Laser fusion of biological materials

Apparatus and methods for laser fusion of biological structures are disclosed employing a laser for delivery of a beam of laser radiation to an anastomotic site, together with a reflectance sensor for measuring light reflected from the site and a controller for monitoring changes in the reflectance of the light of the site and controlling the laser in response to the reflectance changes. In one embodiment, the laser radiation is delivered through a hand-held instrument via an optical fiber. The instrument can also include one or more additional fibers for the delivery of illumination light (which can be broadband or white light or radiation from a laser diode) which is reflected and monitored by the reflectance sensor. Reflectance changes during the course of the fusion operation at one or more wavelengths can be monitored (or compared) to provide an indication of the degree of tissue crosslinking and determine when an optimal state of fusion has occurred.

BACKGROUND OF THE INVENTION 
The technical field of this invention is laser surgery and, in particular, 
laser systems for joining living tissues and promoting the healing of 
small biological structures. 
The conventional approach to joining tissue segments following surgery, 
injury or the like, has been to employ sutures or staples. While these 
techniques are often successful, there are a number of limitations 
inherent in such mechanical approaches. First, the practice of suturing or 
stapling tissue segments together is limited by the eyesight and the 
dexterity of the surgeon which can present a severe constraint when 
anastomosing tiny biological structures. Second, when delicate biological 
tissues or organs are sutured, even minimal scarring can affect the 
function of the structure. Finally, suturing can be less than 
satisfactory, even when properly performed, because of the gaps which are 
left between the stitches, the inherent weakness of the joint, or the 
possibility of progressive structural weakening over time. 
Various researchers have proposed the use of laser energy to fuse 
biological tissues together. For example, Yahr et al. in an article in 
Surgical Forum. pp. 224-226 (1964), described an attempt at laser 
anastomosis of small arterial segments with a neodymium laser. However, 
the neodymium laser used by Yahr et al. operated at a wavelength of about 
1.06 micrometers was not efficiently absorbed by the tissue, requiring 
large amounts of energy to effect fusion, while also affecting too large 
of a tissue volume. 
Further research on laser fusion involving various alternative laser 
sources, such as the carbon dioxide laser emitting laser light at about 
10.6 micrometers, the argon laser emitting light at about 0.50 
micrometers, and the ruby laser emitting light at about 0.70 micrometers, 
continued to encounter problems. In particular, the output of carbon 
dioxide lasers was found to be heavily absorbed by water and typically 
penetrated into water-laden tissue only to a depth to about 20 
micrometers. This penetration depth and the resulting bond induced by 
carbon dioxide laser fusion was too shallow to provide durable bonding in 
a physiological environment. 
Argon and other visible light laser also produced less than satisfactory 
effects. The output of argon lasers and the like was found to be heavily 
absorbed by blood and subject to substantial scattering within the tissue. 
These effects combined to create a narrow therapeutic "window" between a 
proper amount of energy necessary for laser fusion and that which induces 
tissue carbonization, particularly in pigmented tissues and tissues that 
have a high degree of vascularization. Moreover, argon lasers have been 
particularly cumbersome devices, requiring large amounts of electricity 
and cooling water. 
Recently, the development of new solid state laser sources have made 
prospects brighter for efficient, compact laser fusion systems suitable 
for clinical use. Such systems typically employ rare, earth-doped yttrium 
aluminum garnet (YAG) or yttrium lithium fluoride (YLF) or 
yttrium-scadium-golilinium-garnet (YSGG) lasers. See, for example, U.S. 
Pat. Nos. 4,672,969 and 4,854,320 issued to Dew, disclosing the use of a 
neodymium-doped YAG laser to induce laser fusion of biological materials 
and to obtain deeper tissue penetration. However, even with such solid 
state laser sources, the problems of scattering and damage to adjacent 
tissue remain. The Dew patents disclose the use of computer look-up tables 
to control the laser dose based on empirical data. 
The absorptive properties of biological structures differ considerably from 
one tissue type to another, as well as from individual to individual, 
making dosage look-up tables often unreliable. There exists a need for 
better laser fusion systems that can accurately control the formation of 
an anastomotic bond to avoid thermal damage and achieve optimal results. A 
system that could provide real-time feedback to the clinical user would 
satisfy a long-felt need in the art. 
SUMMARY OF THE INVENTION 
Apparatus and methods for laser fusion of biological structures are 
disclosed employing a laser for delivery of a beam of laser radiation to 
an anastomotic site, together with a reflectance sensor for measuring 
light reflected from the site and a controller for monitoring changes in 
the reflectance of the light of the site and controlling the laser in 
response to the reflectance changes. In one embodiment, the laser 
radiation is delivered through a hand-held instrument via an optical 
fiber. The instrument can also include one or more additional fibers for 
the delivery of illumination light or radiation from a laser diode (which 
can be broadband or white light or radiation from a laser diode) which is 
reflected and monitored by the reflectance sensor. Reflectance changes 
during the course of the fusion operation at one or more wavelengths can 
be monitored (or compared) to provide an indication of the degree of 
tissue crosslinking and determine when an optimal state of fusion has 
occurred. 
The present invention permits the creation of anastomoses of biological 
structures with the optimal use of appropriate laser energy, minimizing 
the total energy delivered to the site while obtaining maximum bond 
strength and integrity. The terms "anastomosis" and "anastomotic site" are 
used herein to broadly encompass the joinder of biological structures, 
including, for example, incision and wound healing, repair of blood 
vessels and other tubular structures, sealing of fissures, nerve repairs, 
reconstructive procedures, and the like. 
In the present invention, reflective feedback is used to monitor the state 
of coagulation of the biological structures so as to allow an optimal dose 
by either manipulation of the energy level or exposure time, or by 
controlling the sweep of energy across an exposure path. 
Reflectance changes can also be employed by a control means in the present 
invention to adjust or terminate laser operation. The procedures of the 
present invention can further employ various "biological glue" materials 
in either liquid, gel or powder form to enhance the tissue fusion process. 
Examples of such biological glues include collagen, elastin, fibrin, 
albumin and various synthetic polymeric materials. Moreover, techniques 
are disclosed herein for providing increased tensile support along and 
across the anastomosis by creating coagulated "cross-strips" of annealed 
biological glue and/or connective tissues that enhance the strength of the 
bond. 
Various laser sources can be employed, including gas, liquid and solid 
state laser media. Because the present invention permits the user to 
carefully monitor the laser energy dosage, solid state laser can be 
utilized instead of the more conventional (and cumbersome) gas lasers. 
Such solid state laser include optically-pumped (e.g., lamp or diode 
pumped) laser crystals, diode lasers, and diode pumped optical fibers. 
Tunable laser sources can also be used to practical advantage in the 
present invention. Since the feedback control systems disclosed herein 
eliminate (or reduce) the need for look-up tables, a tunable laser source 
can be used to full advantage by matching the laser output wavelength with 
the absorptive and/or dimensional characteristics of the biological 
structures to be repaired or otherwise joined. In one embodiment of the 
invention, the laser source can be tuned over at least a portion of a 
wavelength range from about 1.4 micrometers to about 2.5 micrometers to 
match particular tissue profiles. 
In another aspect of the invention, a real-time display means is disclosed 
which can be incorporated into a surgical microscope or goggles worn by 
the clinician during the procedure to provide a visual display of the 
state of tissue coagulation simultaneously with the viewing of the 
surgical site. The display can reveal reflectance values at one or more 
specific wavelengths (preferably, chosen for their sensitivity to the 
onset and optimal state of tissue crosslinking), as well as display a 
warning of the onset of tissue carbonization. 
In one method, according to the invention, a technique for laser fusion of 
biological structures is disclosed in which laser energy is applied to 
join together two or more tissue segments (with or without the use of a 
biological glue), while the reflectance of light from the irradiated site 
is monitored. Changes in scattering due to coagulation or crosslinking of 
the tissue (or biological glue) will cause a reflectance change. In 
addition, dehydration due to laser exposure also affects the site's 
reflection. The reflectance can be monitored in real-time to determine the 
optimal exposure duration or aid as visual feedback in the timing used in 
sweeping the energy across the anastomosis during the welding procedure. 
The method can further be enhanced by coating the entire anastomotic site 
with a biological glue and then applying laser energy along paths which 
are generally perpendicular to the joint line. These coagulated strips can 
have high tensile strength and can provide load support across and along 
the repair line. These strips are also shallowly crosslinked to the 
tissue, itself, providing superior bond strength. 
The depth of penetration of the laser energy can be controlled in one 
embodiment by tuning a mid-infrared laser along a range of wavelengths 
from about 1.4 micrometers to about 2.5 micrometers to adjust the 
penetration to match the desired weld depth. Tuning can be accomplished, 
for example, by mechanical or electro-optical variation in the orientation 
of a birefringent crystal disposed in the laser beam path. This allows the 
clinician to select a weld depth appropriate to the size and type of 
structures to be welded. This feature of the invention can be particularly 
advantageous with delicate biological structures where accuracy is needed 
to coagulate only what is necessary for temporary strength, while avoiding 
thermal denaturing of critical structures that cannot function once 
scarred. In most instances, the patient's body will metabolize the 
coagulated glue over time simultaneous with (or following) the natural 
healing of the repair site by physiological processes. 
The invention will next be described in connection with certain illustrated 
embodiments; however, it should be clear by those skilled in the art that 
various modifications, additions and subtractions can be made without 
departing from the spirit or scope of the invention.

DETAILED DESCRIPTION 
In FIG. 1, a schematic block diagram of a laser tissue fusion system 10 is 
shown, including a laser 12, power supply 14, controller 16 and 
reflectance monitor 18. The system can further include a 
beamshaping/delivery assembly 20, illumination source 22, display 24 and 
tuner 26. In use, the output of laser 12 is delivered, preferably via 
beamshaping/delivery assembly 20, to an anastomotic site 30 to fuse 
biological tissue on opposite sides of a fissure or cleavage line 32. As 
the laser beam irradiates exposure zone 34, preferably with the assistance 
of a biological glue 36, a crosslinking reaction occurs to fuse the 
biological tissue in the vicinity of the site 30. The degree of 
crosslinking is determined by the reflectance monitor 18, which provides 
electrical signals to controller 16 in order to control the procedure. The 
reflectance monitor 18 preferably receives light reflected by the site 
from a broadband or white light illumination source 22. In addition to 
controlling the laser operation automatically, the reflectance monitor 18 
and/or controller 16 can also provide signals to a display 24 to provide 
visual (and/or audio) feedback to the clinical user. Tuner 26 can also be 
employed by the user (or automatically controlled by controller 16) to 
adjust the wavelength of the annealing radiation beam. 
FIG. 2 provides further schematic illustration of the laser fusion system 
10 in use. The electrical and optical components of the system can be 
housed in a system cabinet 60 suitable for use in an operating room or 
other clinical environment. The laser output is delivered to the patient 
by an optical fiber cable 62 (which includes multiple optical fibers as 
detailed below) and a handpiece 64. The system is preferably used in 
conjunction with a surgical microscope (or goggles) 66 which are adapted 
to provide a "heads-up" display to the user. Display signals from the 
system cabinet 60 are transmitted to the microscope (or goggles) 66 by 
cable 68. 
The present invention can be practiced with a wide variety of laser 
sources, including both gas and solid state lasers, operating in either 
continuous wave ("c.w.") or pulsed modes. More specifically, the laser 
sources can be carbon monoxide, carbon dioxide, argon lasers or various 
excimer lasers utilizing mixtures of halogen and noble gases, such as 
argon-flouride, krypton-fluoride, xenon-chloride and xenon-fluoride. 
Additionally, the laser can be a solid state laser employing a rare, 
earth-doped Yttrium Aluminum Garnet (YAG) or Yttrium Lithium Fluoride 
(YLF) or a Yttrium-Scandium-Gadolinium-Garnet (YSGG) laser. 
In one preferred embodiment, the laser source is a rare, earth-doped, solid 
state laser, such as a holmium-doped, erbium-doped or thulium-doped solid 
state laser of the YAG, YLF or YSGG type which can be operated in a low 
wattage c.w. or pulsed mode with an output wavelength in the range of 
about 1.4 to about 2.5 micrometers and a power density of about 0.1 
watt/mm.sup.2 to about 1.0 watt/mm.sup.2. Such laser sources are disclosed 
in U.S. Pat. No. 4,917,084 issued on Apr. 17, 1990, to the present 
inventor and incorporated herein by reference. 
The absorption of laser energy from such solid state laser sources by 
biological tissues is relatively high in relation to the absorption of 
such energy by water, thereby providing an absorption length in the 
subject's body of about 100 microns or more. Thus, it is possible to 
operate satisfactorily even with 10-20 micrometers of blood between the 
handpiece tip and the anastomotic site. 
FIG. 3 is a schematic illustration of laser source 12, including a 
solid-state laser crystal 40, vacuum chamber 42 and diode pump source 44. 
The laser crystal 40 is preferably surrounded by a cooling quartz or 
fused-silica jacket 46 having inlet pipe 48 and an outlet pipe 50 for 
circulation of liquid nitrogen or other cryogenic coolant. The laser 
cavity can be formed by input crystal face coating 52 and 
partially-reflective output mirror 54. 
Generally, the laser crystal 40 is excited by optical pumping, that being, 
irradiation of the crystal with light from the laser diode 44. (The diode 
44 can be cooled by a pumped coolant or employ a heatsink). Both ends of 
the laser crystal 40 are preferably polished flat. The input face of the 
crystal 40 is preferably finished with a coating 52 for high transmittance 
at the pump wavelength and high reflectance of the output wavelength. The 
other end of the crystal 40 preferably includes an antireflective coating 
50 for high transmittal of the output wavelength. The entire cavity of the 
reflector preferably is evacuated to provide thermal insulation and avoid 
moisture condensation. 
For further details on the construction of cryogenic, solid-state lasers, 
see, for example, an article by Barnes et al., Vol. 190, Society of the 
Photo-Optical Instrumentation Engineers. pp. 297-304 (1979), NASA/JPL 
Technical Brief No. NPO-17282/6780 by Hemmati (June, 1988) and 
above-referenced U.S. Pat. No. 4,917,084, all of which are herein 
incorporated by reference. 
Also shown in FIG. 3 is a tuning element 26 which can include, for example, 
a birefringent crystal 28 disposed along the beam path 58 at a slight 
offset from Brewster's angle. The crystal 28 can be tuned 
electro-optically by application of a voltage, as shown schematically in 
the figure. Alternatively, the laser wavelength can be tuned mechanically 
by tilting or rotating the crystal 28 relative to the beam path using 
techniques well known in the art. 
In FIG., 4 a partial, cross-sectional side view of a handpiece 64 is shown, 
including a casing 70 adapted for gripping by the clinical user and 
multiple lumens disposed therein. With further reference to FIG. 5 as 
well, the handpiece serves to deliver laser irradiation suitable for 
biological tissue fusion via a central optical fiber 72 connected to laser 
source, as well as one or more additional illumination fibers 74 for the 
delivery of illumination light and the transmittal of reflected light. The 
surgical laser delivery fiber 72 is preferable a low, hydroxyl ion content 
silica fiber. As shown in FIG. 5, the handpiece 64 can deliver 
illumination light via fibers 74. In one embodiment, these fibers 74 can 
also be used to collect reflective light and deliver it to a controller. 
Alternatively, some of the fibers 74 can be devoted entirely to collection 
of reflected light. The handpiece 64 can further include one or more lens 
elements 76, as well as a transparent protective cover element or terminal 
lens 82. 
FIG. 6 is a more detailed schematic diagram of a reflectance monitor 18, 
including a coupling port 90 for coupling with one or more fibers 76 to 
receive reflectance signals from the handpiece of FIG. 4. The reflectance 
monitor 18 can further include a focusing lens 92 and first and second 
beam splitting elements 94 and 96, which serve to divide the reflected 
light into 3 (or more) different beams for processing. As shown in FIG. 6, 
a first beam is transmitted to a first optical filter 98 to detector 102 
(providing, for example, measurement of reflected light at wavelengths 
shorter than 0.7 micrometers). A second portion of the reflected light 
signal is transmitted by beam splitter 96 through a second optical filter 
100 to detector 104 (e.g., providing measurement of light at wavelengths 
shorter than 1.1 micrometers). Finally, a third portion of the reflected 
light is transmitted to photodetector 106 (e.g., for measurement of 
reflected light at wavelengths greater than 1.6 micrometers). Each of the 
detector elements 102, 104, and 106 generate electrical signals in 
response to the intensity of light at particular wavelengths. 
The detector elements 102, 104 and 106 preferably include synchronous 
demodulation circuitry and are used in conjunction with a modulated 
illumination source to suppress any artifacts caused by stray light or the 
ambient environment. (It should be apparent that other optical 
arrangements can be employed to obtain multiple wavelength analysis, 
including the use, for example, of dichroic elements, either as 
beamsplitters or in conjunction with such beamsplitters, to effectively 
pass particular wavelengths to specific detector elements. It should also 
be apparent that more than three discreet wavelengths can be measured, 
depending upon the particular application.) The signals from the detector 
elements can then be transmitted to a controller and/or a display element 
(as shown in FIG. 1). 
In the controller, signals from the reflectance monitor are analyzed (as 
detailed below) to determine the degree of crosslinking which is occurring 
in the biological tissue exposed to the laser radiation. Such analysis can 
generate control signals which will progressively reduce the laser output 
energy over time as a particular site experiences cumulative exposure. The 
control signals can further provide for an automatic shut-off of the laser 
when the optimal state of crosslinking has been exceeded and/or the onset 
of carbonization is occurring. 
As shown in FIG. 7, the data from the reflectance monitor can also be 
provided directly to the clinician. In FIG. 7, a simulated view from an 
eyepiece 110 is shown in which the field of view 112 includes a fissure or 
cleavage line 114 dividing separate bodies at an anastomotic site. Also 
shown within the field of view is a tissue fusion track 116 which has been 
formed by laser radiation and a present exposure zone 118. Also displayed 
within the eyepiece 110 is a "heads-up" display of the reflectance values 
for the reflectance monitor of FIG. 6, including illuminated warning 
lights 122 which serve to indicate the reflectance intensity at particular 
wavelengths or other optical data indicative of the degree of crosslinking 
and/or tissue fusion. 
FIG. 8 is a photograph of a laser suture which was performed using the 
present invention. The biological material shown in this figure had been 
surgically cleaved prior to irradiation. As shown, the cleavage line has 
been fused, and additional "cross-stitches" have been formed by fusion of 
a biological glue and the target material along liens perpendicular to the 
cleavage line. The cross stitches impart additional strength to the repair 
due to their tensile strength and load-bearing properties. 
In FIG. 9, the reflectance intensity of light at various wavelengths is 
shown for a sample of human cadaver aortic tissue before and after laser 
treatment. As can be seen, there are distinct differences in the 
reflectance values that allow the present invention to determine when a 
suitable degree of laser-induced, crosslinking has occurred at the 
anastomotic site. 
In FIG. 10, a further graph of reflectance intensity versus wavelengths for 
a sample blood-containing muscle tissue is shown which illustrates the 
differences not only between the untreated tissue and the laser-fund 
tissue but also reveals the distinct changes on the reflectance profile 
induced by thermal degradation. 
In use, the apparatus of the present invention can be employed to analyze 
the degree of crosslinking by comparing the reflectance ratios of a site 
at two or more wavelengths. Preferably, intensity readings for three or 
more wavelength ranges are employed in order to accurately assess the 
degree of crosslinking and to ensure that the optimal state is not 
exceeded. The particular wavelengths to be monitored will, of course, vary 
with the particular tissue undergoing treatment. Although the tissue type, 
(e.g., blood-containing tissue or that which is relatively blood-free) 
will vary, the general principles of the invention, as disclosed herein, 
can be readily applied by those skilled in the art to diverse procedures 
in which the fusion of biological materials is desired. 
For example, referring again to FIGS. 9 and 10, reflectance spectra are 
presented before and after the application of laser energy. The X axis 
indicates wavelengths ranging from about 0.4 micrometers (visible 
blue-green light) through about 0.6 micrometers (red light), and 1.1 
micrometers (near infrared) to about 1.6 micrometers (infrared). As shown 
in FIG. 10, when carbonization in blood pigmented tissue occurs, the total 
infrared reflectance (e.g., above 1.0 micrometers) continues to increase 
while the visible reflectance decreases. Thus, the analyzing circuitry of 
the controller can be constructed to provide a warning (or automatically 
shut off the laser radiation) when darkening in the visible wavelengths 
occurs or when the ratio of visible to infrared values falls below a 
predefined level. 
Moreover, as shown in FIG. 9, when the material to be joined (e.g., aortic 
tissue) is relatively unpigmented, reliance on changes in the reflectance 
of visible light can be inaccurate, but infrared reflectance changes 
(e.g., above 1.1 micrometers) can reliably indicate the degree of 
crosslinking. (Lack of change in the visible reflectance is one of the 
reasons that tissues of this type are difficult to crosslink, as no change 
in the target's visible properties are observed until the tissue is 
overexposed to laser energy.) Consequently, the analyzing circuitry can 
monitor infrared reflectance changes (e.g., greater than about 1.0 
micrometers) as an indicator of proper crosslinking. 
Finally, the reflectance sensor can also be used as a proximity monitor to 
ensue that the laser is in fact disposed at a proper distance from the 
anastomic site. By measuring total reflectance (over the entire 
visible-infrared range or a portion thereof), a sudden drop in the 
reflectance value will typically be related to incorrect placement of the 
handpiece. Thus, the analyzing circuitry can sense the changes in 
reflectance and generate a warning to the user (or automatically shut off 
the system) until proper placement is achieved.