Faculty Profiles - NAGANAWA, Shinji

Prediction of Intracranial Arterial Stenosis Progression in Patients with Moyamoya Vasculopathy: Contrast-Enhanced High-Resolution Magnetic Resonance Vessel Wall Imaging. International journal

Shinsuke Muraoka, Yoshio Araki, Toshiaki Taoka, Hisashi Kawai, Sho Okamoto, Kenji Uda, Shinji Ota, Shinji Naganawa, Toshihiko Wakabayashi

World neurosurgery Vol. 116 page： e1114 - e1121 2018.8

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

OBJECTIVE: Moyamoya vasculopathy (MMV) is characterized by progressive stenosis of the intracranial arteries. MMV currently has no curative treatments, and cerebral ischemia and hemorrhage are the major outcomes. Evaluation of the stroke risk of each patient resulting from the progression of intracranial arterial stenosis is clinically important. METHODS: We prospectively reviewed patients with intracranial arterial stenosis and already diagnosed MMV. High-resolution magnetic resonance imaging using contrast agent is the novel vessel wall imaging (VWI) technique for directly evaluating vascular walls and intracranial artery disease. All patients underwent high-resolution vessel wall imaging and magnetic resonance angiography at the time of registration, and they underwent follow-up magnetic resonance angiography. The Fisher exact test was used to assess associations between the degrees of wall enhancement and between stable and progressive intracranial arterial stenosis. RESULTS: A total of 24 patients (17 female; mean age, 36.1 ± 16.8 years; range 3-67 years) with MMV were consecutively recruited to this study. Progression of stenosis was shown in 6 lesions (66.6%) on strong enhancement, 2 lesions (12.5%) on mild enhancement, and 1 lesion (4.3%) on lack of enhancement. Arterial vessel wall enhancement in MMV patients correlated closely with progression of intracranial arterial stenosis (P = 0.002). CONCLUSIONS: Arterial vessel wall enhancement in MMV patients was closely related to progression of intracranial arterial stenosis. Strong enhancement of the intracranial vessel wall was associated with intracranial arterial stenosis progression, and lack of enhancement correlated with the stability of intracranial arterial stenosis.

DOI： 10.1016/j.wneu.2018.05.181

Predictive factors for the outcomes of initial I-131 low-dose ablation therapy to Japanese patients with differentiated thyroid cancer.

Shinji Ito, Shingo Iwano, Katsuhiko Kato, Shinji Naganawa

Annals of nuclear medicine Vol. 32 ( 6 ) page： 418 - 424 2018.7

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

OBJECTIVE: To identify prognostic factors associated with a low-iodine diet (LID) and the amount of remnant thyroid tissue in Japanese patients with differentiated thyroid cancer (DTC) who received initial I-131 remnant ablation (RAI) using a fixed low dose of I-131 (1110 MBq). PATIENTS AND METHODS: In this prospective study, we enrolled 45 patients. Patients were classified into a self-managed LID group and a strict LID group. We measured the urinary iodine concentration on the day of RAI after patients consumed LID for 2 weeks. Thyroid-stimulating hormone-induced thyroglobulin (Tg) levels and I-131 uptake by the remnant thyroid tissue were also evaluated. A response-evaluation whole-body scan (WBS) was performed 6-8 months after RAI to determine the outcome of the therapy. RESULTS: Post-LID urinary iodine levels of the strict LID group tended to be lower than those of the self-managed LID group. Twenty-five cases (56%) showed absence of uptake, whereas 20 cases (44%) showed residual uptake on the response-evaluation WBS. There were no significant differences between "absence" and "residual" groups in urinary iodine concentrations and Tg levels (p = 0.253 and p = 0.234, respectively). However, significant differences were observed in I-131 uptake by the thyroid bed (p = 0.035). CONCLUSIONS: For patients following the current Japanese method of a 2-week LID, the urinary iodine concentration was not a predictive factor for the successful outcome of RAI. In contrast, low I-131 uptake by the thyroid bed, revealed by the scintigram after RAI, may serve as a favorable predictive factor.

DOI： 10.1007/s12149-018-1261-0

Study Protocol: Prospective Study of Concurrent Chemoradiotherapy with S-1 and Hypofractionated Radiotherapy for Outpatients with Early Glottic Squamous Cell Carcinomas International journal Open Access

Kana Kimura, Yoshiyuki Itoh, Tohru Okada, Seiji Kubota, Mariko Kawamura, Rie Nakahara, Yumi Oie, Yuka Kozai, Yuuki Takase, Hidenori Tsuzuki, Naoki Nishio, Mariko Hiramatsu, Yasushi Fujimoto, Takefumi Mizutani, Akihiro Hirakawa, Shinji Naganawa

Asian Pacific journal of cancer prevention : APJCP Vol. 19 ( 5 ) page： 1195 - 1199 2018.5

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

Background: The recommended treatment strategies for early glottic carcinoma with intent of larynx preservation are
primarily radiotherapy. However, the outcomes of radiotherapy for bulky T1 or T2 glottic carcinoma are unsatisfactory.
We designed a protocol consisting of concurrent chemoradiotherapy using S-1 as the radiosensitizer. We have performed
this protocol in patients with favorable T2 lesions and demonstrated its efficacy and safety. In contrast, we have
treated non-bulky T1 glottic carcinomas with 2.25 Gy per fraction, for a total of 25-28 fractions, starting in 2011 to
improve efficacy and shorten the treatment period. Since this treatment strategy was implemented for T1 disease, no
local failure has occurred to date, and it appears to be almost as safe as radiotherapy using 2.0 Gy per fraction. With
the aim of improving the local control rate and shortening the treatment period primarily for favorable T2 disease, we
changed the dose of radiation in our protocol from 2.0 Gy to 2.25 Gy per fraction, for a total of 25 fractions (from 30
fractions). The present study aims to evaluate the efficacy and safety of this new protocol. Methods: This study will
be conducted as a clinical, prospective, single-armed, non-randomized trial. Patients are to receive S-1 (55.3 mg /m2
/day, once daily) and radiotherapy (2.25 Gy per fraction, for a total of 25 fractions). S-1 and radiotherapy are started
on the same day that radiotherapy is performed, 3-6 hours after oral administration of S-1. The primary study aim is
the 3-year local control rate. The secondary study aims are overall survival, voice-preservation survival, disease-free
survival, complete response rate, completion rate, and toxicity. Result and conclusion: This is the first single-center,
non-randomized, prospective study of concurrent chemoradiotherapy with S-1 and hypofractionated radiotherapy to
be conducted. The trial will evaluate the efficacy and safety of our protocol.

DOI： 10.22034/APJCP.2018.19.5.1195

Evaluation of the tumoricidal and pain relief effects of Sr-89 on bone metastases of cancer by F-18-fluoride PET/CT, F-18-FDG PET/CT, bone scintigraphy/SPECT, and follow-up Reviewed

Kato Katsuhiko, Odagawa Tetsuro, Fujita Naotoshi, Tsutsumi Yoshinori, Matsuzawa Shinichiro, Mukumoto Ryuto, Hasegawa Chinatsu, Abe Shinji, Naganawa Shinji

JOURNAL OF NUCLEAR MEDICINE Vol. 59 page： . 2018.5

Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer. International journal

Suguru Yamada, Tsutomu Fujii, Yukihiro Yokoyama, Hiroki Kawashima, Osamu Maeda, Kojiro Suzuki, Tohru Okada, Eizaburo Ono, Junpei Yamaguchi, Nao Takano, Hideki Takami, Masamichi Hayashi, Yukiko Niwa, Yoshiki Hirooka, Yoshiyuki Ito, Shinji Naganawa, Yuichi Ando, Masato Nagino, Hidemi Goto, Yasuhiro Kodera

Cancer chemotherapy and pharmacology Vol. 81 ( 5 ) page： 815 - 821 2018.5

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

PURPOSE: For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen. METHODS: Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined. Patients were classified according to the designated dose levels of chemoradiotherapy using the GnP regimen. After additional 6 cycles of the GnP regimen were administered, surgery was considered if the patients had stable disease and tumor marker levels had normalized. RESULTS: DLT (grade 4 thrombocytopenia) was observed only in 1 of 12 patients, and the RD was set at level 3. Grade 3-4 leukopenia was observed in 9 (75.0%) patients, and neutropenia in 7 (58.3%). The response rate was 41.7%, and the disease control rate was 100%. Conversion surgery was performed in 6 (50%) patients, and curative resection (R0) was performed in all 6 patients (100%). Stratification according to the Evans classification system demonstrated one patient with grade 1b, one with grade 2, two with grade 3, and two with grade 4 disease. CONCLUSION: The RD for weekly administration was 800 mg/m2 for gemcitabine and 100 mg/m2 for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.

DOI： 10.1007/s00280-018-3554-3

Efficacy of percutaneous transhepatic portal vein embolization using gelatin sponge particles and metal coils. Reviewed International journal

Tomohiro Komada, Kojiro Suzuki, Takashi Mizuno, Tomoki Ebata, Masaya Matsushima, Shinji Naganawa, Masato Nagino

Acta radiologica open Vol. 7 ( 4 ) page： 2058460118769687 - 2058460118769687 2018.4

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

Background: Percutaneous transhepatic portal vein embolization (PTPE) can increase the future liver remnant (FLR) volume before extended liver resection; however, there is no current consensus regarding the best embolic material for PTPE. Purpose: To evaluate the efficacy of PTPE using gelatin sponge particles and coils. Material and Methods: The medical records of 136 patients who underwent PTPE using gelatin sponge particles and metal coils were retrospectively reviewed. We evaluated the procedural details, liver volume on CT, and clinical status before and after PTPE. Results: The mean FLR volume increased significantly from 390 ± 147 cm3 to 508 ± 141 cm3 (P < 0.001). A mean of 22.1 ± 9.4 days after PTPE, the mean increase in the ratio of FLR volume to total liver volume was 9.4 ± 6.5%. Complications related to PTPE occurred in five patients, including arterial damage (n = 4) and biloma (n = 1). The white blood cell count and C-reactive protein level increased significantly and then returned to baseline within seven days. Aspartate aminotransferase and alanine aminotransferase showed no significant changes. Fever (defined by the Common Terminology Criteria for Adverse Events v4.0) was reported in 74 patients (54%), but it was generally mild (Grade 1/2; n = 72). None of the patients experienced severe complications that required cancellation of surgery. Conclusion: PTPE with gelatin sponge particles and coils may impose low physical stress on patients and is a safe method of inducing a significant increase of FLR.

DOI： 10.1177/2058460118769687

Detecting sub-second changes in brain activation patterns during interictal epileptic spike using simultaneous EEG-fMRI. Reviewed International journal Open Access

Epifanio Bagarinao, Satoshi Maesawa, Yuji Ito, Naotaka Usui, Jun Natsume, Hirohisa Watanabe, Minoru Hoshiyama, Toshihiko Wakabayashi, Gen Sobue, Shinji Naganawa, Haruo Isoda

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology Vol. 129 ( 2 ) page： 377 - 389 2018.2

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

OBJECTIVE: Epileptic spikes are associated with rapidly changing brain activation involving the epileptic foci and other brain regions in the "epileptic network". We aim to resolve these activation changes using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings. METHODS: Simultaneous EEG-fMRI recordings from 9 patients with epilepsy were used in the analysis. Our method employed the whole scalp EEG data to generate regressors for the analysis of fMRI data using the general linear model. RESULTS: We were able to resolve, with milliseconds temporal resolution, changes in activation patterns involving suspected epileptic foci and other brain regions in the epileptic network during spike and slow wave. Using summary maps (called SSWAS maps) which show the activation frequency of voxels, we found that suspected epileptic foci tend to be significantly active during this interval. SSWAS maps also enabled the detection of the epileptic foci in 4 of 5 patients where the conventional event-timing-based analysis failed to identify. CONCLUSION: These findings demonstrated the efficacy of the method and the potential application of SSWAS maps to identify epileptic foci. SIGNIFICANCE: The method could help resolve activation changes during epileptic spike and could provide insights into the underlying pathophysiology of these changes.

DOI： 10.1016/j.clinph.2017.11.018

Imaging of the endolymphatic space in patients with Ménière's disease. International journal

Tadao Yoshida, Satofumi Sugimoto, Masaaki Teranishi, Hironao Otake, Masahiro Yamazaki, Shinji Naganawa, Tsutomu Nakashima, Michihiko Sone

Auris, nasus, larynx Vol. 45 ( 1 ) page： 33 - 38 2018.2

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

OBJECTIVE: To examine endolymphatic hydrops (EH) using magnetic resonance imaging (MRI) in patients with definite Ménière's disease (MD) and those with nonotological diseases. METHODS: We studied 32 patients with unilateral MD, 10 patients with bilateral MD and 21 patients with control ears who had other benign diseases not associated with hearing or vestibular dysfunction. The mean age of the subjects was 54.0 years (range 27-74) in the MD group and 56.1 years (range 24-79) in the control group. Using MRI, the degree of EH was classified as none, mild and significant in the cochlea and vestibule separately. The ratio of the area of endolymphatic space to the vestibular fluid space was calculated for the vestibule. The duration of MD was defined as the months between the first attack of MD and the MRI study. RESULTS: EH was present in the cochlea of 45/52 affected ears of patients with MD (87%) and in 16/42 control ears (38%). Significant cochlear hydrops was present in 37/52 affected ears (71%) and in 4/42 control ears (10%). EH in the vestibule was present in 49/52 affected ears (94%) and in 3/42 control ears (7%). Significant vestibular hydrops was present in 40/52 affected ears (77%) and in none of the 42 control ears. There was no relationship between the degree of EH and its duration. Using a cut off value for the relative size of EH in the vestibule of 41.9%, the test had a sensitivity of 88.5% and a specificity of 100% to diagnose definite MD. CONCLUSION: Cochlear EH was occasionally observed in control ears on MRI, as in normal temporal bone specimens. The presence or absence and degree of vestibular EH were significantly different between ears with MD and control ears. EH in the vestibule might be a specific predictor of definite MD.

DOI： 10.1016/j.anl.2017.02.002

Relationship between Contrast Enhancement of the Perivascular Space in the Basal Ganglia and Endolymphatic Volume Ratio. Open Access

Toshio Ohashi, Shinji Naganawa, Toshio Katagiri, Kayao Kuno

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 17 ( 1 ) page： 67 - 72 2018.1

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

PURPOSE: We routinely obtain the endolymphatic hydrops (EH) image using heavily T2-weighted three dimensional-fluid attenuated inversion recovery (hT2w-3D-FLAIR) imaging at 4 hours after intravenous administration of a single-dose of gadolinium-based contrast media (IV-SD-GBCM). While repeating the examination, we speculated that the contrast enhancement of the perivascular space (PVS) in the basal ganglia might be related to the degree of EH. Therefore, the purpose of this study was to investigate the relationship between the endolymphatic volume ratio (%ELvolume) and the signal intensity of the PVS (SI-PVS). MATERIALS AND METHODS: In 20 patients with a suspicion of EH, a heavily T2-weighted 3D-turbo spin echo sequence for MR cisternography (MRC) and an hT2w-3D-FLAIR as a positive perilymph image (PPI) were obtained at 4 hours after IV-SD-GBCM. The %ELvolume of the cochlea and the vestibule were measured on the previously reported HYDROPS2-Mi2 image. The PVS in the basal ganglia was segmented on MRC using a region-growing method. The PVS regions were copied and pasted onto the PPI, and the SI-PVS was measured. The larger value of the right and the left ears was employed as the %ELvolume, and the weighted average of both sides was employed as the SI-PVS. The correlation between the %ELvolume and the SI-PVS was evaluated. RESULT: There was a strong negative linear correlation between the %ELvolume of the cochlea and the SI-PVS (r = -0.743, P < 0.001); however, there was no significant correlation between the %ELvolume of the vestibule and the SI-PVS (r = -0.267, P = 0.256). CONCLUSION: There was a strong negative correlation between the cochlear %ELvolume and the SI-PVS. Contrast enhancement of PVS might be a biomarker of EH.

DOI： 10.2463/mrms.mp.2017-0001

Effects of Gradient Coil Noise and Gradient Coil Replacement on the Reproducibility of Resting State Networks. International journal Open Access

Epifanio Bagarinao, Erina Tsuzuki, Yukina Yoshida, Yohei Ozawa, Maki Kuzuya, Takashi Otani, Shuji Koyama, Haruo Isoda, Hirohisa Watanabe, Satoshi Maesawa, Shinji Naganawa, Gen Sobue

Frontiers in human neuroscience Vol. 12 page： 148 - 148 2018

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

The stability of the MRI scanner throughout a given study is critical in minimizing hardware-induced variability in the acquired imaging data set. However, MRI scanners do malfunction at times, which could generate image artifacts and would require the replacement of a major component such as its gradient coil. In this article, we examined the effect of low intensity, randomly occurring hardware-related noise due to a faulty gradient coil on brain morphometric measures derived from T1-weighted images and resting state networks (RSNs) constructed from resting state functional MRI. We also introduced a method to detect and minimize the effect of the noise associated with a faulty gradient coil. Finally, we assessed the reproducibility of these morphometric measures and RSNs before and after gradient coil replacement. Our results showed that gradient coil noise, even at relatively low intensities, could introduce a large number of voxels exhibiting spurious significant connectivity changes in several RSNs. However, censoring the affected volumes during the analysis could minimize, if not completely eliminate, these spurious connectivity changes and could lead to reproducible RSNs even after gradient coil replacement.

DOI： 10.3389/fnhum.2018.00148

Dosimetric feasibility of using tungsten-based functional paper for flexible chest wall protectors in intraoperative electron radiotherapy for breast cancer. International journal Open Access

Takeshi Kamomae, Hajime Monzen, Mariko Kawamura, Kuniyasu Okudaira, Takayoshi Nakaya, Takashi Mukoyama, Yoshikazu Miyake, Yoshitomo Ishihara, Yoshiyuki Itoh, Shinji Naganawa

Physics in medicine and biology Vol. 63 ( 1 ) page： 015006 - 015006 2017.12

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

Intraoperative electron radiotherapy (IOERT), which is an accelerated partial breast irradiation method, has been used for early-stage breast cancer treatment. In IOERT, a protective disk is inserted behind the target volume to minimize the dose received by normal tissues. However, to use such a disk, the surgical incision must be larger than the field size because the disk is manufactured from stiff and unyielding materials. In this study, the applicability of newly developed tungsten-based functional paper (TFP) was assessed as an alternative to the existing protective disk. The radiation-shielding performance of the TFP was verified through experimental measurements and Monte Carlo simulations. Percentage depth dose curves and lateral dose profiles with and without TFPs were measured and simulated on a dedicated IOERT accelerator. The number of piled-up TFPs was changed from 1 to 40. In the experimental measurements, the relative doses at the exit plane of the TFPs for 9 MeV were 42.7%, 9.2%, 0.2%, and 0.1% with 10, 20, 30, and 40 TFPs, respectively, whereas those for 12 MeV were 63.6%, 27.1%, 8.6%, and 0.2% with 10, 20, 30, and 40 TFPs, respectively. Slight dose enhancements caused by backscatter radiation from the TFPs were observed at the entrance plane of the TFPs at both beam energies. The results of the Monte Carlo simulation indicated the same tendency as the experimental measurements. Based on the experimental and simulated results, the radiation-shielding performances of 30 TFPs for 9 MeV and 40 TFPs for 12 MeV were confirmed to be acceptable and close to those of the existing protective disk. The findings of this study suggest the feasibility of using TFPs as flexible chest wall protectors in IOERT for breast cancer treatment.

DOI： 10.1088/1361-6560/aa96cf

Longitudinal up-regulation of endolymphatic hydrops in patients with Meniere's disease during medical treatment. International journal

Munehisa Fukushima, Tadashi Kitahara, Ryohei Oya, Shiro Akahani, Hidenori Inohara, Shinji Naganawa, Noriaki Takeda

Laryngoscope investigative otolaryngology Vol. 2 ( 6 ) page： 344 - 350 2017.12

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

Objective/Hypothesis: Meniere's disease (MD) is a common inner ear disease characterized by repeated episodic vertigo, fluctuating sensorineural hearing loss, and tinnitus. Its pathology is defined as endolymphatic hydrops (EH) in the inner ear and EH has been hypothesized to correlate with the clinical symptoms of MD. We presented the dynamics of in vivo EH in MD patients during medical treatments. Study Design: Prospective, single-arm repeated measures. Methods: Eleven MD patients were enrolled. All subjects prospectively underwent gadolinium-enhanced inner ear magnetic resonance (MR) imaging and neuro-otological testing before and after medical treatment. The volume of EH was quantitatively evaluated by processing MR images. All MD patients were administered continuous medication and followed up for more than 12 months. Results: The frequency of vertigo episodes decreased in all patients and vestibular function decreased to 13-91% of the pre-treatment level. The volume ratio of post-treatment EH-to-pre-treatment EH ranged from 1.01-3.22. The total volume of pre-treatment EH was significantly correlated with cochlear symptom disease duration and the affected ear's hearing level. Conclusion: EH in MD patients developed longitudinally with deterioration of inner ear function during medical treatment. The natural course of MD may progress with development of EH at least for a certain period. Level of Evidence: 2b.

DOI： 10.1002/lio2.115