treatment [14]. However, both case reports and larger series
of UAE treatments had detailed several complications. There was an age-related
risk of ovarian failure [15] and increased placentation problems [16]. Randomized
trials comparing UAE with myomectomy for symptomatic fibroids suggested that
UAE might have a detrimental effect on pregnancy outcome [17].
Alternatively, the experience of HIFU treatment for fibroids shows that the
chance of getting pregnant is encouraging and higher than those without any treat-
ment. In the early days of HIFU treatment, clinical reports had concentrated on the
treatment of symptomatic women who had completed their families, and HIFU
ablation was contraindicated for women expecting a baby. With increasing experi-
ence, it is recognized that the safety of pregnancy outcomes may be due to any
tumor necrosis after HIFU ablation is within the fibroid’s pseudo-capsule and that
HIFU does not damage the surrounding healthy tissues; thus, future pregnancy is
not affected. Current case reports and small cohort studies offer no increased risk of
miscarriage, premature labor, and labor complications after HIFU ablation.
Although it has been recommended that patients should use contraception and not
conceive within 1 year after HIFU treatment, many patients get unintended preg-
nancies 3–6 months after HIFU treatment and have a successful pregnancy outcome
without any complication.
The potential HIFU impact on pregnancy, pregnancy outcome, and delivery is
further elaborated as follow:
7.1.1 HIFU Impact on Ovarian Functions
The development of premature menopause would constitute a severe complica-

tion of any treatment of fibroids using UGgHIFU/MRgHIFU. It could be caused
by inadvertent direct sonication of the ovaries or if the fibroid treated is too
close to the ovaries. It can cause a total or partial impairment of ovarian func-
tion. There is however no known case reported on the changes in endocrine
parameters or inadvertent ovarian failure after HIFU treatment for uterine
fibroids. The anti-Mullerian hormone (AMH) is used to measure a woman’s
ovarian reserve or egg count and is often used as a marker of oocyte quantity.
Cheung et al. [2] showed no significant difference in AMH levels before and
after HIFU ablation. No patient became amenorrheic or reported menopausal
symptoms after treatment. Nevertheless, during UGgHIFU/MRgHIFU treat-
ment, we always use real-time monitoring of the treated area to avoid direct
sonication at the neighboring ovaries.
7.1.2 HIFU Impact on Uterine Function
There is no study on the possible adverse impact on uterine function after

USgHIFU/MRgHIFU treatment for fibroids. The changes in sizes and posi-
tions after the fibroids’ coagulation necrosis could result in endometrial
changes and changes in uterine contractility. Thus, it will impair or improve
uterine functions. Direct and excessive ablation of a submucous fibroid could
cause intracavitary adhesions or denuded endometrial lining. However, to date,
no case report demonstrates the impact of HIFU sonication, in particular, on a
submucosal fibroid and its adjacent endometrial tissue, causing any impair-
ment of implantation. Nevertheless, despite a lack of case reports, this possibil-
ity cannot be excluded. Therefore, whether UGgHIFU/MRgHIFU treatment
could create a new risk factor for uterine sterility or abnormal placenta implan-
tation remains to be studied.
7.1.3 Risks of Miscarriage After HIFU Ablation
The Chinese authors reported a high rate of induced abortions in pregnancies

after HIFU treatment, which might be related to the “one-child policy” in China.
The mothers’ age and the presence of sizable fibroids may also influence the
miscarriage rate in any study, as both of these factors can independently adversely
impact miscarriages. However, Bohlmann et al. [9] showed that the risk of mis-
carriage after UGgHIFU/MRgHIFU was 17.8%, which did not appear to be
higher compared to an age-matched control group of patients wanting to have
children. It was because the rate of miscarriages after IVF/ICSI in this group of
women is also around 20%
7.2 The Reproductive Impact After HIFU Ablation for Adenomyosis 85
7.1.4 The Cesarean Section Rate After HIFU Ablation
The elective cesarean section rate appeared to be high among women after
UGgHIFU/MRgHIFU, despite the widespread reassurance that vaginal delivery is
safe. It could be due to the patients’ desire for a healthy baby or the need for more
safety than uncertain labor risks after HIFU treatment. The cesarean section rate
was reported as high as 50–78% [10, 11]. Therefore, after HIFU ablation, all preg-
nancies that reach up to the term would have a high cesarean section rate compared
to term pregnancy without HIFU surgery.
7.2 he Reproductive Impact After HIFU Ablation

T
for Adenomyosis
Adenomyosis commonly occurs in young reproductive-age women, and it can

impair fertility. Adenomyosis is a disease with no distinct boundary, and therefore
HIFU treatment is unable to remove all the lesions raising the possibility of recur-
rence. Surgical treatments are difficult and ineffective, and hysterectomy is the last
resort to remove the lesion. Medical treatments with hormones or progestogen
IUCD will prevent them from conception and pregnancy. HIFU ablation is now
increasingly used for treating adenomyosis. However, all data from case reports or
small series gave limited information on the chances of pregnancy and their out-
comes after HIFU treatment. Adenomyosis was, in the past, mainly a “post-factum”
pathological diagnosis after extensive surgery. Therefore, any analysis of HIFU
treatment’s impact is compounded by the fact that there is no agreed definition of
adenomyosis’s extent and severity. At present, there is no specific HIFU ablation
protocol to set a “gold standard” for comparison. Based on the limited evidence
presented in this chapter, it still seems that adenomyosis has become an entity that
might be treatable by this new noninvasive method without an adverse impact on
fertility and pregnancy.
The early case reports of two individual patients with adenomyosis had normal
pregnancy 3–5 months after the HIFU treatment. They both had an uneventful vagi-
nal delivery [18, 19]. After that, there have now been a few more pregnancies with
good obstetric outcomes after USgHIFU for adenomyosis. However, from these few
reports in the literature, as in Table 7.2, one cannot recommend an appropriate preg-
nancy timing after HIFU ablation. It depends on the size of the treated lesions, loca-
tion, and duration of treatment and follow-up. For those with small adenomyosis
lesions, short treatment time, and lesions that are >1 cm distant from the endome-
trium and uterine surface, the time for contraception can reduce to 3–6 months.
As many above reports were from China, miscarriages and the cesarean section
rate could be biased due to the Chinese Government’s “one-child” policy in the past.
For those with vaginal delivery after HIFU treatment, there was no uterine rupture
during pregnancy or labor. Therefore, these limited data suggest that pregnancy can
occur within 1 year after HIFU treatment and a possible good pregnancy outcome.
Table 7.2 The pregnancy outcomes after MRgHIFU/USgHIFU for adenomyosis

1 Rabinovici Israel Adenomyosis/ 3 months 1 pregnancy, vaginal
(2006) [18] MRgHIFU delivery at term
2 Kim (2011) Korea Adenomyosis/ 5 months 1 pregnancy, vaginal
[19] MRgHIFU delivery at term, no labor
complication
3 Luo (2014) China Adenomyosis/ n.a. 15 pregnancies, 4 full-term
[20] USgHIFU vaginal delivery, 3 cesarean
sections, the remaining 8
are ongoing
4 Lee (2015) Korea Adenomyosis/ n.a. 9 unintended pregnancies
[21] USgHIFU
5 Zhou China Adenomyosis/ Median of 54 pregnancies, 21
(2016) [22] USgHIFU 10 months (range, deliveries healthy babies,
1–31) 20/54 had abortions
compared to 23/54 had
abortions before HIFU
ablation
6 Wang China Adenomyosis/ 8.75 ± 6.23 months 20 pregnancies, 11 normal
(2017) [23] USgHIFU delivery, 5 spontaneous
abortions, 1 ectopic
pregnancy, 1 induced
abortion, and 2 ongoing
pregnancy. No uterine
rupture during pregnancy
or delivery period
7.3 Conclusion
To answer whether pregnancies are at particular risk for those who have previously
had USgHIFU/MRgHIFU treatment, prospective randomized clinical trials should
be performed. However, no such trials have been done yet. The currently existing
but limited evidence suggests that USgHIFU/MRgHIFU treatment for fibroids and
adenomyosis could be a safe alternative to myomectomy or UAE for women who
wish to have babies. However, this is to be confirmed by the current consensus.
However, it appears that HIFU treatment can shorten the treatment to pregnancy
interval after HIFU ablation.
Even though early reports of pregnancies after HIFU interventions for uterine
leiomyoma and adenomyosis appear to be safe. However, these data must be care-
fully studied because a single complication causing maternal or fetal morbidity can
be a disaster in even one out of a thousand cases. Given the large number of women
developing fibroids and adenomyosis before childbearing, addressing these impor-
tant issues in a large clinical trial is critical.
References 87
References
1. Kroon B, et al. Fibroids in infertility–consensus statement from ACCEPT (Australasian CREI
Consensus Expert Panel on Trial evidence). Aust N Z J Obstet Gynaecol. 2011;51(4):289–95.
2. Cheung VY, et al. Ovarian reserve after ultrasound-guided high-intensity focused ultrasound
for uterine fibroids: preliminary experience. J Obstet Gynaecol Can. 2016;38(4):357–61.
3. Qu K, et al. The impact of ultrasound-guided high-intensity focused ultrasound for uterine
fibroids on ovarian reserve. Int J Hyperth. 2020;37(1):399–403.
4. Hanstede MM, Tempany CM, Stewart EA. Focused ultrasound surgery of intramural leiomyo-
mas may facilitate fertility: a case report. Fertil Steril. 2007;88(2):497.e5–7.
5. Morita Y, Ito N, Ohashi H. Pregnancy following MR-guided focused ultrasound surgery for a
uterine fibroid. Int J Gynecol Obstet. 2007;99(1):56–7.
6. Yoon S-W, et al. Pregnancy and natural delivery following magnetic resonance imaging-
guided focused ultrasound surgery of uterine myomas. Yonsei Med J. 2010;51(3):451–3.
7. Rabinovici J, et al. Pregnancy outcome after magnetic resonance–guided focused ultra-
sound surgery (MRgFUS) for conservative treatment of uterine fibroids. Fertil Steril.
2010;93(1):199–209.
8. Qin J, et al. Outcome of unintended pregnancy after ultrasound-guided high-intensity focused
ultrasound ablation of uterine fibroids. Int J Gynecol Obstet. 2012;117(3):273–7.
9. Bohlmann M, et al. High-intensity focused ultrasound ablation of uterine fibroids–potential
impact on fertility and pregnancy outcome. Geburtshilfe Frauenheilkd. 2014;74(02):139–45.
10. Zou M, et al. Pregnancy outcomes in patients with uterine fibroids treated with ultrasound-
guided high-intensity focused ultrasound. BJOG Int J Obstet Gynaecol. 2017;124:30–5.
11. Shu Li J, et al. Pregnancy outcomes in nulliparous women after ultrasound ablation of uterine
fibroids: a single-central retrospective study. Sci Rep. 2017;7(1):1–8.
12. Liu X, et al. Vaginal delivery outcomes of pregnancies following ultrasound-guided

high-intensity focused ultrasound ablation treatment for uterine fibroids. Int J Hyperth.
2018;35(1):510–7.
13. Funaki K, Fukunishi H, Sawada K. Clinical outcomes of magnetic resonance-guided focused
ultrasound surgery for uterine myomas: 24-month follow-up. Ultrasound Obstet Gynecol.
2009;34(5):584–9.
14. Ravina JH, et al. Pregnancy after embolization of uterine myoma: report of 12 cases. Fertil
Steril. 2000;73(6):1241–3.
15. Spies JB, et al. Ovarian function after uterine artery embolization for leiomyomata: assessment
with use of serum follicle stimulating hormone assay. J Vasc Interv Radiol. 2001;12(4):437–42.
16. Pron G, et al. Pregnancy after uterine artery embolization for leiomyomata: the Ontario multi-
center trial. Obstet Gynecol. 2005;105(1):67–76.
17. Mara M, et al. Midterm clinical and first reproductive results of a randomized controlled
trial comparing uterine fibroid embolization and myomectomy. Cardiovasc Intervent Radiol.
2008;31(1):73–85.
18. Rabinovici J, et al. pregnancy and live birth after focused ultrasound surgery for symptomatic
focal adenomyosis: a case report. Hum Reprod. 2006;21(5):1255–9.
19. Kim KA, et al. Short-term results of magnetic resonance imaging-guided focused ultrasound
surgery for patients with adenomyosis: symptomatic relief and pain reduction. Fertil Steril.
2011;95(3):1152–5.
20. Luo S, et al. Pregnancy outcome after high intensity focused ultrasound (HIFU) treatment for
patients with adenomyosis. Chongqing Med. 2014;4:454–5, 458.
21. Lee J-S, et al. Ultrasound-guided high-intensity focused ultrasound treatment for uterine
fibroid & adenomyosis: a single center experience from the Republic of Korea. Ultrason
Sonochem. 2015;27:682–7.
22. Zhou C, Xu X, He J. Pregnancy outcomes and symptom improvement of patients with adeno-
myosis treated with high intensity focused ultrasound ablation. Zhonghua Fu Chan Ke Za Zhi.
2016;51(11):845–9.
23. Wang Z, et al. Observation on pregnancy outcomes after high intensity focused ultrasound
ablation therapy in patients with adenomyosis. Chongqing Med. 2017;46(18):2506–8.
Other Issues of HIFU Treatment
8
HIFU treatment is a revolutionary treatment and utterly different from traditional

surgery. Many people, including doctors, still do not understand how HIFU works.
Hopefully, after reading this book, the clinical applications of this HIFU ablation in
obstetrics and gynecology can now be recognized. This chapter will also help elabo-
rate on some HIFU treatment issues that even those who have learned HIFU abla-
tion may be confused.
8.1 MRI-Guided and Ultrasound-Guided HIFU Ablation
HIFU ablation technology has two monitoring methods during the ablation treat-
ment—the ultrasound-guided (USg) and MRI-guided (MRg) monitoring systems.
The former is commonly used in China because the former USgHIFU system is
independently invented and developed in China. The main difference between the
two is the real-time monitoring methods during the ablation, and each has its advan-
tages and disadvantages.
The ultrasound-guided system (USgHIFU) uses real-time ultrasound monitor-
ing, which obtains real-time ultrasound images within a millisecond delay. The
treatment effect can be instantly judged as gray-scale changes in the targeted area.
In the treatment process, real-time USg monitoring can ensure that any movement
of the HIFU targeted area caused by patients’ involuntary movement or excessive
breathing can be timely visualized. An appropriate stoppage of the treatment can
ensure safety, avoiding injury to the bowel and other surrounding tissues or organs.
This treatment protocol has been widely used and is now a mature technology.
MRI-guided HIFU system monitors the effect of HIFU ablation through the tem-
perature changes within the targeted area. The advantage of this monitoring is that
it can accurately determine the focused area’s temperature within the tumor. On the
other hand, the major disadvantage is the several seconds’ delay needed for the MRI
to capture images after each ablation step. Therefore, if the patient’s body moves
https://doi.org/10.1007/978-981-16-0939-8_8
90 8 Other Issues of HIFU Treatment
during the image updating period by the machine, the doctor will not know the
actual treatment area in a timely manner.
Therefore, the USgHIFU essentially allows the doctor to directly look at the
surgery via ultrasound monitoring through his/her own eyes. MRgHIFU, on the
other hand, is as if the doctor is doing the surgery blind and then only after the treat-
ment step, inspecting the results of color changes of an ablation point. USgHIFU
ablation is effectively a sharp knife that enables the “surgery” to complete in a short
time as a virtually continuous process under real-time monitoring. MRgHIFU, by
analogy, is like a rusty blunt knife, which takes a long time with many discontinu-
ous steps.
8.2 HIFU Ablation and HIFU Hyperthermia
In China, an increasing number of hospitals are offering HIFU treatment for

patients with gynecological tumors. Nevertheless, the actions of some High
Intensity Focused Ultrasound (HIFU) systems do not necessarily belong to the
class of ultrasound ablation. Different HIFU manufacturers have their ultrasound
treatment systems generating different target temperatures, as previously discussed
in Chap. 1. The HAIFU knife® manufactured by Chongqing HAIFU Medical
Technology Co Ltd. can produce the highest focused ultrasound energy up to
90–100 °C. Consequently, the ablation can usually be completed at high ablation
efficiency with a single treatment session. Under such a treatment, fibroids’ resid-
ual and recurrence rate will be lower than the treatment offered by other manufac-
turers whose HIFU machines belong to another category of ultrasonic hyperthermia,
which offers focused ultrasound energy up to 60 °C only. The latter cannot achieve
high ablation efficiency, and thus sometimes, it may need multiple treatment ses-
sions for larger tumors. Thus, they may have a lower percentage of ablation, i.e.,
NPV in the fibroids, and their recurrence rate will be higher.
8.3 Malignant Fibroids
Leiomyosarcoma (LMS) is a rare but highly malignant type of uterine sarcoma. The
probability of uterine sarcoma is relatively low because the reported incidence
ranges from 0.36–0.64 per 100,000 women [1, 2]. Its presenting symptoms may be
vague and mimic other benign uterine conditions. If the uterine sarcoma is sus-
pected, surgical removal of the lesion is strongly recommended to avoid affecting
the prognosis. Surgery will allow the pathology to be analyzed to enhance and avoid
the delay of adjuvant treatments. If one suffers from multiple fibroids, in which one
of the fibroids is suspected malignant, and the others are benign, HIFU treatment
should still be avoided. Even the probability for a fibroid to be a malignant fibroid
is relatively low. If any preoperative assessment suspects a malignant sarcoma, sur-
gical resection of the tumor and removal of the uterus are recommended.
8.5 The Cost of HIFU Treatment 91
After HIFU treatment, ablated fibroids will not develop into cancer. The HIFU
treatment principle is to focus on a small point that causes rapid high temperature-
induced cell lysis and irreversible coagulation necrosis, with cells losing activity
and unable to become cancerous. The probability of benign uterine fibroids becom-
ing cancer is very low. Regardless of whether treatment is by traditional myomec-
tomy or HIFU ablation, patients need to be under close follow-up postoperatively to
assess the treatment effectiveness and chance of recurrence. The preoperative
assessment of a suspected uterine sarcoma has been discussed in Chap. 4.
8.4 Multiple Fibroids
If a hysterectomy is proposed because there are multiple fibroids or fibroids are

large, then patients should be referred for assessment for the suitability of HIFU
ablation. If preoperative HIFU assessment using MRI and simulation test showed
that HIFU treatment is suitable, a hysterectomy could be avoided.
Recurrence of fibroids or a new fibroid can occur because complete ablation of
multiple fibroids can be difficult in one treatment session. Even traditional open or
laparoscopic surgery will not remove all multiple fibroids from a uterus. However,
HIFU treatment can ablate the vast majority of fibroids and achieve excellent con-
trol of fibroid growth and associated clinical symptoms. Any fibroids that recur
following treatment with HIFU can have a repeated HIFU treatment without increas-
ing difficulties like in the previous HIFU ablation.
HIFU ablation of uterine fibroids, which are benign lesions, is affected by the
location, number, size, and blood supply of fibroids. Although the total clinical
effectiveness is 95% or more, sometimes the treatment effect is not as good as
expected. The standards of clinical effectiveness for HIFU ablation are not the dis-
appearance of all fibroids; they include improving the symptoms, reducing the
fibroids’ size, improving reproductive function, etc. The HIFU ablation also has its
limitations. Suppose the therapeutic effect of HIFU treatment is found unsatisfac-
tory. In that case, the following management will depend on individualized situa-
tions: (1) if fibroids are not totally ablated but with no apparent symptoms, the
patient can be kept under observation; (2) if the fibroid is still suitable for HIFU
ablation, it can be treated again with HIFU or treated with medication (such as
GnRH-a) combined with HIFU ablation again; and (3) even if HIFU ablation is suit-
able after reevaluation, the patient can choose another surgical treatment option.
8.5 The Cost of HIFU Treatment
The cost of HIFU ablation is slightly lower than that for traditional surgery in China.
Still, after reimbursement, the patient’s overall cost is far less than the laparoscopic
myomectomy surgery, hysterectomy, etc. The total treatment cost of HIFU ablation
in China varies between about RMB12,000–RMB20,000 depending on the standard
92 8 Other Issues of HIFU Treatment
charges and the differences in treatment plans relating to medication and hospital-
ization time. However, HIFU compared with open or laparoscopic surgery, the treat-
ment time and hospitalization time (generally in the hospital 1–2 days) is much
reduced, and there is no need for specialist care. The postoperative recovery is also
fast, and patients can resume work soon after treatment. The family also does not
need to put too many health carers or material resources for her convalescence;
therefore, it will reduce patients’ overall cost for this noninvasive HIFU surgery [3].
References
1. Harlow BL, Weiss NS, Lofton S. The epidemiology of sarcomas of the uterus. J Natl Cancer
Inst. 1986;76(3):399–402.
2. Skorstad M, Kent A, Lieng M. Uterine leiomyosarcoma–incidence, treatment, and the impact
of morcellation. A nationwide cohort study. Acta Obstet Gynecol Scand. 2016;95(9):984–90.
3. Zhang X, et al. Effective ablation therapy of adenomyosis with ultrasound-guided high-
intensity focused ultrasound. Int J Gynecol Obstet. 2014;124(3):207–11.
Other HIFU Ablation Applications
in Gynecology and Related to Obstetrics 9
Applications of HIFU ablation have been reported to treat placenta accreta, abdomi-
nal wall endometriotic lesions, and cesarean scar pregnancy. HIFU ablation is a new
treatment for these conditions that may require more evidence to prove its safety
and effectiveness. These treatments are elaborated and described in this chapter
as follow:
9.1 Abnormal Placenta Attachment—Placenta Accreta
The retained placenta is a common complication where the placenta remains in the
uterus after delivery. Placenta accreta is diagnosed when there is abnormal adher-
ence of placenta villi to the myometrium. According to the depth of the chorionic
villi penetration, there are three types of abnormal placental adherence. Figure 9.1
illustrates the three types of placenta attachments; type 1-placenta accreta (b) with
the placenta slightly attached to the myometrium, type 2-placenta increta (c) with
the placenta invading into the myometrium, and type 3-placenta percreta (d) with
the placenta deeply penetrates through the uterine serosa.
Because placenta accreta and increta cannot be individually diagnosed with clar-
ity before treatment, they are often treated as one as “placenta accreta.” Thus, pla-
centa accreta accounts for approximately 75% of all cases of abnormal placental
attachments.
Placenta accreta occurs after delivering a baby with an incidence of 1 in 2510
and 1 in 4017 pregnancies [1]. Ultrasound is a first-line method for diagnosing pla-
centa accreta. Before the availability of MRI, it is most useful and accurate to diag-
nose this disease. An abdominal or vaginal ultrasound examination will show a
large hyperechogenic shadow in the endometrial cavity. The definite diagnosis can
be confirmed by hysteroscopic examination and biopsy.
Placenta accreta is a challenging disorder to treat because its chorionic villi have
penetrated the uterine muscular layer, causing its failure to detach from the uterus.
https://doi.org/10.1007/978-981-16-0939-8_9
94 9 Other HIFU Ablation Applications in Gynecology and Related to Obstetrics
a b c d
Fig. 9.1 Abnormal placenta attachments. (a) normal; (b) accreta; (c) increta; (d) percreta
Any partial detachment will cause heavy uterine bleeding. It sometimes leads to
heavy postpartum hemorrhage, secondary infection, shock, uterine perforation due
to surgical intervention, and even maternal death. In the past, hysterectomy is the
only surgical treatment to remove the placenta accreta. However, for those who
want to retain the uterus, if there is only a small area of the penetrating placenta and
no bleeding or signs of infection, conservative treatment can be instituted with
ongoing monitoring of the vital signs. However, postpartum management of pla-
centa accreta can be tricky because of the risks of bleeding, infection, prolonged
hospitalization, and needing an urgent hysterectomy [2]. Some authors have pro-
posed hysteroscopic resection as a conservative treatment for retained placenta
accreta [3], but it can lead to repeated hysteroscopic procedures, intrauterine adhe-
sions, or delayed hysterectomy. Other conservative treatments with uterine artery
embolization (UAE) or methotrexate therapy should not be offered to women who
want to have future pregnancies because of the potential impairment of ovarian
function after treatment. These treatments might also result in secondary hysterec-
tomy, occurring in 18% of UAE and 6% of methotrexate therapy [4].
HIFU ablation has been used in China to manage this difficult situation.
Figure 9.2 shows the HIFU ablation of placenta accreta before uterine curettage to
remove the adherent placental tissue.
Bai et al. [5] reported their preliminary study of 12 patients receiving HIFU treat-
ment of placenta accreta after vaginal delivery. There were no increased risks of
infection or hemorrhage, and no patient required a hysterectomy. Two of the 12
patients became pregnant during the follow-up period. Ye et al. [6] used USgHIFU
to treat 25 patients with placenta accreta. HIFU procedure was successfully per-
formed in all patients. After HIFU ablation, 16 patients required only one hystero-
scopic resection session, while nine patients had to undergo a second hysteroscopic
resection to remove the placenta accreta. Two uterine perforations occurred during
the first hysteroscopy operation, but no other severe complications were observed.
The median volume of blood loss was 20 mL.
The advantages of HIFU ablation for placenta accreta are (1) It can effec-
tively ablate placenta accreta under real-time monitoring and make its placenta
lining quickly and partially separated to be easily detached by surgery. (2) HIFU
9.1 Abnormal Placenta Attachment—Placenta Accreta 95
a b
Fig. 9.2 (a) MRI scan of placenta accreta (b) gray-scale changes in the placental tissue (white
arrows) during HIFU ablation (c) post-HIFU ablation assessment with microbubble infusion
(small white arrows) showing non-perfused placental tissues
ablation can reduce the implanted placenta’s blood supply and avoid heavy
bleeding while removing the placenta by D&C or hysteroscopic resection,
avoiding a hysterectomy [2, 5, 6].
All HIFU ablation procedures for placenta accreta are similar to those for fibroids
and adenomyosis. The operation is performed under conscious sedation, and the
patient is required to lie prone on the treatment bed. A real-time ultrasound scan is
to determine the location of the placenta lesion in a sagittal view. The treatment plan
is made by dividing the placenta into slices with a thickness of 3–5 mm each,
depending on the size of the placental lesion. A hypervascular placental bed may
require higher energy at 400 W. The lesion’s coagulation necrosis will be deter-
mined by observing gray-scale changes in the lesion. The HIFU treatment stops
when the placental blood flow disappears on color Doppler monitoring or absence
of microbubble perfusion in the lesion. All patients will take antibiotics for 5 days
after treatment.
So far, the mechanism of its successful treatment in placenta accreta remains
unclear. HIFU treatment may impact the vascular bed, leading to endothelial dam-
age and thrombogenesis of the placental vessels. This may have a role in vascular
occlusion at the placental bed [7]. For a small area of placenta attachment, HIFU
can accelerate the process of placental involution by causing extensive necrosis of
the residual placenta and stimulating aseptic inflammation and absorption of the
necrotic tissue. However, for a large area of placenta accreta, careful and gentle
D&C removal of the placental tissue under ultrasound guidance will be necessary
3–7 days after HIFU treatment.
Therefore, HIFU is a safe and effective method for managing placenta accreta to
prevent bleeding, infection, and other complications from remaining placental tis-
sue and improve fertility. Being a noninvasive approach to treat placenta accreta,
HIFU is a promising treatment. Before it is widely adopted to treat this condition, it

deserves further research and clinical trials.
9.2 Cesarean Scar Pregnancy (CSP)
Cesarean scar pregnancy (CSP) is an ectopic pregnancy implanted in the myome-

trium at the site of a previous cesarean section scar. It is a rare ectopic pregnancy
and may lead to severe complications, such as uterine rupture and severe hemorrhage.
With the high incidence rate of cesarean section nowadays, the cesarean scar
defect (CSD) and CSP are likely to increase. In pregnant women, the CSP can
become easily diagnosed by ultrasound scans due to the distending amniotic fluid
filling the CSD [8]. Armstrong et al. [9] stated that transvaginal ultrasound (TVU)
was useful and highly accurate in detecting CSP defined by the presence of fluid
within the scar niche (Fig. 9.3a). MRI scans had been used to analyze the CSD find-
ings [10] and used to confirm CSP in the lower part of the anterior uterine wall. The
gestational sac can be seen as a mass extended beyond the expected uterine cavity,
and thin overlying myometrial tissue can be seen anteriorly (Fig. 9.3b). At the cra-
nial and caudal border of the sac, non-enhancing T2-weighted fibrous bands were
noted, consistent with the previous cesarean section’s scar tissue. Sometimes T1
hyperintense, hemorrhagic fluid and fetal pole can be found [11].
At present, CSP treatments are (1) direct dilatation and curettage (D&C): it may
cause uncontrollable massive hemorrhage or uterine perforation; (2) bilateral uter-
ine artery embolization (UAE) + D&C: UAE can effectively reduce the bleeding
during D&C. However, UAE has long-term premature ovarian failure
a b
Fig. 9.3 (a) An ultrasound image of CSP as defined by the presence of fluid within the CS scar
niche. (b) MRI scan showed a cystic mass extended beyond the expected uterine cavity anteriorly,
with thin overlying myometrial tissue seen
9.2 Cesarean Scar Pregnancy (CSP) 97
complications, and a high failure rate [12]; (3) local or systemic administration of
methotrexate (MTX): MTX plays a role in killing off the chorionic villi, but it has a
high failure rate and a high complication rate [13]; (4) laparoscopy: if the embryo
grows toward the serosa of the uterus, laparoscopic surgery is suitable to remove the
lesion [14]. However, it requires high surgical skills and may be associated with
heavy intraoperative bleeding. (5) Hysterectomy is the definite treatment, but it is
generally not suitable for many young patients with the desire for future pregnancy;
(6) HIFU ablation for CSP.
HIFU ablation is a new technique for managing CSP. Huang et al. [15] reported
the successful management of four patients with CSP followed by dilatation and
curettage. The study by Xiao et al. [16] investigated the role of HIFU in treating 16
patients with CSP. They defined successful treatment as the disappearance of CSP
mass, undetectable serum beta-human chorionic gonadotropin (beta-HCG), and no
serious complications such as severe bleeding, uterine rupture, or hysterectomy.
This small study showed that CSP mass disappeared at 2–14 weeks after 2–5 ses-
sions of HIFU treatment, and beta-hCG returned to normal in 2–10 weeks. Even
though the treatment was successful in all patients, the number of HIFU sessions
needed to achieve the above results was undesirable. Zhu et al. [17] studied 53
patients with CSP treated with HIFU and suction curettage. All patients had one
session of HIFU ablation under conscious sedation. The median blood loss was
20 mL, the average time for beta-hCG to return to normal was 27.5 (range 12–40)
days, and the average hospital stay was 7.8 (range 5–11) days.
The adverse side effects, hot skin, lower abdominal pain, and vomiting were
common, probably due to uterine contraction during or after HIFU. Patients were
well within 1 day without any therapy. No severe HIFU-related complications
occurred. Therefore, they had demonstrated that HIFU ablation, combined with suc-
tion curettage under hysteroscopic guidance, was effective and safe in treating
patients with CSP at gestational ages <8 weeks in their study group.
The HIFU treatment includes making a treatment plan on a sagittal ultrasound
view over the CSP mass. The mass will be divided into different slices with 3 mm
thickness. The ablation procedure will begin from the innermost slice using acoustic
power of 350–400 W. Under color Doppler ultrasound, the blood flow of the preg-
nancy tissue was monitored. Treatment will end when there is a gray-scale change
at the tissue or cessation of blood flow as demonstrated by microbubble imaging
post-HIFU ablation (Fig. 9.4). Antibiotics will be given for 3 days after HIFU treat-
ment to prevent any infection. Suction evacuation of the gestational product under
hysteroscopic guidance is done 3 days after HIFU treatment.
The HIFU ablation aims to heat the pregnancy tissue at a target point of 60–90 °C,
stop the viability of embryonic tissue, and lead to a rapid reduction of chorionic villi
activities. Subsequent D&C under hysteroscopic guidance will enable the complete
removal of gestational products to speed up the recovery time. The placental tissue’s
blood supply and surrounding myometrium are significantly reduced after HIFU
treatment, making the dead embryo’s attachment or placenta loosen and easy to be
detached and separable without heavy bleeding. Several clinical studies have also
confirmed that the average amount of blood loss in D&C after HIFU treatment was
a b
Fig. 9.4 (a) Microbubble image of CSP with increased vascularity (b) microbubble image of CSP
showing non-perfused area after HIFU ablation
much less than that of other surgical procedures [16–18]. Chen et al. analyzed the
reproductive outcome of CSP patients treated by HIFU ablation in previous
CSP. HIFU seemed to be superior to the UAE in reducing the risk of recurrent
CSP [19].
Although HIFU treatment is a noninvasive technique, it can damage surrounding
normal tissue surrounding the small CSP area. Furthermore, due to the small num-
ber of patients treated with this new surgical technology, there has not been a uni-
versal guideline on managing this condition. Further cohort studies are necessary to
confirm the effectiveness and complications of HIFU treatment for CSP and iden-
tify those most suitable for this treatment.
9.3 Abdominal Wall Endometriosis
Abdominal wall endometriosis (AWE) is a rare condition defined as the implanta-

tion of endometrial tissue outside the abdominal peritoneum, including lesions sec-
ondary to a surgical incision and those that arise spontaneously. It has an incidence
of 0.03–0.4% in women with previous cesarean delivery [20]. After a cesarean sec-
tion, a patient sometimes feels a mass in the abdominal cesarean wound or the lower
abdominal wall close to a wound. This mass could be abdominal wall endometrio-
sis, which presents with pain during the menstrual periods, and it grows slowly in
size. It is often found in the suprapubic area during excisional surgery, with some of
those invading the abdominal fascia and/or rectus muscle.
An ultrasound scan is the first-line AWE diagnostic method, which showed a
hypoechoic or heterogeneous echoic, cystic, or completely solid lesion. MRI scan
showed abdominal wall endometriosis as a hypointense lesion in the subcutaneous
layer in the rectus muscle or just in the extraperitoneal space (Fig. 9.5). The patho-
logical diagnosis, if necessary, can be confirmed by needle aspiration biopsy or
excisional pathology.
9.3 Abdominal Wall Endometriosis 99
Fig. 9.5 MRI image of

the abdominal wall
endometriosis beneath a
cesarean scar wound Abdominal wall
measuring 3.1 cm A marker on the wound endometriosis
(W) × 1.6 cm (H) × 2 cm
(T) in the extraperitoneal
space. It is a hypointense
lesion observed on
T2-weighted images
a b
Fig. 9.6 (a) Ultrasound image of abdominal wall endometriosis before HIFU ablation, (b) gray-
scale change at the AWE lesion during HIFU ablation. (white circles)
Medical management, including nonsteroidal anti-inflammatory drugs

(NSAIDs), oral contraceptives, gonadotropin-releasing hormone agonists, and aro-
matase inhibitors, is the first-line treatment. However, when symptoms become
more severe and affect life quality, surgical management is recommended for diag-
nosis and definitive treatment. Treatment modalities include surgical excision of the
lesion and/or hormonal therapies. Wide surgical excision with en bloc removal of
AWE is still the treatment of choice in the literature [21]. If the patient does not
want to remove it with open surgery, HIFU ablation is an alternative treatment. The
treatment involves no scar, no bleeding, minimal discomfort, and the skin’s surface
intact without a wound [22, 23].
Regarding HIFU ablation for AWE, because the AWE lesion is superficially
located, there may be a risk of skin burn for a lesion in close contact with the skin,
particularly if the focused area is too hot not accurately targeted. Then, HIFU treat-
ment should use a lower energy power at approximately 100–150 W to reduce the
risk, with each exposure time-limited to 1 s (Fig. 9.6).
If the skin overlying the treated area does not absorb too much ultrasound energy,
skin burn can be effectively prevented. The treated patient should lie in a prone posi-
tion on the treatment bed with the anterior abdominal wall in contact with degassed
water. The ablated area should involve a 1 cm margin around the lesion to eradicate
possible microscopic loci; this agrees with the surgical resection’s surgical princi-
ple. The treatment time usually will not take more than half an hour. The pain relief
after HIFU treatment is as high as 90–100%, with the gradual disappearance of the
lesion or become symptom-free.
Wang et al. [23] reported 21 consecutive patients with AWE treated by USgHIFU
ablation under sedation and analgesia. All AWE were successful ablation with one
session of HIFU ablation. The cyclic pain disappeared after a mean follow-up of
18.7 (range 3–31) months. Sixteen treated AWE masses became unnoticeable on
ultrasound scan follow-up. Luo et al. [22] evaluated USgHIFU treatment for AWE
in a retrospective study of 32 patients. They achieved ablation completeness ranging
from 87% to 100% (median 94%). After treatment, 32 patients reported mild pain
or discomfort in the treated region, with local edema in the skin lasting for 1–3 days
only. No severe complications occurred during and after the HIFU ablation.
Follow-up visits showed that the AWE lesions shrank in size, and the pain scores
were significantly lower at 6 months after HIFU ablation.
HIFU ablation is a safe and effective treatment for abdominal wall endometriosis
compared to traditional surgical treatment [24]. In addition to its advantages of no
new scar on the skin, no blood loss, and wound complications, it also avoids possi-
ble reimplantation of the endometriosis in the open wound, causing a recurrence.
HIFU ablation is less invasive and repeatable. Therefore, it may become an alterna-
tive treatment option for women with AWE. However, there are limitations in its use
in AWE because of the small number of patients treated and the lack of clinical
treatment standards. Comparative cohort studies with surgical resection or other
conservative treatments are warranted to observe these treatments’ complications
and long-term efficacy.
References
1. Cahill AG, et al. Placenta accreta spectrum. Am J Obstet Gynecol. 2018;219(6):B2–B16.
2. Lee J-S, et al. High-intensity focused ultrasound combined with hysteroscopic resection to
treat retained placenta accreta. Obstet Gynecol Sci. 2016;59(5):421–5.
3. Rein DT, et al. Hysteroscopic management of residual trophoblastic tissue is superior to
ultrasound-guided curettage. J Minim Invasive Gynecol. 2011;18(6):774–8.
4. Bisschop CNS, et al. Invasive placentation and uterus preserving treatment modalities: a sys-
tematic review. Arch Gynecol Obstet. 2011;284(2):491–502.
5. Bai Y, et al. High-intensity focused ultrasound treatment of placenta accreta after vaginal
delivery: a preliminary study. Ultrasound Obstet Gynecol. 2016;47(4):492–8.
6. Ye M, et al. High-intensity focused ultrasound combined with hysteroscopic resection for the
treatment of placenta accreta. BJOG Int J Obstet Gynaecol. 2017;124:71–7.
7. Shaw C, et al. Pathophysiological mechanisms of high-intensity focused ultrasound-
mediated vascular occlusion and relevance to non-invasive fetal surgery. J R Soc Interface.
2014;11(95):20140029.
References 101
8. Mohammed ABF, et al. Ultrasonographic evaluation of lower uterine segment thickness in
pregnant women with previous cesarean section. Middle East Fertil Soc J. 2010;15(3):188–93.
9. Armstrong V, et al. Detection of cesarean scars by transvaginal ultrasound. Obstet Gynecol.
2003;101(1):61–5.
10. Wong W, Fung W. Magnetic resonance imaging in the evaluation of cesarean scar defect.
Gynecol Minim Invasive Ther. 2018;7(3):104–7.
11. Osborn DA, Williams TR, Craig BM. Cesarean scar pregnancy: sonographic and magnetic reso-
nance imaging findings, complications, and treatment. J Ultrasound Med. 2012;31(9):1449–56.
12. Zhu X, et al. A comparison of high-intensity focused ultrasound and uterine artery embolisa-
tion for the management of caesarean scar pregnancy. Int J Hyperth. 2016;32(2):144–50.
13. Li N, et al. Transvaginal ultrasound-guided embryo aspiration plus local administration of low-
dose methotrexate for caesarean scar pregnancy. Ultrasound Med Biol. 2012;38(2):209–13.
14. Maheux-Lacroix S, et al. Cesarean scar pregnancies: a systematic review of treatment options.
J Minim Invasive Gynecol. 2017;24(6):915–25.
15. Huang L, Du Y, Zhao C. High-intensity focused ultrasound combined with dilatation and
curettage for cesarean scar pregnancy. Ultrasound Obstet Gynecol. 2014;43(1):98–101.
16. Xiao J, et al. Cesarean scar pregnancy: non-invasive and effective treatment with high-intensity
focused ultrasound. Am J Obstet Gynecol. 2014;211(4):356.e1–7.
17. Zhu X, et al. High-intensity focused ultrasound combined with suction curettage for the treat-
ment of cesarean scar pregnancy. Medicine. 2015;94(18):e854.
18. Hong Y, et al. Outcome of high-intensity focused ultrasound and uterine artery embolization
in the treatment and management of cesarean scar pregnancy: a retrospective study. Medicine.
2017;96(30):e7687.
19. Chen L, et al. Analysis of the reproductive outcome of patients with cesarean scar pregnancy
treated by high-intensity focused ultrasound and uterine artery embolization: a retrospective
cohort study. J Minim Invasive Gynecol. 2019;26(5):883–90.
20. Saliba C, et al. Abdominal wall endometriosis: a case report. Cureus. 2019;11(2):e4061.
21. Horton JD, et al. Abdominal wall endometriosis: a surgeon’s perspective and review of 445
cases. Am J Surg. 2008;196(2):207–12.
22. Luo S, et al. Ultrasound-guided high-intensity focused ultrasound treatment for abdominal
wall endometriosis: a retrospective study. BJOG Int J Obstet Gynaecol. 2017;124:59–63.
23. Wang Y, et al. Ultrasound-guided high-intensity focused ultrasound treatment for abdominal
wall endometriosis: preliminary results. Eur J Radiol. 2011;79(1):56–9.
24. Zhu X, et al. A comparison between high-intensity focused ultrasound and surgical treat-
ment for the management of abdominal wall endometriosis. BJOG Int J Obstet Gynaecol.
2017;124:53–8.

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Focused

Introduction and Application

ISBN 978-981-16-0938-1 ISBN 978-981-16-0939-8 (eBook)

The range of applications of the Haifu® Focused Ultrasound Tumor Therapeutic

promoting good practice in management. We honored him with the Chinese

Sydney, NSW, Australia Felix Wong

1 An Introduction������������������������������������������������������������������������������������������ 1

3.4 Transvaginal Ultrasound Appearances of Adenomyosis�������������������� 30

6 Complications of HIFU Ablation�������������������������������������������������������������� 71

Felix Wong is at present the Adjunct Professor at the

Lian Zhang graduated from Chongqing Medical

Science Foundation of China. He was the recipient of

CNS Central nervous system

When an object vibrates between 20 and 20,000 Hz, it produces an audible sound.

20 Hz 20,000 Hz (20 kHz)

0 10 100 1000 10000 100000 1000000 10000000

1.1 The HAIFU Knife®

1.2 The “HAIFU Knife®”

Several different models of the HAIFU knife® are manufactured by Chongqing

United Kingdom, Germany, Italy, Bulgaria, Argentina, Japan, South Korea,

1.2.2 Ultrasound-Guided (USg) HIFU Systems

1.3 MRgHIFU Systems

Fig. 1.7 The Sonalleve MRgHIFU system from Philips Healthcare

system (Koninklijke Philips Electronics, Eindhoven, the Netherlands) based on the

Fig. 1.8 The InSightec ExAblate® 2000 MRI-guided FUS system

While USgHIFU was the original image-guided system, MRg-FUS(MR-HIFU)

Features MRgHIFU USgHIFU

Single-chip HIFU system has an ultrasonic transducer mediated by a single

Single chip ultrasound transducer Multiphase array ultrasound transducer

Synchronous in phase 180° phase difference

The transducers’ position, i.e., whether it is top-mounted and bottom-mounted,

1. A top-mounted ultrasound transducer requires a sealed water bag to put between

Water layer, enclosed

Ultrasonic media layer

1.4  ocused Ultrasound Hyperthermia Therapy and High

Sizes of the HIFU focal point

7 . There is no risk of radiation; and

Sedation reduces irritability or agitation by administering sedative drugs; generally,

2.1 The Choice of Drugs for Sedation and Analgesia

Table 2.1 Ramsay sedation score

2.2 First-Line Drugs

(a) Midazolam (trade name: Dormicum)

powerful respiratory depressant with little effect on the cardiovascular system.

2.3 Second-Line Drugs

2.4 Other Auxiliary Drugs Should Be Available

2.4.1 Sedation and Analgesia Protocol for HIFU Ablation

Adjuvant medications, like anticholinergic (atropine) and antiemetic drugs (ondan-

2.5 Midazolam and Fentanyl Sedation Protocol

Table 2.2 ABCD steps of Midazolam and Fentanyl

2.6  ther Sedation and Analgesic Regimes:

2.7 Monitoring During HIFU Surgery Under Sedation

(a) The degree of consciousness

be relied on to assess the adequacy of ventilation (PaCO2), especially if the

2.8 Treatment of Complications

2.8.1 Respiratory Depression

1 . The number of breaths per minute is less than 12 times;

It is particularly noteworthy that after using fentanyl, a patient may forget to

2.8.2 Muscle Stiffness

2.9 Factors Affecting the Effects of Sedation and Analgesia

At present, the commonly used diagnostic examination of fibroids and adenomyosis

3.1 Imaging for Uterine Fibroids

3.1.1 Ultrasound Imaging

• Grade 0: no blood flow signal is seen within the lesion;

The characteristic vascular distribution of a uterine fibroid is either scanty or in

Sydney, NSW, Australia Felix Wong

1 An Introduction�� 1

3.4 Transvaginal Ultrasound Appearances of Adenomyosis�� 30

6 Complications of HIFU Ablation�� 71

1.1 The HAIFU Knife®

1.2 The “HAIFU Knife®”

1.2.2 Ultrasound-Guided (USg) HIFU Systems

1.3 MRgHIFU Systems

1.4 ocused Ultrasound Hyperthermia Therapy and High

2.1 The Choice of Drugs for Sedation and Analgesia

2.2 First-Line Drugs

2.3 Second-Line Drugs

2.4 Other Auxiliary Drugs Should Be Available

2.4.1 Sedation and Analgesia Protocol for HIFU Ablation

2.5 Midazolam and Fentanyl Sedation Protocol

2.6 ther Sedation and Analgesic Regimes:

2.7 Monitoring During HIFU Surgery Under Sedation

2.8 Treatment of Complications

2.8.1 Respiratory Depression

2.8.2 Muscle Stiffness

2.9 Factors Affecting the Effects of Sedation and Analgesia

3.1 Imaging for Uterine Fibroids

3.1.1 Ultrasound Imaging

3.2 Locations of Fibroids

3.2.1 MRI Imaging

3.3 Uterine Adenomyosis

3.4 Transvaginal Ultrasound Appearances of Adenomyosis

3.5 MRI Appearances of Adenomyosis

3.6 eiomyosarcoma and Endometrial Stromal Sarcoma—

4.1 Symptoms of Uterine Fibroids

4.2 Indications for Treatment

4.3 Investigative Methods

4.5 HIFU Treatment

4.6 The USgHIFU Ablation Procedure

4.7 The Indications for HIFU Treatment

4.8 The Contraindications for HIFU Ablation

4.9 Preparation Before HIFU Ablation

4.9.1 Simulation Test

4.10 Other Preparations

4.11 HIFU Ablation

4.12 Factors Influencing HIFU Effectiveness

4.15 Post-HIFU Ablation Care

4.16 Postoperative Follow-up

4.17 Results of HIFU Ablation on Follow-up

4.17.1 The Non-perfused Volume Ratio

4.17.2 The Volume Reduction After HIFU Ablation

4.18 Other Issues of Fibroid Ablation

4.19 Recurrence of Fibroids

4.20 Pregnancy After HIFU Ablation

5.1 The Symptoms of Adenomyosis

5.2 Treatment of Adenomyosis

5.2.1 Drug Treatment

5.2.1.1 Mirena (LNG-IUS)

5.2.1.2 Gonadotropin-Releasing Hormone Agonist (GnRH-a)

5.2.1.3 Oral Contraceptives

5.2.2 Surgical Treatment