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Preoperative imaging assessment influences the decision to perform mastoidectomy for the mastoid extension of middle ear cholesteatoma. This study compared the performance of temporal subtraction CT (TSCT) and non-echoplanar diffusion-weighted imaging (non-EP DWI) in evaluating such mastoid extensions.We retrospectively evaluated 239 consecutive patients with surgically proven middle ear cholesteatoma between April 2016 and April 2021. The diagnostic performance of TSCT, wherein the presence of black color indicated progressive bone erosion, and non-EP DWI, wherein high signal intensity in the mastoid region suggested mastoid extension, was compared using Fisher's exact test.In 34 patients with evaluable TSCT images, black color was significantly more common in patients with mastoid extension than in those without; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of TSCT were 1.00, 0.95, 0.94, 1.00, and 0.97, respectively. In 90 patients with evaluable non-EP DWI, high signal intensity was significantly more common in patients with mastoid extension than in those without; the sensitivity, specificity, PPV, NPV, and accuracy of non-EP DWI were 0.88, 0.85, 0.91, 0.81, and 0.87, respectively. In 16 patients with both evaluable TSCT and non-EP DWI, the diagnostic performance of the TSCT was slightly superior to that of the non-EP DWI for predicting mastoid extension, although the difference was not significant.TSCT images generated using consecutively acquired preoperative high-resolution CT images are useful for predicting mastoid extension of middle ear cholesteatoma, and the diagnostic performance of TSCT is non-inferior to that of non-EP DWI.

The aim of the study was to evaluate the cross-sectional area of the cauda equina in amyotrophic lateral sclerosis (ALS) on routine lumbar magnetic resonance imaging and investigate the diagnostic accuracy in comparison with age- and sex-matched non-ALS controls.This retrospective study included 15 ALS patients and 15 age- and sex-matched non-ALS controls. Two independent neuroradiologists measured and compared the total cross-sectional area of the cauda equina of ALS patients and the non-ALS controls at the level of the L3 and L4 using axial T2-weighted images. The cutoff value, sensitivity, specificity, and area under the curve were measured. The interobserver reproducibility of the 2 independently obtained measurements was evaluated.The total cross-sectional area of the cauda equina in the ALS group was significantly smaller than that in the non-ALS group (L3: median, 66.73 vs 90.19 mm 2 , P0.001; L4: median, 52.9 vs 67.63 mm 2 , P0.001). The cutoff values at L3 and L4 were 76.95 and 61.04 mm 2 with a sensitivity and specificity of 1 and 0.87 and 0.8 and 0.87, respectively. The area under the curve at L3 and L4 were high at 0.96 and 0.94, respectively. The interobserver reproducibility was 0.88 at L3 and 0.89 at L4.The ALS patients showed significant atrophy of the cauda equina compared with non-ALS patients.

This study investigated the utility of temporal subtraction computed tomography (TSCT) obtained with temporal bone high-resolution computed tomography (HRCT) for the preoperative prediction of mastoid extension of middle ear cholesteatomas.Twenty-eight consecutive patients with surgically proven middle ear cholesteatomas were retrospectively evaluated. The presence of black color in the mastoid region on TSCT suggested progressive changes caused by bone erosion. Enlarged width of the anterior part of mastoid on HRCT was interpreted as suggestive of mastoid extension. Fisher's exact test was used to compare the widths and black color on TSCT for cases with and without mastoid extension. The diagnostic accuracy of TSCT and HRCT for detecting mastoid extension and interobserver agreement during the evaluation of black color on TSCT were calculated.There were 15 cases of surgically proven mastoid extension and 13 cases without mastoid extension. Patients with black color on TSCT were significantly more likely to have a mastoid extension (p0.001). The sensitivity and specificity of TSCT were 0.93 and 1.00, respectively. Patients in whom the width of the anterior part of the mastoid was enlarged were significantly more likely to have a mastoid extension (p = 0.007). The sensitivity and specificity of HRCT to detect the width of the anterior part of the mastoid were 0.80 and 0.77, respectively. Interobserver agreement during the evaluation of TSCT findings was good (k = 0.71).This novel TSCT technique and preoperative evaluations are useful for assessing mastoid extension of middle ear cholesteatomas and making treatment decisions.•TSCT shows a clear black color in the mastoid region when the middle ear cholesteatoma is accompanied by mastoid extension. •TSCT obtained with preoperative serial HRCT of the temporal bone is useful for assessing mastoid extension of middle ear cholesteatomas.

Purpose The purpose of this study was to investigate the usefulness of temporal subtraction CT (TSCT) of temporal bone CT for the detection of postoperative recurrent/residual cholesteatoma of the middle ear. Methods Thirty-two consecutive patients with surgically proven postoperative recurrent/residual cholesteatoma and 14 consecutive patients without recurrent/residual lesion matched the selection criteria and were retrospectively evaluated. TSCT imaging was generated with the use of serial postoperative CT. Two experienced radiologists and two residents evaluated the presence of bone erosive change by comparison serial CT studies, and CT and TSCT. The detection rate of bone erosive change, sensitivity and specificity of the recurrence/residual lesions, and reading time for each reader were evaluated. Results TSCT + CT significantly improved the detection of bone erosive changes compared to CT-only evaluation (17.4–41.3% vs. 37.0–58.7%, p = 0.008–0.046). The mean sensitivity and specificity of TSCT + CT for experienced radiologists were 0.77 and 1.00, and 0.52 and 0.97 without TSCT. The mean sensitivity and specificity of TSCT + CT for residents were 0.64 and 1.00, and 0.41 and 1.00 without TSCT. Sensitivity showed an increase in all readers. The use of TSCT significantly reduced the reading time per case in all readers (p Conclusion TSCT improves the depiction of newly occurring progressive bone erosive changes, and detection sensitivity and reading time in postoperative recurrence/residual cholesteatoma of middle ear.

Objectives We aimed to clarify the usefulness of high-resolution computed tomography (HRCT) and establish HRCT criteria for presurgical assessment of the mastoid extension in pars flaccida cholesteatomas of the middle ear. Methods Retrospective observational study. Patients who underwent primary surgery for pars flaccida cholesteatoma and those who underwent temporal bone HRCT for pretreatment evaluation were reviewed. The distance in the anterior-most portion of the mastoid sinus on HRCT was measured, and the presence of surgically verified mastoid extension of cholesteatoma was evaluated. All cases were subclassified as M+ (surgically mastoid extension-positive) or M- (surgically mastoid extension-negative). Results A total of 107 patients with pars flaccida cholesteatoma were included. The distance in the M+ cases was significantly longer than that in the M- cases, and the cutoff value was 3.6 mm. The difference between the ipsilateral/diseased-side distance and the contralateral/evaluable side (difference value) in M+ cases was larger than that in M- cases, with a cutoff value of 0.6 mm. The inter-rater reliability of this distance measurement was excellent, regardless of imaging experience. Conclusions The cutoff values of the distance and the difference value can be used for pretreatment HRCT evaluation of mastoid extension in middle ear cholesteatoma with relatively high accuracy, regardless of the experience and skill levels of the evaluator.

Purpose We aimed to use magnetic resonance imaging (MRI) to determine the relationship between the pathological depth of invasion (DOI), undetectability, and tumor thickness of squamous cell carcinoma of the floor of the mouth. Materials and methods We retrospectively evaluated the relationship between pathological DOI and MRI detectability, as well as the relationship between pathological DOI and tumor thickness on coronal fat-suppressed contrast-enhanced T1-weighted imaging or coronal T2-weighted imaging. Results We analyzed 30 patients with squamous cell carcinoma of the floor of the mouth; MRI revealed that the pathological DOI of the 11 undetectable lesions (median 2 mm) was smaller than that of the 19 detectable lesions (median 14 mm) (p Conclusions Undetectability on MRI indicates superficial lesions with a pathological DOI value that is less than 3 mm. In detectable lesions, tumor thickness on coronal fat-suppressed contrast-enhanced T1-weighted imaging is associated with pathological DOI.

The objective of this study was to determine correlations between magnetic resonance imaging (MRI) features including radiologic depth of invasion (r-DOI) and pathologic DOI (p-DOI) of squamous cell carcinoma of the buccal mucosa.In total, 31 lesions were retrospectively evaluated. MRI findings included detectability, buccinator muscle invasion (positive: BMI+, negative: BMI-), buccal fat pad invasion (positive: BFPI+, negative: BFPI-), and r-DOI measured on T2-weighted images (T2-DOI) and contrast-enhanced T1-weighted images (CET1-DOI). These findings were compared to the p-DOI of the tumors.The p-DOI values of undetectable lesions were smaller than those of detectable lesions (P.001), and the cutoff value was 1 mm. BMI+ and BFPI+ lesions had significantly larger p-DOI values than the corresponding BMI- and BFPI- lesions (P.001), with cutoff values of 5 and 6 mm, respectively. The correlation coefficient between CET1-DOI and p-DOI was 0.68 (P.001). CET1-DOI values were larger than p-DOI (P.001) and the average difference between them was 3.4 mm. T2-DOI was inconclusive in 50% of cases. Interobserver agreements of MRI evaluation were good to very good.MRI-derived parameters were useful in estimating p-DOI and may be helpful in predicting the depth of invasion of tumors and the risk of lymph node metastasis.

Objectives In daily clinical practice, the assessment of the thickness of the cauda equina on lumbar spine magnetic resonance imaging is an important parameter. However, its relevance to the size of the dural sac in non-pathological conditions is unknown. To examine the relationship between the size of the dural sac and the apparent thickness of the cauda equina nerve root using lumbar spine magnetic resonance imaging in non-pathological conditions. Methods We retrospectively measured the dural sac diameter and vertebral body diameter, counted the apparent number, and calculated total cross-sectional area of the cauda equina, dural sac ratio and the area of one apparent nerve root of cauda equina in 100 cases. Spearman's rank correlation coefficient ( ρ) was used. Results Dural sac ratio and diameter were positively correlated with the area of one apparent nerve root ( ρ=0.77, PConclusions A larger dural sac ratio and diameter was associated with an apparently thicker cauda equina and lower visible number. In a larger dural sac, the physiologically clumped and apparently thicker cauda equina should not be misdiagnosed as pathological.

We aimed to evaluate pre-treatment MRI predictors of high-grade malignant parotid gland cancer by comparing MRI findings and texture parameters between high-grade and intermediate/low-grade parotid gland cancers. Patients underwent a pre-treatment MRI and had a parotid gland cancer resection with pathological evaluation. Evaluation objectives included attributive factors such as age and gender, several MRI findings of T1- and T2-weighted images, post-contrast fat suppression T1-weighted images, ADC value and 40 texture parameters calculated from T2-weighted axial images. Such objects were compared between high-grade and intermediate/low-grade lesions. Of the parotid gland cancers surveyed, 39 were included for analysis. Of these, 18 were high-grade lesions, 2 were intermediate-grade lesions, and 19 were low-grade lesions. The high-grade group was significantly older than the low- and intermediate-grade groups (p = 0.01). There were more males in the high-grade group than in the low- and intermediate-grade groups (p = 0.01). There were also significantly more MRI findings of neck lymph node metastases in the high-grade group than in the low- and intermediate-grade groups (p

Introduction and Objectives: The clinical characteristics of convexity subarachnoid hemorrhage (cSAH) accompanying hyperacute ischemic stroke are unknown. We aimed to investigate the incidence and clinical characteristics of cSAH with hyperacute ischemic stroke. Methods: Participants comprised symptomatic ischemic stroke patients with ≤4.5 h from onset to door who also underwent initial MRI ≤4.5 h from onset. We reviewed initial and follow-up MRI during admission to identify cSAH. Retrospective reviews of cSAH incidence and clinical characteristics were performed. Results: We screened 1,249 consecutive symptomatic ischemic stroke patients, including 384 patients (279 males [73%]; median age, 67 years). Of the 384 patients, arterial ischemic stroke was seen in 382 patients, and venous ischemic stroke in 2 patients. Of the hyperacute arterial ischemic stroke, cSAH was identified within 4.5 h of ischemic stroke onset in 2 patients (0.5%) and around 6 days from ischemic stroke onset in 2 patients (0.5%). Of the hyperacute venous ischemic stroke, cSAH was observed in 1 patient on initial MRI. Comparing the clinical characteristics of hyperacute arterial ischemic stroke with and without cSAH, patients with cSAH were more likely to have arterial stenosis or occlusion ipsilateral to the cSAH (100 vs. 47%, p = 0.048), and the ischemic lesion only in the right hemisphere (100 vs. 33%, p = 0.013). In all cases, outcomes were favorable (modified Rankin Scale 0–1 at 3 months from onset). Conclusions: Convexity SAH was observed in 0.5% of hyperacute ischemic patients within 4.5 h of ischemic stroke onset and in 0.5% around 6 days from ischemic stroke onset.

To comprehensively summarize the characteristic radiological findings of laryngeal sarcoidosis.We reviewed patients with laryngeal sarcoidosis who underwent computed tomography (CT) and/or magnetic resonance imaging (MRI) and included 8 cases from 8 publications that were found through a systematic review and 6 cases from our institutions. Two board-certified radiologists reviewed and evaluated the radiological images.Almost all cases exhibited supraglottic lesions 13/14 (92.9%) and most of them involved aryepiglottic folds (12/13, 92.3%), epiglottis (11/14, 78.6%), and arytenoid region (10/14, 71.4%). Most lesions were bilateral (12/14, 85.7%). All cases showed well-defined margins and a diffuse swelling appearance (14/14, 100%). Non-contrast CT revealed a low density (4/5, 80%). The contrast-enhanced CT showed a slight patchy enhancement predominantly at the margin of the lesion in most cases (12/13, 92.3%). In one case, T2-weighted images showed high signal intensity peripherally and low signal intensity centrally (1/1, 100%). Gadolinium-enhanced MRI showed moderate heterogeneous enhancement predominantly at the margin of the lesion (2/2, 100%). In one case, diffusion-weighted imaging showed intermediate signal intensity; the apparent diffusion coefficient value was 2.4 × 10We summarized the CT and MRI findings of patients with laryngeal sarcoidosis. Knowledge of these characteristics is expected to facilitate prompt diagnosis and appropriate management.

Objective Meningioma-related skull magnetic resonance imaging findings other than hyperostosis are not widely recognized. We evaluated the novel findings of the skull adjacent to meningiomas. Methods Records from patients with meningiomas located adjacent to the skull on magnetic resonance imaging (n = 32) were included. Three skull findings (intramedullary prominent vessel, intramedullary enhancement, intramedullary T2-hyperintensity) and the widely known hyperostosis were retrospectively visually assessed. The frequency of these 3 findings and the relevance to each other, and their relationships with hyperostosis, size, length adjacent to the skull, and relative signal intensity of the meningioma were examined. Results The incidence of the three findings was 46.88%, 53.13%, and 62.5%, respectively, and that of hyperostosis was 46.88%. Each association involving the findings was strong, and they were significantly related to the size and length. Conclusions Intramedullary prominent vessel, intramedullary enhancement, and intramedullary T2-hyperintensity may be novel characteristic skull findings associated with meningioma.

Objectives A broad mastoid extension limits cholesteatoma resection via a transmeatal approach including endoscopic ear surgery. Therefore, a preoperative diagnosis of mastoid extension is a the most critical factor to determine whether to perform mastoidectomy. The purpose of this study was to assess the efficacy of non-echoplanar diffusion-weighted imaging (non-EPI DWI) and T1-weighted imaging in the evaluation of mastoid extension in cholesteatomas of the middle ear. Methods Patients who underwent magnetic resonance imaging (MRI) for pretreatment evaluation before primary surgery for pars flaccida or tensa cholesteatoma, which revealed a high-signal intensity in the mastoid on T2-weighed imaging were retrospectively evaluated. Two board-certified radiologists retrospectively evaluated the extent of cholesteatomas on MRI with non-EPI DWI, non-EPI DWI- and T1-weighted axial imaging. The presence of a high signal intensity on non-EPI DWI or low or high signal intensity on T1-weighted imaging in the mastoid was evaluated. All cases were subclassified as M+ (surgically mastoid extension-positive) or M- (surgically mastoid extension-negative). Results A total of 59 patients with middle ear cholesteatoma were evaluated. There were 37 M+ cases and 22 M- cases. High-signal intensity on non-EPI DWI exhibited a sensitivity of 0.89 and specificity of 0.82, whereas partial low-signal intensity on T1-weighted imaging exhibited a sensitivity of 0.84 and specificity of 0.91 for detecting mastoid involvement. Complete high-signal intensity on T1-weighted imaging exhibited a sensitivity of 0.73 and specificity of 0.89 for detecting non-involvement of the mastoid. The sensitivity (0.92) and specificity (0.96) of combined non-EPI DWI and T1-weighted imaging evaluation were higher than those of with non-EPI DWI or T1-weighted imaging alone. The interobserver agreement for the presence of high-signal intensity in the mastoid cavity on non-EPI DWI was very good at 0.82, that of a partial low-signal intensity area in the mastoid cavity lesions on T1-weighted imaging was good, at 0.76 and that of complete high-signal intensity in the mastoid cavity lesions on T1-weighted imaging was good, at 0.67. Conclusions The signal intensity on non-EPI DWI and T1-weighted imaging of the mastoid could be used to accurately assess the extent of middle ear cholesteatoma, which could facilitate surgical treatment planning.

Various studies using advanced techniques have estimated the isocitrate dehydrogenase (IDH) gene mutation status in glioblastoma (GBM) from preoperative images. However, it is important to be able to predict mutation status using conventional MRI, which is more widely used in clinical practice. In this study, we examined the features of GBM with and without IDH gene mutation on conventional MRI. Twenty-three patients with GBM in whom IDH gene mutation status had been pathologically and molecularly confirmed in tumor specimens were included. The cases were divided into an IDH-wildtype group (n = 17) and an IDH-mutant group (n = 6). We retrospectively compared the following imaging parameters between the two groups: tumor location (superficial or deep), borders on T2-weighted images (regular or irregular), borders of enhancing lesions (regular or irregular), number of lesions showing contrast enhancement (solitary or multiple), presence or absence of intralesional bleeding, and presence or absence of a low-grade glioma in the background around the enhancing lesion. IDH-wildtype tumors were significantly more likely to be superficial than were IDH-mutant tumors (p 0.05). Enhancing lesions in the IDH-wildtype group were less likely to have an irregular border (p = 0.059). Low-grade glioma was a background lesion in 5 patients (83.3%) in the IDH-mutant group and 9 (52.9%) in the IDH-wildtype group. The IDH mutation status is likely to be wildtype in patients with superficial GBM in which the enhancing lesion has a regular border and when low-grade glioma is not found as a background lesion on MRI.

The safety and efficacy ofThe favorable safety profile and initial antitumor activity observed for

The purpose of this study was to present the novel MRI findings of palatine gland lesion-associated IgG4-related disease (PGL-IgG4-RD) and to compare the imaging features with those in normal individuals. We retrospectively evaluated the MRI scans of 12 patients with PGL-IgG4-RD and 12 control individuals. We measured the thickness of the palatal regions and calculated the T2-weighted signal intensity ratio of palatal regions to cerebral white matter (HWR) and compared them between the PGL-IgG4-RD and control groups. In univariate analysis, the HWR of the palatal regions on T2-weighted imaging was smaller in the PGL-IgG4-RD group than in the control group (average = 1.2 vs. 1.9, p

ObjectiveTo define the characteristic findings on MRI of skeletal muscles in patients with dermatomyositis (DM) relative to those in patients with other idiopathic inflammatory myopathies (IIMs) and to assess their diagnostic performance in DM.MethodsThirty-six patients with DM, 17 patients with amyopathic DM, 19 patients with polymyositis and 16 patients with non-IIM classified by the 2017 European League Against Rheumatism/American College of Rheumatology criteria were included in this study. The following MRI findings (short-tau inversion recovery [STIR] and gadolinium-enhanced fat-suppressed T1-weighted imaging [Gd-T1WI]) for proximal limb muscles were compared between the disease groups and between myositis-specific autoantibodies/myositis-associated autoantibodies (MSAs/MAAs)-positive and MSAs/MAAs-negative groups: structures with high signal intensity (HSI) (subcutaneous, fascia, muscle); distributions of HSI areas in muscle (diffuse, patchy, peripheral) and patterns of HSI in muscle (honeycomb, foggy, strong HSI). Univariate, multivariate and receiver-operating characteristic [ROC] analyses were performed to assess the diagnostic performance of MRI in DM.ResultsThe characteristic MRI findings in patients with DM were subcutaneous HSI, fascial HSI, peripheral distribution and honeycomb pattern. The MRI findings in the MSAs/MAAs-positive group included more frequent fascial HSI but less frequent foggy pattern compared with the MSAs/MAAs-negative group. Likelihood of DM score ≥ 3 (obtained by counting the number of characteristic MRI findings in patients with DM) showed good diagnostic performance in DM (STIR: sensitivity 72.2%, specificity 88.5%, area under ROC curve [AUC] 84.9%; Gd-T1WI: sensitivity 81.2%, specificity 91.5%, AUC 89.9%).ConclusionThe characteristic MRI findings of skeletal muscles can predict patients with DM as well as patients with MSAs/MAAs.

Recent advances in genomic technology and genome-wide analysis have identified key molecular alterations that are relevant to the diagnosis and prognosis of brain tumors. Molecular information such as mutations in isocitrate dehydrogenase (IDH) genes or 1p/19q co-deletion status will be more actively incorporated into the histological classification of diffuse gliomas. BRAF V600E mutations are found frequently in circumscribed low-grade gliomas such as pleomorphic xanthoastrocytoma (PXA) and extra-cerebellar pilocytic astrocytoma, or epithelioid glioblastomas (E-GBM), a rare variant of GBM. This mutation is relatively rare in other types of diffuse gliomas, especially in adult onset cases. Here, we present an adult onset case of IDH wild-type/BRAF V600E-mutated diffuse glioma, evolving from grade III to grade IV. The tumor displayed atypical exophytic growth and had unusual histological features not fully compatible with, but indicative of PXA and E-GBM. We discuss differential diagnosis of the tumor, and review previously described diffuse gliomas with the BRAF V600E mutation.

Objective The purpose of this study is to evaluate whether laterality of the superficial cerebral veins can be seen on susceptibility-weighted imaging (SWI) in patients with no intracranial lesions that affect venous visualization. Methods We retrospectively evaluated 386 patients who underwent brain magnetic resonance imaging including SWI in our institute. Patients with a lesion with the potential to affect venous visualization on SWI were excluded. Two neuroradiologists visually evaluated the findings and scored the visualization of the superficial cerebral veins. Results Of the 386 patients, 315 (81.6%) showed no obvious laterality on venous visualization, 64 (16.6%) showed left-side dominant laterality, and 7 (1.8%) showed right-side dominant laterality. Conclusions Left-side dominant physiological laterality exists in the visualization of the superficial cerebral veins on SWI. Therefore, when recognizing left-side dominant laterality of the superficial cerebral veins on SWI, the radiologist must also consider the possibility of physiological laterality.

Background/Aims: The factors related to cerebrovascular complications in cerebral venous sinus thrombosis (CVST) are controversial. We focused on venous stasis and investigated its relationship with cerebrovascular complications in CVST. Methods: CVST patients between June 2013 and October 2016 were enrolled. Relationships between cerebrovascular complications, defined as cerebral venous infarction, intracerebral hemorrhage, or subarachnoid hemorrhage, and cerebrum venous stasis and other clinical information were retrospectively analyzed. Venous stasis was evaluated by the prominence of the veins on susceptibility-weighted imaging (SWI). The cerebrum was divided into 10 regions according to the venous drainage territories, and venous stasis was quantified by adding one point for venous prominence on SWI for each region (CVST SWI score). Results: All 5 cases in the noncomplicated group had a CVST SWI score of 0. The 3 patients with CVST SWI scores higher than 0 had cerebrovascular complications. The CVST SWI scores were higher in the complicated group than in the noncomplicated group (3.0 vs. 0, p = 0.010). Seizures were seen in all patients with complications and in none of the patients without complications (3 vs. 0, p = 0.018). Conclusion: Venous stasis evaluated by SWI can help predict cerebrovascular complications in CVST. A seizure is an important initial symptom that suggests cerebrovascular complications in CVST.

Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention for Alzheimer's disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 ((123/125)I-DRM106 [6-iodo-2-[4-(1H-3-pyrazolyl)phenyl]imidazo[1,2-a]pyridine]), a compound with sufficient affinity for the synthesis of human Aβ fibrils and satisfactory metabolic stability, as a SPECT ligand in living brains.The sensitivity of (125)I-DRM106 for detecting Aβ deposition was compared with that of (125)I-IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-mo-old amyloid precursor protein transgenic mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of Aβ plaques with (123)I-DRM106 and a well-known amyloid PET agent, (11)C-labeled Pittsburgh compound B ((11)C-PiB), in 29-mo-old transgenic mice and age-matched nontransgenic littermates. Additionally, we compared the binding characteristics of (125)I-DRM106 with those of (11)C-PiB and (11)C-PBB3, which selectively bind to Aβ plaques and preferentially to tau aggregates, respectively, in postmortem AD brain sections.Ex vivo autoradiographic analysis showed that measurement with (125)I-DRM106 has a higher sensitivity for detecting Aβ accumulation than with (125)I-IMPY in transgenic mice. SPECT imaging with (123)I-DRM106 also successfully detected Aβ deposition in living aged transgenic mice and showed strong correlation (R = 0.95, P0.01) in quantitative analysis for Aβ plaque detection by PET imaging with (11)C-PiB, implying that sensitivity and quantitation of SPECT imaging with (123)I-DRM106 are almost as good as (11)C-PiB PET for the detectability of Aβ deposition. Further, the addition of nonradiolabeled DRM106 fully blocked the binding of (125)I-DRM106 and (11)C-PiB, but not (11)C-PBB3, to AD brain sections, and (125)I-DRM106 showed a lower binding ratio of the diffuse plaque-rich lateral temporal cortex to the dense-cored/neuritic plaque-rich hippocampal CA1 area, compared with (11)C-PiB.All of these data demonstrated the high potential of (123)I-DRM106 for amyloid imaging in preclinical and clinical application, and it might more preferentially detect dense-cored/neuritic amyloid deposition, which is expected to be closely associated with neuropathologic changes of AD.

A 76-year-old woman was admitted to our hospital because of convulsions that developed after a 1-month history of progressive right-leg palsy. MRI showed thickening of the meninges with gadolinium enhancement in the left parietal lobe and it revealed pia-subarachnoid space pattern. A lumbar puncture was performed, and cerebrospinal fluid analysis revealed no abnormality. Her serum adenosine deaminase level was elevated (28.7 IU/l). The results of serum cultures were normal. To differentially diagnose collagen disease, infection, malignancy, and inflammation of uncommon causes, we conducted brain and meningeal biopsies on the 15th hospital day. Histopathological examination of the brain tissue showed mainly necrosis and inflammation. There was severe pachymeningeal thickening without necrosis. Although it was difficult to reach a definitive diagnosis, a tissue sample taken from under the leptomeninges tested positive for mycobacterium on Ziehl-Neelsen staining. The results of polymerase chain reaction for mycobacterium were negative in the meningeal tissue. The patient received anti-tuberculous drugs, anti-nontuberculous mycobacteriosis drugs, and corticosteroids to treat Mycobacterium tuberculosis and nontuberculous mycobacterium. After starting treatment, the findings on magnetic resonance imaging improved dramatically, and no convulsions occurred during hospitalization. She was discharged on the 153rd hospital day without any neurological deficit. Because previous studies have reported that isolated mycobacterium meningitis is a diagnostically challenging condition, brain and meningeal biopsies should be considered in patients with gadolinium enhancement in the meninges.

Stent-assisted coil embolization has enabled the endovascular treatment of wide-necked cerebral aneurysms. Moreover, recent reports demonstrated that stent-assisted coil embolization was associated with a significant decrease in angiographic recurrences of coiled cerebral aneurysms. One of the possible explanations for this adjunctive effect of stent-assisted coil embolization is changes in the local hemodynamics caused by placing intracranial stents. This study investigated the hemodynamic effect of intracranial stents using computational fluid dynamics (CFD) analysis. The geometry of the intracranial stent, Enterprise(TM) VRD, was acquired by using micro computed tomography and virtually placed across the aneurysm orifice of a saccular aneurysm model (saccular model) and a blister-like aneurysm model (blister-like model) constructed from patient-specific three-dimensional (3D) rotational angiography data. Transient CFD analysis was performed with these models with and without stents. Stent placement induced no significant changes in the 3D streamline in the saccular model and slight changes in the blister-like model. Both saccular and blister-like models with stents had lower wall shear stress (WSS) and flow velocity, and higher oscillatory shear index, WSS gradient, and relative residence time than the equivalent models without stents, indicating the possibility that stent placement induced stagnant and disturbed blood flow. Cross-sectional vector velocity around the stent strut revealed complex blood flow patterns with variable direction and velocity. Although this study was a simulation under limited conditions, similar hemodynamic changes might be induced in the neck remnants treated with stent-assisted coil embolization.

Slow-flow phenomenon is frequently observed during carotid artery stenting (CAS) with a filter embolic protection device. It results in technical difficulties and can lead to adverse neurological events. Flow impairment is thought to be caused by plaque entrapped by the filter and/or blood coagulation on the filter. Characteristics of heparin- or urokinase-treated polyurethanes were analyzed by surface plasmon resonance, and the fibrinolytic activity of the urokinase-treated filter of Angioguard XP was estimated by the fibrin plate assay. A filter membrane of Angioguard XP protection device was treated with a heparin or urokinase solution. In clinical studies, six and nine patients were treated by CAS using Angioguard XP modified with heparin and urokinase, respectively. Filter membranes were examined by scanning electron microscopy (SEM). From in vitro studies, it appeared that urokinase adsorbed and remained on the Angioguard XP filter, and its fibrinolytic activity was demonstrated even after washing with saline; heparin, however, was easily washed out from the surface. From clinical study, some filter pores were obstructed in all six patients in the heparin group and in three patients in the urokinase group. Fibrin net was found on the filter in five of six patients in the heparin group and in one of nine patients in the urokinase group. Treatment of an Angioguard XP filter with a urokinase solution is effective in preventing pore occlusion and may reduce occurrence of the slow-flow phenomenon.

Carotid angioplasty and stenting is used for treatment of carotid stenosis. Stent deployment may induce HDI and thereby cause systemic or neurologic deficits. This study defines characteristics and predictors of HDI with CAS.A total of 132 patients who had undergone CAS were evaluated for periprocedural and postprocedural HDI (hypertension, systolic blood pressure160 mm Hg; hypotension, systolic blood pressure90 mm Hg; or bradycardia, heart rate60 beats per minute).Frequencies of HDI were 6.8% for hypertension, 32.6% for hypotension, and 15.9% for bradycardia. In addition, CAS of the right side (P.01), carotid bulb lesions (P.05), eccentric posterior carotid plaque (P.0001), and general anesthesia (P.05) were associated significantly with postprocedural HDI. Male sex (OR, 3.4; 95% CI, 1.8-67.2; P.001), age of 80 years or older (OR, 0.4; 95%CI, 0.1-1.4; P = .011), and plaque ulceration (OR, 0.5; 95% CI, 0.1-9.5; P = .008) independently predicted postprocedural hypertension. Male sex (OR, 2.5; 95% CI, 1.3-24.9; P.001), preprocedural major stroke (OR, 0.1; 95% CI, 0.01-0.8; P = .002), carotid bulb lesions (OR, 1.6; 95% CI, 1.1-25.9; P = .024), and contralateral carotid occlusion (OR, 0.6; 95% CI, 0.2-4.9; P = .040) all predicted postprocedural hypotension. Bradycardia was associated with diabetes mellitus (OR, 0.7; 95% CI, 0.3-2.4; P = .033), preprocedural TIA (OR, 1.7; 95% CI, 1.4-17.9; P = .020), and minor stroke (OR, 1.5; 95% CI, 1-10.9; P = .037). In 5 patients, HDI predisposed neurologic or systemic deterioration.Hemodynamic instability is common with CAS; hypotension and bradycardia are more frequent than hypertension. Some clinical, angiographic, and procedural variables can predict these HD changes.

✓ Despite the high technical success rates and the acceptable morbidity and mortality rates that are associated with carotid artery (CA) stent implantation, morphological changes in the vessel wall after this procedure are still unknown. The authors describe histopathological findings of the CA after stent implantation in a human autopsy specimen. A 75-year-old man with asymptomatic CA stenosis underwent successful CA stent implantation, but died 8 months afterward of complications surrounding treatment of a thoracic aortic artery aneurysm. The stented CA was isolated from the autopsy specimen and was analyzed macroscopically and with the aid of scanning electron microscopy and histopathological methods. Although there was focal persistence of a chronic inflammatory reaction around the stent struts, a stabilized neointima overlying the stent, which was principally composed of cells that stained positively for α—smooth muscle actin and collagen deposition with complete reendothelialization of the luminal surface, was confirmed in the internal CA. In contrast, residual mural thrombus around the stent struts in the common CA led to a concern about the potential risk for distal embolism in the future. The present case provides supportive evidence of stabilized neointima overlying the stent and valuable information regarding morphological characteristics useful for selecting a stent of an appropriate size.

Background: Trigeminal neuralgia is usually treated by the padding method using Teflon felt. However this can not be done in certain cases in whom a large tortuous vertebrobasilar artery compresses the fifth nerve. The transposition method using the sling may be an alternative method. But this method is not an easy procedure and requires a relatively large craniotomy. Two cases were treated by a new and simpler effective technique. Clinical presentation: Two cases of the trigeminal neruralgia were treated. The first case was a 71 year-old male and the second case was a 63 year-old male. The history of the medical treatments were similar and both cases had had trigeminal nerve blocks and were prescribed carbamazepin. However, the pain control was insufficient in both cases. In both cases, three dimensional computerized tomography showed the large tortuous right vertebral artery ran just behind the clivus and compressed the right trigeminal nerve. In the second case past history showed a recent hypertensive cerebellar hemorrhage. Technique and results: A right suboccipital craniotomy were performed in both cases. In both cases, the right vertebral artery compressed the trigeminal nerve in a rostral direction. The sling technique with nylon sutures was tried in both cases but failed during surgery. Then, the bone fixation stainless plate was cut to 10 cm in length and pre-shaped with pliers. After being shaped, the distal end of the plate was inserted between the vertebral artery and fifth nerve and the proximal end of the plate was fixed to the skull by screw. The fifth nerve was completely isolated from the artery as they were in direct contact. After surgery, the pain disappeared completely during the follow-up of one and a half year in the first case and 9 months in the second case. Conclusion: The plate can be bent and curved with plier to suit each individual case. This technique is easily applied even when the slings or other isolation technique is not available and appeared to achieve the mechanically stronger reposition and fixation of a very large and tortuous artery away from the trigeminal nerve.

Objective This study aimed to examine whether the volume of the olfactory bulbs and tracts (OB & T) on magnetic resonance imaging (MRI) is useful for differentiating Parkinson's disease (PD) from PD-related disorders. Methods The study group comprised 13 patients with PD, 11 with multiple system atrophy (MSA), five with progressive supranuclear palsy, and five with corticobasal degeneration (PSP/CBD). All patients were evaluated using the odor stick identification test for Japanese (OSIT-J), 123I-meta-iodobenzylguanidine (MIBG) scintigraphy, and brain MRI. OB & T areas on 1-mm-thick coronal images were measured and summed for volumes. We examined relationships between olfactory function and volume, and cardiovascular dysautonomia. We defined the cut-off values for OSIT-J score or MIBG uptake and OB & T volume to discriminate PD from PD-related disorders and calculated the proportional rate of PD in four categorized groups. Results OB & T volume was smaller in PD than in MSA or PSP/CBD (p

We herein report that the clinical, laboratory, and radiographic features and positron emission tomography (PET) imaging may provide valuable clues to the pathogenesis of cerebral amyloid angiopathy (CAA)-associated encephalopathy, which currently remains unclear. We herein describe two cases of encephalopathy with CAA, with an emphasis on PET imaging with (11)C-Pittsburgh compound B ((11)C-PiB) and (18)F-fluorodeoxyglucose ((18)F-FDG). One case of Alzheimer's disease for which a brain biopsy was performed showed CAA-related inflammation. Another case that had developed sudden sensory aphasia presented with posterior reversible encephalopathy syndrome-like vasogenic edema in the left temporal region with (11)C-PiB uptake and microhemorrhages. (11)C-PiB and (18)F-FDG PET are useful for detecting CAA-associated encephalopathy, including atypical CAA cases.

Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aβ 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region of AD enriched with Aβ plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aβ deposition in AD brain.

Cerebral aneurysms are the predominant cause of spontaneous subarachnoid hemorrhage (SAH). However, if an aneurismal cause has been excluded, there remains but a short list of meningiomas or metastatic lesions as possible causes. This article details a case of neoplasm that presented exclusively with SAH. A 31-year-old male presented with a SAH with normal cerebral angiography. The initial magnetic resonance image (MRI) revealed a lesion in the left uncus thought to be recovering hemorrhage. Subsequent MRI, however revealed the mass to be expanding. A neuroendoscopical biopsy of the lesion established a diagnosis of glioblastoma. An affirmation is made that patients experiencing "angiographically-negative" SAH should undergo MRI, occasionally on a serial basis, to exclude other etiologies for hemorrhage, including neoplasma.

Background and Purpose— We determined which hemodynamic parameter independently characterizes the rupture status of middle cerebral artery (MCA) aneurysms using computational fluid dynamics analysis. Methods— In 106 patient-specific geometries of MCA aneurysms (43 ruptured, 63 unruptured), morphological and hemodynamic parameters were compared between the ruptured and unruptured groups. Multivariate logistic regression analysis was performed to determine parameters that independently characterized the rupture status of MCA aneurysms. Results— Univariate analyses showed that the aspect ratio, wall shear stress (WSS), normalized WSS, oscillatory shear index, WSS gradient, and aneurysm-formation index were significant parameters. The size of the aneurysmal dome and the gradient oscillatory number were not significantly different between the 2 groups. With multivariate analyses, only lower WSS was significantly associated with the rupture status of MCA aneurysms. Conclusions— WSS may be the most reliable parameter characterizing the rupture status of MCA aneurysms.

Background and Purpose— Preventing cerebral embolisms is a major concern with carotid artery stenting (CAS). This study evaluated 3-dimensional T1-weighted gradient echo (3D T1GRE) sequence to predict cerebral embolism related to CAS. Methods— We performed quantitative analyses of the characteristics of 47 carotid plaques before CAS by measuring the signal intensity ratio (SIR) and plaque volume using 3D T1GRE images. We used T1-weighted turbo field echo sequence to obtain 3D T1GRE images. We also evaluated diffusion-weighted images (DWI) of the brain before and after CAS to detect ischemic lesions (DWI lesions) from cerebral emboli. Results— SIR (2.17 [interquartile range 1.50–3.07] versus 1.35 [interquartile range 1.08–1.97]; P =0.010) and plaque volume (456 mm 3 [interquartile range 256–696] versus 301 mm 3 [interquartile range 126–433]; P =0.008) were significantly higher in the group of patients positive for DWI lesions (P-group: n=26) than DWI lesion-negative patients (N-group: n=21). In multivariate logistic regression analysis, SIR ( P =0.007) and plaque volume ( P =0.042) were independent predictors of DWI lesions with CAS. Furthermore, SIR ( r s=0.42, P =0.005) and plaque volume ( r s=0.36, P =0.012) were positively correlated with the number of DWI lesions. From analysis of a receiver-operating characteristic curve, the most reliable cutoff values of SIR and plaque volume to predict DWI lesions related to CAS were 1.80 and 373 mm 3 , respectively. Conclusions— Quantitative evaluation of carotid plaques using 3D T1GRE images may be useful in predicting cerebral embolism related to CAS.

Although rupture of cerebral aneurysms typically occurs at the fragile wall at the apex or pole, some aneurysms rupture through the body or the neck. The purpose of this study was to clarify the association between aneurysm rupture points and hemodynamic features through the use of computational fluid dynamics (CFD) analysis.Twelve ruptured middle cerebral artery bifurcation aneurysms were analyzed by 3-dimensional computed tomographic angiography and CFD. Rupture points were evaluated on intraoperative videos by 3 independent neurosurgeons. Wall shear stress (WSS) was calculated at the rupture point, aneurysm dome, and parent artery. Intra-aneurysmal flow patterns were evaluated with cross-sectional velocity vector planes that included the rupture points.The mean WSS at the rupture point (0.29 Pa) was significantly lower than that at the dome (2.27 Pa) and the parent artery (8.19 Pa) (P.01). All rupture points were located within the area of WSS ≤ 11.2% of the WSS at the parent artery. WSS at the rupture point was correlated with the minimum WSS at the dome (r = 0.64, P.05), but not with aneurysm size (r = 0.26) or the aspect ratio (r = 0.16). Flow patterns revealed that all rupture points were located in lower-velocity area, which was associated with complex flow patterns and/or deviating necks.This study highlights the relationship between the local hemodynamic features and the rupture points observed during the microsurgical clipping. CFD may determine a rupture point of aneurysms using the feature of markedly low WSS.

Background and Purpose— We developed a novel dynamic 4-dimensional CT angiography to accurately evaluate dynamics in cerebral aneurysm. Methods— Dynamic 4-dimensional CT angiography achieved high-resolution 3-dimensional imaging with temporal resolution in a beating heart using dynamic scanning data sets reconstructed with a retrospective simulated R-R interval reconstruction algorithm. Results— Movie artifacts disappeared on dynamic 4-dimensional CT angiography movies of 2 kinds of stationary phantoms (titanium clips and dry bone). In the virtual pulsating aneurysm model, pulsation on the dynamic 4-dimensional CT angiography movie resembled actual movement in terms of pulsation size. In a clinical study, dynamic 4-dimensional CT angiography showed 2-type motions: pulsation and anatomic positional changes of the cerebral artery. Conclusions— This newly developed 4-dimensional visualizing technique may deliver some clues to clarify the pathophysiology of cerebral aneurysms.

Management of Vertebral Artery (VA) dissections remains controversial. The clinical and angiographic variables of VA dissections were evaluated to demonstrate the safety and efficacy of endovascular intervention in treatment of VA dissecting aneurysms.25 patients with 27 VAdissecting aneurysms were treated with endovascular intervention during the last 10 years.17 patients were admitted with subarachnoid hemorrhage. 23 aneurysms treated using destructive endovascular trapping, while reconstructive techniques were used in 3 aneurysms treated with stent-assisted coiling and one aneurysm treated with false lumen embolization.The right VA was involved in 14 patients, the left VA in 9 patients, while 2 patients had bilateral VA dissection. The pearl and string sign was the commonest angiographic sign in 12 aneurysms. Perioperative complications included; rebleeding in one patient, symptomatic brain stem infarction in two patients and silent cerebellar ischemic lesion in one patient. Afavorable outcome was evident more in patients with unruptured VA dissection (100%) versus (76.5%) in patients presented with SAH.The endovascular technique should be individualized according to the clinical status of the patient, angiographic variables, condition of the posterior circulation and the available supplies.

Distal embolism is an important periprocedural technical complication with carotid angioplasty and carotid artery stenting (CAS). We evaluated the safety and efficacy of protection devices used during CAS by detecting new cerebral ischemic lesions using diffusion-weighted magnetic resonance imaging in 95 patients who underwent 98 CAS procedures: 34 using single PercuSurge GuardWire, 31 using double balloon protection, 15 using proximal flow reverse protection devices, 14 using Naviballoon, and 4 using filter anti-embolic devices. Diffusion-weighted imaging was performed preoperatively and postoperatively to evaluate the presence of any new embolic cerebral lesions. Postoperative diffusion-weighted imaging revealed 117 new ischemic lesions. Three patients had new ischemic stroke, two minor and one major, all ipsilateral to the treated carotid artery. The remaining patients had clinically silent ischemia. The incidence of new embolic lesions was lower using the proximal flow reverse protection device than with the double balloon protection (33% vs. 48.4%), but the volume of ipsilateral new ischemic lesions per patient was 136.6 mm(3) vs. 86.9 mm(3), respectively. Neuroprotection with Naviballoon yielded ipsilateral lesions of large volume (86.6 mm(3)) and higher number (5.7 lesions per patient) than using the filter anti-embolic device (34.8 mm(3) and 1 lesion per patient). New cerebral ischemic lesions after neuroprotected CAS are usually silent. The lower incidence of distal ischemia using proximal flow reverse and double balloon protection devices is limited by the larger volume and higher number of ischemic lesions.

Background The metabolism of dietary fatty acids in human has been measured so far using human blood cells and stable-isotope labeled fatty acids, however, no direct data was available for human peripheral tissues and other major organs. To realize the role of dietary fatty acids in human health and diseases, it would be eager to develop convenient and suitable method to monitor fatty acid metabolism in human. Results We have developed the measurement system in situ for human lip surface lipids using the Fourier transform infrared spectroscopy (FTIR) – attenuated total reflection (ATR) detection system with special adaptor to monitor metabolic changes of lipids in human body. As human lip surface lipids may not be much affected by skin sebum constituents and may be affected directly by the lipid constituents of diet, we could detect changes of FTIR-ATR spectra, especially at 3005~3015 cm-1, of lip surface polyunsaturated fatty acids in a duration time-dependent manner after intake of the docosahexaenoic acid (DHA)-containing triglyceride diet. The ingested DHA appeared on the lip surface and was detected by FTIR-ATR directly and non-invasively. It was found that the metabolic rates of DHA for male volunteer subjects with age 60s were much lower than those with age 20s. Lipid hydroperoxides were found in lip lipids which were extracted from the lip surface using a mixture of ethanol/ethylpropionate/iso-octane solvents, and were the highest in the content just before noon. The changes of lipid hydroperoxides were detected also in situ with FTIR-ATR at 968 cm-1. Conclusion The measurements of lip surface lipids with FTIR-ATR technique may advance the investigation of human lipid metabolism in situ non-invasively.

The objective of this study was to evaluate the usefulness of the nonenhanced 3-dimensional heavily T2-weighted images obtained with 2-dimensional prospective acquisition and correction in visualization of the lymphatic system of the trunk. The thoracic duct, cisterna chyli, and lumbar lymphatics were well shown in 9 healthy volunteers. This nonenhanced magnetic resonance lymphoductography is thought to be a suitable method in visualization of the lymphatic system of the trunk.

Background Carotid angioplasty and stenting is a relatively new therapeutic alternative to CEA for treatment of carotid stenosis. The percutaneous transfemoral approach, the standard technique for angioplasty and stent deployment, may not be feasible in all patients. We present our experience with access site complications that occurred with CAS. Methods One hundred thirty-two CAS procedures were performed at our institution in the past 5 years for symptomatic (62.1%) or asymptomatic (37.9%) carotid stenosis. Mean age of patients was 70.72 ± 6.53 years and the mean degree of stenosis of the treated carotids was 80.74% ± 11.83%. The transfemoral approach was the access route in 126 CAS, the transbrachial approach was used in 2 CAS procedures, and direct carotid exposure was used in 5 patients. Results All CAS procedures were done successfully; 4 (3%) access site complications were detected, 3 (2.4%) groin hematomas with transfemoral approach and 1 hematoma on the left side of the neck, in patients treated with direct carotid cutdown. Surgical repair of FSA was successfully performed for the patients with groin hematoma, whereas surgical wound exploration in the neck for the remaining patient revealed no identifiable cause. All patients received blood transfusion for correction of associated hypovolemia or hemorrhagic anemia. No patients had experienced access site–related additional cardiac, systemic, or neurologic events. Conclusions The authors' experience demonstrates that access site complications are rare events with CAS despite the large diameter of implantable devices and liberal anticoagulant and antiplatelet therapy. Transbrachial and direct carotid approaches are relatively safe, accepted alternatives in the setting of contraindicated femoral access.

Prostacyclin, one of the cyclooxygenase metabolites, causes various biological effects, including vasodilation and antithrombogenicity, and is also involved in several pathophysiological effects, such as inflammatory pain and bladder disorders. The prostacyclin receptor (IP receptor) agonists iloprost, cicaprost, and carbacyclin have been useful for clarifying the role of the IP receptor signaling, since the endogenous ligand, prostacyclin, is very unstable. On the other hand, only a few IP receptor antagonists have been reported to date. Here, we characterized the biological activities of 2-[4-(1H-indol-4-yloxymethyl)-benzyloxycarbonylamino]-3-phenyl-propionic acid (compound A) in various in vitro systems. Compound A inhibited the accumulation of the second messenger cyclic AMP in the UMR-108 rat osteosarcoma cell line and primary cultured rat dorsal root ganglion (DRG) neurons in a concentration-dependent manner up to 10 microM, without affecting other eicosanoid receptors. Functionally, the IP receptor plays an important role in DRG neuron sensitization, which is measured by release of the neurotransmitter substance P. Although the effects of iloprost or Lys-bradykinin, an inflammatory peptide, alone on substance P release were limited, stimulation of the neurons with both these ligands induced substantial amounts of substance P release. This synergistic effect was suppressed by compound A. Collectively, these results suggest that compound A is a highly selective IP receptor antagonist that inhibits iloprost-induced sensitization of sensory neurons. Furthermore, these findings suggest that IP receptor antagonist administration may be effective for abnormal neural activities of unmyelinated sensory afferents. Compound A should prove useful for further investigations of the IP receptor in various biological processes.

To assess a new interpretation model combining kinetic pattern and morphologic characteristics using high-spatial-resolution MR imaging.Breast MR imaging was performed in 58 patients with 63 pathologically proved focal breast masses (49 malignant and 14 benign). MR imaging was performed on a 1.5-Tesla system using the volumetric interpolated breath-hold examination (VIBE) sequence. Morphological parameters were lesion shape, mass margin, rim enhancement (RE), enhancing internal septations, and internal signal on T2-weighted images. Lesion shape/margin was classified into four categories as follows: smooth (smooth/round or smooth/oval), lobulated (lobular shape), irregular (irregular margin or irregular shape), and spiculated (spiculated margin). RE was sub-classified as early RE at 60 sec and delayed RE at 4 min. Strongly high signal and the presence of internal black septations were evaluated over the entire lesion on T2-weighted images. The kinetic parameter was visually assessed as follows: washout, plateau, and progressive.The most frequent types of lesion shape/margin in the malignant lesions were irregular (47%) and spiculated (43%), whereas 13 of the benign lesions had smooth or lobular margins (93%). The most frequent characteristics in breast cancers with lobulated configuration were washout pattern (80%), whereas 78% of the lobulated benign lesions were negative for visual washout. The positive predictive value (PPV) was 98% (49/50)."Washout with enhancing septations" is thought be specific for carcinoma with a lobulated configuration (80%). A combination of morphological criteria (including lesion shape/margins, strongly high signal on T2-weighted images) and visual washout is useful for differentiating between benign and malignant lesions.

We compared the results of two procedures to protect against distal embolism caused by embolic debris from carotid angioplasty with stent deployment (CAS) using diffusion-weighted magnetic resonance imaging (MRI). The study group comprised 39 men and 3 women (42 and 3 CAS procedures, respectively) with severe carotid stenosis (average age 70.0 +/- 6.6 years). During 20 CAS procedures the internal carotid artery was protected with a single balloon. A PercuSurge GuardWire was used for temporary occlusion. During 25 CAS procedures the internal and external carotid arteries were simultaneously temporarily occluded with a PercuSurge GuardWire and a Sentry balloon catheter, respectively. Diffusion-weighted MRI was performed 1 to 3 days after CAS. Data from 26 patients undergoing conventional angiography for diagnosis of cerebral ischemic disease, cerebral aneurysm or brain tumors were included as controls. Diffusion-weighted MRI after conventional diagnostic angiography showed ischemic spots in 3 of the 26 controls (11.5%). Ischemic spots were observed during 11 of 20 CAS procedures with the internal carotid artery protected with a single balloon (55.0%), and were observed during 9 of 25 CAS procedures with both the internal and external carotid arteries protected (36.0%). This difference was significant (P = 0.0068). Ischemic lesions appeared not only ipsilateral to the carotid stenosis but also in the contralateral carotid artery (31.9%) and vertebrobasilar territory (25.3%). Better protection was obtained with simultaneous double occlusion of both the internal and external carotid artery than with single protection of the internal carotid artery during CAS.

Densin-180, a brain-specific protein highly concentrated at the postsynaptic density (PSD), belongs to the LAP [leucine-rich repeats and PSD-95/Dlg-A/ZO-1 (PDZ) domains] family of proteins, some of which play fundamental roles in the establishment of cell polarity.To identify new Densin-180-interacting proteins, we screened a yeast two-hybrid library using the COOH-terminal fragment of Densin-180 containing the PDZ domain as bait, and we isolated MAGUIN-1 as a Densin-180-binding protein. MAGUIN-1, a mammalian homologue of Drosophila connector enhancer of KSR (CNK), is known to interact with PSD-95 and has a short isoform, MAGUIN-2. The Densin-180 PDZ domain bound to the COOH-terminal PDZ domain-binding motif of MAGUIN-1. Densin-180 co-immunoprecipitated with MAGUIN-1 as well as with PSD-95 from the rat brain. In dissociated hippocampal neurones Densin-180 co-localized with MAGUINs and PSD-95, mainly at neuritic spines. In transfected cells, Densin-180 formed a ternary complex with MAGUIN-1 and PSD-95, whereas no association was detected between Densin-180 and PSD-95 in the absence of MAGUIN-1. MAGUIN-1 formed a dimer or multimer via the COOH-terminal leucine-rich region which is present in MAGUIN-1 but not in -2. Among the PDZ domains of PSD-95, the first was sufficient for interaction with MAGUIN-1.These results suggest that the potential to dimerize or multimerize allows MAGUIN-1 to bind simultaneously to both Densin-180 and PSD-95, leading to the ternary complex assembly of these proteins at the postsynaptic membrane.

A novel method was developed for cloning of zinc-binding proteins. We used65Zn2+as a probe to screen a human lung cDNA library, and isolated QM using this approach. QM appears to be a negative regulator of c-Jun that acts by binding to the leucine zipper region of c-Jun. We demonstrated that QM bound zinc ions and that such binding was necessary for the interaction of QM with c-Jun. We also showed that protein kinase C introduced about 1 mol of phosphate into 1 mol of QM. The binding of QM to c-Jun was decreased by 60% when QM had been phosphorylated. These results suggest that QM is a novel zinc-binding transcription regulatory protein and that interaction between QM and c-Jun is regulated by zinc ions and phosphorylation.

Systematically synthesized derivatives of ML-9, 1-(5-chloronaphthalenesulfonyl)-1H-hexahydro-1,4-diazepine, were found to inhibit both Ca2+-calmodulin-dependent and -independent smooth muscle myosin light chain kinases with a similar concentration dependence, and their inhibitions were of the competitive type with respect to ATP. Moreover, ML-9 as well as ATP or ADP exhibited an effective protection to inactivation of smooth muscle myosin light chain kinase by the nucleotide affinity label 5'-p-fluorosulfonylbenzoyladenosine, suggesting that ML-9 binds at or near the ATP-binding site on the kinase molecule. These derivatives, which were structurally unrelated to ATP and exhibited more hydrophobic properties detected by reverse-phase high-performance liquid chromatography, exhibited more potent inhibition toward smooth muscle myosin light chain kinase, indicating that the hydrophobic properties of these derivatives positively correlated well with their potencies of inhibiting the catalytic activity for the enzyme. These findings suggest that the ATP-binding site at the active center of smooth muscle myosin light chain kinase is located in a hydrophobic environment. The potent vaso-relaxing effect of ML-9 on rabbit vascular strips and on saponin-treated skinned smooth muscle cells was discussed in relation to the in vivo inhibition by this drug of smooth muscle myosin light chain kinase.

The results of treatment for 182 patients with hypertensive putaminal hemorrhage are described. The patients are graded according to the level of consciousness on admission; grade 1, fully conscious; grade 2, somnolent; grade 3, stuporous; grade 4, semicomatose; and grade 5, deeply comatose. Removal of hemorrhage was performed in 44 patients (24%), and conservative treatment was given in 138 patients (76%). One-month mortality in the surgical group was 27%; it was 22% in the conservative group. At 6 months after surgical treatment, the percentages of patients who returned to full-time work or independent life without disability or with minimal disability (good recovery) were 40% in grade 1, 30% in grade 2, 22% in grade 3, 11% in grade 4, and 0% in grade 5; after conservative treatment, percentages with good recovery were 77% in grade 1, 56% in grade 2, 29% in grade 3, 7% in grade 4, and 0% in grade 5. This study shows that surgical treatment does not give better results in the management of hypertensive putaminal hemorrhage.