General principles of quantitative

Nuclear Medicine
Stephan G. Nekolla
Nuklearmedizinische Klinik und Poliklinik
Technische Universität München

ESMIT Online Courses - Advanced Features of Quantification - 01.07.2021

 Nuclear Medicine in a Nutshell

• Background and history of the method

• Concepts of single photon and positron emission
• Principal setup of detection and spatial encoding
• Correction schemes

Slide 2
Motivation
Motivation 2.0
Motivation 3.0
Diagnostics

Physics Physiology

Therapy
 Nuclear Medicine in a Nutshell
Pubmed query: „nuclear medicine“

• Medical imaging using gamma and

positron emitting isotopes were used
already in the 1950s
• In the 1960-1970s dedicated imaging
hardware became available to for use in
neurological, cardiac and oncological
applications
• Since 2000 with the integration of CT
and 2010 with MR scanners into hybrid
systems, nuclear medicine represents a
powerful , imaging and therapeutic
modality with numerous applications
and wide-spread clinical use.

Slide 6
Nuclear Medicine and the others
in a Nutshell

Slide 7
Nuclear Medicine and the others
in a Nutshell

MRI

CT

NM

Slide 8
 Nuclear Medicine in a Nutshell

128I !

Hertz, S., Roberts, A., & Evans, R. D. (1938). Radioactive Iodine as an Indicator in the Study of Thyroid Physiology. Experimental Biology and Medicine, 38(4), 510–513
Slide 9
Nuclear Medicine in a Nutshell

Treatment of hyperthyroidism with radioactive iodine; I130, 12-hour half-life and I131, 8-
day half-life. CHAPMAN EM, SKANSE BN, EVANS RD. Radiology. 1948 Oct;51(4):558-63

Slide 10
Nuclear Medicine in a Nutshell

Treatment of hyperthyroidism with radioactive iodine; I130, 12-hour half-life and I131, 8-
day half-life. CHAPMAN EM, SKANSE BN, EVANS RD. Radiology. 1948 Oct;51(4):558-63

Slide 11
 Nuclear Medicine in a Nutshell
Benedict Cassen: the father
of body organ imaging. Blahd
WH. Cancer Biother
Radiopharm. 2000
Oct;15(5):423-9

The scintillation counter in clinical studies of human thyroid physiology using I131.
ALLEN HC Jr, LIBBY RL, CASSEN B.
J Clin Endocrinol Metab. 1951 May;11(5):492-511

Slide 12
Nuclear Medicine in a Nutshell

Benedict Cassen: the father of body organ imaging. Blahd WH.

Cancer Biother Radiopharm. 2000 Oct;15(5):423-9

Slide 13
Nuclear Medicine in a Nutshell

Slide 14
A high-contrast photographic recorder for scintillation counter scanning.
KUHL DE, CHAMBERLAIN RH, HALE J, GORSON RO. Radiology. 1956 May;66(5):730-9
 The Anger Camera
camera head photomultiplier

“Light
guide”

NaI(Tl) crystal Target organ

Bed
Patient

Slide 15
 The Anger Camera
camera head photomultiplier

Note bene:
Hal Anger: American electrical engineer and biophysicist
(1920-2005): Among many other systems in 1957, he
developed the Anger camera named after him
“Light
Pierre Auger: French physicist (1899-1993): Discovered
guide”
the non-radiative transition in the electron shell of an excited
atomcrystal
NaI(Tl) in 1926 the "Auger-Meitner effect" - which Liseorgan
Target Meitner
had already described in 1922 by the way…

Bed
Patient

Slide 16
 The Anger Camera
camera head photomultiplier

“Light
guide”
✗ ✗ ✔ ✔ ✗
NaI(Tl) crystal
collimator
Target organ

Bed Patient

Slide 17
 The Anger principle
X1
X2
X3
X4 ෍ X
X5

Z1 Z2 Z3 Z4 Z5 σ𝑛 𝑍𝑛∙𝑋𝑛
𝑋= σ𝑛 𝑍𝑛

𝐸 = ෍ 𝑍𝑛
𝑛

Slide 18

http://www.lbl.gov/Science-Articles/Archive/nuclear-med-history.html
 Nuclear Medicine in a Nutshell

Image courtesy of L. Shao, Philips Medical Systems

Slide 19
Going from 2D to 3D

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 Nuclear Medicine in a Nutshell

THEORY OF THE PERFORMANCE CHARACTERISTICS OF RADIOISOTOPE

DISTRIBUTION IMAGING SYSTEMS. CASSEN B. J Nucl Med. 1964 Feb;5:95-10 Slide 21
 PET – The Isotopes
In contrast to earlier methods utilizing isotopes emitting
“only” a single photon, it uses positron emitting isotopes
which in turn result in the simultaneous emission of two
high energy photons with 511keV

Technically:
18F -> 18O + e+ + v
18F 18O e
9 8

+
+
e+ (or β+ ) Antimatter has been used for a variety of purposes.
Depending on the type of antimatter in use it can interact
with, modify, or destroy normal matter. As a result, it has
been used for everything from a component of weapons of
mass destruction, to a fuel source, to scanning technology,
to medical uses. (http://memory-
alpha.wikia.com/wiki/Antimatter, Slide 22
https://commons.wikimedia.org/wiki/File:Survol_de_Saint_
 PET – The Basic Principle
PET isotopes emit a positron which result in the simultaneous
emission of two high energy photons with 511keV.

18F
9
e+ meets e- : E=mc2
+-
+
+

e+ +
+

Up to several millimeters depending

on positron energy and tissue type

Slide 23
 PET – Early Applications
Regional myocardial perfusion assessed with N-13 labeled
ammonia and positron emission computerized axial
tomography. Schelbert HR, Phelps ME, Hoffman EJ, Huang
SC, Selin CE, Kuhl DE. Am J Cardiol. 1979 Feb;43(2):209-16

FIGURE 3. Dog 25. Sequence of five typical cross-sectional images recordedat the
same level through the left ventricle at 1 hour intervals. Flow in the left circumflex
coronary artery was either decreased by transient coronary occlusion (first image
on the left) or increased by intracoronary papaverine. N-13 ammonia was injected The [18F]fluorodeoxyglucose method for the
at the time of transient ischemia or of peak or intermediate hyperemia. In measurement of local cerebral glucose
contrast to the results in the control study, no N-13 ammonia was visible at the utilization in man. Reivich M, Kuhl D, Wolf A,
time of ischemia in the portion of the myocardium supplied by the left circumflex Greenberg J, Phelps M, Ido T, Casella V, Fowler
coronary artery (posterior half of cross section). Conversely, activity in the same J, Hoffman E, Alavi A, Som P, Sokoloff L. Circ
portion of the myocardium was greatly increased when N-13 ammonia was Res. 1979 Jan;44(1):127-37.
injected during various degrees of hyperemia of the left circumflex coronary artery
(third to fifth images).

Slide 24
 PET – The Detection
The 511 keV photon hits the crystal and interacts with its material,
giving rise to many more photons (i.e. light), which are amplified in
the photomultiplier (PM) and finally yield an electrical signal

Photomultiplier

Electric
signal
Crystals

Slide 25
 PET – The Coincidence Detection
The detection of those photons require a sophisticated approach
utilizing a so-called electronic collimation with a temporal resolution
of a few nanoseconds (or even less for time-of-flight).

Coincidence
detection circuitry

Slide 26
 PET – The Coincidence Detection
The detection of those photons require a sophisticated approach
utilizing a so-called electronic collimation with a temporal resolution
of a few nanoseconds (or even less for time-of-flight).

Coincidence
detection circuitry

Slide 27
 PET – Some details
If all goes OK, the system adds this event as so-called LOR (line of
response) and continues collecting data.
However, there are a few exceptions:

True
Crystal
✔ ✔

Scattered
✗ ✗

Random
✗ ✗

Slide 28
 Attenuation + Scatter Correction
Attenuation correction makes PET and also SPECT quantitative: tracer concentrations can be
measured in Becquerel per millilitre (Bq/ml) from which parameters such as SUV (standard
uptake value) is derived by normalizing tracer uptake with the injected dose and the patient
weight. Depending on the setting, absolute parameters such as myocardial or cerebral blood
flow can be derived as well. PET NAC PET AC

NAC PET

AC PET
Bq/ml ->
Cts/sec SUV, MBF, CBF
Slide 29
 Normalisation / Calibration
More on this later: but basically, we put into our system
an object with known activity (e.g. homogeneous
phantom) and use this to generate the necessary
correction to produce – exactly – a homogeneously
image/volume with the exact activity
Biological Targets
 Isotopes and Radiopharmaceuticals
Nuclear imaging utilizes a wide range of isotopes and
radiopharmaceuticals and some examples are shown below.
Isotope Half-life Energy Typical Example Local
radiopharma- applications Production
ceuticals
18F 110 min 633 keV Fluorodeoxyglucose Glucose-
(FDG) metabolism
11C Cyclotron
20.3 min 960 keV Choline Aminoacids
13N 10 min 1200keV Ammonia Perfusion
68Ga 68 min 1900keV DOTA-XXX, PSMA Receptors
Generator
82Rb 76 sec 3150 keV Rubidiumchloride Perfusion
99mTc 6h 140keV Bisphosphonates Tumor
MIBI, MAA, MAG3, Perfusion, Generator
MIBG Innervation
I Iodine Thyroid
Delivery
Ioflupan (DatSCAN) Neurodegen.
Lu, Ac Tumor Delivery Slide 32
 Hybrid Imaging
With the integration of SPECT and CT as well as PET and CT scanners
into single devices around 2000, PET/CT and SPECT/CT became a
major player in the field of molecular imaging with several 1000s
scanners installed world wide.
SPECT CT MR PET
CT PET

The approach yields two distinct advantages:

• Rapid assessment of data for attenuation and scatter correction
• Integration of functional and morphological information for
excellent diagnosis and therapy monitoring

Slide 33
SUV: basic version

add 200 MBq FDG

stir well
SUV=1

Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with
body weight and a method for correction. Zasadny KR, Wahl RL. Radiology. 1993 Dec;189(3):847-50.
 The „Standard“: SUV

Is the standard uptake value (SUV) appropriate for quantification in clinical PET imaging? - Variability induced by different SUV
measurements and varying reconstruction methods. Brendle C, Kupferschläger J, Nikolaou K, la Fougère C, Gatidis S, Pfannenberg C.
Eur J Radiol. 2015 Jan;84(1):158-62. doi: 10.1016/j.ejrad.2014.10.018. Epub 2014 Nov 1.
Different flavours of SUV

add 200 MBq FDG

stir well

SUV<1

Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with
body weight and a method for correction. Zasadny KR, Wahl RL. Radiology. 1993 Dec;189(3):847-50.
 Summary
• Nuclear medicine imaging is since more than
half a century a corner stone of molecular
medicine
• Quantification was from day one on an integral
element
• Today, a wide variety of imaging methods are
available
• The future is bright especially in the light of
personalized medicine for both diagnostics and
therapy
• However, a solid understanding of the methods
is required to deliver reproducible content