Alma Spahic1, Grant Steven Roberts1, Tanya Wolfson2, David T Harris3, Nikolaos T Panagiotopoulos3,4, Alejandro Roldán-Alzate3,5,6, Kevin M Johnson1,3, Oliver T Wieben1,3, Claude B Sirlin7, Scott B Reeder1,3,5,6,8, and Thekla Helene Oechtering3,4
1Medical Physics, University of Wisconsin- Madison, Madison, WI, United States, 2Computational and Applied Statistics Laboratory, University of California San Diego, La Jolla, CA, United States, 3Radiology, University of Wisconsin- Madison, Madison, WI, United States, 4Radiology and Nuclear Medicine, Universität zu Lübeck, Lübeck, Germany, 5Mechanical Engineering, University of Wisconsin- Madison, Madison, WI, United States, 6Biomedical Engineering, University of Wisconsin- Madison, Madison, WI, United States, 7Radiology, University of California San Diego, San Diego, CA, United States, 8Emergency Medicine, University of Wisconsin- Madison, Madison, WI, United States
Synopsis
4D flow MRI of the portal vein has the
potential to provide diagnostic value for detecting and staging certain liver
diseases. To date, it is unknown whether weight loss influences portal flow in
obese patients. We aimed to investigate the effect of weight loss on portal
flow rate measured by non-contrast 4D flow MRI in obese patients undergoing weight
loss surgery. Preliminary data of this ongoing study detected no statistically
significant change in the mean volumetric portal flow rate in
subjects during 2-6 months of weight loss. However, portal flow
rate normalized to body weight or BMI increased significantly.
Introduction
Obese
individuals have an increased prevalence of non-alcoholic fatty liver disease
(NAFLD) which puts them at higher risk for developing cirrhosis.1 Cirrhosis is characterized by flow changes in the portal
vein that can be measured using 4D flow MRI. Typical findings include abnormal flow,
flow reversal, and portosystemic shunts.2-4
Weight loss
surgery (WLS) is an effective method to reduce body weight and decrease the risk
of NAFLD, in obese individuals. To date, little is known about flow changes in the
portal vein in response to changes in body weight because routine Doppler-ultrasound
exams are challenging, particularly in severe obesity. 4D flow MRI in patients
with high BMI is also challenging because of challenging background phase
corrections and residual streaking artifacts from fat.
The purpose of
this study was to investigate the mid- and long-term
effect of weight loss on portal venous flow rate determined by non-contrast
4D flow MRI in obese patients without known liver disease undergoing WLS.Methods
Patient
cohort: In this
ongoing, IRB-approved study, severely obese patients (BMI>35) who were
scheduled for WLS were included between 12/2020-9/2021. Patients were imaged
upon enrollment (visit 1), 1-3 days prior to surgery after a 2-week low-calorie
diet (visit 2), 2-2.5 months after the surgery (visit 3), and 5.5-6 months
after surgery (visit 4), (Fig.1).
Image
Acquisition: 4D flow MRI
was acquired at 3.0T after 12 hours of fasting using a 5-point encoded radially
undersampled trajectory (PC-VIPR)5,6 covering the upper abdomen: imaging
volume=48x48x24cm; resolution=1.25mm3 isotropic; flip=6˚; scan
time=11min; TR/TE=6.5ms/2.4ms; fat saturation; retrospective ECG and
respiratory gating. Importantly, no intravenous contrast was used.
Data
analysis: Offline CINE-reconstruction
(conjugate gradient iterative SENSE7, 14 frames) was performed including standard
corrections for Maxwell terms and gradient non-linearity. Third-order polynomial
background phase correction8 was applied using a custom MATLAB (Mathworks, Natick, MA)
tool. Streamline visualizations and measurements were obtained using EnSight
(ANSYS, Canonsburg, PA). Volumetric flow rates were measured in the portal
venous system with 3 cross sections of interest: caudal (PV1), middle (PV2),
and cranial portal vein (PV3), Fig.2a.
Statistical analysis: The mean volumetric flow rate of the portal vein was determined as the
mean from planes PV1, PV2, and PV3. We applied single-factor ANOVA to analyze
significance of flow and BMI changes over time. We fit patient-specific ordinary
least squares (OLS) regressions modeling flow and BMI as a function of time to estimate
each patient’s rate of change of the respective measures. Subsequently, we
examined the relationship between the BMI and flow rates of change
(patient-specific OLS-slopes) using Pearson’s correlation. Values are given as
mean±SD.Results
To date, 15
patients (13 female; 49.4±9.0 years), have been included in this
study. Forty-four 4D flow MRI exams were successfully conducted (Fig.2b). Six datasets
(14%) were excluded due to insufficient image quality. We analyzed N=11 4D flow
MRI datasets from visit 1, N=13 from visit 2, N=15 from visit 3, and N=5 from
visit 4, respectively. Patient BMI decreased significantly from 44.6±5.5kg/m² at visit 1 to 36.9±4.8kg/m²
at visit 3 (paired t-test, p-value≤0.001, Fig.3a).
Mean portal
flow rate at visit 1 was 1.15±0.28 L/min. Flow rate did not change
significantly over time (p-value=0.67, Fig.3b). Portal flow rate normalized by body
weight or BMI demonstrated a significant change over the course of the study
(p-value=0.03, and p-value=0.04, respectively, Fig.4). Normalized portal flow
rate increased in 10/15 subjects over the course of the study.
There was a weak
correlation between flow change and BMI change (Pearson’s r=0.46, p=0.11): Flow
decreased more in patients who lost more weight (Fig.5). This relationship did
not reach significance, possibly due to small sample size. Discussion
The mid- and long-term analysis of
absolute portal venous flow rate showed no statistically significant changes after
weight loss and WLS. Portal flow rate normalized to body
weight or BMI increased significantly.
To our knowledge, this is the first study
quantifying portal venous flow before and after WLS. 4D flow MRI is challenging
in the abdomen, particularly in obese subjects without the use of contrast
agents. This makes the rate of 86% diagnostic datasets noteworthy.
Obese
study participants presented with portal flow rates within the range of normal
reference values reported for 4D flow MRI (mean 0.93-1.1L/min, SD
0.14-0.54L/min)3,9-12. Also, normalized values were within
the range of normal as reported for ultrasound measurements (10.5±2.3ml/min/kg13, 13.5±2.9ml/min/kg14).
Three
subjects presented with a notable decrease in absolute portal flow rate after
the surgery. In contrast, the other subjects did not show relevant change between
visit 2 and 3. To date, the relevance of this observation remains unclear. We
will review the outcome of these patients after 1 year and compare with other
clinical markers such as proton density fat fraction.
The main limitation of this preliminary
analysis is the small sample size. However, this is an ongoing study with an
enrollment target of 100 subjects. We will investigate a possible correlation
of portal flow with other imaging findings and with clinical outcome.Conclusion
Abdominal non-contrast 4D flow MRI is
feasible in severely obese patients. Preliminary results show no significant
change in the mean volumetric portal venous flow rate in subjects undergoing
weight loss surgery. However, portal flow rate normalized to body
weight or BMI increased significantly.Acknowledgements
The authors wish to acknowledge the NIH
(R01 DK088925, R01 DK125783) and Pfizer Healthcare for supporting this study,
as well as GE Healthcare who provides research support to the University of Wisconsin. Dr.
Reeder is a Romnes Faculty Fellow and has received an award provided by the
University of Wisconsin-Madison Office of the Vice Chancellor for Research and
Graduate Education with funding from the Wisconsin Alumni Research Foundation.
Dr. Oechtering receives funding from the German Research Foundation (OE
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