Quantitative estimates of mechanical properties from in vivo tumors of rodent animals
Quantitative estimates of mechanical properties from in vivo tumors of rodent animals
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发表时间：
2012-05
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通讯作者：
Yue Wang
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作者：
Yue Wang
肿瘤力学性质的图像提供了重要的见解恶性过程的特点是细胞外基质重塑和硬化。本论文的重点是使用超声工具成像自发性啮齿动物乳腺肿瘤中产生的剪切波，以估计实际条件下的复剪切模量，并评估与基质粘弹性肿瘤类型和阶段的敏感性。通过多普勒超声在体内跟踪振动针（50-450 Hz）产生的圆柱形谐波剪切波。空间相梯度的估计产生的剪切速度色散曲线拟合的Kelvin-Voigt流变模型的预测值，找到弹性和粘性系数的复模量。随后，切除肿瘤进行流变测试以独立验证系数估计值，随后进行组织学处理以评价肿瘤类型。研究了4例良性乳腺纤维腺瘤（直径2-4 cm）、1例良性小叶增生（直径3 cm）和4例4 T1细胞系诱导的癌（直径1-2 cm）。在大鼠肿瘤中，平均测量的弹性（1.18 kPa）和粘性（1.79 Pa·s）系数与标准流变仪进行了比较。粘弹性与纤维化等级相关;两个系数均随纤维化水平单调增加。在模型小鼠癌，诊断特异性的粘弹性行为的变化。讨论了ECM成分、流变学模型、非线性波传播以及边界反射等因素对组织力学特性估计的影响。解决这些问题对于通过做出关于机械激励方法和本构模型的正确决定来提高模量iii测量精度和病变图像对比度非常重要。动态剪切波估计复数模量已被证明能够描述乳腺肿瘤。病变类型之间的可测量差异大于动物间或技术变异性。然而，为了使用弹性成像可靠地对肿瘤进行分类，需要更多关于组织机械特性中的生物对比机制的知识。未来的工作将是发现机械性能如何随着癌症进展而变化，以及通过评估机械环境来监测这种变化的方法。四、鸣谢
Images of tumor mechanical properties provide important insights into malignant processes characterized by extracellular matrix remodeling and stiffening. This thesis focuses on using ultrasonic tools to image shear waves generated in spontaneous rodent mammary tumors to estimate the complex shear modulus under realistic conditions, and to assess the sensitivity for relating matrix viscoelasticity to tumor type and stage. Cylindrical, harmonic shear waves generated by a vibrating needle (50-450 Hz) were tracked by Doppler-ultrasound in vivo. Estimates of spatial-phase gradients yielded shear-speed dispersion curves that were fit to values predicted from a Kelvin-Voigt rheological model to find the elastic and viscous coefficients of the complex modulus. Subsequently, tumors were excised for rheometry testing to independently validate coefficient estimates and later histologically processed to evaluate tumor type. Four benign mammary fibroadenomas (2-4 cm diameter), one benign lobular hyperplasia (3 cm diameter) and four 4T1 cell line induced carcinomas (1-2 cm diameter) were studied. In rat tumors the average measured elastic (1.18 kPa) and viscous (1.79 Pa·s) coefficients compared well with standard rheometry. Viscoelastic properties correlated with fibrosis grade; both coefficients were seen to increase monotonically with fibrotic levels. In modeled mice carcinomas, diagnostic-specific changes of viscoelastic behavior were seen. Factors which might lead to variation in tissue mechanical property estimation are discussed, including ECM composition, rheological model, nonlinear wave propagation as well as boundary reflection. Addressing these issues is of great importance in enhancing modulus iii measurement accuracy and lesion image contrast by making the right decisions about mechanical excitation methods and constitutive models. Dynamic shear-wave estimation of complex modulus has demonstrated an ability to describe mammary tumors. The measurable differences between lesion types are greater than inter-animal or technique variabilities. Nevertheless, to reliably classify tumors using elasticity imaging, more knowledge on the biological contrast mechanism in tissue mechanical properties is needed. Future work will be on discovering how mechanical properties change with cancer progression and the way to monitor this change by assessing mechanoenvironment. iv ACKNOWLEDGMENTS