Biomedical subjects

Ton G van Leeuwen

Publications and source records attributed to Ton G van Leeuwen.

16 recordsLinked to original sources

PubMed2006

Recent developments in optical coherence tomography for imaging the retina.

Optical coherence tomography (OCT) was introduced in ophthalmology a decade ago. Within a few years in vivo imaging of the healthy retina and optic nerve head and of retinal diseases was a fact. In particular the ease with which these images can be acquired considerably changed the diagnostic strategy used by ophthalmologists. The OCT technique currently available in clinical practice is referred to as time-domain OCT, because the depth information of the retina is acquired as a sequence of samples, over time. This can be done either in longitudinal cross-sections perpendicular to, or in the coronal plane parallel to the retinal surface. Only recently, major advances have been made as to image resolution with the introduction of ultrahigh resolution OCT and in imaging speed, signal-to-noise ratio and sensitivity with the introduction of spectral-domain OCT. Functional OCT is the next frontier in OCT imaging. For example, polarization-sensitive OCT uses the birefringent characteristics of the retinal nerve fibre layer to better assess its thickness. Blood flow information from retinal vessels as well as the oxygenation state of retinal tissue can be extracted from the OCT signal. Very promising are the developments in contrast-enhanced molecular optical imaging, for example with the use of scattering tuneable nanoparticles targeted at specific tissue or cell structures. This review will provide an overview of these most recent developments in the field of OCT imaging focussing on applications for the retina.

Humans↗

PubMed2006

In vivo photoacoustic imaging of blood vessels with a pulsed laser diode.

Photoacoustic imaging is a hybrid imaging modality that is based on the detection of acoustic waves generated by absorption of pulsed light by tissue chromophores such as hemoglobin in blood. For this technique, usually large and costly Q-switched Nd:YAG lasers are used. These lasers provide a pulse energy of at least several milliJoules. In search of alternative light sources, we investigated the use of a small and compact pulsed laser diode to image blood vessels. We proved that a pulsed laser diode can be applied for imaging blood vessels in vivo.

Acoustics↗

PubMed2006

Photoacoustic imaging of valves in superficial veins.

BACKGROUND AND OBJECTIVES: In intravenous access to veins there is a risk of puncturing venous valves or blocking of the catheter by the valves. Therefore, we have investigated whether and how photoacoustic imaging (PAI), which visualizes the lumen of blood vessels, can be used to detect these valves. STUDY DESIGN/MATERIALS AND METHODS: Venous valves in superficial veins on the dorsal side of the hand of human volunteers were located by palpation and visual inspection. Next, this location was imaged using PAI. RESULTS: In 16 of 21 human volunteers venous valves that were found by palpation could be observed by PAI as local discontinuities in the imaged vessel. From these images, four characteristic features by which venous valves can be recognized in photoacoustic images were identified. CONCLUSIONS: PAI has the potential to be applied in the detection of venous valves.

Acoustics↗

PubMed2006

Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX.

Molecular oxygen is the primary oxidant in biological systems. The ultimate destination of oxygen in vivo is the mitochondria where it is used in oxidative phosphorylation. The ability of this process to produce an amount of high-energy phosphates adequate to sustain life highly depends on the available amount of oxygen. Despite a vast array of techniques to measure oxygen, major (patho)physiological questions remain unanswered because of the unavailability of quantitative techniques to measure mitochondrial oxygen in situ. Here we demonstrate that mitochondrial PO(2) can be directly measured in living cells by harnessing the delayed fluorescence of endogenous protoporphyrin IX (PpIX), thereby providing a technique with the potential for a wide variety of applications. We applied this technique to different cell lines (V-79 Chinese hamster lung fibroblasts, HeLa cells and IMR 32-K1 neuroblastoma cells) and present the first direct measurements of the oxygen gradient between the mitochondria and the extracellular volume.

Animals↗

PubMed2005

The Twente Photoacoustic Mammoscope: system overview and performance.

We present PAM, the Photoacoustic Mammoscope developed at the University of Twente, intended for initial retrospective clinical studies on subjects with breast tumours. A parallel plate geometry has been adopted and the breast will be gently compressed between a glass plate and a flat ultrasound detector matrix. Pulsed light (5 ns) from an Nd:YAG laser will impinge the breast through the glass plate in regions of interest; an appropriate number of the 590 elements of the detector matrix will be activated in succession to record photoacoustic signals. Three-dimensional image reconstruction employs a delay-and-sum beamforming algorithm. We discuss various instrumental aspects and the proposed imaging protocol. Performance studies of the ultrasound detector are presented in terms of sensitivity, frequency response and resolution. Details of the patient-instrument interface are provided. Finally some imaging results on well-characterized breast tissue phantoms with embedded tumour simulating inserts are shown.

Acoustics↗

PubMed2005

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.

Algorithms↗

PubMed2005

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 +/- 1.2 mm(-1)) and lipid-rich regions (3.2 +/- 1.1 mm(-1)), the attenuation differed significantly from media (9.9 +/- 1.8 mm(-1)), calcifications (11.1 +/- 4.9 mm(-1) ) and thrombi (11.2 +/- 2.3 mm(-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.

Algorithms↗

PubMed2004

Photoacoustic determination of blood vessel diameter.

A double-ring sensor was applied in photoacoustic tomographic imaging of artificial blood vessels as well as blood vessels in a rabbit ear. The peak-to-peak time (tau(pp)) of the laser (1064 nm) induced pressure transient was used to estimate the axial vessel diameter. Comparison with the actual vessel diameter showed that the diameter could be approximated by 2ctau(pp), with c the speed of sound in blood. Using this relation, the lateral diameter could also precisely be determined. In vivo imaging and monitoring of changes in vessel diameters was feasible. Finally, acoustic time traces were recorded while flushing a vessel in the rabbit ear with saline, which proved that the main contribution to the laser-induced pressure transient is caused by blood inside the vessel and that the vessel wall gives only a minor contribution.

Acoustics↗

PubMed2004

Quantitative determination of localized tissue oxygen concentration in vivo by two-photon excitation phosphorescence lifetime measurements.

This study describes the use of two-photon excitation phosphorescence lifetime measurements for quantitative oxygen determination in vivo. Doubling the excitation wavelength of Pd-porphyrin from visible light to the infrared allows for deeper tissue penetration and a more precise and confined selection of the excitation volume due to the nonlinear two-photon effect. By using a focused laser beam from a 1,064-nm Q-switched laser, providing 10-ns pulses of 10 mJ, albumin-bound Pd-porphyrin was effectively excited and oxygen-dependent decay of phosphorescence was observed. In vitro calibration of phosphorescence lifetime vs. oxygen tension was performed. The obtained calibration constants were kq = 356 Torr(-1) x s(-1) (quenching constant) and tau0 = 550 micros (lifetime at zero-oxygen conditions) at 37 degrees C. The phosphorescence intensity showed a squared dependency to the excitation intensity, typical for two-photon excitation. In vivo demonstration of two-photon excitation phosphorescence lifetime measurements is shown by step-wise PO2 measurements through the cortex of rat kidney. It is concluded that quantitative oxygen measurements can be made, both in vitro and in vivo, using two-photon excitation oxygen-dependent quenching of phosphorescence. The use of two-photon excitation has the potential to lead to new applications of the phosphorescence lifetime technique, e.g., noninvasive oxygen scanning in tissue at high spatial resolution. To our knowledge, this is the first report in which two-photon excitation is used in the setting of oxygen-dependent quenching of phosphorescence lifetime measurements.

Animals↗

PubMed2004

Oxygen saturation-dependent absorption and scattering of blood.

We report on the scattering properties of oxygenated and deoxygenated whole blood from 250 to 1000 nm. We determine the complex refractive index of oxygenated and deoxygenated hemoglobin using a Kramers-Kronig analysis and optical coherence tomography measurements. Combining these data with Mie theory, the scattering properties are calculated. The strong oxygen saturation dependent scattering effects should be taken into account in the data analysis of optical oxymetry.

Absorption↗

PubMed2003

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.

Absorption↗

PubMed2003

Function and structure of pressurized and perfused porcine carotid arteries: effects of in vitro balloon angioplasty.

In this report we describe the application of an in vitro pressure-perfusion system for study of functional/structural changes after in vitro balloon dilation injury. Pig carotid arteries were perfused at P = 100 mm Hg and Q = 100 ml/min, balloon angioplastied (BA), and cultured under these hemodynamic conditions for 4 or 8 days (n = 5 BA and 6 controls for each time point). To assess endothelial function, outer diameter changes in response to bradykinin (BK) were measured daily. Remodeling was determined from the shift in pressure-passive diameter relation, as obtained after papaverine addition. Arterial samples were processed for histology. Control arteries showed spontaneous tone, BK-induced relaxation, and inward remodeling that was more pronounced at day 8 (ratio end-to-start passive diameter at P = 100 mm Hg, 0.69 +/- 0.04; P < 0.001) than at day 4 (0.85 +/- 0.03, P = 0.03). Intimal hyperplasia was detectable in these control vessels at day 8 with accumulation of alpha-smooth muscle actin-positive cells around the lumen. Angioplasty caused ruptures and dissections and abolished tone that returned after 5 days of perfusion along with BK-dependent relaxation. No significant inward remodeling or intimal hyperplasia was observed at day 8 after angioplasty. Thus, BA inhibits remodeling, which occurs after in vitro perfusion of conductance arteries.

Angioplasty, Balloon↗

PubMed2002

UVB-activated psoralen reduces luminal narrowing after balloon dilation because of inhibition of constrictive remodeling.

In this study we have explored the potential of PUVB (8-MOP + UVB) therapy for the reduction of luminal narrowing after arterial injury. In 15 rabbits, balloon dilation of iliac arteries was performed. In 20 arteries, dilation was combined with the delivery of pulsed ultraviolet light B (UVB) irradiation with 10 arteries being previously subjected to sensitizer infusion. Changes in vessel diameter, proliferation and extracellular matrix protein content at 6 weeks were evaluated by means of angiography and histomorphometry-immunohistochemistry. We found that PUVB, applied at the time of dilation, induced reduction in late loss (LL) at 6 weeks (percutaneous transluminal angioplasty vs UVB vs PUVB: 0.64 +/- 0.15 mm vs 0.61 +/- 0.05 mm vs 0.29 +/- 0.05 mm; p = 0.018). The same holds true for constrictive remodeling (0.53 +/- 0.15 mm vs 0.45 +/- 0.06 mm vs 0.15 +/- 0.05 mm; p = 0.016). In the irradiation groups, LL was independent of acute gain (AG), as opposed to the control. Collagen content increased significantly after PUVB in media and adventitia, without increased cellular proliferation in all vessel layers. Thus, PUVB at the time of dilation reduced luminal narrowing at follow-up without effecting proliferation. This effect was independent of AG and was associated with increased collagen content in media and adventitia.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Photoacoustic mammography laboratory prototype: imaging of breast tissue phantoms.

We present a laboratory version of a photoacoustic mammoscope, based on a parallel plate geometry. The instrument is built around a flat high-density ultrasound detector matrix. The light source is a Q-switched Nd:YAG laser with a pulse duration of 5 ns. To test the instrument, a novel photoacoustic phantom is developed using poly(vinyl alcohol) gel, prepared by a simple procedure that imparts optical scattering suggestive of breast tissue to it without the requirement for extraneous scattering particles. Tumor simulating poly(vinyl alcohol) gel spheres appropriately dyed at the time of preparation are characterized for optical absorption coefficients. These are then embedded in the phantom to serve as tumors with absorption contrasts ranging from 2 to 7, with respect to the background. Photoacoustic studies in transmission mode are performed, by acquiring the laser-induced ultrasound signals from regions of interest in the phantom. Image reconstruction is based on a delay-and-sum beamforming algorithm. The results of these studies provide an insight into the capabilities of the prototype. Various recommendations that will guide the evolving of our laboratory prototype into a clinical version are also discussed.

Acoustics↗

PubMedDate not supplied

Photoacoustic imaging of blood vessels with a double-ring sensor featuring a narrow angular aperture.

A photoacoustic double-ring sensor, featuring a narrow angular aperture, is developed for laser-induced photoacoustic imaging of blood vessels. An integrated optical fiber enables reflection-mode detection of ultrasonic waves. By using the cross-correlation between the signals detected by the two rings, the angular aperture of the sensor is reduced by a factor of 1.9, from 1.5 to 0.8 deg. Consequently, photoacoustic images could be obtained in a manner analogous to the ultrasound B-scan mode. Next, the cross section of artificial blood vessels is visualized by reconstruction of the absorbed energy distribution. Finally, in vivo imaging and the subsequent reconstruction of the absorbed energy distribution is demonstrated for superficial blood vessels in the human wrist.

Algorithms↗

PubMedDate not supplied

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.

Body Temperature↗