Treating Primary aldosteronism-induced hypertension via microwave thermal therapy

微波热疗治疗原发性醛固酮增多症高血压

基本信息

批准号：
10320833
负责人：
Punit Prakash
金额：
$ 33.07万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-04 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10320833
关键词：
3-Dimensional Adrenal Cortex Adrenal Gland Adenoma Adrenal Gland Neoplasms Adrenal Glands Adrenalectomy Affect Aftercare Age Aldosterone Androgen Antagonists Animal Model Benign Bilateral Blood Pressure Cell Cycle Cell Survival Cell physiology Cells Computer Models Contrast Media Data Data Set Development Diagnosis Disease Dose Endocrine Gland Neoplasms Essential Hypertension Evaluation Event Excision Family suidae Frequencies Future Heating Human Hyperaldosteronism Hypertension Image Image Analysis In Vitro Individual Ireland Lesion Magnetic Resonance Imaging Mediastinum Medical Modeling Mus Operative Surgical Procedures PET/CT scan Parathyroid Adenoma Pathologic Patient imaging Patients Positioning Attribute Research Research Project Grants Risk Series Steroid biosynthesis System Systemic hypertension Techniques Technology Temperature Testing Time Tissues Translating Treatment outcome X-Ray Computed Tomography Xenograft Model adenoma base cardiovascular risk factor cell injury cerebrovascular design effective therapy experimental study first-in-human functional status high risk hypertensive image guided improved in vivo microwave electromagnetic radiation minimally invasive nanomaterials novel porcine model pre-clinical preservation real-time images research and development spatiotemporal tumor

项目摘要

PROJECT SUMMARY In this tripartite US-Ireland R&D partnership program R01 research plan, we propose the development, optimization, and evaluation of a minimally-invasive microwave thermal therapy (MWT) system for definitive treatment of primary aldosteronism. Primary aldosteronism (PA) accounts for 5 - 12% of all hypertension and confers a higher risk for cardiovascular and cerebrovascular complications compared to age and blood pressure (BP) matched essential hypertension. Yet PA remains under-diagnosed and under-treated, largely due to the lack of definitive management options for the majority of affected individuals. The current definitive approach to unilateral PA is surgical adrenalectomy, while bilateral disease is managed medically; medical therapy is often poorly tolerated due to off target anti-androgen effects. Only ~30% of all individuals diagnosed with PA undergo surgery, and collateral resection of normal cortex limits the option of surgery to unilateral disease, given the inevitable risk for adrenocortical insufficiency with bilateral adrenalectomy. Therefore, the overall objective of this proposal is the development, optimization, and experimental evaluation of an image-guided approach for sub-ablative MWT of APAs, and for post-treatment assessment of adrenal function. First, we will employ a series of in vitro studies to determine the optimal range of thermal doses for rendering hyperfunctioning adrenal cells defunct, at sub-ablative thermal doses. We will then verify the ability to disrupt adrenal cell function at these thermal doses in an in vivo mouse tumor model, with thermal dose tracked via MRI temperature imaging. Next, we will develop a system employing microwave applicators with precise spatio-temporal control of microwave radiation to deliver MWT to hyperfunctioning adrenal cells. We will develop real-time techniques for identifying the targeted tissue from real-time imaging, informed by pre-procedural PET/CT imaging localizing the hyperfunctioning adrenal cells, in order to guide applicator placement and energy delivery. Finally, we will develop a non-iodinated contrast agent suitable for verifying adrenal cell function, immediately post MWT, thereby providing a means for assessing treatment outcome. The overall system will be evaluated in a large animal model. If successful, and translated to humans in future studies, this approach will, for the first time, extend definitive management of PA to individuals with unilateral and bilateral APAs. !

项目概要在这个美国-爱尔兰三方研发合作伙伴计划 R01 研究计划中，我们提出开发，微创微波热疗（MWT）系统的优化和评估原发性醛固酮增多症的彻底治疗。原发性醛固酮增多症 (PA) 占所有醛固酮增多症的 5 - 12% 与高血压相比，心脑血管并发症的风险更高年龄和血压（BP）与原发性高血压相匹配。然而，PA 的诊断率仍然不足，并且治疗不足，主要原因是大多数受影响者缺乏明确的管理方案个人。目前单侧 PA 的最终治疗方法是手术肾上腺切除术，而双侧 PA 疾病得到医疗控制；由于抗雄激素药物脱靶，药物治疗的耐受性通常很差影响。在所有诊断为 PA 的个体中，只有约 30% 接受手术和并行切除术考虑到不可避免的风险，正常皮质限制了针对单侧疾病的手术选择肾上腺皮质功能不全双侧肾上腺切除术。因此，本次活动的总体目标提案是图像引导方法的开发、优化和实验评估用于 APA 的亚消融 MWT，以及肾上腺功能的治疗后评估。首先，我们将采用一系列体外研究来确定渲染热剂量的最佳范围在亚消融热剂量下，功能亢进的肾上腺细胞会失效。然后我们将验证是否有能力在体内小鼠肿瘤模型中，这些热剂量会破坏肾上腺细胞功能通过 MRI 温度成像进行跟踪。接下来，我们将开发一种采用微波施加器的系统精确时空控制微波辐射，将 MWT 传送至功能亢进的肾上腺细胞。我们将开发实时技术，通过实时成像识别目标组织，通过术前 PET/CT 成像来定位功能亢进的肾上腺细胞，以便指导施药器的放置和能量输送。最后，我们将开发一种非碘造影剂适用于在 MWT 后立即验证肾上腺细胞功能，从而提供了一种方法评估治疗结果。整个系统将在大型动物模型中进行评估。如果这种方法取得了成功，并在未来的研究中转化为人类，将首次扩展对具有单边和双边 APA 的个人进行明确的 PA 管理。！