Chemical Composition Assessment of Structural Parts (Seeds, Peel, Pulp) of Physalis alkekengi L. Fruits.

In recent years there has been an extensive search for nature-based products with functional potential. All structural parts of Physalis alkekengi (bladder cherry), including fruits, pulp, and less-explored parts, such as seeds and peel, can be considered sources of functional macro- and micronutrients, bioactive compounds, such as vitamins, minerals, polyphenols, and polyunsaturated fatty acids, and dietetic fiber. The chemical composition of all fruit structural parts (seeds, peel, and pulp) of two phenotypes of P. alkekengi were studied. The seeds were found to be a rich source of oil, yielding 14-17%, with abundant amounts of unsaturated fatty acids (over 88%) and tocopherols, or vitamin E (up to 5378 mg/kg dw; dry weight). The predominant fatty acid in the seed oils was linoleic acid, followed by oleic acid. The seeds contained most of the fruit's protein (16-19% dw) and fiber (6-8% dw). The peel oil differed significantly from the seed oil in fatty acid and tocopherol composition. Seed cakes, the waste after oil extraction, contained arginine and aspartic acid as the main amino acids; valine, phenylalanine, threonine, and isoleucine were present in slightly higher amounts than the other essential amino acids. They were also rich in key minerals, such as K, Mg, Fe, and Zn. From the peel and pulp fractions were extracted fruit concretes, aromatic products with specific fragrance profiles, of which volatile compositions (GC-MS) were identified. The major volatiles in peel and pulp concretes were ß-linalool, α-pinene, and γ-terpinene. The results from the investigation substantiated the potential of all the studied fruit structures as new sources of bioactive compounds that could be used as prospective sources in human and animal nutrition, while the aroma-active compounds in the concretes supported the plant's potential in perfumery and cosmetics.

Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy.

Previous neuroimaging studies have detected markers of neuroinflammation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring brain metabolites linked to inflammation, but has only been applied to discrete regions of interest in ME/CFS. We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain. Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients. Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). Choline (CHO), myo-inositol (MI), lactate (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over creatine (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups. Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate (p < 0.001). Metabolite ratios in seven regions were correlated with fatigue (p < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p < 0.05), which was not attributable to increased body temperature or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p < 0.05). We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.

Microwave Assisted Synthesis of N-Doped Carbon Dots: an Easy, Fast and Cheap Sensor for Determination of Aspartic Acid in Sport Supplements.

In this work, determination of aspartic acid by N-doped carbon dots (N-CDs) was studied at optimum condition. Characterization and morphology of surface of N-CDs were carried out by FT-IR and HRTEM. N-doped carbon dots size was 10 nm. Quenching was very fast after addition of aspartic acid that is an important property of this sensor. Optimum conditions for pH and excitation wavelength were 8 and 360 nm, respectively. Linear dynamic range and limit of detection for aspartic acid were 0.5-50 µM and 90 nM, respectively. This method was used for aspartic acid determination in human serum and sport supplement powder as real samples. Performance of this sensor was also compared with other fluorescent sensors.

Value of assessment of multivoxel proton chemical shift imaging to predict long term outcome in patients after out-of-hospital cardiac arrest: A preliminary prospective observational study.

BACKGROUND: Existing methods to predict recovery after out-of-hospital cardiac arrest (OHCA) lack of accuracy. The aim of this study was to determine whether quantitative proton chemical shift imaging (1H-CSI) during the subacute stage of OHCA can predict neurological outcome of such patients. METHODS: This monocentric prospective observational study was conducted in a Intensive Care Unit of a teaching hospital. Forty consecutive patients with OHCA were enrolled between January 1st 2011-December 31st 2013. Multivoxel 1H-CSI values were compared to structural magnetic resonance imaging (MRI) sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging). Ratios of N-acetyl-aspartate (NAA) to creatine (Cr) and choline compounds were analyzed using region of interest in bilateral lenticular cores and thalami. The outcome evaluated was the Cerebral Performance Category (CPC) at 6 months, dichotomized as favorable (CPC 1-2) and unfavorable outcome (CPC 3-5). The performance was compared by area under the receiver operating characteristic (ROCAUC) curves analysis. RESULTS: Twenty nine OHCA had an interpretable MRI. Eight patients (28%) had favorable outcome at 6 months. The worst NAA/Cr in lenticular cores was the best 1H-CSI marker, with 80% sensitivity (95% confidence interval (CI), 57-94) and a 100% specificity (95% CI, 63-100) with a positive predictive value of 100%. Prognostic accuracy, as quantified by the ROCAUC, was higher with the worst NAA/Cr in lenticular cores (ROCAUC 0.88; 95% CI, 0.70-0.97) than with the structural MRI sequences. CONCLUSION: In this preliminary study we found that multivoxel 1H-CSI in lenticular cores was highly predictive of unfavorable outcome at 6 months.

Simultaneous determination of metabolite concentrations, T1 and T2 relaxation times.

PURPOSE: To simultaneously measure concentration and T1 and T2 values of metabolites in the human brain in a single scan session. METHODS: A new pulse sequence with multiple variable acquisition parameters was proposed to encode metabolite T1 and T2 information into the acquired data. A linear combination-fitting algorithm was developed in-house to simultaneously determine metabolite concentrations and relaxation times. RESULTS: Concentration, T1 , and T2 values of N-acetyl-aspartate, total creatine, total choline, and glutamate were reliably measured in the frontal gray matter and white matter regions of nine healthy volunteers at 7 tesla in less than 10 minutes of scan time per voxel. T1 and T2 values of glutamine, as well as T1 of glutathione, were also measured in the frontal gray matter region with reasonable precision. CONCLUSION: The proposed technique allows multiparametric characterization of brain metabolites in a single scan session, making it possible to measure both levels and intracellular microenvironments of brain chemicals in clinical MR spectroscopy studies. Magn Reson Med 78:2072-2081, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Hippocampal proton MR spectroscopy as a novel approach in the assessment of radiation injury and the correlation to neurocognitive function impairment: initial experiences.

BACKGROUND: The hippocampus is considered as the main radiosensitive brain structure responsible for postradiotherapy cognitive decline. We prospectively assessed correlation of memory change to hippocampal N-acetylaspartate (h-tNAA) concentration, a neuronal density and viability marker, by (1)H-MR spectroscopy focused on the hippocampus. METHODS: Patients with brain metastases underwent whole brain radiotherapy (WBRT) to a dose of 30 Gy in ten fractions daily. Pre-radiotherapy (1)H-MR spectroscopy focused on the h-tNAA concentration and memory testing was performed. Memory was evaluated by Auditory Verbal Learning Test (AVLT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Total recall, recognition and delayed recall were reported. The both investigation procedures were repeated 4 months after WBRT and the h-tNAA and memory changes were correlated. RESULTS: Of the 20 patients, ten passed whole protocol. The h-tNAA concentration significantly decreased from pre-WBRT 8.9, 8.86 and 8.88 [mM] in the right, left and both hippocampi to 7.16, 7.65 and 7.4 after WBRT, respectively. In the memory tests a significant decrease was observed in AVLT total-recall, BVMT-R total-recall and BVMT-R delayed-recall. Weak to moderate correlations were observed between left h-tNAA and AVLT recognition and all BVMT-R subtests and between the right h-tNAA and AVLT total-recall. CONCLUSIONS: A significant decrease in h-tNAA after WBRT was proven by (1)H-MR spectroscopy as a feasible method for the in vivo investigation of radiation injury. Continuing patient recruitment focusing on other cognitive tests and metabolites is needed.

Viability assessment of magnetic resonance spectroscopy for the detection of minimal hepatic encephalopathy severity.

OBJECTIVE: To evaluate regional cerebral metabolic changes in minimal hepatic encephalopathy (MHE) patients using magnetic resonance spectroscopy (MRS) in 3T scanner. MATERIALS AND METHODS: This study comprised 30 cirrhotic patients with MHE, 29 cirrhotic patients without MHE and 30 healthy volunteers. Single-voxel proton MRS data in the anterior cingulate cortex (ACC) and basal ganglia were acquired using a 3-T scanner. The concentrations of N-acetylaspartate (NAA), mI (myo-inositol), glutamate (Glu), glutamine (Gln) and creatine (Cr) were obtained by LC-model software. Statistical analysis was performed to evaluate the differences between the three groups. RESULTS: There was a significant increase in Glu for the cirrhotic patients, particularly the MHE patients. There was an elevation of Gln in the cirrhotic patients, but not in all cirrhotic patients or controls. There was a significant decrease in mI for the cirrhotic patients, but no significant difference between the two cirrhosis groups. There was no significant difference in NAA between the three groups. CONCLUSIONS: MRS using a 3-T MR scanner could detect cerebral metabolic changes in cirrhotic patients with MHE. Glu levels were elevated in cirrhotic patients with MHE; Glu levels could be used as a sensitive indicator to evaluate the severity of MHE in patients with cirrhosis.

Assessment of changes in brain metabolites in Indian patients with type-2 diabetes mellitus using proton magnetic resonance spectroscopy.

BACKGROUND: The brain is a target for diabetic end-organ damage, though the pathophysiology of diabetic encephalopathy is still not well understood. The aim of the present study was to investigate the effect of diabetes on the metabolic profile of brain of patients having diabetes in comparison to healthy controls, using in-vivo magnetic resonance spectroscopy to get an insight into the pathophysiology of cerebral damages caused due to diabetes. METHODS: Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed at 1.5 T on right frontal, right parieto-temporal and right parieto-occipital white matter regions of the brain of 10 patients having type-2 diabetes along with 7 healthy controls. Absolute concentration of N-acetylaspartate (NAA), choline (cho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln), creatine (Cr) and glucose were determined using the LC-Model and compared between the two groups. RESULTS: The concentration of N-acetylaspartate was significantly lower in the right frontal [4.35 ±0.69 vs. 5.23 ±0.74; p = 0.03] and right parieto-occipital region [5.44 ±0.52 vs.6.08 ±0.25; p = 0.02] of the brain of diabetics as compared to the control group. The concentrations of glutamate and glutamine were found to be significantly higher in the right frontal region of the brain [7.98 ±2.57 vs. 5.32 ±1.43; P = 0.01] in diabetics. Glucose levels were found significantly elevated in all the three regions of the brain in diabetics as compared to the control group. However, no significant changes in levels of choline, myo-inositol and creatine were observed in the three regions of the brain examined among the two groups. CONCLUSIONS: 1H-MRS analysis indicates that type-2 diabetes mellitus may cause subtle changes in the metabolic profile of the brain. Decreased concentrations of NAA might be indicative of decreased neuronal viability in diabetics while elevated concentrations of Gln and Glu might be related to the fluid imbalance resulting from disruption of glucose homeostasis.

Low docosahexaenoic acid status is associated with reduced indices in cortical integrity in the anterior cingulate of healthy male children: a 1H MRS Study.

Docosahexaenoic acid (DHA, 22:6n-3) is the principal omega-3 fatty acid in mammalian brain gray matter, and emerging preclinical evidence suggests that DHA has neurotrophic and neuroprotective properties. This study investigated relationships among DHA status, neurocognitive performance, and cortical metabolism measured with proton magnetic resonance spectroscopy (1H MRS) in healthy developing male children (aged 8-10 years, n = 38). Subjects were segregated into low-DHA (n = 19) and high-DHA (n = 19) status groups by a median split of erythrocyte DHA levels. Group differences in 1H MRS indices of cortical metabolism, including choline (Cho), creatine (Cr), glutamine + glutamate + γ-aminobutyric acid (Glx), myo-inositol (mI), and n-acetyl aspartate (NAA), were determined in the right and left dorsolateral prefrontal cortex (R/L-DLPFC, BA9) and bilateral anterior cingulate cortex (ACC, BA32/33). Group differences in neurocognitive performance were evaluated with the Kaufman Brief Intelligence Test and identical-pairs version of the continuous performance task (CPT-IP). Subjects in the low-DHA group consumed fish less frequently (P = 0.02), had slower reaction times on the CPT-IP (P = 0.007), and exhibited lower mI (P = 0.007), NAA (P = 0.007), Cho (P = 0.009), and Cr (P = 0.01) concentrations in the ACC compared with the high-DHA group. There were no group differences in ACC Glx or any metabolite in the L-DLPFC and R-DLPFC. These data indicate that low-DHA status is associated with reduced indices of metabolic function in the ACC and slower reaction time during sustained attention in developing male children.

Multiple Sclerosis Severity Scale and whole-brain N-acetylaspartate concentration for patients' assessment.

BACKGROUND: The ability to predict the course of multiple sclerosis (MS) is highly desirable but lacking. OBJECTIVE: To test whether the MS Severity Scale (MSSS) and global neuronal viability, assessed through the quantification of the whole-brain N-acetylaspartate concentration (WBNAA), concur or complement the assessment of individual patients' disease course. METHODS: The MSSS and average WBNAA loss rate (ΔWBNAA, extrapolated based on one current measurement and the assumption that at disease onset neural sparing was similar to healthy controls, obtained with proton magnetic resonance (MR) spectroscopy and magnetic resonance imaging (MRI)) from 61 patients with MS (18 male and 43 female) with long disease duration (15 years or more) were retrospectively examined. Some 27 patients exhibited a 'benign' disease course, characterized by an Expanded Disability Status Scale score (EDSS) of 3.0 or less, and 34 were 'non-benign': EDSS score higher than 3.0. RESULTS: The two cohorts were indistinguishable in age and disease duration. Benign patients' EDSS and MSSS (2.1 ± 0.7, 1.15 ± 0.60) were significantly lower than non-benign (4.6 ± 1.0, 3.6 ± 1.2; both p < 10(-4)). Their respective average ΔWBNAA, 0.10 ± 0.16 and 0.11 ± 0.12 mM/year, however, were not significantly different (p > 0.7). While MSSS is both sensitive to (92.6%) and specific for (97.0%) benign MS, ΔWBNAA is only sensitive (92.6%) but not specific (2.9%). CONCLUSION: Since the WBNAA loss rate is similar in both phenotypes, the only difference between them is their clinical classification, characterized by MSSS and EDSS. This may indicate that 'benign' MS probably reflects fortuitous sparing of clinically eloquent brain regions and better utilization of brain plasticity.

Metabolic assessment of the brain using proton magnetic resonance spectroscopy in a growth-restricted human fetus: case report.

Proton magnetic resonance spectroscopy (MRS) is a noninvasive method to assess concentrations of different metabolites in tissues, including the brain. We evaluated a fetus with growth restriction using Doppler ultrasound and proton MRS. Doppler assessment revealed absent end diastolic flow in the umbilical artery. Diastolic flow was increased in the middle cerebral artery. Proton MRS of the fetal brain showed lactate and a low N-acetylaspartate/choline index, metabolic markers of starvation/hypoxia. Proton MRS gave us in vivo metabolic information of the brain of a fetus under starvation/hypoxic conditions. It is potentially a new tool for fetal surveillance. To our knowledge, this is the first report of cerebral lactate detection using proton MRS in a growth-restricted human fetus with no associated malformations in the English literature. Further experimental and clinical longitudinal investigations are needed to evaluate its efficacy in the clinical setting.

1H MR spectroscopy in the assessment of gliomatosis cerebri.

OBJECTIVE: Gliomatosis cerebri is a rare brain tumor with a short survival time; for this reason, it is difficult to establish the degree of aggressivity in vivo. The MR spectroscopic findings on this tumor often do not agree with choline level. The purpose of this study was to evaluate whether MR spectroscopy can be used to measure tumor choline levels and whether the findings give useful information about tumor growth rate and patient survival time. SUBJECTS AND METHODS: We performed MRI and 1H MR spectroscopic studies on seven treatment-naive patients with gliomatosis cerebri and on 16 healthy volunteers. We then analyzed the association between survival time and levels of choline (Cho) and N-acetyl aspartate (NAA) normalized to creatine (Cr). RESULTS: The results showed a statistically significant (p = 0.05) inverse relation between Cho/Cr ratio and survival time. In addition, NAA/Cr ratio was significantly lower in the patient group than in the control group (p = 0.001). CONCLUSION: Cho/Cr ratio measured with MR spectroscopy seems to be related to survival time, possibly explaining the inconsistent findings previously reported for this parameter.

Assessment with magnetic resonance imaging and spectroscopy in Lhermitte-Duclos disease.

Lhermitte-Duclos disease (LDD) is a rare benign lesion of uncertain pathogenesis characterized by distortion of the normal cerebellar laminar cytoarchitecture. We report a 22-year-old man admitted for injury sustained in a traffic accident with the incidental finding of a cerebellar mass. Magnetic resonance imaging (MRI) revealed a mass lesion within the right cerebellar hemisphere. The final diagnosis of LDD was made by obtaining a surgical specimen and identifying the characteristic appearance of the lesion by MRI study. The images showed the typical striated pattern of hyperintensity on T2-weighted images and corresponding hypointensity on T1-weighted images, as well as the typical absence of enhancement following gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) administration. In addition, no disturbance of water diffusion on diffusion-weighted MRI, and associations of decreases in the N-acetylaspartate/creatine (NAA/Cr) and NAA/Choline (Cho) ratios with near normal values of Cho/Cr, as well as an obvious lactate peak gave supplemental information for diagnosis.

Multiparametric 3T MR approach to the assessment of cerebral gliomas: tumor extent and malignancy.

INTRODUCTION: Contrast-enhanced MR imaging is the method of choice for routine assessment of brain tumors, but it has limited sensitivity and specificity. We verified if the addition of metabolic, diffusion and hemodynamic information improved the definition of glioma extent and grade. METHODS: Thirty-one patients with cerebral gliomas (21 high- and 10 low-grade) underwent conventional MR imaging, proton MR spectroscopic imaging ((1)H-MRSI), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) at 3 Tesla, before undergoing surgery and histological confirmation. Normalized metabolite signals, including choline (Cho), N-acetylaspartate (NAA), creatine and lactate/lipids, were obtained by (1)H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. RESULTS: Perienhancing areas with abnormal MR signal showed 3 multiparametric patterns: "tumor", with abnormal Cho/NAA ratio, lower ADC and higher rCBV; "edema", with normal Cho/NAA ratio, higher ADC and lower rCBV; and "tumor/edema", with abnormal Cho/NAA ratio and intermediate ADC and rCBV. Perienhancing areas with normal MR signal showed 2 multiparametric patterns: "infiltrated", with high Cho and/or abnormal Cho/NAA ratio; and "normal", with normal spectra. Stepwise discriminant analysis showed that the better classification accuracy of perienhancing areas was achieved when regarding all MR variables, while (1)H-MRSI variables and rCBV better differentiated high- from low-grade gliomas. CONCLUSION: Multiparametric MR assessment of gliomas, based on (1)H-MRSI, PWI and DWI, discriminates infiltrating tumor from surrounding vasogenic edema or normal tissues, and high- from low-grade gliomas. This approach may provide useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Assessment of glutamate and glutamine contribution to in vivo N-acetylaspartate quantification in human brain by (1)H-magnetic resonance spectroscopy.

N-Acetylaspartate (NAA) is one of the most important metabolites detectable by brain (1)H-MRS being considered an index of neuronal integrity. At the low magnetic field used in most clinical settings beta,gamma-glutamate/glutamine (Glx) resonances are very close and partially overlap the methyl-NAA resonance interfering with NAA quantification especially at low TE and in the presence of increased Glx signals. NAA overestimation due to Glx on a set of model solutions containing NAA, glutamate, and glutamine in variable amounts was evaluated and the result tested in vivo in six healthy controls and five age- and sex-matched patients with hepatic encephalopathy (HE), the latter having an increased Glx content. A method to assess in vivo the NAA overestimation caused by Glx is proposed. A perfect match was obtained between the assessment of Glx contamination on the NAA of healthy controls and that obtained on the model solutions. However, a substantial difference in NAA overestimation was found between controls and HE patients that cannot be explained by our model. An interpretative hypothesis is provided.

Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients.

BACKGROUND: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed early in the disease course. OBJECTIVE: To establish reliable biochemical markers of cerebral disease progression in patients with ALD to aid in treatment planning. METHODS: The authors used proton magnetic resonance spectroscopy (MRS) in combination with LCModel analysis to quantify brain metabolites in small volumes (3 to 16 mL) in the occipital and frontal white matter and the splenium of the corpus callosum of 17 unsedated patients and 26 healthy volunteers (adult n = 21, age-matched n = 5) at 4 tesla. RESULTS: Absolute concentrations of 12 metabolites were reliably determined, seven of which were established as markers of lesion development. Among these, creatine and choline containing compounds were the weakest markers while N-acetylaspartate, glutamine, and lipids + lactate were the strongest. The large extent of changes in the markers enabled detection of early neurochemical changes in lesion formation prior to detection of abnormalities by conventional MRI. Concentrations of a number of metabolites were also significantly different between normal appearing white matter of patients and controls indicating biochemical alterations in the absence of cerebral disease. Neurochemical improvements following HCT were measured in six patients. CONCLUSIONS: The progression of adrenoleukodystrophy, as well as effectiveness of its treatment, can be assessed with high precision using high field 1H magnetic resonance spectroscopy in individual patients without the need for sedation.

Quantitative assessment of localization and colocalization of glutamate, aspartate, glycine, and GABA immunoreactivity in the chick retina.

We examined the posthatch chick retina for the frequency of occurrence of localization and colocalization of four amino acid transmitter candidates: glutamate (Glu), aspartate (Asp), gamma aminobutyric acid (GABA), and glycine (Gly) using postembedding methods. We support previous studies of Glu, Asp, GABA, and Gly localization in the direct and indirect functional pathways of the chick retina and extend these studies with new qualitative and quantitative observations. We found that photoreceptors show distinct cellular immunoreactivity for both Glu (Glu+) and Asp+, but not for Gly (Gly-) or GABA. Moreover, there is compartmentalization of Glu and Asp staining within the photoreceptors. All horizontal cells react strongly with Asp and Glu, about three-fourths are GABA+ and three-fourths of these are Gly+. Bipolar cells are uniformly Glu+, heterogeneously Asp+, occasionally Gly+, but GABA-. A majority of amacrine cells stain heterogeneously with all antibodies: 90% are Gly+, slightly more than half colocalize Glu, GABA, and Gly. Furthermore, amacrine cells in the outer two or three rows of cells are more likely to be stained by Gly than Glu, Asp, or GABA. Confirming previous studies, ganglion cells were mostly immunoreactive for Glu and Asp with fewer reactive for GABA and Gly. Strong and distinctly cellular immunoreactivity was found in both central and peripheral retina. Our findings show: 1) there is extensive colocalization of Glu, Asp, GABA, and Gly among most retinal neurons, including some cells that contain all four; 2) cells of the direct functional pathway tend to be labeled by Glu and Asp generally to the exclusion of GABA and Gly, while those of the indirect pathway tend to be labeled by GABA+ and/or Gly+ in addition to Glu+ and Asp+; 3) different cell body layers have distinct patterns of colocalization; and 4) there is no qualitative difference in staining patterns between peripheral and central retina.

Combined magnetization transfer and proton spectroscopic imaging in the assessment of pathologic brain lesions in multiple sclerosis.

BACKGROUND AND PURPOSE: Conventional MR imaging of multiple sclerosis (MS) provides relatively poor pathologic specificity, which has led to the investigation of more sophisticated MR techniques. The purpose of this study was to combine magnetization transfer (MT) imaging and proton MR spectroscopic imaging (MRSI) to evaluate the specific pathologic features of myelination and neuronal integrity in patients with MS and to determine the relationship between these measures within plaques. METHODS: We acquired conventional MR, MT, and proton MRSI data and evaluated clinical disability in 30 patients with MS, whose conditions were categorized as relapsing-remitting, primary progressive, or secondary progressive. The lesions were classified, using a semiautomated edge-following technique, on T2-weighted MR images, and an analysis of MT and proton MRSI data was conducted for lesion regions as well as for tissue that was categorized as normal. RESULTS: The MT ratio (MTR) of normal-appearing white matter in the patients with MS was significantly lower than in the healthy participants, whereas gray matter values were unchanged. MS lesions showed a large reduction in MTR, with old lesions exhibiting a lower MTR than new lesions. The average lesion MTR and the MR spectroscopic imaging-measured relative concentration of N-acetylaspartate, a marker of neuronal integrity, was positively correlated in patients with relapsing-remitting MS. This relationship was strengthened in regions containing new lesions. CONCLUSION: The integrated use of MT and MR spectroscopic imaging provides a more complete description of the pathologic features of MS than does conventional MR imaging alone, and our data suggest that axonal damage occurs in step with new demyelination and is not a late feature of the disease.

Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy.

Quantitative measurement of MRI-defined brain lesions can provide an index of the extent and activity of disease in multiple sclerosis patients. However, the relationships between these indices and clinical features are not well-understood. Heterogeneity of the pathological changes underlying MRI lesions may be an important factor determining the correlation between MRI lesion volumes and clinical measures. Recent studies have suggested that with magnetic resonance spectroscopy (MRS), it may be possible to define chemical changes that better reflect the pathological changes in multiple sclerosis. Here we report results of combined quantitative brain T2-weighted MRI lesion volume and proton MRS examinations that demonstrate heterogeneity of the chemical pathology underlying brain lesions in patients selected on the basis of similar clinical disability but differing with respect to the presence or absence of clinical relapses. We examined 29 patients with disease characterized by either clear relapses with at least partial remissions (RR) or secondary, chronic progression after an earlier history of a more relapsing and remitting course (SP). Total hemispheric lesion volume was greater (P < 0.04) in the RR (32.5 +/- 20.9 cm3) than in the SP (16.2 +/- 9.0 cm3) patients, despite the longer duration of disease in the latter group. Central brain N-acetyl aspartate: creatine (NAA:Cr) ratios were reduced relative to normal controls (4.0 +/- 0.3, n = 19) by similar amounts in the two patients groups (RR, 3.1 +/- 0.5; SP, 3.2 +/- 0.4; P < 0.0001). The ratio lesion volume:(NAA:Cr) was greater for the RR group (11.7 +/- 9.3 cm3) than for the SP group (5.4 +/- 3.3 cm3, P < 0.05), implying a greater average degree of axonal loss per unit lesion volume defined by MRI for subjects in the SP group or, alternatively, a greater proportion of lesions without axonal damage or loss in the RR group. Our results emphasize a limitation of using T2-weighted MRI lesion volume alone and suggest that combined analysis of MR-based chemical and imaging data might allow improved non-invasive assessment of lesion pathology in order to better understand its relationship to clinical features of multiple sclerosis.

Regional metabolic assessment of human brain during development by proton magnetic resonance spectroscopy in vivo and by high-performance liquid chromatography/gas chromatography in autopsy tissue.

To study the course of regional metabolite concentrations during early brain development, we measured in vivo metabolites [N-acetyl-aspartate (NAA), choline-containing compounds, and myoinositol (M-Ino)] in the precentral area of the cerebrum by short echo-time single volume proton magnetic resonance spectroscopy and compared in vivo established spectroscopic data with classic chromatographic data (HPLC) on age-corresponding autopsy tissue in different regions of the brain. In autopsy tissue, regional (frontal lobe, precentral area, basal ganglia, thalamus) and age-dependent differences of the concentration of creatine, NAA, and M-Ino were determined. In vivo measurement of NAA by proton magnetic resonance spectroscopy shows a significant increase of NAA by increasing postconceptional age. M-Ino shows a weak correlation and a nonsignificant decrease with increasing postconceptional age. Choline shows no age-dependent changes. Creatine concentrations measured by HPLC in different regions of the developing brain at autopsy showed an age-dependent increase that was identical for the left and right side and similar for the precentral area and frontal lobe and more pronounced for the basal ganglia and thalamus. Comparison of the results obtained by the two methods shows agreement for the age-dependent changes and the absolute concentration of M-Ino. NAA determined in autopsy tissue by HPLC is significantly lower than that measured in vivo by proton magnetic resonance spectroscopy. A comparison of the concentrations measured by HPLC in frontal lobe, basal ganglia, and thalamus with the results obtained from the precentral area showed significant regional differences in all measured metabolites. These results define important age-dependent changes detected with both methods and further indicate limitations of both methods that have to be considered when presenting absolute concentration values.