Development of Advanced Multi-parametric MRI Biomarkers in Alzheimer’s Disease
It has been estimated that a 10-year delay in the onset of Alzheimer’s disease (AD) may essentially eliminate the disease, highlighting the importance of early detection. Structural MRI is widely used in the assessment of AD-induced morphological changes such as brain atrophy, which is indicative of neuronal loss. However, morphological changes are minimal during the mild cognitive impairment (MCI) phase, with more substantial morphological changes occurring once the patient reaches the clinical threshold for a diagnosis of AD. Functional and molecular changes precede brain atrophy and may be detectable in the earlier MCI phases when intervention would prove most beneficial.
To that end, we are evaluating imaging-based signatures of disease progression, including measures of:
- Microvascular blood volume
- Blood flow
- Molecular species
- Iron deposition
We also are exploring the sensitivity and specificity of advanced MRI and PET metrics in preclinical animal models of AD.
Advanced Perfusion Biomarkers in Multiple Sclerosis
MS is a chronic debilitating disease of the central nervous system and has a highly variable clinical trajectory. Diagnosis is often aided by magnetic resonance imaging (MRI), but conventional MRI lacks the pathological specificity required for a diagnostic biomarker. The development of MS-specific biomarkers remains a highly relevant target and may impact patient diagnosis, prognosis, disease management, therapeutic planning, and clinical trial outcomes.
Cerebral perfusion characteristics may be indicative of chronic inflammation, a key feature in MS pathology, and a method to investigate vascular abnormalities may provide a more comprehensive understanding of MS pathology. To that end, we have developed a novel MRI acquisition and analysis method that will allow us to characterize perfusion changes across MS-affected lesions and throughout normal-appearing brain regions.
Multi-parametric MR Imaging Signatures of Brain Tumor Burden
High-grade gliomas (HGG) are the most common brain tumors and are almost universally lethal. Two persistent issues that limit effective brain cancer patient care are the need to pre-operatively identify tumor biopsy sites that accurately represent the vast tumor heterogeneity and the need for more accurate methods to assess treatment response. Conventional magnetic resonance imaging (MRI) is the current imaging standard to address both of these issues, but it lacks sensitivity to the underlying molecular and cellular tumor characteristics that are critical for reliably addressing these two issues.
The goal of this work is to develop advanced MRI signatures to
- Improve tumor characterization through improved image-guided biopsy sampling
- Assess treatment response in brain tumor patients
The ability to probe pathologically relevant tumor characteristics, including cellularity, vasculature, and metabolism, could improve tumor localization and offer more specific indicators of treatment response. We are working to both develop advanced analysis methods for current standard-of-care imaging and enhance our pathological specificity using more advanced image acquisition methods.