Whole‐brain atrophy assessed by proportional‐ versus registration‐based pipelines from 3TMRIin multiple sclerosis

Abstract

Background and PurposeWhole‐brain atrophy is a standard outcome measure in multiple sclerosis (MS) clinical trials as assessed by various software tools. The effect of processing method on the validity of such data obtained from high‐resolution 3T MRI is not known. We compared two commonly used methods of quantifying whole‐brain atrophy.MethodsThree‐dimensional T1‐weighted and FLAIR images were obtained at 3T in MS (n = 61) and normal control (NC, n = 30) groups. Whole‐brain atrophy was assessed by two automated pipelines: (a) SPM8 to derive brain parenchymal fraction (BPF, proportional‐based method); (b) SIENAX to derive normalized brain parenchymal volume (BPV, registration method). We assessed agreement between BPF and BPV, as well their relationship to Expanded Disability Status Scale (EDSS) score, timed 25‐foot walk (T25FW), cognition, and cerebral T2 (FLAIR) lesion volume (T2LV).ResultsBrain parenchymal fraction and BPV showed only partial agreement (r = 0.73) in the MS group, and r = 0.28 in NC. Both methods showed atrophy in MS versus NC (BPF p < 0.01, BPV p < 0.05). Within MS group comparisons, BPF (p < 0.05) but not BPV (p > 0.05) correlated with EDSS score. BPV (p = 0.03) but not BPF (p = 0.08) correlated with T25FW. Both metrics correlated with T2LV (p < 0.05) and cognitive subscales. BPF (p < 0.05) but not BPV (p > 0.05) showed lower brain volume in cognitively impaired (n = 23) versus cognitively preserved (n = 38) patients. However, direct comparisons of BPF and BPV sensitivities to atrophy and clinical correlations were not statistically significant.ConclusionWhole‐brain atrophy metrics may not be interchangeable between proportional‐ and registration‐based automated pipelines from 3T MRI in patients with MS.

Whole brain and deep gray matter atrophy detection over 5 years with 3T MRI in multiple sclerosis using a variety of automated segmentation pipelines

“…Currently, global and regional brain atrophy can be assessed using a wide variety of MRI post-processing algorithms [ 1 – 8 , 11 , 14 , 16 – 19 ]. Automated or semi-automated measurement techniques fall mainly into two categories: registration- and segmentation-based [ 20 ]. Registration-based methods measure within-subject change in brain volume between scans on a voxel-by-voxel basis, to identify shifts in brain structure [ 21 ].…”

“…Segmentation techniques using static comparisons of volumetric data between two scans of the same subject, with each scan usually normalized to the subject’s intracranial cavity; such normalization may be residual [atlas-based: e.g. normalized brain parenchymal volume (BPV)] [ 20 , 22 ] or proportional [scaled to the patient’s own intracranial cavity; e.g. brain parenchymal fraction (BPF)] [ 20 , 23 ].…”

“…normalized brain parenchymal volume (BPV)] [ 20 , 22 ] or proportional [scaled to the patient’s own intracranial cavity; e.g. brain parenchymal fraction (BPF)] [ 20 , 23 ]. The measurement of regional brain atrophy also includes a variety of approaches/pipelines [ 24 – 26 ].…”

“…The measurement of regional brain atrophy also includes a variety of approaches/pipelines [ 24 – 26 ]. Studies have shown that the results from different pipelines to measure brain atrophy are not necessarily interchangeable [ 20 , 26 , 27 ] and may lead to divergent conclusions regarding MS therapeutic efficacy [ 28 , 29 ].…”

Interpretation of Brain Volume Increase in Multiple Sclerosis

“…Second, we observed a higher proportion of BVI scans if analyzed using the segmentation-based ScanView technique that has slightly lower precision than SIENA. 17,20 This finding was expected, given that correlation between brain percent volume changes (related to the previous MRI scans) from both techniques was only moderately strong (r = .50). Moreover, there was only partial overlap between BVI scans identified by both techniques.…”