Freek J. van der Meer

Temperature-dependent optical properties of individual vascular wall components measured by optical coherence tomography

Optical properties of tissues and tissue components are important parameters in biomedical optics. We report measurements of tissue refractive index n and the attenuation coefficient mu(t) using optical coherence tomography (OCT) of individual vascular wall layers and plaque components. Moreover, since the temperature dependence of optical properties is widely known, we compare measurements at room and body temperatures. A decrease of n and mu(t) is observed in all samples, with the most profound effect on samples with high lipid content. The sample temperature is of influence on the quantitative measurements within OCT images. For extrapolation of ex-vivo experimental results, especially for structures with high lipid content, this effect should be taken into account.

Changes in optical properties of cells and tissue after induction of apoptosis

Apoptosis is the effector of regulated cell death and plays a role in many physiologic and pathologic processes. It is characterized by a highly regulated condensation and fragmentation of the cell nucleus, and breakup of the entire cell into vesicles, (apoptotic bodies) containing cell organelles and fragments of the nucleus. Previous experiments indicate that changes in optical properties after induction of apoptosis might be detected using optical imaging systems, such as optical coherence tomography (OCT), due to an increase in scattering of apoptotic cells. The previous in vitro experiments are extended to ex vivo and in vivo experiments. A nearly two-fold increase in attenuation coefficient is observed in a tissue culture of porcine carotid artery, in which apoptosis is induced by balloon dilation, and a significant 20 % increase in an in vivo setup. The preliminary results of this study indicate that the apoptotic process may also be detected ex vivo and in vivo using optical imaging systems, such as optical coherence tomography (OCT), due to an increase in scattering by the typical disintegration of cellular material.

Detection of apoptosis by optical coherence tomography (OCT)

Apoptosis is the effector of regulated cell death and plays a role in many physiologic and pathologic processes. It is characterized by a highly regulated condensation and fragmentation of the cell nucleus, a large scatterer, and breakup of the entire cell into vesicles, (apoptotic bodies) containing cell organelles and fragments of the nucleus. A two-fold increase in attenuation coefficient ((mu) ) is observed in cell culture after chemical induction of apoptosis. An identical increase in scattering is observed in a tissue culture of porcine carotid artery, in which apoptosis is induced by balloon dilation. These observations are theoretically supported by calculations based on MIE theory. The preliminary results of this study indicate that the apoptotic process may be detected using OCT due to an increase in scattering by the typical disintegration of cellular material. The described increase in scattering may also be detected by other optical techniques.

Hematocrit-dependence of the scattering coefficient of blood determined by optical coherence tomography

We determined the scattering coefficient and scattering anisotropy of blood samples with varying hematocrit using optical coherence tomography measurements and a curve fitting procedure. Initial results show much lower scattering coefficient and scattering anisotropy than theoretically expected, which are likely attributed to the highly forward scattering nature of blood.

Discrimination of atherosclerotic plaque constituents based on local measurements of optical attenuation coefficients by OCT

Imaging of human autopsy samples was performed from the luminal side with a high (3.5 μm axial and 7 μm lateral) resolution OCT system (around 800 nm) or a regular (15-20 μm axial and 20 μm lateral resolution) OCT system (around 1300 nm). For each sample, dimensions were measured by histomorphometry and OCT and the optical attenuation was measured. Quantitative analysis showed a strong and significant correlation between OCT and histology cap thickness measurements for both OCT systems. For both systems, the measured attenuation coefficients of diffuse intimal thickening and lipid-rich regions differed significantly from media and calcifications. Both the high and regular resolution OCT systems can precisely image the atherosclerotic plaques. Quantitative analysis of the OCT signals allowed in situ determination of the intrinsic optical attenuation coefficient of atherosclerotic tissue components within regions of interest, which can further help to discriminate the plaque and arterial wall components.

Temperature dependent optical properties of individual vascular wall components measured by OCT

Optical properties of tissues and tissue components are important parameters in biomedical optics. We report measurements of tissue refractive index n, and the attenuation coefficient μt using optical coherence tomography of individual vascular wall layers and plaque components. Moreover, since the temperature dependence of optical properties is widely known, we compared measurements at room and body temperatures. A decrease of n and μt was observed in all samples, with most profound effect on samples with high lipid content. The sample temperature is of influence on the quantitative measurements within OCT images. For extrapolation of ex vivo experimental results, especially for structures with high lipid content, this effect should be taken into account.

Apoptosis induces temporal increase in attenuation as measured by optical coherence tomography

Optical coherence tomography (OCT) was used to determine optical properties of pelleted human fibroblasts in which necrosis or apoptosis was induced. We analyzed the OCT data including both the scattering properties of the medium and the axial point spread function of the OCT system. We measured that the optical attenuation coefficient in necrotic cells decreased from 2.2 ± 0.3 mm-1 to 1.3 ± 0.6 mm-1, whereas with the apoptotic cells a clear increase (up to 6.4 ± 1.7 mm-1) in scattering was observed. The results on cultured cells a presented in this study indicate the ability of OCT to detect and differentiate between viable, apoptotic and necrotic cells based on their backscatter properties. This functional supplement to high-resolution OCT imaging can be of great clinical benefit, enabling on line monitoring of tissues, e.g. for feedback in cancer treatment.

Quantitative attenuation measurements with single-mode fiber-based OCT

We studied the axial point spread function of OCT 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.

Using optical coherence tomography (OCT) for quantitative measurement of attenuation coefficients of the arterial wall

The feasibility to detect and characterize vulnerable plaques by Optical Coherence Tomography (OCT) is currently under investigation. It has been shown that in some cases, by using qualitative criteria, the OCT images can be used to differentiate between different types of plaque. However, the quality of the image and the experience of the observer greatly influences the interpretation of the images, which indicates the necessity of a quantitative analysis of the OCT data. As OCT measures the depth resolved backscattering it is possible to calculate the light attenuation coefficient (μt) in the different areas in the image and use that to identify the different plaque constituents in the target tissue. In this study, we present in vitro data on μt, measured in atherosclerotic lesions.

Oxygenation measurements with optical coherence tomography

The feasibility of using Optical Coherence Tomography (OCT) for oxygenation determination of whole blood was investigated on porcine blood samples. Our data show a sensitivity in the OCT spectral content to changes in oxygenation that qualitatively correspond to expectations based on the absorption spectra of oxidized hemoglobin and hemoglobin.