Proton MR spectroscopy in multiple sclerosis: value in establishing diagnosis, monitoring progression, and evaluating therapy

MR imaging is currently the technique of choice for evaluating brain lesions in patients with multiple sclerosis (MS). In addition to MR imaging, proton MR spectroscopy has shown potential in diagnosing MS and monitoring the progression of treatment. Spatially localized proton spectroscopy has been used to evaluate changes in choline, creatine, N-acetyl aspartate (NAA), lipids, and lactate in MS patients and in animal models of MS. The main spectroscopic findings are a decrease in the NAA:creatine ratio and an increase in the choline:creatine ratio in brain regions that include plaques defined by MR imaging. Proton MR spectroscopy along with MR imaging may be helpful in distinguishing those early lesions that might respond to therapy from late irreversible lesions. Preliminary evidence suggests that although the proton spectra acquired from patients with various brain diseases are similar (high choline, low NAA), there are differences in other resonances (lipids, lactate, glutamate, inositol) that could potentially help in diagnosing MS. Changes in proton metabolites potentially can be used to differentiate between the different stages of the MS lesion (hyperacute and edematous lesions, demyelinated lesions, and subacute to chronic plaques). It is hypothesized that successful treatment of demyelination and neuronal damage will be accompanied by changes in the proton spectrum (high choline:creatine ratio will lower to normal values and low NAA:creatine values will rise to normal values).     

Proton MR spectroscopy and magnetization transfer ratio in multiple sclerosis: correlative findings of active versus irreversible plaque disease.

PURPOSETo characterize plaques of multiple sclerosis (MS) using both proton MR spectroscopy and magnetization transfer (MT) imaging.METHODSThe magnetization transfer ratio (MTR) was calculated from two series of three-dimensional gradient-recalled acquisition in the steady state (GRASS) images obtained with and without an MT saturation pulse. Proton spectra were acquired using the point-resolved spectroscopy (PRESS) sequence with a voxel size of 1.5 x 1.5 x 1.5 cm3. A total of 28 spectra were obtained in 13 patients who had clinically definitive MS. The spectra were analyzed together with the MTR.RESULTSA positive relationship was found between the N-acetylaspartate (NAA)/creatine (Cr) ratio and the MTR in MS plaques, whereas no significant correlation was found between the metabolite ratios and the signal intensity on fast spin-echo T2-weighted MR images.CONCLUSIONSmall changes in the MTR of MS plaques relative to the MTR of normal white matter may reflect inflammatory changes and edema, whereas larger changes in MTR correlate with decreased NAA/Cr ratio and therefore suggest demyelination and irreversible damage from chronic MS plaques.     

MR imaging,MR angiography,and MR spectroscopy of the brain in eclampsia.

PURPOSETo compare the MR imaging and MR angiographic changes with in vivo proton MR spectroscopic findings and to determine the spectral differences between edema and ischemia in patients with eclampsia.METHODSSpin-echo MR imaging, MR angiography, and single-voxel proton MR spectroscopy were performed in 10 patients with eclampsia. MR studies were obtained within 3 to 5 days of diagnosis and repeated after 2 weeks with identical parameters.RESULTSMultifocal subcortical/cortical hyperintensities were noted in all 10 patients on T2-weighted images; in two patients, hyperintensities were seen in both cerebral hemispheres. In nine patients, MR angiograms showed narrowing of the major vessels constituting the circle of Willis that resolved after 2 weeks. In one patient with subtle imaging changes, MR angiography showed mild bilateral narrowing of the proximal middle and posterior cerebral arteries that did not change after 2 weeks, whereas imaging abnormalities worsened. Findings at single-voxel MR spectroscopy of the reversible T2 hyperintense lesions were significantly different from findings in the control group for N-acetylaspartate (NAA)/creatine ratios. One patient with mild abnormalities at MR imaging and MR angiography had lactate and decreased creatine and NAA, and on a follow-up study had a further decrease of NAA and creatine as well as a decrease in lactate.CONCLUSIONIn vivo proton MR spectroscopy may help to differentiate cerebral edema from ischemia in patients with eclampsia and thus may help to determine the prognosis for these patients.     

MR proton spectroscopy in multiple sclerosis.

PURPOSE: To elucidate the natural history of visualized MR abnormalities in patients with multiple sclerosis using proton spectroscopy. METHODS: MR imaging and proton spectroscopy (1H spectroscopy) were performed on 16 patients with clinically definite multiple sclerosis. All patients received gadopentetate dimeglumine (Gd-DTPA). RESULTS: Decreased levels of N-acetylaspartate (NAA) were demonstrated in 17 out of 21 lesions. No correlation was found between decreased NAA and Gd-DTPA enhancement. In five out of seven enhancing lesions, abnormal 1H spectra with extra peaks (termed marker peaks) at 2.1-2.6 ppm (ranging in absolute concentration from 10-50 mM protons) were observed. In nine out of 14 unenhancing lesions, no elevated marker peaks were observed. In the five other unenhancing lesions, the levels of these marker peaks were generally lower than the enhancing group. No correlation was found between the NAA levels and the levels of the marker peaks. We suggest two distinct biochemical processes: 1) decreased NAA reflecting neuronal cell loss, and 2) elevated marker peaks reflecting ongoing demyelination. CONCLUSIONS: Based upon these observations we infer that 1) the majority of enhancing lesions are demyelinating with extra peaks at 2.1-2.6 ppm representing a marker of this process, 2) enhancing lesions without this marker most likely represent edematous regions without significant demyelination, and 3) demyelination may be long in duration compared with transient blood-brain barrier disruption manifested by Gd-DTPA enhancement. Our results suggest that 1H spectroscopy has the ability to further categorize MR-demonstrated enhancing and unenhancing lesions in patients with multiple sclerosis and that it may be more sensitive than contrast enhancement in revealing the true time course of demyelination.     

Relapsing-remitting multiple sclerosis: metabolic abnormality in nonenhancing lesions and normal-appearing white matter at MR imaging: initial experience

PURPOSE: To quantify, with three-dimensional proton magnetic resonance (MR) spectroscopy, metabolic characteristics of normal-appearing white matter and nonenhancing lesions in patients with relapsing-remitting multiple sclerosis (MS). MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. Nine patients with relapsing-remitting MS (six women, three men) and nine age-matched control subjects (seven women, two men) were studied with T1- and T2-weighted MR imaging and three-dimensional proton MR spectroscopy at spatial resolution less than a cubic centimeter. Absolute N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were obtained from 171 voxels: 66 from lesions on T2-weighted MR images (43 hypointense and 23 isointense on T1-weighted MR images), 31 from normal-appearing white matter, and 74 from analogous normal white matter regions on images in control subjects. RESULTS: Mean NAA level in hypointense lesions (5.30 mmol/L +/- 2.27 [standard deviation]) was significantly lower (P < or = .05) than that in isointense lesions (7.82 mmol/L +/- 2.28), normal-appearing white matter (7.37 mmol/L +/- 1.71), and normal white matter in control subjects (8.89 mmol/L +/- 1.54). Cho (1.79 mmol/L +/- 0.65) and Cr (5.64 mmol/L +/- 1.50) levels in isointense lesions were indistinguishable from those in normal-appearing white matter (1.74 mmol/L +/- 0.46 and 4.99 mmol/L +/- 0.97, respectively) but were significantly higher (Cho, 20%; Cr, 24%) than those in normal white matter in control subjects (1.44 mmol/L +/- 0.40 and 4.30 mmol/L +/- 1.32, respectively). NAA, Cho, and Cr levels in normal-appearing white matter were significantly different than those in normal white matter in control subjects (NAA, 20% lower; Cho, 14% higher; and Cr, 17% higher). CONCLUSION: Abnormal metabolic activity persists in all MS tissue types. Increased Cr and Cho levels suggest (a) ongoing gliosis and attempted remyelination in isointense lesions on T1-weighted MR images and (b) membrane turnover (de- and remyelination), in addition to increased cellularity (gliosis, inflammation) in normal-appearing white matter.     

Functional MR spectroscopy of the auditory cortex in healthy subjects and patients with sudden hearing loss.

PURPOSETo use MR spectroscopy to study the biochemical changes produced by auditory stimuli in patients with sudden sensorineural hearing loss and to compare these findings with the biochemical changes seen in healthy volunteers.METHODSSingle-voxel MR spectroscopy was used to study biochemical changes in the auditory cortex in 11 control subjects and 19 patients with sudden sensorineural hearing loss. MR spectroscopic signals were measured during three different sound conditions (scanner noise, music, and sirens).RESULTSA lower MR spectroscopic lactate signal was observed in control subjects during the music stimulus than during the other sound conditions. This music-induced lactate change was not observed in patients with hearing loss. The other proton metabolites (choline, creatine, N-acetylaspartate [NAA]) remained stable during the different auditory stimuli. However, the NAA/creatine ratio was higher in the auditory cortex of patients than in the control subjects, and was not dependent on the sound condition.CONCLUSIONThe detection of stimulus-induced and stable biochemical MR spectroscopic changes in patients with hearing loss may be useful in assessing disease activity.     

Noninvasive evaluation of malignancy of brain tumors with proton MR spectroscopy.

PURPOSETo test clinical proton MR spectroscopy as a noninvasive method for predicting tumor malignancy.METHODSWater-suppressed single-voxel point resolved spectroscopy in the frontal white matter of 17 healthy volunteers and 25 patients with brain tumors yielded spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cre), and lactate. These peak intensities were semiquantitated as a ratio to that of the external reference. The validity of the semiquantitation was first evaluated through phantom and volunteer experiments.RESULTSThe variation in measurements of the designated region in the volunteers was less than 10%. Normal ranges of NAA/reference, Cho/reference, and Cre/reference were 3.59 +/- 0.68, 1.96 +/- 0.66, and 1.53 +/- 0.64 (mean +/- SD), respectively. In 17 gliomas, the Cho/reference value in high-grade gliomas was significantly higher than in low-grade gliomas. Levels of NAA/reference were also significantly different in low-grade and high-grade malignancy. In eight meningiomas (four newly diagnosed and four recurrent), the level of Cho/reference was significantly higher in recurrent meningiomas than in normal white matter or in newly diagnosed meningiomas.CONCLUSIONSHigher grades of brain tumors in this study were associated with higher Cho/reference and lower NAA/reference values. These results suggest that clinical proton MR spectroscopy may help predict tumor malignancy.     

Serial proton MR spectroscopy of contrast-enhancing multiple sclerosis plaques: absolute metabolic values over 2 years during a clinical pharmacological study

BACKGROUND AND PURPOSE: The time courses of total creatine (Cr), N-acetylaspartate (NAA), choline (Cho), and myo-inositol have not previously been investigated in the follow-up of contrast-enhancing multiple sclerosis (MS) plaques. Therefore, over a period of 2 years, we compared the absolute concentrations of these metabolites between patients treated with a placebo or 15 +/- deoxyspergualin (DSG) and between clinical groups with relapsing-remitting or secondary-progressive MS. METHODS: Sixteen patients, recruited from a pharmacological study of DSG, and 11 healthy control subjects were investigated by a stimulated-echo acquisition mode sequence (TR/TE = 3000/20). The selected volume initially contained a contrast-enhancing plaque, which was followed up for a period of 2 years. RESULTS: In contrast-enhancing plaques, Cho was significantly elevated and showed a significant reduction after both 3 and 12 months. The initially normal Cr significantly increased between 3 and 12 months, and was negatively correlated with plaque volume on T1-weighted MR images. NAA initially showed normal values, a significant decrease at 1 month, and a slow recovery over 2 years. Myo-inositol did not show a clear tendency. The placebo group did not differ from the treated group, nor did the relapsing-remitting group differ from the secondary-progressive group. CONCLUSION: The contradictory time courses of Cr and NAA show that an absolute quantification in proton MR spectroscopy in MS is necessary to avoid a false interpretation of reduced NAA/Cr ratios. The increase in Cr is probably due to remyelination. The initial dip and later recovery of NAA seem to be related to diminishing edema and remyelination.     

Proton MR spectroscopic characteristics of pediatric pilocytic astrocytomas.

PURPOSEWe report the common characteristics of juvenile pilocytic astrocytomas revealed by proton MR spectroscopy.METHODSEight children with pilocytic astrocytomas were studied with proton MR spectroscopy. The selected sampling volume was approximately 4 cm3, obtained from solid tumor. To localize the sampling volume, we used point-resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) techniques to acquire long- and short-TE spectra, respectively. Spectra from PRESS and STEAM sequences were processed using Lorentzian-to-Gaussian transformation and exponential apodization, respectively. For PRESS (2000/270) spectra, peaks of creatine, choline, N-acetylaspartate (NAA), and lactate resonances were integrated; for STEAM (2000/20) spectra, we measured the amplitude of the peaks at 3.2, 2.0, 1.3 and 0.9 ppm.RESULTSAn elevated lactate doublet was observed in the PRESS spectra. The choline/NAA ratio was 3.40. The amplitude ratios of the lipid pattern (0.9, 1.3 and 2.0 ppm) to choline were all below one.CONCLUSIONDespite the benign histology of the tumor, which generally lacks necrosis, a lactate signal was detected in all eight patients studied. A dominant lipid pattern was not observed.     

White matter disease induced by high-dose chemotherapy: longitudinal study with MR imaging and proton spectroscopy.

PURPOSEThe purpose of this study was to determine the time course for development of white matter changes induced by high-dose chemotherapy.METHODSEight patients with advanced breast cancer were entered into a prospective, longitudinal trial that included examination by MR imaging and proton MR spectroscopy before chemotherapy and through 12 months after treatment with carmustine, cyclophosphamide, and cisplatin, combined with autologous hematopoietic progenitor cell support (AHPCS).RESULTSSix patients completed induction chemotherapy, at which time all MR imaging studies appeared normal. At 3 months after the conclusion of high-dose chemotherapy and beyond, three of the four patients remaining in the study showed an increasing volume of white matter changes, which appeared to stabilize during the period from 6 months to 1 year. Maximal volumes of abnormal white matter ranged from 73 to 166 cm3. MR spectroscopy showed little or no change in metabolic ratios through the period of observation, although there was a suggestion of small transient treatment-related decreases in the ratio of N-acetyl aspartate (NAA) to creatine.CONCLUSIONWhite matter changes are common sequelae of treatment with high-dose chemotherapy combined with AHPCS, occurring early in the period following high-dose chemotherapy, with a rapid and progressive accumulation to about 6 months, but not accompanied by persistent neurologic symptoms. The MR spectroscopic analyses suggest a minimal disturbance of the neuronal marker NAA, a finding that may in part explain the good neurologic outcome.     

Proton MR spectroscopy of gadolinium-enhanced multiple sclerosis plaques.

Magnetic resonance (MR) imaging and proton MR spectroscopy were performed in 14 patients with clinically definite multiple sclerosis (MS). Prominent resonances in the 0.5-2.0-ppm region were seen in the spectra of six of nine gadopentetate dimeglumine-enhanced plaques in seven patients. These resonances were presumed to originate in lipids and other myelin breakdown products. Similar resonances were detected in only seven of 21 unenhancing plaques. The more frequent presence of such signals in the gadolinium-enhanced regions indicates that myelin breakdown is often associated with the inflammation that occurs in early stages of MS plaque evolution. It remains uncertain, however, whether active inflammation as indicated by gadolinium enhancement is a necessary precursor of myelin breakdown as detected at MR spectroscopy. Quantitative spectral analysis did not indicate statistically significant differences in N-acetyl aspartate and choline levels relative to creatine plus phosphocreatine between healthy volunteers and MS patients.     

Proton MR spectroscopy in patients with neurofibromatosis type 1: evaluation of hamartomas and clinical correlation.

PURPOSETo use proton MR spectroscopy in patients with neurofibromatosis type 1 to determine: (a) the spectroscopic characteristics of hamartomas and compare them with that of gliomas; (b) whether differences exist between patients with and without learning disabilities; and (c) spectroscopic patterns in normal-appearing brain (by MR imaging) in patients with and without focal lesions.METHODSSeventeen proton MR spectroscopy volumes were obtained in 10 patients with neurofibromatosis type 1 (including hamartomas, N = 7; normal-appearing brain, N = 10). Seven patients had learning disorders, and 3 were mentally normal. Ten healthy volunteers and 10 patients with pathologically proved gliomas (all grades) were also examined. N-Acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were calculated for all samples.RESULTS(a) Hamartomas showed higher N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios than gliomas. Hamartomas showed N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios similar to those of healthy volunteers. (b) No significant differences in N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were found in patients who had neurofibromatosis type 1 with and without learning disabilities. (c) N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were similar for patients who had neurofibromatosis type 1 with and without focal hamartomas and in healthy volunteers.CONCLUSIONS(a) Hamartomas have a proton MR spectroscopy pattern different from that of glioma and similar to that of normal brain. (b) As performed in this study, proton MR spectroscopy did not show significant differences in patients who had neurofibromatosis type 1 with and without learning disabilities. (c) Patients who have neurofibromatosis type 1 with and without hamartomas seem to have normal intervening brain by proton MR spectroscopy when compared with healthy volunteers.     

Proton MR spectroscopy of brain abnormalities in neonates born to HIV-positive mothers.

PURPOSETo examine the sensitivity of proton MR spectroscopy for detecting early central nervous system abnormalities in neonates born to human immunodeficiency virus (HIV)-positive mothers.METHODSAsleep, unsedated, and continuously monitored by electrocardiography, 10 newborns, 5 with HIV-positive and 5 with HIV-negative mothers, were studied within the first 10 days of life in a 1.5-T scanner. After T1- and T2-weighted images were obtained, proton spectra were performed using voxels of interest (3.4 cm3) in the deep parietooccipital white matter. Peaks were identified as N-acetyl-aspartate (2.0 ppm), creatine and phosphocreatine (3.0 ppm), choline (3.2 ppm), and inositol (3.5 ppm). Peak areas were used to calculate metabolic ratios: N-acetyl-aspartate to creatine, inositol to creatine, and creatine to choline.RESULTSAll newborns of HIV-positive mothers had abnormal proton spectra compared with control infants; a nonspecific amino acid peak in the 2.1- to 2.6-ppm area was elevated, broad, and overlapping the N-acetyl-aspartate peak in all the HIV-exposed newborns and in only 1 of the 5 control newborns. The choline-to-creatine ratio was higher in HIV-exposed newborns at 2.3 +/- 0.4 (normal term, 0.9 +/- 0.3), as was the N-acetyl-aspartate-to-creatine ratio at 2.6 +/- 0.9 (for control subjects, 1.2 +/- 0.4). MR images from these brain regions were all considered normal. Because acquired immunodeficiency syndrome develops in only a small fraction of neonates born to HIV-seropositive mothers, the above spectral abnormalities found in all our subjects may result from indirect effects of HIV, such as intrauterine growth retardation.CONCLUSIONSThese findings indicate that proton MR spectroscopy might play an important role in detecting early central nervous system complications in newborns of HIV-seropositive mothers.     

MR imaging and localized proton MR spectroscopy in late infantile neuronal ceroid lipofuscinosis.

PURPOSELate juvenile neuronal ceroid lipofuscinosis (NCL) is a lysosomal neurodegenerative disorder caused by the accumulation of lipopigment in neurons. Our purpose was to characterize the MR imaging and spectroscopic findings in three children with late infantile NCL.METHODSThree children with late infantile NCL and three age-matched control subjects were examined by MR imaging and by localized MR spectroscopy using echo times of 135 and 5. Normalized peak integral values were calculated for N-acetylaspartate (NAA), choline, creatine, myo-inositol, and glutamate/glutamine.RESULTSMR imaging revealed volume loss of the CNS, most prominently in the cerebellum. The T2-weighted images showed a hypointense thalamus and hyperintense periventricular white matter. Proton MR spectra revealed progressive changes, with a reduction of NAA and an increase of myo-inositol and glutamate/glutamine. In long-standing late infantile NCL, myo-inositol became the most prominent resonance. Lactate was not detectable.CONCLUSIONMR imaging in combination with proton MR spectroscopy can facilitate the diagnosis of late infantile NCL and help to differentiate NCL from other neurometabolic disorders, such as mitochondrial or peroxisomal encephalopathies.     

Localized proton MR spectroscopy of the brain in children

Small-voxel (3.0–8.0 cm³), magnetic resonance (MR) imaging–guided proton MR spectroscopy was performed in 54 patients (aged 6 days to 19 years) with intracranial masses (n = 16), neurodegenerative disorders (n = 34), and other neurologic diseases (n = 4) and in 23 age-matched control subjects without brain disease. A combined short TE (18 msec) stimulatedecho acquisition mode (STEAM) and long TE (135 and/or 270 msec) spin-echo point-resolved spatially localized spectroscopy (PRESS) protocol, using designed radio-frequency pulses, was performed at 1.5 T. STEAM spectra revealed short T2 and/or strongly coupled metabolites; prominent resonances were obtained from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and total creatine (tCr). Lactate was well resolved with the long TE PRESS sequence. Intracranial tumors were readily differentiated from cerebrospinal fluid (CSF) collections. All tumors showed low NAA, high Cho, and reduced tCr levels. Neurodegenerative disorders showed low or absent NAA levels and enhanced mobile lipid, glutamate and glutamine, and inositol levels, consistent with neuronal loss, gliosis, demyelination, and amino acid neuro-toxicity. Preliminary experience indicates that proton MR spectroscopy can contribute in the evaluation of central nervous system abnormalities of infants and children.     

Multivoxel proton MR spectroscopy and hemodynamic MR imaging of childhood brain tumors: preliminary observations.

PURPOSETo assess multivoxel proton MR spectroscopy combined with MR imaging and hemodynamic MR imaging in the evaluation of brain tumors in children and young adults.METHODSFifteen patients with brain tumors and 10 healthy children underwent MR imaging and MR spectroscopy on a 1.5-T system. Ten patients with tumors had both MR spectroscopy and hemodynamic MR imaging. MR spectroscopy data sets with 1 cm3 to 3.4 cm3 resolution were acquired within 8.5 minutes by using a point-resolved spectroscopic, chemical-shift imaging technique in two dimensions with volume preselection. MR imaging was performed using fast spin-echo techniques. Hemodynamic MR imaging data were acquired every 2.5 seconds at one anatomic level using a spoiled gradient-echo sequence during intravenous bolus administration of contrast material.RESULTSAssessment with multivoxel MR spectroscopy and hemodynamic MR imaging added about 30 minutes to the total MR examination time. Normal tissue exhibited spectral peaks from biologically significant compounds such as N-acetylaspartate (NAA), choline-containing compounds (Cho), and total creatine (tCr). Twelve biopsy-proved tumors exhibited prominent Cho, reduced NAA, variable tCr, and/or lactate or lipids, and two showed increased hemodynamic parameters. Three of the tumors treated with radiation did not reveal prominent levels of Cho. Tissue necrosis had no Cho, NAA, or tCr, and reduced hemodynamics.CONCLUSIONSPreliminary findings by MR spectroscopy combined with MR imaging and hemodynamic MR imaging suggest that regions of active tumor may be differentiated from areas of normal tissue and areas of necrosis. These findings may enable metabolic and hemodynamic characterization of childhood brain tumors as well as suggest their response to therapy.     

Neurometabolism of active neuropsychiatric lupus determined with proton MR spectroscopy.

PURPOSETo determine the neurometabolism of patients with active neuropsychiatric systemic lupus erythematosus (NPSLE) by using proton MR spectroscopy.METHODSThirty-six patients with SLE and eight control subjects were studied with proton MR spectroscopy to measure brain metabolites. Peaks from N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and at 1.3 parts per million (ppm) lipid, macromolecules, and lactate were measured. Patients were classified as having major NPSLE (seizures, psychosis, major cognitive dysfunction, delirium, stroke, or coma) (n = 15) or minor NPSLE (headache, minor affective disorder, or minor cognitive disorder) (n = 21). Patients with major NPSLE were severely ill and hospitalized.RESULTSSLE patients had lower NAA and increased metabolites at 1.3 ppm than did control subjects (NAA/Cr(SLE) = 1.90 +/- 0.35, NAA/Cr(Control) = 2.16 +/- 0.26; 1.3 ppm/Cr(SLE) = 0.49 +/- 0.41, 1.3 ppm/Cr(Control) = 0.27 +/- 0.05). NAA/Cr in patients with current or prior major NPSLE was lower than in patients without major NPSLE. Increased peaks at 1.3 ppm were present in all SLE subgroups, but particularly in patients with major NPSLE. These resonances were not evident at an echo time of 136, indicating that these signals were not lactate.CONCLUSIONMajor NPSLE, past or present, is associated with decreased levels of NAA. Elevated peaks around 1.3 ppm do not represent lactate even in severely ill patients, indicating that global ischemia is not characteristic of NPSLE. Neurochemical markers determined by MR spectroscopy may be useful for determining activity and degree of brain injury in NPSLE.     

Localized brain proton NMR spectroscopy in young adult phenylketonuria patients

Localized proton magnetic resonance spectroscopy with short echo time (TE = 20 ms) was used to investigate biochemical changes in the cerebral white matter of 20 young adult patients (median 19 years) with phenylketonuria (PKU). Results were compared with those of a group of 12 age-matched healthy volunteers (median 25 years). Concentrations of Nacetyl-aspartate (NAA) and choline (Cho) relative to creatine (Cr) were unchanged. However, concentrations of inositol (Ins) relative to creatine were found to be significantly lower (P < 0.001) in the PKU patients (0.30 ± 0.09 versus 0.57 ± 0.17). Individual inositol concentrations did not correlate with age, diet, serum phenylalanine (Phe) levels or extent of pathological regions in the T,-weighted images. The lack of correlation with individual data suggests that the decreased inositol concentration could be related to a metabolic deficiency during fetal development. No signal from the phenyl ring protons of phenylalanine was detected in the PKU patients (phenylalanine serum concentration ? 1.27 mM), which suggests that concentration of phenylalanine may be lower in brain than in serum.     

Single-voxel proton MR spectroscopy and positron emission tomography for lateralization of refractory temporal lobe epilepsy.

PURPOSEWe compared the metabolic information obtained from single-voxel proton MR spectroscopy and positron emission tomography (PET) in patients with temporal lobe epilepsy.METHODSTwenty-nine patients with temporal lobe epilepsy were screened for metabolic abnormalities with both proton MR spectroscopy and PET. Lateralization with MR spectroscopy was possible by using NAA/(Cho+Cr) and an asymmetry index. Hypometabolism as determined by PET was classified as typical or complex.RESULTSTwenty-four (96%) of 25 patients whose seizure onset could be lateralized to one temporal lobe showed ipsilateral lateralization with either MR spectroscopy or PET, whereas concordant lateralization with both techniques was possible only in 14 (56%) of the 25 patients. MR spectroscopy showed 42 abnormal temporal lobes whereas PET showed only 25 lobes with decreased metabolism. All temporal lobes with hypometabolism at PET also had a low NAA/(Cho+Cr). Five patients (20%) with negative PET studies had seizures lateralized correctly with MR spectroscopy.CONCLUSIONProton MR spectroscopy is more sensitive in depicting metabolic abnormalities than is PET in patients with temporal lobe epilepsy. Patients with negative PET studies will benefit from MR spectroscopy for the purpose of lateralization.     

Increased spatial resolution using a three-dimensional T1-weighted gradient-echo MR sequence results in greater hypointense lesion volumes in multiple sclerosis.

PURPOSEOur goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS).METHODSA magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman''s rank correlation coefficient.RESULTSThe median volume of hypointense lesions increased from 1.2 mL (range, 0 to 14.9 mL) on the 5-mm-thick MP-RAGE images to 1.7 mL (range, 0 to 15.8 mL) on the 3-mm-thick images, and to 1.9 mL (range, 0 to 16.2 mL) on the 1-mm-thick images. The hypointense lesion volumes measured on the three MP-RAGE images correlated significantly with the degree of disability, whereas this correlation was not significant with the T2-weighted lesion load.CONCLUSIONOur findings indicate that a significant increase in the volume of potentially disabling MS lesions is observed when obtaining MR images with thin sections.