Publications by authors named "Sylvain Gioux"

59 Publications

Contact, high-resolution spatial diffuse reflectance imaging system for skin condition diagnosis: a first-in-human clinical trial.

J Biomed Opt 2021 Jan;26(1)

Université Grenoble Alpes, France-CEA, LETI, MINATEC Campus, Grenoble, France.

Significance: Oxygenation is one of the skin tissue physiological properties to follow for patient care management. Furthermore, long-term monitoring of such parameters is needed at the patient bed as well as outside the hospital. Diffuse reflectance spectroscopy has been widely used for this purpose.

Aim: The aim of the study is to propose a low-cost system for the long-term measurement of skin physiological parameters in contact.

Approach: We have developed a low-cost, wearable, CMOS-based device. We propose an original method for processing diffuse reflectance data to calculate the tissue oxygen saturation (StO2).

Results: We tested the device for the assessment of tissue oxygenation during a first-in-human clinical trial that took place at the Grenoble University Hospital France.

Conclusions: The results of this clinical trial show a good accordance between our sensor and commercial devices used a reference.
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http://dx.doi.org/10.1117/1.JBO.26.1.012706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846121PMC
January 2021

Real-time, wide-field and high-quality single snapshot imaging of optical properties with profile correction using deep learning.

Biomed Opt Express 2020 Oct 18;11(10):5701-5716. Epub 2020 Sep 18.

University of Strasbourg, ICube Laboratory, 300 Boulevard Sébastien Brant, 67412 Illkirch, France.

The development of real-time, wide-field and quantitative diffuse optical imaging methods to visualize functional and structural biomarkers of living tissues is a pressing need for numerous clinical applications including image-guided surgery. In this context, Spatial Frequency Domain Imaging (SFDI) is an attractive method allowing for the fast estimation of optical properties using the Single Snapshot of Optical Properties (SSOP) approach. Herein, we present a novel implementation of SSOP based on a combination of deep learning network at the filtering stage and Graphics Processing Units (GPU) capable of simultaneous high visual quality image reconstruction, surface profile correction and accurate optical property (OP) extraction in real-time across large fields of view. In the most optimal implementation, the presented methodology demonstrates megapixel profile-corrected OP imaging with results comparable to that of profile-corrected SFDI, with a processing time of 18 ms and errors relative to SFDI method less than 10% in both profilometry and profile-corrected OPs. This novel processing framework lays the foundation for real-time multispectral quantitative diffuse optical imaging for surgical guidance and healthcare applications. All code and data used for this work is publicly available at www.healthphotonics.org under the resources tab.
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http://dx.doi.org/10.1364/BOE.397681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587245PMC
October 2020

Near infrared fluorescence imaging of the urethra: a systematic review of the literature.

Minim Invasive Ther Allied Technol 2020 Oct 1:1-8. Epub 2020 Oct 1.

Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France.

Background: Urethral injury is a dreaded complication during laparoscopic, perineal and transanal surgery and is mainly a result of a failed visualization of the urethra. The aim of this systematic review is to provide an overview of the available literature on the near-infrared fluorescence (NIRF) imaging technique using contrast agents for the intra-operative visualization of the urethra.

Material And Methods: A systematic review of the literature was conducted including studies on NIRF imaging using contrast agents to visualize the urethra. All studies describing a NIRF imaging technique and demonstrating visual findings of the urethra were included.

Results: Five studies were identified. Four studies examined indocyanine green, one of which also studied the IRDye 800BK agent and one examined the CP-IRT dye. All studies showed that the NIRF imaging technique was feasible for an early identification of the urethra. No complications related to NIRF imaging were reported.

Conclusion: We conclude that the use of a NIRF imaging technique is feasible and that it can contribute to prevent iatrogenic injury to the urethra. However, based on the limited available data, no solid conclusion can yet be drawn and further translation to the clinical practice is necessary.
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http://dx.doi.org/10.1080/13645706.2020.1826974DOI Listing
October 2020

Hyperspectral evaluation of hepatic oxygenation in a model of total vs. arterial liver ischaemia.

Sci Rep 2020 09 22;10(1):15441. Epub 2020 Sep 22.

Institute of Physiology, EA3072 Mitochondria Respiration and Oxidative Stress, University of Strasbourg, Strasbourg, France.

Liver ischaemia reperfusion injury (IRI) is a dreaded pathophysiological complication which may lead to an impaired liver function. The level of oxygen hypoperfusion affects the level of cellular damage during the reperfusion phase. Consequently, intraoperative localisation and quantification of oxygen impairment would help in the early detection of liver ischaemia. To date, there is no real-time, non-invasive, and intraoperative tool which can compute an organ oxygenation map, quantify and discriminate different types of vascular occlusions intraoperatively. Hyperspectral imaging (HSI) is a non-invasive optical methodology which can quantify tissue oxygenation and which has recently been applied to the medical field. A hyperspectral camera detects the relative reflectance of a tissue in the range of 500 to 1000 nm, allowing the quantification of organic compounds such as oxygenated and deoxygenated haemoglobin at different depths. Here, we show the first comparative study of liver oxygenation by means of HSI quantification in a model of total vascular inflow occlusion (VIO) vs. hepatic artery occlusion (HAO), correlating optical properties with capillary lactate and histopathological evaluation. We found that liver HSI could discriminate between VIO and HAO. These results were confirmed via cross-validation of HSI which detected and quantified intestinal congestion in VIO. A significant correlation between the near-infrared spectra and capillary lactate was found (r = - 0.8645, p = 0.0003 VIO, r = - 0.7113, p = 0.0120 HAO). Finally, a statistically significant negative correlation was found between the histology score and the near-infrared parameter index (NIR) (r = - 0.88, p = 0.004). We infer that HSI, by predicting capillary lactates and the histopathological score, would be a suitable non-invasive tool for intraoperative liver perfusion assessment.
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http://dx.doi.org/10.1038/s41598-020-72915-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509803PMC
September 2020

Simultaneous multipurpose fluorescence imaging with IRDye® 800BK during laparoscopic surgery.

Surg Endosc 2020 Aug 28. Epub 2020 Aug 28.

Institute of Image-Guided Surgery, IHU Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg, France.

Background: IRDye® 800BK is a fluorophore, currently undergoing clinical translation, which has both biliary and renal clearance. To date, there is no description of a fluorophore, which can be simultaneously used for non-invasive, near-infrared fluorescence-based (NIRF) visualization of different structures and perfusion evaluation. The purpose of this study was to evaluate IRDye® 800BK for the simultaneous assessment of bowel perfusion, lymphography, ureter and bile duct delineation.

Methods: Six pigs received a 0.15 mg/kg dye as a single bolus intravenous injection (IV). With the FLER (fluorescence-based enhanced reality) software, fluorescence intensity (FI) of 5 regions of interest (ROI) in an ischemic bowel loop was measured along with the time to reach the FI peak, and capillary lactate was measured from the same ROI, followed by the assessment of the ureters and bile ducts for a maximal duration of 180 min after dye administration. In 3 animals, the procedure was initiated via gastroscopic injection of a 0.6 mg (1 mg/mL) dye in the gastric submucosa followed by lymphography in a NIRF setting.

Results: Excellent visualization of the ureters and bowel perfusion was obtained under NIRF imaging. Additionally, the bile duct and gastric lymph ducts and nodes were visualized. A positive correlation was found between the time to peak FI in the ischemic bowel loop and the corresponding capillary lactate levels (rho 0.59, p < 0.001).

Conclusion: In this study, we successfully demonstrated the simultaneous multipurpose IRDye® 800BK applicability during laparoscopic surgery. This fluorophore has the potential to become a powerful and versatile image-guided surgery tool.
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http://dx.doi.org/10.1007/s00464-020-07931-8DOI Listing
August 2020

Macroscopic fluorescence lifetime topography enhanced via spatial frequency domain imaging.

Opt Lett 2020 Aug;45(15):4232-4235

We report on a macroscopic fluorescence lifetime imaging (MFLI) topography computational framework based around machine learning with the main goal of retrieving the depth of fluorescent inclusions deeply seated in bio-tissues. This approach leverages the depth-resolved information inherent to time-resolved fluorescence data sets coupled with the retrieval of in situ optical properties as obtained via spatial frequency domain imaging (SFDI). Specifically, a Siamese network architecture is proposed with optical properties (OPs) and time-resolved fluorescence decays as input followed by simultaneous retrieval of lifetime maps and depth profiles. We validate our approach using comprehensive in silico data sets as well as with a phantom experiment. Overall, our results demonstrate that our approach can retrieve the depth of fluorescence inclusions, especially when coupled with optical properties estimation, with high accuracy. We expect the presented computational approach to find great utility in applications such as optical-guided surgery.
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http://dx.doi.org/10.1364/OL.397605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935427PMC
August 2020

Noninvasive Near-Infrared Fluorescence Imaging of the Ureter During Robotic Surgery: A Demonstration in a Porcine Model.

J Laparoendosc Adv Surg Tech A 2020 Sep 21;30(9):962-966. Epub 2020 Jul 21.

Institute of Image-Guided Surgery, IHU Strasbourg, Strasbourg, France.

Iatrogenic ureteral injury is one of the feared complications during intrapelvic surgery. There are limited data on the use of novel near-infrared fluorescence (NIRF) imaging dyes for the purpose of noninvasive ureteral visualization in robot-assisted laparoscopic surgery (RALS). In this study, we evaluated the feasibility of NIRF imaging of the ureter using the IRDye 800BK dye as the fluorescence dye and a robotic platform with Firefly™ technology as an imaging system. An intravenous dose of 0.15 mg/kg was administered in 3 pigs and NIRF imaging was performed for a total duration of 60 minutes. The intraoperative video recordings were analyzed to determine fluorescence intensities and the target-to-background ratio (TBR). In all included animals, a clear delineation of the ureter was achieved from 5 minutes after dye administration until the end of the study. During this time period, the ureter was clearly distinguishable from its surroundings and no statistical differences in TBR were observed. The IRDye 800BK dye, a novel NIRF dye currently undergoing clinical translation, is a promising contrast agent used for noninvasive ureteral imaging, which has the potential to be valuable during RALS.
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http://dx.doi.org/10.1089/lap.2020.0399DOI Listing
September 2020

OpenSFDI: an open-source guide for constructing a spatial frequency domain imaging system.

J Biomed Opt 2020 01;25(1):1-13

Boston Univ., United States.

: Spatial frequency domain imaging (SFDI) is a diffuse optical measurement technique that can quantify tissue optical absorption (μ) and reduced scattering () on a pixel-by-pixel basis. Measurements of μ at different wavelengths enable the extraction of molar concentrations of tissue chromophores over a wide field, providing a noncontact and label-free means to assess tissue viability, oxygenation, microarchitecture, and molecular content. We present here openSFDI: an open-source guide for building a low-cost, small-footprint, three-wavelength SFDI system capable of quantifying μ and as well as oxyhemoglobin and deoxyhemoglobin concentrations in biological tissue. The companion website provides a complete parts list along with detailed instructions for assembling the openSFDI system.

: We describe the design of openSFDI and report on the accuracy and precision of optical property extractions for three different systems fabricated according to the instructions on the openSFDI website.

: Accuracy was assessed by measuring nine tissue-simulating optical phantoms with a physiologically relevant range of μ and with the openSFDI systems and a commercial SFDI device. Precision was assessed by repeatedly measuring the same phantom over 1 h.

: The openSFDI systems had an error of 0  ±  6  %   in μ and -2  ±  3  %   in , compared to a commercial SFDI system. Bland-Altman analysis revealed the limits of agreement between the two systems to be   ±  0.004  mm for μ and -0.06 to 0.1  mm for . The openSFDI system had low drift with an average standard deviation of 0.0007  mm and 0.05  mm in μ and , respectively.

,

: The openSFDI provides a customizable hardware platform for research groups seeking to utilize SFDI for quantitative diffuse optical imaging.

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http://dx.doi.org/10.1117/1.JBO.25.1.016002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008504PMC
January 2020

Real-time optical properties and oxygenation imaging using custom parallel processing in the spatial frequency domain.

Biomed Opt Express 2019 Aug 11;10(8):3916-3928. Epub 2019 Jul 11.

University of Strasbourg, ICube Laboratory, 300 Boulevard Sébastien Brant, 67412 Illkirch, France.

The development of real-time, wide-field and quantitative diffuse optical imaging methods is becoming increasingly popular for biological and medical applications. Recent developments introduced a novel approach for real-time multispectral acquisition in the spatial frequency domain using spatio-temporal modulation of light. Using this method, optical properties maps (absorption and reduced scattering) could be obtained for two wavelengths (665 nm and 860 nm). These maps, in turn, are used to deduce oxygen saturation levels in tissues. However, while the acquisition was performed in real-time, processing was performed post-acquisition and was not in real-time. In the present article, we present CPU and GPU processing implementations for this method with special emphasis on processing time. The obtained results show that the proposed custom direct method using a General Purpose Graphic Processing Unit (GPGPU) and C CUDA (Compute Unified Device Architecture) implementation enables 1.6 milliseconds processing time for a 1 Mega-pixel image with a maximum average error of 0.1% in extracting optical properties.
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http://dx.doi.org/10.1364/BOE.10.003916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701546PMC
August 2019

Special Section Guest Editorial: Special Section on Spatial Frequency Domain Imaging.

J Biomed Opt 2019 07;24(7):1-2

ModulimIrvine, California, United States.

This guest editorial introduces the Special Section on Spatial Frequency Domain Imaging.
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http://dx.doi.org/10.1117/1.JBO.24.7.071601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995872PMC
July 2019

Quantitative Wide-Field Imaging Techniques for Fluorescence Guided Neurosurgery.

Front Surg 2019 6;6:31. Epub 2019 Jun 6.

Department of Neurosurgery, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United States.

Fluorescence guided surgery (FGS) has fueled the development of novel technologies aimed at maximizing the utility of fluorescence imaging to help clinicians diagnose and in certain cases treat diseases across a breadth of disciplines such as dermatology, gynecology, oncology, ophthalmology, and neurosurgery. In neurosurgery, the goal of FGS technologies is to provide the neurosurgeon with additional information which can serve as a visual aid to better identify tumor tissue and associated margins. Yet, current clinical FGS technologies are qualitative in nature, limiting the ability to make accurate, reliable, and repeatable measurements. To this end, developments in fluorescence quantification are needed to overcome current limitations of FGS. Here we present an overview of the recent developments in quantitative fluorescence guidance technologies and conclude with the most recent developments aimed at wide-field quantitative fluorescence imaging approaches in neurosurgery.
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http://dx.doi.org/10.3389/fsurg.2019.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563771PMC
June 2019

Spatial frequency domain imaging in 2019: principles, applications, and perspectives.

J Biomed Opt 2019 06;24(7):1-18

Modulim, Irvine, California, United States.

Spatial frequency domain imaging (SFDI) has witnessed very rapid growth over the last decade, owing to its unique capabilities for imaging optical properties and chromophores over a large field-of-view and in a rapid manner. We provide a comprehensive review of the principles of this imaging method as of 2019, review the modeling of light propagation in this domain, describe acquisition methods, provide an understanding of the various implementations and their practical limitations, and finally review applications that have been published in the literature. Importantly, we also introduce a group effort by several key actors in the field for the dissemination of SFDI, including publications, advice in hardware and implementations, and processing code, all freely available online.
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http://dx.doi.org/10.1117/1.JBO.24.7.071613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995958PMC
June 2019

Single snapshot imaging of optical properties using a single-pixel camera: a simulation study.

J Biomed Opt 2019 04;24(7):1-6

University of Strasbourg, ICube Laboratory, Illkirch, France.

We present the effects of using a single-pixel camera approach to extract optical properties with the single-snapshot spatial frequency-domain imaging method. We acquired images of a human hand for spatial frequencies ranging from 0.1 to 0.4  mm  -  1 with increasing compression ratios using adaptive basis scan wavelet prediction strategy. In summary, our findings indicate that the extracted optical properties remained usable up to 99% of compression rate at a spatial frequency of 0.2  mm  -  1 with errors of 5% in reduced scattering and 10% in absorption.
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http://dx.doi.org/10.1117/1.JBO.24.7.071612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995955PMC
April 2019

Single snapshot of optical properties image quality improvement using anisotropic two-dimensional windows filtering.

J Biomed Opt 2019 03;24(7):1-21

University of Strasbourg, ICube Laboratory, Illkirch, France.

Imaging methods permitting real-time, wide-field, and quantitative optical mapping of biological tissue properties offer an unprecedented range of applications for clinical use. Following the development of spatial frequency domain imaging, we introduce a real-time demodulation method called single snapshot of optical properties (SSOPs). However, since this method uses only a single image to generate absorption and reduced scattering maps, it was limited by a degraded image quality resulting in artifacts that diminished its potential for clinical use. We present filtering strategies for improving the image quality of optical properties maps obtained using SSOPs. We investigate the effect of anisotropic two-dimensional filtering strategies for spatial frequencies ranging from 0.1 to 0.4  mm  -  1 directly onto N  =  10 hands. Both accuracy and image quality of the optical properties are quantified in comparison with standard, multiple image acquisitions in the spatial frequency domain. Overall, using optimized filters, mean errors in predicting optical properties using SSOP remain under 8.8% in absorption and 7.5% in reduced scattering, while significantly improving image quality. Overall this work contributes to advance real-time, wide-field, and quantitative diffuse optical imaging toward clinical evaluation.
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http://dx.doi.org/10.1117/1.JBO.24.7.071611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996016PMC
March 2019

Real-time, wide-field, and quantitative oxygenation imaging using spatiotemporal modulation of light.

J Biomed Opt 2019 03;24(7):1-7

University of Strasbourg, ICube Laboratory, Strasbourg, France.

Quantitative diffuse optical imaging has the potential to provide valuable functional information about tissue status, such as oxygen saturation or blood content to healthcare practitioners in real time. However, significant technical challenges have so far prevented such tools from being deployed in the clinic. Toward achieving this goal, prior research introduced methods based on spatial frequency domain imaging (SFDI) that allow real-time (within milliseconds) wide-field imaging of optical properties but at a single wavelength. However, for this technology to be useful to clinicians, images must be displayed in terms of metrics related to the physiological state of the tissue, hence interpretable to guide decision-making. For this purpose, recent developments introduced multispectral SFDI methods for rapid imaging of oxygenation parameters up to 16 frames per seconds (fps). We introduce real-time, wide-field, and quantitative blood parameters imaging using spatiotemporal modulation of light. Using this method, we are able to quantitatively obtain optical properties at 100 fps at two wavelengths (665 and 860 nm), and therefore oxygenation, oxyhemoglobin, and deoxyhemoglobin, using a single camera with, at most, 4.2% error in comparison with standard SFDI acquisitions.
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http://dx.doi.org/10.1117/1.JBO.24.7.071610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995963PMC
March 2019

Machine learning approach for rapid and accurate estimation of optical properties using spatial frequency domain imaging.

J Biomed Opt 2018 12;24(7):1-6

University of Strasbourg, ICube Laboratory, Strasbourg, France.

Fast estimation of optical properties from reflectance measurements at two spatial frequencies could pave way for real-time, wide-field and quantitative mapping of vital signs of tissues. We present a machine learning-based approach for estimating optical properties in the spatial frequency domain, where a random forest regression algorithm is trained over data obtained from Monte-Carlo photon transport simulations. The algorithm learns the nonlinear mapping between diffuse reflectance at two spatial frequencies, and the absorption and reduced scattering coefficient of the tissue under consideration. Using this method, absorption and reduced scattering properties could be obtained over a 1 megapixel image in 450 ms with errors as low as 0.556% in absorption and 0.126% in reduced scattering.
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http://dx.doi.org/10.1117/1.JBO.24.7.071606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995874PMC
December 2018

Contact, high-resolution spatial diffuse reflectance imaging system for skin condition diagnosis.

J Biomed Opt 2018 11;23(11):1-9

Univ. Grenoble Alpes, France.

Spatially resolved diffuse reflectance spectroscopy (srDRS) is a well-established technique for noninvasive, in vivo characterization of tissue optical properties toward diagnostic applications. srDRS has a potential for depth-resolved analysis of tissue, which is desired in various clinical situations. However, current fiber-based and photodiode-based systems have difficulties achieving this goal due to challenges in sampling the reflectance with a high enough resolution. We introduce a compact, low-cost architecture for srDRS based on the use of a multipixel imaging sensor and light-emitting diodes to achieve lensless diffuse reflectance imaging in contact with the tissue with high spatial resolution. For proof-of-concept, a prototype device, involving a commercially available complementary metal-oxide semiconductor coupled with a fiber-optic plate, was fabricated. Diffuse reflectance profiles were acquired at 645 nm at source-to-detector separations ranging from 480  μm to 4 mm with a resolution of 16.7  μm. Absorption coefficients (μa) and reduced scattering coefficients (μs') of homogeneous tissue-mimicking phantoms were measured with 4.2  ±  3.5  %   and 7.0  ±  4.6  %   error, respectively. The results obtained confirm the potential of our approach for quantitative characterization of tissue optical properties in contact imaging modality. This study is a first step toward the development of low-cost, wearable devices for skin condition diagnosis in vivo.
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http://dx.doi.org/10.1117/1.JBO.23.11.115003DOI Listing
November 2018

Review of structured light in diffuse optical imaging.

J Biomed Opt 2018 09;24(7):1-20

Rensselaer Polytechnic Institute, Department of Biomedical Engineering, Troy, New York, United States.

Diffuse optical imaging probes deep living tissue enabling structural, functional, metabolic, and molecular imaging. Recently, due to the availability of spatial light modulators, wide-field quantitative diffuse optical techniques have been implemented, which benefit greatly from structured light methodologies. Such implementations facilitate the quantification and characterization of depth-resolved optical and physiological properties of thick and deep tissue at fast acquisition speeds. We summarize the current state of work and applications in the three main techniques leveraging structured light: spatial frequency-domain imaging, optical tomography, and single-pixel imaging. The theory, measurement, and analysis of spatial frequency-domain imaging are described. Then, advanced theories, processing, and imaging systems are summarized. Preclinical and clinical applications on physiological measurements for guidance and diagnosis are summarized. General theory and method development of tomographic approaches as well as applications including fluorescence molecular tomography are introduced. Lastly, recent developments of single-pixel imaging methodologies and applications are reviewed.
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http://dx.doi.org/10.1117/1.JBO.24.7.071602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676045PMC
September 2018

Fluorescence-guided surgery and intervention - An AAPM emerging technology blue paper.

Med Phys 2018 Jun 25;45(6):2681-2688. Epub 2018 Apr 25.

Department of Physics, University of Pennsylvania, Philadelphia, PA, USA.

Fluorescence-guided surgery (FGS) and other interventions are rapidly evolving as a class of technologically driven interventional approaches in which many surgical specialties visualize fluorescent molecular tracers or biomarkers through associated cameras or oculars to guide clinical decisions on pathological lesion detection and excision/ablation. The technology has been commercialized for some specific applications, but also presents technical challenges unique to optical imaging that could confound the utility of some interventional procedures where real-time decisions must be made. Accordingly, the AAPM has initiated the publication of this Blue Paper of The Emerging Technology Working Group (TETAWG) and the creation of a Task Group from the Therapy Physics Committee within the Treatment Delivery Subcommittee. In describing the relevant issues, this document outlines the key parameters, stakeholders, impacts, and outcomes of clinical FGS technology and its applications. The presentation is not intended to be conclusive, but rather to inform the field of medical physics and stimulate the discussions needed in the field with respect to a seemingly low-risk imaging technology that has high potential for significant therapeutic impact. This AAPM Task Group is working toward consensus around guidelines and standards for advancing the field safely and effectively.
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http://dx.doi.org/10.1002/mp.12909DOI Listing
June 2018

Quantitative real-time optical imaging of the tissue metabolic rate of oxygen consumption.

J Biomed Opt 2018 03;23(3):1-12

Beckman Laser Institute and Medical Clinic, Laser Microbeam and Medical Program, Irvine, California, United States.

The tissue metabolic rate of oxygen consumption (tMRO2) is a clinically relevant marker for a number of pathologies including cancer and arterial occlusive disease. We present and validate a noncontact method for quantitatively mapping tMRO2 over a wide, scalable field of view at 16  frames  /  s. We achieve this by developing a dual-wavelength, near-infrared coherent spatial frequency-domain imaging (cSFDI) system to calculate tissue optical properties (i.e., absorption, μa, and reduced scattering, μs', parameters) as well as the speckle flow index (SFI) at every pixel. Images of tissue oxy- and deoxyhemoglobin concentration (  [  HbO2  ]   and [HHb]) are calculated from optical properties and combined with SFI to calculate tMRO2. We validate the system using a series of yeast-hemoglobin tissue-simulating phantoms and conduct in vivo tests in humans using arterial occlusions that demonstrate sensitivity to tissue metabolic oxygen debt and its repayment. Finally, we image the impact of cyanide exposure and toxicity reversal in an in vivo rabbit model showing clear instances of mitochondrial uncoupling and significantly diminished tMRO2. We conclude that dual-wavelength cSFDI provides rapid, quantitative, wide-field mapping of tMRO2 that can reveal unique spatial and temporal dynamics relevant to tissue pathology and viability.
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http://dx.doi.org/10.1117/1.JBO.23.3.036013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866507PMC
March 2018

Real-time endoscopic optical properties imaging.

Biomed Opt Express 2017 Nov 19;8(11):5113-5126. Epub 2017 Oct 19.

Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

With almost 50% of all surgeries in the U.S. being performed as minimally invasive procedures, there is a need to develop quantitative endoscopic imaging techniques to aid surgical guidance. Recent developments in widefield optical imaging make endoscopic implementations of real-time measurement possible. In this work, we introduce a proof-of-concept endoscopic implementation of a functional widefield imaging technique called 3D single snapshot of optical properties (3D-SSOP) that provides quantitative maps of absorption and reduced scattering optical properties as well as surface topography with simple instrumentation added to a commercial endoscope. The system's precision and accuracy is validated using tissue-mimicking phantoms, showing a max error of 0.004 mm, 0.05 mm, and 1.1 mm for absorption, reduced scattering, and sample topography, respectively. This study further demonstrates video acquisition of a moving phantom and an sample with a framerate of approximately 11 frames per second.
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http://dx.doi.org/10.1364/BOE.8.005113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695957PMC
November 2017

qF-SSOP: real-time optical property corrected fluorescence imaging.

Biomed Opt Express 2017 Aug 10;8(8):3597-3605. Epub 2017 Jul 10.

Department of Surgery, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02115, USA.

Fluorescence imaging is well suited to provide image guidance during resections in oncologic and vascular surgery. However, the distorting effects of tissue optical properties on the emitted fluorescence are poorly compensated for on even the most advanced fluorescence image guidance systems, leading to subjective and inaccurate estimates of tissue fluorophore concentrations. Here we present a novel fluorescence imaging technique that performs real-time (i.e., video rate) optical property corrected fluorescence imaging. We perform full field of view simultaneous imaging of tissue optical properties using Single Snapshot of Optical Properties (SSOP) and fluorescence detection. The estimated optical properties are used to correct the emitted fluorescence with a quantitative fluorescence model to provide quantitative fluorescence-Single Snapshot of Optical Properties (qF-SSOP) images with less than 5% error. The technique is rigorous, fast, and quantitative, enabling ease of integration into the surgical workflow with the potential to improve molecular guidance intraoperatively.
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http://dx.doi.org/10.1364/BOE.8.003597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560828PMC
August 2017

Ultrafast optical property map generation using lookup tables.

J Biomed Opt 2016 11;21(11):110501

Beth Israel Deaconess Medical Center, Department of Surgery, 330 Brookline Avenue, Boston, Massachusetts 02215, United StateseUniversity of Strasbourg, ICube Laboratory, 300 Boulevard Sébastien Brant, 67412 Illkirch, France.

Imaging technologies working in the spatial frequency domain are becoming increasingly popular for generating wide-field maps of optical properties, enabling rapid analysis of tissue parameters. While acquisition methods have become faster and are now performing in real-time, processing methods remain slow, precluding real-time display of information. We present solutions that rapidly solve the inverse problem for extracting optical properties by use of advanced lookup tables (LUTs). We present methods and results based on a dense, linearly sampled lookup table and an analytical representation that generate maps of absorption and reduced scattering in ?10??ms, which is 100× faster than the standard method, with ?4% error compared to the Monte-Carlo simulation. Combined with real-time acquisition methods, the proposed techniques enable video-rate feedback of real-time property maps, enabling full video-rate guidance in the clinic.
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http://dx.doi.org/10.1117/1.JBO.21.11.110501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997006PMC
November 2016

Endocrine-specific NIR fluorophores for adrenal gland targeting.

Chem Commun (Camb) 2016 Aug;52(67):10305-8

Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA and Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

The adrenal glands (AGs) are relatively small yet require definitive identification during their resection, or more commonly their avoidance. To enable image-guided surgery involving the AGs, we have developed novel near-infrared (NIR) fluorophores that target the AGs after a single intravenous injection, which provided dual-NIR image-guided resection or avoidance of the AGs during both open and minimally-invasive surgery.
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http://dx.doi.org/10.1039/c6cc03845jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982771PMC
August 2016

Renal Clearable Organic Nanocarriers for Bioimaging and Drug Delivery.

Adv Mater 2016 Oct 14;28(37):8162-8168. Epub 2016 Jul 14.

Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.

Renally cleared zwitterionic nanocarriers (H-Dots) are composed of ε-polylysine backbone for charge variations, near-infrared fluorophores for bioimaging, and β-cyclodextrins for potential drug delivery. H-Dots show ideal systemic circulation and rapid distribution and excrete from normal tissue/organ via renal excretion after complete targeting to the tumor site without nonspecific uptake by the immune system.
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http://dx.doi.org/10.1002/adma.201601101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155334PMC
October 2016

Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI).

Biomed Opt Express 2016 Mar 16;7(3):870-82. Epub 2016 Feb 16.

Laser Microbeam and Medical Program, Beckman Laser Institute, 1002 Health Sciences Road, Irvine, California 92612, USA; Department of Biomedical Engineering, University of California, Irvine, California 92697, USA; Department of Surgery, University of California, Irvine Medical Center, Orange, California 92868, USA.

In this work we present and validate a wide-field method for the real-time mapping of tissue absorption, scattering and blood flow properties over wide regions of tissue (15 cm x 15 cm) with high temporal resolution (50 frames per second). We achieve this by applying Fourier Domain demodulation techniques to coherent spatial frequency domain imaging to extract optical properties and speckle flow index from a single snapshot. Applying this technique to forearm reactive hyperemia protocols demonstrates the ability to resolve intrinsic physiological signals such as the heart beat waveform and the buildup of deoxyhemoglobin associated with oxygen consumption.
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http://dx.doi.org/10.1364/BOE.7.000870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866462PMC
March 2016

Real-time, profile-corrected single snapshot imaging of optical properties.

Biomed Opt Express 2015 Oct 21;6(10):4051-62. Epub 2015 Sep 21.

Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA ; ICube Laboratory, University of Strasbourg, 300 Bd S. Brant, 67412 Illkirch cedex, France.

A novel acquisition and processing method that enables real-time, single snapshot of optical properties (SSOP) and 3-dimensional (3D) profile measurements in the spatial frequency domain is described. This method makes use of a dual sinusoidal wave projection pattern permitting to extract the DC and AC components in the frequency domain to recover optical properties as well as the phase for measuring the 3D profile. In this method, the 3D profile is used to correct for the effect of sample's height and angle and directly obtain profile-corrected absorption and reduced scattering maps from a single acquired image. In this manuscript, the 3D-SSOP method is described and validated on tissue-mimicking phantoms as well as in vivo, in comparison with the standard profile-corrected SFDI (3D-SFDI) method. On average, in comparison with 3D-SFDI method, the 3D-SSOP method allows to recover the profile within 1.2mm and profile-corrected optical properties within 12% for absorption and 6% for reduced scattering over a large field-of-view and in real-time.
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http://dx.doi.org/10.1364/BOE.6.004051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605062PMC
October 2015

Laser line illumination scheme allowing the reduction of background signal and the correction of absorption heterogeneities effects for fluorescence reflectance imaging.

J Biomed Opt 2015 Oct;20(10):106003

University Grenoble Alpes, F-38000 Grenoble, France CEA, LETI, MINATEC Campus, 17 rue des Martyrs, Grenoble 38054, France.

Intraoperative fluorescence imaging in reflectance geometry is an attractive imaging modality as it allows to noninvasively monitor the fluorescence targeted tumors located below the tissue surface. Some drawbacks of this technique are the background fluorescence decreasing the contrast and absorption heterogeneities leading to misinterpretations concerning fluorescence concentrations. We propose a correction technique based on a laser line scanning illumination scheme. We scan the medium with the laser line and acquire, at each position of the line, both fluorescence and excitation images. We then use the finding that there is a relationship between the excitation intensity profile and the background fluorescence one to predict the amount of signal to subtract from the fluorescence images to get a better contrast. As the light absorption information is contained both in fluorescence and excitation images, this method also permits us to correct the effects of absorption heterogeneities. This technique has been validated on simulations and experimentally. Fluorescent inclusions are observed in several configurations at depths ranging from 1 mm to 1 cm. Results obtained with this technique are compared with those obtained with a classical wide-field detection scheme for contrast enhancement and with the fluorescence by an excitation ratio approach for absorption correction.
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http://dx.doi.org/10.1117/1.JBO.20.10.106003DOI Listing
October 2015

Intraoperative Hemifacial Composite Flap Perfusion Assessment Using Spatial Frequency Domain Imaging: A Pilot Study in Preparation for Facial Transplantation.

Ann Plast Surg 2016 Feb;76(2):249-55

From the *Division of Plastic and Reconstructive Surgery, Department of Surgery, †Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; ‡Division of Cancer Diagnostics and Therapeutics, Hokkaido University Graduate School of Medicine, Sapporo, Japan; §Department of Biomedical Engineering, Boston University; ∥Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston; and ¶Curadel, LLC, Worcester, MA.

Background: Vascularized composite allotransplantation represents an important advancement in the field of reconstructive microsurgery and has continued to increase in popularity. The significant clinical morbidity associated with flap failure represents an important barrier to even more widespread use of these techniques. Early identification of vascular compromise has been associated with a higher salvage rate, yet most surgeons rely only on clinical assessment intraoperatively. Spatial frequency domain imaging (SFDI) presents a noncontact, objective measurement of tissue oxygenation over a large field of view. This study aims to evaluate the use of SFDI technology in hemifacial composite flap compromise as could occur during facial transplant.

Methods: Six composite hemifacial flaps were created in three 35-kg Yorkshire pigs and continuously imaged using SFDI before, during, and after 15-minute selective vascular pedicle occlusion. Arterial and venous clamping trials were performed for each flap. Changes in oxyhemoglobin concentration, deoxyhemoglobin concentration, and total hemoglobin were quantified over time.

Results: The SFDI successfully measured changes in oxygenation parameters in all 6 composite tissue flaps. Significant changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin were seen relative to controls. Early and distinct patterns of alteration were noted in arterial and in venous compromise relative to one another.

Conclusions: The need for noninvasive, reliable assessment of composite tissue graft viability is apparent, given the morbidity associated with flap failure. The results of this study suggest that SFDI technology shows promise in providing intraoperative guidance with regard to pedicle vessel integrity during reconstructive microsurgery.
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http://dx.doi.org/10.1097/SAP.0000000000000631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712079PMC
February 2016

Sentinel Lymph Node Mapping of Liver.

Ann Surg Oncol 2015 Dec 13;22 Suppl 3:S1147-55. Epub 2015 May 13.

Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Background: Although the sentinel lymph node (SLN) hypothesis has been applied to many tissues and organs, liver has remained unstudied. Currently, it is unclear whether hepatic SLNs even exist. If so, they could alter the management of intrahepatic cholangiocarcinoma and other hepatic malignancies by minimizing the extent of surgery while still providing precise nodal staging. This study investigated whether invisible yet tissue-penetrating near-infrared (NIR) fluorescent light can provide simultaneous identification of both the SLN and all other regional lymph nodes (RLNs) in the liver.

Methods: In 25 Yorkshire pigs, this study determined whether SLNs exist in liver and compared the effectiveness of two clinically available NIR fluorophores [methylene blue and indocyanine green (ICG)], and two novel NIR fluorophores previously described by our group (ESNF14 and ZW800-3C) for SLN and RLN mapping.

Results: In this study, ESNF14 showed the highest signal-to-background ratio and the longest retention time in SLNs without leakage to second-tier lymph nodes. The findings showed that ICG had apparent leakage to second-tier nodes, and ZW800-3C had poor migration after intraparenchymal injection. However, when injected intravenously, ZW800-3C was able to highlight all RLNs in liver during a 4- to 6-h period. Simultaneous dual-channel imaging of SLN (ESNF14) and RLN (ZW800-3C) permitted unambiguous identification and image-guided resection of SLNs and RLNs in liver.

Conclusion: The NIR imaging technology enables real-time intraoperative identification of SLNs and RLNs in the liver of swine. If these results are confirmed in patients, new strategies for the surgical management of intrahepatic malignancies should be possible.
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http://dx.doi.org/10.1245/s10434-015-4601-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644113PMC
December 2015