N-acetylaspartate as an in vivo marker of neuronal viability in kainate-induced status epilepticus: 1H magnetic resonance spectroscopic imaging.

N-acetylaspartate (NAA) has been proposed as a marker of neuronal density. Therefore, regional measurement of NAA by magnetic resonance spectroscopic imaging (MRSI) may provide a sensitive method for detection of selective neuronal loss, in contrast to conventional imaging techniques such as magnetic resonance imaging (MRI). To test this hypothesis, we produced selective neuronal injury by kainate-induced status epilepticus. Three days later three-dimensional 1H-MRSI was obtained and compared with conventional T2-weighted MRI and histological findings in normal and kainate-treated rats. Reduction of NAA determined by MRSI in piriform cortex, amygdala, and hippocampus correlated well with neuronal injury determined from histology. Changes of NAA, without any MRI changes in hippocampus, indicated greater sensitivity of MRSI for detection of neuronal injury. These results are consistent with the hypothesis that reduction of NAA measured by MRSI may be a sensitive marker of neuronal injury in vivo in a variety of disease states.

Cerebral hemodynamics and metabolism of severe diffuse brain injury measured by PET.

Cerebral hemodynamics and metabolism in three patients with severe diffuse brain injury were measured 10 days after onset using PET. In this study, regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral blood volume (rCBV), cerebral metabolic rate for oxygen (rCMRO2), cerebral metabolic rate for glucose (rCMRglc) and cerebral metabolic ratio (rCMRO2/rCMRglc) were measured. The Glasgow Coma Scale scores on admission were 4, 5 and 5, respectively, and CT on admission showed typical findings of diffuse brain injury. As a result, PET revealed misery perfusion and hyperglycolysis in Patient 1 and matching low perfusion and low glucose metabolism in Patients 2 and 3. Although Patient 1 died, Patients 2 and 3 had good recoveries. We speculate that a long-lasting anaerobic state, indicated by a high OEF value and low metabolic ratio, is an important undesirable factor related to the outcome.

Purification and characterization of macrolide 2'-phosphotransferase type II from a strain of Escherichia coli highly resistant to macrolide antibiotics.

The resistance mechanism of Escherichia coli BM2506 to macrolides was found to be due to inactivation. Inactivated oleandomycin was identified as oleandomycin 2'-phosphate by thin-layer chromatography. A new type of macrolide-phosphorylating enzyme, macrolide 2'-phosphotransferase type II (MPH(2')II), was detected, purified 95-fold and its enzymological properties investigated. MPH(2')II was a constitutive intracellular enzyme which showed high levels of activity with both 14-member-ring and 16-member-ring macrolides. The optimum pH for the inactivation of oleandomycin was 8.2 and the optimum temperature of the reaction was 40 degrees C. Enzyme activity was lost by heat treatment at 60 degrees C for 1 min. The isoelectric point and M(r) of the enzyme were 5.3 and 48,000, respectively. Purine nucleotides, such as ITP, GTP and ATP, were effective as cofactors in the inactivation of macrolides. An inhibitory effect of iodine, EDTA, or divalent cations on MPH(2')II activity was observed.

Positron emission tomographic studies on cerebral hemodynamics in patients with cerebral contusion.

Positron emission tomography is currently one of the most useful methods for measurements of cerebral hemodynamics and oxygen metabolism, because it facilitates accurate analysis of the local cerebral circulation in three-dimensional quantitative images. In this study, we performed positron emission tomography studies to measure cerebral circulation in a total of 11 patients who sustained head injuries with contusion. Several parameters were measured including regional cerebral blood flow, regional cerebral blood volume, permeability, and regional cerebral metabolic rate for oxygen. Data from brains both with and without contusion were analyzed for chronological changes, in the subacute stage from the 8th to 29th day and in the chronic stage until 360 days after the injury and compared with similar data in a group of normal subjects. It was concluded that in the subacute stage, regional cerebral blood flow decreased (26 +/- 7 and 39 +/- 10 ml/100 g/min) and regional cerebral blood volume increased (5.6 +/- 1.8 and 5.4 +/- 0.9 ml/100 g) both in areas of cerebral contusion and in areas remote from cerebral contusion and that permeability increased in areas of contusion but not in remote brain areas. In the chronic stage, these parameters showed a tendency for recovery.

Discrimination of brain abscess from necrotic or cystic tumors by diffusion-weighted echo planar imaging.

Diagnostic difficulties in discriminating brain abscess from necrotic or cystic tumors using conventional CT and MRI have been reported. In this article, we examine the diagnostic ability of diffusion-weighted imaging to discriminate brain abscess from necrotic or cystic tumors. In previous reports, necrotic or cystic tumors show low signal intensity in diffusion-weighted imaging, indicating a high apparent diffusion coefficient (ADC). In contrast, in our study, high signal intensity was observed in the abscess fluid, associated with low ADC.

Early and delayed neuroprotective effects of FK506 on experimental focal ischemia quantitatively assessed by diffusion-weighted MRI.

The immunosuppressive drug FK506 (tacrolimus) has been reported to be a powerful neuroprotective agent in the focal ischemia of animals. However, no report has been published concerning neuroprotective effect of this compound on the morphology in superacute stage. The separate analysis between early and delayed effects of FK506 on the morphology may be helpful in the study of the compound's mechanism of action which is still unknown. The goal of this study was to determine early and delayed effects of pharmacological treatment with FK506 in permanent MCA occlusion using magnetic resonance imaging (MRI). Nineteen rats were subjected to permanent MCA occlusion, and given either intravenous injection of placebo or 1 mg/kg FK506 immediately after occlusion. DWI and T(2)-weighted MRI were performed 3 and 24 h after MCA occlusion, and postmortem histological analysis was also performed. FK506 drastically reduced the ischemic damage in 3-h apparent diffusion coefficient (ADC) map. This is the first report to demonstrate the neuroprotective effects of FK506 on focal cerebral ischemia in superacute stage. In addition, postmortem ischemic damage tended to be smaller than ischemic area indicated by 3-h ADC map in the FK506 group, whereas there was an excellent equality between them in the placebo group, suggesting the possible effect of FK506 on the later ischemic period. Our findings provide direct evidence for the neuroprotective effect of FK506 on ischemic cell damage in both early stage and possibly later stage.

Magnetic resonance imaging of brain contusion.

In this study we investigated the time course of brain contusions using magnetic resonance imaging and compared the findings with those of a computed tomography scan. The lesions, which were demonstrated as homogeneous density areas on the computed tomography scan were demonstrated as different intensity areas in the magnetic resonance image. The intensity of the images varied according to the time at which the images were obtained. The findings indicated changes in the nature of the contusions including hematoma hemoglobin, perifocal edema extension, and so on. In conclusion, magnetic resonance imaging is important in the follow-up of chronological change as well as in original diagnosis of brain contusions.

[Three-dimensional brain mapping using fMRI].

Functional mapping of the activated brain, the location and extent of the activated area were determined, during motor tasks and sensory stimulation using fMRI superimposed on 3 D anatomical MRI. Twelve volunteers were studied. The fMR images were acquired using a 2 D gradient echo echo planar imaging sequence. The 3D anatomical MR images of the whole brain were acquired using a conventional 3D gradient echo sequence. Motor tasks were sequential opposition of fingers, clenching a hand and elbow flexion. Somatosensory stimulation were administered by scrubbing the palm and sole with a washing sponge. Visual stimulation consisted of full visual field stimulation. Data were analyzed by the cross-correlation method. Transversal fMR images and anatomical images were reconstructed using both volume-, surface-rendering methods, and reconstructed for coronal and sagittal sections. Activated areas were expressed using the three primary colors. Motor tasks activated the contralateral primary motor area (M1), the primary somatosensory area (S1) and the supplementary motor area (SMA). Somatosensory tasks activated the contralateral S 1, M1 and secondary sensory area (S2). Activated areas during full visual field stimulation was observed in the bilateral occipital lobe, including both the primary cortex. Three-dimensional brain mapping allowed visualization of the anatomical location and extent of the activated brain during both motor task and sensory stimulation. Using this method we could obtain a functional map similar to the Penfield's schema.

[A case of medial medullary syndrome detected by diffusion-weighted magnetic resonance imaging].

We report an 84-year-old woman with medial medullary syndrome diagnosed by diffusion-weighted magnetic resonance imaging (MRI). She was admitted because of left hemiparesis and hypesthesia. T2-weighted and diffusion-weighted MRI showed a high signal lesion at the right medial medulla oblongata 10 days after the onset. It is well known that diffusion-weighted MRI is useful for detecting supratentrial cerebral ischemic lesions in the extremely acute stage. However, to our knowledge, there have been only a few reports of diffusion-weighted MRI in patients with ischemic stroke of the medulla oblongata. Normal nerve fibers in the direction perpendicular to the motion-probing gradient (MPG) shows a high signal by diffusion-weighted MRI (anisotropy of apparent diffusion cofficient [ADC]). Normal nerve fibers in the pyramidal tract of medulla oblongata also shows a high signal when the MPG pulse is applied in the x and y directions. We solved this problem by using isotropic diffusion-weighted imaging and were able to detect ischemic lesion of medial medullary infarction in the acute phase.

[The application of in vivo diffusion weighted magnetic resonance imaging to intracranial disorders].

We have developed a magnetic resonance (MR) spin echo method to obtain diffusion weighted imaging using motion-probing gradient (MPG) pulses in one or three orthogonal directions before and after a 180 degree pulse. Phantom models containing water and acetone, normal volunteers and patients with brain tumors, brain edema and infarction were examined. Experimental models of brain edema including triethyltin intoxication and cold injuries were also examined in Wistar rats. MRI was performed at a 1.0-T clinical machine or a 4.7-T experimental machine using spin echo pulse sequences with or without additional MPGs on one or three orthogonal axes. The one direction method was useful to define diffusion anisotropy of myelinated axonal fibers in white matter. Faster diffusion was detected in the white matter parallel to the direction of MPGs. On the other hand, slower diffusion was detected perpendicular to the direction of MPGs because the myelin sheath restricted water diffusion. The three orthogonal gradients method was useful to demonstrate the difference in the diffusion coefficients in various diseases due to its larger total gradient strength. The clear distinction between the cytotoxic edema, which revealed slower diffusion, and the vasogenic edema, which revealed faster diffusion, was demonstrated in the experimental models using diffusion weighted image. In the clinical cases, faster diffusion was demonstrated in the brain tumor and perifocal vasogenic edema, which was in agreement with the results in the experimental models of rats. Brain tumors such as low grade astrocytoma with microcysts and perifocal vasogenic edema have very wide extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

[Theory and clinical application of functional MRI: 3D-functional brain mapping].

Functional magnetic resonance imaging (fMRI) was performed using a clinical 1.5 T MR scanner. Normal volunteers and patients with several neurological disorders were studied with somatosensory stimulation using sponge at right hand and visual stimulation using checkerboard pattern. Both fMR images by gradient echo echo planar imaging and three dimensional gradient echo images were studied. Reconstructed 3 dimensional functional brain mapping was superimposed on 3D anatomical images. Apparent signal increase was observed at contra lateral sensorimotor cortex and secondary sensory cortex with sponge stimulation. In the case of left homonymous hemianopia due to cerebral infarction, increasing signal was only observed surrounding left calcarine fissure by using stimulation of all visual field. In conclusion, fMRI and 3-D functional brain mapping has extremely high potentiality to examine pathophysiology of various neurological disorders.

[Principles and clinical applications of diffusion weighted echo planar MR imaging].

The ultrafast capability of echo planar imaging(EPI) made diffusion-weighted MRI (DWI) measurements practical, without the need of head fixation and without the need to exclude patients unable to hold still. The DW hyperintensity and reduced apparent diffusion coefficient(ADC) were observed in all hyperacute strokes, initially at 2.5 hours. In contrast to decreased ADC within 10 days and DW hyperintensity within 30 days, ADC was increased without DW hyperintensity in chronic stage. This suggests that DWI can discriminate between acute and chronic strokes. Furthermore, DWEPI and T2-weighted EPI were also be useful to detect and distinguish acute hemorrhagic stroke from nonhemorrhagic stroke. This review highlighted the promising technique of DWEPI to examine stroke patients in routine clinical practice.

[Detection of pulsated blood flow by cine mode 3D angiography].

The phase contrast(PC) has an advantage to get an information about flow speed of blood along the gradient axis. The cine mode 3D-PC MRA was performed by a 1.5T clinical MR system(GE; Signa) using multi-slices gradient echo sequence with ECG gating and velocity-encoding gradient along three orthogonal axes. The cine mode 3D-PC data in three axes was constructed from 10 cardiac phases, respectively. The black and white cine mode 3D-PC MRA enabled to get an information of blood flow speed. The color MRA, in which flow direction was assigned with RGB colors, enabled to observe flow orientation of blood. Furthermore, the flow speed vector in each pixel showed a detail flow information in the intravascular space.

[Mapping of cerebral metabolism on cerebral disorders using multi-slice proton magnetic resonance spectroscopic imaging].

Multi-slice proton magnetic resonance spectroscopic imaging(MRSI) was performed using a 1.5 T clinical MR apparatus. Normal volunteer and several kinds of cerebral disorders were examined using following parameters; Tr/Te = 2.3 s/280 ms, slice thickness/gap/slices = 15/3.5 mm/4, 32 phase encoding and 24 cm FOV. Every 4 slice images of NAA, Cr, Cho and Lip/Lac were obtained in about 34 minutes. In control cases, images of Cr and Cho showed very high intensity at cerebellum comparing with cerebrum. This means high concentration or changes of relaxation times of both Cr and Cho. In cerebral infarction and brain tumor, though NAA images showed no signal intensity, Cr and Cho images showed small iso-or mild high-signal intensity areas. These findings suggest neuronal loss and gliosis or tumor growth in the lesions. In conclusion, MRSI has extremely high potential to evaluate metabolism of brain and cerebral disorders.

[Functional brain mapping in motor task and somatosensory stimulation using echo planar MRI].

Functional brain mapping was performed with a 1.5T clinical MRI apparatus. Single shot gradient echo echo-planar imaging (EPI) sequence was employed. Normal volunteers were studied with the task of grasping hand or opposition of fingers at the frequency of 3 Hz, median nerve electro-stimulation, pure somatosensory stimulation by roller for acupuncture. Apparent signal increase was observed at contralateral sensorimotor cortex with motor task. Signal changes delayed about 5 seconds compared with the start and the cessation of the task, which may suggest that regional changes of CBF and blood oxygen level in capillary and/or in venule lag behind electrical excitation. It was hard to detect the activated area with median nerve electro-stimulation. On the other hand, roller stimulation provoked distinct activated areas at contralateral sensorimotor cortex. The activated areas caused by the roller stimulation and the motor task coincided entirely, which suggests the possibility of the intermixed localization of primary areas of motor and somatosensory. It was also clearly demonstrated that the activated area was broader with quick (3 Hz) and complicated motor task (finger opposition) than with slow (1Hz) and simple motor task (hand grasping).

The investigation of experimental brain tumours using 31P-MRS and 1H-MRI.

In vivo 31P-magnetic resonance spectra (MRS) were obtained by the surface coil method from rat glioma, human glioblastoma, and human neuroblastoma inoculated subcutaneously in CD Fisher rats and hamsters, and the effects of chemotherapy, photoradiation therapy, and radiofrequency hyperthermia as well as 60Co-irradiation were evaluated by sequentially observing spectral changes. In the 31P-spectra of tumour tissue, the nucleoside triphosphate (NTP), phosphomonoesters (PME) peaks were high and the phosphocreatine peak was low compared to those of normal brain. When the antitumour agents were given and were effective, NTP peaks decreased, and inorganic phosphate increased remarkably within several hours after the treatment. 1H-magnetic resonance imaging (MRI) were also obtained in some cases. Necrotic regions was detected by the 1H-MRI as image changes which appeared later than those detected by MRS. It proved practical to monitor the effect of therapy by employing either 31P-MRS or 1H-MRI. However, the image changes which demonstrated the effect of the therapy used closely resembled those changes which occurred with the onset of necrosis in tumour tissue during tumour growth. Several problems for future application of these techniques to human brain tumours are also mentioned.

Pathophysiological investigation of experimental cerebral ischaemia using in vivo 31P-NMR spectroscopy and 1H-MRI.

The cerebral energy metabolism and brain oedema were investigated in three experimental cerebral ischaemia models using 31P-NMR spectroscopy (MRS) and 1H-NMR imaging (MRI) in the same subject animal. These measurements were performed also in experimental brain oedema models and the findings were compared with each other. 31P-MRS showed an ischaemic pattern in all of the cerebral ischaemia models, that is, ATP and PCr peaks decreased, and the Pi peak increased and shifted to a higher resonant frequency. However, 31P-MRS did not show any remarkable change in the brain oedema models. On the other hand, 1H-MRI clearly demonstrated brain oedema in the brain oedema model. In the cerebral ischaemia models, 1H-MRI findings differed depending upon the type of model, namely the most marked brain oedema was detected in the unilateral middle cerebral arterial occlusion model and no marked change was detected in the temporary four vessel occlusion model. It was thought that this difference depended on the severity of the ischaemic insult. Accordingly, the fundamental pathophysiological problem of cerebral ischaemia was the energy metabolism disturbance with the brain oedema being associated with this disturbance but occurring secondarily. However, in the brain oedema model the main pathological change was the increase in tissue water.

Purification and characterization of macrolide 2'-phosphotransferase from a strain of Escherichia coli that is highly resistant to erythromycin.

Macrolide 2'-phosphotransferase [MPH(2')] was purified 90-fold from an erythromycin-resistant strain of Escherichia coli, and its enzymatic properties were investigated. MPH(2') is an inducible intracellular enzyme which showed high levels of activity with 14-member-ring macrolides and extremely low levels with 16-member-ring macrolides. The optimum pH for inactivation of oleandomycin was 8.2, and the optimum temperature of the reaction was 40 degrees C. Enzyme activity was lost by heat treatment at 50 degrees C for 1 min. The isoelectric point and molecular weight of the enzyme were 5.3 and 34,000, respectively. Purine nucleotides, such as GTP, ITP, and ATP, were effective as cofactors in the inactivation of macrolides. Iodine, EDTA, or divalent cations inhibited MPH(2') activity.

Lactate discrimination incorporated into echo-planar spectroscopic imaging.

A technique for discriminating a lactate signal from overlapping lipid signals in (1)H spectroscopic imaging is presented. It is based on J-coupling between lactate protons and on the broad spectral bandwidth of lipid signal. Measurement parameters used in the technique are determined so that TE is separated from n/J (n: a natural number, J: J-coupling constant) enough to suppress the lipid signal at the time when the lactate signal is strongest. Data processing is used to calculate the lactate signal intensity from the reconstructed spectra. This technique enables lactate to be discriminated in a single measurement and enables spectra of other metabolites to be acquired simultaneously. However, it necessitates a homogeneous magnetic field, long TE, and supplementary lipid suppression. Discrimination of the lactate signal is demonstrated by applying lactate-discriminating echo-planar spectroscopic imaging (EPSI), which combines this discrimination technique with the standard EPSI, to rat focal cerebral ischemia models. Magn Reson Med 45:568-574, 2001.

Neurenteric cysts with meningomyelocele or meningocele. Split notochord syndrome.

Two rare cases of neurenteric cysts with meningomyelocele and meningocele were treated. The mechanism of the development of these anomalies is discussed. It is considered that the terminal, dorsal part of the enteric fistula, which is produced between the endoderm and the ectoderm through a partially duplicated notochord in the development of the embryo, remains after obliteration of the fistula and, consequently, that the mucosa of the enteric remnant is inverted and projects through the skin of the back.