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Karp, J. S.

Publications and source records attributed to Karp, J. S..

2 recordsLinked to original sources

A multi-modal flow phantom for quantitative PET/Spectral CT

PurposeIn this work, we aimed to establish a flow phantom for multi-modal PET and spectral CT imaging to improve blood flow quantification. MethodsA modular flow phantom was built with materials compatible with both PET and spectral CT. A peristaltic pump was used to allow for recirculation. Pores were installed through the aorta to allow for tissue exchange between the blood and tissue compartments, and valves were placed in line with the aorta to control the pressure gradient between compartments. We characterized the system using saline bolus experiments, dynamic PET imaging, and iodine-based spectral CT acquisitions. A blood flow (K1) of 1.0 mL/min/mL with a pressure range of approximately 1.0-3.0 psi was targeted. Using compartmental modeling, we estimate K1 across phantom configurations and evaluate the consistency of perfusion-related parameters derived from saline, PET, and spectral CT measurements. ResultsWith the four pore, two valve configuration, target K1 of 1.0 mL/min/mL was achieved with a physiologic pressure range (2.2-3.5 psi) and a pump speed of 150 rpm. Further, the flow phantom was also able to recapitulate K1 across a range of values through adjustable modifications to the phantom configuration. ConclusionsWe present a modular multimodal flow phantom with a tissue-mimicking compartment, vascular tubing with an adjustable number of pores and valves, and 3D-printed components to support tunable exchange between blood-pool and tissue compartments and controlled dynamic perfusion imaging with same-session PET and spectral CT. Such a setup will enable the development of multi-modal approaches for evaluating tissue perfusion.

bioengineering↗

In vivo imaging of reactive oxygen species after myocardial ischemia-reperfusion injury: a large animal multimodal imaging and transcriptomic study

BackgroundReactive oxygen species (ROS) contribute to myocardial ischemia-reperfusion injury (IRI), but in-vivo data on the spatial myocardial distribution and systemic effects of ROS after IRI remain limited. This multimodal CMR and PET/CT study aimed to non-invasively image ROS activity in a clinically-relevant swine model of IRI using [18F]ROStrace, a fluorine-18-labeled analogue of dihydroethidium (DHE), and to investigate regional changes in ROS activity in the infarcted myocardium during the subacute post-IRI phase. MethodsIRI was induced by percutaneous occlusion of the left anterior descending artery for 90 minutes in swine (N=9). CMR and whole-body PET/CT imaging with [18F]ROStrace were performed before myocardial infarction (MI) and 3-5 days post-MI to assess ROS in non-infarct myocardium, lungs, bone marrow, spleen and skeletal muscle. Late gadolinium enhanced CMR was performed to structurally characterize infarct regions. Post-MI, in vivo [18F]ROStrace signal in infarcted myocardium was compared with remote, non-infarcted myocardium and validated via ex vivo DHE fluorescent imaging. Bulk RNA-sequencing (RNA-seq) and Gene Ontology pathway analysis were conducted on biopsies from infarct and remote myocardial tissue to identify differentially expressed genes and pathways connected to oxidative stress. ResultsDuring the subacute phase following MI, [18F]ROStrace fractional uptake rate (FUR; min-1) was significantly increased in skeletal muscle, compared to baseline (0.011{+/-}0.003 vs 0.016{+/-}0.005, p=0.04), with a trend toward increased FUR in bone marrow (0.046{+/-}0.009 vs 0.056{+/-}0.011, p=0.12) and the left ventricular free wall (0.067{+/-}0.007 vs 0.073{+/-}0.010, p=0.15). Within the myocardium, [18F]ROStrace FUR ((min-1)/(mL/min/g)) was significantly higher in infarcted compared to non-infarcted myocardium regions (0.110{+/-}0.034, vs 0.148{+/-}0.035, p=0.0005). DHE staining confirmed elevated ROS levels in the infarcted myocardium. RNA-seq identified 8,707 differentially expressed genes between infarct and remote myocardium, with downregulated pathways in the infarct associated with mitochondrial function, cellular respiration, and metabolic adaptation. ConclusionThis study demonstrated MI ROS imaging using [18F]ROStrace using a whole-body PET/CT scanner and structural assessment with CMR. Systemic and myocardial increases in ROS activity were observed post-MI, accompanied by substantial molecular alterations in infarcted tissue. These findings show potential imaging strategies to evaluate therapeutic targets that can mitigate oxidative stress after MI.

bioengineering↗