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MRI Assessment of Associations between Brown Adipose Tissue and Cachexia in Murine Pancreatic Ductal Adenocarcinoma

Yaqi Zhang, Su Hu, Junjie Shangguan, Liang Pan, Xin Zhou, Vahid Yaghmai, Yuri Velichko, Chunhong Hu, Jia Yang and Zhuoli Zhang

Objective: As the major thermogenic tissue in body, the brown adipose tissue (BAT) was recently identified as an important factor to induce the rapid weight loss and malnutrition in malignancy. Current methods for detecting and quantifying brown adipose tissue (BAT) are in limited use. The aim of this study was to evaluate the changes of BAT tissue and its function in the development of pancreatic ductal adenocarcinoma (PDAC) by using magnetic resonance imaging (MRI).

Methods: Ten-week-old female C57BL/6 mice were inoculated orthotopically with Pan02 tumor cells. R2* maps and two-point Dixon MRI were performed weekly for evaluation of BAT function and volume, respectively. The T2- weighted MRI was applied weekly for monitoring tumor growth. Meanwhile, the body weight was measured daily as another indication of malnutrition. The UCP1 levels in BAT and white adipose tissue (WAT) were assessed. The serum IL-6 was also measured as the biomarker of cancer-associated cachexia.

Results: T2-weighted MRI indicated the rapid tumor growth from week 3 to week 5 after tumor cell inoculation. The water-fat separated MRI could clearly identify and quantify the BAT. The function and volume of BAT could be monitored by weekly MRI measurement in tumor-bearing mice. The total body weights of PDAC tumor-bearing mice were relatively stable, however, was significantly lower than that of control C57BL/6 mice.

Conclusion: The results of this study demonstrated the feasibility of detection and quantification of BAT in vivo by MRI during the development of pancreatic cancer.