Developing near-infrared excitable dyes for non-invasive diagnostic imaging of myelination

With currently available medical technologies, diagnosis of MS is difficult and uncertain. Many of the symptoms of MS have other possible causes and therefore a battery of tests, procedures, and exclusion of other causes needs to be preformed to firmly establish a diagnosis of MS. In addition, clinical evidence has to be shown that the neurological deficits involve at least two different areas of the central nervous system (CNS), with documented neurological signs occurring at two separate and distinct time periods. The intervals between symptoms may span months to years, and the inability to establish an early diagnosis of MS may have profound implications for some individuals responsive to immune-based therapies and who would benefit from early therapeutic intervention. 

Unfortunately, no specific tests for MS are currently available, and of those used no test is 100% conclusive. Conventional MRI with contrast of the brain and spinal cord is commonly used for MS diagnosis. However, MRI can only image large (macroscopic) lesions and cannot detect small microscopic lesions. Moreover, while MRI can clearly image inflammation, this type of imaging may not necessarily represent demyelination.

The only universally common symptom of MS is demyelination in the CNS and therefore the CNS Laboratory in collaboration with Dr. Brian J. Bacskai here at the MassGeneral Institute for Neurodegenerative Disease (MIND) have begun developing near-infrared excitable dyes for diagnostic imaging of demyelination. These dyes have been specifically designed to stain myelin and emit florescence when excited by non-invasive infrared light. In conjunction with sophisticated hardware and software, the emitted florescence from these dyes can be mapped in 3-D space and quantified. Thus, we believe these dyes will provide a means of accurately determining the myelination status in the CNS in a non-invasive manner.

Lipophillic dye staining of myelin bundles in the corpus callosum. Left panel is a section from an untreated mouse. Right section is from a mouse treated with cuprizone, which induces massive demyelination in the corpus callosum.