Center for Optical Diagnostics and Therapy

Rotterdam, Netherlands

Center for Optical Diagnostics and Therapy

Rotterdam, Netherlands
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Robinson D.J.,Center for Optical Diagnostics and Therapy | Hoy C.L.,Center for Optical Diagnostics and Therapy | Amelink A.,Center for Optical Diagnostics and Therapy
Nederlands Tijdschrift voor Dermatologie en Venereologie | Year: 2013

The human eye is the primary optical diagnostic instrument used in dermatological practice. Despite the ease of a visual skin inspection, it is important to recognise that in many cases the eye or a simple imaging device is not well suited for distinguishing subtle differences in erythema, scaliness or melanin content between dermatoses. The subjectivity of visual analysis remains the primary challenge with the majority of clinical diagnoses. In the present article we describe the underlying interaction between light and the physio-anatomical structure of the skin, the nature and limitations of a visual skin assessment and identify the potential for more advanced approaches. Specifically we make the case for the use of fiber optic spectroscopy, utilising two or more optical fibers with different diameters. When combined with the use of theoretical models, which describe the way that light interacts with tissue, spectroscopy enables the quantification of the absorption, fluorescence and scattering properties of skin. We illustrate the potential benefit of quantitative reflectance and fluorescence spectroscopy in patients with actinic keratosis undergoing optical diagnosis and aminolevulinic acid photodynamic therapy and highlight how these approaches may be implemented in longitudinal population based studies.


Ismail N.,MESA Institute for Nanotechnology | Baclig A.C.,Center for Optical Diagnostics and Therapy | Caspers P.J.,Center for Optical Diagnostics and Therapy | Sun F.,MESA Institute for Nanotechnology | And 4 more authors.
Optics InfoBase Conference Papers | Year: 2010

An integrated low-loss arrayed waveguide grating is designed for Raman spectroscopy of the human skin. The device layout targets spectral analysis of Raman-scattered light for in vivo determination of water concentration in the stratum corneum. © 2010 Optical Society of America.


van Leeuwen-van Zaane F.,Center for Optical Diagnostics and Therapy | de Bruijn H.S.,Erasmus University Rotterdam | van der Ploeg-van den Heuvel A.,Center for Optical Diagnostics and Therapy | Sterenborg H.J.M.C.,Center for Optical Diagnostics and Therapy | Robinson D.J.,Erasmus University Rotterdam
Photodiagnosis and Photodynamic Therapy | Year: 2014

Background: In a previous study it is shown that for topically applied ALA-PDT, PpIX concentration correlates with vascular changes including vasoconstriction and/or vascular leakage of small vessels and arterioles in the mouse epidermis and dermis. In this study we report on vascular responses induced by ALA-PDT for different fluence rates, including both changes in vessel diameter and dynamics in RBC velocity in arterioles, imaged using intra-vital confocal microscopy in skinfold chambers in hairless mice. Our interest is in the dynamics of vascular changes in the early stages of illumination. Methods: We have determined the total PDT dose to be relatively low, 13Jcm-2, and fluence rates of 26, 65 and 130mWcm-2 were investigated. Local vascular effects occurred very soon after the start of the therapeutic illumination in ALA-PDT. Results: In this study, we did not find a significant difference between fluence rates. Arterioles were particularly sensitive to vasoconstriction during low dose PDT, often resulting in complete vasoconstriction. When we observed complete vasoconstriction, this coincided with changes in RBC velocity. Conclusion: Since the therapeutic effects of PDT are dependent on a fine balance between the need for oxygen during illumination and disruption of the vasculature, the results of the present study add to our understanding of acute vascular effects during ALA-PDT and aid our efforts to optimize PDT using porphyrin pre-cursors. © 2014 Elsevier B.V.


Keereweer S.,Leiden University | Keereweer S.,Erasmus Medical Center | Van Driel P.B.A.A.,Leiden University | Robinson D.J.,Center for Optical Diagnostics and Therapy | Lowik C.W.G.M.,Leiden University
Molecular Imaging and Biology | Year: 2014

Abstract: Cancer patients could benefit from a surgical procedure that helps the surgeon to determine adequate tumor resection margins. Systemic injection of tumor-specific fluorescence agents with subsequent intraoperative optical imaging can guide the surgeon in this process. However, tumor heterogeneity hampers tumor-specific targeting. In addition, determination of adequate resection margins can be very challenging due to invasive tumor strands that are difficult to resolve and because of the confounding effect of variations in tissue optical properties in the surgical margin. We provide an overview of the "classic approach" of imaging tumor-specific targets or tumor-associated pathophysiological processes, and explain the limitations of these targeting strategies. It is proposed that problems of tumor heterogeneity can theoretically be circumvented by shifting focus of tumor targeting towards the follicle-stimulating hormone receptor (FSHR). Furthermore, we discuss why objective determination of resection margins is required to improve resection of the invasive strands, a goal that may be achieved by targeting the FSHR. When invasive strands would nevertheless extend beyond such a standardized resection margin, we suggest that adjuvant photodynamic therapy would be a very suitable therapeutic regimen. Finally, we describe how point optical spectroscopy can be used to scrutinize suspect tissue that is difficult to differentiate from normal tissue by measuring the local tissue optical properties to recover a local intrinsic fluorescence measurement. © 2013 World Molecular Imaging Society.


Van Leeuwen-Van Zaane F.,Center for Optical Diagnostics and Therapy | Van Driel P.B.A.A.,Leiden University | Gamm U.A.,Center for Optical Diagnostics and Therapy | Snoeks T.J.A.,Leiden University | And 6 more authors.
Lasers in Surgery and Medicine | Year: 2014

Background and Objective The effect of photodynamic therapy (PDT) is dependent on the localization of photosensitizer in the treatment volume at the time of illumination. Investigation of photosensitizer pharmacokinetics in and around the treatment volume aids in determining the optimal drug light interval for PDT. Materials and Methods In this paper we have investigated the distribution of the photosensitizers chlorin e6 and Bremachlorin in the oral squamous cell carcinoma cell-line OSC19-Luc-Gfp in a tongue tumor, tumor boundary, invasive tumor boundary, and normal tongue tissue by the use of confocal microscopy of frozen sections. Tongues were harvested at t = [3, 4.5, 6, 24, 48] hours after injection. Results Both photosensitizers showed a decreasing fluorescence with increasing incubation time, and at all time points higher fluorescence was measured in tumor boundary than in tumor itself. For short incubation times, a higher fluorescence intensity was observed in the invasive tumor border and normal tissue compared to tumor tissue. Bremachlorin showed a small increase in tumor to normal ratio at 24 and 48 hours incubation time. Ce6 was undetectable at 48 hours. We did not find a correlation between photosensitizer localization and the presence of vasculature. Conclusion The modest tumor/tumor boundary to normal selectivity of between 1.2 and 2.5 exhibited by Bremachlorin 24 and 48 hours after administration may allow selective targeting of tongue tumors. Further studies investigating the relationship between Bremachlorin concentration and therapeutic efficacy PDT with long incubation times are warranted. © 2014 Wiley Periodicals, Inc.


Scheepe J.R.,Center for Optical Diagnostics and Therapy | Amelink A.,Erasmus Medical Center | De Jong B.W.D.,Center for Optical Diagnostics and Therapy | Wolffenbuttel K.P.,Center for Optical Diagnostics and Therapy | Kok D.J.,Center for Optical Diagnostics and Therapy
Journal of Urology | Year: 2011

Purpose: Several studies suggest that hypoxia of the bladder wall contributes to bladder dysfunction but the exact relation between bladder function and blood oxygen saturation, a surrogate marker for hypoxia, is not known. We determined bladder wall blood oxygen saturation in vivo in an animal model of bladder outlet obstruction to establish the exact relation between blood oxygen saturation and bladder function. Materials and Methods: In 8 sham operated and 8 urethrally obstructed guinea pigs we measured blood oxygen saturation of the bladder wall by differential path length spectroscopy before surgery and 8 weeks postoperatively. Urodynamic investigations performed during the whole 8-week period provided data on bladder function. Results: Before surgery and 8 weeks after sham surgery blood oxygen saturation in the bladder wall was between 88% and 95% during filling. It decreased during voiding and returned to greater than 90% within 30 seconds. Eight weeks after obstruction saturation was significantly lower than in the sham operated group during filling and voiding. The decrease was positively related to bladder pressure during filling and voiding, and was more pronounced when overactivity was present. Local bladder contractions occurred without a measurable increase in bladder pressure but were associated with a decrease in saturation. Conclusions: A normal bladder maintains a high oxygen saturation level during filling. Bladder obstruction compromises this ability, especially when it involves overactivity. Local bladder contractions without a measurable increase in bladder pressure were associated with a decrease in blood saturation. © 2011 American Urological Association Education and Research, Inc.


Van Leeuwen-Van Zaane F.,Center for Optical Diagnostics and Therapy | Gamm U.A.,Center for Optical Diagnostics and Therapy | Van Driel P.B.A.A.,Leiden University | Snoeks T.J.,Leiden University | And 6 more authors.
Journal of Biomedical Optics | Year: 2014

Quantification of fluorescence in vivo is complicated by the influence of tissue optical properties on the collected fluorescence signal. When tissue optical properties in the measurement volume are quantified, one can obtain the intrinsic fluorescence, which equals the product of fluorophore absorption coefficient and quantum yield. We applied this method to in vivo single-fiber fluorescence spectroscopy measurements on mouse tongue, skin, liver, and oral squamous cell carcinoma, where we detected intrinsic fluorescence spectra of the photosensitizers chlorin e6 and Bremachlorin at t = [3; 4.5; 6; 24; 48] h incubation time. We observed a tissue-dependent maximum of 35% variation in the total correction factor over the visible wavelength range. Significant differences in spectral shape over time between sensitizers were observed. Although the wavelength position of the fluorescence intensity maximum for ce6 shifted to the red, Bremachlorin showed a blue shift. Furthermore, the Bremachlorin peak appeared to be broader than the ce6 fluorescence peak. Intrinsic fluorescence intensity, which can be related to photosensitizer concentration, was decreasing for all time points but showed significantly more Bremachlorin present compared to ce6 at long incubation times. Results from this study can be used to define an optimal treatment protocol for Bremachlorin-based photodynamic therapy. © 2014 Society of Photo-Optical Instrumentation Engineers.

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