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.

项目总结/摘要 肝癌是全球癌症相关死亡的第二大常见原因， 鉴于B型和C型肝炎的流行程度以及非酒精性肝炎的出现， 脂肪性肝炎（NASH）是由于美国的肥胖。大多数肝癌患者的疾病不能 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）已成为主流疗法，并被纳入所有治疗指南，因为 它们实现局部肿瘤控制和延长生存期的能力。TACE克服了化疗耐药性问题 通过图像引导和肿瘤栓塞， 供血血管TACE最常使用油性介质（碘油）作为不透射线的药物输送材料- 通过在药物和油之间制造乳液来实现。介绍了近年来药物洗脱微球（DEB）技术的发展， ogy提供了一个机会，以实现控制和可持续的药物释放到肿瘤的目标，这是 不可能使用油性TACE。尽管TACE明显改善了患者生存率，但局限性仍然存在-特别是， 治疗不完全和肿瘤复发-归因于血管生成的刺激。这些问题多数 可以通过更好地了解肿瘤微环境来解决，特别是 存在于缺氧、酸中毒和血管生成之间。事实上，成像生物标志物的发展反映了 肿瘤微环境内的变化越来越多地被追求以个体化癌症治疗， 增加其效力。然而，我们利用当前成像技术表征肿瘤微环境的能力- nology是非常有限的。TACE不得不依赖于2D X射线血管造影术，直到最近， 术中双相锥形束CT（DP-CBCT）显著改善了肿瘤可视化， 微导管引导和治疗终点。正是通过长期的密切合作关系， 飞利浦，约翰霍普金斯和现在的耶鲁大学之间，这项技术是优化的，并成为广泛接受的， TACE实践的新标准，展示了研究结果的迅速成功转化， 临床实践然而，肿瘤的靶向和结果的评估仍然是有限的， 基于DP-CBCT和单参数MR图像的定性/半定量增强模式。的 耶鲁大学和飞利浦公司之间的独特合作伙伴关系提供了创新技术，将直接提高 图像引导的干预，并通过定量表征肿瘤微环境来解决这一未满足的需求， 肿瘤组织成分，以最大化治疗效力并改善结果。我们将 将先进的多参数MR与主动CBCT成像相结合， 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， 可以最大限度地将药物递送到肿瘤，因为它将基于固有的肿瘤特性。在同一 这样，对治疗的评估将更加精确，因此有助于识别应答者。