Mustafi Devkumar, Shiou Sheng-Ru, Fan Xiaobing, Markiewicz Erica, Karczmar Gregory S, Claud Erika C
Department of Radiology, University of Chicago, Chicago, IL, USA.
NMR Biomed. 2014 Mar;27(3):272-9. doi: 10.1002/nbm.3060. Epub 2013 Dec 8.
Neonatal necrotizing enterocolitis (NEC) is a poorly understood life-threatening illness afflicting premature infants. Research is hampered by the absence of a suitable method to monitor disease progression noninvasively. The primary goal of this research was to test in vivo MRI methods for the noninvasive early detection and staging of inflammation in the ileum of an infant rat model of NEC. Neonatal rats were delivered by cesarean section at embryonic stage of day 20 after the beginning of pregnancy and stressed with formula feeding, hypoxia and bacterial colonization to induce NEC. Naturally born and dam-fed neonatal rats were used as healthy controls. In vivo MRI studies were performed using a Bruker 9.4-T scanner to obtain high-resolution anatomical MR images using both gradient echo and spin echo sequences, pixel-by-pixel T2 maps using a multi-slice-multi-echo sequence, and maps of the apparent diffusion coefficient (ADC) of water using a spin echo sequence, to assess the degree of ileal damage. Pups were sacrificed at the end of the MRI experiment on day 2 or 4 for histology. T2 measured by MRI was increased significantly in the ileal regions of pups with NEC by histology (106.3 ± 6.1 ms) compared with experimentally stressed pups without NEC (85.2 ± 6.8 ms) and nonstressed, control rat pups (64.9 ± 2.3 ms). ADC values measured by diffusion-weighted MRI were also increased in the ileal regions of pups with NEC by histology [(1.98 ± 0.15) × 10(-3) mm(2)/s] compared with experimentally stressed pups without NEC [(1.43 ± 0.16) × 10(-3) mm(2)/s] and nonstressed control pups [(1.10 ± 0.06) × 10(-3) mm(2)/s]. Both T2 and ADC values between these groups were found to be significantly different (p < 0.03). The correlation of MRI results with histologic images of the excised ileal tissue samples strongly suggests that MRI can noninvasively identify NEC and assess intestinal injury prior to clinical symptoms in a physiologic rat pup model of NEC.
新生儿坏死性小肠结肠炎(NEC)是一种威胁早产儿生命且了解甚少的疾病。由于缺乏一种合适的非侵入性方法来监测疾病进展,研究受到阻碍。本研究的主要目的是在新生大鼠坏死性小肠结肠炎模型的回肠中,测试用于炎症非侵入性早期检测和分期的体内MRI方法。在怀孕开始后第20天的胚胎期通过剖宫产分娩新生大鼠,并通过配方奶喂养、低氧和细菌定植使其产生应激以诱导坏死性小肠结肠炎。自然分娩并由母鼠喂养的新生大鼠用作健康对照。使用布鲁克9.4-T扫描仪进行体内MRI研究,使用梯度回波和自旋回波序列获取高分辨率解剖学MR图像,使用多层多回波序列逐像素获取T2图,并使用自旋回波序列获取水的表观扩散系数(ADC)图,以评估回肠损伤程度。在MRI实验第2天或第4天结束时处死幼崽进行组织学检查。与无坏死性小肠结肠炎的实验性应激幼崽(85.2±6.8毫秒)和无应激的对照幼鼠(64.9±2.3毫秒)相比,经组织学检查,坏死性小肠结肠炎幼崽回肠区域通过MRI测量的T2显著增加(106.3±6.1毫秒)。与无坏死性小肠结肠炎的实验性应激幼崽[(1.43±0.16)×10⁻³平方毫米/秒]和无应激对照幼崽[(1.10±0.06)×10⁻³平方毫米/秒]相比,坏死性小肠结肠炎幼崽回肠区域通过扩散加权MRI测量的ADC值也增加[(1.98±0.15)×10⁻³平方毫米/秒]。发现这些组之间的T2和ADC值均存在显著差异(p<0.03)。MRI结果与切除的回肠组织样本的组织学图像之间的相关性强烈表明,在坏死性小肠结肠炎的生理性幼鼠模型中,MRI可以在临床症状出现之前非侵入性地识别坏死性小肠结肠炎并评估肠道损伤。