Download 3rd year - Module MPY301

NUCLEAR MEDICINE
INTRODUCTION
What is nuclear medicine?
The use of radioactive tracers (radiopharmaceuticals) to obtain diagnostic
information [and for targeted radiotherapy].
Tracers :-
Trace the paths of various biochemical molecules in our body.
Hence can obtain functional information about the bodies workings (i.e.
physiology).
---------------------------------------------------------------------------------------------------Example of a radiopharmaceutical used for diagnosis in nuclear medicine
BONE SCANNING :- I.V. injection of radioactively-labelled phosphate compound.
Phosphate
Extracted from the blood
stream and incorporated
into active bone
Radioactive nuclide (99Tcm)
+
Emits radiation which can be detected
outside the body to “show” the
distribution of the phosphate in the body
The skeletal distribution of phosphate can yield vital physiological information relating to bone
growth. Bone scans can be used to aid in the detection of :Fractures, tumours, arthritis, inflammation etc…..
---------------------------------------------------------------------------------------------------
Detection of the radiopharmaceutical distribution
In Vivo (when the tracer is still in the body)
Imaging - the gamma camera
Gamma
rays
Radioactive
tracer
Image
COMPUTER
Gamma
camera
Patient
Non-imaging
e.g. Uptake measurements in organs using a radiation detector probe
Collimator
Scintillation
probe
Electronics and
count-rate meter
In-vitro (measuring radiation levels in bodily fluids outside the body)
e.g. Blood sample counting :
Inject radioactive
tracer
Measure fluid sample
in sample detector
Electronics and
count-rate meter
Extract sample of
bodily fluid
(e.g. blood)
Patient
Radiotherapy using radiopharmaceuticals
>>
Unsealed source therapy
Uses similar pharmaceutical tracers as used for diagnostic investigations but with
radionuclides which emit less penetrating radiation (mainly beta particles) and using
higher activities.
Beta
particles
Gamma
rays
Energy of beta particles is deposited very locally
---------------------------------------------------------------------------------------------------Example of a radiopharmaceutical used for therapy in nuclear medicine
THYROID THERAPY using radioactive iodine
131
I
----------
|
|
Iodine is taken up by
the thyroid (and some
thyroid tumours) to be
converted into thyroid
hormone
Radionuclide emits  particles (and ’s) which deposit
a large localised radiation dose to the thyroid/tumour
Used to treat thyrotoxicosis and some thyroid cancers
----------------------------------------------------------------------------------------------------
THE RADIOPHARMACEUTICAL
Pharmaceutical
+
Radioactive nuclide
Traces physiology/
localises in organs
of interest
Biochemical
bonding
Emits radiation for
detection or therapy
The pharmaceutical and bonding
The ideal tracer/pharmaceutical should follow only the specific pathways of interest.
E.g. there is uptake of the tracer only in the organ of interest and nowhere else in the
body. In reality this is never actually achieved.
Usually, a non-radioactive pharmaceutical kit is supplied to a hospital. The
radionuclide is then added on site using a suitable procedure and in a suitable
environment - sterile rooms/cabinets etc.
OR
Sometimes, for the longer half-life isotopes, the full radiopharmaceutical can be
obtained directly from the manufacturer.
Diagnostic radiopharmaceuticals can be obtained for investigating :
Skeleton, brain/CNS, lungs, liver, gastro-intestinal tract, urinary tract, heart,
blood disorders, endocrine glands, various tumours etc…
Therapy radiopharmaceuticals can be obtained for treating :Thyroid, various tumours, blood disorders, joint problems, bone disease etc…..
Radionuclides in Nuclear Medicine
The ideal radionuclide for in-vivo diagnosis :
Optimum half life out
of same order as the length of the test being carried
(this minimises the radiation dose to the patient)
Pure gamma emitter -
No alpha or beta particles
Optimum energy for to be
 emissions
High enough to exit the body but low enough
easily detected. Useful range for gamma cameras
is 50 -300 KeV (optimum ~ 150 KeV).
Good potential for biochemically “gluing“ to radiopharmaceuticals
Readily and cheaply available on the hospital site.
Some commonly used radionuclides
Radionuclide
Half-life
Tcm (Technecium)
111
In (Indium)
123
I (Iodine)
131
I
201
Tl (Thallium)
6h
2.8 days
13 h
8 days
73.5 h
99
Pure 
emissions ?
y
y
y
n
y
Energy of main
’s (KeV)
Source of
production
140
173, 247
160
280, 360, 640
68-80
On site generator
Cyclotron
Cyclotron
Reactor
Cyclotron
THE SCINTILLATION CRYSTAL
Basic principle:
Scintillation
crystal
Incident
gamma
ray
Light
photons
No of light photons produced  E
Hence, this is an energy discriminating detector
The ideal scintillator would have a high atomic number and efficiently absorb -ray energy. The
light photons should be produced efficiently, and should be able to pass through the scintillator
without attenuation. The wavelength of the light photons produced should correspond to that at
which the photomultiplier is most sensitive.
In practice Sodium Iodide impregnated with a small amount of thallium is as close to this ideal as
is possible to achieve. >> NaI(Tl)
Using a scintillation crystal in conjunction with a P.M. tube
NaI crystal
Light
pipe
P.M. tube
Dynodes
e-
E.H.T. supply,
pulse amplifier
and other electronics
Al can
Light diffusing
surface
Photocathode
Resulting output
pulse from an
incident gamma ray
Anode
collector
How energy is deposited in the crystal - the gamma spectrum
Distribution showing the energy
deposited in the crystal per gamma ray
from a monoenergetic gamma source
The photo-electric effect
Eo
No of
gammas
e-
Eo Energy (keV)
Compton scatter
e-
Eo
Pair production
(for Eo > 1.02 MeV)
e-
511 keV
e+
(Eo- 1020) (Eo- 511)
Eo
511 keV
Example output spectrum from a scintillation crystal - P.M. tube assembly
in response to a monoenergetic source
No
Photopeak
Compton plateau
Pulse height
THE GAMMA CAMERA
Collimator
NaI
Crystal
PM
Tubes
ADC’s
Position
circuitry
X Y Z
Digital
circuitry
Output position
& energy signals
THE COLLIMATOR
The purpose of the collimator is to project an image of the radioactive distribution
in the patient onto the scintillation crystal.
It is a crude and inefficient device, which is required because no gamma-ray lens
exists.
PARALLEL
COLLIMATOR
LENS
Object
Image
Object
Image
The large image-acquisition times and poor count statistics in nuclear medicine
images is largely due to the inefficiency of the collimators.
The parallel-hole collimator
Only -rays passing perpendicular to the camera face are allowed to pass through to
the crystal.
Resolution and sensitivity of the parallel-hole collimator
Spatial resolution of an imaging device defines its ability to distinguish between
two structures close together and is characterised by the blurred image response to a
point-source input. For a gamma camera, the overall spatial resolution in the image
depends on the collimator (collimator resolution) and the other gamma-camera
components (intrinsic resolution).
Collimator
Output from
collimator
Radioactive
pt. source
Spread of response
to pt. source defines
collimator resolution
s
d
Spatial distance
Collimator resolution is improved with deeper septa (i.e. greater d) and smaller hole
sizes (s).
Resolution worsens as the source is moved increasing distances away. (This is why
it is very important for camera to be as close to the patient as possible when
imaging).
Collimator sensitivity relates to the proportion of gamma rays passing through the
crystal, and is improved with larger hole sizes and smaller length septa.
Sensitivity is independent of distance from the collimator face.
Therefore resolution and sensitivity are conflicting parameters and different
collimators need to be available , the choice of which to use depending on which
parameter is the more important for a particular scan. There are high resolution
collimators, high sensitivity collimators and general purpose collimators between
the two.
The collimator also has to be tailored to the energy of the gamma-rays being
imaged. The thickness of the septa should be such as to reduce septal penetration
(see diagram) to a minimum since this will degrade resolution. Higher energy -rays
are more penetrating , and hence require thicker septa. However, thicker septa
reduce the overall “transparent” area of the collimator, and hence reduce sensitivity.
As usual a compromise is required, and low energy ( ), medium energy ( ), and
high energy collimators are usually available.
GAMMA CAMERA ACQUISTION PARAMETERS
The following parameters have to be considered when acquiring a patient image on a gamma
camera






Collimator type
Time per view (seconds > hours) or total counts per view.
Position and width of energy acceptance window (usually 20% centred over photopeak).
Digital matrix size
Word or Byte mode
Zoom factor (magnification with which to acquire image).
The optimum parameters to use depend on the type of scan being performed and the information
required from it.
STORING DIGITAL DATA AND THE COMPUTER
IMAGE
ACQUISITION
COMPUTER
OUTPUT
DISPLAY
CAMERA
Storage
V.D.U
Camera
Controle
Image
Processing
LONG
TERM
STORAGE
Floppy discs
Optical discs
Tape etc.
Hard copy
DISPLAYING IMAGE DATA
Digital image data can be displayed on a V.D.U. of on some form of hard copy (e.g. x-ray film,
paper etc.).
The display can be in black and white or colour. Either way, a look-up-table (LUT) is used such
that for any count value there is a corresponding shade of grey or a distinct colour. Thus, each pixel
in the image is displayed with the shade of grey or colour corresponding to the count value in that
pixel.
Examples:
Counts
B/W
Colour
255
0
STATIC IMAGES
i.e. The distribution of the radiopharmaceutical is fixed over the imaging period.
Multiple images can be acquired, viewing the structure-of-interest from different angles (e.g. front,
back and sides). Sometimes the camera scans over the whole body to cover more widespread
distributions such as the entire skeleton when performing a bone scan.
Bone scan :
Usually using a 99Tcm-phosphate compound injected I.V.
Radiopharmaceutical is incorporated into active bone, and can help in the diagnosis of :
Bone metastesis, fractures, arthritis, primary bone tumours, inflamation etc.
VQ lung scan (ventilation and perfusion):
Usually using either a radioactive gas (e.g. 81Krm) or an aerosol (99Tcm) which is breathed in
by the patient to look at air supply to the lungs.
AND
Tc particles injected I.V. which get trapped in the small blood vessels in the lung and
demonstrate the pulmonary blood supply (perfusion)
99
m
A missmatch in the perfusion and ventilation images can be used to diagnose blood clots in
the lungs (pulmonary embolus).
Infection imaging:
Using radioactively-labelled (111In) white cells injected I.V. back into the patient
Used to show any sights of infection within the body, which may be causing a fever in the
patient etc.
DYNAMIC IMAGES
Consecutive images are acquired over a period of time (with the camera in a fixed position)
showing the changing disribution of the radiopharmaceutical in the organ of interest. Diagnostic
information can be obtained by analysing the changing distribution visually (qualitative analysis) or
by performing some computer processing on the image data to obtain quantitative information on
organ function.
Renography
Using radioactive tracers (usually based on 99Tcm) injected I.V., which are filtered out of the
blood by the kidneys. Use a gamma camera facing the patient’s back to look at the changing
distribution of tracer in the urinary system (kidneys, ureters & bladder) for ~ 30 minutes after
the injection. Usually, a sequence such as 30 one minute images is acquired. These can be
analysed in order to assess kidney function and drainage from the kidneys through the ureters
into the bladder.
Region-of -interest analysis of dynamic images
This is a commonly-used technique for obtaining quantitative information from nuclear medicine
images:
A specified area in the camera’s FOV is defined (i.e. a group of pixels), and the total counts
contained within this area is recorded for each image in the dynamic sequence. i.e. Can obtain a
count curve which shows change in radiopharmaceutical uptake within a given organ or system
over time.
IMAGE 9 in dynamic sequence of 30
Counts
in ROI 1
Time
ROI defined
around R kidney
DIGITAL IMAGE PROCESSING
This is general terminology for mathematical manipulation of digital image data in
order to:
1. Improve image quality
2. Extract quantitative data from the images
Examples of 1:
Image filtering.
Image rotation and translation.
Examples of 2:
Manual ROI analysis.
Automated ROI analysis - i.e. edge-detection etc.
SPECT
Single Photon
Technique is based on the use of radionuclides which emit independent (i.e. single) gamma
rays. e.g. 99Tcm. This definition is used to make the distinction between this technique and
positron emission tomography (PET) which is based on using positron emitting nuclides that
annihilate producing two simultaneous back-to-back gamma rays. i.e. the two gamma rays in
this case are not independent.
Emission
As with all nuclear medicine imaging, SPECT is based on using internal radioactive sources
which emit radiation out of the body which can be detected. This distinguishes the technique
from X-ray CT which is based on external radiation.
Computed
Requires the use of a computer to mathematically recreate the final image data from the
gamma-camera images acquired.
Tomography
Tomo is Greek for slice. Tomography means the creation of slice images through the body.
Basically, SPECT is an imaging technique used in nuclear medicine to obtain slice views through
the body showing the distribution of radioactive tracer in these slices. Putting contiguous slices
together produces a 3-D distribution of radiopharmaceutical, so in effect SPECT allows us to
obtain 3-D images.
Required equipment for SPECT - Data acquisition
To create a three-dimensional picture of any structure, need to view that structure from multiple,
different perspectives.
Therefore with SPECT, we need to acquire a set of images showing the structure-of-interest from
all different angles. Since we are using the same radiopharmaceuticals and radionuclides as for
normal imaging, we can therefore acquire SPECT data using a normal gamma camera, as long as it
has the capability to rotate around the patient acquiring images at pre-set intervals during the
rotation.
The set of images acquired for SPECT are known as projections.
Camera
rotation
Set of acquired
projection images
Acquisition parameters:
Parameter
Choice
Consideration
Collimator
Usually High resolution or
General purpose.
Depends on size of structures
looking at.
Acquisition time
per projection
Usually 10-30 seconds per
projection
Depends on activity given, collimator
used etc.
Image matrix size
Usually 642 or 1282
Depends on desired resolution,
collimator used, number of
projections acquired, computer
memory available etc..
Usually between 32 and 128
Depends on desired resolution,
matrix size used, computer memory
etc.
Circular, elliptical or body
contouring
Want camera head to be as close to
the patient as possible for the entire
rotation (resolution). Contouring
always best if available.
Step-and-shoot or continuous
rotation
With continuous rotation don't waste
time moving between projection
images, but step-and-shoot usually
preferred because not dependent on
steady camera motion.
Number of
projections
Rotational orbit of
camera
Mode of image
acquisition
RECONSTRUCTION
Mathematically combining the data from the set of projection images to recreate the 3-D
radiopharmaceutical distribution in the patient.
Most commonly-used reconstruction methods are based on filtered back-projection:
Back-projection
Acquiring
projection
images
Resulting
slice
image
Backprojection
Filtered back-projection
Filtering is applied to each projection image before back-projection is performed. It is required to:
1. Remove the star artefact and hence improve contrast and resolution in the final slice images.
2. Smooth the final slice images (i.e. to reduce statistical noise).
Typical filter shape used prior to back-projection:
Real space
F(x)
Frequency space
F’(f)
x
Ramp
High frequency
cut-off
f
Examples of filter-types used include:
Ramp-Butterworth and Ramp-Hamming
Attenuation correction
Applied in order to correct for the fact that gamma-rays from deep tissue in the patient will be
attenuated more than those from superficial tissue.
Attenuation of
gamma rays
Uncorrected
image
Correction
matrix
Corrected
image
The commonest method of attenuation correction is known as the Chang method. Chang
attenuation correction is applied after back-projection to the final slice images. For each transaxial
slice, the patients body outline has to be defined, and using the linear attenuation coefficient for the
gamma radiation in tissue () the computer then calculates a pixel correction matrix for within the
body outline, which can be applied pixel-by-pixel to the image data in order to correct for the
effect( see figure above).
Displaying SPECT data
The image data obtained from SPECT is essentially a 3-D map showing tracer distribution, and
hence slices in any orientation can be obtained. The three standard orthogonal orientations are
transaxial (or transverse), sagittal and coronal.
Transaxial
Sagittal
Coronal
Display packages are also available these days for 3-D visualisation of SPECT data using surface
shading techniques.
Advantages of SPECT compared to normal planar imaging:
1)
Improved contrast
Image contrast refers to the target-to-background count ratio in the image, where the target is
uptake in the organ/structure of interest and the background is due to undesired uptake in
surrounding tissue.
Resulting gammacamera image
Target countdensity in image
Camera
PLANAR
IMAGING
organ of
interest
Background
count-density
in image
Tissue
background
Resulting SPECT
slice image
SPECT
IMAGING
2)
Three-Dimensional localisation
Because SPECT produces essentially 3-D images clinicians can use this imaging technique to
accurately locate the position of tumours or other structures in the body.
3)
Quantitation
SPECT image data can yield more accurate measurements of organ/structure volume and
tracer uptake than normal planar imaging. This is largely due to the 3-dimensional nature of
the images and the fact that contributions from overlying tissue are removed.
COMMON USES OF SPECT IN NUCLEAR MEDICINE
Brain blood flow
Uses 99Tcm-based agent given I.V. which circulates in the blood and passes through the bloodbrain-barrier in to the brain's vessels.
Can be used for diagnosing and investigating tumours, strokes, and dementia etc.
Heart myocardial imaging
Using either 201Tl or a 99Tcm-based agent given I.V. to look at the blood supply to the heart
muscle (myocardium).
Can be used to investigated various forms of coronary heart disease.