Liver fat response to two days fasting and two days isocaloric high-carbohydrate refeeding in lean and obese women.

BACKGROUND AND AIMS: Prolonged fasting, which leads to the mobilization of fat from adipose tissue, can result in the development of hepatosteatosis. However, it is not yet known whether the accumulation of fat in the liver after fasting can be affected by concurrent obesity. Therefore, this study aimed to assess how excessive adiposity influences changes in liver fat content induced by fasting and subsequent refeeding. METHODS AND RESULTS: Ten lean women and eleven women with obesity (age: 36.4 ± 7.9 and 34.5 ± 7.9 years, BMI: 21.4 ± 1.7 and 34.5 ± 4.8 kg/m2) underwent a 60-h fasting period followed by 2 days of isocaloric high-carbohydrate refeeding. Magnetic resonance spectroscopy (MRS) examinations of liver were conducted at baseline, after 48 h of fasting, and at the end of refeeding period. Hepatic fat content (HFC) increased in lean women after fasting, whereas no statistically significant change in HFC was observed in women with obesity. Additionally, fasting led to significant reductions in liver volume in both groups, likely attributable to glycogen depletion, with subsequent restoration upon refeeding. Notably, changes in hepatic fat volume (HFV) rather than HFC inversely correlated with baseline liver fat content and HOMA-IR. CONCLUSION: We demonstrated that prolonged fasting results in accumulation of fat in the liver in lean subjects only and that this accumulation is inversely related to baseline fat content and insulin resistance. Moreover, the study underscored the importance of evaluating hepatic fat volume rather than hepatic fat content in studies that involve considerable changes in hepatic lean volume.

Semaglutide Treatment Effects on Liver Fat Content in Obese Subjects with Metabolic-Associated Steatotic Liver Disease (MASLD).

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) represents a major clinical complication of obesity. Methods: In this study, we used magnetic resonance (MR) methods to determine the effect of obesity treatment with semaglutide, a GLP-1 receptor agonist, on the liver fat content and selected metabolic variables. We investigated whether treatment would affect the acute response of liver fat to glucose and fructose administration and whether it would affect the fatty acid profile of VLDL-triglycerides. Sixteen obese non-diabetic men underwent a 16-week dietary intervention and 16-week treatment with subcutaneous semaglutide in a crossover design without a washout period. The order of the interventions was randomized. Results: After treatment, body weight of the subjects decreased by 5% and liver fat by a third, whereas dietary intervention had no impact on these parameters. The decrease in liver fat with semaglutide did not correlate with changes in body weight and other measures of adiposity and was unrelated to improved insulin sensitivity. Conclusions: The proportion of palmitic and palmitoleic acids in VLDL-triglycerides decreased after treatment, suggesting that the beneficial effects of semaglutide on liver fat are mediated by the suppression of de novo lipogenesis.

Metabolic changes assessed by 1H MR spectroscopy in the corpus callosum of post-COVID patients.

OBJECTIVE: Many patients with long COVID experience neurological and psychological symptoms. Signal abnormalities on MR images in the corpus callosum have been reported. Knowledge about the metabolic profile in the splenium of the corpus callosum (CCS) may contribute to a better understanding of the pathophysiology of long COVID. MATERIALS AND METHODS: Eighty-one subjects underwent proton MR spectroscopy examination. The metabolic concentrations of total N-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr), myo-inositol (mI), and NAA/Cho in the CCS were statistically compared in the group of patients containing 58 subjects with positive IgG COVID-19 antibodies or positive SARS-CoV-2 qPCR test at least two months before the MR and the group of healthy controls containing 23 subjects with negative IgG antibodies. RESULTS: An age-dependent effect of SARS-CoV-2 on Cho concentrations in the CCS has been observed. Considering the subjective threshold of age = 40 years, older patients showed significantly increased Cho concentrations in the CCS than older healthy controls (p = 0.02). NAA, Cr, and mI were unchanged. All metabolite concentrations in the CCS of younger post-COVID-19 patients remained unaffected by SARS-CoV-2. Cho did not show any difference between symptomatic and asymptomatic patients (p = 0.91). DISCUSSION: Our results suggest that SARS-CoV-2 disproportionately increases Cho concentration in the CCS among older post-COVID-19 patients compared to younger ones. The observed changes in Cho may be related to the microstructural reorganization in the CCS also reported in diffusion measurements rather than increased membrane turnover. These changes do not seem to be related to neuropsychological problems of the post-COVID-19 patients. Further metabolic studies are recommended to confirm these observations.

Technical note: MR-compatible pedal ergometer with electromechanical pedal resistance and exercise triggering enhanced by visual feedback via video display.

BACKGROUND: During and after exercise, dynamic 31 P MR parameters are typically measured using an MR-compatible ergometer. Self-built equipment for local condition can be constructed where possible. PURPOSE: To develop a pedal resistance ergometer with rocker arm based on a system that combines electric weight displacement, visual self-monitoring, and exercise triggering. The repeatability and reproducibility were tested. METHODS: The hardware and software for the ergometer were constructed from commercial components in a home laboratory. Twelve volunteers participated in the testing of the ergometer. RESULTS: A fully automated ergometer system was developed, allowing the pedal resistance to be adjusted during the examination. The system includes a self-monitoring and triggering mechanism that enables both the operator and subject to monitor pedal frequency and force. The operator can modify the pedal resistance as desired during the exercise. This self-monitoring solution is simple and cost-effective, requiring only a commercial potentiometer, an Arduino converter, and a conventional video projector with a personal computer (PC). Additionally, all system components are located outside the magnetic resonance (MR) room, avoiding interference with the MR system. Results of several test of the reproducibility/repeatability of power at three pedal resistance values (15%, 24%, 25% maximal voluntary force) were expressed both as a coefficient of variation ranging from 6% to 3.1% and as an intraclass correlation of coefficient ranging from 0.96 to 0.99. Similar values were also found for other dynamic parameters of 31 P MR spectroscopy. These findings are similar to published data obtained on different types of ergometers. CONCLUSIONS: Based on more than 1 year of usage, the ergometer proved successful in handling stationary and variable loads, and can be easily operated by a single user.

Effect of Omega-3 Polyunsaturated Fatty Acids on Lipid Metabolism in Patients With Metabolic Syndrome and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. n-3 polyunsaturated fatty acids (n-3-PUFAs) have been reported to ameliorate the progression of NAFLD in experimental studies; however, clinical trials have yielded contradictory results. The aim of our study was to assess the effects of n-3-PUFA administration on lipid metabolism and the progression of NAFLD in patients with metabolic syndrome. Sixty patients with metabolic syndrome and NAFLD were randomized in a double-blind placebo-controlled trial (3.6 g/day n-3-PUFA vs. placebo). During the 1-year follow-up, the patients underwent periodic clinical and laboratory examinations, liver stiffness measurements, magnetic resonance spectroscopy of the liver, and plasma lipidomic analyses. After 12 months of n-3-PUFA administration, a significant decrease in serum GGT activity was recorded compared with the placebo group (2.03 ± 2.8 vs. 1.43 ± 1.6; P < 0.05). Although no significant changes in anthropometric parameters were recorded, a significant correlation between the reduction of liver fat after 12 months of treatment-and weight reduction-was observed; furthermore, this effect was clearly potentiated by n-3-PUFA treatment (P < 0.005). In addition, n-3-PUFA treatment resulted in substantial changes in the plasma lipidome, with n-3-PUFA-enriched triacylglycerols and phospholipids being the most expressed lipid signatures. Conclusion: Twelve months of n-3-PUFA treatment of patients with NAFLD patients was associated with a significant decrease in GGT activity, the liver fat reduction in those who reduced their weight, and beneficial changes in the plasma lipid profile.

In Vitro 31P MR Chemical Shifts of In Vivo-Detectable Metabolites at 3T as a Basis Set for a Pilot Evaluation of Skeletal Muscle and Liver 31P Spectra with LCModel Software.

Most in vivo 31P MR studies are realized on 3T MR systems that provide sufficient signal intensity for prominent phosphorus metabolites. The identification of these metabolites in the in vivo spectra is performed by comparing their chemical shifts with the chemical shifts measured in vitro on high-field NMR spectrometers. To approach in vivo conditions at 3T, a set of phantoms with defined metabolite solutions were measured in a 3T whole-body MR system at 7.0 and 7.5 pH, at 37 °C. A free induction decay (FID) sequence with and without 1H decoupling was used. Chemical shifts were obtained of phosphoenolpyruvate (PEP), phosphatidylcholine (PtdC), phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), glycerophosphoetanolamine (GPE), uridine diphosphoglucose (UDPG), glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), 2,3-diphosphoglycerate (2,3-DPG), nicotinamide adenine dinucleotide (NADH and NAD+), phosphocreatine (PCr), adenosine triphosphate (ATP), adenosine diphosphate (ADP), and inorganic phosphate (Pi). The measured chemical shifts were used to construct a basis set of 31P MR spectra for the evaluation of 31P in vivo spectra of muscle and the liver using LCModel software (linear combination model). Prior knowledge was successfully employed in the analysis of previously acquired in vivo data.

Lipid Profile and Hepatic Fat Content Measured by 1H MR Spectroscopy in Patients before and after Liver Transplantation.

Increased hepatic fat content (HFC) is a hallmark of non-alcoholic fatty liver (NAFL) disease, a common condition in liver transplant recipients. Proton MR spectroscopy (1H MRS) and MR imaging-based proton density fat fraction as the only diagnosis modality enable precise non-invasive measurement of HFC and, also, fatty acid profiles in vivo. Using 1H MRS at 3T, we examined 47 liver transplantation candidates and 101 liver graft recipients. A point-resolved spectroscopy sequence was used to calculate the steatosis grade along with the saturated, unsaturated and polyunsaturated fractions of fatty acids in the liver. The steatosis grade measured by MRS was compared with the histological steatosis grade. HFC, represented by fat fraction values, is adept at distinguishing non-alcoholic steatohepatitis (NASH), NAFL and non-steatotic liver transplant patients. Relative hepatic lipid saturation increases while unsaturation decreases in response to increased HFC. Additionally, relative hepatic lipid saturation increases while unsaturation and polyunsaturation both decrease in liver recipients with histologically proven post-transplant NASH or NAFL compared to non-steatotic patients. HFC, measured by in vivo 1H MRS, correlated well with histological results. 1H MRS is a simple and fast method for in vivo analysis of HFC and its composition. It provides non-invasive support for NAFL and NASH diagnoses.

Associations of Brain Atrophy and Cerebral Iron Accumulation at MRI with Clinical Severity in Wilson Disease.

Background Abnormal findings at brain MRI in patients with neurologic Wilson disease (WD) are characterized by signal intensity changes and cerebral atrophy. T2 signal hypointensities and atrophy are largely irreversible with treatment; their relationship with permanent disability has not been systematically investigated. Purpose To investigate associations of regional brain atrophy and iron accumulation at MRI with clinical severity in participants with neurologic WD who are undergoing long-term anti-copper treatment. Materials and Methods Participants with WD and controls were compared in a prospective study performed from 2015 to 2019. MRI at 3.0 T included three-dimensional T1-weighted and six-echo multigradient-echo pulse sequences for morphometry and quantitative susceptibility mapping, respectively. Neurologic severity was assessed with the Unified WD Rating Scale (UWDRS). Automated multi-atlas segmentation pipeline with dual contrast (susceptibility and T1) was used for the calculation of volumes and mean susceptibilities in deep gray matter nuclei. Additionally, whole-brain analysis using deformation and surface-based morphometry was performed. Least absolute shrinkage and selection operator regression was used to assess the association of regional volumes and susceptibilities with the UWDRS score. Results Twenty-nine participants with WD (mean age, 47 years ± 9 [standard deviation]; 15 women) and 26 controls (mean age, 45 years ± 12; 14 women) were evaluated. Whole-brain analysis demonstrated atrophy of the deep gray matter nuclei, brainstem, internal capsule, motor cortex and corticospinal pathway, and visual cortex and optic radiation in participants with WD (P < .05 at voxel level, corrected for family-wise error). The UWDRS score was negatively correlated with volumes of putamen (r = -0.63, P < .001), red nucleus (r = -0.58, P = .001), globus pallidus (r = -0.53, P = .003), and substantia nigra (r = -0.50, P = .006) but not with susceptibilities. Only the putaminal volume was identified as a stable factor associated with the UWDRS score (R2 = 0.38, P < .001) using least absolute shrinkage and selection operator regression. Conclusion Individuals with Wilson disease (WD) had widespread brain atrophy most pronounced in the central structures. The putaminal volume was associated with the Unified WD Rating Scale score and can be used as a surrogate imaging marker of clinical severity. © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Du and Bydder in this issue.

Magnetic resonance markers of bilateral neuronal metabolic dysfunction in patients with unilateral internal carotid artery occlusion.

OBJECTIVES: To evaluate cerebral hemodynamic, metabolic and anatomic changes occurring in patients with unilateral occlusion of the internal carotid artery (ICA). MATERIALS AND METHODS: Twenty-two patients with unilateral occlusion of ICA and twenty age and sex matched healthy subjects were included in the study. Single voxel proton magnetic resonance spectroscopy (1H-MRS) of the centrum semiovale, semi-automated hippocampal volumetry in T1-weighted scans and transcranial Doppler examination (TCD) with calculation of Breath Holding Index (BHI) were performed in both groups. Metabolic, anatomic, and hemodynamic features were compared between the two groups. RESULTS: The N-acetylaspartate (NAA)/choline (Cho) ratio was significantly lower in both hemispheres of enrolled patients compared to controls (p = 0.005 for the side with occlusion, p = 0.04 for the side without occlusion). The hippocampus volume was significantly reduced bilaterally in patients compared to healthy subjects (p = 0.049). A statistically significant difference in BHI values was observed between the side with occlusion and without occlusion (p = 0.037) of the patients, as well as between BHI values of the side with occlusion and healthy volunteers (p = 0.014). DISCUSSION: Patients with unilateral ICA occlusion have reduced NAA/Cho ratio in the white matter of both hemispheres and have bilateral atrophy of hippocampus. The alteration of hemodynamics alone cannot explain these changes.

Implant-forming polymeric 19F MRI-tracer with tunable dissolution.

Magnetic resonance imaging (MRI) using 19F-based tracers has emerged as a promising multi-purpose noninvasive diagnostic tool and its application requires the use of various 19F-based tracers for the intended diagnostic purpose. In this study, we report a series of double-stimuli-responsive polymers for use as injectable implants, which were designed to form implants under physiological conditions, and to subsequently dissolve with different dissolution rates (t1/2 ranges from 30 to more than 250 days). Our polymers contain a high concentration of fluorine atoms, providing remarkable signal detectability, and both a hydrophilic monomer and a pH-responsive monomer that alter the biodistribution properties of the implant. The implant location and dissolution were observed using 19F MRI, which allows the anatomic extent of the implant to be monitored. The dissolution kinetics and biocompatibility of these materials were thoroughly analyzed. No sign of toxicity in vitro or in vivo or pathology in vivo was observed, even in chronic administration. The clinical applicability of our polymers was further confirmed via imaging of a rat model by employing an instrument currently used in human medicine.

Glycogen as an advantageous polymer carrier in cancer theranostics: Straightforward in vivo evidence.

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.

Origin of the 31 P MR signal at 5.3 ppm in patients with critical limb ischemia.

An unknown intense signal (Pun ) with a mean chemical shift of 5.3 ppm was observed in 31 P MR spectra from the calf muscles of patients with the diabetic foot syndrome. The aim of the study was to identify the origin of this signal and its potential as a biomarker of muscle injury. Calf muscles of 68 diabetic patients (66.3 ± 8.6 years; body mass index = 28.2 ± 4.3 kg/m2 ) and 12 age-matched healthy controls were examined by (dynamic) 31 P MRS (3 T system, 31 P/1 H coil). Phantoms (glucose-1-phosphate, Pi and PCr) were measured at pH values of 7.05 and 7.51. At rest, Pun signals with intensities higher than 50% of the Pi intensity were observed in 10 of the 68 examined diabetic subjects. We tested two hypothetical origins of the Pun signal: (1) phosphorus from phosphoesters and (2) phosphorus from extra- and intracellular alkaline phosphate pools. 2,3-diphosphoglycerate and glucose-1-phosphate are the only phosphoesters with signals in the chemical shift region close to 5.3 ppm. Both compounds can be excluded: 2,3-diphosphoglycerate due to the missing second signal component at 6.31 ppm; glucose-1-phosphate because its chemical shifts are about 0.2 ppm downfield from the Pi signal (4.9 ppm). If the Pun signal is from phosphate, it represents a pH value of 7.54 ± 0.05. Therefore, it could correspond to signals of Pi in mitochondria. However, patients with critical limb ischemia have rather few mitochondria and so the Pun signal probably originates from interstitia. Our data suggest that the increased Pun signal observed in patients with the diabetic foot syndrome is a biomarker of severe muscular damage.

Multiparametric Quantitative Brain MRI in Neurological and Hepatic Forms of Wilson's Disease.

BACKGROUND: In Wilson's disease (WD), demyelination, rarefaction, gliosis, and iron accumulation in the deep gray matter cause opposing effects on T2 -weighted MR signal. However, the degree and interplay of these changes in chronically treated WD patients has not been quantitatively studied. PURPOSE: To compare differences in brain multiparametric mapping between controls and chronically treated WD patients with neurological (neuro-WD) and hepatic (hep-WD) forms to infer the nature of residual WD neuropathology. STUDY TYPE: Cross-sectional. POPULATION/SUBJECTS: Thirty-eight WD patients (28 neuro-WD, 10 hep-WD); 26 healthy controls. FIELD STRENGTH/SEQUENCE: 3.0T: susceptibility, T2 *, T2 , T1 relaxometry; 1.5T: T2 , T1 relaxometry. ASSESSMENT: The following 3D regions of interest (ROIs) were manually segmented: globus pallidus, putamen, caudate nucleus, and thalamus. Mean bulk magnetic susceptibility, T2 *, T2 , and T1 relaxation times were calculated for each ROI. STATISTICAL TESTS: The effect of group (neuro-WD, hep-WD, controls) and age was assessed using a generalized least squares model with different variance for each ROI and quantitative parameter. A general linear hypothesis test with Tukey adjustment was used for post-hoc between-group analysis; P < 0.05 was considered significant. RESULTS: Susceptibility values were higher in all ROIs in neuro-WD compared to controls and hep-WD (P < 0.001). In basal ganglia, lower T2 and T2 * were found in neuro-WD compared to controls (P < 0.01) and hep-WD (P < 0.05) at 3.0T. Much smaller intergroup differences for T2 in basal ganglia were observed at 1.5T compared to 3.0T. In the thalamus, increased susceptibility in neuro-WD was accompanied by increased T1 at both field strengths (P < 0.001 to both groups), and an increased T2 at 1.5T only (P < 0.001 to both groups). DATA CONCLUSION: We observed significant residual brain MRI abnormalities in neuro-WD but not in hep-WD patients on chronic anticopper treatment. Patterns of changes were suggestive of iron accumulation in the basal ganglia and demyelination in the thalamus; 3.0T was more sensitive for detection of the former and 1.5T of the latter abnormality. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1829-1835.

Different acute effects of fructose and glucose administration on hepatic fat content.

BACKGROUND: Diets rich in fat and added sugars (especially fructose) play an important role in the pathogenesis of nonalcoholic liver disease (NAFLD), but there is only limited information on the acute effects of these nutrients on hepatic fat content (HFC). OBJECTIVES: We therefore explored how the administration of high-fat load, glucose, fructose, and combinations thereof affects HFC measured in vivo using proton magnetic resonance spectroscopy (1H-MRS) in healthy subjects. METHODS: Ten healthy nonsteatotic male volunteers (age 38.5 ± 9.6 y, body mass index [BMI, kg/m2] 26.9 ± 2.7) underwent, in random order, 6 experiments, each lasting 8 h, that included: 1) fasting; 2) a high-fat load (150 g of fat [dairy cream] at time 0); 3) glucose (3 doses of 50 g at 0, 2, and 4 h); 4) a high-fat load with glucose; 5) fructose (3 doses of 50 g at 0, 2, and 4 h); and 6) a high-fat load with fructose. HFC was measured using 1H-MRS prior to test meal administration (before time 0) and at 3 and 6 h. Plasma concentrations of triglycerides, nonesterified fatty acids, glucose, and insulin were monitored throughout each experiment. RESULTS: HFC increased to 119 ± 19% (P < 0.05) and 117 ± 17% (P < 0.01) of baseline when subjects consumed a high-fat load alone or a high-fat load with fructose, respectively, but was not affected when glucose was coadministered with a high-fat load. HFC was not affected when subjects had fasted or had consumed repeated doses of fructose. When subjects were administered 3 doses of glucose, HFC dropped to 85 ± 13% (P < 0.05) of baseline. CONCLUSIONS: Our results demonstrate that fructose and glucose have a different immediate impact on HFC in humans in vivo. Clinical trial registry: The study was registered at clinicaltrials.gov and obtained clinicaltrials.gov identifier: NCT03680248.

MR compatible ergometers for dynamic 31P MRS.

Magnetic Resonance (MR) compatible ergometers are specialized ergometers used inside the MR scanners for the characterization of tissue metabolism changes during physical stress. They are most commonly used for dynamic phosphorous magnetic resonance spectroscopy (31P MRS), but can also be used for lactate production measurements, perfusion studies using arterial spin labelling or muscle oxygenation measurements by blood oxygen dependent contrast sequences. We will primarily discuss the importance of ergometers in the context of dynamic 31P MRS. Dynamic 31P MRS can monitor muscle fatigue and energy reserve during muscle contractions as well as the dynamics of recuperation of skeletal muscle tissue during the following recovery through signal changes of phosphocreatine (PCr), inorganic phosphate and adenosine triphosphate (ATP). Based on the measured data it is possible to calculate intracellular pH, metabolic flux of ATP through creatine-kinase reaction, anaerobic glycolysis and oxidative phosphorylation and other metabolic parameters as mitochondrial capacity. This review primarily focuses on describing various technical designs of MR compatible ergometers for dynamic 31P MRS that must be constructed with respect to the presence of magnetic field. It is also expected that the construction of ergometers will be easy for the handling and well accepted by examined subjects.

Low-molecular-weight paramagnetic 19F contrast agents for fluorine magnetic resonance imaging.

OBJECTIVE: 19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested. METHODS: Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T. RESULTS: 19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe. CONCLUSION: DOTP-based 19F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.

Ultralong TE In Vivo 1 H MR Spectroscopy of Omega-3 Fatty Acids in Subcutaneous Adipose Tissue at 7 T.

BACKGROUND: Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly. PURPOSE: To detect omega-3 (n-3 CH3 ) and non-omega-3 (CH3 ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo. STUDY TYPE: Prospective technical development. POPULATION: Three oils with different n-3 FA content and 24 healthy subjects. FIELD STRENGTH/SEQUENCE: Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T. ASSESSMENT: Knowledge about the J-coupling evolution of both CH3 resonances was used for the optimal detection of the n-3 CH3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis. STATISTICAL TESTS: SVS data were compared to gas chromatography with the Pearson correlation coefficient. RESULTS: T2 relaxation times in oils were assessed as follows: CH2 , 65 ± 22 msec; CH3 , 325 ± 7 msec; and n-3 CH3 , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029). DATA CONCLUSION: PRESS with ultralong-TE can detect and quantify the n-3 CH3 signal in vivo at 7 T. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82.

Skeletal Muscle Abnormalities and Iron Deficiency in Chronic Heart FailureAn Exercise 31P Magnetic Resonance Spectroscopy Study of Calf Muscle.

BACKGROUND: Heart failure (HF) is often associated with iron deficiency (ID). Skeletal muscle abnormalities are common in HF, but the potential role of ID in this phenomenon is unclear. In addition to hemopoiesis, iron is essential for muscle bioenergetics. We examined whether energetic abnormalities in skeletal muscle in HF are affected by ID and if they are responsive to intravenous iron. METHODS AND RESULTS: Forty-four chronic HF subjects and 25 similar healthy volunteers underwent 31P magnetic resonance spectroscopy of calf muscle at rest and during exercise (plantar flexions). Results were compared between HF subjects with or without ID. In 13 ID-HF subjects, examinations were repeated 1 month after intravenous ferric carboxymaltose administration (1000 mg). As compared with controls, HF subjects displayed lower resting high-energy phosphate content, lower exercise pH, and slower postexercise PCr recovery. Compared with non-ID HF, ID-HF subjects had lower muscle strength, larger PCr depletion, and more profound intracellular acidosis with exercise, consistent with an earlier metabolic shift to anaerobic glycolysis. The exercise-induced PCr drop strongly correlated with pH change in HF group ( r=-0.71, P<0.001) but not in controls ( r=0.13, P=0.61, interaction: P<0.0001). Short-term iron administration corrected the iron deficit but had no effect on muscle bioenergetics assessed 1 month later. CONCLUSIONS: HF patients display skeletal muscle myopathy that is more severe in those with iron deficiency. The presence of ID is associated with greater acidosis with exercise, which may explain early muscle fatigue. Further study is warranted to identify the strategy to restore iron content in skeletal muscle.