Axial diffusivity is increased in the degenerating superior cerebellar peduncles of Friedreich's ataxia

IntroductionDecreased fractional anisotropy (FA) demonstrated by diffusion tensor MR imaging (DTI) in areas of white matter (WM) damage is generally associated with increase of radial diffusivity, while axial diffusivity is reported to be decreased, unchanged, or increased. Aiming to better define the type of axial diffusivity change occurring in a typical human neurodegenerative disease, we investigated axial and radial diffusivity in Friedreich's ataxia (FRDA) which is characterized by selective neuronal loss of the dentate nuclei and atrophy and decreased FA of the superior cerebellar peduncles (SCPs).MethodsAxial and radial diffusivity of the whole-brain WM were evaluated in 14 patients with FRDA and 14 healthy volunteers using DTI at 1.5 T and the tract-based spatial statistics (TBSS) method, part of FSL software.ResultsTBSS analysis showed a single area in the central midbrain corresponding to the decussation of the SCPs which exhibited lower FA in patients than in controls. In this area, a significant increase of both axial and radial diffusivity was observed. No clusters of significantly decreased axial diffusivity were observed, while additional clusters of increase of radial diffusivity were present throughout the brain.ConclusionsThe selective decrease of FA in SCPs of FRDA patients reflecting chronic WM tract damage is associated with increase of both the axial and radial diffusivity, the latter more pronounced than the former. The ultrastructural and biophysical bases of the increased axial diffusivity in chronically degenerating WM tracts deserve further studies.

[1]  G. Campanella,et al.  Genetic data and natural history of Friedreich's disease: a study of 80 Italian patients , 1990, Journal of Neurology.

[2]  Kurt E. Weaver,et al.  Longitudinal diffusion tensor imaging in Huntington's Disease , 2009, Experimental Neurology.

[3]  B. Fischl,et al.  White matter pathology isolates the hippocampal formation in Alzheimer's disease , 2010, Neurobiology of Aging.

[4]  Guy B. Williams,et al.  Absolute diffusivities define the landscape of white matter degeneration in Alzheimer's disease. , 2010, Brain : a journal of neurology.

[5]  L. Testut,et al.  Traité d'anatomie humaine , 1905 .

[6]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[7]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[8]  A. Pfefferbaum,et al.  Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance , 2010, Neurobiology of Aging.

[9]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[10]  Sheng-Kwei Song,et al.  Axial Diffusivity Is the Primary Correlate of Axonal Injury in the Experimental Autoimmune Encephalomyelitis Spinal Cord: A Quantitative Pixelwise Analysis , 2009, The Journal of Neuroscience.

[11]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[12]  R. E. Schmidt,et al.  Toward accurate diagnosis of white matter pathology using diffusion tensor imaging , 2007, Magnetic resonance in medicine.

[13]  P. Patel,et al.  The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. , 1998, American journal of human genetics.

[14]  M Filippi,et al.  Regional Distribution and Clinical Correlates of White Matter Structural Damage in Huntington Disease: A Tract-Based Spatial Statistics Study , 2010, American Journal of Neuroradiology.

[15]  M. Catani,et al.  Diffusion-based tractography in neurological disorders: concepts, applications, and future developments , 2008, The Lancet Neurology.

[16]  Kathryn Trinkaus,et al.  Diffusion tensor imaging at 3 hours after traumatic spinal cord injury predicts long-term locomotor recovery. , 2010, Journal of neurotrauma.

[17]  Luis Concha,et al.  Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients , 2006, NeuroImage.

[18]  Carlo Bartolozzi,et al.  Diffusion-tensor MR imaging of corticospinal tract in amyotrophic lateral sclerosis and progressive muscular atrophy. , 2005, Radiology.

[19]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[20]  R. Davis,et al.  Textbook of Neuropathology , 1996 .

[21]  Shu-Wei Sun,et al.  Evolving Wallerian degeneration after transient retinal ischemia in mice characterized by diffusion tensor imaging , 2008, NeuroImage.

[22]  M. Giannelli,et al.  Brain structural damage in Friedreich’s ataxia , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[23]  Thomas E. Nichols,et al.  Acquisition and voxelwise analysis of multi-subject diffusion data with Tract-Based Spatial Statistics , 2007, Nature Protocols.

[24]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[25]  Glen Gillen,et al.  Degenerative Diseases of the Central Nervous System * , 2005 .

[26]  Mark Hallett,et al.  Increased iron in the dentate nucleus of patients with Friedreich's ataxia , 1999, Annals of neurology.

[27]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[28]  Mario Mascalchi,et al.  Brain white matter tracts degeneration in Friedreich ataxia. An in vivo MRI study using tract-based spatial statistics and voxel-based morphometry , 2008, NeuroImage.

[29]  K. Bushara,et al.  1H MR spectroscopy in Friedreich's ataxia and ataxia with oculomotor apraxia type 2 , 2010, Brain Research.

[30]  E. Larsson,et al.  Diffusion tensor MRI post mortem demonstrated cerebral white matter pathology , 2004, Journal of Neurology.

[31]  Peng Yu,et al.  Altered white matter microstructure in the corpus callosum in Huntington's disease: Implications for cortical “disconnection” , 2010, NeuroImage.

[32]  M. Filippi,et al.  Assessment of brain white matter fiber bundle atrophy in patients with Friedreich ataxia. , 2010, Radiology.