In Vivo diagnostics

Principle of examination

In the in vivo examination, a suitable chemical substance with a bound radionuclide, called a radiopharmaceutical (RAF), is injected into the body. This substance enters the metabolism and is distributed in the body according to the pharmacokinetics of the radiopharmaceutical. Nuclear medicine uses different types of radiopharmaceuticals with affinities, e.g. to kidney, bone, lung, thyroid, heart, liver, certain inflammatory or tumour tissues for which the substance is an indicator. The degree of local accumulation depends on the intensity of local metabolic and functional processes in organs and tissues, and possible disturbances can be localised and quantified (curves, accumulation ratios, magnitude…). In this way, physiological, biochemical and pathological processes in the body are studied in a non-invasive way. RAF injected into the body emits gamma radiation, which is only partially absorbed by the body. This penetrating gamma radiation passes through the tissue and out of the body, where it is registered by scintillation detectors placed close to the body, allowing a planar or spatial image to be obtained (SPECT – Single Photon Emission Computed Tomography – gamacamera).

Scitigraphic examinations are one of the types of imaging methods used in medical diagnostics, which are divided into static and dynamic according to the nature of the process. Static (localization) scans are performed with a time interval (minutes, hours, days) after the application of RAF, whereby the selected area of interest is scanned for a certain period of time (they are mainly used to show the shape, size, location, but also the function of the examined organ and to detect bearing processes, i.e. anomalies of shape, size and localization, also detection of post-inflammatory residual changes and expansive foci), while dynamic ones are started immediately after RAF application (a series of gammagraphic images are acquired at certain time intervals, the time course of RAF over a certain organ or body region is recorded). Dynamic methods are mainly used to assess the function of the organ under investigation.

RAF is most commonly administered intravenously, other routes of administration are inhalation, intradermal, oral, intrathecal. RAF is mainly eliminated from the body by the kidneys and urine.

A separate field of nuclear medicine is the therapy of certain malignant and benign diseases, where the radioactive substance – beta-emitter or mixed beta/gamma-emitter – is injected in the form of a solution into the vicinity of the cells to be irradiated. Because beta radiation has a range of only a few millimetres in the tissue, virtually all the energy is absorbed in the target lesion. Therapy with nuclear medicine methods is used for the treatment of differentiated thyroid carcinomas, thyrotoxicosis, palliative treatment of bone metastases, radiation synoviorthesis, therapy of follicular lymphoma with labelled monoclonal antibodies.

Types of examinations

Perfusion scintigraphy of myocardium stress and resting by gated SPECT method – after intravenous administration of radiopharmaceutical its uptake by myocardial cells occurs. The uptake is directly proportional to the perfusion in the myocardial area at the time of application. Accumulation of the radiopharmaceutical does not occur in necrotic or scarred areas of the myocardium. In ischaemic areas, accumulation is reduced. The examination is performed in two phases, first a stress phase and then a rest phase. Their comparison evaluates the presence of reversible or fixed defects of radiopharmaceutical accumulation. These are indicative of ischaemic or necrotic deposits in the myocardium or postinfarction scarring.

Radionuclide ventriculography (MUGA scan) – imaging of the cardiac cavities using circulating labelled autologous erythrocytes in the bloodstream. Quantification of the recording makes it possible to determine the ejection fraction of the left ventricle, the ejection fraction of the right ventricle. 

Perfusion scintigraphy of the lungs ( + SPECT) – this is the imaging of the distribution of pulmonary capillary perfusion and the detection of blood flow disturbances through the pulmonary vasculature. RAF is picked up in well-perfused areas and conversely does not reach poorly perfused areas.

Pulmonary ventilation scintigraphy – This is the imaging of the distribution of pulmonary alveolar ventilation and the detection of pulmonary ventilation disturbances. The radiopharmaceutical is inhaled as an aerosol using a mask. The examination complements perfusion scintigraphy of the lungs and increases the specificity of the examination.

Dynamic scitigraphy of the kidneys – the method allows for a functional-morphological examination of the kidneys. On the basis of the administered RAF, perfusion, filtration and excretion into the hollow system are monitored, outflow parameters, separated renal function (the share of the left and right kidneys in the total function) and total glomerular filtration are assessed.

Static renal scintigraphy ( + SPECT) – RAF is accumulated and fixed for a certain period of time in the cells of the proximal tubules of the kidneys depending on their functional status, which allows to visualize the state of the functional renal parenchyma, to assess the localization, shape and size of the kidneys, to calculate the separated function and to detect focal lesions.

Dynamic renal scintigraphy with captopril test – the examination is indicated in patients with hemodynamically significant stenosis of the renal artery or its branch with probable renovascular hypertension. The principle of the examination is to compare the parameters evaluated during dynamic renal gammagraphy performed after ACEI administration (captopril study) and those obtained under basal conditions (basal study). The examination is performed on 2-fold. The captopril study is performed first. If the captopril study is negative, the likelihood that the patient has renovascular hypertension is low and there is no need to perform a basal study. If pathological findings are found, the study is repeated without administration of captopril.

Dynamic renal scintigraphy with furosemide test – intravenous application of furosemide during dynamic renal scintigraphy is used to monitor the renal response to its administration. In non-obstructive hydronephrosis, there is a runoff of retinated urine and a decrease in the renographic curve after administration of furosemide (a diuretic).

Whole-body scintigraphy of the skeleton, three-phase scintigraphy of a part of the skeleton, SPECT of a part of the skeleton – the distribution of osteotropic RAF in the skeleton, which accumulates to an increased extent in areas with high metabolic activity, is displayed… The examination has a high sensitivity, but low specificity.

Perfusion scintigraphy of soft tissues – The examination is used for detection of focal processes in soft tissues (muscles, joints) and for determination of their metabolic activity. Radioactive pertechnenate (99mTc O4- ) accumulates at an increased rate in areas of hyperaemia and with increased metabolic activity.

Thyroid scintigraphy – administered pertechnetate (99mTc O4- ) accumulates in the thyroid gland (Tg). Scintigraphy of the thyroid gland provides a functional-morphological image of the thyroid tissue, its size, shape and localization are assessed; it allows detection of foci with reduced accumulation (cold nodes – cysts, tumors…), or foci with increased accumulation of RAF (warm nodes -hyperfunctional tissue).

Parathyroid scintigraphy – RAF that accumulates in the parathyroid glands also accumulates in the thyroid gland. Therefore, subtraction or biphasic scintigraphy is used. In the subtraction method, 99mTc-Myoview is first applied, after 20 min the thyroid gland is scanned together with the parathyroid glands, then pertechnetate is applied, and after 15 min the parathyroid gland is scanned. The thyroid gland is imaged; subtraction of the images yields an image of the parathyroid glands (if enlarged); biphasic scintigraphy takes advantage of the observation that 99mTc-Myoview is more rapidly cleared from thyroid tissue than from hyperplastic tissue or parathyroid adenoma. Acquisition images are obtained at 20-30 min and then at approximately 2 h after RAF application.

Scintigraphy of endocrine and neuroendocrine tumors and tumors arising from the neural tube – The radiopharmaceutical 123I-MIBG (noradrenaline analogue) accumulates in catecholamine secretory granules of neuroendocrine tissues. Omni-radiation is indicated in suspected adrenal medullary hyperplasia, pheochromocytoma/paraganglioma, malignant pheochromocytoma, neuroblastoma, medul. thyroid carcinoma, and others. 99mTc – Tektrotyd is used to image GEP tumors with increased density of somatostatin receptors.

Cholescintigraphy – the examination allows to evaluate the hepatobiliary system, the patency of the bile ducts and the function of the gallbladder; it provides information about the size, shape and location of the liver, the location and size of the gallbladder and the morphology of the bile ducts… The administered RAF is taken up by the hepatocytes and its excretion into the bile ducts and its passage through the ductus choledochus into the duodenum is monitored. To stimulate gallbladder emptying, a fatty diet (dark chocolate, cheese) is given during the examination. If necessary, a static scan is performed in 2-4 hours.

Static scintigraphy of the liver and spleen ( + SPECT) – The administered RAF is taken up by Kupffer cells in the liver (reticuloendothelial system – RES). RES cells phagocytose labelled radionuclides. Due to the presence of RES cells also in the spleen, we obtain an image of the liver together with the spleen. To assess changes in size, shape and distribution of activity, we obtain 5 projections, which allow us to evaluate the liver/spleen activity ratio, their length, cold foci (hyperplastic nodules, fibrous tissue), sites of increased activity….

Scintigraphy of Meckel’s diverticulum – Meckel’s diverticulum is a relatively common malformation, occurring in about 2% of the population. In 20%, it contains functional ectopic gastric mucosa that uptakes the radiopharmaceutical 99mTc O4- and can be visualized gammagraphically (localized increase in activity).

Salivary gland scintigraphy – this is a functional and morphological examination of the salivary glands based on their ability to uptake 99mTc O4- from the bloodstream. It is performed as a dynamic study during which lemon juice is orally administered to stimulate salivary secretion.

After intradermal application into the interstitial space of the lower or upper limb, the radioactive colloid is transported by lymphatic vessels to the lymph nodes, which allows imaging of the lymphatic system in the respective catchment area (retroperitoneal, axillary, cervical, parasternal or iliopelvic). We take static images at rest and afterload (gesture: most commonly walking).

Sentinel node evidence – the sentinel lymph node is the first sentinel lymph node to receive lymphatic drainage directly from the tumor. The aim of this method is to determine the number and location of these nodes. Subsequently, an operative biopsy and histology are performed. If the sentinel lymph node does not contain metastatic cells, the other LUs in the catchment area do not have them either. The examination is mainly used in malignant melanoma and breast cancer. It is also used in cervical cancer. The sentinel lymph node is demonstrated peroperatively using a special probe, therefore, possession of this probe at the time of surgery is a prerequisite for performing this examination.

Scintigraphic imaging of dopamine transporters in the basal ganglia (striatum) of the brain is evaluated using 123I-labeled ioflupane : 123I-FP-CIT ( DaTSCAN ©). Prior to the examination, we block the accumulation of free 123I in the thyroid gland by administering perchlorate. After i.v. application of DaTSCAN© (usually 185 MBq), the injected substance accumulates in the striatum for about 3-4 hours. This is followed by a SPECT scan of the brain lasting about 45 minutes. The patient lies motionless on his back.  The scintigram is assessed visually, quantitatively or semi-quantitatively using ROI techniques for the nucleus caudatus and putamen. The indication is the differential diagnosis of movement disorders with deficit (Parkinson’s disease, parkinsonian symdromes) and without dopamine transporter deficit ( mainly essential tremor).

Preparing patients for examination

Most nuclear medicine examinations do not require special preparation for the examination. In special cases where special preparation is needed, the patient is informed about the method of preparation at the time of the appointment (most often it is an examination that needs to be performed fasting, or after good hydration, after skipping a certain group of drugs, after using laxatives….). These specific conditions of the examination are indicated for each of the methodologies performed in our department.

Contraindication to examinations

Contraindications to the examination are absolute and relative. An absolute contraindication is pregnancy, and a relative one is breastfeeding a child.

Examinations of pregnant women should be carefully considered as the radiation burden to the unborn child poses a certain risk. An examination should only be performed if the risk of not making a correct diagnosis for the pregnant woman is greater than the radiation burden to the foetus. If the patient is uncertain about her pregnancy, the examination should be postponed until after the next menstrual period or after delivery, in collaboration with the referring physician.

If the patient is breastfeeding a young child, breastfeeding should be discontinued for 12-24 hours after the nuclear medicine examination. In the case of RAF with a longer half-life, the patient will be specifically informed about the length of the interruption.

Instructions before the examination

The patient is referred to nuclear medicine by a specialist physician. For in vivo examinations, the patient himself is examined by administering a small amount of radiopharmaceutical (RAF). A radiopharmaceutical is a chemical substance with bound radioactivity that is taken up in the organ under investigation and allows its imaging. The radiation dose to the patient is similar and in most cases several times lower than that of a conventional X-ray examination. The examination is non-invasive, painless.
On arrival for the examination, the patient reports to the attending staff member, gives him/her the examination request form (if any), the insurance card and follows the instructions of the attending staff member. He/she waits in the waiting room for his/her examination. The administered radioactive substance is usually excreted from the body biologically, so it is necessary to increase drinking and urinate more frequently on the day of the examination. On arrival at the outpatient clinic, each patient is instructed in the diagnostic procedure, informed of the possible risks and signs the so-called Informed Patient Consent. Pregnancy is a contraindication to the examination. Breastfeeding mothers should discontinue breastfeeding for 12-24 hours. Different examinations have different time sequences and are performed on different machines, so you may find that the arrival time sequence of individual patients is not followed. This is due to the nature of the examination and the busy nature of the equipment available. Priority is given to patients with serious medical conditions where appropriate.
Most workplace examinations do not require any special preparation, so you are allowed to eat, drink fluids or take your regular medication. The results of the examination are sent to the referring physician within a week (but most often within two working days). However, personal collection is also possible by arrangement with the examining nuclear medicine physician. For the staff of the University Hospital in Prešov, the results are available in electronic form and are also sent by internal mail. For other workplaces, the results are sent daily via Slovak Post. If necessary, it is possible to hand the result directly to the patient or to make a duplicate.