Digital holographic microscopy quantifies the degree of inflammation in experimental colitis

Abstract

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.

Holotomography: refractive index as an intrinsic imaging contrast for 3-D label-free live cell imaging

“…For example, 2-D and 3-D RI distributional maps can be utilized in label-free cellular identification (Chalut et al 2012;Jo et al 2015;Jo et al 2014;Jo et al 2017;Yoon et al 2017) and long-term growth monitoring (Bettenworth et al 2014;Chalut et al 2012). In addition, RI itself can be used as a new marker which represents cellular states or abnormalities (Lenz et al 2013;Schürmann et al 2016), and the factors which change the intracellular RI are being actively studied (Ekpenyong et al 2013;Wang et al 2011b).…”

“…The RI information, for example, was used to quantify the weight loss in the inflammation-induced colitis (Lenz et al 2013). Besides the dry mass information, the measurements of optical phase delay maps of a tissue slice could precisely be utilized to extract the scattering parameters such as scattering coefficients (μs) and anisotropies (g) (Ding et al 2011;Wang et al 2011a;Wang et al 2011b).…”

Quantitative Stain-Free and Continuous Multimodal Monitoring of Wound Healing In Vitro with Digital Holographic Microscopy

“…Recently, it has been demonstrated that DHM provides quantitative monitoring of physiological processes through structural analysis and functional imaging which, for example, gives new insight into signaling of cellular water permeability [19], [20], cell morphology changes due to toxins [21]–[24] and infections [25]–[27] as well as micro-calcification, cancer and inflammation mediated tissue alterations [12], [28] and bacteria and mammalian single cell growth [29]–[32].…”

Identification of amyloid plaques in mouse brain tissue slides using quantitative phase imaging

“…Because the quantitative optical phase contains quantitative information about morphology and optical properties of the samples, QPI has been widely imported into biological and medical research field in recent years [5]. Its applications of imaging range from small biological cells such as red blood cells [6] and pathological bacteria [7] to large field-of-view samples such as a neuronal network [8] or biological tissues such as a breast tissue, a prostate tissue and colitis-induced murine colon [9,10]. Its application to pathological brain tissue, however, is unprecedented.…”