Multiple sclerosis (MS) is a demyelinating disease of the central nervous system affecting more than 2.3 million people worldwide. The pathogenic mechanism is not well understood and the diagnosis does not occur early enough to prevent further neurodegeneration. Evidence suggests that demyelination in the cerebrum is an important lesion of MS correlating well with cognitive defects in the disease. However, the clinical significance has not been fully established because cortical myelin cannot be observed in vivo over a long period. Here we propose to develop optical methods for studying cortical myelin in living animals. A new imaging modality will be employed, namely third-harmonic generation microscopy (THGM), which we recently demonstrated for label-free visualization of myelin in intact nerves of the peripheral nervous system. Powerful imaging capabilities will be developed suitable for advancing our knowledge of cortical myelination. First, THGM will be validated for probing cortical demyelination and remyelination in living MS animal models. Second, wavefront control will be implemented to facilitate large-scale THGM imaging of cortical myelin in deep mouse brain. Third, super-resolution THGM morphometry will be achieved by image restoration and probabilistic modeling. Upon successful completion, this project will open a new field of investigations in basic science as well as translational medicine to elucidate the axon-glial cell interaction underlying cortical demyelination and remyelination.

Public Health Relevance

Statement Multiple sclerosis (MS) is a disease displaying demyelination in the central nervous system and affects more than 2.3 million people worldwide. Although the loss of myelin in the cerebral cortex has been suggested as a lesion of MS, the clinical significance remains unclear due to the lack of technologies to observe the pathology over time. The objective of this research is to develop innovative methods suitable for large-scale imaging and quantitative analysis of cortical myelin in living animals so that better understanding can be gained about the mechanism of disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Enhancement Award (SC1)
Project #
1SC1GM121198-01
Application #
9208294
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Krasnova, Irina N
Project Start
2017-06-01
Project End
2021-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Hunter College
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
620127915
City
New York
State
NY
Country
United States
Zip Code
10065