23Na MRI of human skeletal muscle using long inversion recovery pulses.

23Na inversion recovery (IR) imaging allows for a weighting toward intracellular sodium in the human calf muscle and thus enables an improved analysis of pathophysiological changes of the muscular ion homeostasis. However, sodium signal-to-noise ratio (SNR) is low, especially when using IR sequences. 23Na has a nuclear spin of 3/2 and therefore experiences a strong electrical quadrupolar interaction. This results in very short relaxation times as well as in possible residual quadrupolar splitting. Consequently, relaxation effects during a radiofrequency pulse can no longer be neglected and even allow for increasing SNR as has previously been shown for human brain and knee. The aim of this work was to increase the SNR in 23Na IR imaging of the human calf muscle by using long inversion pulses instead of the usually applied short pulses. First, the influence of the inversion pulse length (1 to 20 ms) on the SNR as well as on image contrast was simulated for different model environments and verified by phantom measurements. Depending on the model environment (agarose 4% and 8%, xanthan 2% and 3%), SNR values increased by a factor of 1.15 up to 1.35, while NaCl solution was successfully suppressed. Thus, image contrast between the non-suppressed model compartments changes with IR pulse length. Finally, in vivo measurements of the human calf muscle of ten healthy volunteers were conducted at 3 Tesla. On average, a 1.4-fold increase in SNR could be achieved by increasing the inversion pulse length from 1 ms to 20 ms, leaving all other parameters - including the scan time - constant. This enables 23Na IR MRI with improved spatial resolution or reduced acquisition time.

Combined imaging biomarkers for therapy evaluation in glioblastoma multiforme: correlating sodium MRI and F-18 FLT PET on a voxel-wise basis.

We evaluate novel magnetic resonance imaging (MRI) and positron emission tomography (PET) quantitative imaging biomarkers and associated multimodality, serial-time-point analysis methodologies, with the ultimate aim of providing clinically feasible, predictive measures for early assessment of response to cancer therapy. A focus of this work is method development and an investigation of the relationship between the information content of the two modalities. Imaging studies were conducted on subjects who were enrolled in glioblastoma multiforme (GBM) therapeutic clinical trials. Data were acquired, analyzed and displayed using methods that could be adapted for clinical use. Subjects underwent dynamic [(18)F]fluorothymidine (F-18 FLT) PET, sodium ((23)Na) MRI and 3-T structural MRI scans at baseline (before initiation of therapy), at an early time point after beginning therapy and at a late follow-up time point after therapy. Sodium MRI and F-18 FLT PET images were registered to the structural MRI. F-18 FLT PET tracer distribution volumes and sodium MRI concentrations were calculated on a voxel-wise basis to address the heterogeneity of tumor physiology. Changes in, and differences between, these quantities as a function of scan timing were tracked. While both modalities independently show a change in tissue status as a function of scan time point, results illustrate that the two modalities may provide complementary information regarding tumor progression and response. Additionally, tumor status changes were found to vary in different regions of tumor. The degree to which these methods are useful for GBM therapy response assessment and particularly for differentiating true progression from pseudoprogression requires additional patient data and correlation of these imaging biomarker changes with clinical outcome.

Advanced MR methods at ultra-high field (7 Tesla) for clinical musculoskeletal applications.

OBJECTIVES: This article provides an overview of the initial clinical results of musculoskeletal studies performed at 7 Tesla, with special focus on sodium imaging, new techniques such as chemical exchange saturation transfer (CEST) and T2* imaging, and multinuclear MR spectroscopy. METHODS: Sodium imaging was clinically used at 7 T in the evaluation of patients after cartilage repair procedures because it enables the GAG content to be monitored over time. Sodium imaging and T2* mapping allow insights into the ultra-structural composition of the Achilles tendon and help detect early disease. Chemical exchange saturation transfer was, for the first time, successfully applied in the clinical set-up at 7 T in patients after cartilage repair surgery. The potential of phosphorus MR spectroscopy in muscle was demonstrated in a comparison study between 3 and 7 T, with higher spectral resolution and significantly shorter data acquisition times at 7 T. RESULTS: These initial clinical studies demonstrate the potential of ultra-high field MR at 7 T, with the advantage of significantly improved sensitivity for other nuclei, such as (23)Na (sodium) and (31)P (phosphorus). CONCLUSIONS: The application of non-proton imaging and spectroscopy provides new insights into normal and abnormal physiology of musculoskeletal tissues, particularly cartilage, tendons, and muscles. KEY POINTS : • 7 T magnetic resonance provides significantly improved sensitivity for ( 23 ) Na and ( 31 ) P. • Initial clinical studies have now demonstrated ultra-high field MR operating at 7 T. • 7 T provides new insights into normal and abnormal physiology of musculoskeletal tissues.

Quantitative model of NMR chemical shifts of 23Na+ induced by TmDOTP: applications in studies of Na+ transport in human erythrocytes.

The change in the NMR chemical shift of (23)Na(+) induced by the shift reagent TmDOTP was examined under various experimental conditions typical of cells, including changed Na(+), K(+), PO(4)(3-), and Ca(2+) concentrations, pH and temperature. A mathematical model was developed relating these factors to the observed chemical shift change relative to a capillary-sphere reference. This enabled cation concentrations to be deduced quantitatively from experimental chemical shifts, including those observed during biological time courses with cell suspensions containing TmDOTP DOTP, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylenephosphonate) [corrected]. The model was applied to a (23)Na NMR time course in which monensin, a sodium ionophore, was introduced to human erythrocytes, changing the concentration of cations which may bind TmDOTP, and also resulting in cell volume changes. Using the model with experimentally determined conditions, the chemical shift was predicted and closely followed the experimental values over time. In addition to the model, parameter fitting was achieved by calculating the likelihood distribution of parameters, and seeking the maximum likelihood with a Bayesian type of analysis.