IMAGINOSTICS, INC. - Florida Company Profile

2024-05-29

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Department of Health and Human Services

VALIDATION OF A NOVEL MAGNETIC RESONANCE IMAGING (MRI) TECHNOLOGY FOR BOTH DIAGNOSTIC SCREENING AND QUANTIFICATION OF BRAIN VASCULAR PHYSIOLOGY IN ALZHEIMER'S-DISEASE-RELATED DEMENTIAS - PROJECT SUMMARY ALZHEIMER’S DISEASE (AD), A DEGENERATIVE BRAIN DISORDER, IS RESPONSIBLE FOR 60-70% OF ALL DEMENTIA. CURRENTLY NO RELIABLE BIOMARKERS EXIST FOR PRECISION-MEDICINE-LEVEL, SINGLE-PATIENT DIAGNOSTICS FOR THE EARLY DETECTION OF ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (AD/ADRD). IMAGINOSTICS PROPOSES TO CLINICALLY VALDIATE NOVEL MAGNETIC RESONANCE IMAGING (MRI)-BASED PROPRIETARY BIOMARKERS FOR THE EARLY DETECTION OF VASCULAR PATHOLOGY THAT PREDISPOSES INDIVIDUALS TO DEVELOP DEMENTIA IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT (MCI). FURTHER, WE WILL VALIDATE BIOMARKERS FOR MEASURING VASCULAR ABNORMALITY IN VASCULAR DEMENTIA (VAD), WHICH ACCOUNTS FOR 10% OF ALL DEMENTIA. QUANTITATIVE ULTRA-SHORT TIME-TO-ECHO CONTRAST-ENHANCED (QUTE-CE) MRI IS UNIQUE IN THAT IT GENERATES A QUANTITATIVE SIGNAL DIRECTLY REPRESENTATIVE OF PHYSIOLOGICAL INFORMATION. THE OVERALL OBJECTIVE OF PHASE I PROPOSAL: OBTAIN CLINICAL VALIDATION OF THE QUTE-CE IMAGING APPROACH FOR OUR PANEL OF BIOMARKERS FOR MEASURING MICROVASCULAR STRUCTURE, FUNCTION AND LEAKAGE. THIS FIRST VALIDATION IS TARGETED AT TWO GROUPS: 1) MCI: FOR EVALUATING THE PROSPECTS OF DETECTING ABNORMALITY BEFORE DEMENTIA ONSET AND 2) VAD: FOR EVALUATING THE PROSPECT OF CHARACTERIZING VASCULAR RELATED COGNITIVE IMPAIRMENT (VCID) IN THE MOST PERTINENT DEMENTIA POPULATION. THEIR ABILITY TO DETECT DEMENTIA WILL BE COMPARED TO AGE-MATCHED INDIVIDUALS AND ALSO COMPARED TO STATE-OF-THE ART NEUROIMAGING BIOMARKER APPROACHES TO MORE FULLY EVALUATE THE POTENTIAL OF QUTE- CE MRI. SPECIFIC AIM 1: ESTABLISH THE MERIT AND FEASIBILITY OF QUTE-CE MRI VASCULAR IMAGING BIOMARKERS FOR DETECTING VASCULAR ABNORMALITY IN VASCULAR DEMENTIA. THE STUDY WILL INCLUDE (N=24; 12M/12F) VASCULAR DEMENTIA SUBJECTS AND (N=24; 12M/12F) AGE-MATCHED CONTROL SUBJECTS. SPECIFIC AIM 2: ESTABLISH THE MERIT AND FEASIBILITY OF QUTE-CE MRI VASCULAR IMAGING BIOMARKERS FOR DETECTING VASCULAR ABNORMALITY IN MILD COGNITIVE IMPAIRMENT (MCI). THE STUDY WILL INCLUDE (N=24; 12M/12F) MCI SUBJECTS AND (N=24; 12M/12F) AGE-MATCHED CONTROL SUBJECTS. PRIMARY ENDPOINTS (SPECIFIC AIMS 1 AND 2): (1) STRUCTURE: CEREBRAL BLOOD VOLUME (QC-CBV) & SMALL VESSEL DENSITY (QC-SVD): (HYPOTHESIS 1) WE WILL TEST OUR HYPOTHESES THAT QUTE-CE MRI CAN DETECT SMALL AND LARGE VESSEL ABNORMALITY. (2) FUNCTION: CEREBROVASCULAR REACTIVITY (QC-CVR) & CBV-BASED FUNCTIONAL MRI (QC-FMRI): (HYPOTHESIS 2) WE WILL TEST OUR HYPOTHESES THAT QUTE-CE MRI WILL OUTPERFORM EPI-FMRI FOR CEREBROVASCULAR REACTIVITY AT THE GROUP LEVEL, AND THAT QC-CVR CAN BE MAPPED IN INDIVIDUALS MCI AND VAD FOR PRECISION MEDICINE. (3) LEAKAGE: BLOOD-BRAIN BARRIER LEAKAGE (QC-BBB): (HYPOTHESIS 3) WE WILL TEST OUR HYPOTHESES THAT QUTE- CE MRI WILL OUTPERFORM DCE-MRI FOR DETECTING BBB LEAKAGE AT THE GROUP LEVEL, AND THAT BBB LEAKAGE CAN BE MAPPED IN INDIVIDUALS MCI AND VAD FOR PRECISION MEDICINE. FURTHER, WE WILL TEST OUR HYPOTHESIS (HYPOTHESIS 4) THAT A MULTIVARIATE MODEL (CBV, CVR, BBB PERMEABILITY) OF NEUROVASCULAR UNIT DYSFUNCTION WILL PROVIDE DIAGNOSTIC MAPS INDICATING ABNORMALITY AND CORRELATE TO COGNITIVE DECLINE BETTER THAN ANY INDIVIDUAL IMAGING MEASURES DUE TO THEIR COMPLEMENTARY NATURE IN ASSESSMENT VASCULAR RELATED NEUROPATHOLOGY. IN ADDITION, FLUID-ATTENUATED INVERSION RECOVERY (FLAIR), SUSCEPTIBILITY-WEIGHTED IMAGING (SWI) AND DIFFUSION- WEIGHTED IMAGING (DWI) SCANS WILL BE ACQUIRED TO IDENTIFY WHITE MATTER HYPERINTENSITIES (WMHS), CEREBRAL MICROBLEEDS (CMBS) AND ISCHEMIC LESIONS TO QUANTIFY THE FOCAL BURDEN OF MICROVASCULAR CHANGES FROM CBV MAPS. QUANTITATIVE PERFORMANCE MILESTONES WILL BE COMPARATIVE WHOLE-BRAIN BIOMARKER ANALYTICS AND THE ANALYSIS OF FOCAL BURDEN AS IDENTIFIED IN FLAIR, SWI AND DWI USING CBV FOR IDENTIFYING THE SPATIAL-EXTENT-OF-BURDEN, INTRA- SUBJECT LEFT-RIGHT BRAIN COMPARISON, AND VOLUME-OF-INTEREST COMPARISON TO THE HEALTHY CONTROLS. WE WILL ALSO PERFORM COGNITIVE TESTING ON ALL PATIENTS TO EVALUATE THE CORRELATION TO VASCULAR PATHOLOGY - AS MEASURED WITH QUTE-CE MRI VASCULAR BIOMARKERS - TO CLINICAL MEASURES. WE CAN MEASURE VASCULAR ABNORMALITY AND METABOLIC DYSFUNCTION THROUGHOUT THE WHOLE BRAIN, SO WE SHOULD HAVE A GAMUT OF TESTS THAT CAN EVALUATE ALL COGNITIVE DOMAINS: MEMORY, LANGUAGE, ATTENTION, EXECUTIVE FUNCTION, VISUOSPATIAL SKILLS.

915931.00

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2024-06-26

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Department of Health and Human Services

DEVELOPMENT OF A FRONTIER MAGNETIC RESONANCE (MR) IMAGING TECHNOLOGY AS A TOOL FOR VISUALIZATION AND QUANTIFIED VASCULAR-FEATURE MEASUREMENT FOR USE IN BRAIN AND BEHAVIORAL RESEARCH ON SMALL ANIMALS - PROJECT SUMMARY THE BURDEN OF MENTAL ILLNESS CONTINUES TO BE A GROWING CHALLENGE IN THE UNITED STATES. AT THE SAME TIME, THE SCIENTIFIC COMMUNITY CONTINUES TO STUDY THE BRAIN AND BEHAVIOR, REVEALING RELATIONSHIPS BETWEEN BRAIN STRUCTURE AND FUNCTION AND PHYSIOLOGY AND ILLNESS. THE OUTER SCOPE OF BRAIN AND BEHAVIOR RESEARCH IS GOVERNED BY THE IMAGING AND ANALYTICAL TOOLS AVAILABLE TO SCIENTISTS. MAGNETIC RESONANCE IMAGING (MRI) HAS GREATLY IMPROVED THE STUDY OF THE BRAIN. HOWEVER, EVEN ADVANCED FORMS OF THE TECHNOLOGY HAVE SIGNIFICANT LIMITATIONS. SPECIFICALLY, ALL MRI TECHNIQUES RELY ON A QUALITATIVE SIGNAL FOR SEMI-QUANTITATIVE MEASUREMENTS. MOREOVER, STANDARD MRI ACQUISITION EXHIBIT AS MUCH AS 70% SIGNAL AMPLITUDE BIAS CHANGE WITH THE ORIENTATION OF THE CEREBRAL CORTICAL (AND HENCE THE LARGE PIAL VESSELS) RELATIVE TO MAGNETIC FIELD. QUANTITATIVE ULTRA-SHORT TIME-TO-ECHO CONTRAST-ENHANCED (QUTE-CE, PRONOUNCED “CUTE-SEE”) MRI IS A NOVEL IMAGING MODALITY THAT GENERATES A QUANTITATIVE SIGNAL DIRECTLY REPRESENTATIVE OF PHYSIOLOGICAL INFORMATION THAT CAN BROADEN THE OUTER LIMIT OF WHAT CURRENT TECHNOLOGY MAKES POSSIBLE. QUTE-CE ADVANTAGES, THUS FAR, INCLUDE PRODUCTION OF THE HIGHEST QUANTITATIVE MEASUREMENT OF CA CONCENTRATION IN MICE; DEVELOPMENT OF UNPRECEDENT NON-INVASIVE IN VIVO MAPS OF BRAIN VASCULAR STRUCTURE (CBV); MAPPING OF NEUROFUNCTIONAL RESPONSE; BIOMARKERS FOR CANCER TREATMENT EFFICACY; AND, MEASUREMENT OF BLOOD- BRAIN BARRIER (BBB) LEAKAGE. THIS PROJECT STRIVES TO CREATE A ROBUST SOFTWARE SUITE TO OVERCOME CURRENT LIMITATIONS UNLOCKING THE POTENTIAL OF PHMRI AND FMRI MEASUREMENT WITH HIGHER SAMPLING TIME, INCREASING SIGNAL-TO-NOISE BY 1.67 COMPARED TO RADIAL SAMPLING AND ENABLING SLIDING-WINDOW RECONSTRUCTION FOR SIMULTANEOUS HIGH-SPATIAL AND TEMPORAL IMAGE RECONSTRUCTION USING THE SAME DATA SET. TO ACHIEVE THIS, THE PROJECT AIMS TO DEVELOP AND OPTIMIZE A SOFTWARE PROTOTYPE FOR USE WITH INDUSTRY-STANDARD 7T SMALL ANIMAL RESEARCH SCANNERS, IMPLEMENTING IMAGINOSTICS’ PROPRIETARY 3D UTE RADIAL CONES PULSE SEQUENCE. NEXT, THE PROJECT STRIVES TO TEST SOFTWARE PROTOTYPES AND ANALYTICALLY CHARACTERIZE BIOMARKERS. THE GOAL OF THE PROJECT IS TO ULTIMATELY IMPROVE AND STANDARDIZE MEASUREMENTS TO COMPLEMENT OR REPLACE EXISTING OPTIONS FOR A MORE PRECISE APPROACH THAT IS UNIQUELY QUANTITATIVE AT BOTH THE INDIVIDUAL AND GROUP LEVELS. THIS MEANS POTENTIALLY FEWER ANIMALS WOULD BE NEEDED TO ARRIVE AT MEANINGFUL RESULTS. MOREOVER, STRUCTURAL, FUNCTIONAL AND BBB LEAKAGE METRICS CAN BE CAPTURED WITHIN ONE IMAGING SESSION, GREATLY ENRICHING THE STUDY OF HEALTHY AND DISORDERED BRAINS. OVERALL, THESE EFFORTS CAN HELP ADVANCE PRE-CLINICAL AND RELATED BRAIN RESEARCH EFFORTS ON SMALL ANIMALS, BY INCORPORATING A NOVEL MRI IMAGING TECHNOLOGY INTO THE REPERTOIRE OF RESEARCHERS.

436556.00

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