FIELD OF THE INVENTION This mvention relates to an improved method and device for laser induced sliπnktng of collagen in humans and other animals A preferred embodiment of this novel method is directed to the shrinking of collagen in the skin for removing wrinkles and other aesthetic and medical applications, without causing superficial stun damage Another preferred embodiment of this novel method is directed to the therapeutic contraction of the collagen connective tissue withm the musculoskeletal system

BACKGROUND OF THE INVENTION The use of lasers for cosmetic surgery by dermatologists and plastic surgeons is expanding rapidly Despite the fact that reimbursement for these procedures is often not covered under third- party payor health plans, other socio-economic factors seem to be driving the mcreased demand for these services Such procedures include laser dosimetry to safely treat and remove vascular lesions (port wine stain and other red marks), benign pigmented lesions (brown marks) and in some cases, tattoo markmgs from skin surfaces These procedures, though recently developed, are highly controllable and well known

Collagen is the single most abundant animal protein in mammals, accounting for up to 30%

of all proteins The collagen molecule, after being secreted by the fibroblast cell, assembles into charactenstic fibers responsible for the functional integnty of tissues making up most organs in the body The skin is the largest organ of the body occupying the greatest surface area withm the human body As age advances and as a result of other noxious stimuli, such as the increased concentration of the ultraviolet part of the electromagnetic spectrum as radiated from the sun, structural integnty and elasticity of skin diminishes

Crosslinks between adjacent molecules are a prerequisite for this integnty of the collagen fibers to withstand the physical stresses to which they arc exposed A variety of human conditions, normal and pathological, involve the ability of tissues to repair and regenerate their collagenous framework In the human, 13 collagen types have been identified Of the different identifiable types, type I is the most abundant in skin where it makes up 80 to 90 % of the total collagen connective tissue This type of collagen, however, is less dynamic in the full-grown individual than its counterparts in which collagen is involved in active remodeling In this case the normal collagen synthesizing activities in skin is relatively quiescent exhibiting slow, almost negligible, turnover The extra-cellular matnx of the various connective tissues, such as skin, consists of complex macromolecules, collagen, elastin and glycosaminoglycans (GAGs) The biosynthesis of these macromolecules involves several specific reactions that are often under stnngent enzymatic control The net accumulation of connective tissues is thus, dependent upon the precise balance between the synthesis and the degradation of the connective tissue components Previous disclosures, such as U S Patents No 4,976,799 and No 5,137,539 have descnbed methods and apparatus for achieving controlled shrinkage of collagen tissue These pnor inventions have applications to collagen shrinkage in many parts of the body and desenbe specific references to the cosmetic and therapeutic contraction of collagen connective tissue withm the skin In the early 1980's it was found that by matching appropnatc laser exposure parameters with these conditions, one had a novel process for the nondestructive thermal modification of collagen connective tissue within the human body to provide beneficial changes The first clinical application

of the process was for the non-destructive modification of the radius of curvature of the cornea of the eye to correct refractive errors, such as myopia, hyperopia, astigmatism and presbyopia. New studies of this process for the previously unobtainable tightening of the tympanic membrane or ear drum for one type of deafness have been made. In addition to addressing the traditional method of collagen shrinkage wherein the ambient temperature is elevated within the target tissue by about 23 degrees Celsius, the "thermal shrinkage temperature" of collagen, T _s , a novel method for obtaining controlled contraction of collagen at a much lower temperature has been developed. Evidence exists to elevate the mechanical role played by the GAGs in the collagcnous matrix. Removing or altering these interstitial chemicals by enzymes or other reagents as disclosed in U.S. Patent No. 5,304, 169 considerably weakens die connective tissue integrity and influences the thermal transformation temperature (T _s ). Shrinkage temperature may be defined, therefore, as the specific point at which disruptive tendencies exceed the cohesive forces in this tissue. This temperature, thus, makes this an actual measurement of the stability of the collagen bearing tissue expressed in thermal units. The cause of wrinkles around the eyelids, mouth and lips is multifactorial: photodamage, smoking and muscular activity such as squinting and smiling all contribute. The end result is a general loss of elasticity, which is a textural skin condition as opposed to a skin redundancy or excess of skin tissue. The surgical injection of reconstituted collagen is commonly used in order to flatten the penoral lines. While oculoplastic surgeons may treat this problem around the eye inappropriately by blepharoplasty, it has been observed that even transconjunctival blepharoplasty for removal of prolapsed retrobulbar fat fails to address the fine periocular lines or wrinkles. Until recently, the main approach to treating these blemishes has been chemical peeling by means of trichloroacetic acid or phenol. Complications of chemical peels may include hypopigmentation, scarring, cicatricial ectropion and incomplete removal of the wrinkles. Many patients are acutely aware of these cosmetic blemishes as evidenced by the large quantity of money spent each year in the U.S. and abroad upon home and spa remedies for a more

youthful appearance With the advent of laser technology as an alternative to chemical peels or dermabrasion, dermal ablation techniques with both the conventional carbon ώoxide lasers and the high energy, short duration pulse waveform C02 lasers, high tech solutions appear to provide substantial benefits to patients C02 laser resurfacing is not a new technique C02 lasers have been used for several years, but regular continuous wave C02 lasers can cause scarnng due to the tissue destruction caused as heat as conducted to adjacent tissue Even superpulse C02 lasers produce excessive thermal damage The Ultrapulse C02 laser introduced by Coherent, Inc is an attempt to assuage these drawbacks by offeπng a high energy, short duration pulse waveform limiting the damage to less than 50 microns allowing a char-free, layer by layer vaporization of the skin tissue

All of the foregoing procedures depend for their success upon primary damage and the reparative potential induced by the inflammatory process in the tissue Associated with inflammation are, of course, the four cardinal signs of inflammation of rubor ( hypcremia ), calor (thermal response ), dolor ( pain ), and tumor or edema or swelling Coincident with these manifestations is the nsk of reduced resistance to infection One must not forget that these collateral effects accompany a cosmetic enhancement procedure and, for the most part, are not associated with a therapeutic procedure Therefore, the development of a more efficacious method would be beneficial in this regard

With regard to jomt disease and musculoskclctal complications, previous expenence in the laboratory with other coUagenous tissues has demonstrated the importance of understanding the mechanical response of connective tissues in terms of their hierarchical structure The fiber morphology is reflected in d e shape of the stress-strain curve

Within the musculo-skeleton system of the human body, tendons serve as the mechanical link connecting muscle with skeleton and, thus, must possess high tensile modulus, high toughness and good resistance to tensile creep, fatigue and shock Tendon, however, must be flexible enough to bend at joints and absorb slack when muscle tone is relaxed This is true, also, of ligaments

which serve to connect individual bones and are important in maintaining the integnty of joint structures It is the hierarchical organization of ligamcntous and tendon collagen, as well as the annulus fibrosis component of the intervertebral disc which permit their unique qualities

SUMMARY OF THE INVENTION

The present invention is an improved method and device for shrinking collagen In a preferred embodiment, collagen connective tissue in skin can be contracted or shrunk instantaneously, thus tightening the overlying tissue without the superficial damage or destruction associated with other techniques of superficial skin resurfacing In another preferred embodiment, the method and device is highly beneficial in therapeutic contraction of die collagen connective tissue within the musculo-skelctal system These techniques match the thickness of the target tissue with the extinction depth or the spectral absoφtion coefficient of the specific laser wave length to gently heat the collagen molecule to the thermal shrinkage temperature, thus resulting m shrinkage of the underlying tissue while tightening the overlying skin Superficial heat exchange either by means of passive, or more effectively, by means of a dynamic cooling process enhance this modality by eliminating pain or discomfort and reducing any nsk of superficial destruction of the skin tissue

The present invention is a method for shπnking connective collagen tissue compnsing the step of irradiating the tissue with laser energy having a wavelength in the range of about 1 to about 12 microns. In a preferred embodiment, the temperature of the collagen to be shrunk is raised to between about 58 and about 62 degrees Celsius In a preferred embodiment, the temperature of the collagen to be shrunk is raised to about 60 degrees Celsius In a preferred embodiment, the energy has a wavelength in the range of about 1.2 to about 1 8 microns In a preferred embodiment, the energy has a wavelength of about 1 3-1 4 microns In a preferred embodiment, the energy is delivered in a contmuous wave In a preferred embodiment, the energy is delivered in a pulsed mode. In a preferred embodiment, the pulse rate of delivery of the laser energy is such that the

pulses of energy are delivered within the thermal relaxation time period for the given volume of tissue being thermally treated. In a preferred embodiment, the total energy delivered is in the range of about 4 to about 50 joules per square centimeter.

The present invention is a method of removing wrinkles or other tissue by shrinking the connective collagen of the target tissue comprising the step of delivering laser radiation having a thermal extinction coefficient such that the laser energy is absorbed by the target tissue below the surface of the skin. In a preferred embodiment, the laser energy is absorbed a t a depth of between about 0.01 and about 25 millimeters which corresponds to the extinction coefficient of the energy having a wavelength of between 1 and 12 microns. In a preferred embodiment, the method comprises the step of providing a heat sink on the surface of the skin to prevent significant thermal increase at the surface of the skin. In a preferred embodiment, the heat sink is a suitable laser transparent material. In a preferred embodiment, the heat sink is a suitable dynamic cooling system. In a preferred embodiment, the energy has a wavelength in the range of about 1 to about 12 microns. In a preferred embodiment, the energy has a wavelength in the range of about 1.2 to about 1.8 microns. In a preferred embodiment, the energy has a wavelength of about 1.3- 1.4 microns. It has been observed that laser energy having a wavelength of between about 1.3 and 1.4 microns has an extinction coefficient of about 1.8 cm ^"1 . This corresponds to a depth of penetration of about 5.5 millimeters, the inverse of the extinction coefficient.

The present invention is a novel method for shrinking collage in joints, ligaments and musculoskclctal tissue comprising the step of irradiating the tissue with laser energy having a wavelength in the range of about 1 to about 12 microns. In a preferred embodiment, the energy has a wavelength in the range of about 1.2-1.8 microns. In a preferred embodiment, the energy has a wavelength of about 1.3-1.4 microns.

The present invention is a novel system for shrinking collagen tissue comprising a source of laser energy, the laser energy having a predetermined wavelength such that the laser energy is absorbed at a point in the tissue significantly below tiie surface of the skin, thereby preventing

ablation or charring of the surface tissue, and a laser delivery device, the laser delivery device capable of dehveπng a precise amount of laser energy to the tissue to be shrunk at a predeteirriined rate In a preferred embodiment, the laser energy has a wavelength in the range of about 1 and about 12 microns In a preferred embodiment, d e laser energy has a wavelength in the range of about 1 2 and about 1 8 microns In a preferred embodiment, the energy has a wavelength of about 1 3-1 4 microns In a preferred embodiment, the invention further compnses a passive heat sink. In a preferred embodiment, the invention further comprises a dynamic heat sink In a preferred embodiment, the invention further comprises a microprocessor and a controller for controlling d e delivery of laser energy by die laser delivery device to the tissue In a preferred embodiment, die mvention further compπses a thermal scnsmg system

Numerous other advantages and features of the present invention will become readily apparent from die followmg detailed description of me invention and the embodiments thereof, from the claims and from the accompanying drawings in which tiie details of the invention are fully and completely disclosed as a part of this specification

BRIEF DESCRIPTION OF THE DRAWINGS FIG 1 is a cross-section view of typical skin tissue

FIG 2 is a diagram showing collagen phase transition from d e molecule's tnple helical extra-cellular matrix native state at normal body temperature to states at the thermal shrinkage temperature wherein the collagen fibnls are both under tension and relaxed

FIG 3 is a schematic representation of die hierarchical structure of collagen in d e tendon FIG 4 is a schematic representation of e macromolecular structure of the lntervertebral

FIG 5 is a graph demonstrating the temperature gradient through a portion of die skin as a function of both die wavelength of incident laser energy and die depth of laser radiation penetration

FIG 6 is a schematic view of a hand held temperature controlled collagen shπnkage device

used in die method of the present invention.

FIG. 7 is a graph demonstrating d e temperature gradient through a portion of die skin widi precooling as a function of both the wavelength of incident laser energy and die depth of laser radiation penetration. FIG. 8 is a schematic view of a microscope mounted scanner for a temperature controlled collagen shrinkage device used in die present invention.

DETAILED DESCRIPTION OF THE INVENTION I. COLLAGEN SHRINKAGE IN SKIN TISSUE FIG. 1 is a cross-section view of typical skin tissue. The uppermost layer 98 of typical skin tissue is composed of dead cells which form a tough, horny protective coating. A dun outer layer, e epidermis 100 and a thicker inner layer, the dermis 102. Intertwining S-like finger shaped portions 104 are at d e interface between die epidermal papillary layer 106 and die dermal papillary layer 108, and extend downward. Beneadi die dermis is die subcutaneous tissue 110, which often contains a significant amount of fat. It is the dermis layer which contains the major part of die connective collagen which is to be shrunk, in a preferred embodiment at an approximate target depd of between about 100 and 300 microns, according to die method of the present invention, d ough viable collagen connective tissue also exists to a certain degree in die lower subcutaneous layer as well. Other structures found in typical skin include hair and an associated follicle 112, sweat or sebaceous glands and associated pores 114, blood vessels 116 and nerves 118.

Additionally, a pigment layer 120 might be present. It will be understood mat die drawing is representative of typical skin and mat die collagen matrix will take different forms in different parts of the body. For example, in die eyelids and cheeks die dermis and subcutaneous layers are significantly thinner with less fat dian in otiier areas. The target depdi will be a function of die amount of scattering in the particular skin type and die associated absoφtion coefficient of d e tissue. Furthermore, in some cases d e actual target depdi will correspond to one half d e thickness

of die subject tissue For example, die target depdi of tissue '/. inch duck might be about % inch below die surface of die skin

FIG 2 is a diagram showing collagen phase transition from die molecule's tnple helical extra-cellular matnx native state 30 at normal body temperature to states at the tiiermal shrinkage temperature wherem die collagen fibrils are bodi under tension 32 and relaxed 34 The molecular structure of collagen in its native state is mat of a triple coiled or helical crystalline protem structurally embedded widnn a umque ground substance Among these unique properties are its strength and its elasticity which an analogy to nylon might be drawn Anodicr significant similanty with nylon is collagen's ability to undergo diermal modification resulting in the contraction or shrmking of d e molecule without die substantial loss of its strength and elasticity Widnn a small diermal window of 4 to 5 degrees Celsius at about 23 degrees Celsius above body temperature, die collagen molecule will undergo a contraction to 1/3 of its oπginal lengdi, without biochemical change If this "diermal shπnkage temperature" (T _s ) is not reached widnn die appropnate quantity of tissue, physical dimensional changes within the organ will either not occur or will not be sustained If T _s is exceeded, diermal melting or denaturation of die molecule will occur with subsequent inflammation and tissue destruction, Therefore, it follows diat if these conditions are satisfactory met, die target tissue will shrink without attendant damage and destruction

The procedure, while laser based, is basically non-destructive using die fact diat normal tissue hydration acts as an universal chromophore to die wavelength of die laser The appropπate wave lengdi is approximately between about 1 and about 12 microns, preferably between about 1 2 and about 1 8 microns, and more preferably about 1 3-1 4 microns This ideal wavelength depends upon die absoφtion of die radiation by water order to elevate die temperature of die target tissue to T _s for collagen shπnkage - a temperature below that which results in protein denaturation

The Nd YAG, Nd YAP and Nd YALO- ype lasers are such sources of coherent energy This wavelength of 1 3-1 4 microns is absorbed relatively well by water, and as a result is attractive for tissue interaction It is also easily transmitted through a fiber optic delivery system as

opposed to die ngid articulated arm required for me C0 ₂ laser Very precise mediods of controlling laser systems and optically filtering produced light currently exist By selecting die appropπate combination of resonance optics and/or anti-reflection coatings, wavelengths in die range of 1 3-1 4 microns and even 1 32-1 34 microns can be produced

II COLLAGEN SHRINKAGE OF MUSCULOSKELETAL TISSUE

Many problems anse from die instability of joint structures resulting from laxity or stretching of die supporting hgamentous and capsular structures These so-called lax ligaments frequently occur following chronic elbow, knee, and ankle mjuncs where a ligament has been stretched but not fractured or disrupted Even if disruption has occurred with repair resultmg from fibrosis, shortening tiiese structures and thereby increasing dicir mechanical advantage widiout resorting to more destructive surgical intervention man endoscopic visualization and energy delivery would be of inestimable benefit

FIG 3 is a schematic representation of the hierarchical structure of collagen in die tendon The hierarchical orgamzation of connective tissues is illustrated in die tendon 130 However, virtually all connective tissues, whether soft or hard, have hierarchical structural designs arranged at discrete levels of structure This hierarchical organization of diesc and other collagen bearing tissues have been widely studied and reviewed Beginning at die molecular level with tropocollagcn, progressively larger and more complex structures are built up on die nano- and microscopic scales At die most fundamental level is die tropocollagcn helix 132 These molecules aggregate to form microfibnls 134 which, m turn, are packed into a lattice structure forming a subfibπl 136 The subfibπls are men joined to form fibrils 138 in which die characteristic structural 64-nannometer banding pattern is evident It is tiiese basic building blocks that, in the tendon, form a unit called a fascicle 140 At the fascicular level the wavy nature 142 of die collagen fibrils is evident Two or three fascicles together form die structure referred to as a tendon It is tins multi-level orgamzation diat imparts toughness to die tendon If the tendon is subjected to excessive stresses, individual

elements at different levels of die hierarchical structure can fail independently. In tiiis way, die elements absorb energy and protect die tendon as a whole from catastrophic failure. It is die current view diat proteoglycans in association witii copious amounts of water come into play as a matrix binding die fibrils togetiier. Proceeding toward macroscopic dimensions, die fascicles comprising crimped collagen fibrils are embedded in die proteoglycan-water gel witii several fascicles in turn making up the functioning tendon or ligament.

FIG. 4 is a schematic representation of the macromolecular structure of the intervertebral disc 150. In a stacked configuration, intervertebral discs are interspersed between die vertebral bones in die spinal column. One of the functions of the discs is to absorb compressive forces or loads placed on die spine and skeletal structure while moving or performing functions. It was recently shown diat the annulus fibrosis 152, the outer component of die intervertebral disc diat is made up of discrete layers or lamellae 154 of fibrous collagen arrayed around die nucleus like the layers of an onion skin. The hierarchical structure with gradient characteristics at die various levels of organization is not unlike that of tendon or ligamentous tissues. In the intervertebral disc, the collagen fibrils organized into lamellar sheets in die annulus fibrosus surround a gelatinous and highly hydrated nucleus pulposis 156. The thickness of lamellae vary with location and are thicker at the anterior and lateral aspects of die disc than at the posterior. With lamellae, fibrils are parallel and inclined with respect to die axis of die spinal column by an intcrlamcllar angle A which alternates in successive lamellae. This angle decreases from die edge of the disc inward. At higher magnification, die fibrils have a planar zig-zag waveform. The crimp angle B is largest in fibrils close into tiie nucleus and decreases toward die periphery. The orientation of die collagen fibrils in the annulus gives the disc strength and stability in tension, bending, and torsional motions. Based upon optical microscope observations of die moφhology of die collagen fibrils, die levels of structural hierarch below die fibrils are assumed to be identical to diat of the tendon and intestine. Axial compression, in addition to torsion and bending, is a mode of deformation normally experienced by the disc. It is generally believed diat compressive forces are transmitted across the

disc to the fibers of die outer lamellae, which are held in tension Although die nucleus is thought to play a major role in the transmission of forces, die restoring force of die stretched fibers of the annulus is considered to balance die effects of nuclear pressure The fibers of die lamellae are constrained at the cartilage end-plates of the vertebral bodies, so they must extend in length to accommodate die bulging Even though the disc undergoes macroscopic compression, die fibers of the lamellae are loaded in tension and their mode of deformation can be compared witii other connective tissues such as tendon and intestine

This type of tissue belongs to die family of umaxial composites The significant aspect of a composite is its unique set of mechamcal properties This is achieved through die synergistic mechamcal inteφlay between structural elements

When tendon or ligament is deformed beyond its elastic limit, permanent elongation occurs Individual elongated collagen fibrils have been observed Elongations of up to 900% have been reported The fibril banding was proportionately extended, though above 200% extension when observed durmg expenmental conditions, certain band regions extended slightly more man otiiers under electron microscopy

Small angle x-ray diffraction patterns revealed diat even though there is definite crystallographic damage withm the collagen fibnls, tiicy are still entirely capable of bearing load To impart tensile strength in the collagen fibril, which is constructed of discrete structural umts, the tropocollagcn macromolecules, some type of lateral bonding force is required where tropocollagen umts overlap. The slippage mechamsm by which a collagen fibril elongates involves slippage of the tropocollagen umts within die microfibπl This requires over coming the lateral bonding forces but does not result in tiiese forces being completely and permanently destroyed Load bearing ability is maintained, or even improved, when uitrafibnllar stra hardemng occurs Although it is evident that the principal deformation events take place within the collagen molecule, the mucopolysacchaπde matnx plays a secondary role The most obvious mechamcal function of die matnx is to bind the collagen fibrils into a functional sliding cord This matrix, which is more

currently charactenzed as glycosaminoglycan or GAG, serves to cement the fibers together into fiber bundles and provides the lateral bonding force required for load bearing

Evidence exists to elevate the mechanical role played by die GAGs in the tendon as it does m other collagen bearing tissues Removing tins matnx by enzymes or other reagents as disclosed in U S Patent No 5,304, 169, considerably weakens the connective tissue and influences die diermal transformation temperature or shrinkage temperature Shnnkage temperature, therefore, in certain instances and mechanisms of collagen shnnkage in die human body, may be defined as the specific point at which disruptive tendencies exceed die cohesive forces in die tissue This temperature tiius makes tins an actual measurement of die stability of die collagen bearing tissue expressed m diermal units

In die traditional treatment of disc prolapse, or hermated intervertebral disc, the disc is removed surgically although, paradoxically, die pathological process resides in die annulus fibrosis and not m the disc It is, in fact, a disruption in die annulus, usually in the posterior-lateral aspect, which secondanly results in bulgmg of die disc Herruation and finally extrusion of a fragment of die disc is the ultimate result At the level of the disc bulge and hcrniation, shnnkage of the stretched coUagenous annulus fibrosis would be the procedure of choice The appropπate approach for this intervention would be by means of direct mycloscopy or percutaneous endoscopy in order to shrink this tissue and tiius contain the nucleus pulposis Exposing the weakened annulus to the mid-infrared laser energy while retracting the nerve root would avoid violation of the disc and creation of segmental instability

Additional specific examples of die benefit of die use of mid-infrared laser energy withm the spectra absoφtion or extinction coefficient range of 0 4 cm ' - 1000 cm ' , corresponding to the wavelength range withm the electromagnetic spectrum of 1 0 microns to 12 0 microns for the shrinkage of collagen connective tissues are as follows shnnkage of the medial or lateral collateral , or the anteπor cruciate ligament of the unstable knee joint and the treatment of the chrome unidirectional and multidirectional glcnohumeral instability or tightening of die shoulder capsule in

recurrent dislocation.

III. OPTIMUM WAVELENGTH: 1.3- 1.4 MICRONS

FIG. 5 is a graph demonstrating the temperature gradient through a portion of the skin as a function of both the wavelength of incident laser energy and die depth of laser radiation penetration. No external cooling is used. The graph demonstrates a change in temperature (ΔT) of about 60 degrees Celsius and all curves are shown for die time point 1 millisecond following exposure to the laser energy. The graph shows three lines corresponding to laser wavelengths of 10.6 microns, 1.3- 1.4 microns and 1.06 microns. The present invention utilizes laser energy having a wavelength between about 1 and about

12 microns, more preferably between about 1.2 and about 1.8 microns, and more preferably about 1.3-1.4 microns. This type of laser energy is most frequently produced by a Nd:YAG, Nd:YAP or Nd:YALO-type laser. A iaser operating at these wavelengths may either have a high repetition pulse rate or operate in a continuous wave mode. This laser has been investigated in die medical community as a general surgical and tissue welding device, but has not been used for collagen tissue shrinkage in the past. Indeed, die prior art teaches away from the use of laser energy at 1.3- 1.4 microns for shrinking human collagen.

As early as 1989, studies related to tissue fusion have been performed with lasers operating at 1.3-1.4 microns. The use of laser radiation at this wavelength for shrinking collagen in any application is heretofore essentially unknown. One author discloses results to prove efficacy of such a laser in rupturing secondary membranes after extracapsular surgery. Others have disclosed the use of the 1.3- 1.4 micron laser for the treatment of rectosigmoideal tumors. Numerous tissue welding applications of the 1.3-1.4 micron laser such as wound healing, cosmetic skin closure, vascular surgery and minimally invasive surgical procedures normally performed with resorbable and removable sutures or staples have also been studied. However, these surgical procedures including incision, excision, ablation and cauterization of tissue are essentially disruptive processes.

IV HEAT SINK METHODOLOGY

Studies have shown that the CW laser with an appropnate heat sink produced a more optimum thermal profile for collagen shrinkage It has been shown that irradiating tissue with a midinfrared laser source through a surface thermal absoφtion element or heat sink permits an optimum thermal profile widiin die target tissue with near physiologic temperature at the surface of the irradiated surface thus minimizing surface thermal damage In die case of desired diermal collagen shnnkage, this is clearly the desired condition Attenuating die surface temperature before laser irradiation and therefore creating a boundary layer on the skin surface can result in selective cooling of the target tissue thus preserving the normal overlying epidermis Providing a glass or sapphire tip probe to the surface of the tissue bemg lased, while transparent to the laser radiation bemg delivered to the tissue, will act as an efficient and convenient heat sink for the surface layers of the skin

FIG 6 is a schematic view of a hand held temperature controlled collagen shnnkage device used in the method of die present mvention Modern instruments to provide dynamic cooling of the surface layers of tissue are well suited to these applications A typical handpiece 40 compnses the laser delivery device as well as vanous pcnpheral systems A fiber optic cable 42 guides the laser light mto the device A preferred embodiment of such a device contains a focusmg lens 44 and, optionally, other laser optics or mechamcal equipment including a beam splitter, focusmg knob and adjustable mounting means, thereby producing a laser focus spot 46 on the surface of the tissue above the collagen to be shrunk If the laser source does not have a fiber tip thermal protection system to monitor the surface temperature as well as to prevent thermal runaway in certain situations, a separate electronic or other thermal detector 48 is useful Additionally a coolant spiay 50 can be provided through the handpiece or it could be provided witii another separate device Finally, a connection to a computer and the laser 52 will allow the device to utilize the electromc or other thermal sensing means and obtain feedback control signals for the handpiece With respect to studies performed removing sub-dermal skin lesions, such as port wine stains and other red or

brown marks, an optimum cooling strategy might be one diat uses a short spurt of cryogen (e.g., 5-20 ms) to reduce the local temperature in the pigmented epidermis, while minimizing attenuation of the laser light by the boundary layer, followed by post-irradiation cooling spurt that provides a heat sink for dissipation of the epidermal heat generated by melanin absoφtion. An appropriate cryogen spray would be tetrafluoroediane, C ₂ H ₂ F ₄ , an environmentally compatible, non-toxic, non-flammable freon substitute. In clinical application the distance between die aperture of the spray valve and the skin surface should be maintained at about 20 millimeters.

Dunng a typical dynamic cooling process, die surface of die skin is pre-cooled to as low as 0 degrees Celsius or lower, at a rate fast enough to cool the surface only but not dissipate heat from below about 400-500 microns below the surface. In a preferred embodiment, dunng the cooling step the target tissue remains at body temperature and is not cooled at all. By applying cooling to die surface of the skin fo ^r a short period of tune, typically between about 5 and 100 milliseconds and then delivering laser energy, the surface is initially cooled but die target tissue never is. Generally, the surface layer of skin is rapidly cooled. A high rate of cooling will prevent local and vicinal hypothermia and will also tend to have a numbing, anesthetic or analgesic effect. It will be understood diat in at least one preferred embodiment of the method of the present invention, since only a relatively very thin outer layer of skin is cooled in a relatively very rapid period of time, laser energy must be applied cither contemporaneously with or immediately after termination of passive or dynamic cooling. Therefore, upon delivery of laser energy onto the surface and therethrough, the target tissue will be raised to the optimal thermal shrinkage temperature and generally not any higher, in an adequately rapid process, with the surface temperature of the skin remaining unelevated from body temperature, or if elevated at all, not elevated to a temperature which would have any adverse effect on the tissue Adverse effects of elevated tissue surface temperature include discomfort or pain, thermal denaturing of proteins and necrosis of individual cells at the surface. In a preferred cmbodunent of die method of the present invention, cooling and heating are performed in a predetermined timing sequence, optionally with die use of timer circuits

and/or otiier controller means.

Thus, it will be obvious to those skilled in die art that a passive heat sink includes glass or sapphire tip probes, and otiier types of devices to lay on the surface of the skin. It will also be obvious that a dynamic type of heat sink will refer to those actively cooled by flowing gas or liquid, jets or spurts of coolant such as freon, and otiier active types of heat exchangers suitable for surface cooling while irradiating sub-surface portions of collagen tissue.

FIG. 7 is a graph demonstrating the temperature gradient through a portion of the skin with precooling as a function of both the wavelength of incident laser energy and the deptii of laser radiation penetration. The graph demonstrates a change in temperature (ΔT) of about 60 degrees Celsius. In tiiese experiments, precooling of the skin surface tissue for a period of 20 milliseconds was conducted immediately prior to exposure to laser energy. All curves arc shown for a time point 1 millisecond following exposure to the laser energy. The graph shows three lines corresponding to laser wavelengths of 10.6 microns, 1.3-1.4 microns and 1.06 microns.

V. SCANNING AND THERMAL SENSING METHODOLOGY

Scanners such as those manufactured by Shaφlan and Reliant Technologies are presently available. These devices utilize one or more rotating mirrors to scan the beam over a circular or other shaped area. Power density of the beam incident on die tissue can be adjusted manually or by computer control. Automatically scanned systems previously used to vaporize holes into tissue with complex shapes and precisely defined dimensions, can be used in collagen shrinking applications as well. Applications where large areas of tissue are to be irradiated with a certain predetermined spectrum or gradient of power density over those areas are particularly well suited for computer- controlled laser scanner systems.

By combining an electronic thermal sensing and feedback loop in the application probe and, optionally, precooling the tissue by means of a freon spray, the physician has exquisite control over the thermal shrinking modality in his hand. The electronic diermal sensor can be a fast

response thermocouple like the OS40 series devices from Omega. This detector will analyze a 0.125 inch spot from 1 " away and accurately indicate temperature within 0.1 seconds, fast enough to servo the applied laser energy or to simply turn it off when the desired temperature has been reached. In addition to precooling tissue, the safe and appropriate application of the laser energy requires accurate delivery of the laser energy to the target tissue. The laser energy can be delivered in a continuous or pulsed wave by means of a highly accurate fiber optic microprocessor controlled delivery system known. Various devices are currently being sold for such applications. A coherent energy source with the efficiency of a smaller physical foot-print avoiding the cryogenic cooling and energy requirements of the laser, itself, would be die solid state 1.2-1.8 micron emitting laser diode (which can be precisely tuned across almost it ^' s entire range of possible wavelengths). The integration of an aiming beam such as that provided by a He.Ne laser, or more effectively from a visible light emitting diode, would complete die package.

FIG. 8 is a schematic view of a microscope mounted scanner for a temperature controlled collagen shrinkage device used in the present invention. In this view, a laser console 60 is installed adjacent a floor-mounted microscope 62. A fiber optic cable 64 conducts laser energy from the laser source to the scanner 66. A laser delivery attachment 68 may be necessary to conduct die laser energy in an appropriate beam pattern and focus. In this embodiment of the invention, servo feedback 70 signals are also conducted along die fiber optic back to the laser console. The servo feedback signals could also be directed back to the laser console via an additional fiber optic or other wiring or cabling. This servo feedback may comprise thermal or optical data obtained via exter.—i sensors or via internal systems, such as a fiber-tip protection system which attenuates die laser energy transmitted, to provide control in operation and to prevent thermal runaway in the laser delivery device. Thus, a thermal feedback controller 72 will regulate die laser energy being transmitted. This controller can comprise an analog or digital PI, PD or PID-type controller, a microprocessor and set of operating instructions, or any other controller known to those skilled in

the art Other preferred embodiments can also be provided with additional features For example, die surgeon or technician operating the laser could also manipulate an energy adjust knob 74, a calibration knob 76 and a footpedal 78 Thus, in a preferred embodiment, a very accurately adjustable system is provided which allows a surgeon to deliver laser energy via a computer controlled scanning device, accordmg to mstructions given by the surgeon or an observer mspectmg the region of the skin where collagen is to be shrunk through a very accurate microscope Once a region to be treated is located, die scanner can deliver a very precise, predetermined amount of laser energy, m precisely chosen, predetermined regions of the skin over specific, predetermined penods of time It will be understood that, while the procedures descπbed herein may vary slightly in die equipment required, their energy transmission rates, times, powers and otiier factors, the above descπbed parameters can be adapted easily to perform a great number of operations, more efficiently and more safely than before Another modification to die procedure will be the adaptation of the procedure to photodynamic therapies (PDT) The tissue of interest can be infused with a photoactive agent pπor to delivery of laser energy thereto

While the prmciples of this invention have been made clear in illustrative embodiments, there will be immediately obvious to tiiose skilled m die art many modifications of structure, arrangement, proportions, die elements, materials, and components used in the practice of the mvention, and otherwise, which are particularly adapted to specific environments and operative requirements without departmg from those prmciples The appended claims are mtended to cover and embrace any and all such modifications, within the limits only of the true spint and scope of the mvention