3D Whole-Pancreas Analysis of Mouse Models of Pancreatic Cancer

项目摘要 本申请是为了响应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 23-045，是细胞癌症生物学成像研究（CCBIR）计划和 胰腺导管腺癌间质重编程联盟（PSRC）。胰腺癌是一 一种致命的疾病，预后不佳，但由缺乏扩散能力的癌前病变引起 胰腺以外，强调癌症拦截的机会在这种疾病。基因 基因工程小鼠模型为研究胰腺癌前病变的发生提供了关键机会 为这种拦截方法提供合理的基础，作为这些时间的系列组织样本， 点不能从人类患者获得。然而，在小鼠中量化癌前负担的工具， 目前缺乏通过整个胰腺的单细胞水平;这些工具将大大提高 对这些模型进行评估。因此，我们将利用我们最近开发的3D深度学习工具CODA 重建和细胞量化，这是正在扩大的应用和验证的一部分， CCBIR计划。使用CODA，我们将分析来自诱导型KRAS（iKRAS）小鼠的全胰腺 模型，该模型允许在多个时间点评估上皮微环境串扰， 肿瘤发生，PSRC的关键目标。CCBIR计划和PSRC之间的合作将 将新型癌症成像技术应用于胰腺癌的创新小鼠模型， 深入了解早期胰腺肿瘤发生中的细胞变化。这些研究还将提供更多的 CODA管道的验证，并平衡这种方法更广泛地应用于小鼠模型， 癌

Project Summary This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 23-045 and is a collaboration between the Cellular Cancer Biology Imaging Research (CCBIR) Program and the Pancreatic Ductal Adenocarcinoma Stroma Reprogramming Consortium (PSRC). Pancreatic cancer is a deadly disease with a dismal prognosis but arises from precancerous lesions that lack the ability to spread beyond the pancreas, underscoring the opportunity for cancer interception in this disease. Genetically engineered mouse models provide a key opportunity to study premalignant pancreatic tumorigenesis over time to provide a rational foundation for such interception approaches, as serial tissue samples from these time points are not available from human patients. However, tools to quantify precancer burden in mice at the single-cell level through the whole pancreas are currently lacking; such tools would greatly improve the rigor of evaluation of these models. As such, we will leverage our recently developed deep learning tool CODA for 3D reconstruction and cellular quantification, which is undergoing expanded application and validation as part of the CCBIR Program. Using CODA, we will analyze whole pancreata from the inducible KRAS (iKRAS) mouse model, which allows assessment of epithelial-microenvironment cross talk at multiple time points in early tumorigenesis, a key goal of the PSRC. This collaboration between the CCBIR Program and the PSRC will apply novel cancer imaging technologies to innovative mouse models of pancreatic cancer, providing important insights into the cellular alterations in early pancreatic tumorigenesis. These studies will also provide additional validation of the CODA pipeline and poise this approach for application more broadly across mouse models of cancer.