Localized Proton NMR Spectroscopy Research Articles

Localized proton NMR spectroscopy in the striatum of patients with idiopathic spasmodic torticollis.

Single voxel proton spectroscopy was used to study brain metabolism in idiopathic spasmodic torticollis. Peak metabolite ratios in long echo time (135 ms) spectra were evaluated in the basal ganglia of 16 patients (29-65 years). Eight of them were untreated; the other eight were examined 4-6 weeks after administration of botulinum toxin type A. As compared with 60 control spectra, patients showed a significant, therapy-resistant decrease in N-acetyl-L-aspartate (NAA)/choline (Cho). NAA/creatine (Cr) and Cho/Cr were close to normal in the post-treatment group but significantly reduced in untreated patients. This result is consistent with the hypothesis that striatal Cr is reversibly elevated in chronic muscle stimulation. The right and left striatum were affected to the same extent.

Dynamic monitoring of cerebral metabolites during and after transient global ischemia in rats by quantitative proton NMR spectroscopy in vivo

Localized proton NMR spectroscopy was used to dynamically monitor alterations of cerebral metabolites before, during, and after a 10 min period of global forebrain ischemia in anesthetized rats. Metabolic assessment was based on user-independent determination of absolute brain concentrations at a nominal temporal resolution of 1.6 min. While the concentrations of N-acetyl aspartate (neuronal marker), creatines, cholines, and myo-inositol (glial marker) remained constant, ischemia induced a rapid decline of brain glucose. One hour after reperfusion, glucose recovered to 4.1 +/- 2.2 mmol/kg wet weight significantly above the basal value of 2.3 +/- 1.3 mmol/kg wet weight. Mirroring glucose depletion, lactate increased from 1.0 +/- 0.6 to 13.5 +/- 1.5 mmol/kg wet weight 10-15 min after the onset of ischemia. During reperfusion lactate clearance was characterized by a first-order rate constant of 0.03/min. The time courses of glucose and lactate reflect the rapid onset of anaerobic glycolysis during states of critically diminished blood flow. Assuming complete ischemia the production of lactate from glucose and cerebral glycogen stores yields a brain glycogen concentration of 4.7 +/- 0.9 mmol glycosyl unit/kg wet weight. Elevation of brain glucose during early reperfusion suggests a transient mismatch of glucose uptake and consumption during the first 1-2 hours post ischemia.

In Vivo localized proton NMR spectroscopy of thiamine‐deficient rat brain

Thiamine deficiency (TD) in rats produces lesions similar to those found in humans suffering from Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 29) were deprived of thiamine via a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist pyrithiamine hydrobromide. Spectra were obtained by using the STEAM sequence. No significant change occurred in the ratio of Cr/NAA, while the ratio of Cho/NAA declined significantly (60 +/- 11%) on Day 14. Eleven rats received intraperitoneal injections of thiamine hydrochloride at the end of 12 days, and dose-dependent recovery in Cho/NAA was observed.

Localized proton NMR spectroscopy in the striatum of patients with idiopathic parkinson's disease: a multicenter pilot study

Single voxel proton MRS was used to study brain metabolism in the striatum of patients diagnosed with idiopathic Parkinson's disease (PD). Peak metabolite ratios in long echo time spectra were evaluated in 151 patient spectra and 97 age-matched control spectra collected at four participating institutions using identical hardware and clinical protocols. Combining data from all ages (27-83 years old) showed no significant difference between patient and control ratios. However, in an elderly subset of patients (51-70 years old), a significant decrease in striatal N-acetylaspartate (NAA)/choline (Cho) was observed. Also, a significant decrease in the mean NAA/Cho ratio was observed in patients versus controls for patients not being treated with Sinemet (Du Pont Pharm, Wilmington, DE) (hereafter referred to as levodopa/carbidopa). This result is consistent with the hypothesis that NAA may provide a reversible spectroscopic marker for neuronal dysfunction, although a prospective follow-up study will be needed to confirm this. Quantitation of MRS would be useful to exclude the possibility that a change in Cho levels affected the NAA/Cho ratios.

Absolute quantitative proton NMR spectroscopy based on the amplitude of the local water suppression pulse. Quantification of brain water and metabolites

Quantification in localized proton NMR spectroscopy has been achieved by various methods in recent years. A new method for absolute quantification is described in this paper. The method simultaneously rules out problems with B1 field inhomogeneity and coil loading, utilizing a relation between the locally optimized amplitude of a chemical shift selective water suppression pulse and the acquired signal. Validity and feasibility of quantification using the method of the water suppression pulse is demonstrated. Brain water and cerebral metabolites have been quantified in a study of 12 healthy volunteers. Localized proton NMR spectra were obtained from a region of primarily white matter in the occipital lobe. The observable water content in the NMR spectra was 0.685 +/- 0.025. The absolute metabolite concentrations were: [total choline] = 1.25 +/- 0.21 nM, [total creatine] = 6.71 +/- 0.59 nM and [NAA] = 9.15 +/- 0.74 nM. It is concluded that the quantification method is easily applied in vivo, and that the absolute concentrations obtained are similar to results in other studies except those relying on assumptions of the concentration of an internal reference. The advantage of the quantification method reported here is that it is independent of the assumptions needed for other methods.

In vivo localized proton NMR spectroscopy of silicone.

1H NMR localized spectroscopy (STEAM) can assess unambiguously the presence of free chemically unchanged silicone in animal tissue after injection of silicone oil. Although the signal-to-noise ratio obtained in 1H imaging is sufficient to detect the distribution of relatively large amounts of silicone in vivo, the specificity of silicone detection can be improved by using 1H localized spectroscopy techniques. The sensitivity of the STEAM experiments is sufficient to detect silicone at a concentration of 0.5% in a voxel of 27 mm3. Preliminary results from rats with silicone gel-filled implants show no detectable amounts of silicone in sites such as lymph nodes, the liver or the spleen, 3 or 6 months after implantation.

On the interpretation of proton NMR spectra from brain tumours in vivo and in vitro.

Localized proton NMR spectroscopy in vivo allows focal studies of cerebral metabolites in both man and laboratory animals from image-defined regions as small as 1 mL or 64 microL, respectively. Although brain tumours lead to remarkable spectral alterations relative to normal brain, a number of problems may compromise the interpretation of the results. Potential complications arise from the chosen experimental conditions (method, TE, size and location of volume of interest), from regional metabolic heterogeneity in and around tumours, from differences between human tumours and animal models, and from discrepancies between in vivo and in vitro findings. Strategies and pitfalls are illustrated with use of selected examples from primary brain tumours, a rat tumour model and perchloric acid extracts of resected specimens.

Decrease of glucose in the human visual cortex during photic stimulation.

Localized proton NMR spectroscopy was used to study cerebral metabolism in the visual cortex of healthy adults during rest and photic stimulation. Basal lactate levels showed considerable interindividual differences ranging from below detectability (less than 0.3 mM) to about 1 mM without consistent alteration during photic stimulation. Local brain glucose levels were significantly reduced (approximately 50%) during the entire period of photic stimulation and recovered to resting levels (approximately 0.8 mM) within 10 min after the end of stimulation. This decrease reflects the establishment of a new equilibrium due to enhanced delivery (blood flow) and enhanced consumption. The absence of lactate accumulation supports the hypothesis of a rapid efflux of lactate from brain tissue under activated conditions.

Localized double spin echo spectroscopy of weakly homonuclear coupled spin systems: Influence of chemical shift artifacts

In localized double spin echo proton NMR spectroscopy of weakly homonuclear coupled spin systems unusual echo time dependent signal intensity modulations can be observed. Recently a model for a theoretical description assuming rectangular slice profiles and exact pulse angles was published. Here we use the product operator formalism to calculate the intensity modulations caused by the chemical shift between weakly coupled spins. We point out that the effects of this chemical shift artifact should be dependent on the size of the selected volume. A quantification of the effect is given, and experiments with different voxel sizes are performed with a solution of calcium lactate using a 1.5 T SIEMENS whole-body imager. The experimental results do not show the theoretically expected effects. It can be stated that the proposed model very well enables understanding of some dynamical properties of coupled spin systems in volume selective spectroscopy, but it does not solve the problem of sufficient theoretical description of the double spin echo spectroscopy.

Localized Proton NMR Spectroscopy of Brain Tumors Using Short-Echo Time STEAM Sequences

Recent progress in localized proton NMR spectroscopy has been utilized to improve the spatial resolution and the metabolic specificity in a study of 19 patients with intracranial tumors. Selected examples demonstrate that short echo time stimulated echo acquisition mode sequences are able (a) to account for macroscopic tissue heterogeneity by reducing the volume of interest to 2-8 ml and (b) to facilitate a reasonable characterization of tumor metabolism by increasing the number of accessible metabolites. Proton NMR spectra were acquired within measuring times of 6.5 min on a 2.0 T whole-body system using the imaging headcoil.

Cerebral glucose is detectable by localized proton NMR spectroscopy in normal rat brain in Vivo

This contribution reports the first direct and noninvasive observation of cerebral glucose in normal anesthetized rats (n = 16) using short-echo-time localized proton NMR spectroscopy (2.35 T, STEAM, TR = 6000 ms, TE = 20 ms, 125 microliters). In addition to resonances from N-acetyl aspartate (NAA), glutamate, total creatine, cholines, taurine, and myoinositol, all spectra exhibit strongly coupled resonances from glucose (3.43, 3.80 ppm) that are readily identifiable using model solutions. The observed level of cerebral glucose in fasted rats covered a range of 15-40% of that of NAA giving absolute concentrations of 1.1-2.8 mM when NAA is taken to be 7 mM. The arterial blood glucose concentration was 7.7 +/- 0.8 mM in the same group of animals.

Acquisition and quantitation in proton spectroscopy.

Localized proton NMR spectroscopy in the human brain is one of the more technically advanced applications of human in vivo NMR spectroscopy. Spin/echo techniques introduced reliable localization procedures, whereas the introduction of phase encoding techniques improved the spatial information content considerably. Using the sensitivity of the 1H NMR signal, a spatial resolution of 7 X 7 X 15 mm can be obtained. Chemical shift images can be reconstructed to represent the choline, creatine, N-acetyl aspartate and lactate distribution in the human brain. These low resolution images may be used as a new functional imaging modality to visualize and derive quantitative biochemical information from focal brain lesions under normal and pathological conditions.

Localized proton NMR spectroscopy using stimulated echoes: applications to human skeletal muscle in vivo.

Localized proton NMR spectroscopy using stimulated echoes (STEAM) has been used to study metabolites in different proximal skeletal muscles of normal volunteers at rest. Single scan water-suppressed proton NMR spectra obtained at 1.5 and 2.0 T (Siemens Magnetom) from a 64-ml volume-of-interest (VOI) yield resonances due to triglycerides, phosphocreatine plus a minor contribution from creatine, and betaines comprising carnitine and choline-containing compounds. The observation of the pH-dependent resonances of carnosine required multiple acquisitions and echo times as short as 20 ms. T1 and T2 relaxation times of muscle metabolites were obtained by varying the repetition time and echo time of the STEAM sequence, respectively. Although rather long T2 values such as 180 ms for (phospho-) creatine correspond to natural resonance linewidths of only 2 Hz, the observed linewidths of typically 10-12 Hz are entirely determined by the short T2 relaxation times (25-30 ms) of the water protons used for shimming. The spectroscopic results from 24 muscle studies on 17 young male volunteers show remarkable intra- and interindividual differences in the absolute signal intensities of mobile lipids. Further metabolic variations were observed for the relative concentrations of betaines (by a factor of 2) and carnosine (by a factor of 3) when total creatine is assumed to be constant.

Improvements in localized proton NMR spectroscopy of human brain. Water suppression, short echo times, and 1 ml resolution

Considerable technical improvements are reported for localized proton NMR spectroscopy using stimulated echoes. When compared to previous results, proton NMR spectra of the human brain are now obtainable (i) with in vivo water suppression factors of ⩾1000, (ii) with only minor T 2 losses and negligible distortions due to J modulation at short echo times of 10–20 ms, and (iii) from volumes of interest as small as 1–8 ml within measuring times of 1–10 min. As a consequence, the detection of cerebral metabolites is greatly facilitated. This particularly applies to the assignment of those resonances (e.g., glutamate, taurine, inositols) that suffer from strong spin-spin coupling at the field strengths commonly in use for NMR in man. Studies of regional metabolite differences, tissue heterogeneity, and focal lesions in patients benefit from the increased spatial resolution and a concomitant reduction of partial volume effects. Localized proton NMR spectroscopy was performed on young healthy volunteers. Experiments were carried out on a 2.0 T whole-body MRI/MRS system using the standard headcoil for both imaging and spectroscopy.

A homonuclear shift correlated and spatially localized spectroscopy using stimulated echoes

A new method which combines localized high-resolution proton NMR spectroscopy with two-dimensional correlated spectroscopy using stimulated echoes is presented. Stimulated-echo correlated spectroscopy (STECSY) is a straightforward extension of the STEAM method. Experiments with phantoms illustrate the efficacy of STECSY. An in situ application on rat adipose tissue demonstrates that STECSY is a helpful tool with which to select and assign resonances in complex 1H NMR spectra.

Localized proton NMR spectroscopy in different regions of the human brain in vivo. Relaxation times and concentrations of cerebral metabolites.

High-resolution proton NMR spectra of normal human brain in vivo have been obtained from selected 27- and 64-ml volumes-of-interest (VOI) localized in the insular area, the occipital area, the thalamus, and the cerebellum of normal volunteers. Localization was achieved by stimulated echo (STEAM) sequences using a conventional 1.5-T whole-body MRI system (Siemens Magnetom). The proton NMR spectra show resonances from lipids, lactate, acetate, N-acetylaspartate (NAA), gamma-aminobutyrate, glutamine, glutamate, aspartate, creatine and phosphocreatine, choline-containing compounds, taurine, and inositols. While T1 relaxation times of most of these metabolites were about 1100-1700 ms without significant regional differences, their T2 relaxation times varied between 100 and 500 ms. The longest T2 values of about (500 +/- 50) ms were observed for the methyl protons of NAA in the white matter of the occipital lobe compared to (320 +/- 30) ms in the other parts of the brain. No significant regional T2 differences were found for choline and creatine methyl resonances. The relative concentrations of NAA in gray and white matter were found to be 35% higher than those in the thalamus and cerebellum. Assuming a concentration of 10 mM for total creatine the resulting NAA concentrations of 13-18 mM are by a factor of 2-3 higher than previously reported using analytical techniques. Cerebral lactate reached a maximum concentration of about 1.0 mM.

Cerebral metabolism in man after acute stroke: New observations using localized proton NMR spectroscopy

Localized proton NMR spectroscopy at 1.5 T using stimulated echoes has been applied to study metabolic alterations in the postischemic phase of patients with acute cerebral infarction. A complete depletion of N-acetyl aspartate in the area of infarction has been observed in a patient studied 4 days after stroke. This finding was paralleled by a dramatic increase in the concentration of lactic acid to about 16 mM within the lesion, indicating continued anaerobic glycolysis. The diluting effect of the edema has been estimated to reduce average metabolite concentrations by about a factor of 3.

Localized high‐resolution proton NMR spectroscopy using stimulated echoes: Initial applications to human brain in vivo

Water-suppressed localized proton NMR spectroscopy using stimulated echoes has been successfully applied to detect metabolites in the human brain in vivo. The STEAM spectroscopy sequence allows single-step localization by exciting three intersecting slices. Water suppression is achieved by preceding chemical-shift-selective (CHESS) rf pulses. High-resolution (0.05 ppm) proton NMR spectra of healthy volunteers have been High-resolution (0.05 ppm) proton NMR spectra of healthy volunteers have been obtained on a conventional 1.5-T whole-body MRI system (Siemens Magnetom). Volumes-of-interest (VOI) of 64 ml (4 x 4 x 4 cm3) were localized in the occipital area of the brain and spectra were recorded within measuring times ranging from 1 s (single scan) to about 10 min. The experimental procedure is described in detail. Resonance assignments include acetate, N-acetyl aspartate, gamma-amino butyrate, glutamine, glutamate, aspartate, creatine and phosphocreatine, choline-containing compounds, taurine, and inositols. Cerebral lactate was found to be at a maximum concentration of 0.5 mM when assuming N-acetyl aspartate in white matter to be 6 mM.