McBride Devin W, Klebe Damon, Tang Jiping, Zhang John H
Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, 92350, USA.
Transl Stroke Res. 2015 Aug;6(4):323-38. doi: 10.1007/s12975-015-0400-3. Epub 2015 May 3.
Evaluating infarct volume is the primary outcome for experimental ischemic stroke studies and is a major factor in determining translation of a drug into clinical trials. Numerous algorithms are available for evaluating this critical value, but a major limitation of current algorithms is that brain swelling is not appropriately considered. The model by Lin et al. is widely used, but overestimates swelling within the infarction, yielding infarct volumes which do not reflect the true infarct size. Herein, a new infarct volume algorithm is developed to minimize the effects of both peri-infarct and infarct core swelling on infarct volume measurement. 2,3,5-Triphenyl-2H-tetrazolium chloride-stained brain tissue of adult rats subjected to middle cerebral artery occlusion was used for infarct volume analysis. When both peri-infarct swelling and infarction core swelling are removed from infarct volume calculations, such as accomplished by our algorithm, larger infarct volumes are estimated than those of Lin et al.'s algorithm. Furthermore, the infarct volume difference between the two algorithms is the greatest for small infarcts (<10% of brain volume) when peri-infarct swelling is the greatest. Finally, using data from four published studies, our algorithm is compared to Lin et al.'s algorithm. Our algorithm offers a more reliable estimation of the infarct volume after ischemic brain injury, and thus may provide the foundation for comparing infarct volumes between experimental studies and standardizing infarct volume quantification to aid in the selection of the best candidates for clinical trials.
评估梗死体积是实验性缺血性中风研究的主要结果，也是决定药物能否进入临床试验的一个主要因素。有许多算法可用于评估这一关键值，但当前算法的一个主要局限性是未适当考虑脑肿胀情况。Lin等人的模型被广泛使用，但该模型高估了梗死区内的肿胀程度，得出的梗死体积并不能反映真正的梗死大小。在此，我们开发了一种新的梗死体积算法，以尽量减少梗死周边和梗死核心肿胀对梗死体积测量的影响。将成年大鼠大脑中动脉闭塞后经2,3,5-氯化三苯基四氮唑染色的脑组织用于梗死体积分析。当在梗死体积计算中去除梗死周边肿胀和梗死核心肿胀时，比如通过我们的算法来实现，所估计的梗死体积比Lin等人的算法得出的梗死体积更大。此外，当梗死周边肿胀最严重时，对于小梗死（<脑体积的10%），两种算法之间的梗死体积差异最大。最后，利用四项已发表研究的数据，将我们的算法与Lin等人的算法进行比较。我们的算法能更可靠地估计缺血性脑损伤后的梗死体积，因此可为比较实验研究之间的梗死体积以及标准化梗死体积量化提供基础，以帮助选择临床试验的最佳候选药物。
