Moccia, Marcello;
(2020)
Improving longitudinal spinal cord atrophy measurements for clinical trials in multiple sclerosis by using the generalised boundary shift integral (GBSI).
Doctoral thesis (M.D(Res)), UCL (University College London).
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Abstract
Spinal cord atrophy is a common and clinically relevant feature of multiple sclerosis (MS), and can be used to monitor disease progression and as an outcome measure in clinical trials. Spinal cord atrophy is conventionally estimated with segmentation-based methods (e.g., cross-sectional spinal cord area (CSA)), where spinal cord change is calculated indirectly by numerical difference between timepoints. In this thesis, I validated the generalised boundary shift integral (GBSI), as the first registration-based method for longitudinal spinal cord atrophy measurement. The GBSI registers the baseline and follow-up spinal cord scans in a common half-way space, to directly determine atrophy on the cord edges. First, on a test dataset (9 MS patients and 9 controls), I have found that GBSI presented with lower random measurement error, than CSA, reflected by lower standard deviation, coefficient of variation and median absolute deviation. Then, on multi-centre, multi-manufacturer, and multi–field‐strength scans (282 MS patients and 82 controls), I confirmed that GBSI provided lower measurement variability in all MS subtypes and controls, than CSA, resulting into better separation between MS patients and controls, improved statistical power, and reduced sample size estimates. Finally, on a phase 2 clinical trial (220 primary-progressive MS patients), I demonstrated that spinal cord atrophy measurements on GBSI could be obtained from brain scans, considering their quality and association with corresponding spinal cord MRI-derived measurements. Not least, 1-year spinal cord atrophy measurements on GBSI, but not CSA, were associated with upper and lower limb motor function. In conclusion, spinal cord atrophy on the GBSI had higher measurement precision and stronger clinical correlates, than the segmentation method, and could be derived from high-quality brain acquisitions. Longitudinal spinal cord atrophy on GBSI could become a gold standard for clinical trials including spinal cord atrophy as an outcome measure, but should remain a secondary outcome measure, until further advancements increase the ease of acquisition and processing.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D(Res) |
| Title: | Improving longitudinal spinal cord atrophy measurements for clinical trials in multiple sclerosis by using the generalised boundary shift integral (GBSI) |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10094368 |
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