Chapter 16 Nuclear Medicine Radiopharmaceuticals and Imaging Equipment PDF

Radiopharmaceuticals: Substances used in nuclear medicine to image organ or tissue function. Nuclear Medicine Imaging: Maps organ specific functions using radiopharmaceuticals (e.g., PET, SPECT). CT/X-ray: Structural or anatomical imaging for anatomy. PET/SPECT (Nucle...

Radiopharmaceuticals: Substances used in nuclear medicine to image organ or tissue function. Nuclear Medicine Imaging: Maps organ specific functions using radiopharmaceuticals (e.g., PET, SPECT). CT/X-ray: Structural or anatomical imaging for anatomy. PET/SPECT (Nuclear Medicine): Functional or physiological imaging for physiological processes. Structural Imaging (Anatomy): Shows tissue/organ types and their positions (e.g., bones, heart, muscles, kidneys, liver, blood vessels). Functional Imaging (Physiology): Detects biological/physiological changes and underlying diseases (e.g., cancerous or benign tumors). Nuclear Medicine Imaging Planar Imaging: uses gamma camera to capture 2D images. ○ Static Planar: Captures single images using a gamma camera. ○ Dynamic Planar: Records a series of images over time to show how something in the body (like blood flow) changes or moves with gamma camera imaging. Single Photon Emission Computed Tomography (SPECT): Uses rotating gamma cameras to create 3D images. Positron Emission Tomography (PET): Utilizes fixed rings of detectors to capture detailed 3D images of functional processes. Radiopharmaceuticals: Easy Notes Purpose: Used to create images in nuclear medicine. Administration: Injected into the patient's vein. Components: A chemical compound with specific biological properties, combined with a radioactive isotope (e.g., 18F, 99mTc). Function: The chemical acts as a probe (to see biological processes) to study specific body functions, such as: ○ Metabolism ○ Cell differentiation  ○ Cell division Radiopharmaceutical Accumulation continued….. Accumulation: Radiopharmaceuticals gather in tissues/cells with high activity related to specific functions (e.g., metabolism, cell division). Radiation Detection: The radiation emitted from the radioactive isotope's decay is detected to create an image. ○ Different scanners are used based on the decay process. Image Formation: The image maps the distribution of the radiopharmaceutical in the body, providing insights into the function of organs and tissues. Factors to Consider in Radiopharmaceuticals: Easy Notes a. Preparation: Biologically useful compound: Should serve a specific biological purpose. Single target organ: Aims at one specific organ. Easy labeling: Labeling should be simple and quick. Short reaction time: Quick reaction for labeling. Room temperature reconstitution: no boiling water bath. Useful reconstituted life: Stable for use after reconstitution. b. Application in Patients: No toxic/allergic reactions: Should not cause harm or allergic responses. Good shelf-life (unreconstituted): Stays usable without reconstitution (does not need to be mixed with anything). Stable in vivo: Minimizes free isotopes inside the body. Pathology (diseases) seen as increased activity: Detectable by increased activity in areas of concern. Multiple patients per vial: Can be used for more than one patient from a single vial. Commonly Used Radiopharmaceuticals (Tracers) - 99mTc: ○ Most commonly used radiopharmaceutical (tracer). ○ Gamma energy = 140 keV. ○ Widely used for imaging in nuclear medicine due to its effective properties. Planar Imaging Planar Imaging: ○ Captures images of activity in the body projected onto a 2D plane. ○ Uses a gamma camera with a collimator to detect gamma events. ○ NaI(Tl) scintillation detector used to capture signals. ○ Photomultiplier tubes (PMTs) collect and convert the signals to images.  ○ The x and y positions of gamma events are calculated and displayed. Challenges: ○ Overlapping tissue activity reduces image contrast. ○ Circulating blood activity adds background noise. Examples: ○ Liver images (oncology) ○ Lung images (pulmonary embolism) ○ DMSA dimercaptosuccinic acid (kidney function) ○ Myocardial activity (using 201Tl for heart imaging) Static Planar Imaging Static Planar Imaging: ○ Conventional method for tracking tracer distribution. ○ Views commonly taken: anterior, posterior, lateral, and oblique projections. ○ Used for diagnostic and therapeutic information, such as: Presence of blockages Increased or decreased tracer uptake Response to treatment Matrix Size: The gamma camera image is digitized and represented as a 2D matrix. ○ Common matrix sizes: 64 x 64 128 x 128 256 x 256 ○ If the pixel density is low, the image will appear noisy. Pixel Noise: The 64 x 64 matrix (12 bit) is considered the equivalent-noise reference. Similar to the CT the pixel size is related to the FOV and the matrix size Contrast Limit and Matrix Size Contrast Limit: ○ It is a Measure of visible contrast difference relative to the background.It means how much an object stands out compared to its background, based on visible contrast differences. ○ Higher contrast limit = Noisier image, making it harder to detect low-contrast structures. ○ Proportional to pixel noise: As noise increases, contrast limit also increases. ○ In order to have the same contrast limit, N for other image matrix sizes has to be increased accordingly. Matrix Size and Pixel Count Density: (Diagram) ○ The contrast limit affects pixel count density: Matrix 128x128 (14 bit):  N must increase by a factor of 4 (from 61 to 244) to maintain a contrast limit of 10%. This increases patient dose (total counts = 4 × 10⁶) means 4 million. Matrix 256x256 (16 bit): N must increase by a factor of 4 (61/15). 4 million. Matrix Sizes and Pixel Count: Diagram Values (Don't memorize) ○ 64x64: Pixel size 6mm, pixel count = 244 ○ 128x128: Pixel size 3mm, pixel count = 61 ○ 256x256: Pixel size 1.5mm, pixel count = 15 1. What is the pixel size in the x-direction (sp)? 64x64 Matrix: Pixel size = 6mm 128x128 Matrix: Pixel size = 3mm 256x256 Matrix: Pixel size = 1.5mm 2. What is the count density per pixel? 64x64 Matrix: Pixel count = 244 → Count density per pixel = 244 counts/pixel 128x128 Matrix: Pixel count = 61 → Count density per pixel = 61 counts/pixel 256x256 Matrix: Pixel count = 15 → Count density per pixel = 15 counts/pixel 3. What is the pixel noise? 64x64 Matrix: Pixel noise is defined as equivalent to the reference noise. Largest pixel (6 mm), highest count density (244 counts/pixel), most noisy. 128x128: Medium pixel (3 mm), moderate density (61 counts/pixel), lower noise. 256x256: Smallest pixel (1.5 mm), lowest density (15 counts/pixel), least noisy. 4. Which image will be the nosiest? The 64x64 matrix will be the noisiest because it has the largest pixel size and the highest pixel noise. 5. If the contrast limit is at 1.5 times the pixel noise, what is its value? 64x64 Matrix: Contrast limit = 1.5 × pixel noise (since pixel noise is the reference for this matrix). 128x128 Matrix: Contrast limit = 1.5 × lower pixel noise. 256x256 Matrix: Contrast limit = 1.5 × lowest pixel noise. Contrast and Resolution in Nuclear Medicine: Both contrast and resolution in a nuclear medicine image depend on whether the lesions (abnormal areas) show a negative or positive uptake. ○ Negative uptake: Indicates areas with no tracer absorption, such as pulmonary emboli and liver metastases. ○ Positive uptake: Indicates areas with high tracer absorption, such as bony metastases (occur when cancer cells spread from their original site to the bones). Resolution: The clarity or sharpness of the image, which helps in identifying and distinguishing lesions. It depends on the matrix size, pixel density, and image quality. Dynamic Planar Imaging: Uses high activities of 99mTc-labeled tracers. Captures rapid changes in tracer distribution (e.g., kidney studies) or moving organs (e.g., heart) through a sequence of image frames. Single Photon Emission Computed Tomography (SPECT): SPECT Tracers: Special radiopharmaceuticals used in SPECT imaging to capture detailed functional information of organs. SPECT Imaging System: A system that captures 3D images of the body using rotating gamma cameras. SPECT Image Quality and Image Properties: Refers to how clearly and accurately the images represent organ function, influenced by the tracer, the equipment, and the patient’s condition. Production of SPECT Tracers: 99mTc is one of the most common isotopes used in SPECT imaging. It is typically produced from 99Mo in generators. Step 1: Irradiation: Stable or unstable elements (like 235U) are irradiated with neutrons in a nuclear reactor. The neutrons cause 235U fission, producing 99Mo and other isotopes (e.g., 131I, 133Xe). These isotopes are separated and recovered using a chemical generator. Step 2: Generators: 99Mo is adsorbed onto an alumina (Al₂O₃) column inside a cylinder. The cylinders (known as technetium generators) are shipped to radiopharmacies and hospitals in radiation-shielded cartridges for use in producing 99mTc tracers. Technetium Generator (Tc Generator): External View: Produced by the Australian Nuclear Science and Technology Organization (ANSTO). 99mTc Radiopharmaceuticals: MIBI (Tc-99m-Sestamibi): ○ Used in myocardial perfusion imaging. ○ Diagnosis myocardial ischemia or infarction (reversible or non-reversible defects). ○ Most commonly used tracer. MDP (Tc-99m-methylene diphosphonate): ○ Used for bone scans and diagnosing bone disorders. PERT (Tc-99m-pertechnetate): ○ Used for thyroid imaging (anion solution). ECD (Tc-99m-ethylene cysteine diethylester): ○ Used in neuroimaging (brain perfusion) to assess blood flow and neural activity. SPECT Imaging: Gamma Camera System: ○ Modern SPECT scanners have two gamma camera tomographic systems mounted on a gantry. Rotational Movement: ○ Cameras rotate 360° around the patient, capturing images at equal angular spacing (projections). Step-and-Shoot Mode: Camera stops at each projection for data collection during rotation. Improved Image Quality: Reducing the camera/patient distance and using elliptical or non circular orbits improves image quality. Sensitivity Improvement: Using 2- or 3-head cameras significantly increases sensitivity. Machine Performance and Image Quality: Resolution: SPECT images have worse resolution than planar images due to count limitations. Contrast: SPECT images have improved contrast levels compared to planar images. Resolution Non-Uniformity: SPECT images show non-uniform resolution with depth. Emission vs Scattered Events: SPECT images consist of both emission (useful) and scattered (unwanted) events. Attenuation: ○ The patient’s body attenuates the emission data, affecting image quality. Pre-processing corrections are needed to be done. Attenuation Correction: 2D Data Collection: The gamma camera captures data in 2D format. 3D Distribution Issues: Calculating a 3D distribution from 2D data can be challenging. Cupping Effect: ○ Tissue near the surface of the body contributes stronger data than deeper tissue due to attenuation, causing image distortion (cupping). Correction Challenges: ○ Correcting attenuation is difficult and often assumes tissue distribution is uniform. SPECT Advantages: ○ Improved contrast ○ High sensitivity ○ Multi-planar reconstruction (like CT and MRI) ○ Dual-energy (dual-tracer) studies Disadvantages: ○ Non-uniform sensitivity ○ Slow process ○ Low photon density (low count rates) ○ Variable resolution with depth ○ Accurate attenuation correction needed Multimodality SPECT/CT: ○ Combines SPECT and CT to improve attenuation correction. CT provides an attenuation map. PET (Positron Emission Tomography): 1. PET Technique: a. A technique for imaging metabolic or functional processes in the body. 2. PET Tracers: a. Radioactive substances used to observe metabolic activity.  3. PET Imaging Principles: a. Detects radiation emitted by positron-emitting tracers. 4. PET Imaging System: a. Uses detectors to capture the signals from tracers. 5. PET Image Quality and Properties: a. High-resolution images, useful for detecting diseases like cancer. 1.PET (Positron Emission Tomography): Uses Cyclotron-Produced Isotopes: ○ Positron-emitting isotopes are used for imaging. Unique Coincidence Gamma Radiation: ○ Positron-electron annihilation creates 511-keV gamma rays (180° apart). ○ Provides self-collimation, improving detection sensitivity. ○ Simplifies attenuation correction. ○ Reduces resolution loss with depth. Advantages: ○ Superior resolution and contrast compared to SPECT. ○ Quantification of activity in the body with accurate attenuation correction. Applications: ○ Used in clinical and research settings to assess metabolic activity and disease. Positron Emission: Positrons are emitted with varying kinetic energies. Annihilation Process: Positrons eventually annihilate with electrons, forming positronium. Location of Annihilation: In soft tissue or bone, annihilation usually occurs within 1 mm of the positron's origin. This contributes to the spatial resolution of PET images. Annihilation Time: Annihilation happens within a few picoseconds (10⁻¹² seconds), the lifespan of positronium. 2.PET Tracers: PET Imaging: Uses positron-emitting isotopes of low atomic number elements like: ○ Carbon ○ Nitrogen ○ Oxygen ○ Fluorine Tracers: These elements are used to create tracers with chemical structures similar to naturally occurring biological substances. Production of PET Tracers: 1. Step 1: Produce positron-emitting isotopes in a cyclotron. 2. Step 2: Synthesize (combines) PET tracers using radiochemistry techniques. Common PET Tracer: 8F-FDG (Fluorodeoxyglucose): Analog (similar) of Glucose: 8F-FDG is similar chemical structure to glucose, gives accurate pictures of regional metabolism in brain, heart, organs, and tumors. Difference: Unlike glucose, FDG does not undergo glycolysis (not metabolized by the cells). Action: Traps FDG in cells, acting as a marker of glucose metabolism. Widely Used: FDG is the most commonly used PET tracer. Half-Life: 18F has a half-life of 110 minutes, which allows transport to hospitals with PET facilities. Applications: ○ Detects tumors and metastases. ○ Used in whole-body PET scans at sequential bed positions (~10-15 cm range) depending on the detector size of the PET scanner too! 3. PET Imaging Principles (Event Location): 3 main Requirements for Positron Imaging: 1. Distinguishing the Opposed Gamma Photons: Identify the opposed 180° gamma photons from background non-positron derived gamma photons using geometry or time of flight information. 2. Angle of Travel: Determine the path (line of response) of the detected photons. 3. Reconstruction: Create an image showing the distribution of positron-emitting activity in the scanned area. How It’s Done: a. Ring-detector geometry. b. Detector arrays: Groups of detectors pinpoint the annihilation e- e+ event location accurately. 4.PET System: Key Notes 1. Detection of Photons: ○ Positron-electron (B+ e-) annihilation produces back-to-back photons. ○ Detected using rings of detectors. 2. Line of Response (LOR): ○ The origin of photons lies on the line connecting the two detectors called line of response. 3. Coincidence Events: ○ An event is considered a coincidence when two photons are detected within a time window (6-24 ns).  4. Image Formation: ○ Coincidence events are recorded to create the image data. PET Detection System Detectors consist of scintillator crystal arrays. Interaction of the photons with the scintillator crystals create visible lights. Photomultiplier tubes attached to the crystals convert the light into an electronic signal. PET Detector Design: Key Notes 1. Block Design: Detector arrays are arranged in blocks. Each block contains scintillation crystals that detect the photons. Scintillation crystals are connected to photo-multiplier tubes (PMTs) or solid-state photo diodes to convert light into electronic signals. PET Image Reconstruction: Key Notes 1. Sinogram: Coincidence events are organized into a sinogram. ○ A sinogram shows the radial (r) and angular (q) position of each point. 2. Reconstruction Methods: uses algorithms ○ Analytical: Uses methods like Filtered Back Projection (FBP). ○ Iterative: Uses methods like Ordered-Subset Estimation Maximization (OSEM). Both methods help reconstruct the PET image from the sinogram data. Main Events in PET: 1. Types of Events: ○True Coincidence Events: Both photons detected in the correct position. ○Single Events: Only one photon detected, not a complete pair. ○Random Events: Photons detected at the wrong time or position, not related to the same annihilation. 2. Data Sorting and Correction:  ○ The image data are sorted and corrected to fix any mismatched coincidence events. Image Data Corrections in PET: Key Notes 1. Attenuation: Accounts for energy loss of 511-keV photons as they pass through the body. 2. Scattering: Accounts for energy loss of 511-keV photons due to scattering inside the body. 3. Normalization: Corrects for the uniform response of detectors in recording coincidence events. 4. Electronic Dead Time: refers to the time interval during which a detector cannot register or process new signals due to ongoing processing of previous events. Accounts for the electronic response of the detectors in recording and processing the signals. Spatial Resolution in PET: Key Notes 1. Factors Affecting Resolution: ○ Intrinsic Resolution: Size of the detector elements. ○ Photon Scattering: How photons scatter in the patient. ○ Positron Travel Distance: Distance positrons travel before annihilation. ○ Photon Emission Direction: Annihilation photons are not always emitted exactly opposite to each other. Sensitivity of PET Imaging: Key Notes PET imaging is the most sensitive diagnostic imaging technique. FDG-PET Imaging: Key Notes 18F-FDG Imaging helps in diagnosing and managing tumors by identifying: ○ Tumor site ○ Whether the tumor is malignant, benign, or scar tissue ○ The effectiveness of therapy ○ Spread of cancer (metastasis) Definition: FDG-PET Imaging is a type of PET scan that uses 18F-FDG to detect and measure tumor activity, helping in the diagnosis, treatment planning, and monitoring of cancer. FDG-PET is a type of imaging that uses fluorodeoxyglucose (FDG) to detect areas of abnormal metabolic activity, useful in diagnosing cancer and heart conditions. PET scans offer high sensitivity and resolution for assessing disease activity and tissue viability. Clinical Applications of PET: Key Notes Oncology: FDG-PET is mainly used for cancer detection. The higher aerobic glycolytic rate of most tumors means that there is a much higher uptake of FDG in malignant tumors than in normal tissues. Tumor Evaluation: PET is useful for non-invasive assessment of tumor size and grade. Necrotic Tissue: PET helps distinguish necrotic (dead or scar) tissue from active tumor growth. Differentiates recurrent tumours from necrotic tissue following radiation therapy. Cardiology: Cardiac PET advantages over SPECT: ○ Higher spatial resolution ○ More accurate attenuation correction ○ Ability to perform quantitative measurements. Regional Myocardial Flow: PET is highly sensitive for detecting coronary artery disease. Myocardial Tissue Viability: PET can determine if heart tissue is metabolically active or dead. Cardiac Viability PET Imaging: Key Notes Pioneer in Canada: The University of Ottawa Heart Institute is the leader in this technology in Canada. Purpose: PET viability imaging helps assess heart muscle damage caused by heart attack or disease. Clinical Use: It helps decide if the patient needs angiography, cardiac bypass surgery, heart transplant, or other procedures. Techniques Used: ○ 82Rb or 13N is used to map blood flow in the heart. ○ FDG is used to assess the degree of damage to heart muscle. Cardiac Viability PET Imaging is a PET scan that evaluates the health and functionality of heart tissue after damage, helping guide treatment decisions like surgery or transplants. It uses 82Rb/13N for blood flow and FDG to detect muscle damage. Neurology Central Nervous System (CNS Imaging) with PET: Key Notes PET is valuable for Brain Imaging like: ○ Regional Distribution: of cerebral blood volume (CBV) and cerebral blood flow (CBF). ○ Cerebral Metabolic Rate: Assesses glucose metabolism in the brain. Dementia Diagnosis: ○ PET is useful in diagnosing and differentiating types of dementia. ○ It helps diagnose Alzheimer's and multi-infarct dementia.  Psychiatric Disorders: PET detects functional changes in brain biochemistry linked to behavioral disorders. Epilepsy: PET identifies brain lesions (injury), aiding in the diagnosis and treatment of epilepsy. Cerebrovascular Disease (e.g vessel blockage): ○ PET helps understand conditions like transient ischemic attacks (TIA) and acute infarction. ○ Valuable for studying and tracking brain injury during these disorders. Neurology PET Imaging uses positron emission tomography to assess brain function, blood flow, and metabolism. It is crucial for diagnosing brain conditions like dementia, psychiatric disorders, epilepsy, and cerebrovascular diseases. Advantages of PET: Key Notes 1. Quantitative Measurements: PET measures functional processes in the body, such as: ○ Perfusion (blood flow) ○ Metabolism (energy use) ○ Receptors (neuroreceptors) 2. Neuroreceptor Localization: PET can localize and measure the distribution of neuroreceptors by detecting sub-nanomolar concentrations of labeled tracers. 3. Superior Spatial Resolution: PET has better spatial resolution compared to SPECT. 4. High Temporal Resolution: PET's high count rate allows dynamic imaging of processes over time. 5. Reformatted Images: PET images can be viewed in sagittal, coronal, or oblique sections. Advantages of SPECT: Key Notes 1. Longer Half-Life Radiotracers: SPECT uses radiotracers with a longer half-life, allowing longer imaging. 2. Monitoring Multiple Functions: Each SPECT tracer has its own energy, allowing multiple processes to be monitored at once (Can monitor more than one thing at a time). E.g., 99mTc (140 keV), 111In (171 keV or 245 keV). 3. Lower Cost: SPECT is less expensive compared to PET. 4. Longer Use: SPECT has been in use since the 1950s, making it a well-established technique with more studies. 5. Heart Perfusion: Heart perfusion imaging is primarily done using SPECT. PET (Positron Emission Tomography) is an imaging technique that measures functional processes like blood flow and metabolism, providing high-resolution, dynamic images. It is particularly useful for studying brain activity and disease. SPECT (Single-Photon Emission Computed Tomography) is another imaging technique that uses longer-lasting tracers, is cost-effective, and has been widely used for monitoring functions like heart perfusion. Combined Imaging Systems: Diagnostic imaging can be divided into two broad categories 1. Types of Imaging: ○ Anatomical Imaging: CT (Computed Tomography) MRI (Magnetic Resonance Imaging) ○ Functional Imaging: SPECT (Single Photon Emission Computed Tomography) PET (Positron Emission Tomography) MRI (developing for functional use) 2. Hybrid Imaging: ○ Combines anatomical and functional imaging in one system. ○ The idea of hybrid imaging systems is to incorporate two different but complementary modalities into a system that, in one single study, can produce images showing functional data mapped precisely onto the corresponding anatomy. PET/CT System: Key Notes 1. System Setup: ○ CT Components: CT X-ray tube and detectors are mounted on a rotating gantry. ○ PET Components: PET detectors are mounted on a separate gantry. ○ Both gantries share the same bore opening and are attached at a fixed distance. 2. Imaging Process: ○ The CT scanner is in the front, and the PET system is in the back. ○ The CT scan is done first, then the table is moved and then PET imaging is done. Combined Imaging Systems integrate both anatomical (CT, MRI) and functional (PET, SPECT) imaging to provide detailed images showing both structure and function. A PET/CT system combines CT's anatomical images with PET's functional data, allowing for precise mapping of body processes on anatomical structures.