Laser Technologies as a New Direction in Transcatheter Interventions

Abstract

Medical laser energy applications began in the 1960s, immediately after the discovery of the laser. The output power of medical lasers is from several milliwatts to several tens of watts, depending on the intended use. In 1967, Mester et al. were the first to use a ruby low output power laser for the healing of superficial wounds; and in 1968, Makeeva and Schur used a helium–neon laser for the same purpose.^1,2 This field of photonic medicine is now referred to as photobiomodulation therapy (PBMT).^3
–5 Lasers used for PBMT do not have damaging effects on biological tissues.^2,4,5

Many authors noted the pronounced positive effect of extracorporeal PBMT in the treatment of vascular lesions, cerebral ischemic, and neurodegenerative diseases.^3
–5 The mechanism of therapeutic effects of low output power laser improves the blood supply, stimulates and restores adenosine triphosphate metabolism in cell mitochondria and regenerative processes in tissues.^2,3,5 The penetration depth of laser energy is related to the degree of light absorption by tissues and this is dictated by the wavelength. Thus, it became clear that during “in vitro” exposure to light of different wavelengths on the arterial wall affected by atherosclerosis, in the ultraviolet region of the spectrum, that light absorption was maximal both in atherosclerotic tissues and in all vascular wall layers.

There is a separation of these indicators and a decrease in the absorption of vascular wall tissues in the blue spectral region. The absorption of atherosclerotic tissues remains fairly high, but the absorption of the intima, as well as the muscular vascular wall layer, is significantly reduced in the green region. As the wavelength increases to red, and especially to the near-infrared region, the absorption progressively lessens in all tissues and the penetration depth of laser energy increases significantly.⁶ These indicators change if laser energy goes through other kinds of tissues. With PBMT, low absorption and, consequently, larger penetration depth of laser energy are of high priority, since it allows to influence not only the irradiated surface, but also more deeply located tissues.

In 1982–1984, research on transcatheter endovascular applications of various lasers with low output power was conducted. These studies have shown that laser exposure at a wavelength of 633 nm stimulates angiogenesis and causes collateral and capillary tissue revascularization.⁶ That discovery led to the development of the method of transcatheter endovascular PBMT, which is used in the treatment of various atherosclerotic lesions of the lower limbs, coronary heart disease, ischemic, and neurodegenerative cerebral lesions.^6,7

In addition to low output power laser, high output power laser is also used in medicine. High output power laser is associated with high power density at the site of exposure, which can lead to thermal or photocoagulation effect. With high output power laser, of primary importance are high absorption and, therefore, low penetration depth of laser energy, because they allow to selectively affect the irradiated surface having a much less impact on deeper tissues.

In 1980, Choy⁸ was the first to come up with the idea of using high output power laser in endovascular interventions. He patented the “Laser Tunneling Device” for conducting transluminal laser tunnelization of atherosclerotic affected vessels.⁸ The essence of the laser tunneling method was as follows: under fluoroscopic control, transcutaneously, translumenally, a fibrous fiber light guide laser tunneling device connected to the 6 W argon laser was brought to the site of the atherosclerotic occlusion; then laser irradiation was carried out, with the help of which atherosclerotic tissue was destroyed. This method was later called “Percutaneous Transluminal Laser Angioplasty (PTLA).”⁹ PTLA is a rather aggressive laser method aimed at atherosclerotic tissues destruction, which should not cause damage to the vascular wall and surrounding tissues of the body.

Developing the method, it was necessary to take into account a large number of indicators such as wavelength, radiation power, continuous or pulsed generation character, impulse frequency, energy per impulse, power density, contact or noncontact exposure type, degree of absorption, specific wavelength of laser energy by atherosclerotic tissues and different vascular wall layers, and the predominance of thermal or photochemical mechanism of atherosclerotic tissues destruction.

For PTLA development, various types of continuous and pulsed lasers operating in various modes and ranges from infrared to ultraviolet were tested. Great problems in developing the method were phenomena such as the opacity of the blood as the medium for laser treatment, the complexity of the choice of power density due to changes in the vessel diameter, the need to remove the products of atherosclerotic tissues destruction, as well as the complexity of visualization of laser exposure process.

To take the blood away from the site of the laser exposure, various designs of transparent balloon catheters with fiber-optic optics inside were developed. To get rid of thermal effect various mono- or poly-fiber-optic instruments were devised. Devices at the distal end of the optics were worked out, which were supposed to focus or, on the contrary, scatter the laser radiation at the exposure place. To visually control the process, research aimed at creation of various types of endovascular angioscopes was conducted. All that has significantly complicated the laser procedure. The use of lasers with continuous generation at practically any wavelength proved to be of little prospect, due to the fact that the continuous nature of the radiation causes increased thermal effect.⁶ The contact mode of conducting laser energy, in which the distal end of the fiberglass fiber-optic instrument is in direct contact with the exposed area, also turned out to be not very promising, since it significantly increases the power density in the exposed area, which also leads to thermal destruction of tissues.⁶ The use of lasers operating in the red and near-infrared spectrum regions turned out to be quite difficult, since in these spectral regions the degree of energy absorption is low both in atherosclerotic tissues and in all vascular wall layers. Energy penetration depth is quite high, which can lead to irreversible damage to both the vascular wall and surrounding tissues. The use of these lasers requires special tools at the distal end of fiber optics.^6,9

What turned out to be much more promising was contactless application under the fluoroscopic control of XeCl excimer lasers with a wavelength of 308 nm, pulse repetition rate of 20–80 Hz, pulse energy of 30–80 mJ, pulse duration of 185 ns, as well as solid-state YAP:Nd lasers (yttrium aluminum perovskite with conversion to the second harmonic on a nonlinear lithium iodate (LiYO₃) crystal with a wavelength of 539 nm, pulse repetition rate of 6–9 mJ, pulse duration 140–200 ns).⁶ It is important that excimer lasers have no pronounced thermal effect, but in the ultraviolet spectrum area, both atherosclerotic tissues and all vascular wall layers equally absorb laser energy to the maximum, which does not lead to selective effects on atherosclerotic tissues. At the same time, excimer lasers have a lot of energy in the impulse, which can lead not only to atherosclerotic tissues destruction, but also to vascular wall damage.⁶

The use of YAP:Nd lasers operating in the green spectral region leads to a high degree of absorption of laser energy by atherosclerotic tissues. In this case, the muscular layer of the vascular wall and especially the intimal layer absorb laser energy to a much lesser extent, which does not cause their destruction. As a result, when using the contactless method, there is a selective effect that destroys atherosclerotic tissues. Using 6–9 mJ impulse energy, with 3–6 kHz impulse frequency, allows to avoid gross exposure, so that the products of atherosclerotic tissue destruction are 2–4 μm in size, which does not cause the embolism of the distal arterial bed.⁶

Currently, the most common method of transcatheter treatment of atherosclerotic lesions is vascular stenting. It is a very important technically simple method. However, stents are foreign to the human body.⁹ PTLA is a technically more complicated method that does not require the implantation of foreign bodies. Naturally, each method has its own indications. PTLA restores arterial permeability, removes atherosclerotic tissue from the lumen, and restores the arterial and collateral blood flow.^7,9 Good results after PTLA are maintained for >6 or even 10 years.^6,9,10 Thus, at present, transcatheter laser interventions have two directions:

Transcatheter endovascular PBMT using low output power laser aimed at stimulating angiogenesis, developing collateral and capillary blood supply to ischemic tissues, stimulating and restoring the exchange of adenosine triphosphate (ATP) in the mitochondria of ischemic tissue cells, restoring tissue metabolism, and stimulating tissue regeneration.

PTLA using high output power laser aimed at the destruction of atherosclerotic tissues occlusing the lumen of the arterial vessel and at the restoration of the main blood supply.

In conclusion, it is reasonable to say that after many years of research and the development of transcatheter laser technologies for the treatment of various vascular lesions and related diseases, PBMT, as well as PTLA, when taking into account all the features of laser irradiation, already occupies an important place in modern laser medicine attracting increasing attention of scientists and practitioners.

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