A novel way to enhance the diagnosis of early stage of colorectal cancer through micro-computed tomography imaging

患有长期（>8年）炎症性肠病（IBD）的患者有20%的终生发生结直肠癌（CRC）的风险。CRC的早期诊断至关重要，因为它可以带来更好的治疗和生存。因此，IBD患者目前通过使用定期监测结肠镜检查（摄像机测试）和活检（组织取样）进行筛查，以在癌前或早期癌症阶段进行诊断。尽管有监测筛查和生化检测，晚期癌症仍有报道，监测计划的价值仍存在争议。基于此，早期诊断CRC的可靠标记物仍然需要更好的治疗和提高生存率。为此，我们提出了一种新的方法，以提高早期诊断结直肠癌通过显微计算机断层扫描（microCT）：目的1：我们将使用小鼠模型炎症诱导的CRC成像结肠在不同的时间点的CRC进展。早期CRC的新的微结构标记将来自microCT数据，如病变纹理。这些微结构标志物的CRC特异性将通过与共同注册的组织学切片的交叉相关来测试。目标2：我们将开发一种microCT协议，用于对未造影结肠组织的微观结构进行成像，通过调整UoS先前使用基于实验室的microCT对未造影肺组织进行成像的工作。这与我们目前的Wellcome Pathfinder Award（2016 - 2017）一致，在该奖项中，我们与Nikon Metrology UK合作开发了第一个与现有组织病理学工作流程完全兼容的microCT系统。目标3：由于发育不良相关病变肿块（DALM）的存在高度提示潜在或相关CRC，因此我们将招募参加长期（>8年）IBD监测筛查计划的IBD患者进行小型研究。来自DALM样本、非DALM和CRC晚期的MicroCT结果将通过诊断证据进行验证，这些诊断证据已经通过组织学获得，这将为microCT成像在CRC诊断中的实用性提供证据。

Patients with long-term (>8 years) inflammatory bowel disease (IBD) have a 20% lifetime risk of developing colorectal cancer (CRC). Early diagnosis of CRC is essential as it leads to better therapy and survival. Therefore, IBD patients are currently screened by using regular surveillance colonoscopies (camera test) and biopsies (tissue sampling) for diagnosis at a pre-cancerous or early cancer stage. Despite surveillance screening and biochemical tests, advanced cancers are still reported and the value of surveillance program remains controversial. On this account, reliable markers for early diagnosis of CRC are still required for better therapy and increased survival rate.To this end, we propose a novel way to enhance the early diagnosis of colorectal cancer through micro-computed tomography (microCT):- AIM 1: We will use a mouse model for inflammatory-induced CRC to image the colon by microCT at different time points of CRC progression. New microstructural markers for early-stage CRC will be derived from microCT data, such as lesion textures. CRC specificity of these microstructural markers will be tested by cross-correlation with co-registered histological sections.- AIM 2: We will develop a microCT protocol for imaging microstructures of un-contrasted colon tissue, by adapting previous work at UoS on imaging of un-contrasted lung tissue using lab-based microCT. This is aligned with our current Wellcome Pathfinder Award (2016 - 2017), where in collaboration with Nikon Metrology UK, we develop the first microCT system that is fully compatible with existing histopathological workflows.- AIM 3: As the presence of dysplasia-associated lesion mass (DALM) is highly indicative of underlying or associated CRC, we will recruit IBD patients attending the surveillance screening program with long-term (>8 years) IBD for a small study. MicroCT results from DALM samples, non-DALM, and CRC advanced stage will be validated through proof of diagnosis, already obtained through histology, which will provide evidence for the utility of microCT imaging in CRC diagnosis.