Dataset Information

Influence of equipment changes on MRI measures of brain atrophy and brain microstructure in a placebo-controlled trial of ibudilast in progressive multiple sclerosis.

ABSTRACT:

Background

Hardware changes can be an unavoidable confound in imaging trials. Understanding the impact of such changes may play an important role in the analysis of imaging data.

Objective

To characterize the effect of equipment changes in a longitudinal, multi-site multiple sclerosis trial.

Methods

Using data from a clinical trial in progressive multiple sclerosis, we explored how major changes in imaging hardware affected data. We analyzed the extent to which these changes affected imaging biomarkers and the estimated treatment effects by including such changes as a time-dependent covariate.

Results

Significant differences whole brain atrophy (brain parenchymal fraction, BPF) and microstructure (transverse diffusivity, TD) between scans with and without changes were found and depended on the type of hardware change. A switch from GE HDxt to Siemens Skyra led to significant shifts in BPF (p < 0.04) and TD (p < 0.0001). However, we could not detect the influence of hardware changes on overall trial outcomes- differences between placebo and treatment arms in change over time of BPF and TD (p > 0.5).

Conclusions

The results suggest that differences among hardware types should be considered when planning and analyzing brain atrophy and diffusivity in a longitudinal clinical trial.

SUBMITTER: Sakaie K

PROVIDER: S-EPMC8138298 | biostudies-literature | 2021 Apr-Jun

REPOSITORIES: biostudies-literature

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Publications

Influence of equipment changes on MRI measures of brain atrophy and brain microstructure in a placebo-controlled trial of ibudilast in progressive multiple sclerosis.

Sakaie Ken K Fedler Janel K JK Yankey Jon W JW Nakamura Kunio K Debbins Josef J Lowe Mark J MJ Raska Paola P Fox Robert J RJ

Multiple sclerosis journal - experimental, translational and clinical 20210401 2

<h4>Background</h4>Hardware changes can be an unavoidable confound in imaging trials. Understanding the impact of such changes may play an important role in the analysis of imaging data.<h4>Objective</h4>To characterize the effect of equipment changes in a longitudinal, multi-site multiple sclerosis trial.<h4>Methods</h4>Using data from a clinical trial in progressive multiple sclerosis, we explored how major changes in imaging hardware affected data. We analyzed the extent to which these change ...[more]

PMID: 34046185

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Project description:BackgroundThere are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.MethodsWe enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis.ResultsOf 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.ConclusionsIn a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).

Project description:Grey matter atrophy has been shown in primary progressive multiple sclerosis (PPMS), but its association with physical incapacity is unclear. We submitted 19 patients with PPMS to a neurological evaluation and brain magnetic resonance imaging (MRI) with volumetric analysis using FreeSurfer. We found no relation between the Expanded Disability Status Scale or disease duration and the grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes, but not with total white matter volume. We concluded that physical disability in PPMS is not directly related to brain atrophy and that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.Primary progressive multiple sclerosis (PPMS) is characterized by chronic progression since onset, with predominant involvement of the spinal cord and prominent neurodegeneration. Grey matter atrophy has been shown in patients with PPMS, but its association with clinical incapacity is uncertain. We investigated the relationship between regional brain atrophy and physical disability in patients with PPMS.Patients with an established diagnosis of PPMS underwent a neurological evaluation followed by brain MRI at 1.5 T. Volumetric analysis was performed with FreeSurfer software, and evaluated the neocortex, total white matter, total subcortical grey matter, putamen, caudate, globus pallidus, thalamus, hippocampus, brainstem, corpus callosum and pre-central gyrus volumes. Clinical data obtained included physical disability as measured by the Expanded Disability Status Scale (EDSS).Nineteen patients were included, 14 female (73.7%), mean age of 55.7 (SD 7.6) and mean disease duration of 13.0 years (SD 8.8). Median EDSS score was 6.0 (3.5-8.0). The average T1 lesion load (4.9 cm³, SD 3.4) and T2 load (10.5 cm³, SD 9.9) did not relate to disease duration. There was no significant correlation between EDSS score or disease duration and the cortical grey matter, deep grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes (p < 0.05), but not with total white matter volume.Physical disability in PPMS is not directly related to brain volume loss. Grey matter atrophy correlates with lesion load in patients with PPMS, indicating that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.

Dataset Information

Influence of equipment changes on MRI measures of brain atrophy and brain microstructure in a placebo-controlled trial of ibudilast in progressive multiple sclerosis.

Background

Objective

Methods

Results

Conclusions

Publications

Influence of equipment changes on MRI measures of brain atrophy and brain microstructure in a placebo-controlled trial of ibudilast in progressive multiple sclerosis.

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