Diffusion-Tensor Magnetic Resonance Imaging in Tau-Related Neurodegenerative Diseases
Abstract & Commentary
By Michael Lin, MD, PhD
Assistant Professor of Neurology and Neurosciences, Weill Cornell Medical College
Dr. Lin reports no financial relationships relevant to this field of study.
Synopsis: Diffusion-tensor MRI can reliably distinguish amyloid-associated neurodegenerative disorders, such as Alzheimer’s disease, from tau-associated disorders, such as corticobasal gangionic degeneration and progressive supranuclear palsy.
Source: Sajjadi SA, et al. Diffusion tensor magnetic resonance imaging for single subject diagnosis in neurodegenerative diseases. Brain 2013:136:2253-2261.
A major frustration in the diagnosis of neurodegen-
erative disorders is the paucity of biomarker tests. Amyloid PET and CSF A-beta and tau analysis now provide ways to assess Alzheimer’s disease (AD) pathophysiology in vivo, but similar tests are lacking for other common neurodegenerative diseases, since there are currently no ligands for inclusions composed of tau, TDP-43, alpha-synuclein, etc.
An interesting study by Sajjadi and colleagues suggests that abnormalities on diffusion tensor magnetic resonance imaging (DTI) may be sensitive and specific for corticobasal ganglionic degeneration (CBGD) and progressive supranuclear palsy (PSP). They performed DTI on nine patients with progressive nonfluent aphasia (PNFA, all of whom later met clinical criteria for CBGD or PSP), nine patients with AD, nine patients with semantic dementia (SD), and 26 control subjects. MRIs were performed at 3 tesla, with diffusion measured in 63 directions.
Remarkably, the PNFA (CBGD/PSP) subjects all showed a qualitatively distinct pattern of DTI abnormalities that completely separated them from the AD, SD, and control groups, without any overlap. All PNFA (CBGD/PSP) subjects showed increased radial diffusivity and decreased fractional anisotropy throughout essentially all the white matter of the hemispheres. This pattern was seen even in PNFA subjects with very mild symptoms. None of the AD or SD subjects showed this pattern of diffuse white matter involvement. As expected, AD subjects had patchy DTI abnormalities in posterior cingulate and parieto temporal white matter, and SD subjects had abnormalities in anterior temporal white matter. Because there was no overlap between the PNFA (CBGD/PSP) group and the other groups, a pattern of DTI abnormalities throughout all the white matter of the hemispheres might potentially be useful in diagnosing CBGD/PSP at the level of individual subjects.
However, a number of caveats are in order. First, pathological verification of diagnosis was obtained in only one case. Diagnosis was made clinically in all other cases. Thus, the clear distinction in DTI abnormalities between CBGD/PSP and other groups thus far only has been seen in cases where the clinical classification is evident. Whether the DTI pattern holds in cases where the clinical classification is ambiguous remains to be seen. Second, subjects with white matter abnormalities on T2 images were excluded. Unfortunately, such abnormalities are quite common, so replication with subjects having these abnormalities will be important. Third, it is still unclear whether these findings are dependent on technical details of the DTI acquisition — magnet strength, resolution, directions, etc. Fourth, the pathological basis for the diffuse DTI abnormalities seen in the CBGD/PSP cases is unknown. The authors speculate that they are due to glial pathology rather than axonal abnormalities.
If these issues can be resolved, DTI may become a useful biological test to aid in diagnosis of neurodegenerative disorders.