Myelin Imaging of the Spinal Cord in Animal Models and Patients with Multiple Sclerosis Using [¹¹C]MeDAS PET: A Translational Study.

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelinated lesions in the brain and spinal cord. A few clinical studies using PET to image myelin in the brain have been performed, but none investigated the spinal cord. Because clinically relevant motor symptoms are primarily due to spinal cord damage, this translational study evaluated [¹¹C]<i>N</i>-methyl-4,4'-diaminostilbene (MeDAS) as a PET tracer for myelin imaging in the rat and human spinal cord. <b>Methods:</b> [¹¹C]MeDAS PET of the spinal cord was conducted in experimental autoimmune encephalomyelitis, lysophosphatidylcholine, and spinal cord injury animal models of focal demyelination. Then, 6 healthy controls and 11 MS patients were subjected to MRI and [¹¹C]MeDAS PET of the spinal cord between C5 and T6 vertebrae. Regions of interest covering 100%, 60%, and 40% of the diameter of the spinal canal were drawn, and tracer uptake was normalized to the activity in the blood pool, muscle, or injected dose per unit of body weight (SUV). <b>Results:</b> [¹¹C]MeDAS uptake was significantly reduced in spinal cord lesions in all animal models. In humans, tracer uptake was significantly higher in the cervical than the thoracic spinal cord, which corresponds well with the known physiologic rostral-caudal gradient in myelin density. MS patients had significantly lower [¹¹C]MeDAS uptake in the upper spinal cord (C5-T3) than did controls. The [¹¹C]MeDAS PET signal was inversely correlated with the presence of MS lesions in specific sections of the spinal cord. The best differentiation among regions with different myelin density was obtained when the smallest region of interest was used and spinal cord uptake was expressed as SUV. <b>Conclusion:</b> [¹¹C]MeDAS PET shows the potential to quantify myelin density in the spinal cord. It enables detection of physiologic differences in myelin density between spinal cord segments and between MS patients and healthy controls, which warrants further evaluation of this technique.