PROJECT SUMMARY White adipose tissue (WAT) is a complex organ with functional roles beyond storing energy and insulating organs. Recent studies have demonstrated the critical role of WAT in supporting systemic health through secretion of biologically active substances (adipokines). WAT dysfunction can arise from tissue expansion through increased adipocyte size or number density. While the systemic expansion of WAT is typically caused by increased energy intake, localized diseases like cancerous tumors or coronary artery disease can affect the microstructure of nearby adipocytes. Systemic WAT dysfunction correlates with levels of certain adipokines measurable in blood serum, but local microstructural changes of adipocytes associated with local disease do not necessarily correlate with blood serum adipokine levels, requiring direct evaluation of WAT microstructure to quantify changes through biopsy or tissue resection. No methods exist to directly characterize the microstructural properties of adipocytes in WAT non- invasively and in vivo. Given the importance of WAT to human health and the relationship between WAT microstructural changes and dysfunction, there is clearly a need for methods to rapidly and non-invasively quantify adipocyte size, number density, and spatial organization in vivo for detecting and monitoring both systemic and local disease. We propose to develop quantitative ultrasound (QUS) imaging methods for this purpose. We hypothesize that 1) QUS parameters correlate with adipocyte size, number density, and spatial organization in WAT and 2) QUS can non-invasively detect local microstructural changes in adipocytes not measurable through blood serum biomarkers which are typically associated with systemic WAT dysfunction. Aim 1 will test the first hypothesis by comparing QUS parameters computed from WAT regions in breast tissues with adipocyte size and number density measurements computed from digital image analysis of H&E-stained tissue sections of the same regions. The second hypothesis will be tested in aim 2 by comparing QUS parameters from WAT regions near cancerous breast lesions – where microstructural properties of adipocytes are known to change locally – and several millimeters away from lesions (not affected by cancerous tumors) to measurements of adipokine levels in blood serum. Aim 1 validates QUS as a method to characterize adipocyte microstructure in vivo whereas Aim 2 demonstrates the efficacy of QUS parameters to detect local, not systemic, microstructural changes. The expected outcome of this work is the validation of QUS as a non-invasive method to characterize the microstructural properties of adipocytes in WAT. If successful, QUS could become a meaningful tool for routine clinical care and for supporting other research efforts attempting to uncover the relationship between alterations in WAT microstructure and disease.

PROJECT NARRATIVE Recent studies have demonstrated the importance of white adipose tissue, the most common type of body fat, in human health. Changes in the cellular structure of white adipose tissue can be indicative of disease, but there are currently no methods to quickly and non-invasively evaluate these changes in vivo. This project aims to develop rapid and inexpensive ultrasonic imaging methods to directly assess fat tissue non-invasively.