Herscovitch P, Raichle M E, Kilbourn M R, Welch M J
Department of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.
J Cereb Blood Flow Metab. 1987 Oct;7(5):527-42. doi: 10.1038/jcbfm.1987.102.
We have previously adapted Kety's tissue autoradiographic method for measuring regional CBF in laboratory animals to the measurement of CBF in humans with positron emission tomography (PET) and H2(15)O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H2(15)O, may lead to an underestimation of CBF. We therefore validated the use of [11C]butanol as an alternative freely diffusible tracer for PET. We then used it in humans to determine the underestimation of CBF that occurs with H2(15)O, and thereby were able to calculate the extraction Ew and permeability-surface area product PSw of H2(15)O. Measurements of the permeability of rhesus monkey brain to [11C]butanol, obtained by means of an intracarotid injection, external detection technique, demonstrated that this tracer is freely diffusible up to a CBF of at least 170 ml/min-100 g. CBF measured in baboons with the PET autoradiographic method and [11C]butanol was then compared with CBF measured in the same animals with a standard residue detection method. An excellent correspondence was obtained between both of these measurements. Finally, paired PET measurements of CBF were made with both H2(15)O and [11C]butanol in 17 normal human subjects. Average global CBF was significantly greater when measured with [11C]butanol (53.1 ml/min-100 g) than with H2(15)O (44.4 ml/min-100 g). Average global Ew was 0.84 and global PSw was 104 ml/min-100 g. Regional measurements showed a linear relationship between local PSw and CBF, while Ew was relatively uniform throughout the brain. Simulations were used to determine the potential error associated with the use of an incorrect value for the brain-blood partition coefficient for [11C]butanol and to calculate the effect of tissue heterogeneity and errors in flow measurement on the calculation of PSw.
我们之前已将凯蒂的组织放射自显影法（用于测量实验动物的局部脑血流量），改编为利用正电子发射断层扫描（PET）和H₂¹⁵O来测量人体脑血流量的方法。由于该模型假定组织与静脉血之间存在扩散平衡，使用扩散受限示踪剂（如H₂¹⁵O）可能会导致脑血流量被低估。因此，我们验证了[¹¹C]丁醇作为PET替代自由扩散示踪剂的用途。然后我们将其用于人体，以确定使用H₂¹⁵O时发生的脑血流量低估情况，从而能够计算H₂¹⁵O的提取率Ew和通透表面积乘积PSw。通过颈内注射、外部检测技术获得的恒河猴脑对[¹¹C]丁醇的通透性测量结果表明，该示踪剂在脑血流量至少为170 ml/min - 100 g时可自由扩散。然后将用PET放射自显影法和[¹¹C]丁醇在狒狒中测量的脑血流量，与用标准残留检测法在同一动物中测量的脑血流量进行比较。这两种测量结果之间具有极好的一致性。最后，对17名正常人类受试者进行了H₂¹⁵O和[¹¹C]丁醇的成对PET脑血流量测量。用[¹¹C]丁醇测量时的平均全脑血流量（53.1 ml/min - 100 g）显著高于用H₂¹⁵O测量时的（44.4 ml/min - 100 g）。平均全脑Ew为0.84，全脑PSw为104 ml/min - 100 g。区域测量显示局部PSw与脑血流量之间呈线性关系，而Ew在整个大脑中相对均匀。通过模拟来确定与使用不正确的[¹¹C]丁醇脑血分配系数值相关的潜在误差，并计算组织异质性和血流测量误差对PSw计算的影响。
