Bedside ultrasound system for 3D guidance of bone marrow aspiration and biopsy procedures

项目摘要/摘要 骨髓环钻活检(BMTB)是诊断和监测的金标准 血液系统疾病和恶性肿瘤。尽管BMTB程序很少会导致严重的不良事件， 非诊断性活组织检查的数量应尽量减少，因为重复检测会延误诊断和 治疗，消耗额外的医疗资源，并造成不必要的患者焦虑和不适。 世界卫生组织指南建议骨髓活检核心长度超过1.5厘米， 然而，多项临床试验报告说，20-50%的核心长度是≤1.0厘米，这表明这些 临床建议没有定期得到满足。这一结论进一步得到以下发现的支持： 5-25%的牛结核杆菌标本被病理认为是非诊断性的，经常需要重复检查 BMTB程序，转诊为BMTB程序的放射学指导，或最终导致 不明确的或假阴性的诊断。 这一第二阶段项目的目标是最终完成临床试验就绪的成像的设计和制造。 系统(Accuro 3S)用于实时3D图像引导骨髓环钻活检术 在床边。本项目的关键技术创新包括：(I)小型化3D的设计 超声成像探头，(Ii)先进的骨骼特异性成像和3D渲染的发展 用于实时生成患者的髂骨的体积重建的技术，以及(Iii) 一种自动检测髂骨后缘并辅助的图像处理算法的实现 通过自动针导引至目标解剖结构，以方便活检获取。这些计划的目的是 技术是提供对髂骨的直观可视化，并避免与 进行影像引导介入治疗时的超声影像解译。核心技术 将通过对解剖学上正确的幻影进行广泛的体外成像研究来开发和测试 在一具人类身体标本中进行临床前验证。 建议的解决方案的影响是显著提高了BMTB成功率，并降低了 射线照相指导的转诊速率。这些影响预计将减少BMTB收购中的延迟， 减少患者对电离辐射的暴露，并由于需要更少的重复活组织检查和 更少的放射学指导转诊。加在一起，每年因转诊放射学指导而产生的费用， 重复BMTB程序，诊断错误导致的成本超过4.8亿美元/年。出于这些原因， 在血液学诊所的床边取材是首选的活检技术。这个 在第二阶段申请中提出的技术解决方案寻求改善BMTB的结果 在床边进行的手术。最后，这款设备在美国的总市场规模估计为 2.3亿美元/年，支持拟议技术开发努力的商业可行性。

PROJECT SUMMARY/ABSTRACT Bone marrow and trephine biopsy (BMTB) is the gold standard for diagnosing and monitoring hematological disorders and malignancies. Although BMTB procedures rarely cause serious adverse events, the number of non-diagnostic biopsies should be minimized because repeated testing delays diagnosis and treatment, consumes additional healthcare resources, and causes unnecessary patient anxiety and discomfort. World Health Organization guidelines recommend that bone marrow biopsy cores exceed 1.5 cm in length, however multiple clinical trials have reported that 20 – 50 % of core lengths are ≤ 1.0 cm, suggesting that these clinical recommendations are not regularly met. This conclusion is further supported by the finding that between 5 – 25 % of BMTB specimens are deemed non-diagnostic by pathology, often necessitating a repeat BMTB procedure, referral for radiographic guidance of the BMTB procedure, or ultimately resulting in an ambiguous or false negative diagnosis. The goal of this Phase II project is to finalize the design and fabrication of a clinical-trial-ready imaging system (Accuro 3S) for real-time 3D image guidance of bone marrow trephine biopsy procedures at the bedside. The key technological innovations of this project include: (i) the design of a miniaturized 3D ultrasound imaging probe, (ii) the development of advanced bone-specific imaging and 3D rendering technologies for generating volumetric reconstructions of the patient's iliac crest in real-time, and (iii) the implementation of an image processing algorithm that automatically detects the posterior iliac crest and assists with automated needle guidance to the target anatomy to facilitate biopsy acquisition. The intent of these technologies is to provide an intuitive visualization of the iliac crest and to avoid difficulties associated with ultrasound image interpretation when conducting an image-guided interventional procedure. Core technologies will be developed and tested via extensive in vitro imaging studies of anatomically correct phantoms prior to pre-clinical validation in a human cadaveric specimens. The impact of the proposed solution is a significant improvement in BMTB success rates and a reduced rate of referral for radiographic guidance. These effects are expected to reduce delays in BMTB acquisition, reduce patient exposure to ionizing radiation, and reduce costs due to the need for fewer repeat biopsies and fewer referrals for radiographic guidance. Together, the annual costs due to referral for radiographic guidance, repeat BMTB procedures, and costs stemming from diagnostic errors exceed $480M/yr. For these reasons, BMTB specimen retrieval at the bedside in the hematology clinic is the preferred biopsy technique. The technological solutions proposed in this Phase II application seek to enable improved outcomes of BMTB procedures performed at the bedside. Finally, the total US market size for this device is estimated to be $230M/yr, supporting the commercial viability of the proposed technology development efforts.