Clinical value of proton magnetic resonance spectroscopy for differentiating recurrent or residual brain tumor from delayed cerebral necrosis

PURPOSE: Delayed cerebral necrosis (DN) is a significant risk for brain tumor patients treated with high-dose irradiation. Although differentiating DN from tumor progression is an important clinical question, the distinction cannot be made reliably by conventional imaging techniques. We undertook a pilot study to assess the ability of proton magnetic resonance spectroscopy (1H MRS) to differentiate prospectively between DN or recurrent/residual tumor in a series of children treated for primary brain tumors with high-dose irradiation. METHODS AND MATERIALS: Twelve children (ages 3-16 years), who had clinical and MR imaging (MRI) changes that suggested a diagnosis of either DN or progressive/recurrent brain tumor, underwent localized 1H MRS prior to planned biopsy, resection, or other confirmatory histological procedure. Prospective 1H MRS interpretations were based on comparison of spectral peak patterns and quantitative peak area values from normalized spectra: a marked depression of the intracellular metabolite peaks from choline, creatine, and N-acetyl compounds was hypothesized to indicate DN, and median-to-high choline with easily visible creatine metabolite peaks was labeled progressive/recurrent tumor. Subsequent histological studies identified the brain lesion as DN or recurrent/residual tumor. RESULTS: The patient series included five cases of DN and seven recurrent/residual tumor cases, based on histology. The MRS criteria prospectively identified five out of seven patients with active tumor, and four out of five patients with histologically proven DN correctly. Discriminant analysis suggested that the primary diagnostic information for differentiating DN from tumor lay in the normalized MRS peak areas for choline and creatine compounds. CONCLUSIONS: Magnetic resonance spectroscopy shows promising sensitivity and selectivity for differentiating DN from recurrent/progressive brain tumor. A novel diagnostic index based on peak areas for choline and creatine compounds may provide a simple discriminant for differentiating DN from recurrent or residual primary brain tumors.     

Dissociation between lactate accumulation and acidosis in middle cerebral artery-occluded rats assessed by 31P and 1H NMR metabolic images under a 2-T magnetic field

The relationships among tissue edema, lactate accumulation, and intracellular pH in middle cerebral artery (MCA)-occluded rats were investigated with multiecho 1H magnetic resonance imaging and spatially resolved metabolic images constructed by 1H and 31P nuclear magnetic resonance (NMR) chemical shift imaging (CSI). For the effective and sensitive detection of NMR signals from the brain, outer volume suppression (OVS), reduced k-space sampling and proton irradiation were incorporated into the CSI sequences. The consecutive three measurements of calculated T2 image, lactate image, and pH image which were required for 3.75 h were repeated for four cycles of 1-16 h after MCA occlusion. Tissue edema and lactate accumulation in the infarcted region were gradually and consistently increased during the 15-h observation period. In contrast, severe acidosis was already detected on the first pH image (2-4.7 h after MCA occlusion); thereafter, the degree of acidosis became milder and showed no further progression. The dissociation between the time courses of the lactate accumulation and pH decrease was clearly demonstrated by the NMR metabolic images. Acid-base balance in cerebral infarction might be affected not only by lactate production but also by complicated interactions with tissue edema and some other factors.     

Daily variations in pineal melatonin concentrations in inbred and outbred mice

Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS) were successively recorded in a 3-year-old girl with the acute hemiplegia syndrome. She was admitted to our hospital with complaints of fever, loss of consciousness and right side dominant clonic convulsions evolving into status epilepticus, and then recovered with sequelae of aphasia and right hemiparesis. Electroencephalography showed a generalized slow rhythm at the onset, and very low activities on the left hemisphere in the follow-up records. Brain CT and MRI revealed edema of the left hemisphere initially, followed by left side dominant brain atrophy. No cerebral vascular lesion was detected by magnetic resonance angiography. N-Isopropyl-[123I]-iodoamphetamine SPECT showed marked hypoperfusion of the left hemisphere accompanied by crossed cerebellar diaschisis. MRS at the initial stage detected decreased N-acetyl-aspartic acid and increased lactic acid signals in the bilateral hemisphere, which subsequently normalized only on the right side. These findings suggested brain damage and neural cell death in the left cerebral hemisphere, caused by acute encephalopathy. SPECT and MRS are useful new techniques to study the pathophysiology of the acute hemiplegia syndrome.     

Nuclear magnetic resonance spectroscopy: methodology and applications to the study of asphyxia neonatorum

Cerebral metabolism has been extensively studied by magnetic resonance spectroscopy (MRS). MRS allows the study of neonates brain maturation as well as the onset and the evolution of brain injury. The use of phosphorous spectroscopy allows the quantification of phosphorylated metabolites. Thus, the measurement of the relative concentrations of creatine-phosphate and inorganic-phosphate is a prognostic factor of the outcome of a neonate after birth asphyxia. Absolute concentrations have more recently been studied and seem to be more significant. Proton MRS gives access to brain metabolites such as choline, lactate, N-acetyl aspartate and taurine. Its use is more recent than the phosphorous spectroscopy but first results already show its potential in neonatology.     

The role of magnetic resonance spectroscopy in the investigation of lactic acidosis and inborn errors of energy metabolism

Magnetic resonance spectroscopy (MRS) provides a non-invasive method of investigating disordered energy metabolism in vivo. Here, we briefly outline some MRS studies of skeletal muscle and brain metabolism that have been carried out in patients with inborn errors of energy metabolism. We concentrate in particular on the use of 1H MRS for the detection of elevated brain lactate in these patients.     

Proton magnetic resonance spectroscopy: a metabolic approach of cerebral tumors and their follow-up after external radiation therapy

The same physical principles are the basis of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). Proton MRS is easily performed with clinical magnets (> or = 1.5 T) and may be added to routine MRI studies to provide metabolic information on pathological tissues. It represents an important tool to detect several metabolic compounds. The article will review the current status of proton MRS with a particular emphasis upon its clinical utility for the diagnosis of brain tumors and for the evaluation of the efficacy of radiotherapy.     

In vivo 1H MR spectroscopic imaging and diffusion weighted MRI in experimental hydrocephalus

The severity and progression of ventricular enlargement, the occurrence of cerebral edema, and the localization of ischemic metabolic changes were investigated in a rat model of hydrocephalus, using in vivo 1H MR spectroscopic imaging (SI) and diffusion weighted MRI (DW MRI). Hydrocephalic rats were studied 1, 2, 4, and 8 weeks after injection of kaolin into the cisterna magna. Parametric images of the apparent diffusion coefficient (ADC) revealed a varying degree of ventriculomegaly in all rats, with different time courses of ventricular expansion. Extracellular white matter edema was observed during the early stages of hydrocephalus, most extensively in cases of progressive ventriculomegaly. In gray matter regions, ADC values were not changed, compared with controls. In case of fatal hydrocephalus, high lactate levels were observed throughout the whole brain. In all other rats, at all time points after kaolin injection, lactate was detected only in voxels containing cerebrospinal fluid. This suggests accumulation of lactate in the ventricles, and/or an ongoing periventricular production of lactate as a consequence of cerebral ischemia in experimental hydrocephalus.     

Effect of brain edema on the recurrence pattern of malignant gliomas

PURPOSE: To assess the influence of initial preoperative brain edema in malignant gliomas on regrowth patterns. SUBJECTS AND METHODS: 79 patients with histologically verified supratentorial malignant glioma were prospectively studied by magnetic resonance imaging (MRI) before and every 2-3 months after surgery. The median follow-up time was 11 months. We correlated the configuration of the initial vasogenic edema on T2-weighted images with tumor regrowth patterns on contrast-enhanced T1-weighted images. RESULTS: 35/47 tumor regrowths (75%) imitated the initial edema configuration, while 11/47 occurred within the initial tumor bed; in one case tumor recurrence was multilocal. CONCLUSION: In glioblastoma, tumor regrowth patterns correlate positively with the configuration of the initial vasogenic brain edema. The initial, "presurgical" peritumoral edema should thus be considered when planning further treatment.     

Brain proton magnetic resonance spectroscopy. Indications for diagnosis and follow-up of HIV-related encephalopathy in the adult

NONINVASIVE EXPLORATION: Proton localized magnetic resonance spectroscopy (MRS) is a noninvasive human neurochemistry method based on the magnetic resonance phenomenon. ADVANTAGES: This exploration of brain metabolism, performed without any injection, detects neuronal, glial, and membrane markers, and can be performed after an MRI examination without moving the patient. INDICATIONS: In vivo brain MRS plays a major role (i) in early diagnosis of HIV-related encephalopathy, (ii) in differential diagnosis of HIV-related encephalopathy versus psychiatric symptoms or occurring in AIDS patients, (iii) in differential diagnosis of HIV-related encephalopathy versus other brain lesions related to AIDS, and (iv) in the follow-up of patient response to therapy. In these indications, MRS is frequently more reliable than neuropsychologic testing and more sensitive than MRI.     

Perceptual similarity of shapes generated from Fourier descriptors

BACKGROUND: Growth rates and tumor aggressiveness of meningiomas are thought to be closely related to brain edema development. However, histopathologic data alone are not consistently accurate predictors of the behavior and clinical course of a meningioma. METHODS: The authors examined 57 histologically proven intracranial meningiomas to identify factors, including growth fractions determined by MIB-1 immunostaining, that may influence the development of meningioma-associated peritumoral brain edema. There were 54 benign, 2 atypical, and 1 anaplastic meningiomas. The MIB-1 staining index (SI) percentage was defined as the number of MIB-1 positive cells divided by the total number of tumor cells in a 1.037-square millimeter area on the slide. The extent of peritumoral brain edema was determined using preoperative magnetic resonance imaging. The extent of edema was classified as Grade 0,1, or 2 (GR0, GR1, or GR2), in order of increasing severity. RESULTS: The MIB-1 SIs of the 57 cases ranged from 0.06-6.8% (median, 0.80%). There were 26 GR0, 20 GR1, and 11 GR2 edema cases. The MIB-1 SI rose in order of increasing edema severity. There was a statistically significant correlation between the MIB-1 SI and the extent of brain edema (P<0.0001), and also between the tumor size and the extent of brain edema (P=0.001). Meningothelial and atypical/anaplastic meningiomas were associated with peritumoral brain edema more often than any other subtype (P<0.005). CONCLUSIONS: Growth fractions, as determined by MIB-1 immunostaining, rise with increasing severity of peritumoral brain edema, indicating a close relationship between tumor aggressiveness and edema development.     

MRI of focal cortical dysplasia

We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain.     

Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: A proton magnetic resonance spectroscopic study

The CNS is frequently involved in human immunodeficiency virus (HIV) infection. In recent studies using proton magnetic resonance spectroscopy, investigators found a significant reduction in N-acetyl aspartate, a metabolic marker of neurons, in late stages of dementia. To further understand the relationship between proton magnetic resonance spectroscopy changes and clinical disease and dementia, we compared 20 HIV-infected patients presenting at varying stages of acquired immunodeficiency syndrome (AIDS) dementia complex and infection to 10 age-matched controls. We found a significant reduction in N-acetyl aspartate/creatine only in patients who had advanced dementia and CD4 counts less that 200/microliter. By contrast, a significant elevation in compounds containing choline was present in patients in the early stages of HIV infection of who had CD4 counts greater than 200/microliter, in patients with normal MRI scans, and in all AIDS dementia complex groups, including subjects with no or minimal cognitive impairment. An elevated choline level also occurred in later stages of HIV infection (CD4 < 200/microliter). Our results suggest that an increase in choline occurs before N-acetyl aspartate decrements, MRI abnormalities, and the onset of dementia, and may therefore provide a useful marker for early detection of brain injury associated with HIV infection.     

Proton magnetic resonance spectroscopy in the evaluation of children with congenital heart disease and acute central nervous system injury

We studied nine infants and children, aged 1 week to 42 months, with severe acute central nervous system injuries associated with cardiac disease or corrective operations by means of single-voxel proton magnetic resonance spectroscopy to determine whether this technique would be useful in predicting neurologic outcome. Proton magnetic resonance spectroscopic data were acquired from the occipital gray and parietal white matter (8 cm3 volume, stimulated echo-acquisition mode sequence with echo time of 20 msec and repetition time of 3.0 seconds) a median of 9 days after operation (range 3 to 42 days). Data were expressed as ratios of areas under metabolite peaks, including N-acetyl compounds, choline-containing compounds, creatine and phosphocreatine, and lactate. Four patients had cerebral insults before operation, one had both a preoperative and a perioperative insult, three had perioperative insults, and one had a prolonged cardiac arrest 2 days after operation. Outcomes (Glasgow Outcome Scale scores) were assigned at discharge and 6 to 12 months after injury. Six patients were in a vegetative state or had severe impairment at discharge, and two still had severe impairment at 6- to 12-month follow-up. Proton magnetic resonance spectroscopy showed lactate in these two patients, along with markedly reduced ratios of N-acetyl compounds to creatine compounds. The other four patients with severe impairment recovered to a level of mild disability at follow-up. Proton magnetic resonance spectroscopy showed no lactate in these four patients; however, one patient showed moderately reduced ratio of N-acetyl compounds to creatine compounds. The three patients who had mild or moderate impairment at discharge showed no lactate and mild or no changes in metabolite ratios; follow-up revealed normal or mild outcomes. Overall, we found that the presence of lactate and markedly reduced ratios of N-acetyl compounds to creatine compounds were predictive of severe outcomes at discharge and long-term follow-up, whereas no lactate and mild or no changes in ratios suggested potential for recovery with at least a mild disability. Continuing investigations are in progress to determine the optimal selection of candidates and timing of proton magnetic resonance spectroscopic studies.     

Evidence of multiple ethanol pools in the brain: an in vivo proton magnetization transfer study

Studies of isolated cell membranes and animal brain extracts have shown that ethanol (EtOH) partitions into cell membranes. We tested the hypothesis that EtOH in the living brain after EtOH administration exists in two or more pools: a free, mobile pool of EtOH and one or more EtOH pools that are restricted in their molecular mobility, possibly because of association with membranes. In vivo brain proton magnetic resonance spectroscopy (1H MRS) routinely detects the methyl protons of the mobile EtOH pool but does not detect motionally restricted EtOH. We used in vivo brain 1H MRS in rat brain (n = 11) after intraperitoneal EtOH administration to measure the signal intensity of methyl EtOH protons in the presence and absence of off-resonance saturation. Off-resonance saturation resulted in a 33 +/- 4% decrease of the EtOH methyl proton signal. We interpret this signal reduction as a magnetization transfer effect. It is consistent with the existence of an MRS-invisible EtOH pool with restricted molecular mobility, which is in exchange with the free EtOH pool. Off-resonance saturation at the water frequency resulted in an even larger decrease of the EtOH methyl signal, consistent with water molecules being in close proximity to EtOH molecules at the restricted motion site(s). These results provide support for the hypothesis that partial MRS-invisibility of brain EtOH is at least to some extent caused by the presence of a (MRS-invisible) pool of motionally restricted EtOH. They also strongly suggest that water suppression, routinely used in in vivo 1H MRS, may reduce the observable EtOH methyl signal intensity through a magnetization transfer mechanism. These studies may provide both a mechanism of, and a means to investigate the alterations of EtOH MRS visibility observed in heavy drinkers.     

In vivo neurochemistry of the brain in schizophrenia as revealed by magnetic resonance spectroscopy

Magnetic resonance spectroscopy (MRS), an application of the methods of nuclear magnetic resonance (NMR), is a functional imaging modality that provides a view of localized biochemistry in vivo. A number of studies applying MRS to the neurochemistry of schizophrenia have been reported, which encompass a range of patient populations, states of medication, anatomic regions, nuclear species, and MRS techniques. A brief review of the history and methodology of NMR and MRS is presented. Comparison is made of MRS capabilities with other functional imaging modalities. Aspects of the neurochemistry of schizophrenia relevant to MRS studies are reviewed, as are the reported MRS studies involving patients with schizophrenia. Areas of consistent findings include decreased phosphomonoesters and increased phosphodiesters in frontal lobes, and decreases in the putative neuronal cell marker, N-acetylaspartate, in temporal lobes. Studies of neurotransmitters such as glutamate, gamma-aminobutyric acid, and glutamine have generated inconsistent results. New insights into alterations in neurochemistry in schizophrenia have been provided by MRS. Studies of neurotransmitters have future potential with improvements in field strength and in spectral editing techniques. MRS has the potential to measure brain medication levels and simultaneous effects on neurochemistry. MRS may assist in characterizing high-risk populations, and ultimately guide medication use.     

In vivo quantitation of cerebral metabolite concentrations using natural abundance 13C MRS at 1.5 T

A method for the quantitation of cerebral metabolites on a clinical MR scanner by natural abundance 13C MRS in vivo is described. Proton-decoupled spectra were acquired with a power deposition within FDA guidelines using a novel coil design. myo-Inositol, quantified by a separate proton MRS, and readily detectable in 13C MRS, was used as an internal reference. Normal concentrations, measured in four control subjects, age 7 months to 12 years, were glutamate 9.9 +/- 0.7, glutamine 5.6 +/- 1.0, and NAA 8.8 +/- 2.8 mmol/kg. In a patient diagnosed with Canavan disease, examined four times, glutamate was reduced to 46% of normal, 4.6 +/- 0.5 mmol/kg. NAA was increased by 50% to 13.2 +/- 1.6 mmol/kg in 13C MRS, consistent with the 41% increase to 12.3 +/- 1.1 from control 8.7 +/- 1.1 mmol/kg assayed by 1H MRS. Limited concentration of glutamate may impact on glutamatergic neurons and excitatory neurotransmission in Canavan disease. Quantitation of cerebral glutamate in human brain may have clinical value in human neuropathologies in which glutamate is believed to play a central role.     

Structural integrity of implanted WMT infinity hip and Osteonics Omnifit hip in fresh cadaveric femurs

OBJECTIVES: To evaluate the role of proton MR spectroscopy (1H-MRS) in detecting metabolic changes in diffuse or focal lesions in the brain of patients infected with HIV. METHODS: Sixty HIV seropositive patients (25 with HIV related encephalopathies, 20 with toxoplasmosis, eight with progressive multifocal leukoencephalopathies (PMLs), and seven with lymphomas) and 22 HIV seronegative neurological controls were examined with a combined MRI and 1H-MRS technique using a Siemens 1.5 Tesla Magnetom. Spectra (Spin Echo sequence, TE 135 ms) were acquired by single voxel, localised on focal lesions in toxoplasmosis, PML, lymphomas, and HIV encephalopathies and on the centrum semiovale of neurological controls. Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate, and lipids were evaluated in each spectrum and NAA/Cr, NAA/Cho, and Cho/Cr ratios were calculated. RESULTS: A significant decrease in NAA/Cr and NAA/Cho ratios were found in all HIV diagnostic groups in comparison with neurological controls (p<0.003), suggesting neuronal or axonal damage independent of brain lesion aetiology. However, the NAA/Cr ratio was significantly lower in PML and lymphomas than in HIV encephalopathies (p<0.02) and toxoplasmosis (p<0.05). HIV encephalopathies, lymphomas, and toxoplasmosis showed a significant increase in the Cho/Cr ratio in comparison with neurological controls (p<0.03) without between group differences. The presence of a lipid signal was more frequent in lymphomas (71%) than in other HIV groups (Fisher's test, p=0.00003). The presence of mobile lipid resonance together with a high Cho/Cr ratio in lymphomas may be related to an increased membrane synthesis and turnover in tumour cells. A lactate signal (marker of inflammatory reaction), was found in all but one patient with PML lesions (75%), but had a lower incidence in the other HIV diagnostic groups (Fisher's test, p=0.00024). CONCLUSION: 1H-MRS shows a high sensitivity in detecting brain involvement in HIV related diseases, but a poor specificity in differential diagnosis of HIV brain lesions. Nevertheless, the homogeneous metabolic pattern that characterises PML suggests the usefulness of 1H-MRS as an adjunct to MRI in differentiating CNS white matter lesions, such as HIV encephalopathies, from PML.     

Magnetic resonance imaging of cold injury-induced brain edema in rats

The chronological changes of blood-brain barrier disruption, and diffusion and absorption of edema fluid were investigated in rats with cold-induced brain injury (vasogenic edema) using magnetic resonance imaging. Contrast medium was administered intravenously at 3 and 24 hours after lesioning as a tracer of edema fluid. Serial T1-weighted multiple-slice images were obtained for 180 minutes after contrast administration. Disruption of the blood-brain barrier was more prominent at 24 hours after lesioning than at 3 hours. Contrast medium leaked from the periphery of the injury and gradually diffused to the center of the lesion. Contrast medium diffused into the corpus callosum and the ventricular system (cerebrospinal fluid). Disruption of the blood-brain barrier induced by cold injury was most prominent at the periphery of the vasogenic edema. Edema fluid subsequently extended into the center of the lesion and was also absorbed by the ventricular system. Magnetic resonance imaging is a useful method to assess the efficacy of therapy for vasogenic edema.     

In vivo injection of [1-13C]glucose and [1,2-13C]acetate combined with ex vivo 13C nuclear magnetic resonance spectroscopy: a novel approach to the study of middle cerebral artery occlusion in the rat

Astrocytes play a pivotal role in cerebral glutamate homeostasis. After 90 minutes of middle cerebral artery occlusion in the rat, the changes induced in neuronal and astrocytic metabolism and in the neuronal-astrocytic interactions were studied by combining in vivo injection of [1-13C]glucose and [1,2-13C]acetate with ex vivo 13C nuclear magnetic resonance spectroscopy and HPLC analysis of amino acids of the lateral caudoputamen and lower parietal cortex, representing the putative ischemic core, and the upper frontoparietal cortex, corresponding to the putative penumbra. In the putative ischemic core, evidence of compromised de novo glutamate synthesis located specifically in the glutamatergic neurons was detected, and a larger proportion of glutamate was derived from astrocytic glutamine. In the same region, pyruvate carboxylase activity, representing the anaplerotic pathway in the brain and exclusively located in astrocytes, was abolished. However, astrocytic glutamate uptake and conversion to glutamine took place, and cycling of intermediates in the astrocytic tricarboxylic acid cycle was elevated. In the putative penumbra, glutamate synthesis was improved compared with the ischemic core, the difference appeared to be brought on by better neuronal de novo glutamate synthesis, combined with normal levels of glutamate formed from astrocytic glutamine. In both ischemic regions, gamma-aminobutyric acid synthesis directly from glucose was reduced to about half, indicating impaired pyruvate dehydrogenase activity; still, gamma-aminobutyric acid reuptake and cycling was increased. The results obtained in the current study demonstrate that by combining in vivo injection of [1-13C]glucose and [1,2-13C]acetate with ex vivo 13C nuclear magnetic resonance spectroscopy, specific metabolic alterations in small regions within the rat brain suffering a focal ischemic lesion can be studied.     

Neurochemical alterations in asymptomatic abstinent cocaine users: a proton magnetic resonance spectroscopy study

Cocaine can cause a variety of neuropsychiatric and neurobehavioral complications; however, it is uncertain whether cocaine causes persistent cerebral structural and neurochemical abnormalities in asymptomatic users. We studied 52 African-American men (26 human immunodeficiency virus-negative asymptomatic heavy cocaine users and 26 normal subjects). Ventricle-to-brain ratio (VBR) and white matter lesions (WML) were quantified on magnetic resonance imaging. N-acetyl-containing compounds (NA), total creatine, choline-containing compounds, myo-inositol, and glutamate + glutamine were measured with in vivo proton magnetic resonance spectroscopy, VBR and WML were not significantly different in the cocaine users compared to the normal controls. Elevated creatine (+7%; p = .05) and myo-inositol (+18%; p = .01) in the white matter were associated with cocaine use. NA, primarily a measure of N-acetyl aspartate and neuronal content, was normal. Normal NA suggest no neuronal loss or damage in the brain regions examined in these cocaine users. Therefore, we conclude that neurochemical abnormalities observed might result from alterations in nonneuronal brain tissue.