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Updated: Jun 5, 2025
Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis
Published on: February 28, 2021
Myelin Imaging of the Spinal Cord in Animal Models and Patients with Multiple Sclerosis Using [11C]MeDAS PET: A
Chris W J van der Weijden1,2, Ahmed K M A Ahmed3,4, Anouk van der Hoorn2
1Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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]N-methyl-4,4'-diaminostilbene (MeDAS) as a PET tracer for myelin imaging in the rat and human spinal cord. Methods: [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). Results: [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. Conclusion: [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.
Insights
This study introduces [11C]N-methyl-4,4'-diaminostilbene (MeDAS) PET as a novel tool for imaging spinal cord myelin. It successfully detected myelin loss in animal models and multiple sclerosis patients, showing potential for clinical use.
Area of Science:
- Neuroimaging
- Neurodegenerative diseases
- Radiochemistry
Background:
- Multiple sclerosis (MS) is a neurodegenerative disease impacting the brain and spinal cord, with motor symptoms primarily linked to spinal cord damage.
- Current PET imaging for myelin primarily focuses on the brain, leaving spinal cord myelin visualization largely unexplored.
- There is a need for advanced imaging techniques to assess spinal cord myelin integrity in diseases like MS.
Purpose of the Study:
- To evaluate [11C]N-methyl-4,4 '-diaminostilbene (MeDAS) as a PET tracer for imaging myelin in the rat and human spinal cord.
- To assess the tracer's ability to detect demyelination in animal models and correlate with disease markers in MS patients.
- To investigate the physiological gradient of myelin density in the human spinal cord using PET.
Main Methods:
- [11C]MeDAS PET imaging of the spinal cord was performed in animal models of demyelination (experimental autoimmune encephalomyelitis, lysophosphatidylcholine, spinal cord injury).
- Human studies involved 6 healthy controls and 11 MS patients undergoing MRI and [11C]MeDAS PET of the cervical to thoracic spinal cord (C5-T6).
- Tracer uptake was quantified using standardized uptake values (SUV) within defined regions of interest, normalized to blood pool or muscle activity.
Main Results:
- [11C]MeDAS uptake was significantly reduced in spinal cord lesions across all animal models.
- In humans, a physiological rostral-caudal gradient of myelin density was observed, with higher uptake in the cervical compared to the thoracic spinal cord.
- MS patients exhibited significantly lower [11C]MeDAS uptake in the upper spinal cord (C5-T3) compared to controls, correlating inversely with MS lesions.
Conclusions:
- [11C]MeDAS PET is a promising technique for quantifying spinal cord myelin density.
- The tracer can detect physiological myelin variations and pathological changes in MS.
- Further evaluation of [11C]MeDAS PET is warranted for its clinical application in neurodegenerative diseases affecting the spinal cord.
