Longitudinal change of pancreatic proton density fat fraction (PDFF) and its correlates during weight loss in initially obese adults
Yesenia Covarrubias1, Alexandra N Schlein1, William M Haufe1, Catherine A Hooker1, Adrija Mamidipalli1, Tanya Wolfson2, Garth Jacobson3, Santiago Horgan3, Jeffrey B Schwimmer4, Scott B Reeder5, and Claude B Sirlin1

1Liver Imaging Group, Department of Radiology, University of California, San Diego, School of Medicine, San Diego, CA, United States, 2Computational and Applied Statistics Laboratory (CASL), SDSC, University of California, San Diego, La Jolla, CA, United States, 3Department of Surgery, University of California, San Diego, La Jolla, CA, United States, 4Division of Gastroenterology, Hepatology, and Nutrition & Department of Pediatrics, University of California, San Diego, School of Medicine, San Diego, CA, United States, 5Departments of Radiology, Medical Physics, Biomedical Engineering, Medicine, Emergency Medicine, University of Wisconsin, Madison, WI, United States

Synopsis

This pilot, prospective, longitudinal study in 9 obese adults explored the relationship between weight loss and longitudinal change in MRI-determined pancreatic proton density fat fraction (PDFF), as well as the relationships between rates of change in pancreatic PDFF, hepatic PDFF, and anthropometric measures. Pancreatic PDFF decreased in every subject from a mean of 15.5% at the first study visit to a mean of 8.6% at the last study visit (p=0.006). Further research in larger cohorts is needed to confirm our findings and to understand the clinical and biological relevance of pancreatic PDFF reduction.

Target Audience

Radiologists and clinicians with an interest in pancreatic fat quantification.

Purpose

Elevated pancreatic fat has been associated with increased insulin resistance, type 2 diabetes, and pancreatic cancer.1,2 A recent study demonstrated that patients undergoing bariatric weight loss surgery experience a concomitant decrease in both pancreatic ectopic fat and hepatic steatosis as measured by 1H MRS;2 that study assessed only two time points (baseline, six-months post-surgery) and so did not examine in detail the time course of pancreatic fat reduction. The primary purpose of this pilot study was to explore in greater detail the time course of pancreatic fat reduction during weight loss in initially obese adults in a surgical weight loss program. The secondary purpose was to explore the relationship between rates of change in pancreatic PDFF, hepatic PDFF, and anthropometric measures. Pancreatic and hepatic fat was measured at multiple time points (baseline, 1 month, 2 months, 4 months, and 7 months). We used MRI rather than MRS to measure pancreatic fat because, as suggested in other work being submitted as a scientific abstract to this meeting, MRI may provide more repeatable measurements of pancreatic fat than MRS.

Methods

Nine obese adults (7 female, 2 male, mean age 49.6 years) scheduled for weight loss surgery were prospectively recruited to undergo non-contrast MR examinations on a 3T scanner (GE Signa EXCITE HDxt, GE Healthcare, Waukesha, WI) at multiple time points before and after surgery. Hepatic and pancreatic fat quantification were performed using complex-based MRI (C-MRI) methods.3 The C-MRI technique originally developed for liver imaging was optimized to quantify pancreatic fat by eliminating parallel imaging to boost signal to noise ratio, and adjusting voxel size to minimize volume-averaging effects around the pancreas (Table 1). The entire pancreas was covered in 2-3 overlapping single breath-hold acquisitions. A specialized reconstruction algorithm4 automatically generated T2* corrected multi-fat-peak model PDFF maps, which were then transferred off line for further analysis. Regions of interest (ROIs) with areas of 100mm2 were placed in the head, body, and tail of the pancreas, with care to include only pancreatic parenchyma and to exclude vasculature and surrounding adipose tissue. Each ROI was co-localized to the first visit. Monthly rate of change of pancreatic PDFF, waist circumference, hepatic PDFF, and BMI were computed for each subject as a slope of a linear regression line over the first three study visits where the change is usually linear and most acute. T-test was used to test significance of slopes. Spearman’s rank-order correlation (ρ) was used to test the association between pancreatic PDFF waist circumference, hepatic PDFF, and BMI slopes.

Results

At their first visit, the 9 subjects had an average BMI of 44.1 kg/m2 and pancreatic PDFF value of 15.5% (range 5.0 – 32.2%), and at 7 months an average BMI of 32.9 kg/m2 and pancreatic PDFF value of 8.6% (range 3.7 - 16.4 %). All 9 subjects had lower pancreatic PDFF at the last visit than at the first visit (range of reduction 0.77% - 17.7%). Figure 1 illustrates the longitudinal changes in a representative subject. Figure 2 plots the longitudinal change of pancreatic PDFF values for all 9 subjects. Over all, patients lost an average absolute PDFF of 2.8% in the first two months and 4.1% in the last five months. Rate of change of pancreatic PDFF was significant (p=0.006). As shown in Figure 3, the rate of change in pancreatic PDFF was not significantly correlated with the rate of change in waist circumference, hepatic PDFF or BMI.

Discussion

Our study was limited by small sample size. While the associations between slopes of pancreatic PDFF and BMI, waist circumference, and hepatic PDFF did not reach statistical significance, ρ=037 suggests a potential relationship between pancreatic PDFF and waist circumference, changes that will need to be confirmed with a larger sample size. Another limitation was that although a high spatial resolution technique was used, we could not resolve intracellular fat from extracellular fat (adipose tissue) within the intercalations of the pancreatic parenchyma.

Conclusion

Pancreatic PDFF declines with weight loss. This pilot study offers a descriptive exploration of how C-MRI measured pancreatic fat content changes longitudinally in obese adults who undergo weight loss. Further research in larger cohorts is needed to confirm our findings and to understand the clinical and biological relevance of pancreatic PDFF reduction.

Acknowledgements

R01-DK088925/DK/NIDDK NIH HHS/United States

References

1. Gaborit, B., et al., Ectopic fat storage in the pancreas using 1H-MRS: importance of diabetic status and modulation with bariatric surgery-induced weight loss. Int J Obes (Lond), 2015. 39(3): p. 480-7.

2. Patel, N.S., et al., Insulin Resistance Increases MRI-Estimated Pancreatic Fat in Nonalcoholic Fatty Liver Disease and Normal Controls. Gastroenterol Res Pract, 2013. 2013: p. 498296.

3. Reeder, S.B. and C.B. Sirlin, Quantification of liver fat with magnetic resonance imaging. Magn Reson Imaging Clin N Am, 2010. 18(3): p. 337-57, ix.

4. Yu, H., et al., Multiecho water-fat separation and simultaneous R2* estimation with multifrequency fat spectrum modeling. Magn Reson Med, 2008. 60(5): p. 1122-34.

Figures

Table 1. Sequence scanning parameter for hepatic and pancreatic image acquisition

Figure 1. T2* corrected multi-fat-peak model PDFF maps from a 39-year old subject at five time points. Individual PDFF values for the head, body, and tail of the pancreas are shown for each time point.

Figure 2. Longitudinal change of pancreatic PDFF (%). 7 of 9 patients had a pancreatic measurement at all time points. 2 of 9 did not have a pancreatic measurement at baseline


Figure 3. Longitudinal change in the association between pancreatic PDFF, waist circumference, hepatic PDFF, and BMI



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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