|
1
|
Mendes ACM, Monte AFG, Saager RB. Innovative methodology for noninvasive spatial mapping of gold nanoparticle distribution in tissues: potential applications in biomedical imaging and therapy. JOURNAL OF THE OPTICAL SOCIETY OF AMERICA. A, OPTICS, IMAGE SCIENCE, AND VISION 2024; 41:1337-1346. [PMID: 39889120 DOI: 10.1364/josaa.523717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 05/20/2024] [Indexed: 02/02/2025]
Abstract
Gold nanoparticles (AuNPs) have emerged as versatile agents in biomedical applications, particularly for enhancing contrast in tagged biological tissues for tumor imaging and diagnostics due to their strong absorption cross-section. In this study, we present a methodology for quantifying the spatial distribution of AuNPs within superficial tissue volumes. Utilizing silicone tissue phantoms as a background medium and spatial frequency domain imaging (SFDI) to measure the tissues' optical properties, we constructed a lookup table (LUT) to infer the optical properties of embedded AuNPs with varying spatial concentrations and depths across multiple spatial frequencies. An analytical solution derived from the LUT facilitated the determination of embedded NP concentration in-depth as a function of measured spatial frequency-dependent optical absorption. Notably, SFDI enabled the spatial localization of NPs in three dimensions. These findings lay the foundation for future in vivo studies on mapping NPs and hold significant promise for advancing biomedical imaging techniques.
Collapse
|
|
2
|
Belcastro L, Jonasson H, Saager RB. Multi-frequency spatial frequency domain imaging: a depth-resolved optical scattering model to isolate scattering contrast in thin layers of skin. JOURNAL OF BIOMEDICAL OPTICS 2024; 29:046003. [PMID: 38650893 PMCID: PMC11033580 DOI: 10.1117/1.jbo.29.4.046003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 03/24/2024] [Accepted: 03/28/2024] [Indexed: 04/25/2024]
Abstract
Significance Current methods for wound healing assessment rely on visual inspection, which gives qualitative information. Optical methods allow for quantitative non-invasive measurements of optical properties relevant to wound healing. Aim Spatial frequency domain imaging (SFDI) measures the absorption and reduced scattering coefficients of tissue. Typically, SFDI assumes homogeneous tissue; however, layered structures are present in skin. We evaluate a multi-frequency approach to process SFDI data that estimates depth-specific scattering over differing penetration depths. Approach Multi-layer phantoms were manufactured to mimic wound healing scattering contrast in depth. An SFDI device imaged these phantoms and data were processed according to our multi-frequency approach. The depth sensitive data were then compared with a two-layer scattering model based on light fluence. Results The measured scattering from the phantoms changed with spatial frequency as our two-layer model predicted. The performance of two δ - P 1 models solutions for SFDI was consistently better than the standard diffusion approximation. Conclusions We presented an approach to process SFDI data that returns depth-resolved scattering contrast. This method allows for the implementation of layered optical models that more accurately represent physiologic parameters in thin tissue structures as in wound healing.
Collapse
Affiliation(s)
- Luigi Belcastro
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Hanna Jonasson
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Rolf B. Saager
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| |
Collapse
|
|
3
|
Shugar AL, Konger RL, Rohan CA, Travers JB, Kim YL. Mapping cutaneous field carcinogenesis of nonmelanoma skin cancer using mesoscopic imaging of pro-inflammation cues. Exp Dermatol 2024; 33:e15076. [PMID: 38610095 PMCID: PMC11034840 DOI: 10.1111/exd.15076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 03/24/2024] [Accepted: 03/30/2024] [Indexed: 04/14/2024]
Abstract
Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.
Collapse
Affiliation(s)
- Andrea L. Shugar
- Department of Pharmacology & Toxicology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA
| | - Raymond L. Konger
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Pathology, Richard L. Roudebush Veterans Administration Hospital, Indianapolis, Indiana, USA
| | - Craig A. Rohan
- Department of Pharmacology & Toxicology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA
- Department of Dermatology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA
- Department of Medicine, Dayton Veterans Affairs Medical Center, Dayton, Ohio, USA
| | - Jeffrey B. Travers
- Department of Pharmacology & Toxicology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA
- Department of Dermatology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA
- Department of Medicine, Dayton Veterans Affairs Medical Center, Dayton, Ohio, USA
| | - Young L. Kim
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
- Purdue Institute for Cancer Research, Purdue University, West Lafayette, Indiana, USA
| |
Collapse
|
|
4
|
Crowley J, Gordon GSD. Ultra-miniature dual-wavelength spatial frequency domain imaging for micro-endoscopy. JOURNAL OF BIOMEDICAL OPTICS 2024; 29:026002. [PMID: 38312854 PMCID: PMC10832795 DOI: 10.1117/1.jbo.29.2.026002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 11/08/2023] [Accepted: 11/14/2023] [Indexed: 02/06/2024]
Abstract
Significance There is a need for a cost-effective, quantitative imaging tool that can be deployed endoscopically to better detect early stage gastrointestinal cancers. Spatial frequency domain imaging (SFDI) is a low-cost imaging technique that produces near-real time, quantitative maps of absorption and reduced scattering coefficients, but most implementations are bulky and suitable only for use outside the body. Aim We aim to develop an ultra-miniature SFDI system comprising an optical fiber array (diameter 0.125 mm) and a micro camera (1 × 1 mm package) to displace conventionally bulky components, in particular, the projector. Approach First, we fabricated a prototype with an outer diameter of 3 mm, although the individual component dimensions could permit future packaging to a < 1.5 mm diameter. We developed a phase-tracking algorithm to rapidly extract images with fringe projections at three equispaced phase shifts to perform SFDI demodulation. Results To validate the performance, we first demonstrate comparable recovery of quantitative optical properties between our ultra-miniature system and a conventional bench-top SFDI system with an agreement of 15% and 6% for absorption and reduced scattering, respectively. Next, we demonstrate imaging of absorption and reduced scattering of tissue-mimicking phantoms providing enhanced contrast between simulated tissue types (healthy and tumour), done simultaneously at wavelengths of 515 and 660 nm. Using a support vector machine classifier, we estimate that sensitivity and specificity values of > 90 % are feasible for detecting simulated squamous cell carcinoma. Conclusions This device shows promise as a cost-effective, quantitative imaging tool to detect variations in optical absorption and scattering as indicators of cancer.
Collapse
Affiliation(s)
- Jane Crowley
- University of Nottingham, Department of Electrical and Electronic Engineering, Optics and Photonics Group, Nottingham, United Kingdom
| | - George S. D. Gordon
- University of Nottingham, Department of Electrical and Electronic Engineering, Optics and Photonics Group, Nottingham, United Kingdom
| |
Collapse
|
|
5
|
Crouzet C, Phan T, Wilson RH, Shin TJ, Choi B. Intrinsic, widefield optical imaging of hemodynamics in rodent models of Alzheimer's disease and neurological injury. NEUROPHOTONICS 2023; 10:020601. [PMID: 37143901 PMCID: PMC10152182 DOI: 10.1117/1.nph.10.2.020601] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/30/2023] [Indexed: 05/06/2023]
Abstract
The complex cerebrovascular network is critical to controlling local cerebral blood flow (CBF) and maintaining brain homeostasis. Alzheimer's disease (AD) and neurological injury can result in impaired CBF regulation, blood-brain barrier breakdown, neurovascular dysregulation, and ultimately impaired brain homeostasis. Measuring cortical hemodynamic changes in rodents can help elucidate the complex physiological dynamics that occur in AD and neurological injury. Widefield optical imaging approaches can measure hemodynamic information, such as CBF and oxygenation. These measurements can be performed over fields of view that range from millimeters to centimeters and probe up to the first few millimeters of rodent brain tissue. We discuss the principles and applications of three widefield optical imaging approaches that can measure cerebral hemodynamics: (1) optical intrinsic signal imaging, (2) laser speckle imaging, and (3) spatial frequency domain imaging. Future work in advancing widefield optical imaging approaches and employing multimodal instrumentation can enrich hemodynamic information content and help elucidate cerebrovascular mechanisms that lead to the development of therapeutic agents for AD and neurological injury.
Collapse
Affiliation(s)
- Christian Crouzet
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Thinh Phan
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
- University of California, Irvine, Department of Biomedical Engineering, Irvine, California, United States
| | - Robert H. Wilson
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
- University of California, Irvine, Department of Medicine, Irvine, California, United States
| | - Teo Jeon Shin
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
- Seoul National University, Department of Pediatric Dentistry and Dental Research Institute, Seoul, Republic of Korea
| | - Bernard Choi
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
- University of California, Irvine, Department of Biomedical Engineering, Irvine, California, United States
- University of California, Irvine, Department of Surgery, Irvine, California, United States
- University of California, Irvine, Edwards Lifesciences Foundation Cardiovascular Innovation Research Center, California, United States
| |
Collapse
|
|
6
|
Majedy M, Das NK, Johansson J, Saager RB. Influence of optical aberrations on depth-specific spatial frequency domain techniques. JOURNAL OF BIOMEDICAL OPTICS 2022; 27:116003. [PMID: 36358008 PMCID: PMC9646941 DOI: 10.1117/1.jbo.27.11.116003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/24/2022] [Indexed: 06/16/2023]
Abstract
SIGNIFICANCE Spatial frequency domain imaging (SFDI) and spatial frequency domain spectroscopy (SFDS) are emerging tools to non-invasively assess tissues. However, the presence of aberrations can complicate processing and interpretation. AIM This study develops a method to characterize optical aberrations when performing SFDI/S measurements. Additionally, we propose a post-processing method to compensate for these aberrations and recover arbitrary subsurface optical properties. APPROACH Using a custom SFDS system, we extract absorption and scattering coefficients from a reference phantom at 0 to 15 mm distances from the ideal focus. In post-processing, we characterize aberrations in terms of errors in absorption and scattering relative to the expected in-focus values. We subsequently evaluate a compensation approach in multi-distance measurements of phantoms with different optical properties and in multi-layer phantom constructs to mimic subsurface targets. RESULTS Characterizing depth-specific aberrations revealed a strong power law such as wavelength dependence from ∼40 to ∼10 % error in both scattering and absorption. When applying the compensation method, scattering remained within 1.3% (root-mean-square) of the ideal values, independent of depth or top layer thickness, and absorption remained within 3.8%. CONCLUSIONS We have developed a protocol that allows for instrument-specific characterization and compensation for the effects of defocus and chromatic aberrations on spatial frequency domain measurements.
Collapse
Affiliation(s)
- Motasam Majedy
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Nandan K. Das
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Johannes Johansson
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Rolf B. Saager
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| |
Collapse
|
|
7
|
Wang Y, Kang X, Zhang Y, Shi Z, Ren H, Wang Q, Chen M, Zhang Y. Wavelength and frequency optimization in spatial frequency domain imaging for two-layer tissue. BIOMEDICAL OPTICS EXPRESS 2022; 13:3224-3242. [PMID: 35781948 PMCID: PMC9208585 DOI: 10.1364/boe.455386] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/19/2022] [Accepted: 04/11/2022] [Indexed: 06/15/2023]
Abstract
Spatial frequency domain imaging is a non-contact, wide-field, fast-diffusion optical imaging technique, which in principle uses steady-state spatially modulated light to irradiate biological tissue, reconstruct two-dimensional or three-dimensional tissue optical characteristic map through optical transmission model, and further quantify the spatial distribution of tissue physiological parameters by multispectral imaging technique. The selection of light source wavelength and light field spatial modulation frequency is directly related to the accuracy of tissue optical properties and tissue physiological parameters extraction. For improvement of the measurement accuracy of optical properties and physiological parameters in the two-layer tissue, a multispectral spatial frequency domain imaging system is built based on liquid crystal tunable filter, and a data mapping table of spatially resolved diffuse reflectance and optical properties of two-layer tissue is established based on scaling Monte Carlo method. Combined with the dispersion effect and window effect of light-tissue interaction, the study applies numerical simulation to optimize the wavelength in the 650-850 nm range with spectral resolution of 10 nm. In order to minimize the uncertainty of the optical properties, Cramér-Rao bound is used to optimize the optical field spatial modulation frequency by transmitting the uncertainty of optical properties. The results showed that in order to realize the detection of melanin, oxyhemoglobin, deoxyhemoglobin, water and other physiological parameters in two-layer tissue, the best wavelength combination was determined as 720, 730, 760 and 810 nm according to the condition number. The findings of the Cramér-Rao bound analysis reveal that the uncertainty of optical characteristics for the frequency combinations [0, 0.3] mm-1, [0, 0.2] mm-1, and [0, 0.1] mm-1 increases successively. Under the optimal combination of wavelength and frequency, the diffuse reflectance of the gradient gray-scale plate measured by the multi-spectral spatial frequency domain imaging system is linearly correlated with the calibration value. The error between the measured liquid phantom absorption coefficient and the collimation projection system based on colorimetric dish is less than 2%. The experimental results of human brachial artery occlusion indicate that under the optimal wavelength combination, the change of the second layer absorption coefficient captured by the three frequency combinations decreases in turn, so as the change of oxygen saturation.
Collapse
Affiliation(s)
- Yikun Wang
- Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Anhui Provincial Engineering Technology Research Center for Biomedical Optical Instrument, Anhui Provincial Engineering Laboratory for Medical Optical Diagnosis Treatment Technology and Instrument, Hefei 230031, China
- These authors contributed equally to this work and should be considered co-first authors
| | - Xu Kang
- Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Anhui Provincial Engineering Technology Research Center for Biomedical Optical Instrument, Anhui Provincial Engineering Laboratory for Medical Optical Diagnosis Treatment Technology and Instrument, Hefei 230031, China
- Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, China
- These authors contributed equally to this work and should be considered co-first authors
| | - Yang Zhang
- Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Anhui Provincial Engineering Technology Research Center for Biomedical Optical Instrument, Anhui Provincial Engineering Laboratory for Medical Optical Diagnosis Treatment Technology and Instrument, Hefei 230031, China
| | - Zhiguo Shi
- Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Anhui Provincial Engineering Technology Research Center for Biomedical Optical Instrument, Anhui Provincial Engineering Laboratory for Medical Optical Diagnosis Treatment Technology and Instrument, Hefei 230031, China
- School of Biomedical Engineering, Anhui Medical University, Hefei 230009, China
| | - Huiming Ren
- Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Anhui Provincial Engineering Technology Research Center for Biomedical Optical Instrument, Anhui Provincial Engineering Laboratory for Medical Optical Diagnosis Treatment Technology and Instrument, Hefei 230031, China
- Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, China
| | - Quanfu Wang
- Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Anhui Provincial Engineering Technology Research Center for Biomedical Optical Instrument, Anhui Provincial Engineering Laboratory for Medical Optical Diagnosis Treatment Technology and Instrument, Hefei 230031, China
| | - Mingwei Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
| | - Yuanzhi Zhang
- Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Anhui Provincial Engineering Technology Research Center for Biomedical Optical Instrument, Anhui Provincial Engineering Laboratory for Medical Optical Diagnosis Treatment Technology and Instrument, Hefei 230031, China
| |
Collapse
|
|
8
|
Phan T, Rowland R, Ponticorvo A, Le BC, Sharif SA, Kennedy GT, Wilson RH, Durkin AJ. Quantifying the confounding effect of pigmentation on measured skin tissue optical properties: a comparison of colorimetry with spatial frequency domain imaging. JOURNAL OF BIOMEDICAL OPTICS 2022; 27:JBO-210337GR. [PMID: 35324096 PMCID: PMC8942554 DOI: 10.1117/1.jbo.27.3.036002] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 02/16/2022] [Indexed: 05/20/2023]
Abstract
SIGNIFICANCE Spatial frequency domain imaging (SFDI) is a wide-field diffuse optical imaging technique for separately quantifying tissue reduced scattering (μs ' ) and absorption (μa) coefficients at multiple wavelengths, providing wide potential utility for clinical applications such as burn wound characterization and cancer detection. However, measured μs ' and μa can be confounded by absorption from melanin in patients with highly pigmented skin. This issue arises because epidermal melanin is highly absorbing for visible wavelengths and standard homogeneous light-tissue interaction models do not properly account for this complexity. Tristimulus colorimetry (which quantifies pigmentation using the L * "lightness" parameter) can provide a point of comparison between μa, μs ' , and skin pigmentation. AIM We systematically compare SFDI and colorimetry parameters to quantify confounding effects of pigmentation on measured skin μs ' and μa. We assess the correlation between SFDI and colorimetry parameters as a function of wavelength. APPROACH μs ' and μa from the palm and ventral forearm were measured for 15 healthy subjects with a wide range of skin pigmentation levels (Fitzpatrick types I to VI) using a Reflect RS® (Modulim, Inc., Irvine, California) SFDI instrument (eight wavelengths, 471 to 851 nm). L * was measured using a Chroma Meter CR-400 (Konica Minolta Sensing, Inc., Tokyo). Linear correlation coefficients were calculated between L * and μs ' and between L * and μa at all wavelengths. RESULTS For the ventral forearm, strong linear correlations between measured L * and μs ' values were observed at shorter wavelengths (R > 0.92 at ≤659 nm), where absorption from melanin confounded the measured μs ' . These correlations were weaker for the palm (R < 0.59 at ≤659 nm), which has less melanin than the forearm. Similar relationships were observed between L * and μa. CONCLUSIONS We quantified the effects of epidermal melanin on skin μs ' and μa measured with SFDI. This information may help characterize and correct pigmentation-related inaccuracies in SFDI skin measurements.
Collapse
Affiliation(s)
- Thinh Phan
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Rebecca Rowland
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Adrien Ponticorvo
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Binh Cong Le
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Seyed A. Sharif
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Gordon T. Kennedy
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Robert H. Wilson
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
- University of California, Irvine, Department of Medicine, Irvine, California, United States
- University of California, Irvine, Health Policy Research Institute, Irvine, California, United States
| | - Anthony J. Durkin
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
- University of California, Irvine, Department of Biomedical Engineering, Irvine, California, United States
| |
Collapse
|
|
9
|
Jonasson H, Anderson CD, Saager RB. Water and hemoglobin modulated gelatin-based phantoms to spectrally mimic inflamed tissue in the validation of biomedical techniques and the modeling of microdialysis data. JOURNAL OF BIOMEDICAL OPTICS 2022; 27:074712. [PMID: 35106979 PMCID: PMC8804337 DOI: 10.1117/1.jbo.27.7.074712] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 01/10/2022] [Indexed: 06/14/2023]
Abstract
SIGNIFICANCE Tissue simulating phantoms are an important part of validating biomedical optical techniques. Tissue pathology in inflammation and oedema involves changes in both water and hemoglobin fractions. AIM We present a method to create solid gelatin-based phantoms mimicking inflammation and oedema with adjustable water and hemoglobin fractions. APPROACH One store-bought gelatin and one research grade gelatin were evaluated. Different water fractions were obtained by varying the water-to-gelatin ratio. Ferrous stabilized human hemoglobin or whole human blood was added as absorbers, and the stability and characteristics of each were compared. Intralipid® was used as the scatterer. All phantoms were characterized using spatial frequency domain spectroscopy. RESULTS The estimated water fraction varied linearly with expected values (R2 = 0.96 for the store-bought gelatin and R2 = 0.99 for the research grade gelatin). Phantoms including ferrous stabilized hemoglobin stayed stable up to one day but had methemoglobin present at day 0. The phantoms with whole blood remained stable up to 3 days using the store-bought gelatin. CONCLUSIONS A range of physiological relevant water fractions was obtained for both gelatin types, with the stability of the phantoms including hemoglobin differing between the gelatin type and hemoglobin preparation. These low-cost phantoms can incorporate other water-based chromophores and be fabricated as thin sheets to form multilayered structures.
Collapse
Affiliation(s)
- Hanna Jonasson
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Chris D. Anderson
- Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden
| | - Rolf B. Saager
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| |
Collapse
|
|
10
|
Lin W, Zheng Y, Li Z, Jin X, Cao Z, Zeng B, Xu M. In vivo two-dimensional quantitative imaging of skin and cutaneous microcirculation with perturbative spatial frequency domain imaging (p-SFDI). BIOMEDICAL OPTICS EXPRESS 2021; 12:6143-6156. [PMID: 34745727 PMCID: PMC8547977 DOI: 10.1364/boe.428243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 08/22/2021] [Accepted: 08/26/2021] [Indexed: 06/13/2023]
Abstract
We introduce perturbative spatial frequency domain imaging (p-SFDI) for fast two-dimensional (2D) mapping of the optical properties and physiological characteristics of skin and cutaneous microcirculation using spatially modulated visible light. Compared to the traditional methods for recovering 2D maps through a pixel-by-pixel inversion, p-SFDI significantly shortens parameter retrieval time, largely avoids the random fitting errors caused by measurement noise, and enhances the image reconstruction quality. The efficacy of p-SFDI is demonstrated by in vivo imaging forearm of one healthy subject, recovering the 2D spatial distribution of cutaneous hemoglobin concentration, oxygen saturation, scattering properties, the melanin content, and the epidermal thickness over a large field of view. Furthermore, the temporal and spatial variations in physiological parameters under the forearm reactive hyperemia protocol are revealed, showing its applications in monitoring temporal and spatial dynamics.
Collapse
Affiliation(s)
- Weihao Lin
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Yang Zheng
- The Second People's Hospital of Hefei, Hefei, Anhui, 230011, China
| | - Zhenfang Li
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Xin Jin
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Zili Cao
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Bixin Zeng
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - M. Xu
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- Dept. of Physics and Astronomy, Hunter College and the Graduate, Center of The City University of New York, 695 Park Avenue, New York, NY 10065, USA
| |
Collapse
|
|
11
|
Chiba T, Murata M, Kawano T, Hashizume M, Akahoshi T. Reflectance spectra analysis for mucous assessment. World J Gastrointest Oncol 2021; 13:822-834. [PMID: 34457188 PMCID: PMC8371524 DOI: 10.4251/wjgo.v13.i8.822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/26/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
This review report represents an overview of research and development on medical hyperspectral imaging technology and its applications. Spectral imaging technology is attracting attention as a new imaging modality for medical applications, especially in disease diagnosis and image-guided surgery. Considering the recent advances in imaging, this technology provides an opportunity for two-dimensional mapping of oxygen saturation (SatO2) of blood with high accuracy, spatial spectral imaging, and its analysis and provides detection and diagnostic information about the tissue physiology and morphology. Multispectral imaging also provides information about tissue oxygenation, perfusion, and potential function during surgery. Analytical algorithm has been examined, and indication of accurate map of relative hemoglobin concentration and SatO2 can be indicated with preferable resolution and frame rate. This technology is expected to provide promising biomedical information in practical use. Several studies suggested that blood flow and SatO2 are associated with gastrointestinal disorders, particularly malignant tumor conditions. The use and analysis of spectroscopic images are expected to potentially play a role in the detection and diagnosis of these diseases.
Collapse
Affiliation(s)
- Toru Chiba
- Pentax_LifeCare, HOYA Corporation, Akishima-shi 196-0012, Tokyo, Japan
| | - Masaharu Murata
- Center for Advanced Medical Innovation, Kyushu University, Fukuoka-shi 812-8582, Fukuoka, Japan
| | - Takahito Kawano
- Center for Advanced Medical Innovation, Kyushu University, Fukuoka-shi 812-8582, Fukuoka, Japan
| | - Makoto Hashizume
- Center for Advanced Medical Innovation, Kyushu University, Fukuoka-shi 812-8582, Fukuoka, Japan
| | - Tomohiko Akahoshi
- Department of Disaster and Emergency Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka_shi 812-8582, Fukuoka, Japan
| |
Collapse
|
|
12
|
Zeng B, Guo M, Yu K, Sun L, Lin W, Pan D, Chen X, Xu M. Handheld spatial frequency domain imager for noninvasive Sjögren's syndrome labial salivary gland biopsy. BIOMEDICAL OPTICS EXPRESS 2021; 12:5057-5072. [PMID: 34513242 PMCID: PMC8407847 DOI: 10.1364/boe.426683] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 06/17/2021] [Accepted: 07/07/2021] [Indexed: 06/13/2023]
Abstract
A labial salivary gland biopsy (LSGB) plays an essential role in diagnosing Sjögren's syndrome (SS), but its clinical application is limited due to its invasiveness. Here, we present a handheld single snapshot multiple-frequency demodulation-spatial frequency domain imaging (SSMD-SFDI) device for a rapid optical biopsy of labial salivary glands noninvasively. The structural and physiological parameters of lower lip mucosa were obtained from the light reflectance of the layered oral mucosa. The recovered parameters were found to correlate strongly with the progression of SS. In our pilot study on 15 healthy subjects and 183 SS patients, a support vector machine (SVM) classifier using the measured parameters distinguished healthy subjects, LSGB I, II, III, and IV patients in sequence with AUCs of 0.979, 0.898, 0.906, and 0.978, respectively. Critical structural and physiological alterations in the mucosa due to SS were further identified and used to assess its risk using an explainable neural network. The handheld spatial frequency domain imager may serve as a valuable label-free and noninvasive tool for early diagnosing and surveying SS.
Collapse
Affiliation(s)
- Bixin Zeng
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- These authors contributed equally
| | - Mingrou Guo
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- These authors contributed equally
| | - Kangyuan Yu
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Li Sun
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Weihao Lin
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Da Pan
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Xiaowei Chen
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Min Xu
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- Department of Physics and Astronomy, Hunter College and the Graduate Center, The City University of New York, 695 Park Avenue, New York, NY 10065, USA
| |
Collapse
|
|
13
|
Hohmann M, Hecht D, Lengenfelder B, Späth M, Klämpfl F, Schmidt M. Proof of Principle for Direct Reconstruction of Qualitative Depth Information from Turbid Media by a Single Hyper Spectral Image. SENSORS 2021; 21:s21082860. [PMID: 33921629 PMCID: PMC8073672 DOI: 10.3390/s21082860] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/12/2021] [Accepted: 04/14/2021] [Indexed: 01/14/2023]
Abstract
In medical applications, hyper-spectral imaging is becoming more and more common. It has been shown to be more effective for classification and segmentation than normal RGB imaging because narrower wavelength bands are used, providing a higher contrast. However, until now, the fact that hyper-spectral images also contain information about the three-dimensional structure of turbid media has been neglected. In this study, it is shown that it is possible to derive information about the depth of inclusions in turbid phantoms from a single hyper-spectral image. Here, the depth information is encoded by a combination of scattering and absorption within the phantom. Although scatter-dominated regions increase the backscattering for deep vessels, absorption has the opposite effect. With this argumentation, it makes sense to assume that, under certain conditions, a wavelength is not influenced by the depth of the inclusion and acts as an iso-point. This iso-point could be used to easily derive information about the depth of an inclusion. In this study, it is shown that the iso-point exists in some cases. Moreover, it is shown that the iso-point can be used to obtain precise depth information.
Collapse
Affiliation(s)
- Martin Hohmann
- Institute of Photonic Technologies (LPT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Konrad-Zuse-Strasse 3/5, 91052 Erlangen, Germany; (D.H.); (B.L.); (M.S.); (F.K.); (M.S.)
- Erlangen Graduate School in Advanced Optical Technologies (SAOT), Paul-Gordon-Strasse 6, 91052 Erlangen, Germany
- Correspondence:
| | - Damaris Hecht
- Institute of Photonic Technologies (LPT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Konrad-Zuse-Strasse 3/5, 91052 Erlangen, Germany; (D.H.); (B.L.); (M.S.); (F.K.); (M.S.)
| | - Benjamin Lengenfelder
- Institute of Photonic Technologies (LPT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Konrad-Zuse-Strasse 3/5, 91052 Erlangen, Germany; (D.H.); (B.L.); (M.S.); (F.K.); (M.S.)
- Erlangen Graduate School in Advanced Optical Technologies (SAOT), Paul-Gordon-Strasse 6, 91052 Erlangen, Germany
| | - Moritz Späth
- Institute of Photonic Technologies (LPT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Konrad-Zuse-Strasse 3/5, 91052 Erlangen, Germany; (D.H.); (B.L.); (M.S.); (F.K.); (M.S.)
- Erlangen Graduate School in Advanced Optical Technologies (SAOT), Paul-Gordon-Strasse 6, 91052 Erlangen, Germany
| | - Florian Klämpfl
- Institute of Photonic Technologies (LPT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Konrad-Zuse-Strasse 3/5, 91052 Erlangen, Germany; (D.H.); (B.L.); (M.S.); (F.K.); (M.S.)
- Erlangen Graduate School in Advanced Optical Technologies (SAOT), Paul-Gordon-Strasse 6, 91052 Erlangen, Germany
| | - Michael Schmidt
- Institute of Photonic Technologies (LPT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Konrad-Zuse-Strasse 3/5, 91052 Erlangen, Germany; (D.H.); (B.L.); (M.S.); (F.K.); (M.S.)
- Erlangen Graduate School in Advanced Optical Technologies (SAOT), Paul-Gordon-Strasse 6, 91052 Erlangen, Germany
| |
Collapse
|
|
14
|
Boonya-ananta T, Rodriguez AJ, Ajmal A, Du Le VN, Hansen AK, Hutcheson JD, Ramella-Roman JC. Synthetic photoplethysmography (PPG) of the radial artery through parallelized Monte Carlo and its correlation to body mass index (BMI). Sci Rep 2021; 11:2570. [PMID: 33510428 PMCID: PMC7843978 DOI: 10.1038/s41598-021-82124-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 01/14/2021] [Indexed: 01/30/2023] Open
Abstract
Cardiovascular disease is one of the leading causes of death in the United States and obesity significantly increases the risk of cardiovascular disease. The measurement of blood pressure (BP) is critical in monitoring and managing cardiovascular disease hence new wearable devices are being developed to make BP more accessible to physicians and patients. Several wearables utilize photoplethysmography from the wrist vasculature to derive BP assessment although many of these devices are still at the experimental stage. With the ultimate goal of supporting instrument development, we have developed a model of the photoplethysmographic waveform derived from the radial artery at the volar surface of the wrist. To do so we have utilized the relation between vessel biomechanics through Finite Element Method and Monte Carlo light transport model. The model shows similar features to that seen in PPG waveform captured using an off the shelf device. We observe the influence of body mass index on the PPG signal. A degradation the PPG signal of up to 40% in AC to DC signal ratio was thus observed.
Collapse
Affiliation(s)
- Tananant Boonya-ananta
- grid.65456.340000 0001 2110 1845Department of Biomedical Engineering, Florida International University, 10555 W Flagler St, Miami, FL 33174 USA
| | - Andres J. Rodriguez
- grid.65456.340000 0001 2110 1845Department of Biomedical Engineering, Florida International University, 10555 W Flagler St, Miami, FL 33174 USA
| | - Ajmal Ajmal
- grid.65456.340000 0001 2110 1845Department of Biomedical Engineering, Florida International University, 10555 W Flagler St, Miami, FL 33174 USA
| | - Vinh Nguyen Du Le
- grid.65456.340000 0001 2110 1845Department of Biomedical Engineering, Florida International University, 10555 W Flagler St, Miami, FL 33174 USA
| | - Anders K. Hansen
- grid.5170.30000 0001 2181 8870Department of Photonics Engineering, Technical University of Denmark, Frederiksborgvej 399, 4000 Roskilde, Denmark
| | - Joshua D. Hutcheson
- grid.65456.340000 0001 2110 1845Department of Biomedical Engineering, Florida International University, 10555 W Flagler St, Miami, FL 33174 USA
| | - Jessica C. Ramella-Roman
- grid.65456.340000 0001 2110 1845Department of Biomedical Engineering, Florida International University, 10555 W Flagler St, Miami, FL 33174 USA ,grid.65456.340000 0001 2110 1845Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th St, Miami, FL 33199 USA
| |
Collapse
|
|
15
|
Towards shifted position-diffuse reflectance imaging of anatomically correctly scaled human microvasculature. Sci Rep 2020; 10:17391. [PMID: 33060791 PMCID: PMC7567838 DOI: 10.1038/s41598-020-74447-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 09/30/2020] [Indexed: 11/10/2022] Open
Abstract
Due to significant advantages, the trend in the field of medical technology is moving towards minimally or even non-invasive examination methods. In this respect, optical methods offer inherent benefits, as does diffuse reflectance imaging (DRI). The present study attempts to prove the suitability of DRI—when implemented alongside a suitable setup and data evaluation algorithm—to derive information from anatomically correctly scaled human capillaries (diameter: \documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$10\,\upmu \hbox {m}$$\end{document}10μm, length: \documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$45\,\upmu \hbox {m}$$\end{document}45μm) by conducting extensive Monte–Carlo simulations and by verifying the findings through laboratory experiments. As a result, the method of shifted position-diffuse reflectance imaging (SP-DRI) is established by which average signal modulations of up to 5% could be generated with an illumination wavelength of \documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$\lambda =424\,\hbox {nm}$$\end{document}λ=424nm and a core diameter of the illumination fiber of \documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$50\,\upmu \hbox {m}$$\end{document}50μm. No reference image is needed for this technique. The present study reveals that the diffuse reflectance data in combination with the SP-DRI normalization are suitable to localize human capillaries within turbid media.
Collapse
|
|
16
|
Li Y, Guo M, Qian X, Lin W, Zheng Y, Yu K, Zeng B, Xu Z, Zheng C, Xu M. Single snapshot spatial frequency domain imaging for risk stratification of diabetes and diabetic foot. BIOMEDICAL OPTICS EXPRESS 2020; 11:4471-4483. [PMID: 32923057 PMCID: PMC7449725 DOI: 10.1364/boe.394929] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 06/24/2020] [Accepted: 06/25/2020] [Indexed: 05/29/2023]
Abstract
Diabetic foot is one of the major complications of diabetes. In this work, a real-time Single Snapshot Multiple-frequency Demodulation (SSMD) - Spatial Frequency Domain Imaging (SFDI) system was used to image the forefoot of healthy volunteers, diabetes, and diabetic foot patients. A layered skin model was used to obtain the 2D maps of optical and physiological parameters, including cutaneous hemoglobin concentration, oxygen saturation, scattering properties, melanin content, and epidermal thickness, from every single snapshot. We observed a strong correlation between the measured optical and physiological parameters and the degree of diabetes. The cutaneous hemoglobin concentration, oxygen saturation, and epidermal thickness decrease, whereas the melanin content increases with the progress of diabetes. The melanin content further increases, and the reduced scattering coefficient and scattering power are lower for diabetic foot patients than those of both healthy and diabetic subjects. High accuracies (AUC) of 97.2% (distinguishing the diabetic foot patients among all subjects), 95.2% (separating healthy subjects from the diabetes patients), and 87.8% (classifying mild vs severe diabetes), respectively, are achieved in binary classifications in sequence using the SSMD-SFDI system, demonstrating its applicability to risk stratification of diabetes and diabetic foot. The prognostic value of the SSMD-SFDI system in the prediction of the occurrence of the diabetic foot and other applications in monitoring tissue microcirculation and peripheral vascular disease are also addressed.
Collapse
Affiliation(s)
- Ying Li
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Mingrou Guo
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Xiafei Qian
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Weihao Lin
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Yang Zheng
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Kangyuan Yu
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Bixin Zeng
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Zhang Xu
- The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Chao Zheng
- The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - M. Xu
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- Dept. of Physics and Astronomy, Hunter College and the Graduate Center, The City University of New York, 695 Park Avenue, New York, NY 10065, USA
| |
Collapse
|
|
17
|
Belcastro L, Jonasson H, Strömberg T, Saager RB. Handheld multispectral imager for quantitative skin assessment in low-resource settings. JOURNAL OF BIOMEDICAL OPTICS 2020; 25:1-12. [PMID: 32755076 PMCID: PMC7399474 DOI: 10.1117/1.jbo.25.8.082702] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 07/06/2020] [Indexed: 05/28/2023]
Abstract
SIGNIFICANCE Spatial frequency domain imaging (SFDI) is a quantitative imaging method to measure absorption and scattering of tissue, from which several chromophore concentrations (e.g., oxy-/deoxy-/meth-hemoglobin, melanin, and carotenoids) can be calculated. Employing a method to extract additional spectral bands from RGB components (that we named cross-channels), we designed a handheld SFDI device to account for these pigments, using low-cost, consumer-grade components for its implementation and characterization. AIM With only three broad spectral bands (red, green, blue, or RGB), consumer-grade devices are often too limited. We present a methodology to increase the number of spectral bands in SFDI devices that use RGB components without hardware modification. APPROACH We developed a compact low-cost RGB spectral imager using a color CMOS camera and LED-based mini projector. The components' spectral properties were characterized and additional cross-channel bands were calculated. An alternative characterization procedure was also developed that makes use of low-cost equipment, and its results were compared. The device performance was evaluated by measurements on tissue-simulating optical phantoms and in-vivo tissue. The measurements were compared with another quantitative spectroscopy method: spatial frequency domain spectroscopy (SFDS). RESULTS Out of six possible cross-channel bands, two were evaluated to be suitable for our application and were fully characterized (520 ± 20 nm; 556 ± 18 nm). The other four cross-channels presented a too low signal-to-noise ratio for this implementation. In estimating the optical properties of optical phantoms, the SFDI data have a strong linear correlation with the SFDS data (R2 = 0.987, RMSE = 0.006 for μa, R2 = 0.994, RMSE = 0.078 for μs'). CONCLUSIONS We extracted two additional spectral bands from a commercial RGB system at no cost. There was good agreement between our device and the research-grade SFDS system. The alternative characterization procedure we have presented allowed us to measure the spectral features of the system with an accuracy comparable to standard laboratory equipment.
Collapse
Affiliation(s)
- Luigi Belcastro
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Hanna Jonasson
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Tomas Strömberg
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Rolf B. Saager
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| |
Collapse
|
|
18
|
Zherebtsov E, Dremin V, Popov A, Doronin A, Kurakina D, Kirillin M, Meglinski I, Bykov A. Hyperspectral imaging of human skin aided by artificial neural networks. BIOMEDICAL OPTICS EXPRESS 2019; 10:3545-3559. [PMID: 31467793 PMCID: PMC6706048 DOI: 10.1364/boe.10.003545] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 06/06/2019] [Accepted: 06/11/2019] [Indexed: 05/06/2023]
Abstract
We developed a compact, hand-held hyperspectral imaging system for 2D neural network-based visualization of skin chromophores and blood oxygenation. State-of-the-art micro-optic multichannel matrix sensor combined with the tunable Fabry-Perot micro interferometer enables a portable diagnostic device sensitive to the changes of the oxygen saturation as well as the variations of blood volume fraction of human skin. Generalized object-oriented Monte Carlo model is used extensively for the training of an artificial neural network utilized for the hyperspectral image processing. In addition, the results are verified and validated via actual experiments with tissue phantoms and human skin in vivo. The proposed approach enables a tool combining both the speed of an artificial neural network processing and the accuracy and flexibility of advanced Monte Carlo modeling. Finally, the results of the feasibility studies and the experimental tests on biotissue phantoms and healthy volunteers are presented.
Collapse
Affiliation(s)
- Evgeny Zherebtsov
- Opto-Electronics and Measurement Techniques Research Unit, Faculty of Information Technology and Electrical Engineering, University of Oulu, PO Box 4500, 90014 Oulu, Finland
| | - Viktor Dremin
- Opto-Electronics and Measurement Techniques Research Unit, Faculty of Information Technology and Electrical Engineering, University of Oulu, PO Box 4500, 90014 Oulu, Finland
| | - Alexey Popov
- Opto-Electronics and Measurement Techniques Research Unit, Faculty of Information Technology and Electrical Engineering, University of Oulu, PO Box 4500, 90014 Oulu, Finland
| | - Alexander Doronin
- School of Engineering and Computer Science, Victoria University of Wellington, PO Box 600, 6140 Wellington, New Zealand
| | - Daria Kurakina
- Institute of Applied Physics of the Russian Academy of Sciences, 46 Ul’yanov Street, 603950 Nizhny Novgorod, Russia
| | - Mikhail Kirillin
- Institute of Applied Physics of the Russian Academy of Sciences, 46 Ul’yanov Street, 603950 Nizhny Novgorod, Russia
- Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Avenue, 603950 Nizhny Novgorod, Russia
| | - Igor Meglinski
- Opto-Electronics and Measurement Techniques Research Unit, Faculty of Information Technology and Electrical Engineering, University of Oulu, PO Box 4500, 90014 Oulu, Finland
- Institute of Engineering Physics for Biomedicine, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409 Moscow, Russia
| | - Alexander Bykov
- Opto-Electronics and Measurement Techniques Research Unit, Faculty of Information Technology and Electrical Engineering, University of Oulu, PO Box 4500, 90014 Oulu, Finland
| |
Collapse
|
|
19
|
Gioux S, Mazhar A, Cuccia DJ. Spatial frequency domain imaging in 2019: principles, applications, and perspectives. JOURNAL OF BIOMEDICAL OPTICS 2019; 24:1-18. [PMID: 31222987 PMCID: PMC6995958 DOI: 10.1117/1.jbo.24.7.071613] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 05/09/2019] [Indexed: 05/20/2023]
Abstract
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.
Collapse
Affiliation(s)
- Sylvain Gioux
- University of Strasbourg, ICube Laboratory, Strasbourg, France
- Address all correspondence to Sylvain Gioux, E-mail:
| | | | | |
Collapse
|
|
20
|
Gioux S, Mazhar A, Cuccia DJ. Spatial frequency domain imaging in 2019: principles, applications, and perspectives. JOURNAL OF BIOMEDICAL OPTICS 2019. [PMID: 31222987 DOI: 10.1117/1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
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.
Collapse
Affiliation(s)
- Sylvain Gioux
- University of Strasbourg, ICube Laboratory, Strasbourg, France
| | | | | |
Collapse
|
|
21
|
Hu D, Lu R, Ying Y, Fu X. A stepwise method for estimating optical properties of two-layer turbid media from spatial-frequency domain reflectance. OPTICS EXPRESS 2019; 27:1124-1141. [PMID: 30696182 DOI: 10.1364/oe.27.001124] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 12/23/2018] [Indexed: 06/09/2023]
Abstract
This research was conducted to estimate the optical absorption and reduced scattering coefficients of two-layer turbid media using a stepwise method from the spatial-frequency domain reflectance generated by Monte Carlo (MC) simulation. The stepwise method's feasibility for optical property estimations was first investigated by comparing the reflectance generated by the diffusion model and MC simulation for one-layer and two-layer turbid media. The results showed that, with proper frequency selection, the one-layer model could be used for estimating the optical properties of the first layer of the two-layer turbid media. A sample-based calibration method was proposed for calibrating discrepancies of the reflectance between the diffusion model and MC simulation. This significantly improved the parameter estimation accuracy. Results showed that the stepwise method's parameter estimation efficacy and accuracy were much better than that for the one-step method. This was especially true when estimating the absorption coefficient. Absolute error contour maps were generated in order to determine the constraining conditions for the first-layer thickness. It was found that, when each layer's optical properties are within the range of 0.005 mm-1 ≤ μa ≤ 0.04 mm-1 and 0.69 mm-1 ≤ μs'≤ 2.2 mm-1, the first-layer's minimum thickness-for which the first layer's optical properties could be accurately estimated-could be as small as 0.2 mm. Further, the first layer's maximum thickness could not exceed 2.0 mm, in order to have acceptable estimations of the optical properties of the second layer.
Collapse
|
|
22
|
Horan ST, Gardner AR, Saager R, Durkin AJ, Venugopalan V. Recovery of layered tissue optical properties from spatial frequency-domain spectroscopy and a deterministic radiative transport solver. JOURNAL OF BIOMEDICAL OPTICS 2018; 24:1-11. [PMID: 30456934 PMCID: PMC6995875 DOI: 10.1117/1.jbo.24.7.071607] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 10/12/2018] [Indexed: 05/26/2023]
Abstract
We present a method to recover absorption and reduced scattering spectra for each layer of a two-layer turbid media from spatial frequency-domain spectroscopy data. We focus on systems in which the thickness of the top layer is less than the transport mean free path ( 0.1 - 0.8l * ) . We utilize an analytic forward solver, based upon the N'th-order spherical harmonic expansion with Fourier decomposition ( SHEFN ) method in conjunction with a multistage inverse solver. We test our method with data obtained using spatial frequency-domain spectroscopy with 32 evenly spaced wavelengths within λ = 450 to 1000 nm on six-layered tissue phantoms with distinct optical properties. We demonstrate that this approach can recover absorption and reduced scattering coefficient spectra for both layers with accuracy comparable with current Monte Carlo methods but with lower computational cost and potential flexibility to easily handle variations in parameters such as the scattering phase function or material refractive index. To our knowledge, this approach utilizes the most accurate deterministic forward solver used in such problems and can successfully recover properties from a two-layer media with superficial layer thicknesses.
Collapse
Affiliation(s)
- Sean T. Horan
- University of California, Department of Mathematics, Irvine, California, United States
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States
| | - Adam R. Gardner
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States
- University of California, Department of Chemical Engineering and Materials Science, Irvine, California, United States
| | - Rolf Saager
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States
- Linköping University, Department of Biomedical Engineering, Linköping, Sweden
| | - Anthony J. Durkin
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States
- University of California, Department of Biomedical Engineering, Irvine, California, United States
| | - Vasan Venugopalan
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States
- University of California, Department of Chemical Engineering and Materials Science, Irvine, California, United States
- University of California, Department of Biomedical Engineering, Irvine, California, United States
| |
Collapse
|
|
23
|
Angelo JP, Chen SJ, Ochoa M, Sunar U, Gioux S, Intes X. Review of structured light in diffuse optical imaging. JOURNAL OF BIOMEDICAL OPTICS 2018; 24:1-20. [PMID: 30218503 PMCID: PMC6676045 DOI: 10.1117/1.jbo.24.7.071602] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 05/31/2018] [Indexed: 05/11/2023]
Abstract
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.
Collapse
Affiliation(s)
- Joseph P. Angelo
- National Institute of Standards and Technology, Sensor Science Division, Gaithersburg, Maryland, United States
- Address all correspondence to: Joseph P. Angelo, E-mail: ; Sez-Jade Chen, E-mail:
| | - Sez-Jade Chen
- Rensselaer Polytechnic Institute, Department of Biomedical Engineering, Troy, New York, United States
- Address all correspondence to: Joseph P. Angelo, E-mail: ; Sez-Jade Chen, E-mail:
| | - Marien Ochoa
- Rensselaer Polytechnic Institute, Department of Biomedical Engineering, Troy, New York, United States
| | - Ulas Sunar
- Wright State University, Department of Biomedical Industrial and Human Factor Engineering, Dayton, Ohio, United States
| | - Sylvain Gioux
- University of Strasbourg, ICube Laboratory, Strasbourg, France
| | - Xavier Intes
- Rensselaer Polytechnic Institute, Department of Biomedical Engineering, Troy, New York, United States
| |
Collapse
|
|
24
|
Sorgato V, Berger M, Emain C, Vever-Bizet C, Dinten JM, Bourg-Heckly G, Planat-Chrétien A. Validation of optical properties quantification with a dual-step technique for biological tissue analysis. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-14. [PMID: 30232845 DOI: 10.1117/1.jbo.23.9.096002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 08/06/2018] [Indexed: 06/08/2023]
Abstract
To approach wide-field optical properties quantification in real heterogeneous biological tissue, we developed a Dual-Step setup that couples a punctual diffuse reflectance spectroscopy (DRS) technique with multispectral imaging (MSI). The setup achieves wide-field optical properties assessment through an initial estimation of scattering with DRS, which is used to estimate absorption with MSI. The absolute quantification of optical properties is based on the ACA-Pro algorithm that has been adapted both for DRS and for MSI. This paper validates the Dual-Step system not only on homogeneous Intralipid phantoms but also on a heterogeneous gelatine phantom with different scattering and absorbing properties.
Collapse
Affiliation(s)
| | | | | | - Christine Vever-Bizet
- Sorbonne Universités, UPMC University Paris 06, CNRS UMR 8237, Laboratoire Jean Perrin, Paris, France
| | | | - Geneviève Bourg-Heckly
- Sorbonne Universités, UPMC University Paris 06, CNRS UMR 8237, Laboratoire Jean Perrin, Paris, France
| | | |
Collapse
|
|
25
|
Greening G, Mundo A, Rajaram N, Muldoon TJ. Sampling depth of a diffuse reflectance spectroscopy probe for in-vivo physiological quantification of murine subcutaneous tumor allografts. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-14. [PMID: 30152204 PMCID: PMC8357195 DOI: 10.1117/1.jbo.23.8.085006] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 07/23/2018] [Indexed: 05/04/2023]
Abstract
Diffuse reflectance spectroscopy (DRS) is a probe-based spectral biopsy technique used in cancer studies to quantify tissue reduced scattering (μs') and absorption (μa) coefficients and vary in source-detector separation (SDS) to fine-tune sampling depth. In subcutaneous murine tumor allografts or xenografts, a key design requirement is ensuring that the source light interrogates past the skin layer into the tumor without significantly sacrificing signal-to-noise ratio (target of ≥15 dB). To resolve this requirement, a DRS probe was designed with four SDSs (0.75, 2.00, 3.00, and 4.00 mm) to interrogate increasing tissue volumes between 450 and 900 nm. The goal was to quantify percent errors in extracting μa and μs', and to quantify sampling depth into subcutaneous Balb/c-CT26 colon tumor allografts. Using an optical phantom-based experimental method, lookup-tables were constructed relating μa,μs', diffuse reflectance, and sampling depth. Percent errors were <10 % and 5% for extracting μa and μs', respectively, for all SDSs. Sampling depth reached up to 1.6 mm at the first Q-band of hemoglobin at 542 nm, the key spectral region for quantifying tissue oxyhemoglobin concentration. This work shows that the DRS probe can accurately extract optical properties and the resultant physiological parameters such as total hemoglobin concentration and tissue oxygen saturation, from sufficient depth within subcutaneous Balb/c-CT26 colon tumor allografts. Methods described here can be generalized for other murine tumor models. Future work will explore the feasibility of the DRS in quantifying volumetric tumor perfusion in response to anticancer therapies.
Collapse
Affiliation(s)
- Gage Greening
- University of Arkansas, Department of Biomedical Engineering, Fayetteville, Arkansas, United States
| | - Ariel Mundo
- University of Arkansas, Department of Biomedical Engineering, Fayetteville, Arkansas, United States
| | - Narasimhan Rajaram
- University of Arkansas, Department of Biomedical Engineering, Fayetteville, Arkansas, United States
| | - Timothy J. Muldoon
- University of Arkansas, Department of Biomedical Engineering, Fayetteville, Arkansas, United States
- Address all correspondence to: Timothy J. Muldoon, E-mail:
| |
Collapse
|
|
26
|
Saager RB, Baldado ML, Rowland RA, Kelly KM, Durkin AJ. Method using in vivo quantitative spectroscopy to guide design and optimization of low-cost, compact clinical imaging devices: emulation and evaluation of multispectral imaging systems. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-12. [PMID: 29633609 PMCID: PMC5890028 DOI: 10.1117/1.jbo.23.4.046002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 03/16/2018] [Indexed: 05/30/2023]
Abstract
With recent proliferation in compact and/or low-cost clinical multispectral imaging approaches and commercially available components, questions remain whether they adequately capture the requisite spectral content of their applications. We present a method to emulate the spectral range and resolution of a variety of multispectral imagers, based on in-vivo data acquired from spatial frequency domain spectroscopy (SFDS). This approach simulates spectral responses over 400 to 1100 nm. Comparing emulated data with full SFDS spectra of in-vivo tissue affords the opportunity to evaluate whether the sparse spectral content of these imagers can (1) account for all sources of optical contrast present (completeness) and (2) robustly separate and quantify sources of optical contrast (crosstalk). We validate the approach over a range of tissue-simulating phantoms, comparing the SFDS-based emulated spectra against measurements from an independently characterized multispectral imager. Emulated results match the imager across all phantoms (<3 % absorption, <1 % reduced scattering). In-vivo test cases (burn wounds and photoaging) illustrate how SFDS can be used to evaluate different multispectral imagers. This approach provides an in-vivo measurement method to evaluate the performance of multispectral imagers specific to their targeted clinical applications and can assist in the design and optimization of new spectral imaging devices.
Collapse
Affiliation(s)
- Rolf B. Saager
- University of California, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Melissa L. Baldado
- University of California, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Rebecca A. Rowland
- University of California, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Kristen M. Kelly
- University of California, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
- University of California, Department of Dermatology, Irvine, California, United States
| | - Anthony J. Durkin
- University of California, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
- University of California, Department of Biomedical Engineering, Irvine, California, United States
| |
Collapse
|
|
27
|
Chen X, Lin W, Wang C, Chen S, Sheng J, Zeng B, Xu M. In vivo real-time imaging of cutaneous hemoglobin concentration, oxygen saturation, scattering properties, melanin content, and epidermal thickness with visible spatially modulated light. BIOMEDICAL OPTICS EXPRESS 2017; 8:5468-5482. [PMID: 29296481 PMCID: PMC5745096 DOI: 10.1364/boe.8.005468] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 10/20/2017] [Accepted: 10/24/2017] [Indexed: 05/04/2023]
Abstract
We present the real-time single snapshot multiple frequency demodulation - spatial frequency domain imaging (SSMD-SFDI) platform implemented with a visible digital mirror device that is capable of imaging and monitoring dynamic turbid medium and processes over a large field of view. One challenge in quantitative imaging of biological tissue such as the skin is the complex structure rendering techniques based on homogeneous medium models to fail. To address this difficulty we have also developed a novel method that maps the layered structure to a homogeneous medium for spatial frequency domain imaging. The varying penetration depth of spatially modulated light on its wavelength and modulation frequency is used to resolve the layered structure. The efficacy of the real-time SSMD-SFDI platform and this two-layer model is demonstrated by imaging forearms of 6 healthy subjects under the reactive hyperemia protocol. The results show that our approach not only successfully decouples light absorption by melanin from that by hemoglobin and yields accurate determination of cutaneous hemoglobin concentration and oxygen saturation, but also provides reliable estimation of the scattering properties, the melanin content and the epidermal thickness in real time. Potential applications of our system in imaging skin physiological and functional states, cancer screening, and microcirculation monitoring are discussed at the end.
Collapse
Affiliation(s)
- Xinlin Chen
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Weihao Lin
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Chenge Wang
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Shaoheng Chen
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Jing Sheng
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Bixin Zeng
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - M. Xu
- Institute of Lasers and Biomedical Photonics, Biomedical Engineering College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- Dept. of Physics, Fairfield University, 1073 North Road, Fairfield, CT 06824, USA
| |
Collapse
|
|
28
|
Saager RB, Dang AN, Huang SS, Kelly KM, Durkin AJ. Portable (handheld) clinical device for quantitative spectroscopy of skin, utilizing spatial frequency domain reflectance techniques. THE REVIEW OF SCIENTIFIC INSTRUMENTS 2017; 88:094302. [PMID: 28964218 PMCID: PMC5589466 DOI: 10.1063/1.5001075] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Spatial Frequency Domain Spectroscopy (SFDS) is a technique for quantifying in-vivo tissue optical properties. SFDS employs structured light patterns that are projected onto tissues using a spatial light modulator, such as a digital micromirror device. In combination with appropriate models of light propagation, this technique can be used to quantify tissue optical properties (absorption, μa, and scattering, μs', coefficients) and chromophore concentrations. Here we present a handheld implementation of an SFDS device that employs line (one dimensional) imaging. This instrument can measure 1088 spatial locations that span a 3 cm line as opposed to our original benchtop SFDS system that only collects a single 1 mm diameter spot. This imager, however, retains the spectral resolution (∼1 nm) and range (450-1000 nm) of our original benchtop SFDS device. In the context of homogeneous turbid media, we demonstrate that this new system matches the spectral response of our original system to within 1% across a typical range of spatial frequencies (0-0.35 mm-1). With the new form factor, the device has tremendously improved mobility and portability, allowing for greater ease of use in a clinical setting. A smaller size also enables access to different tissue locations, which increases the flexibility of the device. The design of this portable system not only enables SFDS to be used in clinical settings but also enables visualization of properties of layered tissues such as skin.
Collapse
Affiliation(s)
- Rolf B Saager
- Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA
| | - An N Dang
- Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA
| | - Samantha S Huang
- Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA
| | - Kristen M Kelly
- Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA
| | - Anthony J Durkin
- Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA
| |
Collapse
|
|
29
|
Lu Y, Lu R. Using composite sinusoidal patterns in structured-illumination reflectance imaging (SIRI) for enhanced detection of apple bruise. J FOOD ENG 2017. [DOI: 10.1016/j.jfoodeng.2016.12.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
|
|
30
|
Zhang S, Zhang L, Li G, Lin L. Suppression of inter-device variation for component analysis of turbid liquids based on spatially resolved diffuse reflectance spectroscopy. THE REVIEW OF SCIENTIFIC INSTRUMENTS 2017; 88:033104. [PMID: 28372427 DOI: 10.1063/1.4977788] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Diffuse reflectance spectroscopy is a useful tool for obtaining quantitative information in turbid media, which is always achieved by developing a multivariate regression model that links the spectral signal to the component concentrations. However, in most cases, variations between the actual measurement and the modeling process of the device may cause errors in predicting a component's concentration. In this paper, we propose a data-processing method to resist these variations. The method involves performing a curve fitting of the multiple-position diffuse reflectance spectral data. One of the parameters in the fitting function was found to be insensitive to inter-device variations and sensitive to the component concentrations. The parameter of the fitted equation was used in the modeling instead of directly using the spectral signal. Experiments demonstrate the feasibility of the proposed method and its resistance to errors induced by inter-device variations.
Collapse
Affiliation(s)
- Shengzhao Zhang
- State Key Laboratory of Precision Measurement Technology and Instrument, Tianjin 300072, China
| | - Linna Zhang
- State Key Laboratory of Precision Measurement Technology and Instrument, Tianjin 300072, China
| | - Gang Li
- State Key Laboratory of Precision Measurement Technology and Instrument, Tianjin 300072, China
| | - Ling Lin
- State Key Laboratory of Precision Measurement Technology and Instrument, Tianjin 300072, China
| |
Collapse
|
|
31
|
Vasefi F, MacKinnon N, Saager R, Kelly KM, Maly T, Booth N, Durkin AJ, Farkas DL. Separating melanin from hemodynamics in nevi using multimode hyperspectral dermoscopy and spatial frequency domain spectroscopy. JOURNAL OF BIOMEDICAL OPTICS 2016; 21:114001. [PMID: 27830262 PMCID: PMC5103103 DOI: 10.1117/1.jbo.21.11.114001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 10/07/2016] [Indexed: 05/20/2023]
Abstract
Changes in the pattern and distribution of both melanocytes (pigment producing) and vasculature (hemoglobin containing) are important in distinguishing melanocytic proliferations. The ability to accurately measure melanin distribution at different depths and to distinguish it from hemoglobin is clearly important when assessing pigmented lesions (benign versus malignant). We have developed a multimode hyperspectral dermoscope (SkinSpect™) able to more accurately image both melanin and hemoglobin distribution in skin. SkinSpect uses both hyperspectral and polarization-sensitive measurements. SkinSpect’s higher accuracy has been obtained by correcting for the effect of melanin absorption on hemoglobin absorption in measurements of melanocytic nevi. In vivo human skin pigmented nevi (N=20) were evaluated with the SkinSpect, and measured melanin and hemoglobin concentrations were compared with spatial frequency domain spectroscopy (SFDS) measurements. We confirm that both systems show low correlation of hemoglobin concentrations with regions containing different melanin concentrations (R=0.13 for SFDS, R=0.07 for SkinSpect).
Collapse
Affiliation(s)
- Fartash Vasefi
- Spectral Molecular Imaging Inc., 13412 Ventura Boulevard, Suite 250, Sherman Oaks, California 91423, United States
- Address all correspondence to: Fartash Vasefi, E-mail: ; Daniel L. Farkas, E-mail:
| | - Nicholas MacKinnon
- Spectral Molecular Imaging Inc., 13412 Ventura Boulevard, Suite 250, Sherman Oaks, California 91423, United States
| | - Rolf Saager
- University of California, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
| | - Kristen M. Kelly
- University of California, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
| | - Tyler Maly
- University of California, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
| | - Nicholas Booth
- Spectral Molecular Imaging Inc., 13412 Ventura Boulevard, Suite 250, Sherman Oaks, California 91423, United States
| | - Anthony J. Durkin
- University of California, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
| | - Daniel L. Farkas
- Spectral Molecular Imaging Inc., 13412 Ventura Boulevard, Suite 250, Sherman Oaks, California 91423, United States
- University of Southern California, Department of Biomedical Engineering, 1042 Downey Way, Los Angeles, California 90089, United States
- Address all correspondence to: Fartash Vasefi, E-mail: ; Daniel L. Farkas, E-mail:
| |
Collapse
|
|
32
|
Saager RB, Sharif A, Kelly KM, Durkin AJ. In vivo isolation of the effects of melanin from underlying hemodynamics across skin types using spatial frequency domain spectroscopy. JOURNAL OF BIOMEDICAL OPTICS 2016; 21:57001. [PMID: 27143641 PMCID: PMC4890358 DOI: 10.1117/1.jbo.21.5.057001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Accepted: 04/13/2016] [Indexed: 05/03/2023]
Abstract
Skin is a highly structured tissue, raising concerns as to whether skin pigmentation due to epidermal melanin may confound accurate measurements of underlying hemodynamics. Using both venous and arterial cuff occlusions as a means of inducing differential hemodynamic perturbations, we present analyses of spectra limited to the visible or near-infrared regime, in addition to a layered model approach. The influence of melanin, spanning Fitzpatrick skin types I to V, on underlying estimations of hemodynamics in skin as interpreted by these spectral regions are assessed. The layered model provides minimal cross-talk between melanin and hemodynamics and enables removal of problematic correlations between measured tissue oxygenation estimates and skin phototype.
Collapse
Affiliation(s)
- Rolf B. Saager
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612, United States
- Address all correspondence to: Rolf B. Saager, E-mail:
| | - Ata Sharif
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612, United States
| | - Kristen M. Kelly
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612, United States
- University of California, Irvine, Department of Dermatology, 118 Medical Surge 1, Irvine, California 92697, United States
| | - Anthony J. Durkin
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612, United States
| |
Collapse
|
|
33
|
Diep P, Pannem S, Sweer J, Lo J, Snyder M, Stueber G, Zhao Y, Tabassum S, Istfan R, Wu J, Erramilli S, Roblyer D. Three-dimensional printed optical phantoms with customized absorption and scattering properties. BIOMEDICAL OPTICS EXPRESS 2015; 6:4212-20. [PMID: 26600987 PMCID: PMC4646531 DOI: 10.1364/boe.6.004212] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 09/24/2015] [Accepted: 09/29/2015] [Indexed: 05/13/2023]
Abstract
Three-dimensional (3D) printing offers the promise of fabricating optical phantoms with arbitrary geometry, but commercially available thermoplastics provide only a small range of physiologically relevant absorption (µa) and reduced scattering (µs`) values. Here we demonstrate customizable acrylonitrile butadiene styrene (ABS) filaments for dual extrusion 3D printing of tissue mimicking optical phantoms. µa and µs` values were adjusted by incorporating nigrosin and titanium dioxide (TiO2) in the filament extrusion process. A wide range of physiologically relevant optical properties was demonstrated with an average repeatability within 11.5% for µa and 7.71% for µs`. Additionally, a mouse-simulating phantom, which mimicked both the geometry and optical properties of a hairless mouse with an implanted xenograft tumor, was printed using dual extrusion methods. 3D printed tumor optical properties matched the live tumor with less than 3% error at a wavelength of 659 nm. 3D printing with user defined optical properties may provide a viable method for durable optically diffusive phantoms for instrument characterization and calibration.
Collapse
Affiliation(s)
- Phuong Diep
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
- These authors contributed equally to this work
| | - Sanjana Pannem
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
- These authors contributed equally to this work
| | - Jordan Sweer
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
- These authors contributed equally to this work
| | - Justine Lo
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
| | - Michael Snyder
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
| | - Gabriella Stueber
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
| | - Yanyu Zhao
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
| | - Syeda Tabassum
- Department of Electrical Engineering, Boston University, Boston, MA 02115, USA
| | - Raeef Istfan
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
| | - Junjie Wu
- Department of Biology, Boston University, Boston, MA 02115, USA
| | - Shyamsunder Erramilli
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
- Department of Physics, Boston University, Boston, MA 02115, USA
| | - Darren Roblyer
- Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA
| |
Collapse
|
|
34
|
Lin AJ, Ponticorvo A, Durkin AJ, Venugopalan V, Choi B, Tromberg BJ. Differential pathlength factor informs evoked stimulus response in a mouse model of Alzheimer's disease. NEUROPHOTONICS 2015; 2:045001. [PMID: 26835482 PMCID: PMC4718154 DOI: 10.1117/1.nph.2.4.045001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 09/15/2015] [Indexed: 05/03/2023]
Abstract
Baseline optical properties are typically assumed in calculating the differential pathlength factor (DPF) of mouse brains, a value used in the modified Beer-Lambert law to characterize an evoked stimulus response. We used spatial frequency domain imaging to measure in vivo baseline optical properties in 20-month-old control ([Formula: see text]) and triple transgenic APP/PS1/tau (3xTg-AD) ([Formula: see text]) mouse brains. Average [Formula: see text] for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text], respectively, at 460 nm; and [Formula: see text] and [Formula: see text], respectively, at 530 nm. Average [Formula: see text] for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text], respectively, at 460 nm; and [Formula: see text] and [Formula: see text], respectively, at 530 nm. The calculated DPF for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text] OD mm, respectively, at 460 nm; and [Formula: see text] and [Formula: see text] OD mm, respectively, at 530 nm. In hindpaw stimulation experiments, the hemodynamic increase in brain tissue concentration of oxyhemoglobin was threefold larger and two times longer in the control mice compared to 3xTg-AD mice. Furthermore, the washout of deoxyhemoglobin from increased brain perfusion was seven times larger in controls compared to 3xTg-AD mice ([Formula: see text]).
Collapse
Affiliation(s)
- Alexander J. Lin
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
- University of California, Irvine, Department of Biomedical Engineering, 3120 Natural Sciences II, Irvine, California 92697-2715, United States
| | - Adrien Ponticorvo
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
| | - Anthony J. Durkin
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
| | - Vasan Venugopalan
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
- University of California, Irvine, Department of Chemical Engineering and Materials Science, 916 Engineering Tower, Irvine, California 92697-2575, United States
| | - Bernard Choi
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
- University of California, Irvine, Department of Biomedical Engineering, 3120 Natural Sciences II, Irvine, California 92697-2715, United States
- University of California, Irvine, Edwards Lifesciences Center for Advanced Cardiovascular Technology, 2400 Engineering Hall, Irvine, California 92697-2730, United States
| | - Bruce J. Tromberg
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612, United States
- University of California, Irvine, Department of Biomedical Engineering, 3120 Natural Sciences II, Irvine, California 92697-2715, United States
- Address all correspondence to: Bruce J. Tromberg, E-mail:
| |
Collapse
|
|
35
|
Saager RB, Balu M, Crosignani V, Sharif A, Durkin AJ, Kelly KM, Tromberg BJ. In vivo measurements of cutaneous melanin across spatial scales: using multiphoton microscopy and spatial frequency domain spectroscopy. JOURNAL OF BIOMEDICAL OPTICS 2015; 20:066005. [PMID: 26065839 PMCID: PMC4463032 DOI: 10.1117/1.jbo.20.6.066005] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 05/18/2015] [Indexed: 05/19/2023]
Abstract
The combined use of nonlinear optical microscopy and broadband reflectance techniques to assess melanin concentration and distribution thickness in vivo over the full range of Fitzpatrick skin types is presented. Twelve patients were measured using multiphoton microscopy (MPM) and spatial frequency domain spectroscopy (SFDS) on both dorsal forearm and volar arm, which are generally sun-exposed and non-sun-exposed areas, respectively. Both MPM and SFDS measured melanin volume fractions between (skin type I non-sun-exposed) and 20% (skin type VI sun exposed). MPM measured epidermal (anatomical) thickness values ~30-65 μm, while SFDS measured melanin distribution thickness based on diffuse optical path length. There was a strong correlation between melanin concentration and melanin distribution (epidermal) thickness measurements obtained using the two techniques. While SFDS does not have the ability to match the spatial resolution of MPM, this study demonstrates that melanin content as quantified using SFDS is linearly correlated with epidermal melanin as measured using MPM (R² = 0.8895). SFDS melanin distribution thickness is correlated to MPM values (R² = 0.8131). These techniques can be used individually and/or in combination to advance our understanding and guide therapies for pigmentation-related conditions as well as light-based treatments across a full range of skin types.
Collapse
Affiliation(s)
- Rolf B. Saager
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, 92612, United States
- Address all correspondence to: Rolf B. Saager, E-mail:
| | - Mihaela Balu
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, 92612, United States
| | - Viera Crosignani
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, 92612, United States
| | - Ata Sharif
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, 92612, United States
| | - Anthony J. Durkin
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, 92612, United States
| | - Kristen M. Kelly
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, 92612, United States
- University of California, Department of Dermatology, Irvine, California, 92697, United States
| | - Bruce J. Tromberg
- University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, 92612, United States
| |
Collapse
|
|
36
|
Polarization-sensitive hyperspectral imaging in vivo: a multimode dermoscope for skin analysis. Sci Rep 2014; 4:4924. [PMID: 24815987 PMCID: PMC4017245 DOI: 10.1038/srep04924] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 04/23/2014] [Indexed: 11/08/2022] Open
Abstract
Attempts to understand the changes in the structure and physiology of human skin abnormalities by non-invasive optical imaging are aided by spectroscopic methods that quantify, at the molecular level, variations in tissue oxygenation and melanin distribution. However, current commercial and research systems to map hemoglobin and melanin do not correlate well with pathology for pigmented lesions or darker skin. We developed a multimode dermoscope that combines polarization and hyperspectral imaging with an efficient analytical model to map the distribution of specific skin bio-molecules. This corrects for the melanin-hemoglobin misestimation common to other systems, without resorting to complex and computationally intensive tissue optical models. For this system's proof of concept, human skin measurements on melanocytic nevus, vitiligo, and venous occlusion conditions were performed in volunteers. The resulting molecular distribution maps matched physiological and anatomical expectations, confirming a technologic approach that can be applied to next generation dermoscopes and having biological plausibility that is likely to appeal to dermatologists.
Collapse
|
|
37
|
Saager RB, Cuccia DJ, Saggese S, Kelly KM, Durkin AJ. A light emitting diode (LED) based spatial frequency domain imaging system for optimization of photodynamic therapy of nonmelanoma skin cancer: quantitative reflectance imaging. Lasers Surg Med 2013; 45:207-15. [PMID: 23619900 DOI: 10.1002/lsm.22139] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/24/2013] [Indexed: 01/10/2023]
Abstract
BACKGROUND Photodynamic therapy (PDT) offers the potential for enhanced treatment of nonmelanoma skin cancer (NMSC) with minimal scarring. Yet, PDT has not achieved consistent long term effectiveness to gain widespread clinical acceptance for treatment of skin cancer. Therapeutic response varies between practitioners, patients and lesions. One important contributing factor is the absence of quantitative tools to perform in vivo dosimetry. To this end, we have developed a new quantitative imaging device that can be used to investigate parameters related to optimizing dosimetry. METHODS We present a spatial frequency domain imaging (SFDI) based device designed to: (1) determine the optical properties at the therapeutic wavelength, which can inform variations in light penetration depth and (2) measure the spatially resolved oxygen saturation of the skin cancer lesions and surrounding tissue. We have applied this system to a preliminary clinical study of nine skin cancer lesions. RESULTS Optical properties vary greatly both spatially [101%, 48% for absorption and reduced scattering, respectively] and across patients [102%, 57%]. Blood volume maps determined using visible wavelengths (460, 525, and 630 nm) represent tissue volumes within ∼1 mm in tissue (1.17 ± 0.3 mm). Here the average total hemoglobin concentration is approximately three times greater in the lesion than that detected in normal tissue, reflecting increased vasculature typically associated with tumors. Data acquired at near infrared wavelengths (730 and 850 nm) reports tissue blood concentrations and oxygenations from the underlying dermal microvasculature (volumes reaching 4.36 ± 1.32 mm into tissue). CONCLUSIONS SFDI can be used to quantitatively characterize in vivo tissue optical properties that could be useful for better informing PDT treatment parameters. Specifically, this information provides spatially resolved insight into light delivery into tissue and local tissue oxygenation, thereby providing more quantitative and controlled dosimetry specific to the lesion. Ultimately, by optimizing the execution of PDT, this instrument has the potential to positively improve treatment outcomes.
Collapse
Affiliation(s)
- R B Saager
- Beckman Laser Institute, UC Irvine, Irvine, California, USA
| | | | | | | | | |
Collapse
|
|
38
|
Lin AJ, Ponticorvo A, Konecky SD, Cui H, Rice TB, Choi B, Durkin AJ, Tromberg BJ. Visible spatial frequency domain imaging with a digital light microprojector. JOURNAL OF BIOMEDICAL OPTICS 2013; 18:096007. [PMID: 24005154 PMCID: PMC3762936 DOI: 10.1117/1.jbo.18.9.096007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Revised: 07/16/2013] [Accepted: 07/31/2013] [Indexed: 05/18/2023]
Abstract
There is a need for cost effective, quantitative tissue spectroscopy and imaging systems in clinical diagnostics and pre-clinical biomedical research. A platform that utilizes a commercially available light-emitting diode (LED) based projector, cameras, and scaled Monte Carlo model for calculating tissue optical properties is presented. These components are put together to perform spatial frequency domain imaging (SFDI), a model-based reflectance technique that measures and maps absorption coefficients (μa) and reduced scattering coefficients (μs') in thick tissue such as skin or brain. We validate the performance of the flexible LED and modulation element (FLaME) system at 460, 530, and 632 nm across a range of physiologically relevant μa values (0.07 to 1.5 mm-1) in tissue-simulating intralipid phantoms, showing an overall accuracy within 11% of spectrophotometer values for μa and 3% for μs'. Comparison of oxy- and total hemoglobin fits between the FLaME system and a spectrophotometer (450 to 1000 nm) is differed by 3%. Finally, we acquire optical property maps of a mouse brain in vivo with and without an overlying saline well. These results demonstrate the potential of FLaME to perform tissue optical property mapping in visible spectral regions and highlight how the optical clearing effect of saline is correlated to a decrease in μs' of the skull.
Collapse
Affiliation(s)
- Alexander J. Lin
- University of California, Beckman Laser Institute and Medical Clinic, Department of Surgery, Irvine, California
- University of California, Department of Biomedical Engineering, Irvine, California
| | - Adrien Ponticorvo
- University of California, Beckman Laser Institute and Medical Clinic, Department of Surgery, Irvine, California
| | - Soren D. Konecky
- University of California, Beckman Laser Institute and Medical Clinic, Department of Surgery, Irvine, California
| | - Haotian Cui
- University of California, Beckman Laser Institute and Medical Clinic, Department of Surgery, Irvine, California
- University of California, Department of Biomedical Engineering, Irvine, California
| | - Tyler B. Rice
- University of California, Beckman Laser Institute and Medical Clinic, Department of Surgery, Irvine, California
| | - Bernard Choi
- University of California, Beckman Laser Institute and Medical Clinic, Department of Surgery, Irvine, California
- University of California, Department of Biomedical Engineering, Irvine, California
- University of California, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Irvine, California
| | - Anthony J. Durkin
- University of California, Beckman Laser Institute and Medical Clinic, Department of Surgery, Irvine, California
| | - Bruce J. Tromberg
- University of California, Beckman Laser Institute and Medical Clinic, Department of Surgery, Irvine, California
- University of California, Department of Biomedical Engineering, Irvine, California
- Address all correspondence to: Bruce J. Tromberg, Beckman Laser Institute, 1002 Health Sciences Road, Irvine, California 92612. Tel: +949-824-8705; Fax: +949-824-8413; E-mail:
| |
Collapse
|
|
39
|
Saager RB, Cuccia DJ, Saggese S, Kelly KM, Durkin AJ. A light emitting diode (LED) based spatial frequency domain imaging system for optimization of photodynamic therapy of nonmelanoma skin cancer: quantitative reflectance imaging. Lasers Surg Med 2013. [PMID: 23619900 DOI: 10.1002/lsm.v45.4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
BACKGROUND Photodynamic therapy (PDT) offers the potential for enhanced treatment of nonmelanoma skin cancer (NMSC) with minimal scarring. Yet, PDT has not achieved consistent long term effectiveness to gain widespread clinical acceptance for treatment of skin cancer. Therapeutic response varies between practitioners, patients and lesions. One important contributing factor is the absence of quantitative tools to perform in vivo dosimetry. To this end, we have developed a new quantitative imaging device that can be used to investigate parameters related to optimizing dosimetry. METHODS We present a spatial frequency domain imaging (SFDI) based device designed to: (1) determine the optical properties at the therapeutic wavelength, which can inform variations in light penetration depth and (2) measure the spatially resolved oxygen saturation of the skin cancer lesions and surrounding tissue. We have applied this system to a preliminary clinical study of nine skin cancer lesions. RESULTS Optical properties vary greatly both spatially [101%, 48% for absorption and reduced scattering, respectively] and across patients [102%, 57%]. Blood volume maps determined using visible wavelengths (460, 525, and 630 nm) represent tissue volumes within ∼1 mm in tissue (1.17 ± 0.3 mm). Here the average total hemoglobin concentration is approximately three times greater in the lesion than that detected in normal tissue, reflecting increased vasculature typically associated with tumors. Data acquired at near infrared wavelengths (730 and 850 nm) reports tissue blood concentrations and oxygenations from the underlying dermal microvasculature (volumes reaching 4.36 ± 1.32 mm into tissue). CONCLUSIONS SFDI can be used to quantitatively characterize in vivo tissue optical properties that could be useful for better informing PDT treatment parameters. Specifically, this information provides spatially resolved insight into light delivery into tissue and local tissue oxygenation, thereby providing more quantitative and controlled dosimetry specific to the lesion. Ultimately, by optimizing the execution of PDT, this instrument has the potential to positively improve treatment outcomes.
Collapse
Affiliation(s)
- R B Saager
- Beckman Laser Institute, UC Irvine, Irvine, California, USA
| | | | | | | | | |
Collapse
|
|
40
|
Sunar U, Rohrbach DJ, Morgan J, Zeitouni N, Henderson BW. Quantification of PpIX concentration in basal cell carcinoma and squamous cell carcinoma models using spatial frequency domain imaging. BIOMEDICAL OPTICS EXPRESS 2013; 4:531-7. [PMID: 23577288 PMCID: PMC3617715 DOI: 10.1364/boe.4.000531] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Revised: 03/05/2013] [Accepted: 03/05/2013] [Indexed: 05/17/2023]
Abstract
5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is an attractive treatment option for nonmelanoma skin tumors, especially for multiple lesions and large areas. The efficacy of ALA-PDT is highly dependent on the photosensitizer (PS) concentration present in the tumor. Thus it is desirable to quantify PS concentration and distribution, preferably noninvasively to determine potential outcome. Here we quantified protoporphyrin IX (PpIX) distribution induced by topical and intra-tumoral (it) administration of the prodrug ALA in basal and squamous cell carcinoma murine models by using spatial frequency domain imaging (SFDI). The in vivo measurements were validated by analysis of the ex vivo extraction of PpIX. The study demonstrates the feasibility of non-invasive quantification of PpIX distributions in skin tumors.
Collapse
Affiliation(s)
- Ulas Sunar
- Department of Cell Stress Biology & PDT Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
| | - Daniel J. Rohrbach
- Department of Cell Stress Biology & PDT Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
| | - Janet Morgan
- Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
| | - Natalie Zeitouni
- Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
| | - Barbara W. Henderson
- Department of Cell Stress Biology & PDT Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
| |
Collapse
|
|
41
|
Saager RB, Cuccia DJ, Saggese S, Kelly KM, Durkin AJ. A light emitting diode (LED) based spatial frequency domain imaging system for optimization of photodynamic therapy of nonmelanoma skin cancer: quantitative reflectance imaging. Lasers Surg Med 2013. [PMID: 23619900 DOI: 10.1364/fio.2010.ftus2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
Abstract
BACKGROUND Photodynamic therapy (PDT) offers the potential for enhanced treatment of nonmelanoma skin cancer (NMSC) with minimal scarring. Yet, PDT has not achieved consistent long term effectiveness to gain widespread clinical acceptance for treatment of skin cancer. Therapeutic response varies between practitioners, patients and lesions. One important contributing factor is the absence of quantitative tools to perform in vivo dosimetry. To this end, we have developed a new quantitative imaging device that can be used to investigate parameters related to optimizing dosimetry. METHODS We present a spatial frequency domain imaging (SFDI) based device designed to: (1) determine the optical properties at the therapeutic wavelength, which can inform variations in light penetration depth and (2) measure the spatially resolved oxygen saturation of the skin cancer lesions and surrounding tissue. We have applied this system to a preliminary clinical study of nine skin cancer lesions. RESULTS Optical properties vary greatly both spatially [101%, 48% for absorption and reduced scattering, respectively] and across patients [102%, 57%]. Blood volume maps determined using visible wavelengths (460, 525, and 630 nm) represent tissue volumes within ∼1 mm in tissue (1.17 ± 0.3 mm). Here the average total hemoglobin concentration is approximately three times greater in the lesion than that detected in normal tissue, reflecting increased vasculature typically associated with tumors. Data acquired at near infrared wavelengths (730 and 850 nm) reports tissue blood concentrations and oxygenations from the underlying dermal microvasculature (volumes reaching 4.36 ± 1.32 mm into tissue). CONCLUSIONS SFDI can be used to quantitatively characterize in vivo tissue optical properties that could be useful for better informing PDT treatment parameters. Specifically, this information provides spatially resolved insight into light delivery into tissue and local tissue oxygenation, thereby providing more quantitative and controlled dosimetry specific to the lesion. Ultimately, by optimizing the execution of PDT, this instrument has the potential to positively improve treatment outcomes.
Collapse
Affiliation(s)
- R B Saager
- Beckman Laser Institute, UC Irvine, Irvine, California, USA
| | | | | | | | | |
Collapse
|
|
42
|
O’Sullivan TD, Cerussi AE, Cuccia DJ, Tromberg BJ. Diffuse optical imaging using spatially and temporally modulated light. JOURNAL OF BIOMEDICAL OPTICS 2012; 17:071311. [PMID: 22894472 PMCID: PMC3607494 DOI: 10.1117/1.jbo.17.7.071311] [Citation(s) in RCA: 131] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2012] [Accepted: 06/28/2012] [Indexed: 05/18/2023]
Abstract
The authors describe the development of diffuse optical imaging (DOI) technologies, specifically the use of spatial and temporal modulation to control near infrared light propagation in thick tissues. We present theory and methods of DOI focusing on model-based techniques for quantitative, in vivo measurements of endogenous tissue absorption and scattering properties. We specifically emphasize the common conceptual framework of the scalar photon density wave for both temporal and spatial frequency-domain approaches. After presenting the history, theoretical foundation, and instrumentation related to these methods, we provide a brief review of clinical and preclinical applications from our research as well as our outlook on the future of DOI technology.
Collapse
Affiliation(s)
- Thomas D. O’Sullivan
- University of California, Irvine, Laser Microbeam and Medical Program (LAMMP), Beckman Laser Institute and Medical Clinic, Irvine, California
| | - Albert E. Cerussi
- University of California, Irvine, Laser Microbeam and Medical Program (LAMMP), Beckman Laser Institute and Medical Clinic, Irvine, California
| | | | - Bruce J. Tromberg
- University of California, Irvine, Laser Microbeam and Medical Program (LAMMP), Beckman Laser Institute and Medical Clinic, Irvine, California
- Address all correspondence to: Bruce J. Tromberg, University of California, Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road, Irvine, California 92612. Tel: +949 824 8705; Fax: 949 824 8413; E-mail:
| |
Collapse
|