Nuclear Medicine Imaging

1
Nuclear Medicine Imaging
2
Overview

• Nuclear medicineTherapeutic 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
• 1947 - Kohman Radionuclide nucleus of
  measurable half-life
• 1935 - Hevesy uses 32P for metabolic studies with
  Geiger-Muller counter
• 1949 - First radionuclide imaging by Cassen of
  131I uptake in thyroid gland(scintillatorPMT,
  scanner, collimator,1/4 spatial resolution)
• 1957 - Anger camera (planar imaging)
• 1960 - 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)

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)

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.

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

Neutrino means little neutral particle in
Italian.
6
Nuclear Stability
Neutron rich unstable element
Proton rich unstable element
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 Even 165
Even Odd 57
Odd Even 53
Odd Odd 6
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.

9
Examples of Radioactive Decay
10
Decay Schemes
11
Examples

• ?-decay

Decay scheme (Hendee)
12

• Positron decay
• Electron capture

Decay scheme
13

• Negatron decay

Decay scheme
14
Competing processes of negatron emission,
positron emission and electron capture
Decay scheme
15

• Isomeric transitions after negatron decays

Decay schemes
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
17
Interaction of Nuclear Particles and Matter

• Alpha particles
• Helium nucleus (4He), mostly occurring for
  parent with Z gt 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 (? lt 0.1 nm, E gt 10 keV)
• Identical to x-ray interaction (for E gt 1.02 MeV
  pair production and photo disintegration
  emission of alpha, n, or p from nucleus)

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)

19
Radionuclide Generator

• On-site production of 99mTc
• 99mTc is the single most important radionuclide
  in clinical use (gamma _at_ 140 keV)

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 it is preferentially absorbed by
part of the body. The chemicals to which
radipactive labels are attached are called
radiopharmaceuticals.
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 100-300 keV.
Efficiency drops beyond this range
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.
23

• 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

24

• Positron emitters
• 11 C , T1/2 20 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)

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).
26
Conventional or planar imaging
The three-dimensionally distributed
radiopharmaceutical is imaged onto a planar
or two-dimensional surface producing a projection
image.
27
A single detector system for rectilinear scan
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.

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

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.

31
Pulse Height Analyzers (PHA)
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

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

1. Enclosure
2. Shielding
3. Collimator
4. NI(Ti) Crystal
5. PMT

34
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.

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.
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

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.
37

• Iodine is trapped in the thyroid.
• Approximately, 20 -30 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.

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.

39

• Normal image
• uniform distribution throughout both lobes
• the isthmus is well defined
• Abnormal image
• GRAVES 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

40

• 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.

41

• The perfusion image
• 120 MBq of 99mTc labelled MAA (macroalbumin
  agregate) is administered IV with the patient
  supine.
• MAA are 10-30 ?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

42

• 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

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

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

45
Collimators for SPECT
Collimator restricts the acceptance angle
Geometry
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

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
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.
49
Iterative Reconstruction method
50
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
51

• 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,

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)

53
PET Detectors

• Individual CouplingExpensive, packing
  problematic, high count rate
• Block DesignDigital encoding, longer dead time,
  more economic, somewhat reduced resolution

54
PET Resolution compared to MRI

• Modern PET 2-3 mm resolution

55
Functional Imaging