1H-magnetic resonance spectroscopy-determined cerebral lactate and poor neurological outcomes in children with central nervous system disease

By using proton magnetic resonance spectroscopy ((1)H-MRS), cerebral lactate has been shown to be elevated in a wide variety of pediatric and adult neurological diseases. In this study we compared 36 newborns, infants, and children with elevated lactate peaks on (1)H-MRS with 61 patients without an identifiable lactate signal. (1)H-MRS was acquired from the occipital gray and parietal white matter (8 cm3 volume, STEAM sequence with echo time = 20 msec, repetition time = 3.0 seconds) and data were expressed as ratios of different metabolite peak areas (N-acetylaspartate [NA]/creatine [Cr], NA/choline [Ch], and Ch/Cr) and the presence of a characteristic lactate doublet peak at 1.3 ppm. Outcomes (Pediatric Cerebral Performance Category Scale score; PCPCS) were assigned 6 to 12 months after injury. Patients with lactate peaks were more likely to have suffered a cardiac arrest, were more often hyperglycemic, and had lower Glasgow Coma Scale scores on admission. They were also more likely to have abnormal metabolite ratios when compared with age-matched controls or with patients without detectable lactate. Of prognostic importance, patients with increased lactate were more likely to be severely disabled (39% vs 10%), survive in a persistent vegetative state (13% vs 2%), or have died (39% vs 7%). In contrast, patients with similar conditions without increased lactate were more likely to have had a good outcome (23% vs 3%) or recovered to a mild (38% vs 6%) or moderate disability (20% vs 0%). Our data suggest that (1)H-MRS is useful in the prediction of long-term outcomes in children with neurological disorders. Patients with elevated cerebral lactate are more likely to die acutely or are at greater risk for serious long-term disability.     

Proton MR spectroscopy of childhood adrenoleukodystrophy

PURPOSE: To determine the potential of proton MR spectroscopy to monitor patients with childhood-onset cerebral adrenoleukodystrophy (COCALD). METHODS: Single-voxel MR spectroscopy was performed in 16 children with COCALD (24 examinations) who had had no treatment and in 7 children (13 examinations) who had had bone marrow transplantation. RESULTS: In the untreated children with clinically active COCALD, the metabolite ratios N-acetyl-aspartate (NAA)/creatine (Cr) and NAA/choline (Ch) were decreased while Ch/Cr was increased. This trend agrees well with those reported by other researchers, although different experimental sequences and parameters were used in our study. Comparison of these ratios with those from a control group yielded significant differences in the occipital region. In the children who were clinically stable after bone marrow transplantation, the mean levels of the three ratios were between those of the control subjects and the patients with untreated COCALD: the differences in these ratios approached significance. In patients who had been monitored periodically, MR spectroscopy metabolite ratios correlated well with the dementia rating score, reflecting clinical status. CONCLUSION: There is good correlation between MR spectroscopy metabolite ratios and a patient's clinical status. MR spectroscopy appears to be a useful, noninvasive tool to monitor patients with adrenoleukodystrophy, and it increases the overall sensitivity of MR techniques in clinical applications.     

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) stimulated-echo 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 neurotoxicity. 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

PURPOSE: To assess multivoxel proton MR spectroscopy combined with MR imaging and hemodynamic MR imaging in the evaluation of brain tumors in children and young adults. METHODS: Fifteen 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. RESULTS: Assessment 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. CONCLUSIONS: Preliminary 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.     

MR of hypoxic encephalopathy in children after near drowning: correlation with quantitative proton MR spectroscopy and clinical outcome

BACKGROUND AND PURPOSE: Quantitative MR spectroscopy has a proved role in the investigation of hypoxia caused by near drowning. To date, no studies have addressed the MR imaging changes that may also accompany this condition. The purpose of this study was to describe the MR imaging findings in children with hypoxic encephalopathy caused by near drowning and to compare these findings with the results of qualitative and quantitative proton MR spectroscopy and clinical outcome. METHODS: Twenty-two children (6 months to 11 years old) admitted to the pediatric intensive care unit after near drowning incidents underwent cerebral MR imaging and quantitative proton MR spectroscopy. Clinical and imaging studies were reviewed retrospectively, and subjects were grouped according to outcome: good result, persistent vegetative state, and death. Images were scored for edema, basal ganglia changes, and cortical changes, and were compared with MR spectra and outcome at days 1 to 2, 3 to 4, and 5 or more. RESULTS: Six patients had a good outcome, four remained in a persistent vegetative state, and 12 died. Generalized/occipital edema correlated with poor outcome. Indistinct lentiform nuclei margins on T1-weighted images were a frequent finding (78%). Basal ganglia T2 hyperintensity correlated with poor outcome, progressing from a patchy/peripheral distribution to diffuse high intensity. Patchy high T2 signal in the cortex or subcortical lines were specific but insensitive for poor outcome, as were brain stem infarcts. CONCLUSION: MR images in children with hypoxic encephalopathy after near drowning show a spectrum of changes. The most sensitive prognostic result may be achieved by combining MR imaging with qualitative and quantitative MR spectroscopic data.     

Characterization of Trichomonas vaginalis virus proteins in the pathogenic protozoan T. vaginalis

PURPOSE: Children who have brain tumors are at risk for a variety of treatment-related sequelae, including neuropsychological and cognitive impairment, neurologic deficits, and neuroendocrinologic disturbances. We sought to determine the value of proton MR spectroscopy in assessing brain tissue remote from the tumor site to ascertain the effects of chemotherapy and radiation treatment in these patients. METHODS: Single-voxel proton MR spectra from 70 patients (111 spectra) and 11 healthy volunteers (11 spectra) were analyzed. NAA/Cr, NAA/Cho, and Cho/Cr ratios based on peak areas were obtained from nonneoplastic regions of the frontal lobe. The relationship between MR spectroscopic ratios and treatment was determined. RESULTS: NAA-containing ratios were decreased in patients as compared with control subjects. The presence of gadolinium-based contrast material did not cause significant changes in the ratios as compared with precontrast data. When chemotherapy was a component of a child's treatment protocol, we found a significant decline in NAA/Cr ratios. Patients who underwent both chemotherapy and radiation therapy showed a trend toward lower NAA-containing ratios if the chemotherapy was administered before the radiation therapy. Patients receiving whole-brain radiation had a trend toward lower NAA-containing ratios than did those who had only focal tumor treatment. CONCLUSION: In children with brain tumors, MR spectroscopy of brain tissue remote from the tumor reveals treatment-related biochemical changes.     

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

PURPOSE: Late 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. METHODS: Three 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. RESULTS: MR 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. CONCLUSION: MR 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.     

Proton magnetic resonance spectroscopy in children with Sturge-Weber syndrome

Quantitative proton magnetic resonance spectroscopy was performed on six children with Sturge-Weber syndrome following gadolinium enhanced magnetic resonance imaging (MRI). MRI revealed only unilateral involvement in all cases. The mean concentration (mmol/kg wet weight) of the neuronal marker N-acetyl-aspartate was significantly reduced by 37% in the ipsilateral gadolinium enhanced volume of interest compared to a similarly placed contralateral volume of interest (5.39 +/- 1.70 [SD] vs 8.50 +/- 1.14, P < .005, two-tailed paired Student's t-test). Decreased N-acetyl-aspartate in the ipsilateral volume of interest was observed in all patients studied. No significant differences were found in the concentrations of creatine/phosphocreatine or choline compounds between the ipsilateral and contralateral volumes of interest. These findings give possible new insight into the pathophysiology of this disease and suggest that quantitative proton magnetic resonance spectroscopy may be useful for the early characterization and monitoring of neuronal dysfunction or loss in infants and children with Sturge-Weber syndrome.     

Ovarian cancer: comparison of findings with perfluorocarbon-enhanced MR imaging, In-111-CYT-103 immunoscintigraphy, and CT

PURPOSE: To determine the accuracy of breath-hold gadolinium- and perflubron-enhanced magnetic resonance (MR) imaging, immunoscintigraphy with indium-111-CYT-103 (planar and single photon emission computed tomography [CT]), and contrast material-enhanced CT for the detection of ovarian cancer prior to laparotomy. MATERIALS AND METHODS: Sixteen patients with primary (n = 3) or treated (n = 13) ovarian cancer underwent imaging of the abdomen and pelvis with each modality. All images were reviewed prospectively for tumor location, and results were compared with findings at surgery. RESULTS: With CT or MR imaging, tumor was detected in 11 of 13 (85%) patients compared with 11 of 12 patients (92%) with immunoscintigraphy. Per patient accuracy for CT was 81% compared with 75% for MR imaging and 86% for immunoscintigraphy. For detection of individual sites of tumor, the sensitivity of MR imaging was highest (81%) compared with CT (51%, P < .001) and immunoscintigraphy (50%, P < .01). The combination of MR imaging and immunoscintigraphy depicted 89% of sites of tumor involvement confirmed at laparotomy. CONCLUSION: MR imaging and immunoscintigraphy show promise for the evaluation of patients with ovarian cancer.     

Cerebral metabolic alterations in human immunodeficiency virus-related encephalopathy detected by proton magnetic resonance spectroscopy. Comparison between sequences using short and long echo times

RATIONALE AND OBJECTIVES: The aim of this study is to evaluate comparatively the metabolic information afforded by proton magnetic resonance (MR) spectroscopy with stimulated-echo acquisition mode (STEAM) (echo time [TE], 20 mseconds) and point-resolved spectroscopy sequence (PRESS) (TE, 135 mseconds) spectra in HIV-related encephalopathy. METHODS: Sixty-three human immunodeficiency virus (HIV) patients and 8 controls were examined by single-voxel proton MR spectroscopy at 1.5 tesla, using both PRESS (TE, 135 mseconds) and STEAM (TE, 20 mseconds) sequences performed during the same MR examination, in the same volume of interest. Cerebral atrophy was quantitated using bicaudate ratio (BCR) and bifrontal ratio (BFR). RESULTS: With the STEAM (TE, 20 mseconds) spectra, mean N-acetylaspartate (NAA)/choline (Cho) and NAA/creatine and phosphocreatine (Cr-PCr) ratios are reduced in acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) patients but not in neuroasymptomatics. The proportion of inositol signal is increased, that of NAA decreased in ADC patients. NAA/Cho and NAA/ Cr-PCr mean values measured with PRESS (TE, 135 mseconds) spectra are significantly reduced in ADC and neuroasymptomatic patients. Bifrontal ratio only correlates with NAA/Cr-PCr and NAA/Cho measured on the PRESS spectrum. PRESS (TE, 135 mseconds) spectra allow a definition of different metabolic patterns in HIV-related encephalopathy. At last, no correlation has been found between the NAA raw signals measured on the PRESS (TE, 135 mseconds) and STEAM (TE, 20 mseconds) spectra obtained in the same MR examination. CONCLUSIONS: STEAM (TE, 20 mseconds) spectra provide more metabolic information-namely an evaluation of glial-neuronal status-than PRESS (TE, 135 mseconds) spectra, which afford a metabolic classification of the HIV-related encephalopathy. Because both sequences afford a similar diagnostic gain, MR spectroscopy examination probably requires spectrum acquisition with both sequences.     

Use of self-expanding metallic stents in the management of obstruction of the sigmoid colon

PURPOSE: To compare the occurrence at magnetic resonance (MR) imaging of clinically important knee abnormalities in patients referred by orthopedic surgeons with that in patients referred by other physicians. MATERIALS AND METHODS: Knee MR images in all patients referred for evaluation of internal derangement for 12 months were retrospectively reviewed. Meniscus, ligament, and articular cartilage abnormalities were tabulated. The numbers of abnormalities detected in the patients referred by orthopedic surgeons were compared with those in the patients referred by all other physicians by using chi(2) analysis. Significance was defined at P less than .05. RESULTS: Knee MR images in 439 patients were reviewed; 328 patients were referred by orthopedic surgeons, and 111 were referred by other physicians. There was no significant difference in the rates of occurrence of meniscus tear (149 [45%; orthopedic surgeon referrals] vs 50 [45%; other physician referrals], P = .96); ligament tear (82 [25%] vs 21 [19%], P = .25); isolated hyaline cartilage defect (77 [23%] vs 20 [18%], P = .29); meniscus or ligament tear (167 [51%] vs 55 [50%], P = .86); or meniscus, ligament, or articular cartilage tear (242 [74%] vs 72 [65%], P = .34). The proportion of patients who subsequently underwent surgery of the knee was also similar (39% [118 of 300] vs 28% [23 of 82], P = .14). CONCLUSION: There was no significant difference in the occurrences of clinically important knee internal derangement at MR imaging between patients referred by orthopedic surgeons and those referred by other physicians.     

Neuronal metabolic dysfunction in patients with cortical developmental malformations: a proton magnetic resonance spectroscopic imaging study

Cortical developmental malformations are best diagnosed by MRI and are often the cause of refractory epilepsy. Little is known about the metabolic cell function on MR spectroscopy of these types of brain anomaly. We studied 23 patients with cortical developmental malformations and refractory epilepsy using proton MR spectroscopic imaging. Mean age was 28 years (range, 9 to 47 years). The lesions examined were focal cortical dysplasia (n = 5), heterotopia (four band, six periventricular, two subcortical), polymicrogyria (n = 3), tuberous sclerosis (n = 2), and polymicrogyria and periventricular nodular heterotopia (n = 1). We measured the relative signal intensity of N-acetylaspartate/creatine (NAA/Cr) in the lesion, in the perilesional region, and in the region remote from the visible lesion. The values were compared with those from similar brain regions of 25 normal control subjects. The mean NAA/Cr z score values for the 23 patients were as follows: lesion, -2.20 +/- 0.32 (mean +/- SE), n = 21; perilesional region, -1.01 +/- 0.38, n = 15; and distant region, -0.03 +/- 0.34, n = 18 (p < 0.0002). Despite the presence of a large number of neurons, heterotopia showed a relative decrease of NAA in some patients, suggesting that the neurons present were dysfunctional. The maximal NAA/Cr decrease, indicating metabolic dysfunction, colocalized to the structural malformation as defined by MRI and extended to normal-appearing regions adjacent to the visible lesion.     

Pharmacokinetics and systemic effect on calcium homeostasis of 1 alpha,24-dihydroxyvitamin D2 in rats. Comparison with 1 alpha,25-dihydroxyvitamin D2, calcitriol, and calcipotriol

The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.     

Activin B: detection by an immunoenzymometric assay in human serum during ovarian stimulation and late pregnancy

Cerebral 1H MR spectra were recorded in 13 children and adolescents with schizophrenia and 12 healthy children and adolescents. Stimulated echo acquisition mode (STEAM) sequence was used to localize an 8-ml voxel bilaterally in the frontal gray matter. The frontal gray matter metabolite ratios for NAA/Cr, Ch/Cr, Glx/Cr, and mI/Cr in schizophrenic children and adolescents were 1.08 +/- .28, .64 +/- .23, 1.09 +/- .30, and .60 +/- .24, respectively. In comparison, these ratios were 1.59 +/- .35, .74 +/- .27, 1.23 +/- .36, and .58 +/- .29 in healthy children and adolescents. Decrease in the frontal lobe NAA/Cr of schizophrenic children and adolescents was statistically significant (P < .001). In contrast, the MR spectra localized bilaterally in the occipital gray matter (8 ml) showed no significant changes between the patients and the controls. In the occipital gray matter, the metabolite ratios were 1.21 +/- .26,.52 +/- .08, 1.00 +/- .11, and.55 +/- .12 inpatients versus 1.30 +/- .23, .45 +/- .10, 1.15 +/- .20, and .48 +/- .19 in controls. Our preliminary finding of reduced NAA/Cr ratio in the frontal gray matter is consistent with the neurodevelopmental models emphasizing dysfunction of frontal lobe areas in patients with schizophrenia.     

Chromosome 18 breakpoint in t(11;18)(q21;q21) translocation associated with MALT lymphoma is proximal to BCL2 and distal to DCC

OBJECTIVE: To identify independent predictors of intracranial hemorrhage (ICH) during neonatal extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: This retrospective cohort consisted of all neonates who did not have an ICH before treatment with ECMO identified in the Extracorporeal Life Support Organization Registry from 1992 to 1995 (n = 4550). Multiple logistic regression analysis was used to identify factors independently correlated with ICH and to develop a model that could be used to predict the risk of ICH in neonates treated with ECMO. RESULTS: ICH was identified in 9.9% of patients. The factors associated with ICH remaining after adjusting for other significant variables (P <.01) were gestational age (GA) <34 weeks (odds ratio [OR] 12.1, 95% confidence intervals [CI] [6.6, 22]), GA 34 to <36 weeks (OR 4.1, CI [2.9, 5.8]), GA 36 to <38 weeks (OR 2.1, CI [1.6, 2.8]) primary diagnosis of sepsis (OR 1.8, CI [1.4, 2.3]), epinephrine use (OR 1.9, CI [1.5, 2.5]), coagulopathy (OR 1. 6, CI [1.1, 2.2]), arterial pH <7.0 (OR 2.5, CI [1.6, 3.9]), and arterial pH 7.0 to <7.2 (OR 1.8 CI [1.3, 2.5]). ICH rates for neonates receiving venovenous versus venoarterial ECMO and for those treated with or without cephalic jugular venous drainage were not significantly different. CONCLUSIONS: Gestational age, acidosis, sepsis, coagulopathy, and treatment with epinephrine are major independent factors associated with ICH in neonates treated with ECMO. In particular, GA <34 weeks remains a major barrier for use of current ECMO technologies.     

Employment outcomes following spinal cord injury

PURPOSE: We determined the clinical utility of proton MR spectroscopy in defining the extent of disability in benign versus secondary-progressive multiple sclerosis (MS). METHODS: Thirty patients with clinically definite MS, including 16 patients with benign MS and 14 with secondary-progressive MS, and a group of 13 healthy volunteers were studied with combined stimulated-echo acquisition mode proton MR spectroscopy and MR imaging (all patients received contrast material). RESULTS: Acute enhancing lesions of benign and secondary-progressive MS were characterized by a reduction in N-acetylaspartate (NAA)/choline and NAA/creatine and an increase in inositol compounds/creatine as compared with normal white matter. Such variations were also detected in chronic unenhancing lesions in patients with secondary-progressive MS, although they were not found in chronic unenhancing lesions in patients with benign MS. Chronic lesions of the two forms of the disease have significative differences in NAA and inositol signals. CONCLUSION: Proton MR spectroscopy is able to show metabolic changes occurring in the white matter of patients with MS. Such changes differ according to the phase (acute versus chronic) and the clinical form (benign versus secondary-progressive) of the disease.     

Neurometabolism of active neuropsychiatric lupus determined with proton MR spectroscopy

PURPOSE: To determine the neurometabolism of patients with active neuropsychiatric systemic lupus erythematosus (NPSLE) by using proton MR spectroscopy. METHODS: Thirty-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. RESULTS: SLE 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. CONCLUSION: Major 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.     

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

PURPOSE: To characterize plaques of multiple sclerosis (MS) using both proton MR spectroscopy and magnetization transfer (MT) imaging. METHODS: The 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. RESULTS: A 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. CONCLUSION: Small 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.     

A proton magnetic resonance spectroscopic study in ALS: correlation with clinical findings

OBJECTIVE: To evaluate neuronal dysfunction in the motor region subcortical white matter in ALS using volumetric localized proton magnetic resonance spectroscopy (1H-MRS). METHODS: Sixteen patients with E1 Escorial definite, probable, or possible ALS and eight healthy age-matched control subjects were studied. The ALS patients were divided into those with limb onset (n = 8) and those with bulbar onset (n = 8). Measurements of the metabolic ratios N-acetylaspartate (NAA)/creatine and phosphocreatine (Cr+PCr), NAA/choline (Cho), and Cho/(Cr+PCr) were correlated with clinical assessments. RESULTS: We found no differences in the metabolic peak area ratios in the motor region when comparing the total ALS group and the control subjects. However, correlations were found between the NAA/(Cr+PCr) ratio and the E1 Escorial category (p = 0.03), the ALS severity scale (p = 0.01), and the Medical Research Council score (p = 0.06). No correlations were found between the NAA/(Cr+PCr) ratio and the Ashworth Spasticity Scale, reflex score, or disease duration (p > 0.16). Bulbar-onset patients had a lower NAA/(Cr+PCr) ratio in the motor region compared with limb-onset patients (p = 0.03). CONCLUSION: In vivo 1H-MRS of the subcortical white matter in the motor region is unlikely to be sensitive enough to detect early disease changes in ALS because there is considerable overlap between the metabolic peak area ratios from patients with ALS and normal control subjects. However, changes in the NAA/(Cr+PCr) metabolic peak area ratios correlate with clinical measures of disease severity, and this measure may be useful in monitoring disease progression.     

Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging

OBJECT: Pituitary surgery has been reported to produce remission of Cushing's disease with preservation of pituitary function in only 60 to 70% of patients. The inability to identify an adenoma accounts for most failed sellar explorations. Most negative surgical explorations occur in patients in whom magnetic resonance (MR) imaging of the pituitary demonstrates normal findings, which happens in at least 35 to 45% of patients with Cushing's disease. METHODS: To examine the usefulness of intraoperative ultrasonography (IOUS) for identifying an adenoma in patients with no demonstrable tumor (negative findings) on pituitary MR imaging. we prospectively assessed the results of IOUS in 68 patients with a negative (59 patients) or equivocal (nine patients) MR image from a consecutive series of 107 patients with Cushing's disease (64%). We compared surgical findings and outcomes in these 68 patients with a group of 68 patients with Cushing's disease and negative findings on MR imaging in whom IOUS was not available. Intraoperative ultrasonography localized a tumor in 47 (69%) of 68 patients with negative findings on MR imaging. Surprisingly, the size of the adenomas that were detected with IOUS compared with the size of those not detected did not differ (6.8+/-3.4 mm compared with 6.1+/-2.8 mm [mean+/-standard deviation], respectively [p=0.51). In four patients, no adenoma was found at surgery or in the pathological specimen ("true negative"). In eight patients, nine abnormalities detected by IOUS that were suspected adenomas were negative on exploration ("false positive"). Thus, IOUS has a sensitivity of 73% and a positive predictive value of 84% for detecting pituitary adenomas in patients with Cushing's disease and negative findings on MR imaging. Compared with the 68 patients who did not undergo IOUS. remission after surgery was improved (61 patients [90%] compared with 57 patients [84%]), the number of tumors found on exploration was increased (61 tumors compared with 51 tumors, p=0.02), and the number of hemihypophysectomies was decreased (five compared with 15; p=0.02) with IOUS. When the groups were compared after excluding patients with prior pituitary surgery, tumors were found in 91% versus 72% (p=0.008), and remission occurred in 95% versus 87% of patients, respectively, in the groups that had or did not have IOUS. CONCLUSIONS: The IOUS is a sensitive imaging modality when used in patients with Cushing's disease in whom findings on pituitary MR imaging are negative. The improved ability to detect and localize these tumors by using IOUS positively affects surgical outcome.