Erwin Hondebrink

Review of laser speckle contrast techniques for visualizing tissue perfusion

When a diffuse object is illuminated with coherent laser light, the backscattered light will form an interference pattern on the detector. This pattern of bright and dark areas is called a speckle pattern. When there is movement in the object, the speckle pattern will change over time. Laser speckle contrast techniques use this change in speckle pattern to visualize tissue perfusion. We present and review the contribution of laser speckle contrast techniques to the field of perfusion visualization and discuss the development of the techniques.

In vivo photoacoustic imaging of blood vessels using an extreme-narrow aperture sensor

We applied photoacoustics for noninvasive two-dimensional imaging of blood vessels in vivo, using near infrared light. This study was undertaken to develop photoacoustic tomography of tissue for the detection of embedded blood vessels using a newly developed piezoelectric double ring detector, featuring an extremely narrow aperture.

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.

Twente Optical Perfusion Camera: system overview and performance for video rate laser Doppler perfusion imaging.

We present the Twente Optical Perfusion Camera (TOPCam), a novel laser Doppler Perfusion Imager based on CMOS technology. The tissue under investigation is illuminated and the resulting dynamic speckle pattern is recorded with a high speed CMOS camera. Based on an overall analysis of the signal-to-noise ratio of CMOS cameras, we have selected the camera which best fits our requirements. We applied a pixel-by-pixel noise correction to minimize the influence of noise in the perfusion images. We can achieve a frame rate of 0.2 fps for a perfusion image of 128x128 pixels (imaged tissue area of 7x7 cm2) if the data is analyzed online. If the analysis of the data is performed offline, we can achieve a frame rate of 26 fps for a duration of 3.9 seconds. By reducing the imaging size to 128x16 pixels, this frame rate can be achieved for up to half a minute. We show the fast imaging capabilities of the system in order of increasing perfusion frame rate. First the increase of skin perfusion after application of capsicum cream, and the perfusion during an occlusion-reperfusion procedure at the fastest frame rate allowed with online analysis is shown. With the highest frame rate allowed with offline analysis, the skin perfusion revealing the heart beat and the perfusion during an occlusion-reperfusion procedure is presented. Hence we have achieved video rate laser Doppler perfusion imaging.

Correcting photoacoustic signals for fluence variations using acousto-optic modulation.

We present a theoretical concept which may lead to quantitative photoacoustic mapping of chromophore concentrations. The approach supposes a technique capable of tagging light in a well-defined tagging volume at a specific location deep in the medium. We derive a formula that expresses the local absorption coefficient inside a medium in terms of noninvasively measured quantities and experimental parameters and we validate the theory using Monte Carlo simulations. Furthermore, we performed an experiment to basically validate the concept as a strategy to correct for fluence variations in photoacoustics. In the experiment we exploit the possibility of acousto-optic modulation, using focused ultrasound, to tag photons. Results show that the variation in photoacoustic signals of absorbing insertions embedded at different depths in a phantom, caused by fluence variations of more than one order of magnitude, can be corrected for to an accuracy of 5%.We propose a strategy for quantitative photoacoustic mapping of chromophore concentrations that can be performed purely experimentally. We exploit the possibility of acousto-optic modulation using focused ultrasound, and the principle that photons follow trajectories through a turbid medium in two directions with equal probability. A theory is presented that expresses the local absorption coefficient inside a medium in terms of noninvasively measured quantities and experimental parameters. Proof of the validity of the theory is given with Monte Carlo simulations.

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.

Monitoring cerebral perfusion using near-infrared spectroscopy and laser Doppler flowmetry

This paper describes the simultaneous use of two, noninvasive, near-infrared techniques near-infrared spectroscopy (NIRS) and a continuous wave NIR laser Doppler flow system (LDF) to measure changes in the blood oxygenation, blood concentration and blood flow velocity in the brain. A piglet was used as animal model. A controlled change in the arterial CO2 pressure (PaCO2) was applied for achieving changes in the listed cerebrovascular parameters. The time courses of blood concentration parameters (NIRS) and RMS blood flow velocity (LDF) were found to correspond closely with those of carotid blood flow and arterial carbon dioxide pressure (PaCO2). This result shows the additional value of LDF when combined with NIRS, preferably in one instrument. Development of pulsed LDF for regional blood flow measurement is indicated.

Burn imaging with a whole field laser Doppler perfusion imager based on a CMOS imaging array

Laser Doppler perfusion imaging (LDPI) has been proven to be a useful tool in predicting the burn wound outcome in an early stage. A major disadvantage of scanning beam LDPI devices is their slow scanning speed, leading to patient discomfort and imaging artifacts. We have developed the Twente Optical Perfusion Camera (TOPCam), a whole field laser Doppler perfusion imager based on a CMOS imaging array, which is two orders of magnitude faster than scanning beam LDPI systems. In this paper the first clinical results of the TOPCam in the setting of a burn centre are presented. The paper shows perfusion images of burns of various degrees. While our system encounters problems caused by blisters, tissue necrosis, surface reflection and curvature in a manner similar to scanning beam imagers, it poses a clear advantage in terms of procedure time. Image quality in terms of dynamic range and resolution appears to be sufficient for burn diagnosis. Hence, we made important steps in overcoming the limitations of LDPI in burn diagnosis imposed by the measurement speed.

Quantitative blood oxygen saturation imaging using combined photoacoustics and acousto-optics

In photoacoustic spectroscopy (PAS), wavelength dependent optical attenuation of biological tissue presents a challenge to measure the absolute oxygen saturation of hemoglobin (sO2). Here, we employ the combination of photoacoustics and acousto-optics (AO) at two optical wavelengths to achieve quantification, where AO serves as a sensor for the relative local fluence. We demonstrate that our method enables compensation of spatial as well as wavelength dependent fluence variations in PAS without a priori knowledge about the optical properties of the medium. The fluence compensated photoacoustic images at two excitation wavelengths are used to estimate the absolute oxygen saturation of blood in a spatially and spectroscopically heterogeneous phantom.

Photoacoustic measurement of the Grüneisen parameter using an integrating sphere

A method that uses an integrating sphere as a platform for photoacoustic measurement of the Grüneisen parameter Γ of absorbing liquids is developed. Derivation of a simple equation for determining Γ is presented. This equation only requires the voltage peak-to-peak value of the photoacoustic signal detected by a flat transducer and the relative energy of the incident light measured by a photodetector. Absolute detector sensitivities are not required. However, a calibration procedure is necessary. An experimental setup is constructed in order to implement and verify the method. Aqueous ink solutions are used as absorbing liquids to determine the calibration (instrument) constants. Validation of the equation is done by determining Γ of ethanol at room temperature. The obtained value of Γ(ethanol) = 0.72 ± 0.06 has a 7% relative difference to the calculated value from known thermal properties reported in literature.