Language：English   Publisher：Japanese Society for Medical and Biological Engineering  

<p>Surgical cameras and endoscopes provide important imaging information about a patient's anatomy and pathology, but most of the data are limited to 2D textured representations of visible tissue surfaces. Conversely, research is progressing in the information acquisition field by using spectrum data to obtain more detailed disease diagnostic support information. Spectroscopic information reflects the chemical and physical information of substances. Research is expanding from conventional single-point spectroscopic information to acquisition of two-dimensional spectroscopic information, called hyperspectral data. However, this type of information typically takes a relatively long time to acquire and analyze, which has limited its practical use. Particularly, compensation for the continuous motions of the camera and tissue occurring during acquisition of numerous images as well as the analysis time slow delivery of real-time information. Due to these disadvantages, the use of analyzed hyperspectral data information in medicine has been limited to the research stage. This study aimed to use this system to visualize blood phantoms and biological information from small animals. We developed a 3-band spectral imaging method for measuring relative blood concentration and oxygen saturation, and modified white light images. Real-time information display is possible by limiting the target information and speeding up image acquisition and processing. We also developed an existing red-green-blue (RGB) wavelength-band digital imaging system, in which an optical filter is used to limit the wavelength range to effectively capture the spectral changes associated with oxygen saturation and concentration. Since the three-wavelength information is in the wavelength range of the RGB channels of the image sensor, single-frame data capture was achieved. An analytical method for 3-band spectral data was also developed, which contributed to fast image processing. Further development of this technology can eliminate the disadvantages associated with conventional spectroscopic imaging and analysis. Consequently, we expect that it will contribute to practical use of spectral information in the medical field. The method developed in this study can be applied to general purpose cameras and is highly practical as a display technology for diagnostic support information.</p>

DOI： 10.14326/abe.13.389

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Association for Cancer Research (AACR)  

Abstract

Purpose: An accurate and non-invasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H-tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice. Experimental Design: A MIA PaCa-2 pancreatic carcinoma and C26 colorectal carcinoma models of BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days of free drinking of 30% D2O to track 2H distribution in tissues. 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration was also measured in MIA PaCa-2 bearing mice. Confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS and histopathology were performed. Results: The mouse’s whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments. Conclusions: Deuterium MRI at 1.5T proved feasibility to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for preliminary assessment of radiotherapy and chemotherapy of cancer.

DOI： 10.1158/1078-0432.CCR-23-1635

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Language：English   Publisher：(公社)日本分析化学会  

水性二相(ATP)分離法を用いて、流れ場における相分離によるバイオ成分の分離と回復について検討した。管径方向分配現象(TRDF)におけるポリエチレングリコール(PEG)/リン酸塩(PP)系を用いて、赤血球の分離と回復について検討した。ATPはPPリッチ内相とPEGリッチ外相で構成され、その組成、流量、粘度、接触角などの条件がTRDFに及ぼす影響を調べた。PEGリッチ液粘度はPPリッチ液より高いが、TRDFの相配置は未処理マイクロチャンネル(MC)や溶融シリカ毛細管(CT)内で粘性消散(VD)則に必ずしも従わず、PEG/PP混液の全タイプはVD則に反してPEGリッチ液がMCとCTの両ODS処理内壁付近の外相を占めていた。PSMFを内相と外相における赤血球分布の調査に適用すると、異なる内径の二重CTに供給した時の分布はPEGリッチ外相と比べてPPリッチ内相に比率1.8で集中した。

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

Phase-separation multiphase flow at a liquid-liquid interface was successfully formed in an aqueous two-phase system of polyethylene glycol/phosphate mixed solutions when fed into a microchannel (100 µm wide and 40 µm deep) on a microchip and a fused-silica capillary tube (100 µm ID). As one example, tube radial distribution flow (annular flow) was observed when 10.0 wt% polyethylene glycol 6000 and 8.5 wt% dipotassium hydrogen phosphate aqueous solution containing 1.0 mM Rhodamine B was fed at 40 ℃, recorded by bright field microscopy. It exhibited a dipotassium hydrogen phosphate-rich inner phase and polyethylene glycol-rich outer phase. Effects of conditions including composition, flow rate, viscosity, and contact angle on tube radial distribution flow were analyzed. It was found out that although the viscosity of PEG-rich solution was much higher than that of phosphate-rich one, the phase configuration in tube radial distribution flow did not necessarily obey the viscous dissipation law in untreated microchannel and capillary tube, as well as for all the types of PEG/phosphate mixed solution the PEG-rich solution occupied the outer phase near the ODS-treated inner wall of both microchannel and capillary tube against the law. To assess the use of microfluidic flow in applications, we examined the distribution of red blood cells in the inner and outer phases fed into double capillary tubes with different inner diameters. Cell distribution was found to concentrate in the inner (dipotassium hydrogen phosphate-rich) phase compared to the outer (polyethylene glycol-rich) phase at a ratio of 1.8.

DOI： 10.1007/s44211-022-00259-4

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Language：Japanese   Publisher：(一社)日本外科学会  

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DOI： 10.12938/bmfh.2022-056

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DOI： 10.1016/j.freeradbiomed.2022.10.184

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

Protein kinase C (PKC) is a large family of calcium- and phospholipid-dependent serine/threonine kinases that consists of at least 11 isozymes. Based on their structural characteristics and mode of activation, the PKC family is classified into three subfamilies: conventional or classic (cPKCs; α, βI, βII, and γ), novel or non-classic (nPKCs; δ, ε, η, and θ), and atypical (aPKCs; ζ, ι, and λ) (PKCλ is the mouse homolog of PKCι) PKC isozymes. PKC isozymes play important roles in proliferation, differentiation, survival, migration, invasion, apoptosis, and anticancer drug resistance in cancer cells. Several studies have shown a positive relationship between PKC isozymes and poor disease-free survival, poor survival following anticancer drug treatment, and increased recurrence. Furthermore, a higher level of PKC activation has been reported in cancer tissues compared to that in normal tissues. These data suggest that PKC isozymes represent potential diagnostic and prognostic biomarkers and therapeutic targets for cancer. This review summarizes the current knowledge and discusses the potential of PKC isozymes as biomarkers in the diagnosis, prognosis, and treatment of cancers.

DOI： 10.3390/cancers14215425

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

Doxorubicin (DOX) induces dose-dependent cardiotoxicity via oxidative stress and abnormal mitochondrial function in the myocardium. Therefore, a noninvasive in vivo imaging procedure for monitoring the redox status of the heart may aid in monitoring diseases and developing treatments. However, an appropriate technique has yet to be developed. In this study, we demonstrate a technique for detecting and visualizing the redox status of the heart using in vivo dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) with 3-carbamoyl-PROXYL (CmP) as a molecular imaging probe. Male C57BL/6N mice were administered DOX (20 mg/kg) or saline. DNP-MRI clearly showed a slower DNP signal reduction in the DOX group than in the control group. Importantly, the difference in the DNP signal reduction rate between the two groups occurred earlier than that detected by physiological examination or clinical symptoms. In an in vitro experiment, KCN (an inhibitor of complex IV in the mitochondrial electron transport chain) and DOX inhibited the electron paramagnetic resonance change in H9c2 cardiomyocytes, suggesting that the redox metabolism of CmP in the myocardium is mitochondrion-dependent. Therefore, this molecular imaging technique has the potential to monitor the dynamics of redox metabolic changes in DOX-induced cardiomyopathy and facilitate an early diagnosis of this condition.

DOI： 10.3390/antiox11081454

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Language：Japanese   Publisher：The Mt. Fuji Workshop on CVD事務局  

もやもや病に対するSTA-MCAバイパス術後の過灌流症候群(CHS)の発症を術前に予測することは現在困難である。以前、ハイパースペクトルカメラ(HSC)によって脳表血流を評価できることを報告した。HSCは、可視域にわたる脳皮質表面の連続スペクトルデータ(ハイパースペクトル画像データ)を撮影し、このデータを光学的固有信号に変換することで、脳表の酸素飽和度を算出することができる。今回、HSCを用いてSTA-MCAバイパス術前後の脳表皮質の酸素飽和度を算出し、脳血流を評価することでCHSを予測できるのではないかと考え、自験例で検証を行った。対象は2018～2020年にSTA-MCAバイパス術を行った患者29例とした。神経学的症状やSPECT所見からCHSと診断されたのは5例で、この5例(CHS群)と他の24例(非CHS群)とで脳表皮質の酸素飽和度を比較するとCHS群が有意に高かった(33±28% vs 8±14%)。酸素飽和度増加率のROC分析を行った結果、酸素飽和度の15%以上の増加があれば術後CHSを予測しうることが示された(感度85.0%、特異度81.3%)。

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

Cancer-associated fibroblasts (CAFs) play an important role in cancer progression. However, the origin of CAFs remains unclear. This study shows that macrophages in malignant ascites and pleural effusions (cavity fluid-associated macrophages: CAMs) transdifferentiate into fibroblast-like cells. CAMs obtained from gastrointestinal cancer patients were sorted by flow cytometry and cultured in vitro. CD45+CD14+ CAMs transdifferentiated into CD45-CD90+ fibroblast-like cells that exhibited spindle shapes. Then, cDNA microarray analysis showed that the CD45-CD90+ fibroblast-like cells (macrophage-derived CAFs: MDCAFs) had a fibroblast-specific gene expression signature and produced growth factors for epithelial cell proliferation. Human colon cancer cells transplanted into immunodeficient mice with MDCAFs formed larger tumors than cancer cells alone. Gene ontology analyses showed the involvement of TGFβ signaling and cell-matrix adhesion in MDCAFs, and transdifferentiation of CAMs into MDCAFs was canceled by inhibiting TGFβ and cell adhesion. Furthermore, the acquired genetic alterations in hematopoietic stem cells (HSCs) were shared in CAMs and MDCAFs. Taken together, CAMs could be a source of CAFs and might originate from HSCs. We propose the transdifferentiation process of CAMs into MDCAFs as a new therapeutic target for fibrosis associated with gastrointestinal cancer.

DOI： 10.1016/j.canlet.2022.215597

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

When ternary mixed solutions of water/acetonitrile/ethyl acetate are delivered into a microspace under laminar flow conditions, the solvent molecules show specific microfluidic flows, such as microfluidic inverted flow and tube radial distribution flow, which have been applied to novel analytical methods. In this paper, inverted flow was examined using various Y-type microchannels that had mixing angles of 0°, 90°, 180°, and 270°. Inverted flow was experimentally observed and the trigger phenomenon was also successfully expressed through computer simulations. Tube radial distribution flow, that is, annular flow, in a capillary tube is reported to cause exchange of the inner and outer phases based on the solvent composition of the ternary mixed solution. Tube radial distribution flow for an organic solvent-rich inner and a water-rich outer phases, as well as for a water-rich inner and an organic solvent-rich outer phases, could be well recreated by computer simulations for a ternary mixed solution. This highlights the effectiveness of computer simulations for such flow scenarios and will allow optimization of the operating conditions and design of microfluidic analytical devices. Graphical abstract: [Figure not available: see fulltext.]

DOI： 10.1007/s44211-022-00083-w

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Other Link： https://link.springer.com/article/10.1007/s44211-022-00083-w/fulltext.html

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DOI： 10.1016/j.freeradbiomed.2021.12.191

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Free Radical Biology and Medicine  

In general, the effectiveness of radiation treatment is evaluated through the observation of morphological changes with computed tomography (CT) or magnetic resonance imaging (MRI) images after treatment. However, the evaluation of the treatment effects can be very time consuming, and thus can delay the verification of patient cases where treatment has not been fully effective. It is known that the treatment efficacy depends on redox modulation in tumor tissues, which is an indirect effect of oxidizing redox molecules such as hydroxyl radicals and of reactive oxygen species generated by radiation treatment. In vivo dynamic nuclear polarization-MRI (DNP-MRI) using carbamoyl-PROXYL (CmP) as a redox sensitive DNP probe enables the accurate monitoring of the anatomical distribution of free radicals based on interactions of electrons and nuclear spin, known as Overhauser effect. However, spatiotemporal response of the redox status in tumor tissues post-irradiation remains unknown. In this study, we demonstrate the usefulness of spatiotemporal redox status as an early imaging biomarker of tumor response after irradiation using in vivo DNP-MRI. Our results highlight that in vivo DNP-MRI/CmP allowed us to visualize the tumor redox status responses significantly faster and earlier compared to the verification of morphological changes observed with 1.5 T MRI and cancer metabolism (Warburg effect) obtained by hyperpolarized 13C pyruvate MRS. Our findings suggest that the early assessment of redox status alterations with in vivo DNP-MRI/CmP probe may provide very efficient information regarding the effectiveness of the subsequent radiation treatment.

DOI： 10.1016/j.freeradbiomed.2021.12.311

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Antioxidants and Redox Signaling  

Significance: In vivo molecular and metabolic imaging is an emerging field in biomedical research that aims to perform noninvasive detection of tissue metabolism in disease states and responses to therapeutic agents. The imbalance in tissue oxidation/reduction (Redox) states is related to the onset and progression of several diseases. Tissue redox metabolism provides biomarkers for early diagnosis and drug treatments. Thus, noninvasive imaging of redox metabolism could be a useful, novel diagnostic tool for diagnosis of redox-related disease and drug discovery. Recent Advances: In vivo dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) is a technique that enables the imaging of free radicals in living animals. DNP enhances the MRI signal by irradiating the target tissue or solution with the free radical molecule's electron paramagnetic resonance frequency before executing pulse sequence of the MRI. In vivo DNP-MRI with redox-sensitive nitroxyl radicals as the DNP redox contrast agent enables the imaging of the redox metabolism on various diseases. Moreover, nitroxyl radicals show antioxidant effects that suppress oxidative stress. Critical Issues: To date, considerable progress has been documented preclinically in the development of animal imaging systems. Here, we review redox imaging of in vivo DNP-MRI with a focus on the recent progress of this system and its uses in patients with redox-related diseases. Future Directions: This technique could have broad applications in the study of other redox-related diseases, such as cancer, inflammation, and neurological disorders, and facilitate the evaluation of treatment response as a theranostic tool. Antioxid. Redox Signal. 36, 172-184.

DOI： 10.1089/ars.2021.0087

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DOI： 10.2116/analsci.19.1569

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DOI： 10.1246/cl.2003.266

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DOI： 10.1016/j.bmcl.2003.08.062

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DOI： 10.1246/cl.2003.986

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DOI： 10.1246/bcsj.77.525

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DOI： 10.2116/analsci.19.1355

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DOI： 10.1021/bm025532h

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DOI： 10.2116/analsci.18.1295

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DOI： 10.2116/analsci.17.387

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DOI： 10.1295/polymj.31.1109

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DOI： 10.1246/bcsj.69.637

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DOI： 10.2116/analsci.10.583

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DOI： 10.2116/analsci.10.113

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DOI： 10.1252/jcej.27.436

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Presentation type：Oral presentation (general)  

Venue：日本科学未来館   Country：Japan  

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Venue：早稲田大学   Country：Japan  

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Venue：北海道大学   Country：Japan  

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Venue：高分子年次大会   Country：Japan  

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Country：China  

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Venue：北九州国際会議場   Country：Japan  

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Venue：宮城教育大学   Country：Japan  

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Venue：早稲田大学   Country：Japan  

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Venue：Kyungsung University   Country：Korea, Republic of  

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Language：Japanese   Publisher：放射線生物研究会  

核磁気共鳴画像化法(MRI)は臨床画像診断において必須の医療機器として汎用されている。しかしながら、MRIでの画像化には生体内に多量に存在するプロトン核スピン由来の信号が必要となるため、これまで主として体内の水分子を対象として機能や形態的な診断画像を得ており、MRIで生体内の反応・代謝を可視化することは困難であった。超偏極法(Hyperpolarization)は核磁気共鳴信号を数十倍～数万倍に増幅する技術をいう。近年様々な超偏極手法が開発され、超偏極技術とMRIを組み合わせた超偏極MRIイメージングにより癌代謝、細胞死、およびエネルギー代謝など生体反応をMRIで検出することが可能となってきた。故に、超偏極MRIは代謝に基づく新たなMRI診断法として病気の早期診断や早期治療効果の判別などへの応用が期待されている。小動物から臨床研究に応用されている超偏極MRIイメージングには、電子スピン(フリーラジカル)と核スピンの相互作用を利用する動的核偏極法(Dynamic Nuclear Polarization:以下DNPと略す)がある。DNP法には大きく分けて2種の生体応用に有用な方法がある。(1)偏極装置内でDNP現象を惹起し、超偏極された13C標識化合物を機能造影剤として投与して、13CMRIにより13C化合物の動態を観察して代謝イメージングを行うdissolution DNP法および(2)安定なフリーラジカル分子(電子スピン)を予め注射し、体内でDNP現象を誘発するin vivo DNP法である。本稿では、放射線生物学研究にも資する技術として筆者らが進めているDNP法を用いた最新のMRI装置および疾患への応用例を紹介する。(著者抄録)

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