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A comparison of automated atrophy measures across the frontotemporal dementia spectrum: Implications for trials
BACKGROUND: Frontotemporal dementia (FTD) is a common cause of young onset dementia, and whilst there are currently no treatments, there are several promising candidates in development and early phase trials. Comprehensive investigations of neuroimaging markers of disease progression across the full...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503665/ https://www.ncbi.nlm.nih.gov/pubmed/34626889 http://dx.doi.org/10.1016/j.nicl.2021.102842 |
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author | Gordon, Elizabeth Bocchetta, Martina Nicholas, Jennifer Cash, David M Rohrer, Jonathan D |
author_facet | Gordon, Elizabeth Bocchetta, Martina Nicholas, Jennifer Cash, David M Rohrer, Jonathan D |
author_sort | Gordon, Elizabeth |
collection | PubMed |
description | BACKGROUND: Frontotemporal dementia (FTD) is a common cause of young onset dementia, and whilst there are currently no treatments, there are several promising candidates in development and early phase trials. Comprehensive investigations of neuroimaging markers of disease progression across the full spectrum of FTD disorders are lacking and urgently needed to facilitate these trials. OBJECTIVE: To investigate the comparative performance of multiple automated segmentation and registration pipelines used to quantify longitudinal whole-brain atrophy across the clinical, genetic and pathological subgroups of FTD, in order to inform upcoming trials about suitable neuroimaging-based endpoints. METHODS: Seventeen fully automated techniques for extracting whole-brain atrophy measures were applied and directly compared in a cohort of 226 participants who had undergone longitudinal structural 3D T1-weighted imaging. Clinical diagnoses were behavioural variant FTD (n = 56) and primary progressive aphasia (PPA, n = 104), comprising semantic variant PPA (n = 38), non-fluent variant PPA (n = 42), logopenic variant PPA (n = 18), and PPA-not otherwise specified (n = 6). 49 of these patients had either a known pathogenic mutation or postmortem confirmation of their underlying pathology. 66 healthy controls were included for comparison. Sample size estimates to detect a 30% reduction in atrophy (80% power; 0.05 significance) were computed to explore the relative feasibility of these brain measures as surrogate markers of disease progression and their ability to detect putative disease-modifying treatment effects. RESULTS: Multiple automated techniques showed great promise, detecting significantly increased rates of whole-brain atrophy (p<0.001) and requiring sample sizes of substantially less than 100 patients per treatment arm. Across the different FTD subgroups, direct measures of volume change consistently outperformed their indirect counterparts, irrespective of the initial segmentation quality. Significant differences in performance were found between both techniques and patient subgroups, highlighting the importance of informed biomarker choice based on the patient population of interest. CONCLUSION: This work expands current knowledge and builds on the limited longitudinal investigations currently available in FTD, as well as providing valuable information about the potential of fully automated neuroimaging biomarkers for sporadic and genetic FTD trials. |
format | Online Article Text |
id | pubmed-8503665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85036652021-10-15 A comparison of automated atrophy measures across the frontotemporal dementia spectrum: Implications for trials Gordon, Elizabeth Bocchetta, Martina Nicholas, Jennifer Cash, David M Rohrer, Jonathan D Neuroimage Clin Regular Article BACKGROUND: Frontotemporal dementia (FTD) is a common cause of young onset dementia, and whilst there are currently no treatments, there are several promising candidates in development and early phase trials. Comprehensive investigations of neuroimaging markers of disease progression across the full spectrum of FTD disorders are lacking and urgently needed to facilitate these trials. OBJECTIVE: To investigate the comparative performance of multiple automated segmentation and registration pipelines used to quantify longitudinal whole-brain atrophy across the clinical, genetic and pathological subgroups of FTD, in order to inform upcoming trials about suitable neuroimaging-based endpoints. METHODS: Seventeen fully automated techniques for extracting whole-brain atrophy measures were applied and directly compared in a cohort of 226 participants who had undergone longitudinal structural 3D T1-weighted imaging. Clinical diagnoses were behavioural variant FTD (n = 56) and primary progressive aphasia (PPA, n = 104), comprising semantic variant PPA (n = 38), non-fluent variant PPA (n = 42), logopenic variant PPA (n = 18), and PPA-not otherwise specified (n = 6). 49 of these patients had either a known pathogenic mutation or postmortem confirmation of their underlying pathology. 66 healthy controls were included for comparison. Sample size estimates to detect a 30% reduction in atrophy (80% power; 0.05 significance) were computed to explore the relative feasibility of these brain measures as surrogate markers of disease progression and their ability to detect putative disease-modifying treatment effects. RESULTS: Multiple automated techniques showed great promise, detecting significantly increased rates of whole-brain atrophy (p<0.001) and requiring sample sizes of substantially less than 100 patients per treatment arm. Across the different FTD subgroups, direct measures of volume change consistently outperformed their indirect counterparts, irrespective of the initial segmentation quality. Significant differences in performance were found between both techniques and patient subgroups, highlighting the importance of informed biomarker choice based on the patient population of interest. CONCLUSION: This work expands current knowledge and builds on the limited longitudinal investigations currently available in FTD, as well as providing valuable information about the potential of fully automated neuroimaging biomarkers for sporadic and genetic FTD trials. Elsevier 2021-10-05 /pmc/articles/PMC8503665/ /pubmed/34626889 http://dx.doi.org/10.1016/j.nicl.2021.102842 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Regular Article Gordon, Elizabeth Bocchetta, Martina Nicholas, Jennifer Cash, David M Rohrer, Jonathan D A comparison of automated atrophy measures across the frontotemporal dementia spectrum: Implications for trials |
title | A comparison of automated atrophy measures across the frontotemporal dementia spectrum: Implications for trials |
title_full | A comparison of automated atrophy measures across the frontotemporal dementia spectrum: Implications for trials |
title_fullStr | A comparison of automated atrophy measures across the frontotemporal dementia spectrum: Implications for trials |
title_full_unstemmed | A comparison of automated atrophy measures across the frontotemporal dementia spectrum: Implications for trials |
title_short | A comparison of automated atrophy measures across the frontotemporal dementia spectrum: Implications for trials |
title_sort | comparison of automated atrophy measures across the frontotemporal dementia spectrum: implications for trials |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503665/ https://www.ncbi.nlm.nih.gov/pubmed/34626889 http://dx.doi.org/10.1016/j.nicl.2021.102842 |
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