Faculty Profiles - NAGANAWA, Shinji

Glymphatic imaging using MRI. Reviewed International journal Open Access

Toshiaki Taoka, Shinji Naganawa

Journal of magnetic resonance imaging : JMRI Vol. 51 ( 1 ) page： 11 - 24 2020.1

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

In recent years, the existence of a mass transport system in the brain via cerebrospinal fluid (CSF) or interstitial fluid (ISF) has been suggested by many studies. The glymphatic system is hypothesized to be a waste clearance system of the CSF through the perivascular and interstitial spaces in the brain. Tracer studies have primarily been used to visualize or evaluate the waste clearance system in the brain, and evidence for this system has accumulated. The initial study that identified the glymphatic system was an in vivo tracer study in mice. In that study, fluorescent tracers were injected into the cisterna magna and visualized by two-photon microscopy. MRI has also been used to evaluate glymphatic function primarily with gadolinium-based contrast agents (GBCAs) as tracers. A number of GBCA studies evaluating glymphatic function have been conducted using either intrathecal or intravenous injections. Stable isotopes, such as 17 O-labeled water, may also be used as tracers since they can be detected by MRI. In addition to tracer studies, several other approaches have been used to evaluate ISF dynamics within the brain, including diffusion imaging. Phase contrast evaluation is a powerful method for visualizing flow within the CSF space. In order to evaluate the movement of water within tissue, diffusion-weighted MRI represents another promising technique, and several studies have utilized diffusion techniques for the evaluation of the glymphatic system. This review will discuss the findings of these diffusion studies. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;51:11-24.

DOI： 10.1002/jmri.26892

中枢神経系原発anaplastic lymphoma kinase陽性未分化大細胞リンパ腫の1例 Reviewed

Celebrating the beginning of international journal collaboration. Reviewed Open Access

Shinji Naganawa, Yukunori Korogi

Japanese journal of radiology Vol. 38 ( 1 ) page： 1 - 2 2020.1

佐々木裕太郎, 中道玲瑛, 伊藤信嗣, 川井恒, 岩野信吾, 田岡俊昭, 加藤克彦, 川島直美, 下山芳江, 長縄慎二

映像情報Medical Vol. 52 ( 1 ) page： 82 - 83 2020.1

Quantification of Endolymphatic Space Volume after Intravenous Administration of a Single Dose of Gadolinium-based Contrast Agent: 3D-real Inversion Recovery versus HYDROPS-Mi2. Reviewed Open Access

Toshio Ohashi, Shinji Naganawa, Ai Takeuchi, Toshio Katagiri, Kayao Kuno

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 19 ( 2 ) page： 119 - 124 2020

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Recently, the use of 3D real inversion recovery (3D-real IR) imaging has been proposed for the evaluation of endolymphatic hydrops (EH). This method shows similar contrast between the endolymphatic and perilymphatic spaces and surrounding bone compared with the hybrid of reversed image of positive endolymph signal and native image of perilymph signal multiplied with heavily T2-weighted MR cisternography (HYDROPS-Mi2) image. We measured the volume of the endolymphatic space using 3D-real IR and HYDROPS-Mi2 images, and compared the measurements obtained with both techniques. METHODS: HYDROPS-Mi2 and 3D-real IR images were obtained for 30 ears from 15 patients with clinical suspicion of EH; imaging was performed 4 h after intravenous administration of a single dose of gadolinium-based contrast agent. We measured the volume of the endolymphatic space in the cochlea and vestibule by manually drawing the regions of interest. The correlation between endolymphatic volume determined from HYDROPS-Mi2 images and 3D-real IR images was calculated. RESULTS: There was a strong positive linear correlation between the cochlear and vestibular endolymphatic volume determined from HYDROPS-Mi2 and 3D-real IR images. The Spearman's rank correlation coefficient (ρ) between the measurements obtained with both images was 0.805 (P < 0.001) for the cochlea and 0.826 (P < 0.001) for the vestibule. CONCLUSION: The endolymphatic volume measured using 3D-real IR images strongly correlated with that measured using HYDROPS-Mi2 images. Thus, 3D-real IR imaging might be a suitable method for the measurement of endolymphatic volume.

DOI： 10.2463/mrms.mp.2019-0013

The Space between the Pial Sheath and the Cortical Venous Wall May Connect to the Meningeal Lymphatics. Reviewed Open Access

Shinji Naganawa, Rintaro Ito, Toshiaki Taoka, Tadao Yoshida, Michihiko Sone

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 19 ( 1 ) page： 1 - 4 2020

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

We currently obtain pre- and post-contrast enhanced whole brain 3D-real inversion recovery images for the evaluation of endolymphatic hydrops. We noticed that the space between the pial sheath surrounding the cortical veins and the cortical venous wall is enhanced and this enhancement seems to connect to the meningeal lymphatics along superior sagittal sinus. This new anatomical concept regarding the outflow from the glymphatic system might be important for the future research in neuroscience.

DOI： 10.2463/mrms.bc.2019-0099

Detection of IV-gadolinium Leakage from the Cortical Veins into the CSF Using MR Fingerprinting. Reviewed Open Access

Shinji Naganawa, Toshiki Nakane, Hisashi Kawai, Toshiaki Taoka, Hirokazu Kawaguchi, Katsuya Maruyama, Katsutoshi Murata, Gregor Körzdörfer, Josef Pfeuffer, Mathias Nittka, Michihiko Sone

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 19 ( 2 ) page： 141 - 146 2020

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: It has been reported that leakage of intravenously administered gadolinium-based contrast agents (IV-GBCAs) into the cerebrospinal fluid (CSF) from the cortical veins even in healthy subjects can be detected using a highly sensitive pulse sequence such as heavily T2-weighted 3D fluid-attenuated inversion recovery and 3D-real inversion recovery (IR). The purpose of this study was to evaluate the feasibility of MR fingerprinting to detect GBCA leakage from the cortical veins after IV-GBCA. MATERIALS: Fourteen patients with suspected endolymphatic hydrops (EH) who received a single dose of IV-GBCA (39-79 years old) were included. The real IR images as well as MR fingerprinting images were obtained at 4 h after IV-GBCA. T1 and T2 values were obtained using MR fingerprinting and analyzed in ROIs covering intense GBCA leakage, and non-leakage areas of the CSF as determined on real IR images. The scan time for real IR imaging was 10 min and that for MR fingerprinting was 41 s. RESULTS: The mean T1 value of the ROI in the area of GBCA leakage was 2422 ± 261 ms and that in the non-leakage area was 3851 ± 235 ms (P < 0.01). There was no overlap between the T1 values in the area of GBCA leakage and those in the non-leakage area.The mean T2 value in the area of GBCA leakage was 319 ± 90 ms and that in the non-leakage area was 670 ± 166 ms (P < 0.01). There was some overlap between the T2 values in the area of GBCA leakage and those in the non-leakage area. CONCLUSION: Leaked GBCA from the cortical veins into the surrounding CSF can be detected using MR fingerprinting obtained in <1 min.

DOI： 10.2463/mrms.mp.2019-0048

Confirmation of Age-dependence in the Leakage of Contrast Medium around the Cortical Veins into Cerebrospinal Fluid after Intravenous Administration of Gadolinium-based Contrast Agent. Reviewed Open Access

Shinji Naganawa, Rintaro Ito, Hisashi Kawai, Toshiaki Taoka, Tadao Yoshida, Michihiko Sone

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 19 ( 4 ) page： 375 - 381 2020

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: It has been reported previously that intravenously administered gadolinium-based contrast agent (GBCA) leaks into the subarachnoid space around the cortical veins at 4 h after injection in all old people over 37 years, but not in younger people up to 37 years of age in 3D-real IR images. The purpose of this study was to investigate whether there was a strict threshold of 37 years of age for the leakage of the GBCA into the subarachnoid space. METHODS: The subjects included 190 patients, that were scanned for 3D-real IR images at 4 hours after intravenous injection of GBCA as a diagnostic test for endolymphatic hydrops. The patient's age ranged from 14 to 81 years. Two experienced neuroradiologists evaluated the images to determine whether the GBCA leakage around the cortical veins was positive or negative. Any discrepancies between the two observers were discussed and a consensus was obtained.A Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were used to compare the positive and the negative group and to set the age cut-off value for the prediction of GBCA leakage. RESULTS: The GBCA leakage around the cortical veins was negative in 35 patients and positive in 155 patients. The average age was 33 ± 11 years in the negative group, and 55 ± 12 years in the positive group (P < 0.01). In the ROC analysis for the age and leakage of the GBCA, an area under the curve was 0.905 and the cut-off age was 37.317 years (sensitivity of 0.942 and specificity of 0.771). CONCLUSION: Intravenously administered GBCA leaks into the subarachnoid space around the cortical veins in most patients over 37 years of age. However, it should be noted that it can be found occasionally in patients under 37 years of age.

DOI： 10.2463/mrms.mp.2019-0182

Comprehensive Evaluation of B1+-corrected FISP-based Magnetic Resonance Fingerprinting: Accuracy, Repeatability and Reproducibility of T1 and T2 Relaxation Times for ISMRM/NIST System Phantom and Volunteers. Reviewed Open Access

Yutaka Kato, Kazushige Ichikawa, Kuniyasu Okudaira, Toshiaki Taoka, Hirokazu Kawaguchi, Katsutoshi Murata, Katsuya Maruyama, Gregor Koerzdoerfer, Josef Pfeuffer, Mathias Nittka, Shinji Naganawa

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 19 ( 3 ) page： 168 - 175 2020

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: This study aimed to evaluate comprehensively; accuracy, repeatability and reproducibility of T1 and T2 relaxation times measured by magnetic resonance fingerprinting using B1+-corrected fast imaging with steady-state precession (FISP-MRF). METHODS: The International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) phantom was scanned for 100 days, and six healthy volunteers for 5 days using a FISP-MRF prototype sequence. Accuracy was evaluated on the phantom by comparing relaxation times measured by FISP-MRF with the reference values provided by the phantom manufacturer. Daily repeatability was characterized as the coefficient of variation (CV) of the measurements over 100 days for the phantom and over 5 days for volunteers. In addition, the cross-scanner reproducibility was evaluated in volunteers. RESULTS: In the phantom study, T1 and T2 values from FISP-MRF showed a strong linear correlation with the reference values of the phantom (R2 = 0.9963 for T1; R2 = 0.9966 for T2). CVs were <1.0% for T1 values larger than 300 ms, and <3.0% for T2 values across a wide range. In the volunteer study, CVs for both T1 and T2 values were <5.0%, except for one subject. In addition, all T2 values estimated by FISP-MRF in vivo were lower than those measured with conventional mapping sequences reported in previous studies. The cross-scanner variation of T1 and T2 showed good agreement between two different scanners in the volunteers. CONCLUSION: B1+-corrected FISP-MRF showed an acceptable accuracy, repeatability and reproducibility in the phantom and volunteer studies.

DOI： 10.2463/mrms.mp.2019-0016

Assessing the Risk of Intracranial Aneurysm Rupture Using Morphological and Hemodynamic Biomarkers Evaluated from Magnetic Resonance Fluid Dynamics and Computational Fluid Dynamics. Reviewed Open Access

Roshani Perera, Haruo Isoda, Kenta Ishiguro, Takashi Mizuno, Yasuo Takehara, Masaki Terada, Chiharu Tanoi, Takehiro Naito, Harumi Sakahara, Hisaya Hiramatsu, Hiroki Namba, Takashi Izumi, Toshihiko Wakabayashi, Takafumi Kosugi, Yuki Onishi, Marcus Alley, Yoshiaki Komori, Mitsuru Ikeda, Shinji Naganawa

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 19 ( 4 ) page： 333 - 344 2020

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Evaluate in vivo hemodynamic and morphological biomarkers of intracranial aneurysms, using magnetic resonance fluid dynamics (MRFD) and MR-based patient specific computational fluid dynamics (CFD) in order to assess the risk of rupture. METHODS: Forty-eight intracranial aneurysms (10 ruptured, 38 unruptured) were scrutinized for six morphological and 10 hemodynamic biomarkers. Morphological biomarkers were calculated based on 3D time-of-flight magnetic resonance angiography (3D TOF MRA) in MRFD analysis. Hemodynamic biomarkers were assessed using both MRFD and CFD analyses. MRFD was performed using 3D TOF MRA and 3D cine phase-contrast magnetic resonance imaging (3D cine PC MRI). CFD was performed utilizing patient specific inflow-outflow boundary conditions derived from 3D cine PC MRI. Univariate analysis was carried out to identify statistically significant biomarkers for aneurysm rupture and receiver operating characteristic (ROC) analysis was performed for the significant biomarkers. Binary logistic regression was performed to identify independent predictive biomarkers. RESULTS: Morphological biomarker analysis revealed that aneurysm size [P = 0.021], volume [P = 0.035] and size ratio [P = 0.039] were statistically significantly different between the two groups. In hemodynamic biomarker analysis, MRFD results indicated that ruptured aneurysms had higher oscillatory shear index (OSI) [OSI.max, P = 0.037] and higher relative residence time (RRT) [RRT.ave, P = 0.035] compared with unruptured aneurysms. Correspondingly CFD analysis demonstrated significant differences for both average and maximum OSI [OSI.ave, P = 0.008; OSI.max, P = 0.01] and maximum RRT [RRT.max, P = 0.045]. ROC analysis revealed AUC values greater than 0.7 for all significant biomarkers. Aneurysm volume [AUC, 0.718; 95% CI, 0.491-0.946] and average OSI obtained from CFD [AUC, 0.774; 95% CI, 0.586-0.961] were retained in the respective logistic regression models. CONCLUSION: Both morphological and hemodynamic biomarkers have significant influence on intracranial aneurysm rupture. Aneurysm size, volume, size ratio, OSI and RRT could be potential biomarkers to assess aneurysm rupture risk.

DOI： 10.2463/mrms.mp.2019-0107

Kinetic volume analysis on dynamic contrast-enhanced MRI of triple-negative breast cancer: associations with survival outcomes. Reviewed International journal Open Access

Yoko Hayashi, Hiroko Satake, Satoko Ishigaki, Rintaro Ito, Mariko Kawamura, Hisashi Kawai, Shingo Iwano, Shinji Naganawa

The British journal of radiology Vol. 93 ( 1106 ) page： 20190712 - 20190712 2020

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To evaluate the associations between computer-aided diagnosis (CAD)-generated kinetic volume parameters and survival in triple-negative breast cancer (TNBC) patients. METHODS: 40 patients with TNBC who underwent pre-operative MRI between March 2008 and March 2014 were included. We analyzed CAD-generated parameters on dynamic contrast-enhanced MRI, visual MRI assessment, and histopathological data. Cox proportional hazards models were used to determine associations with survival outcomes. RESULTS: 12 of the 40 (30.0%) patients experienced recurrence and 7 died of breast cancer after a median follow-up of 73.6 months. In multivariate analysis, higher percentage volume (%V) with more than 200% initial enhancement rate correlated with worse disease-specific survival (hazard ratio, 1.12; 95% confidence interval, 1.02-1.22; p-value, 0.014) and higher %V with more than 100% initial enhancement rate followed by persistent curve type at 30% threshold correlated with worse disease-specific survival (hazard ratio, 1.33; 95% confidence interval, 1.10-1.61; p-value, 0.004) and disease-free survival (hazard ratio, 1.27; 95% confidence interval, 1.12-1.43; p-value, 0.000). CONCLUSION: CAD-generated kinetic volume parameters may correlate with survival in TNBC patients. Further study would be necessary to validate our results on larger cohorts. ADVANCES IN KNOWLEDGE: CAD generated kinetic volume parameters on breast MRI can predict recurrence and survival outcome of patients in TNBC. Varying the enhancement threshold improved the predictive performance of CAD generated kinetic volume parameter.

DOI： 10.1259/bjr.20190712

Optimal Plane Selection for Measuring Post-prandial Blood Flow Increase within the Superior Mesenteric Artery: Analysis Using 4D Flow and Computational Fluid Dynamics. Reviewed Open Access

Masataka Sugiyama, Yasuo Takehara, Masanori Kawate, Naoki Ooishi, Masaki Terada, Haruo Isoda, Harumi Sakahara, Shinji Naganawa, Kevin M Johnson, Oliver Wieben, Tetsuya Wakayama, Atsushi Nozaki, Hiroyuki Kabasawa

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 19 ( 4 ) page： 366 - 374 2020

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: 2D cine phase contrast (PC)-MRI is a standard velocimetry for the superior mesenteric artery (SMA); however, the optimal localization of the measurement plane has never been fully discussed previously. The purpose of this Institutional Review Board approved prospective and single arm study is to test whether flow velocimetry of the SMA with combined use of 2D cine PC-MRI and meal challenge is dependent on the localizations of the measurement planes and to seek optimal section for velocimetry. METHODS: Seven healthy volunteers underwent cardiac phase resolved ECG gated 2D cine PC-MRI pre- and 30 min post-meal challenge at three measurement planes: proximal, curved mid section and distal straight section of the SMA at 3T. 4D Flow using 3D cine PC-MRI with vastly undersampled isotropic projection imaging (PC VIPR) was also performed right after 2D cine PC-MRI to delineate the flow dynamics within the SMA using streamline analysis. Two radiologists measured flow velocities, and rated the appearances of the abnormal flow in the SMA on streamlines derived from the 4D Flow and the computational fluid dynamics (CFD). RESULTS: 2D cine PC-MRI measured increased temporally averaged flow velocity (mm/s) after the meal challenge only in the proximal (129.3 vs. 97.8, P = 0.0313) and distal section (166.9 vs. 96.2, P = 0.0313), not in the curved mid section (113.1 vs. 85.5, P = 0.0625). The average velocities were highest and their standard errors (8.5-26.5) were smallest at the distal straight section both before and after the meal challenge as compared with other sections. The streamline analysis depicted more frequent appearances of vertical or helical flow in the curved mid section both on 4D Flow and CFD (κ: 0.27-0.68). CONCLUSION: SMA velocimetry with 2D cine PC-MRI was dependent on the localization of the measurement planes. Distal straight section, not in the curved mid section is recommended for MR velocimetry.

DOI： 10.2463/mrms.mp.2019-0089

Assessment of Severity in Chronic Thromboembolic Pulmonary Hypertension by Quantitative Parameters of Dual-Energy Computed Tomography Reviewed Open Access

Tsutsumi Yoshinori, Iwano Shingo, Okumura Naoki, Adachi Shiro, Abe Shinji, Kondo Takahisa, Kato Katsuhiko, Naganawa Shinji

JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Vol. 44 ( 4 ) page： 578 - 585 2020

Abnormal Flow Dynamics Result in Low Wall Shear Stress and High Oscillatory Shear Index in Abdominal Aortic Dilatation: Initial in vivo Assessment with 4D-flow MRI. Reviewed Open Access

Yasuo Takehara, Haruo Isoda, Mamoru Takahashi, Naoki Unno, Norihiko Shiiya, Takasuke Ushio, Satoshi Goshima, Shinji Naganawa, Marcus Alley, Tetsuya Wakayama, Atsushi Nozaki

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 19 ( 3 ) page： 235 - 246 2020

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To characterize the non-laminar flow dynamics and resultant decreased wall shear stress (WSS) and high oscillatory shear index (OSI) of the infrarenal abdominal aortic dilatation, cardiac phase-resolved 3D phase-contrast MRI (4D-flow MRI) was performed. METHODS: The prospective single-arm study was approved by the Institutional Review Board and included 18 subjects (median 67.5 years) with the dilated infrarenal aorta (median diameter 35 mm). 4D-flow MRI was conducted on a 1.5T MRI system. On 3D streamline images, laminar and non-laminar (i.e., vortex or helical) flow patterns were visually assessed both for the dilated aorta and for the undilated upstream aorta. Cardiac phase-resolved flow velocities, WSS and OSI, were also measured for the dilated aorta and the upstream undilated aorta. RESULTS: Non-laminar flow represented by vortex or helical flow was more frequent and overt in the dilated aorta than in the undilated upstream aorta (P < 0.0156) with a very good interobserver agreement (weighted kappa: 0.82-1.0). The WSS was lower, and the OSI was higher on the dilated aortic wall compared with the proximal undilated segments. In mid-systole, mean spatially-averaged WSS was 0.20 ± 0.016 Pa for the dilated aorta vs. 0.68 ± 0.071 Pa for undilated upstream aorta (P < 0.0001), and OSI on the dilated aortic wall was 0.093 ± 0.010 vs. 0.041 ± 0.0089 (P = 0.013). The maximum values and the amplitudes of the WSS at the dilated aorta were inversely proportional to the ratio of dilated/undilated aortic diameter (r = -0.694, P = 0.0014). CONCLUSION: 4D-flow can characterize abnormal non-laminar flow dynamics within the dilated aorta in vivo. The wall of the infrarenal aortic dilatation is continuously and increasingly affected by atherogenic stimuli due to the flow disturbances represented by vortex or helical flow, which is reflected by lower WSS and higher OSI.

DOI： 10.2463/mrms.mp.2019-0188