Cerebral white matter lesions may be partially reversible in patients with carotid artery stenosis.

Contrary to the common belief that age-related WMLs (also known as leukoaraiosis) are a progressive condition, a case of partial reversal of WMLs shortly after carotid artery stenting is described. A 75-year-old man presented with frequent TIAs, which were attributed to right ICA stenosis. He subsequently underwent successful carotid artery stenting. Follow-up MR imaging a week after the procedure showed improvement of WMLs in the right cerebral hemisphere. Pixel-by-pixel image analysis showed that the reversed WMLs tended to have higher lambda1 and lower signal intensity on b = 0 images compared with nonreversed lesions, but by only approximately 10%.

MR imaging of ventral thalamic nuclei.

BACKGROUND AND PURPOSE: The Vim and VPL are important target regions of the thalamus for DBS. Our aim was to clarify the anatomic locations of the ventral thalamic nuclei, including the Vim and VPL, on MR imaging. MATERIALS AND METHODS: Ten healthy adult volunteers underwent MR imaging by using a 1.5T whole-body scanner. The subjects included 5 men and 5 women, ranging in age from 23 to 38 years, with a mean age of 28 years. The subjects were imaged with STIR sequences (TR/TE/TI = 3200 ms/15 ms/120 ms) and DTI with a single-shot echo-planar imaging technique (TR/TE = 6000 ms/88 ms, b-value = 2000 s/mm(2)). Tractography of the CTC and spinothalamic pathway was used to identify the thalamic nuclei. Tractography of the PT was used as a reference, and the results were superimposed on the STIR image, FA map, and color-coded vector map. RESULTS: The Vim, VPL, and PT were all in close contact at the level through the ventral thalamus. The Vim was bounded laterally by the PT and medially by the IML. The VPL was bounded anteriorly by the Vim, laterally by the internal capsule, and medially by the IML. The posterior boundary of the VPL was defined by a band of low FA that divided the VPL from the pulvinar. CONCLUSIONS: The ventral thalamic nuclei can be identified on MR imaging by using reference structures such as the PT and the IML.

Incidental acute infarcts identified on diffusion-weighted images: a university hospital-based study.

BACKGROUND AND PURPOSE: Pathogenesis of leukoaraiosis is incompletely understood and accumulation of small infarctions may be one of the possible sources of such white matter lesions. Thus, the purpose of this study was to identify the rate of incident infarction as depicted on diffusion-weighted images (DWIs) obtained from a general patient population. MATERIALS AND METHODS: During the 4-year study period, a total of 60 patients (36 men and 24 women) had an incidental DWI-defined infarction without overt clinical symptoms suggestive of a stroke or a transient ischemic attack. All of the MR images were obtained by using a similar protocol on 2 identical 1.5T whole-body scanners. The patient's vascular risk factors, as well as the presence of white matter lesions (WMLs) on MR imaging and atheromatous changes on MR angiography, were assessed retrospectively. The incidental DWI-defined infarcts were also characterized in terms of their lateralization, lobe, and specific location. RESULTS: A total of 16,206 consecutive brain MR images were done during the study period; the overall incidence of incidental infarcts was 0.37%. Most of these patients with an incidental infarct had vascular risk factors and WMLs on MR images. Most of these patients (80%) had a single lesion on DWI. A total of 88 lesions were identified; most were located in the white matter of the supratentorial brain, primarily in the frontoparietal lobes. There were also lesions involving the brain stem (n = 2). The lesions involving cerebrum were more commonly located in the right side (right to left = 52:34). CONCLUSION: Small, DWI-defined acute brain infarctions can be found incidentally in an asymptomatic population; this finding may account, at least in part, for the pathogenesis of WMLs identified on MR imaging.

Multitensor tractography enables better depiction of motor pathways: initial clinical experience using diffusion-weighted MR imaging with standard b-value.

BACKGROUND AND PURPOSE: The purpose of this work was to test the feasibility of using high angular resolution diffusion imaging (HARDI)-based multitensor tractography to depict motor pathways in patients with brain tumors. MATERIALS AND METHODS: Ten patients (6 males and 4 females) with a mean age of 52 years (range, 9-77 years) were scanned using a 1.5T clinical MR unit. Single-shot echo-planar imaging was used for diffusion-weighted imaging (repetition time, 6000 ms; excitation time, 88 ms) with a diffusion-sensitizing gradient in 32 orientations and a b-value of 1000 s/mm(2). Data postprocessing was performed using both the conventional single- and multitensor methods. The depiction rate of the 5 major components of the motor pathways, that is, the lower extremity, trunk, hand, face, and tongue, was assessed. RESULTS: Motor fibers on both lesional and contralesional sides were successfully depicted by both the single-tensor and multitensor techniques. However, with the single-tensor model, the depiction of motor pathways was typically limited to the fibers of trunk areas. With the multitensor technique, at least 4 of 5 major fiber bundles arising from the primary motor cortex could be identified. CONCLUSION: HARDI-based multitensor tractography using a standard b-value (1000 s/mm(2)) can depict the fiber tracts from the face and tongue regions of the primary motor cortex.

Oxygen metabolism changes in patients with idiopathic normal pressure hydrocephalus before and after shunting operation.

OBJECTIVE: The present study revealed the changes in cerebral oxygen metabolism before and after ventriculo-peritoneal shunt (VPS) using (15)O positron emission tomography ((15)O-PET). METHODS: Eight patients with idiopathic normal pressure hydrocephalus (i-NPH) underwent VPS. A (15)O-PET study was undertaken before and approximately 3 months after VPS. In five patients, the symptoms improved based on the classification by Krauss et al. [Neurosurgery 1996;39:292] (good responders) after VPS. In three patients, the symptoms improved subjectively following VPS (poor responders). The changes in oxygen metabolism before and after VPS were analyzed. RESULTS: The postoperative regional cerebral metabolic rate of oxygen (rCMRO(2)) of the good responders increased significantly. The postoperative regional oxygen extraction fraction (rOEF) is reduced in the poor responders. CONCLUSION: The improvement of rCMRO(2) correlated with the response to VPS. Significant changes in rOEF might predict poor response to VPS.

Combined surgical and intraoperative endovascular approach for a giant internal carotid artery aneurysm in the high cervical region.

For the obliteration of a large aneurysm located at the cranial base or high cervical region, several therapeutic strategies including a parent vessel ligation, and endovascular occlusion have been reported, because it is difficult to access the aneurysm itself. We used a combined surgical and endovascular approach for the treatment of a large internal carotid artery aneurysm in the high cervical region. In the present case, we performed superficial temporal artery to middle cerebral artery bypass, then obliterated the aneurysm with distal coil embolization and proximal ligation in one session, using portable digital subtraction angiography. The combined endovascular and surgical approach involves less invasive surgery for complex cerebrovascular lesions.

A case of diastematomyelia associated with myeloschisis in a hemicord.

We report a case of myeloschisis on the right hemicord in a patient with diastematomyelia. The patient was a female neonate with myeloschisis visible at birth in the upper lumbar region. Radiological examination, including three-dimensional CT and MRI, clearly revealed a bony septum as well as the myeloschisis on the right hemicord, which enabled us to make a precise preoperative diagnosis of this complex anomaly. Closure of the myeloschisis and removal of the septum were successfully accomplished in one stage to prevent subsequent infection and neurological deterioration. The presence of combined diastematomyelia and myeloschisis is consistent with the hypothesis of an ontogenic basis of development and emphasizes the importance of early imaging for diagnosis in this complex anomaly.

Mismatch between lactate and the apparent diffusion coefficient of water in progressive focal ischemia.

In this study, we examined mismatch in the area indicated by the normal apparent diffusion coefficient (ADC) of water and increased lactate in the early stage of focal cerebral ischemia. Five rats were subjected to permanent middle cerebral artery (MCA) occlusion. Diffusion-weighted echo planar imaging (DWEPI) and proton echo planar spectroscopic imaging (EPSI) were performed from 20 to 170 min after MCA occlusion, and lactate and N-acetyl asparate images were obtained by EPSI. Postmortem histological analysis was also performed. The areas of increased lactate and normal ADC were observed in the surrounding border zone of ischemia at approximately 20 min after MCA occlusion. This initial lactate in the border zone was significantly higher than that in the normal area, but lower than that in the ischemic core, which showed a reduction of ADC. However, this area was progressively involved in the ischemic core at 170 min without any treatment. The lactate-ADC mismatch in the initial period of ischemia may offer unique diagnostic information for ischemic tissue at high risk, followed by progressive involvement in the ischemic core without treatment. Considering that the accumulation of initial lactate in this area was not excessive, our findings may suggest that the lactate-ADC mismatch in the early period of ischemia indicates potentially salvageable tissue at high risk, requiring aggressive treatment.

[Relationship of postoperative residual air and recurrence in chronic subdural hematoma].

The possibility exists that residual air after surgery is one cause of recurrence of chronic subdural hematoma. We have devised a new simple method which decreases postoperative residual air, using external drainage and an endoscope. First, we make endoscopic observations of the inner aspect of the hematoma cavity. Then, we insert external drainage apparatus into the most frontal area of the hematoma cavity, we regard this location as the most appropriate place to ensure most effective drainage. The present study included 37 chronic subdural hematomas in 32 patients who had been treated between January and December, 1999. Their ages ranged from 48 to 86 years old, with an average of 72 years. Insertion of external drainage in the most frontal area of the hematoma cavity was successfully achieved in 27 (73%, Group I) out of 37 cases and resulted in no recurrence. In the remaining 10 hematomas (27%, Group II), external drainage was not able to be inserted in the most frontal area, and four hematomas (40%) had recurrence (p < 0.01 vs Group I). Insertion in the most frontal area of the hematoma cavity decreases residual air after surgery, and may be effective for the prevention of recurrence of chronic subdural hematoma.

Haemodynamic evaluation of cerebral arteriovenous malformations by quantification of transit time using high speed digital subtraction angiography: basic considerations.

It is important to evaluate the haemodynamics of cerebral arteriovenous malformations (AVMs) in order to predict and avoid complications following surgical intervention. This study measured the transit time of each component of AVMs by high-speed digital subtraction angiography (DSA) to understand the haemodynamics and to evaluate which parameter is an appropriate indicator for the monitoring. Eleven cases of cerebral AVMs were studied. Haemodynamics were evaluated by analysis of tracer transit using DSA. Tracer transit parameters including transit time and peak time were calculated by application of gamma fitting to time density curve, and measured in the following compartments; feeding artery, nidus and draining vein. Significant correlations of tracer transit parameters were present among compartments. Although there was no significant correlation of nidus volume and tracer transit parameters, the peak time was shorter in haemorrhage cases than in non-haemorrhage cases. Measurements of tracer transit parameters by high-speed DSA may be a useful tool for characterising and monitoring the haemodynamics of AVMs following surgical intervention.

Simplification for measuring input function of FDG PET: investigation of 1-point blood sampling method.

UNLABELLED: The current method for quantitative FDG PET study requires application of multiple arterial blood sampling for measuring the input function, but the procedure is invasive and complicated. The purpose of this study was to establish a 1-point blood sampling technique that gives data comparable with the data of more elaborate serial arterial sampling. METHODS: We established a time point for 1-point arterial sampling that exhibited the highest correlation between plasma radioactivity at the time point and the real integrated value (IV) of the measured input function obtained by multiple arterial sampling in 120 patients and the smallest coefficient of variation of the real IV divided by plasma radioactivity at the time point in 120 patients. Scaling factors for estimation at each sampling point were determined, and a reference table was established to make the supposed input function. RESULTS: The optimal time for 1-point arterial sampling was 12 min after FDG injection. A good correlation was observed between the real IVs and those estimated from 1-point arterial blood sampling at 12 min using the supposed input function (n = 120; P < 0.001). The time point at which the difference between values of arterial and venous blood disappeared was 40 min after FDG injection. The percentage errors of IV estimation by 1-point sampling were 1.70% (n = 120) for arterial blood at 12 min and 3.64% (n = 10) for venous blood at 40 min. CONCLUSION: We conclude that the simplified 1-point sample method works in a manner that is comparable with serial arterial sampling and should be useful for clinical PET.

O6-(fluorobenzyl)guanine and chloroethylnitrosourea in xenografted rat brain tumor in vivo.

O6-methylguanine-DNA methyltransferase (MGMT), one of the DNA repair enzymes, potently repairs DNA damage induced by chloroethylnitrosoureas (CENUs). Depletion of MGMT activity after treatment with MGMT inhibitors increases the sensitivity of tumor cells to CENUs. We tested the effect of O6-(4-, 3- and 2-fluorobenzyl)guanines (4F, 3F and 2F, respectively), three newly synthesized MGMT inhibitors, on 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nit rosoureahydrochloride (ACNU) therapy in C6 tumor xenografts. Treatment with 4F + ACNU and 3F + ACNU significantly decreased tumor volume and extended the delay of growth in comparison to untreated mice (control group, p < 0.05). Both groups showed significantly lower proliferating indices than the control group (p < 0.05) 12 h after treatment. In contrast, 2F did not enhance the ACNU anti-tumor effect. These results indicate that O6-(4- and 3-fluorobenzyl)guanines as well as O6-benzylguanines enhance the effect of ACNU on the growth of C6 tumor xenografts in vivo.

Visualization of mRNA expression in CNS using 11C-labeled phosphorothioate oligodeoxynucleotide.

Antisense phosphorothioate oligodeoxynucleotide for mRNA of glial fibrillary acidic protein (GFAP) was labeled with the positron emitter 11C and administered i.v. to rats bearing glioma, which were expected to exhibit active expression of GFAP. Antisense oligodeoxynucleotide was retained in tumor cells, yielding clear images of tumors, while the control 20% mismatch oligodeoxynucleotide and sense-strand oligodeoxynucleotide were not retained in tumor cells. Findings revealed sequence-specific binding of the antisense oligodeoxynucleotide to the GFAP mRNA. Our methods can be used directly for non-invasive imaging of human gene expression using PET, a frequently used method of clinical examination.

Evaluation of phosphoinositide turnover on ischemic human brain with 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol using PET.

UNLABELLED: It is important to evaluate cerebral function from neural signal transduction in ischemic brain in judging morbid state and prognosis. We synthesized 1-[1-(11)C]-butyryl-2-palmitoyl-rac-glycerol (DAG) for the purpose of imaging the second messenger on PET and applied it to clinical cases of cerebral infarction. METHODS: Five patients, who had ischemic stroke, were examined with PET. [15O]-CO2 and [15O]-O2 inhalation methods were applied to cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2). For the measurement of phosphoinositide turnover after intravenous injection of DAG, dynamic PET data were collected continuously for 46 min. Arterial blood samples were taken to evaluate changes in the serum concentration of DAG. To quantify the metabolic activity of inositol phospholipid, the incorporation constant k*(DAG) was calculated on the basis of the kinetics of DAG. RESULTS: The plasma concentration of DAG increased rapidly and peaked 30 s after injection of DAG solution. In the normal cortex, DAG concentration increased gradually and reached a plateau between 15 and 20 min after injection. In the ischemic core (infarction), DAG concentration increased slowly, and its peak concentration was lower than that in normal tissue. In comparison with blood flow and metabolic parameters, k*(DAG) showed the best correlation with CMRO2, suggesting a reflection of neuronal activity. Locally, CBF and CMRO2 gradually decreased from the normal area toward the ischemic center (infarction), whereas k*(DAG) and OEF significantly decreased only in the ischemic center. CONCLUSION: The k*(DAG) of ischemic brain, including that caused by infarction, significantly correlated with CMRO2, suggesting that metabolic activity of inositol phospholipid reflects neural viability. Maintained metabolic activity of inositol phospholipid in the region around the ischemic core indicated preservation of the signal transduction system through the metabotropic receptor.

Blood flow and metabolism of oligodendrogliomas: a positron emission tomography study with kinetic analysis of 18F-fluorodeoxyglucose.

To accurately characterize the pathophysiology and proliferating activity of oligodendrogliomas, we studied cerebral blood flow and metabolism using positron emission tomography (PET) in five patients with this tumor. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and cerebral metabolic rates of oxygen (rCMRO2) and of glucose (rCMRGl) were quantitatively measured in tumor lesions and the contralateral gray matter, rCMRGl was analyzed based on both kinetic and autoradiographic methods. Tumor rCBF and rCBV were lower than in the contralateral gray matter in all preoperatively examined patients. Oxygen metabolism, determined by rCMRO2 and rOEF, was consistently reduced in the tumor (rCMRO2, P<0.05 vs. gray matter, determined by the Student's t-test). Tumor rCMRGl was significantly lower than the gray matter rCMRGl in both kinetic (P<0.01) and autoradiographic (P<0.05) analyses. Kinetic tumor rCMRGl varied between 1.22 and 4.13 mg/100 ml/min, but was lower than the gray matter value in all patients. Autoradiographic tumor rCMRGl, which ranged from 1.02 to 5.79 mg/100 ml/min, was also reduced in all tumors but one; the remaining tumor, which had a relatively high value of autoradiographic rCMRGl (comparable to gray matter rCMRGl), infiltrated the contralateral hemisphere through the corpus callosum, and was characterized by high cellular density. In one patient who suffered from tumor recurrence 8 years and 10 months after initial treatment, phosphorylation constant (K3) and kinetic rCMRGl of the recurring tumor were higher than those of the original tumor. No other tumors have regrown or recurred during the postoperative follow-up periods, which ranged from 22 to 130 months (median = 101 months). Circulation and metabolism measured by PET provide in vivo biological characteristics, including proliferating activity, in oligodendrogliomas.

Significant increase of adenovirus infectivity in glioma cell lines by extracellular domain of hCAR.

Recombinant adenoviruses are highly advantageous as vectors for transferring genes into mammalian cells, but the transfer is not efficient in all types of cells. We investigated the effects of four adenoviral receptors [integrinalphav, integrinbeta3, integrinbeta5, and human coxsackievirus and adenovirus receptor (hCAR)] on adenovirus-mediated transfer of exogenous cDNA into each of 10 glioma cell lines. Transfection efficiency varied widely from one cell line to another (0-100%) when we measured it by infection with AdLacZ, a vector designed to express beta-galactosidase. Levels of integrinalphav and integrinbeta5 expression were similar among the 10 cell lines, but expression of hCAR and integrinbeta3 varied significantly. As these observations indicated a possible correlation between expression of hCAR and the efficiency of gene transfer, we induced the hCAR gene into three glioma cell lines (T98G, U118MG, and U138MG) that expressed hCAR at very low levels and had also revealed low efficiencies of adenoviral gene transfer. In U118MG- and U138MG-derived cells that had regained the ability to express hCAR in stable fashion, adenovirus-mediated gene transfer became highly efficient. Moreover, addition of the peptide corresponding to the extracellular domain of hCAR (ECD-hCAR) by preincubation significantly increased the adenovirus infectivity to these adenovirus-tolerant cells. These results suggest that hCAR could be one of important determinants of the infectivity of adenovirus, and that the ECD-hCAR might be a novel useful tool for improvement of adenovirus-mediated gene therapy against the adenovirus-tolerant cancer cells.

p53 tumor suppressor gene in acoustic neuromas.

Alterations of the p53 tumor suppressor gene in 21 cases with acoustic neuroma were investigated by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) and single strand conformation polymorphism (PCR-SSCP). Neither mutation nor deletion was found. In 13 informative cases, no loss of heterozygosity (LOH) was confirmed. Thus our results further substantiate the scant contribution of p53 gene tumorigenesis and cell proliferation to acoustic neuromas.

Significance of hearing preservation in acoustic neuroma surgery.

In the past 10 years, 43 patients with acoustic neuroma have been operated on by the middle cranial fossa approach. In all cases, meticulous care was taken to preserve the cochlear function regardless of the degree of preoperative hearing disorder. Thirty-nine of 43 patients had various degrees of residual hearing, hearing was preserved in 16 of these (41%). The best result was obtained in patients with a tumor located less than 1 cm from the porus. The hearing preservation rate was 64% (11/17). The patients recovered hearing acuity quite well, especially at low frequencies in 2 cases who had a pure tone hearing level of more than 50 dB and less than 50% of speech discrimination. These 2 cases had a history of sudden deafness that was intractable 5 months preoperatively. Thus it is not correct to set certain criteria for hearing preservation for patients whose preoperative hearing may not be serviceable.

Therapeutic results of intra-arterial chemotherapy in patients with malignant glioma.

Thirty-three adult patients with anaplastic astrocytoma or glioblastoma multiforme, verified between 1990 and 1997, received postoperative intra-arterial ACNU chemotherapy and irradiation. Since our previous strategies to malignant gliomas had included intra-venous ACNU, the purpose of the present study is to evaluate the advantage of intra-arterial ACNU over its intra-venous counterpart as the historical control (37 patients). The median survival was 74.7 weeks for the former and 81.7 weeks for the latter. Although both groups were equivalent in survival, toxicity was less frequent in the intra-arterial group. Histopathological diagnosis, patient age and the Karnofsky's performance status related well with the survival.