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. !

项目摘要 在这个三方美国 - 爱尔兰研发伙伴计划R01研究计划中，我们建议开发， 优化和评估最小侵入性微波热疗法（MWT）系统 原发性醛固酮主义的确切治疗。原发性醛固酮主义（PA）占全部的5-12％ 高血压并赋予心血管和脑血管并发症的较高风险 年龄和血压（BP）与必不可少的高血压相匹配。然而，PA仍未诊断，并且 经过不足的治疗，主要是由于大多数受影响的大多数管理选择 个人。当前单侧PA的确定方法是手术肾上腺切除术，而双侧 疾病是在医学上管理的；由于关闭目标抗雄激素，医疗疗法通常耐受性不佳 效果。在所有被诊断为PA的人中，只有约30％接受手术，以及 正常皮质将手术的选择限制为单侧疾病，鉴于不可避免的风险 双侧肾上腺切除术的肾上腺皮质不足。因此，总体目标 建议是图像引导方法的开发，优化和实验评估 用于APA的燃烧性MWT，以及肾上腺功能的治疗后评估。首先，我们会的 采用一系列体外研究来确定呈现的最佳热剂量范围 在亚燃料下热剂量下，肾上腺细胞过度功能。然后，我们将验证能力 在体内小鼠肿瘤模型中，这些热剂量的肾上腺细胞功能在热剂量 通过MRI温度成像跟踪。接下来，我们将开发一个使用微波涂抹器的系统 具有微波辐射的精确时空控制，以将MWT递送至肾上腺功能过度 细胞。我们将开发实时技术来从实时成像中识别目标组织， 通过术前PET/CT成像，将肾上腺功能过度的肾上腺细胞进行了成像，以便 指导涂抹器的放置和能量输送。最后，我们将开发一种非固化的对比剂 适合验证MWT后立即验证肾上腺细胞功能，从而提供一种手段 评估治疗结果。总体系统将在大型动物模型中进行评估。如果 成功并在未来的研究中转化为人类，这种方法将首次扩展 对单侧和双侧APA的个体对PA的确定管理。 呢