Xie Luke, Cianciolo Rachel E, Hulette Brian, Lee Ha Won, Qi Yi, Cofer Gary, Johnson G Allan
Department of Radiology, Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina, USA.
Toxicol Pathol. 2012 Jul;40(5):764-78. doi: 10.1177/0192623312441408. Epub 2012 Apr 13.
Magnetic resonance histology (MRH) has become a valuable tool in evaluating drug-induced toxicity in preclinical models. However, its application in renal injury has been limited. This study tested the hypothesis that MRH could detect image-based biomarkers of chronic disease, inflammation, or age-related degeneration in the kidney, laying the foundation for more extensive use in evaluating drug toxicity. We examined the entire intact kidney in a spontaneous model of chronic progressive nephropathy. Kidneys from male Sprague Dawley rats were imaged at 8 weeks (n = 4) and 52 weeks (n =4) on a 9.4 T system dedicated to MR microscopy. Several potential contrast mechanisms were explored to optimize the scanning protocols. Full coverage of the entire kidney was achieved with isotropic spatial resolution at 31 microns (voxel volume = 30 pL) using a gradient recalled echo sequence. Isotropic spatial resolution of 15 microns (voxel volume < 4 pL) was achieved in a biopsy core specimen. Qualitative age-related structural changes, such as renal cortical microvasculature, tubular dilation, interstitial fibrosis, and glomerular architecture, were apparent. The nondestructive 3D images allowed measurement of quantitative differences of kidney volume, pelvis volume, main vessel volume, glomerular size, as well as thickness of the cortex, outer medulla, and inner medulla.
磁共振组织学（MRH）已成为评估临床前模型中药物诱导毒性的一种有价值的工具。然而，其在肾损伤中的应用一直有限。本研究检验了以下假设：MRH能够检测出肾脏中慢性疾病、炎症或年龄相关退变的基于图像的生物标志物，为其在评估药物毒性方面更广泛的应用奠定基础。我们在慢性进行性肾病的自发模型中检查了整个完整的肾脏。对雄性斯普拉格-道利大鼠的肾脏在8周龄（n = 4）和52周龄（n = 4）时，在一台专门用于磁共振显微镜检查的9.4 T系统上进行成像。探索了几种潜在的对比机制以优化扫描方案。使用梯度回波序列，以31微米的各向同性空间分辨率（体素体积 = 30 pL）实现了对整个肾脏的全面覆盖。在活检核心样本中实现了15微米的各向同性空间分辨率（体素体积 < 4 pL）。与年龄相关的定性结构变化，如肾皮质微血管、肾小管扩张、间质纤维化和肾小球结构，清晰可见。这些无损三维图像能够测量肾脏体积、肾盂体积、主要血管体积、肾小球大小以及皮质、外髓和内髓厚度的定量差异。
