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 algorithm
4 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 100mm
2 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/m
2 and pancreatic
PDFF value of 15.5% (range 5.0 – 32.2%), and at 7 months an average BMI of 32.9
kg/m
2 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 StatesReferences
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