Decreased Compressional Sound Velocity Is an Indicator for Compromised Bone Stiffness in X-Linked Hypophosphatemic Rickets (XLH)

Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia. Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (νFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean νFAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (-6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (-4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021). Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patients

Non-Water-Suppressed 1H MR Spectroscopy with Orientational Prior Knowledge Shows Potential for Separating Intra- and Extramyocellular Lipid Signals in Human Myocardium

Conditions such as type II diabetes are linked with elevated lipid levels in the heart, and significantly increased risk of heart failure; however, metabolic processes underlying the development of cardiac disease in type II diabetes are not fully understood. Here we present a non-invasive method for in vivo investigation of cardiac lipid metabolism: namely, IVS-McPRESS. This technique uses metabolite-cycled, non-water suppressed 1H cardiac magnetic resonance spectroscopy with prospective and retrospective motion correction. High-quality IVS-McPRESS data acquired from healthy volunteers allowed us to investigate the frequency shift of extramyocellular lipid signals, which depends on the myocardial fibre orientation. Assuming consistent voxel positioning relative to myofibres, the myofibre angle with the magnetic field was derived from the voxel orientation. For separation and individual analysis of intra- and extramyocellular lipid signals, the angle myocardial fibres in the spectroscopy voxel take with the magnetic field should be within ±24.5°. Metabolite and lipid concentrations were analysed with respect to BMI. Significant correlations between BMI and unsaturated fatty acids in intramyocellular lipids, and methylene groups in extramyocellular lipids were found. The proposed IVS-McPRESS technique enables non-invasive investigation of cardiac lipid metabolism and may thus be a useful tool to study healthy and pathological conditions

Reduced NAA-Levels in the NAWM of Patients with MS Is a Feature of Progression. A Study with Quantitative Magnetic Resonance Spectroscopy at 3 Tesla

Reduced N-acetyl-aspartate (NAA) levels in magnetic resonance spectroscopy (MRS) may visualize axonal damage even in the normal appearing white matter (NAWM). Demyelination and axonal degeneration are a hallmark in multiple sclerosis (MS).To define the extent of axonal degeneration in the NAWM in the remote from focal lesions in patients with relapsing-remitting (RRMS) and secondary progressive MS (SPMS).H-MR-chemical shift imaging (TR = 1500ms, TE = 135ms, nominal resolution 1ccm) operating at 3Tesla to assess the metabolic pattern in the fronto–parietal NAWM. Ratios of NAA to creatine (Cr) and choline (Cho) and absolute concentrations of the metabolites in the NAWM were measured in each voxel matching exclusively white matter on the anatomical T2 weighted MR images.No significant difference of absolute concentrations for NAA, Cr and Cho or metabolite ratios were found between RRMS and controls. In SPMS, the NAA/Cr ratio and absolute concentrations for NAA and Cr were significantly reduced compared to RRMS and to controls.In our study SPMS patients, but not RRMS patients were characterized by low NAA levels. Reduced NAA-levels in the NAWM of patients with MS is a feature of progression

In-vivo 31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism

In addition to direct assessment of high energy phosphorus containing metabolite content within tissues, phosphorus magnetic resonance spectroscopy (31P-MRS) provides options to measure phospholipid metabolites and cellular pH, as well as the kinetics of chemical reactions of energy metabolism in vivo. Even though the great potential of 31P-MR was recognized over 30 years ago, modern MR systems, as well as new, dedicated hardware and measurement techniques provide further opportunities for research of human biochemistry. This paper presents a methodological overview of the 31P-MR techniques that can be used for basic, physiological, or clinical research of human skeletal muscle and liver in vivo. Practical issues of 31P-MRS experiments and examples of potential applications are also provided. As signal localization is essential for liver 31P-MRS and is important for dynamic muscle examinations as well, typical localization strategies for 31P-MR are also described

In-vivo 31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism

In addition to direct assessment of high energy phosphorus containing metabolite content within tissues, phosphorus magnetic resonance spectroscopy (31P-MRS) provides options to measure phospholipid metabolites and cellular pH, as well as the kinetics of chemical reactions of energy metabolism in vivo. Even though the great potential of 31P-MR was recognized over 30 years ago, modern MR systems, as well as new, dedicated hardware and measurement techniques provide further opportunities for research of human biochemistry. This paper presents a methodological overview of the 31P-MR techniques that can be used for basic, physiological, or clinical research of human skeletal muscle and liver in vivo. Practical issues of 31P-MRS experiments and examples of potential applications are also provided. As signal localization is essential for liver 31P-MRS and is important for dynamic muscle examinations as well, typical localization strategies for 31P-MR are also described

On conserved quantities for the Schwarzschild black hole in teleparallel gravity

We examine various methods of constructing conserved quantities in the Teleparallel Equivalent of General Relativity (TEGR). We demonstrate that in the covariant formulation the preferred method are the Noether charges that are true invariant quantities. The Noether charges depend on the vector field ξ and we consider two different options where ξ is chosen as either a Killing vector or a four-velocity of the observer. We discuss the physical meaning of each choice on the example of the Schwarzschild solution in different frames: static, freely falling Lemaitre frame, and a newly obtained generalised freely falling frame with an arbitrary initial velocity. We also demonstrate how to determine an inertial spin connection for various tetrads used in our calculations, and find a certain ambiguity in the “switching-off” gravity method where different tetrads can share the same inertial spin connection

On the Schwarzschild solution in TEGR

Conserved currents, superpotentials and charges for the Schwarzschild black hole in the Teleparallel Equivalent of General Relativity (TEGR) are constructed. We work in the covariant formalism and use the Noether machinery to construct conserved quantities that are covariant/invariant with respect to both coordinate and local Lorentz transformations. The constructed quantities depend on the vector field ? and we consider two different possibilities, when ? is chosen as either a timelike Killing vector or a four-velocity of an observer. We analyze and discuss the physical meaning of each choice in different frames: static and freely falling Lemaitre frame. Moreover, a new generalized free-falling frame with an arbitrary initial velocity at infinity is introduced. We derive the inertial spin connection for various tetrads in different frames and find that the “switching-off” gravity method leads to ambiguities

Feasibility and repeatability of localized 3^31^1P-MRS four-angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T

Phosphorus (31P) MRS, combined with saturation transfer (ST), provides non-invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T1app 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.</p