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

• 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
• 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

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. !

项目总结 在这项美国-爱尔兰三方研发伙伴计划R01研究计划中，我们提出了发展， 微创微波热疗(MWT)系统的优化与评价 明确治疗原发性醛固酮增多症。原发性醛固酮增多症(PA)占总数的5%-12% 高血压和心脑血管并发症的风险更高 与年龄和血压(BP)相匹配的是高血压。然而，PA仍然没有得到充分的诊断 治疗不足，主要是因为大多数受影响的人缺乏明确的管理选择 个人。目前治疗单侧PA的最终方法是手术切除肾上腺，而双侧 疾病是由医学控制的；由于偏离目标的抗雄激素药物，药物治疗往往耐受性差。 效果。在所有被诊断为PA的患者中，只有30%接受了手术和侧枝切除术。 考虑到不可避免的风险，正常的皮质将手术的选择限制在单侧疾病上 双侧肾上腺切除术后肾上腺皮质功能不全。因此，这一总体目标是 建议是图像引导方法的开发、优化和实验评估 用于APAs的亚消融MWT，以及用于治疗后的肾上腺功能评估。首先，我们将 采用一系列体外研究来确定渲染的最佳热剂量范围 在亚消融热剂量下，功能亢进的肾上腺细胞死亡。然后我们将验证是否有能力 热剂量对体内小鼠肿瘤模型肾上腺细胞功能的影响 通过核磁共振温度成像进行追踪。接下来，我们将开发一个使用微波辐射器的系统 通过精确的时空控制微波辐射将MWT输送到功能亢进的肾上腺 细胞。我们将开发用于从实时成像识别目标组织的实时技术， 通过术前PET/CT成像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。 适合于在MWT后立即验证肾上腺细胞功能，从而提供了一种 评估治疗结果。整个系统将在一个大型动物模型中进行评估。如果 成功，并在未来的研究中应用于人类，这种方法将第一次扩展 对患有单边和双边动植物抗凝血障碍的个人进行明确的个人保护管理。 好了！