Chen Qiyang, Yu Jaesok, Rush Brittney M, Stocker Sean D, Tan Roderick J, Kim Kang
Department of Bioengineering, University of Pittsburgh School of Engineering, Pittsburgh, Pennsylvania, USA; Center for Ultrasound Molecular Imaging and Therapeutics, Department of Medicine, Heart and Vascular Institute, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Kidney Int. 2020 Aug;98(2):355-365. doi: 10.1016/j.kint.2020.02.011. Epub 2020 Mar 3.
Acute kidney injury (AKI) is a risk factor for the development of chronic kidney disease (CKD). One mechanism for this phenomenon is renal microvascular rarefaction and subsequent chronic impairment in perfusion. However, diagnostic tools to monitor the renal microvasculature in a noninvasive and quantitative manner are still lacking. Ultrasound super-resolution imaging is an emerging technology that can identify microvessels with unprecedented resolution. Here, we applied this imaging technique to identify microvessels in the unilateral ischemia-reperfusion injury mouse model of AKI-to-CKD progression in vivo. Kidneys from 21 and 42 day post- ischemia-reperfusion injury, the contralateral uninjured kidneys, and kidneys from sham-operated mice were examined by ultrasound super-resolution and histology. Renal microvessels were successfully identified by this imaging modality with a resolution down to 32 μm. Renal fibrosis was observed in all kidneys with ischemia-reperfusion injury and was associated with a significant reduction in kidney size, cortical thickness, relative blood volume, and microvascular density as assessed by this imaging. Tortuosity of the cortical microvasculature was also significantly increased at 42 days compared to sham. These vessel density measurements correlated significantly with CD31 immunohistochemistry (R=0.77). Thus, ultrasound super-resolution imaging provides unprecedented resolution and is capable of noninvasive quantification of renal vasculature changes associated with AKI-to-CKD progression in mice. Hence, this technique could be a promising diagnostic tool for monitoring progressive kidney disease.
急性肾损伤（AKI）是慢性肾脏病（CKD）发生发展的一个危险因素。这一现象的一种机制是肾微血管稀疏以及随后的慢性灌注受损。然而，仍缺乏以非侵入性和定量方式监测肾微血管的诊断工具。超声超分辨率成像作为一种新兴技术，能够以前所未有的分辨率识别微血管。在此，我们应用这种成像技术在体内识别单侧缺血再灌注损伤小鼠模型中从AKI进展到CKD过程中的微血管。在缺血再灌注损伤后21天和42天的肾脏、对侧未受伤的肾脏以及假手术小鼠的肾脏，均通过超声超分辨率成像和组织学检查。利用这种成像方式成功识别了肾微血管，分辨率低至32μm。在所有经历缺血再灌注损伤的肾脏中均观察到肾纤维化，并且通过该成像评估发现其与肾脏大小、皮质厚度、相对血容量和微血管密度的显著降低有关。与假手术组相比，在42天时皮质微血管的迂曲度也显著增加。这些血管密度测量结果与CD31免疫组化显著相关（R=0.77）。因此，超声超分辨率成像提供了前所未有的分辨率，并且能够对与小鼠从AKI进展到CKD相关的肾血管变化进行非侵入性定量分析。因此，这项技术可能是监测进行性肾脏疾病的一种有前景的诊断工具。
