Tadayyon Hadi, Gangeh Mehrdad J, Vlad Roxana, Kolios Michael C, Czarnota Gregory J
Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue T2, Toronto, ON, Canada, M4N 3M5.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, M4N 3M5.
Methods Mol Biol. 2017;1644:41-60. doi: 10.1007/978-1-4939-7187-9_4.
In this chapter, we describe two new methodologies: (1) application of high-frequency ultrasound spectroscopy for in vivo detection of cancer cell death in small animal models, and (2) extension of ultrasound spectroscopy to the lower frequency range (i.e., 1-10 MHz range) for the detection of cell death in vivo in preclinical and clinical settings. Experiments using tumor xenografts in mice and cancer treatments based on chemotherapy are described. Finally, we describe how one can detect cancer response to treatment in patients noninvasively early (within 1 week of treatment initiation) using low-frequency ultrasound spectroscopic imaging and advanced machine learning techniques. Color-coded images of ultrasound spectroscopic parameters, or parametric images, permit the delineation of areas of dead cells versus viable cells using high ultrasound frequencies, and the delineation of areas of therapy response in patient tumors using clinically relevant ultrasound frequencies. Depending on the desired resolution, parametric ultrasound images can be computed and displayed within minutes to hours after ultrasound examination for cell death. A noninvasive and express method of cancer response detection using ultrasound spectroscopy provides a framework for personalized medicine with regards to the treatment planning of refractory patients resulting in substantial improvements in patient survival.
在本章中，我们描述了两种新方法：（1）应用高频超声光谱技术在小动物模型中对癌细胞死亡进行体内检测，以及（2）将超声光谱技术扩展到较低频率范围（即1 - 10兆赫兹范围），用于在临床前和临床环境中对体内细胞死亡进行检测。描述了使用小鼠肿瘤异种移植模型的实验以及基于化疗的癌症治疗方法。最后，我们描述了如何使用低频超声光谱成像和先进的机器学习技术在患者中早期（在治疗开始后1周内）无创地检测癌症对治疗的反应。超声光谱参数的彩色编码图像，即参数图像，能够使用高超声频率描绘死细胞与活细胞的区域，以及使用临床相关超声频率描绘患者肿瘤中的治疗反应区域。根据所需分辨率，可在超声检查后几分钟到几小时内计算并显示用于细胞死亡检测的参数超声图像。使用超声光谱技术进行癌症反应检测的无创且快速的方法为难治性患者的治疗规划提供了个性化医疗框架，从而显著提高患者生存率。
