Pericardial Fat Relates to Disturbances of Glucose Metabolism in Women with the Polycystic Ovary Syndrome, but Not in Healthy Control Subjects.

OBJECTIVE: The objective of the present study is to investigate the relationship of cardiac fat depots with disturbances of the carbohydrate metabolism in women with PCOS. METHODS: An oral glucose tolerance test (OGTT) was realized, and metabolic parameters were collected in 48 women with PCOS and in 20 controls. Intramyocardial fat (MYCL) and pericardial fat (PERI) were measured using 1H-magnetic resonance spectroscopy and imaging. RESULTS: Only in PCOS women, PERI was positively and independently related to parameters of glucose metabolism (HbA1c: p = 0.001, fasting plasma glucose: p < 0.001, stimulated glucose at 30 and 60 minutes in the OGTT). Thus, the disposition index, insulin sensitivity, and adiponectin also declined with the increase of PERI in women with PCOS; however, these results were not independent of BMI and age. In addition, PERI was positively related to atherogenic lipid profiles, BMI, waist circumference, CRP, and liver fat in women with PCOS. A negative relation of PERI with triglycerides and a positive relation with BMI and waist circumference could be observed in the controls. No relationship of MYCL with diabetes-specific parameters could be found in the study population. CONCLUSION: PERI is related to metabolic disturbances in women with PCOS, but not in metabolically healthy lean subjects. This clinical trial was registered at ClinicalTrials.gov and has the registration number NCT03204461.

Improved spectral resolution and high reliability of in vivo (1) H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle.

The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by (1) H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times - before and twice after (approximately 20 and 40 min) a 1-h submaximal street run and additional toe-hopping. The measured T1 relaxation times for the C2-H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T2 times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by (1) H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise-induced change in pH. Our results support the application of the MRS-based assessment of carnosine for pH measurement in muscle compartments.

Depth-resolved surface coil MRS (DRESS)-localized dynamic (31) P-MRS of the exercising human gastrocnemius muscle at 7 T.

Dynamic (31) P-MRS with sufficiently high temporal resolution enables the non-invasive evaluation of oxidative muscle metabolism through the measurement of phosphocreatine (PCr) recovery after exercise. Recently, single-voxel localized (31) P-MRS was compared with surface coil localization in a dynamic fashion, and was shown to provide higher anatomical and physiological specificity. However, the relatively long TE needed for the single-voxel localization scheme with adiabatic pulses limits the quantification of J-coupled spin systems [e.g. adenosine triphosphate (ATP)]. Therefore, the aim of this study was to evaluate depth-resolved surface coil MRS (DRESS) as an alternative localization method capable of free induction decay (FID) acquisition for dynamic (31) P-MRS at 7 T. The localization performance of the DRESS sequence was tested in a phantom. Subsequently, two dynamic examinations of plantar flexions at 25% of maximum voluntary contraction were conducted in 10 volunteers, one examination with and one without spatial localization. The DRESS slab was positioned obliquely over the gastrocnemius medialis muscle, avoiding other calf muscles. Under the same load, significant differences in PCr signal drop (31.2 ± 16.0% versus 43.3 ± 23.4%), end exercise pH (7.06 ± 0.02 versus 6.96 ± 0.11), initial recovery rate (0.24 ± 0.13 mm/s versus 0.35 ± 0.18 mm/s) and maximum oxidative flux (0.41 ± 0.14 mm/s versus 0.54 ± 0.16 mm/s) were found between the non-localized and DRESS-localized data, respectively. Splitting of the inorganic phosphate (Pi) signal was observed in several non-localized datasets, but in none of the DRESS-localized datasets. Our results suggest that the application of the DRESS localization scheme yielded good spatial selection, and provided muscle-specific insight into oxidative metabolism, even at a relatively low exercise load. In addition, the non-echo-based FID acquisition allowed for reliable detection of ATP resonances, and therefore calculation of the specific maximum oxidative flux, in the gastrocnemius medialis using standard assumptions about resting ATP concentration in skeletal muscle.

Cardiometabolic phenotyping of patients with familial hypocalcuric hypercalcemia.

CONTEXT: Heterozygous inactivating mutations of the calcium-sensing receptor (CaSR) gene cause alterations in calcium metabolism [familial hypocalciuric hypercalcemia (FHH)]. In addition, calcium-sensing receptor is expressed in the myocardium and endocrine cells including pancreatic islets, enteroendocrine cells, and adipose tissue. OBJECTIVE: To discern whether FHH is associated with cardiometabolic alterations of clinical significance, endocrine responses to systemic calcium stimulation and oral glucose tolerance tests were performed. Ectopic lipid deposition and heart function were assessed using magnetic resonance spectroscopy/imaging. PARTICIPANTS: Eight FHH patients and nine controls matched for anthropometric characteristics (age 45 ± 18 y; body mass index 29 ± 4 vs 29 ± 6 kg/m(2)) were studied to determine cardiac function, ectopic and visceral lipid content, and insulin sensitivity and secretion. RESULTS: Insulin sensitivity (clamp-like index: 4.5 ± 0.6 vs 4.3 ± 0.4 mg/kg · min), basal (insulin secretion rate: 266 ± 33 vs 218 ± 25 pmol/min), and glucose-stimulated ß-cell function (adaptation index: 180.2 ± 12.2 vs 176.2 ± 17.4) as well as calcium-stimulated insulin secretion were comparable between FHH and controls, respectively. Ectopic lipid content in liver [3.75% (1.4%; 34%) vs 4.18% (0.9%; 28%)], soleus muscle (1.07% ± 0.38% vs 1.02% ± 0.56 %), and myocardium (0.39% ± 0.3% vs 0.32% ± 0.1 %), visceral and sc adipose tissue distribution (0.51 ± 0.16 vs 0.47 ± 0.17) as well as heart function (ejection fraction: 71.5% ± 8% vs 72.8% ± 8 %; E to A ratio: 1.4% ± 0.6% vs 1.3% ± 0.7%) were not different between the groups. CONCLUSION: Despite comprehensive cardiometabolic phenotyping, no alterations in myocardial function, lipid distribution, or glucose metabolism were observed in FHH. Thus, FHH might reflect a laboratory finding without any relevant cardiometabolic alterations.

Two-dimensional spectroscopic imaging with combined free induction decay and long-TE acquisition (FID echo spectroscopic imaging, FIDESI) for the detection of intramyocellular lipids in calf muscle at 7 T.

The aim of this study was to introduce a two-dimensional chemical shift imaging (2D CSI) sequence, with simultaneous acquisition of free induction decay (FID) and long TEs, for the detection and quantification of intramyocellular lipids (IMCLs) in the calf at 7 T. The feasibility of the new 2D CSI sequence, which acquires FID (acquisition delay, 1.3 ms) and an echo (long TE) in one measurement, was evaluated in phantoms and volunteers (n = 5): TR/TE*/TE = 800/1.3/156 ms; 48 × 48 matrix; field of view, 200 × 200 × 20 mm(3) ; Hamming filter; no water suppression; measurement time, 22 min 2 s. The IMCL concentration and subcutaneous lipid contamination were assessed. Spectra in the tibialis anterior (TA), gastrocnemius (GM) and soleus (SOL) muscles were analyzed. The water signal from the FID acquisition was used as an internal concentration reference. In the spectra from subcutaneous adipose tissue (SUB) and bone marrow (BM), an unsaturation index (UI) of the vinyl-H (5.3 ppm) to methyl-CH3 ratio, and a polyunsaturation index (pUI) of the diallylic-H (2.77 ppm) to -CH3 ratio, were calculated. Long-TE spectra from muscles showed a simplified spectral pattern with well-separated IMCL for several muscle groups in the same scan. The IMCL to water ratio was largest in SOL (0.66% ± 0.23%), and lower in GM (0.37% ± 0.14%) and TA (0.36% ± 0.12%). UI and pUI for SUB were 0.65 ± 0.06 and 0.18 ± 0.04, respectively, and for BM were 0.60 ± 0.16 and 0.18 ± 0.08, respectively. The new sequence, with the proposed name 'free induction decay echo spectroscopic imaging' (FIDESI), provides information on both specific lipid resonances and water signal from different tissues in the calf, with high spectral and spatial resolution, as well as minimal voxel bleeding and subcutaneous lipid contamination, in clinically acceptable measurement times.

Flip-angle mapping of 31P coils by steady-state MR spectroscopic imaging.

PURPOSE: Phosphorus ((31)P) MR spectroscopic imaging (MRSI) is primarily applied with sensitive, surface radiofrequency (RF) coils that provide inhomogeneous excitation RF field (B1(+)) and rough localization due to their B1(+) and sensitivity (B1(-)) profiles. A careful and time-consuming pulse adjustment and an accurate knowledge of flip angle (FA) are mandatory for quantification corrections. MATERIALS AND METHODS: In this study, a simple, fast, and universal (31)P B1(+) mapping method is proposed, which requires fast steady-state MRSI (typically one sixth of normal measurement time) in addition to the typical MRSI acquired within the examination protocol. The FA maps are calculated from the ratio of the signal intensities acquired by these two measurements and were used to correct for the influence of B1(+) on the metabolite maps. RESULTS: In vitro tests were performed on two scanners (3 and 7 Tesla) using a surface and a volume coil. The calculated FA maps were in good agreement with adjusted nominal FAs and the theoretical calculation using the Biot-Savart law. The method was successfully tested in vivo in the calf muscle and the brain of healthy volunteers (n = 4). The corrected metabolite maps show higher homogeneity compared with their noncorrected versions. CONCLUSION: The calculated FA maps helped with B1(+) inhomogeneity corrections of acquired in vivo data, and should also be useful with optimization and testing of pulse performances, or with the construction quality tests of new dual-channel (1)H/(31)P coils.

Pathophysiological rat model of vascular dementia: magnetic resonance spectroscopy, microimaging and behavioral study.

Chronic cerebral hypoperfusion and aging can be related to vascular dementia manifested by the decline in cognitive abilities and memory impairment. The identification of specific biomarkers of vascular disorder in early stages is important for the development of neuroprotective agents. In the present study, a three-vessel occlusion (3-VO) rat model of vascular dementia in the middle-aged rat brain was used to investigate the effect of global cerebral hypoperfusion. A multimodal study was performed using magnetic resonance spectroscopy, MR-microimaging, histology and behavioral tests. Our measurements showed a signal alteration in T2-weighted MR images, the elevation of T2 relaxation times and histologically proven neural cell death in the hippocampal area, as well as mild changes in concentration of proton and phosphorus metabolites. These changes were accompanied by mild behavioral alterations in the open field and slightly decreased habituation. The analysis of the effects of vascular pathology on cognitive functions and neurodegeneration can contribute to the development of new treatment strategies for early stages of neurodegeneration.

In vivo relaxation behavior of liver compounds at 7 Tesla, measured by single-voxel proton MR spectroscopy.

PURPOSE: To assess the proton T1 and T2 relaxation of in vivo hepatic water, choline and lipid resonances with possible J-coupling behavior of lipids in healthy volunteers at 7 Tesla (T). MATERIALS AND METHODS: Relaxation measurements were conducted on corn oil phantoms and on the hepatic tissue of 11 healthy volunteers at 7 T using a surface coil and a STEAM sequence. T1 's were determined by monoexponential fitting, and T2 's by both monoexponential and enhanced-exponential fitting (empirically designed to consider J-coupling of lipid resonances). RESULTS: In vivo T1 's at 7 T were estimated as follows: water (4.70 ppm), 1362 ± 83 ms; methyl- (0.90 ppm), 1026 ± 162 ms; methylene- (1.30 ppm), 514 ± 25 ms; α-olefinic- (2.02 ppm), 488 ± 220 ms; α-carboxyl- (2.24 ppm), 476 ± 89 ms; diacyl- (2.77 ppm), 479 ± 260 ms group of lipid chains; and choline compounds (3.22 ppm), 1084 ± 52 ms. The T2 's calculated with enhanced fitting were as follows: water, 15 ± 2 ms; methyl-, 34 ± 10 ms; methylene-, 41 ± 8 ms; α-olefinic-, 44 ± 19 ms; α-carboxyl-, 39 ± 15 ms; diacyl-, 44 ± 5 ms group of lipid chains; and choline compounds, 32 ± 9 ms. CONCLUSION: An accurate knowledge of in vivo relaxation and J-coupling behavior will significantly improve the quantification of an extended number of resolved liver metabolites at 7 T.

Time-resolved phosphorous magnetization transfer of the human calf muscle at 3 T and 7 T: a feasibility study.

Phosphorous ((31)P) magnetization transfer (MT) experiments enable the non-invasive investigation of human muscle metabolism in various physiological and pathological conditions. The purpose of our study was to investigate the feasibility of time-resolved MT, and to compare the results of MT experiments at 3 T and 7 T. Six healthy volunteers were examined on a 3T and a 7 T MR scanner using the same setup and identical measurement protocols. In the calf muscle of all volunteers, four separate MT experiments (each ∼10 min duration) were performed in one session. The forward rate constant of the ATP synthesis reaction (kATP) and creatine kinase reaction (kCK), as well as corresponding metabolic fluxes (FATP, FCK), were estimated. A comparison of these exchange parameters, apparent T1s, data quality, quantification precision, and reproducibility was performed. The data quality and reproducibility of the same MT experiments at 7 T was significantly higher (i.e., kATP 2.7 times higher and kCK 3.4 times higher) than at 3 T (p<0.05). The values for kATP (p=0.35) and kCK (p=0.09) at both field strengths were indistinguishable. Even a single MT experiment at 7 T provided better data quality than did a 4 times-longer MT experiment at 3T. The minimal time-resolution to reliably quantify both FATP and FCK at 7 T was ∼6 min. Our results show that MT experiments at 7 T can be at least 4 times faster than 3 T MT experiments and still provide significantly better quantification. This enables time-resolved MT experiments for the observation of slow metabolic changes in the human calf muscle at 7 T.