A tissue viability imaging biomarker for use in non-invasive breast cancer therapy

摘要/摘要 虽然改进的早期检测方法和治疗方法降低了乳腺癌的死亡率， 部分患者仍然过度诊断和过度治疗，阻碍了更保守的发展。 乳腺癌的治疗磁共振引导的聚焦超声（MRgFUS）是目前 有吸引力的，新兴的乳腺癌手术，因为它可以安全有效地治疗局部乳腺癌 非侵入性地治疗肿瘤。目前，临床MRgFUS消融治疗使用MRI指标进行评估， 主要量化热效应和血管效应。虽然MR对诱导的组织变化具有明显的敏感性， 通过MRgFUS热消融，没有任何单一指标或指标组合证明充分 MRgFUS消融治疗期间或消融治疗后即刻预测组织活力的准确性。此外该 使用基于钆造影剂的评估技术，如果阳性，则排除进一步消融治疗 怀疑有肿瘤边缘。这项工作建议通过制定一项 深度神经网络非对比成像生物标志物，可提供即时和准确的 并且可以重复应用于组织活力的迭代评估 在MRgFUS消融过程中，确保完整的非侵入性肿瘤治疗。这一目标将是 实现了三个具体目标。 目的1：开发并验证3D多参数MRI方案，用于有效采集定性和 乳腺MRgFUS治疗环境中的定量MR图像。 目标2：开发、训练和验证用于预测肿瘤组织活力的深度神经网络生物标志物 MRgFUS消融治疗期间的模型。 目的3：将组织活力生物标志物整合到现有乳腺MRgFUS消融临床工作流程中， 使用非造影剂、深度神经网络生物标志物证明完全治疗体积消融， 治疗评估指标。 我们开发了一种创新的体积组织病理学形态学配准程序， 体内MR图像与组织病理学数据的体素比较，提供标记的金标准 开发这种成像生物标志物所需的数据集。将对成像生物标志物进行培训和验证 在临床前模型中进行，旨在允许立即推广并转化为正在进行的临床 审判该成像生物标志物将在MRgFUS消融期间提供组织活力的准确评估 治疗，彻底改变微创乳腺癌治疗，并直接解决关键的 过度治疗的问题。

Summary/Abstract While improved early detection methods and treatments have reduced breast cancer mortality, a sizable portion of patients remains overdiagnosed and overtreated, warranting the development of more conservative breast cancer treatments. Magnetic resonance guided focused ultrasound (MRgFUS) is one of the most attractive, emerging procedures for breast cancer as it can safely and efficaciously treat localized breast tumors non-invasively. Currently, clinical MRgFUS ablation treatments are assessed with MRI metrics that primarily quantify thermal and vascular effects. While there is evident MR sensitivity for tissue changes induced by MRgFUS thermal ablation, no single metric or combination of metrics have demonstrated adequate accuracy in predicting tissue viability during or immediately post-MRgFUS ablation treatment. In addition, the use of gadolinium contrast agent-based assessment techniques precludes further ablation treatment if positive tumor margins are suspected. This work proposes to address this critical unmet need through developing a deep neural network non-contrast imaging biomarker that would provide an immediate and accurate assessment of tissue viability and could be applied repeatedly for an iterative assessment of tissue viability during the MRgFUS ablation procedure, assuring complete non-invasive tumor treatment. This objective will be accomplished with three specific aims. Aim 1: Develop and validate a 3D multiparametric MRI protocol for efficient acquisition of qualitative and quantitative MR images in the breast MRgFUS therapeutic environment. Aim 2: Develop, train and validate a deep neural network biomarker for predicting tissue viability in a tumor model during MRgFUS ablation treatments. Aim 3: Integrate the tissue viability biomarker in an existing breast MRgFUS ablation clinical workflow and demonstrate complete treatment volume ablation using the non-contrast, deep neural network biomarker as the treatment assessment metric. We have developed an innovative, volumetric histopathology diffeomorphic registration procedure that allows the voxel-wise comparison of in vivo MR images to histopathological data, providing the gold-standard labeled data set needed to develop this imaging biomarker. Training and validation of the imaging biomarker will be performed in preclinical models designed to allow immediate generalizability and translation to ongoing clinical trials. This imaging biomarker will provide accurate assessment of tissue viability during MRgFUS ablation treatments, revolutionizing minimally invasive breast cancer treatments and directly addressing the critical issue of overtreatment.