Vinayagamani S2021-03-122021-03-122019-12https://dspace.sctimst.ac.in/handle/123456789/11026Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system. Majority of the patients start with a relapsing –remitting course, which has clearly defined episode of neurologic disability and recovery. Pathologic hallmark of MS was presence of focal plaques in white and gray matter associated with heavy infiltration of macrophages with myelin debris, lymphocytes, and large reactive multinucleated astrocytes called Creutzfeldt-Peters cells1 . The etiologic mechanism underlying this demyelinating disease is generally believed to be autoimmune inflammation however the intial triggerer and the further development of CNS plaques are not well established1 . Conventional magnetic resonance imaging (MRI) has been used routinely to diagnose and monitor the disease spatially and temporally. The use of conventional MRI to measure the disease activity and assess effects of therapy is now standard in clinical practice and drug trials. T2-weighted imaging (T2WI) is highly sensitive in the detection of hyperintensities in white matter but, hyperintensities on T2WI can correspond to a wide spectrum of pathology, ranging from edema and mild demyelination to lesions in which the neurons and supporting glial cells are replaced by glial scars or liquid necrosis. In MS , gadolinium enhancement on T1-weighted imaging (T1WI) can suggest an acute inflammation, which is a marker of disease activity2,3. It is becoming a consensus among many studies that iron is enriched within oligodendrocytes and myelin in both normal and diseased tissue. One explanation for such findings proposes that iron is associated with the biosynthetic enzymes of myelinogenesis4 . In MS , stages of relapse and remission alternate during disease progression, identification and characterization of active lesions are critical for correct diagnosis and therapy. In clinical practice, current active lesion assessment is based on gadolinium (Gd) enhancement on T1-weighted MR imaging2,3. However, because Gd enhancement reflects leakage of the blood-brain barrier, it is considered as an indirect measure of inflammation that is preceded and outlasted by infiltration of immune cells. The 8 activation of resident innate immune cells may not be captured on T1WI Gd5 . In addition, concerns over repeated Gd exposure have recently been raised, as new data showing long term Gd retention in the brain of patients with normal renal function who have undergone multiple Gd injections is emerging. In patients with MS in whom Gd retention seems also to be associated with secondary progression of the disease. 6,7 Therefore it has become a necessity to identify a ‗Gd-enhancing‘ or ‗active MS‘ lesions without the use of a contrast agent to reduce scan time, cost, Gd accumulation and adverse effects. A non-contrast based imaging modality to detect active lesions also helps in routine follow up / monitoring of MS patients on therapy. It is known that microglia and macrophages in an alternative activation, M2 type macrophages (ferritin poor macrophages) remove myelin debris from MS lesions which usually accumulate in the periphery of the active lesion, 8 whereas the classic pro inflammatory M1 type macrophages (ferritin rich macrophages)- which tend to accumulate iron- was more commonly present in the chronic lesions9 . Both M1 and M2 type macrophage accumulation varies in different types of lesions which may result in change in susceptibility values and iron content in them. Susceptibility weighted imaging (SWI) has been shown to be very sensitive to iron in the form of hemosiderin, ferritin, and deoxyhemoglobin, offering the ability to measure iron on the order of several µg/g of tissue in vivo10,11. SWI is a 3D, high-resolution, fully flow compensated gradient-echo sequence that uses magnitude and phase data both separately and together to enhance information about local tissue susceptibility. In the past, phase images were seldom used because artifacts from the background field destroyed the integrity of small changes seen in pristine tissue. As we know now, phase images contain a wealth of information that may not be observed from the magnitude images. Recently, SWI-filtered phase images were used to map out putative iron content in the brain11,12. Phase images are a direct measure of the sources of local susceptibility changes. MR imaging have demonstrated 9 that, the magnetic susceptibility of an MS lesion changes rapidly as the lesion evolves longitudinally which can be measured by various iron quantification methods. Our study was designed to assess whether Quantitative SWI (Routine SWI) is a viable technique to identify active enhancing MS lesions without Gd injection. In this study, we explore the routine SWI imaging with quantification of phase values and iron content. To best of our knowledge, this is the first study , in which the routinely available SWI sequence was used for quantification of iron content in MS lesions. The goal of this study is to investigate whether the measured phase values and iron content in the lesions will differentiate active lesions from inactive lesions.enThesis