1H MR Spectroscopy of the Brain in HIV-1-Seropositive Subjects: Evidence for Diffuse Metabolic Abnormalities

PURPOSE: To analyze brain metabolite changes in HIV-1-seropositive subjects in order to define whether the neuronal impairment is a localized or more diffuse process.MATERIALS and METHODS: 15 patients and 18 volunteers underwent multivoxel proton magnetic resonance (MR) spectroscopy at 1.5T. Nine patients were classified as being neuropsychiatrically unimpaired and six as having HIV-1-associated dementia on the basis of a full neuropsychological examination. Spectra were analysed from multiple voxels located in the fronto-parietal cortex and white matter at the level of centrum semiovale.RESULTS: A significant reduction in mean peak area ratios of NAA/Cr (p<0.005 in the grey matter, p<0.01 in the white matter) and an elevation in mean Cho/Cr (p<0.005 in both grey matter and white matter) were observed in patients with HIV-1-associated dementia when compared to healthy volunteers. No significant metabolite abnormalities were detected in the neuropsychiatrically unimpaired group, although there was a similar trend in the metabolite ratios. The changes in metabolite ratios were of the same order of magnitude in the cortical grey matter and subcortical white matter as in the deeper white matter in all patients. There were also no significant regional variations in mean metabolite ratios between right and left hemispheres or anterior and posterior voxels at the level of the brain studied. There were no abnormalities in Glx/Cr in any spectra analysed from either patient group.CONCLUSION: The absence of significant regional variation in metabolite ratios at the level of the centrum semiovale provides some evidence that abnormalities of cerebral metabolites in HIV-infected patients may be part of a diffuse process.     

A Proton Magnetic Resonance Spectroscopy Study of the Striatum and Cerebral Cortex in Parkinson's Disease

Animal studies have suggested an increased striatal glutamate activity in Parkinson's disease models, although this has not been substantiated in magnetic resonance spectroscopy studies in patients. Our initial aim was to assess glutamate and glutamine levels in the striatum of patients with idiopathic Parkinson's disease, using multivoxel proton magnetic resonance spectroscopy techniques. Since data were collected from other areas of the brain without a priori selection, information on the cortex was also obtained. Twelve healthy volunteers, seven dyskinetic and five non-dyskinetic patients were studied. Peak area ratios of choline-containing compounds (Cho), glutamine and glutamate (Glx) and N-acetyl moieties including N-acetylaspartate (NAx), relative to creatine (Cr) were calculated. Spectra were analysed from the corpus striatum, the occipital cortex and the temporo-parietal cortex. The median Glx/Cr ratio was unaltered in the striatal spectra of Parkinson's disease patients compared to healthy controls. However, the more severely affected patients had significantly reduced NAx/Cr ratios in spectra localised to the temporo-parietal cortex, compared to healthy controls. Furthermore, the entire patient population had significantly reduced Cho/Cr ratios in spectra from the temporo-parietal cortex, compared to the reference population. We found no evidence of increased striatal glutamate in either dyskinetic or non-dyskinetic Parkinson's disease. However, the low NAx/Cr and Cho/Cr ratios in the temporo-parietal cortex may indicate the presence of subclinical cortical dysfunction.     

The human motor cortex after incomplete spinal cord injury: an investigation using proton magnetic resonance spectroscopy

OBJECTIVES—(1) A biochemical investigation of themotor cortex in patients with incomplete spinal cord injury and normalcontrol subjects using proton magnetic resonance spectroscopy (MRS).(2) To relate any altered biochemistry with the physiological changesin corticospinal function seen after spinal cord injury.
METHODS—a group of six patients with incompletespinal cord injury who showed good recovery of motor function wereselected. The patients were compared with five healthy controlsubjects. Electromyographic (EMG) responses of thenar muscles totranscranial magnetic stimulation (TMS) of the motor cortex showed thatinhibition of cortical output was weaker in the patients than thecontrols. Proton MRS data were collected from a plane at the level ofthe centrum semiovale. Two 4.5 cm³ voxels in the motorcortex and a third voxel in the ipsilateral occipital cortex wereexamined in the patients and control subjects.
RESULTS—The mean level ofN-acetylaspartate (NAA), expressed relative to thecreatine (Cr) peak (NAA/Cr), was significantly increased in the motorcortex of the patients compared with their ipsilateral occipital cortexor either cortical area in the controls. No differences betweenpatients and controls were seen for any of the other metabolite peaks(choline (Cho), glutamate/glutamine (Glx) or the aspartate component ofNAA (Asp^NAA)) relative to Cr. Choline relative to Cr(Cho/Cr) was higher in the motor cortex of the control subjects than intheir ipsilateral occipital cortex. This difference was not present inthe patients.
CONCLUSIONS—Raised NAA/Cr in the motorcortex of the patients probably results from increased NAA rather thana decrease in the more stable Cr. The possible relevance of a raisedNAA/Cr ratio is discussed, particularly with regard to the changedcorticospinal physiology and the functional recovery seen in the patients.

     

Proton MR spectroscopy in herpes simplex encephalitis: assessment of neuronal loss

We present here the case of an 11-year-old boy with herpes simplex encephalitis diagnosed on the basis of clinical features, serology, and response to acyclovir, who relapsed after 3 weeks of therapy. In vivo proton magnetic resonance spectroscopy (1H MRS) of the brain, at 8 and 16 weeks after the onset of symptoms, showed abnormalities, most prominently a reduction in the N-acetylaspartate/choline ratio. The role of 1H MRS in assessing disease activity is discussed.     

Proton MR spectroscopy of the brain in infants

Proton magnetic resonance spectroscopy (MRS) was used to study the brain of 2 normal and 15 abnormal infants aged from 33 weeks postmenstrual age (PMA) to 14 months postnatal age. Eleven of the infants were examined on at least two occasions. The principal clinical diagnoses in the abnormal infants were perinatal ischemic and hemorrhagic brain injury. All proton spectra demonstrated peaks that were assigned to N-acetylaspartate (NAA), choline containing compounds (Cho), and creatine plus phosphocreatine (Cr). The NAA/Cho and NAA/Cr ratios increased with age, while the Cho/Cr ratio decreased with age in the majority of infants. The NAA/Cho ratio was generally lower in abnormal infants, but the difference was not apparent before 40 weeks (PMA). This ratio was lowest in infants with the severest degree of neurological abnormality. Proton and phosphorus MRS was compared in seven infants. In those with severe brain lesions, early phosphorus spectra were abnormal. On follow-up the phosphorus spectra became normal, but the proton spectra showed persistently low NAA/Cho and NAA/Cr ratios. Proton MRS provides new information that may be complementary to phosphorus MRS in the diagnosis and monitoring of brain development in normal and neurologically damaged infants.     

Effect of L-alanine infusion on 31P nuclear magnetic resonance spectra of normal human liver: towards biochemical pathology in vivo.

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of L-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34-44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of L-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the beta-ATP peak as a reference. 2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean +/- SEM: 98 +/- 12%, P < 0.005) and [Pi]/[ATP] (-33 +/- 3%, P < 0.001) were observed approximately 45 min after the L-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 +/- 6% (P < 0.05), which was independent of the L-alanine dose. Hepatic ATP levels and pH did not change. 3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of L-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after L-alanine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversible Alterations in Brain Metabolites During Therapy for Disseminated Nocardiosis Using Proton Magnetic Resonance Spectroscopy

We report reversible abnormalities in magnetic resonance spectra acquired from a patient with AIDS undergoing antibiotic and corticosteroid therapy for disseminated nocardiosis, a rare opportunistic infection of immunosuppressed patients which can cause cerebral abscess formation. There was no clinical, CT or MRI evidence of HIV-1 encephalitis. MR spectra were acquired before and after treatment using a two-dimensional chemical shift imaging technique (TR 1500ms, TE 130ms). Prior to treatment, a rise in the choline to creatine ratio and a reduction in the N-acetylaspartate to creatine ratio were observed in MR spectra localized to areas of the left anteromedial centrum semiovale that appeared normal on MR imaging. After 16 weeks, the patient had recovered with complete resolution of the cerebral abscesses on MRI. The MR spectral abnormalities also returned to normal. Two months later, the patient had a relapse with focal neurological signs and further abscesses were demonstrated on MRI of the brain. The patient subsequently died and histopathological and microbiological findings at autopsy confirmed the clinical picture of a recurrence of cerebral nocardiosis with no evidence of HIV-1 encephalitis. This case illustrates reversible MR-measurable metabolite changes in the brain of an HIV-seropositive patient without HIV-1 encephalitis who underwent treatment for cerebral nocardiosis.     

In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver

Abstract: In vivo ³¹P magnetic resonance spectroscopy (MRS) provides direct biochemical information on hepatic metabolic processes. To assess in vivo changes in hepatic ³¹P MRS in liver transplant candidates, we studied 31 patients with cirrhosis of varying aetiology; 14 with compensated cirrhosis (Pugh's score <7) and 17 with decompensated cirrhosis (Pugh's score <8). Underlying cellular abnormalities were characterised using in vitro ³¹P MRS and electron microscopy. In vitro spectra were obtained from liver extracts, freeze-clamped at recipient hepatectomy, from all subjects. Electron microscopy of liver tissue was also performed in 17 cases. Relative to nucleotide triphosphates, elevations in phosphomonoesters and reductions in phosphodiesters were observed in vivo with worsening liver function. In vitro spectra showed elevated phosphoethanolamine and phosphocholine, and reduced glycerophosphorylethanolamine and glycerophosphorylcholine, mirroring the in vivo changes, but no distinction was noted between compensated and decompensated cirrhosis. With electron microscopy, functional decompensation was associated with reduced endoplasmic reticulum in parenchymal liver disease, but elevated levels in biliary cirrhosis. We conclude that in vivo spectral abnormalities in cirrhosis are consistent with alterations in phospholipid metabolism and quantity of endoplasmic reticulum. However, in individual patients the biopsy results do not always mirror in vivo findings.     

In vivo fluorine-19 magnetic resonance spectroscopy of cerebral halothane in postoperative patients: Preliminary results

This study reports the use of ¹⁹F MRS to study halothane in the brain of eight patients recovering from halothane anesthesia of short duration. Resonances attributable to halothane were observed up to 90 min after withdrawal of the anesthetic agent. The signal-to-noise ratio for an unlocalized spectrum acquired using a 6 cm surface coil was typically 20 with data collection times of 2 min. In seven patients a single resonance was seen with a mean (±SD) chemical shift of +43.3 (±1.8) ppm, referenced to NaF at 0 ppm. This resonance exhibited a T₁ value of between 0.5 and 1 s, and a T₂* (estimated from the linewidth of the resonance) between 3.5 and 10 ms. In one patient two resonances were observed with chemical shifts of +38 and +41 ppm. Because we cannot exclude the possibility that this was due to field inhomogeneity, the significance of the last finding is uncertain. However, phantom studies show that the chemical shift of halothane in different environments (such as water, olive oil, methanol, and lecithin) can vary to an extent that accounts for the two resonances seen in our patient. These results demonstrate the feasibility of in vivo ¹⁹F MRS studies of fluorinated volatile agents in humans. The potential for clinical ¹⁹F MRS of fluorinated anesthetics is discussed.