grant

Development and Application of T1rho Dispersion Imaging of Aging Muscle

Organization VANDERBILT UNIVERSITY MEDICAL CENTERLocation NASHVILLE, UNITED STATESPosted 1 Jun 2022Deadline 31 May 2027
NIHUS FederalResearch GrantFY202615 year old15 years of age21+ years old3-D3-Dimensional3D6 year old6 years of ageAcademic Medical CentersAdministrative SupplementAdultAdult HumanAffectAgingAnatomic SitesAnatomic structuresAnatomyAnimal ModelAnimal Models and Related StudiesAnimalsBiologicalBiological MarkersBlood VesselsBlood VolumeBlood capillariesBody TissuesCapillarityCausalityCell BodyCell Communication and SignalingCell SignalingCell-Extracellular MatrixCellsChildbirthChronic DiseaseChronic IllnessClinicalClinical EvaluationClinical ResearchClinical StudyClinical TestingClinical assessmentsCollaborationsCollagenComputer AnalysisDataDepositDepositionDeteriorationDevelopmentECMEnsureEtiologyEventExtracellular MatrixF344 RatsFatsFatty acid glycerol estersFibrosisFischer RatsFrequenciesFunctional impairmentGoalsGrantHigh-Risk PregnancyHistologicHistologicallyHistologyHumanHydrogen OxideImageImaging ProceduresImaging TechnicsImaging TechniquesImpairmentInbred CDF RatsInbred F344 RatsInbred Fischer 344 RatsInbred Fisher 344 RatsIntracellular Communication and SignalingKnowledgeLifeLongitudinal StudiesLongitudinal SurveysMR ImagingMR TomographyMRIMRI biomarkerMRI markerMRIsMagnetic Resonance ImagingMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMeasurementMeasuresMedical Imaging, Magnetic Resonance / Nuclear Magnetic ResonanceMembraneMetabolicMethodsModern ManMuscleMuscle AtrophyMuscle Cell ContractionMuscle ContractionMuscle FibersMuscle TissueMuscular AtrophyMuscular ContractionMyotubesNMR ImagingNMR TomographyNoiseNuclear Magnetic Resonance ImagingNutrientO elementO2 elementOxygenPathologicPathologyPatient Self-ReportPhysical activityPrincipal InvestigatorProductivityProtocolProtocols documentationRelaxationResearchResearch ActivityResearch AssistantResearch SupportResolutionResource SharingRestRhabdomyocyteRoleRotationScanningScheduleSelf-ReportSignal TransductionSignal Transduction SystemsSignalingSkeletal FiberSkeletal MuscleSkeletal Muscle CellSkeletal Muscle FiberSkeletal MyocytesStructureSurrogate MarkersTechniquesTherapeuticThighThigh structureTimeTissuesTrainingTranslatingUniversity Medical CentersVisitVoluntary MuscleWaterZeugmatographyadulthoodage 15age 15 yearsage 6age 6 yearsage associatedage associated chronic conditionage associated chronic diseaseage associated chronic disorderage associated chronic health conditionage associated chronic illnessage correlatedage dependentage groupage linkedage relatedage related chronic conditionage related chronic diseaseage related chronic disorderage related chronic health conditionage related chronic illnessage specificaged animalaged animalsaged muscleaging of muscleanimal old agebio-markersbiologicbiologic markerbiological signal transductionbiomarkercapillarycausationchild birthchronic disorderclinical applicabilityclinical applicationclinical testcomputational analysescomputational analysiscomputer analysescost effectivedevelopmentaldiffusion weighteddigitaldigital pathologydisabilitydisease causationelderly animalfifteen year oldfifteen years of agefrailtyhealthy aginghealthy human aginghemodynamicshuman imagingimage-based methodimagingimaging biomarkerimaging markerimaging methodimaging modalityimaging-based biological markerimaging-based biomarkerimaging-based markerimprovedindexinginnovateinnovationinnovativeinterestjuvenile animallong-term studylongitudinal outcome studieslongitudinal research studymacromoleculemagnetic resonance imaging biomarkermagnetic resonance imaging markermembrane structuremicrovascular pathologymid lifemid-lifemiddle agemiddle agedmidlifemitochondrial dysfunctionmodel of animalmuscle agingmuscle breakdownmuscle degradationmuscle deteriorationmuscle lossmuscle wastingmuscularnew approachesnovelnovel approachesnovel strategiesnovel strategyold animalsparametric imagingparent grantprotein distributionquadricepsquadriceps musclerecruitresearch clinical testingresolutionssarcopeniasarcopenicsimulationsix year oldsix years of agesocial rolesuccesssurrogate bio-markerssurrogate biomarkersthree dimensionaltime intervaltoolvascularvolunteerwalking pacewalking speedyoung animal
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Full Description

Project Summary
This administrative supplement is requested to support research continuity and retention of the scientific aims outlined in a K25 NIAAward #1K25AG076864, titled "Development and Application of T1rho Dispersion Imaging of Aging Muscle." The principal investigator is currently managing a high-risk pregnancy and childbirth-related life events that may temporarily affect her research productivity and the success of her K25 grant. The aims of the parent grant are (1) to develop R1p (R1p = 1/T1p - the spin-lattice relaxation rates in the rotating frame) dispersion imaging at weak locking field frequency, a novel approach that can quantify degenerative changes in microvasculature and abnormal macromolecule accumulation in muscle fiber membranes, (2) to validate extracted-MRI indices using gold-standard ex vivo methods through a longitudinal study of skeletal muscle in F344 rats to establish the pathophysiological relevance of these novel MRI biomarkers with aging, and (3) to translate R1p dispersion imaging to human research, utilizing a clinical 3T MRI scanner to assess skeletal muscle changes with healthy aging. The parent grant has enabled successful completion of Aim 1 and Aim 2, and partial progress toward Aim 3. To fully accomplish the objectives outlined in Aim 2, additional computational analysis of histological data is necessary. To support this activity, I have established a collaboration with experts at the Digital Histology Shared Resource (DHSR), in partnership with the Translational Pathology Shared Resource (TPSR) at Vanderbilt University Medical Center. This collaboration will enable cost-effective computational quantification of ex vivo biomarkers, which are essential for interpreting MRI-derived indices from Aim 2. This supplement is also vital for advancing Aim 3 by ensuring continuity of human research activities during a temporary reduction in the principal investigator's availability and productivity. A research assistant (RA) will be hired through this administrative supplement to support subject recruitment, scheduling volunteer visits, and conducting clinical assessments. The RA has received or will receive appropriate training to perform basic clinical evaluation and analyze demographic data, helping to maintain momentum in the human imaging component of the study. Overall, this support is crucial for maintaining the integrity and progress of the parent grant during a period of limited Pl availability.

Grant Number: 3K25AG076864-04S1
NIH Institute/Center: NIH

Principal Investigator: Fatemeh Adelnia

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