Central Nervous System Disorders

We plan to leverage our expertise to expand into additional therapeutic areas and have accumulated experience in the use of multi-modality imaging services for central nervous system research, particularly focusing on multiple sclerosis (MS). Our years of imaging knowledge and our in-house pharmacology resources facilitate the development of novel imaging models and methodologies in an increasing realm of disease states.

In models of MS, imaging provides an opportunity for unique or complementary assessments of disease progression and response. Commonly, Magnetic Resonance Imaging (MRI) can be used to assess brain structure, atrophy, lesion extent, and demyelination. 18F-fluorodeoxyglucose Positron Emission Tomography (FDG PET) can be used to assess the inflammatory component of the disease. Matrix metalloproteinases (MMPs) are specific to the MOG35-55 Induced Experimental Autoimmune Encephalomyelitis (EAE) model and may be imaged using MMP-activated optical probes and Fluorescence Molecular Tomography (FMT).

  • Multiple Sclerosis (MS)

    MS is an autoimmune disease that affects the brain and spinal cord. It is a debilitating, and often fatal, disease with few treatment options. Damage to the myelin sheath (the protective covering that surrounds nerve cells) of the central nervous system is prominent in patients with MS. In vivo imaging strategies, including MRI-based anatomical or water-diffusion assessments, protease-activatable optical-probe imaging and FDG PET imaging, can be used to enhance the quality and richness of study datasets in rodent models of MS. Our MS models include:

  • MOG35-55 Induced Experimental Autoimmune Encephalomyelitis (EAE)

    The MOG35-55 emulsion provides the antigen needed to expand and differentiate MOG-specific autoimmune T cells. Tissue dendritic cells pick up the antigen and take it to the draining lymph nodes, where priming of T cells takes place. Pertussis toxin (PTX) enhances EAE development by providing additional adjuvant. PTX injection affects cell trafficking, Th17 cell development and integrity of the blood-brain barrier. C57BL/6 mice develop chronic paralysis after immunization with MOG35-55 emulsified in Complete Freund’s Adjuvant (CFA). Mice develop EAE 8-14 days after immunization and remain chronically paralyzed for the duration of the study, typically, 30-40 days.

  • Cuprizone Diet-Induced Demyelination

    The cuprizone model characterizes toxic demyelination and also represents a reversible demyelination and remyelination system. A, copper-chelating cuprizone diet induces demyelination and brain atrophy in mice. This well-characterized model allows testing of therapeutic agents that can prevent or repair myelin damage in vivo.

    In models of MS, imaging provides an opportunity for unique or complimentary assessments of disease progression and response. Commonly, MRI can be used to assess brain structure, atrophy, lesion extent, and demyelination. FDG PET can be used to assess the inflammatory component of the disease. MMPs are specific to the EAE model and may be imaged using MMP-activated optical probes and FMT.