Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, TN, 37232, USA.
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, TN, 37232, USA.
NMR Biomed. 2019 Nov;32(11):e4128. doi: 10.1002/nbm.4128. Epub 2019 Jul 29.
Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well-established murine model with progressive renal disease. MR images were acquired from 16-week-old fibrotic hHB-EGF mice and normal wild-type (WT) mice (N = 12) at 7 T. QMT parameters were derived using a two-pool five-parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value (tPSR) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB-EGF mouse kidneys. Moderate increases in mean PSR (mPSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the tPSR were significantly increased in hHB-EGF mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.
过度的组织瘢痕形成，即纤维化，是导致终末期肾病的一个关键因素，但目前的临床检测方法不足以评估肾纤维化。定量磁化转移（qMT）MRI 可提供组织中大分子组成的间接信息。我们评估了 qMT 获得的池大小比（PSR，固定大分子与自由水质子的比值）在具有进行性肾病的成熟小鼠模型中作为肾小管间质纤维化的生物标志物的测量值。在 7T 下，从 16 周龄纤维化 hHB-EGF 小鼠和正常野生型（WT）小鼠（N=12）中采集 MR 图像。使用双池五参数拟合模型得出 qMT 参数。通过在 WT 肾脏内的体素上取平均值来确定皮质和外髓外带（CR+OSOM）的 PSR 值的正常范围（均值±2SD）。确定了超过阈值（tPSR）的正常范围内的病变小鼠中 PSR 值的病变区域，并对其进行了测量。使用苦味酸红染色确认纤维化的空间分布。与正常 WT 小鼠相比，hHB-EGF 小鼠肾脏的 OSOM 中观察到散布的高 PSR 区域簇。在纤维化肾脏中，CR+OSOM 区域的平均 PSR（mPSR）适度增加。tPSR 检测到的异常高 PSR 区域（%面积）在 hHB-EGF 小鼠中显著增加，并且与苦味酸红染色测量的组织纤维化指数检测到的纤维化区域高度相关。因此，可通过 qMT MRI 使用 PSR 的适当分析评估 OSOM 中的肾间质纤维化。该技术可作为慢性肾病的影像学生物标志物。
