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多种不同的临床上确定的疾病有关，例如尿路感染， 感染（UTI）、月经痉挛（MC）、子宫内膜异位症（EM）、膀胱过度活动症（OAB）和间质性 膀胱炎/膀胱疼痛综合征（IC/PBS）。这些痛苦和衰弱的条件往往有一个戏剧性的 对数百万PP患者的生活质量（QOL）产生负面影响，工作效率降低， 在校表现，以性生活和幸福感下降为主。PP也与滥用增加有关 阿片类药物和精神药物，最终导致过量死亡和自杀。除了有 对患者及其家庭的负担，经济直接和间接PP成本是一个显着的一部分（>20%）， 美国有6350亿美元与慢性疼痛有关。在全球范围内，盆腔疼痛影响五分之一的女性和十二分之一的男性。 尽管包括神经刺激在内的治疗方法是可行的，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。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， 缓解他们的虚弱症状显著缓解疼痛和减少排尿频率， 最近与骨盆底的热调节有关。H3 Pelvic已成功开发出一种造影剂 应用治疗（CAT）系统通过水调节快速舒适的温度（冷/暖）- 在柔软的座椅上循环会阴膜。当适当尺寸的阴道或直肠探头具有良好的上级热性能时， 电导率与CAT系统相结合，疼痛缓解效果显著： 难治性IC，对药物或神经刺激无反应，每日阴道冷却45分钟，恢复正常 企业，重新开始学校，工作和性活动，导致整体幸福和富有成效的生活。 我们建议优化探头设计，以最大限度地利用热管有针对性地提供热调制 技术，包括通过被动微波辐射测量进行实时温度跟踪。辐射测量 集成CAT）将使用探头集成智能辐射测量来监测深部组织温度。通过利用 通过机器学习，最小的传感器集应该准确地重建目标区域中的温度， 最大限度地减轻疼痛。第一阶段的具体目标是：1）最佳集成辐射传感器 RICAT原型中的智能规划/控制软件; 2）比较放射性轮廓与侵入性针 传感器，并在离体组织和7头接受阴道或直肠冷却/加温循环的猪中进行组织学检查。 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， 使用健康猪在临床前环境中在骨盆区域提供一致的冷却和加热。数据 收集的数据将使我们进入第二阶段，其中包括在难治性IC患者中进行人体试验。我们预计 动物研究将表明RICAT最佳地为骨盆提供缓解疼痛的热调节 有效和可靠地管理区域。第一阶段的成功完成将为临床转化铺平道路 这是一种安全有效的止痛技术，可以帮助数百万遭受骨盆疼痛的患者。

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.