Comparative evaluation of different modalities for measuring in vivo carnosine levels.

Carnosine is an endogenous di-peptide (ß-alanine -L- histidine) involved in maintaining tissue homeostasis. It is most abundant in skeletal muscle where its concentration has been determined in biopsy samples using tandem mass spectrometry (MS-MS). Carnosine levels can also be assessed in intact leg muscles by proton magnetic resonance spectroscopy (1H-MRS) or in blood and urine samples using mass spectrometry. Nevertheless, it remains uncertain how carnosine levels from these distinct compartments are correlated with each other when measured in the same individual. Furthermore, it is unclear which measurement modality might be most suitable for large-scale clinical studies. Hence, in 31 healthy volunteers, we assessed carnosine levels in skeletal muscle, via 1H-MRS, and in erythrocytes and urine by MS-MS. While muscle carnosine levels were higher in males (C2 peak, p = 0.010; C4 peak, p = 0.018), there was no sex-associated difference in urinary (p = 0.433) or erythrocyte (p = 0.858) levels. In a linear regression model adjusted for age, sex, race, and diet, there was a positive association between erythrocyte and urinary carnosine. However, no association was observed between 1H-MRS and erythrocytes or urinary measures. In the relationship between muscle versus urinary and erythrocyte measures, females had a positive association, while males did not show any association. We also found that 1H-MRS measures were highly sensitive to location of measurement. Thus, it is uncertain whether 1H-MRS can accurately and reliably predict endogenous carnosine levels. In contrast, urinary and erythrocyte carnosine measures may be stable and in greater synchrony, and given financial and logistical concerns, may be a feasible alternative for large-scale clinical studies.

ECG Gating Is More Precise Than Peripheral Pulse Gating When Quantifying Spinal CSF Pulsations Using Phase Contrast Cine MRI.

PURPOSE: To compare accuracy of spinal cerebrospinal fluid (CSF) pulsatile flow measurements at cervical, thoracic, and lumbar levels using Phase Contrast Cine MRI (PCCMRI) with retrospective electrocardiogram (recg) vs. retrospective peripheral pulse gating (rppg) gating. METHODS: We scanned 10 healthy volunteers, ages 23-46 years, using external recg-gated or rppg-gated 2D PCCCMRI at 3T. Transverse scans of CSF, arteries and veins scans were at C1/C4/T1/T7/L1-L3. Data were analyzed with custom Matlab-based software, measuring CSF, arterial (descending aorta, abdominal aorta, common carotid artery, ICA, and vertebral artery) and venous (internal jugular vein and inferior vena cava) flow, velocity and region of interest area. RESULTS: recgPCCMRI produced less quantitative and temporal statistical variation than pcgPCCMRI when analyzing CSF flow. The instantaneous recgPCCMRI CSF flows consistently decreased craniocaudally, while the results with rppgPCCMRI were less consistent. The recgPCCMRI root mean square error values were 6.04, 6.94, 4.81, 4.49, and 4.16 for C1, C4, T1, T7, and L2, compared with 7.24, 8.97, 7.9, 7.82, and 6.68 for rppgPCCMRI. Results were independent of analysts. Summations of standard errors produced similar results. RppgPCCMRI also showed increase variability of CSF flow correlations with arteries and veins compared to recgPCCMRI. None-the-less, when recgPCCMRI is considered the reference standard, there is good correlations between rppgPCCMRI and recgPCCMRIdata sets, when averaged over cohorts of at least five subjects. CONCLUSION: Our results indicated that recgPCCMRI is more quantitatively and temporally precise than rppgPCCMRI in CSF quantitative flow analysis. Pulse-gating CSF flow results are reasonable when averaged over cohorts of at least five subjects, but subtle conclusions should be interpreted with caution.