**2. Positron emission tomography in neurology**

tion of the immune system play a crucial role in the understanding of underlying mechanisms

Traditionally, CNS is considered an immunologically-privileged site, meaning the brain and spinal cord can tolerate the introduction of foreign antigens without eliciting an afferent immune response [29, 34]. Immune privilege is believed to be an active process aiming to protect the brain structures from the harming effect of an inflammation. This immune privilege is thought to be due to a lack of lymphatic drainage and the integrity of blood-brain barrier (BBB) [21]. It varies throughout the different parts of the CNS, being most pointed in the white matter. Among the other factors that also contribute to the maintenance of brain immune privilege are local production of immunosuppressive cytokines, increased expression of surface molecules inhibiting complement activation, low expression of major histocompati‐

Over the last two decades the concept of CNS as an immunologically-privileged site has been reevaluated. Today, experimental and clinical data show evidence suggesting the presence of resident CNS macrophages known as microglia [42]. Although the separation and isolation of CNS from the peripheral immune cells throughout the BBB, certain unique interactions exist due to the sequestration of neuronal antigens in "partially" immune-privilege sites, presence of antigen determinants shared by the nervous and immune systems, and secretion of immunoregulatory mediators by specific nerve cells [19, 29, 34]. Nowadays, it is known that activated lymphocytes are able to pass through the BBB regardless of their antigen specificity, directed by cytokines and adhesion molecules that are expressed on the brain endothelial cells (ICAM-1, VCAM-1) [2]. Normally, MHC class 1 and class 2 molecules are minimally expressed in the CNS, but in pathology the expression induced by proinflammatory cytokines IFN-γ is much higher. Immune surveillance in the CNS is under strong control and its major role is to provide constancy of the homeostasis in relation to the raised vulnerability of the neurons [26]. Immune tolerance is known to protect normal tissues from immune damage by prevention of immune response against a particular antigen to which the human organism is normally responsive. In the past, it was thought that the break of immune tolerance causes the produc‐ tion of autoantibodies and/or sensitized cytotoxic T-lymphocytes, attacking own tissues, the so-called autoreactive lymphocytes. Today, it is evident that these autoreactive cells normally exist in the immune system in a state of anergy and areactivity toward own antigens. Respec‐ tively, the immune tolerance is considered as a result from suppression and elimination of

It is known that autoimmunity represents an abnormal immune response directed against the cells and tissues of the organism. Autoimmune responses are considered an integral part of the immune system and present a survival self-defense mechanism. It is postulated that this aberrant immune response refers to the development of different diseases. The mechanisms of autoimmune disorders of the CNS are associated with molecular mimicry, upregulation of heat shock proteins, the release of so-called "sequestrated" antigens (brain tissue antigens hidden behind the BBB), bystander activation, and production of neoantigens [13, 42]. Most commonly T- and B-cell mediated autoimmune diseases result from the elimination and

inhibition of regulatory T-cells or the dysregulation of humoral immunity.

and treatment of immune-mediated neurological disorders [19, 37].

42 Immunopathology and Immunomodulation

bility complex (MHC) class Ia molecules, presence of neuropeptides, etc. [26].

autoreactive T-lymphocytes [2].

In recent years, a large number of scientific reports confirm the increasing influence of nuclear medicine in the diagnosis and treatment of patients with various neurological diseases [10, 23, 25, 33, 43]. Accordingly, positron emission tomography presents a modern non-invasive technique for investigation in vivo of basic biochemical processes and physiological functions of the CNS [36]. This method provides important information about the cerebral blood flow, permeability of BBB, activity of brain enzymes, and metabolism of glucose, amine and fatty acids, as well as synthesis and metabolism of neurotransmitters, gene expression and density of neuromediators receptors.

PET has a wide clinical application in the understanding of underlying mechanisms of neurological diseases, early and correct diagnosis, monitoring of clinical course and prognosis of outcome, studying of drugs pharmacokinetics and pharmacodynamics, and assessment of therapeutic response. In addition to structural neuroimaging, PET improves the diagnostic accuracy of localization, characterization, and distribution of anatomical and functional cerebral disturbances [17, 33, 36].

PET is realized through intravenous injection of radiotracer, which is a biological marker, labeled with positron emitting isotope [7]. Carbone (11C), nitrogen (13N), oxygen (15O), and fluorine (18F) are among the most frequently used in clinical practice due to their relatively short half-life (up to 110 min) and constant body spread, without prolonged radiation exposure [40].

It is well known that the human brain presents only 2% of body weight, but utilizes about 20% of absorbed oxygen and 60% of glucose, which is a major energy source for the nerve cells. Respectively, (18F)-FDG is the most appropriate radiotracer for functional study of cerebral tissue, because it reflects the level of glucose assimilation by brain neurons. 18F-Fluorodeoxy‐ glucosae - (18)FDG represents deoxyglucosae that is labeled with 18F. FDG is a glucose analogue that biodistribution fully reflects the glucose consumption of different organs and tissues [44]. Its cell's influx is realized through active transport, by means of glucose trans‐ porters in mechanisms that are similar and competing with glucose. After entering the cytosol, the molecule is phosphorylated into a stable form, which has a slower metabolism and prolonged cell's retention than glucose.

The brain tissue is characterized by high glucose activity, mainly in the cortical, thalamic, cerebellar, and basal ganglia gray matter, and relatively lower in the white matter [23]. The distribution in the cerebral cortex is not homogeneous, as the highest activities are realized in the occipital lobes.

New data support the notion that PET is a useful technique for diagnosis, planning treatment, and prognosis in various neurological diseases, including autoimmune disorders of the CNS [3, 8, 24]. By measuring brain and spinal cord metabolism, FDG-PET may demonstrate extensive regions of neurologic dysfunction in patients with multiple sclerosis (MS), immunemediated cerebellar ataxias and autoimmune limbic encephalitis [4, 10, 15, 33, 41].
