Quantification of choline- and ethanolamine-containing metabolites in human prostate tissues using 1H HR-MAS total correlation spectroscopy.

A fast and quantitative 2D high-resolution magic angle spinning (HR-MAS) total correlation spectroscopy (TOCSY) experiment was developed to resolve and quantify the choline- and ethanolamine-containing metabolites in human prostate tissues in approximately 1 hr prior to pathologic analysis. At a 40-ms mixing time, magnetization transfer efficiency constants were empirically determined in solution and used to calculate metabolite concentrations in tissue. Phosphocholine (PC) was observed in 11/15 (73%) cancer tissues but only 6/32 (19%) benign tissues. PC was significantly higher (0.39 +/- 0.40 mmol/kg vs. 0.02 +/- 0.07 mmol/kg, z = 3.5), while ethanolamine (Eth) was significantly lower in cancer versus benign prostate tissues (1.0 +/- 0.8 mmol/kg vs. 2.3 +/- 1.9 mmol/kg, z = 3.3). Glycerophosphocholine (GPC) (0.57 +/- 0.87 mmol/kg vs. 0.29 +/- 0.26 mmol/kg, z = 1.2), phosphoethanolamine (PE) (4.4 +/- 2.2 mmol/kg vs. 3.4 +/- 2.6 mmol/kg, z = 1.4), and glycerophosphoethanolamine (GPE) (0.54 +/- 0.82 mmol/kg vs. 0.15 +/- 0.15 mmol/kg, z = 1.8) were higher in cancer versus benign prostate tissues. The ratios of PC/GPC (3.5 +/- 4.5 vs. 0.32 +/- 1.4, z = 2.6), PC/PE (0.08 +/- 0.08 vs. 0.01 +/- 0.03, z = 3.5), PE/Eth (16 +/- 22 vs. 2.2 +/- 2.0, z = 2.4), and GPE/Eth (0.41 +/- 0.51 vs. 0.06 +/- 0.06, z = 2.6) were also significantly higher in cancer versus benign tissues. All samples were pathologically interpretable following HR-MAS analysis; however, degradation experiments showed that PC, GPC, PE, and GPE decreased 7.7 +/- 2.2%, while Cho+mI and Eth increased 18% in 1 hr at 1 degrees C and a 2250 Hz spin rate.

Quantitative analysis of prostate metabolites using 1H HR-MAS spectroscopy.

A method was developed to quantify prostate metabolite concentrations using (1)H high-resolution magic angle spinning (HR-MAS) spectroscopy. T(1) and T(2) relaxation times (in milliseconds) were determined for the major prostate metabolites and an internal TSP standard, and used to optimize the acquisition and repetition times (TRs) at 11.7 T. At 1 degrees C, polyamines (PAs; T(1mean) = 100 +/- 13, T(2mean) = 30.8 +/- 7.4) and citrate (Cit; T(1mean) = 237 +/- 39, T(2mean) = 68.1 +/- 8.2) demonstrated the shortest relaxation times, while taurine (Tau; T(1mean) = 636 +/- 78, T(2mean) = 331 +/- 71) and choline (Cho; T(1mean) = 608 +/- 60, T(2mean) = 393 +/- 81) demonstrated the longest relaxation times. Millimolal metabolite concentrations were calculated for 60 postsurgical tissues using metabolite and TSP peak areas, and the mass of tissue and TSP. Phosphocholine plus glycerophosphocholine (PC+GPC), total choline (tCho), lactate (Lac), and alanine (Ala) concentrations were higher in prostate cancer ([PC+GPC](mean) = 9.34 +/- 6.43, [tCho](mean) = 13.8 +/- 7.4, [Lac](mean) = 69.8 +/- 27.1, [Ala](mean) = 12.6 +/- 6.8) than in healthy glandular ([PC+GPC](mean) = 3.55 +/- 1.53, P < 0.01; [tCho](mean) = 7.06 +/- 2.36, P < 0.01; [Lac](mean) = 46.5 +/- 17.4, P < 0.01; [Ala](mean) = 8.63 +/- 4.91, P = 0.051) and healthy stromal tissues ([PC+GPC](mean) = 4.34 +/- 2.46, P < 0.01; [tCho](mean) = 7.04 +/- 3.10, P < 0.01; [Lac](mean) = 45.1 +/- 18.6, P < 0.01; [Ala](mean) = 6.80 +/- 2.95, P < 0.01), while Cit and PA concentrations were significantly higher in healthy glandular tissues ([Cit](mean) = 43.1 +/- 21.2, [PAs](mean) = 18.5 +/- 15.6) than in healthy stromal ([Cit](mean) = 16.1 +/- 5.6, P < 0.01; [PAs](mean) = 3.15 +/- 1.81, P < 0.01) and prostate cancer tissues ([Cit](mean) = 19.6 +/- 12.7, P < 0.01; [PAs](mean) = 5.28 +/- 5.44, P < 0.01). Serial spectra acquired over 12 hr indicated that the degradation of Cho-containing metabolites was minimized by acquiring HR-MAS data at 1 degree C compared to 20 degrees C.

Feasibility of magnetic resonance spectroscopy for evaluating fetal lung maturity.

BACKGROUND/PURPOSE: Amniocentesis is an invasive procedure with inherent risks. Magnetic resonance (MR) spectroscopy is a safe noninvasive way of measuring levels of choline-containing compounds (including surfactant) and other metabolites. The purpose of this study was to test the feasibility of assessing fetal lung maturity in vivo and ex vivo using MR spectroscopy to determine differences in amniotic fluid choline concentrations between the second and third trimesters. METHODS: Magnetic resonance spectroscopy was performed on ex vivo samples of amniotic fluid from second- and third-trimester fetuses. In vivo MR spectroscopy was performed on amniotic fluid and fetal lungs in third-trimester fetuses. Spectral acquisition and analysis were performed by an attending radiologist in conjunction with an MR spectroscopist. RESULTS: Choline-containing compounds were observed from 3.20 to 3.25 ppm. Comparison of spectra from second- and third-trimester amniocentesis revealed a trend toward increased choline at later gestational ages. Spectra from amniotic fluid and lungs of a third-trimester fetus showed that choline can be detected in the in vivo setting. CONCLUSIONS: Magnetic resonance spectroscopy is a safe noninvasive procedure that enables measurement of choline-containing compounds in fetal lung and amniotic fluid. Magnetic resonance spectroscopy shows a trend toward an increased quantity of choline in third- vs second-trimester amniocentesis.

Characterization of intervertebral disc degeneration by high-resolution magic angle spinning (HR-MAS) spectroscopy.

The goal of this study was to determine the ability of high-resolution magic angle spinning (HR-MAS) NMR spectroscopy to distinguish different stages of intervertebral disc degeneration (IVDD). 17 discs were removed from human cadavers and analyzed them using 1D and 2D (total correlation spectroscopy (TOCSY)) (1)H HR-MAS spectroscopy, and T(1) and T(2) relaxation time measurements to determine the chemical composition and changes in chemical environment of discs with increasing levels of degeneration (Thompson grade). Among the significant findings were that spectra were very similar for samples taken from annular and nuclear regions of discs, and that visually apparent changes were observed in the spectra of the annular and nuclear samples from discs with increasing Thompson grade. Area ratios of the N-acetyl to choline (Cho) regions, and Cho to carbohydrate (Carb) regions of the spectra allowed us to discriminate between discs of increasing Thompson grade with minimal overlap of individual ratios. Changes in T(1) and T(2) relaxation times of the chemical constituents of disc spectra were not significantly correlated to the degree of degeneration. The results of this study support the feasibility of using in vivo spectroscopy for detecting chemical changes associated with disc degeneration.

Improved signal to noise in high-resolution magic angle spinning total correlation spectroscopy studies of prostate tissues using rotor-synchronized adiabatic pulses.

A rotor-synchronized WURST-8 adiabatic pulse scheme was compared to the conventional MLEV-17 hard pulse scheme for isotropic mixing in total correlation spectroscopy (TOCSY) studies of intact human prostate tissues under high-resolution magic angle spinning (HR-MAS) conditions. Both mixing schemes were extremely sensitive to the rotational resonance condition and dramatic reductions in signal to noise were observed when pulse durations deviated from 1/(spin rate). A significant increase in cross-peak intensities was observed using rotor-synchronized WURST-8 adiabatic pulses versus those observed using the rotor-synchronized MLEV-17 hard pulse scheme in both solution and tissue. In tissue, absolute signal intensities ranged from 1.5x to 10.5x greater (average: 4.75x) when WURST-8 was used in place of MLEV-17. Moreover, the difference was so dramatic that several metabolite cross peaks observed using WURST-8 pulses were not observed using MLEV-17 pulses, including cross peaks corresponding to many of the choline- and ethanolamine-containing metabolites. Due to the complex modulation of TOCSY cross peaks for multiply coupled spins and the shorter T(2) relaxation times of tissue metabolites, maximum cross-peak intensities occurred at shorter mixing times than predicted by theory. In summary, a WURST-8 adiabatic mixing scheme produced significantly greater absolute cross-peak signal intensities than MLEV-17 hard pulse mixing, and maximum cross-peak intensity versus mixing time must be established for specific spin systems and T(2) relaxation times.