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Tomas Uher

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5 papers

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YNICL Journal 2022 Journal Article

Periventricular gradient of T1 tissue alterations in multiple sclerosis

Manuela Vaneckova
Gian Franco Piredda
Michaela Andelova
Jan Krasensky
Tomas Uher
Barbora Srpova
Eva Kubala Havrdova
Karolina Vodehnalova

OBJECTIVE: relaxometry is already present in early multiple sclerosis patients, (ii) how it differs between early and progressive multiple sclerosis patients, and (iii) whether the gradient-derived metrics in normal-appearing white matter and lesions correlate better with physical disability than conventional MRI-based metrics. METHODS: atlas. Individual comparisons of each multiple sclerosis patient against the atlas were performed by computing z-scores. Equidistant bands of voxels were defined around the ventricles in the supratentorial white matter; the z-scores in these bands were analysed and compared between the early and progressive multiple sclerosis cohorts. Correlations between both conventional and z-score-gradient-derived MRI metrics and the Expanded Disability Status Scale were assessed. RESULTS: relaxation time z-scores. In progressive multiple sclerosis, z-score-derived metrics reflecting the gradient of tissue abnormality in normal-appearing white matter were more strongly correlated with disability (maximal rho = 0.374) than the conventional lesion volume and count (maximal rho = 0.189 and 0.21 respectively). In early multiple sclerosis, the gradient of normal-appearing white matter volume with z-scores > 2 at baseline correlated with clinical disability assessed at two years follow-up. CONCLUSION: Our results suggest that the surface-in white matter gradient of tissue alteration is detectable with T1 relaxometry and is already present at clinical disease onset. The periventricular gradients correlate with clinical disability. The periventricular gradient in normal-appearing white matter may thus qualify as a promising biomarker for monitoring of disease activity from an early stage in all phenotypes of multiple sclerosis.

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YNICL Journal 2021 Journal Article

Validating atlas-based lesion disconnectomics in multiple sclerosis: A retrospective multi-centric study

Veronica Ravano
Michaela Andelova
Mário João Fartaria
Mazen Fouad A-Wali Mahdi
Bénédicte Maréchal
Reto Meuli
Tomas Uher
Jan Krasensky

The translational potential of MR-based connectivity modelling is limited by the need for advanced diffusion imaging, which is not part of clinical protocols for many diseases. In addition, where diffusion data is available, brain connectivity analyses rely on tractography algorithms which imply two major limitations. First, tracking algorithms are known to be sensitive to the presence of white matter lesions and therefore leading to interpretation pitfalls and poor inter-subject comparability in clinical applications such as multiple sclerosis. Second, tractography quality is highly dependent on the acquisition parameters of diffusion sequences, leading to a trade-off between acquisition time and tractography precision. Here, we propose an atlas-based approach to study the interplay between structural disconnectivity and lesions without requiring individual diffusion imaging. In a multi-centric setting involving three distinct multiple sclerosis datasets (containing both 1.5 T and 3 T data), we compare our atlas-based structural disconnectome computation pipeline to disconnectomes extracted from individual tractography and explore its clinical utility for reducing the gap between radiological findings and clinical symptoms in multiple sclerosis. Results using topological graph properties showed that overall, our atlas-based disconnectomes were suitable approximations of individual disconnectomes from diffusion imaging. Small-worldness was found to decrease for larger total lesion volumes thereby suggesting a loss of efficiency in brain connectivity of MS patients. Finally, the global efficiency of the created brain graph, combined with total lesion volume, allowed to stratify patients into subgroups with different clinical scores in all three cohorts.

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YNICL Journal 2018 Journal Article

Establishing pathological cut-offs for lateral ventricular volume expansion rates

Michael G. Dwyer
Jesper Hagemeier
Niels Bergsland
Dana Horakova
Jonathan R. Korn
Nasreen Khan
Tomas Uher
Jennie Medin

Background: A percent brain volume change (PBVC) cut-off of -0.4% per year has been proposed to distinguish between pathological and physiological changes in multiple sclerosis (MS). Unfortunately, standardized PBVC measurement is not always feasible on scans acquired outside research studies or academic centers. Percent lateral ventricular volume change (PLVVC) is a strong surrogate measure of PBVC, and may be more feasible for atrophy assessment on real-world scans. However, the PLVVC rate corresponding to the established PBVC cut-off of -0.4% is unknown. Objective: To establish a pathological PLVVC expansion rate cut-off analogous to -0.4% PBVC. Methods: We used three complementary approaches. First, the original follow-up-length-weighted receiver operating characteristic (ROC) analysis method establishing whole brain atrophy rates was adapted to a longitudinal ventricular atrophy dataset of 177 relapsing-remitting MS (RRMS) patients and 48 healthy controls. Second, in the same dataset, SIENA PBVCs were used with non-linear regression to directly predict the PLVVC value corresponding to -0.4% PBVC. Third, in an unstandardized, real world dataset of 590 RRMS patients from 33 centers, the cut-off maximizing correspondence to PBVC was found. Finally, correspondences to clinical outcomes were evaluated in both datasets. Results: was 0.71 (p < 0.001) and a - 0.4% PBVC corresponded to a PLVVC of 3.51%. A peak in accuracy in the real-world dataset was found at a 3.51% PLVVC cut-off. Accuracy of a 3.5% cut-off in predicting clinical progression was 0.62 (compared to 0.68 for PBVC). Conclusions: Ventricular expansion of between 3.09% and 3.51% on T2-FLAIR corresponds to the pathological whole brain atrophy rate of 0.4% for RRMS. A conservative cut-off of 3.5% performs comparably to PBVC for clinical outcomes.

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YNICL Journal 2018 Journal Article

Gray matter atrophy patterns in multiple sclerosis: A 10-year source-based morphometry study

Niels Bergsland
Dana Horakova
Michael G. Dwyer
Tomas Uher
Manuela Vaneckova
Michaela Tyblova
Zdenek Seidl
Jan Krasensky

OBJECTIVES: To investigate spatial patterns of gray matter (GM) atrophy and their association with disability progression in patients with early relapsing-remitting multiple sclerosis (MS) in a longitudinal setting. METHODS: = 67) at the end of the study. An optimized, longitudinal source-based morphometry (SBM) pipeline, which utilizes independent component analysis, was used to identify eight spatial patterns of common GM volume co-variation in a data-driven manner. GM volume at baseline and rates of change were compared between patients with CDP and those without CDP. RESULTS: -values of 0.001 and 0.007). The patterns of GM atrophy associated with the development of CDP included areas involved in motor functioning and cognitive domains such as learning and memory. CONCLUSION: SBM analysis offers a novel way to study the temporal evolution of regional GM atrophy. Over 10 years of follow-up, disability progression in MS is related to GM atrophy in areas associated with motor and cognitive functioning.

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YNICL Journal 2014 Journal Article

MRI correlates of disability progression in patients with CIS over 48 months

Tomas Uher
Dana Horakova
Niels Bergsland
Michaela Tyblova
Deepa P. Ramasamy
Zdenek Seidl
Manuela Vaneckova
Jan Krasensky

BACKGROUND: Gray matter (GM) and white matter (WM) pathology has an important role in disease progression of multiple sclerosis (MS). OBJECTIVES: To investigate the association between the development of GM and WM pathology and clinical disease progression in patients with clinically isolated syndrome (CIS). METHODS: This prospective, observational, 48-month follow-up study examined 210 CIS patients treated with 30 µg of intramuscular interferon beta-1a once a week. MRI and clinical assessments were performed at baseline, 6, 12, 24, 36 and 48 months. Associations between clinical worsening [24-weeks sustained disability progression (SDP) and occurrence of a second clinical attack] and longitudinal changes in lesion accumulation and brain atrophy progression were investigated by a mixed-effect model analysis after correction for multiple comparisons. RESULTS: SDP was observed in 32 (15.2%) CIS patients, while 146 (69.5%) were stable and 32 (15.2%) showed sustained disability improvement. 112 CIS patients (53.3%) developed clinically definite MS (CDMS). CIS patients who developed SDP showed increased lateral ventricle volume (p < .001), and decreased GM (p = .011) and cortical (p = .001) volumes compared to patients who remained stable or improved in disability. Converters to CDMS showed an increased rate of accumulation of number of new/enlarging T2 lesions (p < .001), decreased whole brain (p = .007) and increased lateral ventricle (p = .025) volumes. CONCLUSIONS: Development of GM pathology and LVV enlargement are associated with SDP. Conversion to CDMS in patients with CIS over 48 months is dependent on the accumulation of new lesions, LVV enlargement and whole brain atrophy progression.

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