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Detection of antecedent myocardial ischemia with multiselectin molecular imaging.

ABSTRACT: Our aim was to develop an echocardiographic molecular imaging approach for detecting recent myocardial ischemia by using recombinant P-selectin glycoprotein ligand (PSGL)-1 as a targeting ligand, which is a feasible approach for human use.Ischemic memory imaging using human PSGL-1 as a targeting moiety may extend the time window for postischemic detection by targeting the early (P-selectin) and late (E-selectin) endothelial ischemic response.Lipid microbubbles bearing recombinant human PSGL-1 (MB(YSPSL)) or P-selectin antibody (MB(Ab)) were prepared. Targeted attachment was evaluated by using flow chamber and intravital microscopy. In vivo ultrasound molecular imaging was first performed in the hindlimb in wild-type and P-selectin-deficient (P(-/-)) mice 45 to 360 min after brief ischemia-reperfusion injury. Myocardial contrast echocardiography molecular imaging was performed 1.5, 3, 6, and 18 h after brief left anterior descending coronary artery ischemia-reperfusion.Microbubble attachment to P-selectin-immunoglobulin G fusion protein in flow chamber experiments (shear stress 0.5 to 8.0 dyne/cm(2)) and to activated venular endothelium on intravital microscopy were similar for MB(Ab) and MB(YSPSL). Intense enhancement was seen for MB(Ab) and MB(YSPSL) in postischemic muscle and was more stable over time for MB(YSPSL). On myocardial contrast echocardiography, both MB(YSPSL) and MB(Ab) produced similar signal enhancement at 90 min and 3 h after ischemia, which spatially correlated with the postischemic risk area. Signal significantly decreased but was still present at 6 to 18 h.Echocardiographic molecular imaging with a human multi-selectin-targeted contrast agent bearing recombinant human PSGL-1 can detect myocardial ischemia hours after resolution. This approach may potentially be used for rapid bedside evaluation of patients with recent chest pain.

SUBMITTER: Davidson BP

PROVIDER: S-EPMC3856914 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Detection of antecedent myocardial ischemia with multiselectin molecular imaging.

Davidson Brian P BP Kaufmann Beat A BA Belcik J Todd JT Xie Aris A Qi Yue Y Lindner Jonathan R JR

Journal of the American College of Cardiology 20120926 17

<h4>Objectives</h4>Our aim was to develop an echocardiographic molecular imaging approach for detecting recent myocardial ischemia by using recombinant P-selectin glycoprotein ligand (PSGL)-1 as a targeting ligand, which is a feasible approach for human use.<h4>Background</h4>Ischemic memory imaging using human PSGL-1 as a targeting moiety may extend the time window for postischemic detection by targeting the early (P-selectin) and late (E-selectin) endothelial ischemic response.<h4>Methods</h4> ...[more]

PMID: 23021335

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Project description:IntroductionThe electrocardiogram (ECG) is a valuable tool for the diagnosis of myocardial ischemia as it presents distinctive ischemic patterns. Deep learning methods such as convolutional neural networks (CNN) are employed to extract data-derived features and to recognize natural patterns. Hence, CNN enable an unbiased view on well-known clinical phenomenon, e.g., myocardial ischemia. This study tested a novel, hypothesis-generating approach using pre-trained CNN to determine the optimal ischemic parameter as obtained from the highly susceptible intracoronary ECG (icECG).MethodThis was a retrospective observational study in 228 patients with chronic coronary syndrome. Each patient had participated in clinical trials with icECG recording and ST-segment shift measurement at the beginning (i.e., non-ischemic) and the end (i.e., ischemic) of a one-minute proximal coronary artery balloon occlusion establishing the reference. Using these data (893 icECGs in total), two pre-trained, open-access CNN (GoogLeNet/ResNet101) were trained to recognize ischemia. The best performing CNN during training were compared with the icECG ST-segment shift for diagnostic accuracy in the detection of artificially induced myocardial ischemia.ResultsUsing coronary patency or occlusion as reference for absent or present myocardial ischemia, receiver-operating-characteristics (ROC)-analysis of manually obtained icECG ST-segment shift (mV) showed an area under the ROC-curve (AUC) of 0.903±0.043 (p<0.0001, sensitivity 80%, specificity 92% at a cut-off of 0.279mV). The best performing CNN showed an AUC of 0.924 (sensitivity 93%, specificity 92%). DeLong-Test of the ROC-curves showed no significant difference between the AUCs. The underlying morphology responsible for the network prediction differed between the trained networks but was focused on the ST-segment and the T-wave for myocardial ischemia detection.ConclusionsWhen tested in an experimental setting with artificially induced coronary artery occlusion, quantitative icECG ST-segment shift and CNN using pathophysiologic prediction criteria detect myocardial ischemia with similarly high accuracy.

Dataset Information

Detection of antecedent myocardial ischemia with multiselectin molecular imaging.

Publications

Detection of antecedent myocardial ischemia with multiselectin molecular imaging.

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