Evaluating multicenter DTI data in Huntington's disease on site specific effects: An ex post facto approach☆

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Abstract

Purpose

Assessment of the feasibility to average diffusion tensor imaging (DTI) metrics of MRI data acquired in the course of a multicenter study.

Materials and methods

Sixty-one early stage Huntington's disease patients and forty healthy controls were studied using four different MR scanners at four European sites with acquisition protocols as close as possible to a given standard protocol. The potential and feasibility of averaging data acquired at different sites was evaluated quantitatively by region-of-interest (ROI) based statistical comparisons of coefficients of variation (CV) across centers, as well as by testing for significant group-by-center differences on averaged fractional anisotropy (FA) values between patients and controls. In addition, a whole-brain based statistical between-group comparison was performed using FA maps.

Results

The ex post facto statistical evaluation of CV and FA-values in a priori defined ROIs showed no differences between sites above chance indicating that data were not systematically biased by center specific factors.

Conclusion

Averaging FA-maps from DTI data acquired at different study sites and different MR scanner types does not appear to be systematically biased. A suitable recipe for testing on the possibility to pool multicenter DTI data is provided to permit averaging of DTI-derived metrics to differentiate patients from healthy controls at a larger scale.

Highlights

► Alternative procedure to evaluate prerequisites for multicenter DTI data pooling. ► Procedure may serve as reference for future multicenter MRI-DTI trials in HD. ► FA differences between HD and controls consistent with single center reports.

Related collections

Most cited references 24

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The effect of filter size on VBM analyses of DT-MRI data.

Malcolm K. Jones, J. Howard, M. Symms … (2005)

Voxel-based morphometry (VBM) has been used to analyze diffusion tensor MRI (DT-MRI) data in a number of studies. In VBM, following spatial normalization, data are smoothed to improve the validity of statistical inferences and to reduce inter-individual variation. However, the size of the smoothing filter used for VBM of DT-MRI data is highly variable across studies. For example, a literature review revealed that Gaussian smoothing kernels ranging in size (full width at half maximum) from zero to 16 mm have been used in DT-MRI VBM type studies. To investigate the effect of varying filter size in such analyses, whole brain DT-MRI data from 14 schizophrenic patients were compared with those of 14 matched control subjects using VBM, when the filter size was varied from zero to 16 mm. Within this range of smoothing, four different conclusions regarding apparent patient control differences could be made: (i) no significant patient-control differences; (ii) reduced FA in right superior temporal gyrus (STG) in patients; (iii) reduced FA in both right STG and left cerebellum in patients; and (iv) reduced FA only in left cerebellum in patients. These findings stress the importance of recognizing the effect of the matched filter theorem on VBM analyses of DT-MRI data. Finally, we investigated whether one of the underlying assumptions of parametric VBM, i.e., the normality of the residuals, is met. Our results suggest that, even with moderate smoothing, a large number of voxels within central white matter regions may have non-normally distributed residuals thus making valid statistical inferences with a parametric approach problematic in these areas.

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The optimal trackability threshold of fractional anisotropy for diffusion tensor tractography of the corticospinal tract.

Osamu Abe, Akira Kunimatsu, Kuni Ohtomo … (2004)

In order to ensure that three-dimensional diffusion tensor tractography (3D-DTT) of the corticospinal tract (CST), is performed accurately and efficiently, we set out to find the optimal lower threshold of fractional anisotropy (FA) below which tract elongation is terminated (trackability threshold). Thirteen patients with acute or early subacute ischemic stroke causing motor deficits were enrolled in this study. We performed 3D-DTT of the CST with diffusion tensor MR (magnetic resonance) imaging. We segmented the CST and established a cross-section of the CST in a transaxial plane as a region of interest. Thus, we selectively measured the FA values of the right and left corticospinal tracts at the level of the cerebral peduncle, the posterior limb of the internal capsule, and the centrum semiovale. The FA values of the CST were also measured on the affected side at the level where the clinically relevant infarction was present in isotropic diffusion-weighted imaging. 3D-DTT allowed us to selectively measure the FA values of the CST. Among the 267 regions of interest we measured, the minimum FA value was 0.22. The FA values of the CST were smaller and more variable in the centrum semiovale than in the other regions. The mean minus twice the standard deviation of the FA values of the CST in the centrum semiovale was calculated at 0.22 on the normal unaffected side and 0.16 on the affected side. An FA value of about 0.20 was found to be the optimal trackability threshold.

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Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures.

David S. Tuch, Mark Vangel, D Salat … (2006)

Atrophy of cortical and subcortical gray matter is apparent in Huntington's disease (HD) before symptoms manifest. We hypothesized that the white matter (WM) connecting cortical and subcortical regions must also be affected early and that select clinical symptoms were related to systems degeneration. We used diffusion tensor magnetic resonance imaging (DTI) to examine the regional nature of WM abnormalities in early HD, including the preclinical period, and to determine whether regional changes correlated with clinical features. We studied individuals in early stages (HD), presymptomatic individuals known to carry the genetic mutation that causes HD (Pre-HD), and matched healthy controls. DTI indices of tissue integrity were obtained from several regions of interest, including the corpus callosum (CC), internal capsule (IC), and basal ganglia, were compared across groups by t tests, and were correlated to cognitive and clinical measures. WM alterations were found throughout the CC, in the anterior and posterior limbs of the IC, and in frontal subcortical WM in HD subjects, supporting the selective involvement of the pyramidal tracts in HD; a similar distribution of changes was seen in Pre-HD subjects, supporting presymptomatic alterations. There was a significant relationship between select DTI measures and cognitive performance. Alterations in diffusion indices were also seen in the striatum that were independent of atrophy. Our findings support that WM alterations occur very early in HD. The distribution of the changes suggests that these changes contribute to the disruption of pyramidal and extrapyramidal circuits and also support a role of compromised cortical circuitry in early cognitive and subtle motor impairment during the preclinical stages of HD. (c) 2006 Movement Disorder Society.

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Author and article information

Contributors

Hans-Peter Müller

Journal

Journal ID (nlm-ta): Neuroimage (Amst)

Journal ID (iso-abbrev): Neuroimage (Amst)

Title: NeuroImage : Clinical

Publisher: Elsevier

ISSN (Electronic): 2213-1582

Publication date PMC-release: 3 January 2013

Publication date (Electronic): 3 January 2013

Publication date Collection: 2013

Volume: 2

Pages: 161-167

Affiliations

[a ]Department of Neurology, University of Ulm, Germany

[b ]Section for Neuropsychology and Functional Imaging, Department of Psychiatry, University of Ulm, Germany

[c ]Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK

[d ]Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

[e ]Neuroimaging Centre, CENIR, Paris, France

[f ]School of Psychology and Neuroscience, University of St Andrews, Scotland, UK

Author notes

[* ]Corresponding author at: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. Tel.: + 49 731 1771206. hans-peter.mueller@ 123456uni-ulm.de

[1]

Shared first authorship.

Article

Publisher ID: S2213-1582(12)00047-2

DOI: 10.1016/j.nicl.2012.12.005

PMC ID: 3777841

PubMed ID: 24179771

SO-VID: 9ffac7f6-5714-4168-8e2b-ce04f1e800af

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 24 August 2012

Date revision received : 11 December 2012

Date accepted : 21 December 2012

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