Researcher Profile and Settings

Affiliation

• Faculty of Dental Medicine　Division of Dental Medicine　Department of Pathobiological Science

Job Title

• Assistant Professor

Research funding number

• 70829887

J-Global ID

• 201801008950465513

Research Interests

• 生化学   分子生物学   分子イメージング   画像   神経放射線   MRI   

Research Areas

• Life sciences / Radiology

Educational Organization

•  Bachelor's degree program　School of Dental Medicine
•  Doctoral (PhD) degree program　Graduate school of Dental Medicine

Academic & Professional Experience

• 2019/07 - Today 北海道大学大学院歯学研究院 口腔病態学分野 放射線学教室 助教
• 2016/04 - Today Hokkaido University Hokkaido University Hospital
• 2015/04 - 2016/03 Iwate Medical University
• 2014/04 - 2015/03 Hokkaido University Hokkaido University Hospital

Education

• 2014/04 - 2018/03  Hokkaido University
• 2006/04 - 2012/03  Hokkaido University  School of Medicine

Association Memberships

• 日本インターベンショナルラジオロジー学会   THE NUCLEAR MAGNETIC RESONANCE SOCIETY OF JAPAN   JAPANESE SOCIETY FOR MAGNETIC RESONANCE IN MEDICINE   日本神経放射線学会   JAPAN RADIOLOGICAL SOCIETY   

Research Activities

Published Papers

• Imaging of 17O-labeled Water Using Fast T2 Mapping with T2-preparation: A Phantom Study.

  Hiroyuki Kameda, Yumi Nakada, Yuta Urushibata, Hiroyuki Sugimori, Takaaki Fujii, Naoya Kinota, Daisuke Kato, Minghui Tang, Keita Sakamoto, Kohsuke Kudo

  Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 2024/03/15 

  17O-labeled water is a T2-shortening contrast agent used in proton MRI and is a promising method for visualizing cerebrospinal fluid (CSF) dynamics because it provides long-term tracking of water molecules. However, various external factors reduce the accuracy of 17O-concentration measurements using conventional signal-intensity-based methods. In addition, T2 mapping, which is expected to provide a stable assessment, is generally limited to temporal-spatial resolution. We developed the T2-prepared based on T2 mapping used in cardiac imaging to adapt to long T2 values and tested whether it could accurately measure 17O-concentration in the CSF using a phantom. The results showed that 17O-concentration in a fluid mimicking CSF could be evaluated with an accuracy comparable to conventional T2-mapping (Carr-Purcell-Meiboom-Gill multi-echo spin-echo method). This method allows 17O-imaging with a high temporal resolution and stability in proton MRI. This imaging technique may be promising for visualizing CSF dynamics using 17O-labeled water.
• Improved image quality in contrast-enhanced 3D-T1 weighted sequence by compressed sensing-based deep-learning reconstruction for the evaluation of head and neck.

  Noriyuki Fujima, Junichi Nakagawa, Yohei Ikebe, Hiroyuki Kameda, Taisuke Harada, Yukie Shimizu, Nayuta Tsushima, Satoshi Kano, Akihiro Homma, Jihun Kwon, Masami Yoneyama, Kohsuke Kudo

  Magnetic resonance imaging 108 111 - 115 2024/02/09 

  PURPOSE: To assess the utility of deep learning (DL)-based image reconstruction with the combination of compressed sensing (CS) denoising cycle by comparing images reconstructed by conventional CS-based method without DL in fat-suppressed (Fs)-contrast enhanced (CE) three-dimensional (3D) T1-weighted images (T1WIs) of the head and neck. MATERIALS AND METHODS: We retrospectively analyzed the cases of 39 patients who had undergone head and neck Fs-CE 3D T1WI applying reconstructions based on conventional CS and CS augmented by DL, respectively. In the qualitative assessment, we evaluated overall image quality, visualization of anatomical structures, degree of artifacts, lesion conspicuity, and lesion edge sharpness based on a five-point system. In the quantitative assessment, we calculated the signal-to-noise ratios (SNRs) of the lesion and the posterior neck muscle and the contrast-to-noise ratio (CNR) between the lesion and the adjacent muscle. RESULTS: For all items of the qualitative analysis, significantly higher scores were awarded to images with DL-based reconstruction (p < 0.001). In the quantitative analysis, DL-based reconstruction resulted in significantly higher values for both the SNR of lesions (p < 0.001) and posterior neck muscles (p < 0.001). Significantly higher CNRs were also observed in images with DL-based reconstruction (p < 0.001). CONCLUSION: DL-based image reconstruction integrating into the CS-based denoising cycle offered superior image quality compared to the conventional CS method. This technique will be useful for the assessment of patients with head and neck disease.
• Automated Detection of Cerebral Microbleeds on Two-dimensional Gradient-recalled Echo T2* Weighted Images Using a Morphology Filter Bank and Convolutional Neural Network

  Noriko Nishioka, Yukie Shimizu, Toru Shirai, Hisaaki Ochi, Yoshitaka Bito, Kiichi Watanabe, Hiroyuki Kameda, Taisuke Harada, Kohsuke Kudo

  Magnetic Resonance in Medical Sciences 1347-3182 2024
• Magnetic Resonance Water Tracer Imaging Using 17 O-Labeled Water.

  Hiroyuki Kameda, Naoya Kinota, Daisuke Kato, Takaaki Fujii, Taisuke Harada, Yuji Komaki, Hiroyuki Sugimori, Tomohiro Onodera, Moyoko Tomiyasu, Takayuki Obata, Kohsuke Kudo

  Investigative radiology 59 (1) 92 - 103 2024/01/01 

  Magnetic resonance imaging (MRI) is a crucial imaging technique for visualizing water in living organisms. Besides proton MRI, which is widely available and enables direct visualization of intrinsic water distribution and dynamics in various environments, MR-WTI (MR water tracer imaging) using 17 O-labeled water has been developed, benefiting from the many advancements in MRI software and hardware that have substantially improved the signal-to-noise ratio and made possible faster imaging. This cutting-edge technique allows the generation of novel and valuable images for clinical use. This review elucidates the studies related to MRI water tracer techniques centered around 17 O-labeled water, explaining the fundamental principles of imaging and providing clinical application examples. Anticipating continued progress in studies involving isotope-labeled water, this review is expected to contribute to elucidating the pathophysiology of various diseases related to water dynamics abnormalities and establishing novel imaging diagnostic methods for associated diseases.
• Improvement of image quality in diffusion-weighted imaging with model-based deep learning reconstruction for evaluations of the head and neck.

  Noriyuki Fujima, Junichi Nakagawa, Hiroyuki Kameda, Yohei Ikebe, Taisuke Harada, Yukie Shimizu, Nayuta Tsushima, Satoshi Kano, Akihiro Homma, Jihun Kwon, Masami Yoneyama, Kohsuke Kudo

  Magma (New York, N.Y.) 2023/11/21 

  OBJECTIVES: To investigate the utility of deep learning (DL)-based image reconstruction using a model-based approach in head and neck diffusion-weighted imaging (DWI). MATERIALS AND METHODS: We retrospectively analyzed the cases of 41 patients who underwent head/neck DWI. The DWI in 25 patients demonstrated an untreated lesion. We performed qualitative and quantitative assessments in the DWI analyses with both deep learning (DL)- and conventional parallel imaging (PI)-based reconstructions. For the qualitative assessment, we visually evaluated the overall image quality, soft tissue conspicuity, degree of artifact(s), and lesion conspicuity based on a five-point system. In the quantitative assessment, we measured the signal-to-noise ratio (SNR) of the bilateral parotid glands, submandibular gland, the posterior muscle, and the lesion. We then calculated the contrast-to-noise ratio (CNR) between the lesion and the adjacent muscle. RESULTS: Significant differences were observed in the qualitative analysis between the DWI with PI-based and DL-based reconstructions for all of the evaluation items (p < 0.001). In the quantitative analysis, significant differences in the SNR and CNR between the DWI with PI-based and DL-based reconstructions were observed for all of the evaluation items (p = 0.002 ~ p < 0.001). DISCUSSION: DL-based image reconstruction with the model-based technique effectively provided sufficient image quality in head/neck DWI.
• Blockage of CSF Outflow in Rats after Deep Cervical Lymph Node Ligation Observed Using Gd-based MR Imaging.

  Naoya Kinota, Hiroyuki Kameda, Bai Xiawei, Takaaki Fujii, Daisuke Kato, Bunya Takahashi, Ryo Morita, Daisuke Abo, Ryusei Majima, Hiroshi Ishii, Kazuyuki Minowa, Kohsuke Kudo

  Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 2023/05/30 

  PURPOSE: To investigate whether deep cervical lymph node (DCLN) ligation alters intracranial cerebrospinal fluid (CSF) tracer dynamics and outflow using a rat model with intrathecal dynamic contrast-enhanced (DCE) MRI. METHODS: Six bilateral DCLN-ligated and six sham-operated rats were subjected to DCE MRI with Gd-BTDO3A, and dynamic T1-weighted images were acquired. ROIs were collected from the CSF at the C1 level (CSF_C1), CSF between the olfactory bulbs (CSF_OB), CSF at the pituitary recess (CSF_PitR), and CSF at the pineal recess (CSF_PinR), upper nasal turbinate (UNT), olfactory bulbs, cerebrum, and the jugular region. Time-intensity curves were evaluated, and the maximum slope, peak timing, peak signal ratio, and elimination half-life for the four CSF ROIs and UNT were calculated and compared. RESULTS: Delayed tracer arrival in the rostral CSF space and the nasal cavity with tracer retention in the ventral CSF space were observed in the ligation group. The maximum slopes were smaller in the ligation group at UNT (sham: 0.075 ± 0.0061, ligation: 0.044 ± 0.0086/min, P = 0.011). A significant difference was not detected in peak timings. The peak signal ratio values were lower in the ligation group at UNT (sham: 2.12 ± 0.19, ligation: 1.72 ± 0.11, P = 0.011). The elimination half-life was delayed in the ligation group at CSF_C1 (sham: 30.5 ± 2.70, ligation: 44.4 ± 12.6 min, P = 0.043), CSF_OB (sham: 30.2 ± 2.67, ligation: 44.8 ± 7.47 min, P = 0.021), and CSF_PitR (sham: 30.2 ± 2.49, ligation: 41.3 ± 7.57 min, P = 0.021). CONCLUSION: The DCLN ligation in rats blocked CSF outflow into the nasal cavity and caused CSF retention.
• Rapid and Reliable Steatosis Rat Model Shrsp5-Dmcr for Cold Storage Experiment.

  Moto Fukai, Hiroyuki Sugimori, Sodai Sakamoto, Kengo Shibata, Hiroyuki Kameda, Takahisa Ishikawa, Norio Kawamura, Masato Fujiyoshi, Sunao Fujiyoshi, Kohsuke Kudo, Tsuyoshi Shimamura, Akinobu Taketomi

  Transplantation proceedings 55 (4) 1032 - 1035 2023/04/10 

  Interventions for liver grafts with moderate macrovesicular steatosis have been important in enlarging donor pools. Here, we tested a high-fat and cholesterol (HFC) diet to create a steatosis model for cold hepatic preservation and reperfusion experiments. The aim of the present study was to assess the steatosis model's reliability and to show the resulting graft's quality for cold preservation and reperfusion experiment. Male SHRSP5-Dmcr rats were raised with an HFC diet for up to 2 weeks. The fat content was evaluated using magnetic resonance imaging (MRI) proton density fat fraction (PDFF). The nonalcoholic fatty liver disease activity score (NAS) was evaluated after excision. Steatosis created by 2 weeks of HFC diet was subjected to 24-hour cold storage in the University of Wisconsin and the original test solution (new sol.). Grafts were applied to isolated perfused rat livers for simulating reperfusion. The NAS were 2.2 (HFC 5 days), 3.3 (HFC 1 week), and 5.0 (HFC 2 weeks). Ballooning and fibrosis were not observed in any group. An MRI-PDFF showed 0.2 (HFC 0 days), 12.0 (HFC 1 week), and 18.9 (HFC 2 weeks). The NAS and MRI-PDFF values correlated. Many indices in the isolated perfused rat liver experiment tended to improve in the new sol. group but were insufficient. Although the new sol. failed to be effective, it acted at multiple sites under difficult conditions. In conclusion, the HFC diet for 2 weeks in SHRSP5-Dmcr rats, together with MRI-PDFF evaluation, is a reliable method for creating simple steatosis and provides good-quality cold preservation and reperfusion experiments.
• Non-Gaussian model-based diffusion-weighted imaging of oral squamous cell carcinoma: associations with Ki-67 proliferation status.

  Tomoka Shima, Noriyuki Fujima, Shigeru Yamano, Hiroyuki Kameda, Masaaki Suzuka, Akiko Takeuchi, Yurika Kinoshita, Nanami Iwai, Kohsuke Kudo, Kazuyuki Minowa

  Oral radiology 39 (4) 661 - 667 2023/03/27 

  OBJECTIVES: To investigate possible associations between diffusion-weighted imaging (DWI) parameters derived from a non-Gaussian model fitting and Ki-67 status in patients with oral squamous cell carcinoma (OSCC). METHODS: Twenty-four patients with newly diagnosed OSCC were prospectively recruited. DWI was performed using six b-values (0-2500). The diffusion-related parameters of kurtosis value (K), kurtosis-corrected diffusion coefficient (DK), diffusion heterogeneity (α), distributed diffusion coefficient (DDC), slow diffusion coefficient (Dslow), and apparent diffusion coefficient (ADC) were calculated from four diffusion fitting models. Ki-67 status was categorized as low (Ki-67 percentage score < 20%), middle (20-50%), or high (> 50%). Kruskal-Wallis tests were performed between each non-Gaussian diffusion model parameters and Ki-67 grade. RESULTS: The Kruskal-Wallis tests revealed that multiple parameters (K, ADC, Dk, DDC and Dslow) showed statistically significant differences between the three levels of Ki-67 status (K: p = 0.020, ADC: p = 0.012, Dk: p = 0.027, DDC: p = 0.007 and Dslow: p = 0.026). CONCLUSIONS: Several non-Gaussian diffusion model parameters and ADC values were significantly associated with Ki-67 status and have potential as promising prognostic biomarkers in patients with OSCC.
• The utility of diffusion-weighted T2 mapping for the prediction of histological tumor grade in patients with head and neck squamous cell carcinoma.

  Noriyuki Fujima, Yukie Shimizu, Masami Yoneyama, Junichi Nakagawa, Hiroyuki Kameda, Taisuke Harada, Seijiro Hamada, Takayoshi Suzuki, Nayuta Tsushima, Satoshi Kano, Akihiro Homma, Kohsuke Kudo

  Quantitative imaging in medicine and surgery 12 (8) 4024 - 4032 2022/08 

  Background: In head and neck cancers, histopathological information is important for the determination of the tumor characteristics and for predicting the prognosis. The aim of this study was to assess the utility of diffusion-weighted T2 (DW-T2) mapping for the evaluation of tumor histological grade in patients with head and neck squamous cell carcinoma (SCC). Methods: The cases of 41 patients with head and neck SCC (21 well/moderately and 17 poorly differentiated SCC) were retrospectively analyzed. All patients received MR scanning using a 3-Tesla MR unit. The conventional T2 value, DW-T2 value, ratio of DW-T2 value to conventional T2 value, and apparent diffusion coefficient (ADC) were calculated using signal information from the DW-T2 mapping sequence with a manually placed region of interest (ROI). Results: ADC values in the poorly differentiated SCC group were significantly lower than those in the moderately/well differentiated SCC group (P<0.05). The ratio of DW-T2 value to conventional T2 value was also significantly different between poorly and moderately/well differentiated SCC groups (P<0.01). Receiver operating characteristic (ROC) curve analysis of ADC values showed a sensitivity of 0.76, specificity of 0.67, positive predictive value (PPV) of 0.62, negative predictive value (NPV) of 0.8, accuracy of 0.71 and area under the curve (AUC) of 0.73, whereas the ROC curve analysis of the ratio of DW-T2 value to conventional T2 value showed a sensitivity of 0.76, specificity of 0.83, PPV of 0.76, NPV of 0.83, accuracy of 0.8 and AUC of 0.82. Conclusions: DW-T2 mapping might be useful as supportive information for the determination of tumor histological grade in patients with head and neck SCC.
• Amide proton transfer imaging for the determination of human papillomavirus status in patients with oropharyngeal squamous cell carcinoma.

  Noriyuki Fujima, Yukie Shimizu, Masami Yoneyama, Junichi Nakagawa, Hiroyuki Kameda, Taisuke Harada, Seijiro Hamada, Takayoshi Suzuki, Nayuta Tsushima, Satoshi Kano, Akihiro Homma, Kohsuke Kudo

  Medicine 101 (28) e29457  2022/07/15 

  The aim of this study was to investigate the utility of amide proton transfer (APT) imaging for the determination of human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (SCC). Thirty-one patients with oropharyngeal SCC were retrospectively evaluated. All patients underwent amide proton transfer imaging using a 3T magnetic resonance (MR) unit. Patients were divided into HPV-positive and -negative groups depending on the pathological findings in their primary tumor. In APT imaging, the primary tumor was delineated with a polygonal region of interest (ROI). Signal information in the ROI was used to calculate the mean, standard deviation (SD) and coefficient of variant (CV) of the APT signals (APT mean, APT SD, and APT CV, respectively). The value of APT CV in the HPV-positive group (0.43 ± 0.04) was significantly lower than that in the HPV-negative group (0.48 ± 0.04) (P = .01). There was no significant difference in APT mean (P = .82) or APT SD (P = .13) between the HPV-positive and -negative groups. Receiver operating characteristic (ROC) curve analysis of APT CV had a sensitivity of 0.75, specificity of 0.8, positive predictive value of 0.75, negative predictive value of 0.8, accuracy of 0.77 and area under the curve (AUC) of 0.8. The APT signal in the HPV-negative group was considered heterogeneous compared to the HPV-positive group. This information might be useful for the determination of HPV status in patients with oropharyngeal SCC.
• Establishment of a New Qualitative Evaluation Method for Articular Cartilage by Dynamic T2w MRI Using a Novel Contrast Medium as a Water Tracer

  Yoshiaki Hosokawa, Tomohiro Onodera, Kentaro Homan, Jun Yamaguchi, Kohsuke Kudo, Hiroyuki Kameda, Hiroyuki Sugimori, Norimasa Iwasaki

  CARTILAGE 13 (3) 19476035221111503 - 19476035221111503 1947-6035 2022/07 

  Objective In the early stages of cartilage damage, diagnostic methods focusing on the mechanism of maintaining the hydrostatic pressure of cartilage are thought to be useful. O-17-labeled water, which is a stable isotope of oxygen, has the advantage of no radiation exposure or allergic reactions and can be detected by magnetic resonance imaging (MRI). This study aimed to evaluate MRI images using O-17-labeled water in a rabbit model. Design Contrast MRI with O-17-labeled water and macroscopic and histological evaluations were performed 4 and 8 weeks after anterior cruciate ligament transection surgery in rabbits. A total of 18 T2-weighted images were acquired, and O-17-labeled water was manually administered on the third scan. The O-17 concentration in each phase was calculated from the signal intensity at the articular cartilage. Macroscopic and histological grades were evaluated and compared with the O-17 concentration. Results An increase in O-17 concentration in the macroscopic and histologically injured areas was observed by MRI. Macroscopic evaluation showed that the O-17 concentration significantly increased in the damaged site group. Histological evaluations also showed that O-17 concentrations significantly increased at 36 minutes 30 seconds after initiating MRI scanning in the Osteoarthritis Research Society International (OARSI) grade 3 (0.493 in grade 0, 0.659 in grade 1, 0.4651 in grade 2, and 0.9964 in grade 3, P < 0.05). Conclusion O-17-labeled water could visualize earlier articular cartilage damage, which is difficult to detect by conventional methods.
• Phase I Randomized Trial of ¹⁷ O ‐Labeled Water: Safety and Feasibility Study of Indirect Proton MRI for the Evaluation of Cerebral Water Dynamics

  Taisuke Harada, Kohsuke Kudo, Hiroyuki Kameda, Ryota Sato, Toru Shirai, Yoshitaka Bito, Noriyuki Fujima, Satonori Tsuneta, Toshifumi Nogawa, Kenichiro Maeda, Hiroshi Hayashi, Makoto Sasaki

  Journal of Magnetic Resonance Imaging 56 (6) 1874 - 1882 1053-1807 2022/04/30 

  BACKGROUND: 17 O-labeled water (PSO17) is a contrast agent developed to measure brain water dynamics and cerebral blood flow. PURPOSE: To evaluate the safety and feasibility of PSO17. STUDY TYPE: Prospective study. SUBJECTS: A total of 12 male healthy volunteers (23.1 ± 1.9 years) were assigned to three groups of four subjects: placebo (normal saline), PSO17 10%, and PSO17 20%. FIELD STRENGTH/SEQUENCE: Dynamic 3D fluid attenuated inversion recovery (FLAIR, fast spin echo with variable refocusing flip angle) scans of the brain were performed with 3-T MRI. ASSESSMENT: Contrast agents were injected 5 minutes after the start of a 10-minute scan. Any symptoms, vital signs, and blood and urine tests were evaluated at five timepoints from preinjection to 4 days after. Blood samples for pharmacokinetic analysis, including half-life (T1/2), maximum fraction (Cmax ), time-to-maximum fraction (Tmax ), and area under the curve (AUC), were collected at 13 timepoints from preinjection to 168 hours after. Regions of interest were set in the cerebral cortex (CC), basal ganglia/thalamus (BG/TM), and white matter (WM), and 17 O concentrations were calculated from signal changes and evaluated using Cmax . STATISTICAL TESTS: All items were compared among the three groups using Tukey-Kramer's honestly significant difference test. Statistical significance was defined as P < 0.5. RESULTS: No safety issues were noted with the intravenous administration of PSO17. The T1/2 was approximately 160 hours, and the AUCs were 1.77 ± 0.10 and 3.75 ± 0.36 in the PSO17 10% and 20% groups, respectively. 17 O fractions calculated from MRI signals were higher in the PSO17 20% group than in the 10% and placebo groups. Significant differences were noted between all pairs of groups in the CC and BG/TM, and between PSO17 20% and both placebo and 10% groups in the WM. DATA CONCLUSION: PSO17 might be considered safe as a contrast medium. Dynamic 3D-FLAIR might detect dose-dependent signal changes and estimate 17 O. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.
• Quantitative magnetic resonance imaging for evaluating of the cerebrospinal fluid kinetics with 17O-labeled water tracer: A preliminary report.

  Hiroyuki Sugimori, Hiroyuki Kameda, Taisuke Harada, Kinya Ishizaka, Masayoshi Kajiyama, Tasuku Kimura, Niki Udo, Masaaki Matsushima, Azusa Nagai, Masahiro Wakita, Ichiro Kusumi, Ichiro Yabe, Kohsuke Kudo

  Magnetic resonance imaging 87 77 - 85 2022/04 

  The aim of this study was to evaluate the feasibility of kinetic analysis of cerebrospinal fluid (CSF) using 17O-labeled water tracer. Four subjects (two idiopathic normal pressure hydrocephalus (iNPH) and two possible AD dementia patients) were prospectively included. Injectable formulation of 17O-labeled water containing 10 mol% of H217O (PSO17), was intrathecally administered to the subjects with the lateral decubitus position between the 3rd and 4th lumbar vertebrae. MRI acquisitions were performed in four-time points, before PSO17 administration, 1, 8, and 24 h after PSO17 administration. The 3-dimensional fast spin echo sequence was used. After image registration for all four-time points data, polygonal regions of interest (ROIs) were set in the 14 regions to obtain the signal intensity of CSF. Each signal intensity within the ROI was converted to 17O concentration [%]. The peak concentration at one hour after administration, the slope of concentration changes after PSO17 administration [%/s], and the root mean square error (RMSE) for evaluating the performance of a fitting were calculated. There was no significant difference in peak concentration between the iNPH and AD group. The slope in the AD group (-2.25 ± 1.62 × 10-3 [%/h]) was significantly smaller than in the iNPH group (-1.21 ± 2.31 × 10-3 [%/h]), which suggests the speed of CSF clearance in the iNPH group was slower than AD group. The RMSE indicating the fit to the concentration change in the AD group (4.86 ± 4.74 × 10-3) was also significantly smaller than in the iNPH group (8.64 ± 7.56 × 10-3). The kinetic evaluation of CSF using 17O-labeled water was feasible, and this preliminary study suggests that the differentiation of iNPH and possible AD dementia can be achieved using this method.
• Variations and natural history of primary intraparenchymal lesions associated with neurofibromatosis type 2.

  Yukitomo Ishi, Taisuke Harada, Hiroyuki Kameda, Hiromi Okada, Isao Yokota, Michinari Okamoto, Ryosuke Sawaya, Hiroaki Motegi, Shigeru Yamaguchi, Shunsuke Terasaka, Kohsuke Kudo, Miki Fujimura

  Neuroradiology 64 (2) 393 - 396 2021/11/23 

  The study aimed to investigate the clinical implications and natural history of primary intraparenchymal lesions in patients with neurofibromatosis type 2. Radiological findings of 15 neurofibromatosis type 2 cases were retrospectively collected. Twenty-seven primary intraparenchymal lesions were observed in 7 out of 15 patients (47%). Cortical/subcortical T2 hyperintense lesions and enlarged Virchow-Robin spaces were the most common findings in five and four patients, respectively. During the follow-up period (median 84 months), one new primary intraparenchymal lesion was identified and increased lesions were observed in two cases on contrast-enhanced MRI. Surgical resection was performed in one case pathologically diagnosed with atypical meningioma. Twenty-five other lesions without contrast enhancement presented no apparent growth during follow-up. Although most primary intraparenchymal lesions are benign, a subset of cases would present newly developed or increased lesions on contrast-enhanced MRI. Careful monitoring is necessary for such cases, and pathological confirmation should be considered.
• Extramedullary hematopoiesis of the cranial dura.

  Keito Suto, Junichi Sugita, Daigo Hashimoto, Hiroyuki Kameda, Tomoko Mitsuhashi, Takanori Teshima

  International journal of hematology 113 (3) 315 - 317 2021/03
• Detection of impaired cerebrovascular reactivity in patients with chronic cerebral ischemia using whole-brain 7T MRA.

  Ikuko Uwano, Hiroyuki Kameda, Taisuke Harada, Masakazu Kobayashi, Wataru Yanagihara, Kengo Setta, Kuniaki Ogasawara, Kunihiro Yoshioka, Fumio Yamashita, Futoshi Mori, Tsuyoshi Matsuda, Makoto Sasaki

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 (9) 105081 - 105081 2020/09 [Refereed][Not invited]
   

  BACKGROUND: Cerebrovascular reactivity (CVR) to acetazolamide (ACZ) on single-photon emission computed tomography (SPECT) can be used to assess the severity of chronic cerebral ischemia; however, this is an invasive method. We examined whether whole-brain magnetic resonance angiography (MRA) at 7T could non-invasively detect impaired CVR in patients with chronic cerebral ischemia by demonstrating the leptomeningeal collaterals (LMCs). METHODS: Fifty-seven patients with symptomatic unilateral cervical stenosis underwent whole-brain time-of-flight MRA at 7T and cerebral perfusion SPECT before/after the ACZ challenge. MRA images were visually assessed based on 6-point grading systems to evaluate the development of LMCs toward the middle cerebral artery (MCA) and antegrade flow of MCA. CVR of the affected side was calculated from the SPECT data. Subsequently, we compared the LMC grades on MRA with CVR on SPECT. RESULTS: CVR was significantly lower in grades ≥ 2 of LMCs than in grades 0-1 (P < 0.05) when applying LMCs from the anterior cerebral artery (ACA) and/or posterior cerebral artery (PCA). These differences were more evident than those in the grading of the antegrade MCA flow. The LMC grades from ACA/PCA readily detected reduced CVR (< 18.4%) with a sensitivity/specificity of 0.79/0.82. CONCLUSION: The development of LMCs on whole-brain MRA at 7T can non-invasively detect reduced CVR with a high sensitivity/specificity in patients with unilateral cervical stenosis.
• Improvement of image quality on low-dose dynamic myocardial perfusion computed tomography with a novel 4-dimensional similarity filter.

  Satonori Tsuneta, Noriko Oyama-Manabe, Hiroyuki Kameda, Taisuke Harada, Fumi Kato, Ewoud J Smit, Mathias Prokop, Kohsuke Kudo

  Medicine 99 (26) e20804  2020/06/26 

  The aim of this study was to evaluate the effect of a novel 4-dimensional similarity filter (4DSF) on quantitative and qualitative parameters of low-dose dynamic myocardial computed tomography perfusion (CTP) images.In this retrospective study, medical records of 32 patients with suspected or known coronary artery disease who underwent dynamic myocardial CTP at 80 kV were included. The 4DSF reduces noise by averaging voxels that have similar dynamic behavior after adaptive iterative dose reduction 3D (AIDR3D) and deformable image registration were applied. Qualitative (artefact, contour sharpness, and myocardial homogeneity [1 = poor; 2 = intermediate; 3 = good]) and quantitative measurement (standard deviation [SD] and signal-to-noise ratio [SNR]) were compared between the 4DSF and AIDR3D. Contrast-to-noise ratio (CNR) between ischemic and normal remote myocardium was also assessed using myocardial perfusion magnetic resonance imaging as the reference standard in seven patients.The 4DSF was successfully applied to all the images. Improvement in subjective image quality yielded by 4DSF was higher than that yielded by AIDR3D (homogeneity, 1.0 [3 vs 2]; artefact, 1.5 [3 vs 1.5]; P < .001) in all patients. The 4DSF significantly decreased the SD by 59% (AIDR3D vs 4DSF: 33.5 ± 0.4 vs 13.8 ± 0.4, P < .001), increased the SNR by 134% (AIDR3D vs 4DSF: 4.4 ± 0.2 vs 10.3 ± 0.2, P < .001), and increased the CNR by 131% (AIDR3D vs 4DSF: 1.6 ± 0.2 vs 3.7 ± 0.2, P < .001).The 4DSF improved the qualitative and quantitative parameters of low-dose dynamic myocardial CTP images.
• Utility of a diffusion-weighted arterial spin labeling (DW-ASL) technique for evaluating the progression of brain white matter lesions.

  Noriyuki Fujima, Hiroyuki Kameda, Yukie Shimizu, Taisuke Harada, Khin Khin Tha, Masami Yoneyama, Kohsuke Kudo

  Magnetic resonance imaging 69 81 - 87 2020/06 [Refereed][Not invited]
   

  PURPOSE: To investigate the utility of diffusion-weighted arterial spin labeling (DW-ASL) for detecting the progression of brain white matter lesions. MATERIALS AND METHODS: A total of 492 regions of interest (ROIs) in 41 patients were prospectively analyzed. DW-ASL was performed using the diffusion gradient prepulse of five b-values (0, 25, 60, 102, and 189) before the ASL readout. We calculated the water exchange rate (Kw) with post-processing using the ASL signal information for each b-value. The cerebral blood flow (CBF) was also calculated using b0 images. Using the signal information in FLAIR (fluid-attenuated inversion recovery) images, we classified the severity of white matter lesions into three grades: non-lesion, moderate, and severe. In addition, the normal Kw level was measured from DW-ASL data of 60 ROIs in five control subjects. The degree of variance of the Kw values (Kw-var) was calculated by squaring the value of the difference between each Kw value and the normal Kw level. All patient's ROIs were divided into non-progressive and progressive white matter lesions by comparing the present FLAIR images with those obtained 2 years before this acquisition. RESULTS: Compared to the non-progressive group, the progressive group had significantly lower CBF, significantly higher severity grades in FLAIR, and significantly greater Kw-var values. In a receiver operator characteristic curve analysis, a high area under the curve (AUC) of 0.89 was obtained with the use of Kw-var. In contrast, the AUCs of 0.59 for CBF and 0.72 for severity grades in FLAIR were obtained. CONCLUSIONS: The DW-ASL technique can be useful to detect the progression of brain white matter lesions. This technique will become a clinical tool for patients with various degrees of white matter lesions.
• Computational Fluid Dynamics Analysis of Lateral Striate Arteries in Acute Ischemic Stroke Using 7T High-resolution Magnetic Resonance Angiography.

  Futoshi Mori, Fujimaro Ishida, Tatsunori Natori, Haruna Miyazawa, Hiroyuki Kameda, Taisuke Harada, Kunihiro Yoshioka, Fumio Yamashita, Ikuko Uwano, Kenji Ito, Makoto Sasaki

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 28 (11) 104339 - 104339 1052-3057 2019/11 [Refereed][Not invited]
   

  BACKGROUND: Infarcts in the lateral striate artery (LSA) territory can be caused by several pathological changes, including lipohyalinosis and microatheroma. However, fluid dynamic effects on these changes remain unknown. Thus, we investigated whether the fluid dynamic metrics of the LSAs were altered in patients with acute ischemic stroke using computational fluid dynamics (CFD) analysis. METHODS: Fifty-one patients with acute ischemic stroke confined in the basal ganglia and/or corona radiata underwent high-resolution magnetic resonance angiography (HR-MRA) at 7T. We performed CFD analyses to obtain indices including the wall shear stress (WSS), WSS gradient (WSSG), and flow velocity (FV) and compared these values between the ipsilesional and contralesional sides in the patients with infarcts in the LSA or non-LSA territories. RESULTS: In patients with LSA-territory infarcts, the WSS, WSSG, and FV values were significantly lower in the ipsilesional LSAs than in the contralesional LSAs (P = .01-.03), while these values in the proximal middle cerebral arteries showed no significant lateralities. In contrast, in patients with non-LSA-territory infarcts, there were no significant lateralities in the metrics between the ipsilesional and contralesional sides. CONCLUSIONS: The CFD analyses using HR-MRA revealed significantly low WSS and WSSG values of the ipsilesional LSAs compared with that of the contralesional side in patients with LSA-territory infarcts, suggesting that fluid dynamic factors of LSAs can be one of the risk factors for LSA-territory infarctions.
• Prediction of Hypoxia in Brain Tumors Using a Multivariate Model Built from MR Imaging and 18F-Fluorodeoxyglucose Accumulation Data.

  Yukie Shimizu, Kohsuke Kudo, Hiroyuki Kameda, Taisuke Harada, Noriyuki Fujima, Takuya Toyonaga, Khin Khin Tha, Hiroki Shirato

  Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 19 (3) 227 - 234 1347-3182 2019/10/15 [Refereed][Not invited]
   

  PURPOSE: The aim of this study was to generate a multivariate model using various MRI markers of blood flow and vascular permeability and accumulation of 18F-fluorodeoxyglucose (FDG) to predict the extent of hypoxia in an 18F-fluoromisonidazole (FMISO)-positive region. METHODS: Fifteen patients aged 27-74 years with brain tumors (glioma, n = 13; lymphoma, n = 1; germinoma, n = 1) were included. MRI scans were performed using a 3T scanner, and dynamic contrast-enhanced (DCE) perfusion and arterial spin labeling images were obtained. Ktrans and Vp maps were generated using the DCE images. FDG and FMISO positron emission tomography scans were also obtained. A model for predicting FMISO positivity was generated on a voxel-by-voxel basis by a multivariate logistic regression model using all the MRI parameters with and without FDG. Receiver-operating characteristic curve analysis was used to detect FMISO positivity with multivariate and univariate analysis of each parameter. Cross-validation was performed using the leave-one-out method. RESULTS: The area under the curve (AUC) was highest for the multivariate prediction model with FDG (0.892) followed by the multivariate model without FDG and univariate analysis with FDG and Ktrans (0.844 for all). In cross-validation, the multivariate model with FDG had the highest AUC (0.857 ± 0.08) followed by the multivariate model without FDG (0.834 ± 0.119). CONCLUSION: A multivariate prediction model created using blood flow, vascular permeability, and glycometabolism parameters can predict the extent of hypoxia in FMISO-positive areas in patients with brain tumors.
• Detecting lenticulostriate artery lesions in patients with acute ischemic stroke using high-resolution MRA at 7 T.

  Haruna Miyazawa, Tatsunori Natori, Hiroyuki Kameda, Makoto Sasaki, Hideki Ohba, Shinsuke Narumi, Kohei Ito, Mitsunobu Sato, Takafumi Suzuki, Keisuke Tsuda, Kunihiro Yoshioka, Yasuo Terayama

  International journal of stroke : official journal of the International Stroke Society 14 (3) 290 - 297 1747-4930 2019/04 [Refereed][Not invited]
   

  BACKGROUND: Recent advances in high-resolution (HR) magnetic resonance angiography (MRA) using ultrahigh-field systems enable direct visualization of the lenticulostriate arteries (LSAs), which had been hardly achieved by conventional MRA. Hence, by using HR-MRA at 7 T, we attempted to assess occlusive changes in the LSAs in patients with LSA territorial infarcts. METHODS: We prospectively examined 34 consecutive patients with acute ischemic stroke in the LSA territory using a 7 T scanner. We measured the lengths of the relevant LSAs on HR-MRA and the diameters/volume of the infarcts and compared these between the patients with/without occlusive changes in the LSAs. RESULTS: On HR-MRA, occlusion of the LSAs was observed in 19 (59%) of 32 patients who were eligible for the analyses. The curved/straight lengths of the LSAs in the patients with LSA occlusion (23.1-31.1/17.8-24.3 mm) were significantly shorter than in those without apparent LSA occlusion (25.8-39.5/24.0-30.4 mm) ( P = 0.027/0.003). The anteroposterior/superoinferior diameters of the infarcts were significantly larger in the occluded-LSA group (14.5-21.4/14.9-22.2 mm) than in the intact-LSA group (10.9-16.8/10.8-16.2 mm) ( P = 0.041/0.011). In addition, the curved lengths of the relevant LSAs showed significant correlations with the superoinferior diameters of the infarcts ( r = 0.38, P = 0.034). CONCLUSION: Occlusive changes in the LSAs were frequently found in patients with acute ischemic stroke within the LSA territory when using HR-MRA at 7 T and were substantially related to superoinferior extension of the infarcts.
• Evaluation of Lenticulostriate Arteries Changes by 7 T Magnetic Resonance Angiography in Type 2 Diabetes.

  Satoshi Yashiro, Hiroyuki Kameda, Ai Chida, Yusuke Todate, Yutaka Hasegawa, Kan Nagasawa, Ikuko Uwano, Makoto Sasaki, Kuniaki Ogasawara, Yasushi Ishigaki

  Journal of atherosclerosis and thrombosis 25 (10) 1067 - 1075 1340-3478 2018/10/01 [Refereed][Not invited]
   

  AIM: Progress in neuroimaging techniques allows us to investigate the microvasculature characteristics including lenticulostriate arteries (LSA), which are closely associated with lacunar infarction. Because ischemic stroke is a more critical health problem in East Asian than in other populations, in order to clarify pathological changes underlying cerebral small vessel disease (SVD), we projected an imaging analysis of LSA using high-resolution brain magnetic resonance imaging (MRI) in middle-aged Japanese subjects with type 2 diabetes. METHODS: Twenty-five subjects with type 2 diabetes and 25 non-diabetic control subjects underwent 7 Tesla (7 T) brain MRI. The prevalences of SVD and LSA structural changes were determined in each group. RESULTS: SVD prevalence did not differ significantly between the type 2 diabetes and control groups. The average numbers of stems, as well as numbers of branches, of LSA were significantly smaller in diabetic subjects than non-diabetic control subjects. The signal intensity of LSA was markedly decreased, indicating reduced blood flow in type 2 diabetes. CONCLUSION: In spite of the prevalence of SVD being similar, structural changes and decreased signal intensity of LSA were highly detected in diabetic subjects compared with non-diabetic controls, suggesting that 7 T MRA enables us to determine LSA impairment prior to the development of SVD. Early detection of LSA impairment allows us earlier interventions aimed at the prevention of atherosclerotic events.
• Indirect Proton MR Imaging and Kinetic Analysis of 17O-Labeled Water Tracer in the Brain.

  Kohsuke Kudo, Taisuke Harada, Hiroyuki Kameda, Ikuko Uwano, Fumio Yamashita, Satomi Higuchi, Kunihiro Yoshioka, Makoto Sasaki

  Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 17 (3) 223 - 230 1347-3182 2018/07/10 [Refereed][Not invited]
   

  PURPOSE: The feasibility of steady-state sequences for 17O imaging was evaluated based on a kinetic analysis of the brain parenchyma and cerebrospinal fluid (CSF). MATERIALS AND METHODS: The institutional review board approved this prospective study with written informed consent. Dynamic 2D or 3D steady-state sequences were performed in five and nine participants, respectively, with different parameters using a 3T scanner. During two consecutive dynamic scans, saline was intravenously administered for control purposes in the first scan, and 20% 17O-labeled water (1 mL/Kg) was administered in the second scan. Signal changes relative to the baseline were calculated, and kinetic analyses of the curves were conducted for all voxels. Region of interest analysis was performed in the brain parenchyma, choroid plexus, and CSF spaces. RESULTS: Average signal drops were significantly larger in the 17O group than in the controls for most of the imaging parameters. Different kinetic parameters were observed between the brain parenchyma and CSF spaces. Average and maximum signal drops were significantly larger in the CSF spaces and choroid plexus than in the brain parenchyma. Bolus arrival, time to peak, and the first moment of dynamic curves of 17O in the CSF space were delayed compared to that in the brain parenchyma. Significant differences between the ventricle and subarachnoid space were also noted. CONCLUSION: Steady-state sequences are feasible for indirect 17O imaging with reasonable temporal resolution; this result is potentially important for the analysis of water kinetics and aquaporin function for several disorders.
• Improvement of the repeatability of parallel transmission at 7T using interleaved acquisition in the calibration scan.

  Hiroyuki Kameda, Kohsuke Kudo, Tsuyoshi Matsuda, Taisuke Harada, Yuji Iwadate, Ikuko Uwano, Fumio Yamashita, Kunihiro Yoshioka, Makoto Sasaki, Hiroki Shirato

  Journal of magnetic resonance imaging : JMRI 48 (1) 94 - 101 1053-1807 2018/07 [Refereed][Not invited]
   

  BACKGROUND: Respiration-induced phase shift affects B0 /B1+ mapping repeatability in parallel transmission (pTx) calibration for 7T brain MRI, but is improved by breath-holding (BH). However, BH cannot be applied during long scans. PURPOSE: To examine whether interleaved acquisition during calibration scanning could improve pTx repeatability and image homogeneity. STUDY TYPE: Prospective. SUBJECTS: Nine healthy subjects. FIELD STRENGTH/SEQUENCE: 7T MRI with a two-channel RF transmission system was used. ASSESSMENT: Calibration scanning for B0 /B1+ mapping was performed under sequential acquisition/free-breathing (Seq-FB), Seq-BH, and interleaved acquisition/FB (Int-FB) conditions. The B0 map was calculated with two echo times, and the B1+ map was obtained using the Bloch-Siegert method. Actual flip-angle imaging (AFI) and gradient echo (GRE) imaging were performed using pTx and quadrature-Tx (qTx). All scans were acquired in five sessions. Repeatability was evaluated using intersession standard deviation (SD) or coefficient of variance (CV), and in-plane homogeneity was evaluated using in-plane CV. STATISTICAL TESTS: A paired t-test with Bonferroni correction for multiple comparisons was used. RESULTS: The intersession CV/SDs for the B0 /B1+ maps were significantly smaller in Int-FB than in Seq-FB (Bonferroni-corrected P < 0.05 for all). The intersession CVs for the AFI and GRE images were also significantly smaller in Int-FB, Seq-BH, and qTx than in Seq-FB (Bonferroni-corrected P < 0.05 for all). The in-plane CVs for the AFI and GRE images in Seq-FB, Int-FB, and Seq-BH were significantly smaller than in qTx (Bonferroni-corrected P < 0.01 for all). DATA CONCLUSION: Using interleaved acquisition during calibration scans of pTx for 7T brain MRI improved the repeatability of B0 /B1+ mapping, AFI, and GRE images, without BH. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017.
• Indirect MRI of 17 o-labeled water using steady-state sequences: Signal simulation and preclinical experiment.

  Kohsuke Kudo, Taisuke Harada, Hiroyuki Kameda, Ikuko Uwano, Fumio Yamashita, Satomi Higuchi, Kunihiro Yoshioka, Makoto Sasaki

  Journal of magnetic resonance imaging : JMRI 47 (5) 1373 - 1379 1053-1807 2018/05 [Refereed][Not invited]
   

  BACKGROUND: Few studies have been reported for T2 -weighted indirect 17 O imaging. PURPOSE/HYPOTHESIS: To evaluate the feasibility of steady-state sequences for indirect 17 O brain imaging. STUDY TYPE: Signal simulation, phantom measurements, and prospective animal experiments were performed in accordance with the institutional guidelines for animal experiments. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Signal simulations of balanced steady-state free precession (bSSFP) were performed for concentrations of 17 O ranging from 0.037-1.600%. Phantom measurements with concentrations of 17 O water ranging from 0.037-1.566% were also conducted. Six healthy beagle dogs were scanned with intravenous administration of 20% 17 O-labeled water (1 mL/kg). FIELD STRENGTH/SEQUENCE: Dynamic 3D-bSSFP scans were performed at 3T MRI. 17 O-labeled water was injected 60 seconds after the scan start, and the total scan duration was 5 minutes. ASSESSMENT: Based on the result of signal simulation and phantom measurement, signal changes in the beagle dogs were measured and converted into 17 O concentrations. STATISTICAL TESTS: The 17 O concentrations were averaged for every 15 seconds, and compared to the baseline (30-45 sec) with Dunnett's multiple comparison tests. RESULTS: Signal simulation revealed that the relationships between 17 O concentration and the natural logarithm of relative signals were linear. The intraclass correlation coefficient between relative signals in phantom measurement and signal simulations was 0.974. In the animal experiments, significant increases in 17 O concentration (P < 0.05) were observed 60 seconds after the injection of 17 O. At the end of scanning, mean respective 17 O concentrations of 0.084 ± 0.026%, 0.117 ± 0.038, 0.082 ± 0.037%, and 0.049 ± 0.004% were noted for the cerebral cortex, cerebellar cortex, cerebral white matter, and ventricle. DATA CONCLUSION: Dynamic steady-state sequences were feasible for indirect 17 O imaging, and absolute quantification was possible. This method can be applied for the measurement of permeability and blood flow in the brain, and for kinetic analysis of cerebrospinal fluid. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1373-1379.
• 肝腫瘍術後の肝部下大静脈狭窄に対してステント留置を施行した1例

  亀田 浩之, 阿保 大介, 曽山 武士, 森田 亮, 作原 祐介, 工藤 與亮, 若山 顕治, 蒲池 浩文, 神山 俊哉

  IVR: Interventional Radiology (一社)日本インターベンショナルラジオロジー学会 32 (4) 326 - 326 1340-4520 2018/01
• Differential diagnosis of parkinsonism by a combined use of diffusion kurtosis imaging and quantitative susceptibility mapping

  Kenji Ito, Chigumi Ohtsuka, Kunihiro Yoshioka, Hiroyuki Kameda, Suguru Yokosawa, Ryota Sato, Yasuo Terayama, Makoto Sasaki

  NEURORADIOLOGY 59 (8) 759 - 769 0028-3940 2017/08 [Refereed][Not invited]
   

  Purpose We investigated whether diffusion kurtosis imaging (DKI) and quantitative susceptibility mapping (QSM) could detect pathological changes that occur in Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA-P) or predominant cerebellar ataxia (MSA-C), and progressive supranuclear palsy syndrome (PSPS) and thus be used for differential diagnosis that is often difficult. Methods Seventy patients (41 with PD, 6 with MSA-P, 7 with MSA-C, 16 with PSPS) and 20 healthy controls were examined using a 3.0 T MRI scanner. From DKI and QSM data, we automatically obtained mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) values of the midbrain tegmentum (MBT), pontine crossing tract (PCT), and superior/middle cerebellar peduncles (CPs), which were used to calculate diffusion MBT/PCT ratios (dMPRs) and diffusion superior/middle CP ratios (dCPRs), as well as MS (magnetic susceptibility) values of the anterior/posterior putamen (PUa and PUp) and globus pallidus (GP). Results dMPRs of MK were significantly decreased in PSPS and increased in MSA-C compared with the other groups, while dCPRs of MK showed significant differences only between MSA-C and PD, PSPS, or control. MS values were significantly increased in the PUp of MSA-P and in the PUa and GP of PSPS compared with those in PD. The combined use of MK-dMPR and MS-PUp showed sensitivities of 83-100% and specificities of 81-100% for discriminating among the disease groups, respectively. Conclusion A quantitative assessment using DKI and QSM analyses, particularly MK-dMPR and MS-PUp values, can readily identify patients with parkinsonism.
• Noninvasive Assessment of Oxygen Extraction Fraction in Chronic Ischemia Using Quantitative Susceptibility Mapping at 7 Tesla

  Ikuko Uwano, Kohsuke Kudo, Ryota Sato, Kuniaki Ogasawara, Hiroyuki Kameda, Jun-ichi Nomura, Futoshi Mori, Fumio Yamashita, Kenji Ito, Kunihiro Yoshioka, Makoto Sasaki

  STROKE 48 (8) 2136 - 2141 0039-2499 2017/08 [Refereed][Not invited]
   

  Background and Purpose-The oxygen extraction fraction (OEF) is an effective metric to evaluate metabolic reserve in chronic ischemia. However, OEF is considered to be accurately measured only when using positron emission tomography (PET). Thus, we investigated whether OEF maps generated by magnetic resonance quantitative susceptibility mapping (QSM) at 7 Tesla enabled detection of OEF changes when compared with those obtained with PET. Methods-Forty-one patients with chronic stenosis/occlusion of the unilateral internal carotid artery or middle cerebral artery were examined using 7 Tesla-MRI and PET scanners. QSM images were obtained from 3-dimensional T2*-weighted images, using a multiple dipole-inversion algorithm. OEF maps were generated based on susceptibility differences between venous structures and brain tissues on QSM images. OEF ratios of the ipsilateral middle cerebral artery territory against the contralateral side were calculated on the QSM-OEF and PET-OEF images, using an anatomic template. Results-The OEF ratio in the middle cerebral artery territory showed significant correlations between QSM-OEF and PET-OEF maps (r=0.69; P<0.001), especially in patients with a substantial increase in the PET-OEF ratio of 1.09 (r=0.79; P=0.004), although showing significant systematic biases for the agreements. An increased QSM-OEF ratio of >1.09, as determined by receiver operating characteristic analysis, showed a sensitivity and specificity of 0.82 and 0.86, respectively, for the substantial increase in the PET-OEF ratio. Absolute QSM-OEF values were significantly correlated with PET-OEF values in the patients with increased PET-OEF. Conclusions-OEF ratios on QSM-OEF images at 7 Tesla showed a good correlation with those on PET-OEF images in patients with unilateral steno-occlusive internal carotid artery/middle cerebral artery lesions, suggesting that noninvasive OEF measurement by MRI can be a substitute for PET.
• Tmax Determined Using a Bayesian Estimation Deconvolution Algorithm Applied to Bolus Tracking Perfusion Imaging: A Digital Phantom Validation Study

  Ikuko Uwano, Makoto Sasaki, Kohsuke Kudo, Timothe Boutelier, Hiroyuki Kameda, Futoshi Mori, Fumio Yamashita

  MAGNETIC RESONANCE IN MEDICAL SCIENCES 16 (1) 32 - 37 1347-3182 2017 [Refereed][Not invited]
   

  Purpose: The Bayesian estimation algorithm improves the precision of bolus tracking perfusion imaging. However, this algorithm cannot directly calculate Tmax, the time scale widely used to identify ischemic penumbra, because Tmax is a non-physiological, artificial index that reflects the tracer arrival delay (TD) and other parameters. We calculated Tmax from the TD and mean transit time (MTT) obtained by the Bayesian algorithm and determined its accuracy in comparison with Tmax obtained by singular value decomposition (SVD) algorithms. Methods: The TD and MTT maps were generated by the Bayesian algorithm applied to digital phantoms with time-concentration curves that reflected a range of values for various perfusion metrics using a global arterial input function. Tmax was calculated from the TD and MTT using constants obtained by a linear least-squares fit to Tmax obtained from the two SVD algorithms that showed the best benchmarks in a previous study. Correlations between the Tmax values obtained by the Bayesian and SVD methods were examined. Results: The Bayesian algorithm yielded accurate TD and MTT values relative to the true values of the digital phantom. Tmax calculated from the TD and MTT values with the least-squares fit constants showed excellent correlation (Pearson's correlation coefficient = 0.99) and agreement (intraclass correlation coefficient = 0.99) with Tmax obtained from SVD algorithms. Conclusions: Quantitative analyses of Tmax values calculated from Bayesian-estimation algorithm derived TD and MTT from a digital phantom correlated and agreed well with Tmax values determined using SVD algorithms.
• Breath-holding during the Calibration Scan Improves the Reproducibility of Parallel Transmission at 7T for Human Brain

  Taisuke Harada, Kohsuke Kudo, Ikuko Uwano, Fumio Yamashita, Hiroyuki Kameda, Tsuyoshi Matsuda, Makoto Sasaki, Hiroki Shirato

  MAGNETIC RESONANCE IN MEDICAL SCIENCES 16 (1) 23 - 31 1347-3182 2017 [Refereed][Not invited]
   

  Purpose: The B0 and B1+ maps required for calculation of the radiofrequency (RF) pulse of parallel transmission (pTx) are obtained in calibration scans; however, they may be affected by respiratory motion. We aimed to compare the reproducibility of B0 and B1+ maps and gradient echo (GRE) images of the brain scanned with pTx at 7T between free-breathing (FB) and breath-holding (BH) conditions during the calibration scan. Methods: Nine healthy volunteers were scanned by 7T MRI using a two-channel quadrature head coil. In the pTx calibration scans performed with FB and BH, the B0 map was obtained from two different TE images and the B1+ map was calculated by the Bloch-Siegert method. A GRE image (gradient-recalled acquisition in steady state) was also obtained with RF shimming and RF design of pTx with spoke method, as well as quadrature transmission (qTx). All the scans were repeated over five sessions. The reproducibility of the B0 and B1+ maps and GRE image was evaluated with region-of-interest measurements using inter-session standard deviation (SD) and coefficient of variation (CV) values. Intensity homogeneity of GRE images was also assessed with in-plane CV. Results: Inter-session SDs of B0 and B1+ maps were significantly smaller in BH (P < 0.01). Inter-session CVs of GRE images were significantly smaller in qTx than BH and FB (P < 0.01, both); however, the CVs of BH were significantly smaller (P < 0.01). In-plane CVs of FB and BH with RF shimming were not significantly different with qTx; however, CVs of FB and BH with RF design were significantly smaller than those of qTx (P < 0.05 and P < 0.01, respectively). Conclusion: BH could improve the reproducibility of B0 and B1+ maps in pTx calibration scans and GRE images. These results might facilitate the development of pTx in human brain at 7T.
• Amplatzer vascular plug 4(AVP4)を用いた腹腔動脈瘤に対する塞栓術の経験

  木村 輔, 阿保 大介, 亀田 浩之, 高橋 文也, 曽山 武士, 作原 祐介, 工藤 與亮

  IVR: Interventional Radiology (一社)日本インターベンショナルラジオロジー学会 31 (2) 175 - 175 1340-4520 2016/06
• Detection of changes in the ventral tegmental area of patients with schizophrenia using neuromelanin-sensitive MRI.

  Fumio Yamashita, Makoto Sasaki, Kentaro Fukumoto, Kotaro Otsuka, Ikuko Uwano, Hiroyuki Kameda, Jin Endoh, Akio Sakai

  Neuroreport 27 (5) 289 - 94 0959-4965 2016/03/23 [Refereed][Not invited]
   

  The ventral tegmental area (VTA), one of the neuromelanin-containing dopaminergic nuclei in the midbrain, is closely related to the pathogenesis of schizophrenia, but its imaging findings remain unclear. Here, we investigated whether neuromelanin-sensitive MRI can detect alterations in the signals of the VTA of patients with schizophrenia. Neuromelanin-sensitive T1-weighted images at 3 T were obtained in 14 patients with schizophrenia and 22 healthy individuals. After signal inhomogeneity correction, brain signal rescaling of the images, and spatial normalization, signal intensity of the VTA and substantia nigra pars compacta (SNc) was automatically measured using the regions-of-interest constructed from the images of the healthy individuals. The normalized signal intensity of the VTA in patients with schizophrenia (median ± quartile deviation, 998 ± 10) was significantly decreased compared with that in healthy controls (1018 ± 15) (P=0.010), whereas that of the SNc was not significantly different between the groups (1093 ± 6 and 1098 ± 10, respectively, P=0.84). The VTA/SNc ratio was also significantly lower in patients with schizophrenia (0.916 ± 0.007) than in the control participants (0.934 ± 0.010) (P=0.010). In addition, the scores of the Scale for the Assessment of Positive Symptoms showed an independent negative correlation with VTA signaling (r=-0.69, P=0.012). Neuromelanin-sensitive MRI enables direct visualization of the selective signal attenuation in the VTA, which was correlated with positive symptoms, in patients with schizophrenia.
• Detection of changes in the periaqueductal gray matter of patients with episodic migraine using quantitative diffusion kurtosis imaging: preliminary findings

  Kenji Ito, Masako Kudo, Makoto Sasaki, Ayumi Saito, Fumio Yamashita, Taisuke Harada, Suguru Yokosawa, Ikuko Uwano, Hiroyuki Kameda, Yasuo Terayama

  NEURORADIOLOGY 58 (2) 115 - 120 0028-3940 2016/02 [Refereed][Not invited]
   

  The periaqueductal gray matter (PAG) is considered to play an important role in generating migraine, but findings from imaging studies remain unclear. Therefore, we investigated whether diffusion kurtosis imaging (DKI) can detect changes in the PAG of migraine patients. We obtained source images for DKI from 20 patients with episodic migraine and 20 healthy controls using a 3 T magnetic resonance imaging scanner. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) maps were generated, and the values of the PAG and other deep gray and white matter structures were automatically measured using an atlas-based region-of-interest analysis. The metrics of these structures were compared between the patients and controls. The MK and MD values of the PAG were significantly increased in the migraine patients compared with the controls (p < 0.05). The FA values were not significantly different. There were no significant differences in the metrics of the other structures between the patients and controls. The MK values of the PAG were significantly positively correlated with both age and the untreated period in the patient group under univariate analysis (r = 0.53 and 0.56, respectively; p < 0.05) but not multivariate analysis. DKI detected significant increases in the MK and MD values of the PAG in patients with migraine, which suggests that structural changes in the PAG are associated with the pathophysiological mechanisms of migraine.
• CTが診断に有用であった繰り返す消化管出血症例

  亀田 浩之, 真鍋 徳子, 菊池 穏香, 坂本 圭太, 三村 理恵, 加藤 扶美, 工藤 與亮, 藪崎 哲史, 宮本 憲幸, 西田 睦, 畑中 佳奈子, 大野 正芳, 高橋 典彦

  Japanese Journal of Radiology (公社)日本医学放射線学会 34 (Suppl.) 3 - 3 1867-1071 2016/02
• Diagnostic value of tumor blood flow and its histogram analysis obtained with pCASL to differentiate sinonasal malignant lymphoma from squamous cell carcinoma

  Noriyuki Fujima, Hiroyuki Kameda, Akiko Tsukahara, Daisuke Yoshida, Tomohiro Sakashita, Akihiro Homma, Khin Khin Tha, Kohsuke Kudo, Hiroki Shirato

  EUROPEAN JOURNAL OF RADIOLOGY 84 (11) 2187 - 2193 0720-048X 2015/11 [Refereed][Not invited]
   

  Objectives: To investigate the diagnostic value of tumor blood flow (TBF) obtained with pseudocontinuous arterial spin labeling (pCASL) for the differentiation of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the nasal or sinonasal cavity. Methods: Thirty-three patients with SCC and 6 patients with ML in the nasal or sinonasal cavity were retrospectively analyzed. Quantitative TBF values were obtained using whole-tumor region of interest (ROI) from pCASL data. The histogram analysis of TBF values within the tumor ROI was also performed by calculating the coefficient of variation (CV), kurtosis, and skewness. The mean TBF value, histogram CV, kurtosis and skewness of the patients with SCC were compared with those of the ML patients. The diagnostic accuracy to differentiate SCC from ML was also calculated by receiver operating characteristic (ROC) curve analysis. In addition, multiple logistic regression models were also performed to determine their independent predictive value, and diagnostic accuracy with the combined use of these parameters. Results: Between the SCC and ML groups, significant differences were observed in mean TBF, CV, and kurtosis, but not in skewness. In ROC curve analysis, the diagnostic accuracy values for the differentiation of SCC from ML in mean TBF, CV, and kurtosis were all 0.87, respectively. Multiple logistic regression models revealed TBF and CV were respectively independent predictive value. With the combination of these parameters, the diagnostic accuracy was elevated to 0.97. Conclusions: The TBF value and its histogram analysis obtained with pCASL can help differentiate SCC and ML. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
• 頭頸部における扁平上皮癌と悪性リンパ腫の腫瘍血流の違い

  亀田 浩之, 藤間 憲幸, 吉川 仁人, 吉田 篤司, 清水 幸衣, 吉田 大介, 塚原 亜希子, 工藤 與亮, Tha Khin Khin, 白土 博樹

  Japanese Journal of Radiology (公社)日本医学放射線学会 33 (Suppl.) 1 - 1 1867-1071 2015/02
• TRIM67 Protein Negatively Regulates Ras Activity through Degradation of 80K-H and Induces Neuritogenesis

  Hiroaki Yaguchi, Fumihiko Okumura, Hidehisa Takahashi, Takahiro Kano, Hiroyuki Kameda, Motokazu Uchigashima, Shinya Tanaka, Masahiko Watanabe, Hidenao Sasaki, Shigetsugu Hatakeyama

  JOURNAL OF BIOLOGICAL CHEMISTRY 287 (15) 12050 - 12059 0021-9258 2012/04 [Refereed][Not invited]
   

  Tripartite motif (TRIM)-containing proteins, which are defined by the presence of a common domain structure composed of a RING finger, one or two B-box motifs and a coiled-coil motif, are involved in many biological processes including innate immunity, viral infection, carcinogenesis, and development. Here we show that TRIM67, which has a TRIM motif, an FN3 domain and a SPRY domain, is highly expressed in the cerebellum and that TRIM67 interacts with PRG-1 and 80K-H, which is involved in the Ras-mediated signaling pathway. Ectopic expression of TRIM67 results in degradation of endogenous 80K-H and attenuation of cell proliferation and enhances neuritogenesis in the neuroblastoma cell line N1E-115. Furthermore, morphological and biological changes caused by knockdown of 80K-H are similar to those observed by overexpression of TRIM67. These findings suggest that TRIM67 regulates Ras signaling via degradation of 80K-H, leading to neural differentiation including neuritogenesis.
• Expression of recombinant sea urchin cellulase SnEG54 using mammalian cell lines

  Fumihiko Okumura, Hiroyuki Kameda, Takao Ojima, Shigetsugu Hatakeyama

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 395 (3) 352 - 355 0006-291X 2010/05 [Refereed][Not invited]
   

  We previously identified the cellulase SnEG54 from Japanese purple sea urchin Strongylocentrotus nudus, the molecular mass of which is about 54 kDa on SDS-PAGE. It is difficult to express and purify a recombinant cellulase protein using bacteria such as Escherichia coli or yeast. In this study, we generated mammalian expression vectors encoding SnEG54 to transiently express SnEG54 in mammalian cells. Both SnEG54 expressed in mammalian cells and SnEG54 released into the culture supernatant showed hydrolytic activity toward carboxymethyl cellulose. By using a retroviral expression system, we also established a mammalian cell line that constitutively produces SnEG54. Unexpectedly, SnEG54 released into the culture medium was not stable, and the peak time showing the highest concentration was approximately 1-2 days after seeding into fresh culture media. These findings suggest that non-mammalian sea urchin cellulase can be generated in human cell lines but that recombinant SnEG54 is unstable in culture medium due to an unidentified mechanism. (C) 2010 Elsevier Inc. All rights reserved.
• Inhibition of NF-kappa B signaling via tyrosine phosphorylation of Ymer

  Hiroyuki Kameda, Masashi Watanabe, Miyuki Bohgaki, Tadasuke Tsukiyama, Shigetsugu Hatakeyama

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 378 (4) 744 - 749 0006-291X 2009/01 [Refereed][Not invited]
   

  Cytoplasmic zinc finger protein A20 functionally dampens inflammatory signals and apoptosis via inhibition of NF-kappa B activation. We have reported that Ymer interacts with A20 and lysine (K)-63-linked polyubiquitin chain and that Ymer inhibits NF-kappa B signaling in collaboration with A20. It has also been reported that Ymer is phosphorylated by EGF stimulation. We found that Ymer was considerably phosphorylated on tyrosine residues also via Src family kinases such as Lck. A luciferase reporter assay showed that mutation of tyrosines on Ymer (YmerY217/279/304F) results in loss of the inhibitory activity for NF-kappa B signaling. Furthermore, a soft agar colony formation assay showed that the combination of SFCY527F and YmerY217/279/304F has no ability for anchorage-independent growth, suggesting that tyrosine phosphorylation of Ymer is important for inhibition of the NF-kappa B-mediated apoptotic pathway. These findings demonstrate that Ymer is likely to be a negative regulator for the NF-kappa B signaling pathway. (C) 2008 Elsevier Inc. All rights reserved

Books etc

• Annual Review神経

  亀田浩之, 工藤 與亮 (ContributorBasic Neuroscience 画像 酸素の安定同位体17Oによる脳水動態イメージング(解説))
  中外医学社 2022/05 (ISBN: 9784498328822) xi, 331p

Conference Activities & Talks

• 17O標識水とMRIを用いたneurofluidsの可視化  [Invited]

  第51日本磁気共鳴医学会大会
• 17O標識水とMRIを用いた髄液循環の可視化  [Invited]

  第53日本神経精神薬理学会年会
• Neurofluids dynamics by MR imaging  [Invited]

  Hiroyuki Kameda

  the 10th GCB Biomedical Science and Engineering Symposium  2023/08
• Visualization of Human Neurofluids Using Intrathecal 17O-Labelled Water and MRI:A Preliminary Study

  Hiroyuki Kameda

  Joint Annual Meeting ISMRM-ESMRMB & ISMRT Annual Meeting
• Increased Vascular Permeability of 17O-labeled Water in the Amyotrophic Lateral Sclerosis Model Mice using Indirect Proton MRI

  Hiroyuki Kameda

  Joint Annual Meeting ISMRM-ESMRMB & ISMRT Annual Meeting
• 17O-Proton MRIによる中枢神経系の水動態イメージングの試み  [Invited]

  亀田浩之

  第44日本脳神経CI学会総会
• Challenges of glymphatic imaging with 17O-Proton MRI  [Invited]

  Hiroyuki Kameda

  AIMS Neuro Imaging 2020  2020/10
• 17O-Proton MR Imaging of Aqua Dynamics in Central Nerve System  [Invited]

  亀田浩之

  第48回日本磁気共鳴医学会大会
• Detection of Metabolic Water Generated from 17O2 and 17O-Labeled Glucose in Cultured Cells by Indirect Proton MRI

  Hiroyuki Kameda

  ISMRM JPC 2019
• Indirect Proton MRI with 17O-labeled Water Can Detect Blood-Spinal Cord Barrier Abnormalities in the Amyotrophic Lateral Sclerosis Mouse Model

  Hiroyuki Kameda

  ISMRM JPC 2019

MISC

• 酸素-17安定同位体標識水を水トレーサーとして用いたMRIによる関節軟骨病変評価法の確立

  細川吉暁, 小野寺智洋, 亀田浩之, 宝満健太郎, 山口純, 工藤與亮, 杉森博之, 岩崎倫政  日本整形外科学会雑誌  96-  (8)  2022
• ¹⁷O標識水を水トレーサーとして用いたMRIによる関節軟骨病変評価法の確立

  細川吉暁, 小野寺智洋, 宝満健太郎, 工藤與亮, 亀田浩之, 杉森博行  北海道整形災害外科学会  141st-  2022
• 乳房専用超音波CTにおける高精細音速像の有用性(第2報)

  加藤 扶美, 佐藤 恵美, 西田 睦, 山下 啓子, 竹下 卓志, 萩尾 加奈子, 押野 智博, 亀田 浩之, 常田 慧徳, 堀江 達則, 寺田 崇秀, 坪田 悠史, 川畑 健一, 田中 宏樹, 工藤 與亮  日本乳癌学会総会プログラム抄録集  29回-  72  -72  2021/07
• 乳房専用超音波CTの初期使用経験 高精細音速像の有用性

  加藤 扶美, 山下 啓子, 佐藤 恵美, 西田 睦, 竹下 卓志, 萩尾 加奈子, 押野 智博, 亀田 浩之, 常田 慧徳, 堀江 達則, 寺田 崇秀, 坪田 悠史, 川畑 健一, 工藤 與亮  日本乳癌学会総会プログラム抄録集  28回-  144  -144  2020/10
• Dynamic心筋CT perfusionに対するfour-dimensional similarity filterの画質改善効果の検討

  常田慧徳, 常田慧徳, 真鍋徳子, 亀田浩之, 原田太以佑, 加藤扶美, 工藤與亮  日本心血管画像動態学会プログラム・抄録集  30th-  2020
• Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)

  星野豊, 亀田浩之, 原田太以佑, 工藤與亮, 伊師雪友, 三橋智子, 杉野弘和  画像診断  40-  (13)  2020
• 17O標識水の第1相臨床試験 安全性および脳血流MRIの実現可能性に関する検討

  原田 太以佑, 工藤 與亮, 亀田 浩之, 佐藤 良太, 白猪 亨, 尾藤 良孝, 藤間 憲幸, 常田 慧徳, 野川 敏史, 前田 憲一郎, 林 宏至, 佐々木 真理  日本磁気共鳴医学会雑誌  39-  (2)  66  -66  2019/05
• 超高磁場7-テスラMRIを用いた2型糖尿病患者のレンズ核線条体動脈(LSA)の評価

  八代諭, 亀田浩之, 千田愛, 外舘祐介, 長谷川豊, 長澤幹, 高橋義彦, 武部典子, 小田知靖, 冨樫弘文, 村井智美, 上野育子, 佐々木真理, 小笠原邦昭, 石垣泰  日本動脈硬化学会総会・学術集会プログラム・抄録集(Web)  49th-  2017
• MDCTによる膵神経内分泌腫瘍(PNET)の組織学的grade、肝転移に関する検討

  宮本 憲幸, 坂本 圭太, 藪崎 哲史, 亀田 浩之, 豊永 拓哉, 吉野 裕紀, 木村 輔, 菊池 穏香, 三村 理恵, 加藤 扶美, 真鍋 徳子, 工藤 與亮, 土川 貴裕, 中村 透, 岡村 圭祐, 平野 聡  Japanese Journal of Radiology  34-  (Suppl.)  13  -13  2016/02  [Not refereed][Not invited]
  
• 術前MRIによる膵頭部切除後膵液漏発生の検討

  宮本 憲幸, 坂本 圭太, 薮崎 哲史, 高橋 文也, 木村 輔, 亀田 浩之, 菊池 穏香, 三村 理恵, 加藤 扶美, 真鍋 徳子, 工藤 與亮, 白土 博樹, 中村 透, 松本 譲, 岡村 圭祐, 平野 聡  IVR: Interventional Radiology  30-  (3)  271  -271  2015/09  [Not refereed][Not invited]
  

Industrial Property Rights

• 特願2020-180918:軟骨の損傷を検出するための造影剤、並びに当該造影剤を利用した軟骨の損傷を検査する方法及びプログラム  

  小野寺智洋, 工藤興亮, 細川吉暁, 岩崎倫政, 亀田浩之

Awards & Honors

• 2024/02 日本神経放射線学会 令和5 (2023)年度 日本神経放射線学会研究助成金制度
   「17O標識水を用いた髄液動態の可視化」
• 2020/05 2) 第79回日本医学放射線学会総会イメージインタープリテーションセッション 成績優秀賞（第1位）
  
• 2015 アジア・オセアニア神経放射線学会 Magna Cum Laude
  

Research Grants & Projects

• Proton isotope effect as the method to repair marginal liver graft by extracorporeal perfusion

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2023/04 -2026/03 

  Author : 嶋村 剛, 深井 原, 惠 淑萍, 暮地本 宙己, 亀田 浩之, 西川 祐司
• Exploration of the optimal pH for the graft during cold storage and machine perfusion

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2023/04 -2026/03 

  Author : 深井 原, 暮地本 宙己, 亀田 浩之
• 歯周病細菌の脳への移行トレース

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2022/04 -2025/03 

  Author : 箕輪 和行, 亀田 浩之, 長谷部 晃

   

  令和4年度は、in vitroで使用する細菌の種類、造影剤の種類や濃度、細菌への造影剤標識方法、MRI撮像用のサンプル作製方法、MRIの撮像方法を検討した。 使用する細菌の種類としてはPorphyromonas gingivalis（ATCC 33277）、Aggregatibacter actinomycetemcomitans(ATCC 29522)、Streptcoccs mitis(ATCC 9811)を使用した。造影剤の種類および濃度の検討ではGd系としてプリモビスト、マグネビスト、Mn系としてボースデル、Fe系としてリゾビストを使用し、各造影剤を7.7μmol/L、0.77μmol/L、0.077μmol/L、0.0077μmol/Lの濃度で各細菌に使用した。また、細菌への造影剤標識方法の検討では上記の造影剤の条件下で、造影剤と液体培地の混合液での培養、あるいは、ヒートショックを行った。処理後の各サンプルの菌体はホルマリンにて失活・固定した後、複数回洗浄を行い、加温したアガロース溶液で可及的速やかに均一に懸濁した後、プラスチックサンプル管内で硬化させた。各固形サンプルを配列し、その周囲をさらに寒天で充填させ、MRI撮像用のサンプルとした。作製したサンプルを研究用3T-MRI装置で撮像した。撮像シークエンスは、T2 map、T2*map、マルチエコー3D-T1強調像を用いた。Matlab上で、定量的磁化率マッピング画像（QSM画像）を計算し、各条件において定量値に有意な変化があるかどうかを検討した。 以上の結果より、使用する細菌としてはPorphyromonas gingivalis（ATCC 33277）およびStreptcoccs mitis(ATCC 9811)が妥当であり、使用する造影剤としてはFe系であるリゾビストが妥当であると考えられた。
• 水と溶質の同位体イメージングによる脳間質の恒常性維持機構の解明

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2022/04 -2025/03 

  Author : 亀田 浩之

   

  T2-preparationパルスを利用した高速T2 mapping法の17O濃度計測における精度を既知のT2 mapping法（CPMG法）と比較したところ、短時間でほぼ同等の精度で17O濃度計測ができることを確認した。野生型ラットに対する17O水髄注モデルでの少数の検討では、有意なT2値変化を検出することができず、脳実質に併せた適切なTEポイントでの計測が必要であり、追加の条件検討が必要であると考えられた。その他、複数の17O水投与経路として、ラットの外頚動脈経由で片側の内頚動脈内に17O水動注を行いながらMRI撮像ができるモデルを確立した。また、脳内水動態異常を簡便に検証するモデルとして、片側頚部リンパ節結紮モデルラットを確立し、Gd髄注MRIを用いた検討で、同モデルは野生型ラットと比較して、鼻腔からの頭蓋内CSFの排泄が遅延することを明らかにした。今後、17O-MRIでの検討を予定している。 組織レベルでの脳内17O分布をクライオ同位体顕微鏡でみるために、サンプル処理も含めたいくつかの条件検討を行った。脳サンプルは本検討で扱いが難しかったため、18O標識水をラットの肝臓内に注入し、血管内や細胞間隙、細胞内の18O分布のミクロの可視化を試みたところ、肝血管内に一致した18O分布を可視化することができた。しかし、脳サンプルでは肝臓サンプルよりも組織構築が複雑なためか、やや複雑な18O水の分布がどのような組織分布に対応しているのかの推定が難しく、組織情報をもつ対比画像が必要であると考えられた。
• Multi-scale Imaging of Water Molecules using MRI and Isotope Microscope

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2021/04 -2024/03 

  Author : 工藤 與亮, 亀田 浩之, 杉森 博行, 村上 正晃, 坂本 直哉, 小牧 裕司, 小畠 隆行, 安井 正人

   

  ①MRI撮像法開発：O-17標識水の存在によるT2値の短縮を定量的に計測してO-17濃度を定量解析するため、プリパルスを利用した高速T2 mapping法の最適化を行い、精度検証を行った。った。異なる濃度のO-17標識水を含有した濃度ファントムを作成し、高速T2 mapping法と従来のFSE法によるT2 mapping法の精度を比較した。従来法と比較して高精度のT2値測定が可能となったが、低濃度域での精度が十分ではなく、安定性なども改善が必要と考えられた。 ②正常動物・疾患モデル動物でのMRI撮像：正常マウスやラットにてO-17標識水の静脈内投与や髄腔内投与、頸動脈内投与などを行い、脳脊髄液腔や脳実質のMRI信号変化を確認し、O-17濃度に変換することも可能になった。ALSモデルマウス・ラットにてO-17標識水を静脈内投与、髄腔内投与してMRI撮像を行った。野生型と比較して小脳でのO-17濃度上昇が認められ、臨床研究に応用することが可能になった。 ③同位体顕微鏡による水分子イメージング：多機能コーティング装置を用いて凍結下での標本作成から同位体顕微鏡によるイメージングまでの解析手順の確認や最適化を行った。 ④ヒトでのMRI撮像：認知症患者を対象にしたO-17標識水の髄腔内投与研究にて、特発性正常圧水頭症患者とアルツハイマー型認知症患者で研究を継続しており、間接法によるR2変化からの濃度計測に加えて、R2直接計測法も追加して検討を行った。安定性には改善が必要であるが、脳内のO-17濃度変化を捉えることに成功した。
• 全身主要血管壁内における歯周病原性菌の存在分布ー脳血管障害による死亡例をもとに

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  Date (from‐to) : 2020/04 -2023/03 

  Author : 竹内 明子, 的場 光太郎, 箕輪 和行, 兵頭 秀樹, 亀田 浩之, 長谷部 晃

   

  ご遺体（法医解剖体）における死後画像取得（CTおよびMRI）により、大血管壁の肥厚・狭窄部の画像的検索を行い、血管プラークを含む主要大血管の血管壁を検体として採取した。これらの検体数は前年よりも5例追加され23例となった。 採取した検体から血管内皮を剥離し、DNA抽出・リアルタイムPCRにて菌体量を測定した。採取した血管壁のうち、頸動脈、胸部大動脈、腹部大動脈では、血管内皮の剥離は比較的容易であるのに対し、脳血管においては、血管内皮の剥離が困難な場合が多く、またDNA抽出時に十分な組織重量を確保するため、血管内皮を剥離せずに用いることとした。 胸部大動脈・腹部大動脈では特に血管内皮に石灰化プラークがみられることが多く、血管壁の石灰化部分では、DNA採取（抽出）が困難となる場合があった。このため、判別可能な範囲で石灰化を含まない血管プラークを検体として採取したが、採取した検体に目視困難な微細石灰化が存在することがあり、DNA採取（抽出）の精度が下がる事例があるため、工夫が必要である。個人差があるが、一般には高齢であるほど血管壁の石灰化傾向がみられるため、死後画像（CT画像）にて血管壁の石灰化が認められる症例では、石灰化部を画像ワークステーション上で抽出し、検索・計測を行い、スコア化を検討している。 また、法医解剖時にご遺体（法医解剖体）の歯科所見を採取し、残存歯数や歯科治療痕等のデータ取得をさらに進めている。さらに、症例増加により調整が必要となっていた残存歯における歯周病進行度のスコアを修正した。さらに、口腔内（歯周ポケット含む）細菌の採取とこれら細菌叢に対してPCRを行い、死後の口腔内細菌叢についての分析・検証を進めている。
• 酸素の安定同位体O-17標識水による筋萎縮性側索硬化症の早期診断MRI

  国立研究開発法人日本医療研究開発機構：難治性疾患等実用化研究事業

  Date (from‐to) : 2020/04 -2023/03
• O-17標識水を用いたMRIと同位体顕微鏡による中枢神経系の水動態の解明

  日本学術振興会：科学研究費助成事業, 若手研究

  Date (from‐to) : 2019/04 -2021/03 

  Author : 亀田 浩之

   

  17O-MRI間接法による脳脊髄液動態の画像解析法を確立する上で、MRI装置の高い信号感度が必要なことが分かり、特注の小動物用8chコイル(高島製作所)で撮影条件を最適化し、ラットの髄液中に投与した17O水（10mol%, 90mol%）によると考えられる信号変化を脳実質に検出することができた。筋萎縮性側索硬化症（Amyotrophic Lateral Sclerosis, ALS）モデルラットを用いた検討では、ALSラット群で17O水の脳内への移行が速い傾向にあることが分かった。同様の検討を研究協力施設の実験動物中央研究所の小動物用7T-MRIでも行い、同様の結果を確認した。 組織レベルでの脳内17O分布をクライオ同位体顕微鏡でみるために、18O標識水をラットの脳内に直接注入し分析したところ、常温条件よりも高感度な18O分布を可視化することができた。これには分析面の処理のさらなる工夫が必要であり、本分析における脳の取り扱いがやや難しかったため、肝臓をターゲットとした。ラットのグラフト肝の門脈から18O標識水を注入し、クライオ同位体顕微鏡で観察を行ったところ、肝血管内に一致した18O分布を可視化することができた。ただし、脳においては、17O水や18O水のミクロ分布がどのようなミクロの構造に一致して分布しているのか確認する手段がなく、モデル動物での検証には至らなかった。内因性同位体イメージングによる組織イメージの同時取得や、その他の装置（クライオ電子顕微鏡など）とも連携した解析系の開発が必要であると考えられた。

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