Photon-counting CT using multi-material decomposition algorithm enables fat quantification in the presence of iron deposits.

PURPOSE: A new generation of CT detectors were recently developed with the ability to measure individual photon's energy and thus provide spectral information. The aim of this work was to assess the performance of simultaneous fat and iron quantification using a clinical photon-counting CT (PCCT) and its comparison to dual-energy CT (DECT), MRS and MRI at 3 T. METHODS: Two 3D printed cylindrical phantoms with 32 samples (n = 12 fat fractions between 0 % and 100 %, n = 20 with mixtures of fat and iron) were scanned with PCCT and DECT scanners for comparison. A three-material decomposition approach was used to estimate the volume fractions of fat (FF), iron and soft tissue. The same phantoms were examined by MRI (6-echo DIXON, a.k.a. Q-DIXON) and MRS (multi-echo STEAM, a.k.a. HISTO) at 3 T for comparison. RESULTS: PCCT, DECT, MRI and MRS computed FFs showed correlation with reference fat fraction values in samples with no iron (r > 0.98). PCCT decomposition showed slightly weaker correlation with FFref in samples with added iron (r = 0.586) compared to MRI (r = 0.673) and MRS (r = 0.716) methods. On the other hand, it showed no systematic over- or underestimation. Surprisingly, DECT decomposition-derived FF showed strongest correlation (r = 0.758) in these samples, however systematic overestimation was observed. FF values computed by three-material PCCT decomposition, DECT decomposition, MRI and MRS were unaffected by iron concentration. CONCLUSIONS: This in-vitro study shows for the first time that photon-counting computed tomography may be used for quantification of fat content in the presence of iron deposits.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1.

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

Concentration of Gallbladder Phosphatidylcholine in Cholangiopathies: A Phosphorus-31 Magnetic Resonance Spectroscopy Pilot Study.

BACKGROUND: Biliary phosphatidylcholine (PtdC) concentration plays a role in the pathogenesis of bile duct diseases. In vivo phosphorus-31 magnetic resonance spectroscopy (31 P-MRS) at 7 T offers the possibility to assess this concentration noninvasively with high spectral resolution and signal intensity. PURPOSE: Comparison of PtdC levels of cholangiopathic patient groups to a control group using a measured T1 relaxation time of PtdC in healthy subjects. STUDY TYPE: Case control. SUBJECTS: Two patient groups with primary sclerosing cholangitis (PSC, 2f/3 m; age: 43 ± 7 years) and primary biliary cholangitis (PBC, 4f/2 m; age: 57 ± 6 years), and a healthy control group (CON, 2f/3 m; age: 38 ± 7 years). Ten healthy subjects for the assessment of the T1 relaxation time of PtdC. FIELD STRENGTH/SEQUENCE: A 3D phase-encoded pulse-acquire 31 P-MRSI sequence for PtdC quantification and a 1D image-selected in vivo 31 P spectroscopy for T1 estimation at 7 T, and a T2-weighted half-Fourier single-shot turbo spin echo MRI sequence for volumetry at 3 T. ASSESSMENT: Calculation of gallbladder volumes and PtdC concentration in groups using hepatic gamma-adenosine triphosphate signal as an internal reference and correction for insufficient relaxation of PtdC with a T1 value assessed in healthy subjects. STATISTICAL TESTS: Group comparison of PtdC content and gallbladder volumes of the PSC/PBC and CON group using Student's t-tests with a significance level of 5%. RESULTS: PtdC T1 value of 357 ± 85 msec in the gallbladder. Significant lower PtdC content for the PSC group, and for the female subgroup of the PBC group compared to the CON group (PSC/CON: 5.74 ± 0.73 mM vs. 9.64 ± 0.97 mM, PBC(f)/CON: 5.77 ± 1.44 mM vs. 9.64 ± 0.97 mM). Significant higher gallbladder volumes of the patient groups compared to the CON group (PSC/CON: 66.3 ± 15.8 mL vs. 20.9 ± 2.2 mL, PBC/CON: 49.8 ± 18.2 mL vs. 20.9 ± 2.2 mL). DATA CONCLUSION: This study demonstrated the application of a 31 P-MRSI protocol for the quantification of PtdC in the human gallbladder at 7 T. Observed differences in PtdC concentration suggest that this metabolite could serve as a biomarker for specific hepatobiliary disorders. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue.

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as 'chemo fog'. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially permit taking these treatment side effects into account, paving the way towards a more personalized treatment planning.This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side effects of cancer therapy in normal-appearing brain tissue. Seventy studies were obtained from the MEDLINE and Web of Science databases. Studies reporting changes in normal-appearing brain tissue using MRI, PET, or SPECT quantitative biomarkers, related to radio-, chemo-, immuno-, or hormone therapy for any kind of solid, cystic, or liquid tumor were included. The main findings of the reviewed studies were summarized, providing also the risk of bias of each study assessed using a modified QUADAS-2 tool. For each imaging method, this review provides the methodological background, and the benefits and shortcomings of each method from the imaging perspective. Finally, a set of recommendations is proposed to support future research.

Absolute Quantification of Phosphor-Containing Metabolites in the Liver Using 31 P MRSI and Hepatic Lipid Volume Correction at 7T Suggests No Dependence on Body Mass Index or Age.

BACKGROUND: Hepatic disorders are often associated with changes in the concentration of phosphorus-31 (31 P) metabolites. Absolute quantification offers a way to assess those metabolites directly but introduces obstacles, especially at higher field strengths (B0 ≥ 7T). PURPOSE: To introduce a feasible method for in vivo absolute quantification of hepatic 31 P metabolites and assess its clinical value by probing differences related to volunteers' age and body mass index (BMI). STUDY TYPE: Prospective cohort. SUBJECTS/PHANTOMS: Four healthy volunteers included in the reproducibility study and 19 healthy subjects arranged into three subgroups according to BMI and age. Phantoms containing 31 P solution for correction and validation. FIELD STRENGTH/SEQUENCE: Phase-encoded 3D pulse-acquire chemical shift imaging for 31 P and single-volume 1 H spectroscopy to assess the hepatocellular lipid content at 7T. ASSESSMENT: A phantom replacement method was used. Spectra located in the liver with sufficient signal-to-noise ratio and no contamination from muscle tissue, were used to calculate following metabolite concentrations: adenosine triphosphates (γ- and α-ATP); glycerophosphocholine (GPC); glycerophosphoethanolamine (GPE); inorganic phosphate (Pi ); phosphocholine (PC); phosphoethanolamine (PE); uridine diphosphate-glucose (UDPG); nicotinamide adenine dinucleotide-phosphate (NADH); and phosphatidylcholine (PtdC). Correction for hepatic lipid volume fraction (HLVF) was performed. STATISTICAL TESTS: Differences assessed by analysis of variance with Bonferroni correction for multiple comparison and with a Student's t-test when appropriate. RESULTS: The concentrations for the young lean group corrected for HLVF were 2.56 ± 0.10 mM for γ-ATP (mean ± standard deviation), α-ATP: 2.42 ± 0.15 mM, GPC: 3.31 ± 0.27 mM, GPE: 3.38 ± 0.87 mM, Pi : 1.42 ± 0.20 mM, PC: 1.47 ± 0.24 mM, PE: 1.61 ± 0.20 mM, UDPG: 0.74 ± 0.17 mM, NADH: 1.21 ± 0.38 mM, and PtdC: 0.43 ± 0.10 mM. Differences found in ATP levels between lean and overweight volunteers vanished after HLVF correction. DATA CONCLUSION: Exploiting the excellent spectral resolution at 7T and using the phantom replacement method, we were able to quantify up to 10 31 P-containing hepatic metabolites. The combination of 31 P magnetic resonance spectroscopy imaging data acquisition and HLVF correction was not able to show a possible dependence of 31 P metabolite concentrations on BMI or age, in the small healthy population used in this study. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:597-607.

Feasibility and repeatability of localized (31) P-MRS four-angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T.

Phosphorus ((31) P) MRS, combined with saturation transfer (ST), provides non-invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T1 (app) measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four-angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra-high-field MR system, to accelerate the measurement of both Pi -to-ATP and PCr-to-ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth-resolved surface coil MRS (DRESS)-localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, Pi -to-ATP and PCr-to-ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS-localized FAST method. The repeatability of PCr-to-ATP and Pi -to-ATP exchange rate constants, determined by the slab-selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr-to-ATP metabolic flux decreased (from FCK = 8.21 ± 1.15 mM s(-1) to FCK = 3.86 ± 1.38 mM s(-1) ) and the Pi -to-ATP flux increased (from FATP = 0.43 ± 0.14 mM s(-1) to FATP = 0.74 ± 0.13 mM s(-1) ). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS-localized FAST method at 7 T.

Dixon imaging-based partial volume correction improves quantification of choline detected by breast 3D-MRSI.

OBJECTIVES: Our aim was to develop a partial volume (PV) correction method of choline (Cho) signals detected by breast 3D-magnetic resonance spectroscopic imaging (3D-MRSI), using information from water/fat-Dixon MRI. METHODS: Following institutional review board approval, five breast cancer patients were measured at 3 T. 3D-MRSI (1 cm(3) resolution, duration ~11 min) and Dixon MRI (1 mm(3), ~2 min) were measured in vivo and in phantoms. Glandular/lesion tissue was segmented from water/fat-Dixon MRI and transformed to match the resolution of 3D-MRSI. The resulting PV values were used to correct Cho signals. Our method was validated on a two-compartment phantom (choline/water and oil). PV values were correlated with the spectroscopic water signal. Cho signal variability, caused by partial-water/fat content, was tested in 3D-MRSI voxels located in/near malignant lesions. RESULTS: Phantom measurements showed good correlation (r = 0.99) with quantified 3D-MRSI water signals, and better homogeneity after correction. The dependence of the quantified Cho signal on the water/fat voxel composition was significantly (p < 0.05) reduced using Dixon MRI-based PV correction, compared to the original uncorrected data (1.60-fold to 3.12-fold) in patients. CONCLUSIONS: The proposed method allows quantification of the Cho signal in glandular/lesion tissue independent of water/fat composition in breast 3D-MRSI. This can improve the reproducibility of breast 3D-MRSI, particularly important for therapy monitoring.

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.

In vivo (31)P magnetic resonance spectroscopy of the human liver at 7 T: an initial experience.

Phosphorus ((31) P) MRS is a powerful tool for the non-invasive investigation of human liver metabolism. Four in vivo (31) P localization approaches (single voxel image selected in vivo spectroscopy (3D-ISIS), slab selective 1D-ISIS, 2D chemical shift imaging (CSI), and 3D-CSI) with different voxel volumes and acquisition times were demonstrated in nine healthy volunteers. Localization techniques provided comparable signal-to-noise ratios normalized for voxel volume and acquisition time differences, Cramer-Rao lower bounds (8.7 ± 3.3%1D-ISIS , 7.6 ± 2.5%3D-ISIS , 8.6 ± 4.2%2D-CSI , 10.3 ± 2.7%3D-CSI ), and linewidths (50 ± 24 Hz1D-ISIS , 34 ± 10 Hz3D-ISIS , 33 ± 10 Hz2D-CSI , 34 ± 11 Hz3D-CSI ). Longitudinal (T1 ) relaxation times of human liver metabolites at 7 T were assessed by 1D-ISIS inversion recovery in the same volunteers (n = 9). T1 relaxation times of hepatic (31) P metabolites at 7 T were the following: phosphorylethanolamine - 4.41 ± 1.55 s; phosphorylcholine - 3.74 ± 1.31 s; inorganic phosphate - 0.70 ± 0.33 s; glycerol 3-phosphorylethanolamine - 6.19 ± 0.91 s; glycerol 3-phosphorylcholine - 5.94 ± 0.73 s; γ-adenosine triphosphate (ATP) - 0.50 ± 0.08 s; α-ATP - 0.46 ± 0.07 s; ß-ATP - 0.56 ± 0.07 s. The improved spectral resolution at 7 T enabled separation of resonances in the phosphomonoester and phosphodiester spectral region as well as nicotinamide adenine dinucleotide and uridine diphosphoglucose signals. An additional resonance at 2.06 ppm previously assigned to phosphoenolpyruvate or phosphatidylcholine is also detectable. These are the first (31) P metabolite relaxation time measurements at 7 T in human liver, and they will help in the exploration of new, exciting questions in metabolic research with 7 T MR.

Dynamic contrast-enhanced magnetic resonance imaging of breast tumors at 3 and 7 T: a comparison.

OBJECTIVES: The objective of this study was to compare the image quality, contrast enhancement behavior, and diagnostic value of bilateral 3-dimensional dynamic contrast-enhanced breast magnetic resonance imaging (MRI), with high spatial and temporal resolution, at 3 and 7 T, in the same patient group. MATERIALS AND METHODS: Twenty-four consecutive patients (mean [SD] age, 57 [17] years) were included in this prospective institutional review board-approved study. Written informed consent was obtained from all patients. T1-weighted 3-dimensional sequences (time-resolved angiography with stochastic trajectories) were optimized at 3 and 7 T, with high temporal (both 14 seconds) and spatial resolution (1.1 × 1.1 × 1.1 mm [3 T], 0.7 × 0.7 × 0.7 mm [7 T]): echo time/repetition time, 2.84/6.01 milliseconds (3 T) and 2.5/4.75 milliseconds (7 T); acquisition time, 9 minutes (3 T/7 T). Dotarem (gadoterate meglumine, Guerbet, Roissy CdG, France) contrast agent was injected intravenously as a bolus (0.2 mL/kg of body weight) after 3 baseline images. The images were rated according to breast imaging-reporting and data system by 2 radiologists in consensus. Signal-to-noise ratio and average enhancement ratios were measured quantitatively by means of region of interest analysis. In addition, B1 mapping was done in the same 5 healthy subjects at both field strengths. RESULTS: Twenty-eight enhancing lesions were detected in the 24 patients at both field strengths (16 malignant, 12 benign). At 7 T, higher contrast than that at 3 T and good image quality were achieved. With the high spatial isotropic resolution of 0.7 mm at 7 T, images with more detailed information could be acquired when compared with those acquired at 3 T. Sensitivity was 93.75% and 100%, at 3 and 7 T, respectively. Specificity was 91.67% at both field strengths. The signal-to-noise ratio at both field strengths was comparable, but at 7 T, the spatial resolution was 3.2-times higher than that at 3 T. A signal-to-noise ratio decrease toward prepectoral breast regions due to B1 inhomogeneities was observed at both field strengths but was stronger at 7 T (51%) than at 3 T (19%)(P = 0.0002). At 7 T, B1+ dropped by 20.7% and 32.8% in the prepectoral and lateral region of the breast in healthy subjects. CONCLUSIONS: Our comparison study shows that 7-T DCE-MRI provides simultaneous high temporal and spatial resolution that is significantly improved compared with lower field strengths, but further technical improvements are necessary to overcome B1 inhomogeneity problems at 7 T to fully unfold the potential of breast MRI at 7 T.

Application of localized ³¹P MRS saturation transfer at 7 T for measurement of ATP metabolism in the liver: reproducibility and initial clinical application in patients with non-alcoholic fatty liver disease.

OBJECTIVES: Saturation transfer (ST) phosphorus MR spectroscopy ((31)P MRS) enables in vivo insight into energy metabolism and thus could identify liver conditions currently diagnosed only by biopsy. This study assesses the reproducibility of the localized (31)P MRS ST in liver at 7 T and tests its potential for noninvasive differentiation of non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH). METHODS: After the ethics committee approval, reproducibility of the localized (31)P MRS ST at 7 T and the biological variation of acquired hepato-metabolic parameters were assessed in healthy volunteers. Subsequently, 16 suspected NAFL/NASH patients underwent MRS measurements and diagnostic liver biopsy. The Pi-to-ATP exchange parameters were compared between the groups by a Mann-Whitney U test and related to the liver fat content estimated by a single-voxel proton ((1)H) MRS, measured at 3 T. RESULTS: The mean exchange rate constant (k) in healthy volunteers was 0.31 ± 0.03 s(-1) with a coefficient of variation of 9.0 %. Significantly lower exchange rates (p < 0.01) were found in NASH patients (k = 0.17 ± 0.04 s(-1)) when compared to healthy volunteers, and NAFL patients (k = 0.30 ± 0.05 s(-1)). Significant correlation was found between the k value and the liver fat content (r = 0.824, p < 0.01). CONCLUSIONS: Our data suggest that the (31)P MRS ST technique provides a tool for gaining insight into hepatic ATP metabolism and could contribute to the differentiation of NAFL and NASH. KEY POINTS: • 1D localized (31) P MRS saturation transfer in the liver is reproducible at 7 T • NASH patients have decreased hepatic Pi-to-ATP exchange rate • In this study, hepatic metabolic activity correlates with liver fat content.

One-dimensional image-selected in vivo spectroscopy localized phosphorus saturation transfer at 7T.

PURPOSE: To evaluate the feasibility of a one-dimensional image-selected in vivo spectroscopy (1D-ISIS) saturation transfer (ST) sequence at 7T for localized in vivo measurements of energy metabolism in different tissues in clinically reasonable examination times. METHODS: The performance of a gradient offset independent adiabacity-based 1D-ISIS localization was tested on phantom and the localized ST sequence was compared with the nonlocalized version in vivo. We performed localized measurements of basal metabolism of human liver and different muscle groups of the calf. Localized ST experiments took 15-25 minutes. RESULTS: The selectivity of the 1D-ISIS sequence was 81.63% and the outer volume suppression was 97.57%. The ST parameters acquired with the 1D-ISIS sequence and with the nonlocalized acquisition in the muscle were not statistically different. The forward rate constants for phosphocreatine (PCr)-adenosine triphosphate (ATP) and inorganic phosphate (Pi)-ATP exchange reactions were measured in the soleus (kCK = 0.30 ± 0.06 s(-1) and kATP = 0.11 ± 0.02 s(-1) , respectively) and in the medial gastrocnemius (kCK = 0.27 ± 0.06 s(-1) and kATP = 0.09 ± 0.03s(-1) , respectively) in 15 minutes per muscle group. The corresponding fluxes were FCK = 6.26 ± 1.28 µmol/g/s, FATP = 0.22 ± 0.05 µmol/g/s and FCK = 6.29 ± 1.66 µmol/g/s, FATP = 0.21 ± 0.07 µmol/g/s, for soleus and gastrocnemius, respectively. The hepatic ATP synthesis measurement was feasible in 24 minutes. CONCLUSION: The fast assessment of PCr-ATP and Pi-ATP exchange rates at 7T makes the 1D-ISIS ST sequence a promising tool for examining local resting-state metabolism in clinically acceptable measurement times.

Interrelation of 31P-MRS metabolism measurements in resting and exercised quadriceps muscle of overweight-to-obese sedentary individuals.

Phosphorus magnetic resonance spectroscopy ((31)P-MRS) enables the non-invasive evaluation of muscle metabolism. Resting Pi-to-ATP flux can be assessed through magnetization transfer (MT) techniques, and maximal oxidative flux (Q(max)) can be calculated by monitoring of phosphocreatine (PCr) recovery after exercise. In this study, the muscle metabolism parameters of 13 overweight-to-obese sedentary individuals were measured with both MT and dynamic PCr recovery measurements, and the interrelation between these measurements was investigated. In the dynamic experiments, knee extensions were performed at a workload of 30% of maximal voluntary capacity, and the consecutive PCr recovery was measured in a quadriceps muscle with a time resolution of 2 s with non-localized (31)P-MRS at 3 T. Resting skeletal muscle metabolism was assessed through MT measurements of the same muscle group at 7 T. Significant linear correlations between the Q(max) and the MT parameters k(ATP) (r = 0.77, P = 0.002) and F(ATP) (r = 0.62, P = 0.023) were found in the study population. This would imply that the MT technique can possibly be used as an alternative method to assess muscle metabolism when necessary (e.g. in individuals after stroke or in uncooperative patients).

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.

Readout-segmented echo-planar imaging improves the diagnostic performance of diffusion-weighted MR breast examinations at 3.0 T.

PURPOSE: To qualitatively and quantitatively compare the diagnostic value of diffusion-weighted (DW) magnetic resonance (MR) imaging based on standard single-shot echo-planar imaging and readout-segmented echo-planar imaging in patients with breast cancer at 3.0 T. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Forty-seven patients with 49 histopathologically verified lesions were included in this study. In all patients, DW imaging, with single-shot echo-planar imaging and readout-segmented echo-planar imaging with comparable imaging parameters, was performed with a 3.0-T MR imager. Two independent readers visually assessed image quality and lesion conspicuity, and image properties (ie, signal-to-noise ratio, contrast, geometric distortions) were quantified. Regions of interest were drawn in all lesions (28 malignant, 21 benign) and in the normal breast parenchyma to investigate differences in apparent diffusion coefficient (ADC). Diagnostic accuracy was calculated on the basis of an ADC threshold of 1.25 × 10(-3) mm(2)/sec. RESULTS: Each reader found a higher diagnostic accuracy for readout-segmented (96%) than for single-shot (90%) echo-planar imaging. The area under the curve for readout-segmented echo-planar imaging (0.981) was significantly larger than for single-shot echo-planar imaging (0.867) (P = .026). There was no significant difference in the ADC obtained by using either DW imaging method. Lesion conspicuity and image quality of readout-segmented echo-planar imaging were rated superior to those of single-shot echo-planar imaging (P < .001). Readout-segmented echo-planar imaging reduced geometric distortions by a factor of three. CONCLUSION: DW imaging based on readout-segmented echo-planar imaging provided significantly higher image quality and lesion conspicuity than single-shot echo-planar imaging by reducing geometric distortions, image blurring, and artifact level with a clinical high-field-strength MR imager. Thereby, readout-segmented echo-planar imaging reached a higher diagnostic accuracy for the differentiation of benign and malignant breast lesions.

A single nucleotide polymorphism associates with the response of muscle ATP synthesis to long-term exercise training in relatives of type 2 diabetic humans.

OBJECTIVE: Myocellular ATP synthesis (fATP) associates with insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Short-term endurance training can modify their fATP and insulin sensitivity. This study examines the effects of moderate long-term exercise using endurance or resistance training in this cohort. RESEARCH DESIGN AND METHODS: A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (VO(2)) during incremental tests and from maximal torque of knee flexors (MaxT(flex)) and extensors (MaxT(ext)) using isokinetic dynamometry. fATP and ectopic lipids were measured with (1)H/(31)P magnetic resonance spectroscopy. RESULTS: Endurance training increased power output and VO(2) by 44 and 30%, respectively (both P < 0.001), whereas resistance training increased MaxT(ext) and MaxT(flex) by 23 and 40%, respectively (both P < 0.001). Across all groups, insulin sensitivity (382 ± 90 vs. 389 ± 40 mL · min(-1) · m(-2)) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 ± 2.3 to 11.9 ± 2.4 µmol · mL(-1) · m(-1) (P < 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I. CONCLUSIONS: Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.

Three-dimensional proton MR spectroscopic imaging at 3 T for the differentiation of benign and malignant breast lesions.

PURPOSE: To evaluate the diagnostic accuracy of quantitative, three-dimensional (3D) magnetic resonance (MR) spectroscopic imaging at 3 T for the differentiation of benign and malignant breast lesions, on the basis of choline (Cho) signal-to-noise ratio (SNR) threshold levels, in a clinically feasible measurement time. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained from all subjects. Fifty female patients (mean age, 50 years; age range, 25-82 years) with mammographic or ultrasonographic (US) abnormalities were successfully examined in the prone position with a 3-T MR system by using a dedicated breast coil. Lesions were verified by either histopathologic examination or follow-up of at least 24 months. For 3D MR spectroscopic imaging, a point-resolved spectroscopic sequence (repetition time msec/echo time msec, 750/145; field of view, 12 × 12 × 12 cm(3); matrix size, 12 × 12 × 12, interpolated to 16 × 16 × 16; acquisition time, 11 minutes 17 seconds) was used. The maximum Cho SNR was assessed in all lesions and correlated with the histopathologic results. RESULTS: Thirty-two malignant and 12 benign lesions were confirmed in 43 patients with histopathologic examination. Seven patients without biopsy underwent imaging follow-up. In 31 of 32 (97%) malignant and 10 of 19 (53%) benign lesions, Cho was detected. The median Cho SNR in malignant lesions was 5.7, compared with 2.0 in benign lesions. With a Cho SNR threshold level of 2.6, 3D MR spectroscopic imaging provided a sensitivity of 97% and a specificity of 84% for the differentiation of benign and malignant breast lesions. CONCLUSION: At 3T, 3D MR spectroscopic imaging yields high diagnostic sensitivity and specificity for discrimination of benign and malignant breast lesions within reasonable measurement times. This technique allows the study of heterogeneous and multicentric breast tumors and simplifies acquisition planning.

Liver ATP synthesis is lower and relates to insulin sensitivity in patients with type 2 diabetes.

OBJECTIVE: Steatosis associates with insulin resistance and may even predict type 2 diabetes and cardiovascular complications. Because muscular insulin resistance relates to myocellular fat deposition and disturbed energy metabolism, we hypothesized that reduced hepatic ATP turnover (fATP) underlies insulin resistance and elevated hepatocellular lipid (HCL) contents. RESEARCH DESIGN AND METHODS: We measured hepatic fATP using (31)P magnetic resonance spectroscopy in patients with type 2 diabetes and age- and body mass-matched controls. Peripheral (M and M/I) and hepatic (suppression of endogenous glucose production) insulin sensitivity were assessed with euglycemic-hyperinsulinemic clamps. RESULTS: Diabetic individuals had 29% and 28% lower peripheral and hepatic insulin sensitivity as well as 42% reduced fATP than controls. After adjusting for HCL, fATP correlated positively with peripheral and hepatic insulin sensitivity but negatively with waist circumference, BMI, and fasting plasma glucose. Multiple regression analysis identified waist circumference as an independent predictor of fATP and inorganic phosphate (P(I)) concentrations, explaining 65% (P = 0.001) and 56% (P = 0.003) of the variations. Hepatocellular P(I) primarily determined the alterations in fATP. CONCLUSIONS: In patients with type 2 diabetes, insulin resistance relates to perturbed hepatic energy metabolism, which is at least partly accounted for by fat depots.

Vascular function in obese children with non-alcoholic fatty liver disease.

OBJECTIVE: To test whether obese children with non-alcoholic fatty liver disease have impaired vascular function compared with obese children with normal liver fat content. METHODS: Obese children (n = 28, 16 males, mean age 10.9 ± 0.7 years, body mass index [BMI] 31.9 ± 4.5 kg/m(2)) with normal (HCLn) and increased hepatocellular lipid content (HCLi, 2.6 ± 0.8 vs. 12.4 ± 8.2%) were recruited, outcome measures being flow-mediated dilation of the brachial artery [FMD] measured by ultrasound, biochemical markers of inflammation (hs-CRP, hs-IL6) and cell adhesion molecules [CAMs], hepatocellular lipids, visceral and subcutaneous fat quantified by nuclear magnetic resonance spectroscopy and imaging. RESULTS: HCLi and HCLn groups showed no significant differences in terms of age, gender, BMI, waist circumference and subcutaneous fat. Subjects in the HCLi group had significantly higher amounts of visceral fat and higher fasting glucose, insulin and triglyceride, but lower adiponectin levels and were more insulin resistant than their HCLn controls. Hepatic fat fraction (HFF) correlated positively with fasting plasma glucose, HOMA-IR, adiponectin, visceral fat, negatively with WBISI independent of BMI. HFF was not associated with subcutaneous fat, fasting insulin, FFA, HDL-C, TG, hs-CRP, hs-IL6, vCAM, iCAM, and FMD. HCLi patients had significantly higher serum levels of hs-CRP and hs-IL6 than HCLn controls. FMD and serum levels of vCAM and iCAM were comparable between groups. CONCLUSIONS: Obese children with simple steatosis rather than steatohepatitis seem to have intact vascular function. Further studies in obese children with different grades of NAFLD are warranted to elucidate the role of fatty liver as a marker of risk for future cardiovascular events.