Publications by authors named "Tomohiko Masumoto"

68 Publications

The utility of dynamic MRI in differentiating the hormone-producing ability of pituitary adenomas.

Jpn J Radiol 2021 Apr 21. Epub 2021 Apr 21.

Department of Diagnostic and Interventional Radiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Purpose: To investigate the relationship between dynamic magnetic resonance imaging (MRI) findings and hormonal activity in pituitary adenomas.

Methods: We retrospectively evaluated the dynamic MRI findings in 244 patients with pathologically confirmed pituitary adenomas and a diagnosis of clinically active prolactin (PRL)-producing adenomas. Among the 244 pituitary adenomas, 55, 16, 6, and 4 produced growth hormone (GH), PRL, adrenocorticotropic hormone, and thyroid-stimulating hormone, respectively, while 163 were non-functioning (NF) adenomas. For each adenoma, we calculated the washout rate (WR) and early (EER) and delayed (DER) tumour-to-normal-tissue enhancement ratios.

Results: The respective mean values of the WR, EER, and DER were 9.4%, 75.2%, and 64.5% for GH-producing adenomas; 6.2%, 117.1%, and 106.2% for PRL-producing adenomas; and 5.4%, 116.7%, and 108.7% for NF adenomas. GH-producing adenomas had significantly lower EER and DER values than PRL-producing (P < 0.001) and NF adenomas (P < 0.001). In ROC analysis of GH-producing and non-GH-producing adenomas, the areas under the curves of WR, EER, and DER were 0.593, 0.825, and 0.857, respectively.

Conclusion: There are differences in dynamic MRI features between GH-producing and non-GH-producing adenomas, which suggests that EER and DER may be useful for diagnosing GH-producing adenomas.
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http://dx.doi.org/10.1007/s11604-021-01121-9DOI Listing
April 2021

Diagnosing uterine cervical cancer on a single T2-weighted image: Comparison between deep learning versus radiologists.

Eur J Radiol 2021 Feb 5;135:109471. Epub 2020 Dec 5.

Department of Radiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Department of Radiology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.

Purpose: To compare deep learning with radiologists when diagnosing uterine cervical cancer on a single T2-weighted image.

Methods: This study included 418 patients (age range, 21-91 years; mean, 50.2 years) who underwent magnetic resonance imaging (MRI) between June 2013 and May 2020. We included 177 patients with pathologically confirmed cervical cancer and 241 non-cancer patients. Sagittal T2-weighted images were used for analysis. A deep learning model using convolutional neural networks (DCNN), called Xception architecture, was trained with 50 epochs using 488 images from 117 cancer patients and 509 images from 181 non-cancer patients. It was tested with 60 images for 60 cancer and 60 non-cancer patients. Three blinded experienced radiologists also interpreted these 120 images independently. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were compared between the DCNN model and radiologists.

Results: The DCNN model and the radiologists had a sensitivity of 0.883 and 0.783-0.867, a specificity of 0.933 and 0.917-0.950, and an accuracy of 0.908 and 0.867-0.892, respectively. The DCNN model had an equal to, or better, diagnostic performance than the radiologists (AUC = 0.932, and p for accuracy = 0.272-0.62).

Conclusion: Deep learning provided diagnostic performance equivalent to experienced radiologists when diagnosing cervical cancer on a single T2-weighted image.
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http://dx.doi.org/10.1016/j.ejrad.2020.109471DOI Listing
February 2021

Carcinosarcoma of the ovary: MR and clinical findings compared with high-grade serous carcinoma.

Jpn J Radiol 2021 Apr 20;39(4):357-366. Epub 2020 Nov 20.

Department of Radiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Purpose: To clarify imaging and clinical characteristics of ovarian carcinosarcoma (CS) compared with high-grade serous carcinoma (HGSC).

Methods: We retrospectively reviewed MR imagings of 12 patients with CS and 30 patients with HGSC and evaluated tumor size, shape, appearance, nature of cystic and solid components, hemorrhage, and necrosis. Age, premenopausal or postmenopausal, histologic subtype, presence of endometriosis, tumor markers, and stage were also evaluated. These parameters were compared using the Mann-Whitney U test and the chi-square test/Fisher's exact test.

Results: The mean size of CSs was 13.6 cm, and significantly larger than that of HGSCs (mean 9.0 cm, p = 0.022). The stained-glass appearance (67% vs. 23%, p = 0.013), hemorrhage (100% vs. 50%, p = 0.003), necrosis (75.0% vs. 13%, p = 0.000), and endometriosis (33% vs. 7%, p = 0.012) were significantly more common in CSs. The postmenopausal ratio of CSs was 100% and significantly higher than that of HGSCs (70.0%, p = 0.041). Among the tumor makers, only CA-125 was significantly lower in CSs than in HGSCs (mean 715.1 U/ml vs. 1677.1 U/ml, p = 0.009). The stage distribution was similar and was not significantly different.

Conclusion: CSs formed larger masses, and the stained-glass appearance, hemorrhage, and necrosis were more frequently observed in CSs.
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http://dx.doi.org/10.1007/s11604-020-01072-7DOI Listing
April 2021

Ovarian and non-ovarian teratomas: a wide spectrum of features.

Jpn J Radiol 2021 Feb 1;39(2):143-158. Epub 2020 Sep 1.

Department of Radiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Teratoma is a germ cell tumor (GCT) derived from stem cells of the early embryo and the germ line. Teratoma is the most common neoplasm of the ovaries and is usually diagnosed easily using imagings by detecting fat components. However, there are various histopathological types and the imaging findings differ according to the type. Teratoma usually occurs in the gonads or in the midline due to migration of primordial germ cells during development. The clinical course of teratomas depends on the age of the patient, histological type, and anatomical site. Sometimes teratomas show unusual manifestations, such as mature teratoma without demonstrable fat components, torsion, rupture, growing teratoma syndrome, anti-N-methyl-D-aspartate receptor encephalitis, and autoimmune hemolytic anemia. For all of these reasons, teratomas demonstrate a wide spectrum of imaging features and radiologists should be familiar with these variabilities. The present article aims to introduce a model encompassing types of GCTs based on their developmental potential, and to review several histopathological types in various anatomical sites and unusual manifestations of teratomas, with representative imaging findings.
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http://dx.doi.org/10.1007/s11604-020-01035-yDOI Listing
February 2021

Detection of the artery of Adamkiewicz using multidetector row computed tomography in patients with spinal arteriovenous shunt disease.

Pol J Radiol 2020 19;85:e163-e168. Epub 2020 Mar 19.

Department of Radiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Purpose: To plan a treatment strategy for a spinal arteriovenous shunt (SAVS), identifying the artery of Adamkiewicz (AKA) and its origin is indispensable. However, detecting the AKA is very difficult in patients with an SAVS when using computed tomography angiography (CTA) by the usual method to find the hairpin curved artery because dilated drainage veins nearly always coexist with the hairpin curved AKA. We designed a method to identify the AKA by focusing on the diameter and pathway of the anterior radiculomedullary arteries (RMAs).

Material And Methods: Seven consecutive patients with an SAVS were surveyed. They underwent contrast-enhanced CTA and conventional angiography from January 2009 to December 2012. Two readers evaluated the CTA images and assumed that the AKA was the artery that ran through the anterior portion of the neural foramen and continued to pass on the ventral side of the spinal cord.

Results: Among the seven patients, nine AKAs were detected with conventional angiography. When using our method, seven AKAs and six AKAs were identified on CTA by Reader 1 and Reader 2, respectively. The average sensitivity was 72.3%, and the specificity, accuracy, positive predictive value, and negative predictive value were sufficiently high (i.e. > 85%) for both readers. The kappa value for detecting the AKA was 0.98.

Conclusions: Detecting the origin of the AKA with CTA is challenging in patients with an SAVS. However, focusing on the diameter and pathway of the RMAs may allow successful identification.
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http://dx.doi.org/10.5114/pjr.2020.94075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172874PMC
March 2020

Urgent Proton Beam Therapy With Interinstitutional Transfer for Patients With Intracranial Rhabdomyosarcoma: Report of 3 Cases.

J Pediatr Hematol Oncol 2020 01;42(1):e12-e17

Departments of Pediatrics.

A number of cases have been reported in recent years regarding the use of proton beam therapy to mitigate adverse events affecting important cranial organs in cases of rhabdomyosarcoma at parameningeal sites. However, few reports have described the use of proton beam therapy as urgent radiotherapy for parameningeal rhabdomyosarcoma with intracranial extension. We treated 3 patients diagnosed with parameningeal rhabdomyosarcoma extending into the cranium who were assessed at other hospitals as suitable for urgent radiotherapy and transferred to our hospital for proton beam therapy. These patients comprised 2 boys and 1 girl 6 to 12 years of age at diagnosis, and proton beam therapy was started on days 5, 11, and 23 after diagnosis, respectively. Patients with parameningeal rhabdomyosarcoma extending into the cranium can be transferred to institutions equipped to perform proton beam therapy. To minimize the interval to starting therapy, medical information should be shared with institutions capable of providing such therapy as soon as the possibility of intracranial soft-tissue sarcoma is recognized. Proton beam therapy is 1 option for radiotherapy in cases of intracranial rhabdomyosarcoma.
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http://dx.doi.org/10.1097/MPH.0000000000001620DOI Listing
January 2020

Endoscopic endonasal cyst fenestration into the sphenoid sinus using the mucosa coupling method for symptomatic Rathke's cleft cyst: a novel method for maintaining cyst drainage to prevent recurrence.

J Neurosurg 2019 Nov 1:1-11. Epub 2019 Nov 1.

1Departments of Neurosurgery.

Objective: Rathke's cleft cyst (RCC) is a benign cystic lesion with a relatively high incidence of local recurrence that occasionally requires repeat surgery. To prevent recurrence, simple cyst fenestration and drainage of the cyst contents to the sphenoid sinus is recommended, but it occasionally recurs. The authors postulated that obstruction of fenestration is a main cause of recurrence, and they developed a method, named the "mucosa coupling method (MC method)," that maintains persistent drainage. In this method, the RCC epithelium and the mucosa of the sphenoid sinus are connected, which promotes re-epithelialization between the two epithelia, maintaining persistent drainage. The outcome of this method was compared with that of conventional cyst fenestration.

Methods: In a consecutive series of 40 patients with RCC, the surgical strategy was changed during the study period: from December 2009 to September 2014 (the conventional period), 24 patients were scheduled to be treated using the conventional fenestration method, whereas from September 2014 to September 2017 (the MC period), 16 patients were scheduled to be treated using the MC method. However, because of an intraoperative CSF leak, the fenestration was closed during surgery in 3 patients in the conventional period and 2 in the MC period; therefore, these 5 patients were excluded from the analysis. Twenty-one patients treated with the conventional fenestration method (conventional group) and 14 patients treated with the MC method (MC group) were analyzed. All patients regularly underwent MRI after surgery to detect reaccumulation of cyst contents. The rate of reaccumulation with and without reoperation, visual outcomes, endocrinological outcomes, and postoperative complications were compared between these two groups.

Results: The median follow-up period in all 35 patients was 48.0 months (range 1-96 months), 54.0 months (range 1-96 months) in the conventional group and 35.5 months (range 12-51 months) in the MC group. No reaccumulation was detected on MRI in the 14 patients in the MC group, whereas it was noted in 9 (42.9%) of 21 patients in the conventional group, and 2 of these 9 patients required repeat surgery. There were no significant differences in visual and endocrinological outcomes and complications between these two groups.

Conclusions: The MC method for RCC is effective for preventing obstruction of cyst fenestration, which contributes to preventing cyst reaccumulation. Furthermore, this method is equivalent to the conventional fenestration method in terms of visual and endocrinological outcomes and the complication rate.
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http://dx.doi.org/10.3171/2019.8.JNS191103DOI Listing
November 2019

Clinical usefulness of temporal subtraction CT in detecting vertebral bone metastases.

Eur J Radiol 2019 Sep 19;118:175-180. Epub 2019 Jul 19.

Department of Radiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Purpose: The purpose of this study was to determine whether temporal subtraction (TS) computed tomography (CT) contributes to the detection of vertebral bone metastases.

Method: The calculation of TS CT was composed of bony landmark detection, bone segmentation with a multiatlas-based method, and spatial registration. Temporal increase and decrease of the CT values were visualized in blue and red, respectively. Paired CT images of 20 patients with cancer and newly-developed vertebral metastases were analyzed. Control CT examinations of 20 different patients were also included. The presence of vertebral metastases on the TS CT was evaluated by two board-certified radiologists. Five additional board-certified radiologists and five radiology residents independently interpreted the 40 paired CT images with and without TS CT.

Results: In the lesion conspicuity evaluation, 96% of vertebral metastases were scored as excellent or good. In the image interpretation examination, according to free-response receiver operating characteristics analysis, the overall figure of merit (FOM) of the board-certified radiologist group was 0.892 and 0.898 with and without TS CT, respectively. The FOM of the resident group improved from 0.849 to 0.902 with viewing TS CT. In the sub-analysis focusing on the location of the lesion, the FOM of the resident group significantly improved from 0.75 to 0.92 in vertebral arch lesions (p = 0.001).

Conclusions: The TS CT may be useful to detect vertebral metastases because almost all the vertebral metastases were shown to be favorable visualization. The TS CT was proven to be especially helpful for radiology residents in detecting vertebral arch metastases.
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http://dx.doi.org/10.1016/j.ejrad.2019.07.024DOI Listing
September 2019

Primary cavernous sinus germinoma with atypical extension pattern: a case report and review of the literature.

Childs Nerv Syst 2019 09 22;35(9):1615-1619. Epub 2019 Feb 22.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Primary intracranial germinoma is a rare central nervous system tumor that usually arises in the pineal and the supra-sellar region. Here, we report a rare case of primary intracavernous sinus germinoma with an atypical extension pattern, with a comparison to germinomas originating from the cavernous sinus as described in the existing literature. A 12-year-old boy was admitted to our hospital with the chief complaint of the left-side ptosis and double vision. Magnetic resonance imaging showed homogenous enhanced mass lesion in the pineal region together with mass lesions in the lateral ventricle, left cavernous sinus, and temporal lobe, extending into the left masticator space. The enhanced mass in the intracavernous sinus originated from the cavernous sinus. Endoscopic third ventriculostomy and tumor biopsy was done. Pathological diagnosis was pure germinoma. After six courses of chemotherapy followed by radiation therapy, all the lesions decreased in size significantly. Only faint enhancement around the masticator space remained. We report a rare case of a germinoma that developed mainly in the cavernous sinus with additional tumor masses in the pineal region, ventricles, and temporal lobe. Although the lesions shrank significantly on the post-chemoradiation imaging, a long follow-up is necessary not only to check for symptoms, but also monitor imaging findings for possible serial changes in the residual region of the masticator space.
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http://dx.doi.org/10.1007/s00381-019-04092-5DOI Listing
September 2019

Interinstitutional patient transfers between rapid chemotherapy cycles were feasible to utilize proton beam therapy for pediatric Ewing sarcoma family of tumors.

Rep Pract Oncol Radiother 2018 Sep-Oct;23(5):442-450. Epub 2018 Sep 5.

Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Aim: To assess the feasibility of transferring to the University of Tsukuba Hospital for proton beam therapy (PBT) during intensive chemotherapy in children with Ewing sarcoma family of tumors (ESFT) who had been diagnosed and started their first-line treatment at prefectural or regional centers for pediatric oncology.

Background: The treatment of ESFT relies on a multidisciplinary approach using intensive neoadjuvant and adjuvant chemotherapies with surgery and radiotherapy. Multi-agent chemotherapy comprising vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE) is widely used for ESFT, and the interval between each course is very important for maintaining the intensity and effect of chemotherapy.

Materials And Methods: Clinical information of patients who received PBT and VDC-IE between April 2009 and May 2016 was collected retrospectively. The intervals between each course of VDC-IE and adverse events were assessed.

Results: Fifteen patients were evaluated. No delays in the intervals of chemotherapy due to transfer were observed. There were no adverse events caused during/just after transfer and no increases in adverse events. The estimated 4-year overall and event-free survival rates were 94.6% and 84.8%, respectively.

Discussion: Although the results of efficacy are preliminary, survival rates were comparable with past studies. More experience and follow-up are required to further assess the efficacy of PBT for patients with ESFT.

Conclusion: Multidisciplinary therapy for children with ESFT involving transfer to our hospital for PBT during VDC-IE was feasible without treatment delay or an increase in adverse events.
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http://dx.doi.org/10.1016/j.rpor.2018.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126410PMC
September 2018

Evaluation of the extent of resection and detection of ischemic lesions with intraoperative MRI in glioma surgery: is intraoperative MRI superior to early postoperative MRI?

J Neurosurg 2018 Aug;131(1):209-216

Departments of1Neurosurgery and.

Objective: MRI scans obtained within 48-72 hours (early postoperative MRI [epMRI]), prior to any postoperative reactive changes, are recommended for the accurate assessment of the extent of resection (EOR) after glioma surgery. Diffusion-weighted imaging (DWI) enables ischemic lesions to be detected and distinguished from the residual tumor. Prior studies, however, revealed that postoperative reactive changes were often present, even in epMRI. Although intraoperative MRI (iMRI) is widely used to maximize safe resection during glioma surgery, it is unclear whether iMRI is superior to epMRI when evaluating the EOR, because it theoretically shows fewer postoperative reactive changes. In addition, the ability to detect ischemic lesions using iMRI has not been investigated.

Methods: The authors retrospectively analyzed prospectively collected data in 30 patients with glioma (22 and 8 patients with enhancing and nonenhancing lesions, respectively) who underwent tumor resection. These patients had received preoperative MRI within 24 hours prior to surgery, postresection radiological evaluation with iMRI during surgery, and epMRI within 24 hours after surgery, with all neuroimaging performed using identical 1.5T MRI scanners. The authors compared iMRI or epMRI with preoperative MRI, and defined a postoperative reactive change as a new postoperative enhancement or T2 high-intensity area (HIA), if this lesion was outside of the preoperative original tumor location. In addition, postoperative ischemia was evaluated on DWI. The iMRI and epMRI findings were compared in terms of 1) postoperative reactive changes, 2) evaluation of the EOR, and 3) presence of ischemic lesion on DWI.

Results: In patients with enhancing lesions, a new enhancement was seen in 8 of 22 patients (36.4%) on iMRI and in 12 of 22 patients (54.5%) on epMRI. In patients with nonenhancing lesions, a new T2 HIA was seen in 4 of 8 patients (50.0%) on iMRI and in 7 of 8 patients (87.5%) on epMRI. A discrepancy between the EOR measured on iMRI and epMRI was noted in 5 of the 22 patients (22.7%) with enhancing lesions, and in 3 of the 8 patients (37.5%) with nonenhancing lesions. The occurrence of ischemic lesions on DWI was found in 5 of 30 patients (16.7%) on iMRI, whereas it was found in 16 of 30 patients (53.3%) on epMRI (p = 0.003); ischemic lesions were underestimated on iMRI in 11 patients.

Conclusions: Overall, given the lower incidence of postoperative reactive changes on iMRI, it was superior to epMRI in evaluating the EOR in patients with glioma, both with enhancing and nonenhancing lesions. However, because ischemic lesions can be overlooked on iMRI, the authors recommend only the additional DWI scan during the early postoperative period. Clinicians need to be mindful about not overestimating the presence of residual tumor on epMRI due to the high incidence of postoperative reactive changes.
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http://dx.doi.org/10.3171/2018.3.JNS172516DOI Listing
August 2018

Clinical and biological significance of adamantinomatous craniopharyngioma with CTNNB1 mutation.

J Neurosurg 2018 Aug;131(1):217-226

Departments of1Neurosurgery.

Objective: The Wnt/β-catenin signaling pathway is strongly implicated in the pathogenesis of adamantinomatous craniopharyngioma (adaCP). However, there is no evidence that the CTNNB1 mutation activates the target gene of Wnt/β-catenin signaling, and it is unknown whether it affects the tumorigenesis of adaCP. To assess the effect of the CTNNB1 mutation of adaCP, the authors analyzed the correlation between the mutation and clinical, radiological, pathological, and biological findings.

Methods: Between 2003 and 2015, 42 patients (24 male and 18 female, median age 42 years) with either papillary craniopharyngioma (papCP) or adaCP underwent tumor resection at the authors' institution. BRAF V600E and CTNNB1 in papCP and adaCP samples were sequenced by next-generation sequencing and the Sanger method, and mRNA expression levels of Axin2 and BMP4 were evaluated by RT-PCR. Axin2, BMP4, β-catenin, and BRAF expression were evaluated by immunohistochemistry. Other data were collected from clinical reports.

Results: The BRAF V600E mutation was detected in all 10 cases of papCP (100%). CTNNB1 exon 3 mutations were detected in 21 of 31 (68%) cases of adaCP, excluding 1 case for which there were no available sequence data. The mRNA expression level of Axin2 was significantly higher in adaCPs with a CTNNB1 mutation than in those without (p < 0.05). The immunohistochemical findings of Axin2 and BMP4 did not correlate with CTNNB1 mutation positivity. When patients who received adjuvant radiation therapy were excluded, progression-free survival was shorter in the mutation-positive group than in the mutation-negative group (log-rank test, p = 0.031). Examination of clinical characteristics and immunohistochemical findings of adaCPs showed that there was no significant correlation between CTNNB1 mutation positivity and age, sex, tumor volume, gross-total resection, optic tract edema, calcification, or T1 signal intensity of cyst fluid on MRI, β-catenin, and MIB-1 index.

Conclusions: These results raise the possibility that the CTNNB1 mutation in adaCP may be associated with disease recurrence, and genes related to the Wnt/β-catenin signaling pathway might represent a therapeutic target.
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http://dx.doi.org/10.3171/2018.3.JNS172528DOI Listing
August 2018

Treatment Strategy Based on Plaque Vulnerability and the Treatment Risk Evaluation for Internal Carotid Artery Stenosis.

Neurol Med Chir (Tokyo) 2018 May 3;58(5):191-198. Epub 2018 Mar 3.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba.

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are not appropriate treatment procedure for internal carotid artery stenosis (ICAS) in some patients. The importance of plaque vulnerability and the treatment risk evaluation has been reported. We analyzed whether treatment selection contributes to the outcome. We retrospectively examined 121 patients who underwent CEA or CAS. Treatment was selected based on plaque vulnerability and the treatment risk evaluation. We selected CAS for patients with stable plaques and CEA for patients with unstable plaques, and considered the other treatment for high-risk patients. The patients were classified as the stable plaque (Stable: n = 42), the unstable plaque and CEA low risk (Unstable/Low: n = 30), and the CEA high-risk (Unstable/High: n = 49). Frequency of perioperative stroke, myocardial infarction, death, and systemic complications was examined. CEA and CAS were performed in 35 and 86 patients, respectively. One patient (2.9%) had a stroke in CEA and five patients (5.8%) in CAS (P = 0.50). Systemic complications were observed in two patients (5.7%) in CEA and six (7.1%) in CAS (P = 0.80). There were no differences in stroke (Stable; 2.4%, Unstable/Low; 3.2%, and Unstable/High; 8.2%) and systemic complications (Stable; 9.5%, Unstable/Low; 3.3%, and Unstable/High; 6.1%) among three groups (P = 0.44 and P = 0.59, respectively). The treatment selection based on plaque vulnerability and the treatment risk evaluation could provide good treatment outcome for high-risk patients. It is ideal to select an appropriate treatment for ICAS by one neurovascular team.
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http://dx.doi.org/10.2176/nmc.oa.2017-0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958040PMC
May 2018

Intradiploic Arachnoid Cyst with Meningothelial Hyperplasia: A Case Report.

NMC Case Rep J 2017 Jan 5;4(1):19-22. Epub 2016 Dec 5.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

We report the case of a 40-year-old man presenting with focal headache and a bulge at the right parietal bone, diagnosed as an intradiploic arachnoid cyst. The cyst wall included "meningothelial hyperplasia," which is a rare finding. While over 40 cases of intradiploic arachnoid cysts have been reported to date, meningothelial hyperplasia in an intradiploic arachnoid cyst does not appear to have been reported. We also discuss the pathological findings of arachnoid cysts with meningothelial hyperplasia and mechanisms of enlargement of the arachnoid cyst.
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http://dx.doi.org/10.2176/nmccrj.cr.2016-0147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364902PMC
January 2017

Enlargement of the brachial plexus on magnetic resonance imaging: a novel finding in adult-onset Krabbe disease.

BJR Case Rep 2016 28;2(3):20150213. Epub 2016 Jul 28.

Department of Radiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.

Adult-onset Krabbe disease is an autosomal recessive degenerative leukodystrophy that presents with bilateral corticospinal tract involvement on MRI. Although peripheral nerve involvement is a known manifestation of Krabbe disease, MRI findings of peripheral nerve abnormalities are limited to the cranial nerves and spinal nerve roots. In this case report, we discuss two cases of adult-onset Krabbe disease with brachial plexus enlargement on MRI. Adult-onset Krabbe disease should be included in the differential diagnoses when brachial plexus enlargement and white matter lesions involving corticospinal tracts present simultaneously.
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http://dx.doi.org/10.1259/bjrcr.20150213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243345PMC
July 2016

Early Postoperative Expansion of Parenchymal High-intensity Areas on T2-weighted Imaging Predicts Delayed Cerebral Edema Caused by Carmustine Wafer Implantation in Patients with High-grade Glioma.

Magn Reson Med Sci 2016 Jul 28;15(3):299-307. Epub 2015 Dec 28.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba.

Background: Carmustine (BCNU) wafer (Gliadel(®) Wafer) implantation after tumor resection is an approved treatment for high-grade glioma (HGG). These wafers change various characteristics on early postoperative magnetic resonance imaging (ep-MRI) including slight expansion of high-intensity areas on T2-weighted imaging (ep-T2-HIAs) into adjacent parenchyma without restricted diffusivity. We assessed the frequency of the ep-T2-HIAs after BCNU wafer implantation in HGG patients. Moreover, we focused on ep-T2-HIA expansion and its relation to delayed cerebral edema.

Methods: Twenty-five consecutive HGG patients who underwent BCNU wafer implantation were assessed. First, patients were divided into ep-T2-HIA and non-ep-T2-HIA groups, and the incidence of delayed adverse effects was compared between the two groups. Subsequently, the patients were divided into delayed edema and non-delayed edema groups, and pre-, intra-, and postoperative data were compared between the two groups.

Results: The ep-T2-HIA expansion and the delayed edema were evident in 9 cases (36%) and 12 cases (48%), respectively. In comparison of the ep-T2-HIA and non-ep-T2-HIA groups, delayed edema was the only delayed adverse effect associated with ep-T2-HIA expansion (P = 0.004). Univariate analysis showed a significantly higher ratio of delayed edema in the subgroups with maximal diameter of removed cavity ≤40 mm (P = 0.047) and the ep-T2-HIA expansion in comparison of the delayed edema and non-delayed edema groups. Multivariate analysis showed that the ep-T2-HIA expansion was the only independent factor associated with delayed edema (P = 0.021).

Conclusion: In BCNU wafer implantation cases, ep-T2-HIA expansion was a predictive factor for delayed cerebral edema.
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http://dx.doi.org/10.2463/mrms.mp.2015-0054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608126PMC
July 2016

Essentials of Brain MRS: Fundamentals and Clinical Applications.

Igaku Butsuri 2016 ;36(2):85-91

Faculty of Medicine, University of Tsukuba.

H-MRS (proton magnetic resonance spectroscopy) is a method for analyzing material components using the difference of the frequency (chemical shift) in magnetic resonance. H-MRS for human body is able to diagnose the clinical conditions by non-invasive analysis of materials in organs. However, the mechanical limitations and complexity in analyses prevented it from becoming popular as MRI (magnetic resonance imaging). Recently, an ideal environment for H-MRS is commonly available such as stronger magnetic field and improved software, yet we still lack common knowledges about H-MRS which makes whom plans to start it difficult. In this article, the principle, tips, clinical applications and spectrum evaluations were explained focusing on novice users.
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http://dx.doi.org/10.11323/jjmp.36.2_85DOI Listing
June 2017

A Japanese, Multicenter, Open-label, Phase 3 Study to Investigate the Safety and Efficacy of Gadobutrol for Contrast-enhanced MR Imaging of the Central Nervous System.

Magn Reson Med Sci 2016 21;15(2):227-36. Epub 2015 Dec 21.

Department of Radiology, Ota Memorial Hospital.

Purpose: Gadobutrol 1.0 M is macrocyclic gadolinium-based contrast agent for magnetic resonance imaging (MRI). This multicenter, open-label, phase 3 study aimed to investigate the efficacy and safety of gadobutrol-enhanced versus unenhanced MRI in the visualization and diagnosis of central nervous system (CNS) lesions in Japanese patients.

Methods: A total of 223 patients referred for contrast-enhanced MRI of the CNS underwent unenhanced and gadobutrol-enhanced (0.1 mmol/kg body weight) MRI. The unenhanced and combined (unenhanced and enhanced) images were evaluated by three independent readers in a blinded manner for degree of contrast enhancement, border delineation, internal morphology, and number of detected lesions (primary variables), and for primary diagnosis and diagnostic confidence. Final clinical diagnoses were established by an independent truth committee consisting of two neurosurgeons. Sensitivity, specificity, and accuracy were calculated for the detection of malignancy and the preciseness of diagnoses (secondary variables) by comparing the results obtained by the blinded readers and the truth committee.

Results: Gadobutrol enhancement significantly improved three visualization parameters in MR images: contrast enhancement, border delineation, and internal morphology (P < 0.0001). Non-inferiority was achieved for mean number of lesions detected. Gadobutrol-enhanced imaging provided significant improvements in sensitivity and accuracy for the detection of malignant disease with no loss in specificity, and also improvements in accuracy of exact match diagnosis and diagnostic confidence. Drug-related adverse events were reported in 6 out of 223 patients (2.7%); all were non-serious.

Conclusion: Gadobutrol is an effective and well-tolerated contrast agent for MR imaging of the CNS.
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http://dx.doi.org/10.2463/mrms.mp.2015-0083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600060PMC
December 2016

Radiation-induced angiosarcoma of the brain.

BJR Case Rep 2016 1;2(2):20150374. Epub 2015 Dec 1.

Department of Diagnostic and Interventional Radiology, University of Tsukuba Hospital, Ibaraki, Japan.

Primary angiosarcoma of the central nervous systemis unusual.We encountered a case of radiation-induced angiosarcoma of the brain. A 65-year-old male was referred to our hospital with drowsiness for the last 6 months. He had undergone radiation therapy for pituitary adenoma 43 years ago. An MRI revealed a right temporal lobe tumour that consisted of a well-demarcated haemorrhagic lesion and an avid contrast enhancement, with significant vasogenic oedema. Surgical resection was performed and a post-operative pathological diagnosis of an angiosarcoma was made. A Thorotrast-associated angiosarcoma has been, hitherto, the only reported case of radiation-induced angiosarcoma of the brain. We present an extremely rare case of primary angiosarcoma of the brain, occurring after external beam radiotherapy.
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http://dx.doi.org/10.1259/bjrcr.20150374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180856PMC
December 2015

Movable intraoperative magnetic resonance imaging incorporating a seismic system.

Clin Neurol Neurosurg 2015 Aug 14;135:57-61. Epub 2015 May 14.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Introduction: A high-field ceiling-mounted and movable intraoperative MR imaging (iMRI) can minimize additional risks for MRI and enhance safety by not moving the patient. In this system, hanging the heavy magnet from the ceiling requires structural stability; this stability was confirmed in earlier studies, but not proved during a seismic event.

Objective: We have installed a 1.5 T movable iMRI system with an incorporated seismic system in our hospital in Japan, a seismic event-prone region. This arrangement is the first in the world, to our knowledge. The objective of this study was to describe the mechanism of this seismic system and the first clinical experience using this system.

Methods: The seismic system consists of a stabilizer pad that is mounted directly under the magnet, in addition to the structural stability. The seismic system was tested with using a shaker table testing at a test laboratory.

Results: Ninety-one patients underwent neurosurgical intervention using this iMRI and seismic system at our hospital. In all patients, intra-, pre, and/or postoperative MR images were successfully obtained, and image quality was excellent. The workflow of moving the magnet and scanning were smooth and unproblematic. We had 169 seismic events in our city during this time period, but had no incidental or accidental events related to the seismic events.

Conclusion: With the use of the seismic system, a ceiling-mounted, movable iMRI system can be more safely used. This seismic system may contribute to the spread of movable iMRI systems in countries where seismic events occur.
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http://dx.doi.org/10.1016/j.clineuro.2015.05.003DOI Listing
August 2015

Optic chiasmal edema observed on T2-weighted MR images: a reversible finding in obstructive hydrocephalus.

Jpn J Radiol 2015 Mar 29;33(3):140-5. Epub 2015 Jan 29.

Department of Radiology, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-0005, Japan,

Purpose: To evaluate the clinical significance of optic chiasmal edema (OCE) observed in hydrocephalus.

Materials And Methods: Twenty patients with obstructive hydrocephalus and eight patients with communicating hydrocephalus were recruited. We classified both groups into OCE-positive and negative subgroups on three-dimensional T2-weighted images. In the obstructive hydrocephalus group, the pre- and postoperative periventricular hyperintensity (PVH) grade, Evans index, and third ventricle diameter were compared between the subgroups. The visual disturbances were reviewed in the medical records.

Results: Eleven obstructive hydrocephalus patients (55 %) had OCE, while none of communicating hydrocephalus patients did. OCE was improved in all patients postoperatively. Preoperative PVH grade was significantly higher in the OCE-positive subgroup (p < 0.01). There were no statistically significant differences in the other indices. Visual disturbances were observed in two OCE-negative patients alone.

Conclusion: OCE is a reversible finding frequently observed in obstructive hydrocephalus and may not be associated with visual disturbances.
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http://dx.doi.org/10.1007/s11604-015-0393-6DOI Listing
March 2015

Influence of echo time in quantitative proton MR spectroscopy using LCModel.

Magn Reson Imaging 2015 Jun 23;33(5):644-8. Epub 2015 Jan 23.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba.

Objective: The objective of this study was to elucidate the influence on quantitative analysis using LCModel with the condition of echo time (TE) longer than the recommended values in the spectrum acquisition specifications.

Methods: A 3T magnetic resonance system was used to perform proton magnetic resonance spectroscopy. The participants were 5 healthy volunteers and 11 patients with glioma. Data were collected at TE of 72, 144 and 288ms. LCModel was used to quantify several metabolites (N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds). The results were compared with quantitative values obtained by using the T2-corrected internal reference method.

Results: In healthy volunteers, when TE was long, the quantitative values obtained using LCModel were up to 6.8-fold larger (p<0.05) than those obtained using the T2-corrected internal reference method. The ratios of the quantitative values obtained by the two methods differed between metabolites (p<0.05). In patients with glioma, the ratios of quantitative values obtained by the two methods tended to be larger at longer TE, similarly to the case of healthy volunteers, and large between-individual variation in the ratios was observed.

Conclusions: In clinical practice, TE is sometimes set longer than the value recommended for LCModel. If TE is long, LCModel overestimates the quantitative value since it cannot compensate for signal attenuation, and this effect is different for each metabolite and condition. Therefore, if TE is longer than recommended, it is necessary to account for the possibly reduced reliability of quantitative values calculated using LCModel.
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http://dx.doi.org/10.1016/j.mri.2015.01.015DOI Listing
June 2015

Anatomical risk factors for ischemic lesions associated with carotid artery stenting.

Interv Neuroradiol 2014 Dec 5;20(6):746-54. Epub 2014 Dec 5.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba; Ibaraki, Japan.

The purpose of this study was to investigate the anatomical risk factors for ischemic lesions detected by diffusion-weighted imaging (DWI) associated with carotid artery stenting (CAS). DWI was performed within four days after CAS in 50 stenotic lesions between January 2008 and September 2013. We retrospectively analyzed the correlation between the anatomical factors and ischemic lesions associated with CAS. Post-procedural DWI revealed new ischemic lesions after 24 (48%) of the 50 CAS procedures. All three patients with common carotid artery tortuosity, defined as the presence of severe angulation (less than 90 degrees) in the common carotid artery, developed new ischemic lesions. However, there were no significant differences between the patients with and without tortuosity, likely due to the small number of cases. Meanwhile, seven of eight patients with internal carotid artery tortuosity, defined as the presence of severe angulation (less than 90 degrees) in the cervical segment of the internal carotid artery, developed new ischemic lesions. A multivariate analysis showed internal carotid artery tortuosity (odds ratio: 11.84, 95% confidence interval: 1.193-117.4, P= 0.035) to be an independent risk factor for the development of ischemic lesions associated with CAS. Anatomical factors, particularly severe angulation of the internal carotid artery, have an impact on the risk of CAS. The indications for CAS should be carefully evaluated in patients with these factors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295248PMC
http://dx.doi.org/10.15274/INR-2014-10075DOI Listing
December 2014

Bevacizumab in Japanese patients with malignant glioma: from basic research to clinical trial.

Onco Targets Ther 2014 5;7:1551-62. Epub 2014 Sep 5.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

An antiangiogenic approach is especially suitable for the treatment of malignant gliomas. Recently, two large clinical trials in newly diagnosed glioblastoma (the Avastin in Glioblastoma study and Radiation Therapy Oncology Group 0825 study) showed a 3- to 4-month prolongation of progression-free survival (PFS) with bevacizumab, but no significant effect on overall survival (OS). Japan is the first, and so far only, country to approve the use of bevacizumab in newly diagnosed glioblastoma in combination with radiotherapy and temozolomide chemotherapy. The drug is also approved for use as monotherapy for recurrent glioblastoma and certain other types of high-grade glioma after previous therapy. The effectiveness of bevacizumab on Japanese malignant glioma patients was reviewed. The Phase II clinical trial demonstrated that the PFS with bevacizumab alone was 34% at 6 months and 3.3 months at median for 32 patients with recurrent malignant gliomas. In the Avastin in Glioblastoma study, 44 Japanese patients were registered from Japan. PFS and OS for bevacizumab combined with standard temozolomide and radiotherapy were 12.2 months and 29.2 months at median, respectively, for the patients with newly diagnosed glioblastoma. PFS and OS tended to be longer for those treated with bevacizumab than for those not treated with the drug. In addition, biomarkers of bevacizumab effectiveness were investigated in Japanese patients. Vascular endothelial growth factor concentration, matrix metalloproteinase 9 activities in urine, and apparent diffusion coefficient values on magnetic resonance imaging may be biomarkers that predict patient prognosis. Finally, novel experiments for vascular endothelial growth factor antibody action were described; these include the induction of glioma cell apoptosis, an antibody treatment failure model, and a study of the synergistic effect with chemotherapeutic agents.
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http://dx.doi.org/10.2147/OTT.S67621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161529PMC
September 2014

A new mechanism of cerebrospinal fluid leakage after lumboperitoneal shunt: a theory of shunt side hole--case report.

Neurol Med Chir (Tokyo) 2014 5;54(7):572-7. Epub 2013 Dec 5.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba.

Cerebrospinal fluid (CSF) overdrainage after lumboperitoneal (LP) shunt placement for the patients with idiopathic normal pressure hydrocephalus (iNPH) is mainly caused by insufficient management of pressure settings of the shunt valve and/or siphon effect of shunt systems induced by the patient's postural changes. We here report a unique case of intracranial hypotension (IH) due to CSF leakage after LP shunt placement in which another mechanism leads to the CSF leakage. A 67-year-old man suffered from persistent headache worsening with postural change 2 months after LP shunt reconstruction for iNPH. Brain computed tomography scan showed bilateral chronic subdural hematomas (CSDH). Lumbar images including shuntography and magnetic resonance imaging showed the tip of the lumbar catheter was spontaneously pulled out close to the dura mater with expansion of the epidural space due to CSF leakage from a shunt side hole of the lumbar catheter to the epidural space. Shunt removal and subsequent irrigation of CSDH improved his headache. CSF leakage in our case differs from those in previous reports, because early and enormous CSF leakage into the epidural space can be explained only by a different mechanism through a side hole just located in the epidural space in our case. We must pay attention to the possibility of this rare cause of IH due to CSF leakage in patients suffering from postural headache after LP shunt placement.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533463PMC
http://dx.doi.org/10.2176/nmc.cr2013-0067DOI Listing
October 2016

Clinical characteristics and neuroimaging findings in 12 cases of recurrent glioblastoma with communicating hydrocephalus.

Neurol Med Chir (Tokyo) 2013 ;53(7):474-81

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Clinically, recurrent glioblastoma multiforme (GBM) is often associated with communicating hydrocephalus. We hypothesized that there are specific magnetic resonance (MR) imaging findings at the diagnosis of recurrent GBM that predict subsequent hydrocephalus. Various clinical characteristics were investigated including outcome and MR imaging findings in 12 patients with recurrent GBM followed by hydrocephalus (Hydro group) and 21 patients with recurrent GBM without hydrocephalus (Non-hydro group). Patient age and presence of communicating hydrocephalus were significantly associated with poor outcome. Median survival with recurrent GBM was longer in the Non-hydro group than in the Hydro group. Low Karnofsky performance status (KPS) and poor recursive partitioning analysis (RPA) class (RPA class 3, 5, 6, or 7) at the diagnosis of recurrent GBM were associated with the presence of hydrocephalus. The incidence of leptomeningeal dissemination after recurrent GBM was higher in the Hydro group than in the Non-hydro group. Evans index and fractional anisotropy value showed no difference at the diagnosis of recurrent GBM, but some MR imaging findings indicated that lesion attached to the basal cistern and/or ventricle was closely associated with subsequent hydrocephalus. We recommend careful monitoring of the ventricle size and leptomeningeal dissemination, especially in patients with low KPS and/or poor RPA class, if MR imaging indicates that the lesion is attached to the basal cistern and/or ventricle at recurrence of GBM.
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http://dx.doi.org/10.2176/nmc.53.474DOI Listing
April 2014

Risk factors of ischemic lesions related to cerebral angiography and neuro-interventional procedures.

Neurol Med Chir (Tokyo) 2013 ;53(6):381-7

Department of Neurosurgery, University of Tsukuba, Japan.

Embolic stroke is not a rare complication of cerebral angiography. The risk factors for incidental embolism after cerebral angiography were retrospectively examined using diffusion-weighted magnetic resonance imaging (DWI) in 180 patients who underwent 247 angiography procedures, consisting of 174 diagnostic angiography and 73 interventional procedures, and magnetic resonance imaging including DWI within 72 hours after angiography. The two neuroradiologists in our hospital detected embolism after cerebral angiography as high-intensity lesions (HIL) on DWI. The relationships between HIL on DWI and procedural factors were evaluated. DWI after cerebral angiography revealed HIL related to the procedure in 72 of 247 angiographies. In all procedures, age (p < 0.01), past history of cerebral infarction (p < 0.05), anti-platelet therapy (p < 0.05), neuro-intervention (p < 0.01), and total amount of contrast medium (odds ratio [OR] 2.125, 95% confidence interval [CI] 1.045-4.321) were significantly correlated with HIL. In diagnostic angiography, the performance of the procedure by a resident operator (OR 2.526, 95% CI 1.214-5.254) was significantly correlated with HIL. Age, past history of cerebral infarction, and previous anti-platelet therapy determined the risk of atherosclerotic changes in patients. The neuro-intervention and total amount of contrast medium used could predict the risk of time limitations for angiography. Resident operator is also a risk factor. This study demonstrates the importance of improving the risk of time limitations for angiography and the risk due to operator inexperience. Further training of residents may be needed to reduce the occurrence of embolic complications.
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http://dx.doi.org/10.2176/nmc.53.381DOI Listing
April 2014

Spinal dural arteriovenous fistula with lipomyelodysplasia.

Neurol Med Chir (Tokyo) 2013 ;53(2):107-9

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

A 72-year-old man presented with a very rare case of spinal dural arteriovenous fistula (AVF) with lipomyelodysplasia manifesting as progressive paraparesis and bladder dysfunction. Magnetic resonance imaging revealed a spinal lipoma associated with tethered cord and spinal cord swelling with dilated perimedullary veins. Embolization of the spinal dural AVF was successfully performed, and is an optional treatment for coexisting spinal dural AVF and lipomyelocele in adults.
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http://dx.doi.org/10.2176/nmc.53.107DOI Listing
January 2014

[Recently developed MR imaging sequences and clinical applications].

No Shinkei Geka 2012 Oct;40(10):859-69

Department of Radiology, University of Tsukuba, Ibaraki Japan.

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October 2012

Elevated diffusion anisotropy in gray matter and the degree of brain compression.

J Neurosurg 2012 Aug 8;117(2):363-71. Epub 2012 Jun 8.

Department of Neurosurgery, University of Tsukuba, Tsukuba, Japan.

Object: For several decades, clinicians have predicted intraparenchymal brain pressure or brain tissue compression indirectly based on the degree of distortion of the midline structures (midline shift) and ventricle wall (ventriculomegaly) observed on conventional MRI. However, this method has several limitations. Diffusion tensor imaging (DTI) is a novel MRI technique that can provide information about the microstructural properties of compressed tissue. In this study, the authors evaluated whether DTI can precisely define the degree of tissue compression in patients with chronic subdural hematoma (CSDH).

Methods: The study sample consisted of 18 patients (mean age 71 years, 10 men and 8 women) with unilateral CSDH and 12 age-matched volunteers. Diffusion tensor imaging results were acquired before and after the surgical irrigation in the CSDH group. Subdural pressure during the operation was also measured. Fractional anisotropy (FA) values were evaluated at several locations, including the gray matter.

Results: The FA values of the gray matter, especially in the caudate nucleus and putamen, were increased in the patients with CSDH compared with the control group. The change in FA data before and after surgery (ΔFA) correlated with the degree of tissue compression evaluated by measurement of the subdural pressure. Furthermore, the increased FA values in patients with CSDH decreased after surgery.

Conclusions: These findings indicate that FA values of the gray matter, especially in the caudate nucleus and putamen, may be important markers of tissue compression. The assessment of FA values of the gray matter will result in a new, less-invasive diagnostic technique to evaluate the degree of brain compression.
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http://dx.doi.org/10.3171/2012.4.JNS112305DOI Listing
August 2012