九州大学 研究者情報
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山下 孝二(やました こうじ) データ更新日:2024.04.10



主な研究テーマ
神経膠腫における遺伝子変異とMRI
キーワード:神経膠腫、MRI、ラジオゲノミクス
2017.04~2020.06.
IVIM MR画像を用いた脳腫瘍鑑別に関する研究
キーワード:IVIM; MR; 灌流強調画像; 拡散強調画像; 脳腫瘍
2014.04~2017.03.
Arterial spin labelingを用いた脳腫瘍の鑑別に関する研究
キーワード:ASL、MRI、脳腫瘍
2013.04~2016.03.
拡散強調画像を用いた真珠腫性中耳炎検出に関する研究

キーワード:真珠腫性中耳炎、側頭骨、MRI、拡散強調画像
2010.10.
従事しているプロジェクト研究
MRI IVIM法を用いた脳腫瘍診断への包括的アプローチ
2014.04~2017.03, 代表者:山下 孝二, 九州大学病院
MRI拡散強調像は脳腫瘍の質的診断や治療効果判定等、広く臨床的に使用されている。定量値としてみかけ上の拡散係数(ADC値)が利用されているが、実際には、現在汎用されている拡散強調像は基本的には分子拡散と毛細血管による血流(灌流)を区別する事はできない。これまで、拡散強調像は組織内の水分子拡散をターゲットに行うため灌流の影響がなるべく少なくなるようにパラメータを設定していた。しかし組織灌流はそれ自体が有用な情報であり,複数のb値を用いた拡散強調像をbi-exponential curveに近似する事で、灌流および真の拡散の両者を同時に定量するIVIM法が1980年代にLe Bihanらによって提唱された。ただ当時は、撮像時間が非常に長くなる事や大きな渦電流の影響などの問題があり、定着しなかった。近年3T MRIの普及により、拡散強調像の撮像時間は飛躍的に短縮され、非侵襲的な血流測定法として、IVIM法が最近になって再び注目されつつある。
 IVIM法はD値、D*値、f値を測定する事により組織の微小循環を定量可能であるとされるが、その生理学的な意義は解明されていない。従来の定量値測定法として、dynamic susceptibility contrast(DSC)法を用いた脳血液量測定、Arterial spin labeling(ASL)法を用いた脳血流量測定があるが、定量の際は動脈入力関数に依存し、特にASL法では脳血管障害を有する患者での定量性は疑問視されている。
本研究の成功により、脳腫瘍診断におけるIVIM法から得られるパラメータの意義が明らかとなれば、同時取得可能な拡散情報とあわせて脳腫瘍の診断・治療法および予後推定に有用となるだけでなく、将来的な医療費抑制にも貢献する事が期待される。
以下の3点をエンドポイントとしている。
1.脳腫瘍診断において高い再現性を実現できる実用的なIVIM画像の撮影法の最適化を行う
2.IVIM画像から得られる微小循環指標の生理学的な意義を明らかにする
3.脳腫瘍診断におけるIVIM画像の有用性を明らかにする.
研究業績
主要著書
主要原著論文
1. Koji Yamashita, Osamu Togao, Kazufumi Kikuchi, Daisuke Kuga MD, Yuhei Sangatsuda, Yutaka Fujioka, Koji Yoshimoto, Kousei Ishigami, The cortical high-flow sign of oligodendroglioma, IDH-mutant and 1p/19q codeleted: comparison between arterial spin labeling and dynamic susceptibility contrast methods, Neuroradiology, 10.1007/s00234-023-03267-x, 66, 2, 187-192, 10.1007/s00234-023-03267-x, 2024.02, Purpose: The cortical high-flow sign with the non-enhancing area was reportedly found to be more frequent with oligodendroglioma, IDH-mutant and 1p/19q codeleted (ODG IDHm-codel) than with IDH-wildtype or astrocytoma, IDH-mutant on arterial spin labeling (ASL) in diffuse gliomas. This study aimed to compare the identification rate of the cortical high-flow sign on ASL in patients with ODG IDHm-codel to that on dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI). Methods: Participants consisted of 32 adult ODG IDHm-codel patients with pathologically confirmed. Subtraction images were generated from paired control and label images on ASL. For DSC, dynamic T2*-weighted perfusion weighted images were obtained after pre-bolus of gadolinium-based contrast agent. Regional cerebral blood flow/volume maps were generated based on the concentration-time curve and arterial input function. Tumor-affecting cortices without contrast enhancement on conventional MR imaging were targeted. The identification rate of the cortical high-flow sign was compared between ASL and DSC using the Pearson’s Chi-Square test. Results: Frequency of the cortical high-flow sign was significantly higher on ASL (18/32, 56.3%; p
2. Koji Yamashita, Osamu Togao, Kazufumi Kikuchi, Daisuke Kuga, Yuhei Sangatsuda, Yutaka Fujioka, Izumi Kinoshita, Makoto Obara, Koji Yoshimoto, Kousei Ishigami, Cortical high-flow sign on arterial spin labeling: a novel biomarker of IDH-mutation and 1p/19q-codeletion status in diffuse gliomas without intense contrast enhancement., Neuroradiology., 10.1007/s00234-023-03186-x, 65, 9, 1415-1418, 2023.09, This study aimed to investigate whether arterial spin labeling (ASL) features allow differentiation of oligodendroglioma, IDH-mutant and 1p/19q-codeleted (IDHm-codel) from diffuse glioma with IDH-wildtype (IDHw) or astrocytoma, IDH-mutant (IDHm-noncodel). Participants comprised 71 adult patients with pathologically confirmed diffuse glioma, classified as IDHw, IDHm-noncodel, or IDHm-codel. Subtraction images were generated from paired-control/label images on ASL and used to assess the presence of a cortical high-flow sign. The cortical high-flow sign was defined as increased ASL signal intensity within the tumor-affecting cerebral cortex compared with normal-appearing cortex. Regions without contrast enhancement on conventional MR imaging were targeted. The frequency of the cortical high-flow sign on ASL was compared among IDHw, IDHm-noncodel, and IDHm-codel. As a result, the frequency of the cortical high-flow sign was significantly higher for IDHm-codel than for IDHw or IDHm-noncodel. In conclusion, the cortical high-flow sign could represent a hallmark of oligodendroglioma, IDH-mutant, and 1p/19q-codeleted without intense contrast enhancement..
3. Koji Yamashita, Ryotaro Kamei, Hiroshi Sugimori, Takahiro Kuwashiro, So Tokunaga, Keisuke Kawamata, Kiyomi Furuya, Shino Harada, Junki Maehara, Yasushi Okada, Tomoyuki Noguchi, Interobserver reliability on intravoxel incoherent motion imaging in patients with acute ischemic stroke., AJNR Am J Neuroradiol., 10.3174/ajnr.A7486, 43, 5, 696-700, 10.3174/ajnr.A7486, 2022.05, BACKGROUND AND PURPOSE: Noninvasive perfusion-weighted imaging with short scanning time could be advantageous in order
to determine presumed penumbral regions and subsequent treatment strategy for acute ischemic stroke (AIS). Our aim was to
evaluate interobserver agreement and the clinical utility of intravoxel incoherent motion MR imaging in patients with acute ischemic
stroke.
MATERIALS AND METHODS: We retrospectively studied 29 patients with AIS (17 men, 12 women; mean age, 75.2 [SD, 12.0 ] years;
median, 77 years). Each patient underwent intravoxel incoherent motion MR imaging using a 1.5T MR imaging scanner. Diffusion-sensitizing
gradients were applied sequentially in the x, y, and z directions with 6 different b-values (0, 50, 100, 150, 200, and 1000 seconds/
mm2). From the intravoxel incoherent motion MR imaging data, diffusion coefficient, perfusion fraction, and pseudodiffusion
coefficient maps were obtained using a 2-step fitting algorithm based on the Levenberg-Marquardt method. The presence of
decreases in the intravoxel incoherent motion perfusion fraction and pseudodiffusion coefficient values compared with the contralateral
normal-appearing brain was graded on a 2-point scale by 2 independent neuroradiologists. Interobserver agreement on the
rating scale was evaluated using the k statistic. Clinical characteristics of patients with a nondecreased intravoxel incoherent
motion perfusion fraction and/or pseudodiffusion coefficient rated by the 2 observers were also assessed.
RESULTS: Interobserver agreement was shown for the intravoxel incoherent motion perfusion fraction (k = 0.854) and pseudodiffusion
coefficient (k = 0.789) maps, which indicated almost perfect and substantial agreement, respectively. Patients with a nondecreased
intravoxel incoherent motion perfusion fraction tended to show recanalization of the occluded intracranial arteries more
frequently than patients with a decreased intravoxel incoherent motion perfusion fraction.
CONCLUSIONS: Intravoxel incoherent motion MR imaging could be performed in ,1 minute in addition to routine DWI. Intravoxel
incoherent motion parameters noninvasively provide feasible, qualitative perfusion-related information for assessing patients with
acute ischemic stroke..
4. Yamashita Koji, Hiwatashi Akio, Osamu Togao, Kazufumi Kikuchi, Koji Yoshimoto, Satoshi O Suzuki, Hiroshi Honda, MR imaging Based Analysis of Glioblastoma multiforme: Estimation of IDH1 Mutation Status., AJNR Am J Neuroradiol., 37, 1, 58-65, 37(1):58-65, 2016.01, BACKGROUND AND PURPOSE: Glioblastoma multiforme is highly aggressive and the most common type of primary malignant brain tumor in adults. Imaging biomarkers may provide prognostic information for patients with this condition. Patients with glioma with isocitrate dehydrogenase 1 (IDH1) mutations have a better clinical outcome than those without such mutations. Our purpose was to investigate whether the IDH1 mutation status in glioblastoma multiforme can be predicted by using MR imaging.

MATERIALS AND METHODS: We retrospectively studied 55 patients with glioblastoma multiforme with wild type IDH1 and 11 patients with mutant IDH1. Absolute tumor blood flow and relative tumor blood flow within the enhancing portion of each tumor were measured by using arterial spin-labeling data. In addition, the maximum necrosis area, the percentage of cross-sectional necrosis area inside the enhancing lesions, and the minimum and mean apparent diffusion coefficients were obtained from contrast-enhanced T1-weighted images and diffusion-weighted imaging data. Each of the 6 parameters was compared between patients with wild type IDH1 and mutant IDH1 by using the Mann-Whitney U test. The performance in discriminating between the 2 entities was evaluated by using receiver operating characteristic analysis.

RESULTS: Absolute tumor blood flow, relative tumor blood flow, necrosis area, and percentage of cross-sectional necrosis area inside the enhancing lesion were significantly higher in patients with wild type IDH1 than in those with mutant IDH1 (P
CONCLUSIONS: Tumor blood flow and necrosis area calculated from MR imaging are useful for predicting the IDH1 mutation status..
5. Yamashita Koji, Takashi Yoshiura, Hiwatashi Akio, Osamu Togao, Kazufumi Kikuchi, Makoto Obara, Nozomu Matsumoto, Hiroshi Honda, High-resolution Three-dimensional Diffusion-weighted Imaging of Middle Ear Cholesteatoma at 3.0 T MRI: Usefulness of 3D Turbo Field-echo with Diffusion-Sensitized Driven-equilibrium Preparation (TFE-DSDE) Compared to Single-shot Echo-planar Imaging., Eur J Radiol., pii: S0720-048X(13)00214-3. 10.1016/j.ejrad.2013.04.018. , 82, 9, 471-475, 2013.09, Objective: To prospectively evaluate the usefulness of a newly developed high-resolution three-dimensional diffusion-weighted imaging method, turbo field-echo with diffusion-sensitized driven-equilibrium (TFE–DSDE) in diagnosing middle-ear cholesteatoma by comparing it to conventionalsingle-shot echo-planar diffusion-weighted imaging (SS-EP DWI).Materials and methods: Institutional review board approval and informed consent from all participantswere obtained. We studied 30 patients with preoperatively suspected acquired cholesteatoma. Eachpatient underwent an MR examination including both SS-EP DWI and DSDE-TFE using a 3.0 T MR scan-ner. Images of the 30 patients (60 temporal bones including 30 with and 30 without cholesteatoma) werereviewed by two independent neuroradiologists. The confidence level for the presence of cholesteatomawas graded on a scale of 0–2 (0 = definite absence, 1 = equivocal, 2 = definite presence). Interobserveragreement as well as sensitivity, specificity, and accuracy for detection were assessed for the two review-ers.Results: Excellent interobserver agreement was shown for TFE–DSDE ( = 0.821) whereas fair agreementwas obtained for SS-EP DWI ( = 0.416). TFE–DSDE was associated with significantly higher sensitivity(83.3%) and accuracy (90.0%) compared to SS-EP DWI (sensitivity = 35.0%, accuracy = 66.7%; p
6. Yamashita K, Yoshiura T, Hiwatashi A, Togao O, Yoshimoto K, Suzuki SO, Abe K, Kikuchi K, Maruoka Y, Mizoguchi M, Iwaki T, Honda H, Differentiating primary central nervous system lymphoma from glioblastoma multiforme: assessment using arterial spin labeling, diffusion weighted imaging, and 18F-fluorodeoxyglucose positron emission tomography., Neuroradiology, 55, 2, 135-143, 2013.02, Introduction: Our purpose was to evaluate the diagnostic performance of arterial spin labeling (ASL) perfusion imaging, diffusion-weighted imaging (DWI), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastoma multiformes (GBMs). Methods: Fifty-six patients including 19 with PCNSL and 37 with GBM were retrospectively studied. From the ASL data, an absolute tumor blood flow (aTBF) and a relative tumor blood flow (rTBF) were obtained within the enhancing portion of each tumor. In addition, the minimum apparent diffusion coefficient (ADCmin) and the maximum standard uptake value (SUVmax) were obtained from DWI and FDG-PET data, respectively. Each of the four parameters was compared between PCNSLs and GBMs using Kruskal–Wallis test. The performance in discriminating between PCNSLs and GBMs was evaluated using the receiver-operating characteristics analysis. Area-under-the curve (AUC) values were compared among the four parameters using a nonparametric method.
Results: The aTBF, rTBF, and ADCmin were significantly higher in GBMs (mean aTBF ± SD = 91.6±56.0 mL/100 g/ min, mean rTBF ± SD = 2.61±1.61, mean ADCmin ± SD = 0.78±0.19×10^−3 mm^2/s) than in PCNSLs (mean aTBF ± SD = 37.3±10.5 mL/100 g/min, mean rTBF ± SD = 1.24±0.37, mean ADCmin ± SD = 0.61±0.13×10^−3 mm^2/s) (plower in GBMs (mean ± SD = 13.1±6.34) than in PCNSLs (mean ± SD = 22.5±7.83) (pConclusion: ASL perfusion imaging is useful for differentiating PCNSLs from GBMs as well as DWI and FDG-PET..
7. Yamashita K, Yoshiura T, Hiwatashi A, Kamano H, Dashjamts T, Shibata S, Tamae A, Honda H., Detection of Middle Ear Cholesteatoma by Diffusion-Weighted MR Imaging: Multishot Echo-Planar Imaging Compared with Single-Shot Echo-Planar Imaging., AJNR Am J Neuroradiol., 32, 10, 1915-1918, 2011.11.
8. Yamashita K, Yoshiura T, Arimura H, Mihara F, Noguchi T, Hiwatashi A, Togao O, Yamashita Y, Shono T, Kumazawa S, Higashida Y, Honda H, Performance evaluation of radiologists with artificial neural network for differential diagnosis of intra-axial cerebral tumors on MR images, Am J Neuroradiol., 2008.06.
主要総説, 論評, 解説, 書評, 報告書等
主要学会発表等
1. Yamashita K, Wu Z, Zhang H, Yin W, Zhu Z, Luo T, Wen X, Jing B, Kam TE, Ksu LM, Yap PT, Wang L, Li G, Li T, Baluyot KR, Howell BR, Styner MA, Yacoub E, Chen G, Potts T, Gilmore JH, Piven J, Smith JK, Ugurbil K, Hazlett H, Zhu H, Elison JT, Shen D, Lin W, Prediction of Motor Function Development in Infants Using the Thickness of the Primary Motor Cortex, 25th Annual Meeting of the Organization for Human Brain Mapping, 2019.06.
2. Yamashita Koji, Predicting IDH1 and TERT Mutation Status in the patients with Glioblastoma, AIMS Neuro Imaging 2017, 2017.10.
3. Yamashita Koji, Hiwatashi Akio, Osamu Togao, Kazufumi Kikuchi, Ryusuke Hatae, Koji Yoshimoto, Masahiro Mizoguchi, Satoshi O Suzuki, Takashi Yoshiura, Hiroshi Honda, MR imaging Based Analysis of Glioblastoma multiforme: Estimation of IDH1 Mutation Status, ASNR 52th Annual Meeting & NER Foundation Symposium 2014, 2014.05.
4. Koji Yamashita, Takashi Yoshiura, Akio Hiwatashi, Hironori Kamano, Yukihisa Takayama, Eiki Nagao, Hiroshi Honda, Ultrashort echo time imaging of middle ear ossicle: a pilot study. , International Society for Magnetic Resonance in Medicine, 2010.05.
学会活動
所属学会名
日本IVR学会
日本神経放射線学会
日本医学放射線学会
学会大会・会議・シンポジウム等における役割
2023.06.10~2023.06.11, 第197回日本医学放射線学会九州地方会, 座長.
2023.05.27~2023.05.27, 第65回北部九州画像診断フォーラム, 特別講演演者.
2023.02.16~2023.02.18, 第52回日本神経放射線学会, 座長.
2019.11.03~2019.11.05, ASFNR 13th Annual Meeting:, Moderator.
2014.11.07~2014.11.07, 第50回北部九州画像診断フォーラム, 司会(Moderator).
2012.05.01~2013.04.14, 第72回日本医学放射線学会総会, 実行委員/プログラム委員.
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2024年度      
2023年度 19        19 
2022年度 15        15 
2021年度 21        21 
2020年度 24        24 
2019年度 13        13 
2018年度      
2017年度      
2016年度      
2015年度      
2013年度    
受賞
九州神経放射線研究会ベストプレゼンテーター賞, 九州神経放射線研究会, 2017.05.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2022年度~2024年度, 基盤研究(C), 代表, 急性期脳梗塞と無症候性脳血管障害の病態解明に向けた高速MR灌流画像撮像法の開発.
2017年度~2019年度, 基盤研究(C), 代表, ラジオゲノミクス、定量的画像解析に基づく多角的な脳腫瘍診断法の開発.
2014年度~2016年度, 基盤研究(C), 代表, MRI微小灌流・拡散定量による脳腫瘍診断への包括的アプローチ.
2011年度~2013年度, 若手研究(B), 代表, 高磁場MRIを用いた微小再発真珠腫の検出法および術前診断支援システムの開発.
共同研究、受託研究(競争的資金を除く)の受入状況
2022.03~2023.02, 代表, 機械学習アルゴリズムを活用した加齢・変性疾患早期発見および診断指標の開発.
2021.01~2022.03, 代表, 深層学習モデルによる高分解能MRIを用いた神経疾患早期診断法の構築.
2011.03~2012.12, 代表, CT/MRIフュージョン画像を用いた真珠腫性中耳炎手術診断支援システムの開発.

九大関連コンテンツ

pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。