Novel mr imaging techniques to visualize inflammatory/degenerative mechanisms
Current therapies alter neuro-inflammatory/degenerative diseases (such as Multiple Sclerosis, MS) , however, little is known about their impact on neuroprotection and repair. Further, the development of effective therapies for these important components of MS has been hampered by the lack of sensitive clinical response criteria. We propose new methods aimed at associating changes in magnetic resonance (MR) detectable white/gray matter disease activity with pathological outcomes enhancing our understanding of degenerative processes resulting in tissue atrophy. We present novel protocols for existing MR scanning systems providing the ability to visualize structures that are impossible with current methods. Using techniques to concurrently stain and three-dimensionally analyze many cell types and structures related to auto-inflammatory pathology (glial cells, neurons, myelin, microvessels, infiltrates) and correlate these changes with existing and novel MR modalities will provide new ways of processing, acquiring, analyzing and understanding data from existing MRI hardware. Spinal cords from control mice and mice with induced autoimmune encephalomyelitis (EAE) were subjected to MR imaging using T1, T2, PD and DW protocols and newly developed MR imaging sequences. Novel imaging sequences were designed to resolve tissues with short T2 (invisible in conventional MRI) using new signal excitation methods. After MR acquisition, spinal cords were sectioned and immunofluorescently probed to concurrently label neurons, glial cells, microvessels, cellular infiltrates and myelin. 3D laser scanning microscopy and digital reconstruction were utilized to generate high resolution volumetric data. MR and multichannel microscopy data were co-registered and analyzed to identify novel cellular phenomena/structures related to autoimmune inflammatory diseases visible in the newly developed MR acquisition sequences that resolves tissue with a short T2.