1. Nuclear Medicine Imaging

2. Overview
Nuclear medicine: Therapeutic and diagnostic use of radioactive substances
Radioactivity:
Naturally occurring radioisotopes (radioactive isotopes) discovered 1896 by Becquerel
First artificial radioisotopes produced by the Curies 1934 (32P)  “Radioactivity,” “Radioactive”
Kohman: “Radionuclide” = nucleus of measurable half-life
Hevesy uses 32P for metabolic studies with Geiger-Muller counter
First radionuclide imaging by Cassen of 131I uptake in thyroid gland (scintillator+PMT, scanner, collimator,1/4” spatial resolution)
Anger camera (planar imaging)
Kuhl & Edwards construct Mark IV scanner (~10 years before x-ray CT)
1977 – Kayes & Jaszczak develop SPECT independently
1950 – first PET attempts
1976 – First commercial PET (Phelps & Hoffman at CTI)
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3. Radionuclide Imaging Characteristics:
The distribution of a radioactive agent inside the body is imaged
Projection and CT imaging methods
Imaging of functional or metabolic contrasts (not anatomic)
Brain perfusion, function
Myocardial perfusion
Tumor detection (metastases)
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4. Nuclear Stability
The neutrons and protons which form the nucleus of an atom are held together by a combination of forces. Protons have alike charges and repel each other by the electrostatic force of repulsion. However, once the protons are put very close to each other an attractive force comes into play. This force is called the strong nuclear force, and is 100 times greater than the electrostatic force of repulsion. Neutrons are affected by a different weak nuclear force. The weak nuclear force causes neutrons to change spontaneously into protons plus almost massless nontinteracting particles called neutrinos. The gravitational force plays essentially no role in nuclear stability.
The laws of nuclear forces are very complex; the whole problem of analyzing the fundamental machinery behind nuclear forces is unsolved (Feynmann).
As a general rule, there are about equal number of neutrons and protons in a nucleus. But, in heavier atoms, a greater proportion of neutrons have to be added to maintain the stability of the atom.
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5. Nuclear stability
The nucleus of many atoms is not stable. Nuclei with infavourable neutron/proton ratio will disintegrate or decay into stable nuclei by spontaneous emission of nuclear particles.
Example:
neutron rich nucleus :
proton rich nucleus :
electron
Antineutrino (massless, neutral particle)
Positron neutrino
Neutrino means “little neutral particle” in Italian.
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6. Nuclear Stability Neutron rich unstable element Proton rich
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7. Nuclear Stability
Nuclei tend to be most stable if they contain even numbers of protons and neutrons, and least stable if they contain an odd number of both.
Number of protons
Number of neutrons
Number of
stable nuclei
Even
165
Odd 57 53 6
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8. Definitions
Isotope: Nuclides of same atomic number Z but different N (and A)  same element
Nuclide: Species of atom characterized by the constitution of its nucleus (in particular N, Z)
Radionuclide: Nuclide of measurable half time
Radioactive decay : the process by which an unstable nucleus is transformed into a more stable daughter nucleus by emitting nuclear particles.
Isomeric decay: If a nucleus gains stability by transition of a neutron between neutron energy levels, or a proton between proton energy levels, the process is termed an isomeric transition. In an isomeric transition, the nucleus releases energy without a change in its number of protons (Z) or neutrons (N). The initial and final energy states of the nucleus are said to be isomers.
Electron capture: Absorbtion of an extranuclear electron into the nucleus.
Decay scheme: depiction of nuclear mass energy plotted against the atomic number of the nuclei.
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9. Examples of Radioactive Decay
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10. Decay Schemes
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11. Examples:
-decay:
Decay scheme (Hendee)
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12. Positron decay:
Electron capture:
Decay scheme
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13. Negatron decay:
Decay scheme
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14. Competing processes of negatron emission, positron emission and electron capture
Decay scheme
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15. Isomeric transitions after negatron decays
Decay schemes
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16. Nuclear Activity Radioactive decay is described by
N(t), N0: number of radionuclide at time t = 0 and t, respectively.
: decay constant [1/t]
Activity A = average decay rate [decays per second]
Nuclear activity is measured in curie: 1 [Ci] = 3.7  1010 decays/sec (originated from the activity of 1 g of 226Ra)
Practical: 1 mCi, mCi. SI unit is becquerel [Bq] = 1 decay/second
99mTc
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17. Interaction of Nuclear Particles and Matter
Alpha particles
Helium nucleus (4He++), mostly occurring for parent with Z > 82
~ 3-9 MeV (accounts for the kinetic energy of the alpha particle kinetic energy of the product nucleus)
+ 2 charge large mass  strong interaction (ionisation: attracts electrons from other atoms which become cations)
Poorly penetrating type of radiation (can be stopped by a sheet of paper).
Beta particles
Causes Bremsstrahlung (white, characteristic)
“Wiggly” motion in matter (low mass)
Gamma rays
Electromagnetic waves produces in nuclear processes ( < 0.1 nm, E > 10 keV)
Identical to x-ray interaction (for E > 1.02 MeV: pair production and photo disintegration [emission of alpha, n, or p from nucleus])
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18. Radionuclides in Clinical Use
Most naturally occurring radioactive isotopes not clinically useful (long T1/2, charged particle emission)
Artificial radioactive isotopes produced by bombarding stable isotopes with high-energy protons or charged particles
Nuclear reactors (n), charged particle accelerators (Linacs, Cyclotrons)
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19. Radionuclide Generator
On-site production of 99mTc
99mTc is the single most important radionuclide in clinical use 140 keV)
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20. Radiopharmaceuticals and their uptake in the body
In nuclear medicine imaging a radioactive isotope is introduced into
the particular part of the body which is to be investigated.
Ex: in order to follow heart, introduce the activity into the blood stream.
Ex: In order to follow tyroid gland, introduce radioactive iodine (as tyroid
absorb iodine)
In some cases, neither of the two methods are possible.
 attach the radioactive subtance to another chemical which is chosen
because ıt is preferentially absorbed by part of the body. The chemicals to
which radipactive labels are attached are called radiopharmaceuticals.
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21. Radiopharmaceuticals (cont.)
If a chemical compound has one or more of its atoms substituted by
a radioactive atom then the results is a radiopharmaceutical.
For more detailed information: see Belcher & Velter “Radionuclides in
medical diagnosis”, 1971
Selection of isotopes:
1) choose an isotope so that the resultant radiopharmaceutical is in the correct
chemical form which will allow it to be absorbed by the particular organ to be
imaged.
2) the energy of radiation must be suitable to the detectors to be used. Optimum
energy range for gamma cameras is keV. Efficiency drops beyond this
range
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22. Selection of isotopes (cont.)
3) T1/2 must not be too short, otherwise it will decay before the radiopharmaceutical
can be delivered. It must not be too long, otherwise the patient will be unnecessarily
exposed to ionization.
T1/2 (ideal) is a few hours.
Exception: Se is used for pancreas scanning. T1/2 is 120 days.
4) radiation dose delivered to patient must be as low as possible
5) radiopharmaceutical must be available, it should be cheap.
The radionuclide that fulfills most of the above criteria is Technetium _ 99m (99m Tc),
which is used in more than 90% of all nuclear medicine studies.
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23. 99mTc-Sestamibi (myocardial perfusion, cancer)
Properties of 99mTc:
T1/2 = 6 h
radiates 140 keV gamma ray
the short half time and absence of Beta emission allows low radiation dose to patient.
The 140 keV gamma radiation allows for 50% penetration of tissue at a thickness of 4.6 cm.
Applications:
99mTc-Sestamibi (myocardial perfusion, cancer)
99mTc-labeled hexamethyl-propyleneamine (brain perfusion)
Other gamma emitters:
123 I, 111 In, 67 Ga, 201 Tl, 81 Kr m
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24. Positron emitters: 11 C , T1/2 = 20 min 13 N , T1/2 = 10 min
many organic compounds (binding to nerve receptors, metabolic activity)
13 N , T1/2 = 10 min
NH3 (blood flow, regional myocardial perf.)
15 O , T1/2 = 2.1 min
CO2 (cerebral blood flow), O2 (myoc. O2 consumption), H2O (myoc. O2 consumption & blood perfusion)
18 F , T1/2 = 110 min
2-deoxy-2-[18F]-fluoroglucose (FDG, neurology, cardiology, oncology, metabolic activity)
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25. Imaging
As long as the photons emanating from the radionuclide have sufficient energy
to escape from the human body in significant numbers, images can be generated
that portray in vivo distribution of the radiopharmaceutical.
Nuclear medical imaging may be divided into three categories:
1) conventional or planar medical imaging,
2) Single photon emission computed tomography (SPECT),
3) Positron emission tomography (PET).
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26. Conventional or planar imaging
The three-dimensionally distributed radiopharmaceutical is imaged onto a planar or
two-dimensional surface producing a projection image.
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27. A single detector system for rectilinear scan
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28. Image formation
A scanning mechanism makes a rectilinear motion above the patient.
The collimator ensures that each small part of the crystal views only a small area of the organ to be imaged.
Gamma rays which pass through a hole in the collimator must interact in the crystal immediately behind that hole.
The electrons involved in the interaction of the gamma ray with the crystal are stopped very close to the point of interaction and hence the scintillations produced originate very close to the point of interaction.
Each gamma ray which interacts in the crystalis called ‘ an event ’ .
Many events in the crystal produce a scintillation image.
Each event must be processed independently to locate the origin of the scintillations for that event, i.e, the point of interaction of the gamma ray. This is accomplished by the PM tube array and associated electronics.
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29. The light scintillations are detected by the PM tube array with the PM tube closest to the origin of the scintillations detecting the most light.
Other PM tubes, further from the origin of the scintillations, will detect lesser amounts of light.
The light detected by each PM tube is proportional to its proximity to the origin of the scintillations.
Each PM tube converts the light detected to a electron pulse. The amplitude of this pulse is proportional to the intensity of the light the particular PM tube detects, i.e, it is related to the proximity of the PM tube to the point of interaction.
Each event is ‘located’ using information from all the PM tubes and finally
the position circuitry processes this information and can locate the point of interaction to within 2-3 mm
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30. Detection of Gamma Radiation
Scintillation detectors are the most commonly used detectors:
Crystals: NaI(Tl) (thallium-activated sodium iodide) , BGO (Bismuth Germanate), CsF, BaF2 (Barium Fluoride)
Criteria: Stopping power, response time, efficiency, energy resolution
Other methods, like ionization chambers and semiconductor detectors can also be used.
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31. Pulse Height Analyzers (PHA)
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32. Pulse Height Analyzers
In NM imaging the pulse height analyser (PHA) is the main component used to reject scatter.
Any gamma-rays which have scattered in the body will strike the crystal and deposit less than the full energy in the crystal.
Most of these events can be rejected by the PHA.
Only those events corresponding to unscattered gamma-rays are used to form the image.
Note that the rejection is not perfect but without the PHA the NM image would be almost useless particularly for large subjects where scatter is very significant
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33. Scintillation Camera (Anger Camera)
Imaging of radionuclide distribution in 2D
Replaced “Rectilinear Scanner”, faster, increased efficiency, dynamic imaging (uptake/washout)
Application in SPECT and PET
One large crystal (38-50 cm Dia.) coupled to array of PMT
Enclosure
Shielding
Collimator
NI(Ti) Crystal
PMT
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34. SCINTILLATING CRYSTAL
Anger Logic
The Anger camera is a system for achieving a large number of resolvable elements with a limited number of detectors. It thus overcomes the previous difficulty of having the resolution limited by the number of discrete detectors.
The principle is based on estimating the position of a single event by measuring the contribution to a number of detectors.
GAMMA-RAY PHOTON x1 x2 I1 I2
SCINTILLATING CRYSTAL
LIGHT PHOTONS
PHOTODETECTOR
x 
I1x1+ I2x2
I1+I2
Cameras of this general
type have a single crystal
viewed by arrays of detectors
with the detected outputs
followed by a position computer
to estimate the position of
each event.
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35. Applications
Thyroid imaging: The thyroid gland is situated in the lower part of the neck at a
depth of about 1 cm. The purpose of thyroid is to secrete the hormone thyroxin
which is carried in the blood stream and controls a number of body functions:
stimulate metabolism
influence growth
control mental development
store iodine
underactive thyroid :
mental dullness,
low temperature
decrease in metabolism
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36. Imaging of thyroid can be useful for the following purposes:
1. To determine the amount of thyroid tissue left after surgery or radiotherapy for thyroid disease,
2. To detect thyroid metastases associated with thyroid cancer,
3. To show the comparative function of different parts of the glands,
4. To measure the size and position of the thyroid prior to surgery or other treatments of the disease.
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37. Iodine is trapped in the thyroid.
Approximately, % of ingested iodine concentrates in the normal thyroid.
Previously used 131I (the most readily available iodine isotope) for thyroid imaging.
However, 131I has unsuitable properties for NM imaging, i.e.,
*long half-life
*emits beta-particles
*emits high energy (364 keV) gamma rays.
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38. 123I has a half-life of 13.3 hr and emits gammas of energy 159 and 28 keV.
123I is possibly the best radionuclide of iodine for imaging but it is expensive and not readily available.
The pertechnetate ion (TcO4) also concentrates in the thyroid. It can also be trapped in the thyroid.
About 2 -3 % of IV administered TcO4 concentrates in the normal thyroid which is sufficient for imaging.
120 MBq of Na99mTcO4 is administered IV and images are obtained 15 min later.
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39. uniform distribution throughout both lobes the isthmus is well defined
Normal image:
uniform distribution throughout both lobes
the isthmus is well defined
Abnormal image:
GRAVE’S DISEASES
increased uptake and general enlargement of the gland.
TUMOUR
usually ‘cold’ spots and the gland is distorted but may be carcinoma,
adenoma or cyst
‘hot’ spots (particularly singular hot spots) are generally benign
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40. * suspected pulmonary emboli (PE) * malignancy
Lung Imaging:
INDICATIONS
* suspected pulmonary emboli (PE)
* malignancy
* emphysema (excess air in lungs)
PROCEDURE FOR VENTILATION IMAGE
* the patient is positioned for imaging and breathes technegas which is
carbon particles labelled with 99mTc
Inhalation continues until a predetermined count rate is obtained then
* multiple views are obtained
* the system is then opened to clean air and the “active” material washes
out from the lungs fairly quickly.
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41. MAA are 10-30 m in size and lodge in the capillaries of the lung.
The perfusion image:
120 MBq of 99mTc labelled MAA (macroalbumin agregate) is administered IV with the patient supine.
MAA are m in size and lodge in the capillaries of the lung.
about 200,000 particles of MAA are administered and block ~ 1 in 1000 capillaries.
they are biodegradable.
T1/2(biol) =6 - 9 hr.
the same views as for the ventilation scan are obtained with the patient supine
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42. the pulmonary angiogram is the ‘gold standard’ for diagnosis of PE
PE detected in the NM image will show little or no radiographic change on a plain x-ray
NM imaging for PE is
* safe
* simple, and
* very sensitive
the pulmonary angiogram is the ‘gold standard’ for diagnosis of PE
however it is
* expensive
* invasive
* involves some risk and
* is used only when the NM image is inconclusive
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43. Imaging kidney cortex:
use 150 MBq of 99mTc-DMSA or GHA
these pharmaceuticals localise in the renal cortex
generally used in combination with an IVP and ultrasound
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44. Single Photon Emission Computed Tomography (SPECT)
If one or more gamma cameras are
attached to a computer controlled
gantry, which allows the detectors to be rotated around a patient, multiple views (or 2D projections) of the 3D pharmacutical distribution can be acquired.
First SPECT 1963 (Mar IV) used array of detectors
Rotation, Translation
High count rates
Many components
Mostly single-slice
Rotating camera:
Multiple slices
Multi-camera systems
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45. Collimators for SPECT Collimator restricts the acceptance angle
Geometry
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46. SPECT Artifacts Reconstruction methods similar to x-ray CT
Attenuation: gamma-ray originating from the source is attenuated
by tissue. Two unknowns: 1)concentration of tracer, and 2) distribution of tissue attenuation coefficients.
Corrective measures:
1) Transmission measurement with external source to determine tissue absorbtion
2) Assume constant absorption and use geometric mean of two measurements 180 apart, which is independent on d
3) Iterative reconstruction
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47. Using the Geometric Mean
Let there be an activity A at depth d from detector I. Assume that the object has
a constant attenuation coefficient. Then the fraction of photons reaching that
detector (C1) is proportional to e-x, that is
Survival
probability
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48. Geometric mean (cont.)
The fraction of photons reaching the second detector (C2) is:
If the geometric mean is used, then
which is totally independent of source depth. Provided an outline of the body,
a simple correction can be applied to the combined opposed projections.
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49. Iterative Reconstruction method
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50. i : the attenuation coefficient of the ith element (corresponding
The image domain can be discretized and acquired ray sums can be expressed by:
where
Ai : activity contained in the ith voxel,
p(k) : projection data at angle , the sum of weighted activity (or ray sum) along the kth ray at angle of view ,
fi k,  : fractional volume of the ith element that is contained within
the kth ray,
i : the attenuation coefficient of the ith element (corresponding
to the energy of the photon),
lj k,  : length of the portion of the kth ray that is contained within
the ith element
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51. Iterative method exp(- j lj k, ) : attenuation factor for radiation
originating from the ith element.
The index j denotes elements lying along the kth ray
between the ith element and the boundary of the object nearest the detector.
Iterative method
Assume attenuation distribution, find Ai
Calculate attenuation distribution using Ai
Find new estimate for Ai using the calculated attenuation coefficients,
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52. Positron Emission Tomography
Use with positron emitters (beta-plus)
Positron annihilates with electron of nearby atom  two gamma quanta each at 511 keV leave under 180
“Tagging” of radiation:
Windowing
Coincidence detection (“electronic collimation”)
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53. PET Detectors
Individual Coupling: Expensive, packing problematic, high count rate
Block Design: Digital encoding, longer dead time, more economic, somewhat reduced resolution
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54. PET Resolution compared to MRI
Modern PET ~ 2-3 mm resolution
MRI
PET
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55. Functional Imaging
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