Photoacoustic in hematological diseases

Review Paper submitted for the award of degree of

Bachelor of Technology
(Biotechnology)

Submitted by
SOUSTAM DE(GF/2020/015)
SHIVANI (GF/2020/6871)
ANHAD(GF/2020/113)
Shikha khajuria (GF/2020/6373)

SCHOOL OF BIOENGINEERING AND FOOD TECHNOLOGY

SHOOLINI UNIVERSITY OF BIOTECHNOLOGY

AND MANAGEMENT SCIENCES
SOLAN, H.P., INDIA
DECEMBER, 2022
 Declaration by the candidate

I hereby declare that the review paper entitled “Photoacoustic in hematological

disease” submitted for the award of degree of Bachelor of Technology in
Biotechnology to Shoolini University of Biotechnology and Management
Sciences, Solan (H.P.) is original review work carried out by me under the
guidance and supervision of Dr.Deblina Biswas. No part of this thesis has been
submitted for any other degree or diploma to this or any other university.

Place: Solan
Name: Soustam De, Shivani, Anhad, shikha Khajuria.
 CERTIFICATE-I

This is to certify that the review paper entitled “Photoacoustic in hematological

disease” submitted for the award of the degree of Bachelor of Technology in
Biotechnology to Shoolini University of Biotechnology and Management
Sciences, Solan (H.P.) is original research work carried out by Soustam De
(GF/2020/015), Shivani (GF/2020/6871), Anhad (GF/2020/113), Shikha
khaguria (GF/2020/6373) under my guidance and supervision. No part of this
thesis has been submitted for any other degree or diploma to this or any other
university.
The assistance and help received during the investigation has been duly
acknowledged.

Research Guide
Date: 07-12-2022
Place: Solan
 PHOTOACOUSTIC IN HEMATOLOGICAL DISEASE.
Faculty of Applied Sciences and Biotechnology, Shoolini University
Solan, Himachal Pradesh, 173229, India

Faculty of Pharmaceutical Sciences, Shoolini University, Solan, Himachal

Pradesh, 173229, India

ABSTRACT

Numerous haematological conditions cause bone marrow (BM) failure when

they emerge in the BM (BMF). Chronic lymphoblastic leukaemia, which causes
an increase of hypoxic areas in the BM, can result in BMF. Due to this hypoxic
presentation, it may be possible to more accurately characterise BMF by
measuring the oxygenation of the BM cavity in vivo. It has been demonstrated
that pimonidazole-evaluated hypoxia correlates with intravascular oxygen
saturation (SO2), which can be locally assessed by photoacoustic (PA) imaging.
In order to monitor SO2 levels in the femoral BM cavity as the disease
progresses in a mouse model of ALL, this study proposes an improved PA
imaging approach. The results demonstrate the potential of PA imaging for non
invasive, label-free monitoring of BMF illnesses by revealing a statistically
significant difference with temporal variations in SO2 (from baseline) between
control and sick groups.
INTRODUCTION

Numerous hematological conditions cause the bone marrow (BM) to fail, which
is indicated by abnormalities in the megakaryocytic, monocyte, and erythroid
cell lineages. Acute lymphoblastic leukaemia (ALL), which causes ALL cells to
engraft in BM and trigger the production of hypoxia-inducible factor 1-alpha
(HIF-1), can occasionally be the cause of BMF. As a result, hypoxic areas grow
and become more permeable to leukemic cells, endangering healthy
hematopoietic cells. Consequently, proper BMF characterization through
evaluation of in vivo oxygenation in the BM stands to help the diagnosis and
treatment of numerous haematological disorders. BOLD-MRI, TOLD-MRI,
18F-FAZA-PET imaging, and 19F-MRI are some of the clinical techniques
currently used to examine hypoxia, or the lack of oxygen available to cells.
Hypoxia immunostaining and (18F-FAZA)-PET imaging have been correlated;
however, the latter involves the administration of a radiotracer and has limited
spatiotemporal resolution by design. Due to susceptibility artefacts, BOLD-
MRI, a label-free method, has problems with quantification, especially at tissue-
bone interfaces. Despite being unaffected by these aberrations, TOLD-poor
MRI's sensitivity hasn't been able to significantly alter the signal in BM .
Dynamic pO2 maps are produced by 19F-MRI using a perfluorocarbon
exogenous reporter and additional imaging hardware that is not included with
an MRI scanner . BOLD-MRI, TOLD-MRI, 18F-FAZA-PET imaging, and 19F-
MRI are some of the clinical techniques currently used to examine hypoxia, or
the lack of oxygen available to cells. Hypoxia immunostaining and (18F-
FAZA)-PET imaging have been correlated; however, the latter involves the
administration of a radiotracer and has limited spatiotemporal resolution by
design. Due to susceptibility artefacts, BOLD-MRI, a label-free method, has
problems with quantification, especially at tissue-bone interfaces. Despite being
unaffected by these aberrations, TOLD-poor MRI's sensitivity hasn't been able
to significantly alter the signal in BM. Dynamic pO2 maps are produced by
19F-MRI using a perfluorocarbon exogenous reporter and additional imaging
hardware that is not included with an MRI scanner. The non-invasive, label-
free, in vivo imaging method known as photoacoustic (PA) imaging has a high
spatiotemporal resolution and can offer optical contrast at far deeper levels than
solely optical methods . Through the PA-based evaluation of oxy- and
deoxyhemoglobin (HbO2 and HHb, respectively), intravascular oxygen
saturation (SO2) can be calculated. Although SO2 is not a direct indicator of
intracellular hypoxia, it has been demonstrated to be linked with pO2 levels
close to capillaries and pimonidazole-assessed hypoxia . As a result, we
speculate that SO2 may act as a non-invasive, label-free biomarker for the
development of leukaemia and its response to treatment. This study shows how
to explore the femoral BM's oxygenation state using a longitudinal PA imaging
technique that has been optimised. This study shows how to explore the femoral
BM's oxygenation state using a longitudinal PA imaging technique that has
been optimised. According to findings from a preclinical pilot investigation, the
course of ALL illness is correlated with temporal changes in intrafemoral SO2.

ABOUT PA.
Photoacoustic imaging which is also called Optoacoustic spectroscopy. The first
person to observe the photoacoustic effect was J. Tyndall in 1881.
Photoacoustic imaging is based on the transmission of radiations on the matters
which can be solid, liquid or gas. It is majorly used in biomedical imaging
techniques. For instance, Melanin the skin's optical absorber, may be used by
PAI to image melanoma, pigmented lesions and hair follicles. It is done by
transmission of radiations on the tissues and tissues will absorb the radiations
upto some number of wavelengths. And after the absorption of particular
number of wavelengths, then some acoustic waves will be produced which is
detected by ultrasonic transducers. The acoustic signal propagates significantly
further and without considerable attenuation in biological tissue. Because
optical scattering prevents pure optical imaging method from maintaining high
resolution imaging in deep biological tissues, PAI is a promising technique for a
variety of clinical imaging applications because it can produce high resolution
optical contrast images in biological tissues up to centimetre depths. In PAI,
nano-second pulsed laser is commonly used to illustrate the biological sample.
Acoustic detector or amplifier or recorser is used as one of the best detector. A
piezoelectric transducer is used as a detector for liquids.

TYPES OF PHOTOACOUSTIC.
Photoacoustic compound tomography and photoacoustic microscopy are two
different types of photoacoustic imaging technologies that have been developed.
Photoacoustic computed tomography: The functional optical contrast of
diffuse optical tomography and the large spatial resolution of ultrasonography
are combined in photoacoustic computed tomography, a non-invasive hybrid
imaging technique. When biological tissues are exposed to a short-pulsed laser
beam, some of the light energy is partially absorbed by the tissue and
transformed into heat. After then, a pressure increase brought on by transitory
thermoelastic expansion travels through the biological tissue as a wideband
ultrasonic wave. In order to rebuild the optical absorption distribution in the
tissue, ultrasonic transducers are then put all around the sample surface to detect
the photoacoustic waves. Because biological tissue is sensitive to optical
absorption, photoacoustic computed tomography may image structural,
functional, and molecular details by using a rich contrast mechanism related to a
variety of intrinsic and extrinsic chromophores. Beyond the 1-mm optical
diffusion regime, which restricts the penetration capabilities of ballistic optical
imaging methods, the conversion from light to ultrasound also gives this
imaging technology rich optical contrast and ultrasonically defined spatial
resolution.

Photoacoustic computed tomography

Photoacoustic microscopy: An imaging technique based on the
photoacoustic effect, photoacoustic microscopy is a subset of
photoacoustic tomography. The local temperature increase brought on
by tissue's light absorption is utilised by photoacoustic microscopy.
Tissues expand due to thermoelasticity when exposed to a nanosecond
pulsed laser beam, which releases a wide-band acoustic wave that can
be picked up by an ultrasound transducer. Compared to traditional
microscopy techniques, photoacoustic microscopy may provide high-
resolution pictures at greater depths because ultrasonic scattering in
tissue is weaker than optical scattering. The scalability of
photoacoustic microscopy is another reason why it is particularly
helpful in the realm of biological imaging. It is possible to maximise
the lateral resolution for the desired imaging depth by altering the
optical and acoustic foci.
 Photoacoustic microscopy

Application of photoacoustic in hematological disease

BLOOD CLOT: Exploration shows that photoacoustic fashion is veritably useful
for identification and discovery of the RBCs clustering and conformation of
clots in highways and modes, which occurs in conditions like infections,
inflammation and cardiovascular complaint. The end of this study is to know
about the RBCs aggregation by the assaying of the Photoacoustic signals with
bitsy images by linking with artificial intelligence technology. Photoacoustic
fashion uses the palpitated ray to get the power of photoacoustic signals for
feting the added up and non- added up RBCs. It also helps in estimating the
density of blood ahead and after ray irradiation. It gives us idea of the RBCs
aggregation situations and bitsy imaging helps us to understand the shape, size
and number of RBCs clusters. The Photoacoustic system explains a new system
to descry the RBCs aggregation as well as (HB) position. The changing power
of photoacoustic signal is associated with the energy absorbance by RBCs
which release as power of photoacoustic signals. This photoacoustic bitsy
imaging is a mongrel modality in biomedical opinion of RBCs morphology,
clustering viscosity and hemoglobin concentration.
APPLICATIONS OF PHOTOACOUSTIC IN
HEMATOLOGICAL DISEASES

The protein haemoglobin, which is responsible for blood and tissue 02-CO2
exchanges tissues, a tetraporphyrin cycle is attached to its amino acid skeleton,
giving it its scarlet colour shade . The amount of hemoprotein in various organs
was determined using photoacoustic spectroscopy . They also share a similar
structure, The selective photosensitization of tumoral tissues is presently
induced by the use of several hematoporphyrin derivatives in cancer research
(Pottier et al., 1988). They were discovered in target tissues and in To provide a
thorough therapy and prevent any negative effects because of their complex
nature, the body conceivable toxicity
Hemoglobin typically has three major bands (415, 540, and 580 nm) in its PA
spectrum, while oxyhemoglobin typically has two bands at 470 and 555 nm .
The following rule was employed by these authors to follow the sedimentation
process of a blood sample: Any change in the number of chromophores in this
area should result in a change in the PA signal since the thermal diffusion depth
in a particular material remains constant for a given modulation frequency.
Erythrocytes (red blood cells) move to the bottom of a liquid like plasma as a
result of sedimentation. As a result, there are less pigments in the sample's
higher layers.
Due to this, the PA signal's amplitude and phase angle both drop, enabling the
determination of the erythrocyles sedimentation rate, which was shown to be in
good agreement with previous methods. Using photoacoustic spectroscopy, it
was possible to detect the presence of Photofrin II and manganese III
hematoporphyrin, two photosensitizers used in photodynamic therapy, in the
liver and kidney, respectively. A study that would have been challenging to
conduct using any other absorbance technique involved monitoring the
photobleaching of another photosensitizer, hematoporphyrin IX, in a highly
scattering medium.
The benefits of PAS in this area of research include its capacity to accurately
detect some substances present in highly diffusive medium, like blood, or in
non-uniform and opaque material, like the surface of organs, as well as the
avoidance of any difficult procedures.chemical extraction and purification
techniques, minimal modifications, and only tiny amount of chemical and isn't
damaging, allowing additional research by other techniques.
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