A population-based study of deep learning derived organ and tissue measures for accelerated aging using repurposed abdominal CT images

项目摘要 身体机能减退和身体不适的人数急剧增加， 与衰老有关的慢性病。如果我们将实足年龄（基于年龄）与生物年龄进行比较， （细胞、组织、器官和系统水平的变化），我们可以将人归类为衰老较快的人。 （加速老化）或比同龄人慢（成功老化）。已经开发出测量方法 基于DNA甲基化、端粒长度和血液生物标志物的生物年龄。然而，这些措施 可能不能准确反映器官和组织水平的变化，从老化。多器官/组织方法是 需要在体征、症状或临床表现出现之前识别全面的年龄相关结构变化， 诊断发生。腹部计算机断层扫描（CT）已广泛用于一般人群（35%） 年龄在20-89岁的成年人在11年期间）。器官和组织的定量测量 腹部CT可以预测器官特异性疾病，或者结合起来，可以用来计算生物学年龄 并预测住院和死亡率的全球结果。因此，我们的中心假设是， 应用于腹部CT的深度学习（DL）模型可以量化器官和组织的结构特征 识别加速老化的人，这些人具有器官特异性疾病、住院和死亡的高风险。 罗切斯特流行病学项目记录链接系统提供了对以下一般人群档案的访问： 423，081例腹部CT图像和181，187例成人（年龄 20-89岁）。我们的团队已经开发并验证了用于测量肝脏的DL工具， 肾脏、主动脉、脂肪、肌肉和骨骼。我们将利用这些资源1）建立 来自健康和一般人群样本的腹部CT生物标志物的数量; 2）确定 在一般人群中通过腹部CT生物标志物确定器官特异性临床疾病的风险;以及3）确定 一般人群中与腹部CT测量相关的住院和死亡风险。如果 成功地将DL工具应用于腹部CT图像将丰富年龄相关性 没有额外的测试负担的健康风险。亚临床腹部CT生物标志物也可以告知 衰老和早期疾病的生物学，改善疾病分类，并提供早期治疗的机会。 干预

PROJECT SUMMARY There has been a dramatic increase in the number of persons living with reduced physical function and with aging-related chronic conditions. If we compare chronological age (calendar-based age) with biological age (changes at the cellular, tissue, organ, and system levels), we can classify persons as aging faster (accelerated aging) or slower (successful aging) than their peers. Methods have been developed to measure biological age based on DNA methylation, telomere length, and blood biomarkers. However, such measures may not accurately reflect organ- and tissue-level changes from aging. A multi-organ/tissue approach is needed to identify comprehensive age-related structural changes before signs, symptoms, or clinical diagnoses occur. Abdominal computed tomography (CT) has widespread use in the general population (35% of adults ages 20-89 years in an 11-year period). Quantitative measures of the organs and tissues on abdominal CT may predict organ-specific diseases, or in combination, may be used to calculate biological age and predict the more global outcomes of hospitalization and mortality. Therefore, our central hypothesis is that deep learning (DL) models applied to abdominal CTs can quantify structural features of the organs and tissues to identify persons with accelerated aging at high-risk for organ-specific disease, hospitalization, and death. The Rochester Epidemiology Project record-linkage system provides access to a general population archive of images for 423,081 abdominal CTs and to comprehensive medical record data among 181,187 adults (ages 20-89 years) between 2010-2020. Our team has already developed and validated DL tools to measure liver, kidney, aorta, fat, muscle, and bone on abdominal CT images. We will leverage these resources to 1) establish percentiles of abdominal CT biomarkers from both healthy and general population samples; 2) determine the risk of organ-specific clinical disease by abdominal CT biomarkers in the general population; and 3) determine the risk of hospitalization and death associated with abdominal CT measures in the general population. If successful, application of DL tools to abdominal CT images will enrich the characterization of age-related health risks without additional testing burden. Subclinical abdominal CT biomarkers may also inform the biology of aging and early disease, improve disease classification, and provide opportunities for early intervention.