Positron Emission Tomography

Positron emission tomography (PET) is a method of intravital study of the metabolic and functional activity of body tissues. The method is based on the phenomenon of positron emission, observed in the radiopharmaceutical introduced into the body with its distribution and accumulation in various organs. In neurology, the main point of application of the method is the study of the metabolism of the brain in a number of diseases. Changes in the accumulation of nuclides in any area of the brain suggest a violation of neuronal activity.

[1], [2], [3], [4], [5], [6]

Indications for positron emission tomography

Indications for positron emission tomography is the analysis of myocardial hibernation in patients who need coronary artery bypass grafting and transplantation or heart transplantation and an analysis of the differentiation of metastasis from necrosis and fibrosis in enlarged lymph nodes in patients with cancer. PET is also used to evaluate pulmonary nodules and determine whether they are metabolically active, diagnosing lung cancer, neck cancer, lymphoma and melanoma. CT can be combined with positron emission tomography to correlate morphological and functional data.

Preparation for Positron Emission Tomography

PET is administered on an empty stomach (the last meal is 4-6 hours before the test). The duration of the study is 30 to 75 minutes, depending on the volume of the procedure. For 30-40 minutes, necessary for inclusion of the injected drug in the metabolic processes of the body, patients should be in conditions that minimize the possibility of motor, speech and emotional activity in order to reduce the likelihood of false positive results. For this, the patient is placed in a separate room with soundproof walls; the patient lies with closed eyes.

Alternative methods

Some alternative methods of functional neuroimaging, such as magnetic resonance spectroscopy, single-photon emission CT, perfusion and functional MRI, may serve as an alternative to PET.

[7], [8], [9], [10], [11], [12], [13]

Single-photon emission tomography

A less expensive variant of the radioisotope study of the intravital structure of the brain is a single-photon emission computed tomography.

This method is based on recording the quantum radiation emitted by radioactive isotopes. In contrast to the PET method, single-photon emission computed tomography uses elements that are not involved in the metabolism (Tc99, TI-01), and not pairs but single quanta (photons) are recorded using a rotating y-camera around the object.

One of the modifications of the single-photon emission computed tomography method is the visualization of local cerebral blood flow. The patient is allowed to inhale a gas mixture containing xenon-133, which dissolves in the blood, and using a computer analysis, a three-dimensional picture of the distribution of photon emission sources in the brain with a spatial resolution of about 1.5 cm is constructed. This method is used, in particular, cerebral blood flow in cerebrovascular diseases and with different types of dementia.

Evaluation of results

Evaluation of PET is carried out by visual and semi-quantitative methods. Visual assessment of PET data is carried out using both black and white, and various color scales, which allow to determine the intensity of accumulation of radiopharmaceutical in various parts of the brain, to identify foci of pathological metabolism, to assess their localization, contours and sizes.

In semi-quantitative analysis, the ratio of the accumulation of the radiopharmaceutical between two equally large regions is calculated, one of which corresponds to the most active part of the pathological process, the other to the unchanged contralateral region of the brain.

The use of PET in neurology can solve the following problems:

• to study the activity of certain zones of the brain upon presentation of various stimuli;
• conduct early diagnosis of diseases;
• To perform differential diagnosis of pathological processes similar in clinical manifestations;
• predict the course of the disease, evaluate the effectiveness of the therapy.

The main indications for using the technique in neurology are as follows:

• cerebrovascular pathology;
• epilepsy;
• Alzheimer's disease and other forms of dementia;
• degenerative diseases of the brain (Parkinson's disease, Huntington's disease);
• demyelinating diseases;
• a tumor of the brain.

[14], [15], [16], [17], [18], [19], [20], [21], [22], [23]

Epilepsy

PET with 18-fluorodeoxyglucose makes it possible to detect epileptogenic foci, especially with focal epilepsy, and to assess the metabolic disturbances in these foci. In the inter-epileptic period, the zone of the epileptogenic focus is characterized by glucometabolic hypometabolism, and the region of reduced metabolism in many cases significantly exceeds the size of the focus, which are established using structural methods of neuroimaging. In addition, PET can detect epileptogenic foci even in the absence of electroencephalographic and structural changes, it can be used in the differential diagnosis of epileptic and non-epileptic attacks of loss of consciousness. Sensitivity and specificity of the method significantly increase with the combined use of PET with electroencephalography (EEG).

At the time of epileptic seizure, an increase in regional glucose metabolism in the epileptogenic focus area is observed, often in combination with suppression in another area of the brain, and after the attack, hypometabism again registers, the severity of which begins to decrease reliably after 24 hours from the moment of seizure.

PET can also be used successfully when deciding the question of indications for surgical treatment of various forms of epilepsy. Preoperative assessment of localization of epileptic foci gives the opportunity to choose the optimal treatment tactics and to make a more objective forecast of the outcomes of the proposed intervention.

[24], [25], [26], [27], [28], [29], [30], [31], [32]

Cerebrovascular pathology

In the diagnosis of ischemic stroke, PET is considered as a method of determining a viable, potentially recoverable brain tissue in the ischemic penumbra, which will help clarify the indications for reperfusion therapy (thrombolysis). The use of ligands of central benzodiazepine receptors serving as markers of neuronal integrity makes it possible to clearly delimit irretrievably damaged and viable brain tissue in the ischemic penumbra in the early stage of a stroke. It is also possible to conduct differential diagnosis between fresh and old ischemic foci in patients with repeated ischemic episodes.

[33], [34], [35], [36], [37], [38], [39], [40]

Alzheimer's disease and other types of dementia

In the diagnosis of Alzheimer's disease, the sensitivity of PET is 76 to 93% (an average of 86%), which is confirmed by the materials of the autopsy study.

PET in Alzheimer's disease is characterized by a pronounced focal decrease in cerebral metabolism, mainly in the neocortical associative areas of the cortex (posterior waist, temporomandibular and frontal multimodal cortex), and changes are more pronounced in the dominant hemisphere. At the same time, the basal ganglia, thalamus, cerebellum and cortex, which are responsible for primary sensory and motor functions, remain relatively preserved. The most typical for Alzheimer's disease is bilateral hypometabolism in the temporomembrane regions of the brain, which in advanced stages can be combined with a decrease in metabolism in the frontal cortex.

Dementia due to cerebrovascular disease is characterized by a predominant lesion of the frontal lobes, including the waist and upper frontal gyrus. Also, patients with vascular dementia usually show "spotted" areas of reduced metabolism in white matter and the cortex, often suffer from the cerebellum and subcortical structures. With frontotemporal dementia, a decrease in metabolism in the frontal, anterior and medial divisions of the temporal cortex is revealed. In patients with dementia with Levi bodies, a bilateral temporal parietal metabolic deficit is noted, reminiscent of the changes in Alzheimer's disease, but often the occipital cortex and cerebellum, which are usually intact in Alzheimer's dementia, are involved.

Pattern of metabolic changes in various conditions accompanied by dementia

Etiology of dementia	Zones of metabolic disorders
Alzheimer's disease	The defeat of the parietal, temporal and posterior cingulate cortex occurs first of all with relative preservation of the primary sensorimotor and primary visual cortex and with the preservation of the striatum, thalamus and cerebellum. In the early stages, the deficiency often manifests itself asymmetrically, but the degenerative process eventually manifests itself bilaterally
Vascular dementia	Hypometabolism and hypoperfusion in the affected cortical, subcortical areas and the cerebellum
Dementia of the frontal type	The frontal cortex, anterior parts of the temporal cortex, the midtemporal parts suffer first with an initially higher severity of lesion than the parietal and lateral temporal cortex, with relative preservation of the primary sensorimotor and visual cortex
Houteon Huntington	The horsetail and lenticular nuclei are previously afflicted with a gradual diffuse involvement of the cortex
Dementia in Parkinson's Disease	Disturbances characteristic of Alzheimer's disease, but with a more preserved mediamotoral area and lesser visual cortical integrity
Dementia with Levy bodies	Disturbances typical of Alzheimer's disease, but with less safety of the visual cortex and, possibly, the cerebellum

 The use of PET as a predictor of the development of Alzheimer's-type dementia is promising, especially in patients with mild to moderate cognitive impairment.

At present, attempts are being made with PET to study in vivo cerebral amyloidosis, using special amyloid ligands, for the purpose of preclinical diagnosis of dementia in persons with risk factors. The study of the severity and localization of cerebral amyloidosis also makes it possible to reliably improve the diagnosis in different stages of the disease. In addition, the use of PET, especially in dynamics, makes it possible to more accurately predict the course of the disease and objectively evaluate the effectiveness of the therapy.

[41], [42], [43], [44], [45]

Parkinson's disease

PET with the use of a specific ligand B18-fluorodepa allows for Parkinson's disease to quantify the deficit of synthesis and storage of dopamine within the presynaptic striatal terminals. The presence of characteristic changes allows already in the early, sometimes preclinical stages of the disease to establish a diagnosis and organize the implementation of preventive and curative measures.

The use of PET allows differential diagnosis of Parkinson's disease with other diseases, in the clinical picture of which there is extrapyramidal symptoms, for example, with multisystem atrophy.

To assess the state of the dopamine receptors themselves, one can use PET with a ligand of H ₂ receptors with raclopride. In Parkinson's disease, the amount of presynaptic dopaminergic endings and the amount of dopamine carrier in the synaptic cleft decreases, while in other neurodegenerative diseases (for example, in multisystem atrophy, progressive supernuclear paralysis and corticobasal degeneration), the number of dopamine receptors in the striatum decreases.

In addition, the use of PET allows you to predict the course and rate of disease progression, evaluate the effectiveness of ongoing drug therapy, and help in determining indications for surgical treatment.

Huntington's chorea and other hyperkinesis

The results of PET with Huntington's chorea are characterized by a decrease in glucose metabolism in the region of caudate nuclei, which makes it possible for preclinical diathesis of diseases in people who have a high risk of developing the disease as a result of DNA research.

In torsion dystonia with PET with 18-fluorodeoxyglucose, a decrease in the regional level of glucose metabolism in the tail and lentiform nuclei, as well as in the frontal projection fields of the medodorsal thalamic nucleus with a preserved overall metabolic rate, is revealed.

Multiple sclerosis

PET with 18-fluorodeoxyglucose in patients with multiple sclerosis demonstrates diffuse changes in brain metabolism, including in gray matter. The revealed quantitative metabolic disturbances can serve as a marker of disease activity, as well as reflect pathophysiological mechanisms of exacerbation, help in predicting the course of the disease and evaluating the effectiveness of the therapy.

Tumors of the brain

CT or MRI allows you to obtain reliable information about the localization and extent of tumor damage to the brain tissue, but it does not fully allow for a high-precision differentiation of a benign lesion from a malignant one. In addition, the structural methods of neuroimaging do not have sufficient specificity to differentiate relapse of the tumor from radiation necrosis. In these cases, PET becomes the method of choice.

Along with 18-fluorodeoxyglucose, other radiopharmaceuticals are used to diagnose brain tumors, for example ¹¹ C-methionine and ¹¹ C-tyrosine. In particular, PET with ¹¹ C-methionine is a more sensitive method of detecting astrocytomas than PET with 18-fluorodeoxyglucose, and it can also be used to evaluate low-grade tumors. PET with ¹¹ C-tyrosine allows to differentiate a malignant tumor from benign brain lesions. In addition, high- and low-grade brain tumors show different kinetics of absorption of this radiopharmaceutical.

At present, PET is one of the most highly accurate and high-tech research for the diagnosis of various diseases of the nervous system. In addition, this method can be used as a study of the functioning of the brain in healthy people for research purposes.

The use of the method due to inadequate equipment and high cost remains extremely limited and available only in large research centers, but the potential of PET is quite high. Extremely promising is the introduction of a technique that involves the simultaneous execution of MRI and PET with subsequent alignment of the images, which will allow obtaining a maximum of information on both structural and functional changes in different parts of the brain tissue.

What is positron emission tomography?

Unlike standard MRI or CT, primarily providing an anatomical image of the organ, PET assesses functional changes at the level of cellular metabolism that can be recognized already in the early, preclinical stages of the disease, when the structural methods of neuroimaging do not reveal any pathological changes.

PET uses a variety of radiopharmaceuticals labeled with oxygen, carbon, nitrogen, glucose, i.e. Natural metabolites of the body, which are included in the metabolism together with their own endogenous metabolites. As a result, it becomes possible to evaluate the processes taking place at the cellular level.

The most common radiopharmaceutical used in PET is fluorodeoxyglucose. Of the most commonly used radiopharmaceuticals for PET, ¹¹ C-methionine (MET) and ¹¹ C-tyrosine can also be mentioned .

The radiation load at the maximum dose of the injected drug corresponds to the radiation load received by the patient with chest x-ray in two projections, so the study is relatively safe. It is contraindicated for people suffering from diabetes, with a sugar content of more than 6.5 mmol / l. Contraindications include pregnancy and lactation.