Volume 29 Issue 6 | Journal of Biomedical Optics

Journal of Biomedical Optics

VOL. 29 · NO. 6 | June 2024

ISSUES IN PROGRESS

IN PROGRESS

SPIE publishes accepted journal articles as soon as they are approved for publication. Journal issues are considered In Progress until all articles for an issue have been published. Articles published ahead of the completed issue are fully citable.

IN THIS ISSUE

Tutorials (1)

General (4)

Imaging (7)

Microscopy (1)

Sensing (1)

Errata (1)

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Tutorials

Tutorial on methods for estimation of optical absorption and scattering properties of tissue

Ran Tao, Janek Gröhl, Lina Hacker, Antonio Pifferi, Darren Roblyer, Sarah E. Bohndiek

Journal of Biomedical Optics, Vol. 29, Issue 06, 060801, (June 2024) https://doi.org/10.1117/1.JBO.29.6.060801

Open Access

TOPICS: Tissues, Scattering, Optical properties, Absorption, Tissue optics, Signal detection, Diffusion, Light scattering, Light sources and illumination, Light absorption

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General

Wearable laser Doppler flowmetry for non-invasive assessment of diabetic foot microcirculation: methodological considerations and clinical implications

Xing-Xi Hu, Xiao-Man Xing, Zhen-Ming Zhang, Chao Zhang, Li Chen, Jia-Zhang Huang, Xu Wang, Xin Ma, Xiang Geng

Journal of Biomedical Optics, Vol. 29, Issue 06, 065001, (May 2024) https://doi.org/10.1117/1.JBO.29.6.065001

Open Access

TOPICS: Heart, Wavelets, Skin, Doppler effect, Statistical analysis, Nerve, Control systems, Blood, Scanning probe lithography, Head

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Stain-free enucleation of mouse and human oocytes with a 1033 nm femtosecond laser

Alina Osychenko, Alexandr Zalessky, Alexey Bachurin, David Yu. Martirosyan, Maria Egorova, Viktor Nadtochenko

Journal of Biomedical Optics, Vol. 29, Issue 06, 065002, (May 2024) https://doi.org/10.1117/1.JBO.29.6.065002

Open Access

TOPICS: Spindles, Femtosecond phenomena, Dyes, Visualization, Polarized light, Polarized microscopy, Confocal microscopy, Laser radiation, Laser irradiation, Animals

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Two-color diffuse in vivo flow cytometer

Amber L. Williams, Augustino V. Scorzo, Rendall R. Strawbridge, Scott C. Davis, Mark Niedre

Journal of Biomedical Optics, Vol. 29, Issue 06, 065003, (May 2024) https://doi.org/10.1117/1.JBO.29.6.065003

Open Access

TOPICS: Cancer detection, Tumors, Green fluorescent proteins, In vivo imaging, Fluorescence, Animals, Tunable filters, Equipment, Blood, In vitro testing

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Macroscopic inelastic scattering imaging using a hyperspectral line-scanning system identifies invasive breast cancer in lumpectomy and mastectomy specimens

Sandryne David, Hugo Tavera, Tran Trang, Frédérick Dallaire, François Daoust, Francine Tremblay, Lara Richer, Sarkis Meterissian, Frédéric Leblond

Journal of Biomedical Optics, Vol. 29, Issue 06, 065004, (June 2024) https://doi.org/10.1117/1.JBO.29.6.065004

Open Access

TOPICS: Cancer, Raman spectroscopy, Hyperspectral imaging, Tissues, Surgery, Breast, Tumor growth modeling, Breast cancer, Adipose tissue, Biological samples

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Imaging

Functional hemodynamic imaging markers for the prediction of pathological outcomes in breast cancer patients treated with neoadjuvant chemotherapy

Bin Deng, Ailis Muldoon, Jayne Cormier, Nathaniel Mercaldo, Elizabeth Niehoff, Natalie Moffett, Mansi A. Saksena, Steven Isakoff, Stefan Carp

Journal of Biomedical Optics, Vol. 29, Issue 06, 066001, (May 2024) https://doi.org/10.1117/1.JBO.29.6.066001

Open Access

TOPICS: Tumors, Breast, Digital breast tomosynthesis, Biomedical optics, Mammography, Tissues, Hemodynamics, Chemotherapy, Breast cancer, Magnetic resonance imaging

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Significance

Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes.

Aim

We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT.

Approach

Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers.

Results

Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles (p=0.042). In addition, the change in normalized tumor StO2 upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle (p=0.038). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI.

Conclusions

These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.

Generalized 3D registration algorithm for enhancing retinal optical coherence tomography images

Tiffany Tse, Yudan Chen, Mahsa Siadati, Yusi Miao, Jun Song, Da Ma, Zaid Mammo, Myeong Jin Ju

Journal of Biomedical Optics, Vol. 29, Issue 06, 066002, (May 2024) https://doi.org/10.1117/1.JBO.29.6.066002

Open Access

TOPICS: Optical coherence tomography, Image registration, 3D image processing, Visualization, Imaging systems, Algorithm development, Image quality, Eye, Detection and tracking algorithms, Signal to noise ratio

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Significance

Optical coherence tomography (OCT) has emerged as the standard of care for diagnosing and monitoring the treatment of various ocular disorders due to its noninvasive nature and in vivo volumetric acquisition capability. Despite its widespread applications in ophthalmology, motion artifacts remain a challenge in OCT imaging, adversely impacting image quality. While several multivolume registration algorithms have been developed to address this issue, they are often designed to cater to one specific OCT system or acquisition protocol.

Aim

We aim to generate an OCT volume free of motion artifacts using a system-agnostic registration algorithm that is independent of system specifications or protocol.

Approach

We developed a B-scan registration algorithm that removes motion and corrects for both translational eye movements and rotational angle differences between volumes. Tests were carried out on various datasets obtained from two different types of custom-built OCT systems and one commercially available system to determine the reliability of the proposed algorithm. Additionally, different system specifications were used, with variations in axial resolution, lateral resolution, signal-to-noise ratio, and real-time motion tracking. The accuracy of this method has further been evaluated through mean squared error (MSE) and multiscale structural similarity index measure (MS-SSIM).

Results

The results demonstrate improvements in the overall contrast of the images, facilitating detailed visualization of retinal vasculatures in both superficial and deep vasculature plexus. Finer features of the inner and outer retina, such as photoreceptors and other pathology-specific features, are discernible after multivolume registration and averaging. Quantitative analyses affirm that increasing the number of averaged registered volumes will decrease MSE and increase MS-SSIM as compared to the reference volume.

Conclusions

The multivolume registered data obtained from this algorithm offers significantly improved visualization of the retinal microvascular network as well as retinal morphological features. Furthermore, we have validated that the versatility of our methodology extends beyond specific OCT modalities, thereby enhancing the clinical utility of OCT for the diagnosis and monitoring of ocular pathologies.

Real-time identification of life-threatening necrotizing soft-tissue infections using indocyanine green fluorescence imaging

Gabrielle Ray, Samuel Streeter, Logan Bateman, Jonathan Elliott, Eric Henderson, NEFARIOUS Study Group

Journal of Biomedical Optics, Vol. 29, Issue 06, 066003, (May 2024) https://doi.org/10.1117/1.JBO.29.6.066003

Open Access

TOPICS: Fluorescence, Tissues, Fluorescence imaging, Targeting Task Performance metric, Fluorescence intensity, Indocyanine green, Imaging systems, Diagnostics, Blood, Biomedical optics

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Significance

Necrotizing soft-tissue infections (NSTIs) are life-threatening infections with a cumulative case fatality rate of 21%. The initial presentation of an NSTI is non-specific, frequently leading to misdiagnosis and delays in care. No current strategies yield an accurate, real-time diagnosis of an NSTI.

Aim

A first-in-kind, observational, clinical pilot study tested the hypothesis that measurable fluorescence signal voids occur in NSTI-affected tissues following intravenous administration and imaging of perfusion-based indocyanine green (ICG) fluorescence. This hypothesis is based on the established knowledge that NSTI is associated with local microvascular thrombosis.

Approach

Adult patients presenting to the Emergency Department of a tertiary care medical center at high risk for NSTI were prospectively enrolled and imaged with a commercial fluorescence imager. Single-frame fluorescence snapshot and first-pass perfusion kinetic parameters—ingress slope (IS), time-to-peak (TTP) intensity, and maximum fluorescence intensity (IMAX)—were quantified using a dynamic contrast-enhanced fluorescence imaging technique. Clinical variables (comorbidities, blood laboratory values), fluorescence parameters, and fluorescence signal-to-background ratios (SBRs) were compared to final infection diagnosis.

Results

Fourteen patients were enrolled and imaged (six NSTI, six cellulitis, one diabetes mellitus-associated gangrene, and one osteomyelitis). Clinical variables demonstrated no statistically significant differences between NSTI and non-NSTI patient groups (p-value≥0.22). All NSTI cases exhibited prominent fluorescence signal voids in affected tissues, including tissue features not visible to the naked eye. All cellulitis cases exhibited a hyperemic response with increased fluorescence and no distinct signal voids. Median lesion-to-background tissue SBRs based on snapshot, IS, TTP, and IMAX parameter maps ranged from 3.2 to 9.1, 2.2 to 33.8, 1.0 to 7.5, and 1.5 to 12.7, respectively, for the NSTI patient group. All fluorescence parameters except TTP demonstrated statistically significant differences between NSTI and cellulitis patient groups (p-value<0.05).

Conclusions

Real-time, accurate discrimination of NSTIs compared with non-necrotizing infections may be possible with perfusion-based ICG fluorescence imaging.

Imperfect refractive index matching in scanning laser optical tomography and a method for digital correction

Ole Hill, Merve Wollweber, Tobias Biermann, Tammo Ripken, Roland Lachmayer

Journal of Biomedical Optics, Vol. 29, Issue 06, 066004, (May 2024) https://doi.org/10.1117/1.JBO.29.6.066004

Open Access

TOPICS: Optical tomography, Simulations, Laser optics, Refractive index, Biological samples, Silicon, Refraction, Image quality, Water, Image restoration

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Intraoperative characterization of cardiac tissue: the potential of light scattering spectroscopy

Brian Cottle, Sarthak Tiwari, Aditya Kaza, Frank Sachse, Robert Hitchcock

Journal of Biomedical Optics, Vol. 29, Issue 06, 066005, (June 2024) https://doi.org/10.1117/1.JBO.29.6.066005

Open Access

TOPICS: Tissues, Biological samples, Image segmentation, 3D modeling, Education and training, Connective tissue, Body composition, Natural surfaces, Muscles, Data modeling

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Comprehensive framework of GPU-accelerated image reconstruction for photoacoustic computed tomography

Yibing Wang, Changhui Li

Journal of Biomedical Optics, Vol. 29, Issue 06, 066006, (June 2024) https://doi.org/10.1117/1.JBO.29.6.066006

Open Access

TOPICS: Image restoration, Photoacoustic tomography, Reconstruction algorithms, Algorithm development, Data acquisition, Sensors, Computer hardware, 3D image reconstruction, Lithium, Detector arrays

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Deformable multi-modal image registration for the correlation between optical measurements and histology images

Lianne Feenstra, Maud Lambregts, Theo J. Ruers, Behdad Dashtbozorg

Journal of Biomedical Optics, Vol. 29, Issue 06, 066007, (June 2024) https://doi.org/10.1117/1.JBO.29.6.066007

Open Access

TOPICS: Image registration, Deformation, Tissues, Optical testing, Machine learning, Image processing, Education and training, Data modeling, RGB color model, Tissue optics

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Microscopy

Deep learning-based spectroscopic single-molecule localization microscopy

Sunil Kumar Gaire, Ali Daneshkhah, Ethan Flowerday, Ruyi Gong, Jane Frederick, Vadim Backman

Journal of Biomedical Optics, Vol. 29, Issue 06, 066501, (May 2024) https://doi.org/10.1117/1.JBO.29.6.066501

Open Access

TOPICS: Image restoration, Education and training, Point spread functions, Dyes, Biological imaging, Spectroscopy, Deep learning, Fluorescence imaging, Single molecule spectroscopy, Image processing

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Significance

Spectroscopic single-molecule localization microscopy (sSMLM) takes advantage of nanoscopy and spectroscopy, enabling sub-10 nm resolution as well as simultaneous multicolor imaging of multi-labeled samples. Reconstruction of raw sSMLM data using deep learning is a promising approach for visualizing the subcellular structures at the nanoscale.

Aim

Develop a novel computational approach leveraging deep learning to reconstruct both label-free and fluorescence-labeled sSMLM imaging data.

Approach

We developed a two-network-model based deep learning algorithm, termed DsSMLM, to reconstruct sSMLM data. The effectiveness of DsSMLM was assessed by conducting imaging experiments on diverse samples, including label-free single-stranded DNA (ssDNA) fiber, fluorescence-labeled histone markers on COS-7 and U2OS cells, and simultaneous multicolor imaging of synthetic DNA origami nanoruler.

Results

For label-free imaging, a spatial resolution of 6.22 nm was achieved on ssDNA fiber; for fluorescence-labeled imaging, DsSMLM revealed the distribution of chromatin-rich and chromatin-poor regions defined by histone markers on the cell nucleus and also offered simultaneous multicolor imaging of nanoruler samples, distinguishing two dyes labeled in three emitting points with a separation distance of 40 nm. With DsSMLM, we observed enhanced spectral profiles with 8.8% higher localization detection for single-color imaging and up to 5.05% higher localization detection for simultaneous two-color imaging.

Conclusions

We demonstrate the feasibility of deep learning-based reconstruction for sSMLM imaging applicable to label-free and fluorescence-labeled sSMLM imaging data. We anticipate our technique will be a valuable tool for high-quality super-resolution imaging for a deeper understanding of DNA molecules’ photophysics and will facilitate the investigation of multiple nanoscopic cellular structures and their interactions.

Sensing

Compact and cost-effective laser-powered speckle contrast optical spectroscopy fiber-free device for measuring cerebral blood flow

Yu Xi Huang, Simon Mahler, Maya Dickson, Aidin Abedi, Julian Michael Tyszka, Yu Tung Lo, Jonathan Russin, Charles Liu, Changhuei Yang

Journal of Biomedical Optics, Vol. 29, Issue 06, 067001, (May 2024) https://doi.org/10.1117/1.JBO.29.6.067001

Open Access

TOPICS: Cameras, Speckle, Laser optics, Head, Blood circulation, Sensors, Heart, Signal detection, Brain, Semiconductor lasers

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Errata

Model for the diffuse reflectance in spatial frequency domain imaging (Erratum)

Anouk L. Post, Dirk J. Faber, Ton G. van Leeuwen

Journal of Biomedical Optics, Vol. 29, Issue 06, 069801, (June 2024) https://doi.org/10.1117/1.JBO.29.6.069801

Open Access

TOPICS: Diffuse reflectance spectroscopy, Biomedical optics, Error analysis, Tumor growth modeling, Surgery, Physics, Cancer, Biomedical engineering

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