Resonance Imaging Response Research Articles

A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: Rationale, study design, and methods

BackgroundObesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity. MethodsWe report the rationale, design, methods, and biostatistical analysis plan of a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin for weight loss (primary endpoint) in adults with obesity. Participants (aged 18–45 years) were randomly allocated (1:1) to oxytocin (four times daily over eight weeks) versus placebo. Randomization was stratified by biological sex and BMI (30 to <35, 35 to <40, ≥40 kg/m2). We investigate the efficacy, safety, and mechanisms of oxytocin administration in reducing body weight. Secondary endpoints include changes in resting energy expenditure, body composition, caloric intake, metabolic profile, and brain activation via functional magnetic resonance imaging in response to food images and during an impulse control task. Safety and tolerability (e.g., review of adverse events, vital signs, electrocardiogram, comprehensive metabolic panel) are assessed throughout the study and six weeks after treatment completion. ResultsSixty-one male and female participants aged 18–45 years were randomized (mean age 34 years, mean BMI 37 kg/m2). The study sample is diverse with 38% identifying as non-White and 20% Hispanic. ConclusionInvestigating intranasal oxytocin's efficacy, safety, and mechanisms as an anti-obesity medication will advance the search for optimal treatment strategies for obesity and its associated severe sequelae.

Myocardial changes on 3T cardiovascular magnetic resonance imaging in response to haemodialysis with fluid removal

BackgroundMapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping.MethodsThis is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2.ResultsTwenty-six participants (16 male, 65 ± 9 years) were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L (IQR 1.8, 2.5), resulting in a median weight reduction at post-dialysis scan of 1.35 kg (IQR 1.0, 1.9), with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L (IQR 0.5, 1.4). Significant reductions were observed in LV end-diastolic volume (− 25 ml, p = 0.002), LV stroke volume (− 13 ml, p = 0.007), global T1 (21 ms, p = 0.02), global T2 (− 1.2 ms, p = 0.02) following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters.ConclusionsAcute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.

The Effects of Kisspeptin on Brain Response to Food Images and Psychometric Parameters of Appetite in Healthy Men.

The hormone kisspeptin has crucial and well-characterized roles in reproduction. Emerging data from animal models also suggest that kisspeptin has important metabolic effects including modulation of food intake. However, to date there have been no studies exploring the effects of kisspeptin on brain responses to food stimuli in humans. This work aims to investigate the effects of kisspeptin administration on brain responses to visual food stimuli and psychometric parameters of appetite, in healthy men. A double-blinded, randomized, placebo-controlled, crossover study was conducted. Participants included 27 healthy, right-handed, eugonadal men (mean ± SEM: age 26.5 ± 1.1 years; body mass index 23.9 ± 0.4 kg/m2). Participants received an intravenous infusion of 1 nmol/kg/h of kisspeptin or rate-matched vehicle over 75 minutes. Measurements included change in brain activity on functional magnetic resonance imaging in response to visual food stimuli and change in psychometric parameters of appetite, during kisspeptin administration compared to vehicle. Kisspeptin administration at a bioactive dose did not affect brain responses to visual food stimuli or psychometric parameters of appetite compared to vehicle. This is the first study in humans investigating the effects of kisspeptin on brain regions regulating appetite and demonstrates that peripheral administration of kisspeptin does not alter brain responses to visual food stimuli or psychometric parameters of appetite in healthy men. These data provide key translational insights to further our understanding of the interaction between reproduction and metabolism.

Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress

BackgroundNon-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms. AimTo develop a noED animal model based on chronic mild stress and investigate brain activity changes. MethodsWe used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state. The apomorphine test and sexual behavior test were used to select male rats with ED. Rats with depression and ED were considered to have noED. Blood oxygen level-dependent–based resting-state functional magnetic resonance imaging (fMRI) studies were conducted on these rats, and the amplitude of low-frequency fluctuations and functional connectivity were analyzed to determine brain activity changes. OutcomesThe sexual behavior test and resting-state fMRI were used for outcome measures. ResultsThe induction of depression was confirmed by the sucrose consumption test. A low intromission ratio and increased mount and intromission latencies were observed in male rats with depression. No erection was observed in male rats with depression during the apomorphine test. Male rats with depression and ED were considered to have noED. The possible central pathologic mechanism shown by fMRI involved the amygdaloid body, dorsal thalamus, hypothalamus, caudate-putamen, cingulate gyrus, insular cortex, visual cortex, sensory cortex, motor cortex, and cerebellum. Similar findings have been found in humans. Clinical TranslationThe present study provided a novel noED rat model for further research on the central mechanism of noED. Strengths and LimitationsThe present study developed a novel noED rat model and analyzed brain activity changes based at fMRI. The observed brain activity alterations might not extend to humans. ConclusionThe present study developed a novel noED rat model with brain activity alterations related to sexual arousal and erection, which will be helpful for further research involving the central mechanism of noED.Chen G, Yang B, Chen J, et al. Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress. J Sex Med 2018;15:136–147.

Brain imaging demonstrates a reduced neural impact of eating in obesity.

This study investigated functional brain response differences to food in women with BMI either <25 kg/m(2) (lean) or >35 kg/m(2) (severe obesity). Thirty women, 18-65 years old, from academic medical centers participated. Baseline brain perfusion was measured with arterial spin labeling. Brain activity was measured via blood-oxygen-level-dependent functional magnetic resonance imaging in response to food cues, and appeal to cues was rated. Subjective hunger/fullness was reported pre- and post-imaging. After a standard meal, measures were repeated. When fasting, brain perfusion did not differ significantly between groups; and both groups showed significantly increased activity in the neo- and limbic cortices and midbrain compared with baseline (P < 0.05, family-wise-error whole-brain corrected). Once fed, the lean group showed significantly decreased activation in these areas, especially the limbic cortex, whereas the group with severe obesity showed no such decreases (P < 0.05, family-wise-error whole-brain corrected). After eating, appeal ratings of food decreased only in lean women. Within groups, hunger decreased (P < 0.001) and fullness increased (P < 0.001) fasted to fed. While fasting, brain response to food cues in women did not differ significantly despite BMI. After eating, brain activity quickly diminished in lean women but remained elevated in women with severe obesity. These brain activation findings confirm previous studies.

Coronary Endothelial Dysfunction in Women With Type 2 Diabetes Measured by Coronary Phase Contrast Flow Velocity Magnetic Resonance Imaging

ObjectiveThe aim of this study was to determine if differences in coronary endothelial function are observed between asymptomatic women with type 2 diabetes mellitus (DM) and control subjects using coronary...

Serum anti-Müllerian hormone and ovarian morphology assessed by magnetic resonance imaging in response to acupuncture and exercise in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial.

To investigate whether electro-acupuncture or physical exercise influence serum anti-Müllerian hormone (AMH), antral follicle count (AFC) or ovarian volume in women with polycystic ovary syndrome (PCOS). Secondary analyses of a prospective, randomized controlled clinical trial. University Hospital, Sweden. Seventy-four women with PCOS recruited from the general population. Women with PCOS were randomized to 16 weeks of electro-acupuncture (14 treatments), exercise (at least three times/week), or no intervention. Serum AMH recorded at baseline, after 16 weeks of intervention, and at follow up at 32 weeks. AFC, and ovarian volume assessed by magnetic resonance imaging at baseline and at follow up at 32 weeks. After 16 weeks of intervention, serum levels of AMH were significantly decreased in the electro-acupuncture group by 17.5% (p < 0.001), and differed from the change in the exercise group. AMH remained decreased by 15% (p = 0.004) also at follow up at 32 weeks, but did not differ from the exercise or the no intervention groups. There was a decrease by 8.5% (p = 0.015) in ovarian volume between baseline and follow up in the electro-acupuncture group, and by 11.7% (p = 0.01) in AFC in the physical exercise group. No other variables were affected. This study is the first to demonstrate that acupuncture reduces serum AMH levels and ovarian volume. Physical exercise did not influence circulating AMH or ovarian volume. Despite a within-group decrease in AFC, exercise did not lead to a between-group difference.

Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem.

During implantation of deep-brain stimulation (DBS) electrodes in the target structure, neurosurgeons and neurologists commonly observe a “microlesion effect” (MLE), which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD). Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC), to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.

Parahippocampal cortex activation during context reinstatement predicts item recollection.

Episodic memory is the binding of an event with information about the context in which that event (or item) was experienced. The context of an event may include its spatial and temporal location as well as goal-directed, conscious thoughts evoked during the event. We call this latter type of information cognitive context. The binding of items and context (BIC) theory of medial temporal lobe function proposes that the parahippocampal cortex (PHc) plays a key role in processing cognitive context. Therefore, we predicted that activity in the PHc during reactivation of a previously experienced cognitive context would be correlated with item recollection, even when the associated item and its episodic binding had not yet been retrieved. Using a novel paradigm, we measured brain activation with functional magnetic resonance imaging in response to covert reinstatement of a cognitive context, prior to presenting an item memory probe. Contexts were studied with multiple items to ensure that spontaneous item retrieval would not occur prior to the test probe. At test, contexts were reinstated for 8 s before the test probe was presented. We manipulated whether the reinstated context matched the encoding context of the test probe that followed. For such matching contexts, we found that increased PHc activation prior to the test probe predicted recollection following the test probe. If a context unrelated to the eventual test item probe was reinstated, there was no such association between PHc activation during context reinstatement and eventual memory judgments. These findings suggest that PHc activation is correlated with cognitive context retrieval.