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Marcello Moccia

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YNIMG Journal 2020 Journal Article

Generalised boundary shift integral for longitudinal assessment of spinal cord atrophy

  • Ferran Prados
  • Marcello Moccia
  • Aubrey Johnson
  • Marios Yiannakas
  • Francesco Grussu
  • Manuel Jorge Cardoso
  • Olga Ciccarelli
  • Sebastien Ourselin

Spinal cord atrophy measurements obtained from structural magnetic resonance imaging (MRI) are associated with disability in many neurological diseases and serve as in vivo biomarkers of neurodegeneration. Longitudinal spinal cord atrophy rate is commonly determined from the numerical difference between two volumes (based on 3D surface fitting) or two cross-sectional areas (CSA, based on 2D edge detection) obtained at different time-points. Being an indirect measure, atrophy rates are susceptible to variable segmentation errors at the edge of the spinal cord. To overcome those limitations, we developed a new registration-based pipeline that measures atrophy rates directly. We based our approach on the generalised boundary shift integral (GBSI) method, which registers 2 scans and uses a probabilistic XOR mask over the edge of the spinal cord, thereby measuring atrophy more accurately than segmentation-based techniques. Using a large cohort of longitudinal spinal cord images (610 subjects with multiple sclerosis from a multi-centre trial and 52 healthy controls), we demonstrated that GBSI is a sensitive, quantitative and objective measure of longitudinal spinal cord volume change. The GBSI pipeline is repeatable, reproducible, and provides more precise measurements of longitudinal spinal cord atrophy than segmentation-based methods in longitudinal spinal cord atrophy studies.

YNICL Journal 2020 Journal Article

Spinal cord atrophy in a primary progressive multiple sclerosis trial: Improved sample size using GBSI

  • Marcello Moccia
  • Nicola Valsecchi
  • Olga Ciccarelli
  • Ronald Van Schijndel
  • Frederik Barkhof
  • Ferran Prados

BACKGROUND: We aimed to evaluate the implications for clinical trial design of the generalised boundary-shift integral (GBSI) for spinal cord atrophy measurement. METHODS: ), acquired separately. We obtained segmentation-based cross-sectional spinal cord area (CSA) at C1-2 (from both brain and spinal cord MRI) and C2-5 levels (from spinal cord MRI) using DeepSeg, and, then, we computed corresponding GBSI. RESULTS: Depending on the spinal cord segment, we included 67.4-98.1% patients for CSA measurements, and 66.9-84.2% for GBSI. Spinal cord atrophy measurements obtained with GBSI had lower measurement variability, than corresponding CSA. Looking at the image noise floor, the lowest median standard deviation of the MRI signal within the cerebrospinal fluid surrounding the spinal cord was found on brain MRI at the C1-2 level. Spinal cord atrophy derived from brain MRI was related to the corresponding measures from dedicated spinal cord MRI, more strongly for GBSI than CSA. Spinal cord atrophy measurements using GBSI, but not CSA, were associated with upper and lower limb motor progression. DISCUSSION: Notwithstanding the reduced measurement variability, the clinical correlates, and the possibility of using brain acquisitions, spinal cord atrophy using GBSI should remain a secondary outcome measure in MS studies, until further advancements increase the quality of acquisition and reliability of processing.

YNICL Journal 2020 Journal Article

Voxel-based analysis of gray matter relaxation rates shows different correlation patterns for cognitive impairment and physical disability in relapsing-remitting multiple sclerosis

  • Maria Teresa Cassiano
  • Roberta Lanzillo
  • Bruno Alfano
  • Teresa Costabile
  • Marco Comerci
  • Anna Prinster
  • Marcello Moccia
  • Rosario Megna

BACKGROUND: Regional analyses of markers of microstructural gray matter (GM) changes, including relaxation rates, have shown inconsistent correlations with physical and cognitive impairment in MS. OBJECTIVE: To assess voxelwise the correlation of the R1 and R2 relaxation rates with the physical and cognitive impairment in MS. METHODS: GM R1 and R2 relaxation rate maps were obtained in 241 relapsing-remitting MS patients by relaxometric segmentation of MRI studies. Correlations with the Expanded Disability Status Scale (EDSS) and the percentage of impaired cognitive test (Brief Repeatable Battery and Stroop Test, available in 186 patients) were assessed voxelwise, including voxel GM content as nuisance covariate to remove the effect of atrophy on the correlations. RESULTS: Extensive clusters of inverse correlation between EDSS and R2 were detected throughout the brain, while inverse correlations with R1 were mostly limited to perirolandic and supramarginal cortices. Cognitive impairment correlated negatively with R1, and to a lesser extent with R2, in the middle frontal, mesial temporal, midcingulate and medial parieto-occipital cortices. CONCLUSION: In relapsing-remitting MS patients, GM microstructural changes correlate diffusely with physical disability, independent of atrophy, with a preferential role of the sensorimotor cortices. Neuronal damage in the limbic system and dorsolateral prefrontal cortices correlates with cognitive dysfunction.