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. Author manuscript; available in PMC: 2017 May 1.
Published in final edited form as: Obesity (Silver Spring). 2016 May;24(5):1054–1060. doi: 10.1002/oby.21464

Changes in neural responsivity to highly-palatable foods following Roux-en-Y gastric bypass, sleeve gastrectomy, or weight stability: An fMRI study

Lucy F Faulconbridge 1,*, Kosha Ruparel 2, James Loughead 2, Kelly C Allison 1, Louise A Hesson 1, Anthony N Fabricatore 1, Amber Rochette 1, Scott Ritter 1, Ryan D Hopson 2, David B Sarwer 1, Noel N Williams 3, Allan Geliebter 4, Ruben C Gur 2, Thomas A Wadden 1
PMCID: PMC4866595  NIHMSID: NIHMS784067  PMID: 27112067

Abstract

Objective

This prospective, observational fMRI study examined changes over time in blood oxygenation level dependent (BOLD) response to high- and low-calorie foods in obese bariatric surgery candidates and weight-stable controls.

Methods

Twenty-two Roux-en-Y gastric bypass (RYGB) participants, 18 vertical sleeve gastrectomy (VSG) participants and 19 weight-stable controls with severe obesity underwent fMRI before and 6 months after surgery/baseline. BOLD signal change in response to images of high-calorie foods (HCF) vs. low-calorie foods (LCF) was examined in a priori regions of interest.

Results

RYGB and VSG participants lost 23.6 and 21.1% of initial weight, respectively, at 6 months and controls gained 1.0%. Liking ratings for HCF decreased significantly in the RYGB and VSG groups but remained stable in the control group. BOLD response in the ventral tegmental area (VTA) to HCF (vs. LCF) declined significantly more at 6 months in RYGB compared to control participants but not in VSG participants. Changes in fasting ghrelin correlated positively with changes in VTA BOLD signal in both RYGB and VSG but not in control participants.

Conclusions

Results implicate the VTA as a critical site for modulating post-surgical changes in liking of highly palatable foods and suggest ghrelin as a potential substrate requiring further investigation.

INTRODUCTION

Bariatric surgery is currently the most effective treatment for severe obesity, typically yielding sustained weight losses of 25 to 35% of initial weight (1,2). Following surgery, patients report marked reductions in hunger and decreased preferences for highly palatable foods (3). Researchers have explored both peripheral (4) and central (5,6) mechanisms for these changes but the exact substrates remain elusive.

Post-operative reductions in preferences for palatable foods are likely mediated by neural networks that control both homeostatic (hypothalamus and brainstem) and hedonic eating (ventral tegmental area [VTA], nucleus accumbens, orbitofrontal cortex, prefrontal cortex, and limbic nuclei). The mesolimbic dopamine pathway, which processes hedonic aspects of both food and non-food rewards, is likely a key contributor. Several research groups (7–10) have shown differences in response to food cues in this pathway in the brains of obese as compared with non-obese individuals. Bariatric surgery may correct these alterations in mesolimbic pathways (and other neural areas) through hormonal and/or neural mechanisms.

Few functional magnetic resonance imaging (fMRI) studies have addressed neural changes after bariatric surgery. Ochner et al. (5) reported pre- to post-operative reductions in brain response to highly palatable food cues in the VTA, striatum, putamen, and posterior cingulate. A second study by Ochner et al. (11) compared neural responsivity to the same cues in the fed and fasted state, pre- and post Roux-en-Y gastric bypass surgery (RYGB), but was underpowered (n=5) to exhibit a broad range of changes. . Both these within-subjects studies were limited by the lack of a control group, an alternative surgery group, small samples, and short follow-up periods (e.g., 1 month). Studies by Scholtz et al. (6) and Frank et al. (12) were retrospective and cross-sectional with no pre-surgical assessments, making it impossible to draw conclusions about surgically-induced changes in brain activity.

The present prospective observational study addressed these limitations by comparing neural response to pictures of high- and low-calorie foods, before and 6 months after surgery, in three groups of individuals with severe obesity: 1) RYGB (n=23); 2) vertical sleeve gastrectomy (VSG; n=19); and 3) non-surgical weight-stable control participants (n=21) matched to surgery participants for baseline age and body mass index (BMI). Our primary hypothesis was that RYGB and VSG participants would show shower greater reductions in blood oxygen level dependent (BOLD) responses to high-calorie food (HCF) vs. low-calorie food (LCF) images, compared to controls, in selected regions of interest (ROIs), which included mesocorticolimbic areas. Secondary analyses examined the correlation between changes over time in BOLD response to HCF, relative to LCF, and changes in fasting ghrelin.

METHODS

Participants

Eligibility criteria included female gender, age ≥ 18 years, a BMI ≥ 40 kg/m2 (or ≤ 35 kg/m2 in the presence of significant medical co-morbidities), and a willingness to undergo MRI procedures. Exclusion criteria were: a weight >159 kg or supine abdominal width > 70 cm (MRI scanner limits); pregnancy or lactation; type 1 or type 2 diabetes (given the profound effects of bariatric surgery on diabetes); evidence of a significant psychiatric disorder that interfered with daily living; any illegal substance abuse (within the past year); current use of nicotine or any illicit drugs; metallic inserts (including pacemaker); claustrophobia; the use of weight-loss medications or any agents known to affect weight or glucose metabolism; and lack of ability to provide informed consent. A total of 63 participants were enrolled in the study, with four excluded due to poor image quality (mean relative motion > 0.5 or temporal signal to noise ratio >3 SD), yielding a final sample of 22 RYGB, 18 VSG, and 19 control participants. The study was approved by the University of Pennsylvania’s Institutional Review Board (Clinical Trials registration number: NCT01228097).

Surgery participants were recruited from the Bariatric Surgery Program at the University of Pennsylvania Health System. In consultation with their surgeon, participants elected to undergo either RYGB or VSG. Surgeons referred participants to the study in consecutive order, and a nurse practitioner reviewed participants’ medical history and most recent physical exam to confirm eligibility. The great majority of surgeries (i.e., both types) were performed by NNW, following methods described previously (13). Surgery participants received 3–6 sessions of weight management in the 3 months prior to surgery, as required by most insurers, but none were provided intensive nutritional (or psychological) counseling in the 6 months following surgery.

Control participants, not seeking weight reduction, were recruited from advertisements in the local media for a study of “how the brain responds to food.” These individuals agreed not to pursue weight loss for the duration of the study, with a goal to remain within 5% of their baseline weight. All control participants completed the same study screening procedures as surgery participants.

Outcomes and Assessments

Participants were assessed within 4 weeks prior to their surgery date (baseline) and at 6 months ± 2 weeks after surgery. Weight-stable controls were assessed at baseline and at 6 months ± 2 weeks later. On scan days, following an overnight fast, participants completed a urine pregnancy and drug screening test, were weighed in a hospital gown on a calibrated scale (BWB 800S, Tanita Corp, Japan), and practiced the fMRI task. Just prior to imaging, blood was drawn from the forearm vein for measurement of ghrelin. Protease inhibitor cocktail (Sigma-Aldrich, St. Louis, MO), with dipeptidyl peptidase-4 inhibitor (Millipore, Billerica, MA) and pefabloc (Roche, Indianapolis, IN), was immediately added, and the samples were centrifuged at 4°C, separated, and frozen at −80°C. Ghrelin assays were measured in duplicate by double-antibody radioimmunoassays (Millipore) at the Penn Diabetes Research Center.

Neuroimaging

fMRI was acquired with a Siemens Trio 3T (Erlangen, Germany) system with 32 channel head coil using the following parameters: TR/TE = 3000/32 ms, FOV = 220 mm, matrix = 64 × 64, slice thickness/gap = 3.0/0 mm, 46 slices. Time series data were analyzed with standard procedures in FSL (FMRIB’s Software Library, Oxford, UK). Image preprocessing included skull stripping, slice time correction, motion correction, high pass filtering (100 s), smoothing (6 mm full-width at half-maximum, isotropic) and mean-based intensity normalization. The participant’s median functional volume was coregistered to her T1 weighted image and transformed into a standard anatomical space (T1 MNI template). Transformation parameters were later applied to statistical maps. Time-series analysis was carried out using general linear model as implemented in FSL. HCF and LCF blocks were modeled separately using a canonical hemodynamic response function with rest condition treated as baseline. Contrast maps for each condition were generated, and percent signal change was calculated. A priori regions of interest (ROIs) included: VTA; nucleus accumbens (NAcc); amygdala; hippocampus; prefrontal cortex (PFC); anterior cingulate cortex (ACC); orbitofrontal cortex (OFC); insula; thalamus; and hypothalamus. These regions were defined using the Harvard-Oxford Atlas except for the VTA and hypothalamus, which were defined by drawing a 2.5 mm radius sphere around x=0,y=−16,z=−8 (14) and x=0,y=−3,z=−6 (15) respectively. (VTA and hypothalamus are not defined in most atlases available for neuroimaging fMRI analysis.) Mean percent signal change for a priori ROIs was exported for graphic presentation and statistical analysis.

fMRI task

The food images task was composed of five HCF and five LCF blocks (30 second duration) presented in pseudorandom order. Each block contained five photographs of food (5 seconds) separated by 1-second inter-stimulus interval (fixation point). Food blocks were followed by a 30-second rest period. Following fMRI, participants rated the palatability of food images (i.e., “How much do you like this food?”), using an 11-point Likert scale with anchors at “not at all” and “very much.”

Statistical Analyses

Changes in percent BOLD signal were assessed by repeated measures group (RYGB, VSG, control) by time (baseline, 6 months) by stimulus class (high-calorie, low-calorie) mixed effects ANOVA. Principal planned contrasts included RYGB vs. controls and VSG vs. controls, with RYGB vs. VSG as secondary contrasts. With each ROI, Holm’s procedure was used to adjust for multiple comparisons and to identify significant differences in at least one of the two between-group comparisons at P≤0.025 (16). Analyses of secondary outcomes were conducted using P≤0.05. Spearman’s rho correlation coefficient was used to assess the relationship between ghrelin and BOLD response.

RESULTS

Baseline demographics for participants are presented in Table 1. Participants had a mean weight of 117.9±13.0 kg, BMI of 44.0±4.2 kg/m2, and age of 37.9±8.8 years. Fifty-nine per cent of participants were African American, 35.6% were Caucasian. A significantly (P<0.05) greater proportion of participants in the control and VSG groups was African American as compared to the RYGB group (78.9%, 66.7%, and 36.4%, respectively). There were no other statistically significant differences between groups.

Table 1.

Baseline characteristics

Total (n=59) Controls (n=19) RYGB (n=22) Sleeve (n=18) p value
Weight (kg) (M ± SD) 117.9 ± 13.0 116.0 ± 14.8 118.9 ± 12.6 118.6 ± 12.0 0.749 F = 0.29
BMI (kg/m2) (M ± SD) 44.0 ± 4.2 43.3 ± 4.4 44.6 ± 4.3 43.9 ± 4.1 0.643 F = 0.445
Age (M ± SD) 37.9 ± 8.8 36.4 ± 8.2 37.2 ± 9.3 40.3 ± 8.9 0.377 F = 0.992
Mean liking HCF (M ± SD) 8.1 ± 1.4 8.0 ± 1.8 7.9 ± 1.3 8.3 ± 0.8 0.493 F = 0.614
Mean liking LCF (M ± SD) 7.2 ± 1.5 6.8 ± 1.8 7.2 ± 1.4 7.5 ± 1.3 0.971 F = 0.385
Ethnicity (n, %)
 Hispanic 1 (1.7%) 1 (5.3%) 0 (0.0%) 0 (0.0%) 0.627 x2 = 2.14
 Not Hispanic 58 (98.3%) 18 (94.7%) 22 (100.0%) 18 (100.0%)
Race (n, %)
 White 21 (35.6%) 3 (15.8%) 14 (63.6%) 4 (22.2%)
 Black 35 (59.3%) 15 (78.9%) 8 (36.4%) 12 (66.7%)
 Asian 1 (1.7%) 1 (5.3%) 0 (0.0%) 0 (0.0%)
 American Indian or Alaskan Native 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0.001 x2 = 17.87
 Pacific Islander or Native Hawaiian 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
 More than one race 2 (3.4%) 0 (0.0%) 0 (0.0%) 2 (11.1%)
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Body Weight

At month 6, RYGB and VSG participants lost 23.6±1.4 and 21.3±1.0% of initial weight, respectively, while the control group gained 1.0±0.6% (Figure 1). Weight changes in both surgically-treated groups differed significantly (both Ps<0.001) from those of the controls but not from each other.

Figure 1.

Figure 1

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Mean (±SEM) change in weight (kg) over time (baseline to 6 months). “RYGB” = Roux-en-Y gastric bypass participants; “Sleeve” = vertical sleeve gastrectomy participants.

Liking Scores of High- vs. Low-Calorie Foods

At baseline, liking of HCF was significantly higher (P=0.0007) than liking of LCF across participants in all three groups. There were no significant differences between treatment groups.

Post-operative changes in liking scores

At month 6, RYGB and VSG participants reported significant reductions from baseline in liking of HCF (both Ps<0.02), but control participants showed no change in their liking of HCF (Figure 2a). Controlling for baseline values, RYGB participants showed a significantly greater reduction in their liking of HCF at 6 months than controls (p=0.017), with no other differences between groups. No groups reported any significant changes in liking of LCF over time (Figure 2b).

Figure 2.

Figure 2

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Figure 2a. Mean (±SEM) change in liking of high-calorie foods over time.

Figure 2b. Mean (±SEM) change in liking of low-calorie foods over time. “RYGB” = Roux-en-Y gastric bypass participants; “Sleeve” = vertical sleeve gastrectomy participants.

At month 6, the difference in how much participants liked HCF relative to LCF (i.e., HCF minus LCF) decreased in both surgery groups (both Ps<0.007), but not in the control group. This decrease in liking of HCF relative to LCF was significantly (P=0.011) greater in the RYGB compared to the control group, with no other differences between groups.

BOLD Response to High- vs. Low-Calorie Foods

Across all participants (n=63) at baseline, viewing HCF induced significantly greater BOLD activation than viewing LCF in several ROIs, including the VTA, NAcc, OFC, ACC, amygdala, and thalamus (all Ps<0.05; see Figure 3). No differences were observed in activation in response to HCF vs. LCF in the PFC, insula, hippocampus, and hypothalamus. At baseline, no significant differences were observed between groups in the greater BOLD response to high- vs. low-calorie foods in any of the brain regions examined.

Figure 3.

Figure 3

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Mean (±SEM) BOLD responses to high-calorie and low-calorie foods at baseline in selected regions of interest (ventral tegmental area [VTA], nucleus accumbens [Nacc], orbitofrontal cortex [OFC], amygdala [Amyg.], anterior cingulate cortex [ACC], insula [Ins.], hippocampus [Hipp.], thalamus [Thal.], prefrontal cortex [PFC], hypothalamus [Hypothal.])

Post-Operative BOLD response

In the VTA, the difference in the BOLD response to HCF relative to LCF (i.e., HCF minus LCF) declined significantly from baseline to 6 months in RYGB compared to control participants (Figure 4). This effect was driven by a post-operative decrease in VTA BOLD response to HCF (p<0.002) and increase in VTA BOLD response to LCF (p<0.005) in the RYGB group, with no change (at 6 months) in response to HCF or LCF in the control group (Figures 5a and 5b). The HCF vs. LCF difference in BOLD response within the VTA also decreased in VSG participants, but the change was not significantly different from baseline or from that observed in control participants. In examining the study’s other nine ROIs, no additional significant differences were observed between groups in changes in BOLD activation to HCF relative to LCF from baseline to month 6.

Figure 4.

Figure 4

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Upper panel: Representative slice showing activation in the ventral tegmental area

Lower panel: Mean (± SEM) change in VTA BOLD response to high-calorie foods compared to low-calorie foods at baseline and 6 months. “RYGB” = Roux-en-Y gastric bypass participants; “Sleeve” = vertical sleeve gastrectomy participants.

Figure 5.

Figure 5

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Figure 5a. Mean (± SEM) changes in VTA BOLD response to high-calorie foods. “RYGB” = Roux-en-Y gastric bypass participants; “Sleeve” = vertical sleeve gastrectomy participants.

Figure 5b. Mean (± SEM) changes in VTA BOLD response to low-calorie foods. “RYGB” = Roux-en-Y gastric bypass participants; “Sleeve” = vertical sleeve gastrectomy participants.

Relationship between Changes in Fasting Ghrelin and VTA BOLD Response

At month 6, mean ghrelin levels, measured in the fasting state, increased by 11.0±6.8 pg/ml in the control group, were essentially unchanged in the RYGB group (+1.50±12.1 pg/ml) and decreased significantly (P<0.007) in the VSG group (−32.6±12.5 pg/ml). Changes in ghrelin correlated positively with the change in BOLD activation in response to HCF, relative to LCF, over time in the VTA in both the RYGB (r=0.42, P<0.05) and VSG groups (r=0.68, P <0.01) (Figure 6a and 6b). No such correlation was observed in the control group (r=0.07, NS; Figure 6c). There was no significant relationship between the change in the liking of HCF relative to LCF and the change in VTA BOLD signal in response to the HCF-LCF contrast in any of the three groups, or in the cohort as a whole (data not shown).

Figure 6.

Figure 6

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Correlations between changes in fasting ghrelin levels (pg/ml) and changes in VTA BOLD response to high-calorie foods minus low-calories foods over time in RYGB (6a), VSG

(6b) and control (6c) participants. “RYGB” = Roux-en-Y gastric bypass participants; “Sleeve” = vertical sleeve gastrectomy participants.

DISCUSSION

Determining how the brain changes following bariatric surgery remains a key research area. This is the first controlled prospective study to evaluate concurrent changes in 1) neural activation in response to images of high- compared to low-calorie foods, 2) liking of those same foods, and 3) fasting ghrelin levels, after bariatric surgery. The present results confirm prior reports of decreased liking of highly palatable foods (17), following surgery, and reveal no change in liking of low palatable foods. Our findings also support prior suggestions (5) that neural processing in the VTA, a central site of reward processing, is altered in response to high-calorie food cues after bariatric surgery. The present results extend those findings by revealing the absence of such neural changes in weight-stable obese controls, and suggest a role for ghrelin as one of several peripheral substrates that may mediate changes in neural function following surgery.

As expected, both RYGB and VSG participants lost significant amounts of weight 6 months after surgery (~23% of initial weight), whereas the control group remained weight stable (~0.1%). Previous studies have reported decreased preferences for highly-palatable foods following surgery (17,18), in contrast to what is observed when weight loss is achieved by non-surgical methods (19). We confirmed the decreased liking (from baseline) of high-calorie foods following RYGB and VSG, compared to a slight increase in liking of HCF in weight-stable obese controls. In contrast, no changes in liking of low-calories foods were observed in any of the treatment groups, indicating a specific reduction in liking of highly palatable foods after bariatric surgery.

The differential changes in liking of high- vs. low-calorie food cues were accompanied by similar changes in BOLD activation to food images in the VTA, although we did not find significant correlations between changes in these variables. While prior to surgery the difference in VTA BOLD response to HCF, compared to LCF, was significant in all three groups, after surgery the difference in BOLD response to HCF relative to LCF decreased significantly more in RYGB participants than in controls. A similar reduction was observed in the VSG group, although it did not reach significance, as compared with controls. No such decrease in BOLD response to HCF relative to LCF was observed in the control group. Thus, after surgery, the VTA showed similar activation to images of high and low-calorie foods, whereas prior to surgery it responded more to HCF than to LCF images. Further study of the relationship between changes in liking of foods and changes in BOLD activation and other sites is needed in postsurgical patients.

Inclusion in this study of a non-surgical weight loss group would have enabled us to conclude definitively that the observed changes in VTA BOLD activation were a function of RYGB, and not of weight loss per se. This will be an important addition for future studies. A recent fMRI study that examined BOLD responses to food cues before and after a 12-week behavioral weight loss program showed reductions in BOLD activation to HCF in the medial prefrontal cortex only, suggesting that VTA activity was not altered by diet and exercise (18). Further research in this area is needed to identify the effects on neural function of weight loss induced by surgical vs. nonsurgical methods

The observed post-surgical reductions in both preference for highly palatable foods and in neural response to high-calorie food images is striking in the face of significant weight loss achieved by RYGB participants. Reductions in liking of (or interest in) highly palatable foods are not typically observed in individuals who lose weight by dieting (i.e., caloric restriction) (19). As participants lose weight by caloric restriction alone, levels of leptin (a satiating hormone) decline, and levels of ghrelin (a meal-initiating signal) rise, together resulting in the experience of increased hunger (21,22). (These changes in appetitive hormones likely contribute to the challenge of maintaining weight lost by nonsurgical means.) In contrast, circulating ghrelin levels decline significantly following VSG surgery (23). There are mixed reports for RYGB participants, with some studies showing clear reductions in ghrelin and others failing to find this effect (for review see reference 24).

At month 6, we observed a significant mean reduction in ghrelin in the VSG group (−32.6 pg/ml), negligible mean change in RYGB participants, and a slight increase in the control group (+11 pg/ml). Despite the lack of mean change in ghrelin in the RYGB group, for both surgery groups there were significant positive correlations between changes in fasting ghrelin levels at month 6 and changes in VTA BOLD response to high- vs. low-calorie foods. No such correlation was observed in the control group. These results raise the possibility that ghrelin may be one of several potential mediators of the decrease in neural response to HCF in patients who undergo bariatric surgery.

A potential role for ghrelin in the mediation of the rewarding properties of food in the VTA following bariatric surgery has considerable empirical support. First, ghrelin receptor mRNA is present in the VTA of rats and humans (25). Second, ghrelin administration directly to the VTA increases consumption of non-food reward reinforcers such as alcohol, while peripheral administration of ghrelin antagonists suppresses reward-relevant responding for alcohol (26). Moreover, ghrelin administration seems to increase cocaine and amphetamine-induced behaviors (27). As such, we hypothesize that post-surgical changes in circulating ghrelin levels may be involved in the altered hedonic response to food cues, and may correlate with the changes in neural activation to high-calorie food images observed in the VTA following surgery. The relationship between ghrelin and these changes is not a simple one, however, given that VSG surgery is equally effective in inducing weight loss in ghrelin-deficient mice as in intact mice, indicating that ghrelin signaling is not required for the effects of VSG surgery (28). This evidence notwithstanding, it is possible that when ghrelin is available, bariatric surgery produces alterations in ghrelin signaling which can have downstream neural and behavioral effects.

We observed significant changes in BOLD response in the VTA only, and not in the other regions relevant to reward processing (e.g., the nucleus accumbens) or to energy homeostasis (e.g., the hypothalamus). The absence of the anticipated findings is difficult to explain, given that the brain likely works in distributed circuits, employing multiple brain regions for any behavioral effect. When examining the surgery groups only, we did observe significant postoperative changes in other brain regions (such as the hippocampus; data not shown), but these effects also were seen in the control group, casting doubt on the significance of such changes. This highlights the importance of including control groups in neuroimaging studies of this kind. Ochner at al. (5) reported significant reductions in post-RYGB BOLD response in the striatum, putamen, and posterior cingulate, as well as the VTA. The potential discrepancy between our results and those of Ochner et al. may be explained by their use of both auditory and visual food cues to stimulate BOLD response, whereas our study used only visual images. A second possible factor is that our participants were scanned in a fasted state, whereas participants in Ochner’s study underwent fMRI approximately 1 hour following consumption of a meal. However, we would expect to observe greater responses in the fasting state, given the possibility of higher sensitivity to food cues in the hungry state.

Strengths of the present study include the prospective design, the large sample size (n=63), inclusion of a weight-stable control group, and the relatively long follow-up period (6 months), compared with prior studies. In addition, we provide data potentially linking behavioral, endocrine, and neural phenomena in humans, thereby contributing to the understanding of the array of changes following bariatric surgery.

Study Importance Questions.

What is already known about this subject?

  • Bariatric surgery yields large, sustainable weight losses, but the mechanisms underlying these changes are poorly understood.

  • Studies examining neural changes after bariatric surgery have implicated brain regions encoding the reward value of food, including the mesolimbic pathway.

  • Prior studies, however, have included very small sample sizes, been limited by short follow-up periods (as little as 1 month) and have failed to include participants receiving vertical sleeve gastrectomy (VSG) and/or appropriate control groups.

What does this study add?

This study provides:

  • a longer follow-up period (6 months), a large sample (n=63) and a control group (obese, weight-stable controls)

  • a prospective, observational design

  • an assessment of concurrent changes in peripheral hormones and preferences of highly palatable foods

Acknowledgments

Grant Numbers: R01-DK085615 (TAW & RCG); K23-HL109235 (LF); R01-DK080153 (AG)

We acknowledge the help of: research coordinators Christina Hopkins, BA, Alyssa Minnick, MA and Emily Phillips, BA; the MRI acquisition team at the University of Pennsylvania including Nick DeLeo, BA, Jeffrey Valdez, MS, Sean Gallagher, MS and Elliott Yodh, BA; and Warren Bilker, Ph.D., Jesse Chittams, M.S., and Therese Sammacco, BA for statistical analysis.

Footnotes

Disclosure: The authors declare no conflict of interest

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