U.S. patent application number 09/006108 was filed with the patent office on 2002-05-16 for near infra-red selective photothermolysis for ectatic vessels and method therefor.
Invention is credited to FURUMOTO, HORACE W..
Application Number | 20020058930 09/006108 |
Document ID | / |
Family ID | 23389679 |
Filed Date | 2002-05-16 |
United States Patent
Application |
20020058930 |
Kind Code |
A1 |
FURUMOTO, HORACE W. |
May 16, 2002 |
NEAR INFRA-RED SELECTIVE PHOTOTHERMOLYSIS FOR ECTATIC VESSELS AND
METHOD THEREFOR
Abstract
Near-infrared selective photothermolysis for the treatment of
ectatic blood vessels, for example, blood vessels of a portwine
stain birthmark. This technique is especially applicable to deeper
lying blood vessels in view of the better penetration of the near
infrared light. Consequently, vessels are below a dermal/epidermal
boundary can be reached. Near-infrared is defined as a range of
approximately 700 to 1,200 nm. The optimal colors are near 760 or
between 980 to 990 nm for most populations.
Inventors: |
FURUMOTO, HORACE W.;
(WELLESLEY, MA) |
Correspondence
Address: |
JAMES M SMITH
HAMILTON BROOK SMITH
& REYNOLDS
TWO MILITIA DRIVE
LEXINGTON
MA
02173
|
Family ID: |
23389679 |
Appl. No.: |
09/006108 |
Filed: |
January 13, 1998 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
09006108 |
Jan 13, 1998 |
|
|
|
08720267 |
Sep 26, 1996 |
|
|
|
08720267 |
Sep 26, 1996 |
|
|
|
08353565 |
Dec 9, 1994 |
|
|
|
Current U.S.
Class: |
606/3 ;
606/9 |
Current CPC
Class: |
A61B 18/22 20130101;
A61B 2018/00458 20130101; A61B 2017/00132 20130101; A61N 2005/0659
20130101; A61B 18/203 20130101; A61B 2018/00452 20130101; A61B
2017/00747 20130101; A61N 5/067 20210801 |
Class at
Publication: |
606/3 ;
606/9 |
International
Class: |
A61B 018/20 |
Claims
I claim:
1. A method for performing selective photothermolysis, comprising:
generating near-infrared laser light; and treating vascular targets
with the laser light.
2. A method as claimed in claim 1, further comprising treating
ectatic blood vessels of vascular lesions with the laser light.
3. A method as claimed in claim 2, further comprising treating
ectatic blood vessels of a portwine stain birthmark.
4. A method as claimed in claim 1, further comprising generating
the laser light with a pulse duration of greater than 0.2
milliseconds.
5. A method as claimed in claim 1, further comprising generating
the laser light with a pulse duration within a range of 1 to 10
milliseconds.
6. A method as claimed in claim 1, comprising irradiating the
targets with laser light having a wavelength within a range of
approximately 700 to 1,200 nm.
7. A method as claimed in claim 1, wherein the laser light has a
wavelength within a range of approximately 700 to 1000 nm.
8. A method as claimed in claim 1, wherein the laser light has a
wavelength within a range of approximately 720-790 nm.
9. A method as claimed in claim 1, wherein the laser light has a
wavelength within a range of approximately 750 to 780 nm.
10. A method as claimed in claim 1, wherein the laser light has a
wavelength of approximately 760 nm.
11. A method as claimed in claim 1, further comprising generating
the laser light with an alexandrite laser.
12. A method as claimed in claim 1, further comprising generating
the laser light with a titanium sapphire laser.
13. A method as claimed in claim 1, further comprising generating
the laser light with a chromium-doped fluoride laser.
14. A method as claimed in claim 1, further comprising generating
the laser light with a semiconductor diode laser.
15. A method as claimed in claim 1, further comprising transmitting
the laser light to the vascular target of a patient with an optical
fiber delivery.
16. A method as claimed in claim 1, further comprising time
multiplexing the output of at least one laser to generate the laser
pulse.
17. A near-infrared selective photothermolysis device for treatment
of vascular lesions, the device comprising: a laser system for
generating near-infrared laser light pulses having durations
greater than 0.2 milliseconds; and a delivery system for
transmitting the laser light pulses to vascular targets of a
patient.
18. A device as claimed in claim 17, wherein the vascular targets
are ectatic blood vessels of a portwine stain birthmark.
19. A device as claimed in claim 17, wherein the laser light pulses
have a wavelength in a range of approximately 700 to 1,200 nm.
20. A device as claimed in claim 17, wherein the laser light pulses
have a wavelength in a range of approximately 700 to 1000 nm.
21. A device as claimed in claim 17, wherein the laser light pulses
have a wavelength in a range of approximately 750 to 780 nm.
22. A device as claimed in claim 17, wherein the laser light pulses
have a wavelength of approximately 760 nm.
23. A device as claimed in claim 17, wherein the laser light pulses
have a wavelength in a range of approximately 800 to 1200 nm.
24. A device as claimed in claim 17, wherein the laser light pulses
have a wavelength in a range of approximately 720-950 nm.
25. A device as claimed in claim 17, wherein the laser system
comprises an Alexandrite laser.
26. A device as claimed in claim 17, wherein the laser system
comprises a titanium sapphire laser.
27. A device as claimed in claim 17, wherein the laser system
comprises a chromium doped fluoride laser.
28. A device as claimed in claim 17, wherein the laser system
comprises a semi-conductor diode laser.
29. A device as claimed in claim 17, wherein the laser system
multiplexes pulses from at least one laser to generate a longer
effective pulse duration.
30. A device as claimed in claim 17, wherein the delivery system
comprises an optical fiber for combining and delivering light from
at least one laser.
31. A device as claimed in claim 17, wherein an effective pulse
duration of the light pulse is between 1 and 10 msec.
32. A method for treating a vascular lesion, the method comprising:
irradiating the lesion with near-infrared laser light pulses; and
controlling a duration of the pulses to approximately match a
thermal relaxation time of blood vessels of the targets.
33. A method as claimed in claim 32, further comprising generating
the laser light pulses at a wavelength in a range of approximately
720 to 790 nm.
Description
RELATED APPLICATION
[0001] This application is a Continuation of U.S. Ser. No.
08/720,267, filed Sep. 26, 1996, the entire teachings of which are
incorporated herein by reference, which is a Continuation of U.S.
Ser. No. 08/353,565, filed Dec. 9, 1994.
BACKGROUND OF THE INVENTION
[0002] Vascular lesions, comprising enlarged or ectatic blood
vessels, pigmented lesions, and tattoos have been successfully
treated with lasers for many years. In the process called selective
photothermolysis, the targeted structure, the lesion tissue or
tattoo pigment particles, and the surrounding tissue are
collectively irradiated with laser light. The wavelength or color
of this laser light, however, is chosen so that its energy is
preferentially absorbed into the target. Localized heating of the
target resulting from the preferential absorption leads to its
destruction.
[0003] Most commonly in the context of vascular lesions, such as
portwine stains for example, hemoglobin of red blood cells within
the ectatic blood vessels serves as the laser light absorber, i.e.,
the chromophore. These cells absorb the energy of the laser light
and transfer this energy to the surrounding vessels as heat. If
this occurs quickly and with enough energy, the surrounding vessels
reach a temperature to denature their proteins. The fluence, Joules
per square centimeter, to reach the denaturation of the vessels is
calculated to be that necessary to raise the temperature of the
targeted volume within the vessel to about 70.degree. C. before a
significant portion of the absorbed laser energy can diffuse out of
the vessel. The fluence must, however, be limited so that the
surrounding tissue is not also denatured.
[0004] As suggested, simply selecting the necessary fluence is not
enough. The intensity and pulse duration of the laser light must
also be optimized for selectivity by both minimizing diffusion into
the surrounding tissue during the pulse while avoiding localized
vaporization. Boiling and vaporization are desirably avoided since
they lead to mechanical, rather than chemical, damage--which can
increase injury and hemorrhage in tissue surrounding the lesion.
These constraints suggest that the pulse duration should be longer
with a correspondingly lower intensity to avoid vaporization.
Because of thermal diffusivity, energy from the laser light pulse
must be deposited quickly, however, to minimize heat dissipation
into the surrounding tissue. The situation becomes more complex if
the chromophore is the blood cell hemoglobin within the lesion
blood vessels, since the vessels are an order of magnitude larger
than the blood cells. Radiation must be added at low intensities so
as to not vaporize the small cells, yet long enough to heat the
blood vessels by thermal diffusion to the point of denaturation and
then terminated before tissue surrounding the blood vessels is
damaged.
[0005] Conventionally, long pulse flashlamp excited dye lasers have
been used as the laser light source. These lasers have the high
spectral brightness required for selective photothermolysis and can
be tuned to the alpha absorption band of hemoglobin. Colors in the
range of 577 to 585 nm are absorbed well by the chromophore, the
red blood cells in the blood vessels. Further, the relative
absorption between the targeted blood and the melanin in the
surrounding tissue is optimum in order to minimize heating of the
melanin.
SUMMARY OF THE INVENTION
[0006] The implementation of dye lasers tuned to the conventional
color range presents a number of drawbacks. Theory dictates that
the length of the light pulse should be on the order of the thermal
relaxation time of the ectatic vessels. Larger ectatic vessels,
greater than 30 microns, consequently require pulse durations of
0.5 msec and longer. Commercially available dye lasers are limited
in pulse durations to approximately 0.5 msec and shorter, however.
Further, current research suggests that pulse durations exceeding
0.7 msec are probably not attainable by these lasers. As a result,
in selective photothermolysis treatment of these larger ectatic
vessels, higher than optimum fluences must be used to compensate
for the pulse duration limitations. This leads to temporary
hyperpigmentation, viz., purpura. Moreover, the molar extinction
coefficient, a measure of a chemical's optical absorption
characteristics, is approximately 0.2 for both melanin and
hemoglobin in the range of 577 to 585 nm. As a result, for fair
Caucasian skin, for example, the effective penetration depth of
light in this wavelength range is limited to less than 0.5 mm.
Therefore, the dye laser treatment techniques work exceptionally
well on vascular lesions comprised of vessels less than 30 microns
in diameter and located above the dermal/epidermal junction. On the
negative side, deep penetration is limited because of the high
absorption, and multiple treatments are necessary to get at deeper
vessels. Further, as previously noted large vessels are
sub-optimally treated with pulses that are too short in time.
[0007] The near infra-red portion of the electromagnetic spectrum,
designated for the purposes of this description as stretching from
approximately 700 to 1200 nm, provides regions of favorable ratios
between competing melanin and hemoglobin absorption. The use of
these wavelengths for the treatment of ectatic blood vessels has
been universally ignored as an alternative to the 577-585 nm
wavelengths because of the poor hemoglobin absorption
characteristics in this area. This conclusion, however, fails to
recognize that the ratio between the absorption characteristics of
the hemoglobin and the melanin is the principle variable in
achieving selectivity, not net absorption. Moreover, in the
treatment of deeper lying vessels, the poor absorption
characteristics can actually be an asset since it enables deeper
overall penetration of the laser light.
[0008] In light of the above, in general, according to one aspect,
the invention is directed to near-infrared selective
photothermolysis for the treatment of vascular lesions. In specific
embodiments, this technique is used to treat ectatic blood vessels,
for example, blood vessels of a portwine stain birthmark. This
technique is especially applicable to deeper lying blood vessels in
view of the better penetration of the near infrared light.
Consequently, vessels below a dermal/epidermal boundary can be
reached.
[0009] In specific embodiments a few different wavelength ranges
are possible. Generally, the near-infrared light is in the range of
approximately 700 to 1,200 nm. More specifically, the range can be
limited to 750 to 780 nm. The best color is 760 nm, however.
Alternatively, a general range of 980 to 990 nm is also
effective.
[0010] The laser light is preferably generated by one of an
alexandrite, titanium sapphire, chromium doped fluoride, or
semiconductor diode laser and conveyed to the patient via an
optical fiber delivery system for transmitting the laser light to a
patient.
[0011] In general according to another aspect, the invention
features a near-infrared selective photothermolysis device for
treatment of ectatic vascular lesions. This device comprises a
laser system for generating near-infrared laser light pulse having
a duration of greater than 0.2 milliseconds and a delivery system
for transmitting the laser light pulse to a patient.
[0012] In specific embodiments, the laser system includes an
alexandrite, titanium sapphire, chromium doped fluoride, or
semi-conductor diode-type laser. If the pulse duration or power
output of the selected laser is inadequate individually, the light
pulses from multiple diode lasers, for example, can be combined.
Time-multiplexing achieves long effective pulse durations.
Consequently, effective pulse durations of between 1 and 10 msec
are achievable when individual laser diodes only produce pulses of
0.5 msec. Combinations of simultaneously generated beams increase
effective power.
[0013] In general according to still another aspect, the invention
features a method for treating a vascular lesion. This method
comprises irradiating the lesion with near-infrared laser light
pulses. The duration of these pulses is controlled to approximately
match a thermal relaxation time of blood vessels of the lesion. The
near-infrared wavelengths stretch from approximately 700 to 1,200
nm.
[0014] The above and other features of the invention including
various novel details of construction and combinations of parts,
and other advantages, will now be more particularly described with
reference to the accompanying drawings and pointed out in the
claims. It will be understood that the particular method and device
embodying the invention is shown by way of illustration and not as
a limitation of the invention. The principles and features of this
invention may be employed in various and numerous embodiments
without the departing from the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] In the accompanying drawings, reference characters refer to
the same parts throughout the different views. The drawings are not
necessarily to scale; emphasis has instead been placed upon
illustrating the principles of the invention. Of the drawings:
[0016] FIG. 1 schematically shows a near-infrared selective
photothermolysis device of the invention using a single laser;
[0017] FIG. 2 is a plot of the molar extinction coefficient as a
function of wavelength, in nanometers, for oxyhemoglobin
HbO.sub.2(solid line), deoxyhemoglobin Hb (dotted line), bilirubin
(dashed line), and DOPA-melanin (the apparently exponentially
falling solid line);
[0018] FIG. 3 schematically shows a near-infrared selective
photothermolysis device of the invention using multiple laser
diodes or diode arrays; and
[0019] FIG. 4 is a plot of TiS laser output as a function of time
for different levels of flashlamp excitation, showing that
relaxation oscillation is not a factor for long pulse
durations.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0020] Turning now to the drawings, a near-infrared selective
photothermolysis device 100, constructed according to the
principles of the present invention, is illustrated in FIG. 1. This
device 100 is generally similar to that found in the prior art
except to the extent that it includes a radiation source that
generates light pulses in the near-infrared region of the
electromagnetic spectrum. More completely, a laser system 110
generates a beam of near-infrared light B, i.e., in the range of
700-1200 nm. The beam of light B is coupled into a delivery system
120, such as a single optical fiber, and transported to the skin 50
of a patient. Because this light beam B is in the near-infrared
region of the spectrum, it can achieve substantial penetration
beyond a dermal/epidermal boundary 55 to treat an entire portion of
a vascular lesion 60. This lesion 60 could be of one of many
different types such as portwine stain birthmarks, hemangiomas,
telangiectasia, idiopathic vulvoddynia, and leg veins. Further, it
could also be vessels in simple wrinkles, caused by age or sun
exposure, or blood vessels in scar tissue.
[0021] The pulse duration of the light beam B is matched to the
thermal relaxation time of the targeted ectatic vessels. Generally,
this requires durations greater than 0.2 msec. For vessels of 30
microns in diameter and larger, as are present in portwine stains
of adult patients, the duration should ideally exceed 0.5 msec,
whereas pulse durations of 1 msec to 10 msec should be selected, if
the vessels are larger than 100 microns.
[0022] Referring to FIG. 2, there are a number of specific ranges
within the near-infrared that will be especially effective in
treating vascular lesions. (Because the molecular weights of
melanin are poorly defined, the spectrum shown is the optical
density on a scale of 0 to 1.5 for a 1.5 mg % solution of
DOPA-melanin.) FIG. 2 is a plot of the molar extinction coefficient
as a function of wavelength in nanometers.
[0023] For an acceptable degree of selectivity in fair Caucasian
skin, the ratio between the molar extinction coefficient of the
hemoglobin and the melanin should be at least 0.05. The ratio of
combined deoxyhemoglobin (Hb) and oxyhemoglobin (HbO.sub.2)
absorption to melanin absorption (DOPA-melanin) is generally
favorable, 0.05 or greater, between 700 and 1,200 nm. If the
deoxyhemoglobin Hb is specifically targeted, the wavelength range
of 700 to 1,000 nm of the laser beam B is acceptable. The
deoxyhemoglobin absorption peaks in the range of 750 to 780 nm with
the best ratios at approximately 760 nm.
[0024] The total absorption of hemoglobin is less in the
near-infrared than the conventional range of 577-585 nm. Therefore,
fluences of the light beam B required to treat ectatic vessels are
higher than fluences used with conventional shorter wavelengths.
Therefore, the light beam B generally provides fluences of between
2 and 20 J/cm.sup.2.
[0025] The laser system 110 can comprise several candidate lasers,
which are available to generate the near-infrared laser light
around 760 nm. For example, alexandrite is tunable within the range
of 720-790 nm. Also tunable titanium sapphire (TiS) produces light
in the range of 720-950 nm. These two lasers appear to be the best
candidates since they are highly developed under current
technology. Other tunable chromium doped fluoride lasers such as
LiCaAlF.sub.6, LiCaGaF.sub.6, LiSrAlF.sub.6, and LiSrGaF.sub.6 in
addition to semiconductor diode lasers are also potential
alternatives.
[0026] Alexandrite lasers are particularly well adapted to
selective photothermolysis since pulse generation in the range of 3
to 10 msec is possible. This pulse duration is most appropriate for
the treatment of ectatic vessels of 100 microns and larger, which
are ineffectively treated by currently available technology. These
lasers, however, exhibit a very spiky behavior in the so-called
normal mode of operation. This results from relaxation
oscillation.
[0027] Semiconductor diode lasers do not store energy in a
metastable upper laser level and consequently do not show the spiky
behavior. The individual power output is, however, too low to reach
the necessary fluences which are necessary to treat ectatic
vessels. Implementation of diode lasers requires the combination of
beams from many lasers to reach the more than 100 watts needed.
Such an embodiment is schematically shown in FIG. 3 in which the
outputs from three diode lasers 210, 212, 214 of the laser system
205 are combined into a single beam and coupled into the delivery
system 220. The diode lasers 210-214, or TiS lasers, are
coordinated by a synchronizer 230 that controls their respective
times of light generation. Alternatively, if still more power is
required the diode lasers 210, 212, 214 are alternatively replaced
with separate arrays of diodes. In either case, the delivery system
220 is a liquid core flexible light guide instead of a single glass
optical fiber. These liquid core guides have large apertures,
typically Smm and still retain flexibility. Thus, beams from the
several diode lasers, or several arrays, are directly focused onto
the liquid light guide, greatly simplifying the transfer optics
between the laser diodes and the ectatic vessels.
[0028] Another device for combining many beams from diode lasers is
specifically disclosed in U.S. patent application Ser. No.
08/163,160, entitled, "Fault Tolerant Optical System Using Diode
Laser Array," of which the present inventor is a co-inventor and
which is incorporated herein by this reference. This application is
directed to the use of corrective micro-optics to mate a
two-dimensional diode array with a masked-produced two-dimensional
array of collimator micro-lens and mass-produced transformer
sets.
[0029] The TiS laser is another viable candidate. In tests, these
lasers have produced 1 to 5 msec pulses and did not exhibit the
spiky behavior that is characteristic of flashlamp excited solid
state laser systems. Most solid state lasers have an upper state
lifetime of approximately 100 .mu.sec. In the TiS laser, however,
this lifetime is only 3 .mu.sec. As a result, if the TiS lasing
medium is pumped hard, as for example how dye lasers are pumped,
the upper state becomes saturated and will not store any more
energy after about 2-3 .mu.sec. This neutralizes most relaxation
oscillation pulsing. For example, as shown in FIG. 4, four
different levels of flashlamp excitation are demonstrated, 2,000,
1,800, 1,600, and 1400 V.D.C. The resulting pulse durations of two
to three msec do not exhibit strong relaxation oscillation pulsing
characteristics. The pulses tended to be limited in duration to
approximately 3 msec, however, by thermal lensing effects.
[0030] If individual TiS lasers are not capable of producing the
necessary pulse durations, the laser system 110 of FIG. 3 may time
multiplex the outputs of several lasers as taught in U.S. Pat. Ser.
No. 08/329,195, filed on Oct. 26, 1994, entitled "Ultra Long Pulsed
Dye Laser for Treatment of Ectatic Vessels and Method Therefor," of
which the present inventor is a co-inventor and which is
incorporated herein by this reference. Specifically, the
synchronizer 230 of FIG. 3 sequentially triggers each of the diode
or TiS lasers 210-214 to thereby generate effective pulse
durations. Alternatively or additionally, to achieve high effective
power output, the synchronize 230 simultaneously triggers all of
some of the lasers 210-214.
[0031] The deoxyhemoglobin HbO.sub.2 can be specifically targeted,
which has a favorable absorption range between 800 and 1200 nm. The
best absorption ratios exist between 980 and 990 nm. Here, the
molar extinction coefficient of the oxyhemoglobin HbO.sub.2 peaks
and the coefficient ratio of oxyhemoglobin to melanin actually
exceeds 0.1. This is a desirable range for diode laser treatment.
50 watt fiber coupled continuous wave diode lasers, stand alone and
fully developed, are commercially available. These state of the art
diode laser arrays can produce 100 watts in a quasi-continuous wave
mode. The pulse duration of these modes is typically around 400
.mu.sec. Therefore, in the treatment of larger ectatic vessels
time-multiplexed arrays of diode lasers, as described above, are
necessary.
[0032] While this invention has been particularly shown and
describe with references to preferred embodiments thereof, it will
be understood by those skilled in the art that various changes in
form and details may be made therein without departing from the
spirit and scope of the invention as defined by the appended
claims.
* * * * *