A new synthetic route to N-benzyl carboxamides through the reverse reaction of N-substituted formamide deformylase.

Previously, we isolated a new enzyme, N-substituted formamide deformylase, that catalyzes the hydrolysis of N-substituted formamide to the corresponding amine and formate (H. Fukatsu, Y. Hashimoto, M. Goda, H. Higashibata, and M. Kobayashi, Proc. Natl. Acad. Sci. U. S. A. 101:13726-13731, 2004, doi:10.1073/pnas.0405082101). Here, we discovered that this enzyme catalyzed the reverse reaction, synthesizing N-benzylformamide (NBFA) from benzylamine and formate. The reverse reaction proceeded only in the presence of high substrate concentrations. The effects of pH and inhibitors on the reverse reaction were almost the same as those on the forward reaction, suggesting that the forward and reverse reactions are both catalyzed at the same catalytic site. Bisubstrate kinetic analysis using formate and benzylamine and dead-end inhibition studies using a benzylamine analogue, aniline, revealed that the reverse reaction of this enzyme proceeds via an ordered two-substrate, two-product (bi-bi) mechanism in which formate binds first to the enzyme active site, followed by benzylamine binding and the subsequent release of NBFA. To our knowledge, this is the first report of the reverse reaction of an amine-forming deformylase. Surprisingly, analysis of the substrate specificity for acids demonstrated that not only formate, but also acetate and propionate (namely, acids with numbers of carbon atoms ranging from C1 to C3), were active as acid substrates for the reverse reaction. Through this reaction, N-substituted carboxamides, such as NBFA, N-benzylacetamide, and N-benzylpropionamide, were synthesized from benzylamine and the corresponding acid substrates.

Novel isonitrile hydratase involved in isonitrile metabolism.

We previously discovered N-substituted formamide deformylase (NfdA) in Arthrobacter pascens F164, which degrades N-substituted formamide (Fukatsu, H., Hashimoto, Y., Goda, M., Higashibata, H., and Kobayashi, M. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 13726-13731). In this study, we found an enzyme involved in the first step of isonitrile metabolism, isonitrile hydratase, that hydrates isonitrile to the corresponding N-substituted formamide. First, we investigated the optimum culture conditions for the production of isonitrile hydratase. The highest enzyme activity was obtained when A. pascens F164 was cultured in a nutrient medium containing N-benzylformamide. This Arthrobacter isonitrile hydratase was purified, characterized, and compared with Pseudomonas putida N19-2 isonitrile hydratase (InhA), which is the sole one reported at present. Arthrobacter isonitrile hydratase was found to have a molecular mass of about 530 kDa and to consist of 12 identical subunits. The apparent K(m) value for cyclohexyl isocyanide was 0.95 ± 0.05 mm. A. pascens F164 grew and exhibited the isonitrile hydratase and N-substituted formamide deformylase activities when cultured in a medium containing an isonitrile as the sole carbon and nitrogen sources. However, both enzyme activities were not observed on culture in a medium containing glycerol and (NH(4))(2)SO(4) as the sole carbon and nitrogen sources, respectively. These findings suggested that the Arthrobacter enzyme is an inducible enzyme, possibly involved in assimilation and/or detoxification of isonitrile. Moreover, gene cloning of the Arthrobacter enzyme revealed no sequence similarity between this enzyme and InhA. Comparison of their properties and features demonstrated that the two enzymes are biochemically, immunologically, and structurally different from each other. Thus, we discovered a new isonitrile hydratase named InhB.

Putaminal magnetic resonance imaging features at various magnetic field strengths in multiple system atrophy.

We delineated the effects of magnetic field strength on signal intensities to facilitate the specific findings of multiple system atrophy (MSA). Fifteen patients with probable MSA were imaged by 0.35T fast spin-echo (FSE), 1.5T FSE, and 3.0T FSE using a consistent protocol, testing all field strengths on the same day. Sixty patients with probable Parkinson's disease (PD) also underwent imaging. Moderate or marked hyperintensity at the dorsolateral outer putaminal margin, hyperintensity of the putaminal body, hypointensity relative to the globus pallidus at the dorsolateral putaminal margin, and infratentorial signal changes were evaluated as specific findings for MSA. As the field strength increased, the occurrence of hyperintensity both at the dorsolateral outer putaminal margin and of the putaminal body decreased, while the occurrence of hypointensity at the dorsolateral putaminal margin increased in MSA. The occurrence of uniform mild hyperintensity of the outer putaminal margin was evident in 7% at 0.35T, 40% at 1.5T, and 47% at 3.0T in MSA and in 5% at 0.35T, 60% at 1.5T, and 75% at 3.0T in PD. However, no PD patients showed hyperintensity at the dorsolateral outer putaminal margin and that of the putaminal body. Putaminal magnetic resonance imaging (MRI) findings in MSA were altered considerably by magnetic field strength. The severity and distribution of signal changes are important for assessing putaminal MRI findings in MSA.

Correlation between pyramidal tract degeneration and widespread white matter involvement in amyotrophic lateral sclerosis: a study with tractography and diffusion-tensor imaging.

Our aim was to evaluate the location and extent of white matter involvement in patients with amyotrophic lateral sclerosis (ALS) using diffusion-tensor magnetic resonance imaging (DTI). We obtained fractional anisotropy (FA) values from the internal capsule and various white matter regions of 46 patients with sporadic ALS and 19 control subjects. In ALS patients, FA values in the internal capsule, frontal white matter, genu and splenium of the corpus callosum (p<0.001), parietal and temporal lobe white matter, and posterior cingulum (p<0.05) were significantly lower than in controls. FA values in frontal white matter were lower than in parietal white matter (p<0.001). Decreased FA values in frontal, parietal, and temporal white matter, and the genu of the corpus callosum, correlated significantly with those in the internal capsule (r=0.66 and p<0.001, r=0.47 and p=0.001, r=0.33 and p=0.021, r=0.41 and p=0.005, respectively). No such correlations were found for FA values in other white matter areas or in controls. Patient FA values generally were not correlated with disease duration. DTI demonstrated more widespread involvement of the cerebral white matter in ALS patients than previously believed. The severity of involvement in the frontal, temporal and parietal white matter correlated with severity in the pyramidal tract.

Increased signal intensity of the cochlea on pre- and post-contrast enhanced 3D-FLAIR in patients with vestibular schwannoma.

INTRODUCTION: In the vestibular schwannoma patients, the pathophysiologic mechanism of inner ear involvement is still unclear. We investigated the status of the cochleae in patients with vestibular schwannoma by evaluating the signal intensity of cochlear fluid on pre- and post-contrast enhanced thin section three-dimensional fluid-attenuated inversion recovery (3D-FLAIR). METHODS: Twenty-eight patients were retrospectively analyzed. Post-contrast images were obtained in 18 patients, and 20 patients had the records of their pure-tone audiometry. Regions of interest of both cochleae (C) and of the medulla oblongata (M) were determined on 3D-FLAIR images by referring to 3D heavily T2-weighted images on a workstation. The signal intensity ratio between C and M on the 3D-FLAIR images (CM ratio) was then evaluated. In addition, correlation between the CM ratio and the hearing level was also evaluated. RESULTS: The CM ratio of the affected side was significantly higher than that of the unaffected side (rho < 0.001). In the affected side, post-contrast signal elevation was observed (rho < 0.005). In 13 patients (26 cochleae) who underwent both gadolinium injection and the pure-tone audiometry, the post-contrast CM ratio correlated with hearing level (rho < 0.05). CONCLUSION: The results of the present study suggest that alteration of cochlear fluid composition and increased permeability of the blood-labyrinthine barrier exist in the affected side in patients with vestibular schwannoma. Furthermore, although weak, positive correlation between post-contrast cochlear signal intensity on 3D-FLAIR and hearing level warrants further study to clarify the relationship between 3D-FLAIR findings and prognosis of hearing preservation surgery.

Aortic pressure augmentation as a marker of cardiovascular risk in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with increases in cardiovascular morbidity and mortality. Vascular changes in individuals with OSAS have not been fully elucidated, however. The possible impact of OSAS on the extent of aortic pressure augmentation (AG), an indicator of cardiovascular risk, was investigated. Forty-five consecutive male patients aged 35 to 78 years (56.0+/-9.6 years) who were referred to the sleep clinic of Nagoya University Hospital for screening and treatment of OSAS and 71 age-matched healthy men were enrolled in the study. AG was derived from the pressure waveform measured at the radial artery by applanation tonometry. The number of apnea and hypopnea episodes per hour (apnea-hypopnea index [AHI]) was determined by standard polysomnography. AG was significantly greater in OSAS patients than in controls (9.0+/-4.1 vs. 6.4+/-3.4 mmHg, p<0.001), and it was significantly reduced in 19 OSAS patients treated with continuous positive airway pressure. AG was also significantly correlated with the AHI (r=0.562, p<0.001) and age (r=0.356, p=0.016) but not with the serum concentrations of low and high density lipoprotein-cholesterol, triglyceride, or glycosylated hemoglobin. Stepwise multiple regression analysis revealed that the AHI was the most significant contributing factor to the increased AG in OSAS patients (beta=0.109, r=0.530, p<0.001). OSAS may thus have an adverse effect on vascular function that can be ameliorated by appropriate treatment.

Fractional anisotropy values detect pyramidal tract involvement in multiple system atrophy.

OBJECTIVE: Pathological studies have shown remarkable pyramidal tract involvement in multiple system atrophy (MSA), while clinical pyramidal signs are relatively rare. We investigated the fractional anisotropy (FA) values to assess the degree of pyramidal tract involvement in MSA, in comparison with amyotrophic lateral sclerosis (ALS) and controls. Furthermore, we compared FA values between MSA patients with or without clinical pyramidal signs and controls, and between MSA patients with or without positive conventional MRI findings and controls. METHODS: We evaluated FA values in the internal capsule, corona radiate and whole pyramidal tract using visualized tractography of 65 subjects (20 probable MSA patients, 28 age-matched ALS patients, and 17 age-matched healthy controls) using a 3.0T magnetic resonance system. RESULTS: The FA values in the internal capsule, corona radiate, and whole pyramidal tract were significantly lower in MSA patients than in controls and were at a level similar to those of ALS patients. In addition, low FA values were prominent in MSA patients, even in those with short duration of illness, lacking precentral gyrus hyperintensity in FLAIR images, and without pyramidal signs. CONCLUSION: FA values could identify pyramidal tract degeneration even in patients with early phase MSA and those without clinical pyramidal signs or abnormal MRI findings. More extensive degeneration of the pyramidal tract occurs in MSA than so far believed.

Development and evaluation of a novel lossless image compression method (AIC: artificial intelligence compression method) using neural networks as artificial intelligence.

PURPOSE: This study was aimed to validate the performance of a novel image compression method using a neural network to achieve a lossless compression. The encoding consists of the following blocks: a prediction block; a residual data calculation block; a transformation and quantization block; an organization and modification block; and an entropy encoding block. The predicted image is divided into four macro-blocks using the original image for teaching; and then redivided into sixteen sub-blocks. The predicted image is compared to the original image to create the residual image. The spatial and frequency data of the residual image are compared and transformed. MATERIALS AND METHODS: Chest radiography, computed tomography (CT), magnetic resonance imaging, positron emission tomography, radioisotope mammography, ultrasonography, and digital subtraction angiography images were compressed using the AIC lossless compression method; and the compression rates were calculated. RESULTS: The compression rates were around 15:1 for chest radiography and mammography, 12:1 for CT, and around 6:1 for other images. This method thus enables greater lossless compression than the conventional methods. CONCLUSION: This novel method should improve the efficiency of handling of the increasing volume of medical imaging data.

Imaging endolymphatic hydrops at 3 tesla using 3D-FLAIR with intratympanic Gd-DTPA administration.

PURPOSE: Visualization of endolymphatic hydrops by 3-dimensional fluid-attenuated inversion recovery-FLAIR using conventional turbo-spin-echo (3D-FLAIR-CONV) after intratympanic injection of Gd-DTPA has been reported in patients with Ménière's disease. Compared to 3D-FLAIR-CONV used in previous studies, the addition of a variable flip-angle technique (3D-FLAIR-VFL) enables very long echo trains and, therefore, shorter scan times. We evaluated whether 3D-FLAIR-VFL could replace 3D-FLAIR-CONV in detecting endolymphatic hydrops after intratympanic Gd-DTPA administration. METHODS: Eleven patients were included in this study. Twenty-four hours after Gd-DTPA injection, we performed 3D-FLAIR-CONV and 3D-FLAIR-VFL imaging at 3T. We compared the contrast-to-noise ratio (CNR) between cochlear fluid and the cerebellum between the 2 FLAIR sequences. We subjectively scored the size of the endolymphatic space in the cochlea and vestibule for each patient and correlated the scores with the clinical diagnoses. RESULTS: The CNR of 3D-FLAIR-CONV was significantly higher than that of 3D-FLAIR-VFL. Scores for the size of endolymphatic space in the vestibule were identical between the 2 sequences; however, those in the cochlea disagreed in 3 cases. 3D-FLAIR-CONV correlated better with the clinical diagnoses. CONCLUSIONS: Currently, we may not be able to replace 3D-FLAIR-CONV with 3D-FLAIR-VFL, at least not with the scanning parameters used in the present study.

Contrast-enhanced MR imaging of metastatic brain tumor at 3 tesla: utility of T(1)-weighted SPACE compared with 2D spin echo and 3D gradient echo sequence.

We evaluated the newly developed whole-brain, isotropic, 3-dimensional turbo spin-echo imaging with variable flip angle echo train (SPACE) for contrast-enhanced T(1)-weighted imaging in detecting brain metastases at 3 tesla (T). Twenty-two patients with suspected brain metastases underwent postcontrast study with SPACE, magnetization-prepared rapid gradient-echo (MP-RAGE), and 2-dimensional T(1)-weighted spin echo (2D-SE) imaging at 3T. We quantitatively compared SPACE, MP-RAGE, and 2D-SE images by using signal-to-noise ratios (SNRs) for gray matter (GM) and white matter (WM) and contrast-to-noise ratios (CNRs) for GM-to-WM, lesion-to-GM, and lesion-to-WM. Two blinded radiologists evaluated the detection of brain metastases by segment-by-segment analysis and continuously-distributed test. The CNR between GM and WM was significantly higher on MP-RAGE images than on SPACE images (P<0.01). The CNRs for lesion-to-GM and lesion-to-WM were significantly higher on SPACE images than on MP-RAGE images (P<0.01). There was no significant difference in each sequence in detection of brain metastases by segment-by-segment analysis and the continuously-distributed test. However, in some cases, the lesions were easier to detect in SPACE images than in other sequences, and also the vascular signals, which sometimes mimic lesions in MP-RAGE and 2D-SE images, were suppressed in SPACE images. In detection of brain metastases at 3T magnetic resonance (MR) imaging, SPACE imaging may provide an effective, alternative approach to MP-RAGE imaging for 3D T(1)-weighted imaging.

Usefulness of combined fractional anisotropy and apparent diffusion coefficient values for detection of involvement in multiple system atrophy.

OBJECTIVE: To determine whether apparent diffusion coefficient (ADC) values and fractional anisotropy (FA) values can detect early pathological involvement in multiple system atrophy (MSA), and be used to differentiate MSA-P (multiple system atrophy if parkinsonian features predominate) from Parkinson's disease (PD). METHODS: We compared ADC and FA values in the pons, cerebellum and putamen of 61 subjects (20 probable MSA patients, 21 age matched PD patients and 20 age matched healthy controls) using a 3.0 T magnetic resonance system. RESULTS: ADC values in the pons, cerebellum and putamen were significantly higher, and FA values lower in MSA than in PD or controls. These differences were prominent in MSA lacking dorsolateral putaminal hyperintensity (DPH) or hot cross bun (HCB) sign. In differentiating MSA-P from PD using FA and ADC values, we obtained equal sensitivity (70%) and higher specificity (100%) in the pons than in the putamen and cerebellum. In addition, all patients that had both significant low FA and high ADC values in each of these three areas were MSA-P cases, and those that had both normal FA and ADC values in the pons were all PD cases. Our diagnostic algorithm based on these results accurately diagnosed 90% of patients with MSA-P. CONCLUSION: FA and ADC values detected early pathological involvement prior to magnetic resonance signal changes in MSA. In particular, low FA values in the pons showed high specificity in discriminating MSA-P from PD. In addition, combined analysis of both FA and ADC values in all three areas was more useful than only one.

Prostate cancer detection with 3-T MRI: comparison of diffusion-weighted and T2-weighted imaging.

OBJECTIVE: To compare the clinical value of diffusion-weighted (DW) and T2-weighted (T2W) imaging in detecting prostate cancer using a 3-Tesla (3T) magnetic resonance (MR) system. MATERIALS AND METHODS: Thirty-seven patients with suspected prostate cancer underwent T2W and DW imaging at 3T using an 8-channel phased-array coil. These images and apparent diffusion coefficient (ADC) maps were read retrospectively and blindly. The results were compared with histopathologic findings, and receiver operating characteristic (ROC) analysis was used to compare the cancer detection performance of T2W and DW imaging. RESULTS: The areas under the ROC curves for DW imaging and T2W imaging were 0.89 and 0.82, respectively. The performance of DW imaging in prostate cancer detection was significantly better than that of T2W imaging (P=0.0371). CONCLUSION: With a 3T MR system, the performance of DW imaging in detecting prostate cancer was better than that of T2W imaging. DW imaging appears to be a robust and reliable method to examine the whole prostate within an acceptable scan time in clinical settings.

Measurement and evaluation of the acoustic noise of a 3 Tesla MR scanner.

We measured the sound level and frequencies of the acoustic noise generated by a 3 Tesla (T) MR scanner, and investigated the subjective sound level for 30 healthy volunteers with either earplugs, headphones or both. The sound level of 3T was found to be higher than that of 1.5T in all sequences. The peak sound pressure level of 3T ranged from 125.7 dB for MR angiography to 130.7 dB for single shot EPI on the linear scale. The equivalent noise level was from 110.0 dB for FLAIR to 115.8 dB for T1-IR on the A-weighted scale, which exceeded 99 dB, the level regulated by the International Electrotechnical Commission (IEC). The study of the subjective sound level showed that the effect of noise reduction was not significantly different between earplugs and headphones. However, the use of both devices could reduce the subjective sound level significantly better than either one alone (P < 0.01). Thus we propose wearing both devices for ear-protection during 3T examinations.

Prompt contrast enhancement of cerebrospinal fluid space in the fundus of the internal auditory canal: observations in patients with meningeal diseases on 3D-FLAIR images at 3 Tesla.

We speculated that meningeal pathologies might facilitate the permeability of cranial nerves at the fundus of the internal auditory canal (IAC), causing prompt enhancement after administration of Gd-DTPA. Using a 3D- fluid-attenuated inversion recovery (FLAIR) sequence, we evaluated the enhancement of the cerebrospinal fluid (CSF) space in the IAC fundus 10 min after Gd-DTPA administration in patients with meningeal diseases. Twenty patients (aged 22 to 79 years) were divided into 2 groups, a group with meningeal disease comprising 9 patients with meningeal abnormalities (6, tumor dissemination; 3, infection) and a control group of 11 patients with unilateral IAC pathology whose healthy sides were included as controls. Six of the 9 patients in the group with meningeal disease showed bilateral enhancement; one showed unilateral enhancement. None of the control group showed enhancement in the healthy side. One patient with Ramsay-Hunt syndrome showed only ipsilateral enhancement. Enhancement in the IAC fundus was frequently observed in patients with meningeal disease, even just 10 min after administration of contrast agent. This enhancement in the IAC fundus was never visible on T1-weighted 3D-FLASH images.

Contralateral and ipsilateral responses in primary somatosensory cortex following electrical median nerve stimulation--an fMRI study.

OBJECTIVE: Ten healthy adult subjects were examined using functional magnetic resonance imaging (fMRI) to investigate responses in the contralateral and ipsilateral primary somatosensory cortex (SI) following electrical stimulation of the median nerve. METHODS: The right and left median nerves were stimulated alternately at the wrist in the different sessions. First, the location of the response in contralateral SI was identified following median nerve stimulation, and then, a spherical search volume with a 10mm radius centered on the region of the contralateral response was determined. Whether or not fMRI activation occurred within this sphere following ipsilateral stimulation was examined using a 3T MR imager. RESULTS: A response in contralateral SI was observed in 8 of the 10 subjects in right and left hemisphere. Responses in ipsilateral SI were observed in 6 of 8 subjects in right hemisphere, and the region of the response tended to be posterior to the contralateral region. On the other hand, in left hemisphere, the ipsilateral responses were found in three. CONCLUSIONS: In the present study, not only contralateral SI but also ipsilateral SI was activated following median nerve. The location of the ipsilateral activation was significantly more posterior than the contralateral one in right hemisphere. SIGNIFICANCE: The region of activation in ipsilateral SI was located in the posterior portion of post central gyrus, corresponding to around BA2 and 5 in human.

Diffusion-weighted imaging of the liver: technical challenges and prospects for the future.

Diffusion-weighted imaging (DWI) has recently been attempted in the abdominal region. We review diffusion-weighted images of the liver, especially from the technical point of view. We discuss selection of pulse sequence parameters, effects of anti-breathing motion technique, tips for measuring apparent diffusion coefficient (ADC), and utility of superparamagnetic iron oxide (SPIO), showing clinical cases, including those at 3T. Our current trial of new pulse sequencing, such as SPIO-mediated breath-holding black-blood fluid-attenuated inversion recovery (BH-BB-FLAIR), imaging is shown. Some prospects for the future in DWI of the liver are also stated.

High-spatial-resolution MR cisternography of the cerebellopontine angle in 90 seconds with a zero-fill interpolated fast recovery 3D fast asymmetric spin-echo sequence.

BACKGROUND AND PURPOSE: Although the 12-minute 3D fast asymmetric spin-echo (FASE) protocol for imaging the inner ear has been satisfactory, reducing imaging time to minimize patient discomfort and maximize system throughput is desirable. We therefore evaluated the performance of a zero-fill interpolated (ZIP) fast recovery 3D FASE sequence in screening for cerebellopontine (CP) angle lesions in 90 seconds. METHODS: Thirty consecutive patients known or suspected to have CP angle lesions underwent MR imaging at 1.5 T with use of bilateral quadrature phased-array coils designed for examination of the CP angle. Conventional 3D FASE images (4000/240/1 [TR/TE/NEX]) were obtained in 11 minutes 48 seconds with a field of view (FOV) of 16 cm, matrix of 512 x 512 x 40, section thickness of 0.8 mm, and echo train length of 80. Then, ZIP fast recovery 3D FASE images (2000/240/1) were obtained in 90 seconds by using the same FOV. Contrast-enhanced T1-weighted 3D spoiled gradient-echo (SPGR) images were obtained as the reference standard. Three radiologists evaluated the images independently. Conventional 3D FASE and ZIP fast recovery 3D FASE images were reviewed at separate sessions. RESULTS: On 3D SPGR images, 10 tumors were detected in 10 of the 30 patients. All lesions were depicted with both 3D FASE protocols. There were no false-positive results with either 3D FASE protocol. Both protocols showed 100% sensitivity and 100% specificity for all three reviewers. CONCLUSION: High-spatial-resolution MR cisternography with the ZIP fast recovery 3D FASE protocol in 90 seconds results in a substantial reduction (by a factor of about eight) in the time required for screening for CP angle lesions compared with the previously reported conventional 3D FASE protocol, while maintaining high sensitivity and specificity.

Fast recovery 3D fast spin-echo MR imaging of the inner ear at 3 T.

High-resolution MR imaging of the inner ear with a heavily T2-weighted 3D fast spin-echo sequence has been performed successfully at 1.5 T. However, at 3 T, the longer T1 time of CSF necessitates a longer TR, resulting in significantly prolonged imaging times. In this study, the fast recovery 3D fast spin-echo sequence, which permits the TR to be reduced while maintaining T2 contrast, was optimized at 3 T for imaging of the inner ear. The optimized sequence parameters are as follows: 1500/294 (TR/TE); echo spacing, 18.1 ms; bandwidth, 38 kHz at 512 readout; and imaging time, 13 minutes.

Enlarged endolymphatic duct and sac syndrome: relationship between MR findings and genotype of mutation in Pendred syndrome gene.

Pendred syndrome (PDS) is characterized by profound deafness in childhood, positive perchlorate challenge, and goiter. PDS is often associated with enlarged endolymphatic duct and sac (EEDS), and recently, PDS gene mutations have been reported even in those patients with EEDS without classic Pendred syndrome. In a previous report, the number of mutant alleles was correlated with the degree of subclinical thyroid abnormality, but not with hearing loss, in patients with missense mutation H723R. It also has been reported that the hearing loss in EEDS was not correlated with the EEDS volume, cochlear modiolar area, or signal intensity of the endolymphatic sac. We evaluated the correlations between the number of mutant alleles and these parameters in patients with EEDS to investigate the mechanisms underlying this condition. The study group was comprised of 16 Japanese patients with EEDS diagnosed by MR imaging. The H723R mutation was homozygous in six patients and heterozygous in six patients, with no mutation found in four patients. The modiolar area, EEDS volume, and signal intensity ratio (sac signal/cerebrospinal fluid signal) were not significantly correlated with the number of mutant alleles. PDS gene mutations may not be the only cause of EEDS, and the mechanisms underlying EEDS remain unclear.

Diffusion tensor imaging in frontal lobe epilepsy.

We report a 13-year-old female with refractory frontal lobe epilepsy in whom diffusion tensor imaging was useful for exploring subtle cortical malformation. She had frequent simple partial seizures characterized by clonic movement of the right upper extremity. Conventional magnetic resonance imaging was not conclusive. A diffusion tensor imaging revealed an increased apparent diffusion coefficient and reduced anisotropy in the left frontal lobe. Positron emission tomography disclosed hypermetabolism in the adjacent area. We could identify the relatively thick cortex with an indistinct gray-white matter junction in a thin-slice T(1)-weighted image.