Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.
Department of Psychiatry and Psychotherapy I (Weissenau), Ulm University, Ravensburg, Germany.
NMR Biomed. 2021 Jul;34(7):e4509. doi: 10.1002/nbm.4509. Epub 2021 Mar 28.
The ischemic penumbra in stroke is not clearly defined by today's available imaging tools. This study aimed to develop a model system and noninvasive biomarkers of ischemic brain tissue for an examination that might potentially be performed in humans, very quickly, in the course of stroke triage. Perfused rat brain slices were used as a model system and P spectroscopy verified that the slices were able to recover from an ischemic insult of about 3.5 min of perfusion arrest. This was indicated as a return to physiological pH and adenosine triphosphate levels. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored and quantified by the metabolic conversions of hyperpolarized [1- C]pyruvate to [1- C]lactate and [ C]bicarbonate, respectively, using C spectroscopy. In a control group (n = 8), hyperpolarized [1- C]pyruvate was administered during continuous perfusion of the slices. In the ischemia group (n = 5), the perfusion was arrested 30 s prior to administration of hyperpolarized [1- C]pyruvate and perfusion was not resumed throughout the measurement time (approximately 3.5 min). Following about 110 s of the ischemic insult, LDH activity increased by 80.4 ± 13.5% and PDH activity decreased by 47.8 ± 25.3%. In the control group, the mean LDH/PDH ratio was 16.6 ± 3.3, and in the ischemia group, the LDH/PDH ratio reached an average value of 38.7 ± 16.9. The results suggest that monitoring the activity of LDH and PDH, and their relative activities, using hyperpolarized [1- C]pyruvate, could serve as an imaging biomarker to characterize the changes in the ischemic penumbra.
目前可用的成像工具无法明确界定中风的缺血半暗带。本研究旨在开发一种模型系统和缺血性脑组织的非侵入性生物标志物，以便在中风分诊过程中，有可能快速对人类进行检查。灌注大鼠脑切片被用作模型系统， P 光谱证实切片能够从大约 3.5 分钟的灌注停止的缺血性损伤中恢复。这表现为生理 pH 和三磷酸腺苷水平的恢复。通过 C 光谱分别监测和量化超极化 [1- C]丙酮酸向 [1- C]乳酸和 [ C]碳酸氢盐的代谢转化，来监测和量化瞬时乳酸脱氢酶 (LDH) 和丙酮酸脱氢酶 (PDH) 活性的变化。在对照组 (n = 8) 中，在切片的连续灌注期间给予超极化 [1- C]丙酮酸。在缺血组 (n = 5) 中，在给予超极化 [1- C]丙酮酸之前 30 秒停止灌注，并且在整个测量时间内 (约 3.5 分钟) 不恢复灌注。在缺血性损伤约 110 秒后，LDH 活性增加了 80.4 ± 13.5%，PDH 活性降低了 47.8 ± 25.3%。在对照组中，平均 LDH/PDH 比值为 16.6 ± 3.3，而在缺血组中，LDH/PDH 比值达到了 38.7 ± 16.9 的平均值。结果表明，使用超极化 [1- C]丙酮酸监测 LDH 和 PDH 的活性及其相对活性，可以作为一种成像生物标志物来表征缺血半暗带的变化。
