Essentials of nuclear medicine

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1 Essentials of nuclear medicine

2 Medical imaging CT Rtg X- rays usg Ultrasound MR Nuclear Magnetic Resonance Nuclear Medicine SPECT PET

3 A conventional radiological, ultrasound and magnetic resonance diagnostics is of morphological character, i.e. the imaging using these modalities gives insight into the structure of human tissues and organs. As such these modalities enable detection of foci or regions of abnormal composition: the radiological image visualises differences in intensity of X-ray absorption ultrasound image reflects different echogenicity by registration of acoustic wave reflection by structures of varying acoustic resistance (impedance) imaging by magnetic resonance modality records local changes in intensity of magnetic field which occur while absorbing electromagnetic waves of radiofrequency by atomic nuclei contained in a uniform magnetic field of high intensity. The resulting image reflects spatial distribution of such atomic nuclei (mostly commonly protons nuclei of hydrogen atoms) and their chemical bounds.

4 Nuclear medicine This modality uses radionuclides (radioactive atoms) introduced into human body in form of unsealed sources of radiation (in form of radiopharmaceuticals and sometimes also in atomic form, e.g. noble gases) for purposes of diagnostics and therapy.

5 Atomic structure A Z X protons electrons neutrons A mass number a sum of protons and neutrons in an atomic nucleus Z-atomic number a number of protons in the atom of a given element

6 Isotopes Variants of the same element differing in numbers of neutrons (A) in the nucleus Hydrogen isotopes

(photons, particles) Atomic nucleus electromagnetic quanta

7 Radionuclides Atoms of elements with unstable nuclei, undergoing spontaneous decay with emission of energy (photons, particles) Atomic nucleus electromagnetic quanta (photons γ) charged particles (β electrons, positrons, α particles)

Radiations emitted as a result of radioactive decay

the body Particles (beta rays) - electrons with

8 Radiations emitted as a result of radioactive decay Photons (gamma) Penetrating the tissue and leaving the body Particles (beta rays) - electrons with negative charge - positrons with positive charge. Maximum range in tissues a few mm. alfa particles (helium nuclei). Maximum range in tissues a few tens of μm

9 Quantities characterizing the radioactive decay - Half-life time needed for decay of 50% of the initially present atoms of radionuclide. - Activity number of radioactive decays in a given sample per unit of time Unit: Becquerel (1 Bq) = 1 decay/sec 1 MBq = 10 6 Becquerel - Energy of emitted photons and particles Unit: ev electronvolt

10 Radionuclides used in nuclear medicine Diagnostics: emitters of gamma rays with half-lives from a few hours to several tens of hours, for instance: technetium - 99m Tc, iodine 131 I, 123 I, indium 111 In, thallium 201 Tl, gallium 67 Ga; emitters of positrons b + particles (PET): 18 F, 11 C, 15 O, 68 Ga, etc. Therapy: emitters of b - particles with range of a few mm, for instance: iodine I, strontium 89 Sr, samarium 153 Sm, renium 186 Re, ytrium - 90 Y, lutetium Lu (emitters of a particles under consideration experimental and clinical tests: astatine At, bismuth - 212/213 Bi)

99m Tc Medycyna Nuclear nuklearna medicine Radioactive technetium 99m Tc, (a metastable radionuclide), is the most frequently used radioisotope in nuclear medicine.

well suited to detection by scintillation camera High chemical reactivity of the element, which is prone to form complexes with a wide range of chemical compounds (ligands) Due to the fact

11 99m Tc Medycyna Nuclear nuklearna medicine Radioactive technetium 99m Tc, (a metastable radionuclide), is the most frequently used radioisotope in nuclear medicine. This is due to: low dose of radiation absorbed in a patient body (short half life of 6h, very low contribution of electrons to the energy emitted) Energy of emitted gamma rays (140 kev) well suited to detection by scintillation camera High chemical reactivity of the element, which is prone to form complexes with a wide range of chemical compounds (ligands) Due to the fact that 99m Tc atoms originate from decay of 99 Mo it can be obtained from Mo/Tc generators in every nuclear medicine lab, day by day for ab 10 days (restoration of the radioactive equilibrium between 99 Mo and 99m Tc)

12 Radiopharmaceutical This is a substance containing a radioactive atom in the molecule, which emits gamma rays that can be utilized for diagnostics or charged particles (alfa, beta minus) of very short range in tissues that may kill cells in the vicinity of deposited molecules, and therefore utilized for treatment of pathological tissue at the site of deposition or in vicinity. RF 131 I 131 I Hippuran

13 Routes of administration of radiopharmaceuticals By inhalation Per os Inj. into vertebral channel Inj. intravenously Introduction into urinary bladder Inj. intraarticularly (joints) Inj. subcutaneously

14 Functions of nuclear medicine Diagnostics Therapy Imaging (scintigraphy) Non-imaging (eg. clearances, metabolism) Static scintigraphy organs whole body } planar emission tomography SPECT emission tomography PET Dynamic scintigraphy

15 Nuclear medicine Diagnostics Imaging (scintigraphy) - image generated by emitted photons - image represents specific function of an organ (normal, pathological) - Scintigraphy: 1) static (planar or tomography) provides distribution of activity (2 or 3D), represents functional state of specific tissues, as well as localization, shape and dimensions of the organ of interest 2) dynamic by providing qualitative or quantitative data on passage of the radiopharmaceutical through a given organ. This may provide information on organ s function, e.g. flow of urine via urinary tract, kinetic behavior of the left heart ventricle, etc, etc. Resolution of scintigraphic images is inferior to that of US, X-rays or MRI.

16 A scintigraphic image (scintigram) presents distribution (2D or 3D) of the activity in a studied organ (or system); such an image reflects always a given function of the organ (normal physiological or pathological)

cancer Developing tumour destroys the tissue (including the cells of R.E.

17 Static scintigraphic image (example) External detection of radiation by means of scintillation camera provides information on distribution of administered activity in a given organ Example: static scintigraphy of the liver Liver normal image Liver cancer Developing tumour destroys the tissue (including the cells of R.E. system) In this case after administration of 99m Tc labelled colloid in the liver (distribution reflects regional phagocytic function of the reticulo-endothelial system in liver)

18 Nonimaging studies utilizing radiopharmaceuticals Investigation of distribution of radiopharmaceuticals in various compartments of the system as well as rates of the transfer between compartments, and elimination from the body (e.g. clearance rates). C p Example 99m Tc DTPA conc. in plasma diethylenetriamine pentaacetic acid time This curve can be used for calculation of glomerular filtration rate (GFR)

19 Nuclear medicine - therapy Therapy of pathologically altered cells and tissues using radiation (beta minus and alfa particles) emitted by radionuclide taken up by the cells or deposited in their vicinity (within the range of particles in question)

20 Nuclear medicine - therapy The therapy is used for treatment of: diseases of the thyroid (benign and malignant) pains due to malignant metastases into the skeleton (paliative treatment) exsudates and proliferation of the synovia in chronic arthritis of selected malignancies (receptor affinity, antibodies)

Scintigraphy Basic tool: SCINTILLATION CAMERA preamplifiers collimator electrical signals to console Gamma ray hits a scintillation crystal, causing emission of light photons by a crystal

22 Scintigraphy Basic tool: SCINTILLATION CAMERA preamplifiers collimator electrical signals to console Gamma ray hits a scintillation crystal, causing emission of light photons by a crystal (scintillations). Those photons are absorbed in photocathodes of photomultiplers releasing electrons, thus forming an electrical current, which is then amplified in photomultipliers and registered in form of electrical signals at the detector output photomultipliers photocatode scintillator (NaI(Tl) crystal) collimator (passes only gamma rays moving in a direction parallel to axes of collimator holes)

Scintigraphy Basic tool: SCINTILLATION CAMERA collimator Light photons (scintillations) scintillator Distribution of a radiopharmaceutical in a given organ is reflected in a scintillation crystal in

23 Scintigraphy Basic tool: SCINTILLATION CAMERA collimator Light photons (scintillations) scintillator Distribution of a radiopharmaceutical in a given organ is reflected in a scintillation crystal in the form of light photons. Coordinates of every flash event are noted by a special electronic system, thus enabling a 2D presentation of a distribution of a radiopharmaceutical in a patient organ. Localization of every flash event in x,y coordinates Origination of a planar scintigram

24 Digital image n 51 cm n 51 cm Komórki matrycy cyfrowej Matrix with pixels Digital images are in fact matrices of pixels, presented in colors.

25 Static scintigraphy Conditions to be met: 1. Distribution of activity in an organ must not change over the interval of image acquisition. 2. The acquisition should only start when stable activity level in an organ has been reached. Information gathered: 1. Presence or absence of regions in an organ of abnormal (reduced or enhanced) uptake of the radiopharmaceutical administered. 2. In addition, data on position, shape and magnitude of the organ are obtained

(small albumin spheres of diameters comparable to diameters of capillary arteries in

26 Normal lung perfusion scintigrams anterior mediastinum Anterior view posterior mediastinum Posterior view R silhouette L L R of heart Technetium labeled microspheres (small albumin spheres of diameters comparable to diameters of capillary arteries in lungs - in micrometers) are trapped in those arteries thus enabling imaging of lung perfusion.

Whole body static scintigraphy (skeletal scanning)

child - normal image Abnormal image: numerous

scintigraphy an image presenting bone metabolism.

27 Whole body static scintigraphy (skeletal scanning) Skeleton of an adult - normal image Skeleton of a child - normal image Abnormal image: numerous metastases to the skeleton (cancer) Bone scintigraphy an image presenting bone metabolism. Abnormal image lesions of enhanced bone metabolism at sites of cancer metastases

Single Photon Emission Computed Tomography (SPECT) Dynamic model of 3D-activity distribution reconstruction A method for presentation of a distribution of a radiopharmaceutical in 3 dimensions.

28 Single Photon Emission Computed Tomography (SPECT) Dynamic model of 3D-activity distribution reconstruction A method for presentation of a distribution of a radiopharmaceutical in 3 dimensions. Study acquisition is performed with a camera detector turning around a patient body. Then, using a special method for tomographic reconstruction, organ cuts along respective planes can be obtained.

29 Single Photon Emission Computed Tomography (SPECT) Various planes of cutting the 3D brain matrix

30 Brain SPECT perfusion study after Tc-HMPAO administration Transverse planes (cuts) From left to right and from top to the bottom: from base to the top of the brain

31 Dynamic scintigraphy The acquisition of scintigraphic information is started (usually) at the moment of i.v. injection of the RPharm. The study consist of a series of scintigraphic image acquisitions. The frequency of image acquisition depends upon the rate of the studied process.

32 Dynamic scintigraphy of the urinary system (renoscintigraphy) Serial acquisition of images takes place continuously over 20 min. (images provide information recorded over 20 minutes at 1 min intervals)

33 Renographic curves counts Left kidney Right kidney Background Ur. bladder time Counts are recorded at acquisition intervals over several regions of interest: kidneys, urinary bladder and over region representing the blood in organs background. Curves of activity in theses regions are automatically converted into renographic curves.

Principles of Positron Emission Tomography (PET) Another kind of tomography used in nuclear medicine. This modality makes advantage of radionuclides emitting positrons.

34 Principles of Positron Emission Tomography (PET) Another kind of tomography used in nuclear medicine. This modality makes advantage of radionuclides emitting positrons. As a result of a phenomenon of annihilation of positron with an electron in a patient body 2 photons appear escaping in opposite directions and they are detected in PET detector ring with a coincidence system. Positron + electron anihilation 2 photons of 512 kev each Detector Coincidence system Detector Radionuclide 18 F 15 O 11 C 13 N 82 Rb T 1/2 [min] ,1-20, ,2 Preconditions: on site production of positron emitting nuclides in a cyclotron; automatic on site synthesis of radiopharmaceuticals. Main benefits: a possibility to use for PET imaging the natural compounds (or their closely related analogues) of well understood physiological and biochemical behavior. Disadvantage: high cost

35 CLEARANCES Definition: The volume of plasma completely cleared of a specific compound (substance S) per minute and measured as a test of kidneys or liver function.

36 There is an obvious relationship between a clearance and rate of the decline of the substance (S) concentration in the plasma Sp(t) (conc. in plasma) lack of kidneys reduced function The faster decline of the curve, the higher the clearance of the substance. A clearance is calculated as a ratio of an activity administered to a patient and a definite integral of a function Sp over the interval from zero ( moment of injection) to infinity CL = I p 0 4 A 0 S (t)dt normal function (Activity of subst. S administered to a patient ) (Area under the curve presenting declining concentration of substance S in plasma) t

37 Determination of kidney and liver clearances - the selected RPhs GFR - 99m Tc DTPA ERPF I orthohipuric acid - 99m Tc MAG3-99m Tc Ethylene dicystein (EC) Cl liver - 99m Tc Hepida (derivative of an imin-bi-acetic acid) Advantages of radionuclide methods: high accuracy of determination of plasma concentrations possibility to measure CL after a single intravenous injection determination of CL is possible without collection of urine or gall low labour input required (particularly for simplified procedure, based on one sample of blood).

38 Patients care in nuclear diagnostics or therapy General information 1. Diagnostics or therapy by means of radiopharmaceuticals are in general non-invasive (there are very few exceptions e.g. intraarticular administration). 2. Majority of diagnostic procedures of nuclear medicine do not require pretreatment of the patient (there are a few exceptions). 3. Administration of a radiopharmaceutical is not followed by complications resulting from hypersensitivity (this applies also to patients hypersensitive to iodine contained in contrast media). 4. Doses to patients of ionizing radiation, resulting from diagnostic procedures are small, comparable to those accompanying most common radiological examinations. 5. Doses to the personnel injecting the radiopharmaceuticals to patients are very small if appropriate syringe shields are used and the patient has been prepared by introduction a venflon needle into his/her vein prior to injection.

Radioisotopes and PET

Radioisotopes and PET 1 Radioisotopes Elements are defined by their number of protons, but there is some variation in the number of neutrons. Atoms resulting from this variation are called isotopes. Consider