首页 > 最新文献

Biomedical optics express最新文献

英文 中文
Longitudinal tracking of perfluorooctanoic acid exposure on mammary epithelial cell spheroids by dynamic optical coherence tomography. 通过动态光学相干断层扫描纵向追踪乳腺上皮细胞球体接触全氟辛酸的情况。
IF 3.4 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-08 DOI: 10.1364/boe.530775
Lin Yang,Pan Ji,Abel A Miranda Buzetta,Haolin Li,Matthew R Lockett,Haibo Zhou,Amy L Oldenburg
We investigated the morphology and intracellular motility of mammary epithelial cell (MCF10DCIS.com) spheroids cultured in 3D artificial extracellular matrix under perfluorooctanoic acid (PFOA) exposure. Dynamic optical coherence tomography (OCT) was employed for real-time, non-invasive imaging of these spheroids longitudinally over 12 days under PFOA exposures up to 500 µM. Despite no significant changes in volume or asphericity of spheroids, morphological alterations were observed in OCT images of spheroids at 100 µM on Day 12 and from Day 4 at 500 µM. Intracellular motility was assessed by the inverse-power-law exponent of the speckle fluctuation spectrum (α), and an autocorrelation-based motility amplitude (M). Linear regression indicated that both PFOA concentration and culture time are highly significant predictors for both α and M (p < 0.001 for all). Both PFOA concentration and culture time have positive associations with α and negative association with M, where increased α indicates suppression of higher frequency fluctuations (∼> 2 Hz) relative to those at lower frequencies, and decreased M indicates overall suppression of intracellular motility. This study can lead to the future development of biomarkers for per- and polyfluoroalkyl substances (PFAS) exposure using dynamic OCT and its associated toolkit of quantitative metrics.
我们研究了在三维人工细胞外基质中培养的乳腺上皮细胞(MCF10DCIS.com)球体在全氟辛酸(PFOA)暴露下的形态和胞内运动。采用动态光学相干断层扫描技术(OCT)对这些球形细胞进行了实时、无创的纵向成像,在PFOA暴露达500 µM的情况下进行了12天的成像。尽管球体的体积或非球面度没有发生明显变化,但在 100 µM 暴露的第 12 天和 500 µM 暴露的第 4 天,从球体的 OCT 图像中观察到了形态学变化。细胞内运动通过斑点波动谱的反幂律指数(α)和基于自相关性的运动幅度(M)进行评估。线性回归结果表明,相对于较低频率的α和M(p 2 Hz),PFOA浓度和培养时间都是非常显著的预测因子,M的降低表明细胞内运动受到了全面抑制。这项研究有助于未来利用动态 OCT 及其相关的定量指标工具包开发全氟和多氟烷基物质(PFAS)暴露的生物标记物。
{"title":"Longitudinal tracking of perfluorooctanoic acid exposure on mammary epithelial cell spheroids by dynamic optical coherence tomography.","authors":"Lin Yang,Pan Ji,Abel A Miranda Buzetta,Haolin Li,Matthew R Lockett,Haibo Zhou,Amy L Oldenburg","doi":"10.1364/boe.530775","DOIUrl":"https://doi.org/10.1364/boe.530775","url":null,"abstract":"We investigated the morphology and intracellular motility of mammary epithelial cell (MCF10DCIS.com) spheroids cultured in 3D artificial extracellular matrix under perfluorooctanoic acid (PFOA) exposure. Dynamic optical coherence tomography (OCT) was employed for real-time, non-invasive imaging of these spheroids longitudinally over 12 days under PFOA exposures up to 500 µM. Despite no significant changes in volume or asphericity of spheroids, morphological alterations were observed in OCT images of spheroids at 100 µM on Day 12 and from Day 4 at 500 µM. Intracellular motility was assessed by the inverse-power-law exponent of the speckle fluctuation spectrum (α), and an autocorrelation-based motility amplitude (M). Linear regression indicated that both PFOA concentration and culture time are highly significant predictors for both α and M (p < 0.001 for all). Both PFOA concentration and culture time have positive associations with α and negative association with M, where increased α indicates suppression of higher frequency fluctuations (∼> 2 Hz) relative to those at lower frequencies, and decreased M indicates overall suppression of intracellular motility. This study can lead to the future development of biomarkers for per- and polyfluoroalkyl substances (PFAS) exposure using dynamic OCT and its associated toolkit of quantitative metrics.","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"107 1","pages":"5115-5127"},"PeriodicalIF":3.4,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Medium-adaptive compressive diffuse optical tomography. 介质自适应压缩漫反射光学断层成像。
IF 2.9 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-08 eCollection Date: 2024-09-01 DOI: 10.1364/BOE.529195
Miguel Mireles, Edward Xu, Rahul Ragunathan, Qianqian Fang

The low spatial resolution of diffuse optical tomography (DOT) has motivated the development of high-density DOT systems utilizing spatially-encoded illumination and detection strategies. Data compression methods, through the application of Fourier or Hadamard patterns, have been commonly explored for both illumination and detection but were largely limited to pre-determined patterns regardless of imaging targets. Here, we show that target-optimized detection patterns can yield significantly improved DOT reconstructions in both in silico and experimental tests. Applying reciprocity, we can further iteratively optimize both illumination and detection patterns and show that these simultaneously optimized source/detection patterns outperform predetermined patterns in simulation settings. In addition, we show media-adaptive measurement data compression methods enable wide-field DOT systems to recover highly complex inclusions inside optically-thick media with reduced background artifacts. Furthermore, using truncated optimized patterns shows an improvement of 2-4× in increased speed of data acquisition and reconstruction without significantly losing image quality. The proposed method can be readily extended for additional data dimensions such as spectrum and time.

漫反射光学断层成像(DOT)的空间分辨率较低,这促使人们利用空间编码照明和检测策略开发高密度 DOT 系统。通过应用傅里叶或哈达玛模式的数据压缩方法已被普遍用于照明和检测,但在很大程度上仅限于预先确定的模式,而与成像目标无关。在这里,我们展示了目标优化检测模式可以在硅学和实验测试中显著改善 DOT 重建。应用互惠原理,我们可以进一步迭代优化照明和检测模式,并表明这些同时优化的光源/检测模式在模拟设置中优于预定模式。此外,我们还展示了介质自适应测量数据压缩方法,该方法使宽视场 DOT 系统能够恢复光学厚介质中的高度复杂夹杂物,并减少背景伪影。此外,使用截断的优化模式可将数据采集和重建速度提高 2-4 倍,而不会明显降低图像质量。所提出的方法可随时扩展到其他数据维度,如光谱和时间。
{"title":"Medium-adaptive compressive diffuse optical tomography.","authors":"Miguel Mireles, Edward Xu, Rahul Ragunathan, Qianqian Fang","doi":"10.1364/BOE.529195","DOIUrl":"https://doi.org/10.1364/BOE.529195","url":null,"abstract":"<p><p>The low spatial resolution of diffuse optical tomography (DOT) has motivated the development of high-density DOT systems utilizing spatially-encoded illumination and detection strategies. Data compression methods, through the application of Fourier or Hadamard patterns, have been commonly explored for both illumination and detection but were largely limited to pre-determined patterns regardless of imaging targets. Here, we show that target-optimized detection patterns can yield significantly improved DOT reconstructions in both <i>in silico</i> and experimental tests. Applying reciprocity, we can further iteratively optimize both illumination and detection patterns and show that these simultaneously optimized source/detection patterns outperform predetermined patterns in simulation settings. In addition, we show media-adaptive measurement data compression methods enable wide-field DOT systems to recover highly complex inclusions inside optically-thick media with reduced background artifacts. Furthermore, using truncated optimized patterns shows an improvement of 2-4× in increased speed of data acquisition and reconstruction without significantly losing image quality. The proposed method can be readily extended for additional data dimensions such as spectrum and time.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"15 9","pages":"5128-5142"},"PeriodicalIF":2.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11407237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Non-degenerate two-photon imaging of deep rodent cortex using indocyanine green in the water absorption window. 利用吲哚菁绿在水吸收窗口对啮齿动物深部皮层进行非退化双光子成像。
IF 2.9 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-06 eCollection Date: 2024-09-01 DOI: 10.1364/BOE.520977
Alankrit Tomar, Shaun A Engelmann, Aaron L Woods, Andrew K Dunn

We present a novel approach for deep vascular imaging in rodent cortex at excitation wavelengths susceptible to water absorption using two-photon microscopy with photons of dissimilar wavelengths. We demonstrate that non-degenerate two-photon excitation (ND-2PE) enables imaging in the water absorption window from 1400-1550 nm using two excitation sources with temporally overlapped pulses at 1300 nm and 1600 nm that straddle the absorption window. We explore the brightness spectra of indocyanine green (ICG) and assess its suitability for imaging in the water absorption window. Further, we demonstrate in vivo imaging of the rodent cortex vascular structure up to 1.2 mm using ND-2PE. Lastly, a comparative analysis of ND-2PE at 1435 nm and single-wavelength, two-photon imaging at 1300 nm and 1435 nm is presented. Our work extends the excitation range for fluorescent dyes to include water absorption regimes and underscores the feasibility of deep two-photon imaging at these wavelengths.

我们提出了一种新方法,利用不同波长光子的双光子显微镜在易受水吸收影响的激发波长下对啮齿类动物皮层的深层血管成像。我们证明了非退化双光子激发(ND-2PE)能在 1400-1550 纳米的水吸收窗口内成像,使用的是 1300 纳米和 1600 纳米两个时间上重叠的激发光源脉冲,它们跨越了吸收窗口。我们探索了吲哚菁绿(ICG)的亮度光谱,并评估了其在水吸收窗口成像的适用性。此外,我们还展示了使用 ND-2PE 对啮齿动物皮层血管结构进行的活体成像,成像范围可达 1.2 毫米。最后,我们对 1435 纳米波长的 ND-2PE 和 1300 纳米波长及 1435 纳米波长的单波长双光子成像进行了比较分析。我们的工作扩展了荧光染料的激发范围,将水吸收机制包括在内,并强调了在这些波长下进行深度双光子成像的可行性。
{"title":"Non-degenerate two-photon imaging of deep rodent cortex using indocyanine green in the water absorption window.","authors":"Alankrit Tomar, Shaun A Engelmann, Aaron L Woods, Andrew K Dunn","doi":"10.1364/BOE.520977","DOIUrl":"https://doi.org/10.1364/BOE.520977","url":null,"abstract":"<p><p>We present a novel approach for deep vascular imaging in rodent cortex at excitation wavelengths susceptible to water absorption using two-photon microscopy with photons of dissimilar wavelengths. We demonstrate that non-degenerate two-photon excitation (ND-2PE) enables imaging in the water absorption window from 1400-1550 nm using two excitation sources with temporally overlapped pulses at 1300 nm and 1600 nm that straddle the absorption window. We explore the brightness spectra of indocyanine green (ICG) and assess its suitability for imaging in the water absorption window. Further, we demonstrate <i>in vivo</i> imaging of the rodent cortex vascular structure up to 1.2 mm using ND-2PE. Lastly, a comparative analysis of ND-2PE at 1435 nm and single-wavelength, two-photon imaging at 1300 nm and 1435 nm is presented. Our work extends the excitation range for fluorescent dyes to include water absorption regimes and underscores the feasibility of deep two-photon imaging at these wavelengths.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"15 9","pages":"5053-5066"},"PeriodicalIF":2.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11407249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Weakly supervised semantic segmentation of leukocyte images based on class activation maps. 基于类激活图的白细胞图像弱监督语义分割。
IF 3.4 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-06 DOI: 10.1364/boe.525294
Rui Feng,Wei Chen,Jie Qi
Leukocytes are an essential component of the human defense system, accurate segmentation of leukocyte images is a crucial step towards automating detection. Most existing methods for leukocyte images segmentation relied on fully supervised semantic segmentation (FSSS) with extensive pixel-level annotations, which are time-consuming and labor-intensive. To address this issue, this paper proposes a weakly supervised semantic segmentation (WSSS) approach for leukocyte images utilizing improved class activation maps (CAMs). Firstly, to alleviate ambiguous boundary problem between leukocytes and background, preprocessing technique is employed to enhance the image quality. Secondly, attention mechanism is added to refine the CAMs generated by improving the matching of local and global features. Random walks, dense conditional random fields and hole filling were leveraged to obtain final pseudo-segmentation labels. Finally, a fully supervised segmentation network is trained with pseudo-segmentation labels. The method is evaluated on BCCD and TMAMD datasets. Experimental results demonstrate that by employing the pseudo segmentation annotations generated through this method can be utilized to train UNet as close as possible to FSSS. This method effectively reduces manual annotation cost while achieving WSSS of leukocyte images.
白细胞是人体防御系统的重要组成部分,准确分割白细胞图像是实现自动检测的关键一步。现有的白细胞图像分割方法大多依赖于全监督语义分割(FSSS)和大量像素级注释,耗时耗力。为解决这一问题,本文提出了一种利用改进的类激活图(CAM)进行白细胞图像弱监督语义分割(WSSS)的方法。首先,为了缓解白细胞与背景之间的模糊边界问题,本文采用了预处理技术来提高图像质量。其次,加入注意力机制,通过改善局部和全局特征的匹配来完善生成的 CAM。利用随机游走、密集条件随机场和洞填充来获得最终的伪分割标签。最后,利用伪分割标签训练出一个完全受监督的分割网络。该方法在 BCCD 和 TMAMD 数据集上进行了评估。实验结果表明,利用该方法生成的伪分割注释,可以训练出尽可能接近 FSSS 的 UNet。该方法在实现白细胞图像 WSSS 的同时,有效降低了人工标注成本。
{"title":"Weakly supervised semantic segmentation of leukocyte images based on class activation maps.","authors":"Rui Feng,Wei Chen,Jie Qi","doi":"10.1364/boe.525294","DOIUrl":"https://doi.org/10.1364/boe.525294","url":null,"abstract":"Leukocytes are an essential component of the human defense system, accurate segmentation of leukocyte images is a crucial step towards automating detection. Most existing methods for leukocyte images segmentation relied on fully supervised semantic segmentation (FSSS) with extensive pixel-level annotations, which are time-consuming and labor-intensive. To address this issue, this paper proposes a weakly supervised semantic segmentation (WSSS) approach for leukocyte images utilizing improved class activation maps (CAMs). Firstly, to alleviate ambiguous boundary problem between leukocytes and background, preprocessing technique is employed to enhance the image quality. Secondly, attention mechanism is added to refine the CAMs generated by improving the matching of local and global features. Random walks, dense conditional random fields and hole filling were leveraged to obtain final pseudo-segmentation labels. Finally, a fully supervised segmentation network is trained with pseudo-segmentation labels. The method is evaluated on BCCD and TMAMD datasets. Experimental results demonstrate that by employing the pseudo segmentation annotations generated through this method can be utilized to train UNet as close as possible to FSSS. This method effectively reduces manual annotation cost while achieving WSSS of leukocyte images.","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"53 1","pages":"5067-5080"},"PeriodicalIF":3.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
3D super-resolution optical fluctuation imaging with temporal focusing two-photon excitation. 利用时间聚焦双光子激发的三维超分辨率光学波动成像。
IF 2.9 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-28 eCollection Date: 2024-07-01 DOI: 10.1364/BOE.523430
Pawel Szczypkowski, Monika Pawlowska, Radek Lapkiewicz

3D super-resolution fluorescence microscopy typically requires sophisticated setups, sample preparation, or long measurements. A notable exception, SOFI, only requires recording a sequence of frames and no hardware modifications whatsoever but being a wide-field method, it faces problems in thick, dense samples. We combine SOFI with temporal focusing two-photon excitation - the wide-field method that is capable of exciting a thin slice in 3D volume. Temporal focusing is simple to implement whenever the excitation path of the microscope can be accessed. The implementation of SOFI is straightforward. By merging these two methods, we obtain super-resolved 3D images of neurons stained with quantum dots. Our approach offers reduced bleaching of out-of-focus fluorescent probes and an improved signal-to-background ratio that can be used when robust resolution improvement is required in thick, dense samples.

三维超分辨率荧光显微镜通常需要复杂的设置、样品制备或长时间测量。但 SOFI 是一个显著的例外,它只需要记录一连串的帧,不需要对硬件进行任何修改,但作为一种宽视场方法,它在厚而密集的样品中面临着问题。我们将 SOFI 与时间聚焦双光子激发相结合,这种宽场方法能够激发三维体积中的薄片。只要能进入显微镜的激发路径,时间聚焦法就很容易实现。SOFI 的实施也很简单。通过合并这两种方法,我们获得了量子点染色神经元的超分辨三维图像。我们的方法减少了焦外荧光探针的漂白现象,提高了信噪比,可用于在厚而密集的样本中提高分辨率。
{"title":"3D super-resolution optical fluctuation imaging with temporal focusing two-photon excitation.","authors":"Pawel Szczypkowski, Monika Pawlowska, Radek Lapkiewicz","doi":"10.1364/BOE.523430","DOIUrl":"10.1364/BOE.523430","url":null,"abstract":"<p><p>3D super-resolution fluorescence microscopy typically requires sophisticated setups, sample preparation, or long measurements. A notable exception, SOFI, only requires recording a sequence of frames and no hardware modifications whatsoever but being a wide-field method, it faces problems in thick, dense samples. We combine SOFI with temporal focusing two-photon excitation - the wide-field method that is capable of exciting a thin slice in 3D volume. Temporal focusing is simple to implement whenever the excitation path of the microscope can be accessed. The implementation of SOFI is straightforward. By merging these two methods, we obtain super-resolved 3D images of neurons stained with quantum dots. Our approach offers reduced bleaching of out-of-focus fluorescent probes and an improved signal-to-background ratio that can be used when robust resolution improvement is required in thick, dense samples.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"15 7","pages":"4381-4389"},"PeriodicalIF":2.9,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adaptive optics in an oblique plane microscope 斜面显微镜中的自适应光学技术
IF 3.4 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-28 DOI: 10.1364/boe.524013
Conor Mcfadden, Zach Marin, Bingying Chen, Stephan Daetwyler, Xiaoding Wang, Divya Rajendran, Kevin M. Dean, Reto Fiolka
Adaptive optics (AO) can restore diffraction-limited performance when imaging beyond superficial cell layers in vivo and in vitro, and as such, is of interest for advanced 3D microscopy methods such as light-sheet fluorescence microscopy (LSFM). In a typical LSFM system, the illumination and detection paths are separate and subject to different optical aberrations. To achieve optimal microscope performance, it is necessary to sense and correct these aberrations in both light paths, resulting in a complex microscope system. Here, we show that in an oblique plane microscope (OPM), a type of LSFM with a single primary objective lens, the same deformable mirror can correct both illumination and fluorescence detection. Besides reducing the complexity, we show that AO in OPM also restores the relative alignment of the light-sheet and focal plane, and that a projection imaging mode can stabilize and improve the wavefront correction in a sensorless AO format. We demonstrate OPM with AO on fluorescent nanospheres and by imaging the vasculature and cancer cells in zebrafish embryos embedded in a glass capillary, restoring diffraction limited resolution and improving the signal strength twofold.
自适应光学(AO)可以恢复体内和体外浅表层细胞成像时的衍射限制性能,因此对光片荧光显微镜(LSFM)等先进的三维显微方法很有意义。在典型的 LSFM 系统中,照明和检测路径是分开的,并受到不同光学像差的影响。为了获得最佳的显微镜性能,有必要感测和校正两条光路中的这些像差,从而形成一个复杂的显微镜系统。在这里,我们展示了在斜面显微镜(OPM)(一种具有单主物镜的 LSFM)中,同一可变形镜可以同时校正照明和荧光检测。除了降低复杂性外,我们还展示了 OPM 中的自动光学还能恢复光片和焦平面的相对对齐,而且投影成像模式可以稳定和改进无传感器自动光学格式中的波前校正。我们演示了在荧光纳米球上使用 AO 的 OPM,并通过对嵌入玻璃毛细管中的斑马鱼胚胎的血管和癌细胞进行成像,恢复了衍射受限的分辨率,并将信号强度提高了两倍。
{"title":"Adaptive optics in an oblique plane microscope","authors":"Conor Mcfadden, Zach Marin, Bingying Chen, Stephan Daetwyler, Xiaoding Wang, Divya Rajendran, Kevin M. Dean, Reto Fiolka","doi":"10.1364/boe.524013","DOIUrl":"https://doi.org/10.1364/boe.524013","url":null,"abstract":"Adaptive optics (AO) can restore diffraction-limited performance when imaging beyond superficial cell layers <jats:italic toggle=\"yes\">in vivo</jats:italic> and <jats:italic toggle=\"yes\">in vitro</jats:italic>, and as such, is of interest for advanced 3D microscopy methods such as light-sheet fluorescence microscopy (LSFM). In a typical LSFM system, the illumination and detection paths are separate and subject to different optical aberrations. To achieve optimal microscope performance, it is necessary to sense and correct these aberrations in both light paths, resulting in a complex microscope system. Here, we show that in an oblique plane microscope (OPM), a type of LSFM with a single primary objective lens, the same deformable mirror can correct both illumination and fluorescence detection. Besides reducing the complexity, we show that AO in OPM also restores the relative alignment of the light-sheet and focal plane, and that a projection imaging mode can stabilize and improve the wavefront correction in a sensorless AO format. We demonstrate OPM with AO on fluorescent nanospheres and by imaging the vasculature and cancer cells in zebrafish embryos embedded in a glass capillary, restoring diffraction limited resolution and improving the signal strength twofold.","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"51 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In vivo imaging of human retinal ganglion cells using optical coherence tomography without adaptive optics 使用光学相干断层成像技术对人类视网膜神经节细胞进行活体成像,无需自适应光学技术
IF 3.4 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-28 DOI: 10.1364/boe.533249
Furu Zhang, Katherine Kovalick, Achyut Raghavendra, Somayyeh Soltanian-Zadeh, Sina Farsiu, Daniel X. Hammer, Zhuolin Liu
Retinal ganglion cells play an important role in human vision, and their degeneration results in glaucoma and other neurodegenerative diseases. Imaging these cells in the living human retina can greatly improve the diagnosis and treatment of glaucoma. However, owing to their translucent soma and tight packing arrangement within the ganglion cell layer (GCL), successful imaging has only been achieved with sophisticated research-grade adaptive optics (AO) systems. For the first time we demonstrate that GCL somas can be resolved and cell morphology can be quantified using non-AO optical coherence tomography (OCT) devices with optimal parameter configuration and post-processing.
视网膜神经节细胞在人类视觉中发挥着重要作用,它们的退化会导致青光眼和其他神经退行性疾病。对活体视网膜中的这些细胞进行成像可大大提高青光眼的诊断和治疗水平。然而,由于神经节细胞体是半透明的,而且在神经节细胞层(GCL)内排列紧密,因此只能通过精密的研究级自适应光学(AO)系统才能成功成像。我们首次证明,使用非自适应光学相干断层扫描(OCT)设备,通过最佳参数配置和后处理,可以分辨 GCL 体节并量化细胞形态。
{"title":"In vivo imaging of human retinal ganglion cells using optical coherence tomography without adaptive optics","authors":"Furu Zhang, Katherine Kovalick, Achyut Raghavendra, Somayyeh Soltanian-Zadeh, Sina Farsiu, Daniel X. Hammer, Zhuolin Liu","doi":"10.1364/boe.533249","DOIUrl":"https://doi.org/10.1364/boe.533249","url":null,"abstract":"Retinal ganglion cells play an important role in human vision, and their degeneration results in glaucoma and other neurodegenerative diseases. Imaging these cells in the living human retina can greatly improve the diagnosis and treatment of glaucoma. However, owing to their translucent soma and tight packing arrangement within the ganglion cell layer (GCL), successful imaging has only been achieved with sophisticated research-grade adaptive optics (AO) systems. For the first time we demonstrate that GCL somas can be resolved and cell morphology can be quantified using non-AO optical coherence tomography (OCT) devices with optimal parameter configuration and post-processing.","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"76 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coagulation depth estimation using a line scanner for depth-resolved laser speckle contrast imaging 利用线扫描仪进行深度分辨激光斑点对比成像的凝固深度估计
IF 3.4 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-27 DOI: 10.1364/boe.529043
Johannes D. Johansson, Martin Hultman, Rolf Saager
Partial-thickness burn wounds extend partially through the dermis, leaving many pain receptors intact and making the injuries very painful. Due to the painfulness, quick assessment of the burn depth is important to not delay surgery of the wound if needed. Laser speckle imaging (LSI) of skin blood flow can be helpful in finding severe coagulation zones with impaired blood flow. However, LSI measurements are typically too superficial to properly reach the full depth of the adult dermis and cannot resolve the flow in depth. Diffuse correlation spectroscopy (DCS) uses varying source-detector separations to allow differentiation of flow depths but requires time-consuming 2D scanning to form an image of the burn area. We here present a prototype for a hybrid DCS and LSI technique called speckle contrast diffuse correlation spectroscopy (scDCS) with the novel approach of using a laser line as a source and using the speckle contrast of averaged images to obtain an estimate of static scattering in the tissue. This will allow for fast non-contact 1D scanning to perform 3D tomographic imaging, making quantitative estimates of the depth and area of the coagulation zone from burn wounds. Simulations and experimental results from a volumetric flow phantom and a gelatin wedge phantom show promise to determine coagulation depth. The aim is to develop a method that, in the future, could provide more quantitative estimates of coagulation depth in partial thickness burn wounds to better estimate when surgery is needed.
部分厚度烧伤的创面部分穿过真皮层,使许多痛觉感受器完好无损,从而使创面非常疼痛。由于疼痛难忍,快速评估烧伤深度非常重要,以免耽误必要的伤口手术。皮肤血流激光斑点成像(LSI)有助于发现血流受损的严重凝固区。不过,LSI 测量通常过于浅表,无法正确触及成人真皮层的全部深度,也无法分辨深度血流。漫射相关光谱(DCS)使用不同的源-检测器分离来区分血流深度,但需要耗时的二维扫描来形成烧伤区域的图像。我们在此介绍一种混合 DCS 和 LSI 技术的原型,称为斑点对比度漫反射相关光谱(scDCS),其新颖之处在于使用激光线作为光源,并利用平均图像的斑点对比度来估算组织中的静态散射。这样就可以通过快速非接触式一维扫描进行三维断层成像,对烧伤创面凝固区的深度和面积进行定量估计。体积流动模型和明胶楔形模型的模拟和实验结果表明,有望确定凝固深度。我们的目标是开发一种方法,将来可以对部分厚度烧伤创面的凝固深度进行更定量的估计,以便更好地估计何时需要手术。
{"title":"Coagulation depth estimation using a line scanner for depth-resolved laser speckle contrast imaging","authors":"Johannes D. Johansson, Martin Hultman, Rolf Saager","doi":"10.1364/boe.529043","DOIUrl":"https://doi.org/10.1364/boe.529043","url":null,"abstract":"Partial-thickness burn wounds extend partially through the dermis, leaving many pain receptors intact and making the injuries very painful. Due to the painfulness, quick assessment of the burn depth is important to not delay surgery of the wound if needed. Laser speckle imaging (LSI) of skin blood flow can be helpful in finding severe coagulation zones with impaired blood flow. However, LSI measurements are typically too superficial to properly reach the full depth of the adult dermis and cannot resolve the flow in depth. Diffuse correlation spectroscopy (DCS) uses varying source-detector separations to allow differentiation of flow depths but requires time-consuming 2D scanning to form an image of the burn area. We here present a prototype for a hybrid DCS and LSI technique called speckle contrast diffuse correlation spectroscopy (scDCS) with the novel approach of using a laser line as a source and using the speckle contrast of averaged images to obtain an estimate of static scattering in the tissue. This will allow for fast non-contact 1D scanning to perform 3D tomographic imaging, making quantitative estimates of the depth and area of the coagulation zone from burn wounds. Simulations and experimental results from a volumetric flow phantom and a gelatin wedge phantom show promise to determine coagulation depth. The aim is to develop a method that, in the future, could provide more quantitative estimates of coagulation depth in partial thickness burn wounds to better estimate when surgery is needed.","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"151 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Monitoring of neoadjuvant chemotherapy through time domain diffuse optics: breast tissue composition changes and collagen discriminative potential 通过时域漫反射光学监控新辅助化疗:乳腺组织成分变化和胶原蛋白鉴别潜力
IF 3.4 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-27 DOI: 10.1364/boe.527968
Nikhitha Mule, Giulia Maffeis, Rinaldo Cubeddu, Carolina Santangelo, Giampaolo Bianchini, Pietro Panizza, Paola Taroni
The purpose of this clinical study is to test a broad spectral range (635-1060 nm) time-domain diffuse optical spectroscopy in monitoring the response of breast cancer patients to neoadjuvant chemotherapy (NAC). The broadband operation allows us to fully analyze tissue composition in terms of hemoglobin, water, lipids and collagen concentration, which has never been systematically studied until now during the course of therapy. Patients are subjected to multiple breast optical imaging sessions, each one performed at different stages of NAC, both on tumor-bearing and contralateral healthy breasts. We correlate the optical results with conventional imaging techniques and pathological response. Preliminary outcomes on 10 patients’ data show an average significant reduction in the concentrations of oxy-hemoglobin (-53%, p = 0.0020), collagen (-36%, p = 0.0039) and water (-15%, p = 0.0195), and increase in lipids (+39%, p = 0.0137) from baseline to the end of therapy in the tumor-bearing breast of patients who responded to therapy at least partially. With respect to scattering, the scattering amplitude, a, increases slightly (+15%, p = 0.0039) by the end of the therapy compared to the baseline, while the scattering slope, b, shows no significant change (+4%, p = 0.9219). Some change in the constituents’ concentrations was also noticed in the contralateral healthy breast, even though it was significant only for oxy-hemoglobin concentration. We observed that collagen seems to be the only component distinguishing between complete and partial responders by the end of 2-3 weeks from the baseline. In the complete responder group, collagen significantly decreased after 2-3 weeks with respect to baseline (p = 0.0423). While the partial responder group also showed a decrease, it did not reach statistical significance (p = 0.1012). This suggests that collagen could serve as a potential biomarker to measure NAC effectiveness early during treatment. Even though obtained on a small group of patients, these initial results are consistent with those of standard medical modalities and highlight the sensitivity of the technique to changes that occur in breast composition during NAC.
这项临床研究的目的是测试宽光谱范围(635-1060 nm)时域漫射光学光谱在监测乳腺癌患者对新辅助化疗(NAC)反应方面的应用。宽带操作使我们能够全面分析血红蛋白、水、脂质和胶原蛋白浓度方面的组织成分,迄今为止,我们从未在治疗过程中对这些成分进行过系统研究。我们对患者进行了多次乳腺光学成像,每次成像都是在新农合的不同阶段对肿瘤患者和对侧健康乳房进行的。我们将光学成像结果与传统成像技术和病理反应相关联。10 名患者数据的初步结果显示,从基线到治疗结束,至少部分对治疗有反应的患者的肿瘤乳房中氧合血红蛋白(-53%,p = 0.0020)、胶原蛋白(-36%,p = 0.0039)和水(-15%,p = 0.0195)的浓度平均显著降低,而脂质(+39%,p = 0.0137)则有所增加。在散射方面,与基线相比,散射振幅a在治疗结束时略有增加(+15%,p = 0.0039),而散射斜率b则无明显变化(+4%,p = 0.9219)。对侧健康乳房中的成分浓度也发生了一些变化,但只有氧合血红蛋白浓度发生了显著变化。我们观察到,从基线算起,2-3 周后,胶原蛋白似乎是区分完全应答者和部分应答者的唯一成分。在完全应答组中,2-3 周后胶原蛋白与基线相比明显减少(p = 0.0423)。虽然部分反应者组也出现了下降,但未达到统计学意义(p = 0.1012)。这表明,胶原蛋白可作为一种潜在的生物标志物,在治疗早期衡量 NAC 的有效性。尽管这只是在一小部分患者身上获得的结果,但这些初步结果与标准医疗模式的结果一致,并凸显了该技术对 NAC 期间乳房成分变化的敏感性。
{"title":"Monitoring of neoadjuvant chemotherapy through time domain diffuse optics: breast tissue composition changes and collagen discriminative potential","authors":"Nikhitha Mule, Giulia Maffeis, Rinaldo Cubeddu, Carolina Santangelo, Giampaolo Bianchini, Pietro Panizza, Paola Taroni","doi":"10.1364/boe.527968","DOIUrl":"https://doi.org/10.1364/boe.527968","url":null,"abstract":"The purpose of this clinical study is to test a broad spectral range (635-1060 nm) time-domain diffuse optical spectroscopy in monitoring the response of breast cancer patients to neoadjuvant chemotherapy (NAC). The broadband operation allows us to fully analyze tissue composition in terms of hemoglobin, water, lipids and collagen concentration, which has never been systematically studied until now during the course of therapy. Patients are subjected to multiple breast optical imaging sessions, each one performed at different stages of NAC, both on tumor-bearing and contralateral healthy breasts. We correlate the optical results with conventional imaging techniques and pathological response. Preliminary outcomes on 10 patients’ data show an average significant reduction in the concentrations of oxy-hemoglobin (-53%, <jats:italic>p</jats:italic> = 0.0020), collagen (-36%, <jats:italic>p</jats:italic> = 0.0039) and water (-15%, <jats:italic>p</jats:italic> = 0.0195), and increase in lipids (+39%, <jats:italic>p</jats:italic> = 0.0137) from baseline to the end of therapy in the tumor-bearing breast of patients who responded to therapy at least partially. With respect to scattering, the scattering amplitude, <jats:italic>a</jats:italic>, increases slightly (+15%, <jats:italic>p</jats:italic> = 0.0039) by the end of the therapy compared to the baseline, while the scattering slope, <jats:italic>b</jats:italic>, shows no significant change (+4%, <jats:italic>p</jats:italic> = 0.9219). Some change in the constituents’ concentrations was also noticed in the contralateral healthy breast, even though it was significant only for oxy-hemoglobin concentration. We observed that collagen seems to be the only component distinguishing between complete and partial responders by the end of 2-3 weeks from the baseline. In the complete responder group, collagen significantly decreased after 2-3 weeks with respect to baseline (p = 0.0423). While the partial responder group also showed a decrease, it did not reach statistical significance (p = 0.1012). This suggests that collagen could serve as a potential biomarker to measure NAC effectiveness early during treatment. Even though obtained on a small group of patients, these initial results are consistent with those of standard medical modalities and highlight the sensitivity of the technique to changes that occur in breast composition during NAC.","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"14 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Learning-based distortion correction enables proximal-scanning endoscopic OCT elastography. 基于学习的失真校正实现了近端扫描内窥镜 OCT 弹性成像。
IF 2.9 2区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-26 eCollection Date: 2024-07-01 DOI: 10.1364/BOE.528522
Haoran Zhang, Chengfu Gu, Qi Lan, Weiyi Zhang, Chang Liu, Jianlong Yang

Proximal rotary scanning is predominantly used in the clinical practice of endoscopic and intravascular OCT, mainly because of the much lower manufacturing cost of the probe compared to distal scanning. However, proximal scanning causes severe beam stability issues (also known as non-uniform rotational distortion, NURD), which hinders the extension of its applications to functional imaging, such as OCT elastography (OCE). In this work, we demonstrate the abilities of learning-based NURD correction methods to enable the imaging stability required for intensity-based OCE. Compared with the previous learning-based NURD correction methods that use pseudo distortion vectors for model training, we propose a method to extract real distortion vectors from a specific endoscopic OCT system, and validate its superiority in accuracy under both convolutional-neural-network- and transformer-based learning architectures. We further verify its effectiveness in elastography calculations (digital image correlation and optical flow) and the advantages of our method over other NURD correction methods. Using the air pressure of a balloon catheter as a mechanical stimulus, our proximal-scanning endoscopic OCE could effectively differentiate between areas of varying stiffness of atherosclerotic vascular phantoms. Compared with the existing endoscopic OCE methods that measure only in the radial direction, our method could achieve 2D displacement/strain distribution in both radial and circumferential directions.

近端旋转扫描主要用于内窥镜和血管内 OCT 的临床实践,这主要是因为与远端扫描相比,探头的制造成本要低得多。然而,近端扫描会导致严重的光束稳定性问题(也称为非均匀旋转变形,NURD),这阻碍了其在功能成像(如 OCT 弹性成像,OCE)方面的应用。在这项工作中,我们展示了基于学习的 NURD 校正方法实现基于强度的 OCE 所需的成像稳定性的能力。与之前使用伪失真向量进行模型训练的基于学习的 NURD 校正方法相比,我们提出了一种从特定内窥镜 OCT 系统中提取真实失真向量的方法,并验证了其在基于卷积神经网络和转换器的学习架构下的准确性优势。我们进一步验证了它在弹性成像计算(数字图像相关性和光流)中的有效性,以及我们的方法与其他 NURD 校正方法相比的优势。利用球囊导管的气压作为机械刺激,我们的近端扫描内窥镜 OCE 可以有效区分动脉粥样硬化血管模型的不同僵硬度区域。与仅在径向进行测量的现有内窥镜 OCE 方法相比,我们的方法可在径向和周向实现二维位移/应变分布。
{"title":"Learning-based distortion correction enables proximal-scanning endoscopic OCT elastography.","authors":"Haoran Zhang, Chengfu Gu, Qi Lan, Weiyi Zhang, Chang Liu, Jianlong Yang","doi":"10.1364/BOE.528522","DOIUrl":"10.1364/BOE.528522","url":null,"abstract":"<p><p>Proximal rotary scanning is predominantly used in the clinical practice of endoscopic and intravascular OCT, mainly because of the much lower manufacturing cost of the probe compared to distal scanning. However, proximal scanning causes severe beam stability issues (also known as non-uniform rotational distortion, NURD), which hinders the extension of its applications to functional imaging, such as OCT elastography (OCE). In this work, we demonstrate the abilities of learning-based NURD correction methods to enable the imaging stability required for intensity-based OCE. Compared with the previous learning-based NURD correction methods that use pseudo distortion vectors for model training, we propose a method to extract real distortion vectors from a specific endoscopic OCT system, and validate its superiority in accuracy under both convolutional-neural-network- and transformer-based learning architectures. We further verify its effectiveness in elastography calculations (digital image correlation and optical flow) and the advantages of our method over other NURD correction methods. Using the air pressure of a balloon catheter as a mechanical stimulus, our proximal-scanning endoscopic OCE could effectively differentiate between areas of varying stiffness of atherosclerotic vascular phantoms. Compared with the existing endoscopic OCE methods that measure only in the radial direction, our method could achieve 2D displacement/strain distribution in both radial and circumferential directions.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"15 7","pages":"4345-4364"},"PeriodicalIF":2.9,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Biomedical optics express
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1