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1
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Hwang J, Cheney P, Kanick SC, Le HND, McClatchy DM, Zhang H, Liu N, John Lu ZQ, Cho TJ, Briggman K, Allen DW, Wells WA, Pogue BW. Hyperspectral dark-field microscopy of human breast lumpectomy samples for tumor margin detection in breast-conserving surgery. JOURNAL OF BIOMEDICAL OPTICS 2024; 29:093503. [PMID: 38715717 PMCID: PMC11075096 DOI: 10.1117/1.jbo.29.9.093503] [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: 12/26/2023] [Revised: 03/18/2024] [Accepted: 03/20/2024] [Indexed: 01/06/2025]
Abstract
Significance Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human post-lumpectomy breast tissues excised during breast-conserving surgeries. Aim We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples. Approach Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed. The performance of the HSDFM is evaluated by comparing the backscattering intensity spectra of polystyrene microbead solutions with the Monte Carlo simulation of the experimental data. For classification algorithms, two analysis approaches, a supervised technique based on the spectral angle mapper (SAM) algorithm and an unsupervised technique based on the K -means algorithm are applied to classify various tissue types including carcinoma subtypes. In the supervised technique, the SAM algorithm with manually extracted endmembers guided by H&E annotations is used as reference spectra, allowing for segmentation maps with classified tissue types including carcinoma subtypes. Results The manually extracted endmembers of known tissue types and their corresponding threshold spectral correlation angles for classification make a good reference library that validates endmembers computed by the unsupervised K -means algorithm. The unsupervised K -means algorithm, with no a priori information, produces abundance maps with dominant endmembers of various tissue types, including carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma. The two carcinomas' unique endmembers produced by the two methods agree with each other within < 2 % residual error margin. Conclusions Our report demonstrates a robust procedure for the validation of an unsupervised algorithm with the essential set of parameters based on the ground truth, histopathological information. We have demonstrated that a trained library of the histopathology-guided endmembers and associated threshold spectral correlation angles computed against well-defined reference data cubes serve such parameters. Two classification algorithms, supervised and unsupervised algorithms, are employed to identify regions with carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma present in the tissues. The two carcinomas' unique endmembers used by the two methods agree to < 2 % residual error margin. This library of high quality and collected under an environment with no ambient background may be instrumental to develop or validate more advanced unsupervised data cube analysis algorithms, such as effective neural networks for efficient subtype classification.
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Affiliation(s)
- Jeeseong Hwang
- National Institute of Standards and Technology, Applied Physics Division, Boulder, Colorado, United States
| | - Philip Cheney
- National Institute of Standards and Technology, Applied Physics Division, Boulder, Colorado, United States
- Battelle Memorial Institute, Columbus, Ohio, United States
| | - Stephen C. Kanick
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
| | - Hanh N. D. Le
- National Institute of Standards and Technology, Applied Physics Division, Boulder, Colorado, United States
| | - David M. McClatchy
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
- Massachusetts General Hospital, Department of Radiation Oncology, Boston, Massachusetts, United States
| | - Helen Zhang
- National Institute of Standards and Technology, Applied Physics Division, Boulder, Colorado, United States
| | - Nian Liu
- National Institute of Standards and Technology, Statistical Engineering Division, Gaithersburg, Maryland, United States
| | - Zhan-Qian John Lu
- National Institute of Standards and Technology, Statistical Engineering Division, Gaithersburg, Maryland, United States
| | - Tae Joon Cho
- National Institute of Standards and Technology, Materials Measurement Science Division, Gaithersburg, Maryland, United States
| | - Kimberly Briggman
- National Institute of Standards and Technology, Applied Physics Division, Boulder, Colorado, United States
| | - David W. Allen
- National Institute of Standards and Technology, Sensor Science Division, Gaithersburg, Maryland, United States
| | - Wendy A. Wells
- Dartmouth Hitchcock Medical Center, Department of Pathology, Lebanon, New Hampshire, United States
| | - Brian W. Pogue
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
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2
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Genina EA, Lazareva EN, Surkov YI, Serebryakova IA, Shushunova NA. Optical parameters of healthy and tumor breast tissues in mice. JOURNAL OF BIOPHOTONICS 2024; 17:e202400123. [PMID: 38925916 DOI: 10.1002/jbio.202400123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/23/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024]
Abstract
Knowledge of the optical parameters of tumors is important for choosing the correct laser treatment parameters. In this paper, optical properties and refraction indices of breast tissue in healthy mice and a 4T1 model mimicking human breast cancer have been measured. A significant decrease in both the scattering and refractive index of tumor tissue has been observed. The change in tissue morphology has induced the change in the slope of the scattering spectrum. Thus, the light penetration depth into tumor has increased by almost 1.5-2 times in the near infrared "optical windows." Raman spectra have shown lower lipid content and higher protein content in tumor. The difference in the optical parameters of the tissues under study makes it possible to reliably differentiate them. The results may be useful for modeling the distribution of laser radiation in healthy tissues and cancers for deriving optimal irradiation conditions in photodynamic therapy.
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Affiliation(s)
- Elina A Genina
- Institute of Physics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Ekaterina N Lazareva
- Institute of Physics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Yuri I Surkov
- Institute of Physics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
- Laboratory of Biomedical Photoacoustic, Saratov State University, Saratov, Russia
| | - Isabella A Serebryakova
- Institute of Physics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Natalya A Shushunova
- Laboratory of Biomedical Photoacoustic, Saratov State University, Saratov, Russia
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3
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Chang S, Krzyzanowska H, Bowden AK. Label-Free Optical Technologies to Enhance Noninvasive Endoscopic Imaging of Early-Stage Cancers. ANNUAL REVIEW OF ANALYTICAL CHEMISTRY (PALO ALTO, CALIF.) 2024; 17:289-311. [PMID: 38424030 DOI: 10.1146/annurev-anchem-061622-014208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
White light endoscopic imaging allows for the examination of internal human organs and is essential in the detection and treatment of early-stage cancers. To facilitate diagnosis of precancerous changes and early-stage cancers, label-free optical technologies that provide enhanced malignancy-specific contrast and depth information have been extensively researched. The rapid development of technology in the past two decades has enabled integration of these optical technologies into clinical endoscopy. In recent years, the significant advantages of using these adjunct optical devices have been shown, suggesting readiness for clinical translation. In this review, we provide an overview of the working principles and miniaturization considerations and summarize the clinical and preclinical demonstrations of several such techniques for early-stage cancer detection. We also offer an outlook for the integration of multiple technologies and the use of computer-aided diagnosis in clinical endoscopy.
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Affiliation(s)
- Shuang Chang
- 1Vanderbilt Biophotonics Center, Vanderbilt University, Nashville, Tennessee, USA;
- 2Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Halina Krzyzanowska
- 1Vanderbilt Biophotonics Center, Vanderbilt University, Nashville, Tennessee, USA;
- 2Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Audrey K Bowden
- 1Vanderbilt Biophotonics Center, Vanderbilt University, Nashville, Tennessee, USA;
- 2Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
- 3Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, Tennessee, USA
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4
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Dao E, Gohla G, Williams P, Lovrics P, Badr F, Fang Q, Farrell T, Farquharson M. Breast tissue analysis using a clinically compatible combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system. Lasers Surg Med 2023; 55:769-783. [PMID: 37526280 DOI: 10.1002/lsm.23710] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 06/29/2023] [Accepted: 07/11/2023] [Indexed: 08/02/2023]
Abstract
OBJECTIVE This work aims to develop a clinically compatible system that can perform breast tissue analysis in a more time efficient process than conventional histopathological assessment. The potential for such a system to be used in vivo in the operating room or surgical suite to improve patient outcome is investigated. METHOD In this work, 80 matched pairs of invasive ductal carcinoma and adjacent normal breast tissue were measured in a combined time-resolved fluorescence and diffuse reflectance (DA) system. Following measurement, the fluorescence intensity of collagen and flavin adenine dinucleotide (FAD); the fluorescence lifetime of collagen, nicotinamide adenine dinucleotide (NADH), and FAD; the DA; absorption coefficient; and reduced scattering coefficient were extracted. Samples then underwent histological processing and H&E staining to classify composition as tumor, fibroglandular, and/or adipose tissue. RESULTS Statistically significant differences in the collagen and FAD fluorescence intensity, collagen and FAD fluorescence lifetime, DA, and scattering coefficient were found between each tissue group. The NADH fluorescence lifetime and absorption coefficient were statistically different between the tumor and fibroglandular groups, and the tumor and adipose groups. While many breast tissue analysis studies label fibroglandular and adipose together as "normal" breast tissue, this work indicates that some differences between tumor and fibroglandular tissue are not the same as differences between tumor and adipose tissue. Observations of the reduced scatter coefficient may also indicate further classification to include fibro-adipose may be necessary. Future work would benefit from the additional tissue classification. CONCLUSION With observable differences in optical parameters between the three tissue types, this system shows promise as a breast analysis tool in a clinical setting. With further work involving samples of mixed composition, this combined system could potentially be used intraoperatively for rapid margin assessment.
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Affiliation(s)
- Erica Dao
- Department of Physics & Astronomy, McMaster University, Hamilton, Canada
| | - Gabriela Gohla
- St. Joseph's Healthcare, Hamilton, Canada
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
| | - Phillip Williams
- St. Joseph's Healthcare, Hamilton, Canada
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
| | - Peter Lovrics
- St. Joseph's Healthcare, Hamilton, Canada
- Department of Surgery, McMaster University, Hamilton, Canada
| | - Fares Badr
- Department of Engineering Physics, McMaster University, Hamilton, Canada
| | - Qiyin Fang
- Department of Engineering Physics, McMaster University, Hamilton, Canada
| | - Thomas Farrell
- School of Interdisciplinary Science, Hamilton, Canada
- Juravinski Hospital and Cancer Center, Hamilton, Canada
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Shanthakumar D, Leiloglou M, Kelliher C, Darzi A, Elson DS, Leff DR. A Comparison of Spectroscopy and Imaging Techniques Utilizing Spectrally Resolved Diffusely Reflected Light for Intraoperative Margin Assessment in Breast-Conserving Surgery: A Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:cancers15112884. [PMID: 37296847 DOI: 10.3390/cancers15112884] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/12/2023] [Accepted: 05/16/2023] [Indexed: 06/12/2023] Open
Abstract
Up to 19% of patients require re-excision surgery due to positive margins in breast-conserving surgery (BCS). Intraoperative margin assessment tools (IMAs) that incorporate tissue optical measurements could help reduce re-excision rates. This review focuses on methods that use and assess spectrally resolved diffusely reflected light for breast cancer detection in the intraoperative setting. Following PROSPERO registration (CRD42022356216), an electronic search was performed. The modalities searched for were diffuse reflectance spectroscopy (DRS), multispectral imaging (MSI), hyperspectral imaging (HSI), and spatial frequency domain imaging (SFDI). The inclusion criteria encompassed studies of human in vivo or ex vivo breast tissues, which presented data on accuracy. The exclusion criteria were contrast use, frozen samples, and other imaging adjuncts. 19 studies were selected following PRISMA guidelines. Studies were divided into point-based (spectroscopy) or whole field-of-view (imaging) techniques. A fixed-or random-effects model analysis generated pooled sensitivity/specificity for the different modalities, following heterogeneity calculations using the Q statistic. Overall, imaging-based techniques had better pooled sensitivity/specificity (0.90 (CI 0.76-1.03)/0.92 (CI 0.78-1.06)) compared with probe-based techniques (0.84 (CI 0.78-0.89)/0.85 (CI 0.79-0.91)). The use of spectrally resolved diffusely reflected light is a rapid, non-contact technique that confers accuracy in discriminating between normal and malignant breast tissue, and it constitutes a potential IMA tool.
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Affiliation(s)
- Dhurka Shanthakumar
- Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK
- The Hamlyn Centre, Imperial College London, London SW7 2AZ, UK
| | - Maria Leiloglou
- Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK
- The Hamlyn Centre, Imperial College London, London SW7 2AZ, UK
| | - Colm Kelliher
- Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK
| | - Ara Darzi
- Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK
- The Hamlyn Centre, Imperial College London, London SW7 2AZ, UK
| | - Daniel S Elson
- Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK
- The Hamlyn Centre, Imperial College London, London SW7 2AZ, UK
| | - Daniel R Leff
- Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK
- The Hamlyn Centre, Imperial College London, London SW7 2AZ, UK
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6
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Pleskow DK, Sawhney MS, Upputuri PK, Berzin TM, Coughlan MF, Khan U, Glyavina M, Zhang X, Chen L, Sheil CJ, Cohen JM, Vitkin E, Zakharov YN, Itzkan I, Zhang L, Qiu L, Perelman LT. In vivo detection of bile duct pre-cancer with endoscopic light scattering spectroscopy. Nat Commun 2023; 14:109. [PMID: 36611024 PMCID: PMC9825389 DOI: 10.1038/s41467-022-35780-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 12/23/2022] [Indexed: 01/09/2023] Open
Abstract
Bile duct cancer is the second most common primary liver cancer, with most diagnoses occurring in the advanced stages. This leads to a poor survival rate, which means a technique capable of reliably detecting pre-cancer in the bile duct is urgently required. Unfortunately, radiological imaging lacks adequate accuracy for distinguishing dysplastic and benign biliary ducts, while endoscopic techniques, which can directly assess the bile duct lining, often suffer from insufficient sampling. Here, we report an endoscopic optical light scattering technique for clinical evaluation of the malignant potential of the bile duct. This technique employs an ultraminiature spatial gating fiber optic probe compatible with cholangioscopes and endoscopic retrograde cholangiopancreatography (ERCP) catheters. The probe allowed us to investigate the internal cellular composition of the bile duct epithelium with light scattering spectroscopy (LSS) and phenotypic properties of the underlying connective tissue with diffuse reflectance spectroscopy (DRS). In a pilot in vivo double-blind prospective study involving 29 patients undergoing routine ERCP procedures, the technique detected malignant transformation with 97% accuracy, showing that biliary duct pre-cancer can be reliably identified in vivo non-invasively.
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Affiliation(s)
- Douglas K Pleskow
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA.,Center for Advanced Endoscopy, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Mandeep S Sawhney
- Center for Advanced Endoscopy, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Paul K Upputuri
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Tyler M Berzin
- Center for Advanced Endoscopy, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Mark F Coughlan
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Umar Khan
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Maria Glyavina
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Xuejun Zhang
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Liming Chen
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Conor J Sheil
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Jonah M Cohen
- Center for Advanced Endoscopy, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Edward Vitkin
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Yuri N Zakharov
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Irving Itzkan
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Lei Zhang
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA.
| | - Le Qiu
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA.
| | - Lev T Perelman
- Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA. .,Biological and Biomedical Sciences Program, Harvard University, Boston, MA, USA.
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7
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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.
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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
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Voulgarelis S, Fathi F, Stucke AG, Daley KD, Kim J, Zimmerman MA, Hong JC, Starkey N, Allen KP, Yu B. Evaluation of visible diffuse reflectance spectroscopy in liver tissue: validation of tissue saturations using extracorporeal circulation. JOURNAL OF BIOMEDICAL OPTICS 2021; 26:JBO-210019R. [PMID: 34021537 PMCID: PMC8145982 DOI: 10.1117/1.jbo.26.5.055002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/03/2021] [Indexed: 05/13/2023]
Abstract
SIGNIFICANCE Real-time information about oxygen delivery to the hepatic graft is important to direct care and diagnose vascular compromise in the immediate post-transplant period. AIM The current study was designed to determine the utility of visible diffuse reflectance spectroscopy (vis-DRS) for measuring liver tissue saturation in vivo. APPROACH A custom-built vis-DRS probe was calibrated using phantoms with hemoglobin (Hb) and polystyrene microspheres. Ex vivo (extracorporeal circulation) and in vivo protocols were used in a swine model (n = 15) with validation via blood gas analysis. RESULTS In vivo absorption and scattering measured by vis-DRS with and without biliverdin correction correlated closely between analyses. Lin's concordance correlation coefficients are 0.991 for μa and 0.959 for μs ' . Hb measured by blood test and vis-DRS with (R2 = 0.81) and without (R2 = 0.85) biliverdin correction were compared. Vis-DRS data obtained from the ex vivo protocol plotted against the PO2 derived from blood gas analysis showed a good fit for a Hill coefficient of 1.67 and P50 = 34 mmHg (R2 = 0.81). A conversion formula was developed to account for the systematic deviation, which resulted in a goodness-of-fit R2 = 0.76 with the expected oxygen dissociation curve. CONCLUSIONS We show that vis-DRS allows for real-time measurement of liver tissue saturation, an indicator for liver perfusion and oxygen delivery.
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Affiliation(s)
- Stylianos Voulgarelis
- Medical College of Wisconsin, Children’s Wisconsin, Department of Anesthesiology, Milwaukee, Wisconsin, United States
- Address all correspondence to Stylianos Voulgarelis,
| | - Faraneh Fathi
- Marquette University and Medical College of Wisconsin, Department of Biomedical Engineering, Milwaukee, Wisconsin, United States
| | - Astrid G. Stucke
- Medical College of Wisconsin, Children’s Wisconsin, Department of Anesthesiology, Milwaukee, Wisconsin, United States
| | - Kevin D. Daley
- Herma Heart Institute, Children’s Wisconsin, Department of Perfusion, Milwaukee, Wisconsin, United States
| | - Joohyun Kim
- Medical College of Wisconsin, Children’s Hospital of Wisconsin, Department of Surgery, Division of Transplant Surgery, Milwaukee, Wisconsin, United States
| | - Michael A. Zimmerman
- Medical College of Wisconsin, Children’s Hospital of Wisconsin, Department of Surgery, Division of Transplant Surgery, Milwaukee, Wisconsin, United States
| | - Johnny C. Hong
- Medical College of Wisconsin, Children’s Hospital of Wisconsin, Department of Surgery, Division of Transplant Surgery, Milwaukee, Wisconsin, United States
| | - Nicholas Starkey
- Herma Heart Institute, Children’s Wisconsin, Department of Perfusion, Milwaukee, Wisconsin, United States
| | - Kenneth P. Allen
- Biomedical Resource Center, Medical College of Wisconsin, Department of Immunology Microbiology, Milwaukee, Wisconsin, United States
| | - Bing Yu
- Marquette University and Medical College of Wisconsin, Department of Biomedical Engineering, Milwaukee, Wisconsin, United States
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9
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Houhou R, Bocklitz T. Trends in artificial intelligence, machine learning, and chemometrics applied to chemical data. ANALYTICAL SCIENCE ADVANCES 2021; 2:128-141. [PMID: 38716450 PMCID: PMC10989568 DOI: 10.1002/ansa.202000162] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 12/18/2020] [Accepted: 12/21/2020] [Indexed: 11/17/2024]
Abstract
Artificial intelligence-based methods such as chemometrics, machine learning, and deep learning are promising tools that lead to a clearer and better understanding of data. Only with these tools, data can be used to its full extent, and the gained knowledge on processes, interactions, and characteristics of the sample is maximized. Therefore, scientists are developing data science tools mentioned above to automatically and accurately extract information from data and increase the application possibilities of the respective data in various fields. Accordingly, AI-based techniques were utilized for chemical data since the 1970s and this review paper focuses on the recent trends of chemometrics, machine learning, and deep learning for chemical and spectroscopic data in 2020. In this regard, inverse modeling, preprocessing methods, and data modeling applied to spectra and image data for various measurement techniques are discussed.
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Affiliation(s)
- Rola Houhou
- Institute of Physical ChemistryFriedrich‐Schiller‐University JenaJenaGermany
- Department of Photonic Data ScienceMember of Leibniz Research Alliance “Leibniz‐Health Technologies”Leibniz Institute of Photonic TechnologiesJenaGermany
| | - Thomas Bocklitz
- Institute of Physical ChemistryFriedrich‐Schiller‐University JenaJenaGermany
- Department of Photonic Data ScienceMember of Leibniz Research Alliance “Leibniz‐Health Technologies”Leibniz Institute of Photonic TechnologiesJenaGermany
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10
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Olshinka A, Ad-El D, Didkovski E, Weiss S, Ankri R, Goldenberg-Cohen N, Fixler D. Diffusion Reflection Measurements of Antibodies Conjugated to Gold Nanoparticles as a Method to Identify Cutaneous Squamous Cell Carcinoma Borders. MATERIALS 2020; 13:ma13020447. [PMID: 31963462 PMCID: PMC7014005 DOI: 10.3390/ma13020447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 01/06/2020] [Accepted: 01/13/2020] [Indexed: 12/13/2022]
Abstract
Diffusion reflectance spectroscopy measurements targeted with gold nanoparticles (GNPs) can identify residual cutaneous squamous cell carcinoma (SCC) in excision borders. Human SCC specimens were stained with hematoxylin and eosin to identify tumor borders, and reflected onto an unstained deparaffinized section. Diffusion reflection of three sites (normal and SCC) were measured before and after GNPs targeting. Hyperspectral imaging showed a mean of 2.5 sites with tumor per specimen and 1.2 tumor-free (p < 0.05, t-test). GNPs were detected in 25/30 tumor sites (sensitivity 83.3%, false-negative rate 16.6%) and 12/30 non-tumor sites (specificity 60%, false-positive rate 40%). This study verifies the use of nanotechnology in identifying SCC tumor margins. Diffusion reflection scanning has high sensitivity for detecting the residual tumor.
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Affiliation(s)
- Asaf Olshinka
- Department of Plastic Surgery, Rabin Medical Center—Beilinson Hospital, Petach Tikva 4941492, Israel; (A.O.); (D.A.-E.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; (E.D.); (S.W.)
| | - Dean Ad-El
- Department of Plastic Surgery, Rabin Medical Center—Beilinson Hospital, Petach Tikva 4941492, Israel; (A.O.); (D.A.-E.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; (E.D.); (S.W.)
| | - Elena Didkovski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; (E.D.); (S.W.)
- Department of Pathology and Cytology, Rabin Medical Center—Beilinson Hospital, Petach Tikva 4941492, Israel
| | - Shirel Weiss
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; (E.D.); (S.W.)
- The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 49100, Israel
| | - Rinat Ankri
- Faculty of Engineering and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan 5290002, Israel;
| | - Nitza Goldenberg-Cohen
- The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 49100, Israel
- Ruth and Bruce Rappaport Faculty of Medicine, The Technion—Technical Institute of Israel, Haifa 3200003, Israel
- Department of Ophthalmology, Bnai Zion Medical Center, Haifa 3339419, Israel
- Correspondance: (N.G.-C.); (D.F.); Tel.: +972-4-835-9554 (N.G.-C.); +972-3-531-7598 (D.F.)
| | - Dror Fixler
- Faculty of Engineering and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan 5290002, Israel;
- Correspondance: (N.G.-C.); (D.F.); Tel.: +972-4-835-9554 (N.G.-C.); +972-3-531-7598 (D.F.)
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11
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Zhang Y, Moy AJ, Feng X, Nguyen HTM, Reichenberg JS, Markey MK, Tunnell JW. Physiological model using diffuse reflectance spectroscopy for nonmelanoma skin cancer diagnosis. JOURNAL OF BIOPHOTONICS 2019; 12:e201900154. [PMID: 31325232 DOI: 10.1002/jbio.201900154] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/10/2019] [Accepted: 07/17/2019] [Indexed: 05/25/2023]
Abstract
Diffuse reflectance spectroscopy (DRS) is a noninvasive, fast, and low-cost technology with potential to assist cancer diagnosis. The goal of this study was to test the capability of our physiological model, a computational Monte Carlo lookup table inverse model, for nonmelanoma skin cancer diagnosis. We applied this model on a clinical DRS dataset to extract scattering parameters, blood volume fraction, oxygen saturation and vessel radius. We found that the model was able to capture physiological information relevant to skin cancer. We used the extracted parameters to classify (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]) vs actinic keratosis (AK) and (BCC, SCC, AK) vs normal. The area under the receiver operating characteristic curve achieved by the classifiers trained on the parameters extracted using the physiological model is comparable to that of classifiers trained on features extracted via Principal Component Analysis. Our findings suggest that DRS can reveal physiologic characteristics of skin and this physiologic model offers greater flexibility for diagnosing skin cancer than a pure statistical analysis. Physiological parameters extracted from diffuse reflectance spectra data for nonmelanoma skin cancer diagnosis.
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Affiliation(s)
- Yao Zhang
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas
| | - Austin J Moy
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas
| | - Xu Feng
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas
| | - Hieu T M Nguyen
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas
| | | | - Mia K Markey
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - James W Tunnell
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas
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12
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Lariviere B, Garman KS, Ferguson NL, Fisher DA, Jokerst NM. Spatially resolved diffuse reflectance spectroscopy endoscopic sensing with custom Si photodetectors. BIOMEDICAL OPTICS EXPRESS 2018; 9. [PMID: 29541510 PMCID: PMC5846520 DOI: 10.1364/boe.9.001164] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Early detection and surveillance of disease progression in epithelial tissue is key to improving long term patient outcomes for colon and esophageal cancers, which account for nearly a quarter of cancer related mortalities worldwide. Spatially resolved diffuse reflectance spectroscopy (SRDRS) is a non-invasive optical technique to sense biological changes at the cellular and sub-cellular level that occur when normal tissue becomes diseased, and has the potential to significantly improve the current standard of care for endoscopic gastrointestinal (GI) screening. Herein the design, fabrication, and characterization of the first custom SRDRS device to enable endoscopic SRDRS GI tissue characterization using a custom silicon (Si) thin film multi-pixel endoscopic optical sensor (MEOS) is described.
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Affiliation(s)
- Ben Lariviere
- Department of Electrical and Computer Engineering, Duke University, 101 Science Drive, Durham, NC 27708, USA
| | | | | | | | - Nan M. Jokerst
- Department of Electrical and Computer Engineering, Duke University, 101 Science Drive, Durham, NC 27708, USA
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13
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Shalaby N, Al-Ebraheem A, Le D, Cornacchi S, Fang Q, Farrell T, Lovrics P, Gohla G, Reid S, Hodgson N, Farquharson M. Time-resolved fluorescence (TRF) and diffuse reflectance spectroscopy (DRS) for margin analysis in breast cancer. Lasers Surg Med 2018; 50:236-245. [DOI: 10.1002/lsm.22795] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/31/2017] [Indexed: 01/27/2023]
Affiliation(s)
- Nourhan Shalaby
- School of Interdisciplinary Science; McMaster University; Ontario Canada
| | - Alia Al-Ebraheem
- School of Interdisciplinary Science; McMaster University; Ontario Canada
| | - Du Le
- School of Interdisciplinary Science; McMaster University; Ontario Canada
| | - Sylvie Cornacchi
- Faculty of Health Sciences, Department of Surgery; McMaster University; Hamilton Ontario Canada
| | - Qiyin Fang
- Faculty of Engineering; McMaster University; Hamilton Ontario Canada
| | - Thomas Farrell
- Juravinski Hospital and Cancer Centre; Hamilton Ontario Canada
| | - Peter Lovrics
- Faculty of Health Sciences, Department of Surgery; McMaster University; Hamilton Ontario Canada
- St. Joseph's Healthcare; Hamilton Ontario Canada
| | - Gabriela Gohla
- St. Joseph's Healthcare; Hamilton Ontario Canada
- Department of Pathology and Molecular Medicine; McMaster University; Hamilton Ontario Canada
| | - Susan Reid
- Juravinski Hospital and Cancer Centre; Hamilton Ontario Canada
| | - Nicole Hodgson
- Juravinski Hospital and Cancer Centre; Hamilton Ontario Canada
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14
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Miller DM, Jokerst NM. Flexible silicon sensors for diffuse reflectance spectroscopy of tissue. BIOMEDICAL OPTICS EXPRESS 2017; 8:1512-1524. [PMID: 28663846 PMCID: PMC5480561 DOI: 10.1364/boe.8.001512] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 01/28/2017] [Accepted: 02/09/2017] [Indexed: 05/03/2023]
Abstract
Diffuse reflectance spectroscopy (DRS) is being used in exploratory clinical applications such as cancer margin assessment on excised tissue. However, when interrogating nonplanar tissue anomalies can arise from non-uniform pressure. Herein is reported the design, fabrication, and test of flexible, thin film silicon photodetectors (PDs) bonded to a flexible substrate designed for use in conformal DRS. The PDs have dark currents and responsivities comparable to conventional Si PDs, and were characterized while flat and while flexed at multiple radii of curvature using liquid phantoms mimicking adipose and malignant breast tissue. The DRS and nearest neighbor crosstalk results were compared with Monte Carlo simulations, showing good agreement between simulation and experiment.
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15
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Review: in vivo optical spectral tissue sensing-how to go from research to routine clinical application? Lasers Med Sci 2016; 32:711-719. [PMID: 27909918 DOI: 10.1007/s10103-016-2119-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 11/22/2016] [Indexed: 10/20/2022]
Abstract
Innovations in optical spectroscopy have helped the technology reach a point where performance previously seen only in laboratory settings can be translated and tested in real-world applications. In the field of oncology, spectral tissue sensing (STS) by means of optical spectroscopy is considered to have major potential for improving diagnostics and optimizing treatment outcome. The concept has been investigated for more than two decades and yet spectral tissue sensing is not commonly employed in routine medical practice. It is therefore important to understand what is needed to translate technological advances and insights generated through basic scientific research in this field into clinical practice. The aim of the discussion presented here is not to provide a comprehensive review of all work published over the last decades but rather to highlight some of the challenges found in literature and encountered by our group in the quest to translate optical technologies into useful clinical tools. Furthermore, an outlook is proposed on how translational researchers could proceed to eventually have STS incorporated in the process of clinical decision-making.
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16
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Cappon DJ, Farrell TJ, Fang Q, Hayward JE. Distortion correction and cross-talk compensation algorithm for use with an imaging spectrometer based spatially resolved diffuse reflectance system. THE REVIEW OF SCIENTIFIC INSTRUMENTS 2016; 87:123112. [PMID: 28040957 DOI: 10.1063/1.4973122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Optical spectroscopy of human tissue has been widely applied within the field of biomedical optics to allow rapid, in vivo characterization and analysis of the tissue. When designing an instrument of this type, an imaging spectrometer is often employed to allow for simultaneous analysis of distinct signals. This is especially important when performing spatially resolved diffuse reflectance spectroscopy. In this article, an algorithm is presented that allows for the automated processing of 2-dimensional images acquired from an imaging spectrometer. The algorithm automatically defines distinct spectrometer tracks and adaptively compensates for distortion introduced by optical components in the imaging chain. Crosstalk resulting from the overlap of adjacent spectrometer tracks in the image is detected and subtracted from each signal. The algorithm's performance is demonstrated in the processing of spatially resolved diffuse reflectance spectra recovered from an Intralipid and ink liquid phantom and is shown to increase the range of wavelengths over which usable data can be recovered.
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Affiliation(s)
- Derek J Cappon
- Radiation Sciences Graduate Program, McMaster University, 1280 Main St. W, Hamilton, Ontario L8S 4K1, Canada
| | - Thomas J Farrell
- Radiation Sciences Graduate Program, McMaster University, 1280 Main St. W, Hamilton, Ontario L8S 4K1, Canada
| | - Qiyin Fang
- Department of Engineering Physics, McMaster University, 1280 Main St. W, Hamilton, Ontario L8S 4L7, Canada
| | - Joseph E Hayward
- Radiation Sciences Graduate Program, McMaster University, 1280 Main St. W, Hamilton, Ontario L8S 4K1, Canada
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17
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Zhu C, Chen S, Chui CHK, Tan BK, Liu Q. Early detection and differentiation of venous and arterial occlusion in skin flaps using visible diffuse reflectance spectroscopy and autofluorescence spectroscopy. BIOMEDICAL OPTICS EXPRESS 2016; 7:570-80. [PMID: 26977363 PMCID: PMC4771472 DOI: 10.1364/boe.7.000570] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 01/11/2016] [Accepted: 01/13/2016] [Indexed: 05/22/2023]
Abstract
Our previous preclinical study demonstrated that both visible diffuse reflectance and autofluorescence spectroscopy, each of which yields a different set of physiological information, can predict skin flap viability with high accuracy in a MacFarlane rat dorsal skin flap model. In this report, we further evaluated our technique for the early detection and differentiation of venous occlusion and arterial occlusion in a rat groin flap model. We performed both diffuse reflectance and autofluorescence measurements on the skin flap model and statistically differentiated between flaps with and without occlusions as well as between flaps with venous occlusion and those with arterial occlusion based on these non-invasive optical measurements. Our preliminary results suggested that visible diffuse reflectance and autofluorescence spectroscopy can be potentially used clinically to detect both venous and arterial occlusion and differentiate one from the other accurately at an early time point.
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Affiliation(s)
- Caigang Zhu
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 637457, Singapore
- Currently with the Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
| | - Shuo Chen
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 637457, Singapore
- Currently with the Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, 110819 China
| | | | - Bien-Keem Tan
- Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore
| | - Quan Liu
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 637457, Singapore
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18
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Johansson JD, Mireles M, Morales-Dalmau J, Farzam P, Martínez-Lozano M, Casanovas O, Durduran T. Scanning, non-contact, hybrid broadband diffuse optical spectroscopy and diffuse correlation spectroscopy system. BIOMEDICAL OPTICS EXPRESS 2016; 7:481-98. [PMID: 26977357 PMCID: PMC4771466 DOI: 10.1364/boe.7.000481] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 12/19/2015] [Accepted: 01/13/2016] [Indexed: 05/24/2023]
Abstract
A scanning system for small animal imaging using non-contact, hybrid broadband diffuse optical spectroscopy (ncDOS) and diffuse correlation spectroscopy (ncDCS) is presented. The ncDOS uses a two-dimensional spectrophotometer retrieving broadband (610-900 nm) spectral information from up to fifty-seven source-detector distances between 2 and 5 mm. The ncDCS data is simultaneously acquired from four source-detector pairs. The sample is scanned in two dimensions while tracking variations in height. The system has been validated with liquid phantoms, demonstrated in vivo on a human fingertip during an arm cuff occlusion and on a group of mice with xenoimplanted renal cell carcinoma.
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Affiliation(s)
- Johannes D. Johansson
- ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology, 08860, Castelldefels (Barcelona), Spain
| | - Miguel Mireles
- ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology, 08860, Castelldefels (Barcelona), Spain
| | - Jordi Morales-Dalmau
- ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology, 08860, Castelldefels (Barcelona), Spain
| | - Parisa Farzam
- ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology, 08860, Castelldefels (Barcelona), Spain
| | - Mar Martínez-Lozano
- Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Bellvitge Biomedical Research Institute–IDIBELL, 08908, L’Hospitalet de Llobregat (Barcelona), Spain
| | - Oriol Casanovas
- Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Bellvitge Biomedical Research Institute–IDIBELL, 08908, L’Hospitalet de Llobregat (Barcelona), Spain
| | - Turgut Durduran
- ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology, 08860, Castelldefels (Barcelona), Spain
- Institució Catalana de Recerca i Estudis Avançats (ICREA), 08015 Barcelona, Spain
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19
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de Boer LL, Molenkamp BG, Bydlon TM, Hendriks BHW, Wesseling J, Sterenborg HJCM, Ruers TJM. Fat/water ratios measured with diffuse reflectance spectroscopy to detect breast tumor boundaries. Breast Cancer Res Treat 2015; 152:509-18. [PMID: 26141407 DOI: 10.1007/s10549-015-3487-z] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Accepted: 06/15/2015] [Indexed: 12/16/2022]
Abstract
Recognition of the tumor during breast-conserving surgery (BCS) can be very difficult and currently a robust method of margin assessment for the surgical setting is not available. As a result, tumor-positive margins, which require additional treatment, are not found until histopathologic evaluation. With diffuse reflectance spectroscopy (DRS), tissue can be characterized during surgery based on optical parameters that are related to the tissue morphology and composition. Here we investigate which optical parameters are able to detect tumor in an area with a mixture of benign and tumor tissue and hence which parameters are most suitable for intra-operative margin assessment. DRS spectra (400-1600 nm) were obtained from 16 ex vivo lumpectomy specimens from benign, tumor border, and tumor tissue. One mastectomy specimen was used with a custom-made grid for validation purposes. The optical parameter related to the absorption of fat and water (F/W-ratio) in the extended near-infrared wavelength region (~1000-1600 nm) provided the best discrimination between benign and tumor sites resulting in a sensitivity and specificity of 100 % (excluding the border sites). Per patient, the scaled F/W-ratio gradually decreased from grossly benign tissue towards the tumor in 87.5 % of the specimens. In one test case, based on a predefined F/W-ratio for boundary tissue of 0.58, DRS produced a surgical resection plane that nearly overlapped with a 2-mm rim of benign tissue, 2 mm being the most widely accepted definition of a negative margin. The F/W-ratio provided excellent discrimination between sites clearly inside or outside the tumor and was able to detect the border of the tumor in one test case. This work shows the potential for DRS to guide the surgeon during BCS.
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Affiliation(s)
- L L de Boer
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands,
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20
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Nichols BS, Schindler CE, Brown JQ, Wilke LG, Mulvey CS, Krieger MS, Gallagher J, Geradts J, Greenup RA, Von Windheim JA, Ramanujam N. A Quantitative Diffuse Reflectance Imaging (QDRI) System for Comprehensive Surveillance of the Morphological Landscape in Breast Tumor Margins. PLoS One 2015; 10:e0127525. [PMID: 26076123 PMCID: PMC4468201 DOI: 10.1371/journal.pone.0127525] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 04/16/2015] [Indexed: 11/18/2022] Open
Abstract
In an ongoing effort to address the clear clinical unmet needs surrounding breast conserving surgery (BCS), our group has developed a next-generation multiplexed optical-fiber-based tool to assess breast tumor margin status during initial surgeries. Specifically detailed in this work is the performance and clinical validation of a research-grade intra-operative tool for margin assessment based on diffuse optical spectroscopy. Previous work published by our group has illustrated the proof-of-concept generations of this device; here we incorporate a highly optimized quantitative diffuse reflectance imaging (QDRI) system utilizing a wide-field (imaging area = 17cm2) 49-channel multiplexed fiber optic probe, a custom raster-scanning imaging platform, a custom dual-channel white LED source, and an astronomy grade imaging CCD and spectrograph. The system signal to noise ratio (SNR) was found to be greater than 40dB for all channels. Optical property estimation error was found to be less than 10%, on average, over a wide range of absorption (μa = 0–8.9cm-1) and scattering (μs’ = 7.0–9.7cm-1) coefficients. Very low inter-channel and CCD crosstalk was observed (2% max) when used on turbid media (including breast tissue). A raster-scanning mechanism was developed to achieve sub-pixel resolution and was found to be optimally performed at an upsample factor of 8, affording 0.75mm spatially resolved diffuse reflectance images (λ = 450–600nm) of an entire margin (area = 17cm2) in 13.8 minutes (1.23cm2/min). Moreover, controlled pressure application at the probe-tissue interface afforded by the imaging platform reduces repeated scan variability, providing <1% variation across repeated scans of clinical specimens. We demonstrate the clinical utility of this device through a pilot 20-patient study of high-resolution optical parameter maps of the ratio of the β-carotene concentration to the reduced scattering coefficient. An empirical cumulative distribution function (eCDF) analysis is used to reduce optical property maps to quantitative distributions representing the morphological landscape of breast tumor margins. The optimizations presented in this work provide an avenue to rapidly survey large tissue areas on intra-operative time scales with improved sensitivity to regions of focal disease that may otherwise be overlooked.
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Affiliation(s)
- Brandon S. Nichols
- Department of Biomedical Engineering, Duke University, Durham, NC, United States of America
- * E-mail:
| | - Christine E. Schindler
- Department of Biomedical Engineering, Duke University, Durham, NC, United States of America
| | - Jonathon Q. Brown
- Zenalux Biomedical, Research Triangle Park, NC, United States of America
- Department of Biomedical Engineering, Tulane University, New Orleans, LA, United States of America
| | - Lee G. Wilke
- Department of Surgery, The University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
| | - Christine S. Mulvey
- Department of Biomedical Engineering, Duke University, Durham, NC, United States of America
| | - Marlee S. Krieger
- Department of Biomedical Engineering, Duke University, Durham, NC, United States of America
- Zenalux Biomedical, Research Triangle Park, NC, United States of America
| | - Jennifer Gallagher
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Joseph Geradts
- Department of Pathology, Duke University Medical Center, Durham, NC, United States of America
| | - Rachel A. Greenup
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Jesko A. Von Windheim
- Zenalux Biomedical, Research Triangle Park, NC, United States of America
- The Division of Environmental Sciences and Policy, Duke University, Durham, NC, United States of America
| | - Nirmala Ramanujam
- Department of Biomedical Engineering, Duke University, Durham, NC, United States of America
- Zenalux Biomedical, Research Triangle Park, NC, United States of America
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21
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Qualitative and simultaneous quantitative analysis of cimetidine polymorphs by ultraviolet–visible and shortwave near-infrared diffuse reflectance spectroscopy and multivariate calibration models. J Pharm Biomed Anal 2015; 104:112-21. [DOI: 10.1016/j.jpba.2014.11.023] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2014] [Revised: 11/08/2014] [Accepted: 11/11/2014] [Indexed: 11/24/2022]
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22
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Pery E, Blondel WCPM, Tindel S, Ghribi M, Leroux A, Guillemin F. Spectral Features Selection and Classification for Bimodal Optical Spectroscopy Applied to Bladder Cancer In Vivo Diagnosis. IEEE Trans Biomed Eng 2014; 61:207-16. [DOI: 10.1109/tbme.2010.2103559] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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23
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Ankri R, Meiri A, Lau SI, Motiei M, Popovtzer R, Fixler D. Intercoupling surface plasmon resonance and diffusion reflection measurements for real-time cancer detection. JOURNAL OF BIOPHOTONICS 2013; 6:188-96. [PMID: 22461296 DOI: 10.1002/jbio.201200016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2012] [Revised: 03/12/2012] [Accepted: 03/12/2012] [Indexed: 05/11/2023]
Abstract
Spatial diffusion reflection (DR) measurements of gold nanorods (GNR) were recently suggested as a simple and highly sensitive non-invasive and non-ionizing method for real-time cancer detection. In this paper we demonstrate that wavelength dependent DR measurements enable the spectral red-shift observation of highly concentrated GNR. By conjugating targeting moieties to the GNR, large density of GNR can specifically home onto cancer cells. The inter-particle plasmon resonance pattern of the highly concentrated GNR leads to an extension and a red-shift (Δλ) in the absorption spectrum of the concentrated GNR. Dark-field microscopy was used in order to measure the expected Δλ in different GNR concentrations in vitro. Double-wavelength DR measurements of tissue-like phantoms and tumor bearing mice containing different GNR concentrations are presented. We show that the DR profile of the highly concentrated GNR directly correlate with the spectral extension and red-shift. This presented work suggests that wavelength dependent DR method can serve as a promising tool for real-time superficial tumor detection.
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Affiliation(s)
- Rinat Ankri
- Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, 52900, Israel
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24
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Evers D, Nachabé R, Hompes D, van Coevorden F, Lucassen G, Hendriks B, van Velthuysen ML, Wesseling J, Ruers T. Optical sensing for tumor detection in the liver. Eur J Surg Oncol 2013; 39:68-75. [DOI: 10.1016/j.ejso.2012.08.005] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2012] [Revised: 07/25/2012] [Accepted: 08/13/2012] [Indexed: 12/14/2022] Open
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25
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Bydlon TM, Barry WT, Kennedy SA, Brown JQ, Gallagher JE, Wilke LG, Geradts J, Ramanujam N. Advancing optical imaging for breast margin assessment: an analysis of excisional time, cautery, and patent blue dye on underlying sources of contrast. PLoS One 2012; 7:e51418. [PMID: 23251526 PMCID: PMC3519619 DOI: 10.1371/journal.pone.0051418] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Accepted: 11/01/2012] [Indexed: 11/30/2022] Open
Abstract
Breast conserving surgery (BCS) is a recommended treatment for breast cancer patients where the goal is to remove the tumor and a surrounding rim of normal tissue. Unfortunately, a high percentage of patients return for additional surgeries to remove all of the cancer. Post-operative pathology is the gold standard for evaluating BCS margins but is limited due to the amount of tissue that can be sampled. Frozen section analysis and touch-preparation cytology have been proposed to address the surgical needs but also have sampling limitations. These issues represent an unmet clinical need for guidance in resecting malignant tissue intra-operatively and for pathological sampling. We have developed a quantitative spectral imaging device to examine margins intra-operatively. The context in which this technology is applied (intra-operative or post-operative setting) is influenced by time after excision and surgical factors including cautery and the presence of patent blue dye (specifically Lymphazurin™, used for sentinel lymph node mapping). Optical endpoints of hemoglobin ([THb]), fat ([β-carotene]), and fibroglandular content via light scattering (<µs’>) measurements were quantified from diffuse reflectance spectra of lumpectomy and mastectomy specimens using a Monte Carlo model. A linear longitudinal mixed-effects model was used to fit the optical endpoints for the cautery and kinetics studies. Monte Carlo simulations and tissue mimicking phantoms were used for the patent blue dye experiments. [THb], [β-carotene], and <µs’> were affected by <3.3% error with <80 µM of patent blue dye. The percent change in [β-carotene], <µs’>, and [β-carotene]/<µs’> was <14% in 30 minutes, while percent change in [THb] was >40%. [β-carotene] and [β-carotene]/<µs’> were the only parameters not affected by cautery. This work demonstrates the importance of understanding the post-excision kinetics of ex-vivo tissue and the presence of cautery and patent blue dye for breast tumor margin assessment, to accurately interpret data and exploit underling sources of contrast.
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Affiliation(s)
- Torre M. Bydlon
- Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America
| | - William T. Barry
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
| | - Stephanie A. Kennedy
- Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America
| | - J. Quincy Brown
- Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America
- Zenalux, Research Triangle Park, North Carolina, United States of America
| | - Jennifer E. Gallagher
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Lee G. Wilke
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
| | - Joseph Geradts
- Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Nimmi Ramanujam
- Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America
- Zenalux, Research Triangle Park, North Carolina, United States of America
- * E-mail:
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26
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Evers DJ, Nachabe R, Vranken Peeters MJ, van der Hage JA, Oldenburg HS, Rutgers EJ, Lucassen GW, Hendriks BHW, Wesseling J, Ruers TJM. Diffuse reflectance spectroscopy: towards clinical application in breast cancer. Breast Cancer Res Treat 2012; 137:155-65. [PMID: 23225143 DOI: 10.1007/s10549-012-2350-8] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Accepted: 11/18/2012] [Indexed: 10/27/2022]
Abstract
Diffuse reflectance spectroscopy (DRS) is a promising new technique for breast cancer diagnosis. However, inter-patient variation due to breast tissue heterogeneity may interfere with the accuracy of this technique. To tackle this issue, we aim to determine the diagnostic accuracy of DRS in individual patients. With this approach, DRS measurements of normal breast tissue in every individual patient are directly compared with measurements of the suspected malignant tissue. Breast tissue from 47 female patients was analysed ex vivo by DRS. A total of 1,073 optical spectra were collected. These spectra were analyzed for each patient individually as well as for all patients collectively and results were compared to the pathology analyses. Collective patient data analysis for discrimination between normal and malignant breast tissue resulted in a sensitivity of 90 %, a specificity of 88 %, and an overall accuracy of 89 %. In the individual analyses all measurements per patient were categorized as either benign or malignant. The discriminative accuracy of these individual analyses was nearly 100 %. The diagnosis was classified as uncertain in only one patient. Based on the results presented in this study, we conclude that the analysis of optical characteristics of different tissue classes within the breast of a single patient is superior to an analysis using the results of a cohort data analysis. When integrated into a biopsy device, our results demonstrate that DRS may have the potential to improve the diagnostic workflow in breast cancer.
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Affiliation(s)
- Daniel J Evers
- Department of Surgery, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
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Evers DJ, Nachabé R, Klomp HM, van Sandick JW, Wouters MW, Lucassen GW, Hendriks BH, Wesseling J, Ruers TJ. Diffuse Reflectance Spectroscopy: A New Guidance Tool for Improvement of Biopsy Procedures in Lung Malignancies. Clin Lung Cancer 2012; 13:424-31. [DOI: 10.1016/j.cllc.2012.02.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Revised: 01/09/2012] [Accepted: 02/20/2012] [Indexed: 10/28/2022]
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28
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Evers D, Hendriks B, Lucassen G, Ruers T. Optical spectroscopy: current advances and future applications in cancer diagnostics and therapy. Future Oncol 2012; 8:307-20. [PMID: 22409466 DOI: 10.2217/fon.12.15] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Optical spectroscopy (OS) is a tissue-sensing technique that could enhance cancer diagnosis and treatment in the near future. With OS, tissue is illuminated with a selected light spectrum. Different tissue types can be distinguished from each other based on specific changes in the reflected light spectrum that are a result of differences on a molecular level between compared tissues. Therefore, OS has the potential to become an important optical tool for cancer diagnosis and treatment monitoring. In recent years, significant progress has been made in the discriminating abilities of OS techniques between normal and cancer tissues of multiple human tissue types. This article provides an overview of the advances made with diffuse reflectance, fluorescence and Raman spectroscopy techniques in the field of clinical oncology, and focuses on the different clinical applications that OS could enhance.
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Affiliation(s)
- Dj Evers
- Department of Surgery, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
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29
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Liu C, Rajaram N, Vishwanath K, Jiang T, Palmer GM, Ramanujam N. Experimental validation of an inverse fluorescence Monte Carlo model to extract concentrations of metabolically relevant fluorophores from turbid phantoms and a murine tumor model. JOURNAL OF BIOMEDICAL OPTICS 2012; 17:077012. [PMID: 22894524 PMCID: PMC3408318 DOI: 10.1117/1.jbo.17.7.077012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2012] [Revised: 06/07/2012] [Accepted: 07/02/2012] [Indexed: 05/29/2023]
Abstract
An inverse Monte Carlo based model has been developed to extract intrinsic fluorescence from turbid media. The goal of this work was to experimentally validate the model to extract intrinsic fluorescence of three biologically meaningful fluorophores related to metabolism from turbid media containing absorbers and scatterers. Experimental studies were first carried out on tissue-mimicking phantoms that contained individual fluorophores and their combinations, across multiple absorption, scattering, and fluorophore concentrations. The model was then tested in a murine tumor model to determine both the kinetics of fluorophore uptake as well as overall tissue fluorophore concentration through extraction of the intrinsic fluorescence of an exogenous contrast agent that reports on glucose uptake. Results show the model can be used to recover the true intrinsic fluorescence spectrum with high accuracy (R(2)=0.988) as well as accurately compute fluorophore concentration in both single and multiple fluorophores phantoms when appropriate calibration standards are available. In the murine tumor, the model-corrected intrinsic fluorescence could be used to differentiate drug dose injections between different groups. A strong linear correlation was observed between the extracted intrinsic fluorescence intensity and injected drug dose, compared with the distorted turbid tissue fluorescence.
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Affiliation(s)
- Chengbo Liu
- Xi’an Jiaotong University, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Biomedical Analytical Technology and Instrumentation, School of Life Science and Technology, No. 28 Xianning West Road, Xi’an 710049, China
- Duke University, Department of Biomedical Engineering, 136 Hudson Hall, Box 90281, Durham, North Carolina 27708
| | - Narasimhan Rajaram
- Duke University, Department of Biomedical Engineering, 136 Hudson Hall, Box 90281, Durham, North Carolina 27708
| | - Karthik Vishwanath
- Duke University, Department of Biomedical Engineering, 136 Hudson Hall, Box 90281, Durham, North Carolina 27708
| | - Tony Jiang
- Duke University, Department of Biomedical Engineering, 136 Hudson Hall, Box 90281, Durham, North Carolina 27708
| | - Gregory M. Palmer
- Duke University Medical Center, Department of Radiation Oncology, Durham, North Carolina 27710
| | - Nirmala Ramanujam
- Duke University, Department of Biomedical Engineering, 136 Hudson Hall, Box 90281, Durham, North Carolina 27708
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Palmer GM, Vishwanath K, Dewhirst MW. Application of optical imaging and spectroscopy to radiation biology. Radiat Res 2012; 177:365-75. [PMID: 22360397 DOI: 10.1667/rr2531.1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Optical imaging and spectroscopy is a diverse field that has been of critical importance in a wide range of areas in radiation research. It is capable of spanning a wide range of spatial and temporal scales, and has the sensitivity and specificity needed for molecular and functional imaging. This review will describe the basic principles of optical imaging and spectroscopy, highlighting a few relevant applications to radiation research.
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Affiliation(s)
- Gregory M Palmer
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.
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31
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Ankri R, Peretz V, Motiei M, Popovtzer R, Fixler D. A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods. Int J Nanomedicine 2012; 7:449-55. [PMID: 22334777 PMCID: PMC3273979 DOI: 10.2147/ijn.s28424] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
This paper presents a new method for cancer detection based on diffusion reflection measurements. This method enables discrimination between cancerous and noncancerous tissues due to the intense light absorption of gold nanorods (GNRs), which are selectively targeted to squamous cell carcinoma head and neck cancer cells. Presented in this paper are tissue-like phantom and in vivo results that demonstrate the high sensitivity of diffusion reflection measurements to the absorption differences between the GNR-targeted cancerous tissue and normal, noncancerous tissue. This noninvasive and nonionizing optical detection method provides a highly sensitive, simple, and inexpensive tool for cancer detection.
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Affiliation(s)
- Rinat Ankri
- Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan 52900, Israel
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32
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Jayanthi JL, Subhash N, Stephen M, Philip EK, Beena VT. Comparative evaluation of the diagnostic performance of autofluorescence and diffuse reflectance in oral cancer detection: a clinical study. JOURNAL OF BIOPHOTONICS 2011; 4:696-706. [PMID: 21905236 DOI: 10.1002/jbio.201100037] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2011] [Revised: 07/28/2011] [Accepted: 08/22/2011] [Indexed: 05/31/2023]
Abstract
Autofluorescence (AF) and diffuse reflectance (DR) spectroscopic techniques have shown good diagnostic accuracies for noninvasive detection of oral cavity cancer. In the present study, AF and DR spectra recorded in vivo from the same set of sites in 65 patients were analyzed using Principal component analysis (PCA) and linear discriminant analysis (LDA). The effectiveness of these two techniques was assessed by comparison with gold standard and their discrimination efficiency was determined from the area under the receiver operator characteristic (AUC-ROC) curve. Analysis using a DR technique shows a higher AUC-ROC of 0.991 as against 0.987 for AF spectral data.
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Affiliation(s)
- Jayaraj L Jayanthi
- Biophotonics Laboratory, Centre for Earth Science Studies, Akkulam, Trivandrum, India
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33
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Nachabé R, Evers DJ, Hendriks BHW, Lucassen GW, van der Voort M, Rutgers EJ, Peeters MJV, Van der Hage JA, Oldenburg HS, Wesseling J, Ruers TJM. Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods. JOURNAL OF BIOMEDICAL OPTICS 2011; 16:087010. [PMID: 21895337 DOI: 10.1117/1.3611010] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
We report on the use of diffuse optical spectroscopy analysis of breast spectra acquired in the wavelength range from 500 to 1600 nm with a fiber optic probe. A total of 102 ex vivo samples of five different breast tissue types, namely adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ from 52 patients were measured. A model deriving from the diffusion theory was applied to the measured spectra in order to extract clinically relevant parameters such as blood, water, lipid, and collagen volume fractions, β-carotene concentration, average vessels radius, reduced scattering amplitude, Mie slope, and Mie-to-total scattering fraction. Based on a classification and regression tree algorithm applied to the derived parameters, a sensitivity-specificity of 98%-99%, 84%-95%, 81%-98%, 91%-95%, and 83%-99% were obtained for discrimination of adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ, respectively; and a multiple classes overall diagnostic performance of 94%. Sensitivity-specificity values obtained for discriminating malignant from nonmalignant tissue were compared to existing reported studies by applying the different classification methods that were used in each of these studies. Furthermore, in these reported studies, either lipid or β-carotene was considered as adipose tissue precursors. We estimate both chromophore concentrations and demonstrate that lipid is a better discriminator for adipose tissue than β-carotene.
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Affiliation(s)
- Rami Nachabé
- Minimally Invasive Healthcare, Philips Research, 5656AE Eindhoven, The Netherlands.
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Wilson RH, Mycek MA. Models of light propagation in human tissue applied to cancer diagnostics. Technol Cancer Res Treat 2011; 10:121-34. [PMID: 21381790 DOI: 10.7785/tcrt.2012.500187] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Optical methods such as reflectance and fluorescence spectroscopy are being investigated for their potential to aid cancer detection in a quantitative, minimally invasive manner. Mathematical models of reflectance and fluorescence provide an important link between measured optical data and biomedically-relevant tissue parameters that can be extracted from these data to characterize the presence or absence of disease. The most commonly-used mathematical models in biomedical optics are the diffusion approximation (DA) to the radiative transfer equation, Monte Carlo (MC) computational models of light transport, and semi-empirical models. This paper presents a review of the applications of these models to reflectance and endogenous fluorescence sensing for cancer diagnostics in human tissues. Specific examples are given for cervical, breast, and pancreatic tissues. A comparison of the DA and MC methods in two biologically-relevant regimes of optical parameter space will also be discussed.
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Affiliation(s)
- R H Wilson
- Applied Physics Program, University of Michigan, Ann Arbor, MI 48109-1040, USA
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35
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Yu B, Fu HL, Ramanujam N. Instrument independent diffuse reflectance spectroscopy. JOURNAL OF BIOMEDICAL OPTICS 2011; 16:011010. [PMID: 21280897 PMCID: PMC3041242 DOI: 10.1117/1.3524303] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Diffuse reflectance spectroscopy with a fiber optic probe is a powerful tool for quantitative tissue characterization and disease diagnosis. Significant systematic errors can arise in the measured reflectance spectra and thus in the derived tissue physiological and morphological parameters due to real-time instrument fluctuations. We demonstrate a novel fiber optic probe with real-time, self-calibration capability that can be used for UV-visible diffuse reflectance spectroscopy in biological tissue in clinical settings. The probe is tested in a number of synthetic liquid phantoms over a wide range of tissue optical properties for significant variations in source intensity fluctuations caused by instrument warm up and day-to-day drift. While the accuracy for extraction of absorber concentrations is comparable to that achieved with the traditional calibration (with a reflectance standard), the accuracy for extraction of reduced scattering coefficients is significantly improved with the self-calibration probe compared to traditional calibration. This technology could be used to achieve instrument-independent diffuse reflectance spectroscopy in vivo and obviate the need for instrument warm up and post∕premeasurement calibration, thus saving up to an hour of precious clinical time.
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Affiliation(s)
- Bing Yu
- Duke University, Department of Biomedical Engineering, Durham, North Carolina 27708, USA.
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36
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Lim L, Nichols B, Rajaram N, Tunnell JW. Probe pressure effects on human skin diffuse reflectance and fluorescence spectroscopy measurements. JOURNAL OF BIOMEDICAL OPTICS 2011; 16:011012. [PMID: 21280899 PMCID: PMC3041811 DOI: 10.1117/1.3525288] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Diffuse reflectance and fluorescence spectroscopy are popular research techniques for noninvasive disease diagnostics. Most systems include an optical fiber probe that transmits and collects optical spectra in contact with the suspected lesion. The purpose of this study is to investigate probe pressure effects on human skin spectroscopic measurements. We conduct an in-vivo experiment on human skin tissue to study the short-term (<2 s) and long-term (>30 s) effects of probe pressure on diffuse reflectance and fluorescence measurements. Short-term light probe pressure (P0<9 mN∕mm2) effects are within 0 ± 10% on all physiological properties extracted from diffuse reflectance and fluorescence measurements, and less than 0±5% for diagnostically significant physiological properties. Absorption decreases with site-specific variations due to blood being compressed out of the sampled volume. Reduced scattering coefficient variation is site specific. Intrinsic fluorescence shows a large standard error, although no specific pressure-related trend is observed. Differences in tissue structure and morphology contribute to site-specific probe pressure effects. Therefore, the effects of pressure can be minimized when the pressure is small and applied for a short amount of time; however, long-term and large pressures induce significant distortions in measured spectra.
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Affiliation(s)
- Liang Lim
- The University of Texas at Austin, Department of Biomedical Engineering, 1 University Station C0800, Austin, Texas 78712, USA.
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37
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Kennedy S, Geradts J, Bydlon T, Brown JQ, Gallagher J, Junker M, Barry W, Ramanujam N, Wilke L. Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast. Breast Cancer Res 2010; 12:R91. [PMID: 21054873 PMCID: PMC3046432 DOI: 10.1186/bcr2770] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2010] [Revised: 10/05/2010] [Accepted: 11/05/2010] [Indexed: 01/06/2023] Open
Abstract
Introduction Residual cancer following breast conserving surgery increases the risk of local recurrence and mortality. Margin assessment presents an unmet clinical need. Breast tissue is markedly heterogeneous, which makes distinguishing small foci of cancer within the spectrum of normal tissue potentially challenging. This is further complicated by the heterogeneity as a function of menopausal status. Optical spectroscopy can provide surgeons with intra-operative diagnostic tools. Here, we evaluate ex-vivo breast tissue and determine which sources of optical contrast have the potential to detect malignancy at the margins in women of differing breast composition. Methods Diffuse reflectance spectra were measured from 595 normal and 38 malignant sites from the margins of 104 partial mastectomy patients. All statistical tests were performed using Wilcoxon Rank-Sum tests. Normal and malignant sites were compared before stratifying the data by tissue type and depth and computing statistical differences. The frequencies of the normal tissue types were separated by menopausal status and compared to the corresponding optical properties. Results The mean reduced scattering coefficient, < μs' >, and concentration of total hemoglobin, [THb]), showed statistical differences between malignant (< μs' > : 8.96 cm-1 ± 2.24MAD, [THb]: 42.70 μM ± 29.31MAD) compared to normal sites (< μs' > : 7.29 cm-1 ± 2.15MAD, [THb]: 32.09 μM ± 16.73MAD) (P < 0.05). The sites stratified according to normal tissue type (fibro-glandular (FG), fibro-adipose (FA), and adipose (A)) or disease type (invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS)) showed that FG exhibited increased < μs' > and A showed increased [β-carotene] within normal tissues. Scattering differentiated between most malignant sites, DCIS (9.46 cm-1 ± 1.06MAD) and IDC (8.00 cm-1 ± 1.81MAD), versus A (6.50 cm-1 ± 1.95MAD). [β-carotene] showed marginal differences between DCIS (19.00 μM ± 6.93MAD, and FG (15.30 μM ± 5.64MAD). [THb] exhibited statistical differences between positive sites (92.57 μM ± 18.46MAD) and FG (34.12 μM ± 22.77MAD), FA (28.63 μM ± 14.19MAD), and A (30.36 μM ± 14.86MAD). The diagnostic ability of the optical parameters was affected by distance of tumor from the margin as well as menopausal status. Due to decreased fibrous content and increased adipose content, normal sites in post-menopausal patients exhibited lower < μs' >, but higher [β-carotene] than pre-menopausal patients. Conclusions The data indicate that the ability of an optical parameter to differentiate benign from malignant breast tissues may be dictated by patient demographics. Scattering differentiated between malignant and adipose sites and would be most effective in post-menopausal women. [β-carotene] or [THb] may be more applicable in pre-menopausal women to differentiate malignant from fibrous sites. Patient demographics are therefore an important component to incorporate into optical characterization of breast specimens.
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Affiliation(s)
- Stephanie Kennedy
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
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38
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Cunningham V, Lamela H. Laser optoacoustic spectroscopy of gold nanorods within a highly scattering medium. OPTICS LETTERS 2010; 35:3387-9. [PMID: 20967075 DOI: 10.1364/ol.35.003387] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
We describe a spectroscopic comparative analysis based on the optoacoustic technique over the wavelength range from 410nm to 1000nm using a Q-switched Nd:YAG pumped optical parametric oscillator tunable source on a gold nanostructure solution located within a highly scattering medium. The advantages of this method over standard spectroscopy techniques are the possibility to localize and monitor the spectroscopic response of absorbing materials located within turbid media. The operation is confirmed using a comparative analysis with the spectroscopic results obtained from a reference measurement scheme, based on a highly sensitive collimated optical transmission setup in parallel and under the same experimental conditions as the optoacoustic technique.
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Affiliation(s)
- Vincent Cunningham
- Optoelectronic and Laser Technology Group (GOTL), Carlos III de Madrid University, 28911 Leganes, Madrid, Spain.
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39
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Mallia RJ, Subhash N, Mathews A, Kumar R, Thomas SS, Sebastian P, Madhavan J. Clinical grading of oral mucosa by curve-fitting of corrected autofluorescence using diffuse reflectance spectra. Head Neck 2010; 32:763-79. [PMID: 19827122 DOI: 10.1002/hed.21251] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Laser-induced autofluorescence (LIAF) and diffuse reflectance (DR) were collectively used in this clinical study to improve early oral cancer diagnosis and tissue grading. METHODS LIAF and DR emission from oral mucosa were recorded on a fiber-optic spectrometer by illumination with a 404-nm diode laser and tungsten halogen lamp in 36 healthy volunteers and 40 lesions of 20 patients. RESULTS Absorption dips in LIAF spectra at 545 and 575 nm resulting from changes in oxygenated hemoglobin were corrected using DR spectra of the same site. These corrected spectra were curve-fitted using Gaussian spectral functions to determine constituent emission peaks and their relative contribution. The Gaussian peak intensity and area ratios F500/F635 and F500/F685 were found to be useful indicators of tissue transformation. The diagnostic capability of various ratios in differentiating healthy, hyperplastic, dysplastic, and squamous cell carcinomas (SCCs) were examined using discrimination scatterplots. CONCLUSIONS The LIAF/DR technique, in conjunction with curve-fitting, differentiates different grades of dysplasia and SCC in this clinical trial and proves its potential for early detection of oral cavity cancer and tissue grading.
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Fu HL, Yu B, Lo JY, Palmer GM, Kuech TF, Ramanujam N. A low-cost, portable, and quantitative spectral imaging system for application to biological tissues. OPTICS EXPRESS 2010; 18:12630-45. [PMID: 20588390 DOI: 10.1364/oe.18.012630] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
The ability of diffuse reflectance spectroscopy to extract quantitative biological composition of tissues has been used to discern tissue types in both pre-clinical and clinical cancer studies. Typically, diffuse reflectance spectroscopy systems are designed for single-point measurements. Clinically, an imaging system would provide valuable spatial information on tissue composition. While it is feasible to build a multiplexed fiber-optic probe based spectral imaging system, these systems suffer from drawbacks with respect to cost and size. To address these we developed a compact and low cost system using a broadband light source with an 8-slot filter wheel for illumination and silicon photodiodes for detection. The spectral imaging system was tested on a set of tissue mimicking liquid phantoms which yielded an optical property extraction accuracy of 6.40 +/- 7.78% for the absorption coefficient (micro(a)) and 11.37 +/- 19.62% for the wavelength-averaged reduced scattering coefficient (micro(s)').
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Affiliation(s)
- Henry L Fu
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
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41
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Bydlon TM, Kennedy SA, Richards LM, Brown JQ, Yu B, Junker MK, Gallagher J, Geradts J, Wilke LG, Ramanujam N. Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins. OPTICS EXPRESS 2010; 18:8058-76. [PMID: 20588651 PMCID: PMC2939901 DOI: 10.1364/oe.18.008058] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2009] [Revised: 03/19/2010] [Accepted: 03/20/2010] [Indexed: 05/20/2023]
Abstract
As many as 20-70% of patients undergoing breast conserving surgery require repeat surgeries due to a close or positive surgical margin diagnosed post-operatively [1]. Currently there are no widely accepted tools for intra-operative margin assessment which is a significant unmet clinical need. Our group has developed a first-generation optical visible spectral imaging platform to image the molecular composition of breast tumor margins and has tested it clinically in 48 patients in a previously published study [2]. The goal of this paper is to report on the performance metrics of the system and compare it to clinical criteria for intra-operative tumor margin assessment. The system was found to have an average signal to noise ratio (SNR) >100 and <15% error in the extraction of optical properties indicating that there is sufficient SNR to leverage the differences in optical properties between negative and close/positive margins. The probe had a sensing depth of 0.5-2.2 mm over the wavelength range of 450-600 nm which is consistent with the pathologic criterion for clear margins of 0-2 mm. There was <1% cross-talk between adjacent channels of the multi-channel probe which shows that multiple sites can be measured simultaneously with negligible cross-talk between adjacent sites. Lastly, the system and measurement procedure were found to be reproducible when evaluated with repeated measures, with a low coefficient of variation (<0.11). The only aspect of the system not optimized for intra-operative use was the imaging time. The manuscript includes a discussion of how the speed of the system can be improved to work within the time constraints of an intra-operative setting.
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Affiliation(s)
- Torre M Bydlon
- Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC, 27708, USA.
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Mallia RJ, Narayanan S, Madhavan J, Sebastian P, Kumar R, Mathews A, Thomas G, Radhakrishnan J. Diffuse reflection spectroscopy: an alternative to autofluorescence spectroscopy in tongue cancer detection. APPLIED SPECTROSCOPY 2010; 64:409-18. [PMID: 20412626 DOI: 10.1366/000370210791114347] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
Laser-induced autofluorescence (LIAF) and diffuse reflection spectroscopy (DRS) are two emerging noninvasive optical tools that have shown immense potential to detect oral cavity pre-cancer. In a recent study, we have used spectral ratio reference standards (SRRS) of LIAF intensity ratios F500/F635, F500/F685, and F500/F705 for grading of tissues belonging to sites other than dorsal side of tongue (DST), lateral side of tongue (LST), and vermillion border of lip (VBL) that exhibited similar spectral shape for normal and abnormal tissues. This led to dismal diagnostic accuracies, and for the three LIAF-SRRS, normal tissue values were often misclassified as squamous cell carcinoma (SCC), which means that the true negatives were being wrongly identified as true positives. This study examines the applicability of the site-specific diffuse reflection spectral intensity ratio (R545/R575) of the oxygenated hemoglobin bands to classify different DST lesions and compares the results obtained with those obtained using LIAF-SRRS. DRS-SRRS of R545/R575 differentiated benign hyperplastic DST tissues from normal tissue with a sensitivity of 86% and specificity of 80%, which were indistinguishable using LIAF-SRRS. Further, in distinguishing hyperplastic tissues from premalignant dysplastic lesions, DRS-SRRS gave a sensitivity of 90% and a specificity of 86%, as compared to sensitivity of 89% and specificity of 72% shown by the three LIAF-SRRS together. The diagnostic accuracy and statistical adequacy of the two techniques were assessed by receiver operating characteristic curve (ROC-Curve) analysis. Three LIAF ratios gave a low overall ROC area under curve (ROC-AUCs) of 0.521, whereas the DR ratio (R545/R575) has shown an improved accuracy of 0.970 in differentiating different tissue types. While distinguishing hyperplastic from dysplastic tissues, the DR ratio gave a higher discrimination accuracy of 0.9. Based on these findings, it can be concluded that the DRS-SRRS technique by virtue of its low cost and higher diagnostic accuracies could be a viable alternate to LIAF-SRRS for in vivo screening of tongue pre-cancers and grading of different tissue types.
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Brown JQ, Bydlon TM, Richards LM, Yu B, Kennedy SA, Geradts J, Wilke LG, Junker M, Gallagher J, Barry W, Ramanujam N. Optical assessment of tumor resection margins in the breast. IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS : A PUBLICATION OF THE IEEE LASERS AND ELECTRO-OPTICS SOCIETY 2010; 16:530-544. [PMID: 21544237 PMCID: PMC3085495 DOI: 10.1109/jstqe.2009.2033257] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Breast conserving surgery, in which the breast tumor and surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200,000 women annually. Of these nearly 200,000 patients who undergo this surgical procedure, between 20-70% of them may undergo additional surgeries to remove tumor that was left behind in the first surgery, due to the lack of intra-operative tools which can detect whether the boundaries of the excised specimens are free from residual cancer. Optical techniques have many attractive attributes which may make them useful tools for intra-operative assessment of breast tumor resection margins. In this manuscript, we discuss clinical design criteria for intra-operative breast tumor margin assessment, and review optical techniques appied to this problem. In addition, we report on the development and clinical testing of quantitative diffuse reflectance imaging (Q-DRI) as a potential solution to this clinical need. Q-DRI is a spectral imaging tool which has been applied to 56 resection margins in 48 patients at Duke University Medical Center. Clear sources of contrast between cancerous and cancer-free resection margins were identified with the device, and resulted in an overall accuracy of 75% in detecting positive margins.
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Affiliation(s)
- J. Quincy Brown
- Dept. of Biomedical Engineering, Duke University, Durham, NC 27708 USA
| | - Torre M. Bydlon
- Dept. of Biomedical Engineering, Duke University, Durham, NC 27708
| | - Lisa M. Richards
- Dept. of Biomedical Engineering, Duke University, Durham, NC 27708
| | - Bing Yu
- Dept. of Biomedical Engineering, Duke University, Durham, NC 27708
| | | | - Joseph Geradts
- Depts. of Surgery, Pathology, and Biostatistics, respectively; Duke University Medical Center, Durham, NC 27708 USA
| | - Lee G. Wilke
- Depts. of Surgery, Pathology, and Biostatistics, respectively; Duke University Medical Center, Durham, NC 27708 USA
| | - Marlee Junker
- Dept. of Biomedical Engineering, Duke University, Durham, NC 27708
| | - Jennifer Gallagher
- Depts. of Surgery, Pathology, and Biostatistics, respectively; Duke University Medical Center, Durham, NC 27708 USA
| | - William Barry
- Depts. of Surgery, Pathology, and Biostatistics, respectively; Duke University Medical Center, Durham, NC 27708 USA
| | - Nimmi Ramanujam
- Dept. of Biomedical Engineering, Duke University, Durham, NC 27708
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Keller MD, Majumder SK, Kelley MC, Meszoely IM, Boulos FI, Olivares GM, Mahadevan-Jansen A. Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis. Lasers Surg Med 2010; 42:15-23. [DOI: 10.1002/lsm.20865] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Palmer GM, Boruta RJ, Viglianti BL, Lan L, Spasojevic I, Dewhirst MW. Non-invasive monitoring of intra-tumor drug concentration and therapeutic response using optical spectroscopy. J Control Release 2009; 142:457-64. [PMID: 19896999 DOI: 10.1016/j.jconrel.2009.10.034] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2009] [Revised: 10/15/2009] [Accepted: 10/31/2009] [Indexed: 01/23/2023]
Abstract
Optical spectroscopy was used to monitor changes in tumor physiology with therapy, and its influence on drug delivery and treatment efficacy for hyperthermia treatment combined with free doxorubicin or a low-temperature sensitive liposomal formulation. Monte Carlo-based modeling techniques were used to characterize the intrinsic absorption, scattering, and fluorescence properties of tissue. Fluorescence assessment of drug concentration was validated against HPLC and found to be significantly linearly correlated (r=0.88). Cluster analysis on the physiologic data obtained by optical spectroscopy revealed two physiologic phenotypes prior to treatment. One of these was relatively hypoxic, with relatively low total hemoglobin content. This hypoxic group was found to have a significantly shorter time to reach 3 times pre-treatment volume, indicating a more treatment resistant phenotype (p=0.003). Influence of tumor physiology was assessed in more detail for the liposomal doxorubicin+hyperthermia group, which demonstrated a highly significant correlation between pre-treatment hemoglobin saturation and tumor growth delay, and also between post-hyperthermia total hemoglobin content and tumor drug delivery. Finally, it was found that the doxorubicin concentration, measured in vivo using fluorescence techniques significantly predicted for chemoresponse (hazard ratio: 0.34, p=0.0007). The ability to characterize drug delivery and tumor physiology in vivo makes this a potentially useful tool for evaluating the efficacy of targeted delivery systems in preclinical studies, and may be translatable for monitoring and predicting individual treatment responses in the clinic.
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Affiliation(s)
- Gregory M Palmer
- Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
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Rapid noninvasive optical imaging of tissue composition in breast tumor margins. Am J Surg 2009; 198:566-74. [PMID: 19800470 DOI: 10.1016/j.amjsurg.2009.06.018] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2009] [Revised: 06/30/2009] [Accepted: 06/30/2009] [Indexed: 11/20/2022]
Abstract
BACKGROUND In women undergoing breast conserving surgery (BCS), up to 60% can require re-excision. Our objective is to develop an optically based technology which can differentiate benign from malignant breast tissues intraoperatively through differences in tissue composition factors. METHODS A prospective study of optical imaging of BCS margins is being performed. Optical images are transformed into tissue composition maps with parameters of total hemoglobin concentration, b-carotene concentration and scattering. The predicted outcome is then compared to the margin-level pathology. RESULTS Fifty-five margins from 48 patients have undergone assessment. Within 34 specimens with pathologically confirmed positive margins, the ratio map of b-carotene/scattering showed the most significant difference reflecting a decrease in adipose and an increase in cell density within malignant margins (p=.002). These differences were notable in both in-situ and invasive disease. CONCLUSIONS We present a novel optical spectral imaging device that provides a rapid, non-destructive assay of the tissue composition of breast tumor margins.
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Zhu C, Burnside ES, Sisney GA, Salkowski LR, Harter JM, Yu B, Ramanujam N. Fluorescence spectroscopy: an adjunct diagnostic tool to image-guided core needle biopsy of the breast. IEEE Trans Biomed Eng 2009; 56:2518-28. [PMID: 19272976 PMCID: PMC2791790 DOI: 10.1109/tbme.2009.2015936] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
We explored the use of a fiber-optic probe for in vivo fluorescence spectroscopy of breast tissues during percutaneous image-guided breast biopsy. A total of 121 biopsy samples with accompanying histological diagnosis were obtained clinically and investigated in this study. The tissue spectra were analyzed using partial least-squares analysis and represented using a set of principal components (PCs) with dramatically reduced data dimension. For nonmalignant tissue samples, a set of PCs that account for the largest amount of variance in the spectra displayed correlation with the percent tissue composition. For all tissue samples, a set of PCs was identified using a Wilcoxon rank-sum test as showing statistically significant differences between: 1) malignant and fibrous/benign; 2) malignant and adipose; and 3) malignant and nonmalignant breast samples. These PCs were used to distinguish malignant from other nonmalignant tissue types using a binary classification scheme based on both linear and nonlinear support vector machine (SVM) and logistic regression (LR). For the sample set investigated in this study, the SVM classifier provided a cross-validated sensitivity and specificity of up to 81% and 87%, respectively, for discrimination between malignant and fibrous/benign samples, and up to 81% and 81%, respectively, for discriminating between malignant and adipose samples. Classification based on LR was used to generate receiver operator curves with an area under the curve (AUC) of 0.87 for discriminating malignant versus fibrous/benign tissues, and an AUC of 0.84 for discriminating malignant from adipose tissue samples. This study demonstrates the feasibility of performing fluorescence spectroscopy during clinical core needle breast biopsy, and the potential of this technique for identifying breast malignancy in vivo.
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Affiliation(s)
- Changfang Zhu
- Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI 53706 USA
| | | | - Gale A. Sisney
- Department of Radiology, University of Wisconsin, Madison, WI 53706 USA
| | | | | | - Bing Yu
- Department of Biomedical Engineering, Duke University, Durham, NC 27708 USA
| | - Nirmala Ramanujam
- Department of Biomedical Engineering, Duke University, Durham, NC 27708 USA
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Haka AS, Volynskaya Z, Gardecki JA, Nazemi J, Shenk R, Wang N, Dasari RR, Fitzmaurice M, Feld MS. Diagnosing breast cancer using Raman spectroscopy: prospective analysis. JOURNAL OF BIOMEDICAL OPTICS 2009; 14:054023. [PMID: 19895125 PMCID: PMC2774977 DOI: 10.1117/1.3247154] [Citation(s) in RCA: 120] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2009] [Revised: 07/02/2009] [Accepted: 08/05/2009] [Indexed: 05/18/2023]
Abstract
We present the first prospective test of Raman spectroscopy in diagnosing normal, benign, and malignant human breast tissues. Prospective testing of spectral diagnostic algorithms allows clinicians to accurately assess the diagnostic information contained in, and any bias of, the spectroscopic measurement. In previous work, we developed an accurate, internally validated algorithm for breast cancer diagnosis based on analysis of Raman spectra acquired from fresh-frozen in vitro tissue samples. We currently evaluate the performance of this algorithm prospectively on a large ex vivo clinical data set that closely mimics the in vivo environment. Spectroscopic data were collected from freshly excised surgical specimens, and 129 tissue sites from 21 patients were examined. Prospective application of the algorithm to the clinical data set resulted in a sensitivity of 83%, a specificity of 93%, a positive predictive value of 36%, and a negative predictive value of 99% for distinguishing cancerous from normal and benign tissues. The performance of the algorithm in different patient populations is discussed. Sources of bias in the in vitro calibration and ex vivo prospective data sets, including disease prevalence and disease spectrum, are examined and analytical methods for comparison provided.
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Affiliation(s)
- Abigail S Haka
- Massachusetts Institute of Technology, George R. Harrison Spectroscopy Laboratory, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
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Quantitative physiology of the precancerous cervix in vivo through optical spectroscopy. Neoplasia 2009; 11:325-32. [PMID: 19308287 DOI: 10.1593/neo.81386] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2008] [Revised: 01/14/2009] [Accepted: 01/16/2009] [Indexed: 11/18/2022] Open
Abstract
Cervical cancer is the second most common female cancer worldwide. The ability to quantify physiological and morphological changes in the cervix is not only useful in the diagnosis of cervical precancers but also important in aiding the design of cost-effective detection systems for use in developing countries that lack well-established screening and diagnostic programs. We assessed the capability of a diffuse reflectance spectroscopy technique to identify contrasts in optical biomarkers that vary with different grades of cervical intraepithelial neoplasia (CIN) from normal cervical tissues. The technology consists of an optical probe and an instrument (with broadband light source, dispersive element, and detector), and a Monte Carlo algorithm to extract optical biomarker contributions including total hemoglobin (Hb) concentration, Hb saturation, and reduced scattering coefficient from the measured spectra. Among 38 patients and 89 sites examined, 46 squamous normal sites, 18 CIN 1, and 15 CIN 2(+) sites were included in the analysis. Total Hb was statistically higher in CIN 2(+) (18.3 +/- 3.6 microM, mean +/- SE) compared with normal (9.58 +/- 1.91 microM) and CIN 1 (12.8 +/- 2.6 microM), whereas scattering was significantly reduced in CIN 1 (8.3 +/- 0.8 cm(-1)) and CIN 2(+) (8.6 +/- 1.0 cm(-1)) compared with normal (10.2 +/- 1.1 cm(-1)). Hemoglobin saturation was not significantly altered in CIN 2(+) compared with normal and CIN 1. The difference in total Hb is likely because of stromal angiogenesis, whereas decreased scattering can be attributed to breakdown of collagen network in the cervical stroma.
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Brown JQ, Wilke LG, Geradts J, Kennedy SA, Palmer GM, Ramanujam N. Quantitative optical spectroscopy: a robust tool for direct measurement of breast cancer vascular oxygenation and total hemoglobin content in vivo. Cancer Res 2009; 69:2919-26. [PMID: 19293184 PMCID: PMC2677720 DOI: 10.1158/0008-5472.can-08-3370] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
We propose the use of a robust, biopsy needle-based, fiber-optic tool for routine clinical quantification of tumor oxygenation at the time of diagnostic biopsy for breast cancer. The purpose of this study was to show diffuse reflectance spectroscopy as a quantitative tool to measure oxygenation levels in the vascular compartment of breast cancers in vivo via an optical biopsy technique. Thirty-five patients undergoing surgical treatment for breast cancer were recruited for the study at Duke University Medical Center. Diffuse reflectance spectroscopy was performed on the tumors in situ before surgical resection, followed by needle-core biopsy of the optically measured tissue. Hemoglobin saturation and total hemoglobin content were quantified from 76 optical spectra-tissue biopsy pairs, consisting of 20 malignant, 23 benign, and 33 adipose tissues. Hemoglobin saturation in malignant tissues was significantly lower than nonmalignant tissues (P<0.002) and was negatively correlated with tumor size and pathologic tumor category (P<0.05). Hemoglobin saturation was positively correlated with total hemoglobin content in malignant tissues (P<0.02). HER2/neu-amplified tumors exhibited significantly higher total hemoglobin content (P<0.05) and significantly higher hemoglobin saturation (P<0.02), which is consistent with a model of increased angiogenesis and tumor perfusion promoted by HER2/neu amplification. Diffuse reflectance spectroscopy could aid in prognosis and prediction in breast cancer via quantitative assessment of tumor physiology at the time of diagnostic biopsy.
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Affiliation(s)
- J Quincy Brown
- Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
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