Studies in animal models have revealed that long exposures to anesthetics can induce apoptosis in the newborn and young developing brain. These effects have not been confirmed in humans because of the lack of a non-invasive, practical in vivo imaging tool with the ability to detect these changes. Following the successful use of ultrasound backscatter spectroscopy (UBS) to monitor in vivo cell death in breast tumors, we aimed to use UBS to assess the neurotoxicity of the anesthetic sevoflurane (SEVO) in a non-human primate (NHP) model. Sixteen 2- to 7-day-old rhesus macaques were exposed for 5 h to SEVO. Ultrasound scanning was done with a phased array transducer on a clinical ultrasound scanner operated at 10 MHz. Data consisting of 10–15 frames of radiofrequency (RF) echo signals from coronal views of the thalamus were obtained 0.5 and 6.0 h after initiating exposure. The UBS parameter “effective scatterer size" (ESS) was estimated by fitting a scattering form factor (FF) model to the FF measured from RF echo signals. The approach involved analyzing the frequency dependence of the measured FF to characterize scattering sources and selecting the FF model based on a χ² goodness-of-fit criterion. To assess data quality, a rigorous acceptance criterion based on the analysis of prevalence of diffuse scattering (an assumption in the estimation of ESS) was established. ESS changes after exposure to SEVO were compared with changes in a control group of five primates for which ultrasound data were acquired at 0 and 10 min (no apoptosis expected). Over the entire data set, the average measured FF at 0.5 and 6.0 h monotonically decreased with frequency, justifying fitting a single FF over the analysis bandwidth. χ² values of a (inhomogeneous continuum) Gaussian FF model were one-fifth those of the discrete fluid sphere model, suggesting that a continuum scatterer model better represents ultrasound scattering in the young rhesus brain. After application of the data quality criterion, only 5 of 16 subjects from the apoptotic group and 5 of 5 subjects from the control group fulfilled the acceptance criteria. All subjects in the apoptotic group that passed the acceptance criterion exhibited a significant ESS reduction at 6.0 h. These changes (–6.4%, 95% Interquartile Range: –14.3% to –3.3%) were larger than those in the control group (–0.8%, 95% Interquartile Range: –2.0% to 1.5%]). Data with a low prevalence of diffuse scattering corresponded to possibly biased results. Thus, ESS has the potential to detect changes in brain microstructure related to anesthesia-induced apoptosis.

动物模型研究表明，长时间接触麻醉剂可诱导新生儿和年轻发育中的大脑细胞凋亡。由于缺乏能够检测这些变化的非侵入性、实用的体内成像工具，这些影响尚未在人类中得到证实。继成功使用超声反向散射光谱 (UBS) 进行体内监测后乳腺肿瘤中的细胞死亡，我们旨在使用瑞银评估麻醉剂七氟醚 (SEVO) 在非人类灵长类动物 (NHP) 模型中的神经毒性。16 只 2 至 7 天大的恒河猴暴露于 SEVO 5 小时。超声扫描是在以 10 MHz 运行的临床超声扫描仪上使用相控阵换能器完成的。在开始暴露后 0.5 和 6.0 小时获得由来自丘脑冠状位的 10-15 帧射频 (RF) 回波信号组成的数据。UBS 参数“有效散射体尺寸”(ESS) 是通过将散射形状因子 (FF) 模型拟合到从 RF 回波信号测量的 FF 来估计的。该方法涉及分析测量的 FF 的频率依赖性以表征散射源并选择基于 χ ^{2 的}FF 模型拟合优度标准。为了评估数据质量，建立了基于漫散射普遍性分析（ESS 估计中的一个假设）的严格验收标准。将暴露于 SEVO 后的 ESS 变化与在 0 分钟和 10 分钟时获得超声数据的 5 只灵长类动物对照组的变化进行比较（预计无细胞凋亡）。在整个数据集上，在 0.5 和 6.0 小时测得的平均 FF 随频率单调下降，证明在分析带宽上拟合单个 FF 是合理的。χ ²（非均匀连续）高斯 FF 模型的值是离散流体球模型的五分之一，表明连续散射模型更好地代表了年轻恒河猴大脑中的超声散射。应用数据质量标准后，凋亡组的 16 名受试者中只有 5 名和对照组的 5 名受试者中的 5 名符合验收标准。通过接受标准的凋亡组中的所有受试者在 6.0 小时时表现出显着的 ESS 降低。这些变化（–6.4%、95% 四分位距：–14.3% 至 –3.3%）大于对照组（–0.8%、95% 四分位距：–2.0% 至 1.5%]）。漫散射流行率低的数据对应于可能有偏差的结果。因此，