多模态MR成像在对比剂肾病发病机制及早期预测作用中的研究

Contrast induced nephropathy (CIN) is a common iatrogenic event following intravascular injection of iodinated contrast medium (CM). The mechanisms underlying this injury are not completely understood, and there is yet no specific therapy is recommended. Estimate of reanl function is very important in determining the early pathological changes of CIN, and helpful in guiding therapy and prognostic evaluation. However, the existed techniques for such measurements are potentially limited by their invasiveness, low sensibility and specificity. Functional MR techniques further offer the potential for noninvasive measurements of renal parenchymal perfusion, filtration and tubular function. Such assessments of the renal function can assist in evaluation of patients with systemic or renal disease for early detection and monitoring of the therapy. Thus, in this study, we firstly purpose to creat a multimodal radiographic platform for the quantitative estimation of renal function using a series of MR techiniques. And secondly, We put forward a unifying theory as to how CIN comes about, and sought to determine how these physicochemical properties such as osmolality and viscosity of CM may contribute to potential renal damage and hypoxia in rabbits with multimodal MR techniques. We believe the proposed techinques will be of benefit for early diagnosis and this mechanistic study will enable us to control variables and interpret any role of mechanical intervention plays in preventing CIN in clinical patients.

对比剂肾病（CIN）是临床常见的急性药物性肾损害，目前发病机制尚不完全清楚。肾脏功能检测对CIN的早期诊断、治疗及预后评价具有重要价值。传统肾功能指标在敏感性、特异性及可重复性方面均存在缺陷，无法全面反映分肾功能变化。因此，活体下构建无创、简单有效的肾功能测量平台，对于提高早期肾损害的诊断敏感性与特异性尤为重要。本项目拟通过构建碘对比剂急性肾损害动物模型，以多模态MR功能成像为手段，观察注射碘对比剂后肾脏灌注、氧代谢、分肾GFR及肾小管结构功能变化,阐述CIN发病机制的关键环节，评价多模态MR功能成像对CIN的早期预测作用，为临床寻找有效的预防及治疗方案。

碘对比剂高渗透压与高粘滞度是导致急性肾损害（AKI）的直接原因，但机制尚不明确。本研究提出“管-球反馈失衡”概念，通过构建大鼠AKI模型，利用高分辨率DWI及DCE-MRI肾图成像，结合定量分析技术，观察注射不同渗透压、粘滞度碘对比剂下肾小球-肾小管结构功能变化。研究发现：. 1）高渗-中高粘滞度碘对比剂（碘浓度：370 mgI/mL；渗透压：779 mOsm/kg；粘滞度：9.5 mPa.s）导致肾脏内髓一过性小管液流速增高，粘滞度下降，推论与渗透性利尿有关，肾脏皮质、外髓血流动力学指标无显著变化。肾标本Kim-1及NGAL基因表达无异常。提示高渗碘对比剂因具有高渗性利尿作用，中和了高粘滞度的影响，对肾脏损害程度可能低于预估。. 2）高粘滞度-等渗（碘浓度：320 mgI/mL；渗透压：290 mOsm/kg；粘滞度：11.8 mPa.s）、低粘滞度-等渗碘对比剂（碘浓度：270 mgI/mL；渗透压：290 mOsm/kg；粘滞度：6.3 mPa.s）导致肾脏外髓及内髓小管粘滞度显著增高，肾小球滤过率GFR及肾血流量RBF急剧下降，肾标本肾小管细胞水肿及空泡变性明显、Kim-1基因表达异常增高。即使采用等渗-低粘滞度碘对比剂，急性肾损害程度并未减缓。. 研究结果提示肾小管高粘滞度环境可能是导致AKI发生的重要原因，高粘滞度碘对比剂增加了肾小管后负荷，导致小管内压增加，流速减缓，GFR下降，增加了碘对比剂在肾脏内停留时间，增加了AKI风险。上述结果印证我们提出的 “管-球反馈失衡”假说，为临床高危患者的防治提供一个新理论依据。. 项目直接资助发表SCI论文4篇，培养硕士1名，合作博士后1名。