Ton G. van Leeuwen

High-flow-velocity and shear-rate imaging by use of color Doppler optical coherence tomography

Color Doppler optical coherence tomography (CDOCT) is capable of precise velocity mapping in turbid media. Previous CDOCT systems based on the short-time Fourier transform have been limited to maximum flow velocities of the order of tens of millimeters per second. We describe a technique, based on interference signal demodulation at multiple frequencies, to extend the physiological relevance of CDOCT by increasing the dynamic range of measurable velocities to hundreds of millimeters per second. The physiologically important parameter of shear rate is also derived from CDOCT measurements. The measured flow-velocity profiles and shear-rate distributions correlate very well with theoretical predictions. The multiple demodulation technique, therefore, may be useful to monitor blood flow in vivo and to identify regions with high and low shear rates.

Excimer laser induced bubble: Dimensions, theory, and implications for laser angioplasty

Previous studies have demonstrated that during Xenon‐Chloride excimer laser ablation of tissue, rapidly expanding and imploding bubbles (diameter < 3 mm), predominantly containing water vapor, are formed. These short lived bubbles (life time < 300 μs) induce mechanical damage in adjacent tissue. In the present study, a theoretical analysis of the volume of vaporized water is correlated with measured bubble volumes formed in hemoglobin solution.

Partial vaporization model for pulsed mid-infrared laser ablation of water

Previous studies have shown that during pulsed infrared laser ablation of tissue, rapidly expanding and collapsing water vapor bubbles are formed. These bubbles are held responsible for inducing collateral mechanical tissue damage. In this study, a theoretical analysis predicting the volume of vaporized water is correlated with measured bubble volumes in water. Laser induced bubble formation was documented using a time‐resolved flash photography setup. Evidence for a novel ablation model (partial vaporization) is presented in the form of a picture of small bubblets that form at the very beginning of the vaporization process. The dimensions of the rapidly expanding and collapsing bubble (diameter up to 2.5 mm) induced by Q‐switched (500 ns) holmium (2.12 μm) laser pulses, delivered in water via 200, 320, or 400 μm fibers have been measured. The volume of the bubble increases with increasing pulse energy. The partial vaporization theory agreed well with the experimental data. It is concluded that the partia...

Pulsed Laser Ablation of Soft Tissue

The motivation for the material presented in this chapter came initially from the development of a new generation of pulsed lasers for laser angioplasty, in which laser light delivered through a fiberoptic is used to ablate intravascular plaque. In the eighties continuous wave (cw) lasers were used for the ablation task in conjunction with a variety of modified fiber tips. More recently there has been a shift from cw to pulsed lasers for laser angioplasty. In general, pulsed laser ablation seems to be a trade off between thermal and mechanical damage to tissue adjacent to the ablation crater. Currently, pulsed lasers are being used for tissue ablation in many medical applications. Two main groups of pulsed lasers are particularly attractive for photo-ablation of tissue. These operate either in the mid-infrared (IR) or the ultraviolet (UV) region of the spectrum. Even though both types of lasers are employed clinically, the mechanisms of ablation are not fully understood.

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.

Saline flush during excimer laser angioplasty : Short and long term effects in the rabbit femoral artery

Background and Objective: In this study, the effect of flushing saline on arterial wall damage (medial ruptures and necrosis), intimal hyperplasia, and arterial remodeling was determined. During excimer laser coronary angioplasty saline is flushed to reduce the size of explosive water vapor bubbles formed by intraluminal delivery of excimer laser pulses in blood.

Tissue ablation by holmium:YSGG laser pulses through saline and blood

The use of 2.09 micrometers Ho-YSGG laser pulses for intra-vascular non- contact ablation of tissue has been investigated. Therefore the transmission and the temporal shape of the laser pulse transmitted through saline was measured. Also the interaction between the laser pulses (200 microsecond(s) FWHM) and saline was studied by time resolved flash photography. Finally, porcine aorta was ablated (in vitro) through either blood or saline. The lesions and adjacent tissue were examined histologically. The penetration depth (the depth for a decrease to 1/e of the transmitted energy) of the laser pulses in saline depended on the power density (0.01 to 12.4 J/mm2) and varied from 0.33 to 2.2 mm, respectively. The photography showed the development of a transparent water vapor cavity around the fiber tip (320 micrometers ) during the laser pulse. The maximum dimensions of the cavity varied as function of the intensity. Within the vapor cavity the laser pulse was undisturbed. Due to this Moses effect in the microsecond region porcine aorta could be ablated through up to 3 mm of saline and blood. Especially after successive laser pulses, histology showed large fissures in adjacent tissue, presumably due to the expanding vapor cavity and the layered structure of the aorta. In conclusion, the formation of a vapor cavity during Holmium laser irradiation in physiological media enables non- contact tissue ablation and induces fissures into adjacent tissue, that may be undesirable.

Psoralen and long wavelength ultraviolet radiation as an adjuvant therapy for prevention of intimal hyperplasia and constrictive remodeling after balloon dilation: a study in the rabbit iliac artery.

Restenosis after balloon angioplasty is the summated effect of intimal hyperplasia and arterial shrinkage, both caused by hyperproliferation. In the present study, the potential of a photochemotherapeutic modality (Psoralen + UVA: PUVA) for the prevention of angioplasty induced proliferation was explored.

Low dose psoralen and UVA (PUVA) therapy enhanced arterial shrinkage after balloon angioplasty in rabbits

Restenosis after balloon angioplasty is caused by both intimal hyperplasia and arterial shrinkage (constrictive remodeling). Previous studies have indicated the inhibitory effect of photodynamic therapy on intimal hyperplasia development after angioplasty. The potential of a photoactivation regime (Psoralen + UVA irradiation: PUVA), which does not cause unwanted systemic side effects, for the prevention of both intimal hyperplasia formation and constrictive remodeling following balloon dilation was explored in the present study. In the rabbit iliac artery, balloon dilation followed by PUVA- therapy at a radiant exposure of 1 J/cm2 was performed (n equals 10). Control balloon dilation was performed in the contralateral arteries (n equals 10). After 4 weeks of survival, angiographic lumen renarrowing was determined in terms of intimal hyperplasia and constrictive remodeling. Late loss, but not intimal hyperplasia, was significantly larger in the PUVA group as compared to the control group (p less than 0.05). This difference in angiographic lumen loss can only be attributed to the difference in constrictive remodeling (arterial shrinkage). Thus, PUVA-therapy did not prevent intimal hyperplasia following balloon dilation. PUVA-therapy even enhanced luminal narrowing by augmented constrictive arterial remodeling.

Contribution of photothermal and photomechanical effects during tissue ablation by the XeCl-excimer laser

For the XeCl-excimer (308 nm, 115 ns) laser the contribution of photo-thermal and photo- mechanical processes was studied during the penetration of aortic tissue by bare fibers in dependence of fiber diameter, exerted force, pulse repetition rate, and fluence. Though, theoretically, Monte-Carlo simulation shows that the light penetration depth is diameter dependent for fibers up to 550 micrometers , experimentally, tissue penetration was not affected when the fiber diameter increased from 300 to 950 micrometers . Also the change in optical properties of tissue due to denaturation did not affect the penetration behavior significantly. Fiber tissue penetration increased when the exerted force increased, but it started only after a series of 5 - 20 initial pulses. The penetration per pulse became only slightly larger increasing the pulse repetition rate from 2 to 60 Hz while the tissue temperature rise near the fiber was up to 60 degrees. Increasing the temperature of the surrounding tissue itself prior to laser exposure only slightly affected tissue penetration in the case of both normal and denatured tissue. Delivery of laser energy in successive pulse trains, accelerated penetration after the first train. Close-up, high speed video recording showed the presence of rapidly expanding, short-life (50 - 150 microsecond(s) ) vapor bubbles, in the first instance on top of the tissue surface and later in the tissue itself while the fiber was penetrating the tissue. From our measurements and observations it is inferred that the mechanical effect of the bubble is especially important for the penetration of the fiber into the tissue. Theory suggests that the energy is deposited in a 100 - 200 micrometers layer in front of the fiber where the temperature is instantly increased to above boiling temperature inducing a rapid expanding vapor bubble. The mechanical force of the bubble breaks down tissue structures to small pieces creating a channel for the fiber to penetrate the tissue. So the formation of water vapor seems to be the dominant mechanism for tissue ablation.