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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.