George S. Abela

Beta carotene decreases total fluorescence from human arteries

The influence of β-carotene content on laser-induced total fluorescence is evaluated in vitro , using human arteries at 488-nm excitation. The investigation demonstrates that the β-carotene content in normal arteries increases with a longer period of incubation in β-carotene solution. This is associated with a decrease in the total fluorescence emission at 488-nm excitation. A decrease of 52% in the total fluorescence emitted from the arterial tissue is noted with the increased β-carotene deposition after incubation. The experimental data are highly correlated with theoretical analyses, derived by using the Kubelka-Munk and Lambert-Beer models, which incorporate parameters of β-carotene content in arterial tissue ( r = 0.94 and r = 0.91 , respectively). Total fluorescence from 138 samples of various types of atherosclerotic plaques is compared with that from normal arteries used as controls. Total fluorescence gradually decreases with longer incubation periods in β-carotene solution. For all atherosclerotic plaques, the normalized fluorescence of 0.30 ± 0.16 at initial incubation decreases to 0.23 ± 0.12 after 6 d of incubation ( p p < 0.005 compared to the initial and 6 d of incubation). Seventy-nine plaques with surface fissures exhibited an accelerated reduction in total fluorescence when compared to nonfissured plaque.

Fluorescence behaviour of human arterial tissue

Total fluorescence from arterial tissue is influenced by three factors: the absorption coefficient of tissue at a specific excitation wavelength, the laser excitation power and the fluorescence coefficient which is related to chemical species in tissue. These various influences were demonstrated by the following experimental results in vitro: (1) the effect of increasing power on fluorescence intensity, (2) the total fluorescence intensity in normal aorta and plaque and (3) the effect of a chromophore such as β-carotene on total fluorescence intensity. The fluorescence intensity of normal artery is an incremental function of laser excitation power, and the fluorescence emission from normal artery compared to fluorescence emission from plaque is significantly different at the same excitation power. The total fluorescence of normal artery was measured to be twice as great as that of atheromatous plaque (relative mean ratio of 2.58±0.46 compared to unity,p<0.0002 at 488 nm; relative mean ratio of 2.57±0.51 compared to unity,p<0.0009 at 514 nm). The total fluorescence emission decreases with the increase of β-carotene content in arterial tissue (R=0.97). These emission differences, when intensified by an exogenous chromophore of β-carotene, may provide an improved guidance signal for diagnosis of plaque from normal artery during laser angioplasty procedures.

Integral prism-tipped optical fibers

Laser angioplasty has been proposed as a less invasive alternative to bypass surgery for the treatment of occlusive vascular disease in the coronary and peripheral circulation. A major limitation of most laser angioplasty systems has been the inability to create a new lumen, which is larger than the diameter of the laser catheter. The principal reason for this shortcoming has been the fact that most laser angioplasty catheters, yet developed, have projected the laser energy from the distal tip of the catheter, parallel to the central axis of the catheter. This approach works well for the removal of plaque directly in front of the distal tip of the catheter, but it not very effective for debulking eccentric stenoses or lesions larger than the catheter diameter. To address this limitation, we decided to develop a laser angioplasty catheter from which the laser energy exits from the side of the catheter, instead of the tip. The critical element in a lateral-aiming laser catheter is an optical fiber which will project laser energy perpendicularly to its central axis. The fiber design would have to be mechanically stable, heat resistant, and capable of operating with high power cw and pulsed lasers. Thus, a small-diameter catheter including such an optical fiber may be able to effectively debulk large or eccentric stenoses.

Effect of pulse duration on photomechanical response of soft tissue during Ho:YAG laser ablation

Mechanical injury during pulsed holmium laser ablation of tissue is caused by rapid bubble expansion and collapse or by laser-induced pressure waves. In this study the effect of pulse duration on the photomechanical response of soft tissue during holmium:YAG laser ablation has been investigated. The dynamics of laser-induced bubble formation was documented in water and in transparent polyacrylamide tissue phantoms with a water concentration of 84%. Holmium:YAG laser radiation ((lambda) equals 2.12 micrometers ) was delivered in water or tissue phantoms via an optical fiber (200 or 400 micrometers ). The laser was operated in either the Q- switched mode ((tau) p equals 500 ns, Qp equals 14 +/- 1 mJ, 200 micrometers fiber, Ho equals 446 mJ/mm2) or the free-running mode ((tau) p equals 100 - 1100 microsecond(s) , Qp equals 200 +/- 5 mJ, 400 micrometers fiber, Ho equals 1592 mJ/mm2). Bubble formation was documented using a fast flash photography setup while simultaneously a PVDP needle hydrophone (40 ns risetime), recorded pressures. The effect of the pulse duration on the photomechanical response of soft biological tissue was evaluated by delivering 5 pulses of 800 mJ to the intimal side of porcine aorta in vitro, followed by histologic evaluation. It was observed that, as the pulse duration was increased the bubble shape changed from almost spherical for Q-switched pulses to a more elongated, cylindrical shape for the longer pulse durations. The bubble expansion velocity was larger for shorter pulse durations. A thermo- elastic expansion wave was measured only during Q-switched pulse delivery. All pulses that induced bubble formation generated pressure waves upon collapse of the bubble in water as well as in the gel. The amplitude of the pressure wave depended strongly on the size and geometry of the laser-induced bubble. The important findings of this study were (1) the magnitude of collapse pressure wave decreased as laser pulse duration increased, and (2) mechanical tissue damage is reduced significantly by using longer pulse durations (> 460 microsecond(s) , for the pulse energy used).

Plaque cap thickness can be determined by quantitative color analysis of angioscopic images in a plaque model

It has been proposed that atherosclerotic plaques vulnerable to disruption and thrombosis have a lipid-rich core covered by a thin cap. However, a method to detect those plaques has not been established. We hypothesized that such plaques are yellow due to reflection of the yellow lipid core through a thin cap which may be detected by angioscopy. We developed software to quantify yellow color saturation in digitized angioscopic images.

Restenosis Following Laser Angioplasty

Approximately ten years ago, our laboratory initiated work evaluating the use of the laser as a tool for altering vascular tissue biology to reduce the restenosis rate [1]. The attention of laser technology, however, was directed at a device to obtain immediate lumen enlargement by removing plaque [2–5]. Early limitations of laser applications in the cardiovascular system were primarily related to arterial perforation due to optical fiber stiffness and uncontrolled energy delivery [6–9]. As with balloon angioplasty, the use of a guidewire was adapted effectively to maintain coaxiality of the optical fibers within the vessel (Fig. 1) [10]. Thus, most devices currently available are capable of removing plaque and creating a lumen equivalent to the diameter of the catheter device. In addition, numerous studies have been done to evaluate the effects of various laser wavelengths and delivery modes on arterial tissue. The primary focus was on the use of continuous wave vs. pulsed laser systems. The optimum combination of laser wave-lengths and modes for laser angioplasty has been hotly debated. This resulted in the sense that thermal devices were passe and pulsed lasers were the only way to do laser angioplasty. In fact, most studies have demonstrated that there are more similarities than differences among the various laser systems with regard to tissue responses [1, 11, 12]. This chapter will focus primarily on the immediate and chronic tissue effects in the arterial system following laser angioplasty.

Detection and quantification of thermal injury to the myocardium using ultrasound

Selective thermal coagulation of discrete portions of the myocardium is becoming an accepted method for the treatment of various supraventricular tachyarrhythmias. This paper investigates the use of conventional ultrasonography for the detection and measurement of thermally coagulated lesions in myocardial tissue. Lesions were created in necropsied canine myocardium using a side-emitting laser catheter delivering cw Nd:YAG laser energy. Following irradiation, the sites were scanned with a 20 Mhz ultrasound catheter and the maximum depth of thermal damage was measured from the ultrasonographic imagery. The surface dimensions and transmural depth of thermal damage was then measured morphometrically with a video microscopy system. Depth measured by ultrasound was found to correlate well with depth by morphometry (r equals 0.78). Both depth measured by morphometry and by ultrasound were found to correlate well with the volume of thermal damage by morphometry (r equals 0.83 and r equals 0.77 respectively). Intraventricular ultrasonography may prove useful for in-vivo detection and measurement of thermally induced lesions in the myocardium. Additionally, it may also be applied for guidance and real-time monitoring of thermal coagulation of the myocardium during various arrhythmia ablation procedures.

Variation in optical performance of beta-carotene-stained rabbit aorta

A coupled integrating sphere system was used to measure the diffuse reflectance and transmission of rabbit aortae. Tissue absorption coefficients and scattering coefficients were calculated by a Kubelka-Munk model, and the results were compared. The absorption coefficient in (Beta) -carotene stained plaque was found to be greater than that in normal controls by fourfold at 488 nm wavelength, and by threefold at 514 nm wavelength. The scattering coefficient, however, did not change significantly between (Beta) -carotene stained and non-stained rabbit aortae.

Decrease in total fluorescence from human arteries with increasing β-carotene content

The influence of (Beta) -carotene content upon the laser induced total fluorescence was evaluated in human arteries in vitro using 30 mw argon laser beam at 488 nm. Experiments showed that the (Beta) -carotene content in normal arteries increases with longer period of incubation in (Beta) -carotene solution. This is consistently associated with a drop in total fluorescence. The arterial absorption at 488 nm resulting from (Beta) -carotene deposition is twice as great as that before incubation causing a decrease of total fluorescence by 48%. These experimental data were highly correlated with theoretical analysis derived using a multi- layer model by introducing a parameter describing the quantity of (Beta) -carotene bound to the arterial tissue (R=0.94). Total fluorescence from 138 samples of various types of atherosclerotic plaques was compared with that from normal arteries which were used as controls. The total fluorescence gradually decreases with longer incubation period in (Beta) - carotene solution. Seventy-nine plaques with surface fissures exhibited obvious reduction in total fluorescence. This study shows that the pretreatment with (Beta) -carotene may enhance the ability of the diagnosis of atherosclerotic plaque from normal artery using total fluorescence intensity.