Volume 28 Issue 9 | Journal of Biomedical Optics

Journal of Biomedical Optics

VOL. 28 · NO. 9 | September 2023

CONTENTS

IN THIS ISSUE

JBO Letters (1)

Special Section on Short Wave Infrared Techniques and Applications in Biomedical Optics (9)

General (2)

Imaging (7)

Microscopy (2)

Sensing (1)

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JBO Letters

Subsecond lung cancer detection within a heterogeneous background of normal and benign tissue using single-point Raman spectroscopy

Frédéric Leblond, Frédérick Dallaire, Trang Tran, Rajeev Yadav, Kelly Aubertin, Eric Goudie, Philippe Romeo, Christopher Kent, Charles Leduc, Moishe Liberman

Journal of Biomedical Optics, Vol. 28, Issue 09, 090501, (September 2023) https://doi.org/10.1117/1.JBO.28.9.090501

TOPICS: Tissues, Lung cancer, Raman spectroscopy, Cancer detection, Cancer, Tumor growth modeling, Lung, Diagnostics, Data modeling, Education and training

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Special Section on Short Wave Infrared Techniques and Applications in Biomedical Optics

Special Section Guest Editorial: Short Wave Infrared Techniques and Applications in Biomedical Optics

Daniel Fried, Mark Pierce, Darren Roblyer

Journal of Biomedical Optics, Vol. 28, Issue 09, 094800, (September 2023) https://doi.org/10.1117/1.JBO.28.9.094800

TOPICS: Short wave infrared radiation, Biomedical applications, Emission wavelengths, Biomedical optics, Infrared radiation, Tumors, Fluorescence, Autofluorescence, Fluorescence lifetime imaging, Thermography

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Assessment of the activity of secondary caries lesions with short-wavelength infrared, thermal, and optical coherence tomographic imaging

Nai-Yuan N. Chang, Tina Dillas, Yihua Zhu, Daniel Fried

Journal of Biomedical Optics, Vol. 28, Issue 09, 094801, (January 2023) https://doi.org/10.1117/1.JBO.28.9.094801

TOPICS: Short wave infrared radiation, Optical coherence tomography, Thermography, Dental caries, Teeth, Composites, Reflectivity, Permeability, Minerals, Interfaces

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Significance: Leakage in the interfaces between restorative materials and tooth structure allows for fluid and bacterial acid infiltration, causing restoration failure due to secondary caries. Dentists spend more time replacing composite restorations than placing new ones. Previous in vitro and in vivo studies on enamel and root surfaces using shortwave-infrared (SWIR) and thermal imaging during dehydration with forced air have been promising for assessing lesion activity.

Aim: We hypothesized that SWIR reflectance and thermal imaging methods can be used to monitor the activity of secondary caries lesions around composite restorations. The objective of this study was to employ these methods to measure the rate of fluid loss from lesions during dehydration with forced air to assess lesion activity.

Approach: Sixty-three extracted human teeth with total of 109 suspected secondary lesions were examined using SWIR and thermal imaging during dehydration. The thickness of the highly mineralized transparent surface layer (TSL) at lesion interfaces indicative of lesion activity was measured by optical coherence tomography (OCT). Micro-computed tomography (MicroCT) was used to further confirm lesion severity and structure. OCT and MicroCT measurements of lesion structure, depth, and severity were correlated with fluid loss rates measured with SWIR reflectance and thermal imaging.

Results: TSL thickness measured with OCT correlated with both SWIR reflectance and thermal measurements of rates of fluid loss (p < 0.05). Increasing TSL thickness led to decreased permeability of lesions, potentially indicating full lesion arrest at TSL ≥ 70 μm. SWIR performed better than thermal imaging for secondary lesion activity assessment, although both methods performed best on smooth surface lesions.

Conclusions: Nondestructive SWIR reflectance and OCT imaging methods are promising for clinically monitoring the activity of secondary caries lesions.

Large field-of-view short-wave infrared metalens for scanning fiber endoscopy

Ningzhi Xie, Matthew Carson, Johannes Fröch, Arka Majumdar, Eric Seibel, Karl Böhringer

Journal of Biomedical Optics, Vol. 28, Issue 09, 094802, (March 2023) https://doi.org/10.1117/1.JBO.28.9.094802

TOPICS: Short wave infrared radiation, Infrared radiation, Microscopes, Infrared imaging, Endoscopy, Design and modelling, Light sources and illumination, Endoscopes, Zemax, Point spread functions

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Development of a shortwave infrared sinuscope for the detection of cerebrospinal fluid leaks

Tjadina Wencke Klein, Stella Yang, Mahbuba Tusty, Jayakar Nayak, Michael Chang, Oliver Bruns, Thomas Bischof, Tulio Valdez

Journal of Biomedical Optics, Vol. 28, Issue 09, 094803, (May 2023) https://doi.org/10.1117/1.JBO.28.9.094803

TOPICS: Short wave infrared radiation, Endoscopes, Polarizers, Light sources and illumination, Tissues, Water, Cameras, Shortwaves, Reflection, Infrared radiation

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Enhancing intraoperative tumor delineation with multispectral short-wave infrared fluorescence imaging and machine learning

Dale J. Waterhouse, Laura Privitera, John Anderson, Danail Stoyanov, Stefano Giuliani

Journal of Biomedical Optics, Vol. 28, Issue 09, 094804, (March 2023) https://doi.org/10.1117/1.JBO.28.9.094804

TOPICS: Tumors, Short wave infrared radiation, Multispectral imaging, Fluorescence imaging, Tissues, Fluorescence, Image filtering, Image classification, Tunable filters, Infrared radiation

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Minimizing near-infrared autofluorescence in preclinical imaging with diet and wavelength selection

Yidan Sun, Xingjian Zhong, Allison M. Dennis

Journal of Biomedical Optics, Vol. 28, Issue 09, 094805, (April 2023) https://doi.org/10.1117/1.JBO.28.9.094805

TOPICS: Autofluorescence, Emission wavelengths, Fluorescence imaging, Tunable filters, Biological imaging, Imaging systems, Image filtering, Tissues, Preclinical imaging, Light sources and illumination

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Significance

Preclinical fluorescence imaging with NIR-I (700 to 900 nm) illumination and short-wave infrared or NIR-II (1000 to 1700 nm) emission increases tissue penetration depth and improves resolution through decreased scattering. Background autofluorescence decreases signal-to-background ratios (SBR) in fluorescence imaging; maximizing SBR will further improve the impact of deep tissue imaging.

Aim

The impact of rodent diet, illumination wavelength, and emission range on the background fluorescence and contrast agent SBR were determined to assist with the experimental design of future imaging studies.

Approach

Following illumination with 670, 760, or 808 nm, autofluorescence in the NIR-I (<975 nm), NIR-II (>1000 nm), and NIR-II LP (>1250 nm) regions was assessed in mice fed chow or a purified diet using an IR VIVO preclinical imager (Photon, Etc.). Comparison of the SBR of liver-localized indocyanine green in the various imaging conditions indicated when gut autofluorescence was a problematic confounder.

Results

Mice fed chow exhibit high levels of background autofluorescence in the gastrointestinal tract and, to a lesser extent, skin when illuminated with 670 nm light for NIR-I imaging (700 to 975 nm), interfering with the identification of fluorescently labeled tissue. Background autofluorescence was reduced by more than two orders of magnitude by any of the following changes: (1) purified diet; (2) excitation with 760 or 808 nm illumination; or (3) emission in the NIR-II (1000 to 1600 or 1250 to 1600 nm). Although the SBR was generally sufficient for feature identification except when imaging of chow-fed mice with 670 nm excitation and NIR-I emission, switching to a purified diet, using longer excitation wavelengths, or using longer emission wavelengths improved SBR significantly.

Conclusions

Systematic comparison of imaging conditions and diet highlights the reduction in autofluorescence and increase in SBR enabled by intentional choices in the experimental parameters including diet, excitation wavelength, and emission wavelength range.

Characterization of fluorescence lifetime of organic fluorophores for molecular imaging in the shortwave infrared window

Luis Chavez, Shan Gao, Xavier Intes

Journal of Biomedical Optics, Vol. 28, Issue 09, 094806, (April 2023) https://doi.org/10.1117/1.JBO.28.9.094806

TOPICS: Short wave infrared radiation, Fluorophores, Near infrared, Fluorescence, Windows, Multiplexing, Fluorescence intensity, Single photon avalanche diodes, Quantum efficiency, Photons

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Realization of NIR-II 3D whole-body contour and tumor blood vessels imaging in small animals using rotational stereo vision technique

Shih-Po Su, Yun-Chen Lee, Syue-Liang Lin, Yi-Xuan Li, Min-Ying Lin, Yang-Hsiang Chan, Yi-Jang Lee, Muh-Hwa Yang, Huihua Kenny Chiang

Journal of Biomedical Optics, Vol. 28, Issue 09, 094807, (May 2023) https://doi.org/10.1117/1.JBO.28.9.094807

TOPICS: 3D image processing, Imaging systems, Blood vessels, Tumors, Biological imaging, Cameras, Fluorescence imaging, Fluorescence, Biomedical optics, Stereoscopy

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Shortwave infrared diffuse optical wearable probe for quantification of water and lipid content in emulsion phantoms using deep learning

Samuel S. Spink, Anahita Pilvar, Lina Lin Wei, Jodee Frias, Kylee Anders, Sabrina T. Franco, Olivia Claire Rose, Megan Freeman, Grace Bag, Huiru Huang, Darren Roblyer

Journal of Biomedical Optics, Vol. 28, Issue 09, 094808, (June 2023) https://doi.org/10.1117/1.JBO.28.9.094808

TOPICS: Short wave infrared radiation, Near infrared, Scattering, Emulsions, Education and training, Shortwaves, Infrared radiation, Tissues, Absorption, Simulations

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General

Multifocal acoustic radiation force-based reverberant optical coherence elastography for evaluation of ocular globe biomechanical properties

Taye Mekonnen, Christian Zevallos-Delgado, Manmohan Singh, Salavat Aglyamov, Kirill Larin

Journal of Biomedical Optics, Vol. 28, Issue 09, 095001, (September 2023) https://doi.org/10.1117/1.JBO.28.9.095001

TOPICS: Cornea, Biomechanics, Eye, Elasticity, Acoustic waves, Sclera, Acoustics, Optical coherence tomography, Tissues, Iris

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Significance

Quantifying the biomechanical properties of the whole eye globe can provide a comprehensive understanding of the interactions among interconnected ocular components during dynamic physiological processes. By doing so, clinicians and researchers can gain valuable insights into the mechanisms underlying ocular diseases, such as glaucoma, and design interventions tailored to each patient’s unique needs.

Aim

The aim of this study was to evaluate the feasibility and effectiveness of a multifocal acoustic radiation force (ARF) based reverberant optical coherence elastography (RevOCE) technique for quantifying shear wave speeds in different ocular components simultaneously.

Approach

We implemented a multifocal ARF technique to generate reverberant shear wave fields, which were then detected using phase-sensitive optical coherence tomography. A 3D-printed acoustic lens array was employed to manipulate a collimated ARF beam generated by an ultrasound transducer, producing multiple focused ARF beams on mouse eye globes ex vivo. RevOCE measurements were conducted using an excitation pulse train consisting of 10 cycles at 3 kHz, followed by data processing to produce a volumetric map of the shear wave speed.

Results

The results show that the system can successfully generate reverberant shear wave fields in the eye globe, allowing for simultaneous estimation of shear wave speeds in various ocular components, including cornea, iris, lens, sclera, and retina. A comparative analysis revealed notable differences in wave speeds between different parts of the eye, for example, between the apical region of the cornea and the pupillary zone of the iris (p = 0.003). Moreover, the study also revealed regional variations in the biomechanical properties of ocular components as evidenced by greater wave speeds near the apex of the cornea compared to its periphery.

Conclusions

The study demonstrated the effectiveness of RevOCE based on a non-invasive multifocal ARF for assessing the biomechanical properties of the whole eyeball. The findings indicate the potential to provide a comprehensive understanding of the mechanical behavior of the whole eye, which could lead to improved diagnosis and treatment of ocular diseases.

Determination of tissue oxygen saturation by diffuse reflectance spectroscopy

Laura Lucía Sánchez-Ramos, Beatriz Morales-Cruzado, Francisco Gerardo Pérez-Gutiérrez

Journal of Biomedical Optics, Vol. 28, Issue 09, 095002, (September 2023) https://doi.org/10.1117/1.JBO.28.9.095002

TOPICS: Tissues, Oxygen, Skin, Absorption, Oxygenation, Diffuse reflectance spectroscopy, Reflection, Blood pressure, Integrating spheres, Blood

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Imaging

Projection mapping system for laser speckle contrast image: feasibility study for clinical application

Subin Park, Insun Yeum, Donghwan Ko, Byungjo Jung

Journal of Biomedical Optics, Vol. 28, Issue 09, 096001, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096001

TOPICS: Laser speckle contrast imaging, Speckle, Blood circulation, Displays, Tissues, Projection systems, In vivo imaging, Windows, Laser systems engineering, In vitro testing

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Spectroscopic optical coherence tomography at 1200 nm for lipid detection

Vivek Kuttippurath, Nuria Slijkhuis, Shengnan Liu, Gijs van Soest

Journal of Biomedical Optics, Vol. 28, Issue 09, 096002, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096002

TOPICS: Optical coherence tomography, Absorption, Scattering, Spectroscopy, Signal attenuation, Attenuation, Imaging systems, Optical spectroscopy, Signal processing, Statistical modeling

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Fluorescence-guided surgical system using holographic display: from phantom studies to canine patients

Mebin B. George, Benjamin Lew, Zuodong Liang, Steven Blair, Zhongmin Zhu, Nan Cui, Jamie Ludwig, Mohamed Zayed, Laura Selmic, Viktor Gruev

Journal of Biomedical Optics, Vol. 28, Issue 09, 096003, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096003

TOPICS: Holographic displays, Surgery, Holograms, Tumors, Fluorescence, Near infrared, Holography, Goggles, Cancer, Calibration

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Wide field-of-view fluorescence imaging for organ-level lineage tracing of rare intestinal stem cell populations

Noelle Daigle, Suzann Duan, Heyu Song, Natzem Lima, Ricky Sontz, Juanita L. Merchant, Travis W. Sawyer

Journal of Biomedical Optics, Vol. 28, Issue 09, 096004, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096004

TOPICS: Tissues, Fluorescence imaging, Stem cells, Animal model studies, Fluorescence, Intestine, Fluorescence microscopy, Proteins, Animals, Light sources and illumination

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Significance

Lineage tracing using fluorescent reporters is a common tool for monitoring the expression of genes and transcription factors in stem cell populations and their progeny. The zinc-binding protein 89 (ZBP-89/Zfp148 mouse gene) is a transcription factor that plays a role in gastrointestinal (GI) stem cell maintenance and cellular differentiation and has been linked to the progression of colon cancer. While lineage tracing is a useful tool, it is commonly performed with high-magnification microscopy on a small field of view within tissue sections, thereby limiting the ability to resolve reporter expression at the organ level. Furthermore, this technique requires extensive tissue processing, which is time consuming and requires euthanizing the animal. Further knowledge could be elucidated by measuring the expression of fluorescent reporters across entire organs with minimal tissue processing.

Aim

We present the application of wide-field fluorescence imaging for whole-organ lineage tracing of an inducible Zfp148-tdTomato-expressing transgenic mouse line to assess the expression of ZBP-89/Zfp148 in the GI tract.

Approach

We measured tdTomato fluorescence in ex vivo organs at time points between 24 h and 6 months post-induction. Fluctuations in tdTomato expression were validated by fluorescence microscopy of tissue sections.

Results

Quantification of the wide field-of-view images showed a statistically significant increase in fluorescent signal across the GI tract between transgenic mice and littermate controls. The results also showed a gradient of decreasing reporter expression from proximal to distal intestine, suggesting a higher abundance of ZBP-89 expressing stem cells, or higher expression of ZBP-89 within the stem cells, in the proximal intestine.

Conclusions

We demonstrate that wide-field fluorescence imaging is a valuable tool for monitoring whole-organ expression of fluorescent reporters. This technique could potentially be applied in vivo for longitudinal assessment of a single animal, further enhancing our ability to resolve rare stem cell lineages spatially and temporally.

Integration of cellular-resolution optical coherence tomography and Raman spectroscopy for discrimination of skin cancer cells with machine learning

Cian You, Jui-Yun Yi, Ting-Wei Hsu, Sheng-Lung Huang

Journal of Biomedical Optics, Vol. 28, Issue 09, 096005, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096005

TOPICS: Optical coherence tomography, Cancer, Raman spectroscopy, Skin cancer, Skin, Melanoma, 3D image processing, Surface roughness, Machine learning, Tunable filters

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Multiexposure laser speckle contrast analysis system calibration limited by perfusion-dependent scattering on the skin

Tamás Smausz, Bence Kondász

Journal of Biomedical Optics, Vol. 28, Issue 09, 096006, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096006

TOPICS: Skin, Speckle, Scattering, Tissues, Laser scattering, Calibration, Temporal resolution, Light scattering, Emulsions, Red blood cells

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Assessment of open-field fluorescence guided surgery systems: implementing a standardized method for characterization and comparison

Marien Ochoa, Alberto Ruiz, Ethan LaRochelle, Matthew Reed, Eren Berber, George Poultsides, Brian Pogue

Journal of Biomedical Optics, Vol. 28, Issue 09, 096007, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096007

TOPICS: Imaging systems, Surgery, Fluorescence, Tissues, Light sources and illumination, Spatial resolution, Distortion, Contrast agents, Image processing, Visualization

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Microscopy

Analysis of structural effects of sickle cell disease on brain vasculature of mice using three-dimensional quantitative phase imaging

Caroline Filan, Hannah Song, Manu Platt, Francisco Robles

Journal of Biomedical Optics, Vol. 28, Issue 09, 096501, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096501

TOPICS: Blood vessels, Brain, Animals, Single crystal X-ray diffraction, Blood, Vascular diseases, Brain diseases, Neuroimaging, Arteries, Refractive index

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Significance

Although the molecular origins of sickle cell disease (SCD) have been extensively studied, the effects of SCD on the vasculature—which can influence blood clotting mechanisms, pain crises, and strokes—are not well understood. Improving this understanding can yield insight into the mechanisms and wide-ranging effects of this devastating disease.

Aim

We aim to demonstrate the ability of a label-free 3D quantitative phase imaging technology, called quantitative oblique back-illumination microscopy (qOBM), to provide insight into the effects of SCD on brain vasculature.

Approach

Using qOBM, we quantitatively analyze the vasculature of freshly excised, but otherwise unaltered, whole mouse brains. We use Townes sickle transgenic mice, which closely recapitulate the pathophysiology of human SCD, and sickle cell trait mice as controls. Two developmental time points are studied: 6-week-old mice and 20-week-old mice. Quantitative structural and biophysical parameters of the vessels (including the refractive index (RI), which is linearly proportional to dry mass) are extracted from the high-resolution images and analyzed.

Results

qOBM reveals structural differences in the brain blood vessel thickness (thinner for SCD in particular brain regions) and the RI of the vessel wall (higher and containing a larger variation throughout the brain for SCD). These changes were only significant in 20-week-old mice. Further, vessel breakages are observed in SCD mice at both time points. The vessel wall RI distribution near these breaks, up to 350 μm away from the breaking point, shows an erratic behavior characterized by wide RI variations. Vessel diameter, tortuosity, texture within the vessel, and structural fractal patterns are found to not be statistically different. As with vessel breaks, we also observe blood vessel blockages only in mice brains with SCD.

Conclusions

qOBM provides insight into the biophysical and structural composition of brain blood vessels in mice with SCD. Data suggest that the RI may be an indirect indicator of vessel rigidity, vessel strength, and/or tensions, which change with SCD. Future ex vivo and in vivo studies with qOBM could improve our understanding of SCD.

Compressive hyperspectral microscopy for cancer detection

Yaniv Oiknine, Marwan Abuleil, Eugene Brozgol, Isaac August, Iris Barshack, Ibrahim Abdulhalim, Yuval Garini, Adrian Stern

Journal of Biomedical Optics, Vol. 28, Issue 09, 096502, (September 2023) https://doi.org/10.1117/1.JBO.28.9.096502

TOPICS: Microscopes, Microscopy, Light sources and illumination, Cancer detection, Imaging spectroscopy, Imaging systems, Biopsy, Optical filters, Tunable filters, Medical image reconstruction

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Significance

Hyperspectral microscopy grants the ability to characterize unique properties of tissues based on their spectral fingerprint. The ability to label and measure multiple molecular probes simultaneously provides pathologists and oncologists with a powerful tool to enhance accurate diagnostic and prognostic decisions. As the pathological workload grows, having an objective tool that provides companion diagnostics is of immense importance. Therefore, fast whole-slide spectral imaging systems are of immense importance for automated cancer prognostics that meet current and future needs.

Aim

We aim to develop a fast and accurate hyperspectral microscopy system that can be easily integrated with existing microscopes and provide flexibility for optimizing measurement time versus spectral resolution.

Approach

The method employs compressive sensing (CS) and a spectrally encoded illumination device integrated into the illumination path of a standard microscope. The spectral encoding is obtained using a compact liquid crystal cell that is operated in a fast mode. It provides time-efficient measurements of the spectral information, is modular and versatile, and can also be used for other applications that require rapid acquisition of hyperspectral images.

Results

We demonstrated the acquisition of breast cancer biopsies hyperspectral data of the whole camera area within ∼1 s. This means that a typical 1 × 1 cm² biopsy can be measured in ∼10 min. The hyperspectral images with 250 spectral bands are reconstructed from 47 spectrally encoded images in the spectral range of 450 to 700 nm.

Conclusions

CS hyperspectral microscopy was successfully demonstrated on a common lab microscope for measuring biopsies stained with the most common stains, such as hematoxylin and eosin. The high spectral resolution demonstrated here in a rather short time indicates the ability to use it further for coping with the highly demanding needs of pathological diagnostics, both for cancer diagnostics and prognostics.

Sensing

Optical absorption spectra and corresponding in vivo photoacoustic visualization of exposed peripheral nerves

Michelle Graham, Arunima Sharma, William Padovano, Visakha Suresh, Arlene Chiu, Susanna Thon, Sami Tuffaha, Muyinatu Bell

Journal of Biomedical Optics, Vol. 28, Issue 09, 097001, (September 2023) https://doi.org/10.1117/1.JBO.28.9.097001

TOPICS: Nerve, Photoacoustic spectroscopy, Absorbance, Nervous system, In vivo imaging, Photoacoustic imaging, Absorption spectrum, Windows, Tissue optics, Light absorption

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Significance

Multispectral photoacoustic imaging has the potential to identify lipid-rich, myelinated nerve tissue in an interventional or surgical setting (e.g., to guide intraoperative decisions when exposing a nerve during reconstructive surgery by limiting operations to nerves needing repair, with no impact to healthy or regenerating nerves). Lipids have two optical absorption peaks within the NIR-II and NIR-III windows (i.e., 1000 to 1350 nm and 1550 to 1870 nm wavelength ranges, respectively) which can be exploited to obtain photoacoustic images. However, nerve visualization within the NIR-III window is more desirable due to higher lipid absorption peaks and a corresponding valley in the optical absorption of water.

Aim

We present the first known optical absorption characterizations, photoacoustic spectral demonstrations, and histological validations to support in vivo photoacoustic nerve imaging in the NIR-III window.

Approach

Four in vivo swine peripheral nerves were excised, and the optical absorption spectra of these fresh ex vivo nerves were characterized at wavelengths spanning 800 to 1880 nm, to provide the first known nerve optical absorbance spectra and to enable photoacoustic amplitude spectra characterization with the most optimal wavelength range. Prior to excision, the latter two of the four nerves were surrounded by aqueous, lipid-free, agarose blocks (i.e., 3% w/v agarose) to enhance acoustic coupling during in vivo multispectral photoacoustic imaging using the optimal NIR-III wavelengths (i.e., 1630 to 1850 nm) identified in the ex vivo studies.

Results

There was a verified characteristic lipid absorption peak at 1725 nm for each ex vivo nerve. Results additionally suggest that the 1630 to 1850 nm wavelength range can successfully visualize and differentiate lipid-rich nerves from surrounding water-containing and lipid-deficient tissues and materials.

Conclusions

Photoacoustic imaging using the optimal wavelengths identified and demonstrated for nerves holds promise for detection of myelination in exposed and isolated nerve tissue during a nerve repair surgery, with possible future implications for other surgeries and other optics-based technologies.