Preclinical quantitative in-vivo assessment of skin tissue vascularity in radiation-induced fibrosis with optical coherence tomography.

Radiation therapy (RT) is widely and effectively used for cancer treatment but can also cause deleterious side effects, such as a late-toxicity complication called radiation-induced fibrosis (RIF). Accurate diagnosis of RIF requires analysis of histological sections to assess extracellular matrix infiltration. This is invasive, prone to sampling limitations, and thus rarely used; instead, current practice relies on subjective clinical surrogates, including visual observation, palpation, and patient symptomatology questionnaires. This preclinical study demonstrates that functional optical coherence tomography (OCT) is a useful tool for objective noninvasive in-vivo assessment and quantification of fibrosis-associated microvascular changes in tissue. Data were collected from murine hind limbs 6 months after 40-Gy single-dose irradiation and compared with nonirradiated contralateral tissues of the same animals. OCT-derived vascular density and average vessel diameter metrics were compared to quantitative vascular analysis of stained histological slides. Results indicate that RIF manifests significant microvascular changes at this time point posttreatment. Abnormal microvascular changes visualized by OCT in this preclinical setting suggest the potential of this label-free high-resolution noninvasive functional imaging methodology for RIF diagnosis and assessment in the context of clinical RT

Physics in Medicine and Biology 52 6 1659 1674 IOP PUBLISHING LTD BRISTOL; DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND

In an effort to understand dynamic optical changes during laser interstitial thermal therapy ( LITT), we utilize the perturbative solution of the diffusion equation in heterogeneous media to formulate scattering weight functions for cylindrical line sources. The analysis explicitly shows how changes in detected interstitial light intensity are associated with the extent and location of the volume of thermal coagulation during treatment. Explanations for previously reported increases in optical intensity observed early during laser heating are clarified using the model and demonstrated with experimental measurements in ex vivo bovine liver tissue. This work provides an improved understanding of interstitial optical signal changes during LITT and indicates the sensitivity and potential of interstitial optical monitoring of thermal damage.CR: AMIN Z, 1993, INVEST RADIOL, V28, P1148 ANDERSON CD, 2004, J GASTROINTEST SURG, V8, P660, DOI 10.1016/j.gassur.2004.04.009 BEVAN PD, 2001, ULTRASOUND MED BIOL, V27, P809 BOWN SG, 1983, WORLD J SURG, V7, P700 BREMER C, 2001, INVEST RADIOL, V36, P327 CHENG HLM, 2003, J MAGN RESON IMAGING, V18, P585, DOI 10.1002/jmri.10388 CHEONG WF, 1995, OPTICAL THERMAL RESP, P275 CHIN LCL, 2001, PHYS MED BIOL, V46, P2407 CHIN LCL, 2003, PHYS MED BIOL, V48, P543 CHIN LCL, 2004, OPT LETT, V29, P959 CHUNG AH, 1999, MED PHYS, V26, P2017 DAVIDSON SRH, 2005, LASER SURG MED, V36, P297 HAZLE JD, 2002, J MAGN RESON IMAGING, V15, P185 IIZUKA MN, 2000, PHYS MED BIOL, V45, P1335 KAK AC, 1988, PRINCIPLES COMPUTERI LARIN KV, 2005, J PHYS D APPL PHYS, V38, P2645, DOI 10.1088/0022-3727/38/15/017 MALONE DE, 1994, INVEST RADIOL, V29, P915 MCNICHOLS RJ, 2004, LASER SURG MED, V34, P48, DOI 10.1002/lsm.10243 MINHAJ AM, 2002, PHYS MED BIOL, V47, P2987 NTZIACHRISTOS V, 2000, P NATL ACAD SCI USA, V97, P2767 OLEARY M, 1996, THESIS U PENNSYLVANI OLEARY MA, 1995, OPT LETT, V20, P426 OSTERMEYER MR, 1997, J OPT SOC AM A, V14, P255 PEARCE J, 1995, OPTICAL THERMAL RESP PUCCINI S, 2003, MAGNET RESON MED, V49, P351, DOI 10.1002/mrm.10357 RITZ JP, 2001, LASER SURG MED, V29, P205 ROGGAN A, 2001, MED LASER APPL, V16, P65 TERENJI A, 2005, LASER SURG MED, V36, P365, DOI 10.1002/lsm.20178 VERHEY JF, 2003, PHYS MED BIOL, V48, P3595 WHELAN WM, 1995, MED PHYS, V22, P105 WHELAN WM, 2005, INT J THERMOPHYS, V26, P23

Media 2: Rapid time-gated polarimetric Stokes imaging using photoelastic modulators

Originally published in Optics Letters on 15 August 2013 (ol-38-16-2997

Media 1: Rapid time-gated polarimetric Stokes imaging using photoelastic modulators

Originally published in Optics Letters on 15 August 2013 (ol-38-16-2997

Journal of Biomedical Optics 12 6 064027 064027 SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS BELLINGHAM; 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA

Interstitial quantification of the optical properties of tissue is important in biomedicine for both treatment planning of minimally invasive laser therapies and optical spectroscopic characterization of tissues, for example, prostate cancer. In a previous study, we analyzed a method first demonstrated by Dickey et al., [Phys. Med. Biol. 46, 2359 (2001)] to utilize relative interstitial steady-state radiance measurements for recovering the optical properties of turbid media. The uniqueness of point radiance measurements were demonstrated in a forward sense, and strategies were suggested for improving performance under noisy experimental conditions. In this work, we test our previous conclusions by fitting the P3 approximation for radiance to Monte Carlo predictions and experimental data in tissue-simulating phantoms. Fits are performed at: 1. a single sensor position (0.5 or 1 cm), 2. two sensor positions (0.5 and 1 cm), and 3. a single sensor position (0.5 or 1 cm) with input knowledge of the sample's effective attenuation coefficient. The results demonstrate that single sensor radiance measurements can be used to retrieve optical properties to within similar to 20%, provided the transport albedo is greater than similar to 0.9. Furthermore, compared to the single sensor fits, employing radiance data at two sensor positions did not significantly improve the accuracy of recovered optical properties. However, with knowledge of the effective attenuation coefficient of the medium, optical properties can be retrieved experimentally to within similar to 10% for an albedo greater or equal to 0.5. (C) 2007 Society of Photo-Optical Instrumentation Engineers.CR: ALTSCHULER MD, 2005, MED PHYS, V32, P3524, DOI 10.1118/1.2107047 BAJARAS O, 1997, PHYS MED BIOL, V42, P1675 CHANDRASEKHAR S, 1950, RADIATIVE TRANSFER CHIN LC, 2006, APPL OPTICS, V45, P101 CHIN LCL, 2004, OPT LETT, V29, P959 DICKEY DJ, 2001, PHYS MED BIOL, V46, P2359 DIMOFTE A, 2005, PHYS MED BIOL, V50, P2291, DOI 10.1088/0031-9155/50/10/008 FARIS GW, 2005, APPL OPTICS, V44, P2058 FARRELL TJ, 1992, MED PHYS, V19, P879 HAYAKAWA CK, 2004, APPL OPTICS, V43, P4677 HENYEY LG, 1941, ASTROPHYS J, V93, P70 HOLMER C, 2006, COLORECTAL TUMORS HE HULL EL, 1998, PHYS MED BIOL, V43, P3381 HULL EL, 2001, J OPT SOC AM A, V18, P584 IIZUKA MN, 1999, LASER SURG MED, V25, P159 JACQUES SL, 1996, OSA TOPS ADV OPTICAL, V2, P364 LIEBERT A, 2003, APPL OPTICS, V42, P5795 LILGE L, 2004, PHYS MED BIOL, V49, P3209, DOI 10.1088/0031-9155/49/14/014 MARIJNISSEN JPA, 1996, PHYS MED BIOL, V41, P1191 MARIJNISSEN JPA, 2002, PHYS MED BIOL, V47, P2049 MARTELLI F, 2000, PHYS MED BIOL, V45, P1359 MENON S, 2005, PHYS REV LETT, V94, ARTN 153904 PUCCINI S, 2003, MAGNET RESON MED, V49, P351, DOI 10.1002/mrm.10357 RINZEMA K, 1998, J OPT SOC AM A, V15, P2078 VANSTAVEREN HJ, 1991, APPL OPTICS, V30, P4507 VENUGOPALAN V, 1998, PHYS REV E B, V58, P2395 WEERSINK RA, 2005, J PHOTOCH PHOTOBIO B, V79, P211, DOI 10.1016/j.jphotobiol.2005.01.008 WYMAN DR, 1989, APPL OPTICS, V28, P5243 XU HP, 2006, OPT EXPRESS, V14, P6485 YOU JS, 2005, PHYS REV E 1, V72, ARTN 021903 ZHU TC, 2005, J PHOTOCH PHOTOBIO B, V79, P231, DOI 10.1016/j.jphotobiol.2004.09.01

Temperature and hydration effects on absorbance spectra and radiation sensitivity of a radiochromic medium

The effects of temperature on real time changes in optical density (ΔOD) of GAFCHROMIC® EBT film were investigated. The spectral peak of maximum change in absorbance (λmax) was shown to downshift linearly when the temperature of the film was increased from 22 to 38 °C. The ΔOD values were also shown to decrease linearly with temperature, and this decrease could not be attributed to the shift in λmax. A compensation scheme using λmax and a temperature-dependent correction factor was investigated, but provided limited improvement. Part of the reason may be the fluctuations in hydration of the active component, which were found to affect both position of absorbance peaks and the sensitivity of the film. To test the effect of hydration, laminated and unlaminated films were desiccated. This shifted both the major and minor absorbance peaks in the opposite direction to the change observed with temperature. The desiccated film also exhibited reduced sensitivity to ionizing radiation. Rehydration of the desiccated films did not reverse the effects, but rather gave rise to another form of the polymer with absorbance maxima upshifted further 20 nm. Hence, the spectral characteristics and sensitivity of the film can be dependent on its history, potentially complicating both real-time and conventional radiation dosimetry

Preclinical longitudinal imaging of tumor microvascular radiobiological response with functional optical coherence tomography

Abstract Radiation therapy (RT) is widely used for cancer treatment, alone or in combination with other therapies. Recent RT advances have revived interest in delivering higher dose in fewer fractions, which may invoke both cellular and microvascular damage mechanisms. Microvasculature may thus be a potentially sensitive functional biomarker of RT early response, especially for such emerging RT treatments. However it is difficult to measure directly and non-invasively, and its time course, dose dependencies, and overall importance in tumor control are unclear. We use functional optical coherence tomography for quantitative longitudinal in vivo imaging in preclinical models of human tumor xenografts subjected to 10, 20 and 30 Gy doses, furnishing a detailed assessment of vascular remodeling following RT. Immediate (minutes to tens of minutes) and early (days to weeks) RT responses of microvascular supply, as well as tumor volume and fluorescence intensity, were quantified and demonstrated robust and complex temporal dose-dependent behaviors. The findings were compared to theoretical models proposed in the literature

Dual-Agent Photodynamic Therapy with Optical Clearing Eradicates Pigmented Melanoma in Preclinical Tumor Models

Treatment using light-activated photosensitizers (photodynamic therapy, PDT) has shown limited efficacy in pigmented melanoma, mainly due to the poor penetration of light in this tissue. Here, an optical clearing agent (OCA) was applied topically to a cutaneous melanoma model in mice shortly before PDT to increase the effective treatment depth by reducing the light scattering. This was used together with cellular and vascular-PDT, or a combination of both. The effect on tumor growth was measured by longitudinal ultrasound/photoacoustic imaging in vivo and by immunohistology after sacrifice. In a separate dorsal window chamber tumor model, angiographic optical coherence tomography (OCT) generated 3D tissue microvascular images, enabling direct in vivo assessment of treatment response. The optical clearing had minimal therapeutic effect on the in control, non-pigmented cutaneous melanomas but a statistically significant effect (p < 0.05) in pigmented lesions for both single- and dual-photosensitizer treatment regimes. The latter enabled full-depth eradication of tumor tissue, demonstrated by the absence of S100 and Ki67 immunostaining. These studies are the first to demonstrate complete melanoma response to PDT in an immunocompromised model in vivo, with quantitative assessment of tumor volume and thickness, confirmed by (immuno) histological analyses, and with non-pigmented melanomas used as controls to clarify the critical role of melanin in the PDT response. The results indicate the potential of OCA-enhanced PDT for the treatment of pigmented lesions, including melanoma

Changes in optical properties of ex vivo rat prostate due to heating

This study examines the effectiveness of a single, first-order Arrhenius process in accurately modelling the thermally induced changes in the optical properties, particularly the reduced scattering coefficient, μ'(s), and the absorption coefficient, μ(a), of ex vivo rat prostate. Recent work has shown that μ'(s) can increase as much as five-fold due to thermal coagulation, and the observed change in μ'(s) has been modelled well according to a first- order rate process in albumen. Conversely, optical property measurements conducted using pig liver suggest that this change in μ'(s) cannot suitably be described using a single rate parameter. In canine prostate, measurements have indicated that while the absorption coefficient varies with temperature, it does not do so according to first-order kinetics. A double integrating sphere system was used to measure the reflectance and transmittance of light at 810 nm through a thin sample of prostate. Using prostate samples collected from Sprague-Dawley rats, optical properties were measured at a constant elevated temperature. Tissue samples were measured over the range 54-83 °C. The optical properties of the sample were determined through comparison with reflectance and transmittance values predicted by a Monte Carlo simulation of light propagation in turbid media. A first-order Arrhenius model was applied to the observed change in μ'(s) and μ(a) to determine the rate process parameters for thermal coagulation. The measured rate coefficients were E(a) = (7.18 ± 1.74) x 104 J mol-1 and A(freq) = 3.14 x 108 s-1 for μ'(s). It was determined that the change in μ'(s) is well described by a single first-order rate process. Similar analysis performed on the changes in μ(a) due to increased temperatures yielded E(a) = (1.01 ± 0.35) x 105 J mol-1 and A(freq) = 8.92 x 1012 s-1. The results for μ(a) suggest that the Arrhenius model may be applicable to the changes in absorption