Maurice C. G. Aalders

The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy

A method is described for measuring optical properties and deriving chromophore concentrations from diffuse reflection measurements at the surface of a turbid medium. The method uses a diffusion approximation model for the diffuse reflectance, in combination with models for the absorption and scattering coefficients. An optical fibre-based set-up, capable of measuring nine spectra from 400 to 1050 nm simultaneously, is used to test the method experimentally. Results of the analyses of phantom and in vivo measurements are presented. These demonstrate that in the wavelength range from 600 to 900 nm, tissue scattering can be described as a simple power dependence of the wavelength and that the tissue absorption can be accurately described by the addition of water, oxy- and deoxyhaemoglobin absorption.

Covalently assembled NIR nanoplatform for simultaneous fluorescence imaging and photodynamic therapy of cancer cells.

A highly efficient multifunctional nanoplatform for simultaneous upconversion luminescence (UCL) imaging and photodynamic therapy has been developed on the basis of selective energy transfer from multicolor luminescent NaYF(4):Yb(3+),Er(3+) upconversion nanoparticles (UCNPs) to photosensitizers (PS). Different from popular approaches based on electrostatic or hydrophobic interactions, over 100 photosensitizing molecules were covalently bonded to every 20 nm UCNP, which significantly strengthened the UCNP-PS linkage and reduced the probability of leakage/desorption of the PS. Over 80% UCL was transferred to PS, and the singlet oxygen production was readily detected by its feature emission at 1270 nm. Tests performed on JAR choriocarcinoma and NIH 3T3 fibroblast cells verified the efficient endocytosis and photodynamic effect of the nanoplatform with 980 nm irradiation specific to JAR cancer cells. Our work highlights the promise of using UCNPs for potential image-guided cancer photodynamic therapy.

Endoscopic treatment of high-grade dysplasia and early stage cancer in Barrett's esophagus

BACKGROUND The aim of this study was to prospectively evaluate endoscopic resection (ER) combined with photodynamic therapy (PDT) for the treatment of selected patients with early neoplasia in Barretts esophagus. METHODS Patients with Barretts esophagus and neoplastic lesions <2 cm in diameter and no sign of submucosal infiltration, positive lymph nodes, or distant metastasis underwent diagnostic ER (cap technique). Patients with a T1sm tumor in the resection specimen were referred for surgery; those with a T1m or a less invasive tumor underwent additional endoscopic therapy (ER, PDT, and/or argon plasma coagulation [APC]), or they were followed. PDT was performed with 5-aminolevulinic acid and a light dose of 100 J/cm 2 at lambda = 632 nm. RESULTS Thirty-three patients underwent diagnostic ER. Endoscopic treatment was not performed in 5 patients, who underwent surgery (4 T1sm; 1, patient preference). Five patients were immediately entered into a follow-up protocol, and 23 received additional endoscopic treatment (13 additional ER, 19 PDT, 3 APC). Endoscopic treatment was successful in 26/28 patients; no severe complication was observed. During follow-up (median 19 months, range 13-24 months), 5/26 patients had a recurrence of high-grade dysplasia: all were successfully re-treated with ER. At the end of follow-up, 26/33 originally enrolled patients (79%) and 26/28 endoscopically treated patients (93%) were in local remission. CONCLUSIONS Endoscopic therapy is safe and effective for selected patients with early stage neoplasia in Barretts esophagus.

Mechanistic Study of the Photodynamic Inactivation of Candida albicans by a Cationic Porphyrin

ABSTRACT The growing resistance against antifungal agents has renewed the search for alternative treatment modalities, and antimicrobial photodynamic inactivation (PDI) is a potential candidate. The cationic porphyrin 5-phenyl-10,15,20-Tris(N-methyl-4-pyridyl)porphyrin chloride (TriP[4]) is a photosensitizer that in combination with light can inactivate bacteria, fungi, and viruses. For future improvement of the efficacy of PDI of clinically relevant fungi such as Candida albicans, we sought to understand the working mechanism by following the response of C. albicans exposed to PDI using fluorescence confocal microscopy and freeze-fracture electron microscopy. The following events were observed under dark conditions: TriP[4] binds to the cell envelope of C. albicans, and none or very little TriP[4] enters the cell. Upon illumination the cell membrane is damaged and eventually becomes permeable for TriP[4]. After lethal membrane damage, a massive influx of TriP[4] into the cell occurs. Only the vacuole membrane is resistant to PDI-induced damage once TriP[4] passes the plasma membrane. Increasing the incubation time of C. albicans with TriP[4] prior to illumination did not increase the influx of TriP[4] into the cell or the efficacy of PDI. After the replacement of 100% phosphate-buffered saline (PBS) by 10% PBS as the medium, C. albicans became permeable for TriP[4] during dark incubation and the efficacy of PDI increased dramatically. In conclusion, C. albicans can be successfully inactivated by the cationic porphyrin TriP[4], and the cytoplasmic membrane is the target organelle. TriP[4] influx occurred only after cell death.

Light absorption of (oxy-)hemoglobin assessed by spectroscopic optical coherence tomography

The combination of optical coherence tomography and spectroscopy may allow for highly localized, quantitative measurements of tissue spectral properties. We present, for the first time to our knowledge, quantitative measurements of the absorption coefficients of phantoms and of hemoglobin and oxygenated hemoglobin with spectroscopic optical coherence tomography (SOCT). Our results suggest that SOCT will be able to provide localized, quantitative oxygenation measurements.

Localized measurement of optical attenuation coefficients of atherosclerotic plaque constituents by quantitative optical coherence tomography

Optical coherence tomography (OCT) is a novel, high-resolution diagnostic tool that is capable of imaging the arterial wall and plaques. The differentiation between different types of atherosclerotic plaque is based on qualitative differences in gray levels and structural appearance. We hypothesize that a quantitative data analysis of the OCT signal allows measurement of light attenuation by the local tissue components, which can facilitate quantitative spatial discrimination between plaque constituents. High-resolution OCT images (at 800 nm) of human atherosclerotic arterial segments obtained at autopsy were histologically validated. Using a new, simple analysis algorithm, which incorporates the confocal properties of the OCT system, the light attenuation coefficients for these constituents were determined: for diffuse intimal thickening (5.5/spl plusmn/1.2 mm/sup -1/) and lipid-rich regions (3.2/spl plusmn/1.1 mm/sup -1/), the attenuation differed significantly from media (9.9/spl plusmn/1.8 mm/sup -1/), calcifications (11.1/spl plusmn/4.9 mm/sup -1/) and thrombi (11.2/spl plusmn/2.3 mm/sup -1/) (p<0.01). These proof of principle studies show that simple quantitative analysis of the OCT signals allows spatial determination of the intrinsic optical attenuation coefficient of atherosclerotic tissue components within regions of interest. Combining morphological imaging by OCT with the observed differences in optical attenuation coefficients of the various regions may enhance discrimination between various plaque types.

In vitro double-integrating-sphere optical properties of tissues between 630 and 1064 nm

The optical properties (absorption and scattering coefficients and the scattering anisotropy factor) were measured in vitro for cartilage, liver, lung, muscle, myocardium, skin, and tumour (colon adenocarcinoma CC 531) at 630, 632.8, 790, 850 and 1064 nm. Rabbits, rats, piglets, goats, and dogs were used to obtain the tissues. A double-integrating-sphere setup with an intervening sample was used to determine the reflectance, and the diffuse and collimated transmittances of the sample. The inverse adding-doubling algorithm was used to determine the optical properties from the measurements. The overall results were comparable to those available in the literature, although only limited data are available at 790-850 nm. The results were reproducible for a specific sample at a specific wavelength. However, when comparing the results of different samples of the same tissue or different lasers with approximately the same wavelength (e.g. argon dye laser at 630 nm and HeNe laser at 632.8 nm) variations are large. We believe these variations in optical properties should be explained by biological variations of the tissues. In conclusion, we report on an extensive set of in vitro absorption and scattering properties of tissues measured with the same equipment and software, and by the same group. Although the accuracy of the method requires further improvement, it is highly likely that the other existing data in the literature have a similar level of accuracy.

Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography

The use of spectroscopic optical coherence tomography to assess hemoglobin oxygen saturation of whole blood is investigated. We propose to use the differential attenuation coefficient to determine the degree of saturation. Our data show qualitative agreement between the measured differential attenuation coefficients as a function of saturation and predictions based on the oxygen-saturation-dependent absorption and scattering properties of blood.

Measurement of the axial point spread function in scattering media using single-mode fiber-based optical coherence tomography

The authors studied the axial point spread function of optical coherence tomography for Gaussian intensity profiles emitted from and coupled back into single-mode fibers for signals from a scattering medium. The determined Rayleigh length of the axial point spread function was roughly twice the one measured from the reflection of a mirror. Using the measured point spread function in combination with the single backscatter model allowed determination of the attenuation coefficient of the suspension.

Hyperspectral imaging for non-contact analysis of forensic traces

Hyperspectral imaging (HSI) integrates conventional imaging and spectroscopy, to obtain both spatial and spectral information from a specimen. This technique enables investigators to analyze the chemical composition of traces and simultaneously visualize their spatial distribution. HSI offers significant potential for the detection, visualization, identification and age estimation of forensic traces. The rapid, non-destructive and non-contact features of HSI mark its suitability as an analytical tool for forensic science. This paper provides an overview of the principles, instrumentation and analytical techniques involved in hyperspectral imaging. We describe recent advances in HSI technology motivating forensic science applications, e.g. the development of portable and fast image acquisition systems. Reported forensic science applications are reviewed. Challenges are addressed, such as the analysis of traces on backgrounds encountered in casework, concluded by a summary of possible future applications.