Quantifying Brain Myelin Water Fraction in a Guinea Pig Model of Spontaneous Intrauterine Growth Restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) is an obstetrical condition where a fetus has not achieved its genetic potential. A consequence of IUGR is a decrease in brain myelin content. Myelin water imaging (MWI) has been used to assess fetal myelin water fraction (MWF) and might potentially assess myelination changes associated with IUGR. PURPOSE: To quantify and compare the MWF of non-IUGR and IUGR fetal guinea pigs (GPs) in late gestation. STUDY TYPE: Prospective animal model. ANIMAL MODEL: Dunkin-Hartley GP model of spontaneous IUGR (mean ± SD: 60 ± 1.2 days gestation; 19 IUGR, 52 control). FIELD STRENGTH/SEQUENCE: Eight spoiled gradient-recalled (SPGR) gradient echo volumes (flip angles [α]: 2°-16°), and two sets of eight balanced steady-state free precession (bSSFP) gradient echo volumes (α: 8° - 64°), at 0° and 180° phase increments, at 3.0 T. ASSESSMENT: MWF maps were generated for each fetal GP brain using multicomponent driven equilibrium single pulse observation of T1 /T2 (mcDESPOT). MWF was quantified in the fetal corpus callosum (CC), fornix (FOR), parasagittal white matter (PSW), and whole fetal brain. STATISTICAL TESTS: Linear regression was performed between five fetal IUGR markers (body volume, body-to-pregnancy volume ratio, brain-to-liver volume ratio, brain-to-placenta volume ratio, and brain-to-body volume ratio) and MWF (coefficient of determination, R2 ). A t-test with a linear mixed model compared the MWF of non-IUGR and IUGR fetal GPs (significance was determined at α < 0.05). RESULTS: The MWF of the control fetuses are (mean ± SD): 0.23 ± 0.02 (CC), 0.31 ± 0.02 (FOR), 0.28 ± 0.02 (PSW), and 0.20 ± 0.01 (whole brain). The MWF of the IUGR fetuses are (mean ± SD): 0.19 ± 0.02 (CC), 0.27 ± 0.01 (FOR), 0.24 ± 0.03 (PSW), and 0.16 ± 0.01 (whole brain). Significant differences in MWF were found between the non-IUGR and IUGR fetuses in every comparison. DATA CONCLUSION: The mean MWF of IUGR fetal GPs is significantly lower than non-IUGR fetal GPs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

T2* Mapping of Placental Oxygenation to Estimate Fetal Cortical and Subcortical Maturation.

This cohort study investigates the association between T2* mapping of placental oxygenation and cortical and subcortical fetal brain volumes in typically developing fetuses scanned longitudinally in the third trimester.

Sex- and age-based differences in fetal and early childhood hippocampus maturation: a cross-sectional and longitudinal analysis.

The hippocampus, essential for cognitive and affective processes, develops exponentially with differential trajectories seen in girls and boys, yet less is known about its development during early fetal life until early childhood. In a cross-sectional and longitudinal study, we examined the sex-, age-, and laterality-related developmental trajectories of hippocampal volumes in fetuses, infants, and toddlers associated with age. Third trimester fetuses (27-38 weeks' gestational age), newborns (0-4 weeks' postnatal age), infants (5-50 weeks' postnatal age), and toddlers (2-3 years postnatal age) were scanned with magnetic resonance imaging. A total of 133 datasets (62 female, postmenstrual age [weeks] M = 69.38, SD = 51.39, range = 27.6-195.3) were processed using semiautomatic segmentation methods. Hippocampal volumes increased exponentially during the third trimester and the first year of life, beginning to slow at approximately 2 years. Overall, boys had larger hippocampal volumes than girls. Lateralization differences were evident, with left hippocampal growth beginning to plateau sooner than the right. This period of rapid growth from the third trimester, continuing through the first year of life, may support the development of cognitive and affective function during this period.

Default mode network functional connectivity strength in utero and the association with fetal subcortical development.

The default mode network is essential for higher-order cognitive processes and is composed of an extensive network of functional and structural connections. Early in fetal life, the default mode network shows strong connectivity with other functional networks; however, the association with structural development is not well understood. In this study, resting-state functional magnetic resonance imaging and anatomical images were acquired in 30 pregnant women with singleton pregnancies. Participants completed 1 or 2 MR imaging sessions, on average 3 weeks apart (43 data sets), between 28- and 39-weeks postconceptional ages. Subcortical volumes were automatically segmented. Activation time courses from resting-state functional magnetic resonance imaging were extracted from the default mode network, medial temporal lobe network, and thalamocortical network. Generalized estimating equations were used to examine the association between functional connectivity strength between default mode network-medial temporal lobe, default mode network-thalamocortical network, and subcortical volumes, respectively. Increased functional connectivity strength in the default mode network-medial temporal lobe network was associated with smaller right hippocampal, left thalamic, and right caudate nucleus volumes, but larger volumes of the left caudate. Increased functional connectivity strength in the default mode network-thalamocortical network was associated with smaller left thalamic volumes. The strong associations seen among the default mode network functional connectivity networks and regionally specific subcortical volume development indicate the emergence of short-range connectivity in the third trimester.

Feasibility of MRI Quantification of Myelin Water Fraction in the Fetal Guinea Pig Brain.

BACKGROUND: Fetal myelination assessment is important for understanding neurodevelopment and neurodegeneration. Myelin water imaging (MWI) quantifies myelin water fraction (MWF), a validated marker for myelin content, and has been used to assess brain myelin in children and neonates. PURPOSE: To demonstrate that MWI can quantify MWF in fetal guinea pigs (GPs). STUDY TYPE: Animal model. ANIMAL MODEL: Nine pregnant, Dunkin-Hartley GPs with 31 fetuses (mean ± standard deviation = 60 ± 1.5 days gestation). FIELD STRENGTH/SEQUENCE: 3D spoiled gradient echo and balanced steady-state free precession sequences at 3.0 T. ASSESSMENT: MWF maps were reconstructed for maternal and fetal GP brains using the multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) approach. Myelin basic protein (MBP) stain provided histological validation of the MWF. Regions of interest were placed in the maternal corpus callosum (CC), maternal fornix (FOR), fetal CC, and fetal FOR in MWF maps and MBP stains. STATISTICAL TESTS: Linear regression between MWF and MBP stain intensity (SI) of all four regions (coefficient of determination, R2 ). A paired t-test compared the MWF of maternal and mean fetal CC, MBP SI of maternal and mean fetal CC, MWF of maternal and mean fetal FOR, MBP SI of maternal and mean fetal FOR. A paired t-test with a linear mixed model compared the MWF of fetal CC and fetal FOR, and MBP SI of fetal CC and fetal FOR. A  P value < 0.0083 was considered statistically significant. RESULTS: The mean MWF of the analyzed regions are as follows (mean ± standard deviation): 0.338 + 0.016 (maternal CC), 0.340 ± 0.017 (maternal FOR), 0.214 ± 0.016 (fetal CC), and 0.305 ± 0.025 (fetal FOR). MWF correlated with MBP SI in all regions (R2  = 0.81). Significant differences were found between MWF and MBP SI of maternal and fetal CC, and MWF and MBP SI of fetal CC and fetal FOR. DATA CONCLUSION: This study demonstrated the feasibility of MWI in assessing fetal brain myelin content. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 1.

Semi-automatic segmentation of the fetal brain from magnetic resonance imaging.

Background: Volumetric measurements of fetal brain maturation in the third trimester of pregnancy are key predictors of developmental outcomes. Improved understanding of fetal brain development trajectories may aid in identifying and clinically managing at-risk fetuses. Currently, fetal brain structures in magnetic resonance images (MRI) are often manually segmented, which requires both time and expertise. To facilitate the targeting and measurement of brain structures in the fetus, we compared the results of five segmentation methods applied to fetal brain MRI data to gold-standard manual tracings. Methods: Adult women with singleton pregnancies (n = 21), of whom five were scanned twice, approximately 3 weeks apart, were recruited [26 total datasets, median gestational age (GA) = 34.8, IQR = 30.9-36.6]. T2-weighted single-shot fast spin echo images of the fetal brain were acquired on 1.5T and 3T MRI scanners. Images were first combined into a single 3D anatomical volume. Next, a trained tracer manually segmented the thalamus, cerebellum, and total cerebral volumes. The manual segmentations were compared with five automatic methods of segmentation available within Advanced Normalization Tools (ANTs) and FMRIB's Linear Image Registration Tool (FLIRT) toolboxes. The manual and automatic labels were compared using Dice similarity coefficients (DSCs). The DSC values were compared using Friedman's test for repeated measures. Results: Comparing cerebellum and thalamus masks against the manually segmented masks, the median DSC values for ANTs and FLIRT were 0.72 [interquartile range (IQR) = 0.6-0.8] and 0.54 (IQR = 0.4-0.6), respectively. A Friedman's test indicated that the ANTs registration methods, primarily nonlinear methods, performed better than FLIRT (p < 0.001). Conclusion: Deformable registration methods provided the most accurate results relative to manual segmentation. Overall, this semi-automatic subcortical segmentation method provides reliable performance to segment subcortical volumes in fetal MR images. This method reduces the costs of manual segmentation, facilitating the measurement of typical and atypical fetal brain development.

Electric field calculation and peripheral nerve stimulation prediction for head and body gradient coils.

PURPOSE: To demonstrate and validate electric field (E-field) calculation and peripheral nerve stimulation (PNS) prediction methods that are accurate, computationally efficient, and that could be used to inform regulatory standards. METHODS: We describe a simplified method for calculating the spatial distribution of induced E-field over the volume of a body model given a gradient coil vector potential field. The method is easily programmed without finite element or finite difference software, allowing for straightforward and computationally efficient E-field evaluation. Using these E-field calculations and a range of body models, population-weighted PNS thresholds are determined using established methods and compared against published experimental PNS data for two head gradient coils and one body gradient coil. RESULTS: A head-gradient-appropriate chronaxie value of 669 µs was determined by meta-analysis. Prediction errors between our calculated PNS parameters and the corresponding experimentally measured values were ~5% for the body gradient and ~20% for the symmetric head gradient. Our calculated PNS parameters matched experimental measurements to within experimental uncertainty for 73% of ∆Gmin estimates and 80% of SRmin estimates. Computation time is seconds for initial E-field maps and milliseconds for E-field updates for different gradient designs, allowing for highly efficient iterative optimization of gradient designs and enabling new dimensions in PNS-optimal gradient design. CONCLUSIONS: We have developed accurate and computationally efficient methods for prospectively determining PNS limits, with specific application to head gradient coils.

In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [1-13 C]Pyruvate and Proton Density Fat Fraction in a Guinea Pig Model of Non-Alcoholic Fatty Liver Disease Development After Life-Long Western Diet Consumption.

BACKGROUND: Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. PURPOSE: To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. STUDY TYPE: Prospective. ANIMAL MODEL: Twenty-eight male guinea pigs weaned onto a control diet (N = 14) or WD (N = 14). FIELD STRENGTH/SEQUENCE: 3 T; T1-weighted gradient echo, T2-weighted spin-echo, three-dimensional gradient multi-echo fat-water separation (IDEAL-IQ), and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. ASSESSMENT: Median PDFF was calculated in the liver and hind limbs. [1-13 C]pyruvate dynamic MRS in the liver was quantified by the time-to-peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. STATISTICAL TESTS: Unpaired Student's t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. RESULTS: Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. DATA CONCLUSION: PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Long-term inter-platform reproducibility, bias, and linearity of commercial PDFF MRI methods for fat quantification: a multi-center, multi-vendor phantom study.

OBJECTIVES: Proton density fat fraction (PDFF) is a validated biomarker of tissue fat quantification. However, validation has been limited to single-center or multi-center series using non-FDA-approved software. Thus, we assess the bias, linearity, and long-term reproducibility of PDFF obtained using commercial PDFF packages from several vendors. METHODS: Over 35 months, 438 subjects and 16 volunteers from a multi-center observational trial underwent PDFF MRI measurements using a 3-T MR system from one of three different vendors or a 1.5-T system from one vendor. Fat-water phantom sets were measured as part of each subject's examination. Manual region-of-interest measurements on the %fat image, then cross-sectional bias, linearity, and long-term reproducibility were assessed. RESULTS: Three hundred ninety-two phantom measurements were evaluable (90%). Bias ranged from 2.4 to - 3.8% for the lowest to the highest weight %fat. Regression fits of PDFF against synthesis weight %fat showed negligible non-linear effects and a linear slope of 0.94 (95% confidence interval: 0.938, 0.947). We observed significant vendor (p < 0.001) and field strength (p < 0.001) differences in bias and longitudinal variability. When the results were pooled across sites, vendors, and field strengths, the estimated reproducibility coefficient was 6.93% (95% CI: 6.25%, 7.81%). CONCLUSIONS: This study demonstrated good linearity, accuracy, and reproducibility for all investigated manufacturers and field strengths. However, significant vendor-dependent and field strength-dependent bias were found. While longitudinal PDFF measurements may be made using different field strength or vendor MR systems, if the MR system is not the same, based on these results, only PDFF changes ≥ 7% can be considered a true difference. KEY POINTS: • Phantom fat fraction (PDFF) MRI measurements over 35 months demonstrated good linearity, accuracy, and reproducibility for the vendor systems investigated. • Non-linear effects were negligible (linear slope of 0.94) over 0-100% fat; however, significant vendor (p < 0.001) and field strength (p<0.001) differences in bias and longitudinal variability were identified. Bias ranged from 2.4 to - 3.8% for 0-100 weight% fat, respectively. • Measurement bias could affect the accuracy of PDFF in clinical use. As the reproducibility coefficient was 6.93%, only greater changes in % fat can be considered true differences when making longitudinal PDFF measurements on different MR systems.

Quantification of 1.5 T T1 and T2* Relaxation Times of Fetal Tissues in Uncomplicated Pregnancies.

BACKGROUND: Despite its many advantages, experience with fetal magnetic resonance imaging (MRI) is limited, as is knowledge of how fetal tissue relaxation times change with gestational age (GA). Quantification of fetal tissue relaxation times as a function of GA provides insight into tissue changes during fetal development and facilitates comparison of images across time and subjects. This, therefore, can allow the determination of biophysical tissue parameters that may have clinical utility. PURPOSE: To demonstrate the feasibility of quantifying previously unknown T1 and T2* relaxation times of fetal tissues in uncomplicated pregnancies as a function of GA at 1.5 T. STUDY TYPE: Pilot. POPULATION: Nine women with singleton, uncomplicated pregnancies (28-38 weeks GA). FIELD STRENGTH/SEQUENCE: All participants underwent two iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) acquisitions at different flip angles (6° and 20°) at 1.5 T. ASSESSMENT: Segmentations of the lungs, liver, spleen, kidneys, muscle, and adipose tissue (AT) were conducted using water-only images and proton density fat fraction maps. Driven equilibrium single pulse observation of T1 (DESPOT1 ) was used to quantify the mean water T1 of the lungs, intraabdominal organs, and muscle, and the mean water and lipid T1 of AT. IDEAL T2* maps were used to quantify the T2* values of the lungs, intraabdominal organs, and muscle. STATISTICAL TESTS: F-tests were performed to assess the T1 and T2* changes of each analyzed tissue as a function of GA. RESULTS: No tissue demonstrated a significant change in T1 as a function of GA (lungs [P = 0.89]; liver [P = 0.14]; spleen [P = 0.59]; kidneys [P = 0.97]; muscle [P = 0.22]; AT: water [P = 0.36] and lipid [P = 0.14]). Only the spleen and muscle T2* showed a significant decrease as a function of GA (lungs [P = 0.67); liver [P = 0.05]; spleen [P < 0.05]; kidneys [P = 0.70]; muscle [P < 0.05]). DATA CONCLUSION: These preliminary data suggest that the T1 of the investigated tissues is relatively stable over 28-38 weeks GA, while the T2* change in spleen and muscle decreases significantly in that period. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Water-fat magnetic resonance imaging of adipose tissue compartments in the normal third trimester fetus.

BACKGROUND: Assessment of fetal adipose tissue gives information about the future metabolic health of an individual, with evidence that the development of this tissue has regional heterogeneity. OBJECTIVE: To assess differences in the proton density fat fraction (PDFF) between fetal adipose tissue compartments in the third trimester using water-fat magnetic resonance imaging (MRI). MATERIALS AND METHODS: Water-fat MRI was performed in a 1.5-T scanner. Fetal adipose tissue was segmented into cheeks, thorax, abdomen, upper arms, forearms, thighs and lower legs. PDFF and R2* values were measured in each compartment. RESULTS: Twenty-eight women with singleton pregnancies were imaged between 28 and 38 weeks of gestation. At 30 weeks' gestation (n=22), the PDFF was statistically different between the compartments (P<0.0001), with the highest PDFF in cheeks, followed by upper arms, thorax, thighs, forearms, lower legs and abdomen. There were no statistical differences in the rate of PDFF change with gestational age between the white adipose tissue compartments (P=0.97). Perirenal brown adipose tissue had a different PDFF and R2* compared to white adipose tissue, while the rate of R2* change did not significantly change with gestational age between white adipose tissue compartments (P=0.96). CONCLUSION: Fetal adipose tissue accumulates lipids at a similar rate in all white adipose tissue compartments. PDFF variances between the compartments suggest that accumulation begins at different gestational ages, starting with cheeks, followed by extremities, trunk and abdomen. Additionally, MRI was able to detect differences in the PDFF between fetal brown adipose tissue and white adipose tissue.

Seeing the fetus from a DOHaD perspective: discussion paper from the advanced imaging techniques of DOHaD applications workshop held at the 2019 DOHaD World Congress.

Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

Adiposity, Physical Function, and Their Associations With Insulin Resistance, Inflammation, and Adipokines in CKD.

RATIONALE & OBJECTIVES: Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat, and physical function with inflammation, insulin resistance, and adipokine levels in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Participants with stages 3-5 CKD not receiving maintenance dialysis, followed up at one of 8 clinical sites in the Chronic Renal Insufficiency Cohort (CRIC) Study, and who underwent magnetic resonance imaging of the abdomen at an annual CRIC Study visit (n = 419). PREDICTORS: VAT volume, SAT volume, intrahepatic fat, body mass index, waist circumference, and time taken to complete the 400-m walk test (physical function). OUTCOMES: Markers of inflammation (interleukin 1ß [IL-1ß], IL-6, tumor necrosis factor receptor 1 [TNFR1], and TNFR2), insulin resistance (homeostasis model assessment of insulin resistance), and adipokine levels (adiponectin, total and high molecular weight, resistin, and leptin). ANALYTICAL APPROACH: Multivariable linear regression of VAT and SAT volume, intrahepatic fat, and physical function with individual markers (log-transformed values), adjusting for relevant covariates. RESULTS: Mean age of the study population was 64.3 years; 41% were women, and mean estimated glomerular filtration rate was 53.2±14.6 (SD) mL/min/1.73m2. More than 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction were associated with lower levels of total and high-molecular-weight adiponectin, higher levels of leptin and insulin resistance, and lower high-density lipoprotein cholesterol and higher serum triglyceride levels. A slower 400-m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6, and TNFR1 and did not modify the associations between fat measures and cardiometabolic risk factors. LIMITATIONS: Lack of longitudinal data and dietary details. CONCLUSIONS: Various measures of adiposity are associated with cardiometabolic risk factors. Physical function was also associated with the cardiometabolic risk factors studied and does not modify associations between fat measures and cardiometabolic risk factors. Longitudinal studies of the relationship between body fat and aerobic fitness with cardiovascular and kidney disease progression are warranted.

The application of in utero magnetic resonance imaging in the study of the metabolic and cardiovascular consequences of the developmental origins of health and disease.

Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta's transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD.

Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability. METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT. RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT. DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.

Optimizing SNR for multi-metabolite hyperpolarized carbon-13 MRI using a hybrid flip-angle scheme.

PURPOSE: To improve the SNR of hyperpolarized carbon-13 MRI of [1-13 C]pyruvate using a multispectral variable flip angle (msVFA) scheme in which the spectral profile and flip angle vary dynamically with time. METHODS: Each image acquisition in a time-resolved imaging experiment used a unique spectrally varying RF pulse shape for msVFA. Therefore, the flip angle for every acquisition was optimized for pyruvate and each of its metabolites to yield the highest SNR across the acquisition. Multispectral VFA was compared with a spectrally varying constant flip-angle excitation model through simulations and in vivo. A modified broadband chemical shift-encoded gradient-echo sequence was used for in vivo experiments on six pregnant guinea pigs. Regions of interest placed in the placentae, maternal liver, and maternal kidneys were used as areas for SNR measurement. RESULTS: In vivo experiments showed significant increases in SNR for msVFA relative to constant flip angle of up to 250% for multiple metabolites. CONCLUSION: Hyperpolarized carbon-13 imaging with msVFA excitation produces improved SNR for all metabolites in organs of interest.

Fetal Response to a Maternal Internal Auditory Stimulus.

BACKGROUND: Functional MRI (fMRI) is a noninvasive method to investigate the neural correlates of brain development. Insight into the rapidly developing brain in utero is limited, and fetal fMRI can be used to gain a greater understanding of the developmental process. Fetal brain fMRI is typically limited to resting-state fMRI due to the difficulty to instruct or provide a stimulus to the fetus. Previous studies have employed auditory task fMRI with an external sound stimulus directly on the abdomen of the mother; however, this practice has since been deemed unsafe for the developing fetus. PURPOSE: To investigate a reliable and safe paradigm to study the development of fetal brain networks, we postulated that an internal task, such as the mother's singing, as the auditory stimulus would result in activation in the fetal primary auditory cortex. STUDY TYPE: Cohort. POPULATION: Pregnant women with singleton pregnancies (n = 9; 33-38 weeks gestational age). FIELD STRENGTH/SEQUENCE: All subjects underwent two task-based block design blood oxygen level-dependent (BOLD) at 1.5T or 3T. ASSESSMENT: Each volume was assessed for fetal motion and manually reoriented and realigned to correct for fetal motion. Once the motion was corrected, a gestational age-matched parcellated atlas with regions of interest overlaid onto the activation map was used to determine which regions in the brain had activation during task phases. STATISTICAL TESTS: First Level Analysis. MRI data were analyzed using SPM 12 as a task fMRI. RESULTS: Eight subjects had activation on the right Heschl's gyrus; six fetuses demonstrated activation on the left when exposed to the internal acoustic stimulus. Additionally, activation was found on the right and left middle cingulate cortex (MCC) and the left putamen. DATA CONCLUSION: Maternal singing can be used as an internal stimulus to activate the auditory network and Heschl's gyrus during fetal fMRI. Level of Evidence 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2020;52:139-145.

Measuring fetal adipose tissue using 3D water-fat magnetic resonance imaging: a feasibility study.

Purpose: Analysis of fetal adipose tissue volumes may provide useful insight towards assessment of overall fetal health, especially in cases with abnormal fetal growth. Here, we assess whether fetal adipose tissue volume can be reliably measured using 3D water-fat MRI, using a quantitative assessment of the lipid content of tissues.Materials and methods: Seventeen women with singleton pregnancies underwent a fetal MRI and water-only and fat-only images were acquired (modified 2-point Dixon technique). Water and fat images were used to generate a fat signal fraction (fat/(water + fat)) from which subcutaneous adipose tissue was segmented along the fetal trunk. Inter-rater (three readers) and intrarater reliability was assessed using intraclass-correlation coefficients (ICC) for 10 image sets. Relationships between adipose tissue measurements and gestational age and estimated fetal weight percentiles were examined.Results: The ICC of the inter-rater reliability was 0.936 (p < .001), and the ICC of the intrarater reliability was 0.992 (p < .001). Strong positive correlations were found between adipose tissue measurements (lipid volume, lipid volume/total fetal volume, mean fat signal fraction) and gestational age.Conclusions: 3D water-fat MRI can reliably measure volume and quantify lipid content of fetal subcutaneous adipose tissues.

Magnetic resonance imaging of obesity and metabolic disorders: Summary from the 2019 ISMRM Workshop.

More than 100 attendees from Australia, Austria, Belgium, Canada, China, Germany, Hong Kong, Indonesia, Japan, Malaysia, the Netherlands, the Philippines, Republic of Korea, Singapore, Sweden, Switzerland, the United Kingdom, and the United States convened in Singapore for the 2019 ISMRM-sponsored workshop on MRI of Obesity and Metabolic Disorders. The scientific program brought together a multidisciplinary group of researchers, trainees, and clinicians and included sessions in diabetes and insulin resistance; an update on recent advances in water-fat MRI acquisition and reconstruction methods; with applications in skeletal muscle, bone marrow, and adipose tissue quantification; a summary of recent findings in brown adipose tissue; new developments in imaging fat in the fetus, placenta, and neonates; the utility of liver elastography in obesity studies; and the emerging role of radiomics in population-based "big data" studies. The workshop featured keynote presentations on nutrition, epidemiology, genetics, and exercise physiology. Forty-four proffered scientific abstracts were also presented, covering the topics of brown adipose tissue, quantitative liver analysis from multiparametric data, disease prevalence and population health, technical and methodological developments in data acquisition and reconstruction, newfound applications of machine learning and neural networks, standardization of proton density fat fraction measurements, and X-nuclei applications. The purpose of this article is to summarize the scientific highlights from the workshop and identify future directions of work.

Thermoneutral temperature reduces liver volume but increases fat content in a mammalian hibernator.

Hibernators survive challenging winters by entering torpor, which lowers body temperature (Tb) to ∼5 °C for 12-14 days, followed by spontaneous arousals where Tb increases to ∼37 °C for 10-12 h before entering another torpor bout. This Tb cycle is accompanied by significant fluctuations in metabolic rate. Little is known about the role of the liver in lipid metabolism during hibernation. In this study we measured the effect of ambient temperature on liver volume and lipid content in 13-lined ground squirrels (Ictidomys tridecemlineatus). We housed animals at thermoneutral (25 °C) or cold (5 °C) ambient temperatures, with the same photoperiod (12 h light:12 h dark) for an entire year. We determined volume and water-fat ratio of the liver using magnetic resonance imaging (MRI). Ambient temperature significantly affected both liver volume and fat content. From October to August squirrels housed at 25 °C had 25% smaller livers compared to the squirrels housed at 5 °C, but their average lipid content (13.3%) was 37% higher. Because the squirrels housed at 25 °C appeared to continue feeding throughout the winter but did not enter extended torpor, more carbohydrates may have been diverted to lipid stores. By contrast, animals housed at 5 °C did not appear to feed, and carbohydrates would likely be preferentially stored in the liver as glycogen to supply glucose for brain metabolism. These results suggest that the fat burden caused by hibernators preparing for winter can lead to symptoms of metabolic syndrome, but that these symptoms are reversible in the spring.