1H MR spectroscopic imaging with short and long echo time to discriminate glycine in glial tumours

OBJECT: To investigate glycine (Gly) concentrations in low- and high-grade gliomas based on (1)H MR spectroscopic imaging (MRSI) with short and long echo time (TE). Myoinositol (MI) and Gly appear at the same resonance frequency of 3.56 ppm, but due to strong coupling the MI signal dephases more rapidly. Therefore, their contribution to the 3.56 ppm signal should be distinguishable comparing MRSI data acquired at short and long TE. MATERIALS AND METHODS: (1)H MRSI (TE = 30 and 144 ms) was performed at 3 T in 29 patients with histopathological confirmed World Health Organization (WHO) grade II-IV gliomas and in FIVE healthy subjects. All spectra from the gliomas revealed increase of the 3.56 ppm resonance in the short TE spectra. Signal intensities of Gly and MI were differentiated either by analysing the short to long TE ratio of the resonance or by performing a weighted difference. Gly concentrations were compared between high-grade (WHO III-IV) and low-grade gliomas. RESULTS: High-grade gliomas showed significantly higher Gly concentrations compared to low-grade gliomas. CONCLUSION: Appropriate data processing of short and long TE (1)H MRSI provides a tool to distinguish and to quantify Gly and MI concentrations in gliomas. As Gly seems to be a marker of malignancy, more dedicated spectroscopic methods to differentiate these metabolites are justified.     

Physiological constraints on changes in pH and phosphorus metabolite concentrations in ischemically exercising muscle: implications for metabolic control and for the interpretation of31P-magnetic resonance spectroscopic studies

Relationships between pH and the concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), and lactate during ischemic exercise depend on passive buffering, proton consumption as a consequence of net PCr breakdown, the control of glycogenolysis, (particularly in relation to the concentration of Pi, a substrate of glycogen phosphorylase that is produced by net PCr breakdown), and the creatine kinase equilibrium. The author analyzes the implications of these relationships for the interpretation of³¹P-magnetic resonance spectroscopic data and for the control of glycogenolysis. For realistic adenosine diphosphate (ADP) concentrations, given the constraints of the creatine kinase equilibrium, the pH must be near-linear with lactate, with an apparent buffer capacity (i.e., the ratio of lactate accumulation to pH change) that is nearly twice the true buffer capacity (i.e., the ratio of net proton loading to pH change). The implications for glycogenolytic control depend on adenosine triphosphate (ATP) turnover, but an upper limit of activation of glycogen phosphorylase (i.e., the amount of thea form) that would permit no increase in ADP concentration can be calculated. Phosphorylase activation during ischemic exercise seems approximately proportional to the power output, consistent with calcium stimulation of phosphorylaseb kinase. In simulations, ADP concentration is highly sensitive to this proportionality, as (unlike in purely oxidative exercise) ADP concentration is not known to participate in any closed feedback loops in ischemic exercise.     

Mechanisms of31P relaxation in phosphorus metabolites

Measurements have been made of the longitudinal relaxation timeT ₁ of³¹P for the individual resonances of the metabolites AMP, ADP, ATP, P_ir and PCr (phosphocreatine) in H₂O and D₂O solutions from 5 to 60°C at various concentrations and at frequencies of 40 MHz (2.3 T) and 120 MHz (7 T). The contributions of dipolar, chemical shift anisotropy, and spin-rotation mechanisms have been separated, and activation parameters of the underlying molecular reorientations have been determined.     

31P CSI of the human brain in healthy subjects and tumor patients at 9.4 T with a three-layered multi-nuclear coil: initial results

Magnetic Resonance Materials in Physics, Biology and Medicine - Investigation of the feasibility and performance of phosphorus (31P) magnetic resonance spectroscopic imaging (MRSI) at 9.4 T with a...     

Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays

KTCTL-26 and KTCTL-2 are renal cell carcinoma (RCC) lines with high and lowexpression of P-170 glycoprotein, respectively. Inherent differences between the two cell lines in terms of phosphate metabolites and growth characteristics in culture were examined for possible association with multidrug resistance (MDR). Differences in response to drug treatment were investigated for 40 h incubations with various doses of vinblastine (VBL) alone or as cotreatments with various concentrations of the calcium antagonist diltiazem (DIL) and/or interferon–α (IFN-α). Treatment effects were quantitated using the MTT survival assay and ³¹P magnetic resonance spectroscopy (MRS) to determine phosphate metabolite profiles in intact cells. KTCTL-2 and KTCTL-26 cells exhibited significant inherent differences in phosphocholine, glycerophosphocholine, glycerophosphoethanolamine, and phosphocreatine levels. KTCTL-26 cells were more sensitive than KTCTL-2 to 0.011μM VBL alone (87% vs. 102% survival) or to 0.011μM BL + 10μM DIL (55% vs. 80% survival). The latter treatment resulted in a significant decrease in the ratio of phosphocholine to glycerophosphocholine in KTCTL-26 cells but no significant changes in phosphate metabolites in KTCTL-2 cells. Metabolomic ³¹P MRS detects different metabolite profiles for RCC cell lines with different MDR phenotypes and may be useful for noninvasive characterization of tumors in a clinical setting.This revised version was published online in August 2005 with a corrected sequence of authors.     

Role of magnetic resonance methods in the evaluation of prostate cancer: an Indian perspective

The challenges in detection, localization, and staging of prostate cancer have prompted the investigation of the role of various magnetic resonance (MR) methodologies in a large cohort of men prior to biopsy. The identification of suspicious areas of malignancy was carried out using magnetic resonance imaging (MRI), magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). Our data shows that apparent diffusion coefficient (ADC) may be a reliable marker to differentiate normal, benign, and malignant prostate tissues similar to the metabolite ratio. Also, the combined use of MRSI and DWI improves the diagnosis of prostate cancer. In this review, we present our experience on the use of MRI, MRSI and DWI methods in the assessment of prostate cancer in Indian men. Further, analysis of the comparison of the ADC and the metabolite ratio values reported in the literature across various patient populations are presented. An erratum to this article can be found at     

31P-NMR spectroscopy of human blood and serum: first results from volunteers and patients with congestive heart failure,diabetes mellitus and hyperlipidaemia

³¹P-containing metabolites in human blood, serum and erythrocytes were measured or calculated. Phosphodiesters were found in serum, but not in erythrocytes. 2,3-diphosphoglycerate and 2,3-diphosphoglycerate/ATP ratios were increased in patients with congestive heart failure (2,3-diphosphoglycerate by 13% in mild to moderate, 31% in severe congestive heart failure, 2,3-diphosphoglycerate/ATP ratio by 9% in mild to moderate, 38% in severe congestive heart failure); phosphodiesters were increased in diabetes mellitus (by 26%) and even more so in hyperlipidaemia (by 57%). Changes of blood³¹P compounds with disease states may have diagnostic potential and should be recognized for correction of organ spectra.     

In vivo localized1 H spectroscopy of the rat eye at 7 T: preliminary studies

Preliminaryin vivo proton spectroscopic studies of the posterior chamber of the rat eye have been undertaken at 7 T. The Spatial and Chemical shift encoded Excitation (SPACE) localization sequence was used to acquire signals from 10-µl voxels and demonstrate the presence of metabolites associated with the vitreous humor, lens, retina, and the optic nerve. LocalizedT ₂ andT ₁ measurements of water in the vitreous humor indicate a relatively fluid environment. Susceptibility maps are used to demonstrate the difficulties ofin vivo spectroscopic investigations in the anterior regions of the eye. Comments are made concerning the implications for spectral resolution in these regions.     

Long-term sequestration of fluorinated compounds in tissues after fluvoxamine or fluoxetine treatment: a fluorine magnetic resonance spectroscopy study in vivo

Fluorine magnetic resonance spectroscopy (¹⁹F MRS), spectroscopic imaging (MRSI) and proton anatomical magnetic resonance imaging (¹H MRI) were performed on brains and lower extremities of six subjects in vivo concurrently with HPLC of serum to investigate tissue and plasma drug localization and withdrawal kinetics in humans treated with fluvoxamine or fluoxetine. ¹⁹F MRS signal was unexpectedly detected in the lower extremities months after complete disappearance of signal from plasma and brain. MRSI suggested that the lower extremity fluvoxamine signal originated mainly from bone marrow. Results suggest long-term sequestration of these drugs or their metabolites mainly in bone marrow and possibly in surrounding tissue and demonstrate the usefulness of MRS to reveal drug-trapping compartments in the body.     

Evaluating metabolites in patients with major depressive disorder who received mindfulness-based cognitive therapy and healthy controls using short echo MRSI at 7 Tesla

Objectives

Our aim was to evaluate differences in metabolite levels between unmedicated patients with major depressive disorder (MDD) and healthy controls, to assess changes in metabolites in patients after they completed an 8-week course of mindfulness-based cognitive therapy (MBCT), and to exam the correlation between metabolites and depression severity.

Materials and methods

Sixteen patients with MDD and ten age- and gender-matched healthy controls were studied using 3D short echo-time (20 ms) magnetic resonance spectroscopic imaging (MRSI) at 7 Tesla. Relative metabolite ratios were estimated in five regions of interest corresponding to insula, anterior cingulate cortex (ACC), caudate, putamen, and thalamus.

Results

In all cases, MBCT reduced severity of depression. The ratio of total choline-containing compounds/total creatine (tCr) in the right caudate was significantly increased compared to that in healthy controls, while ratios of N-acetyl aspartate (NAA)/tCr in the left ACC, myo-inositol/tCr in the right insula, and glutathione/tCr in the left putamen were significantly decreased. At baseline, the severity of depression was negatively correlated with my-inositol/tCr in the left insula and putamen. The improvement in depression severity was significantly associated with changes in NAA/tCr in the left ACC.

Conclusions

This study has successfully evaluated regional differences in metabolites for patients with MDD who received MBCT treatment and in controls using 7 Tesla MRSI.

     

Phosphorus magnetic resonance spectroscopic imaging using flyback echo planar readout trajectories

Object

To present and evaluate a fast phosphorus magnetic resonance spectroscopic imaging (MRSI) sequence using echo planar spectroscopic imaging with flyback readout gradient trajectories.

Materials and Methods

Waveforms were designed and implemented using a 3 Tesla MRI system. ³¹P spectra were acquired with 2 × 2 cm² and 3 × 3 cm² resolution over a 20- and 21-cm field of view and spectral bandwidths up to 1923 Hz. The sequence was first tested using a 20-cm-diameter phosphate phantom, and subsequent in vivo tests were performed on healthy human calf muscles and brains from five volunteers.

Results

Flyback EPSI achieved 10× and 7× reductions in acquisition time, with 68.0 ± 1.2 and 69.8 ± 2.2% signal-to-noise ratio (SNR) per unit of time efficiency (theoretical SNR efficiency was 74.5 and 76.4%) for the in vivo experiments, compared to conventional phase-encoded MRSI for the 2 × 2 cm² and 3 × 3 cm² resolution waveforms, respectively. Statistical analysis showed no difference in the quantification of most metabolites. Time savings and SNR comparisons were consistent across phantom, leg and brain experiments.

Conclusion

EPSI using flyback readout trajectories was found to be a reliable alternative for acquiring ³¹P-MRSI data in a shorter acquisition time.

     

Estimation of metabolite <Emphasis Type="Italic">T</Emphasis><Subscript>1</Subscript> relaxation times using tissue specific analysis,signal averaging and bootstrapping from magnetic resonance spectroscopic imaging data

Object A novel method of estimating metabolite T ₁ relaxation times using MR spectroscopic imaging (MRSI) is proposed. As opposed to conventional single-voxel metabolite T ₁ estimation methods, this method investigates regional and gray matter (GM)/white matter (WM) differences in metabolite T ₁ by taking advantage of the spatial distribution information provided by MRSI. Material and methods The method, validated by Monte Carlo studies, involves a voxel averaging to preserve the GM/WM distribution, a non-linear least squares fit of the metabolite T ₁ and an estimation of its standard error by bootstrapping. It was applied in vivo to estimate the T ₁ of N-acetyl compounds (NAA), choline, creatine and myo-inositol in eight normal volunteers, at 1.5 T, using a short echo time 2D-MRSI slice located above the ventricles. Results WM-T _1,NAA was significantly (P < 0.05) longer in anterior regions compared to posterior regions of the brain. The anterior region showed a trend of a longer WM T ₁ compared to GM for NAA, creatine and myo-Inositol. Lastly, accounting for the bootstrapped standard error estimate in a group mean T ₁ calculation yielded a more accurate T ₁ estimation. Conclusion The method successfully measured in vivo metabolite T ₁ using MRSI and can now be applied to diseased brain.     

Creatine loading and resting skeletal muscle phosphocreatine flux: a saturation-transfer NMR study

³¹P saturation-transfer nuclear magnetic resonance spectroscopy was used to study skeletal muscle phosphocreatine (PCr) flux in healthy male volunteers. Data analysis included consideration of effects from incomplete saturation and radiofrequency spillover. Spectra were recorded from the resting gastrocnemius muscle before and after 6 days of creatine monohydrate (Cr·H₂O) intake (20 g/day). Parallel to an improved muscle performance during maximal intermittent exercise following Cr·H₂O supplementation, the concentration of PCr increased(P = 0.01) by 23% (34.9 ± 2.8 mmol/ 1 vs. 28.6 + 2.7 mmol/1), whereas other metabolites were unaffected (inorganic phosphate: 4.3± 1.4 mmol/1, free intracellular Mg²⁺: 1.1 ±0.7 mmol 1, cytosolic pH: 7.04 ± 0.02). Forward and reverse fluxes through the creatine kinase (CK) reaction did not change significantly from their baseline levels (v_for: 11.8 ± 5.4 mmol/1 per second vs. 15.3 ± 6.8 mmol 1 per second. (v_rev: 9.5 ± 3.4 mmol/1 per second vs. 10.9 ± 3.7 mmol/ 1 per second). The rate of PCr resynthesis in resting muscle is not limited by the CK reaction, which is near equilibrium. Consequently, the post-load increase in total creatine has no effect on the unidirectional CK reaction rates.     

Fast multiecho balanced SSFP metabolite mapping of 1H and hyperpolarized 13C compounds

Object  To investigate the feasibility of multiecho balanced steady-state free precession (bSSFP)-based fast chemical shift mapping hyperpolarized ¹³C metabolites. The overall goal was to reduce total imaging time and to increase spatial resolution compared to common chemical shift imaging (CSI). Materials and methods  A multiecho bSSFP sequence in combination with an iterative reconstruction algorithm was implemented. ¹H experiments were performed on phantoms and on a human volunteer in order to investigate the feasibility of the method on a system with metabolite maps that are known beforehand. ¹³C experiments were performed in vivo on pigs, where CSI images were acquired also for comparison. Results  Chemical shift images of three and four distinct ¹H resonance frequencies as well as chemical shift images of up to five hyperpolarized ¹³C metabolites were successfully obtained. Conclusion  Fast metabolite mapping based on multiecho balanced SSFP in combination with an iterative reconstruction approach could successfully separate several ¹H resonances and hyperpolarized ¹³C metabolites.     

Signal enhancement through heteronuclear polarisation transfer in in-vivo <Superscript>31</Superscript>P MR spectroscopy of the human brain

Significant ³¹P NMR signal enhancement through heteronuclear polarisation transfer was obtained in model solutions and in vivo on a 1.5-T whole-body MR scanner equipped with two RF channels. The much higher population differences involved in proton Zeeman energy levels can be transferred to the ³¹P levels with the refocused INEPT (insensitive nucleus enhancement by polarisation transfer) double-resonance experiment by means of a series of simultaneously applied broadband RF pulses. INEPT achieves a polarisation transfer from ¹H to ³¹P spin states by directly reordering the populations in spin systems with heteronuclear scalar coupling. Thus, only the ³¹P NMR signal of metabolites with scalar ¹H–³¹P coupling is amplified, while the other metabolite signals in the spectra are suppressed. Compared to Ernst-angle excitation, a repetition-time-dependent signal enhancement of η=(29±3)% for methylene diphosphonic acid (MDPA) and η=(56±1)% for phosphorylethanolamine (PE) was obtained on model solutions through optimisation of the temporal parameters of the pulse experiment. The results are in good agreement with numerical calculations of the theoretical model for the studied spin systems. With optimised echo times, in-vivo ³¹P signal enhancement of the same order was obtained in studies of the human brain.     

Hyperammonemia and chronic hepatic encephalopathy: an in vivo PMRS study of the rat brain

The brain energy metabolism of rats affected by chronic hepatic encephalopathy due to portacaval shunting was monitored by in vivo³¹P-nuclear magnetic resonance spectroscopy before and after ammonium acetate administration. With respect to healthy unoperated and to sham operated controls, portacaval shunting decreased the levels of the nuclear magnetic resonance (NMR) visible brain phosphocreatine and nucleoside phosphates, and the intracellular [free Mg²⁺]. Ammonium acetate induced a further decrease of the levels of the NMR detectable phosphocreatine and nucleoside triphosphates and of the [free Mg²⁺], while the PMR spectra of the brain of non-shunted rats did not show any significant change even after treatment with ammonium acetate.     

Reduced purine catabolite production in the postischemic rat heart: a31P NMR assessment of cytosolic metabolites

Ischemia can cause release of adenosine and purine catabolites from the heart, through the breakdown of ATP. If repeated periods of ischemia are induced, the efflux of purines is markedly reduced, although it is not clear if this is beneficial for the long-term survival of the heart. We have investigated changes in high-energy phosphates and purine release in the isolated perfused rat heart using³¹P NMR spectroscopy and high-performance liquid chromatography. Hearts were subjected to one of the following protocols: Group A—1 min of total global ischemia (TGI) after 40 min, 60 min, and 85 min of perfusion (a total of 3 × 1 min ischemia); Group B—1 min of TGI after 40 min of perfusion, 10 min of TGI after 50 min of perfusion, and a final 1 min of TGI after 85 min of perfusion. The profile of high-energy phosphate metabolites, P_i accumulation and purine release was similar for each 1-min period of TGI in Group A, whereas phosphocreatine content was increased and ATP content reduced by an extended period of TGI in Group B, leading to a less severe acidosis and purine efflux in the final 1 min of TGI at 85 min of perfusion. In conclusion, the reduced purine release observed in Group B may be related to the preischemic ATP pool size and accessibility and the increased myocardial energy reserve in the form of phosphocreatine.     

31P MR spectroscopy and in vitro markers of oxidative capacity in type 2 diabetes patients

Background: Skeletal muscle mitochondrial function in type 2 diabetes (T2D) is currently being studied intensively. In vivo ³¹P magnetic resonance spectroscopy (³¹P MRS) is a noninvasive tool used to measure mitochondrial respiratory function (MIFU) in skeletal muscle tissue. However, microvascular co-morbidity in long-standing T2D can interfere with the ³¹P MRS methodology. Aim: To compare ³¹P MRS-derived parameters describing in vivo MIFU with an in vitro assessment of muscle respiratory capacity and muscle fiber-type composition in T2D patients. Methods: ³¹P MRS was applied in long-standing, insulin-treated T2D patients. ³¹P MRS markers of MIFU were measured in the M. vastus lateralis. Muscle biopsy samples were collected from the same muscle and analyzed for succinate dehydrogenase activity (SDH) and fiber-type distribution. Results: Several ³¹P MRS parameters of MIFU showed moderate to good correlations with the percentage of type I fibers and type I fiber-specific SDH activity (Pearson’s R between 0.70 and 0.75). In vivo and in vitro parameters of local mitochondrial respiration also correlated well with whole-body fitness levels (VO _2peak) in these patients (Pearson’s R between 0.62 and 0.90). Conclusion: Good correlations exist between in vivo and in vitro measurements of MIFU in long-standing insulin-treated T2D subjects, which are qualitatively and quantitatively consistent with previous results measured in healthy subjects. This justifies the use of ³¹P MRS to measure MIFU in relation to T2D.     

MR imaging of the prostate in clinical practice

Magnetic resonance imaging (MRI) is the imaging tool of choice in the evaluation of prostate cancer. The main applications of MR imaging in the management of prostate cancer are: (1) to guide targeted biopsy when prostate cancer is clinically suspected and previous ultrasound-guided biopsy results are negative; (2) to localize and stage prostate cancer and provide a roadmap for treatment planning; and (3) to detect residual or locally recurrent cancer after treatment. Other MR techniques such as proton MR spectroscopic imaging (MRSI), diffusion-weighted imaging (DWI), and contrast-enhanced MRI (CE-MRI) complement conventional MR imaging by providing metabolic and functional information that can improve the accuracy of prostate cancer detection and characterization. In everyday clinical practice, and to account for patient comfort, MR imaging studies are limited to 1 h. To obtain consistently high-quality images, a well-designed protocol is necessary. Routine MR imaging can be supplemented by other MR techniques such as MRSI, DWI or CE-MRI depending on the expertise available and the clinical questions that need to be answered. This review summarizes the role of MR imaging in the management of prostate cancer and describes practical approaches to implementing anatomic, metabolic and functional MR imaging techniques in the clinic.     

Kinetics of PCr to ATP and β-ATP to β-ADP phosphoryl conversion are modified in working rat skeletal muscle after training

Kinetics of phosphoryl transfers from PCr to γ-ATP and from β-ATP to β-ADP were measured by magnetization transfer in an in vivo³¹P NMR experiment in working rat skeletal hind leg muscles. Two groups were examined. One group was submitted to a 6-week training program of treadmill running. The other group was composed of sedentary animals. Metabolic oxidative capacity and mechanical performance were improved greatly by training as shown previously. Phosphoryl transfer of PCr→γ-ATP or β-ATP→β-ADP total fluxes were identical in resting trained and untrained muscles. Under stimulation, the flux of creatine kinase transfer was significantly inhibited by 23% compared with resting level in untrained muscles; by contrast, it was not inhibited and maintained at the high resting level in trained muscles. Thus physiological changes probably linked to a decrease of the production of anions, which could inhibit creatine kinase, were able to maintain creatine kinase flux. The flux of β-ATP to β-ADP transfer were enhanced largely in working muscles from 1.4±0.8 and 2±0.8 at rest to 4±1.6 and 6.6±2.7 mM s⁻¹ for untrained and trained muscles respectively; the effect was more pronounced in trained than in untrained muscles. These results showed an acceleration of phosphoryl turnover in working muscles after training, which could contribute to improve oxidative and mechanical performances. Such kinetic measurements of phosphoryl conversion may provide information on ATP turnover in pathophysiologic situations where ADP accumulates because of impaired ATP synthesis (mitochondrial myopathies, lower perfusion level).