Quantitative Multimodal Image Guidance for Improved Liver Cancer Treatment

定量多模态图像指导改善肝癌治疗

• 批准号: 9982672
• 负责人: JAMES S DUNCAN
• 金额: $ 60.16万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982672
• 关键词: Acidity; Acidosis; Address; Advanced Development; Angiography; Biochemical; Biological Markers; Blood Vessels; Blood flow; Cancer Etiology; Cancer Patient; Catheters; Cellularity; Cessation of life; Chemoembolization; Classification; Clinic; Clinical; Data; Data Analyses; Deposition; Development; Diagnosis; Dictionary; Disease; Drug Delivery Systems; Drug Targeting; Drug usage; Edema; Emulsions; Environment; Epidemic; Evaluation; Excision; Future; Goals; Grant; Hepatitis B; Hepatitis C; High Dose Chemotherapy; Hypoxia; Image; Image Analysis; Imaging Techniques; Imaging technology; Incidence; Industrialization; Intervention; Learning; Liver neoplasms; Local Therapy; Machine Learning; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Maps; Measures; Mediating; Methodology; Methods; Modification; Multimodal Imaging; Necrosis; Normal tissue morphology; Obesity; Oils; Oncology; Operative Surgical Procedures; Outcome; Outcome Assessment; Patient Care; Patient-Focused Outcomes; Patients; Pattern; Pharmaceutical Preparations; Phase; Physiological; Preparation; Property; Recurrence; Roentgen Rays; Role; Stage at Diagnosis; Structure; System; Technology; Therapeutic Embolization; Tissues; Translational Research; Translations; Transplantation; Treatment outcome; Tumor Markers; Tumor Tissue; Tumor-Derived; Tweens; Vascularization; Visualization; Work; X-Ray Computed Tomography; angiogenesis; arm; base; cancer cell; cancer therapy; chemotherapy; clinical practice; cone-beam computed tomography; contrast imaging; curative treatments; extracellular; feeding; image guided; image guided intervention; image processing; image registration; imaging biomarker; improved; improved outcome; innovative technologies; learning strategy; machine learning method; minimally invasive; nonalcoholic steatohepatitis; nonlinear regression; novel; novel strategies; novel therapeutics; outcome prediction; palliative; personalized cancer therapy; random forest; response; systemic toxicity; targeted delivery; treatment guidelines; treatment strategy; tumor; tumor microenvironment; tumor progression

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.

项目摘要/摘要 肝癌是全球与癌症相关死亡的第二大最常见原因，甚至可能增长 鉴于乙型肝炎和C的流行水平以及非酒精性的出现，在接下来的十年中还有更多 由于肥胖症在美国引起的脂肪性肝炎（NASH）。大多数肝癌患者患有疾病 接受外科手术治疗。微创，基于近代的，动脉内疗法，例如TACE（跨性别） 化学栓塞）已成为主要疗法，并被包括在所有治疗指南中 他们实现局部肿瘤控制并扩展生存的能力。 TACE克服了化学抗性的问题 在癌细胞中，通过图像引导和肿瘤栓塞提供高剂量化学疗法 进食血管。 TACE通常使用油性培养基（Lipiodol）作为放射性药物递送伴侣 通过在毒品和石油之间产生乳液来rial。最近引入药物洗脱珠（DEB）技术 - Ogy提供了实现对肿瘤的控制和可持续药物释放目标的机会，这是 用油腻的tace不可能。尽管TACE显然改善了患者的生存，但仍存在局限性 - 特殊的纤维， 不完整的治疗和肿瘤复发 - 归因于血管生成的刺激。这些问题大多 可以对肿瘤微环境有更深入的了解，特别是 缺氧，酸中毒和血管生成之间存在。实际上，成像生物标志物的发展反映 肿瘤微环境中的变化越来越多地被追求以个性化癌症疗法和 增加他们的效力。然而，我们使用当前成像技术来表征肿瘤微环境的能力 - 疾病非常有限。直到最近出现，TACE必须依靠2D X射线血管造影 心脏内部双相锥束CT（DP-CBCT）对改善肿瘤可视化的贡献显着贡献， 微量导管指导和治疗终点。正是通过长期存在的密切合作伙伴关系 推文飞利浦，约翰·霍普金斯（Johns Hopkins）和耶鲁 TACE的新实践标准，证明了将研究发现的成功转换为 临床实践。但是，肿瘤的靶向和结果的评估继续受到限制，依赖 DP-CBCT和单个参数MR图像的定性/半定量增强模式。这 耶鲁大学和飞利浦之间的独特伙伴关系提供了创新的技术，该技术将直接增强 图像引导的干预措施，并通过定量表征肿瘤微环境来解决这种未满足的需求 RONMENT和肿瘤组织组成，以最大程度地提高治疗效力并改善预后。我们将 具有主动CBCT成像的集成高级，多参数MR，并创建从 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信息， 可以将药物输送到肿瘤中，因为它将基于继承肿瘤特性。同样 方式，对治疗的评估将更加精确，因此对于识别响应者有用。