Dataset Information

Echocardiographic Ischemic Memory Molecular Imaging for Point-of-Care Detection of Myocardial Ischemia.

ABSTRACT:

Background

Noninvasive molecular imaging of recent ischemia can potentially be used to diagnose acute coronary syndrome (ACS) with high accuracy.

Objectives

The authors hypothesized that bedside myocardial contrast echocardiography (MCE) ischemic memory imaging could be achieved with phosphatidylserine microbubbles (MB_PS) that are retained in the microcirculation via ischemia-associated endothelial activation.

Methods

A dose-finding study was performed in healthy volunteers (n = 17) to establish optimal MB_PS dosing. Stable patients with ACS (n = 30) and confirmed antecedent but resolved myocardial ischemia were studied within 2 hours of coronary angiography and percutaneous coronary intervention (PCI) when indicated. MCE molecular imaging was performed 8 minutes after intravenous administration of MB_PS. MCE perfusion imaging was used to assess the status of the postischemic microcirculation.

Results

Based on dose-finding studies, 0.10 or 0.15 mL of MB_PS based on body mass was selected. In patients with ACS, all but 2 underwent primary PCI. MCE molecular imaging signal intensity was greater in the postischemic risk area vs remote territory (median [95% CI]: 56 [33-66] vs 8 [2-17] IU; P < 0.001) with a receiver-operating characteristic curve C-statistic of 0.94 to differentiate post-ischemic from remote territory. Molecular imaging signal in the risk area was not related to type of ACS (unstable angina: 3; non-ST-segment elevation myocardial infarction: 14; ST-segment elevation myocardial infarction: 13), peak troponin, time to PCI, post-PCI myocardial perfusion, GRACE (Global Registry of Acute Coronary Events) score, or HEART score.

Conclusions

Molecular imaging with point-of-care echocardiography and MB_PS can detect recent but resolved myocardial ischemia. This bedside technique requires only minutes to perform and appears independent of the degree of ischemia. (Ischemic Memory Imaging With Myocardial Contrast Echocardiography; NCT03009266).

SUBMITTER: Davidson BP

PROVIDER: S-EPMC8597917 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Echocardiographic Ischemic Memory Molecular Imaging for Point-of-Care Detection of Myocardial Ischemia.

Davidson Brian P BP Hodovan James J Layoun Michael E ME Golwala Harsh H Zahr Firas F Lindner Jonathan R JR

Journal of the American College of Cardiology 20211101 20

<h4>Background</h4>Noninvasive molecular imaging of recent ischemia can potentially be used to diagnose acute coronary syndrome (ACS) with high accuracy.<h4>Objectives</h4>The authors hypothesized that bedside myocardial contrast echocardiography (MCE) ischemic memory imaging could be achieved with phosphatidylserine microbubbles (MB<sub>PS</sub>) that are retained in the microcirculation via ischemia-associated endothelial activation.<h4>Methods</h4>A dose-finding study was performed in healthy ...[more]

PMID: 34763776

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Project description:BackgroundSelectins are adhesion molecules that are expressed by the vascular endothelium upon activation and may be an imaging target for detecting myocardial ischemia long after resolution. The aim of this study was to test the hypothesis that molecular imaging of selectins with myocardial contrast echocardiographic (MCE) molecular imaging could be used to detect recent brief ischemia in closed-chest nonhuman primates.MethodsMyocardial ischemia was produced in anesthetized adult rhesus macaques (n = 6) by percutaneous balloon catheter occlusion of the left anterior descending or circumflex coronary artery for 5 to 10 min. Three separate macaques served as nonischemic controls. MCE perfusion imaging was performed during coronary occlusion to measure risk area and at 100 to 110 min to exclude infarction. MCE molecular imaging was performed at 30 and 90 min after reperfusion using a lipid microbubble bearing dimeric recombinant human P-selectin glycoprotein ligand-1 (MB-YSPSL). Collection of blood for safety data, electrocardiography, and echocardiography were performed at baseline and before and 10 min after each MB-YSPSL injection.ResultsVital signs, oxygen saturation, electrocardiographic results, ventricular systolic function, pulmonary vascular resistance, and serum safety markers were unchanged by intravenous injection of MB-YSPSL. On echocardiography, left ventricular dysfunction in the risk area had resolved by 30 min, and there was no evidence of infarction on MCE perfusion imaging. On selectin-targeted MCE molecular imaging, signal enhancement was greater (P < .05) in the risk area than remote territory at 30 min (25 ± 11 vs 11 ± 4 IU) and 90 min (13 ± 3 vs 3 ± 2 IU) after ischemia. There was no enhancement (<1 IU) in control nonischemic subjects.ConclusionsIn primates, MCE molecular imaging of selectins using MB-YSPSL, a recombinant ligand appropriate for humans, is both safe and effective for imaging recent myocardial ischemia. This technique may be useful for detecting recent ischemia in patients with chest pain even in the absence of necrosis.

Project description:BackgroundMicrocirculatory perfusion disorder and inflammatory response are critical links in acute kidney injury (AKI). We aim to construct anti-vascular cell adhesion molecule-1(VCAM-1) targeted microbubbles (TM) to monitor renal microcirculatory perfusion and inflammatory response.MethodsTM carrying VCAM-1 polypeptide was constructed by biological coupling. The binding ability of TM to human umbilical vein endothelial cells (HUVECs) was detected. Bilateral renal ischemia-reperfusion injury (IRI) models of mice were established to evaluate microcirculatory perfusion and inflammatory response using TM. Thirty-six mice were randomly divided into six groups according to the different reperfusion time (0.5, 2, 6, 12, and 24 h) and sham-operated group (Sham group). The correlation of TM imaging with serum and histopathological biomarkers was investigated.ResultsTM has advantages such as uniform distribution, regular shape, high stability, and good biosafety. TM could bind specifically to VCAM-1 molecule expressed by tumor necrosis factor-alpha (TNF-α)-treated HUVECs. In the renal IRI-AKI model, the area under the curve (AUC) of TM significantly decreased both in the renal cortical and medullary after 2 h of reperfusion compared with the Sham group (p < 0.05). Normalized intensity difference (NID) of TM at different reperfusion time was all higher than that of blank microbubbles (BM) and the Sham group (p < 0.05). Ultrasound molecular imaging of TM could detect AKI early before commonly used renal function markers, histopathological biomarkers, and BM imaging. AUC of TM was negatively correlated with serum creatinine (Scr), blood urea nitrogen (BUN), and Cystatin C (Cys-C) levels, and NID of TM was linearly correlated with VCAM-1, TNF-α, and interleukin-6 (IL-6) expression (p < 0.05).ConclusionsUltrasound molecular imaging based on TM carrying VCAM-1 polypeptide can accurately evaluate the changes in renal microcirculatory perfusion and inflammatory response, which might be a promising modality for early diagnosis of AKI.

Dataset Information

Echocardiographic Ischemic Memory Molecular Imaging for Point-of-Care Detection of Myocardial Ischemia.

Background

Objectives

Methods

Results

Conclusions

Publications

Echocardiographic Ischemic Memory Molecular Imaging for Point-of-Care Detection of Myocardial Ischemia.

Similar Datasets

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