Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C.

BACKGROUND: The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival. METHODS: An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ±â€…10 Gy boost (arm A) or WBRT ±â€…boost with concomitant and maintenance TMZ for 2 years (arm B). The primary endpoint was overall survival (OS). RESULTS: Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response. CONCLUSIONS: This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.

IgG4-related brain pseudotumor mimicking CNS lymphoma. A case report.

Here, we report a case of IgG4-related brain pseudotumor (IgG4-BP) in a 39-year-old woman, mimicking central nervous system (CNS) lymphoma. She presented with headache, fever, and fatigue. Her medical history was notable for appearance of a tumefactive brain lesion seven years before. Brain biopsy performed at the age of 32 revealed nonspecific inflammatory changes, and her condition improved with oral low-dose steroid therapy. Magnetic resonance imaging performed at the age of 39 identified a hyperintensity lesion with edema located at the medial temporal lobe region adjacent to the inferior horn of the left lateral ventricle on fluid-attenuated inversion recovery images, which showed gadolinium-contrast enhancement on T1-weighted images and a slightly hyperintensity signal on diffusion-weighted images. Methionine-positron emission tomography (PET) depicted a high methionine uptake in the lesion. Additionally, soluble levels of interleukin (IL)-2 receptor (sIL-2R) and IL-10 were increased in cerebrospinal fluid (CSF). Based on these findings, we suspected CNS lymphoma and performed partial resection of the brain lesion. Pathological examination revealed prominent lymphocytic infiltration associated with plasma cell infiltration. Most of the plasma cells were immunoreactive for IgG4. Storiform fibrosis and partially obliterative phlebitis were concomitantly observed. Thus, the patient was diagnosed as having IgG4-BP. To the best of our knowledge, this is the first case report of IgG4-BP with detailed findings obtained by CSF testing, methionine-PET, and pathological examination. Because IgG4-related diseases can present as a pseudotumor that mimics CNS lymphoma, it is essential to carefully differentiate IgG4-BP from CNS lymphoma.

Glycated Tryptophan PHP-THßC Incorporated into Various Chicken Embryonic Cells Constitutes Cellular Proteins.

Glycation is a non-enzymatic reaction, and amino acids are glycated by glucose in vivo. Tryptophan is glycated with glucose to form two types of glycated compounds, tryptophan-Amadori product and (1R, 3S)-1-(D-gluco-1, 2, 3, 4, 5-pentahydroxypentyl)-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid (PHP-THßC). Although PHP-THßC can be incorporated into various chicken embryonic cells, the mechanism of its incorporation into intracellular fluids has not been clarified. In this study, we examined whether PHP-THßC once incorporated into various chicken embryonic cells can combine with proteins. Embryonic cells from the breast muscle, liver, spleen, kidney, proventriculus, gizzard, and skin were prepared and 3H-PHP-THßC was added to the culture medium at final concentrations of 0, 200, 400, 600, and 800 µM to examine the incorporation of PHP-THßC. After 18 h of incubation, radioactivity was measured in the whole-cell and protein fractions of the chicken embryonic cells. As PHP-THßC concentration increased from 0 to 600 µM, its accumulation in the whole-cell fractions of all types of chicken embryonic cells linearly increased and reached the maximum level. The saturated PHP-THßC accumulation in the whole-cell fractions suggests that PHP-THßC could be incorporated into intracellular fluids across cellular membranes by some transporter proteins. As PHP-THßC concentration increased from 0 to 800 µM, its accumulation in the protein fractions of all types of chicken embryonic cells increased in a linear manner and reached a maximum level in the 800 µM PHPTHßC treatment group. This is the first study to indicate that a part of PHP-THßC incorporated into the whole-cell fraction was detected in the protein fraction of various chicken embryonic cells.

Mucosal thickening of the maxillary sinus is frequently associated with diffuse glioma patients and correlates with poor survival prognosis of GBM patients: comparative analysis to meningioma patients.

Glioma patients were frequently associated with mucosal thickening of the maxillary sinus (MTMS), which reflects mucosal inflammation. We suspected that MTMS is associated with impaired mucosal immune response and correlated with dysfunction in the anti-tumor immune response in diffuse glioma patients. Therefore, the aim of this study was to determine whether the occurrence of diffuse glioma is correlated with MTMS compared to meningioma and control groups. Furthermore, we investigated whether MTMS is associated with overall survival (OS) in glioblastoma (GBM) patients. This study included 343 patients with newly diagnosed diffuse gliomas and 218 patients with meningioma treated at our institution between 2015 and 2018. As control, 201 patients with headache who did not have an intracranial organic lesion were included. Using three-axis MR images, we evaluated the incidence of MTMS in all patients. Additionally, we investigated the relationship between MTMS and OS. The incidence of MTMS in patients with diffuse glioma was significantly higher than that in the meningioma (p < .0001) and control groups (p < .0001). In 128 patients with GBM, MTMS status correlated significantly with OS (p = .0064). We revealed that the incidence of MTMS is significantly associated with patients with diffuse glioma. This suggests that MTMS is indirectly involved in the occurrence of diffuse gliomas. Furthermore, the presence of MTMS correlated significantly with shorter OS in GBM patients, indicating that MTMS is involved in suppression of anti-tumor immune response. Preoperative recognition of MTMS might be useful for improving the clinical management of GBM patients.

Computed tomography perfusion in patients of stroke with left ventricular assist device.

Left ventricular assist devices (LVAD) are widely applied for patients with severe heart failure as a bridge to heart transplantation as well as destination therapy. Patients with implanted LVAD have an increased risk of cerebral thrombosis and computed tomographic perfusion (CTP) has the potential to be performed for early diagnosis and treatment of acute ischemic stroke (AIS), including interventional thrombectomy. Here, we report our series of CTP examination in patients having suspected AIS after LVAD implantation. We retrospectively investigated 33 contrast-enhanced CTPs from January 2017 to December 2018 which were performed in 12 cases of patients because of possible neurological findings leading to suspected AIS during LVAD circulatory support who did not have definite ischemic findings nor intracerebral hemorrhage on non-contrast computed tomography. AIS with perfusion disturbance area was diagnosed in 11 (33.3%) out of a total of 33 CTPs in 4 (33.3%) out of 12 patients. Endovascular thrombectomy (EVT) was successfully performed in this research study four times for three patients. CTP was able to detect and determine the indication for EVT without serious complications. CTP could potentially be the first-choice assessment for early diagnosis of AIS with recoverable ischemic penumbra in patients with LVAD implantation.

Improved visualization of diffusion-prepared MR neurography (SHINKEI) in the lumbosacral plexus combining high-intensity reduction (HIRE) technique.

PURPOSE: This study attempted to improve visualization of the pelvic nervous system using the high-intensity reduction (HIRE)-nerve-SHeath signal increased with INKed rest-tissue RARE Imaging (SHINKEI) technique that involves subtracting signals of 3D heavily T2W images from SHINKEI images. We identified the optimum TE value for 3D heavily T2W images and assessed the usefulness of the HIRE-SHINKEI technique. MATERIALS AND METHODS: Coronal lumbosacral plexus images were acquired from six healthy volunteers at 3 T. We optimized the TE of the 3D heavily T2-weighted (T2W) images in HIRE-SHINKEI and compared HIRE-SHINKEI images with conventional SHINKEI images with respect to nerve depiction, and vein, bladder, and cerebrospinal fluid (CSF) signal suppression using a 5-point scale. RESULTS: In 3D heavily T2W images optimized by HIRE-SHINKEI technique, the signal corresponding to nerves became significantly lower at TE = 400 ms (p < 0.0005), while that of veins occurred at TE = 400 ms and 600 ms (p < 0.05). The suppression of bladder signals was significant at TE = 400, 600, and 800 ms (p < 0.05); however, there was no difference in signal inhibition from CSF at all TEs tested. Based on these results, an optimal TE of 600 ms was identified for 3D heavily T2W images; these images corresponded to the minimal loss of nerve signal and simultaneous maximum subtraction of signals from the bladder, vein, and CSF with dissimilar T2 values. Compared with SHINKEI images, the optimized HIRE-SHINKEI images selectively delineated nerves in greater detail, and along with significant signal suppression of the bladder (p < 0.0001) and veins (p < 0.05). CONCLUSION: HIRE-SHINKEI can be used to better visualize the lumbosacral plexus with higher signal suppression of other pelvic structures. Such detailed Magnetic resonance neurography and selective depiction of nerves are useful for the diagnosis of peripheral nerve disorders.

Dual-Phase Computed Tomography Angiography Enhances Detection of Contrast Extravasation in Subarachnoid Hemorrhage.

BACKGROUND: Contrast-enhanced computed tomography angiography (CTA) can be used to detect contrast extravasation in intracerebral hemorrhage. However, investigation for contrast extravasation in subarachnoid hemorrhage (SAH) is insufficient. We evaluated the efficacy of dual-phase CTA to improve evaluation of contrast extravasation in SAH. METHODS: We retrospectively evaluated 35 patients with SAH who underwent contrast-enhanced dual-phase CTA within 24 hours from onset. The second-phase scan was performed 8 or 15 seconds following the usual CTA. The frequency of contrast extravasation was compared between phases. We also recorded the time from onset, coma level, interventional treatment, and early mortality. RESULTS: Of 35 patients (22.9%) with SAH, 8 showed contrast extravasation in the second phase compared with 3 in the first phase. Contrast extravasation was correlated with clinical coma level (P < 0.05), and all contrast extravasation was found within 6 hours from onset. Early mortality, treatment decision, and hematoma distribution type did not correlate with existence of contrast extravasation. We also observed 4 cases of secondary subpial hematoma due to SAH, with 3 showing extravasation in both phases. CONCLUSIONS: Dual-phase CTA with a short interval enhances detection frequency of contrast extravasation in SAH and might be a better evaluation tool for SAH.

Pulvinar Locus is Highly Relevant to Patients' Outcomes in Surgically Resected Thalamic Gliomas in Children.

OBJECTIVE: Thalamic gliomas in children are less suitable for surgical resection because of their location. In cases of unavoidable resection, careful surgical planning in addition to histology and extent of resection affects prognosis. METHODS: A cohort of 10 pediatric patients with thalamic glioma underwent surgical resection at our department. The predominant location of tumor origins in the thalamus was defined in imaging studies. Histopathology was determined (retrospectively in a subset) according to the World Health Organization classification 2016, including the newly established type of "diffuse midline glioma, H3 K27M-mutant." RESULTS: Three low-grade gliomas (grade I/II) and 7 high-grade gliomas (grade III/IV) were identified. The mean follow-up period was 49.8 months. All 3 low-grade gliomas did not recur (progression-free survival, 58.3 months). Six of 7 high-grade gliomas recurred, and the patients died of the primary disease (overall survival, 28.1 months). Poor outcomes, especially when located at the pulvinar region, were noticeable, with strong predictive power for poor prognosis (P = 0.0018). The presence of H3 K27M mutation and pulvinar location were closely associated (P = 0.0036). Four of 5 patients with pulvinar region tumors developed dissemination and died of the primary disease. CONCLUSIONS: Pulvinar location is specifically associated with a high rate of malignancy in histology, the presence of H3 K27M mutation, and dissemination at an early disease stage. This association suggests that a distinct biological profile affects prognosis depending on location within the thalamus, especially the pulvinar. We report that tumor location is highly relevant to prognosis and should be taken into consideration when planning treatment.

Proton magnetic resonance spectroscopy differentiates tumefactive demyelinating lesions from gliomas.

BACKGROUND: It is often difficult to accurately differentiate tumefactive demyelinating lesions (TDLs) from gliomas using MRI. OBJECTIVE: To investigate the utility of proton magnetic resonance spectroscopy (MRS) in differentiating TDLs from gliomas. METHODS: Cohort 1 included 6 patients with TDLs and 5 with gliomas (3 high-grade), as assessed using a 1.5T MR unit. Cohort 2 included 6 patients with TDLs and 17 patients with gliomas (8 high-grade), as assessed using a 3.0T MR unit. Single-voxel proton MRS was performed to compare the following metabolite area ratios: choline (Cho)/creatine (Cr), N-acetylaspartate (NAA)/Cr, and Cho/NAA in both cohorts. Correlations between the target-to-normal-tissue ratio (TNR) obtained using methionine-positron emission tomography (MET-PET) and each MRS metabolite ratio were examined in a subset of cohort 2 (4 patients with TDLs and 11 with gliomas). RESULTS: Mean Cho/NAA ratio was significantly higher in gliomas than in TDLs or MS in cohort 1 (p < 0.05). Mean Cho/NAA ratio was significantly higher in high-grade gliomas than in TDLs in both cohorts (ps < 0.05). In the receiver operating characteristic analysis, high-grade glioma rather than TDL was indicated when the Cho/NAA ratio was >1.72 (the area under the curve was 0.958, and the maximum sensitivity and specificity were 100% and 87%, respectively). A significant positive correlation was observed between Cho/NAA ratio and the MET-PET TNR (r2 = 0.35, p < 0.05). CONCLUSION: MRS effectively differentiates TDLs from high-grade gliomas. Therefore, the clinical use of MRS is likely to enhance patient outcomes.

Imaging of Intracranial Gliomas.

Combined use of contemporary radiological modalities, particularly integration of structural, metabolic, and functional imaging, provides optimal multifaceted information for detailed characterization of intracranial gliomas. It allows differentiation of the tumor from non-neoplastic pathology, its non-invasive histopathological typing and grading, prediction of patient prognosis and clinical course of the disease, detailed planning of surgical resection or biopsy, critical postoperative assessment of the residual lesion, effective surveillance during follow-up with evaluation of effectiveness of the adjuvant therapy and timely identification of recurrence, and even insights into molecular signatures of the neoplasms. Therefore, advanced neuroimaging is one of the most important cornerstones of the modern neuro-oncology.

The effect of scan interval and bolus length on the quantitative accuracy of cerebral computed tomography perfusion analysis using a hollow-fiber phantom.

The shuttle scan technique is expected to extend scan range in cerebral computed tomography (CT) perfusion by 16- or 64-row multidetector CT (MDCT), but it may affect quantitative accuracy. This study aims to evaluate the effect of long scan interval and bolus length on the quantitative accuracy of perfusion indices using an innovative hollow-fiber phantom.We used an originally developed hollow-fiber hemodialyzer covered with polyurethane resin as a perfusion phantom. We scanned the phantom during various scan intervals (1-13 s) and bolus injection lengths (5, 10, 15, and 20 s), and evaluated cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-peak (TTP). We verified the influence on measured values using a two-way analysis of variance (ANOVA). All measured CBF values were smaller than the theoretical CBF values, and all the measured MTT values were larger that the theoretical MTT values (95% confidence interval). Extended scan intervals resulted in more overestimation of MTT and more underestimation of CBF (p < 0.001). CBV is not affected by the change in scan interval (p < 0.001), and a longer bolus length improved the underestimation of CBV (p < 0.001). Extended scan intervals resulted in the loss of quantitative accuracy in MTT, even with longer bolus injection length, while quantitative CBF values were underestimated and TTP values overestimated. The CBV measurement was not affected by the change in scan interval, and a longer bolus injection improved the accuracy of these measurements.

Quantitative accuracy of computed tomography perfusion under low-dose conditions, measured using a hollow-fiber phantom.

PURPOSE: The purpose of this study was to investigate the quantitative accuracy under low-dose conditions on computed tomography (CT) perfusion using a hollow-fiber phantom that had the theoretical absolute values of perfusion indices. MATERIALS AND METHODS: Our phantom comprised two components, i.e., a hollow-fiber hemodialyzer to pump the diluted contrast material and a surrounding syringe-shaped X-ray-absorbing body to simulate the absorption of X-rays by a brain and cranium. We performed CTP scans on the phantom under various dose conditions ranging from 20 to 140 mA using a 64-row CT scanner, measuring experimental cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) values using a deconvolution algorithm. RESULTS: The theoretical value of the CBV was within the 95% confidence interval of CBV values measured under 80 mA. The CBV measured under low-dose settings and all CBF values measured were smaller than the theoretically calculated ones, and all MTT values measured were larger. All measured values of the CBV, CBF, MTT, and TTP decreased with an increase in image noise under lower dose conditions. CONCLUSION: It is difficult to define a low-dose limit in clinical scan conditions because of the complex characteristics of perfusion indices.

Carnosine activates the CREB pathway in Caco-2 cells.

Imidazole dipeptide, carnosine, is a versatile compound composed of ß-Ala and L-His. A recent study showed that carnosine might benefit the treatment of Alzheimer's disease and the maintenance of cognitive function. Based on the observation that carnosine is immediately degraded by serum carnosinase, we hypothesized that carnosine improves brain function by promoting brain-gut interaction. This study sought to present possible mechanisms regulating carnosine-induced activation of brain-gut interaction. We had previously found that carnosine augmented the expression of BDNF in human colorectal cancer cells, thus we became interested in cAMP-responsive element binding protein (CREB), which is a dominant regulator of BDNF transcription. We found that carnosine activates CREB and CREB-related pathways by activating Ca2+-related pathways. Our findings suggest that carnosine augments the expression of CREB-regulated genes in the intestine; this augmentation contributes to the carnosine-induced activation of brain-gut interaction.

Technique and Theory of Hollow-fiber Phantom for Cerebral CT Perfusion.

We developed a phantom using a hollow-fiber hemodialyzer to evaluate the quantitative reliability of cerebral computed tomography (CT) perfusion. Our phantom consisted of a hollow-fiber hemodialyzer and a syringe-shaped X-ray device made up of resin. The phantom can give theoretical true values for cerebral blood volume, cerebral blood flow, and mean transit time. We compared the values measured in the phantom with predicted theoretical values. The purpose of the current report is to describe the theory and experimental technique used to obtain an absolute value in a phantom.

Roles of the Wada Test and Functional Magnetic Resonance Imaging in Identifying the Language-dominant Hemisphere among Patients with Gliomas Located near Speech Areas.

This study examined the accuracy of functional magnetic resonance imaging (fMRI) in identifying the language-dominant hemisphere and the situations in which the Wada test can be skipped among patients with gliomas located near speech areas. We examined 74 patients [48 men (64.9%); mean ± standard deviation age of 42.7 ± 13.6 years (range: 13 to 70 years); 71 right-handed, 2 left-handed, and 1 ambidextrous] with gliomas located near speech areas. All patients underwent the Wada test and fMRI, and 34 patients underwent awake surgery. The "last-and-first" task was administered during fMRI. The Wada test was successful in determining the language-dominant hemisphere in 73 patients (98.6%): left hemisphere in 68 patients (91.9%), right hemisphere in 4 patients (5.4%), and bilateral in 1 patient (1.4%). The dominant hemisphere for right-handed patients (n = 71) was the left hemisphere in 67 patients (94.3%), right hemisphere in 3 patients (4.2%), and undetectable in 1 patient (1.4%). The fMRI was successful in determining the language-dominant hemisphere in 53 patients (71.6%). The results of the Wada test and fMRI were inconsistent in 5 patients (8.6%), of which 3 (5.2%) exhibited dominance in opposite hemispheres. Furthermore, 2 of these 3 cases (2.7%) were contralateral false positive cases, whereby fMRI identified the right-hemisphere as language dominant for right-handed individuals with tumors in the left hemisphere. Based on these findings, we concluded that the Wada test can be skipped if language dominancy can be detected by fMRI.

The role of 4D CT angiography for preoperative screening in patients with intracranial tumors.

INTRODUCTION: Four-dimensional computed tomography angiography (4D CTA) is now becoming an often used diagnostic imaging modality for the assessment of patients with intracranial tumors. The purpose of this study was to demonstrate the utility of 4D CTA for preoperative screening in patients with intracranial tumors as well as to examine the correlation between perfusion data and grading of gliomas. METHODS: We performed preoperative screening using 320-row detector CT scanner in 186 patients with intracranial tumors, and 115 patients were finally included in the study. Time-resolved subtracted maximum intensity projection images and volume-rendered images were reconstructed to evaluate vascular structures, tumor staining and incidental lesions. We also evaluated the perfusion functional map for gliomas to find correlations between their vascularity and tumor grading. RESULTS: We evaluated gliomas in 70 patients, meningiomas in 29, and other tumors in 16. Patients with gliomas of a pathologically higher grade showed high cerebral blood volume (p < 0.05). Tumor staining was observed on MIP images for 12 meningiomas, 4 gliomas, and 3 other tumors. Fifty patients showed a mass effect on vascular structures, seven had cerebral venous sinus obstruction, and two had aneurysms. No iatrogenic accidents with the CT procedure were reported. CONCLUSIONS: The 4D CTA technique is effective and safe for depicting vascular structures such as arteries, veins, tumor-related vessels, and direct and indirect anatomical complications such as vascular obstruction or vascular compression. This information is useful for preoperative screening. Although 4D CTA also provides perfusion data correlating with the tumor vascularity and grading of gliomas, its clinical value remains limited.

Comparison between Ki67 labeling index determined using image analysis software with virtual slide system and that determined visually in breast cancer.

BACKGROUND: In recent papers, Ki67 labeling index (LI) has been used to classify breast cancer patients into the low and high Ki67LI groups for comparison studies, which showed significant differences in many prognostic factors. It has not been clarified whether image analysis software can be used for calculating LI in breast cancer. In our study, we examined whether Ki67LI in breast cancer calculated using image analysis software correlates with that measured on the basis of visual. METHODS: Fifty patients were randomly selected among breast cancer patients who underwent surgical operation from March, 2010 to May, 2010 in our hospital without preoperative chemotherapy. In this study, for the virtual slide system (VSS: VS120-L100, Olympus, Tokyo, Japan), the high-resolution VSs of all the 50 patients were prepared as samples. The image analysis software use for calculating LI was Tissuemorph Digital Pathology (Tissuemorph DP: Visiopharm, Hoersholm, Denmark). The calculated LI was extracted from 3 to 5 views containing hot spots. The LI calculated using Tissuemorph DP was designed as LI/image/T. The digital image of 3 to 5 LI/image/T views was printed out, and on the digital photograph, we counted visually the number of Ki67-immunopositive cells in exactly the same area, and the percentage of Ki67-immunopositive cells was designed as LI/direct. Moreover, a pathologist's assistant (PA) determined the tumor area in the same specimen using VSS and calculated LI using Tissuemorph DP, which was designed as LI/image/PA. The chief pathologist (CP) similarly calculated LI which was designed as LI/image/CP. We evaluated the degree of agreement between different data sets "LI/image/T and LI/direct" and "LI/image/T, LI/image/CP, and LI/image/PA" by using interclass correlation coefficient (ICC). RESULTS: The average counts of cells were as follows: LI/direct, 3209.7 ± 1970.4 (SD); LI/image/T, 2601.6 ± 1697.1; LI/image/PA, 2886.5 ± 2027.5; LI/image/CP, 18805.5 ± 22293.4. The values of LI/direct and LI/image/T showed almost perfect agreement as showed by an ICC of 0.885 (95 % CI, 0.806-0.933; p < 0.001). The agreement among three investigators was almost perfect. The obtained ICC was 0.825 (95 % CI, 0.739-0.890; p < 0.001) among the data of LI/image/T, LI/image/CP and LI/image/PA. There were five cases that immunopositivity for Ki67 showed a more than 10 % disagreement between LI/direct and LI/image/T. CONCLUSION: The merits of calculating Ki67 LI using Tissuemorph DP are as follows. First, the staining intensity of the cells to be counted can be adjusted. Second, the portion of a tumor including "hot spots" for counting can be chosen. Third, many cancer cells can be counted more rapidly using Tissuemorph DP than by visual observation. However, it is important that pathologist should check and carry out the final decision of the data, when Ki67 LI using Tissuemorph DP is calculated.

Subpial Hematoma and Extravasation in the Interhemispheric Fissure with Subarachnoid Hemorrhage.

A recent report on computed tomography (CT) findings of contrast extravasation in subarachnoid hemorrhage (SAH) with Sylvian hematoma suggests that the occurrence of the hematoma is secondary to bleeding in the subpial space. Our patient was in his sixties and was admitted to the hospital because of loss of consciousness (Glasgow Coma Scale E4V1M4). SAH was diagnosed in plain head CT, and growing hematomas were observed in the Sylvian and interhemispheric fissures following a subarachnoid hemorrhage. CT angiography (CTA) using a dual-phase scan protocol revealed contrast extravasation in both the fissures in the latter phase, and hematoma in the interhemispheric fissure contained multiple bleeding points. This case indicates that the occurrence of subpial hematoma such as Sylvian hematoma can be a secondary event following subpial bleeding from damaged small vessels elsewhere in the cranium. Instead of four-dimensional (4D) CT, the dual-phase CTA technique may help detect minor extravasations with usual helical CT scanner.

Assessment of cerebrospinal fluid flow patterns using the time-spatial labeling inversion pulse technique with 3T MRI: early clinical experiences.

CSF imaging using the time-spatial labeling inversion pulse (time-SLIP) technique at 3T magnetic resonance imaging (MRI) was performed to assess cerebrospinal fluid (CSF) dynamics. The study population comprised 15 healthy volunteers and five patients with MR findings showing expansive dilation of the third and lateral ventricles suggesting aqueductal stenosis (AS). Signal intensity changes were evaluated in the tag-labeled CSF, untagged brain parenchyma, and untagged CSF of healthy volunteers by changing of black-blood time-inversion pulse (BBTI). CSF flow from the aqueduct to the third ventricle, the aqueduct to the fourth ventricle, and the foramen of Monro to the lateral ventricle was clearly rendered in all healthy volunteers with suitable BBTI. The travel distance of CSF flow as demonstrated by the time-SLIP technique was compared with the distance between the aqueduct and the fourth ventricle. The distance between the foramen of Monro and the lateral ventricle was used to calculate the CSF flow/distance ratio (CD ratio). The CD ratio at each level was significantly reduced in patients suspected to have AS compared to healthy volunteers. CSF flow was not identified at the aqueductal level in most of the patients. Two patients underwent time-SLIP assessments before and after endoscopic third ventriculostomies (ETVs). CSF flow at the ETV site was confirmed in each patient. With the time-SLIP technique, CSF imaging is sensitive enough to detect kinetic changes in CSF flow due to AS and ETV.

Brain natriuretic peptide in acute ischemic stroke.

Elevated serum brain natriuretic peptide (BNP) levels are associated with cardioembolic stroke mainly because of atrial fibrillation (AF). However, the mechanisms of increased serum BNP levels are hitherto unclear. We aimed to identify the factors associated with increased BNP levels in patients with acute ischemic stroke. We measured serum BNP levels in consecutive patients aged 18 years or older. Stroke subtypes were classified using the Trial of ORG 10172 in Acute Stroke Treatment criteria. Categorical variables included age, sex, smoking status, alcohol consumption status, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease (CAD), AF, antiplatelet therapy, and anticoagulant therapy. Continuous variables included hemoglobin, creatinine (Cr), ß-thromboglobulin, platelet factor 4, thrombin-antithrombin complex, and d-dimer levels. We further determined the relationship between serum BNP and intima-media thickness, left ventricular ejection fraction, size of infarction, National Institutes of Health Stroke Scale score on admission, and modified Rankin Scale (mRS) score at discharge. Of the 231 patients (mean age, 71 ± 12 years) with acute ischemic stroke (AIS), 36% were women. Serum BNP levels significantly correlated with CAD, AF, Cr, mRS, and cardioembolism (CE) (Dunnett method, P = .004). BNP levels were significantly higher in patients with larger infarcts, higher mRS scores, and higher CHADS2 scores. The levels were higher in patients with larger infarcts, higher mRS scores at discharge, and higher CHADS2 scores among AF patients.