Dataset Information

Pitfalls in the use of voxel-based morphometry as a biomarker: examples from huntington disease.

ABSTRACT:

Background and purpose

VBM is increasingly used in the study of neurodegeneration, and recently there has been interest in its potential as a biomarker. However, although it is largely "automated," VBM is rarely implemented consistently across studies, and changing user-specified options can alter the results in a way similar to the very biologic differences under investigation.

Materials and methods

This work uses data from patients with HD to demonstrate the effects of several user-specified VBM parameters and analyses: type and level of statistical correction, modulation, smoothing kernel size, adjustment for brain size, subgroup analysis, and software version.

Results

The results demonstrate that changing these options can alter results in a way similar to the biologic differences under investigation.

Conclusions

If VBM is to be useful clinically or considered for use as a biomarker, there is a need for greater recognition of these issues and more uniformity in its application for the method to be both reproducible and valid.

SUBMITTER: Henley SM

PROVIDER: S-EPMC7964217 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Publications

Pitfalls in the use of voxel-based morphometry as a biomarker: examples from huntington disease.

Henley S M D SM Ridgway G R GR Scahill R I RI Klöppel S S Tabrizi S J SJ Fox N C NC Kassubek J J

AJNR. American journal of neuroradiology 20091224 4

<h4>Background and purpose</h4>VBM is increasingly used in the study of neurodegeneration, and recently there has been interest in its potential as a biomarker. However, although it is largely "automated," VBM is rarely implemented consistently across studies, and changing user-specified options can alter the results in a way similar to the very biologic differences under investigation.<h4>Materials and methods</h4>This work uses data from patients with HD to demonstrate the effects of several u ...[more]

PMID: 20037137

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Project description:PurposeMRI has become an essential tool for prion disease diagnosis. However there exist only a few serial MRI studies of prion patients, and these mostly used whole brain summary measures or region of interest based approaches. We present here the first longitudinal voxel-based morphometry (VBM) study in prion disease. The aim of this study was to systematically characterise progressive atrophy in patients with prion disease and identify whether atrophy in specific brain structures correlates with clinical assessment.MethodsTwenty-four prion disease patients with early stage disease (3 sporadic, 2 iatrogenic, 1 variant and 18 inherited CJD) and 25 controls were examined at 3T with a T1-weighted 3D MPRAGE sequence at multiple time-points (2-6 examinations per subject, interval range 0.1-3.2 years). Longitudinal VBM provided intra-subject and inter-subject image alignment, allowing voxel-wise comparison of progressive structural change. Clinical disease progression was assessed using the MRC Prion Disease Rating Scale. Firstly, in patients, we determined the brain regions where grey and white matter volume change between baseline and final examination correlated with the corresponding change in MRC Scale score. Secondly, in the 21/24 patients with interscan interval longer than 3 months, we identified regions where annualised rates of regional volume change in patients were different from rates in age-matched controls. Given the heterogeneity of the cohort, the regions identified reflect the common features of the different prion sub-types studied.ResultsIn the patients there were multiple regions where volume loss significantly correlated with decreased MRC scale, partially overlapping with anatomical regions where yearly rates of volume loss were significantly greater than controls. The key anatomical areas involved included: the basal ganglia and thalamus, pons and medulla, the hippocampal formation and the superior parietal lobules. There were no areas demonstrating volume loss significantly higher in controls than patients or negative correlation between volume and MRC Scale score.ConclusionsUsing 3T MRI and longitudinal VBM we have identified key anatomical regions of progressive volume loss which correlate with an established clinical disease severity index and are relevant to clinical deterioration. Localisation of the regions of progressive brain atrophy correlating most strongly with clinical decline may help to provide more targeted imaging endpoints for future clinical trials.

Project description:BackgroundAging is the most significant risk factor for dementia. Alzheimer's disease (AD) accounts for approximately 60-80% of all dementia cases in older adults. This study aimed to examine the relationship between finger movements and brain volume in AD patients using a voxel-based reginal analysis system for Alzheimer's disease (VSRAD) software.MethodsPatients diagnosed with AD at the Center for Comprehensive Care and Research on Memory Disorders were included. The diagnostic criteria were based on the National Institute on Aging-Alzheimer's Association. A finger-tapping device was used for all measurements. Participants performed the tasks in the following order: with their non-dominant hand, dominant hand, both hands simultaneously, and alternate hands. Movements were measured for 15 s each. The relationship between distance and output was measured. Magnetic resonance imaging measurements were performed, and VSRAD was conducted using sagittal section 3D T1-weighted images. The Z-score was used to calculate the severity of medial temporal lobe atrophy. Pearson's product-moment correlation coefficient analyzed the relationship between the severity of medial temporal lobe atrophy and mean values of the parameters in the finger-tapping movements. The statistical significance level was set at <5%. The calculated p-values were corrected using the Bonferroni method.ResultsSixty-two patients were included in the study. Comparison between VSRAD and MoCA-J scores corrected for p-values showed a significant negative correlation with the extent of gray matter atrophy (r = -0. 52; p< 0.001). A positive correlation was observed between the severity of medial temporal lobe atrophy and standard deviation (SD) of the distance rate of velocity peak in extending movements in the non-dominant hand (r = 0. 51; p< 0.001).ConclusionsThe SD of distance rate of velocity peak in extending movements extracted from finger taps may be a useful parameter for the early detection of AD and diagnosis of its severity.

Dataset Information

Pitfalls in the use of voxel-based morphometry as a biomarker: examples from huntington disease.

Background and purpose

Materials and methods

Results

Conclusions

Publications

Pitfalls in the use of voxel-based morphometry as a biomarker: examples from huntington disease.

Similar Datasets

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