Thermal kinetic selectivity and lasers

INTRODUCTION

The concept of selective photothermolysis by Anderson and Parrish revolutionized the use of lasers in dermatology. The specific wavelength-dependent damage to biological tissues based on the concept of thermal relaxation time (TRT) and its relation to pulse width has changed the advanced use of lasers in many indications. The lasers cause selective heat generation. The heat generated causes destruction based on principles of thermal kinetic selectivity. While the concept of selective photothermolysis has attracted much attention, the concept of thermal kinetics is a lesser-known entity. A literature search with the keywords “thermokinetic selectivity” or ‘thermal kinetic selectivity” did not reveal any specific published materials though it has been used occasionally in publications, books, and company manuals.^1,2 This article deals with concepts of thermal kinetic selectivity – diffusion of heat causing destruction of target tissue/chromophore.

THEORY OF SELECTIVE PHOTOTHERMOLYSIS

Laser-induced injury can be induced without aiming the target precisely and this selective radiation injury to the target is directly dependent on the inherent optical and thermal properties of the target. When the target tissue and the targeted chromophore are concentrated in the same area, adequate absorption of photons by the targeted chromophore leads to confined heat generation, leading to confined thermal damage without destruction of the surrounding tissues. Wavelength of the incident laser beam, time of exposure of the laser pulse, and the energy of the laser pulse are important determinants in this laser-mediated selective photothermolysis, a concept first propounded by Anderson and Rox.³ TRT has been defined as the time taken by a target to disperse about 63% of its initial thermal energy. A pulse exposure less than the TRT of the target causes heat confinement within the intended target without heat flow to the surrounding tissues and thus ensures selective destruction.⁴

This concept revolutionized the applications of lasers in different dermatological applications. In reality, however, this concept is not applicable in all situations. The targets are not always homogenous in size and shape, and the target chromophore may be different from the target tissue.

Destruction of a target tissue by lasers can occur in two ways:

1. Heat generation and confined thermal damage. This follows the theory of selective photothermolysis as described above.

2. Heat damage through dissipation occurs when the target is different from the chromophore and when the target-chromophore is not homogenous. This involves several deviations from the above rule and follows thermal kinetic principles as described below.

When the target tissue is situated away from the chromophore, heat generated by the absorption of photons by the chromophore needs to be transferred to the intended target tissue for its selective destruction. A typical example is laser-induced hair removal where the target chromophore melanin is concentrated in the bulb in the lower dermis and the target tissue is the bulge situated higher up above the bulb. Furthermore, the size of hairs varies in a given area and hence is not homogenous. This concept was explained by Altshuler et al. in their landmark paper “Extended theory of selective photothermolysis.”⁵

EXTENDED THEORY OF SELECTIVE PHOTOTHERMOLYSIS

Altshuler et al. performed an experiment using an 800 nm diode laser to irradiate post-mortem scalp hair at a fixed fluence but varying pulse widths to study the extent of hair follicle damage.⁵ It was surprisingly observed that the size of the damaged zone for similar-sized hair follicles was independent of the pulse width. Even when the pulse width was much larger than the TRT of the hair follicle, the ensuing thermal damage was still confined and hence selective, as is observed with uniformly pigmented smaller targets. The damage correlated with the diameter of the hair shaft and the extent of its pigmentation. They proposed that biological targets such as hair follicles and blood vessels are composed of some highly absorbing components (called heaters/ absorbers) and other non-absorbing or weakly absorbing components. The entire structural damage depends on the amount of heat absorption by the heater, the heat exchange, and the distance between the heater and the non-absorbing part of the target [Figure 1].

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Figure 1:

Different positions of target and heater within a nonhomogenous target tissue. Modified from Altshuler et al.

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Heat absorption and diffusion can occur up to a certain maximum temperature beyond which both heat absorption and diffusion become limited in biological tissues. Thus, to reach the maximum temperature of the heater, a lower-power laser pulse needs to be delivered for a longer duration of time to allow optimum heat absorption and desired diffusion. Thus, the concept of thermal damage time (TDT) was introduced.

TDT was defined as the time required for the outermost part of the target to reach the damaged temperature after heat diffusion from the absorber. The TDT is much longer than the TRT and in non-uniform structures, the pulse width should be equal to or less than the TDT to cause selective thermal damage to the target.

ROLE OF GEOMETRY

Aside from the concepts of the heater and the damage temperature, the size and shape (geometry) of the target also direct the TDT. The TDT increases with the dimensionality of the target – planar (one), cylindrical (two), or spherical (three), thus regulating the flow of heat from the absorber to the target. Heating as well as heat dissipation, including thermal damage, is thus more efficient for planar than cylindrical or spherical structures. The TRT ratio for planar, cylindrical, and spherical structures is 1:2:3. Smaller structures can be heated rapidly, but the heat loss is also swift.

The clinical applications of this extended theory of selective photothermolysis have been found in laser hair reduction. The bulb which is spherical absorbs maximum heat, followed by the cylindrical shaft and then the planar epidermis, ensuring a heat gradient from bulb upward toward bulge which lying close to the shaft gets collaterally damaged [Figure 2]. The cooling of the epidermis and upper dermis, done routinely in laser treatments, further ensures this gradient and also protects the epidermis.

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Figure 2:

Comparative geometrical shapes of different cutaneous structures. Hair bulge is the target tissue here.

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This concept also finds application in the treatment of telangiectasias or other vascular lesions such as leg veins. We will now see that this theory is actually an application governed by the concept of thermokinetic selectivity.¹

CONCEPT OF THERMAL KINETIC SELECTIVITY

The human skin is made up of blood vessels of varying sizes and shapes and the selective destruction of one over the other requires specific knowledge regarding the heating properties of such structures and their relation with the duration of a laser pulse.⁶ As we have seen, according to the theory of selective photothermolysis, the optimum pulse width needs to be shorter than that of TRT of a homogenous target. TRT in return relies on the size of the target and is proportional to the square of the diameter of the target. Thus TRT of a larger tissue (T1) with a similar shape is larger than that of a smaller tissue (T2). This means that a given dose to destroy the larger tissue is much larger than the desired dose to damage the smaller tissue and deviates from the concept of TRT. The concept of thermokinetic selectivity becomes useful in such a situation as it directs the heat movement to cause specific damage to the intended tissue permitting the choice of pulse width for the selective destruction of different-sized tissues.

Once laser energy is absorbed by the tissue and tissue temperature rises, the photothermal effect is determined by how heat is lost from the tissues. Heat can be lost through either conduction, convection, or radiation. Heat conduction is the primary mode of heat dissipation where heat is transferred to the adjacent cells. Heat convection is through blood perfusion.⁷ While treating both small and large targets, the pulse width is kept shorter than the TRT of larger vessels (target T1) but longer than that of the TRT of smaller vessels (target T2). Ideally, non-specific damage to both structures should happen. In reality, only the larger vessels are affected, sparing the smaller ones [Figure 3]. The smaller target vessels lose heat as the laser pulse is delivered for a time longer than its TRT. This heat loss is through heat convection and heat radiation. The smaller targets cool down while the larger target gets heated to its damage temperature.

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Figure 3:

Effect of varying pulse width on the vessels with respect to the thermal relaxation time of larger vessel (T1) and smaller vessel (T2).

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In another scenario, when for a given fluence, the pulse width is shorter than the TRT of both large and small targets, the smaller tissue gets damaged, but the temperature spike (ΔT) in the large tissue becomes high. These short-lived spikes cause intravascular cavitation, leading to the rupture of the vessel wall and purpura. Rather than a photothermal effect, a photomechanical effect is observed with physical destruction of the vessel. However, increasing the pulse width to more than the TRT of shorter vessels has been associated with better vessel clearance and lesser purpura and post-inflammatory hyperpigmentation. This is in accordance with Arrhenius damage integral, where the tissue denaturation time is also taken into account, thus linking the tissue temperature with the protein destruction rate.⁸ Thus, to ensure the specific removal of both smaller and larger targets, the larger one is addressed first using a pulse duration between the TRT of both targets (T2 <pulse duration <T1). Once the larger structure is destroyed, the smaller target is thermally damaged by decreasing the pulse duration to less than T2. Therefore, when working with pulse durations in the millisecond range, it is advisable to target larger tissues first, followed by the smaller ones.

Thus, during the treatment of vascular lesions, usage of longer pulse duration in the 20–25 ms range results in selective destruction of the vessels, while smaller vessels and other structures like melanosomes having TRT in the range of 100–250 ns remain unaffected. Furthermore, the larger vessels are targeted first with a longer pulse width, followed by a shorter pulse width for the destruction of the smaller vessels in the treatment of telangiectasias, port wine stains, and leg veins.

These concepts show that while the theory of selective photothermolysis and the relation of pulse width to TRT explain laser-induced thermolysis, there are a number of situations in laser physics that are not adequately explained by the TRT concept. This was explained in the paper by Murphy and Torstensson who questioned the role of TRT and stated that TRT is an outdated concept in photothermal treatments.⁸ They stated that the light-absorption profiles, tissue geometry, heat conduction from the absorber to target tissues, and the light device output temporal profiles all have an effect on this issue. We will see this now, how this concept of thermal kinetics is relevant in several laser applications.

CLINICAL APPLICATIONS

Laser hair reduction and laser therapy of vascular lesions described above are two important clinical scenarios where the above concepts apply.

Another scenario is the treatment of epidermal pigmentation, which was elucidated by Lee and Oh while using a long-pulsed Alexandrite laser in Korean patients. For epidermal lesions such as freckles and lentigines, they used higher fluences of 20 J/cm² or more for a quicker effect. In those with a predisposition to develop post-procedure hyperpigmentation or concomitant melasma, a lower fluence of 15 J/cm² or less was used to ensure delayed perilesional erythema. The pulse width was gradually decreased from 3 ms to 1 ms then to 0.2 or 0.1 ms to target non-responsive, progressively smaller pigmentation.¹

PULSE DURATION AND LASER HAIR REDUCTION-SUBMILLISECOND LASERS

This brings us to the question of whether selective photothermolysis with its TRT concept is always needed for laser hair reduction, where TRT of hair follicles varies between types of hairs, from 10 ms to 100 ms. Conventionally, long pulsed laser is considered the gold standard in laser hair reduction as even without epidermal cooling, epidermis (TRT 1–10 ms) is spared, as hair follicles with longer TRT (30–40 ms) are targeted.

Nevertheless, there are several reports of the effectiveness of short-pulsed/submillisecond neodymium-doped yttrium aluminum garnet (Nd: YAG) lasers for the same.^9-11 Effective results have been obtained using a shorter pulse duration of 0.6–1.6 μs, using a proprietary variable square pulse technology and fluence similar to the ones used with long pulse Nd: YAG lasers [FRAC3^® modality]. The mechanism is that using peak power over a shorter pulse duration thus allowing a constant power to be delivered. A higher peak upsurge in temperature facilitates the effective destruction of the hair follicle. Apart from selective photothermal effects, homogenous heating of the anagen hair bulb with high cellular metabolism and destruction of blood vessels at the follicular base lead to lasting damage to the hair follicles.^9,10

A similar homogenous heating of the hair is observed in laser hair reduction through repeated application of smaller fluences (e.g., super hair removal and Avalanche FRAC3^® mode). Multiple passes of a lower fluence are applied and incremental heat is built up, evolving into an avalanche in the temperature change. This ablates the hair follicles at a lower energy threshold than the usual single pass higher fluence mode.¹²

HOMOGENOUS PHOTOTHERMOLYSIS

It is well established that for a specific chromophore, the wavelength of the laser is fixed and the fluence needs to be appropriately safe and effective. The only adjustable parameter available to the laser physician is the pulse duration. In clinical practice, lasers are being used for varying indications with pulse widths ranging from picoseconds (p icolasers) and nanoseconds (Q-switched lasers) to microseconds to milliseconds (long-pulsed lasers) and even seconds for controlled destruction or denaturation. One such application has been found with a super-long pulse width of Nd: YAG laser (PIANO mode^®, FOTONA XP Dynamis laser system, Ljubljana, Slovenia), where the pulse durations is in the range of 0.3–60 s, much longer than TRT of epidermis or any cutaneous structure. It allows a lower fluence to be delivered for a prolonged duration leading to skin tightening and rejuvenation.¹³

With the increase in pulse duration, thermal diffusion directs the temperature distribution in the tissue. Rather than being unduly heated with a sharp temperature spike, the epidermis gets spared as there is ample time to disperse the heat to the underlying dermis. The rise in temperature is slow and controlled because of the extended superlong pulse duration, thereby resulting in an almost homogenous “bulk” heating of the dermis to a temperature of 43–45° centigrade. The subcoagulative thermal surge only aims to cause biostimulation by inducing a heat shock response with subsequent photothermally-activated neocollagenesis.¹³

Another application of slow homogenous heating is seen with the non-ablative very long-pulsed mode of an erbium-doped yttrium aluminum garnet (Er: YAG) laser system (SMOOTH™ mode), with a pulse duration in the range of 250–350 ms in soft tissue rejuvenation and stimulation of hair growth.²

This has found applications in non-ablative rejuvenation of skin and mucosae.¹⁴ Clinically, significant improvement in periorbital static wrinkles and skin laxity has been noted with this very long pulse non-ablative Er: YAG laser.¹⁴ In ophthalmology, this non-ablative Er: YAG and a super long-pulsed Nd: YAG modes have been used to thereby increase eyelid elasticity in patients with meibomian gland dysfunction, through collagen remodeling and regeneration.¹⁵ Eyebrow elevation, called fox eyes lift by the authors, was attempted with long-pulsed Er: YAG and FRAC3^® Nd: YAG lasers, resulting in safe and effective brow elevation, especially over tail of eyebrows.¹⁶ In gynecology, this non-ablative, thermal-only SMOOTH™ mode is beneficial in treating vaginal laxity and stress urinary incontinence.^17,18 Surface heating of mucosa is associated with immediate collagen shrinkage and prolonged neocollagenesis, contributing to tissue tightening and restoration of the functionality of the pelvic floor.¹⁹

A combination of Er: YAG SMOOTH™ mode and a ND: YAG PIANO^® mode has been found to be effective in lipolysis and non-invasive body contouring with superficial tightening as well as deep tissue heating.²⁰ The 1064 nm Nd: YAG laser not only has lipolytic properties but also stimulates new collagen formulation due to its diffuse, homogenous dermal heating property.²¹

CONCLUSION

The concept of thermal kinetic selectivity expands our existing understanding of laser-mediated tissue destruction, building on the foundational theory of selective photothermolysis. While the concept of TRT is no doubt important, other factors such as light-absorption profiles, tissue geometry, heat conduction from the absorber to target tissues, and the light device output temporal profiles all affect thermolysis. These concepts have been particularly useful in clinical applications such as laser hair reduction, treatment of vascular lesions, and non-ablative tissue tightening where selective damage to larger structures is achieved without affecting smaller, surrounding tissues.