The goal of our Basic Science projects is to build anatomical knowledge of the Human Brain
MRI-based Striatal Parcellation: Striosome vs. Matrix
The mammalian striatum is made up of two tissue compartments, the Matrix and the Striosome. Each compartment has distinct biological properties: from connectivity to surface protein expression to influence on behaviors. However, the two compartmens are virtually indistinguishable through routine histological methods and require that tissue be studied post-mortem – precluding their study in living humans.
We developed an MRI-based method to identify Matrix and Striosome regions for the first time in vivo. Diffusion MRI (probabilistic tractography) was used to identify human striatal voxels whose connectivity is biased (matrix-favoring or striosome-favoring). These results allow for studies of the striatal compartments in living humans, especially their role in health and disease, for the first time.
Histology-based Striatal Parcellation: Human Cadavers
This project involves the imaging (MRI) and histologic characterization of human cadaver brains in order to determine the precise location of two structures: the striosome and matrix compartments of the striatum, and the VIM nucleus of the thalamus. Both of these regions have major influences on movement disorders in humans, but it is impossible to see these structures with routine MRI. By performing both histology and MRI in the same brain, we can correlate MRI findings directly to the anatomic gold-standard – histology. By improving the ability to locate these structures on MRI, we hope to improve targeting and localization for procedures such as Deep Brain Stimulation and High Intensity Focused Ultrasound ablation.
This project is co-directed with Dr. Bhavya Shah.
Improving Volume Measurement in Childhood-onset Diseases
The standard method of comparing volume measures between individuals is to 1) measure the volume of the region of interest, then 2) divide that measure by the total intracranial volume. This is a good approximation of correcting for body size and head size, which are independent drivers of brain size. But what if a degenerative disease causes atrophy of a brain region prior to the head reaching full adult size? Now the denominator in your corrective measure – the total intracranial volume – is compromised alongside the measure of your region of interest. It is not clear how such volumetric measures should be corrected for body size. This confounding of the standard method for volumetric correction makes it difficult to study diseases such as Rett syndrome or childhood-onset Huntington disease. We are developing novel methods for volume correction that avoid this confound. These methods will allow us to distinguish between regional and global volume abnormalities in childhood-onset degenerative and neurodevelopmental syndromes.
Development of the Human Eye
The retina is the only part of the central nervous system that is visible from outside the body. More broadly, the health of the eye is an important indicator of particular neurodegenerative and neurodevelopmental disorders. For example, in neurological disorders such as Fetal Alcohol Spectrum Disorder (FASD) the severity of neurotoxic effects can be estimated by the measurement of the distance between the corners of the eye (a rough correlate of eye size). Some developmental malformation disorders include microphthalmia (small eye) or macrophthalmia (large eye). Therefore, measuring the size of the eye precisely and comparing with age- and gender-normed values is helpful to both making diagnoses and assessing prognosis in childhood neurological disorders. We have developed such a standardized measure – essentially, a growth curve of the eye – which can be used as a diagnostic tool for neurological disorders.