Bo-Young Choe

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.

Intraarterially delivered human umbilical cord blood‐derived mesenchymal stem cells in canine cerebral ischemia

The present study examined the effects of human umbilical cord blood‐derived mesenchymal stem cells (HUCB‐derived MSCs) delivered through the basilar artery in a canine thromboembolic brain ischemia model. Cerebral ischemia was induced through occlusion of the middle cerebral artery by injecting thrombus emboli into 10 beagles. In the HUCBC group (n = 5), 1 × 106 HUCB‐derived MSCs were transplanted through the basilar artery 1 day after ischemic induction using an endovascular interventional approach. In the control group (n = 5), phosphate‐buffered saline (PBS) was injected in the same manner in as the HUCBC group. Upon neurobehavioral examination, earlier recovery was observed in the HUCBC group. The HUCBC group showed a decrease in the infarction volume at 1 week after cerebral ischemic induction, whereas the control group showed an increase in the infarction volume at 1 week, by magnetic resonance image analysis. Transplanted cells had differentiated into neurons and astrocytes and were observed in and around endothelial cells that were positive for von Willebrand factor (vWF). HUCB‐derived MSCs expressed neuroprotective factors, such as brain‐derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), at 4 weeks after the transplantation. The transplanted cells demonstrated their efficacy by reducing the infarction lesion volume and through earlier recovery from the neurological deficit. These results suggest that intraarterial transplantation of HUCB‐derived MSCs could be useful in clinical treatment of cerebral ischemia.

NEURONAL DYSFUNCTION IN PATIENTS WITH CLOSED HEAD INJURY EVALUATED BY IN VIVO 1H MAGNETIC RESONANCE SPECTROSCOPY

RATIONALE AND OBJECTIVESWith 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. METHODSPatients with CHI (n = 10) and healthy control subjects (n= 10) underwent MRS examinations using a stimulated-echo acquisition mode pulse sequence that provided 2 × 2 × 2 cm3 volume of interest in the left frontoparietal white matter. Proton metabolite ratios relative to creatine were obtained using a Marquart algorithm. RESULTSThe 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. CONCLUSIONSResults 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.

Acupuncture Stimulation for Motor Cortex Activities: A 3T fMRI Study

The acupoint, GB34, located in the back of the knee, is known to be effective in recovering motor function after a stroke. This study uses a functional magnetic resonance imaging (fMRI) study with 3T scanner to investigate whether or not acupuncture of GB34 produces a significant response of the modulation of somatomotor areas. A fMRI of the whole brain was performed in ten normal healthy subjects during two task stimulations of acupuncture manipulation on GB34 and sham points, inserting and twisting the needle for 25 seconds at a rate of approximately 120 times per minute; the needle manipulation was paused for a duration of 25 seconds as a control state. The process was repeated four times to have four epochs of stimulation. Bilateral sensorimotor areas (BA 3, 4, 6 and 7) showed approximately 6% of stimulation-related BOLD signal contrast, whereas very few areas were activated when sham stimulation was given. Acupuncture stimulation in GB34 modulates the cortical activities of the somatomotor area in humans. The present findings may shed light on the CNS mechanism of motor function by acupuncture, and form a basis for future investigations of motor modulation circuits in stroke patients.

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 Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons disease with unilateral symptoms. In vivo 1H MRS may provide a diagnostic marker for neuronal dysfunction in Parkinsons disease with unilateral symptoms.

Cerebral glucose metabolism in corticobasal degeneration comparison with progressive supranuclear palsy using statistical mapping analysis

This study measured the cerebral glucose metabolism in patients suffering from corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). The aim was to determine if there is a different metabolic pattern using (18)F-labeled 2-deoxyglucose ((18)F-FDG) positron emission tomography (PET). The regional cerebral glucose metabolism was examined in 8 patients diagnosed clinically with CBD (mean age 69.6 +/- 7.8 years; male/female: 5/3), 8 patients with probable PSP (mean age 67.8 +/- 4.5 years; male/female: 4/4) and 22 healthy controls. The regional cerebral glucose metabolism between the three groups was compared using statistical parametric mapping (SPM) with a voxel-by-voxel approach (p < 0.001, 200-voxel level). Compared with the normal controls, asymmetry in the regional glucose metabolism was observed in the parietal, frontal and cingulate in the CBD patients. In the PSP patients, the glucose metabolism was lower in the orbitofrontal, middle frontal, cingulate, thalamus and mid-brain than their age matched normal controls. A comparison of the two patient groups demonstrated relative hypometabolism in the thalamus, the mid-brain in the PSP patients and the parietal lobe in CBD patients. These results suggest that when making a differential diagnosis of CBD and PSP, voxel-based analysis of the (18)F-FDG PET images using a SPM might be a useful tool in clinical examinations.

In vivo and ex vivo evidence for ketamine-induced hyperglutamatergic activity in the cerebral cortex of the rat: Potential relevance to schizophrenia.

Subanesthetic doses of ketamine, a noncompetitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in patients with schizophrenia. In the present study, in vivo 1H‐MRS and ex vivo 1H high‐resolution magic angle spinning (HR‐MAS) spectroscopy was used to examine the brain metabolism of rats treated with subanesthetic doses of ketamine (30 mg/kg) for 6 days. A single voxel localization sequence (PRESS, TR/TE = 4000/20 ms and NEX = 512) was used to acquire the spectra in a 30‐µl voxel positioned in the cerebral cortex (including mainly PFC) of the rats (ketamine group: n = 12; saline group: n = 12) anesthetized with isoflurane. After the in vivo 1H‐MRS acquisition, the animals were sacrificed and the cerebral cortex tissues were extracted (ketamine group: n = 7; saline group: n = 7) for ex vivo 1H HR‐MAS spectroscopy (CPMG sequence, 2.0‐s presaturation delay, 2.0‐s acquisition time, 128 transients and 4‐ms inter‐pulse delay) using a 500‐MHz NMR spectrometer. All proton metabolites were quantified using the LCModel. For the in vivo spectra, there was a significant increase in glutamate concentration in the cerebral cortex of the ketamine group compared with the controls (p < 0.05). For the ex vivo HR‐MAS spectra, there was a significant increase in the glutamate/total creatine ratio, and a decrease in the glutamine/total creatine and glutamine/glutamate ratios in the cerebral cortex tissue of the ketamine group compared with the controls. The results of the present study demonstrated that administration of subanesthetic doses of ketamine in the rat may exert at least part of their effect in the cerebral cortex by activation of glutamatergic neurotransmission. Copyright

Voxel based comparison of glucose metabolism in the differential diagnosis of the multiple system atrophy using statistical parametric mapping

OBJECTIVE A differential diagnosis of idiopathic parkinsonian disease (IPD) and multiple system atrophy (MSA) is difficult due to their common signs and symptoms. The aim of this 18F-2-fluoro-2 deoxyglucose (18F-FDG) positron emission tomography (PET) study was to compare the regional cerebral glucose metabolism in MSA with that in IPD by statistical parametric mapping (SPM) and image registration. METHODS The 18F-FDG PET images of MSA and IPD patients were assessed by SPM and image registration to determine metabolic patterns that may be useful in differentiating between the two groups. Eleven patients with MSA, eight patients with IPD and 22 healthy controls participated in the study. RESULTS The IPD patients were found to have a significant glucose hypometabolism in comparison with the healthy controls in the prefrontal, lateral frontal, and parietotemporal cortices, and the cingulate and caudate areas (p< or =0.01, 100 voxel-level). In patients with MSA, hypometabolism was observed in the putamen, pons, and cerebellum in comparison with the healthy controls and IPD patients. CONCLUSION The voxel-based analysis of 18F-FDG PET images showed detailed differences between IPD and MSA, which may be useful in differentiating the two disease entities, as evidenced by the correlation of glucose metabolism with disease severity and dopamine agonist medication. The mapping analysis of 18F-FDG PET images might be a useful adjunctive method of a differential diagnosis for parkinsonism in a clinical setting.

Regional metabolic alteration of Alzheimer's disease in mouse brain expressing mutant human APP-PS1 by 1H HR-MAS.

This study aimed to find the most sensitive brain region of APP-PS1 mice in early-stage Alzheimers disease (AD) and to compare the findings with wild-type mouse brain using (1)H high resolution magic angle spectroscopy (HR-MAS). At 18 and 35 weeks of age, the object recognition test was performed with both APP-PS1 and wild-type mice, and the metabolite concentrations were measured in six brain regions at 38-42 weeks using (1)H HR-MAS. Compared to that of wild-type mice, the memory index of the APP-PS1 mice at 18 weeks was not significantly different; however, the memory index of the APP-PS1 mice at 35 weeks was significantly lower. Similar to the results of the (1)H HR-MAS, the [N-acetyl aspartate (NAA)+acetate (Acet)] level in APP-PS1 mice was decreased in the hippocampus and temporal cortex, and the myo-inositol (mIns) level was increased in the entire brain. In addition, scyllo-inositol (sIns) was also elevated in the frontal, occipital, and parietal cortices, hippocampus and thalamus. These findings demonstrated that the behavioral abnormalities of the APP-PS1 mice started at about 30 weeks of age and that the hippocampus and temporal cortex were the most sensitive regions during early-stage AD. In addition, the results of this study confirmed that an increase of mIns and sIns precedes the reduction of the NAA level. These findings demonstrated that the metabolism of the APP-PS1 mouse was associated with early-stage AD. Furthermore, the regional neurochemical profile of APP-PS1 mouse can be used to investigate the pathophysiological mechanisms associated with AD.

Development of an improved canine model of percutaneous spinal cord compression injury by balloon catheter

We developed a minimally invasive canine model of spinal cord injury (SCI). A balloon catheter was inserted into the epidural space via the lumbosacral space, and inflated between L2 and L3 for 30 or 60 min under fluoroscopic guidance. Motor function after SCI was assessed using modified Tarlov scale. All seven dogs showed complete paraplegia after the procedure, neurological problems were evident and the modified Tarlov scores remained at zero after the SCI procedure; no improvement in clinical signs was observed. The dogs underwent 3T MR imaging at 3 days and 1 year after SCI. Histopathologic examinations were conducted at 2 weeks, 12 weeks and 1 year after SCI. In the present study, we described an animal model of minimally invasive spinal cord injury using a balloon catheter without laminectomy under fluoroscopic guidance. And, this percutaneous spinal cord compression injury model has many potential applications. The described percutaneous spinal cord compression injury model offers a new means of administering SCI and has many potential applications.