Development of Tough Hydrogel Phantoms to Mimic Fibrous Tissue for Focused Ultrasound Therapies.
Development of Tough Hydrogel Phantoms to Mimic Fibrous Tissue for Focused Ultrasound Therapies.
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DOI：
10.1016/j.ultrasmedbio.2022.05.002
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发表时间：
2022-09
影响因子：
2.9
通讯作者：
Maxwell AD
中科院分区：
文献类型：
--
作者：
Nanda Kumar Y;Singh Z;Wang YN;Schade GR;Kreider W;Bruce M;Vlaisavljevich E;Khokhlova TD;Maxwell AD
组织模拟凝胶提供了一种经济高效的媒介，可通过即时反馈来优化组织碎屑病治疗参数。琼脂糖凝胶和聚丙烯酰胺凝胶经常被用来评估治疗结果，因为它们模仿了各种软组织的声学特性和硬度，但它们不表现出纤维结缔组织的特征--高韧性。为了模拟良性前列腺增生症(BPH)和其他组织学可能治疗的疾病中发现的病理纤维组织，开发了一种由聚丙烯酰胺和海藻酸盐混合而成的具有高韧性的光学透明水凝胶。硬度是使用剪切波弹性成像(SWE)和压痕测量技术建立的，并被发现代表了人BPH体外前列腺组织。用700 kHz组织摩擦换能器以不同的脉冲重复频率(PRF)处理不同的体模成分和体外切除的BPH组织样本。治疗后，根据SWE的测量，杂化凝胶和组织样本显示出不同程度的硬度降低。在B超上，部分治疗区为高回声区，完全液化区为低回声区。凝胶样品的相差显微镜显示，液化的区域与目标病变尺寸一致，并与组织样品中通过组织学鉴定的结果相关联。在混合凝胶中实现液化所需的剂量与在体外组织中观察到的相似，并且比类似或更高杨氏模数的琼脂糖高10倍。这些结果表明，所开发的水凝胶非常接近于在BPH前列腺体外组织中发现的弹性，并且对组织摩擦学治疗具有类似的反应，从而使它们成为开发和评估不同治疗方案的有用的成本效益的替代方案。
Tissue-mimicking gels provide a cost-effective medium to optimize histotripsy treatment parameters with immediate feedback. Agarose and polyacrylamide gels are often used to evaluate treatment outcomes as they mimic the acoustic properties and stiffnesses of a variety of soft tissues, but they do not exhibit high toughness, a characteristic of fibrous connective tissue. To mimic pathologic fibrous tissue found in benign prostate hyperplasia (BPH) and other diseases that are potentially treatable with histotripsy, an optically transparent hydrogel with high toughness was developed that is a hybrid of polyacrylamide and alginate. The stiffnesses was established using shear wave elastography (SWE) and indentometry techniques and were found to be representative of human BPH ex-vivo prostate tissue. Different phantom compositions and excised ex-vivo BPH tissue samples were treated with a 700 kHz histotripsy transducer at different pulse repetition frequencies (PRF). Post treatment, the hybrid gels and the tissue samples showed differential reduction in stiffness as measured by SWE. On B-Mode ultrasound, partially treated areas were present as hyperechoic zones and fully liquified areas as hypoechoic zones. Phase-contrast microscopy of the gel samples showed liquefaction in regions consistent with the target lesion dimensions and correlated to findings identified in tissue sample via histology. The required dose to achieve liquefaction in the hybrid gel was similar to what has been observed in ex-vivo tissue and greater than agarose of comparable or higher Young’s Modulus by a factor >10. These results indicate that the developed hydrogels closely mimic elasticities found in BPH prostate ex-vivo tissue and have a similar response to histotripsy treatment, thus making them a useful cost-effective alternative for developing and evaluating different treatment protocols.
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