Noninvasive evaluation of cerebral glioma grade by using multivoxel 3D proton MR spectroscopy

Objective

To determine whether metabolite ratios in multivoxel 3D proton MR spectroscopy (¹H MRS) is different between low-grade and high-grade gliomas and may be useful for glioma grading.

Materials and Methods

Thirty-nine patients (23 male and 16 female; 22-75 years old; mean age, 44.92±12.65 years) suspected of having gliomas underwent 3D ¹H MRS examinations. Metabolite ratios [choline (Cho)/creatine (Cr), N-acetylaspartate (NAA)/Cr and Cho/NAA] were measured. Tumor grade was determined by using the histopathologic grading. Receiver operating characteristic analysis of metabolite ratios was performed, and optimum thresholds for tumor grading were determined. The resulting sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for identifying high-grade gliomas were calculated.

Results

Diagnostic-quality 3D ¹H MRS with readily quantifiable Cho, Cr and NAA peaks was obtained in 94.87% of the cases. The Cho/Cr and Cho/NAA ratios were significantly higher in high-grade than in low-grade glioma (P<.001), whereas the NAA/Cr ratios were significantly lower in high-grade than in low-grade glioma (P<.001). Receiver operating characteristic analysis demonstrated a threshold value of 2.04 for Cho/Cr ratio to provide sensitivity, specificity, PPV and NPV of 84.00%, 83.33%, 91.30% and 71.43%, respectively. Threshold value of 2.20 for Cho/NAA ratio resulted in sensitivity, specificity, PPV and NPV of 88.00%, 66.67%, 84.62% and 72.73%, respectively. Overall diagnostic accuracy was not statistically significantly different between Cho/Cr and Cho/NAA ratios (χ²=0.093, P=.76).

Conclusion

Metabolite ratios of low-grade gliomas were significantly different from high-grade gliomas. Cho/Cr and Cho/NAA ratios could have the superior diagnostic performance in predicting the glioma grade.     

Experimental hypoxic–ischemic encephalopathy: comparison of apparent diffusion coefficients and proton magnetic resonance spectroscopy

This study aims to compare the apparent diffusion coefficients (ADCs) and proton magnetic resonance spectroscopy (¹H-MRS) in the first 24 h of acute hypoxic-ischemic brain damage (HIBD) in piglets. Twenty-five 7-day-old piglets were subjected to transient bilateral common carotid artery occlusion followed by ventilation with 4% oxygen for 1 h. Diffusion-weighted imaging (DWI) and ¹H-MRS were performed on cessation of the insult or at 3, 6, 12 or 24 h after resuscitation (all n=5). ADCs, N-acetylaspartate/choline (NAA/Cho), NAA/creatine (NAA/Cr), lactate/NAA (Lac/NAA), Lac/Cho and Lac/Cr were calculated. Cerebral injury was evaluated by pathological study and Hsp70 immunohistochemical analysis. On cessation of the insult, ADCs, NAA/Cho and NAA/Cr reduced, Lac/NAA, Lac/Cho and Lac/Cr increased. From 3 to 12 h after resuscitation, ADCs, Lac/NAA, Lac/Cho and Lac/Cr recovered, NAA/Cho and NAA/Cr reduced. Twenty-four hours after resuscitation, ADCs reduced once more, Lac/NAA, Lac/Cho and Lac/Cr increased again, whereas NAA/Cho and NAA/Cr decreased continuously. Pathological study revealed mild cerebral edema on cessation of the insult and more and more severe cerebral injury after resuscitation. No Hsp70-positive cells were detected on cessation of the insult. From 3 to 12 hours after resuscitation, Hsp70-positive cells gradually increased. Twenty-four hours after resuscitation, Hsp70-positive cells decreased. Throughout the experiment, changes in NAA/Cho and pathology had the best correlation (R=–0.729). In conclusion, NAA/Cho is the most precise ratio to reflect the pathological changes of early HIBD. Transient ADCs and Lac ratios recovery do not predict the reversal of histological damage of early HIBD. Reducing astrocytic swelling is of great clinical significance.     

Serial Precision of Metabolite Peak Area Ratios and Water Referenced Metabolite Peak Areas in Proton MR Spectroscopy of the Human Brain

The precision of cerebral proton magnetic resonance spectroscopy (MRS) measurements is critical both in the clinical setting and for research purposes. Marshall et al. have recently concluded that “disappointing in vivo repeatability…is likely to limit” the ability of MRS to detect modest changes. We present here a comprehensive study of the precision of short- and long-term metabolite peak area ratios and water referenced metabolite peak areas for long echo time point resolved spectroscopy (PRESS) spectra (repetition time (TR) = 2000 ms, echo time (TE) = 136 ms) acquired from the occipital lobes of normal volunteers and a phantom using a conventional whole body 1.5 T MR system and conventional acquisition and analysis protocols. Short-term in vitro precision determined by five repeat scans on five occasions was excellent as measured by a mean coefficient of variation (NAA/Cho = 1.3%, NAA/Cr + PCr = 1.0%, Cho/Cr + PCr = 1.6%, NAA/H₂O = 0.5%, Cho/H₂O = 1.2%, Cr + PCr/H₂O = 0.8%). Long term in vitro precision using 100 spectra acquired over 2 years was also very good (NAA/Cho = 2.7%, NAA/Cr + PCr = 1.4%, Cho/Cr + PCr = 2.2%, NAA/H₂O = 1.5%, Cho/H₂O = 2.4%, Cr + PCr/H₂O = 1.5%). Short-term in vivo precision determined by five repeat scans in a single scanning session on eight subjects was also excellent (NAA/Cho = 5.2%, NAA/Cr + PCr = 3.0%, Cho/Cr + PCr = 6.6%, NAA/H₂O = 1.4%, Cho/H₂O = 4.9%, Cr + PCr/H₂O = 2.7%) and only worsened slightly for long-term in vivo precision determined by five repeat scans on eight subjects over 3 months (NAA/Cho = 5.2%, NAA/Cr + PCr = 4.8%, Cho/Cr + PCr = 7.7%, NAA/H₂O = 2.5%, Cho/H₂O = 6.4%, Cr + PCr/H₂O = 3.8%). We attribute the excellent precision reported here to the use of highly automated techniques for voxel shimming, water suppression and peak area measurements. These results allow us to repudiate Marshall’s assertion regarding disappointing repeatability of in vivo MRS.     

Reversal of myo-inositol metabolic level in the left dorsolateral prefrontal cortex of rats exposed to forced swimming test following desipramine treatment: an in vivo localized H-MRS study at 4.7 T

The forced swimming test (FST) is a useful paradigm that is relatively quick and simple to perform and has been utilized to predict antidepressant activity based on learned helplessness as a model of depression. To date, few studies have used proton magnetic resonance spectroscopy (¹H-MRS) to assess antidepressant effects in rats. The purpose of this study was to assess desipramine (DMI) effects on the left dorsolateral prefrontal cortex (DLPFC) of the rats, which were randomly assigned to three groups (control, n=10; FST+saline, n=10; FST+DMI, n=10), using single-voxel localization technique. All ¹H-MRS experiments were performed on a Bruker 4.7-T scanner with 400 mm bore magnet, allowing for acquisition of in vivo ¹H point-resolved spectroscopy spectra (TR/TE=3000/30 ms, number of data points=2048, NEX=512, voxel volume=27 μl, scan time=25 min). Proton metabolites were quantified automatically using LCModel software and were expressed as ratios to total creatine (Cr+PCr). Major target metabolites such as N-acetyl aspartate (NAA)+N-acetylaspartylglutamate (NAAG), glutamate+glutamine (Glu+Gln), glycerophosphorylcholine+phosphorylcholine (GPC+PCho), myo-inositol (mIns) and taurine (Tau) were successfully quantified with Cramer–Rao lower boundary ≤10%. There were significantly higher mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios in the FST+saline group compared to the control group. In the FST+DMI group, both mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios were significantly decreased to the level similar to those in the control group. No other metabolite ratios were significantly different among the three groups. Our findings suggest a possible role of altered mIns level within the left DLPFC of the rat model for depression.     

Absolute Quantification Using Turbo Spectroscopic Imaging in Multiple Sclerosis Patients

One of the drawbacks of scanning patients using multiple-voxel spectroscopic imaging is the long acquisition time. This is especially true when one is interested in obtaining absolute metabolite concentrations which requires acquisition of unsuppressed water spectra in addition to the suppressed spectra. In our experiment, turbo spectroscopic imaging (TSI) method with acquisition of three echoes per excitation was applied to reduce scanning time without lowering the spatial resolution. In 15 relapsing-remitting multiple sclerosis patients (mean age 37.07 years, mean disease duration 7.67 years), an MRSI scan at the level of centrum semiovale was obtained. The scan time was approximately 7 min including the unsuppressed spectra. Tissue water was used as an internal concentration reference to obtain absolute metabolite concentrations of N-acetyl-aspartate (NAA), creatine (Cr), and choline (Cho). The peak areas were corrected for differences in transversal and longitudinal relaxation times and a water concentration of 55.5 M was assumed. A three-dimensional high-resolution T ₁ scan was acquired and used to segment tissue in gray matter (GM), white matter (WM), and cerebrospinal fluid using FSL’S FAST segmentation method (a software library of the automated segmentation tool by the Center of Functional MRI of the Brain, Oxford, UK). Finally, a regression analysis was employed to address the metabolite concentrations and ratios in GM and WM, respectively. Our study shows that the metabolite concentrations (NAA, Cho, Cr) and metabolite ratios (NAA/Cr and Cho/Cr) in GM and WM obtained using the methods discussed earlier are comparable to the results found in other studies of similar patient groups. It also shows that TSI method can be used to obtain the absolute metabolite ratios in a reasonable scan time.     

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling

Objective

To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis.

Methods

Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis.

Results

Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity.

Conclusion

Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.     

A (1)H magnetic resonance spectroscopy study of aging in parietal white matter: implications for trials in multiple sclerosis

1H magnetic resonance spectroscopy (MRS) provides a unique tool to detect and quantify brain metabolites. In multiple sclerosis it can be used to investigate axonal loss or dysfunction through measurement of N-acetyl aspartate (NAA), a neuronal marker. Previous studies in adults have reported variable effects of aging on metabolite concentrations but have predominantly focused on changes in the elderly. This study has examined a younger adult age group to provide a reference database more applicable to the multiple sclerosis population. Single voxel (1)H MRS was carried out in 44 subjects between 22 and 62 years of age. Sixteen subjects underwent repeat examination after one year. Absolute concentrations of NA (the sum of NAA and N-acetyl aspartate glutamate), NAA, creatine/phosphocreatine (Cr), choline containing compounds (Cho) and myo-inositol (mI) were measured. NA, NAA and mI concentrations did not correlate with age but there were significant correlations between age and Cr (r = 0.43, p = 0.004) and Cho (r = 0.38, p = 0. 011) concentrations. No significant differences in metabolite concentrations were seen over one year. This study provides evidence that age-related changes of metabolite concentrations occur even in a young to middle aged adult population. This emphasizes the need to perform absolute quantification of metabolite concentrations rather than ratios and the importance of age-matching in (1)H MRS studies of multiple sclerosis.     

Occupational prolonged organic solvent exposure in shoemakers: brain MR spectroscopy findings

Our purpose was to investigate, by magnetic resonance (MR) spectroscopy, the metabolite changes in the brains of subjects in the shoemaking industry who had been chronically exposed to organic solvents. A total of 49 male subjects and 30 age-matched healthy volunteers underwent detailed neurological and psychiatric examinations. All subjects had long-echo [repetition time (TR) 2000 ms, echo time (TE) 136 ms] single-voxel MR spectroscopy. Voxels (15 x 15 x 15 mm(3)) were placed in the parietal white matter, thalamus, and basal ganglia. N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were calculated. There was no significant difference between the study subjects and the control group in NAA/Cr ratios obtained from thalamus, basal ganglia, and parietal white matter. Cho/Cr ratios in thalamus, basal ganglia, and parietal white matter were found to be significantly increased compared to controls. There was a positive correlation between basal ganglia Cho/Cr ratio and duration of exposure (r = 0.63). MR spectroscopy should be performed to reveal metabolite changes and determine the degree of brain involvement in solvent-related industry workers.     

3-D echo planar (1)HMRS imaging in MS: metabolite comparison from supratentorial vs. central brain

To determine if metabolite ratios as measured by 3-dimensional echo planar spectroscopy imaging (3D-EPSI) from central brain regions of interest (ROI) centered at the corpus callosum reflect imaging metrics of large volumes of supratentorial brain (STB) from patients with multiple sclerosis. METHODS: 48 MS patients with relapsing-remitting, secondary progressive, and primary progressive disease underwent a 3D-EPSI sequence covering large volumes of STB. Metabolite ratios were first estimated from all voxels within a STB mask using a linear regression of N-acetylaspartate (NAA) over Creatine (Cr), NAA over choline (Cho) and Cho over Cr. Secondly, spectroscopic voxels from a central brain (CB) ROI centered at the corpus callosum were selected within the STB. Ratios were compared using Bland-Altman regression analysis and Spearman's correlation coefficients between STB versus central brain. Ratios from studied ROIs were correlated with the EDSS and compared to normal controls. RESULTS: Very strong correlations ranging from 0.884 and 0.938 (p < 0.0001) were found for all metabolite ratios between STB versus central brain. NAA/Cr ratios were similarly and negatively correlated with the EDSS across all ROIs, trends ranging from -0.257 to -0.314 (p < 0.1). NAA/Cr from all MS patients was similarly decreased compared to controls across all ROIs (p < 0.01). CONCLUSION: Metabolite ratios from a central brain ROI were statistically equivalent and highly correlated with ratios from the STB. The study of NAA/Cr using (1)HMRS from a central brain ROI centered at the corpus callosum seems to be representative of brainwide axonal changes in patients with MS.     

Development of the time course for processing conflict: an event-related potentials study with 4 year olds and adults

Background

The neurological complications of HIV infection remain poorly understood. Clinically, in vivo ¹H magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo ¹H MRS study of the SIV/macaque model of neuroAIDS.

Results

Eight rhesus macaques were infected with SIVmac251 and serially imaged with MRI and ¹H MRS to terminal AIDS or the endpoint of 2 years. During acute infection, there were stereotypical brain MRS changes, dominated by a significant elevation of the Cho/Cr ratio in the frontal cortex. Subsequently, brain metabolic patterns diverged between animals. There was an elevation of basal ganglia Cho/Cr four weeks post-inoculation in 2 animals that developed SIV encephalitis (p = 0.022). Metabolite ratios averaged across all 8 animals were not significantly different from baseline at any time point after 2 weeks post inoculation. However, linear regression analysis on all 8 animals revealed a positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P < 0.001, R = 0.80), and a negative correlation between NAA/Cr in the basal ganglia and the plasma viral load (P < 0.02, R = -0.73). No MRI abnormalities were detected at any time.

Conclusions

After infection with SIV, macaque brain metabolism changes in a complex manner that is dependent on brain region, host factors and viral load. An elevation of basal ganglia Cho/Cr 4 weeks after SIV infection may be marker of a propensity to develop SIV encephalitis. Elevations of Cho/Cr, often observed in CNS inflammation, were associated with increased plasma viral load during acute and chronic infection. Evidence of neuronal injury in the basal ganglia was associated with increased plasma viral load in the chronic stage of infection. These observations support the use of drugs capable of controlling the viral replication and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of those drugs to effectively enter the CNS.     

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.     

Brain metabolite alterations demonstrated by proton magnetic resonance spectroscopy in diabetic patients with retinopathy

Due to the homology between retinal and cerebral microvasculatures, retinopathy is a putative indicator of cerebrovascular dysfunction. This study aimed to detect metabolite changes of brain tissue in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) using proton magnetic resonance spectroscopy (¹H-MRS). Twenty-nine T2DM patients with DR (DR group), thirty T2DM patients without DR (DM group) and thirty normal controls (NC group) were involved in this study. Single-voxel ¹H-MRS (TR: 2000 ms, TE: 30 ms) was performed at 3.0 T MRI/MRS imager in cerebral left frontal white matter, left lenticular nucleus, and left optic radiation. Our data showed that NAA/Cr ratios of the DR group were significantly lower than those of the DM group in the frontal white matter and optic radiation. In the lenticular nucleus, MI/Cr ratios were significantly higher in the DM group than those in the NC group, while MI/Cr ratios were significantly lower in the DR group than those in the DM group. In the frontal white matter, NAA/Cho ratios were found to be decreased in the DR group as compared to the NC group. Additionally, our finding indicated that NAA/Cr ratios were negatively associated with DR severity in both the frontal white matter and optic radiation. A decrease in NAA indicated neuronal loss and the likely explanation for a decrease in MI was glial loss. In conclusion, we inferred that cerebral neurons and glia cells were damaged in patients with DR. Our data support that DR is associated with brain tissue damage.     

Proton MR spectroscopy of cerebellitis

Single voxel proton MR spectroscopy ((1)H-MRS) of the vermis was obtained in two patients with cerebellitis. In the acute phase (1)H-MRS revealed low N-acetyl-aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) and normal Cho/Cr ratios. Decrease of the concentration of NAA was confirmed by quantitative analysis in one patient. The NAA/Cr and NAA/Cho ratios and NAA concentration were increased in (1)H-MRS examinations obtained 10 and 24 months after the acute episode. (1)H-MRS demonstrates reversible metabolite changes in cerebellitis.     

Reproducibility of metabolite peak areas in 1H MRS of brain

We studied the reproducibility of metabolite signals (from N-acetyl aspartate [NAA], choline, and creatine) measured with a standard single-voxel proton magnetic resonance spectroscopy technique (PRESS, TE = 135 ms, 8 ml VOI) in vitro and in two groups of normal volunteers. Spectral peak areas were quantified both by integration and by curve-fitting. In the in vitro study, the “between-days” variability (coefficient of variation [CV]) of measurements ranged from 0.9% to 2.3%. In the first group of volunteers (n = 12), single voxel spectroscopic measurements (8 ml VOI, 256 acquisitions [ACQs]) were made from mirrorimage parts of the right and left hemispheres on 2 separate days. The “between-days” CV of measurements ranged from 9% to 18% for metabolite areas, and from 10% to 26% for metabolite area ratios. There were no significant differences between quantification method or hemisphere. After checking and optimising the MR scanner performance (in fact, it was virtually optimal), the second group (n = 4) each had six sequential single voxel spectroscopic measurements (each of 64 ACQs) from the right hemisphere (without moving the voxel) on each of 4 separate days. Even when the metabolites were measured from the same place in the same hemisphere sequentially six times in a 20-min period, the “within-run” CVs ranged from 4.4% to 17.2% for metabolite areas and from 9.7% to 17.0% for metabolite area ratios. The between-days CVs for the subjects ranged from 7.7% to 25.8% (metabolite areas) and from 10.1% to 22.6% (metabolite area ratios). The variability is due to a combination of random noise, subject motion, baseline artefacts in the spectra, and uncertainties in repositioning the VOIs. It is likely to represent the best reproducibility possible with 8-ml VOIs in cooperative, healthy volunteers carefully positioned on each occasion in a standard clinical scanner. Changes in metabolite levels in individuals must therefore be of the order of 20–40% before we can be reasonably confident of measuring them. Reproducibility in patients, who may be less cooperative, will probably be no better, and this must be taken into account in the interpretation of MRS studies in patients with brain pathology; for example, stroke, head injury, and tumours.     

Proton MR spectroscopy features of normal appearing white matter in neurofibromatosis type 1

To determine whether differences exist between neurofibromatosis type 1 (NF1) patients with or without focal lesions and healthy normal volunteers in the metabolite ratios of normal appearing white matter, 27 patients with NF1 (with parenchymal lesion, MR positive, n: 17; without parenchymal lesions, MR negative, n: 10) and 20 healthy volunteers underwent MRI and short TE (31 ms) proton MR spectroscopy (MRS). In 17 patients with parenchymal lesions, 61 focal lesions were detected by MRI. MRS was performed from normal appearing frontal and posterior parietal white matter (FWM and PWM) in NF1 and from control groups. NAA/Cr, Cho/Cr and MI/Cr ratios were calculated. Significant increase in Cho/Cr and MI/Cr ratios were found in FWM and PWM in MR negative and positive groups when compared to control group. NAA/Cr ratio in MR positive group was significantly decreased in FWM compared to control group. There were no significant differences between FWM and PWM in all metabolite ratios of MR negative group. MI/Cr ratio in MR positive group was significantly elevated in PWM compared to FWM. Metabolite changes detected by MRS could indicate demyelination and gliosis in normal appearing white matter in all NF1 patients, and additionally neuroaxonal damage in the FWM of NF1 patients with focal lesions. For that reason, in the clinical evaluation and follow-up of these patients MRS features of normal appearing white matter should be considered in addition to focal lesions.     

Magnetic resonance spectroscopy study of proton metabolite level changes in sensorimotor cortex after upper limb replantation-revascularization

We aimed to investigate the changes in proton metabolite levels at the motor and somatosensory cortex by magnetic resonance spectroscopy (MRS) after upper extremity replantation or revascularization. Nine patients who referred to our clinic suffering from major total (two) and subtotal (seven) amputation of the upper extremity were enrolled in this study. Mean time value between the injury and operation was 5.1 h. Mean follow-up period or mean time between the injury and MRS analysis was 26.2 months (ranging from 7 to 41 months). Voxels (TR: 2000; TE: 136 ms) were placed onto locations in the bilateral precentral and postcentral cortex area of the cerebral hemispheres that represent the upper extremity. Contralateral sides of the brain hemisphere that represent the injured extremity were accounted as control groups. Metabolite ratios [NAA (N-acetyl aspartate)/Cr (creatine) and Cho (choline)/Cr] of the motor and somatosensory cortex were calculated. The NAA/Cr and Cho/Cr metabolite ratios between the two groups were found to be insignificant, and these results may indicate that there is no remarkable somatosensorial cortex disruption or demyelination in these patients. Fifty-six percent of patients were found as functional according to Chen's scale.     

3D sensitivity encoded ellipsoidal MR spectroscopic imaging of gliomas at 3T

Purpose

The goal of this study was to implement time efficient data acquisition and reconstruction methods for 3D magnetic resonance spectroscopic imaging (MRSI) of gliomas at a field strength of 3T using parallel imaging techniques.

Methods

The point spread functions, signal to noise ratio (SNR), spatial resolution, metabolite intensity distributions and Cho:NAA ratio of 3D ellipsoidal, 3D sensitivity encoding (SENSE) and 3D combined ellipsoidal and SENSE (e-SENSE) k-space sampling schemes were compared with conventional k-space data acquisition methods.

Results

The 3D SENSE and e-SENSE methods resulted in similar spectral patterns as the conventional MRSI methods. The Cho:NAA ratios were highly correlated (P<.05 for SENSE and P<.001 for e-SENSE) with the ellipsoidal method and all methods exhibited significantly different spectral patterns in tumor regions compared to normal appearing white matter. The geometry factors ranged between 1.2 and 1.3 for both the SENSE and e-SENSE spectra. When corrected for these factors and for differences in data acquisition times, the empirical SNRs were similar to values expected based upon theoretical grounds. The effective spatial resolution of the SENSE spectra was estimated to be same as the corresponding fully sampled k-space data, while the spectra acquired with ellipsoidal and e-SENSE k-space samplings were estimated to have a 2.36–2.47-fold loss in spatial resolution due to the differences in their point spread functions.

Conclusion

The 3D SENSE method retained the same spatial resolution as full k-space sampling but with a 4-fold reduction in scan time and an acquisition time of 9.28 min. The 3D e-SENSE method had a similar spatial resolution as the corresponding ellipsoidal sampling with a scan time of 4:36 min. Both parallel imaging methods provided clinically interpretable spectra with volumetric coverage and adequate SNR for evaluating Cho, Cr and NAA.     

Brain metabolite concentration ratios in vivo: multisite reproducibility by single-voxel 1H MR spectroscopy

Ten normal subjects were scanned identically at three separate sites (Little Rock, Houston, and New Orleans) to evaluate the reproducibility of brain metabolite ratios in single-voxel (1)H point-resolved spectroscopy sequence (PRESS) magnetic resonance (MR) spectroscopy in vivo. All scans were processed by a single individual at a single site. Coefficients of variation of the measured metabolite ratios generally were in the range found for previous single-voxel, single-site reproducibility studies. No differences were found among the sites for ratios of N-acetylaspartate to creatine (NAA/Cr) or choline to Cr (Cho/Cr) in left thalamus by multivariate ANOVA. Metabolite ratios of Cr or Cho relative to local brain H(2)O did not vary among the sites. However, by multivariate ANOVA, NAA/H(2)O differed between Little Rock and New Orleans, but not between those sites and Houston. Intraclass correlation coefficients suggested reasonable reproducibility between Little Rock and New Orleans, but not between those sites and Houston.     

In vivo quantification of the metabolites in normal brain and brain tumors by proton MR spectroscopy using water as an internal standard

Metabolite concentrations in normal adult brains and in gliomas were quantitatively analyzed by in vivo proton magnetic resonance spectroscopy (MRS) using the fully relaxed water signal as an internal standard. Between January 1998 and October 2001, 28 healthy volunteers and 18 patients with gliomas were examined by in vivo proton MRS. Single voxel spectra were acquired using the point-resolved spectroscopic pulse sequence with a 1.5-T scanner (TR/TE/Ave = 3000 ms/30 ms/64). The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre), choline (Cho), and water (H2O) in the normal hemispheric white matter were 23.59 +/- 2.62 mM (mean +/- SD), 13.06 +/- 1.8 mM, 4.28 +/- 0.8 mM, and 47280.96 +/- 5414.85 mM, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). The NAA/Cho and NAA/H2O ratios can distinguish the normal brain from gliomas, and low-grade astrocytoma from high-grade group (p < 0.001). The concentration of taurine (Tau) in medulloblastomas was 29.64 +/- 5.76 mM. This is the first quantitative analysis of Tau in medulloblastoma in vivo and confirms earlier in vitro findings.     

Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized,placebo-controlled P MRS study

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy (³¹P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9–5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5–4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.