Regulatory Advancement of HXe as a Diagnostic MRI Contrast Agent

HXe 作为诊断 MRI 造影剂的监管进展

基本信息

批准号：
8323129
负责人：
Iulian Constantin Ruset
金额：
$ 97.47万
依托单位：
XEMED, LLC
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8323129
关键词：
Address Aerosols Agreement Algorithms Alveolar Asthma Biochemical Bolus Infusion Breathing Caliber Caring Categories Chest Chronic Obstructive Airway Disease Clinical Clinical Research Clinical Trials Contrast Media Data Data Analyses Defect Detection Development Devices Diagnosis Diagnostic Diffusion Dimensions Disease Dose Duct (organ) structure Environmental air flow FDA approved Gases Glues Goals Health Care Costs Helium Histology Image Individual Industry Inhalation Device Intervention Investments Label Length Location Lung Lung diseases MRI Scans Magnetic Resonance Imaging Maps Marketing Measurement Measures Medical Medical Device Medical Imaging Methods Metric Monitor Obstructive Lung Diseases Operative Surgical Procedures Pathology Patient Schedules Patients Pentetic Acid Performance Pharmaceutical Preparations Pharmacologic Substance Phase Phase II Clinical Trials Phase III Clinical Trials Physiologic pulse Physiological Pilot Projects Pleural cavity Program Development Protocols documentation Protons Provider Pulmonary Emphysema Pulmonary function tests Quality of life Quantitative Evaluations Radionuclide Imaging Reader Reporting Research Respiratory physiology Risk Safety Scanning Services Statistical Methods Stents Structure System Techniques Therapeutic Thermal Ablation Therapy Time Tissues Transplantation United States Food and Drug Administration Validation Work Xenon commercialization cost cost effective design healthy volunteer image processing imaging modality improved in vivo innovation interest lung volume meetings patient safety prospective prototype research study statistics therapy development

Address Aerosols Agreement Algorithms Alveolar Asthma Biochemical Bolus Infusion Breathing Caliber Caring Categories Chest Chronic Obstructive Airway Disease Clinical Clinical Research Clinical Trials Contrast Media Data Data Analyses Defect Detection Development Devices Diagnosis Diagnostic Diffusion Dimensions Disease Dose Duct (organ) structure Environmental air flow FDA approved Gases Glues Goals Health Care Costs Helium Histology Image Individual Industry Inhalation Device Intervention Investments Label Length Location Lung Lung diseases MRI Scans Magnetic Resonance Imaging Maps Marketing Measurement Measures Medical Medical Device Medical Imaging Methods Metric Monitor Obstructive Lung Diseases Operative Surgical Procedures Pathology Patient Schedules Patients Pentetic Acid Performance Pharmaceutical Preparations Pharmacologic Substance Phase Phase II Clinical Trials Phase III Clinical Trials Physiologic pulse Physiological Pilot Projects Pleural cavity Program Development Protocols documentation Protons Provider Pulmonary Emphysema Pulmonary function tests Quality of life Quantitative Evaluations Radionuclide Imaging Reader Reporting Research Respiratory physiology Risk Safety Scanning Services Statistical Methods Stents Structure System Techniques Therapeutic Thermal Ablation Therapy Time Tissues Transplantation United States Food and Drug Administration Validation Work Xenon commercialization cost cost effective design healthy volunteer image processing imaging modality improved in vivo innovation interest lung volume meetings patient safety prospective prototype research study statistics therapy development

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项目摘要

DESCRIPTION (provided by applicant): New therapies are in development for COPD (endobronchial valves/stents/glue) and asthma (endobronchial thermal ablation). Hyperpolarized xenon-129 (HXe) MRI, a noninvasive method to assess regional lung structure and function, may prove critical in the guidance of these regional treatments. In our prior work we developed an innovative approach to xenon polarization that provides the liter quantities of highly polarized xenon-129 as required for medical imaging. Our prototype system was deployed at UVa where we performed 600 experiments in 64 patient and healthy volunteers and made significant advances in MR acquisition strategies and image quality. These promising results enable us to move to the next step in the commercialization of HXe, the performance of a Phase 2 clinical trial. Our goals for Phase 2 are to collect safety endpoints in patients with obstructive lung diseases, finalize the HXe dosing and MRI methods, and validate the HXe results by comparing with the existing clinical methods for assessing lung function and microstructure. We selected the two most mature and promising HXe techniques for inclusion in the Phase 2 trial: ventilation and diffusion imaging. Obstructive lung diseases such as COPD and asthma have been shown to have regional abnormalities of ventilation and these abnormalities are prime targets for intervention. Thus our first aim is to validate HXe MRI for the intended use of delineating ventilated and unventilated regions of the lung in COPD and asthma patients. For our Phase 2a trial we will compare HXe ventilation MRI and 99Tc DTPA ventilation scintigraphy (a clinical standard for assessing regional lung ventilation) in 10 healthy volunteers and 70 patients with COPD and asthma. In addition to the patient safety data, we will assess total lung volume and ventilated lung volume on MRI, and the congruence of ventilated volume boundaries between HXe MRI and scintigraphy. Recently completed pilot studies show that hyperpolarized helium diffusion imaging with six b-values can separately determine diffusion coefficients along and transverse to acinar ducts, which are related to alveolar depth and duct diameter. Our second aim is to validate HXe diffusion MR for the intended use of quantifying alveolar enlargement in emphysema, a fundamental abnormality that currently is assessed only by histology. For our Phase 2b trial we will perform diffusion HXe MRI in vivo in 18 COPD patients scheduled for lung transplant, and repeat the scan in the ex vivo lung after it is removed, thereby establishing that in vivo and ex vivo HXe measurements are concordant. The final step in the validation of the HXe diffusion measurement is to regionally compare alveolar size with morphometric measurements via histology from the explanted lung. The final portion of the proposed work is to raise quality to Phase 3 level, design a draft Phase 3 trial, meet with the FDA for a pre-Phase 3 meeting, and incorporate the FDA input into the Phase 3 protocol. The completion of the proposed work represents a significant advancement towards commercialization of HXe.

描述（由申请人提供）：开发了针对COPD的新疗法（支架瓣/支架/胶）和哮喘（支撑型热消融）。超极化XENON-129（HXE）MRI是一种评估区域肺结构和功能的无创方法，在这些区域治疗的指导中可能至关重要。在我们先前的工作中，我们开发了一种创新的氙极化方法，该方法根据医学成像所需的需要提供大量高极化的XENON-129。我们的原型系统部署在UVA，在那里我们对64名患者和健康志愿者进行了600次实验，并在MR获得策略和图像质量方面取得了重大进步。这些有希望的结果使我们能够进入HXE商业化的下一步，即2阶段临床试验的性能。我们的第二阶段目标是收集阻塞性肺部疾病患者的安全终点，最终确定HXE剂量和MRI方法，并通过与现有的评估肺功能和微观结构的临床方法进行比较来验证HXE结果。我们选择了两种最成熟和有希望的HXE技术来纳入2阶段试验：通风和扩散成像。阻塞性肺部疾病（例如COPD和哮喘）已显示出通风的区域异常，这些异常是干预的主要目标。因此，我们的第一个目的是验证HXE MRI，以便在COPD和哮喘患者中使用肺部的肺部通风和未通风区域的使用。在我们的2A期试验中，我们将比较10名健康志愿者和70名COPD和哮喘患者的HXE通气MRI和99TC DTPA通风闪烁显像（评估区域肺通风的临床标准）。除了患者安全数据外，我们还将评估MRI的总肺部量和通风肺量，以及HXE MRI和Scintigraphy之间通风量的一致性。最近完成的初步研究表明，具有六个B值的超极化氦扩散成像可以单独确定沿着与肺泡深度和管道直径有关的沿腺导管的扩散系数。我们的第二个目的是验证HXE扩散MR，用于量化肺气肿的预期使用，这是一种基本异常，目前仅通过组织学评估。对于我们的2阶段试验，我们将对计划进行肺移植的18例COPD患者进行扩散HXE MRI，并在去除后体内肺中重复扫描，从而确定体内和离体HXE测量是一致的。 HXE扩散测量验证的最后一步是在区域上比较肺泡大小与外植型肺的组织学测量的形态测量。拟议工作的最后一部分是将质量提高到第3阶段水平，设计草案第三阶段试验，与FDA开会进行第三阶段会议，并将FDA输入纳入第3阶段协议。拟议工作的完成代表了HXE商业化的重大进步。