Lee Myoung Seok, Cho Jeong Yeon, Moon Min Hoan, Lee Jeonghwan, Lee Jung Pyo, Shin Nayeon, Jin Wencheng, Cho Ara
Department of Radiology, Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Radiology, Seoul National University Hospital, Seoul, Korea.
Ultrasonography. 2024 Sep;43(5):314-326. doi: 10.14366/usg.24024. Epub 2024 Jun 21.
This study aimed to establish baseline morphological and functional data for normal mouse kidneys via a clinical 33 MHz ultra-high-frequency (UHF) transducer, compare the data with the findings from fibrotic mice, and assess correlations between ultrasonography (US) parameters and fibrosis-related markers.
This retrospective study aggregated data from three separate experiments (obstructive nephropathy, diabetic nephropathy, and acute-to-chronic kidney injury models). Morphological parameters (kidney size, parenchymal thickness [PT]) and functional (shear-wave speed [SWS], stiffness, resistive index [RI], and microvascular imaging-derived vascular index [VI]) were assessed and compared between normal and fibrotic mouse kidneys. Semi-quantitative histopathologic scores were calculated and molecular markers (epithelial cadherin), Collagen 1A1 [Col1A1], transforming growth factor-β, and α-smooth muscle actin [α-SMA]) were evaluated using western blots. Correlations with US parameters were explored.
Clinical UHF US successfully imaged the kidneys of the experimental mice. A three-layer configuration was prevalent in the normal mouse kidney parenchyma (34/35) but was blurred in most fibrotic mouse kidneys (33/40). US parameters, including size (11.14 vs. 10.70 mm), PT (2.07 vs. 1.24 mm), RI (0.64 vs. 0.77), VI (22.55% vs. 11.47%, only for non-obstructive kidneys), SWS (1.67 vs. 2.06 m/s), and stiffness (8.23 vs. 12.92 kPa), showed significant differences between normal and fibrotic kidneys (P<0.001). These parameters also demonstrated strong discriminative ability in receiver operating characteristic curve analysis (area under the curve, 0.76 to 0.95; P<0.001). PT, VI, and RI were significantly correlated with histological fibrosis markers (ρ=-0.64 to -0.68 for PT and VI, ρ=0.71-0.76 for RI, P<0.001). VI exhibited strong negative correlations with Col1A1 (ρ=-0.76, P=0.006) and α-SMA (ρ=-0.75, P=0.009).
Clinical UHF US effectively distinguished normal and fibrotic mouse kidneys, indicating the potential of US parameters, notably VI, as noninvasive markers for tracking fibrosis initiation and progression in mouse kidney fibrosis models.
本研究旨在通过临床33MHz超高频（UHF）换能器建立正常小鼠肾脏的基线形态学和功能数据，将这些数据与纤维化小鼠的研究结果进行比较，并评估超声（US）参数与纤维化相关标志物之间的相关性。
这项回顾性研究汇总了来自三个独立实验（梗阻性肾病、糖尿病肾病和急性至慢性肾损伤模型）的数据。评估并比较了正常和纤维化小鼠肾脏的形态学参数（肾脏大小、实质厚度[PT]）和功能参数（剪切波速度[SWS]、硬度、阻力指数[RI]以及微血管成像衍生的血管指数[VI]）。计算了半定量组织病理学评分，并使用蛋白质免疫印迹法评估了分子标志物（上皮钙黏蛋白、胶原蛋白1A1[Col1A1]、转化生长因子-β和α平滑肌肌动蛋白[α-SMA]）。探索了与US参数的相关性。
临床UHF US成功对实验小鼠的肾脏进行了成像。正常小鼠肾实质中普遍存在三层结构（34/35），但在大多数纤维化小鼠肾脏中（33/40）则模糊不清。US参数，包括大小（11.14对10.70mm）、PT（2.07对1.24mm）、RI（0.64对0.77）、VI（22.55%对11.47%，仅针对非梗阻性肾脏）、SWS（1.67对2.06m/s）和硬度（8.23对12.92kPa），在正常和纤维化肾脏之间显示出显著差异（P<0.001）。这些参数在受试者工作特征曲线分析中也显示出很强的鉴别能力（曲线下面积，0.76至0.95；P<0.001）。PT、VI和RI与组织学纤维化标志物显著相关（PT和VI的ρ=-0.64至-0.68，RI的ρ=0.71-0.76，P<0.001）。VI与Col1A1（ρ=-0.76，P=0.006）和α-SMA（ρ=-0.75，P=0.009）呈现出很强的负相关性。
临床UHF US有效区分了正常和纤维化小鼠肾脏，表明US参数，尤其是VI，作为小鼠肾纤维化模型中追踪纤维化起始和进展的无创标志物具有潜力。
