Specific hippocampal choline decrease in an animal model of depression.

A decreased level of the hippocampal choline signal was found in patients with depression in previous proton magnetic resonance spectroscopy ((1)H-MRS) studies. The objective of this study is to compare choline levels before and after the forced swimming test (FST), an animal model of depression typically used for assessing antidepressant activity. (1)H-MRS spectra were obtained from both the left and right hippocampus. After the FST, rats showed a significant decrease of the choline/creatine (Cho/Cr, p = 0.037) and choline/N-acetylaspartate (Cho/NAA, p = 0.048) ratios in the left hippocampus, but not in the right hippocampus. This finding was analogous to results from patients with depression. It suggests that decreased Cho/Cr and Cho/NAA ratios in the left hippocampal regions might be considered to be biomarkers in rats with depression.

Magnetic resonance imaging and proton magnetic resonance spectroscopy in neuro-Behçet's disease.

OBJECTIVE: Neuro-Behcet's disease (NBD) is one of the most serious complications of Behcet's disease (BD). Proton magnetic resonance spectroscopy (1H MRS) has been proved to be useful in detecting neuro-metabolic abnormalities in various diseases affecting the brain. In this study, we attempted to characterize the magnetic resonance imaging (MRI) findings in Korean patients with NBD and then examined the usefulness of 1HMRS in evaluating the MRI-negative brain area of NBD patients. METHODS: We performed brain MRI in 18 BD patients with neurologic symptoms and signs. Seven NBD patients without thalamic lesions and 8 healthy controls underwent brain 1H MRS, in which an 8 ml voxel was placed in the left thalamus and the N-acetylaspartate (NAA)/creatine (Cr) ratio was measured. RESULTS: Fourteen of 18 BD patients were diagnosed as having NBD and 12 NBD patients (86%) had brain lesions on MRI. Most lesions were of high signal intensity on T2-weighted images and located in the midbrain, pons, basal ganglia, and white matter. On 1H MRS, the thalamic area without gross abnormalities on MRI showed a significantly lower NAA/Cr ratio in NBD patients compared to healthy controls (1.07 +/- 0.08 versus 1.54 +/- 0.27, P < 0.01). In 2 NBD patients, the NAA/Cr ratios, monitored serially, were normalized along with clinical improvement 6 months after treatment with prednisolone and immune suppressive agents. CONCLUSION: MRI is a very sensitive diagnostic method for NBD, and 1H MRS may be useful for the early detection and follow-up of MRI-negative NBD.

Non-linear registration for brain images by maximising feature and intensity similarities with a Bayesian framework.

The objective of this work was to provide a new, precise registration of the cortical mantle with a non-linear transformation. Image registration is broadly classified into two types, using intensity similarity and feature similarity. Whereas the former approach has merit in global brain matching, the latter provides a fast registration centred on a region of interest. The hybrid registration proposed in this paper was achieved using a Bayesian framework, which consisted of a likelihood model including intensity similarity and a prior model including feature information and a smoothing constraint. In this approach, each voxel was spatially transformed, so that the distance between corresponding features was shortened and also so that the intensity correlation was maximised. The result of the hybrid method clearly showed a good match of global brain (r = 0.930) by including intensity similarity. Moreover, this method compensated for the approximated sulcus of the feature-based method with intensity information, so that the geometric shape and thickness of the sulcus at the feature-defined region was likely to be registered. The accuracy in the feature-defined area was improved by 33.4% and 7.5% compared with feature-based and intensity-based methods, respectively.

Proton magnetic resonance chemical shift imaging (1H CSI)-directed stereotactic biopsy.

INTRODUCTION: To add metabolic information during stereotactic biopsy target selection, the authors adopted proton chemical shift imaging (1H CSI)-directed stereotactic biopsy. Currently, proton single voxel spectroscopy (SVS) technique has been reported in stereotactic biopsy. We performed 1H CSI in combination with a stereotactic headframe and selected targets according to local metabolic information, and evaluated the pathological results. PATIENTS AND METHOD: The 1H CSI-directed stereotactic biopsy was performed in four patients. 1H CSI and conventional Gd-enhancement stereotactic MRI were performed simultaneously after the fitting of a stereotactic frame. After reconstructing the metabolic maps of N-acetylaspartate (NAA)/phosphocreatine (Cr), phosphocholine (Cho)/Cr, and Lactate/Cr ratios, focal areas of increased Cho/Cr ratio and Lac/Cr ratios were selected as target sites in the stereotactic MR images. RESULTS: 1H CSI is possible with the stereotactic headframe in place. No difficulty was experienced performing 1H CSI or making a diagnosis. Pathological samples taken from areas of increased Cho/Cr ratios and decreased NAA/Cr ratios provided information upon increased cellularity, mitoses and cellular atypism, and facilitated diagnosis. Pathological samples taken from areas of increased Lac/Cr ratio showed predominant feature of necrosis. CONCLUSION: 1H CSI was feasible with the stereotactic headframe in place. The final pathological results obtained were concordant with the local metabolic information from 1H CSI. We believe that 1H CSI-directed stereotatic biopsy has the potential to significantly improve the accuracy of stereotactic biopsy targeting.

Metabolic changes in pericontusional oedematous areas in mild head injury evaluated by 1H MRS.

In order to define metabolic brain changes associated with mild traumatic brain injury, proton magnetic resonance spectroscopy (MRS) was performed in patients with regional brain contusion and 13-15 of initial GCS score. The authors measured N-acetylaspartate(NAA)/creatine(Cr) ratio and lactate signal on in vivo proton MRS, which indicated cell loss and ischaemic dAmage respectively, in pericontusional oedematous areas (region of interest; ROI) adjacent to traumatic brain contusion on brain MRI to determine possible metabolic changes. The metabolic ratio of NAA/Cr and lactate/Cr peaks was measured both in the ROI and a corresponding region of the contralateral hemisphere (ROC) in seven patients and twenty-five normal control. In initial NAA/Cr ratios, the values of ROIs were significantly lower than those of the control (p = 0.009), but there was no difference either between ROI and ROC (p = 0.410) or between ROC of patients and the control (p = 0.199). In lactate/Cr ratios, the ROI in all seven patients and the ROC in two showed increased lactate signals. The lacate/Cr ratios of the ROIs were significantly elevated as compared to those of the ROCs (p = 0.02) and the control (p = 0.015). In 2-month follow up, lactate signals were absent or significantly reduced (p = 0.015). In no patients, clinical or radiological deterioration has been observed. Our results demonstrate that there is significant neuronal dysfunction in pericontusional oedematous areas as indicated by NAA/Cr ratios in the patients with mild head injury at both early and late stages. And there are significant ischaemic changes as indicated by increase of lactate level in ROI at early stage. These findings suggest that pericontusional oedematous areas can be vulnerable to secondary brain insults even in the patients with mild head injury.

Nonossifying fibroma: characteristics at MR imaging with pathologic correlation.

PURPOSE: To correlate the findings of nonossifying fibroma at magnetic resonance (MR) imaging with those at pathologic examination. MATERIALS AND METHODS: In 19 patients (age range, 8-25 years; mean age, 14 years) with pathologically proved nonossifying fibroma, MR images were analyzed for signal intensity and patterns of contrast enhancement. Findings at MR imaging and biopsy were correlated. RESULTS: On T1-weighted images, all nonossifying fibromas had low signal intensity compared with that of skeletal muscle. On T2-weighted images, 15 lesions (79%) were hypointense and four (21%) were hyperintense. On gadolinium-enhanced images, intense contrast enhancement was seen throughout 15 lesions (heterogeneous pattern in 12 and homogeneous in three) and in the margins and septa in four. Extensive hypercellular fibrous tissue and hemosiderin seen at pathologic examination were depicted with low signal intensity on T2-weighted MR images. CONCLUSION: The distinguishing features of nonossifying fibroma included hypointensity and septation on T2-weighted images. Signal intensity on T1- and T2-weighted MR images and the patterns of contrast enhancement were dependent on the amounts of hypercellular fibrous tissue, hemosiderin, hemorrhage, collagen, foamy histiocytes, and bone trabeculae.

The plica syndrome: diagnostic value of MRI with arthroscopic correlation.

PURPOSE: Our goal was to evaluate the diagnostic value of MRI in plica syndrome. METHOD: MR images of a patient group (n = 55) with arthroscopically confirmed pathologic mediopatellar plicae were retrospectively analyzed and compared with those of a control group (n = 100). We obtained axial multiplanar gradient-recalled (MPGR), axial T1-weighted, and sagittal T2-weighted MR images. MR images were assessed for the width and length of all medial plicae. RESULTS: In the diagnosis of plica syndrome, sensitivity and specificity were 73 and 78% on axial MPGR images, 71 and 83% on sagittal T2-weighted images, and 95 and 72% on combination of both images, respectively. The incidence of pathologic medial plica increased with a criterion of extension beyond the medial end of the patella on axial MPGR images. CONCLUSION: MRI is a useful screening method in the diagnosis of plica syndrome.

Neuronal laterality in Parkinson's disease with unilateral symptom by in vivo 1H magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: The authors investigate whether there is a lateral effect of 1H-magnetic resonance spectroscopy (MRS) observable metabolite ratios between the symptomatic and the asymptomatic side in Parkinson's disease with unilateral symptoms. METHODS: Localized in vivo 1H MRS was used to measure the metabolite levels in the symptomatic and the asymptomatic sides of the substantia nigra (SN) and putamen-globus pallidus (PG) in Parkinson's disease with unilateral symptom (n = 15). The metabolite ratios of N-acetylasparatate (NAA)/creatine (Cr), and choline-containing compounds (Cho)/Cr in the symptomatic side were compared with those in the asymptomatic side. According to the symptomatic duration, the authors evaluated whether there was a specific correlation between laterality and the clinical stage. RESULTS: Significant metabolic lateral effect of NAA/Cr ratio was established between the symptomatic and the asymptomatic sides of SN and PG in Parkinson's disease with unilateral symptoms (P = 0.03). The decreased NAA/Cr ratio was calculated in at least one of the selected regions in SN and PG, indicating neuronal loss. The main observations were that NAA/Cr ratios were reduced in the left symptomatic side (n = 7; P = 0.001) and reduced to a lesser degree in the right symptomatic side (n = 8; P = 0.03 [PG], P = 0.21 [SN]) and that there was no significant laterality of other metabolite ratios. CONCLUSIONS: On the basis of NAA/Cr ratios between the symptomatic and the asymptomatic sides, the present 1H MRS study shows a significant neuronal laterality in Parkinson's disease with unilateral symptoms. In vivo 1H MRS may provide a diagnostic marker for neuronal dysfunction in Parkinson's disease with unilateral symptoms.

Evaluation of the effects of high dose irradiation on canine thigh muscle by follow-up magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: The authors investigate alterations of proton T1 and T2 relaxation times and phosphorus metabolites of canine thigh muscle tissue after high dose x-ray irradiation by follow-up magnetic resonance imaging (MRI) and phosphorus-31 (31P) magnetic resonance spectroscopy (MRS). METHODS: A group of 20 dogs was used for MRI and in vivo 31P MRS. Single doses of 5,000 and 10,000 cGy were delivered to the right thigh muscle of groups of 10 dogs each. All MRI and 31P MRS examinations were performed before irradiation and 1, 7, 14, 28, 42, and 56 days after irradiation. For measurement of T1, repetition time (TR) was measured at 300, 500, 1000, 1500, 2000 msec and echo time (TE) was fixed at 12 msec. Also, for measurement of T2, TE was measured at 20, 40, 60, and 80 msec and TR was fixed at 2000 msec. Image selected in vivo spectroscopy (ISIS) pulse sequence was used to obtain 31P MR spectra. Peak areas for each phosphorus metabolite were measured using a Marquart algorithm. RESULTS: Magnetic resonance imaging signal began to change at 28 days after a single dose of 10,000 cGy, whereas there was no significant MRI signal change until 56 days after a single dose of 5,000 cGy. Also, extensive MRI signal changes were observed at 42 days after a single dose of 10,000 cGy. Significant correlation was established between T2 and a lapse of time although there was no correlation between T1 and a lapse of time. T2 value increased substantially corresponding to the time period after x-ray irradiation. Although MR spectral change was not observed until 42 days after a single dose of 5,000 cGy, it began at 14 days after a single dose of 10,000 cGy. And, significant MR spectral changes were observed at 28 and 42 days. Inorganic phosphate and phosphodiesters signal intensities increased while phosphocreatine signal intensity decreased. The pH value was 7.22 +/- 0.05 at control, and 6.98 +/- 0.04 at 42 days after a single dose of 10,000 cGy. CONCLUSIONS: The postirradiation follow-up MRI and 31P MRS studies demonstrated that morphologic and metabolic changes were dependent upon the x-ray dose and a lapse of time.

Recurrent parosteal osteosarcoma of the talus in a 2-year-old child.

Parosteal osteosarcoma is an uncommon, low-grade malignant bone tumor and is found in an older age group than conventional osteosarcoma. We present a talar parosteal osteosarcoma that recurred twice in a 2-year-old child. To our knowledge, this is the youngest patient reported with a parosteal osteosarcoma. The talus is an unusual site for parosteal osteosarcoma. Inadequate resection due to a diagnosis of juxtacortical chondroma resulted in recurrence of the tumor. The age of the patient, the thick cartilaginous cap, and well-differentiated trabecular bone all contributed to the critical erroneous diagnosis.

Resistive index of the intrascrotal artery in scrotal inflammatory disease.

PURPOSE: To investigate the utility of the resistive indices (RIs) of the epididymal and intratesticular arteries, and to establish diagnostic criteria for scrotal inflammatory disease on the basis of quantitative color Doppler sonography. MATERIAL AND METHODS: We prospectively examined 29 consecutive patients with scrotal pain, and 15 normal control subjects. The RIs of the intratesticular and epididymal arteries were obtained from color Doppler sonographs. RESULTS: The RIs of the testicular artery in epididymoorchitis were significantly lower than those in normal control subjects and in epididymitis (p < 0.01) while the RIs of the testicular artery in epididymitis and control subjects were similar (p > 0.5). With a cut-off value of RI = 0.5, sensitivity, specificity, accuracy, and positive and negative predictive values were 91%, 94%, 94%, 83%, and 77% respectively. The mean RI of the epididymal arteries in epididymitis and epididymoorchitis was 0.49 +/- 0.11. A high level of diagnostic accuracy in scrotal inflammatory disease was achieved when the RIs of the intratesticular and epididymal arteries were less than 0.5 and 0.7 respectively. CONCLUSION: The RI of the intrascrotal artery would give a more objective evaluation than subjective assessment and could provide diagnostic criteria for scrotal inflammatory disease.

MR imaging analysis of heterogeneous leiomyomas of the uterus.

Thirty-six leiomyomas from the same number of patients that were heterogeneous on MR imaging were evaluated for analyzing their MR patterns and for differentiating each type of secondary changes by means of MR imaging-pathologic correlation. The tumors with a mean diameter of 9 cm could be classified into 4 patterns depending on the morphological appearance of signal intensity: speckled (n = 14); nodular (n = 11); cystic (n = 9); or indeterminate (n = 2). Speckled pattern was associated with a mild degree of hyaline or myxoid degeneration or focal necrosis. Nodular pattern was caused by necrosis or cellular leiomyoma, and cystic pattern was related to severe hyaline or myxoid degeneration or necrosis. Each type of secondary changes within leiomyomas showed distinctive MR findings, if they were severely involved. However, use of an additional contrast-enhanced study was necessary in some instances for further clarification. MR imaging has a potential in distinguishing each type of secondary changes that occur in leiomyomas. Various degenerative changes occur in approximately 65% of uterine leiomyomas, and are caused mainly by alteration in the blood supply originating from rapid growth, pregnancy, mechanical accident, and postmenopausal atrophy. These changes include hyaline, mucoid, or myxoid degeneration, calcification, cystic changes, necrosis (red degeneration), and fatty metamorphosis. It is well known that the presence of degenerative changes within leiomyomas can be predicted on MR imaging by a heterogeneous signal intensity on T2-weighted images, although clear distinction of each type of degeneration can not be made by this modality. Recently, cellular leiomyoma, one of the variants of leiomyomas, was also reported to cause heterogeneous signal intensity. However, because various other uterine tumors can also have similar signal intensity on MR imaging, further evaluation for the heterogeneous leiomyomas appears to be necessary. The purpose of our study was to analyze the patterns of heterogeneous leiomyomas and to differentiate each type of secondary changes by means of MR imaging-pathologic correlation.

Fibrous dysplasia: MR imaging characteristics with radiopathologic correlation.

OBJECTIVE: The purpose of this study was to describe the findings of MR imaging of fibrous dysplasia and to evaluate the correlation between radiologic and pathologic findings. MATERIALS AND METHODS: MR images of 13 proven cases of fibrous dysplasia were analyzed for signal intensity, hypointense rind, internal septations, cystic changes, soft-tissue extension, and patterns of contrast enhancement. RESULTS: All cases of fibrous dysplasia showed low signal intensity on T1-weighted MR images. Five cases (38%) were hypointense on T2-weighted MR images, and the other eight cases (62%) were hyperintense. Hypointense rind was seen in 10 cases (77%); internal septations were seen in three cases (23%); and cystic changes was seen in two cases (15%). Soft-tissue extension was observed in four cases (31%), including one case (8%) with a pathologic fracture. After gadolinium infusion, central contrast enhancement was noted in eight cases (73%), and peripheral rim enhancement was noted in three cases (27%). Numerous bony trabeculae, confirmed pathologically, caused a hypointense signal intensity on T2-weighted images. CONCLUSION: Patients with fibrous dysplasia showed a correlation between radiologic and pathologic findings. Our results showed that T1-weighted images reveal fibrous dysplasia as hypointense, and T2-weighted images reveal fibrous dysplasia as either hyperintense or hypointense. Signal intensity on T1- and T2-weighted images and the degree of contrast enhancement on T1-weighted images depended on the amount and degree of bony trabeculae, cellularity, collagen, and cystic and hemorrhagic changes.

Observation of metabolic changes in chronic schizophrenia after neuroleptic treatment by in vivo hydrogen magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: The authors investigate: (1) whether there is a lateral effect of hydrogen (1H) magnetic resonance (MR) spectroscopy observable metabolite ratios between the right and the left prefrontal lobe in chronic schizophrenia; (2) whether there is a change of proton metabolite ratios in chronic schizophrenia after neuroleptic treatment; (3) whether there is a relation between changes in 1H MR spectra and the clinical assessment of Brief Psychiatric Rating Scale (BPRS); and (4) to investigate a hypofrontality hypothesis in schizophrenia in terms of neurochemical aspects. METHODS: Localized in vivo 1H MR spectroscopy was used to measure the metabolite levels in the prefrontal lobes of control persons (n = 20) and of chronic patients before and after neuroleptic treatment (n = 34). The MR spectra of 8 cm3 voxels were compared with clinical assessment of BPRS in each subject. RESULTS: No significant metabolic lateral effect was established in both schizophrenia and control groups (P > 0.05). After neuroleptic treatment, chronic schizophrenic patients generally demonstrated a decrease of the complex of gamma-aminobutyric acid (GABA) and glutamate (Glu) containing (GABA + Glu)/creatine (Cr) ratio. CONCLUSIONS: The current follow-up 1H MR spectroscopy study shows a significant correlation between alterations of (GABA + Glu)/Cr ratio and BPRS, and supports a hypofrontality hypothesis in chronic schizophrenia. The reduction of (GABA + Glu)/Cr ratio after neuroleptic treatment may implicate the recovery of normal neuronal function in neurotransmitters. In vivo 1H MR spectroscopy may be a useful modality in follow-up evaluation of neuroleptic treatment in chronic schizophrenia.

Computer-aided design optimization with the use of a fast dose model for linear-accelerator-based stereotactic radiosurgery.

In order to efficiently plan non-spherical radiosurgical targets we have used computer-aided design optimization techniques with a fast dose model. A study of the spatial dose distribution for single or multiple non-coplanar arcs was carried out using a 18 cm diameter spherical head model. The dose distribution generated from the 3D dose computation algorithm can be represented by a simple analytic form. Two analytic dose models were developed to represent the dose for preset multiple non-coplanar arcs or a single arc: spherical and cylindrical. The spherical and cylindrical dose models compute dose quickly for each isocentre and single arc. Our approach then utilizes a computer-aided design optimization (CAD) with the use of two fast approximate dose models to determine the positions of isocentres and arcs. The implementation of CAD with fast dose models was demonstrated. While the fast dose models are only approximations of the true dose distribution, it is shown that this approximate model is sufficient to optimize isocentric position, collimator size and arc positions with CAD.

Neuronal dysfunction in patients with closed head injury evaluated by in vivo 1H magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: With the use of localized, water-suppressed in vivo 1H magnetic resonance spectroscopy (MRS), the proton metabolic alterations of white matter in patients with closed head injury (CHI) and healthy controls are evaluated, and metabolic alterations with Glasgow Outcome Scale (GOS) scores are compared. METHODS: Patients with CHI (n = 10) and healthy control subjects (n = 10) underwent MRS examinations using a stimulated-echo acquisition mode pulse sequence that provided 2 x 2 x 2 cm3 volume of interest in the left frontoparietal white matter. Proton metabolite ratios relative to creatine were obtained using a Marquart algorithm. RESULTS: The specific feature in patients with CHI was significant decrease of N-acetylaspartate (NAA)/creatine ratio compared with normal controls. No clear correlation of other metabolite ratios such as choline/creatine and inositols creatine was established. The level of NAA/creatine ratio was significantly correlated with GOS. CONCLUSIONS: Results of this preliminary study suggest that the reduction of NAA/creatine ratio may indicate neuronal loss in patients with CHI. The NAA/creatine ratio may serve as a metabolic criterion to predict the GOS of patients with CHI. Thus, in vivo 1H MRS may be a useful modality in the clinical evaluation of patients with CHI based on the proton metabolite concentrations of cerebral white matter.

Postmortem metabolic and morphologic alterations of the dog brain thalamus with use of in vivo 1H magnetic resonance spectroscopy and electron microscopy.

RATIONALE AND OBJECTIVES: To investigate postmortem metabolic and morphologic alterations in the dog brain thalamus and to contribute diagnostic aids in medicolegal science. METHODS: A homogeneous group of 17 dogs was used for in vivo 1H magnetic resonance (MR) spectroscopy and electron microscopic studies, which were performed under intravenous and intramuscular anesthesia before and after the dogs were killed. All 1H MR spectroscopy and electron microscopy examinations were performed on a 1.5 T MR imaging/MR spectroscopy system using a stimulated-echo acquisition mode pulse sequence and an electron microscope, respectively. RESULTS: The lactate resonance signal, which could be used as a criterion for tissue survival, appeared during the entire postmortem period. The lactate: creatine ratio significantly increased in the early postmortem metabolic process. The inositol: creatine ratio showed a mild gradual increase. However, the N-acetyl-aspartate: creatine and choline/creatine ratios generally were unchanged. The decomposition of proton metabolites was observed in the MR spectrum 48 hours postmortem. In the postmortem period, high power field (x10,000) electron microscopic results showed significant morphologic alterations of the thalamus, revealing nuclear pyknosis and perikaryal condensation, cytoplasmic vacuoles, clumping of nuclear chromatin, and destruction of cellular organelles and nuclear membrane. CONCLUSIONS: Results suggest that the combination of 1H MR spectroscopy and electron microscopy may simultaneously provide good quality metabolic and morphologic information of cerebral tissue in the field of thanatochronology.

1H magnetic resonance spectroscopy characterization of neuronal dysfunction in drug-naive, chronic schizophrenia.

RATIONALE AND OBJECTIVES: We investigated the proton metabolism of right prefrontal white matter in drug-naive, chronic schizophrenic patients (n = 23), compared with healthy normal control subjects (n = 10), by using localized, water-suppressed in vivo 1H magnetic resonance (MR) spectroscopy. METHODS: All 1H MR spectroscopy examinations were performed on a 1.5-T MR imaging/MR spectroscopy system by using a point-resolved spectroscopy pulse sequence for localized volumes of 2 x 2 x 2 cm3. Proton metabolite ratios relative to creatine (Cr) were obtained using a Marquart algorithm. RESULTS: Drug-naive, chronic schizophrenic patients demonstrated a decrease in the N-acetylaspartate (NAA):Cr and choline (Cho):Cr ratios and an increase of the complex of gamma-aminobutyric acid (GABA) and glutamate (Glu)-containing ratio [(GABA + Glu):Cr] as compared with normal control subjects. CONCLUSION: Results suggest that the reduction of NAA and Cho may indicate neuronal dysfunction and that the elevation of GABA and Glu may play a role in chronic schizophrenia. 1H MR spectroscopy may be a useful modality in research and in the clinical evaluation of chronic schizophrenic patients.

Nuclear magnetic resonance and molecular modeling studies on O-beta-D-galactopyranosyl-(1----4)-O-beta-D-xylopyranosyl-(1----0)-L-se rine, a carbohydrate-protein linkage region fragment from connective tissue proteoglycans.

The solution conformation of O-beta-D-galactopyranosyl-(1----4)-O-beta-D-xylopyranosyl-(1----0)-L-ser ine (GXS), a carbohydrate-protein linkage region fragment from connective tissue proteoglycans, was investigated by two-dimensional NMR spectroscopy and molecular modeling calculations. Specifically, the 1H and 13C resonances were assigned by 2D-COSY and by 1H-13C heteronuclear correlation spectroscopy methods. 2D-NOESY was used to generate distance constraints between the galactose and xylose and between the xylose and serine residues. The 1H vicinal coupling constants for the sugars and the serine were also determined. A general molecular modeling methodology suitable for complex carbohydrates was developed. This methodology employed molecular dynamics and energy minimization procedures together with the application of inter-residue spatial constraints across the linkages derived from 2D-NOESY. The first step in this methodology is the generation of a wide variety of starting conformations that span the (phi, psi) space for each linkage. In the present study, nine such conformations were constructed for each linkage using the torsion angles phi and psi corresponding to the gauche+, gauche-, and trans configurations across each of the two bonds constituting the linkage. These conformations were subjected to a combined molecular dynamics/energy minimization refinement using the NOESY derived constraints as pseudoenergy functions. Families of conformations for the whole molecule were then constructed from the structures derived for each linkage. Characterization of GXS using this methodology identified a single family of conformations that are consistent with the solution phase NMR data on this molecule.