Dr. Martin E. Isabelle Profile

Dr. Martin E. Isabelle

Research Associate at Dartmouth College

SPIE Involvement:

Author

Publications (9)

Proceedings Article | 7 March 2016 Presentation + Paper

The road map towards providing a robust Raman spectroscopy-based cancer diagnostic platform and integration into clinic

Katherine Lau, Martin Isabelle, Gavin Lloyd, Oliver Old, Neil Shepherd, Ian Bell, Jennifer Dorney, Aaran Lewis, Riana Gaifulina, Manuel Rodriguez-Justo, Catherine Kendall, Nicolas Stone, Geraint Thomas, David Reece

Proceedings Volume 9704, 97040B (2016) https://doi.org/10.1117/12.2230007

KEYWORDS: Raman spectroscopy, Cancer, Data modeling, Diagnostics, Tissues, Pathology, Tissue optics, Statistical modeling, Remote sensing, Tumor growth modeling

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Proceedings Article | 9 March 2012 Paper

Histologic differences between orthotopic xenograft pancreas models affect Verteporfin uptake measured by fluorescence microscopy and spectroscopy

Julia O'Hara, Kimberley Samkoe, Alina Chen, Martin Isabelle, P. Hoopes, Tayyaba Hasan, Brian Pogue

Proceedings Volume 8210, 821014 (2012) https://doi.org/10.1117/12.913049

KEYWORDS: Tumors, Luminescence, Tissues, Blood vessels, Picosecond phenomena, Photodynamic therapy, Pancreas, Tissue optics, Liver, Laser induced fluorescence

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Proceedings Article | 9 March 2012 Paper

Tissue photosensitizer dosimetry using spectrally-resolved fluorescence for pre-clinical and clinical verteporfin-PDT of pancreatic cancer

Martin Isabelle, Scott Davis, Zan Li, Jason Gunn, P. Hoopes, S. Pereira, C. Mosse, T. Hasan, B. Pogue

Proceedings Volume 8210, 821015 (2012) https://doi.org/10.1117/12.921437

KEYWORDS: Tissue optics, Picosecond phenomena, Tumors, Luminescence, Photodynamic therapy, Tissues, Blood, Spectroscopy, Pancreatic cancer, Skin

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Photodynamic therapy (PDT) mediated with verteporfin is currently being investigated to treat pancreatic cancer in patients who are not surgical candidates. Clinically, interstitial light delivery is administered through a fiber, via percutaneous needle implantation guided by ultrasound and/or verified by CT. Tumor response to PDT is based on photosensitizer (PS) dose, light dose, light dose rate and the timing of light application following PS injection. However, studies have shown that even when matching administered PDT treatment parameters such as drug dose and light level, there can be significant inter-patient variation in tissue damage post-PDT, and this has been primarily attributed to imprecise PS concentration at the target tissue site. In order to achieve optimal tumor response from PDT without causing major damage to surrounding tissue, it would be advantageous to measure the PS concentration in the target tissue just prior to light application. From these measurements, the clinician can adapt the light application dose to the measured target tissue PS concentration (i.e. insufficient target tissue PS concentrations compensated by higher light doses and vice versa.) in order to provide an optimal light dose for each patient. In animal studies, a spectrometer-based in-vivo fluorescence dosimetry system has been used to assess accumulated PS levels (verteporfin) in situ. Measurements are taken from skin, leg muscle, buccal mucosa and tumor tissue locations one hour after injection of the photosensitizer. Real-time spectral fitting, subtraction of background autofluorescence and ratiometric analysis is performed on the raw data to extract out only the photosensitizer fluorescence and therefore concentration. Using a pre-measured calibration data set of varying concentrations for verteporfin in tissue phantoms composed of intralipid and whole blood, it was possible detect concentrations of the photosensitizer below 0.5nM. In the clinical studies being performed at UCL Hospital in which verteporfin-PDT treatment is being given to patients with pancreatic cancer, the dosimetry system is being used to assess PS concentration the pancreatic tumor tissue prior to interstitial light dose treatment. The goal of the work here is to determine whether the dosimetry system can accurately and efficiently be used clinically by evaluating the measured local tissue PS concentration to treatment outcome (area of necrosis established). The results of this study will partially determine the need for fluorescence dosimetry to individualize PDT treatment for patients based on local tissue PS concentration.

Proceedings Article | 11 February 2011 Paper

Assessment of biophysical tumor response to PDT in pancreatic cancer using localized reflectance spectroscopy

Martin Isabelle, William Klubben, Ting He, Ashley Laughney, Adam Glaser, Venkataramanan Krishnaswamy, P. Jack Hoopes, Tayyaba Hasan, Brian Pogue

Proceedings Volume 7886, 78860S (2011) https://doi.org/10.1117/12.876147

KEYWORDS: Tissues, Tumors, Photodynamic therapy, Tissue optics, Reflectivity, Inflammation, Imaging systems, Chromophores, Absorbance, Reflectance spectroscopy

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Biophysical changes such as inflammation and necrosis occur immediately following PDT and may be used to assess the treatment response to PDT treatment in-vivo. This study uses localized reflectance measurements to quantify the scatter changes in tumor tissue occurring in response to verteporfin-based PDT treatment in xenograft pancreas tumors. Nude mice were implanted with subcutaneous AsPC-1 pancreatic tumors cells in matrigel, and allowed to establish solid tumors near 100mm3 volume. The mice were sensitized with 1mg/kg of the active component of verteporfin (benzoporphryin derivative, BPD), one hour before light delivery. The optical irradiation was performed using a 1 cm cylindrical interstitial diffusing tip fiber with 20J of red light (690nm). Tumor tissue was excised progressively and imaged, from 1 day to 4 weeks, after PDT treatment. The tissue sections were stained and analyzed by an expert veterinary pathologist, who provided information on tissue regions of interest. This information was correlated with variations in scattering and absorption parameters elucidated from the spectral images and the degree of necrosis and inflammation involvement was identified. Areas of necrosis and dead cells exhibited the lowest average scatter irradiance signature (3.78 and 4.07 respectively) compared to areas of viable pancreatic tumor cells and areas of inflammation (5.81 and 7.19 respectively). Bilirubin absorbance parameters also showed a lower absorbance value in necrotic tissue and areas of dead cells (0.05 and 0.1 respectively) compared to tissue areas for viable pancreatic tumor cells and areas of inflammation (0.28 and 0.35). These results demonstrate that localized reflectance spectroscopy is an imaging modality that can be used to identify tissue features associated with PDT treatment (e.g. necrosis and inflammation) that can be correlated with histopathologically-reviewed H&E stained slides. Further study of this technique may provide means for automated discrimination of tissue features based on scatter and absorbance maps elucidated from reflectance spectral datasets and provide a valuable tool for treatment response monitoring during PDT and enabling more effective treatment planning. These results are relevant to verteporfin-based PDT trial for treatment pancreatic cancer in non-surgical candidate cases (VERTPAC-1 University College London, PI Pereira), where individualized assessment of damage and response could be beneficial, if this study is proven to be a well-controlled imaging tool.

Proceedings Article | 5 March 2010 Paper

In vivo PDT dosimetry: singlet oxygen emission and photosensitizer fluorescence

Seonkyung Lee, Kristin Galbally-Kinney, Brian Murphy, Steven Davis, Tayyaba Hasan, Bryan Spring, Yupeng Tu, Brian Pogue, Martin Isabelle, Julia O'Hara

Proceedings Volume 7551, 75510F (2010) https://doi.org/10.1117/12.846358

KEYWORDS: Oxygen, Photodynamic therapy, Picosecond phenomena, Semiconductor lasers, Luminescence, In vivo imaging, Sensors, Tumors, Imaging systems, Pulsed laser operation

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Proceedings Article | 5 March 2010 Paper

In vivo sampling of Verteporfin uptake in pancreas cancer xenograft models: comparison of surface, oral, and interstitial measurements

Martin Isabelle, Julia O'Hara, Kimberley Samkoe, P. Jack Hoopes, Sandy Mosse, Stephen Pereira, Tayyaba Hasan, Brian Pogue

Proceedings Volume 7551, 755116 (2010) https://doi.org/10.1117/12.852779

KEYWORDS: Picosecond phenomena, Tissues, Tissue optics, Laser induced fluorescence, Photodynamic therapy, Tumors, Pancreas, Natural surfaces, In vivo imaging, Luminescence

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Proceedings Article | 3 March 2010 Paper

EGF targeted fluorescence molecular tomography as a predictor of PDT outcomes in pancreas cancer models

Kimberley Samkoe, Scott Davis, Subhadra Srinivasan, Martin Isabelle, Julia O'Hara, Tayyaba Hasan, Brian Pogue

Proceedings Volume 7551, 75510Q (2010) https://doi.org/10.1117/12.842934

KEYWORDS: Tumors, Photodynamic therapy, Magnetic resonance imaging, Luminescence, Pancreas, Imaging systems, Tissues, Fluorescence tomography, Tomography, Cancer

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