DETECTION AND MONITORING OF MULTIPLE SCLEROSIS USING COMBINED MRI AND PET IMAGING WITH THE USE OF A DEMYELINATION-DETECTING RADIOACTIVE TRACER
As a first semester senior, I opted to take a graduate level imaging applications course, Multi-Modal Biomedical Imaging Technologies: Functional, Molecular, and Hybrid Imaging Techniques, to challenge myself and diversity my course-load. Within this course, I was exposed to a variety of imaging techniques and the physics behind them. In this course, I was prompted to write an NIH research grant proposal (R03), including Specific Aims (1 page) and Research Strategy (Significance, Innovation, Approach, 6 pages) on a novel multi-modality of my choice.
OBJECTIVE:
Target a specific organ or/and disease or a fundamental biomedical research interest and propose a (new or currently available) multi-modal imaging technique.
Click here to access project proposal:
SPECIFIC AIMS
Multiple sclerosis (MS) is a neurodegenerative demyelinating autoimmune disease that affects nearly 2.8 million people worldwide [1]. Despite its prevalence, MS is often challenging to diagnose, frequently taking years after onset for an accurate diagnosis. Currently, MRI scans are the primary tool for diagnosing and monitoring MS, revealing lesions and neural damage [2]. However, these scans fall short in distinguishing myelin loss, a critical component in the progression of MS. Detecting demyelination sites could significantly enhance the understanding of clinical presentations and improve the monitoring of treatment therapies, particularly those targeting remyelination.
While MRI scans are the current gold standard for locating lesions in the brain and spinal cord, they have limitations in providing detailed information about myelin loss [2]. Recent studies have explored the use of a demyelination-detecting radiotracer with PET imaging, specifically the radioactive tracer [18F]3F4AP, which targets voltage-gated potassium channels in demyelinated axons [3]. We hypothesize that incorporating this demyelination-detection radioactive tracer into PET/MRI scans will enable clinicians to visualize the extent of demyelination at each lesion site, providing crucial information on disease progression and insights into remyelination therapies.
To test these theories, male C57BL/6 mice experiencing induced demyelination will be examined using this novel multi-modality. To induce demyelination, mice will be fed copper chelator cuprizone, leading to reversible demyelination, which mimics relapsing-remitting MS [4,5]. Radiotracer levels will be measured at several time increments to collect quantitative data on demyelination levels. MATLAB will be used to distinguish lesion areas, to calculate demyelination levels, and to visualize the correlation between the MRI and PET scan results.
Aim 1: Develop an imaging system that accurately quantifies demyelination according to levels of radiotracer [18F]3F4AP.
Hypothesis 1: Higher quantities of [18F]3F4AP radiotracer at lesion sites indicate higher levels of demyelination, resulting in higher intensities on the PET scan around demyelinating regions.
Rationale 1: The [18F]3F4AP radiotracer targets voltage-gated potassium channels in demyelinated axons. Higher quantities of this tracer at a lesion site suggest more unprotected voltage-gated potassium channels, indicating higher levels of demyelination. Quantifying this demyelination value will provide numerical insights into MS progression. Additionally, this numerical value has future potential to offer information regarding remyelination.
Aim 2: Characterize regions of demyelination in the central nervous system through the use of MRI in conjunction with [18F]3F4AP radiotracer PET imaging.
Hypothesis 2: PET imaging with tracer [18F]3F4AP allows for the visualization of demyelinating sites, while MRI provides distinct, clear anatomical images of the brain and spinal cord. Lesions on the MRI scan will correspond to areas of higher intensity on the PET scans, and overlaying the images will align lesion locations.
Rationale 2: This multi-modality significantly improves upon current PET/MRI technology by introducing a novel radiotracer for demyelination detection. Valuable visualization of lesion location(s) and areas of demyelination will now be provided to clinicians. By comparing lesion locations on MR scans to the intensity of radiotracer concentration on PET scans, this integrated approach produces more accurate and helpful imaging outputs.