Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington’s Disease

Gregory, Sarah; Cole, James R.; Farmer, Ruth; Rees, Elin M.; Roos, Raymund A.C.; Sprengelmeyer, Reiner; Dürr, Alexandra; Landwehrmeyer, G. Bernhard; Zhang, Hui; Scahill, Rachael I.; Tabrizi, Sarah J.; Frost, Chris; Hobbs, Nicola Z.

doi:10.3233/jhd-150173

Cited by 35 publications

(38 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are preliminary and require replication in a larger prHD cohort, which may also reveal longitudinal changes in other WM tracts. In addition, our cross‐sectional findings revealed prominent diffusivity abnormalities within certain tracts, most of which show 15‐month changes in early HD . This may suggest that longer time windows are needed to better characterize WM progression in prHD.…”

Section: Discussionmentioning

confidence: 64%

Cross‐sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease

et al. 2016

View full text Add to dashboard Cite

Objectives Diffusivity in white-matter tracts is abnormal throughout the brain in cross-sectional studies of prodromal Huntington’s disease. To date, longitudinal changes have not been observed. The present study investigated cross-sectional and longitudinal changes in white-matter diffusivity in relationship to the phase of prodromal Huntington’s progression, and compared them with changes in brain volumes and clinical variables that track disease progression. Methods Diffusion MRI profiles were studied over two years in 37 gene-negative controls and 64 prodromal Huntington’s disease participants in varied phases of disease progression. To estimate the relative importance of diffusivity metrics in the prodromal phase, group effects were rank ordered relative to those obtained from analyses of brain volumes, motor, cognitive and sensory variables. Results First, at baseline diffusivity was abnormal throughout all tracts, especially as individuals approached a manifest Huntington’s disease diagnosis. Baseline diffusivity metrics in six tracts and basal ganglia volumes best distinguished amongst the groups. Second, group differences in longitudinal change in diffusivity were localized to the superior fronto-occipital fasciculus, most prominently in individuals closer to a diagnosis. Group differences were also observed in longitudinal changes of most brain volumes, but not clinical variables. Lastly, increases in motor symptoms across time were associated with greater changes in the superior fronto-occipital fasciculus diffusivity and corpus callosum, cerebrospinal fluid, and lateral ventricle volumes. Conclusions These novel findings provide new insights into changes within two years in different facets of brain structure and their clinical relevance to changes in symptomatology that is decisive for a manifest Huntington’s diagnosis.

show abstract

Section: Discussionmentioning

confidence: 64%

Cross‐sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease

et al. 2016

View full text Add to dashboard Cite

show abstract

“…While research in other neurological disorders such as Parkinson’s [46] and Huntington’s [47] disease have shown that DTI markers of disease can be successfully applied in a mutlicentre study, there have been few studies addressing this issue in SVD. The use of multiple scanners, possibly from different manufacturers, is likely to add noise and may diminish the statistical sensitivity of these metrics.…”

Section: Discussionmentioning

confidence: 99%

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

et al. 2017

View full text Add to dashboard Cite

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.

show abstract

“…ROI analysis was then performed for a set of key white matter tracts chosen a priori according to the literature. 7,8,11,27 The ROIs included the corpus callosum (genu, body, splenium), the internal capsules (anterior and posterior limbs), and the external capsules (bilateral internal/external capsules were analyzed jointly to increase the statistical power). To minimize partial volume effects, ROIs were defined by thinning masks from the ICBM-81 white matter atlas 28 by 1mm.…”

Section: Mri Data Analysismentioning

confidence: 99%

In vivo characterization of white matter pathology in premanifest huntington's disease

Zhang

Gregory

Scahill

et al. 2018

Annals of Neurology

Self Cite

View full text Add to dashboard Cite

ObjectiveHuntington's disease (HD) is a monogenic, fully penetrant neurodegenerative disorder, providing an ideal model for understanding brain changes occurring in the years prior to disease onset. Diffusion tensor imaging (DTI) studies show widespread white matter disorganization in the early premanifest stages (pre‐HD). However, although DTI has proved informative, it provides only limited information about underlying changes in tissue properties. Neurite orientation dispersion and density imaging (NODDI) is a novel magnetic resonance imaging (MRI) technique for characterizing axonal pathology more specifically, providing metrics that separately quantify axonal density and axonal organization. Here, we provide the first in vivo characterization of white matter pathology in pre‐HD using NODDI.MethodsDiffusion‐weighted MRI data that support DTI and NODDI were acquired from 38 pre‐HD and 45 control participants. Using whole‐brain and region‐of‐interest analyses, NODDI metrics were compared between groups and correlated with clinical scores of disease progression. Whole‐brain changes in DTI metrics were also examined.ResultsThe pre‐HD group displayed widespread reductions in axonal density compared with control participants; this correlated with measures of clinical disease progression in the body and genu of the corpus callosum. There was also evidence in the pre‐HD group of increased coherence of axonal packing in the white matter surrounding the basal ganglia.InterpretationOur findings suggest that reduced axonal density is one of the major factors underlying white matter pathology in pre‐HD, coupled with altered local organization in areas surrounding the basal ganglia. NODDI metrics show promise in providing more specific information about the biological processes underlying HD and neurodegeneration per se. Ann Neurol 2018;84:497–504

show abstract

Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington’s Disease

Cited by 35 publications

References 82 publications

Cross‐sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease

Cross‐sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

In vivo characterization of white matter pathology in premanifest huntington's disease

Contact Info

Product

Resources

About