Antenatal proton MR spectroscopy of the human brain in vivo

Introduction The assessment of metabolites in the human fetal brain in utero could have diagnostic value. We explored the feasibility and potentials of proton magnetic resonance spectroscopy (¹H MRS) for this purpose.Results ¹H MRS was successfully performed in the third trimester of pregnancy without using sedation. Signals for inositol, choline, creatine, and N-acetylasparatate (NAA) compounds were detected in MR spectra from single voxels in the brain. Absolute tissue levels of these metabolites resemble values measured in preterm and term babies, especially of relatively more mature brain regions, from which most of the MR spectra have been obtained. Brain maturation between 30 and 41 weeks of gestation was most clearly reflected by increasing levels of the neuronal marker NAA.Conclusion With proper care for the methodological aspects, antenatal ¹H MRS clearly has the potential to evolve into a clinical tool for assessing a number of key metabolites in the human fetal brain in utero.     

In vivo temperature measurements in brain tumors using proton MR spectroscopy

The chemical shift difference between the water resonance and the methyl resonance of N-acetylaspartate was used to determine the in vivo temperature in 43 patients with histologically proven brain tumors. Temperatures were also estimated from the contralateral side in 15 of these patients. There was a significant difference (p < 0.05) ] in temperature between meningiomas and the other tumors viz. low grade astrocytomas, grade IV astrocytomas and oligoastrocytomas. Temperature was also significantly different between the contralateral side and the meningiomas (p < 0.05).     

Cognition in multiple sclerosis: relevance of lesions,brain atrophy and proton MR spectroscopy

The overall burden of brain MRI-visible lesions does not fully account for cognitive impairment in multiple sclerosis (MS). Several MRI studies have highlighted the importance of brain damage in the normal-appearing brain tissue. Brain atrophy (global, cortical, white and deep grey matter) is related to cognitive deficits in MS patients and this holds true since the earliest disease stages. Non-conventional MRI techniques such as proton MR spectroscopy have related metabolic changes in specific brain areas to specific cognitive deficits. Overall, data provided by MRI support the notion that cognitive disturbances need to be considered for a more complete clinical characterisation of patients with MS, including those with “benign” MS.     

Role of diffusion-weighted imaging and proton MR spectroscopy in distinguishing between pyogenic brain abscess and necrotic brain tumor

Brain abscesses and brain tumors may have similar clinical presentations. For example, only 50% brain abscess patients have fever, which could be masked by corticosteroid therapy. Also, the differential diagnosis of brain abscesses versus cystic or necrotic tumors may be difficult based on computed tomography (CT) or magnetic resonance (MR) imaging findings. However, the strategies of management for abscess and neoplasm are very different, and it is especially imperative to have a correct diagnosis before any surgical intervention of cystic brain lesions. The MR special techniques, e.g. diffusion-weighted imaging (DWI) and proton (1H) MR spectroscopy, are useful as additional diagnostic modalities for differentiating brain abscesses from cystic or necrotic brain tumors. DWI shows high signal intensity in most cases of pyogenic abscesses and low signal intensity in most cases of cystic or necrotic tumors. MR spectroscopy shows characteristic metabolites in pyogenic abscesses, distinct from those in cystic or necrotic tumors.     

Distribution of neurochemical abnormalities in patients with narcolepsy with cataplexy: An in vivo brain proton MR spectroscopy study

Narcolepsy with cataplexy is characterised by excessive daytime sleepiness, sudden drops of muscle tone triggered by emotions, termed cataplexy, disrupted nocturnal sleep and other dissociated rapid eye movement (REM) sleep phenomena. Narcolepsy has been linked to a loss of hypothalamic neurons producing hypocretins, neuropeptides implicated in the regulation of the arousal system. Neuroimaging and neurometabolic studies have shown the pathophysiological involvement of other brain structures such as cerebral cortex and thalamus, but, overall with inconsistent results.We investigated, by using an advanced quantitative MR technique, proton MR spectroscopy (¹H-MRS), the distribution of brain neurochemical abnormalities in narcolepsy with cataplexy patients. Single voxel ¹H-MRS study was performed in the thalamus, hypothalamus, and parietal–occipital cortex of hypocretin deficient, narcolepsy with cataplexy patients, HLA-DQB1*0602-positive, drug free. No significant changes were detected in the thalamus and parietal–occipital cortex of the patients. On the other hand, the neuronal marker N-acetyl-aspartate was reduced in the hypothalamus of narcolepsy with cataplexy patients compared to controls.These ¹H-MRS findings further support that in narcolepsy with cataplexy patients, the hypothalamus is the primary site of neural lesions. The absence of ¹H-MRS neurodegenerative changes in the thalamus and cerebral cortex suggests that the abnormalities detected in these brain regions by other neuroimaging techniques are likely of functional nature.     

Epileptogenic brain lesions in children: the added-value of combined diffusion imaging and proton MR spectroscopy to the presurgical differential diagnosis

Purpose  

Focal cortical dysplasia (FCD), dysembryoplastic neuroepithelial tumors (DNTs), and gangliogliomas (GGs) share many clinical features, and the presurgical differential diagnosis of these lesions using conventional magnetic resonance imaging (MRI) is challenging in some cases. The purpose of this work was thus to evaluate the capacity of diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS) to distinguish each lesion from the others.     

Quantitative proton magnetic resonance spectroscopy of focal brain lesions

The diagnostic value of single-voxel proton magnetic resonance spectroscopy (2 T, stimulated echo acquisition mode, TR = 6,000 ms, TE = 20 ms, 4-5 mL volumes-of-interest) was assessed for a differentiation of focal brain lesions of unknown etiology in 17 patients 1-14 years of age. Absolute metabolite concentrations were compared with age-matched control subjects and an individual control region. Most of the brain tumors were characterized by strongly reduced total N-acetylaspartyl compounds and marked increases of myo-inositol and choline-containing compounds, consistent with a lack of neuroaxonal tissue and a proliferation of glial cells. Lactate was elevated in only four patients. When using this pattern for a metabolic discrimination of brain tumors from other focal lesions, proton spectroscopy correctly identified 14 of 17 abnormalities, as confirmed by histologic examination after neurosurgical intervention. One false-positive tumor diagnosis was a severe reactive gliosis mimicking a typical tumor spectrum. Two inconclusive cases comprised an astrocytoma with moderately elevated myo-inositol but reduced choline-containing compounds and a patient with an abscess leading to a marked reduction of all metabolites but strong contributions from mobile lipids. In summary, quantitative proton spectroscopy has considerable clinical value for preoperative characterization of focal brain lesions.     

MRI volumetry and proton MR spectroscopy of the brain in Lafora disease

PURPOSE: To determine brain involvement in Lafora disease by means of 3-T MRI volumetry and 1H magnetic resonance (MR) spectroscopy. METHODS: Ten patients with Lafora disease and 10 healthy controls were included in the study. The diagnosis of Lafora disease was proven genetically by the presence of mutations in the EPM2A gene in all patients, and their evolution was staged in three groups according to their functional state. MRI volumetry was performed by means of AX3DT1 images with assessment of the cerebellum and the brainstem, by using the program Stereonauta, and all the brain structures, by using voxel-based morphometry. [1H]MR spectroscopy was performed by using an Eclipse PRESS sequence probe system with 8-cc voxels positioned in the occipital and frontal cortexes, basal ganglia, pons, and cerebellar hemispheres. Spectral peak areas corresponding to NAA (N-acetylaspartate), creatine, and choline were obtained. RESULTS: MRI volumetry showed no statistically significant differences in patients compared with healthy controls in any of the analyzed structures. Analysis of [1H]MR spectroscopy data showed a statistically significant reduction in the NAA/creatine ratio in patients compared with controls in the frontal (p = 0.001) and occipital cortex (p = 0.043), basal ganglia (p = 0.002), and cerebellar hemispheres (p = 0.007). The NAA/choline and choline/creatine ratios were statistically significantly different in the frontal cortex (p = 0.005). No correlation was observed between the disease-evolution stage and MRI-measured volumes (range, -0.92 to 0.44) or [1H]MR spectroscopy values (range, -0.29 to 0.50). CONCLUSIONS: In our series of Lafora disease patients, [1H]MR spectroscopy was more sensitive than structural MRI to detect brain involvement. The brain cortex, especially frontal cortex, cerebellum, and basal ganglia, showed the greatest metabolic changes.     

Thalamic neurometabolic alterations in tremulous Parkinson's disease: A preliminary proton MR spectroscopy study

IntroductionThe objective of this study was to investigate the thalamic biochemical changes in tremor-dominant Parkinson's disease (tPD) patients in comparison with essential tremor with resting tremor (rET) patients, by using proton MR spectroscopy (¹H-MRS).MethodsFourteen tPD patients, 12 rET patients and 10 controls participated in this study. All patients underwent dopamine transporter single-photon emission computed tomography (DAT-SPECT) with ¹²³I-ioflupane, and a short-echo single-voxel ¹H-MRS on a 3T scanner. A voxel of 10 × 15 × 10 mm involving the Vim nucleus was acquired in both thalami of all subjects. Peak areas of N-acetyl-aspartate (NAA), creatine (Cr), glycerophosphocholine (Cho), and glutamate (Glu) were measured for each voxel using LCModel. The NAA/Cr, Cho/Cr, and Glu/Cr ratios were then calculated.ResultsDAT-SPECT was abnormal in tPD patients, whereas it was normal in rET patients. Patients with tPD showed a significant reduction of NAA/Cr and Cho/Cr in the thalami compared to rET and healthy controls; whereas there were no significant differences between rET patients and controls. The combination of thalamic NAA/Cr and Cho/Cr ratios showed a 100% accuracy in distinguishing tPD patients from rET patients and controls.ConclusionsThis study provides preliminary evidence that thalamic neurometabolic abnormalities occur in tremor-dominant phenotype of PD, and suggests that ¹H-MRS can help differentiate patients with tPD from those with rET.     

Biochemical markers of cognition: a proton MR spectroscopy study of normal human brain

In the current study we explored the relationship between neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) and cognitive ability assessed with a battery of neuropsychological tests. Forty-five participants were recruited from the local college community, and examined utilizing neuropsychological testing and 1H-MRS. Our central finding was that N-acetylaspartate (NAA) was associated with overall neuropsychological performance (F(1,42) = 23.16, p < 0.0001], r2 = 0.35. We found an even stronger association between timed neuropsychological measures and NAA (F(1,42) = 31.15, p < 0.0001], r = 0.43. These results reveal the specific relationship of NAA to neuropsychological functioning in normal human brain. The current observations in healthy individuals are consistent with the hypothesis that variability in NAA levels and neuropsychological performance may be related to mitochondrial function.     

Increased metabolite concentration in migraine rat model by proton MR spectroscopy in vivo and ex vivo

Purpose  To investigate brain metabolite change in rat migraine model by proton magnetic resonance spectroscopy (1H-MRS) in vivo and ex vivo. Methods  18 Adult SD rats were enrolled in the study. After nitroglycerin administration, the migraine rat model was established according to ethology evaluation. 1H-MRS was performed at 3T MR scanner in vivo and 14.7T Bruker MR spectrometer ex vivo. Area of peak for different metabolite material was obtained and compared by using independent-T test. The significance level was set at p<0.05. Results  In thalami of experimental group, areas of peak for Cho, Cr and Glu both in vivo and ex vivo were higher than in control group(p<0.05). In contrast, there was no statistical difference in cerebellum. Conclusion  The elevated Cho and Cr spectral pattern were found in rat migraine model. Neuron activity in thalamus is significantly changeable during attacks.     

Rasmussen's encephalitis: proton MR spectroscopy and diffusion MR findings

Rasmussen's encephalitis is a chronic inflammation of the brain that leads to progressive neurologic deficits. The condition has previously been studied by various imaging modalities including MR imaging and MR spectroscopy. We studied three patients presenting with Rasmussen's encephalitis by using proton MR spectroscopy, and diffusion-weighted MR imaging. In these patients, on diffusion-weighted MR imaging, mean apparent diffusion coefficient (ADC) value was 1.74 x 10(-3) mm(2)/sec within the parenchyma, apparently higher than that of the normal parenchyma (0.88 x 10(-3) mm(2)/sec) of a control group of five healthy subjects. Proton MR spectra were obtained with a TR value of 1,500 msec and differing TE values (135, 40, and 20 msec), and were compared with a control group of fourteen cases. In the affected regions of the brain, MR spectroscopy revealed decreased NAA, and increased Cho peaks associated with apparently decreased NAA/Cho, NAA/Cr ratios, and increased Cho/Cr ratios. Slightly increased mI peaks, and increased mI/NAA ratios were noted. A prominent lactate peak was noted in one of the patients.     

Pelizaeus-Merzbacher disease: diffusion MR imaging and proton MR spectroscopy findings

A 5-Year-old boy is reported with genetically confirmed Pelizaeus-Merzbacher disease. On chemical-shift spectroscopic imaging choline (Cho) peaks were prominently decreased in the white matter resulting in markedly high NAA/Cho ratios, and low Cho/Cr ratios, compared to five control cases. Low Cho levels could be indicative of the dysmyelinating disorder in the disease. On b=1000 s/mm(2) images of diffusion MRI, a tigroid pattern was evident, and there was no apparent signal abnormality. However, on ADC maps high signal and high ADC values were evident in the white matter ranging from 1.16 to 1.52 X 10(-3) mm(2)/s, compared to the ADC values of nine control cases, consistent with some disintegration of the white matter secondary to lack of myelination. On the other hand, the ADC values of the cortex were normal (0.79-0.95 X 10(- 3) mm(2)/s). These findings on spectroscopy and diffusion MRI likely represented deficient myelination in the disease.     

In vivo assessment of focal brain lactate alterations with NMR proton spectroscopy

Spectral editing techniques and localization of 1H signals were applied to monitor lactate accumulation in a circumscribed region of brain damage. The experiments were performed at 2.35 T (100 MHz) in a 40-cm bore magnet. Following unilateral craniectomy in anesthetized adult cats, a two-turn surface coil was positioned over the dural surface. Proton spectra were obtained before and 1-5 h after production of a cortical cold lesion from three curved shells of brain tissue, each approximately 3 mm thick. The localized spectrum was obtained from each region with and without spectral difference editing for the lactate CH3 protons, but always with the maximum excitation produced by the semiselective binomial pulse centered on the lactate CH3 resonance. Region 1 represented the damaged area, Region 2 was located immediately below Region 1, and Region 3 was immediately below Region 2. Spin-echo magnetic resonance imaging was used to confirm the relationship between the location of the lesion and the regions from which the spectra were obtained. Spectra obtained without lactate editing showed, in addition to the N-acetylaspartate peak, a large lactate peak in Region 1 after production of the cold lesion. In Regions 2 and 3, changes in lactate were more difficult to assess owing to the presence of a lipid peak at a similar frequency that results from incomplete suppression by the spin-echo pulse sequence alone. Spectra acquired using lactate editing did not contain the lipid peak and clearly showed relatively small lactate accumulations in Regions 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Indications for cerebral MR proton spectroscopy in 2007

Magnetic resonance spectroscopy (MRS) is being increasingly performed alongside the more conventional MRI sequences in the exploration of neurological disorders. It is however important to clearly differentiate its clinical applications aiming at improving the differential diagnosis or the prognostic evaluation of the patient, from the research protocols, when MRS can contribute to a better understanding of the pathophysiology of the disease or to the evaluation of new treatments. The most important applications in clinical practice are intracranial space occupying lesions (especially the positive diagnosis of intracranial abscesses and gliomatosis cerebri and the differential diagnosis between edema and tumor infiltration), alcoholic, hepatic, and HIV-related encephalopathies and the exploration of metabolic diseases. Among the research applications, MRS is widely used in multiple sclerosis, ischemia and brain injury, epilepsy and neuro degenerative diseases.     

Diffuse axonal injury in mild traumatic brain injury: a 3D multivoxel proton MR spectroscopy study

Since mild traumatic brain injury (mTBI) often leads to neurological symptoms even without clinical MRI findings, our goal was to test whether diffuse axonal injury is quantifiable with multivoxel proton MR spectroscopic imaging (¹H-MRSI). T1- and T2-weighted MRI images and three-dimensional ¹H-MRSI (480 voxels over 360 cm³, about 30 % of the brain) were acquired at 3 T from 26 mTBI patients (mean Glasgow Coma Scale score 14.7, 18–56 years old, 3–55 days after injury) and 13 healthy matched contemporaries as controls. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-matter/white-matter (GM/WM) and cerebrospinal fluid fractions were obtained in each voxel. Global GM and WM absolute metabolic concentrations were estimated using linear regression, and patients were compared with controls using two-way analysis of variance. In patients, mean NAA, Cr, Cho and mI concentrations in GM (8.4 ± 0.7, 6.9 ± 0.6, 1.3 ± 0.2, 5.5 ± 0.6 mM) and Cr, Cho and mI in WM (4.8 ± 0.5, 1.4 ± 0.2, 4.6 ± 0.7 mM) were not different from the values in controls. The NAA concentrations in WM, however, were significantly lower in patients than in controls (7.2 ± 0.8 vs. 7.7 ± 0.6 mM, p = 0.0125). The Cho and Cr levels in WM of patients were positively correlated with time since mTBI. This ¹H-MRSI approach allowed us to ascertain that early mTBI sequelae are (1) diffuse (not merely local), (2) neuronal (not glial), and (3) in the global WM (not GM). These findings support the hypothesis that, similar to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction rather than cell death dominates shortly after injury.     

MR spectroscopy of the brain in Leigh syndrome

Brain magnetic resonance spectroscopy in two patients with Leigh syndrome revealed the presence of lactate in gray and white matter brain tissue and relatively high choline levels in the white matter. The latter observation, most probably related to an ongoing demyelination process, underlines specific involvement of white matter metabolism in Leigh syndrome even in cases without involvement of the white matter as visualized on MRI. Magnetic resonance spectroscopy might thus be of help in differentiating Leigh syndrome from a range of other mitochondrial diseases, such as ophthalmoplegia and Kearns-Sayre syndrome, showing lack of lactate in brain tissues appearing normal on MRI.     

Proton MR spectroscopy of the brain.

Over the past five decades, MR spectroscopy has evolved from an analytical chemistry tool to a noninvasive clinical examination on FDA approved equipment with an AMA billing code. While proton MR spectroscopy has dominated current clinical studies, interest in other nucleii has arisen, particularly P-31 for the evaluation of membrane lipids, and C-13 for the evaluation of glutamate neurotransmission and excitotoxicity. Currently, the most common neuroradiological diagnostic indication is the differentation of suspected cerebral neoplasms for post-treatment effects, abcesses, subacute infarcts, demyelinating disease, and other non-neoplastic processes. Recent recommendations for monitoring multiple sclerosis treatment suggest an increasing role for MR spectroscopy in the future.