This Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) provides $997,410 to Arizona State University to develop MRI-based methods for detecting and differentiating invasive high-grade glioma (HGG) brain tumor subtypes. The specific aims are to: 1) establish and validate quantitative diffusion MRI signatures for the neuronal (NEU) and glycolytic/plurimetabolic (GPM) HGG subtypes based on their microstructural differences, and 2)...
This Project Grant award from the National Cancer Institute (CFDA 93.394 Cancer Detection and Diagnosis Research) provides $677,998 to The Medical College of Wisconsin, Inc. to validate and refine radiopathomic models for characterizing glioma tumor heterogeneity and infiltration. The project aims to: Externally validate radiopathomic maps developed using autopsy/biopsy samples, assessing their ability to identify proliferation, cellularity, and molecular subtypes in newly diagnosed patients...
This $638,804 Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) to Pennsylvania State University's Milton S. Hershey Medical Center aims to integrate cerebrospinal fluid (CSF) proteogenomic analyses to improve diagnosis and management of diffuse gliomas, the most common primary malignant adult brain tumors. The key objectives are to: 1) validate preliminary findings on CSF-based proteomic signatures that can differentiate diffuse...
This federal Project Grant award from the U.S. Department of Health and Human Services' National Cancer Institute provides $547,519 to Oregon Health & Science University (OHSU) to leverage biologically-specific PET/MRI monitoring and therapeutic modulation of the hypoxic glioblastoma tumor immune microenvironment (TIME) in order to improve outcomes for patients with glioblastoma, an aggressive form of brain cancer. The key objectives are to: 1) Define a biologically-specific imaging...
This $399,358 Project Grant awarded by the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) to Cordance Medical Inc. aims to optimize a non-invasive focused ultrasound system, called the "NeuroAccess System," to enable liquid biopsies for brain tumor patients. The key objectives are to demonstrate the safety of repeatedly opening the blood-brain barrier, optimize the opening volume and technique in a rat glioma model, and confirm the system's ability to...
This Project Grant award from the National Cancer Institute (NCI), under the Cancer Detection and Diagnosis Research program (CFDA 93.394), provides $670,904 to The Regents of the University of California, San Francisco (UCSF) to develop metabolic therapy and imaging for diffuse midline gliomas (DMGs), a devastating type of brain cancer in children. The research aims to identify and target the vulnerabilities induced by the H3K27M mutation that drives DMGs, specifically inhibiting the enzymes...
This Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) provides $677,801 to Yale University to conduct research on using deuterium metabolic imaging (DMI) to characterize glioblastoma (GBM) brain tumors based on altered glucose metabolism. The key products and services to be delivered include: Validating the specificity of DMI for detecting active GBM tumor by comparing it to histopathology of excised tumor tissue. Performing...
This Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) provides $609,749 to the University of North Carolina at Chapel Hill to develop a novel combination therapy for the treatment of glioblastoma multiforme (GBM), the most aggressive form of brain cancer. The key products/services to be delivered include: Developing an injectable, biodegradable hydrogel scaffold that can accommodate high concentrations of induced neural stem cells...
The National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded a $1,336,000 Project Grant under CFDA 93.286, Discovery and Applied Research for Technological Innovations to Improve Human Health, to The General Hospital Corporation (doing business as Massachusetts General Hospital) to develop rapid, motion-robust, and low-gadolinium MRI technologies for improved pediatric brain tumor imaging. The project aims to (1) develop cutting-edge technologies for rapid, motion-robust,...
This Project Grant award from the National Cancer Institute (CFDA 93.395 Cancer Treatment Research) provides $686,979 to The Regents of the University of California, San Francisco (UCSF) to conduct research on diffuse midline gliomas (DMGs), a type of malignant brain tumor in children. The key objectives are to: 1) Investigate how the H3K27M mutation in DMGs disrupts tumor metabolism and drives immunosuppression in the tumor microenvironment; 2) Determine if targeting the glycolytic enzyme...
MULTI-PARAMETRIC PERFUSION MRI FOR THERAPY RESPONSE ASSESSMENT IN BRAIN CANCER - THE LONG-TERM GOAL OF THIS PROGRAM IS TO IMPROVE PATIENT CARE BY OPTIMIZING AND VALIDATING QUANTITATIVE MAGNETIC RESONANCE IMAGING METHODS FOR THE EARLY PREDICTION OF BRAIN CANCER RESPONSE TO THERAPY. CURRENTLY, CONTRAST-ENHANCED MRI (CE-MRI) REPRESENTS THE STANDARD FOR GUIDING ALMOST ALL ASPECTS OF BRAIN TUMOR CLINICAL MANAGEMENT, INCLUDING SURGICAL BIOPSY/RESECTION, RADIATION TREATMENT PLANNING, AND POST-TREATMENT SURVEILLANCE FOR RESPONSE ASSESSMENT. UNFORTUNATELY, CE-MRI'S ACCURACY REMAINS LIMITED, WHICH CREATES SIGNIFICANT CLINICAL CHALLENGES. THUS, CLINICAL DECISIONS OFTEN REQUIRE SURGICAL BIOPSY FOR DEFINITIVE DIAGNOSIS, WHICH INCREASES MEDICAL COSTS, PATIENT MORBIDITY/MORTALITY, AND RESOURCE UTILIZATION. TO OVERCOME THE LIMITATIONS OF CE-MRI, DYNAMIC SUSCEPTIBILITY CONTRAST (DSC) MRI AND DYNAMIC CONTRAST ENHANCED (DCE) MRI ARE INCREASINGLY USED TO EVALUATE TUMOR PERFUSION AND PERMEABILITY. STUDIES HAVE SHOWN THAT DSC/DCE PARAMETERS CORRELATE WITH TUMOR GRADE, CAN PREDICT THE LIKELIHOOD OF TUMOR PROGRESSION AFTER THERAPY, AND DIFFERENTIATE TREATMENT RELATED EFFECTS VERSUS TUMOR PROGRESSION. HOWEVER, THE WIDESPREAD CLINICAL ADOPTION AND INCORPORATION OF DSC-MRI INTO MULTI-SITE CLINICAL TRIALS HAS BEEN HINDERED DUE TO VARIABLE ACQUISITION METHODS, CONTRAST AGENT DOSING SCHEMES AND ANALYSIS PROTOCOLS, WHICH TO DATE, HAVE YET TO BE STANDARDIZED AND AUTOMATED FOR CLINICAL USE. THESE ISSUES ARE KNOWN TO AFFECT THE REPEATABILITY AND INTERPRETATION OF DSC-MRI METRICS. SPIN AND GRADIENT ECHO (SAGE) DSC-MRI SEQUENCES ENABLE THE USE OF LOWER DOSES OF GD-BASED CONTRAST AGENTS, REQUIRE LESS SCAN TIME, ARE LESS SENSITIVE TO ACQUISITION PARAMETERS, ARE METHODOLOGICALLY MORE REPRODUCIBLE, YIELD MORE ACCURATE PERFUSION PARAMETERS, PROVIDE SIMULTANEOUS MEASURES OF DCE-MRI, VESSEL SIZE AND VESSEL ARCHITECTURAL IMAGING DATA, OXYGEN DELIVERY AND NOVEL METRICS HIGHLY SENSITIVE TO TUMOR CELLULAR CHARACTERISTICS. ACCORDINGLY, SAGE METHODS ENABLE THE INTERROGATION OF UNIQUE AND COMPLEMENTARY READOUTS ON TUMOR MICROSTRUCTURE AND FUNCTION THAT CORRELATE WITH CLINICAL OUTCOMES AND CAN IDENTIFY PATIENTS RESPONDING TO THERAPY. BEFORE CLINICAL TRIALS CAN BENEFIT FROM SAGE BASED DSC-MRI THE ACQUISITION AND ANALYSIS PROTOCOLS NEED TO BE OPTIMIZED, AUTOMATED AND STANDARDIZED. THUS, WE PROPOSE TO: 1) IMPLEMENT MULTI-VENDOR, SAGE- DSC-MRI PROTOCOLS, 2) ESTABLISH AUTOMATED AND OPEN SOURCE ALGORITHMS FOR QUALITY ASSURANCE AND ANALYSIS, 3) PARTNER WITH IMAGING BIOMETRICS TO DEVELOP A COMMERCIALLY INTEGRATED, VENDOR NEUTRAL IMAGE ANALYSIS PLATFORM FOR ANALYZING SAGE DSC-MRI DATA AND 4) VALIDATE SAGE DSC-MRI TOOLS FOR PREDICTING GLIOMA RESPONSE TO BEVACIZUMAB THERAPY. IMPACT ON HEALTHCARE: WE WILL PROVIDE THE NEURO-ONCOLOGY COMMUNITY WITH VALIDATED, QUANTITATIVE IMAGE ACQUISITION AND ANALYSIS METHODS FOR IDENTIFYING EARLY THERAPEUTIC RESPONSE THAT ARE APPROPRIATE FOR MULTI-SITE CLINICAL TRIALS OF CONVENTIONAL AND TARGETED BRAIN TUMOR THERAPIES, THEREBY ENABLING MORE RAPID DRUG DISCOVERY AND IMPROVED INDIVIDUALIZED CARE FOR PATIENTS.