Journal Articles

McAlpine, JN; Hallani, S El; Lam, SF; Kalloger, SE; Luk, M; Huntsman, DG; MacAulay, C; Gilks, CB; Miller, DM; Lane, PM
In: Gynecologic oncology, vol. 120, no. 3, pp. 385–392, 2011.
@article{mcalpine2011autofluorescence,
title = {Autofluorescence imaging can identify preinvasive or clinically occult lesions in fallopian tube epithelium: a promising step towards screening and early detection},
author = { JN McAlpine and S El Hallani and SF Lam and SE Kalloger and M Luk and DG Huntsman and C MacAulay and CB Gilks and DM Miller and PM Lane},
url = {https://biophotonics.bccrc.ca/pubs/McAlpine-2011.pdf, Full Text (PDF)
http://www.ncbi.nlm.nih.gov/pubmed/ 21237503, PubMed},
doi = {10.1016/j.ygyno.2010.12.333},
year = {2011},
date = {2011-01-01},
journal = {Gynecologic oncology},
volume = {120},
number = {3},
pages = {385--392},
publisher = {Elsevier},
abstract = {Background
Optical imaging systems are robust, portable, relatively inexpensive, and have proven utility in detecting precancerous lesions in the lung, esophagus, colon, oral cavity and cervix. We describe the use of light-induced endogenous fluorescence (autofluorescence) in identifying preinvasive and occult carcinomas in ex vivo samples of human fallopian tube (FT) epithelium.
Methods
Women undergoing surgery for an i) ovarian mass, ii) a history suggestive of hereditary breast-ovarian cancer, or iii) known serous ovarian cancer following neoadjuvant chemotherapy (NAC) were approached for informed consent. Immediately following surgery, FT's were photographed in reflectance and fluorescence at high resolution. Images included: (1) white-light reflectance of luminal/epithelial surface; (2) narrow-band green reflectance (570 nm) (3) green autofluorescence (405/436 nm excitation); and (4) blue autofluorescence (405 nm excitation). Areas revealing a loss of natural tissue fluorescence or marked increase in tissue microvasculature were recorded and compared to final histopathologic diagnosis (SEE-FIM protocol).
Results
Fifty-six cases involving one or both fallopian tubes underwent reflectance and fluorescence visualization. Nine cases were excluded, either secondary to non-ovarian primary pathology (7) or excessive trauma (2) rendering tissue interpretation impossible. Of the 47 cases remaining, there were 11 high grade serous (HGS) and 9 non-serous ovarian carcinomas undergoing primary debulking surgery, 5 serous carcinomas having received NAC, 8 benign ovarian tumors, and 14 women undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). Methodology was feasible, efficient, and reproducible. TIC or carcinoma was identified in 7/11 HGS, 3/5 NAC, and 1/14 RRBSO. Optical images were reviewed to determine test positive or negative based on standardized criteria. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the entire cohort (73%; 83%; 57%; 91%) and in a subgroup that excluded non-serous histology (87.5%; 92%; 78%; 96%).
Conclusions
Abnormal FT lesions can be identified using ex vivo optical imaging technologies. With this platform, we will move towards genomic interrogation of identified lesions, and developing in vivo screening modalities via falloposcopy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Optical imaging systems are robust, portable, relatively inexpensive, and have proven utility in detecting precancerous lesions in the lung, esophagus, colon, oral cavity and cervix. We describe the use of light-induced endogenous fluorescence (autofluorescence) in identifying preinvasive and occult carcinomas in ex vivo samples of human fallopian tube (FT) epithelium.
Methods
Women undergoing surgery for an i) ovarian mass, ii) a history suggestive of hereditary breast-ovarian cancer, or iii) known serous ovarian cancer following neoadjuvant chemotherapy (NAC) were approached for informed consent. Immediately following surgery, FT's were photographed in reflectance and fluorescence at high resolution. Images included: (1) white-light reflectance of luminal/epithelial surface; (2) narrow-band green reflectance (570 nm) (3) green autofluorescence (405/436 nm excitation); and (4) blue autofluorescence (405 nm excitation). Areas revealing a loss of natural tissue fluorescence or marked increase in tissue microvasculature were recorded and compared to final histopathologic diagnosis (SEE-FIM protocol).
Results
Fifty-six cases involving one or both fallopian tubes underwent reflectance and fluorescence visualization. Nine cases were excluded, either secondary to non-ovarian primary pathology (7) or excessive trauma (2) rendering tissue interpretation impossible. Of the 47 cases remaining, there were 11 high grade serous (HGS) and 9 non-serous ovarian carcinomas undergoing primary debulking surgery, 5 serous carcinomas having received NAC, 8 benign ovarian tumors, and 14 women undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). Methodology was feasible, efficient, and reproducible. TIC or carcinoma was identified in 7/11 HGS, 3/5 NAC, and 1/14 RRBSO. Optical images were reviewed to determine test positive or negative based on standardized criteria. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the entire cohort (73%; 83%; 57%; 91%) and in a subgroup that excluded non-serous histology (87.5%; 92%; 78%; 96%).
Conclusions
Abnormal FT lesions can be identified using ex vivo optical imaging technologies. With this platform, we will move towards genomic interrogation of identified lesions, and developing in vivo screening modalities via falloposcopy.

Lane, Pierre M; Lam, Stephen; McWilliams, Annette; LeRiche, Jean C.; Anderson, Marshall W; MacAulay, Calum E
Confocal fluorescence microendoscopy of bronchial epithelium Journal Article
In: Journal of biomedical optics, vol. 14, no. 2, pp. 024008–024008, 2009.
@article{lane2009confocal,
title = {Confocal fluorescence microendoscopy of bronchial epithelium},
author = { Pierre M Lane and Stephen Lam and Annette McWilliams and Jean C. LeRiche and Marshall W Anderson and Calum E MacAulay },
url = {https://biophotonics.bccrc.ca/pubs/Lane-2009.pdf, Full Text (PDF)
http://www.ncbi.nlm.nih.gov/pubmed/19405738, PubMed},
doi = {10.1117/1.3103583},
year = {2009},
date = {2009-01-01},
journal = {Journal of biomedical optics},
volume = {14},
number = {2},
pages = {024008--024008},
publisher = {International Society for Optics and Photonics},
abstract = {Confocal microendoscopy permits the acquisition of high-resolution real-time confocal images of bronchial mucosa via the instrument channel of an endoscope. We report here on the construction and validation of a confocal fluorescence microendoscope and its use to acquire images of bronchial epithelium in vivo. Our objective is to develop an imaging method that can distinguish preneoplastic lesions from normal epithelium to enable us to study the natural history of these lesions and the efficacy of chemopreventive agents without biopsy removal of the lesion that can introduce a spontaneous regression bias. The instrument employs a laser-scanning engine and bronchoscope-compatible confocal probe consisting of a fiber-optic image guide and a graded-index objective lens. We assessed the potential of topical application of physiological pH cresyl violet (CV) as a fluorescence contrast-enhancing agent for the visualization of tissue morphology. Images acquired ex vivo with the confocal microendoscope were first compared with a bench-top confocal fluorescence microscope and conventional histology. Confocal images from five sites topically stained with CV were then acquired in vivo from high-risk smokers and compared to hematoxylin and eosin stained sections of biopsies taken from the same site. Sufficient contrast in the confocal imagery was obtained to identify cells in the bronchial epithelium. However, further improvements in the miniature objective lens are required to provide sufficient axial resolution for accurate classification of preneoplastic lesions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Lane, Pierre M
Terminal reflections in fiber-optic image guides Journal Article
In: Applied optics, vol. 48, no. 30, pp. 5802–5810, 2009.
@article{lane2009terminal,
title = {Terminal reflections in fiber-optic image guides},
author = { Pierre M Lane},
url = {https://biophotonics.bccrc.ca/pubs/Lane-2009b.pdf, Full Text (PDF)
http://www.ncbi.nlm.nih.gov/pubmed/19844318, PubMed},
doi = {10.1364/AO.48.005802},
year = {2009},
date = {2009-01-01},
journal = {Applied optics},
volume = {48},
number = {30},
pages = {5802--5810},
publisher = {Optical Society of America},
abstract = {Fibered image guides for confocal reflectance endomicroscopy suffer from Fresnel reflections at the fiber terminals, which can limit signal-to-noise ratio in these systems. A model that describes these terminal reflections is presented to better understand how they can be managed most effectively. An expression for the refractive index of termination that minimizes the reflection as a function of the fiber's normalized frequency is derived for step-index fibers, while a graphical solution is presented for graded-index fibers. The model predicts that terminal reflections from graded-index fibers are more sensitive to variations in fiber size and changes in wavelength than step-index fibers. A method is also presented to measure the refractive index that allows one to minimize the terminal reflections in an image guide. The technique uses the inherent mode coupling of the fibers in the image guide, allowing the isolation and measurement of reflections from only one end of the fiber. An achievable minimum backreflection of -36 dB was measured at 635 nm in a commercial image guide with 30,000 fibers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Lane, Pierre M; MacAulay, Calum E
Reflection-contrast limit of fiber-optic image guides Journal Article
In: Journal of biomedical optics, vol. 14, no. 6, pp. 064028–064028, 2009.
@article{lane2009reflection,
title = {Reflection-contrast limit of fiber-optic image guides},
author = { Pierre M Lane and Calum E MacAulay},
url = {https://biophotonics.bccrc.ca/pubs/Lane-2009a.pdf, Full Text (PDF)
http://www.ncbi.nlm.nih.gov/pubmed/20059266, PubMed},
doi = {10.1117/1.3269679},
year = {2009},
date = {2009-01-01},
journal = {Journal of biomedical optics},
volume = {14},
number = {6},
pages = {064028--064028},
publisher = {International Society for Optics and Photonics},
abstract = {Fiber-optic image guides in confocal reflectance endomicroscopes introduce background backscatter that limits the achievable contrast in these devices. We show the dominant source of backscatter from the image guide is due to Rayleigh scattering at short wavelengths and terminal reflections of the fibers at long wavelengths. The effective Rayleigh scattering coefficient and the wavelength-independent reflectivity due terminal reflections are measured experimentally in a commercial image guide. The Rayleigh scattering component of backscatter can be accurately predicted using the fractional refractive-index difference and length of the fibers in the image guide. We also presented a simple model that can be used to predict signal-to-background ratio in a fiber-optic confocal reflectance endomicroscope for biologically relevant tissues and contrast agents that cover a wide range of reflectivity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Poh, Catherine F; Ng, Samson P; Williams, P Michele; Zhang, Lewei; Laronde, Denise M; Lane, Pierre; MacAulay, Calum; Rosin, Miriam P
Direct fluorescence visualization of clinically occult high-risk oral premalignant disease using a simple hand-held device Journal Article
In: Head & neck, vol. 29, no. 1, pp. 71–76, 2007.
@article{poh2007direct,
title = {Direct fluorescence visualization of clinically occult high-risk oral premalignant disease using a simple hand-held device},
author = { Catherine F Poh and Samson P Ng and P Michele Williams and Lewei Zhang and Denise M Laronde and Pierre Lane and Calum MacAulay and Miriam P Rosin},
url = {https://biophotonics.bccrc.ca/pubs/Poh-2007.pdf, Full Text (PDF)
http://www.ncbi.nlm.nih.gov/pubmed/16983693, PubMed},
doi = {10.1002/hed.20468},
year = {2007},
date = {2007-01-01},
journal = {Head & neck},
volume = {29},
number = {1},
pages = {71--76},
publisher = {Wiley Online Library},
abstract = {A considerable proportion of oral cancer and precancer is not clinically apparent and could contribute significantly to the late diagnosis and high mortality of oral cancer. A simple method to identify such occult change is needed.
METHODS:
Patients in the Oral Dysplasia Clinics at British Columbia are currently being examined with a simple hand-held device that permits the direct visualization of alterations to autofluorescence in the oral cavity. Tissue showing loss of autofluorescence is biopsied.
RESULTS:
We present 3 representative cases in which occult lesions were identified with fluorescence visualization during longitudinal follow-up, resulting in the diagnosis of a primary dysplasia in case 1, a second primary cancer in case 2, and cancer recurrence in case 3.
CONCLUSIONS:
This is the first report of the diagnosis of occult oral disease using a simple noninvasive device. These early examples indicate the potential value of this technology to guide the management of patients with oral lesions, facilitating the detection of high-risk changes not apparent with white-light visualization.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS:
Patients in the Oral Dysplasia Clinics at British Columbia are currently being examined with a simple hand-held device that permits the direct visualization of alterations to autofluorescence in the oral cavity. Tissue showing loss of autofluorescence is biopsied.
RESULTS:
We present 3 representative cases in which occult lesions were identified with fluorescence visualization during longitudinal follow-up, resulting in the diagnosis of a primary dysplasia in case 1, a second primary cancer in case 2, and cancer recurrence in case 3.
CONCLUSIONS:
This is the first report of the diagnosis of occult oral disease using a simple noninvasive device. These early examples indicate the potential value of this technology to guide the management of patients with oral lesions, facilitating the detection of high-risk changes not apparent with white-light visualization.

Lane, Pierre M; Gilhuly, Terence; Whitehead, Peter; Zeng, Haishan; Poh, Catherine F; Ng, Samson; Williams, P Michele; Zhang, Lewei; Rosin, Miriam P; MacAulay, Calum E
Simple device for the direct visualization of oral-cavity tissue fluorescence Journal Article
In: Journal of biomedical optics, vol. 11, no. 2, pp. 024006–024006, 2006.
@article{lane2006simple,
title = {Simple device for the direct visualization of oral-cavity tissue fluorescence},
author = { Pierre M Lane and Terence Gilhuly and Peter Whitehead and Haishan Zeng and Catherine F Poh and Samson Ng and P Michele Williams and Lewei Zhang and Miriam P Rosin and Calum E MacAulay},
url = {https://biophotonics.bccrc.ca/pubs/Lane-2006.pdf, Full Text (PDF)
http://www.ncbi.nlm.nih.gov/pubmed/16674196, PubMed},
doi = {10.1117/1.2193157},
year = {2006},
date = {2006-01-01},
journal = {Journal of biomedical optics},
volume = {11},
number = {2},
pages = {024006--024006},
publisher = {International Society for Optics and Photonics},
abstract = {Early identification of high-risk disease could greatly reduce both mortality and morbidity due to oral cancer. We describe a simple handheld device that facilitates the direct visualization of oral-cavity fluorescence for the detection of high-risk precancerous and early cancerous lesions. Blue excitation light (400 to 460 nm) is employed to excite green-red fluorescence from fluorophores in the oral tissues. Tissue fluorescence is viewed directly along an optical axis collinear with the axis of excitation to reduce inter- and intraoperator variability. This robust, field-of-view device enables the direct visualization of fluorescence in the context of surrounding normal tissue. Results from a pilot study of 44 patients are presented. Using histology as the gold standard, the device achieves a sensitivity of 98% and specificity of 100% when discriminating normal mucosa from severe dysplasia/carcinoma in situ (CIS) or invasive carcinoma. We envisage this device as a suitable adjunct for oral cancer screening, biopsy guidance, and margin delineation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}