Ultrasound Targeted Molecular Imaging in Large Arteries to Predict AAA Risk

在美国，腹主动脉瘤(AAA)每年导致超过10,000人死亡。AAA中的大多数是 静默且无症状，直至破裂。如果及早发现，外科干预已被证明对 住院死亡率为4%，而已经破裂的AAA的死亡率高于40%。超声波- 基于AAA的最大直径测量目前是其破裂风险的主要决定因素， 常以5.5 cm作为判定标准。然而，据报道，高达23%的AAA在一次手术中破裂 直径小于5厘米和高达60%的直径大于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指标。特别是，一种分子成像阳性 在基于解剖的发现不明确的情况下(例如，主动脉)，发现可能有助于风险分层 直径4.5-6.5厘米)。分子成像是一种有希望的早期检测AAA风险的方法 相比之下，解剖成像只能检测到相对较晚的AAA进展。这种关联性 AAA破裂的风险和生物标志物之间的关系已经被证明。核磁共振、光学和正电子发射计算机断层扫描方法 在检测腹主动脉破裂的标志物方面显示出临床前的成功，但这些方法都没有 同时满足快速、低成本、无辐射的分子标记检测的需要 实现临床广泛采用。基于超声的分子成像是一种理想的方式，因为它 满足上述需求和现有仪器，已用于在 现有的AAA筛选方案只需要很小的修改。不幸的是，现有的超声波- 基于分子成像无法测量大血管中的分子标志物浓度 因此，尚未尝试使用超声波进行AAA风险评估。现在 研究人员最近发明了一种新的基于超声波的分子成像策略，该策略克服了 以前的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 大血管中分子标志物浓度的定量测量(以位点/μm2为单位)。 更早和更准确地预测未来的AAA破裂风险将提高死亡率并降低 与AAA相关的医疗成本。

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.