Volume 28 Issue 12 | Journal of Biomedical Optics

Journal of Biomedical Optics

VOL. 28 · NO. 12 | December 2023

CONTENTS

IN THIS ISSUE

Special Section on Selected Topics in Biophotonics: Translating Novel Photonics Technology into Clinical Applications (8)

General (5)

Imaging (7)

Sensing (1)

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Special Section on Selected Topics in Biophotonics: Translating Novel Photonics Technology into Clinical Applications

Special Section Guest Editorial: Special Section on Selected Topics in Biophotonics: Translating Novel Photonics Technology into Clinical Applications

Stefan Andersson-Engels, Peter E. Andersen

Journal of Biomedical Optics, Vol. 28, Issue 12, 121201, (November 2023) https://doi.org/10.1117/1.JBO.28.12.121201

TOPICS: Biomedical optics, Biomedical applications, Photonics, Physics, Optical coherence tomography, Medical research, Surgery, Reflection, Photoacoustic spectroscopy, Optical imaging

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Interstitial null-distance time-domain diffuse optical spectroscopy using a superconducting nanowire detector

Vamshi Damagatla, Pranav Lanka, Annalisa Brodu, Niels Noordzij, Jessie Qin-Dregely, Andrea Farina, Antonio Pifferi

Journal of Biomedical Optics, Vol. 28, Issue 12, 121202, (April 2023) https://doi.org/10.1117/1.JBO.28.12.121202

TOPICS: Photons, Simulations, Absorption, Diffuse optical spectroscopy, Light absorption, Scattering, Liquids, Superconductors, Signal detection, Nanowires

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Significance

Interstitial fiber-based spectroscopy is gaining interest for real-time in vivo optical biopsies, endoscopic interventions, and local monitoring of therapy. Different from other photonics approaches, time-domain diffuse optical spectroscopy (TD-DOS) can probe the tissue at a few cm distance from the fiber tip and disentangle absorption from the scattering properties. Nevertheless, the signal detected at a short distance from the source is strongly dominated by the photons arriving early at the detector, thus hampering the possibility of resolving late photons, which are rich in information about depth and absorption.

Aim

To fully benefit from the null-distance approach, a detector with an extremely high dynamic range is required to effectively collect the late photons; the goal of our paper is to test its feasibility to perform TD-DOS measurements at null source–detector separations (NSDS).

Approach

In particular, we demonstrate the use of a superconducting nanowire single photon detector (SNSPD) to perform TD-DOS at almost NSDS ( ≈ 150 μm ) by exploiting the high dynamic range and temporal resolution of the SNSPD to extract late arriving, deep-traveling photons from the burst of early photons.

Results

This approach was demonstrated both on Monte Carlo simulations and on phantom measurements, achieving an accuracy in the retrieval of the water spectrum of better than 15%, spanning almost two decades of absorption change in the 700- to 1100-nm range. Additionally, we show that, for interstitial measurements at null source–detector distance, the scattering coefficient has a negligible effect on late photons, easing the retrieval of the absorption coefficient.

Conclusions

Utilizing the SNSPD, broadband TD-DOS measurements were performed to successfully retrieve the absorption spectra of the liquid phantoms. Although the SNSPD has certain drawbacks for use in a clinical system, it is an emerging field with research progressing rapidly, and this makes the SNSPD a viable option and a good solution for future research in needle guided time-domain interstitial fiber spectroscopy.

In vivo microstructural investigation of the human tympanic membrane by endoscopic polarization-sensitive optical coherence tomography

Svea Steuer, Joseph Morgenstern, Lars Kirsten, Matthias Bornitz, Marcus Neudert, Edmund Koch, Jonas Golde

Journal of Biomedical Optics, Vol. 28, Issue 12, 121203, (March 2023) https://doi.org/10.1117/1.JBO.28.12.121203

TOPICS: Polarization, Endoscopy, In vivo imaging, Optical coherence tomography, Ear, Visualization, Tissues, Collagen, Signal detection, GRIN lenses

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Detection of low-frequency oscillations in neonatal piglets with speckle contrast diffuse correlation tomography

Mehrana Mohtasebi, Daniel Irwin, Dara Singh, Siavash Mazdeyasna, Xuhui Liu, Samaneh Rabienia Haratbar, Faraneh Fathi, Chong Huang, Kathryn Saatman, Lei Chen, Guoqiang Yu

Journal of Biomedical Optics, Vol. 28, Issue 12, 121204, (May 2023) https://doi.org/10.1117/1.JBO.28.12.121204

TOPICS: Brain, Ischemia, Simulation of CCA and DLA aggregates, Windows, Speckle, 3D image reconstruction, Sampling rates, Tissues, Reconstruction algorithms, Neuroimaging

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Photoacoustic imaging on its way toward clinical utility: a tutorial review focusing on practical application in medicine

Jonas Riksen, Anton Nikolaev, Gijs van Soest

Journal of Biomedical Optics, Vol. 28, Issue 12, 121205, (June 2023) https://doi.org/10.1117/1.JBO.28.12.121205

TOPICS: Ultrasonography, Imaging systems, Ultrasound transducers, Tissues, Photoacoustic imaging, Tissue optics, Acoustics, Transducers, Absorption, Image restoration

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Iterative prototyping based on lessons learned from the falloposcope in vivo pilot study experience

Andrew D. Rocha, William K. Drake, Photini F. Rice, Dilara J. Long, Hasina Shir, Ryan H. M. Walton, Mary N. Reed, Dominique Galvez, Taliah Gorman, John M. Heusinkveld, Jennifer K. Barton

Journal of Biomedical Optics, Vol. 28, Issue 12, 121206, (August 2023) https://doi.org/10.1117/1.JBO.28.12.121206

TOPICS: Prototyping, Fourier transforms, Optical coherence tomography, Light sources and illumination, Imaging systems, Surgery, Ovarian cancer, Connectors, Equipment, Tissues

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Significance

High grade serous ovarian cancer is the most deadly gynecological cancer, and it is now believed that most cases originate in the fallopian tubes (FTs). Early detection of ovarian cancer could double the 5-year survival rate compared with late-stage diagnosis. Autofluorescence imaging can detect serous-origin precancerous and cancerous lesions in ex vivo FT and ovaries with good sensitivity and specificity. Multispectral fluorescence imaging (MFI) can differentiate healthy, benign, and malignant ovarian and FT tissues. Optical coherence tomography (OCT) reveals subsurface microstructural information and can distinguish normal and cancerous structure in ovaries and FTs.

Aim

We developed an FT endoscope, the falloposcope, as a method for detecting ovarian cancer with MFI and OCT. The falloposcope clinical prototype was tested in a pilot study with 12 volunteers to date to evaluate the safety and feasibility of FT imaging prior to standard of care salpingectomy in normal-risk volunteers. In this manuscript, we describe the multiple modifications made to the falloposcope to enhance robustness, usability, and image quality based on lessons learned in the clinical setting.

Approach

The ∼0.8 mm diameter falloposcope was introduced via a minimally invasive approach through a commercially available hysteroscope and introducing a catheter. A navigation video, MFI, and OCT of human FTs were obtained. Feedback from stakeholders on image quality and procedural difficulty was obtained.

Results

The falloposcope successfully obtained images in vivo. Considerable feedback was obtained, motivating iterative improvements, including accommodating the operating room environment, modifying the hysteroscope accessories, decreasing endoscope fragility and fiber breaks, optimizing software, improving fiber bundle images, decreasing gradient-index lens stray light, optimizing the proximal imaging system, and improving the illumination.

Conclusions

The initial clinical prototype falloposcope was able to image the FTs, and iterative prototyping has increased its robustness, functionality, and ease of use for future trials.

Frameworks of wavelength selection in diffuse reflectance spectroscopy for tissue differentiation in orthopedic surgery

Celina Li, Carl Fisher, Katarzyna Komolibus, Konstantin Grygoryev, Huihui Lu, Ray Burke, Andrea Visentin, Stefan Andersson-Engels

Journal of Biomedical Optics, Vol. 28, Issue 12, 121207, (September 2023) https://doi.org/10.1117/1.JBO.28.12.121207

TOPICS: Bone, Tissues, Principal component analysis, Cements, Diffuse reflectance spectroscopy, Surgery, Data modeling, Education and training, Feature selection, Absorption

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Perspective on the optics of medical imaging

Brian W. Pogue

Journal of Biomedical Optics, Vol. 28, Issue 12, 121208, (September 2023) https://doi.org/10.1117/1.JBO.28.12.121208

TOPICS: Biomedical optics, Medicine, Radio optics, Radiology, Optical components, Medical imaging, Imaging systems, Medical research, Industry, Optical imaging

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General

Nanosecond multipulse retinal damage thresholds of elongated irradiance profiles in explant measurements and simulations

Marc Herbst, Sebastian Kotzur, Annette Frederiksen, Wilhelm Stork

Journal of Biomedical Optics, Vol. 28, Issue 12, 125001, (December 2023) https://doi.org/10.1117/1.JBO.28.12.125001

TOPICS: Laser damage threshold, Biological samples, Tissues, Simulations, Laser safety, Explants, Laser irradiation, Standards development, Eye, LIDAR

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Improved spatial speckle contrast model for tissue blood flow imaging: effects of spatial correlation among neighboring camera pixels

Julio Cesar Juarez-Ramirez, Beatriz Coyotl-Ocelotl, Bernard Choi, Ruben Ramos-Garcia, Teresita Spezzia-Mazzocco, Julio C. Ramirez-San-Juan

Journal of Biomedical Optics, Vol. 28, Issue 12, 125002, (December 2023) https://doi.org/10.1117/1.JBO.28.12.125002

TOPICS: Speckle, Windows, Blood circulation, Tissues, Cameras, Speckle pattern, Data modeling, Laser speckle contrast imaging, Mathematical modeling, Autocorrelation

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Broadband scattering properties of articular cartilage zones and their relationship with the heterogenous structure of articular cartilage extracellular matrix

Iman Kafian-Attari, Ervin Nippolainen, Florian Bergmann, Akuroma George, Petri Paakkari, Arash Mirhashemi, Florian Foschum, Alwin Kienle, Juha Töyräs, Isaac O. Afara

Journal of Biomedical Optics, Vol. 28, Issue 12, 125003, (December 2023) https://doi.org/10.1117/1.JBO.28.12.125003

TOPICS: Cartilage, Tissues, Light scattering, Collagen, Rayleigh scattering, Scattering, Anatomy, Biological samples, Mie scattering, Transmittance

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Significance

Articular cartilage exhibits a zonal architecture, comprising three distinct zones: superficial, middle, and deep. Collagen fibers, being the main solid constituent of articular cartilage, exhibit unique angular and size distribution in articular cartilage zones. There is a gap in knowledge on how the unique properties of collagen fibers across articular cartilage zones affect the scattering properties of the tissue.

Aim

This study hypothesizes that the structural properties of articular cartilage zones affect its scattering parameters. We provide scattering coefficient and scattering anisotropy factor of articular cartilage zones in the spectral band of 400 to 1400 nm. We enumerate the differences and similarities of the scattering properties of articular cartilage zones and provide reasoning for these observations.

Approach

We utilized collimated transmittance and integrating sphere measurements to estimate the scattering coefficients of bovine articular cartilage zones and bulk tissue. We used the relationship between the scattering coefficients to estimate the scattering anisotropy factor. Polarized light microscopy was applied to estimate the depth-wise angular distribution of collagen fibers in bovine articular cartilage.

Results

We report that the Rayleigh scatterers contribution to the scattering coefficients, the intensity of the light scattered by the Rayleigh and Mie scatterers, and the angular distribution of collagen fibers across tissue depth are the key parameters that affect the scattering properties of articular cartilage zones and bulk tissue. Our results indicate that in the short visible region, the superficial and middle zones of articular cartilage affect the scattering properties of the tissue, whereas in the far visible and near-infrared regions, the articular cartilage deep zone determines articular cartilage scattering properties.

Conclusion

This study provides scattering properties of articular cartilage zones. Such findings support future research to utilize optical simulation to estimate the penetration depth, depth-origin, and pathlength of light in articular cartilage for optical diagnosis of the tissue.

Single-distance and dual-slope frequency-domain near-infrared spectroscopy to assess skeletal muscle hemodynamics

Cristianne Fernandez, Giles Blaney, Jodee Frias, Fatemeh Tavakoli, Angelo Sassaroli, Sergio Fantini

Journal of Biomedical Optics, Vol. 28, Issue 12, 125004, (December 2023) https://doi.org/10.1117/1.JBO.28.12.125004

TOPICS: Absorption, Adipose tissue, Muscles, Optical properties, Hemodynamics, Tissues, Near infrared spectroscopy, Scattering, Simulations, Tissue optics

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Plasmon-enhanced optoacoustic transducer with Ecoflex thin film for broadband ultrasound generation using overdriven pulsed laser diode

Hamin Na, Jaehyeok Park, Ki-Hun Jeong

Journal of Biomedical Optics, Vol. 28, Issue 12, 125005, (December 2023) https://doi.org/10.1117/1.JBO.28.12.125005

TOPICS: Optoacoustics, Ultrasound transducers, Ultrasonography, Thin films, Microfluidics, Laser frequency, Acoustics, Modulation, Thermography, Laser irradiation

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Imaging

In vivo burn scar assessment with speckle decorrelation and joint spectral and time domain optical coherence tomography

Qiang Wang, Peijun Gong, Hadi Afsharan, Chulmin Joo, Natalie Morellini, Mark Fear, Fiona Wood, Hao Ho, Dilusha Silva, Barry Cense

Journal of Biomedical Optics, Vol. 28, Issue 12, 126001, (December 2023) https://doi.org/10.1117/1.JBO.28.12.126001

TOPICS: Blood vessels, Tissues, Optical coherence tomography, Skin, Speckle, In vivo imaging, Blood circulation, Velocity measurements, Capillaries, Biological imaging

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Significance

Post-burn scars and scar contractures present significant challenges in burn injury management, necessitating accurate evaluation of the wound healing process to prevent or minimize complications. Non-invasive and accurate assessment of burn scar vascularity can offer valuable insights for evaluations of wound healing. Optical coherence tomography (OCT) and OCT angiography (OCTA) are promising imaging techniques that may enhance patient-centered care and satisfaction by providing detailed analyses of the healing process.

Aim

Our study investigates the capabilities of OCT and OCTA for acquiring information on blood vessels in burn scars and evaluates the feasibility of utilizing this information to assess burn scars.

Approach

Healthy skin and neighboring scar data from nine burn patients were obtained using OCT and processed with speckle decorrelation, Doppler OCT, and an enhanced technique based on joint spectral and time domain OCT. These methods facilitated the assessment of vascular structure and blood flow velocity in both healthy skin and scar tissues. Analyzing these parameters allowed for objective comparisons between normal skin and burn scars.

Results

Our study found that blood vessel distribution in burn scars significantly differs from that in healthy skin. Burn scars exhibit increased vascularization, featuring less uniformity and lacking the intricate branching network found in healthy tissue. Specifically, the density of the vessels in burn scars is 67% higher than in healthy tissue, while axial flow velocity in burn scar vessels is 25% faster than in healthy tissue.

Conclusions

Our research demonstrates the feasibility of OCT and OCTA as burn scar assessment tools. By implementing these technologies, we can distinguish between scar and healthy tissue based on its vascular structure, providing evidence of their practicality in evaluating burn scar severity and progression.

Switchable LED-based laparoscopic multispectral system for rapid high-resolution perfusion imaging

Annekatrin Pfahl, Süleyman Polat, Hannes Köhler, Ines Gockel, Andreas Melzer, Claire Chalopin

Journal of Biomedical Optics, Vol. 28, Issue 12, 126002, (December 2023) https://doi.org/10.1117/1.JBO.28.12.126002

TOPICS: Tissues, Oxygenation, Light emitting diodes, Laparoscopy, Switching, Signal to noise ratio, Light sources and illumination, Imaging systems, Distance measurement, Calibration

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Monte Carlo simulations and phantom modeling for spatial frequency domain imaging of surgical wound monitoring

Lai Zhang, Alistair Bounds, John Girkin

Journal of Biomedical Optics, Vol. 28, Issue 12, 126003, (December 2023) https://doi.org/10.1117/1.JBO.28.12.126003

TOPICS: Scattering, Monte Carlo methods, Tissues, Skin, Wound healing, Spatial frequencies, Modeling, Absorption, Photon transport, Optical properties

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Targeted spectroscopy in the eye fundus

Nicolas Lapointe, Cléophace Akitegetse, Jasmine Poirier, Maxime Picard, Patrick Sauvageau, Dominic Sauvageau

Journal of Biomedical Optics, Vol. 28, Issue 12, 126004, (December 2023) https://doi.org/10.1117/1.JBO.28.12.126004

TOPICS: Eye, Spectroscopy, Fluorescence, Target acquisition, Optic nerve, Light emitting diodes, Head, Eye models, Light sources and illumination, Imaging spectroscopy

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Significance

The assessment of biomarkers in the eye is rapidly gaining traction for the screening, diagnosis, and monitoring of ocular and neurological diseases. Targeted ocular spectroscopy is a technology that enables concurrent imaging of the eye fundus and analysis of high-quality spectra from a targeted region within the imaged area. This provides structural, compositional, and functional information of specific regions of the eye fundus from a non-invasive approach to ocular biomarker detection.

Aim

The aim of our study was to demonstrate the multimodal functionality and validation of targeted ocular spectroscopy. This was done in vitro, using a reference target and a model eye, and in vivo.

Approach

Images and spectra from different regions of a reference target and a model eye were acquired and analyzed to validate the system. Targeted ocular fluorescence spectroscopy was also demonstrated with the same model. Subsequently, in vivo imaging and diffuse reflectance spectra were acquired to assess blood oxygen saturation in the optic nerve head and the parafovea of healthy subjects.

Results

Tests conducted with the reference target showed accurate spectral analysis within specific areas of the imaging space. In the model eye, distinct spectral signatures were observed for the optic disc, blood vessels, the retina, and the macula, consistent with the variations in tissue composition and functions between these regions. An ocular oximetry algorithm was applied to in vivo spectra from the optic nerve head and parafovea of healthy patients, showing significant differences in blood oxygen saturation. Finally, targeted fluorescence spectral analysis was performed in vitro.

Conclusions

Diffuse reflectance and fluorescence spectroscopy in specific regions of the eye fundus open the door to a whole new range of monitoring and diagnostic capabilities, from assessment of oxygenation in glaucoma and diabetic retinopathy to photo-oxidation and photodegradation in age-related macular degeneration.

Comparison of diffuse correlation spectroscopy analytical models for measuring cerebral blood flow in adults

Hongting Zhao, Eashani Sathialingam, Kyle R. Cowdrick, Tara Urner, Seung Yup Lee, Shasha Bai, Feras Akbik, Owen B. Samuels, Prem Kandiah, Ofer Sadan, Erin M. Buckley

Journal of Biomedical Optics, Vol. 28, Issue 12, 126005, (December 2023) https://doi.org/10.1117/1.JBO.28.12.126005

TOPICS: Analytic models, Data modeling, Blood circulation, Skull, Performance modeling, Spectroscopy, Brain, Cerebral blood flow, Signal to noise ratio, Velocity measurements

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Significance

Although multilayer analytical models have been proposed to enhance brain sensitivity of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow, the traditional homogeneous model remains dominant in clinical applications. Rigorous in vivo comparison of these analytical models is lacking.

Aim

We compare the performance of different analytical models to estimate a cerebral blood flow index (CBFi) with DCS in adults.

Approach

Resting-state data were obtained on a cohort of 20 adult patients with subarachnoid hemorrhage. Data at 1 and 2.5 cm source-detector separations were analyzed with the homogenous, two-layer, and three-layer models to estimate scalp blood flow index and CBFi. The performance of each model was quantified via fitting convergence, fit stability, brain-to-scalp flow ratio (BSR), and correlation with transcranial Doppler ultrasound (TCD) measurements of cerebral blood flow velocity in the middle cerebral artery (MCA).

Results

The homogeneous model has the highest pass rate (100%), lowest coefficient of variation (CV) at rest (median [IQR] at 1 Hz of 0.18 [0.13, 0.22]), and most significant correlation with MCA blood flow velocities (R_s = 0.59, p = 0.010) compared with both the two- and three-layer models. The multilayer model pass rate was significantly correlated with extracerebral layer thicknesses. Discarding datasets with non-physiological BSRs increased the correlation between DCS measured CBFi and TCD measured MCA velocities for all models.

Conclusions

We found that the homogeneous model has the highest pass rate, lowest CV at rest, and most significant correlation with MCA blood flow velocities. Results from the multilayer models should be taken with caution because they suffer from lower pass rates and higher coefficients of variation at rest and can converge to non-physiological values for CBFi. Future work is needed to validate these models in vivo, and novel approaches are merited to improve the performance of the multimodel models.

Restoration of metabolic functional metrics from label-free, two-photon human tissue images using multiscale deep-learning-based denoising algorithms

Nilay Vora, Christopher M. Polleys, Filippos Sakellariou, Georgios Georgalis, Hong-Thao Thieu, Elizabeth Genega, Narges Jahanseir, Abani Patra, Eric Miller, Irene Georgakoudi

Journal of Biomedical Optics, Vol. 28, Issue 12, 126006, (December 2023) https://doi.org/10.1117/1.JBO.28.12.126006

TOPICS: Education and training, Data modeling, Denoising, Tissues, Image quality, Wavelets, Nicotinamide adenine dinucleotide, Mitochondria, Image quality standards, Biopsy

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Development of hydrogel-based standards and phantoms for non-linear imaging at depth

Fizza Haseeb, Konstantinos N. Bourdakos, Ewan Forsyth, Kerry Setchfield, Alistair Gorman, Seshasailam Venkateswaran, Amanda J. Wright, Sumeet Mahajan, Mark Bradley

Journal of Biomedical Optics, Vol. 28, Issue 12, 126007, (December 2023) https://doi.org/10.1117/1.JBO.28.12.126007

TOPICS: Standards development, Hydrogels, Second harmonic generation, Biomedical optics, Imaging systems, Microscopes, Fluorescence imaging, Glasses, Fabrication, CARS tomography

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Sensing

Quantifying tissue properties and absolute hemodynamics using coherent spatial imaging

Christian Crouzet, Cody E. Dunn, Bernard Choi

Journal of Biomedical Optics, Vol. 28, Issue 12, 127001, (December 2023) https://doi.org/10.1117/1.JBO.28.12.127001

TOPICS: Blood circulation, Tissues, Optical properties, Hemodynamics, Sensors, Coherence imaging, Tissue optics, Optical testing, In vivo imaging, Reflectivity

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