Faculty Profiles - OOISHI Makoto

Papers - OOISHI Makoto

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がんゲノム医療がもたらす小児脳腫瘍の展開 TP53変異を有する脈絡叢癌培養細胞株の樹立およびマルチオミクス解析

棗田学, 温城太郎, 塚本佳広, 岡田正康, 大石誠, 久保暢大, 申将守, 今村勝, 今井千速, エルナガール・シャヘンダ, 藤井幸彦

小児の脳神経 48 ( 2 ) 156 - 156 2023.4

がんゲノム医療がもたらす小児脳腫瘍の展開 TP53変異を有する脈絡叢癌培養細胞株の樹立およびマルチオミクス解析

棗田学, 温城太郎, 塚本佳広, 岡田正康, 大石誠, 久保暢大, 申将守, 今村勝, 今井千速, エルナガール・シャヘンダ, 藤井幸彦

小児の脳神経 48 ( 2 ) 156 - 156 2023.4

Preoperative three-dimensional multifusion imaging aiding successful microvascular decompression of a cerebellopontine angle lipoma: associated hemifacial spasm. Illustrative case. International journal

Hiroki Seto, Ryosuke Ogura, Tetsuya Hiraishi, Yoshihiro Tsukamoto, Taiki Saito, Satoshi Shibuma, Kohei Shibuya, Kouichirou Okamoto, Makoto Oishi, Yukihiko Fujii

Journal of neurosurgery. Case lessons 5 ( 12 ) 2023.3

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

BACKGROUND: Cerebellopontine angle (CPA) lipoma-associated hemifacial spasm (HFS) is rare. As the removal of CPA lipomas has a high risk of worsening the neurological symptoms, surgical exploration is warranted only in selected patients. Preoperative identification of the lipoma affected site of the facial nerve, and offending artery are crucial for patient selection and successful microvascular decompression (MVD). OBSERVATIONS: Presurgical simulation using three-dimensional (3D) multifusion imaging showed a tiny CPA lipoma wedged between the facial and auditory nerves, as well as an affected facial nerve by the anterior inferior cerebellar artery (AICA) at the cisternal segment. Although a recurrent perforating artery from the AICA anchored the AICA to the lipoma, successful MVD was achieved without lipoma removal. LESSONS: The presurgical simulation using 3D multifusion imaging could identify the CPA lipoma, affected site of the facial nerve, and offending artery. It was helpful for patient selection and successful MVD.

DOI： 10.3171/CASE2318

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Elevated ratio of C-type lectin-like receptor 2 level and platelet count (C2PAC) aids in the diagnosis of post-operative venous thromboembolism in IDH-wildtype gliomas. International journal

Kazuhiro Ando, Manabu Natsumeda, Masahide Kawamura, Kamon Shirakawa, Masayasu Okada, Yoshihiro Tsukamoto, Takeyoshi Eda, Jun Watanabe, Shoji Saito, Haruhiko Takahashi, Akiyoshi Kakita, Makoto Oishi, Yukihiko Fujii

Thrombosis research 223 36 - 43 2023.3

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

INTRODUCTION: Podoplanin (PDPN) is known to induce platelet aggregation via interacting with the C-type lectin-like receptor-2 on platelets and is involved in postoperative venous thromboembolism (VTE) formation. In this study, we investigate the correlation between soluble C-type lectin-like receptor (sCLEC-2) levels and PDPN expression in patients with high grade gliomas and the relationship between sCLEC-2 levels and the occurrence of VTE. MATERIALS AND METHODS: Forty-four patients harboring high grade gliomas, treated surgically at the Department of Neurosurgery, Niigata University from April 2018 to August 2020, were included. Patients with high grade gliomas were divided into isocitrate dehydrogenase (IDH)- wildtype and mutant groups, and the presence or absence of VTE and the intensity of PDPN by immunohistochemistry were confirmed. Platelet counts, as well as plasma sCLEC-2 and PDPN were measured in these patients. Furthermore, the levels of sCLEC-2 concentration were divided by the platelet count (C2PAC index) for comparison. RESULTS: IDH-wildtype glioma patients highly expressed PDPN (P < 0.001) compared to IDH-mutant glioma patients. In total, 9 (20.5 %) patients were diagnosed with VTE during the follow-up period, of which 8 patients harbored IDH-wildtype gliomas, and one patient an IDH-mutant glioma. Mean sCLEC-2 levels and C2PAC index in patients with IDH-wildtype gliomas were significantly higher than that of low or no PDPN expression group, which included patients with IDH-mutant gliomas (P = 0.0004, P = 0.0002). In patients with IDH-wildtype gliomas, the C2PAC index in patients with VTE was significantly higher than in patients without VTE (P = 0.0492). The optimal cutoff point of C2PAC for predicting VTE in IDH-wildtype glioma patients was 3.7 with a sensitivity of 87.5 % and specificity of 51.9 %. CONCLUSION: Platelet activation is strongly involved in the development of VTE in patients with IDH-wildtype high grade gliomas, and C2PAC index is a potential marker to detect VTE formation after surgery.

DOI： 10.1016/j.thromres.2023.01.018

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A Case of Paradoxical Cerebral Embolism Due to Pulmonary Arteriovenous Fistula Mimicking Vertebral Artery Dissection With Wallenberg Syndrome. International journal

Masaru Isogai, Tomoaki Suzuki, Shyunichi Kato, Yoshinori Taniguchi, Hitoshi Hasegawa, Makoto Oishi, Yukihiko Fujii

Cureus 15 ( 2 ) e34564 2023.2

Language：English

Pulmonary arteriovenous fistula (PAVF) leads to paradoxical cerebral embolism, which can be fatal if left untreated. We report a rare case of brainstem infarction with acute severe headache and Wallenberg syndrome caused by a PAVF mimicking vertebral artery (VA) dissection. A 40-year-old man presented with a sudden occipital headache accompanied by right hemisensory disturbance. Magnetic resonance imaging revealed left lateral medullary infarction and poor depiction of the left VA. However, it was clearly recanalized on day six, and there were no findings of VA dissection. Whole-body contrast-enhanced computed tomography (CT) revealed a PAVF in the right lung and a thrombus in the feeding artery. The patient was diagnosed with hereditary hemorrhagic telangiectasia due to recurrent epistaxis and peripheral vasodilation of the tongue. An anticoagulant was administered for preventing further ischemic stroke, and a follow-up CT confirmed the disappearance of the thrombus in three months. Thoracoscopic partial lung resection was performed five months after the onset, and no recurrence of ischemic stroke was observed.

DOI： 10.7759/cureus.34564

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頸部リンパ節転移で"下垂体がん"の診断に至った症例

岡田正康, 棗田学, 大石誠, 米岡有一郎, 藤井幸彦

新潟医学会雑誌 137 ( 2 ) 71 - 71 2023.2

Usefulness of Y-shaped PulseRider-assisted coil embolization for basilar artery tip aneurysm with a misaligned axis: A case report. International journal

Kohei Shibuya, Hitoshi Hasegawa, Tomoaki Suzuki, Hidemoto Fujiwara, Satoshi Shibuma, Kazuki Shida, Makoto Oishi

Surgical neurology international 14 300 - 300 2023

Language：English

BACKGROUND: Endovascular treatment of wide-necked bifurcation aneurysms remains challenging. Although the advent of PulseRider and Web has expanded treatment options, aneurysms with a large deviation from the parent artery axis remains difficult to treat. We present the case of a wide-necked bifurcation aneurysm that was misaligned with the angle between the long axis of the parent artery and the aneurysm and was successfully treated with Y-shaped PulseRider-assisted coil embolization. CASE DESCRIPTION: A 64-year-old woman presented with an unruptured basilar tip aneurysm. Cerebral angiography showed a wide-necked aneurysm measuring 8.1 mm × 6.1 mm, neck 5.7 mm. The aneurysm was strongly tilted to the right and posterior relative to the basilar artery, and the bilateral posterior cerebral artery (PCA) and superior cerebellar artery (SCA) diverged from the aneurysm body. PulseRider-assisted coil embolization was performed. A Y-shaped PulseRider was selected to be placed in a hybrid fashion with the right arch in the aneurysm and the left arch in the branch. Adequate coil embolization with preservation of the bilateral PCA and SCA was possible, and cerebral angiography immediately after the treatment showed slight dome filling. Cerebral angiography 6 months after the procedure showed that the embolic status had improved to complete occlusion. CONCLUSION: For wide-neck bifurcation aneurysms with a misaligned axis, a Y-shaped PulseRider used in a hybrid fashion, in which the leaflet on the side with the tilted axis is placed in the aneurysm, allows the PulseRider to be deployed more closely to the aneurysm, thereby enabling good coil embolization.

DOI： 10.25259/SNI_449_2023

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髄液よりH3K27M変異が検出可能なdiffuse midline gliomaの検討

棗田学, 温城太郎, 渡邉潤, 高橋陽彦, 塚本佳広, 岡田正康, 平石哲也, 吉村淳一, 大石誠, 藤井幸彦

小児の脳神経 47 ( 4 ) 358 - 364 2022.11

Language：Japanese Publisher：(一社)日本小児神経外科学会

Diffuse midline glioma(DMG)の80%以上がヒストンH3K27M変異を有する.橋に局在する病変は摘出術の適応はなく,針生検でも重篤な合併症が生じ得るためDMGに対してliquid biopsyの確立が切望される.我々は初発時に腰椎穿刺で採取した脳脊髄液よりH3K27Mを同定するのは困難と報告した.本稿では,多発病変および播種病変を有しliquid biopsyによりH3K27M変異と同定された2症例を紹介し,liquid biopsyの恩恵を受ける症例の特徴について迫る.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00650&link_issn=&doc_id=20230215270002&doc_link_id=10.34544%2Fjspn.47.4_358&url=https%3A%2F%2Fdoi.org%2F10.34544%2Fjspn.47.4_358&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

M2以遠の閉塞における機械的血栓回収療法は有効か?

渋谷航平, 長谷川仁, 鈴木倫明, 高橋陽彦, 渋間啓, 大石誠, 藤井幸彦

脳血管内治療 7 ( Suppl. ) S134 - S134 2022.11

Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin. Reviewed International journal

Satoshi Nakata, Junko Murai, Masayasu Okada, Haruhiko Takahashi, Tyler H Findlay, Kristen Malebranche, Akhila Parthasarathy, Satoshi Miyashita, Ramil Gabdulkhaev, Ilan Benkimoun, Sabine Druillennec, Sara Chabi, Eleanor Hawkins, Hiroaki Miyahara, Kensuke Tateishi, Shinji Yamashita, Shiori Yamada, Taiki Saito, Jotaro On, Jun Watanabe, Yoshihiro Tsukamoto, Junichi Yoshimura, Makoto Oishi, Toshimichi Nakano, Masaru Imamura, Chihaya Imai, Tetsuya Yamamoto, Hideo Takeshima, Atsuo T Sasaki, Fausto J Rodriguez, Sumihito Nobusawa, Pascale Varlet, Celio Pouponnot, Satoru Osuka, Yves Pommier, Akiyoshi Kakita, Yukihiko Fujii, Eric H Raabe, Charles G Eberhart, Manabu Natsumeda

Neuro-oncology 25 ( 5 ) 899 - 912 2022.10

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

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

DOI： 10.1093/neuonc/noac243

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Elucidating the multiple genetic alterations involved in the malignant transformation of a KRAS mutant neurenteric cyst. A case report. International journal

Shoji Saito, Manabu Natsumeda, Makoto Sainouchi, Toru Takino, Kohei Shibuya, Jotaro On, Yu Kanemaru, Ryosuke Ogura, Masayasu Okada, Makoto Oishi, Yoshifumi Shimada, Toshifumi Wakai, Shujiro Okuda, Yoichi Ajioka, Akiyoshi Kakita, Yukihiko Fujii

Neuropathology : official journal of the Japanese Society of Neuropathology 42 ( 6 ) 519 - 525 2022.9

Language：English

Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65-year-old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium-perfused T1-weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet-like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next-generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.

DOI： 10.1111/neup.12822

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Successful Treatment of Acute Uric Acid Nephropathy with Rasburicase in a Primary Central Nervous System Lymphoma Patient Showing a Dramatic Response to Methotrexate—Case Report

Yoshihiro Mouri, Manabu Natsumeda, Noritaka Okubo, Taro Sato, Taiki Saito, Kohei Shibuya, Shiori Yamada, Jotaro On, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Takeyoshi Eda, Junko Murai, Hiroshi Shimizu, Akiyoshi Kakita, Yukihiko Fujii

Journal of Clinical Medicine 11 ( 19 ) 5548 - 5548 2022.9

Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. The standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSLs. Case presentation: A 54-year-old man with a history of gout presented with a change in character and cognitive dysfunction. MRI showed a large enhancing mass spanning the bilateral frontal lobes and the right temporal lobe. After endoscopic biopsy, an MTX, procarbazine, and vincristine (MPV) regimen was initiated for the treatment of the PCNSL. After the initiation of chemotherapy, the patient experienced a gout attack, and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute uric acid nephropathy. As the dramatic effect of MTX was observed, treatment was continued despite ARF, most probably due to acute hyperuricemia due to tumor lysis, which was treated in parallel. After an improvement in renal function, MTX was resumed, and rasburicase was initiated to control hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase, and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after the initiation of MTX in PCNSLs, especially in newly diagnosed PCNSL patients with large tumors or hyperuricemia.

DOI： 10.3390/jcm11195548

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Characteristics of health-related quality of life and related factors in patients with brain tumors treated with rehabilitation therapy. International journal

Takahiro Watanabe, Shinichi Noto, Manabu Natsumeda, Shinji Kimura, Satoshi Tabata, Fumie Ikarashi, Mayuko Takano, Yoshihiro Tsukamoto, Makoto Oishi

Journal of patient-reported outcomes 6 ( 1 ) 94 - 94 2022.9

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

BACKGROUND: Rehabilitation therapy during hospitalization is effective in improving activities of daily living (ADL) and physical function in patients with brain tumors. However, there are few studies on the effect of rehabilitation therapy on health-related quality of life (HRQOL) in patients with brain tumors. Additionally, the EuroQol-5Dimension-5Level (EQ-5D-5L) index score has not been reported as an outcome. This study aimed to investigate the HRQOL of patients with brain tumors who underwent rehabilitation therapy and investigated the factors affecting the EQ-5D-5L index score from various perspectives, including various brain tumor type and recurrence. In addition, we examined the relationship between the EQ-5D-5L index score, disease-specific HRQOL scale, and ADL. METHODS: Patients with brain tumors who underwent treatment and rehabilitation at Single tertiary care academic medical center were included in this cross-sectional study. We used the EQ-5D-5L, European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire core 30, and EORTC quality of life questionnaire brain cancer module to evaluate HRQOL. ADL were assessed using the functional independence measure (FIM). The relationship between each HRQOL assessment score and the FIM was analyzed, and the influence of related factors was assessed by multiple regression analysis. RESULTS: This study included 76 patients. The EQ-5D-5L index score was 0.689 for all patients with brain tumors and 0.574 for those with glioblastomas, which was the lowest value. There was a moderate correlation between the EQ-5D-5L index score and FIM (r = 0.627, p < 0.001). In addition, the EQ-5D-5L index score was significantly correlated with most of the items of the disease-specific HRQOL scale. Multiple regression analysis revealed that glioblastoma histology (coefficient: - 0.373, p = 0.005) and recurrence (coefficient: - 0.273, p = 0.020) were independent factors affecting the EQ-5D-5L index score. CONCLUSIONS: Patients with glioblastoma undergoing rehabilitation have reduced HRQOL, which was influenced by glioblastoma histology and recurrence.

DOI： 10.1186/s41687-022-00499-y

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髄芽腫におけるSLFN11発現およびDNA障害型抗がん剤への感受性の検討

棗田学, 中田聡, 村井純子, 岡田正康, 塚本佳広, 大石誠, 藤井幸彦, Eberhart Charles G.

新潟医学会雑誌 136 ( 8 ) 273 - 274 2022.8

脳腫瘍研究のcutting edge-先端画像、実験/分子病理、デジタル病理- 髄芽腫におけるGLI3 single cell RNAシーケンス解析細胞レベルから見えて来たこと

棗田学, 宮下聡, 宮原弘明, 高橋晴彦, 塚本佳広, 大石誠, 吉村淳一, 柿田明美, 藤井幸彦

Brain Tumor Pathology 39 ( Suppl. ) 072 - 072 2022.5

小児・AYA世代のヒストン遺伝子変異びまん性神経膠腫症例の後方視的検討

塚本佳広, 高橋陽彦, 温城太郎, 小倉良介, 棗田学, 岡本浩一郎, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 39 ( Suppl. ) 100 - 100 2022.5

Long-Term Characteristics of De Novo Bleb Formation at the Aneurysm Neck After Coil Embolization in Unruptured Cerebral Aneurysms. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

World neurosurgery 161 e767-e775 2022.5

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

OBJECTIVE: De novo bleb formation at the aneurysm neck after coil embolization of unruptured intracranial aneurysms is a rarely observed type of recurrence. The aim of this study was to elucidate the clinical characteristics of recurrent aneurysms in the long-term period. METHODS: Between January 2002 and December 2015, 290 unruptured intracranial aneurysms were treated with coil embolization at our institution. Patients who underwent retreatment due to aneurysm recurrence were divided into 2 patterns of recanalization: de novo bleb formation at the neck of a coiled sac (type DNV) and an enlarged residual cavity without de novo bleb formation (type non-DNV). RESULTS: Twenty-seven patients with aneurysms (9.3%) underwent retreatment (type DNV, 7; type non-DNV, 20). The initial aneurysm size of type DNV aneurysms was significantly smaller than that of type non-DNV (6.1 ± 2.2 mm vs. 10.1 ± 3.6 mm; P < 0.01), and time to retreatment in type DNV was significantly longer than that in type non-DNV (9.4 ± 5.3 years vs. 2.0 ± 2.0 years; P < 0.01). Two type DNV basilar artery (BA) aneurysms ruptured after a few years; however, the other type DNV aneurysms, including 4 anterior circulation aneurysms (including the internal carotid artery), were observed to grow gradually without rupture for >10 years until retreatment. CONCLUSIONS: De novo bleb formation at the neck of a coiled sac emerges with insidious growth during long-term follow-up. Constant caution should be exercised, even in cases of small- and medium-sized anterior circulation aneurysms. A risk of rupture risk may be anticipated, especially in BA lesions.

DOI： 10.1016/j.wneu.2022.02.092

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Non-contrast-enhanced silent magnetic resonance angiography for assessing cerebral aneurysms after PulseRider treatment.

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

Japanese journal of radiology 40 ( 9 ) 979 - 985 2022.4

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

PURPOSE: Conventional time-of-flight (TOF) magnetic resonance angiography (MRA) failed to depict clear visualization of coiled cerebral aneurysms with PulseRider due to metal-induced susceptibility artifacts. Our aim was to overcome the metal artifact using a novel imaging technique of non-contrast-enhanced ultrashort echo-time magnetic resonance angiography (UTE-MRA). MATERIALS AND METHODS: Five unruptured intracranial aneurysms were treated using PulseRider and the patients underwent silent MRA (UTE-MRA). The images were compared with TOF-MRA and digital subtraction angiography (DSA). RESULTS: Silent MRA can visualize the residual cavity of the coiled aneurysms, which was not well visualized and rather defective when using TOF-MRA. While a segment of the proximal marker composed of stainless steel was poorly visualized, the other parts of the parent artery and the arteries of bifurcation, including the aneurysmal neck, were clearly visualized, equivalent to that of DSA. CONCLUSIONS: UTE-MRA achieves better visualization of cerebral aneurysms after PulseRider treatment than TOF-MRA.

DOI： 10.1007/s11604-022-01276-z

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髄芽腫におけるSLFN11発現およびDNA障害型抗がん剤への感受性および予後の検討

棗田学, 中田聡, 村井純子, 岡田正康, 塚本佳広, 大石誠, 吉村淳一, 藤井幸彦, チャールズ・エバーハート

小児の脳神経 47 ( 2 ) 175 - 175 2022.4

Visualization of cortical activation in human brain by flavoprotein fluorescence imaging. International journal

Daiju Mitsuhashi, Ryuichi Hishida, Makoto Oishi, Tetsuya Hiraishi, Manabu Natsumeda, Katsuei Shibuki, Yukihiko Fujii

Journal of neurosurgery 1 - 9 2022.2

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

OBJECTIVE: To develop an innovative brain mapping and neuromonitoring method during neurosurgery, the authors set out to establish intraoperative flavoprotein fluorescence imaging (iFFI) to directly visualize cortical activations in human brain. The significance of iFFI was analyzed by comparison with intraoperative perfusion-dependent imaging (iPDI), which is considered the conventional optical imaging, and by performing animal experiments. METHODS: Seven patients with intracerebral tumors were examined by iFFI and iPDI following craniotomy, using a single operative microscope equipped with a laser light source for iFFI and xenon lamp for iPDI. Images were captured by the same charge-coupled device camera. Responses to bipolar stimulation at selected points on the cortical surface were analyzed off-line, and relative signal changes were visualized by overlaying pseudocolor intensity maps onto cortical photographs. Signal changes exceeding 3 SDs from baseline were defined as significant. The authors also performed FFI and PDI on 10 mice using similar settings, and then compared signal patterns to intraoperative studies. RESULTS: Signals acquired by iFFI exhibited biphasic spatiotemporal changes consisting of an early positive signal peak (F1) and a delayed negative signal peak (F2). In contrast, iPDI signals exhibited only 1 negative peak (P1) that was significantly delayed compared to F1 (p < 0.02) and roughly in phase with F2. Compared to F2 and P1, F1 was of significantly lower amplitude (p < 0.02) and located closer to the bipolar stimulus center (p < 0.03), whereas F2 and P1 were more widespread, irregular, and partially overlapping. In mice, the spatiotemporal characteristics of FFI and PDI resembled those of iFFI and iPDI, but the early positive signal was more robust than F1. CONCLUSIONS: This is the first report in humans of successful intraoperative visualization of cortical activations by using iFFI, which showed rapid evoked cortical activity prior to perfusion-dependent signal changes. Further technical improvements can lead to establishment of iFFI as a real-time intraoperative tool.

DOI： 10.3171/2022.1.JNS212542

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Papers - OOISHI Makoto