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Hans-Peter Müller

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13 papers

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YNICL Journal 2026 Journal Article

Advanced neuroimaging assessment of neurodegenerative dementia syndromes: A framework for comprehensive multimodal FDG-PET, MR-perfusion, and MR-diffusion analysis

Joachim Strobel
Jan Kassubek
Wolfgang Thaiss
Sarah Straub-Anderl
Zeljko Uzelac
Sarah Jesse
Laura Michelberger
Christoph Solbach

BACKGROUND: F]FDG) positron emission tomography (PET). Advanced multimodal magnetic resonance imaging (MRI) may complement PET-derived measures for differential diagnostics. OBJECTIVES: The aim of the present study was to evaluate a new methodological approach integrating metabolic, perfusion, and microstructural parameters from simultaneous FDG-PET/MRI to reveal different imaging signatures for different NDS subtypes. MATERIALS AND METHODS: 66 patients with NDS (Alzheimer's disease: 28; behavioral frontotemporal dementia: 10; semantic variant primary progressive aphasia (PPA): 8; non-fluent variant PPA: 11; logopenic variant PPA: 9) and 10 subjects with subjective cognitive deficits (SCD) underwent combined FDG-PET/MRI with pseudo-continuous arterial spin labeling (pCASL) and diffusion tensor imaging (DTI). Standardized uptake values (SUV), cerebral blood flow (CBF), and fractional anisotropy (FA) were used to separate a respective NDS subgroup from all other NDS subgroups and from SCD based on a support vector machine (SVM) applied on region of interest (ROI)-based parameters. RESULTS: White matter alterations directly adjacent to the regions of alterations in SUV and CBF were identified. The SVM analysis on ROI-based parameters reached accuracies between 81% and 94% for separating an NDS subgroup from all other NDS subgroups and from SCD. CONCLUSIONS: Multimodal neuroimaging by combination of FDG-PET and MRI shows potential to further advance the diagnostic spectrum in NDS. Since particularly early diagnosis of NDS remains key for effective treatment and management of patients with NDS, the present framework appears promising to be developed further until it aligns and integrates with clinical routine.

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YNIMG Journal 2026 Journal Article

In vivo classification of neuropathological disease stages in Parkinson’s disease by diffusion tensor imaging

Hans-Peter Müller
Lavinia A. Bârlescu
Nico Sollmann
Kelly Del Tredici
Heiko Braak
Jan Kassubek

BACKGROUND: A neuropathological staging system for Parkinson's disease (PD) proposes that PD may disseminate in a sequential regional pattern in the brain during six disease stages. Diffusion tensor imaging (DTI) can identify PD-associated patterns of brain alterations at the group level. OBJECTIVE: (1) To develop a framework for a hypothesis-guided DTI-based approach targeted to automatically analyze in vivo the fiber tracts that are typically involved at each neuropathological stage of PD, and (2) to apply this framework to a large sample of MRI datasets of patients with PD in comparison with controls. METHODS: A tract of interest (TOI)-based fiber tracking approach was used to analyze tracts that become involved during the course of PD, representative of the six neuropathological stages. The TOI-based technique of tractwise fractional anisotropy statistics (TFAS) was applied to calculate fractional anisotropy (FA) alterations for the investigated tracts. RESULTS: 206 DTI datasets were analysed (i.e., 102 DTI scans from patients with PD at different clinical and cognitive stages and 104 DTI scans from age- and sex-matched healthy controls). The TOI-related analyses showed differences between PD patients and controls for the tracts corresponding to each neuropathological stage, i.e., in the olfactory tract, the initiation states in the medulla-oblongata, the catecholaminergic tract, the corticopontine tract, the inferior longitudinal fascicle, and the superior longitudinal fascicle. Based on these differences, a sequential pattern classification could be performed into stages with sequentially increased tract alterations, indicating a more advanced neurodegenerative process. CONCLUSIONS: The herein used TOI-based framework could enable tracking disease stages in PD in vivo, as an approach to the propagation concept of neuropathological stages in PD. In future applications, this framework may be used not only for individual clinical work-up purposes, but also may enlarge the spectrum of potential non-invasive surrogate markers as a neuroimaging-based read-out for PD studies at the group level within a clinical context.

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YNICL Journal 2024 Journal Article

Temporal and spatial progression of microstructural cerebral degeneration in ALS: A multicentre longitudinal diffusion tensor imaging study

Hans-Peter Müller
Agessandro Abrahao
Christian Beaulieu
Michael Benatar
Annie Dionne
Angela Genge
Richard Frayne
Simon J. Graham

OBJECTIVE: The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS. METHODS: The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2). DTI and clinical data from a harmonized protocol across 7 centres were collected. Thirty-nine ALS patients and 61 controls completed baseline and two follow-up visits and were included for longitudinal analyses. Whole brain-based spatial statistics and hypothesis-guided tract-of-interest analyses were performed for cross-sectional and longitudinal analyses. RESULTS: FA was reduced at baseline and longitudinally in the CST, mid-corpus callosum (CC), frontal lobe, and other ALS-related tracts, with alterations most evident in the CST and mid-CC. CST and pontine FA correlated with functional impairment (ALSFRS-R), upper motor neuron function, and clinical disease progression rate. Reduction in FA was largely located in the upper CST; however, the longitudinal decline was greatest in the lower CST. Effect sizes were dependent on region, resulting in study group sizes between 17 and 31 per group over a 9-month interval. Cross-sectional effect sizes were maximal in the upper CST; whereas, longitudinal effect sizes were maximal in mid-callosal tracts. CONCLUSIONS: Progressive microstructural alterations in ALS are most prominent in the CST and CC. DTI can provide a biomarker of cerebral degeneration in ALS, with longitudinal changes in white matter demonstrable over a reasonable observation period, with a feasible number of participants, and within a multicentre framework.

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YNICL Journal 2023 Journal Article

Structural and microstructural neuroimaging signature of C9orf72-associated ALS: A multiparametric MRI study

Maximilian Wiesenfarth
Hans-Jürgen Huppertz
Johannes Dorst
Dorothée Lulé
Albert C. Ludolph
Hans-Peter Müller
Jan Kassubek

BACKGROUND: ALS patients with hexanucleotide expansion in C9orf72 are characterized by a specific clinical phenotype, including more aggressive disease course and cognitive decline. Computerized multiparametric MRI with gray matter volumetry and diffusion tensor imaging (DTI) to analyze white matter structural connectivity is a potential in vivo biomarker. OBJECTIVE: The objective of this study was to develop a multiparametric MRI signature in a large cohort of ALS patients with C9orf72 mutations. The aim was to investigate how morphological features of C9orf72-associated ALS differ in structural MRI and DTI compared to healthy controls and ALS patients without C9orf72 mutations. METHODS: Atlas-based volumetry (ABV) and whole brain-based DTI-based analyses were performed in a cohort of n = 51 ALS patients with C9orf72 mutations and compared with both n = 51 matched healthy controls and n = 51 C9orf72 negative ALS patients, respectively. Subsequently, Spearman correlation analysis of C9orf72 ALS patients' data with clinical parameters (age of onset, sex, ALS-FRS-R, progression rate, survival) as well as ECAS and p-NfH in CSF was performed. RESULTS: The whole brain voxel-by-voxel comparison of fractional anisotropy (FA) maps between C9orf72 ALS patients and controls showed significant bilateral alterations in axonal structures of the white matter at group level, primarily along the corticospinal tracts and in fibers projecting to the frontal lobes. For the frontal lobes, these alterations were also significant between C9orf72 positive and C9orf72 negative ALS patients. In ABV, patients with C9orf72 mutations showed lower volumes of the frontal, temporal, and parietal lobe, with the lowest values in the gray matter of the superior frontal and the precentral gyrus, but also in hippocampi and amygdala. Compared to C9orf72 negative ALS, the differences were shown to be significant for cerebral gray matter (p = 0.04), especially in the frontal (p = 0.01) and parietal lobe (p = 0.01), and in the thalamus (p = 0.004). A correlation analysis between ECAS and averaged regional FA values revealed significant correlations between cognitive performance in ECAS and frontal association fibers. Lower FA values in the frontal lobes were associated with worse performance in all cognitive domains measured (language, verbal fluency, executive functions, memory and spatial perception). In addition, there were significant negative correlations between age of onset and atlas-based volumetry results for gray matter. CONCLUSIONS: This study demonstrates a distinct pattern of DTI alterations of the white matter and ubiquitous volume reductions of the gray matter early in the disease course of C9orf72-associated ALS. Alterations were closely linked to a more aggressive cognitive phenotype. These results are in line with an expected pTDP43 propagation pattern of cortical affection and thus strengthen the hypothesis that an underlying developmental disorder is present in ALS with C9orf72 expansions. Thus, multiparametric MRI could contribute to the assessment of the disease as an in vivo biomarker even in the early phase of the disease.

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YNICL Journal 2022 Journal Article

A multivariate Bayesian classification algorithm for cerebral stage prediction by diffusion tensor imaging in amyotrophic lateral sclerosis

Anna Behler
Hans-Peter Müller
Albert C. Ludolph
Dorothée Lulé
Jan Kassubek

BACKGROUND AND OBJECTIVE: Diffusion tensor imaging (DTI) can be used to tract-wise map correlates of the sequential disease progression and, therefore, to assess disease stages of amyotrophic lateral sclerosis (ALS) in vivo. According to a threshold-based sequential scheme, a classification of ALS patients into disease stages is possible, however, several patients cannot be staged for methodological reasons. This study aims to implement a multivariate Bayesian classification algorithm for disease stage prediction at an individual ALS patient level based on DTI metrics of involved tract systems to improve disease stage mapping. METHODS: The analysis of fiber tracts involved in each stage of ALS was performed in 325 ALS patients and 130 age- and gender-matched healthy controls. Based on Bayes' theorem and in accordance with the sequential disease progression, a multistage classifier was implemented. Patients were categorized into in vivo DTI stages using the threshold-based method and the Bayesian algorithm. By the margin of confidence, the reliability of the Bayesian categorizations was accessible. RESULTS: Based on the Bayesian multistage classifier, 88% of all ALS patients could be assigned into an ALS stage compared to 77% using the threshold-based staging scheme. Additionally, the confidence of all classifications could be estimated. CONCLUSIONS: By the application of the multi-stage Bayesian classifier, an individualized in vivo cerebral staging of ALS patients was possible based on the sequentially involved tract systems and, furthermore, the reliability of the respective classifications could be determined. The Bayesian classification algorithm is an improvement of the threshold-based staging method and could provide a framework for extending the DTI-based in vivo cerebral staging in ALS.

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YNICL Journal 2022 Journal Article

Segmental alterations of the corpus callosum in motor neuron disease: A DTI and texture analysis in 575 patients

Maximilian Münch
Hans-Peter Müller
Anna Behler
Albert C. Ludolph
Jan Kassubek

INTRODUCTION: Within the core neuroimaging signature of amyotrophic lateral sclerosis (ALS), the corpus callosum (CC) is increasingly recognized as a consistent feature. The aim of this study was to investigate the sensitivity and specificity of the microstructural segmental CC morphology, assessed by diffusion tensor imaging (DTI) and high-resolution T1-weighted (T1w) imaging, in a large cohort of ALS patients including different clinical phenotypes. METHODS: In a single-centre study, 575 patients with ALS (classical phenotype, N = 432; restricted phenotypes primary lateral sclerosis (PLS) N = 55, flail arm syndrome (FAS) N = 45, progressive bulbar palsy (PBP) N = 22, lower motor neuron disease (LMND) N = 21) and 112 healthy controls underwent multiparametric MRI, i.e. volume-rendering T1w scans and DTI. Tract-based fractional anisotropy statistics (TFAS) was applied to callosal tracts of CC areas I-V, identified from DTI data (tract-of-interest (TOI) analysis), and texture analysis was applied to T1w data. In order to further specify the callosal alterations, a support vector machine (SVM) algorithm was used to discriminate between motor neuron disease patients and controls. RESULTS: The analysis of white matter integrity revealed predominantly FA reductions for tracts of the callosal areas I, II, and III (with highest reductions in callosal area III) for all ALS patients and separately for each phenotype when compared to controls; texture analysis demonstrated significant alterations of the parameters entropy and homogeneity for ALS patients and all phenotypes for the CC areas I, II, and III (with again highest reductions in callosal area III) compared to controls. With SVM applied on multiparametric callosal parameters of area III, a separation of all ALS patients including phenotypes from controls with 72% sensitivity and 73% specificity was achieved. These results for callosal area III parameters could be improved by an SVM of six multiparametric callosal parameters of areas I, II, and III, achieving a separation of all ALS patients including phenotypes from controls with 84% sensitivity and 85% specificity. DISCUSSION: The multiparametric MRI texture and DTI analysis demonstrated substantial alterations of the frontal and central CC with most significant alterations in callosal area III (motor segment) in ALS and separately in all investigated phenotypes (PLS, FAS, PBP, LMND) in comparison to controls, while no significant differences were observed between ALS and its phenotypes. The combination of the texture and the DTI parameters in an unbiased SVM-based approach might contribute as a neuroimaging marker for the assessment of the CC in ALS, including subtypes.

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YNICL Journal 2020 Journal Article

Focal alterations of the callosal area III in primary lateral sclerosis: An MRI planimetry and texture analysis

Hans-Peter Müller
Jens Dreyhaupt
Francesco Roselli
Magdalena Schlecht
Albert C. Ludolph
Hans-Jürgen Huppertz
Jan Kassubek

BACKGROUND: The regional distribution of cerebral morphological alterations in primary lateral sclerosis (PLS) is considered to include the area III of the corpus callosum (CC). OBJECTIVE: The study was designed to investigate regional white matter (WM) alterations in the callosal area III by T1 weighted magnetic resonance imaging (T1w-MRI) data in PLS patients compared with healthy controls, in order to identify atrophy and texture changes in vivo. METHODS: T1w-MRI-based white matter mapping was used to perform an operator-independent CC-segmentation for the different areas of the CC in 67 PLS patients vs 82 matched healthy controls and vs 85 ALS patients. The segmentation was followed by texture analysis of the separated CC areas for the PLS patients vs controls and vs ALS patients. RESULTS: PLS was associated with significant atrophy in the area III of the CC (but not in the other callosal segments), while the alterations in the ALS patients were much more variable and were not significant at the group level. Furthermore, significant regional alterations of the texture parameters entropy and homogeneity in this area were shown in PLS patients and in ALS patients. CONCLUSIONS: This T1w-MRI study demonstrated focused regional CC atrophy and texture alterations limited to the callosal area III (which comprises fibers projecting into the primary motor cortices) in PLS, in comparison to a higher variability in CC size in ALS.

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YNICL Journal 2020 Journal Article

In vivo histopathological staging in C9orf72-associated ALS: A tract of interest DTI study

Hans-Peter Müller
Kelly Del Tredici
Dorothée Lulé
Kathrin Müller
Jochen H. Weishaupt
Albert C. Ludolph
Jan Kassubek

BACKGROUND: Diffusion tensor imaging (DTI) can identify amyotrophic lateral sclerosis (ALS)-associated patterns of brain alterations at the group level according to a neuropathological staging system. OBJECTIVE: The study was designed to investigate the in vivo staging in ALS patients with the C9orf72 expansion and potential differences to ALS patients with the SOD1 mutation. METHODS: DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 27 ALS patients with C9orf72 expansion vs 15 ALS patients with SOD1 mutation vs 32 matched healthy controls. Clinical and neuropsychological data were acquired and correlated to DTI data. RESULTS: The analysis of white matter integrity demonstrated regional FA reductions along the CST and also in frontal and prefrontal brain areas according to the proposed propagation pattern for the ALS patients with C9orf72 expansion and sporadic patients. This pattern could not be identified for the SOD1 mutation at the group level. In contrast, in the tract-specific analysis according to the neuropathological ALS-staging pattern, C9orf72 expansion ALS patients showed significant alterations of ALS-related tract systems similar to sporadic patients. CONCLUSIONS: The DTI study including the tract-of-interest-based analysis showed a microstructural corticoefferent involvement pattern according to the staging scheme in C9orf72-associated ALS patients but not in the SOD1 mutation.

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YNICL Journal 2019 Journal Article

The same cortico-efferent tract involvement in progressive bulbar palsy and in ‘classical’ ALS: A tract of interest-based MRI study

Hans-Peter Müller
Martin Gorges
Kelly Del Tredici
Albert C. Ludolph
Jan Kassubek

BACKGROUND: There is an ongoing debate about the concept of restricted phenotypes of amyotrophic lateral sclerosis (ALS), including progressive bulbar palsy (PBP). OBJECTIVE: The study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from PBP patients using a hypothesis-guided tract-of-interest-based approach (compared with 'classical' ALS patients and controls) to identify in vivo microstructural changes according to the neuropathologically defined ALS-related corticoefferent tract pathology. METHODS: DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 23 PBP and 23 ALS patients vs 23 matched controls. RESULTS: The analysis of white matter integrity demonstrated regional FA reductions along the CST and also in frontal and prefrontal brain areas both in PBP patients and ALS patients with additional regional FA reduction in the pons of the PBP group. In the tract-specific analysis according to the neuropathological ALS-staging pattern, PBP and ALS patients showed identical significant alterations of ALS-related tract systems when compared with controls. CONCLUSIONS: The DTI study including the tract-of-interest-based analysis showed the same microstructural corticoefferent involvement patterns in PBP patients as in ALS, which supports the hypothesis that PBP is a phenotypical variant of ALS.

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YNICL Journal 2018 Journal Article

Cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A two-centre tract of interest-based DTI analysis

Hans-Peter Müller
Federica Agosta
Martin Gorges
Rebecca Kassubek
Edoardo Gioele Spinelli
Nilo Riva
Albert C. Ludolph
Massimo Filippi

BACKGROUND: After the demonstration of a corticoefferent propagation pattern in amyotrophic lateral sclerosis (ALS) by neuropathological studies, this concept has been used for in vivo staging of individual patients by diffusion tensor imaging (DTI) techniques, both in `classical` ALS and in restricted phenotypes such as primary lateral sclerosis (PLS). OBJECTIVE: The study was designed to investigate that microstructural changes according to the neuropathologically defined ALS alteration pattern in PLS patients could be confirmed to be identical to ´classical´ ALS patients. The novelty in this approach is that the results were independent of the subject samples and the data acquisition parameters (as was validated in two samples from two different centres). That way, reproducibility across (international) centres in addition to harmonisation/standardisation of data analysis has been addressed, for the possible use of MRI-based staging to stratify patients in clinical trials. METHODS: Tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern was applied to DTI data (pooled from two ALS centres) of 88 PLS patients and 88 ALS patients with a 'classical' phenotype in comparison to 88 matched controls in order to identify white matter integrity alterations. RESULTS: In the tract-specific analysis, alterations were identical for PLS and ALS in the tract systems corresponding to the ALS staging pattern, independent of the subject samples and the data acquisition parameters. The individual categorisation into ALS stages did not differ between PLS and ALS patients. CONCLUSIONS: This DTI study in a two-centre setting demonstrated that the neuropathological stages can be mapped in vivo in PLS with high reproducibility and that PLS-associated cerebral propagation, although showing the same corticofugal patterns as ALS, might have a different time course of neuropathology, in analogy to its much slower clinical progression rates.

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YNICL Journal 2018 Journal Article

Fast progressive lower motor neuron disease is an ALS variant: A two-centre tract of interest-based MRI data analysis

Hans-Peter Müller
Federica Agosta
Nilo Riva
Edoardo G. Spinelli
Giancarlo Comi
Albert C. Ludolph
Massimo Filippi
Jan Kassubek

BACKGROUND: The criteria for assessing upper motor neuron pathology in pure lower motor neuron disease (LMND) still remain a major issue of debate with respect to the clinical classification as an amyotrophic lateral sclerosis (ALS) variant. OBJECTIVE: The study was designed to investigate white matter damage by a hypothesis-guided tract-of-interest-based approach in patients with LMND compared with healthy controls and ´classical´ ALS patients in order to identify in vivo brain structural changes according to the neuropathologically defined ALS affectation pattern. Data were pooled from two previous studies at two different study sites (Ulm, Germany and Milano, Italy). METHODS: DTI-based white matter integrity mapping was performed by voxelwise statistical comparison and by a tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 65 LMND patients (clinically differentiated in fast and slow progressors) vs. 92 matched controls and 101 ALS patients with a 'classical' phenotype to identify white matter structural alterations. RESULTS: The analysis of white matter structural connectivity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in LMND patients compared to controls and ALS. Fast progressing LMND showed substantial involvement, like in ALS, while slow progressors showed less severe alterations. In the tract-specific analysis according to the ALS-staging pattern, fast progressing LMND showed significant alterations of ALS-related tract systems as compared to slow progressors and controls. CONCLUSIONS: This study showed an affectation pattern for corticoefferent fibers in LMND with fast disease progression as defined for ALS, that way confirming the hypothesis that fast progressing LMND is a phenotypical variant of ALS.

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YNICL Journal 2018 Journal Article

Identical patterns of cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A tract of interest-based MRI study

Hans-Peter Müller
Martin Gorges
Rebecca Kassubek
Johannes Dorst
Albert C. Ludolph
Jan Kassubek

Background: There is an ongoing debate whether primary lateral sclerosis (PLS) should be regarded as an independent disease entity separate from amyotrophic lateral sclerosis (ALS) or as a slowly progressive variant of ALS. Objective: The study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from PLS patients by a hypothesis-guided tract-of-interest-based approach compared with 'classical' ALS patients and healthy controls, in order to identify microstructural changes according to the neuropathologically defined ALS affectation pattern in vivo. Methods: DTI-based white matter mapping was performed both by an unbiased voxelwise statistical comparison and by a hypothesis-guided tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 50 PLS and 50 ALS patients vs 50 matched controls. Results: The analysis of white matter integrity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in PLS patients and ALS patients. In the tract-specific analysis according to the ALS-staging pattern, PLS and ALS affectation patterns showed identical significant alterations of ALS-related tract systems when compared with controls and no differences when compared with each other. Conclusions: This DTI study showed the same microstructural affectation patterns in PLS patients as in ALS, in support of the hypothesis that PLS is a phenotypical variant of ALS.

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YNICL Journal 2013 Journal Article

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

Hans-Peter Müller
Georg Grön
Reiner Sprengelmeyer
Jan Kassubek
Albert C. Ludolph
Nicola Hobbs
James Cole
Raymund A.C. Roos

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.

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