Using DRS during breast conserving surgery: identifying robust optical parameters and influence of inter-patient variation.

Successful breast conserving surgery consists of complete removal of the tumor while sparing healthy surrounding tissue. Despite currently available imaging and margin assessment tools, recognizing tumor tissue at a resection margin during surgery is challenging. Diffuse reflectance spectroscopy (DRS), which uses light for tissue characterization, can potentially guide surgeons to prevent tumor positive margins.

In vivo characterization of colorectal metastases in human liver using diffuse reflectance spectroscopy: toward guidance in oncological procedures.

There is a strong need to develop clinical instruments that can perform rapid tissue assessment at the tip of smart clinical instruments for a variety of oncological applications. This study presents the first in vivo real-time tissue characterization during 24 liver biopsy procedures using diffuse reflectance (DR) spectroscopy at the tip of a core biopsy needle with integrated optical fibers. DR measurements were performed along each needle path, followed by biopsy of the target lesion using the same needle.

Studying skin tumourigenesis and progression in immunocompetent hairless SKH1-hr mice using chronic 7,12-dimethylbenz(a)anthracene topical applications to develop a useful experimental skin cancer model.

Previous studies have established that 7,12-dimethylbenz(a)anthracene (DMBA) can initiate skin tumourigenesis in conventional furred mouse models by acting on hair follicle stem cells. However, further cancer progression depends on repeated applications of tumour promoter agents. This study evaluated the timeline involved in skin tumourigenesis and progression in immunocompetent hairless SKH1-hr mice with dysfunctional hair follicles using only DMBA with no additional tumour promoter agents.

Somatostatin analogues for receptor targeted photodynamic therapy.

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells.

Chromophore based analyses of steady-state diffuse reflectance spectroscopy: current status and perspectives for clinical adoption.

Diffuse reflectance spectroscopy is a rapidly growing technology in the biophotonics community where it has shown promise in its ability to classify different tissues. In the steady-state domain a wide spectrum of clinical applications is supported with this technology ranging from diagnostic to guided interventions. Diffuse reflectance spectra provide a wealth of information about tissue composition; however, extracting biologically relevant information from the spectra in terms of chromophores may be more useful to gain acceptance into the clinical community.

Intrinsic photosensitizer fluorescence measured using multi-diameter single-fiber spectroscopy in vivo.

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.

Microscopic analysis of the localization of two chlorin-based photosensitizers in OSC19 tumors in the mouse oral cavity.

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.

Localization of liposomal mTHPC formulations within normal epithelium, dysplastic tissue, and carcinoma of oral epithelium in the 4NQO-carcinogenesis rat model.

Background And Objective: Foslip and Fospeg are liposomal formulations of the photosensitizer mTHPC (Foscan), which is used for photodynamic therapy (PDT) of malignancies. Literature suggests that liposomal mTHPC formulations have better properties and increased tumor uptake compared to Foscan. To investigate this, we used the 4NQO-induced carcinogen model to compare the localization of the different mTHPC formulations within normal, precancerous, and cancerous tissue.

Method for rapid multidiameter single-fiber reflectance and fluorescence spectroscopy through a fiber bundle.

We have recently demonstrated a means for quantifying the absorption and scattering properties of biological tissue through multidiameter single-fiber reflectance (MDSFR) spectroscopy. These measurements can be used to correct single-fiber fluorescence (SFF) spectra for the influence of optical properties, enabling quantification of intrinsic fluorescence. In our previous work, we have used a series of pinholes to show that selective illumination and light collection using a coherent fiber bundle can simulate a single solid-core optical fiber with variable diameter for the purposes of MDSFR spectroscopy.

Optical image-guided cancer surgery: challenges and limitations.

Optical image-guided cancer surgery is a promising technique to adequately determine tumor margins by tumor-specific targeting, potentially resulting in complete resection of tumor tissue with improved survival. However, identification of the photons coming from the fluorescent contrast agent is complicated by autofluorescence, optical tissue properties, and accurate fluorescent targeting agents and imaging systems. All these factors have an important influence on the image that is presented to the surgeon.

The use of optical spectroscopy for in vivo detection of cervical pre-cancer.

In order to investigate the effectiveness of optical spectroscopy for in vivo diagnosis of cervical pre-cancerous conditions, a series of published studies are surveyed. The six optical technologies investigated include fluorescence spectroscopy, reflectance spectroscopy, and their combination using point probe or multispectral imaging approaches. Searching in the well-known databases, the most recent published works were sought out.

Estimating the risk of squamous cell cancer induction in skin following nonlinear optical imaging.

High power femto-second (fs) laser pulses used for in-vivo nonlinear optical (NLO) imaging can form cyclobutane pyrimidine dimers (CPD) in DNA, which may lead to carcinogenesis via subsequent mutations. Since UV radiation from routine sun exposure is the primary source of CPD lesions, we evaluated the risk of CPD-related squamous cell carcinoma (SCC) in human skin due to NLO imaging relative to that from sun exposure. We developed a unique cancer risk model expanding previously published estimation of risk from exposure to continuous wave (CW) laser.

Single fiber reflectance spectroscopy on cervical premalignancies: the potential for reduction of the number of unnecessary biopsies.

We have assessed the value of single fiber reflectance (SFR) spectroscopy in prediction of cervical squamous intraepithelial lesions (SIL). SFR was used to measure reflected light from 32 patients undergoing standard colposcopy. Seven parameters extracted from the spectra in addition to two biographic parameters were compared in biopsy-confirmed SIL versus nonSIL.

Carcinogenic damage to deoxyribonucleic acid is induced by near-infrared laser pulses in multiphoton microscopy via combination of two- and three-photon absorption.

Nonlinear optical imaging modalities (multiphoton excited fluorescence, second and third harmonic generation) applied in vivo are increasingly promising for clinical diagnostics and the monitoring of cancer and other disorders, as they can probe tissue with high diffraction-limited resolution at near-infrared (IR) wavelengths. However, high peak intensity of femtosecond laser pulses required for two-photon processes causes formation of cyclobutane-pyrimidine-dimers (CPDs) in cellular deoxyribonucleic acid (DNA) similar to damage from exposure to solar ultraviolet (UV) light. Inaccurate repair of subsequent mutations increases the risk of carcinogenesis.

Light fractionated ALA-PDT enhances therapeutic efficacy in vitro; the influence of PpIX concentration and illumination parameters.

Light fractionation, with a long dark interval, significantly increases the response to ALA-PDT in pre-clinical models and in non-melanoma skin cancer. We investigated if this increase in efficacy can be replicated in PAM 212 cells in vitro. The results show a significant decrease in cell survival after light fractionation which is dependent on the PpIX concentration and light dose of the first light fraction.

Light fractionation significantly improves the response of superficial basal cell carcinoma to aminolaevulinic acid photodynamic therapy: five-year follow-up of a randomized, prospective trial.

Photodynamic therapy (PDT) using topical porphyrin-precursors is a promising treatment for superficial basal cell carcinoma (sBCC), but it needs further optimization. The aim of this study was to compare 5-year lesion (complete) response rates of sBCC treated with topical aminolaevulinic acid (ALA)-PDT using a single illumination vs. ALA-PDT using a 2-fold illumination scheme.

Photodynamic therapy with systemic meta-tetrahydroxyphenylchlorin in the treatment of anal intraepithelial neoplasia, grade 3.

Background And Objective: Anal cancer and preneoplastic anal lesions (anal intraepithelial neoplasia, AIN) rising especially in men having sex with men (MSM). There are no widely accepted treatment standards for AIN. Photodynamic therapy (PDT) using the systemic sensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the potential to treat the anal area even when the exact borders of the preneoplastic anal lesion cannot easily be visualized.

In vivo quantification of photosensitizer concentration using fluorescence differential path-length spectroscopy: influence of photosensitizer formulation and tissue location.

In vivo measurement of photosensitizer concentrations may optimize clinical photodynamic therapy (PDT). Fluorescence differential path-length spectroscopy (FDPS) is a non-invasive optical technique that has been shown to accurately quantify the concentration of Foscan® in rat liver. As a next step towards clinical translation, the effect of two liposomal formulations of mTHPC, Fospeg® and Foslip®, on FDPS response was investigated.

Extraction of intrinsic fluorescence from single fiber fluorescence measurements on a turbid medium.

This study utilizes Monte Carlo simulations of single fiber fluorescence to develop an empirical model that corrects for the influence of scattering and absorption on fluorescence intensity (F(SF)). The model expresses F(SF) in terms of the reduced scattering coefficient (μs') and absorption coefficient (μ(a)), each determined independently at excitation and emission wavelengths (λ(x) and λ(m)), and the fiber diameter (d(f)). This model returns accurate descriptions (mean residual <6%) of F(SF) across a biologically relevant range of μs' and μ(a) values and is insensitive to the form of the scattering phase function.

mTHPC mediated interstitial photodynamic therapy of recurrent nonmetastatic base of tongue cancers: Development of a new method.

Background: Interstitial photodynamic therapy (iPDT) can be an option in the management of locally recurrent base of tongue cancer after (chemo)radiation treatment. The purpose of the current study was to develop a technique to implant light sources into the tumor tissue.

Methods: Twenty patients with previously irradiated locally recurrent base of tongue cancers who were not candidates for salvage surgery or reirradiation or refused these therapies were included in this study.

Validation of interventional fiber optic spectroscopy with MR spectroscopy, MAS-NMR spectroscopy, high-performance thin-layer chromatography, and histopathology for accurate hepatic fat quantification.

Objectives: To validate near-infrared (NIR)-based optical spectroscopy measurements of hepatic fat content using a minimally invasive needle-like probe with integrated optical fibers, enabling real-time feedback during percutaneous interventions. The results were compared with magnetic resonance spectroscopy (MRS) as validation and with histopathology, being the clinical gold standard. Additionally, ex vivo magic angle spinning nuclear magnetic resonance spectroscopy and high-performance thin-layer chromatography were performed for comparison.

The future of medical diagnostics: review paper.

While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation.

Clinical feasibility of monitoring m-THPC mediated photodynamic therapy by means of fluorescence differential path-length spectroscopy.

The objective quantitative monitoring of light, oxygen, and photosensitizer is challenging in clinical photodynamic therapy settings. We have previously developed fluorescence differential path-length spectroscopy (FDPS), a technique that utilizes reflectance spectroscopy to monitor microvascular oxygen saturation, blood volume fraction, and vessel diameter, and fluorescence spectroscopy to monitor photosensitizer concentration. In this paper the clinical feasibility of the technique is tested on eight healthy volunteers and on three patients undergoing PDT of oral cavity cancers.

In vivo measurement of bladder wall oxygen saturation using optical spectroscopy.

Current diagnosis, follow-up and treatment of patients suffering from bladder dysfunction are mainly symptom-targeted. A recently recognized cause of continuing bladder function loss is a deteriorated bladder microvasculature. Incorporating this aspect into the clinical diagnostic toolbox may improve treatment results.