Targeted Temperature Modulation with Smart Radiometric Monitoring for Effective and Long-Lasting Opioid-Free Pelvic Pain Relief - A Novel Low-Cost, Portable, Tampon-sized Thermal Transfer Device.

摘要 骨盆疼痛(PP)与20多种不同的临床确认的疾病有关，如尿路 感染(UTI)、月经痉挛(MC)、子宫内膜异位症(EM)、膀胱过度活动症(OAB)和间质 膀胱炎/痛性膀胱综合征(IC/PBS)。这些痛苦和虚弱的情况通常会有戏剧性的 对数百万PP患者的生活质量(QOL)产生负面影响，原因是工作效率下降和 在校表现，到性生活和幸福感下降。PP也与更多的滥用有关 阿片类药物和精神药物，最终导致服药过量和自杀。除 对于患者及其家庭的负担，经济上的直接和间接PP成本是很大一部分(&gt；20%) 在美国，6350亿美元与慢性疼痛有关。在全球范围内，盆腔疼痛影响着五分之一的女性和十二分之一的男性。 虽然包括神经刺激在内的治疗方法是可用的，但它们成本高昂，而且随着时间的推移会失去效果。 30%的患者在住院期间。患有目前无法治疗的慢性PP的患者需要一种新的治疗方法，可以 缓解他们虚弱的症状。疼痛显著缓解，排尿频率减少 最近与盆底的热调节有关。H3Pelvic成功地形成了一种对比 应用治疗(CAT)系统通过水快速而舒适地调节温度(冷/暖)- 会阴膜在软座上循环。当适当大小的阴道或直肠探头具有优越的温度时 将传导性与CAT系统相结合，可以显著缓解疼痛：最初的一组患者 顽固性IC，对药物或神经刺激无反应，每天阴道降温45分钟，恢复正常 事业，重新开始上学、工作和性生活，导致总体上更幸福和更有成效的生活。 我们建议优化探头设计，以最大限度地利用热管定向输送热调制 技术，包括被动微波辐射测量的实时温度跟踪。RICAT(辐射测量 集成CAT)将使用集成探头的智能辐射测量来监测深层组织温度。通过利用 机器学习，一组最小的传感器应该准确地重建目标区域的温度和 最大限度地减轻疼痛。第一阶段的具体目标是：1)以最佳方式集成辐射传感器 和RICAT原型中的智能计划/控制软件；2)比较辐射分布与侵入性针头 传感器并对体外组织和7头正在进行阴道或直肠冷却/升温周期的猪进行组织学研究。 第一阶段的目标是将辐射传感集成到热探头中，并测试探头的能力 在临床前环境中，使用健康的猪在骨盆区域提供一致的冷却和加热。数据 收集到的药物将允许我们进入第二阶段，其中将包括对难治性IC患者的人体试验。我们预计 这项动物研究将表明，RICAT能最佳地将缓解疼痛的热调节传递到骨盆 区域(S)有效、可靠地开展工作。第一阶段的成功完成将为临床翻译铺平道路 为数百万患有衰弱骨盆疼痛的患者提供安全有效的止痛技术。

ABSTRACT Pelvic pain (PP) is associated with more than 20 different, clinically identified, maladies, such as Urinary Tract Infection (UTI), Menstrual Cramps (MC), Endometriosis (EM), Overactive Bladder (OAB) and Interstitial cystitis/Painful bladder syndrome (IC/PBS). These painful and debilitating conditions often have a dramatic negative impact on the quality of life (QOL) of millions of PP sufferers, from decreased work productivity and school performance, to declined sexual life and happiness. PP has been also associated with increased abuse of opioids and psycho-pharmaceuticals, ultimately leading to death by overdose and suicides. In addition to the burden to patients and their family, the economic direct and indirect PP cost is a significant fraction (>20%) of the 635B$ linked to chronic pain in US. Globally, pelvic pain affects one in five women and one in twelve men. Although treatments, including neural stimulation, are available, they are costly and lose effectiveness over time in >30% of patients. Patients with current untreatable chronic PP require a novel treatment approach that can relieve them from their debilitating symptoms. Significant relief of pain and reduced urination frequency has been recently associated with thermal modulation of pelvic floor. H3Pelvic has successfully developed a Contrast Applied Therapy (CAT) system modulating rapidly and comfortably temperature (cold/warm) via a water- circulating perineal membrane in a soft seat. When a properly sized vaginal or rectal probe with superior thermal conductivity is combined with the CAT system, the pain relief can be remarkable: an initial cohort of patients with refractory IC, unresponsive to drugs or neural stimulation, with a daily 45min vaginal cooling, resumed normal undertakings, restarted school, work and sexual activity, leading to an overall happier and productive life. We propose to optimize a probe design to maximize targeted delivery of thermal modulation using heatpipe technology, including real-time temperature tracking by passive microwave radiometry. RICAT (Radiometry Integrated CAT) will use probe-integrated smart radiometry to monitor deep tissue temperature. By leveraging machine learning, a minimal set of sensors shall accurately reconstruct temperature in the target region and maximize pain reduction. The Specific Aims for this first Phase are: 1) Optimally integrate radiometric sensors and smart planning/control software in a RICAT prototype; 2) Compare radiometric profiles with invasive needle sensors and perform histology in ex-vivo tissues and 7 pigs undergoing vaginal or rectal cooling/warming cycle. The goal of this Phase I is to integrate radiometric sensing into the thermal probe and test the probe’s ability to deliver consistent cooling and heating in the pelvic region in pre-clinical settings using healthy pigs. The data collected will allow us to move to Phase II, which will include a human trial in refractory IC patients. We expect that the animal study will show that RICAT optimally delivers pain-relieving thermal modulation to the pelvic region(s) effectively and reliably. Successful Phase I completion will pave the path towards clinical translational of a safe and effective pain-relieving technology to millions of patients suffering from debilitating pelvic pain.