Ultrasound Targeted Molecular Imaging in Large Arteries to Predict AAA Risk

大动脉超声靶向分子成像可预测 AAA 风险

基本信息

批准号：
9194510
负责人：
John A Hossack
金额：
$ 40.57万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-21 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9194510
关键词：
Abdomen Abdominal Aortic Aneurysm Acoustics Adoption Anatomy Animal Model Animals Aorta Arteries Behavior Therapy Biological Markers Blood Vessels Caliber Cessation of life Clinical Data Detection Early Diagnosis Eligibility Determination Environment Exhibits Future Health Health Care Costs Hospital Mortality Image Immunity Individual KDR gene Knowledge Laboratories Length Magnetic Resonance Imaging Measurement Measures Methods Microbubbles Minor Modality Molecular Profiling Molecular Target Operative Surgical Procedures Optics Phase Physiological Positron-Emission Tomography Protocols documentation Pulsatile Flow Radiation Reporting Research Personnel Residual state Risk Risk Assessment Risk Factors Rupture Ruptured Abdominal Aortic Aneurysm Ruptured Aneurysm Site Stratification Systems Development Techniques Technology Testing Time Tissues Translations Ultrasonography United States Work angiogenesis attenuation base blood pressure regulation cost cost effective experience imaging modality improved in vivo innovation instrumentation meetings minimally invasive molecular imaging molecular marker mortality mouse model older patient pre-clinical programs repaired response smoking cessation success technological innovation

项目摘要

Abdominal aortic aneurysm (AAA) causes over 10,000 deaths annually in the US. The majority of AAA are silent and asymptomatic until rupture. If detected early, surgical interventions have been proven effective with in-hospital mortalities < 4% compared to mortality higher than 40% in already ruptured AAAs. Ultrasound- based maximum diameter measurements of AAA is currently the primary determinant of its rupture risk with 5.5 cm often used as the decision criteria. However, it has been reported that up to 23% of AAAs ruptured at a diameter less than 5 cm and up to 60% of AAAs with a diameter greater than 5 cm never experienced rupture Thus, more reliable predictors of rupture risk are urgently needed. In particular, a molecular imaging positive finding may assist with risk stratification in cases where anatomic-based findings are ambiguous (e.g. aortic diameter in range 4.5 - 6.5 cm). Molecular imaging is a promising approach for early detection of AAA risk that contrasts with anatomical imaging in which only relatively late AAA progression is detectable. The correlation between risk of AAA rupture and biomarkers has been demonstrated. MRI, optical, and PET methods have all demonstrated pre-clinical success in detection of markers for AAA rupture but none of these modalities simultaneously meets the need for rapid, low-cost, radiation-free, molecular marker detection necessary to achieve widespread clinical adoption. Ultrasound-based molecular imaging is an ideal modality because it meets the above needs and existing instrumentation, already in use for making diameter measurements during existing AAA screening protocols, requires only very minor adaptation. Unfortunately, existing ultrasound- based molecular imaging is unable to measure molecular marker concentration in large blood vessel environments, and thus AAA risk assessment using ultrasound has not yet been attempted. The present investigators have recently invented a new ultrasound-based molecular imaging strategy that overcomes the limitations of previous techniques in large blood vessel environments. This method, referred to as “modulated Acoustic Radiation Force” (mARF)-based imaging, is the first ultrasound technology to demonstrate quantitative measurements of molecular marker con-centration (in units of sites/μm2) in large blood vessels. Earlier and more accurate prediction of future AAA rupture risk will improve mortality rates and reduce healthcare costs associated with AAA.

腹部主动脉瘤（AAA）每年在美国造成10,000多人死亡。大多数AAA是保持沉默和不对称，直到破裂。如果早期发现，手术干预已被证明有效在已经破裂的AAA中，住院死亡率<4％，而死亡率高于40％。超声波- 目前，基于AAA的最大直径测量是其破裂风险的主要决定因素 5.5厘米通常用作决策标准。但是，据报道，在A时，多达23％的AAA破裂直径小于5厘米，直径超过5厘米的AAA的60％从未经历过破裂这是迫切需要更可靠的破裂风险预测因素。特别是分子成像阳性在基于解剖学的发现模棱两可的情况下，发现可能有助于进行风险分层（例如主动脉直径为4.5-6.5厘米）。分子成像是早期发现AAA风险的有前途的方法与解剖成像形成对比，在解剖学成像中，只有相对较晚的AAA进展才能检测到。相关性已经证明了AAA破裂的风险与生物标志物之间。 MRI，光学和PET方法具有全部在检测AAA破裂的标记方面取得了临床前的成功，但这些方式均未同样，满足需要快速，低成本，无辐射，分子标记的检测实现宽度临床采用。基于超声的分子成像是理想的方式，因为它满足上述需求和现有仪器，已经用于进行直径测量现有的AAA筛选协议仅需要非常小的适应。不幸的是，现有的超声波基于大血管中的分子成像无法测量分子标记浓度尚未尝试使用超声检查的环境以及AAA风险评估。现在研究人员最近发明了一种新的基于超声的分子成像策略，该策略克服了大型血管环境中先前技术的局限性。此方法，称为“调制基于声学辐射力”（MARF）的成像是第一个证明的超声技术大型血管中分子标记中心的定量测量（以/μm2为单位）。对未来AAA破裂风险的较早，更准确的预测将提高死亡率并降低与AAA相关的医疗保健费用。