Noninvasive detection and monitoring of regional myocardial ischemia in situ using depth-resolved 31P NMR spectroscopy.

Abstract

Phosphorus (31P) NMR spectra showing the relative concentrations of phosphocreatine, ATP, and Pi were recorded noninvasively from localized regions in the left ventricles of dog hearts in situ by using depth-resolved surfacecoil spectroscopy at 1.5 T. Proton (1H) NMR surface-coil imaging was used to position 31P NMR coils and to determine the location of depth-resolved volumes immediately prior to 31P examination. Occlusion of the left anterior descending coronary artery produced regional ischemia detected as changes in the ratios of phosphocreatine, ATP, and Pi and by changes in the pH measured from the spectra. Spectral changes were not typically observed in regions adjacent to ischemic myocardium. Reperfusion produced some recovery, and ventricular fibrillation resulted in deterioration in high-energy metabolites. The location and size of ischemic tissue was measured by singlephoton-emission computed tomography (SPECT) and gammaray counting or by staining excised hearts. The technique should permit the long-term noninvasive monitoring of the metabolic response of the heart to pathologic processes and allow assessment of interventions. NMR spectrum is a profile of the relative concentrations of the high-energy phosphate metabolites phosphocreatine (PCr) and ATP as well as inorganic phosphate, Pi (1-6). Such spectra are responsive to changes in myocardial metabolism as early as 90 s after the onset of ischemia (3). To date, applications of 31P NMR spectroscopy to heart metabolism have proved invasive because of (i) the difficulty of achieving adequate spatial localization of the 31p signal to the heart, and (ii) the small magnet apertures of available

The fate of inorganic phosphate and pH in regional myocardial ischemia and infarction: A noninvasive 31P NMR study

“…Our 31P NMR investigations yielded no false-positive or false-negative detections of infarction, including all animals studied here ( Table 1) as well as those reported earlier and corroborated by postmortem staining or by radionuclide scanning (6). Indeed, it is fortuitous for the DRESS technique that the tissues which lie adjacent to the myocardium and which may intersect the depth-resolved volumes are not significant souces of phosphate metabolites ( 5 ) and hence do not overwhelm, obscure, or otherwise prevent detection of ischemic metabolism by 'P NMR.…”

“…Thus no significant spectral changes were observed in the dog which was not infarcted (dog No. 652; P > 0.1) and a significant reduction in pH and in PCr/Pi ratio ensued in spectra from acutely infarcted myocardium (P < 0.05; Table I), as reported previously (6). The shortest spectral acquisition period in which changes in phosphate metabolites associated with coronary occlusion and regional ischemia could be detected was 150 s commencing 50 s postocclusion, as demonstrated in Fig.…”

“…The myocardium was sliced transaxially into 0.5-cmthick sections that included normal and jeopardized tissue and stained by incubation at 37°C in a 1% solution of 2,3,5-triphenyltetrazolium chloride in a phosphate buffer (6,10). Infarcted tissue was manifested by an absence of stain in tissue from animals sacrificed 6 h or more postocclusion (10).…”

“…Eleven mongrel dogs weighing 27 * 6 kg were surgically prepared to enable induction of regional ischemia over less than 20% of the left ventricular myocardium during NMR experiments in the manner described previously (6). A thoracotomy was performed through the fourth intercostal space, and a permanent snare occluder was placed around the proximal left anterior descending coronary artery distal to the first large anterior lateral branch.…”

Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity

“…Secondly, NMR technology will have to be further developed to enable a fully non-invasive and non-destructive measurement of high-resolution NMR spectra of heart in the living subject. Recent reports by Aue et al [33] and Bottomley et al [34,35] employing magnetic field gradients to define the sensitive volume detected by NMR make it feasible that high-quality, localized spectra of deeply buried regions can be routinely obtained in the near future, thereby fully circumventing the surgery used in this study to position the NMR receiver coil around the heart.…”