64 slice MDCT generally underestimates coronary calcium scores as compared to EBT: a phantom study.

The objective of our study was the determination of the influence of the sequential and spiral acquisition modes on the concordance and deviation of the calcium score on 64-slice multi-detector computed tomography (MDCT) scanners in comparison to electron beam tomography (EBT) as the gold standard. Our methods and materials were an anthropomorphic cardio CT phantom with different calcium inserts scanned in sequential and spiral acquisition modes on three identical 64-slice MDCT scanners of manufacturer A and on three identical 64-slice MDCT scanners of manufacturer B and on an EBT system. Every scan was repeated 30 times with and 15 times without a small random variation in the phantom position for both sequential and spiral modes. Significant differences were observed between EBT and 64-slice MDCT data for all inserts, both acquisition modes, and both manufacturers of MDCT systems. High regression coefficients (0.90-0.98) were found between the EBT and 64-slice MDCT data for both scoring methods and both systems with high correlation coefficients (R2>0.94). System A showed more significant differences between spiral and sequential mode than system B. Almost no differences were observed in scanners of the same manufacturer for the Agatston score and no differences for the Volume score. The deviations of the Agatston and Volume scores showed regression dependencies approximately equal to the square root of the absolute score. The Agatston and Volume scores obtained with 64-slice MDCT imaging are highly correlated with EBT-obtained scores but are significantly underestimated (-10% to -2%) for both sequential and spiral acquisition modes. System B is more independent of acquisition mode to calcium score than system A. The Volume score shows no intramanufacturer dependency and its use is advocated versus the Agatston score. Using the same cut points for MDCT-based calcium scores as for EBT-based calcium scores can result in classifying individuals into a too low risk category. System information and scanprotocol is therefore needed for every calcium score procedure to ensure a correct clinical interpretation of the obtained calcium score results.

Sensitivity-enhanced 13C MR spectroscopy of the human brain at 3 Tesla.

A new coil design for sensitivity-enhanced 13C MR spectroscopy (MRS) of the human brain is presented. The design includes a quadrature transmit/receive head coil optimized for 13C MR sensitivity. Loss-less blocking circuits inside the coil conductors allow this coil to be used inside a homogeneous circularly polarized 1H B1 field for 1H decoupled 13C MRS. A quadrature 1H birdcage coil optimized for minimal local RF heating makes broadband 1H decoupling in the entire human brain possible at 3 Tesla while remaining well within international safety guidelines for RF absorption. Apart from a substantial increase in sensitivity compared to conventional small linear coils, the quadrature 13C coil combined with the quadrature 1H birdcage coil allows efficient cross polarization (CP) in the brain, resulting in an additional 3.5-fold sensitivity improvement compared to direct 13C measurements without nuclear Overhauser enhancement (NOE) or polarization transfer. Combined with the gain in power efficiency, this setup allows broadband 1H to 13C CP over large areas of the brain. Clear 13C resonances from glutamate (Glu), glutamine (Gln), aspartate (Asp), lactate (Lac), and gamma-aminobutyrate (GABA) carbon spins in the human brain demonstrate the quality of 13C MR spectra obtained in vivo with this coil setup.

MRS assessment of glutamate clearance in a novel masticatory muscle pain model.

The injection of 1.0 M glutamate into the masseter (jaw-closer) muscle results in a short period of muscle pain (5-10 min) and a prolonged period of mechanical sensitization (> 30 min). It is unclear, however, whether there is a temporal relationship between intramuscular glutamate concentration and either muscle pain or mechanical sensitization. In the present study, (1)H MRS and electrophysiological recording of masticatory muscle nerve fibers were performed in order to monitor glutamate clearance and nerve fiber activity, respectively, after injection of glutamate into rat masticatory muscles. Glutamate signal amplitude was found to decay rapidly (half-life t 1/2 = 108 +/- 42 s), and became indistinguishable from the baseline 10 min after the injection. Glutamate-evoked nerve fiber activity was also found to decay rapidly (t 1/2 = 76 +/- 28 s). These results suggest that glutamate clearance correlates well with the time course of glutamate-evoked muscle pain fiber discharge.

Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain: a quantitative in vivo 1H and 31P magnetic resonance study.

Creatine kinase (CK)-catalysed ATP-phosphocreatine (PCr) exchange is considered to play a key role in energy homeostasis of the brain. This study assessed the metabolic and anatomical consequences of partial or complete depletion of this system in transgenic mice without cytosolic B-CK (B-CK-/-), mitochondrial ubiquitous CK (UbCKmit-/-), or both isoenzymes (CK -/-), using non-invasive quantitative magnetic resonance (MR) imaging and spectroscopy. MR imaging revealed an increase in ventricle size in a subset of B-CK-/- mice, but not in animals with UbCKmit or compound CK mutations. Mice lacking single CK isoenzymes had normal levels of high-energy metabolites and tissue pH. In the brains of CK double knockouts pH and ATP and Pi levels were also normal, even though PCr had become completely undetectable. Moreover, a 20-30% decrease was observed in the level of total creatine and a similar increase in the level of neuronal N-acetyl-aspartate compounds. Although CKs themselves are not evenly distributed throughout the CNS, these alterations were uniform and concordant across different brain regions. Changes in myo-inositol and glutamate peaks did appear to be mutation type and brain area specific. Our results challenge current models for the biological significance of the PCr-CK energy system and suggest a multifaceted role for creatine in the brain.

Presence of (phospho)creatine in developing and adult skeletal muscle of mice without mitochondrial and cytosolic muscle creatine kinase isoforms.

We assessed the relationship between phosphocreatine (PCr) and creatine (Cr) content and creatine kinase (CK) activity in skeletal muscle of mice. The PCr and total Cr (tCr) concentrations, as well as CK activity, in hindlimb muscles of mice, with or without the cytosolic and mitochondrial isoforms of muscle creatine kinase (wild-type or CK--/-- mice), were determined by in vivo magnetic resonance (MR) spectroscopy and by biochemical means during postnatal growth and adulthood. In wild-type muscle the [tCr], PCr/ATP ratio and CK activity increased rapidly in the first 4-7 weeks. Remarkably, CK--/-- mice showed a similar increase in the PCr/ATP ratio during the first month in the presence of only minor brain-type BB-CK activity. Uptake of Cr in muscle was seemingly unrelated to CK activity as tCr increased in the same way in the muscles of both mouse types. At older ages the PCr/ATP ratio decreased in CK--/-- muscles, in contrast to wild-type where it still slowly increased, whereas [tCr] was similar for muscle of both mouse types. Using a new in vivo MR approach with application of [4-13C]Cr, a lower PCr/tCr ratio was also observed in CK--/-- muscle. From these data it follows that in vivo global ATP levels at rest are similar in the presence or absence of CK. Although Cr could still be converted to PCr in mature CK--/-- muscle, the immediate availability of PCr decreased, and PCr became partly inconvertible at older ages. Apparently, catalysis of the CK reaction by BB-CK, although significant in muscles of newborn mice, gradually declines to very low levels in adulthood. Part or all of this BB-CK may arise from satellite cells fusing with myotubes, a process that is most active during the first months of life. Finally, our observation that the MR and chemical assessment of muscle [tCr] and PCr/tCr ratio were similar for all mice does not support the existence of a significant MR-invisible or immobile pool of Cr, with a role for CK in this phenomenon.