Nuclear Medicine Introduction What is nuclear medicine? The use of radioactive tracers (radiopharmaceuticals) to obtain diagnostic information [and for targeted radiotherapy]. Radiation is emitted from inside the human body cf transmitted radiation in x-ray imaging. Tracers :- Trace the paths of various biochemical molecules in our body. Hence can obtain functional information about the bodies workings (i.e. physiology).
Radiopharmaceuticals Traces physiology / localises in organs of interest Radioactive nuclide Emits radiation for detection or therapy + Biochemical Bonding Q. What is a radiopharmaceutical?
The Pharmaceutical 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. Typically want no physiological response from the patient The mechanism of localisation can be as simple as the physical trapping of particles or as sophisticated as an antigen-antibody reaction Why would you only want it to follow only one pathway? - Reduce radiation dose to other organs. - Uptake in other organs may obscure any abnormality.
Radionuclides in Nuclear Medicine The ideal radionuclide for in-vivo diagnosis : Optimum half life of same order as the length of the test (this minimises the radiation dose to the patient) Pure gamma emitter No alpha or beta particles, these do not leave the body so merely increase the radiation dose. Optimum energy for g emissions High enough to exit the body but low enough to be easily detected. Useful range for gamma cameras is 50 - 500 keV (optimum ~ 150 keV). Suitable for incorporating into a pharmaceutical without altering its biochemical behaviour Readily and cheaply available on the hospital site.
Some Commonly Used Radionuclides in Nuclear Medicine Radionuclide Production: Neutron Capture Nuclear Fission Charged Particle Bombardment Radionuclide Generator Q. Do you know of any other radionuclides that are used in nuclear medicine? A. Xenon, Gallium, Fluorine, Selenium, Yittrium, Strontium,
Producing the Radiopharmaceutical Radiopharmaceutical kits Most common radiopharmaceuticals are available as kits. These contain all the necessary freeze-dried ingredients in an air-tight vial, usually the pharmaceutical, a stannous compound and stabilizer. On addition of 99Tcm 04- , the stannous reduces the 99Tcm 04- , makes it charged and "sticky", and Tc forms a bond with the pharmaceutical, labelling it. For the longer half-life isotopes, the full radiopharmaceutical can be obtained directly from the manufacturer, e.g. SeHCAT labelled with 75Se.
Detection of the radiopharmaceutical Non-imaging In-vitro (measuring radiation levels in bodily fluids outside the body) e.g. Blood sample counting for GFR analysis: Patient Electronics and count-rate meter Inject radioactive tracer Extract sample of bodily fluid (e.g. blood) Measure fluid sample in sample detector In its simplest form, a non-imaging nuclear medicine test will involve the administration of a radiopharmaceutical, a delay for the tracer to accumulate or be processed in some way, and then the extraction of a sample (or samples). These are then measured in a sample counter which will indicate the level of activity in the sample. For example: Glomerular Filtration Rate measurement 3 MBq of 51Cr EDTA injected 10ml blood samples collected at 2,3,4 and 5 hours post-injection. Estimate of GFR obtained by linear regression fit to these mesurements.
Detection of the radiopharmaceutical Non-imaging In-vivo (Uptake measurements in organs using a radiation detector probe) e.g. SeHCAT study for bile salt malabsorption . Collimator Scintillation Electronics and probe count-rate meter
Detection of the radiopharmaceutical In Vivo imaging - the gamma camera Patient Radioactive tracer Gamma rays camera Image Vast majority of Nuclear Medicine investigations involve the production of an image using a Gamma Camera Properties of gamma rays High energy electromagnetic radiation Can be scattered and absorbed Cannot be focused
The Gamma Camera X Y Z Collimator NaI Crystal Photo Multiplier Tubes Position circuitry X Y Z Collimator NaI Crystal Photo Multiplier Tubes Analogue to Digital Converters Digital 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 highly inefficient device, which is required because no gamma-ray lens exists. In the parallel hole collimator, only incident photons that are normal to the collimator surface will pass through it. All other photons should be absorbed by the lead septa between the holes The collimator defines the field of view, and essentially determines the system spatial resolution and sensitivity. Collimator efficiency: only ~0.1% of photons incident on the collimator pass through it.
Spatial Resolution & Sensitivity 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). To improve collimator resolution Increase the septa depth (d) Reduce the size of the holes (s) Resolution ↓ as the source is moved away from the collimator - important to image with the camera as close to the patient as possible 0 cm 5 cm 10 cm 15 cm 20 cm Output from Collimator collimator Radioactive pt. source Q. Why would you want to trade sensitivity against resolution? Why would you not want to always obtain the best resolution? A. Acquistion may take too long to get reasonsible number of counts e.g. dynamic imaging (and some SPECT acquisitions) you only have a short time period in which to collect the image information – need to obtain the optimum counts stats (within reason). To improve collimator sensitivity Dependent on the number of photons passing through the collimator Improved with larger hole sizes and smaller length septa Spread of response to pt. source defines s collimator resolution d Spatial distance resolution and sensitivity are conflicting parameters
Scintillation Crystal The gamma ray causes an electron release in the crystal via the Photoelectric Effect, Compton Scattering or the electronpositron pair production (E > 1.022 MeV), this excess energy gives rise to subsequent visible light emission within the crystal (scintillation). Number of light photons produced is roughly E Hence, this is an energy discriminating detector (important feature as we can use this to reject scattered photons) Incident gamma ray NaI(Tl) Scintillation crystal Light Photons (~415nm) Compton Scattering The energy of a gamma photon is partially absorbed by the atom, ejecting an electron from the atom and scattering the photon. Photo-electric Effect The gamma photon is completely absorbed by the atom and the energy is used to eject an electron from the atom. Why dope the NaI crystal with Thallium? Activators are impurities that create special sites in the lattice at which the normal energy band structure is modified from that of the pure crystal. Often, thallium is used as an activator in sodium iodide detectors. In small amounts, these impurities enhance the probability of visible photon emission during the de-excitation process. Once the visible light photons have been produced it is important for them to travel through the crystal unhindered. The crystal therefore needs to be transparent to its own light photons emissions.
Image Types In Nuclear Medicine various forms of data acquisition can be performed: Static Imaging The distribution of the radiopharmaceutical is fixed over the imaging period. Multiple images can be acquired, viewing from different angles (e.g. anterior, oblique). e.g. kidneys (DMSA), thyroids, bone, lung 99Tcm Thyroid Scan Whole Body imaging the camera scans over the whole body to cover more widespread distributions or unknown locations e.g. bone scan, infection imaging, tumour imaging 99Tcm HDP Bone Scan Dynamic Imaging Consecutive images are acquired over a period of time (with the camera in a fixed position) showing the changing distribution of the radiopharmaceutical in the organ of interest. e.g. renogram, GI bleed, meckel’s diverticulum 99Tcm labelled red blood cells – GI bleed