IVUS\IVPA hybrid intravascular molecular imaging of angiogenesis in atherosclerotic plaques via RGDfk peptide-targeted nanoprobes

Abstract

Current intravascular imaging modalities face hurdles in the molecular evaluation of progressed plaques. This study aims to construct a novel hybrid imaging system (intravascular ultrasound/intravascular photoacoustic, IVPA/IVUS) via RGDfk peptide-targeted nanoparticles for monitoring angiogenesis in progressed atherosclerotic plaques in a rabbit model. An atherosclerotic rabbit model was induced by abdominal aorta balloon de-endothelialization followed by a high-fat diet. A human serum albumin (HSA)-based nanoprobe modified with RGDfk peptide was constructed by encapsulating indocyanine green (ICG) via electrostatic force (ICG-HSA-RGDfk NPs, IHR-NPs). A hybrid intravascular imaging system that combined IVUS and IVPA was self-assembled for RGDfk visualization within atherosclerotic plaques in the rabbit abdominal aorta. Through IHR-NPs and the hybrid IVUS/IVPA imaging platform, multiple comprehensive pieces of information on progressed plaques, including anatomical information, composition information and molecular information, can be obtained simultaneously, which may improve the precise diagnosis of plaque characteristics and the evaluation of early interventions for atherosclerosis.

Advances in multimodal imaging assessment of coronary microvascular dysfunction after myocardial infarction

“…环进行定量评估 [36] 。一项荟萃分析结果显示，与静态 CTP 相比，动态 CTP 具有 更高的灵敏性(0.85 vs 0.72)和较低的特异性(0.81 vs 0.90) [37] 。另一项研究表 明，对于预测 CAD 患者发生心血管不良事件方面，动态 CTP 要比冠状动脉 CT 血管造影具有更好的预测价值 [38] 。 CTP 的最大的优势在于空间分辨率高， 且能够区分微循环障碍是否由冠状动 脉狭窄引起的。但由于该方法成像的特殊性，使得持续重复的 CT 扫描给患者带 来较大的辐射，临床应用较为局限。因此，在目前临床实践中不建议将该方法用 于常规评估微循环障碍。 临床常用的微循环功能评估无创影像方法对比见表 1 [14,39] 。 表 1 微循环功能评估的无创影像方法对比 [14,39] Table 1. Comparison of noninvasive imaging for microvascular function assessment [14,39] 成像方法 评估参数 测量方法 备注 像进行降噪、增强、特征分割和提取等，将不同模态图像的的格式、分辨率等参 数进行统一；其次是图像配准，基于图像灰度或内部特征按照特定算法进行空间 变换，使其达到几何空间位置和时间的配准；最后是影像融合，根据不同算法或 规则对配准后的图像进行融合，获取多模态影像融合图片 [41] 。目前该技术已被 用于颅内肿瘤、椎管内病变和肝脏肿瘤等疾病的临床诊疗 [42] 。多模态影像融合 深入 [43] 。作为环化的精氨酸-甘氨酸-天冬氨酸(RGD)序列二聚体 NOTA-PRGD2 探针表现出与 αvβ3 特异性结合的良好靶向性、在体稳定性和安全性 [44,45] 。本课 题组既往将 NOTA-PRGD2、 ICG-HSA-RGDfk NPs 探针用于大鼠心肌缺血再灌注 模型和动脉粥样硬化易损斑块模型的在体血管新生动态观察， 其影像和离体免疫 组化染色结果具有良好的一致性 [45,46] 。新型混合成像工具，是将 PET 与基于 CT 的冠脉造影技术相结合，在获取冠脉解剖信息的同时能够定量心肌血流。 18 F-脱 氧葡萄糖 (fluorodeoxyglucose，FDG) PET/CT 能够提供心肌细胞的糖代谢信息， 是评估心肌代谢、心梗后心肌存活的金标准 [47] 。本课题组前期通过采集小型猪 心梗模型心脏 CT、冠脉 CTA、 18 F-FDG 和 68 Ga-NOTA-PRGD2 PET/CT 图像，利 用多图谱方法对 CT 和 CTA 中心脏和冠脉血管进行分割， 随后将其与 PET/CT 图 像进行配准、融合，最终获取包含心脏与血管解剖、心肌代谢与灌注、血管新生 信息的三维多模态影像融合图像 [48] ，该结果对于我们探索冠脉病变血管、心梗…”

Intra-instrument channel workable, optical-resolution photoacoustic and ultrasonic mini-probe system for gastrointestinal endoscopy

“…After the first idea of applying PAT to endoscopy in 1996 [13] , a variety of device concepts have been proposed to translate its benefits into clinical settings [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] . Among these, the following are notable device concepts that are potentially applicable for GI endoscopy.…”

“…However, due to the accompanying technical challenge in implementing the key mechanical unit, such an endoscopic probe with a sufficiently short rigid distal section that can freely pass through the instrument channel of a video endoscope has not been demonstrated thus far. To avoid such a technical challenge, a torque coil-based proximal actuation mechanism was introduced in 2014 [26] and has become the dominant mechanism for most follow-up mini-probes for PA endoscopy (PAE) [21] , [22] , [23] , [24] , [25] or catheter probes for intravascular photoacoustic (IVPA) imaging application [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] . Although it is expected that it will take a considerable amount of time for commercialized devices based on the related mechanism to be used for real human subjects, one of the key strengths of this probe is a flexible body along with a short rigid distal section.…”

“…Of course, most of the IVPA devices reported in recent years have been implemented based on the same mechanism [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , and one of the reports even successfully obtained the image of a swine coronary artery in vivo [32] . However, none of them has successfully demonstrated the imaging of the upper GI tract of a large animal via the instrument channel of a clinical video endoscope; only the imaging of a rat colorectum has been reported with regard to in vivo GI tract imaging [22] , [23] , [24] .…”

Intracellular Recording of Cardiomyocytes by Integrated Electrical Signal Recording and Electrical Pulse Regulating System

“…Cardiovascular disease is currently the main cause of death in the world, seriously threatening human health ( Lin et al, 2021 ; Mozaffarian et al, 2016 ). In order to prevent and treat cardiovascular diseases, pathologists have carried out more in-depth research on the working mechanism of the heart.…”