A longitudinal diffusion tensor imaging study in symptomatic Huntington's disease
- Anusha Sritharan1,
- Gary F Egan2,3,
- Leigh Johnston2,4,
- Malcolm Horne2,
- John L Bradshaw1,
- India Bohanna2,3,
- Hamed Asadi2,3,
- Ross Cunnington2,
- Andrew J Churchyard5,
- Phyllis Chua1,
- Maree Farrow1,
- Nellie Georgiou-Karistianis1
- 1School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Victoria, Australia
- 2Howard Florey Institute, University of Melbourne, Victoria, Australia
- 3Centre for Neuroscience, University of Melbourne, Victoria, Australia
- 4Department of Electrical and Electronic Engineering, University of Melbourne, Victoria, Australia
- 5Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia
- Correspondence to Professor G Egan, Howard Florey University, Centre for Neuroscience, University of Melbourne, Victoria 3010, Australia;
- Received 18 December 2007
- Revised 9 December 2008
- Accepted 14 January 2009
- Published Online First 22 February 2009
Objective The striatum and its projections are thought to be the earliest sites of Huntington's disease (HD) pathology. This study aimed to investigate progression of striatal pathology in symptomatic HD using diffusion tensor imaging.
Method Diffusion weighted images were acquired in 18 HD patients and in 17 healthy controls twice, 1 year apart. Mean diffusivity (MD) was calculated in the caudate, putamen, thalamus and corpus callosum, and compared between groups. In addition, caudate width was measured using T1 high resolution images and correlated with caudate MD. Correlation analyses were also performed in HD between caudate/putamen MD and clinical measures.
Results MD was significantly higher in the caudate and putamen bilaterally for patients compared with controls at both time points although there were no significant MD differences in the thalamus or corpus callosum. For both groups, MD did not change significantly in any region from baseline to year 1. There was a significant negative correlation between caudate width and MD in patients at baseline but no correlation between these parameters in controls. There was also a significant negative correlation between Mini-Mental State Examination scores and caudate MD and putamen MD at both time points in HD.
Conclusions It appears that microstructural changes influence cognitive status in HD. Although MD was significantly higher in HD compared with controls at both time points, there were no longitudinal changes in either group. This finding does not rule out the possibility that MD could be a sensitive biomarker for detecting early change in preclinical HD.
- Diffusion tensor imaging
- Huntington's disease
- Region of Interest
- mean apparent diffusion coefficient
Funding This study was funded by the Australian National Health and Medical Research Council (NHMRC), grant No 234247, and by Neurosciences Victoria Pty Ltd. GE and RC were supported by an NHMRC Principal Research Fellowship Grant No 400317 and a RD Wright Fellowship grant, respectively.
Competing interests None.
Ethics approval This study was conducted with the approval of the human research ethics committee of Monash University, Calyron Campus, Victoria, Australia and the Howard Florey Institute, Parkville, Victoria, Australia.
Provenance and peer review Not commissioned; externally peer reviewed.