Faculty Profiles - NAGANAWA, Shinji

Clinical outcomes of <SUP>125</SUP>I brachytherapy with and without external-beam radiation therapy for localized prostate cancer: results from 300 patients at a single institution in Japan Reviewed

Maki, S; Itoh, Y; Kubota, S; Okada, T; Nakahara, R; Ito, J; Kawamura, M; Naganawa, S; Yoshino, Y; Fujita, T; Kato, M; Gotoh, M; Ikeda, M

JOURNAL OF RADIATION RESEARCH Vol. 58 ( 6 ) page： 870 - 880 2017.11

Improved HYDROPS: Imaging of Endolymphatic Hydrops after Intravenous Administration of Gadolinium. Open Access

Shinji Naganawa, Hisashi Kawai, Toshiaki Taoka, Michihiko Sone

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 16 ( 4 ) page： 357 - 361 2017.10

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

To improve the imaging protocol for the evaluation of endolymphatic hydrops after intravenous administration of a gadolinium-based contrast agent, we modified our previously reported hybrid of reversed image of positive endolymph signal and native image of positive perilymph signal (HYDROPS) method. Although the scan time of the new protocol was half that of the previous one, there were no significant differences between two protocols in the mean contrast noise ratio between the endolymph and perilymph and the area ratio of the endolymph size values in nine patients.

DOI： 10.2463/mrms.tn.2016-0126

Comparison of I-123-IMP SPECT, F-18-FDG PET/CT, and F-18-FDOPA PET/CT in Detection of Choroidal Malignant Melanoma Reviewed

Kato K., Odagawa T., Tsutsumi T., Honda M., Kunimoto K., Mukumoto R., Matsuzawa S., Abe S., Naganawa S.

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Vol. 44 page： S745 - S745 2017.10

Development of the breast immobilization system in prone setup: The effect of bra in prone position to improve the breast setup error. Reviewed International journal Open Access

Mariko Kawamura, Yoshikazu Maeda, Kazutaka Yamamoto, Shigeyuki Takamatsu, Yoshitaka Sato, Hiroki Minami, Yusuke Saga, Kyo Kume, Yuji Tameshige, Makoto Sasaki, Hiroyasu Tamamura, Kouji Ohta, Yoshiyuki Itoh, Shinji Naganawa

Journal of applied clinical medical physics Vol. 18 ( 4 ) page： 155 - 160 2017.7

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

PURPOSE/OBJECTIVE(S): Accurate and reproducible positioning of the breast is difficult due to its deformability and softness; thus, targeting a breast tumor or tumor bed with fractionated radiotherapy using external beam radiation is difficult. The aim of this study was to develop a novel bra to aid in breast immobilization in the prone position. MATERIALS & METHODS: To assess the accuracy of prone position fixation of breast tumors, 33 breast cancer patients with 34 lesions were recruited. The bra used in this verification was customized from a commercially available bra. Duplicate MRI were acquired in the prone position, alternating with and without the bra, and for each series, patients were asked to step off the MRI table and re-set up in the prone position. Patients were also asked to remove and re-fit the bra for the second MRI. Each pair of images were superimposed to match the shape of the skin surface, and the maximum difference in tumor geometric center in three axes was measured. The required set up margin was calculated as: required margin = mean difference in geometric center + 2.5 standard deviation. The volumetric overlap of the tumor, as well as contouring uncertainties, was evaluated using contour analysis software. RESULTS: The median breast size was 498 cc. The required margins for the lateral, vertical, and longitudinal directions were estimated to be 4.1, 4.1, and 5.0 mm, respectively, with the bra, and 5.1, 6.9, and 6.7 mm, respectively, without the bra. These margins covered the dislocation of more than 33 lesions in total. With the bra, 33 lesions had achieved an objective overlap of 95% and 99% with 2 and 4 mm margins, respectively, whereas 4 and 8 mm, respectively, were needed without the bra. CONCLUSION: The use of an immobilizing bra reduced the setup margin for prone position fixation of breast tumors.

DOI： 10.1002/acm2.12116

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue International coauthorship International journal Open Access

Gregor Jost, Thomas Frenzel, Jessica Lohrke, Diana Constanze Lenhard, Shinji Naganawa, Hubertus Pietsch

EUROPEAN RADIOLOGY Vol. 27 ( 7 ) page： 2877 - 2885 2017.7

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

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study.
GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry.
Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h.
In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs.
aEuro cent Gadolinium-based contrast agents can cross the blood-CSF barrier.
aEuro cent Fluid-attenuated MRI shows GBCA distribution with CSF flow.
aEuro cent GBCA structure and physicochemical properties do not impact CSF penetration and distribution.
aEuro cent GBCA clearance from CSF was almost complete within 24 h in rats.
aEuro cent CSF is a potential pathway of GBCA entry into the brain.

DOI： 10.1007/s00330-016-4654-2

Clinical outcome of definitive radiation therapy for superficial esophageal cancer Reviewed

Clinical outcome of definitive radiation therapy for superficial esophageal cancer. Reviewed

Koide Y, Kodaira T, Tachibana H, Tomita N, Makita C, Itoh M, Abe T, Muro K, Tajika M, Niwa Y, Itoh Y, Naganawa S

Japanese journal of clinical oncology Vol. 47 ( 5 ) page： 393 - 400 2017.5

Koide, Y; Kodaira, T; Tachibana, H; Tomita, N; Makita, C; Itoh, M; Abe, T; Muro, K; Tajika, M; Niwa, Y; Itoh, Y; Naganawa, S

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 47 ( 5 ) page： 393 - 400 2017.5

Lack of Contrast Enhancement in a Giant Perivascular Space of the Basal Ganglion on Delayed FLAIR Images: Implications for the Glymphatic System. Open Access

Shinji Naganawa, Toshiki Nakane, Hisashi Kawai, Toshiaki Taoka

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 16 ( 2 ) page： 89 - 90 2017.4

Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases. Open Access

Toshiaki Taoka, Yoshitaka Masutani, Hisashi Kawai, Toshiki Nakane, Kiwamu Matsuoka, Fumihiko Yasuno, Toshifumi Kishimoto, Shinji Naganawa

Japanese journal of radiology Vol. 35 ( 4 ) page： 172 - 178 2017.4

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

PURPOSE: The activity of the glymphatic system is impaired in animal models of Alzheimer's disease (AD). We evaluated the activity of the human glymphatic system in cases of AD with a diffusion-based technique called diffusion tensor image analysis along the perivascular space (DTI-ALPS). MATERIALS AND METHODS: Diffusion tensor images were acquired to calculate diffusivities in the x, y, and z axes of the plane of the lateral ventricle body in 31 patients. We evaluated the diffusivity along the perivascular spaces as well as projection fibers and association fibers separately, to acquire an index for diffusivity along the perivascular space (ALPS-index) and correlated them with the mini mental state examinations (MMSE) score. RESULTS: We found a significant negative correlation between diffusivity along the projection fibers and association fibers. We also observed a significant positive correlation between diffusivity along perivascular spaces shown as ALPS-index and the MMSE score, indicating lower water diffusivity along the perivascular space in relation to AD severity. CONCLUSION: Activity of the glymphatic system may be evaluated with diffusion images. Lower diffusivity along the perivascular space on DTI-APLS seems to reflect impairment of the glymphatic system. This method may be useful for evaluating the activity of the glymphatic system.

DOI： 10.1007/s11604-017-0617-z

Magnetic resonance imaging evaluation of endolymphatic hydrops andpost-operative findings in cases with otosclerosis

Michihiko Sone, Tadao Yoshida, Satofumi Sugimoto, Kyoko Morimoto, Yuriko Okazaki, Masaaki Teranishi, Shinji Naganawa, Tsutomu Nakashima

ACTA OTO-LARYNGOLOGICA Vol. 137 ( 3 ) page： 242 - 245 2017.3

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Conclusions: The presence of endolymphatic hydrops (EH) in the vestibule on magnetic resonance imaging (MRI) might be a high-risk factor for complications in cases that are candidates for stapes surgery.
Objective: Pre-operative detection of EH could be valuable in cases that are candidates for stapes surgery to prevent unpredictable complications following surgery. Pre-operative MRI findings and post-operative findings following stapes surgery were compared to evaluate the efficacy of such MRI evaluation for the management of cases with otosclerosis.
Subjects and methods: Sixteen cases who underwent pre-operative evaluation by 3T MRI performed 4h after intravenous injection of gadolinium and stapes surgery for otosclerosis were recruited. Imaging data concerning the degree of EH in the vestibule and cochlea were compared with post-operative clinical findings for all cases.
Results: Mild EH in the cochlea or the vestibule was observed in eight ears and one ear, respectively, whereas one ear showed significant EH both in the cochlea and the vestibule. The post-operative course was uneventful in 12 of 14 cases with no EH in the vestibule, and the other two cases had a short period of dizziness, but two cases with EH in the vestibule had a long period of dizziness.

DOI： 10.1080/00016489.2016.1232862

Structure of the Medullary Veins of the Cerebral Hemisphere and Related Disorders

Toshiaki Taoka, Akio Fukusumi, Toshiteru Miyasaka, Hisashi Kawai, Toshiki Nakane, Kimihiko Kichikawa, Shinji Naganawa

RADIOGRAPHICS Vol. 37 ( 1 ) page： 281 - 297 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：RADIOLOGICAL SOC NORTH AMERICA

Deep medullary veins drain into subependymal veins with four convergence zones and show parallel distribution patterns adjacent to the body or inferior horn and a radial pattern in the frontal horn or trigon of the lateral ventricle. As white matter imaging develops such as diffusion tensor imaging or susceptibility-weighted imaging, requirements for understanding of white matter structures are increasing, not only for understanding of neuronal tracts but also for that of other structures including the fine anatomy of white matter vessels. Some disorders are related to deep medullary veins and show characteristic distributions of the lesions indicating the relationship to the medullary veins. When lesions show a parallel or radial distribution pattern in the certebral deep white matter, disorders related to deep medullary veins should be considered for differential diagnosis. In this review, we discuss disorders related to deep medullary veins, including (a) anomalies of the medullary veins, (b) hemorrhagic disorders related to the medullary veins (diffuse vascular injury due to high-energy trauma, deep medullary vein engorgement/thrombosis in neonates), (c) inflammatory changes that spread along the medullary veins, (d) neoplasms within the medullary veins, and (e) metabolic changes that lead to altered visualization of medullary veins. Understanding the anatomic structure of medullary veins in the cerebral hemisphere and becoming familiar with disorders in which the medullary veins play a major role in disease development may be helpful in the interpretation of brain images. (C) RSNA, 2017

DOI： 10.1148/rg.2017160061

Endolymphatic hydrops in patients with unilateral and bilateral Meniere's disease

Kyoko Morimoto, Tadao Yoshida, Saiko Sugiura, Masahiro Kato, Ken Kato, Masaaki Teranishi, Shinji Naganawa, Tsutomu Nakashima, Michihiko Sone

ACTA OTO-LARYNGOLOGICA Vol. 137 ( 1 ) page： 23 - 28 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Conclusion: All definite Meniere's disease (MD) had endolymphatic hydrops (EH) at least in the cochlea or the vestibule. Symptoms of MD may appear after formation of EH. It is assumed that the probability of immediate progression to bilateral MD from unilateral MD is very low in patients without EH on the non-affected side.
Objective: To evaluate the EH on both sides in patients with unilateral and bilateral MD, and to investigate factors with progression to bilateral MD including the degree of EH, hearing level, and the duration of MD.
Patients and methods: The study included 29 patients with unilateral definite MD and 12 patients with bilateral definite MD. The endolymphatic space size was visualized by using 3-Tesla magnetic resonance imaging.
Results: All patients with unilateral and bilateral MD had significant or mild EH at least in the cochlea or the vestibule on the affected side. On the non-affected side, EH was not observed at all in eight patients, but asymptomatic EH was observed in the cochlea in 14 patients and in the vestibule in 16 patients. There was no relationship between the EH on the non-affected side and the duration of MD.

DOI： 10.1080/00016489.2016.1217042

Emerging neuroradiological topics in journals from related societies Open Access

Yukunori Korogi, Shinji Naganawa

JAPANESE JOURNAL OF RADIOLOGY Vol. 35 ( 1 ) page： 1 - 2 2017.1

Thoracic Temporal Subtraction Three Dimensional Computed Tomography (3D-CT): Screening for Vertebral Metastases of Primary Lung Cancers. International journal Open Access

Shingo Iwano, Rintaro Ito, Hiroyasu Umakoshi, Takatoshi Karino, Tsutomu Inoue, Yuanzhong Li, Shinji Naganawa

PloS one Vol. 12 ( 1 ) page： e0170309 2017

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

PURPOSE: We developed an original, computer-aided diagnosis (CAD) software that subtracts the initial thoracic vertebral three-dimensional computed tomography (3D-CT) image from the follow-up 3D-CT image. The aim of this study was to investigate the efficacy of this CAD software during screening for vertebral metastases on follow-up CT images of primary lung cancer patients. MATERIALS AND METHODS: The interpretation experiment included 30 sets of follow-up CT scans in primary lung cancer patients and was performed by two readers (readers A and B), who each had 2.5 years' experience reading CT images. In 395 vertebrae from C6 to L3, 46 vertebral metastases were identified as follows: osteolytic metastases (n = 17), osteoblastic metastases (n = 14), combined osteolytic and osteoblastic metastases (n = 6), and pathological fractures (n = 9). Thirty-six lesions were in the anterior component (vertebral body), and 10 lesions were in the posterior component (vertebral arch, transverse process, and spinous process). The area under the curve (AUC) by receiver operating characteristic (ROC) curve analysis and the sensitivity and specificity for detecting vertebral metastases were compared with and without CAD for each observer. RESULTS: Reader A detected 47 abnormalities on CT images without CAD, and 33 of them were true-positive metastatic lesions. Using CAD, reader A detected 57 abnormalities, and 38 were true positives. The sensitivity increased from 0.717 to 0.826, and on ROC curve analysis, AUC with CAD was significantly higher than that without CAD (0.849 vs. 0.902, p = 0.021). Reader B detected 40 abnormalities on CT images without CAD, and 36 of them were true-positive metastatic lesions. Using CAD, reader B detected 44 abnormalities, and 39 were true positives. The sensitivity increased from 0.783 to 0.848, and AUC with CAD was nonsignificantly higher than that without CAD (0.889 vs. 0.910, p = 0.341). Both readers detected more osteolytic and osteoblastic metastases with CAD than without CAD. CONCLUSION: Our temporal 3D-CT subtraction CAD software easily detected vertebral metastases on the follow-up CT images of lung cancer patients regardless of the osteolytic or osteoblastic nature of the lesions.

DOI： 10.1371/journal.pone.0170309

Japanese Radiology 2025 Updates. Reviewed International journal

Mami Iima, Tsukasa Saida, Yoshitake Yamada, Ryo Kurokawa, Daiju Ueda, Maya Honda, Kentaro Nishioka, Rintaro Ito, Keitaro Sofue, Shinji Naganawa

Canadian Association of Radiologists journal = Journal l'Association canadienne des radiologistes Vol. 77 ( 2 ) page： 309 - 321 2026.5

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

This review provides a comprehensive overview of recent transformative advancements in diagnostic imaging that position Japan at the forefront of radiological innovation. We highlight pivotal innovations that enhance diagnostic capabilities and redefine clinical workflows. The article begins with upright multidetector computed tomography (MDCT), a groundbreaking technology offering novel insights into posture-dependent anatomical and physiological changes. We then explore significant progress in breast and gynecologic imaging, including advancements in artificial intelligence computer-aided (AI-CAD) synthesized mammograms, automated breast ultrasound (ABUS), and abbreviated MRI protocols. These innovations address unique regional challenges in early cancer detection. Significant innovations in abdominal radiology, spanning advanced CT (including photon-counting detector CT), accelerated MRI, and AI applications, are also discussed. The review further delves into glymphatic system research, where advanced MRI techniques, particularly DTI-ALPS, are unraveling new insights into brain waste clearance and neurological disorders. Finally, we examine the future of Japanese radiology through the lens of AI, with a focus on Large Language Models (LLMs). We discuss their growing role in diagnostic support, report generation, and information extraction, as well as important societal and ethical considerations. These collective advancements underscore Japan's dynamic contributions to radiological innovation, poised to significantly impact global healthcare practices by improving disease detection, optimizing workflows, and extending healthy life expectancy in an aging society.

DOI： 10.1177/08465371251374557

Artificial superintelligence alignment in healthcare. Reviewed Open Access

Daiju Ueda, Shannon L Walston, Ryo Kurokawa, Tsukasa Saida, Maya Honda, Mami Iima, Tadashi Watabe, Masahiro Yanagawa, Kentaro Nishioka, Keitaro Sofue, Akihiko Sakata, Shunsuke Sugawara, Mariko Kawamura, Rintaro Ito, Koji Takumi, Seitaro Oda, Kenji Hirata, Satoru Ide, Shinji Naganawa

Japanese journal of radiology Vol. 44 ( 4 ) page： 627 - 640 2026.4

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

The emergence of Artificial Superintelligence (ASI) in healthcare presents unprecedented opportunities for revolutionizing diagnostics, treatment planning, and population health management, but also introduces critical risks if these systems are not properly aligned with human values and clinical objectives. This review examines the theoretical foundations of ASI and the alignment problem in healthcare contexts, exploring how misaligned Artificial Intelligence (AI) systems could optimize for wrong objectives or pursue harmful strategies leading to patient harm and systemic failures. Current challenges in AI alignment are illustrated through real-world examples from radiology and clinical decision-making, where algorithms have demonstrated concerning biases, generalizability failures, and optimization for inappropriate proxy measures. The paper analyzes key alignment challenges including objective complexity and technical pitfalls, bias and fairness issues in healthcare data, ethical integration concerns involving compassion and patient autonomy, and system-level policy challenges around regulation and liability. Technical alignment strategies are discussed including reinforcement learning from human feedback, interpretability requirements, formal verification methods, and adversarial testing approaches. Normative alignment solutions encompass ethical frameworks, professional standards, patient engagement protocols, and multi-level governance structures spanning institutional, national, and international coordination. The review emphasizes that successful ASI alignment in healthcare requires combining cutting-edge AI research with fundamental medical ethics, noting that while proper alignment could enable transformative health improvements and medical breakthroughs, misalignment risks undermining the core purpose of medicine. The stakes of this alignment challenge are characterized as among the highest in both technology and ethics, with implications extending from individual patient safety to public trust and potentially existential risks.

DOI： 10.1007/s11604-025-01907-1

Cervical cancer in the modern era: cutting-edge strategies for diagnosis and treatment. Reviewed Open Access

Tsukasa Saida, Takashi Saitoh, Ayumi Shikama, Michitaka Hayashi, Taichi Ishikawa, Mami Iima, Takahito Nakajima, Shinji Naganawa

Japanese journal of radiology Vol. 44 ( 3 ) page： 491 - 507 2026.3

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

Cervical cancer remains a major cause of mortality among women worldwide, highlighting the need for advances in diagnostic and therapeutic strategies. This review provides a comprehensive overview of recent developments in histopathological classification based on human papillomavirus association, as well as progress in imaging and treatment approaches supported by current research. Emerging technologies, such as artificial intelligence-assisted imaging, targeted molecular therapies, and personalized radiotherapy, hold substantial promise for improving patient outcomes. These innovations offer new possibilities for precision medicine in cervical cancer care, and their current applications are discussed in this review.

DOI： 10.1007/s11604-025-01897-0

Diagonal DWI: A Time-Efficient Alternative to 3-Scan Trace DWI for Breast Lesion Evaluation at 3.0-T MRI-A Phantom Study and Clinical Assessment. Reviewed International journal

Yusuke Jo, Yuki Sato, Mami Iima, Hiroko Satake, Yunhao Zhang, Yutaka Kato, Satoko Ishigaki, Ryota Hyodo, Aki Mano, Yoshito Ichiba, Shinji Naganawa

Journal of magnetic resonance imaging : JMRI Vol. 63 ( 3 ) page： 711 - 718 2026.3

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

BACKGROUND: Diffusion-weighted imaging (DWI) in breast MRI requires balancing image quality with acquisition time. Reducing scan time without sacrificing diagnostic performance could improve patient comfort and workflow. PURPOSE: To compare 3-scan trace DWI (tDWI) and diagonal DWI (dDWI) for breast lesion evaluation using both phantom and clinical assessments, focusing on image quality metrics and diagnostic performance. STUDY TYPE: Retrospective comparative study. POPULATION: A commercially available breast diffusion phantom (Caliber MRI; Boulder, CO, USA) and 92 consecutive participants were initially enrolled. After excluding 23 due to having no confirmed lesion, and 15 with non-mass lesions, 54 patients (median age 55.5 years, range 21-82) were analyzed. FIELD STRENGTH/SEQUENCE: 3-T, tDWI (120 s) and dDWI (74 s) with identical parameters except for diffusion gradient directions, with dDWI reducing scan time by 38%. ASSESSMENT: Phantom studies measured apparent diffusion coefficient (ADC) and estimated signal-to-noise ratio (eSNR). Clinical studies evaluated ADC, contrast-to-noise ratio (CNR), and contrast ratio (CR) from ROIs in lesions, normal breast tissue, and fat. Three radiologists scored lesion conspicuity and image quality. STATISTICAL TESTS: Due to non-normal data distribution, the Wilcoxon signed-rank test compared metrics between sequences. The ADC coefficient of variation (CV) was calculated. A p-value < 0.05 was considered significant. RESULTS: dDWI significantly improved image quality by reducing artifacts, especially those originating from the nipple and in the breast tissue periphery, and slightly better lesion conspicuity. No significant difference was found for eSNR in breast phantom studies (p = 0.31 for b = 0; and p = 0.84 for b = 800 s/mm2). tDWI demonstrated significantly higher CNR for breast tissue and fat. tDWI also showed lower CR values for tumor/breast tissue and lower values for tumor/fat. ADC measurements were similar between techniques (CV = 4.20%). DATA CONCLUSION: dDWI provides a 38% shorter acquisition time than tDWI while maintaining comparable quantitative performance. dDWI demonstrates improved image quality, particularly in challenging anatomical regions, though tDWI yields higher contrast-to-noise ratio values. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY STAGE: 2.

DOI： 10.1002/jmri.70155