Interventional Oncology

美国国立卫生研究院临床中心（CC）成立了介入肿瘤学中心（CIO），以开发和转化用于局部癌症治疗的图像引导技术。该中心是由CC和国家癌症研究所（NCI）以及较小程度上的NIBIB合作建立的。该中心利用每个合作伙伴的优势，研究成像技术和设备如何以精确靶向和微创或非侵入性的方式诊断和治疗局部癌症。在这样做的过程中，CIO在诊断和治疗之间，以及新兴技术和程序性医学之间架起了桥梁。先进的成像技术开创了一个早期检测癌症的时代，这些癌症通常局限于单个器官或区域，如肝脏或前列腺。介入肿瘤学通常为癌症患者提供局部或区域治疗选择，以增加标准的全身或器官癌症治疗。CIO调查员利用CC的跨学科、转化环境来调查和优化如何以及何时结合药物、设备和多模态成像导航。例如，“可激活”的药物可以注射到纳米级或微米级载体或气泡内的静脉或动脉中，然后用针、导管或使用“融合成像”、“增强现实”或“深度学习”的超声直接部署在肿瘤中，使医生能够以更标准化的方式在体内导航，并使用最新的先进成像技术，如磁共振成像（MRI）进行实时可视化。正电子发射断层扫描（PET），计算机断层扫描（CT），锥形束CT (CBCT)，或超声波。手术前的图像被重复使用，以指导设备将靶向治疗送到疾病的位置，使手术更具成本效益，因为它不需要成像系统实际存在，以利用先前的成像信息。例如，先前的前列腺MRI可以通过使用“医疗GPS”启用针和超声来帮助引导活检或局灶消融，而无需在过程中占用或捆绑MRI系统。在另一个例子中，细针或光声或电波可以用来消融肿瘤和增强靶向药物输送。能量来源包括高强度聚焦超声、冷冻、微波、激光、组织切片、电穿孔和射频。研究人员还扩大了对图像引导药物输送或图像引导“药物绘画”的研究，通过将靶向、可成像或可激活的药物与局部能量或热量结合起来，将药物部署在专门设计的微或纳米颗粒中，图像可以用来为特定区域开一种特定的药物。该中心提供了一个论坛，鼓励研究人员和患者护理专家在医学，外科，泌尿外科，放射肿瘤学和介入放射学/分子干预之间的合作。CC为这种类型的合作转化研究提供了一个特殊的环境。其他主要项目包括开发用于个性化药物研究的新图像引导方法（或在药物发现期间跟踪组织对研究药物的反应）和首次人体研究，涉及新的微或纳米级药物和载体、设备、图像引导机器人或增强现实设备，以增强程序的自动化和标准化。靶向序贯活检是跨越时间和空间坐标的药物发现或生物标志物表征的有力工具。

The Center for Interventional Oncology (CIO) was established at the NIH Clinical Center (CC) to develop and translate image-guided technologies for localized cancer treatments. The Center is a collaboration involving the CC and the National Cancer Institute (NCI), and to lesser extent NIBIB. The Center draws on the strengths of each partner to investigate how imaging technologies and devices can diagnose and treat localized cancers in ways that are precisely targeted and minimally or non-invasive. In doing so, CIO bridges the gap between diagnosis and therapy, and between emerging technologies and procedural medicine. Advanced imaging methods have ushered in an era of earlier detection of cancers that are frequently localized to a single organ or region, such as the liver or prostate. Interventional oncology often provides cancer patients with local or regional treatment options to augment the standard systemic or organ based cancer therapies. CIO investigators leverage the interdisciplinary, translational environment at the CC to investigate and optimize how and when to combine drugs, devices, and multimodal imaging navigation. For example, "activatable" drugs can be injected in a vein or artery inside a nanoscale or micron-scale vector or bubble, then deployed directly in the tumor with needles, catheters, or ultrasound using "fusion imaging", "augmented reality", or "deep learning", to enable the physician to navigate through the body in a more standardized fashion, with real-time visualization using the latest advanced imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), cone beam CT (CBCT), or ultrasound. Pre-procedural images are reused to guide devices delivering targeted therapy to the location of the disease, making the procedure more cost-effective because it doesn't require the imaging system to be physically present to take advantage of the prior imaging information. A prior prostate MRI, for example, can be used to help with guided biopsy or focal ablation by using a "medical GPS"-enabled needle and ultrasound, without requiring, occupying or tying up an MRI system during the procedure. In another example, a thin needle or light sound or electrical waves can be used to ablate tumors and enhance targeted drug delivery. Energy sources include high-intensity focused ultrasound, freezing, microwaves, laser, histotripsy, electroporation, and radiofrequency. Researchers also expand investigations into image-guided drug delivery or image-guided "drug painting," where the image can be used to prescribe a particular drug to a specific region, by combining targeted, image-able-able or activate-able drugs with localized energy or heat to deploy the drug within specially engineered micro- or nano-particles. The Center provides a forum to encourage collaborations among researchers and patient-care experts in medical, surgical, urologic, and radiation oncology and interventional radiology / molecular interventions.. The CC provides an exceptional environment for this type of collaborative translational research. Other major program components include the development of new image-guided methods for personalized drug investigations (or tracking tissue responses to investigational drugs during drug discovery) and first-in-human investigations involving new micro- or nano-scale drugs and carriers, devices, image-guided robotics or augmented reality devices for enhanced automation and standardization of procedures. Targeted sequential biopsy is a powerful tool for drug discover or biomarker characterization across time and space coordinates. Education and cross-training is another important part of the program. Significant gaps exist between the various disciplines, between research efforts and patient care, and between diagnosis and treatment. The gaps may be integrated through advanced image methods for localized therapy. CIO trainees are exposed to a wide variety of disciplinary thought, which underlines the unique translational atmosphere at the NIH, where bench-to-bedside is the rule. Specific aims include: 1. Develop training and educational pathways not otherwise available in Interventional Oncology 2. Develop novel image-guided methods for smart biopsy and biomarker procurement to support targeted therapeutics 3. Support patient care using novel minimally invasive Interventional Oncology techniques, especially in the liver, kidney and prostate 4. Pursue research in novel techniques and technologies in Interventional Oncology. This program is ideally and uniquely positioned to provide an interdisciplinary environment that combines training, patient care, and pre-clinical and in-vivo translational research to accelerate progress in interventional oncology and molecular targeted interventions. The focus is upon translational models, translational tools, and actual practical deliverables and multidisciplinary paradigms that meet specific translational milestones to address short term clinical needs. Deep learning in cancer was begun with the goal of defining pathways and toolkits to promote future integration of digital pathology, with molecular and imaging information for specific cancers and cancer interventions. CIO managed 10 preclinical protocols and 5 clinical protocols. The CIO has trained many students, residents, fellows, PhD candidates, junior faculty, visiting scientists, engineers, and collaborating scientists, who have successfully advanced in their academic careers and are practicing in interventional radiology, radiology, urology, radiation oncology, veterinary medicine, and various senior positions in academics and industry. The Woodchuck HCC model was established and characterized for IR and immunomodulatory agents. Heat vs freezing ablation was compared in terms of immune effects and immune resistance. Novel software and hardware were developed for patients. Augmented reality for smartphones was compared to standard guidance systems for composite ablation. CIO linked to the NCI AI Resource,for deep learning tasks within CCR and the data science ecosystem for cancer. Fusion guided ablation was developed and deployed for the office setting, as was prostate biopsy with needle and ultrasound totally outside of the rectum. Smartphone interventions were brought to clinic. CIO accomplished the 1st in human use of artificial intelligence and deep learning for semi-automated segmentation and registration during thermal ablation procedures, Transperineal hand-held ultrasound fusion biopsy without a frame or stepper stage was characterized in clinic, to enable accurate interventions for prostate cancer, without involving the rectum, in any way. In the translational animal lab, CIO characterized molecular immune correlates for woodchuck hepatitis-induced HCC, developed a drug delivery model for drug dose painting with fusion and image-able drug eluting beads, developed and deployed immuno-beads that elute immunomodulatory agents after local catheter-based delivery into woodchuck HCC, characterized preclinical augmentation of check point inhibition with cryo in woodchuck liver cancer and cryo and RFA in mouse tumors in vivo. Immunobubbles for US deployment were designed. Multiple bead chemistries and injectable gel formulations were refined. Multiple devices were developed including a video-based system for bronchoscopic tracking without robotics or EM hardware. Refinements for PercuNav and UroNav were refined, including research biopsy for elucidating tumor heterogeneity and correlative imaging. Augmented reality via smartphone was validated. The CIO team continued with impactful COVID-19 discoveries and assembled multi-national datasets and partnerships, with commercialized output (see COVID-19 annual report).