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    Research Projects: Stokes Laboratory

    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 magnetic resonance imaging (MRI) is widely used in the assessment of Alzheimer’s-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 positron emission tomography (PET) metrics in preclinical models of Alzheimer’s disease.

     

    Figure 1: (Left) Representative images in a cognitively normal (CN) subject and subjects with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Clinical imaging research includes standard structural images to quantify regional atrophy and advanced metrics for diffusion, perfusion, and susceptibility. (Right) Analogous preclinical imaging protocol in a triple transgenic mouse model of AD. Standard structural imaging provides regional atrophy metrics, while DTI provides information about directional water diffusivity.

    Advanced Perfusion Biomarkers in Multiple Sclerosis

    Multiple sclerosis is a chronic debilitating disease of the central nervous system and has a highly variable clinical trajectory. Diagnosis is often aided by MRI, but conventional MRI lacks 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 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 preoperatively identify tumor biopsy sites that accurately represent the vast tumor heterogeneity and the need for more accurate methods to assess treatment response. Conventional 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:

    1. Improve tumor characterization through improved image-guided biopsy sampling
    2. 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.

    Figure 2: Conventional and advanced imaging in a patient with recurrent high-grade glioma. Conventional imaging includes T1-weighted post-contrast and T2-weighted FLAIR images. Advanced images include diffusion (ADC) to characterize cellularity, perfusion imaging to characterize vascular parameters (total and microvascular cerebral blood volume, vessel diameter, Ktrans permeability, and total and microvascular cerebral blood flow), and amide proton transfer (APT) mapping to characterize molecular changes.

    About Barrow

    Since our doors opened as a regional specialty center in 1962, we have grown into one of the premier destinations in the world for neurology and neurosurgery. Our experienced, highly skilled, and comprehensive team of neurological specialists can provide you with a complete spectrum of care–from diagnosis through outpatient neurorehabilitation–under one roof. Barrow Neurological Institute: Discover. Educate. Heal.