Center for Ultrasound Molecular Imaging and Therapeutics, Department of Medicine, University of Pittsburgh School of Medicine, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. Department of Systems and Biomedical Engineering, Cairo University, Giza, 12613, Egypt.
Phys Med Biol. 2014 Feb 21;59(4):881-95. doi: 10.1088/0031-9155/59/4/881. Epub 2014 Feb 3.
Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using US-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5-14 MHz) for both imaging and heating and a high-frequency (13-24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n = 10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n = 10) with low fat content (4.8 ± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ∼ 3 s and ∼ 9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively, to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (-0.065 ± 0.079%) were significantly (p < 0.05) higher than those measured in control livers (-0.124 ± 0.037%). Using histology as a gold standard to classify mouse livers, US-TSI had a sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic curve was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis.
肝脏脂肪变性或脂肪肝疾病发生于肝脏内的脂质堆积，并可导致脂肪性肝炎、肝硬化、肝癌，最终需要进行肝移植以治疗肝功能衰竭。传统的亮度模式（B 型）超声（US）是最常用于临床诊断肝脏脂肪变性的非侵入性诊断成像方式。然而，它主要是主观的，或者需要与肾脏或脾脏等参考器官进行比较。当参考器官发生病变或缺失时，这种比较可能会出现问题。目前的工作提出了一种使用超声诱导热应变成像（US-TSI）无创检测肝脏脂肪含量的替代方法。该技术基于水基组织和脂基组织之间声速随温度变化的差异。US-TSI 分别采用两种系统配置进行，包括用于成像和加热的中频扫描仪和单个线性阵列换能器（5-14 MHz），以及与单独定制的 US 加热换能器阵列相结合的高频（13-24 MHz）小动物成像系统。从肥胖小鼠模型中获得的高脂肪含量（45.6 ± 11.7%）的脂肪肝（n = 10）和从野生型小鼠中获得的低脂肪含量（4.8 ± 2.9%）的正常肝脏（n = 10）被嵌入明胶中。然后，在 US 诱导加热前后进行 US 成像。中频成像系统和高频成像系统分别使用约 3 s 和约 9.2 s 的加热时间周期来产生约 1.5°C 的温度变化。使用二维相位敏感散斑跟踪法估计由于声速变化而引起的明显回波移位。进行 US-TSI 后，对肝脏进行组织学检查以染色脂质并测量小鼠肝脏中的脂肪百分比。脂肪肝（-0.065 ± 0.079%）的热应变测量值明显（p < 0.05）高于正常肝脏（-0.124 ± 0.037%）的测量值。使用组织学作为金标准对小鼠肝脏进行分类，US-TSI 的灵敏度和特异性分别为 70%和 90%。受试者工作特征曲线下面积为 0.775。这项离体研究证明了使用 US-TSI 检测脂肪肝的可行性，并证明了 US-TSI 作为肝脏脂肪变性诊断工具的进一步研究是合理的。
