Magnetic resonance imaging with hyperpolarized [1,4-13C2]fumarate allows detection of early renal acute tubular necrosis
Magnetic resonance imaging with hyperpolarized [1,4-13C2]fumarate allows detection of early renal acute tubular necrosis
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DOI：
10.1073/pnas.1205539109
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发表时间：
2012-08-14
影响因子：
11.1
通讯作者：
Brindle, Kevin M.
中科院分区：
文献类型：
--
作者：
Clatworthy, Menna R.;Kettunen, Mikko I.;Brindle, Kevin M.
急性肾损伤（阿基）是一种常见且重要的医学问题，影响10%的住院患者，并且与显著的发病率和死亡率相关。阿基最常见的原因是急性肾小管坏死（ATN）。目前的成像技术和生物标志物不允许ATN可靠地从重要的鉴别诊断，如急性肾小球肾炎（GN）。我们研究了C-13磁共振波谱成像（MRSI）是否可以无创诊断ATN。超极化[1，4-C-13（2）]富马酸盐和丙酮酸盐的C-13 MRSI用于ATN和急性GN小鼠模型（狼疮肾炎NZM 2410小鼠）。在严重组织学变化发生之前的病程早期，在ATN小鼠的肾脏中发现[1，4-C-13（2）]苹果酸信号显著增加。在急性GN小鼠中未观察到肾脏[1，4-C-13（2）]苹果酸盐的增加。肾脏[1-C-13]丙酮酸/[1-C-13]乳酸比值显示出显著变异性，在ATN动物中未显著降低，在GN动物中未显著升高。总之，在小鼠模型中，超极化[1，4-C-13（2）]富马酸盐的MRSI允许检测早期肾小管坏死及其与肾小球炎症的区别。这项技术可能有潜力确定一个窗口的治疗机会，其中新兴的疗法可能适用于ATN患者，减少急性透析的需要，其伴随的发病率和成本。
Acute kidney injury (AKI) is a common and important medical problem, affecting 10% of hospitalized patients, and it is associated with significant morbidity and mortality. The most frequent cause of AKI is acute tubular necrosis (ATN). Current imaging techniques and biomarkers do not allow ATN to be reliably differentiated from important differential diagnoses, such as acute glomerulonephritis (GN). We investigated whether C-13 magnetic resonance spectroscopic imaging (MRSI) might allow the noninvasive diagnosis of ATN. C-13 MRSI of hyperpolarized [1,4-C-13(2)]fumarate and pyruvate was used in murine models of ATN and acute GN (NZM2410 mice with lupus nephritis). A significant increase in [1,4-C-13(2)]malate signal was identified in the kidneys of mice with ATN early in the disease course before the onset of severe histological changes. No such increase in renal [1,4-C-13(2)]malate was observed in mice with acute GN. The kidney [1-C-13]pyruvate/[1-C-13]lactate ratio showed substantial variability and was not significantly decreased in animals with ATN or increased in animals with GN. In conclusion, MRSI of hyperpolarized [1,4-C-13(2)]fumarate allows the detection of early tubular necrosis and its distinction from glomerular inflammation in murine models. This technique may have the potential to identify a window of therapeutic opportunity in which emerging therapies might be applied to patients with ATN, reducing the need for acute dialysis with its attendant morbidity and cost.