Physics of Nuclear Medicine PDF

Physics of Nuclear Medicine Physics for Biomedical Sciences Dr Irene Polycarpou How molecular imaging is performed Molecular imaging provides functional or metabolic assessment of normal tissue or disease conditions through detection of tracers administered to patients. The tracers are disease-tar...

Physics of Nuclear Medicine Physics for Biomedical Sciences Dr Irene Polycarpou How molecular imaging is performed Molecular imaging provides functional or metabolic assessment of normal tissue or disease conditions through detection of tracers administered to patients. The tracers are disease-targeted compounds involved in the pathophysiology of disease of tissue labeled by radiotracers.  5 Molecular Imaging – Nuclear Medicine Imaging Lets see the Basics of Nuclear Physics  6 Basic Nuclear Physics Atoms are the basic units of matter and the defining structure of elements. The term "atom" comes from the Greek word for indivisible, because it was once thought that atoms were the smallest things in the universe and could not be divided. An atom is the smallest unit of matter that retains all of the chemical properties of an element. What are the elementary particles of an atom? - Electrons - Protons - Neutrons  7 Basic Nuclear Physics What are the elementary particles of an atom? - Electrons - Protons - Neutrons Atoms are formed together to create molecules Matter consists of atoms  9 Basic Nuclear Physics An atom contains protons, neutrons, and electrons. The nucleus of an atom consists of bound protons and neutrons (nucleons). The negatively-charged electrons are attracted to the positively-charged protons and fall around the nucleus, much like a satellite attracted to the gravity of the Earth. The positively-charged protons repel each other and aren't electrically attracted or repelled to the neutral neutrons. The reason protons and neutrons stick together is the strong force (i.e. strong nuclear force). This is the force that holds the nucleus together and the energy associated with this force is called the binding energy.  10 Nucleus numbers representation Atomic Number: Z = number of protons in the nucleus Neutron Number: N = number of neutrons in the nucleus Mass Number: A = Z + N An element is denoted by its A and Z: 12 6 C Stable nucleus Imagine a simple nucleus composed of two protons. The two protons will be repelled from each other due to the positive charge (i.e. Electrostatic repulsion (ESR)) However, there is existence of strong force (SF) that is carried by protons and neutrons. The SF is not strong enough to overcome the ESR and this will not be a stable nucleus. To increase the SF while not increasing the ESR we need neutrons. Neutrons carry SF but not ESR. This is a stable nucleus because the strong force overcomes electrostatic repulsion  12 Stable nucleus: The strong force overcomes electrostatic repulsion The strong force (SF) is much more powerful than the electrostatic repulsion (ESR) between protons, but the particles have to be close to each other for it to stick them together. Do we have unstable nuclei ? Yes! some nuclei are unstable because of insufficient BINDING ENERGY which holds the constituent particles together Unstable nucleus example More protons than neutrons …. However this is not always the case …  14 Line of Stability The nucleus is usually stable when the number of protons equals the number of neutrons. However, this is not the case for heavy nuclei. Nuclei which lie on the stability line are stable nuclei. Nuclei divides into 2 groups: 1. STABLE nuclei have HIGH binding energies (Non-radioactive) 2. UNSTABLE nuclei have LOWER binding energies (Radioactive)  15 Line of Stability Courtesy: Richard Fernandez  16 Line of Stability Courtesy: Richard Fernandez  17 Isotopes definition Each of two or more forms of the same element that contain equal numbers of protons but different numbers of neutrons in their nuclei, and hence differ in relative atomic mass but not in chemical properties; in particular, a radioactive form of an element. Atoms with the same Z but different A. Note: Isotopes of elements can be formed by varying the number of neutrons in the nucleus.  18 Radioactive decay In unstable nuclei the strong nuclear forces do not generate enough binding energy to hold the nucleus together permanently. It is unstable nuclei that are radioactive and are referred to as radioactive nuclei and in the case of their isotopes called radioisotopes. Radioactivity is the spontaneous transformation of an unstable nucleus to a more stable one. To become more stable (lower in energy) the nucleus can decay to a more stable state with an emission of radiation or particles (or a series of both).  19 Modes of radioactive decay  20 There are several modes of radioactive decay. The four main modes are the following: 1) Alpha decay (emits alpha particle) 2) Beta decay (emits positrons or electrons) 3) Gamma decay (gamma ray produced) Medical imaging in Nuclear Medicine is only concerned with: Positrons (PET scan) Gamma rays (SPECT, gamma camera scan)  21 Alpha Decay Alpha decay: the nucleus emits a Helium-4 particle (alpha particle) Alpha decay occurs most often in massive nuclei that have too large a proton to neutron ratio. Alpha radiation reduces the ratio of protons to neutrons in the parent nucleus, bringing it to a more stable configuration. –mostly occurring for parent with Z > 82 From: http://www.lbl.gov/abc/wallchart/chapters/03/1.html  24 Beta Decay Beta decay occurs when, in a nucleus with too many protons or too many neutrons, one of the protons or neutrons is transformed into the other. Mass number A does not change after decay, proton number Z increases or decreases. Beta minus decay A neutron changes into a proton, an electron (beta particle) and a antineutrino Beta Plus decay A proton changes to a neutron, a positron (positive electron), and a neutrino –Mass number A does not change, proton number Z reduces  27 Gamma Decay A nucleus (which is unstable) changes from a higher energy state to a lower energy state through the emission of electromagnetic radiation (photons) (called gamma rays). The daughter and parent atoms are isomers. – Only gamma rays are emitted – No particles are emitted – The gamma photon is used in Single photon emission computed tomography (SPECT) From: http://www.lbl.gov/abc/wallchart/chapters/03/1.html  30 Penetration of different types of radiation Alpha particles, beta particles (Electrons, positrons) and gamma rays, x rays are IONIZING RADIATION but have different penetration. Penetration of the different types of Ionizing Radiation through human body  32 How Unstable nucleus (Radioactive atoms) are used in Medicine ??? Field of Nuclear Medicine The field of medicine that uses radioisotopes for diagnosis and therapy is Nuclear Medicine.  33 Nuclear Medicine Therapeutic  34 Nuclear Medicine Therapeutic  35 Nuclear Medicine Therapeutic  36 Nuclear Medicine Diagnostic  37 Nuclear Medicine Diagnostic  38 Radioisotopes Vs Radiopharmaceuticals A radiopharmaceutical is a molecule that consists of a radioisotope tracer attached to a pharmaceutical. After entering the body, the radio-labelled pharmaceutical will accumulate in a specific organ or tumour tissue. The radioisotope attached to the targeting pharmaceutical will undergo decay and produce specific amounts of radiation that can be used to diagnose or treat human diseases and injuries. The pharmaceutical is specific to metabolic activities (cancer, myocardial perfusion, brain perfusion) and conveys the radioisotope to specific organs, tissues or cells.  39 Administration of radiopharmaceuticals  40 What kind of radioisotopes are used in Nuclear Medicine?  41 Examples of Radiopharmaceuticals  42 Unstable nucleus (Radioactive atoms) in Medicine You need to define the amount of the radionuclide you need -- Activity of the sample The amount of radiopharmaceutical administered is carefully selected to ensure the safety of each patient. The activity defines the amount!!  43 Activity of the sample For a given radioactive sample, the activity (Α) is the number of radioactive atoms. Activities units called a Becquerel (Bq) or a Curie (Ci). decay 1Bq = 1 second 1Ci = 3.7 ´1010 Bq decay constant and varies for each radioisotope  44 Decrease of activity with time Most radionuclides do not become stable with one decay. There is usually a chain of radioactive decays that are done for the radioactive element to become stable For a given radioactive sample, the activity of the sample, number of radioactive atoms, or mass of radioactive atoms in the sample decreases exponentially with time. http://wps.pearsoned.ca/wps/media/objects/4050/4148005/i _decay_curve.gif  45 Decrease of activity with time Radioactivity decreases exponentially with time  46 Half-life The time taken for a half the nuclei to decay is a constant and is called the half-life The half-life is the time it takes for the activity of a radionuclide to decrease to ½ of its initial value. The half-life is characteristic of each radionuclide  47 Half-life The time the body retains a radiolabeled chemical may be very different from the physical half-life of the substance. The biological half-life is defined as TB and the nuclear half-life of an isolated element is defined as T1/2. TB depends on the chemistry and the physiology of the body processes. The effective half-life of a radiolabeled drug is given as: 1 1.1 = + TE TB T1 2 The effective half-life is the time it takes the body to clear ½ of the radiolabeled drug.  48 Medical Imaging  49 Nuclear Medicine Diagnostic  50 How different is Nuclear Medicine from anatomical imaging (i.e. radiography)? Nuclear medicine: injected radiopharmaceutical Gamma rays emitted from within a body (emission imaging) Imaging of functional or metabolic contrasts (not anatomic) Examples: Brain perfusion, function, Myocardial perfusion, Tumor detection (metastases)  51 How different is Nuclear Medicine from anatomical imaging (i.e. radiography)? Radiography: x rays produced by an x ray tube X-ray transmitted through a body from a outside source to a detector (transmission imaging) absorption of radiation is proportional to material density Measuring anatomic structure  52 How different is Nuclear Medicine from radiography?  53 How different is Nuclear Medicine from radiography?  54 How different is Nuclear Medicine from radiography? Imaging Modalities (non – invasive imaging techniques) RADIOGRAPHY (used for Anatomical Imaging): Visualization of body structure; can only diagnose structural abnormalities. – X-ray – Computed tomography (CT) – Magnetic resonance imaging (MRI) NUCLEAR MEDICINE (used for Molecular Imaging): Target unique tissues or cell types with specific probes with the aim to monitor and diagnose diseases, study biological processes, give information for the functionality of tissues. – Positron emission tomography (PET) – Single-photon emission computed tomography (SPECT) – Gamma camera  55 Applications of Nuclear Medicine  56 Applications of Nuclear Medicine Imaging Modalities Positron emission tomography (PET) Single-photon emission computed tomography (SPECT) Gamma camera PET SPECT Applications of Nuclear Medicine  58 Applications of Nuclear Medicine : PET PHYSICS  59 Applications of Nuclear Medicine : PET PHYSICS A positron emitter is injected into the patient A positron is emitted and travels a few mm before encountering an electron. The electron-positron pair annihilates and to conserve momentum and energy produces two high energy gamma rays at almost 180o from each other. The two 511 keV photons are detected coincidently. Two 511 keV photons 18O 18F p n Unstable nucleus electron-positron A positron is pair annihilates emitted  60 Applications of Nuclear Medicine : PET PHYSICS The two 511 keV photons are detected coincidently using a coincidence detection circuit Therefore, PET scans make use out of coincident coupled gamma rays from the annihilation of positron-electron pairs. decay path ν γ γ photon detection β+ β- photon detection annihilation Miller, P. W., et al., Angew. Chem. Int. Ed. 2008, 47, 8998-90  61 Applications of Nuclear Medicine : PET Imaging procedure  62 Applications of Nuclear Medicine : PET Imaging procedure Gamma ray detectors surround the patient. and detect the coincident gamma rays. The detected gamma rays give spatial information about the active metabolic site. PET scans do not give anatomical information only metabolic activity in a given area.  65 Applications of Nuclear Medicine : Gamma camera, SPECT physics  66 Applications of Nuclear Medicine : Gamma camera, SPECT physics  67 Applications of Nuclear Medicine : SPECT imaging procedure Applications of Nuclear Medicine : SPECT imaging procedure Applications of Nuclear Medicine : SPECT Vs PET Applications of Nuclear Medicine : SPECT Vs PET  75 Nuclear Medicine Diagnostic Hybrid systems Examples: - SPECT/CT, SPECT/MRI - PET/CT, PET/MR Hybrid imaging denotes image acquisitions on systems that physically combine complementary imaging modalities A combined, or hybrid, tomograph such as SPECT/CT or PET/CT can acquire co-registered structural and functional information within a single study. The data are complementary allowing CT to accurately localise functional abnormalities and SPECT or PET to highlight areas of abnormal metabolism. emerging dual modality imaging techniques with many established and potential clinical applications in the field of oncology. SPECT/CT co-registration often provides complementary diagnostic information. Collection of both sets of imaging data (PET and CT or SPECT and CT) in the same exam increases the diagnostic accuracy - SPECT/CT - SPECT/CT - SPECT/CT - PET/CT - PET/CT PET Vs SPECT in cancer management For the evaluation of biological processes using radioisotopes, there are two competing technologies: SPECT and PET. Both are tomographic techniques that enable 3D localization and can be combined with CT for hybrid imaging. PET–CT has clear technical superiority including superior resolution, speed and quantitative capability. PET–CT is also changing the paradigm of imaging from lesion measurement to lesion characterization and target quantification, supporting a new era of personalized cancer therapy. The efficiency and cost savings associated with improved diagnosis and clinical decision-making provided by PET–CT make a cogent argument for it becoming the dominant molecular technique in oncology. A PET study consists of: 1) Producing radiotracers 2) Synthesizing radiopharmaceuticals from the tracers 3) Administering the radiopharmaceutical to a patient 4) Measuring the resulting radioactivity distribution in an organ of interest. 5) Interpreting activity distribution as a function of physiologic parameters. Methods of PET quantification in oncology 1. Qualitative: By visual inspection of PET images 2. Semi-quantitative: By estimation of the SUV 3. Quantitative: By analysis of kinetic modelling PET image quantification enables to ascertain a direct link between the time-varying activity concentration in organs/tissues and the fundamental parameters portraying the biological processes at the cellular level being assessed PET quantification with estimation of SUV Tumor segmentation Interpretation of tumor changes (through SUV) during therapy PET/CT in cancer management Where anatomy meets function. Better than PET or CT alone More accurate staging Improved confidence Guided biopsy with Imaging Gold standards PET/CT-guided biopsy is also feasible and may optimize the diagnostic yield of image- guided interventions. Guided biopsy with Imaging PET/CT-guided biopsy ADVANTAGES over gold standards. - PET imaging Various tracers and probes are available Why PET-CT?