Quantitative Multimodal Image Guidance for Improved Liver Cancer Treatment

项目摘要/摘要 肝癌是全球癌症相关死亡的第二大常见原因，而且甚至有可能增长。 考虑到乙型和丙型肝炎的流行水平以及非酒精性肝炎的出现，未来十年会有更多 在美国，肥胖导致的脂肪性肝炎(NASH)。大多数肝癌患者都患有不能 接受手术治疗。微创、基于导管的动脉内治疗，如TACE(经动脉 化疗栓塞术)已成为主要的治疗方法，并被包括在所有治疗指南中，因为 他们有能力实现局部肿瘤控制和延长生存期。TACE克服了化疗耐药问题 通过图像引导和肿瘤栓塞术进行大剂量化疗 供血血管。TACE最常见的使用油性介质(碘化油)作为不透射线的药物输送伙伴- 里亚尔通过在药物和油之间创建乳剂。介绍了药物洗脱微球技术的最新进展。 OGY为实现受控和可持续的药物释放到肿瘤的目标提供了机会，这是 用油性的TACE是不可能的。尽管TACE明显提高了患者的存活率，但局限性仍然存在--尤其是fi， 治疗不彻底和肿瘤复发--归因于血管生成的刺激。大多数这样的问题 可以通过对肿瘤微环境的更多了解来解决，特别是与 存在于缺氧、酸中毒和血管生成之间。事实上，fl成像生物标志物的研究进展 肿瘤微环境的变化越来越多地被追求以使癌症治疗和个体化 增强他们的力量。然而，我们使用目前的成像技术来表征肿瘤微环境的能力- Nology是极其有限的。TACE一直不得不依赖2D-X-射线血管造影，直到最近出现了 术中双期锥束CT(DP-fi)显著提高了肿瘤的显示率， 微导管引导和治疗终点。正是通过长期的密切合作伙伴关系，BE- 飞利浦、约翰斯·霍普金斯大学和现在的耶鲁大学都认为这项技术经过了优化，并被广泛接受为 TACE的新实践标准，展示了研究fi标准迅速成功地翻译为 临床实践。然而，针对肿瘤的靶向和结果评估仍然有限，依赖于 从DP-CBCT和单参数MR图像分析定性/半定量增强模式。这个 耶鲁和飞利浦之间独特的合作伙伴关系提供了创新技术，将直接增强 图像引导介入，并通过定量表征肿瘤微环境来满足这一未得到满足的需求。 为了最大限度地发挥治疗效力和改善结果，我们将在治疗环境和肿瘤组织成分方面采取有效措施。我们会 将先进的多参数MR与主动CBCT成像集成在一起，创建源自 用于图像和数据分析的新型机器学习方法。通过提供基本的、定量的信息， 可以最大限度地将药物输送到肿瘤，因为它将基于肿瘤的固有特性。在相同的 通过这种方式，对治疗的评估将更加准确，因此有助于确定应答者。

Project Summary/Abstract Liver cancer is the second most common cause of cancer-related death worldwide and is likely to grow even more in the next decade given the epidemic levels of hepatitis B and C and the emergence of non-alcoholic steatohepatitis (NASH) due to obesity in the US. Most liver cancer patients present with disease that cannot be treated surgically. Minimally invasive, catheter-based, intra-arterial therapies such as TACE (transarterial chemoembolization) have become the mainstay therapy and are included in all treatment guidelines because of their ability to achieve local tumor control and extend survival. TACE overcomes the problem of chemoresistance in cancer cells by delivering high dose chemotherapy through image guidance and embolization of the tumor feeding blood vessel. TACE most commonly uses an oily medium (Lipiodol) as a radiopaque drug delivery mate- rial by creating an emulsion between drugs and oil. The recent introduction of drug-eluting bead (DEB) technol- ogy provides an opportunity to achieve the goal of controlled and sustainable drug release to tumors, which was not possible with oily TACE. Although TACE clearly improves patient survival, limitations still exist – specifically, incomplete treatment and tumor recurrence – attributed to the stimulation of angiogenesis. Most of these issues can be addressed with a greater understanding of the tumor microenvironment, in particular the relationship that exists between hypoxia, acidosis and angiogenesis. In fact, the development of imaging biomarkers reflecting changes within the tumor microenvironment is increasingly being pursued to individualize cancer therapies and increase their potency. Yet, our ability to characterize the tumor microenvironment using current imaging tech- nology is extremely limited. TACE has had to rely on 2D X-ray angiography until recently when the emergence of intra-procedural dual phase cone beam CT (DP-CBCT) contributed significantly to improving tumor visualization, microcatheter guidance, and treatment endpoint. It is precisely through the longstanding close partnership be- tween Philips, Johns Hopkins and now Yale that this technology was optimized and became broadly accepted as the new standard of practice for TACE, demonstrating the prompt successful translation of research findings to clinical practice. However, the targeting of tumors and assessment of outcomes continues to be limited, relying on qualitative/semi-quantitative enhancement patterns from DP-CBCT and single parameter MR images. The unique partnership between Yale & Philips provides innovative technology that will directly enhance the role of image-guided intervention and address this unmet need by quantitatively characterizing the tumor microenvi- ronment and tumor tissue composition in order to maximize treatment potency and improve outcomes. We will integrate advanced, multiparameter MR with active CBCT imaging and create valuable biomarkers derived from novel machine learning methods for image and data analysis. By providing essential, quantitative information, drug delivery to tumors can be maximized because it will be based on inherent tumor properties. In the same way, the assessment of therapy will be much more precise and therefore useful to identify responders.