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.

在美国，腹主动脉瘤 (AAA) 每年导致超过 10,000 人死亡。在破裂之前一直保持沉默且无症状，如果及早发现，手术干预已被证明是有效的。与已经破裂的 AAA 的死亡率高于 40% 相比，院内死亡率 < 4%。基于 AAA 最大直径测量目前是其破裂风险的主要决定因素 5.5 厘米通常被用作决策标准，但据报道，高达 23% 的 AAA 在 5.5 厘米处破裂。直径小于 5 厘米的 AAA，高达 60% 直径大于 5 厘米的 AAA 从未发生过破裂因此，迫切需要更可靠的破裂风险预测因子，特别是分子成像阳性预测因子。在基于解剖学的发现不明确的情况下（例如，分子成像是早期检测 AAA 风险的一种有前途的方法。与解剖成像相反，在解剖成像中只能检测到相对较晚的 AAA 进展。 MRI、光学和 PET 方法均已证明 AAA 破裂风险与生物标志物之间存在关联。临床前成功检测出 AAA 破裂标记物，但这些方法都没有同时满足快速、低成本、无辐射、分子标记检测的需求基于超声的分子成像是一种理想的方式，因为它能够得到广泛的临床应用。满足上述需求和现有仪器，已用于在期间进行直径测量不幸的是，现有的 AAA 筛查方案只需要很小的调整。基于分子成像无法测量大血管中的分子标志物浓度环境，因此尚未尝试使用超声进行 AAA 风险评估。研究人员最近发明了一种新的基于超声的分子成像策略，克服了先前技术在大血管环境中的局限性，这种方法被称为“调制”。基于声辐射力（mARF）的成像是第一个展示的超声技术大血管中定量分子标记浓度的测量（以位点/μm2为单位）。更早、更准确地预测未来 AAA 破裂风险将提高死亡率并减少与 AAA 相关的医疗保健费用。