Stanford Fiber Tractography Lab - Stroke and Clinical Research
According the Centers for Disease Control (CDC), stroke is the 5th leading cause of death in the United States. Each year it affects 795,000 people and kills 140,000. It is a leading cause of long term disability. One of the devastating long-term complications of stroke is a loss or disruption of one’s ability to speak (aphasia). One does not need to be a medical expert to recognize how significant a loss or impairment in speech is to a person’s everyday life.
Fortunately, the human brain is an ever-adapting organ. Neurons (brain cells) have been shown to change their structure and functionality to support learning and other mental activities. This phenomenon is known as plasticity. Following a stroke, one may undergo intensive physical therapy to address muscle weakness, and speech and language therapy to treat aphasia. We have been awarded an NIH grant to study the language pathways of stroke patients with aphasia undergoing intensive speech and language therapy. By applying a special type of tractography analysis known as connectometry, we have demonstrated that our group of patients show meaningful white matter changes on the stroke-affected sides of their brain, which correlate with improving speech ability. Though our work is still in its early stages, we are hopeful of using tractography to demonstrate the phenomenon of plasticity.
Other proposed applications of the connectometry approach are to track white matter changes in neuro-degenerative conditions such as amyotrophic lateral sclerosis (ALS), Huntington’s disease and chronic traumatic encephalopathy (CTE), amongst others. Though the disease processes and clinical symptoms vary significantly between these diseases, and they affect different groups of people, the one thing they all share in common is progressing damage to white matter pathways. Though ALS (also known as Lou Gehrig’s disease) usually manifests first with peripheral nervous systems, the gradual loss of neuromuscular control also affects the central nervous white matter as the disease progresses. Huntington’s disease is caused by an inherited genetic mutation. Unlike ALS, which causes mainly motor symptoms, Huntington’s produces a range of behavioural, motor and cognitive changes due to accumulation of a pathological protein in the gray matter nuclei located at the center of the brain. As the white matter is responsible for transmitting signals between these nuclei and other brain areas, it is also affected by the Huntington’s disease process. CTE received a certain amount of publicity due to its high-profile victims. Post-mortem dissection of CTE patients’ brains revealed plaque-like abnormalities similar to those afflicting Alzheimer’s sufferers. All three of these conditions are progressive and caused by accumulating damage to neurons. They cannot be definitively diagnosed either until after death or via an invasive biopsy of muscle or brain tissue. As clinical decision making is enhanced by high-quality supporting evidence, the creation of a radiological “biomarker” for neurodegeneration is an active area of current research. By achieving a robust, accurate radiological biomarker, clinicians may be able to diagnose a host of neurological conditions at the onset of, or even prior to symptoms developing.
We have conducted preliminary work of applying our tractographic connectometry technique to ALS, CTE and Huntington’s patients. Though work is still in its early stages, we hope that we may be able to contribute to the development of a radiological neuroimaging biomarker to detect these devastating conditions.
Selected References
1.) Abhinav, K., Yeh, F. C., El-Dokla, A., Ferrando, L. M., Chang, Y. F., Lacomis, D., ... & Fernandez-Miranda, J. C. (2014). Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: development of an imaging biomarker. Frontiers in human neuroscience, 8, 270.
2.) Abhinav, K., Al-Chalabi, A., Hortobagyi, T., & Leigh, P. N. (2006). Electrical injury and ALS: a systematic review of the literature. Journal of Neurology, Neurosurgery & Psychiatry.
3.) Abhinav, K., Yeh, F. C., Pathak, S., Suski, V., Lacomis, D., Friedlander, R. M., & Fernandez-Miranda, J. C. (2014). Advanced diffusion MRI fiber tracking in neurosurgical and neurodegenerative disorders and neuroanatomical studies: a review. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1842(11), 2286-2297.