Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, Building 12, Berlin 4163, Germany.
Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany.
Acta Biomater. 2022 Mar 1;140:389-397. doi: 10.1016/j.actbio.2021.11.026. Epub 2021 Nov 21.
An abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta, usually accompanied by thrombus formation. The current clinical imaging modalities cannot reliably visualize the thrombus composition. Remodeling of the extracellular matrix (ECM) during AAA development leads to stiffness changes, providing a potential imaging marker. 14 apolipoprotein E-deficient mice underwent surgery for angiotensin II-loaded osmotic minipump implantation. 4 weeks post-op, 5 animals developed an AAA. The aneurysm was imaged ex vivo by microscopic multifrequency magnetic resonance elastography (µMMRE) with an in-plane resolution of 40 microns. Experiments were performed on a 7-Tesla preclinical magnetic resonance imaging scanner with drive frequencies between 1000 Hz and 1400 Hz. Shear wave speed (SWS) maps indicating stiffness were computed based on tomoelastography multifrequency inversion. As control, the aortas of 5 C57BL/6J mice were examined with the same imaging protocol. The regional variation of SWS in the thrombus ranging from 0.44 ± 0.07 to 1.20 ± 0.31 m/s was correlated fairly strong with regional histology-quantified ECM accumulation (R = 0.79). Our results suggest that stiffness changes in aneurysmal thrombus reflect ECM remodeling, which is critical for AAA risk assessment. In the future, µMMRE could be used for a mechanics-based clinical characterization of AAAs in patients. STATEMENT OF SIGNIFICANCE: To our knowledge, this is the first study mapping the stiffness of abdominal aortic aneurysms with microscopic resolution of 40 µm. Our work revealed that stiffness critically changes due to extracellular matrix (ECM) remodeling in the aneurysmal thrombus. We were able to image various levels of ECM remodeling in the aneurysm reflected in distinct shear wave speed patterns with a strong correlation to regional histology-quantified ECM accumulation. The generated results are significant for the application of microscopic multifrequency magnetic resonance elastography for quantification of pathological remodeling of the ECM and may be of great interest for detailed characterization of AAAs in patients.
腹主动脉瘤 (AAA) 是腹主动脉的永久性扩张，通常伴有血栓形成。目前的临床成像方式无法可靠地观察到血栓的组成。AAA 发展过程中细胞外基质 (ECM) 的重塑导致硬度变化，为潜在的成像标志物提供了可能性。14 只载有血管紧张素 II 的渗透微型泵植入手术的载脂蛋白 E 缺陷型小鼠。术后 4 周，5 只动物发展为 AAA。使用具有 40 微米面内分辨率的微观多频磁共振弹性成像 (µMMRE) 对动脉瘤进行离体成像。实验在 7T 临床前磁共振成像扫描仪上进行，驱动频率在 1000 Hz 和 1400 Hz 之间。根据 tomoelastography 多频反演计算出表示硬度的剪切波速度 (SWS) 图。作为对照，用相同的成像方案检查了 5 只 C57BL/6J 小鼠的主动脉。血栓中 SWS 的区域变化范围为 0.44±0.07 至 1.20±0.31 m/s，与区域组织学定量 ECM 积累相关性较强 (R=0.79)。我们的结果表明，动脉瘤血栓中的硬度变化反映了 ECM 的重塑，这对 AAA 风险评估至关重要。未来，µMMRE 可用于对患者的 AAA 进行基于力学的临床特征描述。研究意义：据我们所知，这是首次以 40µm 的微观分辨率对腹主动脉瘤的硬度进行映射的研究。我们的工作表明，由于动脉瘤血栓中的细胞外基质 (ECM) 重塑，硬度发生了显著变化。我们能够以与区域组织学定量 ECM 积累呈强相关性的不同剪切波速度模式，对动脉瘤中不同水平的 ECM 重塑进行成像。生成的结果对微观多频磁共振弹性成像用于定量 ECM 的病理性重塑具有重要意义，可能对患者 AAA 的详细特征描述具有重要意义。
