Real-time ultrasound-based targeted molecular imaging in large blood vessels holds promise for early detection and diagnosis of stroke risk by identifying early markers for atherosclerosis prior to plaque formation. Singular spectrum-based targeted molecular (SiSTM) imaging is a recently proposed method that uses changes in statistical dimensionality—quantified by a normalized singular spectrum area (NSSA)—to image receptor-ligand–bound adherent microbubbles. However, the precise physical mechanism responsible for the distinct statistical signature was previously unknown. In this study, in vitro flow phantom experiments were performed to elucidate the physical mechanism in large blood vessel environments. In the absence of flow, an increase in the NSSA of adherent microbubbles with respect to tissue was not observed with increased microbubble concentration or pulse length (p > .23; n = 5) but was observed with increased flow rate (p < .01; n = 10). When observing the dynamics of the adherent microbubble statistics, a good correlation was observed between the NSSA and the derivative of image intensity (R2 > .97). In addition, a monotonic relationship between the NSSA and decorrelation was demonstrated. These findings confirm the hypothesis that the statistical signature of adherent microbubbles is derived from frame-to-frame decorrelation, which is induced by flow shear forces.
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机译:通过在斑块形成之前识别动脉粥样硬化的早期标记物,大型血管中基于实时超声的靶向分子成像有望为中风风险的早期检测和诊断提供依据。基于奇异光谱的靶向分子(SiSTM)成像是最近提出的一种方法,该方法利用统计维数的变化(由归一化奇异光谱区域(NSSA)量化)对受体-配体结合的粘附微气泡进行成像。但是,负责不同统计签名的精确物理机制以前是未知的。在这项研究中,进行了体外流动体模实验以阐明大血管环境中的物理机制。在没有流动的情况下,随着微泡浓度或脉冲长度的增加(p> .23; n = 5),未观察到粘附微泡相对于组织的NSSA升高,但随着流速的增加(p <.01)而观察到; n = 10)。当观察微气泡粘附统计的动态时,NSSA与图像强度的导数之间存在良好的相关性(R 2 sup .97)。另外,证明了NSSA和去相关之间的单调关系。这些发现证实了这样的假说,即粘附的微气泡的统计特征来源于流剪切力引起的帧与帧之间的去相关。
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