Targeted Imaging of Fibrosis in the Left Atrium

Abstract SignificanceAtrial fibrosis plays a central role in the development of atrial fibrillationAFand heart failurewhich are both common conditions in the elderly and associated with significant morbidity and mortalityThis proposal addresses an unmet diagnostic need for non invasive methods to characterize atrial fibrosis through non invasive molecular imaging of typecollagenthe hallmark pathology of atrial fibrosisHypothesisWe hypothesize that a collagen binding gadolinium chelate will localize in fibrotic atrial tissuethus enabling targeted molecular imaging of atrial fibrosis to be performed with a high degree of accuracyPreliminary dataThe affinity and specificity of Collagen Medical s proprietary probe CMfor typecollagen are well establishedOur preliminary efficacy data have established that CMcan quantify fibrosis burden in a rat bile duct ligation modelBDLof chronic liver diseaseAdditionallyCMenhanced differences in Tand signal intensity in a canine myocardial infarct model were shown to be related to the fibrosis burden in the left ventricleHerefor the first timewe propose to use the agent to image left atrial fibrosis using a porcine model of atrial fibrillationSpecific AimsIn PhaseSpecific Aimof this Fast Track proposal we aim to establish that CMspecifically accumulates in regions of atrial fibrosis as compared with a non targeted control and that it can be imaged in vivo with Tweighted sequencesA porcine model of focal left atrial fibrosis created using radiofrequency ablation catheters will be usedThe gating decision criteria for a transition to Phaseare based on quantitative assessment of tissue specificity vsnon targeted control and in vivo imagingIn PhaseSpecific Aimof the grantwe will demonstrate the ability of CMenhanced MRI to quantify patchy and diffuse left atrial fibrosis in a porcine model of atrial fibrillation and will compare the collagen targeted agent to the current gold standardlate gadolinium enhancementLGEusing the non targeted agentGd DOTAOverall ImpactWe anticipate that the targeted and specific nature of CMwill produce significantly more accurate data than LGE using non targeted chelatesthe current gold standardTogetherdata obtained in these studies will support an IND application and accelerate translation into the clinical realm Project Narrative Non invasive characterization of left atrial fibrosis is a significant unmet diagnostic need for elderly patientswho frequently suffer from atrial fibrillation and heart failureThis project employs a new collagen targeted magnetic resonance probe to specifically image left atrial fibrosis in a large animal model of atrial fibrillation