University Hospital of Muenster, Department of Medicine B, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany.
Integr Biol (Camb). 2013 Mar;5(3):624-30. doi: 10.1039/c2ib20227a.
Inflammatory bowel diseases including Crohn's disease and ulcerative colitis resemble a large burden for patients due to the chronic course of disease. Therefore, there is an urgent need to explore new potential drugs and to develop new treatment options. Usually, evaluation of therapeutic potential is performed in murine models of colitis with the challenge of a valid assessment of the ongoing inflammation and the therapeutic response. Digital holographic microscopy (DHM) enables stain-free quantitative phase contrast imaging and provides tissue density assessment by measuring optical path length delay and accordingly refractive index. Dextran sodium sulphate induced colitis was performed in C57Bl/6 wildtype mice and colonic sections were examined by histological analyses and by DHM. This study proves the average refractive index to be an accurate marker to distinguish between different layers of the intestinal wall, such that the stroma is characterized by the highest value and the submucosa by the lowest. Furthermore, DHM allows a reliable detection of inflamed colonic segments (P < 0.001) with a strong correlation between the severity of inflammation and the refractive index, especially in the submucosa (R(2) = 0.639). In conclusion, this approach opens a novel diagnostic option for optical quantification of inflammation in murine models of colitis. Our results pave the way to further studies to elucidate the translational potential of DHM for the clinical management of patients with inflammatory bowel diseases.
炎症性肠病包括克罗恩病和溃疡性结肠炎,由于疾病的慢性病程,给患者带来了巨大的负担。因此,迫切需要探索新的潜在药物并开发新的治疗选择。通常,在结肠炎的小鼠模型中评估治疗潜力,其挑战是对正在进行的炎症和治疗反应进行有效的评估。数字全息显微镜 (DHM) 可实现无染色定量相衬成像,并通过测量光程延迟和相应的折射率来提供组织密度评估。在 C57Bl/6 野生型小鼠中进行葡聚糖硫酸钠诱导的结肠炎,并通过组织学分析和 DHM 检查结肠切片。本研究证明平均折射率是区分肠壁不同层的准确标志物,使得基质的折射率最高,而黏膜下层的折射率最低。此外,DHM 可可靠地检测发炎的结肠节段(P < 0.001),炎症的严重程度与折射率之间具有很强的相关性,尤其是在黏膜下层(R(2) = 0.639)。总之,这种方法为光学定量炎症提供了一种新的诊断选择在结肠炎的小鼠模型中。我们的研究结果为进一步阐明 DHM 在炎症性肠病患者临床管理中的转化潜力铺平了道路。