Volume 28 Issue 10 | Journal of Biomedical Optics

Journal of Biomedical Optics

VOL. 28 · NO. 10 | October 2023

CONTENTS

IN THIS ISSUE

JBO Letters (1)

Special Section on Polarimetry in Biomedical Optics, Part 1 (10)

Imaging (4)

Microscopy (2)

Sensing (1)

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JBO Letters

scatterBrains: an open database of human head models and companion optode locations for realistic Monte Carlo photon simulations

Melissa Wu, Roarke Horstmeyer, Stefan Carp

Journal of Biomedical Optics, Vol. 28, Issue 10, 100501, (October 2023) https://doi.org/10.1117/1.JBO.28.10.100501

TOPICS: Head, Simulations, Data modeling, Databases, Tissues, Monte Carlo methods, Sensors, Magnetic resonance imaging, Near infrared spectroscopy, Spectroscopy

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Special Section on Polarimetry in Biomedical Optics, Part 1

Effect of matrix properties on transmission and reflectance mode division-of-focal-plane Stokes polarimetry

Leanne Iannucci, Matthew Riak, Ethan Meitz, Matthew Bersi, Viktor Gruev, Spencer Lake

Journal of Biomedical Optics, Vol. 28, Issue 10, 102902, (July 2023) https://doi.org/10.1117/1.JBO.28.10.102902

TOPICS: Collagen, Reflectivity, Tissues, Polarimetry, Biological imaging, Matrices, Optical properties, Polarization, Photons, Biomedical optics

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Mueller-matrix imaging polarimetry elevated by wavelet decomposition and polarization-singular processing for analysis of specific cancerous tissue pathology

Anton Sdobnov, Volodymir A. Ushenko, Liliya Trifonyuk, Oksana Bakun, Marta Garazdyuk, Irina V. Soltys, Olexander Dubolazov, Olexander G. Ushenko, Yuriy A. Ushenko, Alexander Bykov, Igor Meglinski

Journal of Biomedical Optics, Vol. 28, Issue 10, 102903, (July 2023) https://doi.org/10.1117/1.JBO.28.10.102903

TOPICS: Tissues, Wavelets, Polarimetry, Biomedical optics, Prostate, Biological samples, Tissue optics, Statistical analysis, Polarization, Actinium

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Polarimetric imaging for cervical pre-cancer screening aided by machine learning: ex vivo studies

Demelza Robinson, Kevin Hoong, Willem Bastiaan Kleijn, Alexander Doronin, Jean Rehbinder, Jeremy Vizet, Angelo Pierangelo, Tatiana Novikova

Journal of Biomedical Optics, Vol. 28, Issue 10, 102904, (July 2023) https://doi.org/10.1117/1.JBO.28.10.102904

TOPICS: Education and training, Polarimetry, Tissues, Machine learning, Biomedical optics, Performance modeling, Biological samples, Data modeling, Cross validation, Histopathology

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Significance

Wide-field imaging Mueller polarimetry is an optical imaging technique that has great potential to become a reliable, fast, non-contact in vivo imaging modality for the early detection of, e.g., deceases and tissue structural malformations, such as cervical intraepithelial neoplasia, in both clinical and low-resource settings. On the other hand, machine learning methods have established themselves as a superior solution in image classification and regression tasks. We combine Mueller polarimetry and machine learning, critically assess the data/classification pipeline, investigate the bias arising from training strategies, and demonstrate how higher levels of detection accuracy can be achieved.

Aim

We aim to automate/assist with diagnostic segmentation of polarimetric images of uterine cervix specimens.

Approach

A comprehensive capture-to-classification pipeline is developed in house. Specimens are acquired and measured with imaging Mueller polarimeter and undergo histopathological classification. Subsequently, a labeled dataset is created within tagged regions of either healthy or neoplastic cervical tissues. Several machine learning methods are trained utilizing different training-test-set-split strategies, and their corresponding accuracies are compared.

Results

Our results include robust measurements of model performance with two approaches: a 90:10 training–test-set-split and leave-one-out cross-validation. By comparing the classifier’s accuracy directly with the ground truth obtained during histology analysis, we demonstrate how conventionally used shuffled split leads to an over-estimate of true classifier performance ( 0.964 ± 0.00 ) . The leave-one-out cross-validation, however, leads to more accurate performance ( 0.812 ± 0.21 ) with respect to newly obtained samples that were not used to train the models.

Conclusions

Combination of Mueller polarimetry and machine learning is a powerful tool for the task of screening for pre-cancerous conditions in cervical tissue sections. Nevertheless, there is a inherent bias with conventional processes that can be addressed using more conservative classifier training approaches. This results in overall improvements of the sensitivity and specificity of the developed techniques for “unseen” images.

Analyzing the influence of oblique incidence on quantitative backscattering tissue polarimetry: a pilot ex vivo study

Zheng Zhang, Conghui Shao, Honghui He, Chao He, Shaoxiong Liu, Hui Ma

Journal of Biomedical Optics, Vol. 28, Issue 10, 102905, (August 2023) https://doi.org/10.1117/1.JBO.28.10.102905

TOPICS: Tissues, Polarimetry, Biological samples, Backscatter, Polarization, Liver, Light sources and illumination, Reflection, Monte Carlo methods, Statistical analysis

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Spatial analysis of polarimetric images to enhance near-surface sampling sensitivity: feasibility in demineralized teeth and other tissue-like media

Michael Singh, Lothar Lilge, Alex Vitkin

Journal of Biomedical Optics, Vol. 28, Issue 10, 102906, (September 2023) https://doi.org/10.1117/1.JBO.28.10.102906

TOPICS: Teeth, Polarization, Polarimetry, Polarized light, Tissues, Spatial analysis, Light sources and illumination, Monte Carlo methods, Microspheres, Enamels

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Significance

Early tooth demineralization may be detectable through spatial analysis of polarized light images as demonstrated in this study. This may also prove useful in the early detection of epithelial tumors that comprise the majority of the cancer burden worldwide.

Aim

The spatial properties of polarized light images have not been greatly exploited in biomedicine to improve sensitivity to superficial tissue regions; therefore, we investigate the optical sampling depth effects as a function of location in the backscattered polarimetric images.

Approach

Backscattered linear polarization intensity distributions exhibit four-lobed patterns arising through single-scattering, multiple-scattering, and geometrical effects. These photon pathway dynamics are investigated through experimental imaging of microsphere suspensions along with corroborative computational polarization-sensitive Monte Carlo modeling. The studied sampling depth effects of linear and circular polarization images (explored in a previous study) are then evaluated on normal and demineralized human teeth, which are known to differ in their surface and sub-surface structures.

Results

Backscattered linear polarization images exhibit enhanced sensitivity to near-surface properties of media (for example, surface roughness and turbidity) at specific locations within the four-lobed patterns. This yields improved differentiation of two tooth types when spatially selecting image regions in the direction perpendicular to the incident linear polarization vector. Circular polarimetric imaging also yields improved differentiation through spatial selection of regions close to the site of illumination. Improved sensitivity to superficial tissues is achieved through a combination of these linear and circular polarimetric imaging approaches.

Conclusions

Heightened sampling sensitivity to tissue microstructure in the surface/near-surface region of turbid tissue-like media and dental tissue is achieved through a judicious spatial selection of specific regions in the resultant co-linear and cross-circular backscattered polarimetric images.

Multiparameter interferometric polarization-enhanced imaging differentiates carcinoma in situ from inflammation of the bladder: an ex vivo study

Shuang Chang, Giovanna A. Giannico, Ezekiel Haugen, Ali Jardaneh, Justin Baba, Anita Mahadevan-Jansen, Sam S. Chang, Audrey K. Bowden

Journal of Biomedical Optics, Vol. 28, Issue 10, 102907, (August 2023) https://doi.org/10.1117/1.JBO.28.10.102907

TOPICS: Tissues, Inflammation, Biological samples, Collagen, Second harmonic generation, Tumors, Birefringence, Copper indium disulfide, Bladder, Biomedical optics

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Impact of corpus callosum fiber tract crossing on polarimetric images of human brain histological sections: ex vivo studies in transmission configuration

Deyan Ivanov, Lu Si, Leonard Felger, Theoni Maragkou, Philippe Schucht, Marie-Claire Schanne-Klein, Hui Ma, Razvigor Ossikovski, Tatiana Novikova

Journal of Biomedical Optics, Vol. 28, Issue 10, 102908, (September 2023) https://doi.org/10.1117/1.JBO.28.10.102908

TOPICS: Brain, Polarimetry, Depolarization, Mueller matrices, Neuroimaging, Biological samples, Tumors, Nerve, Brain tissue, Polarization

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Significance

Imaging Mueller polarimetry is capable to trace in-plane orientation of brain fiber tracts by detecting the optical anisotropy of white matter of healthy brain. Brain tumor cells grow chaotically and destroy this anisotropy. Hence, the drop in scalar retardance values and randomization of the azimuth of the optical axis could serve as the optical marker for brain tumor zone delineation.

Aim

The presence of underlying crossing fibers can also affect the values of scalar retardance and the azimuth of the optical axis. We studied and analyzed the impact of fiber crossing on the polarimetric images of thin histological sections of brain corpus callosum.

Approach

We used the transmission Mueller microscope for imaging of two-layered stacks of thin sections of corpus callosum tissue to mimic the overlapping brain fiber tracts with different fiber orientations. The decomposition of the measured Mueller matrices was performed with differential and Lu–Chipman algorithms and completed by the statistical analysis of the maps of scalar retardance, azimuth of the optical axis, and depolarization.

Results

Our results indicate the sensitivity of Mueller polarimetry to different spatial arrangement of brain fiber tracts as seen in the maps of scalar retardance and azimuth of optical axis of two-layered stacks of corpus callosum sections The depolarization varies slightly (<15 % ) with the orientation of the optical axes in both corpus callosum stripes, but its value increases by 2.5 to 3 times with the stack thickness.

Conclusions

The crossing brain fiber tracts measured in transmission induce the drop in values of scalar retardance and randomization of the azimuth of the optical axis at optical path length of 15 μm. It suggests that the presence of nerve fibers crossing within the depth of few microns will be also detected in polarimetric maps of brain white matter measured in reflection configuration.

Influence of hematoxylin and eosin staining on linear birefringence measurement of fibrous tissue structures in polarization microscopy

Liangyu Deng, Chunyan Chen, Wenxi Yu, Conghui Shao, Zan Shen, Yonggang Wang, Chao He, Hongtao Li, Zhiyan Liu, Honghui He, Hui Ma

Journal of Biomedical Optics, Vol. 28, Issue 10, 102909, (September 2023) https://doi.org/10.1117/1.JBO.28.10.102909

TOPICS: Tissues, Biological samples, Birefringence, Bone, Collagen, Polarization, Dyes, Polarimetry, Statistical analysis, Biological imaging

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Significance

For microscopic polarization imaging of tissue slices, two types of samples are often prepared: one unstained tissue section for polarization imaging to avoid possible influence from staining dyes quantitatively and one hematoxylin-eosin (H&E) stained adjacent tissue section for histological diagnosis and structural feature identification. However, this sample preparation strategy requires high-quality adjacent tissue sections, and labeling the structural features on unstained tissue sections is impossible. With the fast development of data driven-based polarimetric analysis, which requires a large amount of pixel labeled images, a possible method is to directly use H&E stained slices, which are standard samples archived in clinical hospitals for polarization measurement.

Aim

We aim to study the influence of hematoxylin and eosin staining on the linear birefringence measurement of fibrous tissue structures.

Approach

We examine the linear birefringence properties of four pieces of adjacent bone tissue slices with abundant collagen fibers that are unstained, H&E stained, hematoxylin (H) stained, and eosin (E) stained. After obtaining the spatial maps of linear retardance values for the four tissue samples, we carry out a comparative study using a frequency distribution histogram and similarity analysis based on the Bhattacharyya coefficient to investigate how H&E staining affects the linear birefringence measurement of bone tissues.

Results

Linear retardance increased after H&E, H, or E staining (41.7%, 40.8%, and 72.5% increase, respectively). However, there is no significant change in the imaging contrast of linear retardance in bone tissues.

Conclusions

The linear retardance values induced by birefringent collagen fibers can be enhanced after H&E, H, or E staining. However, the structural imaging contrasts based on linear retardance did not change significantly or the staining did not generate linear birefringence on the sample area without collagen. Therefore, it can be acceptable to prepare H&E stained slices for clinical applications of polarimetry based on such a mapping relationship.

Needle guidance with Doppler-tracked polarization-sensitive optical coherence tomography

Danielle Harper, Yongjoo Kim, Alejandra Gómez-Ramírez, Benjamin Vakoc

Journal of Biomedical Optics, Vol. 28, Issue 10, 102910, (October 2023) https://doi.org/10.1117/1.JBO.28.10.102910

TOPICS: Tissues, Optical coherence tomography, Tissue optics, Muscles, Doppler effect, Video, Doppler tomography, Connective tissue, Biological samples, Visualization

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Deep-learning-based cross-modality translation from Stokes image to bright-field contrast

Shilong Wei, Lu Si, Tongyu Huang, Shan Du, Yue Yao, Yang Dong, Hui Ma

Journal of Biomedical Optics, Vol. 28, Issue 10, 102911, (October 2023) https://doi.org/10.1117/1.JBO.28.10.102911

TOPICS: Tissues, Polarimetry, Microscopy, Polarization, Education and training, Breast, Biological samples, Liver, Data modeling, Lung

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Imaging

Quantification of microvascular change of retinal degeneration in Royal College of Surgeons rats using high-resolution spectral domain optical coherence tomography angiography

Zhen-Jie Zhang, You-Ren Wu, Yueh Chien, Yang Chen, Shih-Hwa Chiou, Shih-Jen Chen, Jia-Pu Syu, Wen-Chuan Kuo

Journal of Biomedical Optics, Vol. 28, Issue 10, 106001, (October 2023) https://doi.org/10.1117/1.JBO.28.10.106001

TOPICS: Optical coherence tomography, Retina, Capillaries, Blood vessels, Animal model studies, Retinal diseases, Angiography, Image segmentation, Surgery, Animals

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ArthroNavi framework: stereo endoscope-guided instrument localization for arthroscopic minimally invasive surgeries

Zhongjie Long, Yongting Chi, Xiaotong Yu, Zhouxiang Jiang, Dejin Yang

Journal of Biomedical Optics, Vol. 28, Issue 10, 106002, (October 2023) https://doi.org/10.1117/1.JBO.28.10.106002

TOPICS: Equipment, Endoscopes, Surgery, Cameras, 3D metrology, Point clouds, 3D tracking, Endoscopy, Speckle, Pose estimation

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Significance

As an example of a minimally invasive arthroscopic surgical procedure, arthroscopic osteochondral autograft transplantation (OAT) is a common option for repairing focal cartilage defects in the knee joints. Arthroscopic OAT offers considerable benefits to patients, such as less post-operative pain and shorter hospital stays. However, performing OAT arthroscopically is an extremely demanding task because the osteochondral graft harvester must remain perpendicular to the cartilage surface to avoid differences in angulation.

Aim

We present a practical ArthroNavi framework for instrument pose localization by combining a self-developed stereo endoscopy with electromagnetic computation, which equips surgeons with surgical navigation assistance that eases the operational constraints of arthroscopic OAT surgery.

Approach

A prototype of a stereo endoscope specifically fit for a texture-less scene is introduced extensively. Then, the proposed framework employs the semi-global matching algorithm integrating the matching cubes method for real-time processing of the 3D point cloud. To address issues regarding initialization and occlusion, a displaying method based on patient tracking coordinates is proposed for intra-operative robust navigation. A geometrical constraint method that utilizes the 3D point cloud is used to compute a pose for the instrument. Finally, a hemisphere tabulation method is presented for pose accuracy evaluation.

Results

Experimental results show that our endoscope achieves 3D shape measurement with an accuracy of <730 μm. The mean error of pose localization is 15.4 deg (range of 10.3 deg to 21.3 deg; standard deviation of 3.08 deg) in our ArthroNavi method, which is within the same order of magnitude as that achieved by experienced surgeons using a freehand technique.

Conclusions

The effectiveness of the proposed ArthroNavi has been validated on a phantom femur. The potential contribution of this framework may provide a new computer-aided option for arthroscopic OAT surgery.

Observation and density estimation of a large number of skin capillaries using wide-field portable video capillaroscopy and semantic segmentation

Baku Takimoto, Kotatsu Bito, Sayaka Hari, Hiroyuki Taguchi, Hideaki Haneishi

Journal of Biomedical Optics, Vol. 28, Issue 10, 106003, (October 2023) https://doi.org/10.1117/1.JBO.28.10.106003

TOPICS: Capillaries, Skin, Image segmentation, Image processing, Video, Red blood cells, Semantics, Blood circulation, Education and training, Portability

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Comparison of minimal detectable protoporphyrin IX concentrations with a loupe device and conventional 5-ALA fluorescence microscopy: an experimental study

Mario Mischkulnig, Denise Traxler, Lisa I. Wadiura, Alexandra Lang, Matthias Millesi, Barbara Kiesel, Georg Widhalm

Journal of Biomedical Optics, Vol. 28, Issue 10, 106004, (October 2023) https://doi.org/10.1117/1.JBO.28.10.106004

TOPICS: Fluorescence, Microscopes, Visualization, Light sources and illumination, Tumors, Light sources, Cancer detection, Surgery, Statistical analysis, Fluorescence spectroscopy

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Significance

The 5-aminolevulinic acid (5-ALA) fluorescence technique is now widely applied for intraoperative visualization of specific central nervous system (CNS) tumors. Previous technical implementations of this technique have relied on specifically modified surgical microscopes to visualize intratumoral fluorescent protoporphyrin (PpIX). While this approach evidently allows for reliable intraoperative tumor visualization, it requires the availability of specifically modified surgical microscopes and their use even in cases where the operating neurosurgeon would prefer to use surgical loupes. Recently, a novel loupe device was introduced that is also capable of visualizing 5-ALA fluorescence.

Aim

The aim of this study was therefore to compare the detected PpIX concentrations between the conventional fluorescence microscope and the novel loupe device.

Approach

We used fluorescence phantoms of different PpIX concentrations for comparison between a conventional fluorescence microscope and the novel loupe device. For this purpose, we created fluorescence images using the excitation light sources of the conventional fluorescence microscope and the loupe device with both available background illumination modes (low and high). Subsequently, the minimal detectable PpIX concentrations according to each technique were determined by five independent neurosurgeons.

Results

Using the conventional fluorescence microscope, the median minimal detectable PpIX concentration was 0.16 μg / ml (range: 0.15 to 0.17 μg / ml). By the loupe device, the median minimal detectable PpIX concentration was 0.12 μg / ml (range: 0.10 to 0.12 μg / ml) and 0.08 μg / ml (range: 0.07 to 0.08 μg / ml) for the high- and low-modes, respectively. Altogether, the minimal detectable PpIX concentrations were significantly lower using the loupe device compared to the conventional fluorescence microscope (p = 0.007).

Conclusions

Our data indicate that the novel loupe device is able to visualize 5-ALA fluorescence with high sensitivity and thus might serve as a powerful tool for visualization of specific CNS tumors in the future.

Microscopy

Noise insensitive volumetric fusion method for enhanced photoacoustic microscopy

Sihang Li, Hao Wu, Hongyu Zhang, Zhipeng Zhang, Qiugen Liu, Xianlin Song

Journal of Biomedical Optics, Vol. 28, Issue 10, 106501, (October 2023) https://doi.org/10.1117/1.JBO.28.10.106501

TOPICS: Photoacoustic spectroscopy, Signal to noise ratio, Image fusion, Photoacoustic imaging, Photoacoustic microscopy, Data fusion, Tunable filters, Biomedical optics, Fused deposition modeling, 3D image processing

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Cascaded domain multiphoton spatial frequency modulation imaging

Daniel Scarbrough, Anna Thomas, Jeff Field, Randy Bartels, Jeff Squier

Journal of Biomedical Optics, Vol. 28, Issue 10, 106502, (October 2023) https://doi.org/10.1117/1.JBO.28.10.106502

TOPICS: Modulation, Spatial frequencies, Point spread functions, Resolution enhancement technologies, Optical gratings, Imaging systems, Pulse signals, Nanodiamonds, Multiphoton microscopy, Image resolution

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Sensing

Measuring and imaging of transcutaneous bilirubin, hemoglobin, and melanin based on diffuse reflectance spectroscopy

Masafumi Minakawa, Md. Abdul Wares, Kazuya Nakano, Hideaki Haneishi, Yoshihisa Aizu, Yoshio Hayasaki, Tetsuo Ikeda, Hajime Nagahara, Izumi Nishidate

Journal of Biomedical Optics, Vol. 28, Issue 10, 107001, (October 2023) https://doi.org/10.1117/1.JBO.28.10.107001

TOPICS: Skin, Diffuse reflectance spectroscopy, Tissues, Oxygen, Chromophores, Oxygenation, Absorption, Biomedical optics, Reflectivity, Spectroscopy

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Significance

Evaluation of biological chromophore levels is useful for detection of various skin diseases, including cancer, monitoring of health status and tissue metabolism, and assessment of clinical and physiological vascular functions. Clinically, it is useful to assess multiple different chromophores in vivo with a single technique or instrument.

Aim

To investigate the possibility of estimating the concentration of four chromophores, bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin from diffuse reflectance spectra in the visible region.

Approach

A new diffuse reflectance spectroscopic method based on the multiple regression analysis aided by Monte Carlo simulations for light transport was developed to quantify bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin. Three different experimental animal models were used to induce hyperbilirubinemia, hypoxemia, and melanogenesis in rats.

Results

The estimated bilirubin concentration increased after ligation of the bile duct and reached around 18 mg / dl at 50 h after the onset of ligation, which corresponds to the reference value of bilirubin measured by a commercially available transcutaneous bilirubin meter. The concentration of oxygenated hemoglobin and that of deoxygenated hemoglobin decreased and increased, respectively, as the fraction of inspired oxygen decreased. Consequently, the tissue oxygen saturation dramatically decreased. The time course of melanin concentration after depilation of skin on the back of rats was indicative of the supply of melanosomes produced by melanocytes of hair follicles to the growing hair shaft.

Conclusions

The results of our study showed that the proposed method is capable of the in vivo evaluation of percutaneous bilirubin level, skin hemodynamics, and melanogenesis in rats, and that it has potential as a tool for the diagnosis and management of hyperbilirubinemia, hypoxemia, and pigmented skin lesions.