Development of a Photoacoustic Quantitative Ultrasound (PAQUS) device for clinical use

开发临床用光声定量超声 (PAQUS) 装置

• 批准号: 10258569
• 负责人: Richard Franklin Morris
• 金额: $ 94.27万
• 依托单位: IF, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10258569
• 关键词: Acoustics; Address; Age; Aging; American; Appearance; Architecture; Biological Markers; Bone structure; Chemical Structure; Chemicals; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Correlation Studies; Data; Data Collection; Densitometry; Detection; Development; Devices; Diagnostic Imaging; Diffusion; Dual-Energy X-Ray Absorptiometry; Early Diagnosis; Ensure; Environment; Evaluation; Expenditure; Fatty acid glycerol esters; Female; Food and Drug Administration Device Approval; Frequencies; Goals; Human; Image; Individual; Industry; Lasers; Lead; Light; Magnetic Resonance Imaging; Marrow; Measurement; Measures; Methodology; Methods; Michigan; Modality; Molecular; Monitor; Noise; Osteoblasts; Osteoclasts; Osteoporosis; Patients; Penetration; Performance; Perfusion; Phase; Physiological; Physiology; Population; Property; Public Health; Publications; Research; Roentgen Rays; Sampling; Scanning; Sensitivity and Specificity; Signal Transduction; Site; Small Business Innovation Research Grant; Speed; Structure; System; Techniques; Technology; Testing; Therapeutic; Time; Ultrasonics; Ultrasonography; Universities; Validation; Women' s Group; accurate diagnosis; attenuation; base; bone; bone health; bone mass; calcaneum; chemical property; cost; cost effective; design; diagnostic technologies; experimental study; healthy volunteer; human subject; in vivo; innovation; instrument; multimodality; novel; optical spectra; osteoporosis with pathological fracture; performance tests; phase 1 study; point of care; programs; psychosocial; quantitative ultrasound; screening; sound; tool

TITLE: DEVELOPMENT OF A PHOTOACOUSTIC QUANTITATIVE ULTRASOUND (PAQUS) DEVICE FOR CLINICAL USE Abstract: Osteoporosis is a major public health threat with significant physical, psychosocial, and financial consequences. Technologies that can facilitate population screening, early diagnosis and, more importantly, highly sensitive therapeutic assessment are crucial for achieving optimal management of osteoporosis. Clinically available diagnostic technologies for osteoporosis rely on either X-rays or ultrasound (US) to assess bone mass. Although representing the integrated effects of osteoclast and osteoblast activity and the appearance of altered skeletal structure, these standard clinical techniques have no or limited sensitivity to the real-time cellular activities and physiological properties in bone, resulting in a delay of information relayed to the clinician. Therefore, there is a clear and urgent need to develop alternate methodologies that add diagnostic imaging power using instruments that are cost-effective and accessible for wide-spread use. To fill this long-standing gap in technology, the objective of this program is to develop and commercialize an innovative and cost-effective device for early and accurate diagnosis and treatment monitoring of human osteoporosis. By combining our recently invented photoacoustic (PA) bone assessment techniques with more established quantitative ultrasound (QUS), the proposed PAQUS device can measure a group of biomarkers, including bone mass and bone microstructure, as well as chemical and functional properties which can then be combined with established biomarkers from QUS, such as speed of sound (SOS), broadband ultrasonic attenuation (BUA), and stiffness, to achieve more comprehensive assessment of bone health. In the last two years, sponsored by the Phase I SBIR project, the feasibility of PA assessment of human bone health has been rigorously validated. Experiments conducted in vivo on the calcaneus bones of 20 females (10 healthy volunteers and 10 subjects with osteoporosis) demonstrated that by performing spectral analysis of light-induced acoustic signals from a calcaneus bone over a broad optical spectrum, both chemical and micro-structural information in the bone can be obtained in a non-invasive and non-ionizing manner. Encouraged by the successful Phase I study, we now propose to further develop and commercialize this highly translational PAQUS technique in Phase II, aiming at a comprehensive and objective validation of the overall performance of PAQUS, and to prepare the device for FDA approval. To achieve this goal, three Specific Aims are proposed. Aim 1: Refine and optimize PAQUS method and establish testing phantoms; Aim 2: Develop clinical PAQUS system; and Aim 3: Perform pre-market field evaluation and collect reference data on a minimum of 150 individuals as a representative sampling based on the FDA’s publication “Bone Sonometers - Class II Special Controls Guidance for Industry and FDA Staff” to validate the clinical performance of our proposed PAQUS bone assessment device. Successful accomplishment of these aims would lead to an operationally validated and clinic-ready point of care PAQUS system for multi-site large-scale clinical trials.

标题：光声定量超声（PAQUS）的研制 临床用器械 摘要： 骨质疏松症是一个重大的公共卫生威胁与重大的身体，心理和经济后果。 能够促进人群筛查、早期诊断，更重要的是， 治疗评估对于实现骨质疏松症的最佳管理至关重要。临床可用的诊断 骨质疏松症的技术依赖于X射线或超声波（US）来评估骨量。虽然代表 破骨细胞和成骨细胞活性的综合作用以及改变的骨骼结构的出现， 标准临床技术对实时细胞活动和生理特性没有敏感性或敏感性有限 在骨中，导致延迟信息传递给临床医生。因此，显然迫切需要 开发替代方法，使用具有成本效益的仪器增加诊断成像能力， 可广泛使用。 为了填补这一长期存在的技术空白，该计划的目标是开发一种创新的 和低成本的设备，用于早期和准确地诊断和治疗监测人类骨质疏松症。通过 结合我们最近发明的光声（PA）骨评估技术与更成熟的定量 在超声波（QUS）中，所提出的PAQUS设备可以测量一组生物标志物，包括骨量和骨密度。 微观结构，以及化学和功能特性，然后可以与已建立的生物标志物相结合 从QUS，如声速（SOS），宽带超声衰减（BUA），和刚度，以实现更多 全面评估骨骼健康。 近两年来，在SBIR项目的I期资助下，PA评估人类骨健康的可行性 都经过严格验证对20名女性（10名健康人）的跟骨进行体内实验， 志愿者和10名骨质疏松症受试者）证明，通过对光诱导的 来自跟骨的在宽光谱上的声学信号，包括化学和微观结构信息 可以以非侵入性和非电离的方式获得。在第一阶段研究成功的鼓舞下， 我们现在建议在第二阶段进一步开发和商业化这种高度转化的PAQUS技术， 对PAQUS的整体性能进行全面和客观的验证，并为FDA准备器械 批准为了实现这一目标，提出了三个具体目标。目的1：改进和优化PAQUS方法， 建立测试模型;目标2：开发临床PAQUS系统;目标3：进行上市前现场评价 并收集至少150人的参考数据，作为基于FDA的代表性抽样。 出版物“骨超声仪-行业和FDA工作人员II类特殊控制指南”，以确认临床 我们提出的PAQUS骨评估设备的性能。这些目标的成功实现将导致 到一个经过操作验证和临床准备的PAQUS系统，用于多地点的大规模临床试验。