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Identifier 000432412
Title Multi-parametric analysis of quantitative indexes, using different non-conventional MRI techniques in a study related to patients with Multiple Sclerosis and Clinically Isolated Syndrome / Κοντοπόδης ελευθέριος.
Alternative Title Πολυπαραμετρική ανάλυση των ποσοτικών δεικτών διαφορετικών μη συμβατικών τεχνικών μαγνητικής τομογραφίας στη μελέτη των ασθενών με σκλήρυνση κατά πλάκας και κλινικά μεμονωμένο σύνδρομο
Author Κοντοπόδης, Ελευθέριος
Thesis advisor Παπαδάκη, Εφροσύνη
Μαριάς, Κώστας
Ζαγανάς Ιωάννης
Abstract Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), commonly affecting young adults. Although the etiology of MS is largely unknown, it is considered primarily an autoimmune disease, in which activated myelin-specific T-cells migrate from the periphery to the CNS, by crossing the blood brain barrier (BBB), and induce inflammatory demyelinating lesions. Recent studies, involving the quantitative analysis of perfusion MRI data, emphasized the crucial role of BBB dysfunction in the pathogenesis of MS. However, the quality of perfusion MR imaging data and post-processing techniques highly influence the accuracy and precision of the derived quantitative maps. As a result, design of imaging protocols and analysis methods dedicated to the needs of specific pathologies are of great importance in clinical practice. The main objective of this dissertation is to provide a robust research methodology for applying MR perfusion protocols in MS and CIS patients. For this purpose, the following research methodology was developed: 1) A novel Dynamic Contrast Enhanced (DCE) T1 perfusion MRI protocol was designed. This novel protocol tripled the time of perfusion observation, by minimally extending the MR acquisition time. Due to the extra cost for a commercial Pharmacokinetic (PK) analysis software and the inability to modify the existing computational platforms to process newly developed protocols, an in-house PK analysis computational tool was also developed. 2) The in-house computational software was validated in a cohort with breast cancer, by predicting the therapy outcome at baseline and in the early stages of treatment. Results indicated that the aforementioned quantitative analysis software platform was able to predict the neoadjuvant chemotherapy (NAC) response at baseline and in the early treatment stages. The best pathological complete response (pCR) predictors at first follow-up, achieving high AUC and sensitivity and specificity more than 50%, was the median value of transfer constant from extracellular - extravascular space (EES) to the plasma space, kep (AUC 73.4%), while the 80th percentile of the fractional volume of EES, ve, achieved the highest pCR prediction at baseline with AUC 78.5%. 3) Both the novel time extended (Snaps) and the conventional Dynamic Contrast Enhanced (DCE) protocols were applied in a cohort of MS patients to investigate several protocol and PK analysis factors for the accurate quantification of active demyelinating lesions. According to the results of these studies, Snaps protocol achieved better quantification of the active lesions, by detecting 49% more enhancing pixels on average, compared to the conventional DCE protocol. Furthermore, through an extensive comparative analysis it was demonstrated that extended Tofts model (ETM) was the best PK model for active MS and CIS lesion quantification. 4) The novel time extended and the conventional DCE protocol, were applied in a cohort of MS and CIS patients to quantify PK parameters, such as the volume transfer constant from plasma space to EES (ktrans) and the fractional volume of vascular space (vp) values, of NAWM areas and demyelinating lesions. The PK parameters stemming from the proposed time extended protocol, achieved more accurate characterization of the different lesion types, and better discrimination from NAWM compared to the conventional DCE protocol. 5) Although cognitive impairment is common in MS its underlying pathophysiology is largely unknown, while conventional MRI techniques do not provide strong correlations with clinical variables or neuropsychological deficits. For this purpose, this dissertation examined the correlation of DCE derived PK parameters with several clinical variables, such as illness duration and the expanded disability status scale (EDSS), in MS and CIS patients. Preliminary results from a subgroup of patients, indicate moderate correlations between ktrans in frontal, parietal and occipital NAWM and EDSS. Even more, strong correlations were found between permeability values in NAWM areas and scores on verbal and delayed retention indices, as well as with semantic verbal fluency tests. Associations are reported also among the permeability values and the fine motor efficiency through the Grooved Pegboard test completion time. 6) DCE and Dynamic Susceptibility Contrast perfusion MRI, provide information regarding BBB disruption and cerebral hemodynamics respectively. The correlation of quantitative parameters derived from the application of these two different perfusion techniques in patients of MS and CIS have not been previously studied in the literature. For this purpose, in the context of this dissertation we examined the underlying relationship among the DSC and DCE quantitative maps in a sub cohort of patients and found moderate correlations, while the overall results in the entire patient dataset will be published in the near future. More specifically, positive correlations were found between ktrans, CBF and CBV in NAWM areas when using the NoSnaps protocol, however these were not driven by values in a single group of patients. In summary, the present dissertation provides a novel, time-extended DCE protocol with minimal increment of the MR acquisition time, along with a PK analysis software platform, which achieved to quantify active lesions of MS and CIS patients more accurately in comparison with the conventional protocol. Furthermore, preliminary results demonstrate that the novel time extended protocol provided more accurate classification of MS lesions (iso, mild, severe), and revealed correlations with clinical variables and specific neuropsychological deficits. Future work will aim towards further validation of these preliminary results, by applying the novel DCE protocol in a larger cohort of CIS and RRMS patients, and investigation of the correlation of DCE derived quantitative indices with neuropsychiatric measures, as well as, with the DSC derived hemodynamic parameters.
Language English, Greek
Subject Blood brain barrier
Magnetic resonance imaging
Απεικόνηση μαγνητικού συντονισμού
Issue date 2020-12-17
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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