U.S. patent application number 14/611052 was filed with the patent office on 2015-08-06 for treatment systems and methods for treating cellulite and for providing other treatments.
The applicant listed for this patent is Zeltiq Aesthetics, Inc. Invention is credited to Leonard C. DeBenedictis, George Frangineas, JR., Linda Pham, Kristine Tatsutani.
Application Number | 20150216719 14/611052 |
Document ID | / |
Family ID | 52469360 |
Filed Date | 2015-08-06 |
United States Patent
Application |
20150216719 |
Kind Code |
A1 |
DeBenedictis; Leonard C. ;
et al. |
August 6, 2015 |
TREATMENT SYSTEMS AND METHODS FOR TREATING CELLULITE AND FOR
PROVIDING OTHER TREATMENTS
Abstract
Treatment systems, methods, and apparatuses for improving the
appearance of skin or other target regions are described. Aspects
of the technology are directed to improving the appearance of skin
by tightening the skin, improving skin tone or texture, eliminating
or reducing wrinkles, increasing skin smoothness, or improving the
appearance sites with cellulite. Treatments can include cooling a
surface of a patient's skin and detecting freezing in the cooled
skin. The tissue can be cooled after the freeze event is detected
so to maintain the frozen state of the tissue to improve the
appearance of the treatment site.
Inventors: |
DeBenedictis; Leonard C.;
(Dublin, CA) ; Frangineas, JR.; George; (Fremont,
CA) ; Tatsutani; Kristine; (Redwood City, CA)
; Pham; Linda; (Pleasanton, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Zeltiq Aesthetics, Inc |
Pleasanton |
CA |
US |
|
|
Family ID: |
52469360 |
Appl. No.: |
14/611052 |
Filed: |
January 30, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61934549 |
Jan 31, 2014 |
|
|
|
61943250 |
Feb 21, 2014 |
|
|
|
61943257 |
Feb 21, 2014 |
|
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Current U.S.
Class: |
601/2 ; 601/18;
607/108; 607/96 |
Current CPC
Class: |
A61F 2007/0052 20130101;
A61F 2007/0075 20130101; A61F 2007/0019 20130101; A61F 2007/0093
20130101; A61F 2007/0056 20130101; A61B 90/04 20160201; A61F
2007/0045 20130101; A61B 2090/0463 20160201; A61K 31/045 20130101;
A61B 2018/00464 20130101; A61B 2018/00714 20130101; A61F 2007/0004
20130101; A61B 2018/0262 20130101; A61F 2007/0036 20130101; A61N
7/00 20130101; A61B 2018/00791 20130101; A61B 18/02 20130101; A61B
2018/0237 20130101; A61F 2007/0047 20130101; A61K 31/047 20130101;
A61B 2018/00291 20130101; A61B 18/0206 20130101; A61F 7/00
20130101; A61F 2007/0003 20130101; A61F 2007/0096 20130101; A61B
2018/00875 20130101; A61B 2090/065 20160201; A61F 2007/0087
20130101; A61H 1/006 20130101; A61H 1/008 20130101; A61B 2018/00994
20130101; A61F 7/007 20130101 |
International
Class: |
A61F 7/00 20060101
A61F007/00; A61N 7/00 20060101 A61N007/00; A61H 1/00 20060101
A61H001/00 |
Claims
1. A method for reducing skin surface irregularities of a patient
with gynoid lipodystrophy, the method comprising: cooling a surface
of the patient's skin at a treatment site affected by gynoid
lipodystrophy to a temperature no lower than about -40 degrees C.;
detecting a freeze event at the treatment site; and controlling a
cooling device to continue cooling the surface of the patient's
skin after the freeze event is detected so as to maintain an at
least partially frozen state of the skin for a period of time
longer than about 10 seconds to reduce the skin surface
irregularities.
2. The method of claim 1, wherein the cooling device is controlled
so that the cooling of the surface of the skin does not
significantly lighten or darken in color one of more days after the
freeze event ends.
3. The method of claim 1, wherein cooling the surface of the
patient's skin includes cooling the patient's skin using a
thermoelectric cooler, and wherein the freeze event is detected
using electrical components.
4. The method of claim 1, wherein the period of time is shorter
than about either 30 seconds or either 1, 2, 3, 4, 5 or 10
minutes.
5. The method of claim 1, wherein the period of time is chosen to
be long enough so that lipid rich cells in a subcutaneous layer of
the patient are substantially affected by cooling the surface of
the patient's skin.
6. The method of claim 1, wherein controlling the cooling device
includes cooling the patient's skin using the cooling device such
that ice crystals are present in the skin for a sufficient length
of time to cause a reduction in the skin irregularities without
causing necrosis.
7. The method of claim 1, further comprising thawing the patient's
skin after the period of time has transpired to minimize freeze
damage caused by the skin cooling.
8. The method of claim 1, wherein the freeze event is detected
using optical or thermal detection techniques.
9. The method of claim 1, wherein the method improves the
appearance of cellulite, improves the appearance of skin, improves
skin tone and texture, thickens skin, eliminates deep skin
wrinkles, eliminates fine lines in the skin, tightens skin, and/or
treats sweat glands.
10. The method of claim 1, further comprising controlling the
cooling device so that the freeze event causes apoptotic damage to
tissue at the treatment site and does not cause necrotic damage to
the tissue.
11. The method of claim 1, further comprising controlling the
cooling device so that the freeze event is short enough to prevent
equilibrium temperature gradients from being established in the
skin during the freeze event.
12. The method of claim 1, further comprising controlling the
cooling device so that the freeze event begins within a second
predetermined period of time after the cooling device begins
cooling the surface of the skin, the second predetermined period of
time being shorter than about 30 seconds or shorter than about
either 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 minutes.
13. The method of claim 1, further comprising delivering a
substance, energy, or pressure to the skin to aid in formation of
nucleation sites in the skin to initiate the freeze event.
14. The method of claim 1, further comprising delivering a
cryoprotectant to the surface of the patient's skin for a period of
time which is short enough to prevent the cryoprotectant from
significantly inhibiting initiation of the freeze event at deeper
tissue below epidermal tissue but is long enough to allow the
cryoprotectant to provide substantial freeze protection to the
epidermal tissue.
15. The method of claim 1, further comprising applying a
cryoprotectant to the surface of the patient's skin to inhibit
damage to epidermal tissue at the treatment site without
significantly inhibiting initiation of the freeze event.
16. The method of claim 1, wherein the freeze event creates at
least some microscopic crystal formation in intercellular fluid
and/or extracellular fluid.
17. The method of claim 1, wherein the surface of the skin and
tissue therebeneath is supercooled, then the surface of the skin is
warmed above a freezing temperature, and then the tissue is
nucleated to initiate the freeze event.
18. A treatment system for reducing surface irregularities along
skin of a subject with gynoid lipodystrophy, comprising: an
applicator configured to be applied to the subject and including a
cooling device for cooling the subject's skin at a treatment site;
and a controller programmed with instructions for causing the
cooling device to cool the surface of the subject's skin to a
temperature no lower than about -40 degrees C., and control the
cooling device in response to detection of a freeze event to
maintain at least a partial frozen state at the treatment site for
a period of time longer than about 10 seconds to reduce the skin
surface irregularities.
19. The method of claim 18, wherein the cooling device is
controlled so that the skin does not significantly lighten or
darken in color one of more days after the freeze event ends.
20. The treatment system of claim 18, wherein the period of time is
shorter than 30 seconds or shorter than 1, 2, 3, 4, 5 or 10
minutes.
21. The treatment system of claim 18, wherein the controller is
programmed to cause the applicator to heat the subject's skin at
the treatment site after the period of time has transpired.
22. The treatment system of claim 18, wherein the controller is
programmed with thawing instructions that, when executed, cause the
applicator to heat the treatment site to thaw the subject's frozen
tissue.
23. The treatment system of claim 18, wherein the applicator
includes at least one thermoelectric cooler configured to freeze
skin at the treatment site without freezing a substantial volume of
subcutaneous tissue located beneath the skin.
24. The treatment system of claim 18, wherein the controller is
programmed to control the cooling device such that the freeze event
causes apoptotic damage to tissue at the treatment site and does
not cause necrotic damage to tissue at the treatment site.
25. The treatment system of claim 18, wherein the controller stores
instructions for controlling the cooling device so that the freeze
event begins within a second predetermined period of time after the
cooling device begins cooling the surface of the subject's skin,
and wherein the second predetermined period of time is shorter than
about 30 seconds or shorter than about either 1, 2, 3, 4, 5, 6, 7,
8, 9, or 10 minutes.
26. A method for treating a human subject's body, the method
comprising: cooling a surface of the subject's skin to a
temperature no lower than -40.degree. C. so that at least a portion
of tissue below the surface is in a supercooled state; heating the
surface of the subject's skin an amount sufficient to raise the
temperature of the surface of the skin to a non-supercooled
temperature while the portion of the tissue below the surface
remains in the supercooled state; and nucleating the supercooled
portion of tissue below the surface to cause at least some of the
supercooled portion of tissue to at least partially freeze.
27. The method of claim 26, further comprising maintaining the
supercooled portion of tissue in at least a partially frozen state
for at least 10 seconds.
28. The method of claim 26, further comprising detecting a freeze
event and maintaining the supercooled portion of tissue in at least
a partially frozen state for at least 10 seconds.
29. The method of claim 26, wherein the method does not include
using a chemical cryoprotectant to protect an epidermis of the
human subject's skin from being at least partially frozen.
30. The method of claim 26, further including using a chemical
cryoprotectant to protect an epidermis of the human subject's skin
from being at least partially frozen.
31. The method of claim 26, wherein the tissue that is heated to
the non-supercooled temperature includes epidermal tissue, and the
supercooled portion of tissue includes part of the epidermal
tissue, dermal tissue, subcutaneous tissue, or combinations
thereof.
32. The method of claim 26, wherein the portion of tissue is in the
at least partially frozen state for a duration of time selected to
improve the appearance of the skin.
33. The method of claim 26, wherein the portion of tissue is
maintained in at least a partially frozen state and nucleated (a)
to improve the appearance of skin by tightening the skin, improving
skin tone and texture, eliminating or reducing wrinkles, increasing
skin smoothness, and/or thickening the skin, (b) to improve the
appearance of cellulite, (c) to treat hair follicles, nerves,
and/or sweat glands, and/or (d) to contour a breast and/or reduce a
size of a breast.
34. The method of claim 26, wherein the portion of tissue is
nucleated using a perturbation created by a mechanical vibration
device or ultrasound generator.
35. The method of claim 26, further comprising detecting a freeze
status of the portion of tissue, and controlling heating the
surface of the subject's skin to maintain the portion of tissue in
at least a partially frozen state for a predetermined period of
time that exceeds about 10 seconds.
36. The method of claim 26, further comprising controlling the
cooling and heating to maintain the portion of the tissue in at
least a partially frozen state for a predetermined period of time,
wherein the period of time is longer than about 30 seconds or 1, 2,
3, 4, 5, 6, 7, 8, 9, or 10 minutes.
37. A method for affecting a subcutaneous layer of a human
subject's body, the method comprising: transdermally removing heat
from tissue at a target region such that cells in the target region
are cooled to a supercooled temperature; applying heat to an
epidermis of the target region such that epidermal cells in the
target region are warmed to a temperature above freezing while
target cells in the subcutaneous layer of the target region are at
or near the supercooled temperature; and causing a freeze event in
the subcutaneous layer of the target region to selectively affect
the target cells while epidermal cells are not substantially
affected by the freeze event.
38. The method of claim 37, wherein transdermally removing heat
includes cooling the tissue at the target region to the supercooled
temperature which is from about 0.degree. C. to about -20.degree.
C.
39. The method of claim 37, wherein applying heat includes warming
the epidermal cells to a temperature above either about 20.degree.
C. or 32.degree. C.
40. A system for non-invasive, transdermal removal of heat from
target cells of a subject's body, comprising: an applicator
configured to perturb a target region and having a heat-exchanging
element configured to: reduce a temperature of the target region
beneath a surface of skin of the subject to reduce the temperature
of target cells in the target region from a natural body
temperature to a lower temperature in the target region, and
increase a temperature of the surface of the skin above the target
region to protect cells in an epidermis from a freeze event; and a
controller in communication with the applicator and having
instructions for causing the system to: reduce the temperature of
the target region such that at least the target cells are in a
supercooled state, increase a skin temperature of the epidermis
above a freezing temperature while the target cells are in the
supercooled state, and after increasing the temperature of the
epidermis, perturbing the target region such that supercooled
target cells are selectively affected.
41. The system of claim 40, wherein the heat-exchanging element is
configured to increase a temperature of the surface of the skin to
about 10.degree. C. to about 32.degree. C. while the target tissue
remains at a temperature between about 0.degree. C. to about
-40.degree. C.
42. The system of claim 40, wherein the system is configured to
perturb the target region supercooled by the applicator to cause
ice formation such that target cells are selectively affected by
ice crystals in or near the target cells.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority to U.S. Provisional
Application Ser. No. 61/943,257, filed Feb. 21, 2014, U.S.
Provisional Application Ser. No. 61/934,549, filed Jan. 31, 2014,
and U.S. Provisional Application Ser. No. 61/943,250, filed Feb.
21, 2014, the disclosures of which are incorporated herein by
reference in their entireties.
INCORPORATION BY REFERENCE OF COMMONLY-OWNED APPLICATIONS AND
PATENTS
[0002] The following commonly assigned U.S. patent applications and
U.S. patents are incorporated herein by reference in their
entirety:
[0003] U.S. Patent Publication No. 2008/0287839 entitled "METHOD OF
ENHANCED REMOVAL OF HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS AND
TREATMENT APPARATUS HAVING AN ACTUATOR";
[0004] U.S. Pat. No. 6,032,675 entitled "FREEZING METHOD FOR
CONTROLLED REMOVAL OF FATTY TISSUE BY LIPOSUCTION";
[0005] U.S. Patent Publication No. 2007/0255362 entitled
"CRYOPROTECTANT FOR USE WITH A TREATMENT DEVICE FOR IMPROVED
COOLING OF SUBCUTANEOUS LIPID-RICH CELLS";
[0006] U.S. Pat. No. 7,854,754 entitled "COOLING DEVICE FOR
REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS";
[0007] U.S. Patent Publication No. 2011/0066216 entitled "COOLING
DEVICE FOR REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS";
[0008] U.S. Patent Publication No. 2008/0077201 entitled "COOLING
DEVICES WITH FLEXIBLE SENSORS";
[0009] U.S. Patent Publication No. 2008/0077211 entitled "COOLING
DEVICE HAVING A PLURALITY OF CONTROLLABLE COOLING ELEMENTS TO
PROVIDE A PREDETERMINED COOLING PROFILE";
[0010] U.S. Patent Publication No. 2009/0118722, filed Oct. 31,
2007, entitled "METHOD AND APPARATUS FOR COOLING SUBCUTANEOUS
LIPID-RICH CELLS OR TISSUE";
[0011] U.S. Patent Publication No. 2009/0018624 entitled "LIMITING
USE OF DISPOSABLE SYSTEM PATIENT PROTECTION DEVICES";
[0012] U.S. Patent Publication No. 2009/0018623 entitled "SYSTEM
FOR TREATING LIPID-RICH REGIONS";
[0013] U.S. Patent Publication No. 2009/0018625 entitled "MANAGING
SYSTEM TEMPERATURE TO REMOVE HEAT FROM LIPID-RICH REGIONS";
[0014] U.S. Patent Publication No. 2009/0018627 entitled "SECURE
SYSTEM FOR REMOVING HEAT FROM LIPID-RICH REGIONS";
[0015] U.S. Patent Publication No. 2009/0018626 entitled "USER
INTERFACES FOR A SYSTEM THAT REMOVES HEAT FROM LIPID-RICH
REGIONS";
[0016] U.S. Pat. No. 6,041,787 entitled "USE OF CRYOPROTECTIVE
AGENT COMPOUNDS DURING CRYOSURGERY";
[0017] U.S. Pat. No. 8,285,390 entitled "MONITORING THE COOLING OF
SUBCUTANEOUS LIPID-RICH CELLS, SUCH AS THE COOLING OF ADIPOSE
TISSUE";
[0018] U.S. Provisional Patent Application Ser. No. 60/941,567
entitled "METHODS, APPARATUSES AND SYSTEMS FOR COOLING THE SKIN AND
SUBCUTANEOUS TISSUE";
[0019] U.S. Pat. No. 8,275,442 entitled "TREATMENT PLANNING SYSTEMS
AND METHODS FOR BODY CONTOURING APPLICATIONS";
[0020] U.S. patent application Ser. No. 12/275,002 entitled
"APPARATUS WITH HYDROPHILIC RESERVOIRS FOR COOLING SUBCUTANEOUS
LIPID-RICH CELLS";
[0021] U.S. patent application Ser. No. 12/275,014 entitled
"APPARATUS WITH HYDROPHOBIC FILTERS FOR REMOVING HEAT FROM
SUBCUTANEOUS LIPID-RICH CELLS";
[0022] U.S. Patent Publication No. 2010/0152824 entitled "SYSTEMS
AND METHODS WITH INTERRUPT/RESUME CAPABILITIES FOR COOLING
SUBCUTANEOUS LIPID-RICH CELLS";
[0023] U.S. Pat. No. 8,192,474 entitled "TISSUE TREATMENT
METHODS";
[0024] U.S. Patent Publication No. 2010/0280582 entitled "DEVICE,
SYSTEM AND METHOD FOR REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH
CELLS";
[0025] U.S. Patent Publication No. 2012/0022518 entitled "COMBINED
MODALITY TREATMENT SYSTEMS, METHODS AND APPARATUS FOR BODY
CONTOURING APPLICATIONS";
[0026] U.S. Publication No. 2011/0238050 entitled "HOME-USE
APPLICATORS FOR NON-INVASIVELY REMOVING HEAT FROM SUBCUTANEOUS
LIPID-RICH CELLS VIA PHASE CHANGE COOLANTS, AND ASSOCIATED DEVICES,
SYSTEMS AND METHODS";
[0027] U.S. Publication No. 2011/0238051 entitled "HOME-USE
APPLICATORS FOR NON-INVASIVELY REMOVING HEAT FROM SUBCUTANEOUS
LIPID-RICH CELLS VIA PHASE CHANGE COOLANTS, AND ASSOCIATED DEVICES,
SYSTEMS AND METHODS";
[0028] U.S. Publication No. 2012/0239123 entitled "DEVICES,
APPLICATION SYSTEMS AND METHODS WITH LOCALIZED HEAT FLUX ZONES FOR
REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS";
[0029] U.S. patent application Ser. No. 13/830,413 entitled
"MULTI-MODALITY TREATMENT SYSTEMS, METHODS AND APPARATUS FOR
ALTERING SUBCUTANEOUS LIPID-RICH TISSUE";
[0030] U.S. patent application Ser. No. 13/830,027 entitled
"TREATMENT SYSTEMS WITH FLUID MIXING SYSTEMS AND FLUID-COOLED
APPLICATORS AND METHODS OF USING THE SAME";
[0031] U.S. Provisional Patent Application No. 61/943,251 entitled
"TREATMENT SYSTEMS AND METHODS FOR TREATING CELLULITE"; and
[0032] U.S. Provisional Patent Application No. 61/943,257 entitled
"TREATMENT SYSTEMS, METHODS, AND APPARATUS FOR REDUCING
IRREGULARITIES CAUSED BY CELLULITE."
TECHNICAL FIELD
[0033] The present disclosure relates generally to treatment
systems and methods for cooling targeted tissue. In particular,
several embodiments are directed to treatment systems and methods
for cooling tissue to improve the appearance of treatment sites
with gynoid lipodystrophy or other skin irregularities. Embodiments
are also disclosed for improving the appearance of skin, body
contouring, and treating various skin conditions.
BACKGROUND
[0034] It is often desirable to improve the appearance of bodies in
many respects and treat various skin conditions. One example is the
unattractive appearance of cellulite (gynoid lipodystrophy).
Cellulite can be caused by subcutaneous fat lobules protruding or
penetrating into the dermis and can be the consequence of, for
example, an engorged adipose layer sequestered within the deep
subcutis hypodermal fibrous septa, a weakened and/or degraded
extracellular matrix, microcirculation compression resulting in
decreased oxygen tension and hypoxia, and inflammatory edema.
Cellulite is typically recognized by localized skin surface
nodularity and dimpling considered to be cosmetically unappealing
and often referred to as a cottage cheese appearance or an orange
peel appearance. Unfortunately, cellulite has proved to be a
difficult and vexing problem to treat, although the demand for an
effective treatment has been and remains quite high.
[0035] Other examples where improvement of body appearance are
needed are in the fields of body contouring and skin appearance.
Improvements are also desired in treating various skin conditions,
such as hyperhidrosis. Hyperhidrosis is a condition associated with
excessive sweating that results from the overproduction and
secretion of sweat from sweat glands and can cause discomfort and
embarrassment.
[0036] Accordingly, it is an objective of various embodiments of
the present invention to address these and other needs.
BRIEF DESCRIPTION OF THE DRAWINGS
[0037] In the drawings, identical reference numbers identify
similar elements or acts. The sizes and relative positions of
elements in the drawings are not necessarily drawn to scale.
[0038] FIG. 1A is a schematic cross-sectional view of the skin,
dermis, and subcutaneous tissue of a subject with cellulite.
[0039] FIG. 1B is a schematic cross-sectional view of the skin,
dermis, and subcutaneous tissue of the subject in FIG. 1A showing a
reduction in the appearance of cellulite. A treatment device is
shown applied to the skin.
[0040] FIG. 2 is a partially schematic, isometric view of a
treatment system for non-invasively removing heat from target areas
of a subject in accordance with an embodiment of the
technology.
[0041] FIGS. 3 to 7 are flow diagrams illustrating methods for
treating target areas in accordance with embodiments of the
technology.
[0042] FIG. 8 is a partially schematic, isometric view of a
treatment system for non-invasively removing heat from target areas
of a subject in accordance with an embodiment of the
technology.
[0043] FIG. 9 is a partial cross-sectional view illustrating a
treatment device suitable to be used in treatment systems in
accordance with embodiments of the technology.
[0044] FIGS. 10A to 10C are schematic, cross-sectional views
illustrating treatment devices in accordance with embodiments of
the technology.
[0045] FIG. 11 is a partial cross-sectional view illustrating a
vacuum treatment device in accordance with another embodiment of
the technology.
[0046] FIG. 12 is a schematic block diagram illustrating computing
system software modules and subcomponents of a computing device
suitable to be used in treatment systems in accordance with
embodiments of the technology.
DETAILED DESCRIPTION
A. Overview
[0047] The present disclosure describes treatment systems and
methods for cooling tissue to produce freeze-induced injuries for
improving the appearance of areas with gynoid lipodystrophy or
other irregularities, improving the appearance of skin, body
contouring, treating various skin conditions, or combinations
thereof. Several of the details set forth below are provided to
describe the following examples and methods in a manner sufficient
to enable a person skilled in the relevant art to practice, make,
and use them. Several of the details and advantages described
below, however, may not be necessary to practice certain examples
and methods of the technology. Additionally, the technology may
include other examples and methods that are within the scope of the
technology but are not described in detail.
[0048] Reference throughout this specification to "one example,"
"an example," "one embodiment," or "an embodiment" means that a
particular feature, structure, or characteristic described in
connection with the example is included in at least one example of
the present technology. Thus, the occurrences of the phrases "in
one example," "in an example," "one embodiment," or "an embodiment"
in various places throughout this specification are not necessarily
all referring to the same example. Furthermore, the particular
features, structures, routines, blocks, stages, or characteristics
may be combined in any suitable manner in one or more examples of
the technology. The headings provided herein are for convenience
only and are not intended to limit or interpret the scope or
meaning of the technology.
[0049] Various aspects of the technology are directed to treatment
methods for affecting cellulite of a human subject's body and other
treatments. In one embodiment, the method can include removing heat
from a target region between the subject's epidermis and subdermal
tissue to produce a freeze event localized in the dermal layer
which causes a reduction of visible cellulite. In various
embodiments, the target region can be cooled to a temperature equal
to or less than about -1.degree. C., -2.degree. C., -5.degree. C.,
-10.degree. C., -15.degree. C., -20.degree. C., -30.degree. C., or
-40.degree. C. at a depth equal to or greater than about 1 mm, 2
mm, 3 mm, or 4 mm. In some embodiments, most of the partially or
totally frozen tissue by volume can be in a single layer of tissue,
such as the epidermal layer, dermal layer, or subcutaneous layer.
In other embodiments, multiple layers of tissue can be frozen. The
subject's skin can be periodically or continuously heated to limit
or prevent thermal damage to non-targeted tissue, in particular to
sometimes protect the epidermal layer.
[0050] At least some embodiments are directed to reducing or
eliminating cellulite, wrinkles, loose skin, sagging skin, poor
skin tone or texture, and other skin irregularities often
considered to be cosmetically unappealing. As used herein,
"improving the appearance of cellulite" is intended to include any
combination of improving skin tone, thickening of the skin,
improving tissue elasticity, or other similar effects to reduce
cellulite. As used herein, "improving the appearance of skin" is
intended to include any combination of skin tightening, improving
skin tone or texture, thickening of the skin, elimination or
reducing fine lines and wrinkles or deeper wrinkles, increasing
skin smoothness, or improving the appearance of cellulite, or other
similar effects. What is not included in these terms is treating
the skin to such an extent so as to cause hyperpigmentation (skin
darkening) and/or hypopigmentation (skin lightening) either
immediately after the treatment or hours or a day or days or weeks
thereafter.
[0051] Some aspects of the technology are directed to treatment
methods for affecting tissue of a human subject's body. In one
embodiment, the method can include cooling tissue to produce a
freeze event that reduces or eliminates cellulite by affecting at
least one of skin tone, thicknesses of the tissue layers (e.g.,
increasing the thicknesses of the dermal layer and/or epidermal
layer), and/or tissue elasticity. In certain embodiments, the
method also includes inhibiting damage to non-targeted tissue of
the subject's skin while producing the freeze event. In some
embodiments, the freeze event can include injury to at least some
of the subject's skin (e.g., epidermis, dermis, etc.), subcutaneous
adipose tissue, or other targeted tissue.
[0052] Freeze events can result in freeze trauma and/or freeze
injury that can be contained in a layer of tissue. In embodiments
in which the freeze event is centralized in the dermis, the
treatment method can include inhibiting damage to the epidermis
while producing the freeze event. A cryoprotectant can be applied
to the surface of the subject's skin prior to or during heat
removal to protect an epidermis and possibly other layers. In other
embodiments, energy (e.g., heat, radiofrequency energy,
electromagnetic energy, electric fields, ultrasound energy, light
energy, etc.) can be applied to the subject's skin to inhibit
damage to the epidermis. Excessive damage to the epidermis can
sometimes lead to undesired skin coloration issues. In some
supercooling embodiments, supercooling can be used to target tissue
at the desired depth without using any cryoprotectant. Non-targeted
tissue in the skin, such as the epidermis, can be heated above its
freezing point before initiating crystallization of the remaining
supercooled tissue. Accordingly, crystallization in the supercooled
tissue can be induced without damaging the subject's epidermis and
possibly some deeper skin layers. In some embodiments, the surface
of the skin and tissue therebeneath is supercooled. The surface of
the skin is then warmed above a freezing temperature. After warming
the surface of the skin, the supercooled tissue is nucleated to
initiate a partial or total freeze event.
[0053] With or without freezing, at least some embodiments of the
technology are directed to controlling a cooling device or
providing other means for sufficiently protecting the epidermis
from injuries that cause hyperpigmentation (skin darkening) and/or
hypopigmentation (skin lightening). The other means for protection
can include, without limitation, heating the epidermis to a
non-freezing temperature while deeper tissue remains cold to induce
injury thereto and/or applying a cryoprotectant to a surface of the
skin to provide freeze protection to the epidermis while allowing
deeper tissue to be more affected by the cooling/cold
treatment.
[0054] At least some embodiments of non-invasive treatments for
reducing cellulite can include producing wound remodeling (e.g.,
healing) phase resulting from freeze-induced tissue trauma to
produce enhancements in structural integrity of the
epidermal-dermal junction and/or epidermal textural quality. The
freeze-induced trauma can include thermal injuries that are
selected to reduce skin surface irregularities caused by
cellulite.
[0055] Further aspects of the technology are directed to systems
and methods for affecting a target region of a human subject's body
by removing heat from the target region to alter subdermal
connective tissue while lipid-rich cells in the subcutaneous layer
are not substantially affected. The method can optionally include
applying a cryoprotectant and/or warming the surface of the skin.
For example, in one embodiment, heat removal includes freezing
tissue of the fibrous septum to affect the fibrous septum while the
epidermis is not substantially affected. The thermal injury can
cause beneficially generation of fibrous tissue, remodeling of the
fibrous septum, or the like. In various embodiments, heat can be
removed from the target region to affect cells (e.g., reduce,
destroy, and/or damage cells), alter tissue characteristics, or
combinations thereof. In some embodiments, a treatment system can
(1) reduce fat in the superficial compartment, (2) alter skin
tone/thickness/elasticity due to a freeze event (e.g., cold injury)
and resultant healing cascade, and/or (3) affect connective tissue
(including the septa) as a result of cold injury and resultant
healing.
[0056] Tissue characteristics affected by cryotherapy can include,
without limitation, tissue strength, tissue elasticity, tissue
layer thickness, and/or skin tone. In some embodiments, cryotherapy
can increase the elasticity of a targeted tissue layer, such as the
skin, epidermis, and/or dermis. For example, the dermis can be
cooled to produce a freeze event that causes thermal injury to the
dermal tissue. The resultant wound remodeling can increase the
strength and/or elasticity of the dermis. The severity of the
freeze event can be selected to achieve the desired change in
strength and/or elasticity while non-targeted tissue, such as
epidermal or subdermal tissue, can remain generally unaffected. In
some embodiments, cryotherapy can increase the thicknesses of
multiple layers of tissue. For example, the epidermis and dermis
can be wounded to increase their thicknesses due to wound
remodeling. In yet further embodiments, freeze injury causes
fibrosis in the form of fibroblast proliferation and/or increased
collagen.
[0057] At least some freeze events disclosed herein can promote a
natural body response that reduces an orange peel appearance, a
cottage cheese appearance, etc. The subject's natural body response
can include thickening of the epidermis, dermis, layers of
connective tissue (e.g., regions of cellular matrix overlaying fat
pockets), and/or other subdermal tissues. Layers for thickening can
be selected based on the ability to control the freeze events and
the location and extent of the associated injury/trauma. For
example, one or more layers of the epidermis (e.g., stratum
corneum, stratum lucidum, stratum granlosum, stratum spinosum,
and/or stratum basale) can be the site of wound formation and
remodeling. The papillary layer and/or reticular layer of the
dermis can also be the site of wound formation and remodeling.
[0058] At least some embodiments are systems and methods for
selective non-invasive cooling of tissue to produce a freeze event
at a depth equal to or greater than about 1 mm, 2 mm, 3 mm, or 5
mm. The depth can be selected based on the location of the
treatment site (e.g., hips, buttock, thighs, etc.). The target
region can be cooled to a temperature equal to or lower than about
0.degree. C., -5.degree. C., -10.degree. C., -15.degree. C.,
-20.degree. C., -25.degree. C., -30.degree. C., -35.degree. C., or
-40.degree. C. for a treatment period. The treatment period can be
equal to or longer than about 1 second, 2 seconds, 3 seconds, 5
seconds, 30 seconds, 1 minute, 5 minutes, 10 minutes, 30 minutes,
or other time periods selected based on the location of targeted
tissue and/or desired resultant healing.
[0059] Applicators disclosed herein can include elements (e.g.,
electrodes, vibrators, etc.) for delivering energy, such as
radiofrequency energy, electromagnetic energy, infrared energy,
light energy, ultraviolet energy, microwave energy, ultrasound
energy (e.g., low frequency ultrasound, high frequency ultrasound,
etc.), mechanical massage, and/or electric fields (e.g., AC or DC
electric fields). The energy can inhibit or reduce freeze damage in
non-targeted regions, such as an epidermis, while allowing more
aggressive cooling of a targeted region. In non-targeted cells or
structures, non-thermal energy parameters may be selected to reduce
ice crystal nucleation, size and/or length, reduce freezing
lethality, or the like. In targeted cells or structures,
non-thermal energy may be used to initiate crystal nucleation,
growth, etc. Thus, non-thermal energy can be selectively applied to
control cryotherapy. Thermal energy can be used to protect
non-targeted tissue, such as facial subcutaneous fat, when
cryogenically treating superficial dermal structures and/or
epidermal structures on the face. Additionally or alternatively,
non-targeted tissue can be protected by a chemical cryoprotectant.
Some applicators can treat epidermal and/or dermal structures, such
as collagen and/or elastin for skin tightening and dermal
thickening, glands (e.g., apocrine glands, eccrine glands, etc.),
nerve tissue (e.g., superficial nerves), and/or hair follicles.
[0060] At least some aspects are directed to systems and devices
that enable supercooling of target tissue to alter and reduce
adipose tissue, contour sites, or perform other cryotherapy
procedures. Aspects of the disclosure are further directed to
systems or methods for protecting non-targeted cells, such as
non-lipid-rich cells (e.g., cells in the dermal and/or epidermal
skin layers), by preventing or limiting freeze damage during
dermatological and related aesthetic procedures that require
sustained exposure to cold temperatures. For example, treatment
systems and devices can supercool treatment sites without
nucleating crystals. Non-targeted tissue can be heated to localize
the supercooling, and after localizing the supercooled tissue,
supercooled body fluids/lipids can then be intentionally nucleated
to damage, reduce, disrupt, or otherwise affect targeted cells.
Nucleation can be induced by delivering an alternating current to
the tissue, applying a nucleating solution onto the surface of the
skin (for example one that includes bacteria which initiate
nucleation), and/or by creating a mechanical perturbation to the
tissue, such as by use of vibration, ultrasound energy, etc.
B. Cellulite
[0061] FIG. 1A is a schematic cross-sectional view of tissue with
gynoid lipodystrophy. Gynoid lipodystrophy typically is a
hormonally mediated condition characterized by the uneven
distribution of adipose tissue in the subcutaneous layer that gives
rise to an irregular, dimpled skin surface common in women.
Cellulite-prone tissue can be characterized by the uneven thickness
and distribution of some fibrous septae strands. Pierard, G. E.,
Nizet, J. L, Pierard-Franchimont, C., "Cellulite: From Standing Fat
Herniation to Hypodermal Stretch Marks," Am. J. Dermatol. 22:1,
34-37 (2000). As shown schematically, cottage-cheese like dimpling
of the skin 10 may be located, for example, along the legs (e.g.,
thighs, buttock, etc.). The dermis 12 is between the epidermis 14
and subcutaneous layer 16. The subcutaneous layer 16 has connective
collagenous tissue called fibrous septae 20 that subdivides adipose
tissue into fat cell chambers or lobules 18 (also called "papillae
adiposae"). The fibrous septae 20, which for females tend to
generally be oriented perpendicular to the skin surface and anchor
the dermal layers 12 to the underlying fascia and muscle (not
shown), are organized within the subcutaneous layer 16 to form a
connective web around the fat lobules 18. Subcutaneous adipose
cells and their lobules 18 are not uniformly distributed throughout
the subcutaneous tissue layer 16 and exhibit regional differences
in size and shape. These regional differences can, in part, be due
to gender, age, genetics, hormones and physical conditioning among
other physiological factors.
[0062] The number, sizes, distribution, and orientation of the
fibrous septae 20 also vary by body location, gender, and age.
Histological studies have shown that fibrous septae architecture in
females differs from that in males. In males, fibrous septae 20
tend to form an intersecting network that divide the papillae
adiposae into small, polygonal units. In contrast, fibrous septae
20 in females tend to be oriented perpendicularly to the cutaneous
surface, creating fat cell chambers that are columnar in shape and
sequestered by the connective strands and the overlaying dermis
layer 12. When the intersecting fibrous septae 20 are more uniform
in size and elasticity as is often a characteristic of males, the
forces within and between the fibrous septae and their surrounding
tissue tend to be distributed relatively evenly. However, the
columnar architecture of the fibrous septae 20 found in some
females can result in an uneven distribution of forces throughout
the subcutaneous tissue. In particular, and without being bound by
theory, it is believed that this uneven distribution of forces is
partially manifested by the columnar fibrous septae 20 being held
in a state of tension by the underlying fascia and other tissue,
resulting in a tethering or anchoring effect at the point where
each such septum 20 connects with the dermal tissue 12. This
tethering or anchoring is in turn manifested at the skin surface as
low spots 22. The septae tends to herniate as the papillae adiposae
18 bulge into the dermal tissue 12 and result in high spots 23.
When viewed over a larger area of a few square centimeters, the
non-homogeneous nature of the skin surface's relative high and low
spots results in a dimpled or irregular appearance characteristic
of cellulite often referred to as a cottage cheese appearance or
orange peel appearance.
[0063] The vertical pull of the fibrous septum 20 (e.g., pulling in
a direction substantially perpendicular to the skin) can be reduced
eliminate or reduce bumpiness of the subdermal fat lobules 18.
Wound remodeling affect the tension in connective tissue extending
from the dermis 12 to the subcutaneous muscle (not shown).
Localized freezing of the subcutaneous tissue 16 can reduce the
number and/or size of lipid-rich cells of the fat lobules 18 to
reduce lobule bulging. Additionally or alternatively, vertical
bands of the fibrous septum 20, or portions of the bands, to reduce
pulling on the dermis 12, thus reducing bulging of fat lobules 18.
In some embodiments, the cellular matrix between the fat lobules 18
and the dermis 12 can be damaged in order to produce remodeling
that ultimately increases the strength and/or elasticity of the
cellular matrix. Freezing of dermal tissue can produce wound
healing/remodeling that strengthens and/or thickens the dermal
tissue to help flatten the fat lobules. Freezing of epidermal
tissue can produce wound healing/remodeling that strengthens and/or
thickens the epidermal tissue to further flatten the skin 10.
Accordingly, cryotherapy can be designed to target the epidermis,
dermis, and/or subcutaneous structures.
[0064] FIG. 1B is a schematic cross-sectional view of the skin 10
and subcutaneous adipose tissue 16 of the subject in FIG. 1A
showing a reduction in the appearance of cellulite in accordance
with aspects of the present technology. A treatment device in the
form of a thermoelectric applicator 104 ("applicator 104") has been
applied to and cooled the skin 10 to produce a freeze-induced
injury that affected the epidermis 14, dermis 12, fibrous septae
20, and/or subcutaneous adipose tissue 16 to minimize, reduce, or
eliminate at least the appearance of gynoid lipodystrophy. FIG. 1B
shows the skin 10 after cryotherapy has been performed. The
interface between the lobules 18 and the dermis 12 can be generally
flat to help flatten the surface of skin 10. As shown in FIGS. 1A
and 1B, the lobules 18 have flattened so that lobule flat regions
24 face the dermis 12. As such, the treated skin 10 of FIG. 1B can
have a much more even or regular/smooth appearance than the skin 10
of FIG. 1A.
C. Cryotherapy
[0065] FIG. 2 and the following discussion provide a brief, general
description of an example of a suitable treatment system 100 in
which aspects of the technology can be implemented. The treatment
system 100 can be configured to control hypothermia to treat the
site of cellulite manifested by skin dimpling and nodularity. In
some cellulite treatments, the treatment system 100 can weaken,
destroy, or otherwise injure the tissue (e.g., fibrous septum or
other connective tissue) that pulls on the dermis. It is also
thought that the wound-healing response following a freeze-induced
injury caused by the applicator 104 can result in remodeling of the
underlying connective tissue and changes in skin characteristics
(e.g., increased in thickness) that otherwise reduce or alter the
appearance of cellulite. The freeze wound can result in tissue
damage and/or destruction of the cells and connective tissue with
reference to the superficial skin layers (e.g., epidermis and/or
dermis). The dedicated wound repair and the wound remodeling
process can result in the enhancement of the structural integrity
and textural quality of skin and, thereby, restore the skin to a
desired clinical outcome. The wound remodeling process can be
selected based on the damage potential, repair process, or the
like. The mechanisms of tissue injury in cryotherapy can involve
direct cellular injury (e.g., damage to the cellular machinery),
vascular injury, and/or freeze-stimulated immunologic injury.
[0066] The system 100 can also freeze the upper layers of skin.
Without being bound by theory, it is believed that low temperatures
may potentially cause damage in the epidermis and/or dermis via at
least intracellular and/or extracellular ice formation. The ice may
expand and rupture the cell wall, but it may also form sharp
crystals that locally pierce the cell wall as well as vital
internal organelles, either or both resulting in cell death. When
extracellular water freezes to form ice, the remaining
extracellular fluid becomes progressively more concentrated with
solutes. The high solute concentration of the extracellular fluid
may cause intracellular fluid be driven through the semi-permeable
cellular wall by osmosis resulting in cell dehydration and death.
Such selective tissue injury can induce healing events in the
tissue that has positive effects on skin appearance including a
reduction in surface irregularities in the surface of the skin.
[0067] As shown in FIG. 1B, the applicator 104 has a
heat-exchanging surface 19 in thermal contact with a treatment site
9 along the skin 10. A heat/ing cooling device 103 of the
applicator 104 can cool and affect tissue at a cooling zone 21
(shown in phantom line) with dimensions and shape selected based on
the cryotherapy procedure to be performed. A central region of the
cooling zone 21 can be at a maximum depth of, for example, about
0.25 mm to about 2 mm, about 0.25 mm to about 1 mm, about 0.5 mm to
about 1 mm, about 0.5 mm to about 2 mm, or about 0.5 mm to about 4
mm. In some embodiments, the cooling zone 21 can comprise mostly
epidermal and dermal tissue. Surrounding tissue may also be cooled
but can be at sufficiently high temperatures to avoid thermal
injury. In some procedures, the cooling zone 21 can comprise most
of the tissue located directly between the heat-exchanging surface
19 and a region of the subcutaneous tissue 16 directly beneath the
heat-exchanging surface 19. For example, at least 60%, 70%, 80%,
90%, or 95% of the tissue directly between the heat-exchanging
surface 19 and the subcutaneous tissue can be located within the
cooling zone 21. In other procedures, the cooling zone 21 can be
deep enough to include subcutaneous tissue 16 to target lipid-rich
cells of the lobules 18, the fibrous septum 20, or other
subcutaneous tissue. The temperature profile across the
heat-exchanging surface 19 can be constant or varying to achieve
the desired cooling zone 21.
[0068] The applicator 104 of FIGS. 1B and 2 can also thermally
damage subdermal tissue, such as the connective tissue of the
fibrous septum (i.e., bands of connective tissue extending
generally perpendicular to the skin) to help lengthen the
connective tissue, thereby reducing bulging of the fat lobules
toward the dermis. Additionally, the connective tissue can be
altered without substantially affecting other tissue. In some
procedures, the connective tissue of the fibrous septum is affected
while lipid-rich cells in the subcutaneous adipose tissue are not
substantially affected by controlling the cooling to not
sufficiently cool the deeper subcutaneous adipose tissue to inflict
injury thereto. In other procedures, the connective tissue and the
lipid-rich cells in the subcutaneous layer (e.g., subcutaneous
adipose tissue) are affected in the same cooling routine or
sequentially performed cooling routines while epidermal tissue
and/or dermal tissue are not substantially affected by either
heating these latter layers or using a cryoprotectant to protect
them. The applicator 104 can also be suitable for reducing skin
surface irregularities, such as dimpling and nodularity usually
associated with cellulite, by cooling or freezing cells residing in
the superficial skin layers (e.g., dermal and epidermal layers).
Tissue alteration by cooling and/or freezing is believed to be an
intermediate and/or final result of one or more mechanisms acting
alone or in combination. It is thought that a wound-healing
response following a freeze-induced injury can result in remodeling
of the underlying connective tissue and changes skin
characteristics (e.g., increased in skin thickness) that otherwise
reduce or alter the appearance of cellulite.
[0069] In several embodiments, apoptosis of the subcutaneous
lipid-rich cells is a desirable outcome for beneficially altering
(e.g., sculpting and/or reducing) adipose tissue contributing to
cellulite. Apoptosis, also referred to as "programmed cell death",
is a genetically-induced death mechanism by which cells
self-destruct without incurring damage to surrounding tissues. An
ordered series of biochemical events may induce cells to
morphologically change. These changes include cellular blebbing,
loss of cell membrane asymmetry and attachment, cell shrinkage,
chromatin condensation, and chromosomal DNA fragmentation. Injury
via an external stimulus, such as cold exposure, is one mechanism
that can induce apoptosis in cells. Nagle, W. A., Soloff, B. L.,
Moss, A. J. Jr., Henle, K. J. "Cultured Chinese Hamster Cells
Undergo Apoptosis After Exposure to Cold but Nonfreezing
Temperatures" Cryobiology 27, 439-451 (1990). One aspect of
apoptosis, in contrast to cellular necrosis (a traumatic form of
cell death causing, and sometimes induced by, local inflammation),
is that apoptotic cells express and display phagocytic markers on
the surface of the cell membrane, thus marking the cells for
phagocytosis by, for example, macrophages. As a result, phagocytes
can engulf and remove the dying cells (e.g., the lipid-rich cells)
without eliciting an immune response.
[0070] Without being bound by theory, one mechanism of apoptotic
lipid-rich cell death by cooling is believed to involve localized
crystallization of lipids within the adipocytes or other
lipid-producing cells (e.g., residing in exocrine cells) at
temperatures that do not induce crystallization in non-lipid-rich
cells. The crystallized lipids may selectively injure these cells,
inducing apoptosis (and may also induce necrotic death if the
crystallized lipids damage or rupture the bilayer lipid membrane of
the adipocyte). Another mechanism of injury involves the lipid
phase transition of those lipids within the cell's bilayer lipid
membrane, which results in membrane disruption, thereby inducing
apoptosis. This mechanism is well documented for many cell types
and may be active when adipocytes, or lipid-rich cells, are cooled.
Mazur, P., "Cryobiology: the Freezing of Biological Systems"
Science, 68: 939-949 (1970); Quinn, P. J., "A Lipid Phase
Separation Model of Low Temperature Damage to Biological Membranes"
Cryobiology, 22: 128-147 (1985); Rubinsky, B., "Principles of Low
Temperature Preservation" Heart Failure Reviews, 8, 277-284 (2003).
Other possible mechanisms of adipocyte damage, described in U.S.
Pat. No. 8,192,474, relates to ischemia/reperfusion injury that may
occur under certain conditions when such cells are cooled as
described herein. For instance, during treatment by cooling as
described herein, the targeted adipose tissue (e.g., lipid-rich
cells in the lobules 18 of FIG. 1A) may experience a restriction in
blood supply and thus be starved of oxygen due to isolation while
pulled into, e.g., a vacuum cup, or simply as a result of the
cooling which may affect vasoconstriction in the cooled tissue. In
addition to the ischemic damage caused by oxygen starvation and the
build-up of metabolic waste products in the tissue during the
period of restricted blood flow, restoration of blood flow after
cooling treatment may additionally produce reperfusion injury to
the adipocytes due to inflammation and oxidative damage that is
known to occur when oxygenated blood is restored to tissue that has
undergone a period of ischemia. This type of injury may be
accelerated by exposing the adipocytes to an energy source (via,
e.g., thermal, electrical, chemical, mechanical, acoustic or other
means) or otherwise increasing the blood flow rate in connection
with or after cooling treatment as described herein. Increasing
vasoconstriction in such adipose tissue by, e.g., various
mechanical means (e.g., application of pressure or massage),
chemical means or certain cooling conditions, as well as the local
introduction of oxygen radical-forming compounds to stimulate
inflammation and/or leukocyte activity in adipose tissue may also
contribute to accelerating injury to such cells. Other yet-to-be
understood mechanisms of injury may also exist.
[0071] In addition to the apoptotic mechanisms involved in
lipid-rich cell death, local cold exposure may induce lipolysis
(i.e., fat metabolism) of lipid-rich cells. For example, cold
stress has been shown to enhance rates of lipolysis from that
observed under normal conditions which serves to further increase
the volumetric reduction of subcutaneous lipid-rich cells.
Vallerand, A. L., Zamecnik. J., Jones, P. J. H., Jacobs, I. "Cold
Stress Increases Lipolysis, FFA Ra and TG/FFA Cycling in Humans"
Aviation, Space and Environmental Medicine 70, 42-50 (1999).
[0072] Without being bound by theory, the selective effect of
cooling on lipid-rich cells is believed to result in, for example,
membrane disruption, shrinkage, disabling, destroying, removing,
killing, or another method of lipid-rich cell alteration. For
example, when cooling the subcutaneous tissues to a temperature
lower than 37.degree. C., subcutaneous lipid-rich cells can
selectively be affected. In general, the cells in the epidermis and
dermis of the subject 101 have lower amounts of lipids compared to
the underlying lipid-rich cells forming the subcutaneous tissues.
Since lipid-rich cells are more sensitive to cold-induced damage
than non-lipid-rich epidermal or dermal cells, it is possible to
use non-invasive or minimally invasive cooling to destroy
lipid-rich cells without harming the overlying skin cells. In one
embodiment, thermal conduction can be used to cool the desired
layers of skin to a temperature above the freezing point of water,
but below the freezing point of fat to reduce the number and/or
size of lipid-rich lobules in the subcutaneous layer at a target
region.
[0073] In a typical procedure, a treatment device is positioned at
least proximate to the surface of a subject's skin and heat is
removed from the underlying tissue through the upper layers of the
skin. This creates a thermal gradient with the coldest temperatures
in the uppermost layers of skin near the cooling element. When
cooling subcutaneous lipid-rich cells, the resulting thermal
gradient causes the temperature of the upper layer(s) of the skin
to be lower than that of the targeted underlying lipid-rich cells.
For example, the treatment system 100 can cool the surface of the
skin to about -20.degree. C. to about 20.degree. C. In other
embodiments, the skin temperature can be from about -40.degree. C.
to about 10.degree. C., from about -20.degree. C. to about
10.degree. C., from about -18.degree. C. to about 5.degree. C.,
from about -15.degree. C. to about 5.degree. C., or from about
-15.degree. C. to about 0.degree. C. In further embodiments, the
surface of the skin can be cooled to lower than about -10.degree.
C., or in yet another embodiment, lower than about -15.degree. C.
to about -25.degree. C., -30.degree. C., -35.degree. C., or
-40.degree. C. In further embodiments, the skin temperature can be
lower than -25.degree. C. to induce a deep freeze wound.
[0074] 1. Tissue Injuries
[0075] Mechanisms of tissue injury in cryotherapy can involve
direct cellular injury (e.g., damage to the cellular machinery)
and/or vascular injury. For example, cellular injury can be
controlled by thermal parameters, including (1) cooling rate, (2)
end (or minimum) temperature, (3) time held at the minimum
temperature (or hold time), and (4) thawing rate. In one example,
increasing the hold time (e.g., at the minimum temperature) can
allow the intracellular compartments to equilibrate with the
extracellular space, thereby increasing cellular dehydration.
Likewise, freeze events can also destroy or injure the
microvasculature, the site of nutrient and oxygen delivery, thus
causing necrosis in some examples. A common source for vascular
injury is damage to the vessel wall due to vessel distension and
engorgement from perivascular cellular dehydration. Additionally,
vascular tissue injury can occur during tissue thawing. For
example, high oxygen delivery to the tissue that occurs with
hyperperfusion may cause free radical formation, which can, in
turn, cause endothelial damage. In some embodiments, administration
of free radical inhibitors may be able to limit this form of
endothelial damage.
[0076] Another mechanism of freezing injury is freeze-stimulated
immunologic injury. Without being bound by theory, it is believed
that after cryotherapy, the immune system of the host is sensitized
to the disrupted tissue (e.g., lethally damaged tissue, undamaged
tissue or sublethally injured tissue), which can be subsequently
destroyed by the immune system.
[0077] 2. Freeze Events
[0078] Freeze events can elicit a desired response to minimize,
reduce, or eliminate the appearance of cellulite. The freeze event
can produce enhancements in structural integrity of target regions
(e.g., the epidermal-dermal junction) and epidermal textural
quality in the non-invasive treatment of cellulite. The location
and extent of the crystallization can be selected based on the
desired effects to the skin, epidermis, stratum corneum, or other
targeted or non-targeted tissue.
[0079] One cryotherapy procedure involves at least partially or
totally freezing tissue to form crystals that alter targeted cells
to cause skin tightening, skin thickening, fibrosis, etc. without
destroying a significant amount of cells in the skin. The surface
of the patient's skin can be cooled to temperatures no lower than,
for example, -40.degree. C. for a duration short enough to avoid,
for example, excessive ice formation, permanent thermal damage, or
significant hyperpigmentation or hypopigmentation. In another
embodiment, destruction of skin cells can be avoided by
periodically or continually applying heat to the surface of the
patient's skin to keep or raise the skin's temperature above a
freezing temperature. For example, the skin can be warmed to a
temperature greater than 0.degree. C., greater than 10.degree. C.,
greater than 20.degree. C., greater than 30.degree. C., or other
temperature sufficient to avoid, for example, excessive ice
formation, permanent thermal damage, or significant
hyperpigmentation or hypopigmentation of the non-targeted and/or
epidermal tissue. In some treatments, the surface of the skin can
be cooled to produce partial or total freeze events that cause
apoptotic damage to skin tissue without causing significant damage
to adjacent subcutaneous tissue.
[0080] In some tissue-freezing procedures, the applicator 104 can
controllably freeze tissue and can detect the freezing event. After
detecting the freeze event, the applicator 104 can periodically or
continuously remove heat from the target tissue to keep a volume of
target tissue frozen for a suitable length of time to elicit a
desired response. The detected freeze event can be a partial freeze
event, a complete freeze event, etc. The freezing process can
include forming crystals in intracellular and/or extracellular
fluids (including lipids), and the crystals can be small enough to
avoid disrupting membranes. This can prevent significant permanent
tissue damage, such as necrosis. Some partial freeze events can
include freezing mostly extracellular material without freezing a
substantial amount of intercellular material, but other partial
freeze events can include freezing mostly intercellular material
without freezing a substantial amount of extracellular
material.
[0081] The targeted tissue can remain in the frozen state long
enough to be affected but short enough to avoid damaging
non-targeted tissue. For example, the duration of the freeze event
can be equal to, longer than, or shorter than about 10 seconds, 20
seconds, 30 seconds, or 45 seconds or about 1, 2, 3, 4, 5, or 10
minutes. The frozen tissue can be thawed to prevent necrosis and,
in some embodiments, can be thawed within a period of time (e.g.,
about 20 seconds, about 30 seconds, about 45 seconds, about 1
minute, about 2 minutes, about 3 minutes, about 4 minutes, about 5
minutes, or about 10 minutes) after initiation of the freeze event.
In some embodiments, the controlled freezing causes tightening of
the skin, thickening of the skin, and/or a cold shock response at
the cellular level in the skin. In one tissue-freezing embodiment,
the applicator 104 can produce a freeze event that includes,
without limitation, partial or full thickness freezing (e.g.,
partial or complete freezing) of the patient's skin for a
relatively short period of time to avoid cooling the adjacent
subcutaneous tissue to a low enough temperature for subcutaneous
cell death. A freeze event in the form of freeze injury of short
duration and of mild to moderate intensity may produce, for
example, a thicker, more resilient epidermis, which may improve the
surface textural quality. In one embodiment, the duration of the
freeze event and temperature of the tissue can be selected to
achieve a desired thickened resilient epidermis. The greater the
duration of freezing, the deeper the penetration of the trauma and
tissue destruction.
[0082] The application of simultaneous or successive light to
moderate freeze trauma to skin overlying sites of cellulite, in
conjunction with selective cryotherapy induced reduction of
subcutaneous lipid-rich cells at the sites of cellulite, can drive
the wound remodeling phase in producing desirable structural and
textural enhancements to the unsightly dimpling and nodularity
usually associated with this condition. Selective localized freeze
trauma (e.g., with pre-selected exposure parameters) should not
initially disturb the dermal tensile strength but a transient
increase in ECM structural integrity associated with collagen
synthesis can occur as the result of wound remodeling. The
combination of a structurally competent ECM with a consequential
thickening of the epidermal barrier can provide a desired clinical
outcome.
[0083] 3. Supercooling
[0084] A freezing point of a material is most reliably ascertained
by warming frozen material slowly and measuring a temperature at
which melting begins to occur. This temperature is generally not
ambiguous if the material is slowly warmed. Partial melting will
begin to occur at the freezing/melting point. Conversely, if a
non-frozen material is cooled, its freezing/melting point is harder
to ascertain since it is known that many materials can simply
"supercool," that is they can be cooled to a bulk temperature below
their freezing/melting point and still remain in a non-frozen
state. As used herein, "supercooling," "supercooled," "supercool,"
etc., refers to a condition in which a material is at a temperature
below its freezing/melting point but is still in an unfrozen or
mostly unfrozen state.
[0085] If skin is cooled in a controlled manner, targeted tissues
can generally be supercooled below their freezing points without
forming nucleation sites and/or microscopic crystals in
extracellular fluid and/or intracellular fluid and thereby such
tissues can reside in a supercooled unfrozen state. After
supercooling, the supercooled tissue can then be nucleated via a
mechanical perturbation (e.g., vibration, ultrasound pulse, change
in pressure, etc.) to at least partially freeze that tissue. In one
embodiment, the mechanical perturbation can induce crystallization
to produce a freeze event (e.g., a partial freeze event, a complete
freeze event, etc.) that causes targeted cells to be destroyed or
damaged by ice crystal formation in intracellular and/or
extracellular fluids. Other nucleation methods can also be used,
such as applying a solution with a nucleating agent (such as a
nucleating bacteria) onto the skin, or by applying an electrical
alternating current, RF energy, microwave energy, ultrasound
energy, etc. to the skin.
[0086] The freezing process can include forming ice crystals small
enough to avoid disrupting membranes to prevent significant
permanent tissue damage (e.g., necrosis) but large enough to affect
targeted cells. Some partial freeze events can include freezing
mostly extracellular material without freezing a substantial amount
of intercellular material. In other embodiments, partial freeze
events can include freezing mostly intercellular material without
freezing a substantial amount of extracellular material. Chemical
cryoprotectants can be used to inhibit unwanted freezing of
extracellular and intercellular material. In yet other embodiments,
the partial freeze event can include freezing extracellular and
intercellular material, and in other embodiments the material can
be totally frozen. The frozen targeted tissue can remain in the
frozen state long enough to be affected but short enough to avoid
undesired thermal damage, including necrosis and/or damage to
non-targeted cells. For example, the duration of the freeze event
(e.g., the partial or complete freeze event) can be shorter or
longer than about 10 seconds, 20 seconds, 30 seconds, or 45 seconds
or about 1, 2, 3, 4, 5 or 10 minutes. The frozen tissue can be
thawed to prevent undesired thermal damage and, in some
embodiments, can be thawed within about 5 seconds, 10 seconds, 20
seconds, 30 seconds, or 45 seconds or about 1, 2, 3, 4, 5, or 10
minutes after initiation of the freeze event. In many embodiments,
and as described in further detail herein, non-targeted cells can
be protected by a warming cycle that brings the temperature of
non-targeted cells to a temperature above their freezing
temperatures prior to catalyzing a freeze event in the supercooled
target tissue. For example, non-targeted tissue can be warmed to
temperatures above about -1.8.degree. C., above about 0.degree. C.,
above about 5.degree. C., above about 10.degree. C., above about
20.degree. C., above about 30.degree. C., or above about 32.degree.
C. Warming can be accomplished by thermal heaters disposed on a
surface of the applicator contacting or confronting a skin surface.
Alternatively, if deeper tissue is not targeted, such tissue could
be warmed using focused electrical currents which focus their
energy below the skin surface, focused ultrasound which has a focal
point for its energy below the skin surface, or RF energy.
[0087] As discussed above, deep hypodermal fat cells are more
easily damaged by low temperatures than the overlying dermal and/or
epidermal layers of skin, and, as such, thermal conduction can be
used to cool the desired layers of skin to a supercooled
temperature suitable to freeze lipid-containing cells upon
perturbation (e.g., a nucleating event). However, there is an
associated risk of also freezing the uppermost layers of skin.
Without being bound by theory, it is believed that low temperatures
may potentially cause damage in the epidermis (e.g., stratum
corneum, stratum lucidum, stratum granulosum, stratum spinosum,
stratum basale, etc.) via at least intracellular and/or
extracellular ice formation. The ice may expand and rupture the
cell wall, but it may also form sharp crystals that locally pierce
the cell wall and vital internal organelles, either or both
resulting in cell death. When extracellular liquid, such as water,
freezes to form ice, the remaining extracellular fluid becomes
progressively more concentrated with solutes. The high solute
concentration of the extracellular fluid may cause intracellular
fluid be driven through the semi-permeable cellular wall by osmosis
resulting in cell dehydration and death. Accordingly, in one
embodiment, mechanical perturbation and/or other catalyst for
nucleation (e.g., RF energy, alternating electric fields,
ultrasound energy, etc.) within the target tissue can be provided
only following a protective increase of a temperature of
non-targeted epidermal layers and/or dermal layers. The
non-targeted layers can be warmed enough to avoid freezing of
non-targeted tissue upon nucleation.
[0088] As explained in more detail below, the treatment systems
disclosed herein can employ a temperature treatment cycle to (a)
cool (e.g., supercool) target tissue, for example, to a temperature
below freezing without causing nucleation or microscopic
crystallization of intracellular and/or extracellular fluids and
(b) warm non-targeted tissue to increase its temperature above its
freezing temperature. After warming the non-targeted tissue, the
treatment systems can induce nucleation and hence freezing in the
supercooled target tissue. In certain embodiments, the treatment
system 100 of FIG. 2 can supercool a volume of tissue and can warm
superficial skin layers to prevent injury to those superficial skin
layers without the use of a chemical cryoprotectant. Alternatively,
a cryoprotectant can further be employed to provide an added
element of safety to minimize chances that undesired skin layers
are undesirably damaged, particularly epidermal tissue, so as to
prevent or minimize any chance of creating hyperpigmentation or
hypopigmentation.
[0089] Formation of nucleation sites can be catalyzed by
perturbation of the supercooled tissue. In particular embodiments,
the supercooled region (e.g., body fluids within the targeted
tissue cooled below their freezing temperatures) can be subjected
to vibrations, changes in mechanical pressure, and/or ultrasound
pulse(s) provided by the applicator 104 to catalyze nucleation of
the supercooled extracellular and/or intracellular fluids, lipids,
etc. Nucleation perturbations can also be created by applying a
nucleating solution to the skin, or by using electrical energy. The
extracellular and/or intracellular fluids, lipids, etc. in the
non-targeted skin layers under the applicator 104 can be
conductively warmed during the treatment (e.g., following
transdermal cooling of targeted tissue) such that freeze injury is
avoided in the non-targeted tissue when nucleation is
initiated.
[0090] In one embodiment, to achieve supercooled temperatures of
the targeted tissue without initiating nucleation, the treatment
site can be cooled at a relatively slow rate (e.g., the temperature
profile can cause a slow cooling of the tissue at the target
region). For example, the rate of cooling can be either equal to,
slower or faster than about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10
degrees C. per minute. A preferred rate of cooling is about either
2, 4, or 6 degrees C. per minute. Additionally or alternatively, a
treatment device can apply a generally constant pressure during
cooling to the supercooled temperature range to avoid pressure
changes that would cause inadvertent nucleation. In a further
embodiment, the targeted tissue can be cooled while the patient is
held still (e.g., without movement of the treatment site) to avoid
mechanically disturbing the supercooled tissue and unintentionally
causing crystallization. The temperature of the non-targeted
surface tissue can be warmed to a non-freezing temperature and/or a
non-supercooled temperature prior to perturbation and subsequent
freezing. In one embodiment, the warming cycle of the temperature
profile can occur quickly such that the underlying and/or targeted
tissue remains in the supercooled state throughout the warming
cycle.
[0091] At least some aspects of the technology are directed to
systems and methods of treating a patient by cooling a surface of
the patient's skin to a temperature sufficiently low to cause
supercooling of targeted tissue below the skin surface. The surface
of the skin can then be heated to a non-supercooled temperature
while the targeted tissue remains in a supercooled state. After
heating the non-targeted tissue, the supercooled targeted tissue
can be controllably frozen. In some embodiments, nucleation can be
controlled to cause partial freezing. In some procedures, the
applicator 104 of FIGS. 1B and 2 can be kept generally stationary
relative to the treatment site during cooling to avoid pressure
changes that would cause nucleation. After heating non-targeted
tissue, the applicator 104 can cause nucleation in the supercooled
targeted tissue by, for example, varying applied pressures,
delivering energy (e.g., ultrasound energy, RF energy, ultrasound
energy, microwave energy, etc.), applying fields (e.g., AC electric
fields, DC electric fields, etc.), or providing other perturbations
(e.g., vibrations, pulses, etc.), as well as combinations thereof.
Because the non-targeted tissue has been warmed to a
non-supercooled state, it does not experience a freeze event. In
some embodiments, the applicator 104 can include one or more
movable plates (e.g., plates movable to vary applied pressures),
rotatable eccentric masses, ultrasound transducers, electrical
current generators, or other elements capable of providing
nucleating perturbations. Vacuum applicators can increase and
decrease vacuum levels to massage tissue, vary applied pressures,
etc.
[0092] Once catalyzed, the partial or total freeze event can be
detected, and a cooling device associated with the treatment system
100 can be controlled to continue cooling the patient's skin so as
to maintain a frozen state of targeted tissue for a desired period
of time. The skin can be periodically or continuously cooled to
keep a sufficient volume of the tissue in a frozen state. In some
embodiments, the targeted tissue can be kept frozen for longer or
shorter than about, for example, 1 second, 5 seconds, 10 seconds,
20 seconds, 30 seconds, 1 minute, several minutes, or other time
period selected to reduce or limit frostbite or necrosis. Further,
the temperature of the upper tissue of the skin can be detected,
and the treatment system 100 can be controlled to apply heat to the
surface of the patient's skin for a preselected period of time to
prevent freezing of non-targeted tissue. The preselected period of
time can be longer or shorter than about 1, 2, 3, 4, or 5 seconds.
Accordingly, non-targeted tissue can be protected without using a
chemical cryoprotectant that may cause unwanted side effects.
Alternatively, a cryoprotectant can also be used if an additional
margin of safety for some tissue, such as the epidermis, is
desired.
[0093] As described herein for targeting subcutaneous lipid-rich
tissue, temperature treatment cycles can be used with the treatment
system 100 to transdermally cool (e.g., supercool) and selectively
affect the patient's subcutaneous lipid-rich tissue while
protecting non-lipid rich cells (e.g., residing in epidermal and/or
dermal layers) at a temperature higher than the freezing
temperatures of the subdermal tissue. Subcutaneous lipid-rich
tissue can be supercooled and then frozen for a variety of
therapeutic and cosmetic body-contouring applications, such as
reduction of adipose tissue residing in identified portions of the
patient's body (e.g., chin, cheeks, arms, pectoral areas, thighs,
calves, buttocks, abdomen, "love handles", back, breast, etc.). For
example, use of the temperature treatment cycle with the treatment
system 100 to transdermally cool adipose tissue in the breast can
be used for breast contouring and size reduction in a manner that
facilitates protection of non-target tissue in the breast. Further
examples include use of the temperature treatment cycle and
treatment system 100 to contour and/or reduce a volumetric size of
treatment sites without substantially affecting non-targeted cells
(e.g., cells in the epidermal and/or dermal layers). In some
embodiments, the disclosed methods for therapeutic and cosmetic
body-contouring applications can be performed with or without the
use of chemical cryoprotectants.
[0094] In another embodiment, temperature treatment cycles can be
used with the treatment system 100 to cool the skin to selectively
affect (e.g., injure, damage, and/or kill) secreting exocrine
glandular cells or hair follicles. For example, secreting glandular
cells residing in axilla apocrine sweat glands can be targeted by
the treatment system 100 for the treatment of hyperhidrosis. In
another example, lipid-producing cells residing in or at least
proximate to sebaceous glands (e.g., glandular epithelial cells)
present in the dermis of a target region can be targeted by the
treatment system 100 for the treatment of acne or other skin
condition. For example, the treatment system 100 can be configured
to reduce a temperature of a dermal layer of skin to reduce the
temperature of lipid-producing cells residing in or at least
proximate to sebaceous glands such that the targeted
lipid-producing cells excrete a lower amount of sebum and/or there
are fewer lipid-producing cells resulting in less sebum production
within the targeted sebaceous glands. In another embodiment, the
sebaceous glands are destroyed. The treatment system 100 can be
configured, for example, to reduce a subject's acne by cooling
(e.g., supercooling) acne-prone regions of the body (e.g., the
face, back and chest).
[0095] 4. Healing of Freeze Wounds
[0096] Healing of freeze injuries is different from healing of
other types of injuries. For example, significant freezing can
destroy cells; however, it does not completely or immediately
destroy the surrounding connective tissue matrix. During the
healing process, the cell population lost by freeze injury can be
replaced by fibroblasts that migrate into the wound site. The
degraded matrix and cellular debris at the wound site is removed
and replaced gradually, thus enhancing the structural integrity of
the wound base, as can be evidenced by a recovering wound site's
pattern of birefringence. For example, following freeze injuries,
the connective tissue matrix reveals dermal-like patterns of
birefringence identical to that which is seen in normal, undamaged
skin adjacent to the wound. This is consistent with other findings
that the extracellular matrix is relatively resistant to freeze
damage. Without being bound by theory, it is believed that wound
contraction (e.g., a decrease in the size of the wound) does not
occur following a freezing injury because of the relatively intact
connective tissue matrix at the wound site.
[0097] Freezing will destroy cells (e.g., epidermal keratinocytes),
which are then removed by phagocytosis and replaced gradually, but
freezing relatively spares the connective tissue matrix which can
simulate the effects of a full-thickness skin graft to an open
wound. Freezing of the skin can also promote separation between
dermal and epidermal layers during the post-thaw period. For
example, immediately following a freeze event, epidermal necrosis,
pyknotic dermal fibroblasts and polymorphonuclear leukocytes are
evident at the wound site. As such, inflammation, granulation
tissue formation, and epithelialization are natural processes that
occur during freeze wound healing.
[0098] During the repair process following freeze injuries, the
turnover of connective tissue matrix can be diminished or delayed.
The residual matrix does, however, retain much of its structural
integrity. This is observed by the absence of degradative
denaturation as demonstrated by its patterns of birefringence.
There is little collagenous phase change leading to fibrillar
shrinkage at this stage.
[0099] Wound repair resulting from a freeze event or injury follows
a generalized pattern of healing phases that can be categorized
depending upon the tissue depth of resulting injury. In one example
in which freeze injury is limited to the epithelium, the epithelium
restores or regenerates itself to a structure similar to the
pre-injury state. In contrast, injuries inflicted on deeper
structures or skin layers (e.g., the dermis) typically result in
more extensive tissue repair process. For example, in acute partial
thickness (e.g., superficial) freeze wounds, epithelialization
and/or regeneration occurs by a different mechanism than
full-thickness (e.g., deeper) wounds because adnexal structures are
retained. These adnexal structures can serve as a reservoir of
epithelial cells that migrate across the wound to repopulate the
epidermis. Without being bound by theory, and in a particular
example of wound healing following a freeze event, a wound healing
process may progress through three or more healing phases. The
healing phases may include, without limitation, (1) an inflammatory
phase, (2) a proliferative phase, and (3) a remodeling phase.
[0100] An onset of an inflammatory process can result in localized
edema. Although the scars from the freeze-produced wounds can have
larger surface areas due to the lack of wound contraction as
described above, freeze wounds will, however, often remain more
localized due to the absence of thermal radiation dynamics. For
example, tissue examined 4 days after freeze injury often reveals
edema and inflammatory cells at the interface between dead and
surviving dermal tissue, and viable myofibroblasts can be visible
within the central wound area associated with the residual
connective tissue matrix. Approximately 10 days following a freeze
injury or event, the wound site typically reveal islands of
granulation tissue intermingled with residual connective tissue
matrix within the area of healing. Few viable cells are evident
within this residual matrix, but the islands of granulation tissue
can contain densely packed myofibroblasts. During an inflammatory
phase of healing, platelets are among the first cells to appear at
the wound site. Platelets release platelet derived growth factor
(PDGF), which upregulates soluble fibrinogen production. Fibrinogen
is converted to insoluble strands of fibrin which form a matrix for
the influx of monocytes and fibroblasts.
[0101] During a proliferative phase of healing, cellular activity
promotes epithelialization and fibroplasia. Fibronectin, produced
initially from plasma, promotes epidermal migration by providing
its own lattice. In freeze wounds, basal keratinocytes secrete
collagenase-1 when in contact with fibrillar collagen.
Collagenase-1 disrupts attachment to fibrillar collagen which
allows for continued migration of keratinocytes into the wound
site. It is during the proliferative phase that a healing process
following freezing injury can result in a thicker epidermal layer
with increased cellular activity.
[0102] Extracellular matrix remodeling, cell maturation and cell
apoptosis create the remodeling phase of wound repair, which
processes can also overlap with tissue formation. Tissue remodeling
describes transient to permanent changes in the tissue architecture
that involve breaching of histological barriers, such as basement
membranes, basal lamina, and extracellular matrix. Typically, the
remodeling phase addresses the potential outcome of freeze wound
repair as this phase creates structural integrity and textural
quality enhancement, which can define the clinical outcome.
[0103] Healing of freeze wounds also includes the deposition of
matrix materials. Dermal macromolecules, such as fibronectin,
hyaluronic acid, proteoglycans and collagen, are deposited and
serve as a scaffolding for subsequent cellular migration and tissue
support. Deposition and remodeling of the extracellular matrix
proteins are dynamic processes and differences in the quantity of
matrix proteins are evident between the center and the periphery of
the wound. Since the collagen matrix is retained in freeze wounds
at or near their pre-injury structural integrity levels, its
tensile strength, which is a functional assessment of collagen, can
be enhanced. Therefore, the collagen matrix can provide (in
conjunction with the increase in epithelial layer thickness) a
transient barrier to the pre-injury surface nodularity of
cellulite.
D. Treatment Systems and Methods of Treatment
[0104] FIG. 2 is a partially schematic isometric view of the
non-invasively treatment system 100 for performing cryotherapy
procedures disclosed herein. The term "treatment system", as used
generally herein, refers to cosmetic or medical treatment systems.
The treatment system 100 can be configured to alter a human
subject's subcutaneous adipose tissue, reduce skin surface
irregularities, and/or improve skin characteristics by cooling
targeted cells. The treatment system 100 can include a treatment
unit or tower 102 ("treatment tower 102") connected to the
applicator 104 by supply and return fluid lines 108a-b and
power-lines 109a-b. The applicator 104 can have one or more cooling
devices powered by electrical energy delivered via the power-lines
109a-b. A control line can provide communication between electrical
components of the applicator 104 and a controller 114. Components
of the applicator 104 can be cooled using coolant that flows
between the applicator 104 and the treatment tower 102 via the
supply and return fluid lines 108a-b. In one example, the
applicator 104 has a cooling device (e.g., cooling/heating device
103 of FIG. 1B) with one or more thermoelectric cooling elements
and fluid channels through which the coolant flows to cool the
thermoelectric cooling elements. The thermoelectric cooling
elements can include heat-exchanging plates, Peltier devices, or
the like. In other embodiments, the applicator 104 can be a
non-thermoelectric device that is heated/cooled using only
coolant.
[0105] The treatment tower 102 can include a chiller unit or module
106 ("chiller unit 106") capable of removing heat from the coolant.
The chiller unit 106 can include one or more refrigeration units,
thermoelectric chillers, or any other cooling devices and, in one
embodiment, includes a fluid chamber configured to house the
coolant delivered to the applicator 104 via the fluid lines 108a-b.
In some procedures, the chiller unit 106 can circulate warm coolant
to the applicator 104 during periods of warming. In certain
procedures, the chiller unit 106 can alternatingly provide heated
and chilled coolant for warming and cooling periods. The
circulating coolant can include water, glycol, synthetic heat
transfer fluid, oil, a refrigerant, or any other suitable heat
conducting fluid. Alternatively, a municipal water supply (e.g.,
tap water) can be used in place of or in conjunction with the
treatment tower 102. The fluid lines 108a-b can be hoses or other
conduits constructed from polyethylene, polyvinyl chloride,
polyurethane, and/or other materials that can accommodate the
particular coolant. One skilled in the art will recognize that
there are a number of other cooling technologies that could be used
such that the treatment unit, chiller unit, and/or applicator(s)
need not be limited to those described herein. Additional features,
components, and operation of the treatment tower 102 are discussed
in connection with FIG. 8.
[0106] FIG. 2 shows the applicator 104 positioned to treat tissue
along the leg of the subject 101. Feedback data from sensors of the
applicator 104 can be collected in real-time because real-time
processing of such feedback data can help correctly and
efficaciously administer treatment. In one example, real-time data
processing is used to detect freeze events and to control the
applicator 104 to continue cooling the patient's skin after the
freeze event is detected. Tissue can be monitored to keep the
tissue in the frozen state (e.g., a partial or total frozen state)
for a period of time. The period of time can be selected by the
treatment tower 102 or an operator and can be longer than about,
for example, 10 seconds, 30 seconds, 1 minute, or a few minutes.
Other periods of time can be selected if needed or desired. The
applicator 104 can include sensors configured to measure tissue
impedance, pressure applied to the subject 101, optical
characteristics of tissue, and/or tissue temperatures. As described
herein, sensors can be used to monitor tissue and, in some
embodiments, to detect freeze events. The number and types of
sensors can be selected based on the treatment to be performed.
[0107] Multiple applicators may be concurrently or sequentially
used with the treatment system 100 and applied during a treatment
session, and such applicators can include, without limitation,
vacuum applicators, belt applicators, and so forth. Each applicator
may be designed to treat identified portions of the patient's body,
such as chin, cheeks, arms, pectoral areas, thighs, calves,
buttocks, abdomen, "love handles", back, and so forth. For example,
a vacuum applicator may be applied at the back region, and the belt
applicator may be applied around the thigh region, either with or
without massage or vibration. Exemplary applicators and their
configurations usable or adaptable for use with the treatment
system 100 are described in, e.g., U.S. Pat. No. 8,834,547 and
commonly assigned U.S. Pat. No. 7,854,754 and U.S. Patent
Publication Nos. 2008/0077201, 2008/0077211, and 2008/0287839,
which are incorporated by reference in their entireties.
[0108] In further embodiments, the system 100 may also include a
patient protection device (not shown) incorporated into or
configured for use with the applicator 104 that prevents the
applicator from directly contacting a patient's skin and thereby
reduces the likelihood of cross-contamination between patients and
minimizes cleaning requirements for the applicator. The patient
protection device may also include or incorporate various storage,
computing, and communications devices, such as a radio frequency
identification (RFID) component, to monitor and/or meter use.
Exemplary patient protection devices are described in commonly
assigned U.S. Patent Publication No. 2008/0077201.
[0109] In operation, and upon receiving input to start a treatment
protocol, the controller 114 can cycle through each segment of a
prescribed treatment plan. In so doing, power supply 110 and
chiller unit 106 can provide power and coolant to one or more
functional components of the applicator 104, such as thermoelectric
coolers (e.g., TEC "zones"), to begin a cooling cycle and, in some
embodiments, activate features or modes such as vibration, massage,
vacuum, etc. The controller 114 can monitor treatment by receiving
temperature readings from temperature sensors. The temperature
sensors can be part of the applicator 104 or proximate to the
applicator 104, the patient's skin, a patient protection device,
etc. It will be appreciated that while a target region of the body
has been cooled or heated to the target temperature, in actuality
that region of the body may be close but not equal to the target
temperature, e.g., because of the body's natural heating and
cooling variations. Thus, although the system 100 may attempt to
heat or cool tissue to the target temperature or to provide a
target heat flux, a sensor may measure a sufficiently close
temperature or heat flux. If the target temperature or flux has not
been reached, power can be increased or decreased to change heat
flux to maintain the target temperature or "set-point" selectively
to affect targeted tissue. The system 100 can thus monitor the
treatment site while accurately cooling/heating to perform the
methods disclosed herein.
[0110] The applicator 104 can damage, injure, disrupt or otherwise
reduce subcutaneous lipid-rich cells generally without collateral
damage to non-lipid-rich cells in the treatment region. In other
embodiments, the applicator 104 damages, injures, disrupts, or
otherwise reduces cells in the epidermal and/or dermal layers to
create freeze events (e.g., thermal injuries and/or trauma for
achieving desired effects). A cryoprotectant can be administered
topically to the skin of the subject 101 at the treatment site
and/or used with the applicator 104 to, among other advantages,
assist in preventing or, in other embodiments, controlling freezing
of targeted cells. Supercooling or other techniques can be
performed without the use of topically applied cryoprotectants.
[0111] FIGS. 3 to 7 are flow diagrams illustrating methods for
treating treatment sites in accordance with embodiments of the
technology. Although specific example methods are described herein,
one skilled in the art is capable of identifying other methods that
the system could perform. Moreover, the methods described herein
can be altered in various ways. Even though the methods are
described with reference to the treatment system 100 of FIG. 2, the
methods may also be applied in other treatment systems with
additional or different hardware and/or software components.
[0112] FIG. 3 is a flow diagram illustrating a method 140 for
reducing irregularities in a surface of a subject's skin resulting
from an uneven distribution of adipose tissue in the subcutaneous
layer in accordance with embodiments of the technology. As shown in
FIG. 3, an early stage of the method 140 can include coupling a
heat-exchanging surface of a treatment device with the surface of
the subject's skin at a target region (block 142). FIG. 1B shows
the heat-exchanging surface 19 in the form of an exposed surface of
a heat-exchanging plate thermally coupled to the subject's skin. In
another embodiment, the heat-exchanging surface can be the surface
of an interface layer or a dielectric layer. Coupling of
heat-exchanging surfaces to the skin can be facilitated by using
restraining means, such as a belt or strap. In other embodiments, a
vacuum or suction force can be used to positively couple the
treatment device to the patient's skin. In some methods, a
conductive substance can couple the heat-exchanging surface 19 to
the patient's skin and can be a cryoprotectant. Cryoprotectants and
methods of using cryoprotectants are described in commonly assigned
U.S. Patent Publication No. 2007/0255362.
[0113] At block 144, the method 140 includes removing heat such
that lipid-rich cells in the subcutaneous layer are reduced in
number and/or size to an extent while non-lipid-rich cells and
lipid-rich regions adjacent to the fibrous septae are not reduced
in number or size to the same extent. For example, cooling the
subcutaneous layer in the target region can include cooling the
lipid-rich tissue to a temperature below, for example, about
10.degree. C., 0.degree. C., -5.degree. C., -10.degree. C.,
-15.degree. C., -20.degree. C., -25.degree. C., -30.degree. C.,
-35.degree. C., or -40.degree. C. to disrupt lipid-rich lobules and
the adipose cells. The duration of cooling may vary depending on
the location of the target region and the degree of cooling
required to reduce the number and/or size of the lipid-rich cells,
as well as other parameters.
[0114] FIG. 4 is a flow diagram illustrating a method 150 for
reducing the appearance of cellulite in a target area of a subject
in accordance with embodiments of the technology. As shown in FIG.
4, the method 150 can include coupling a heat-exchanging surface of
a treatment device with the surface of the subject's skin at a
target region (block 152). In one embodiment, the heat-exchanging
surface can be a surface of a heat-exchanging plate. In another
embodiment, the heat-exchanging surface can be the surface of an
interface layer or a dielectric layer. At block 154, the method 150
includes cooling the subject's skin to induce a freeze wound at the
target region and allowing the freeze wound to heal (block 156). As
discussed above, freezing and thawing events can induce injury to
the skin tissue. Such injury can promote natural body responses
(e.g., healing) that can have positive effects on skin appearance.
For example, and in one embodiment, the method can promote
thickening of the epidermal layer to reduce the appearance of
cellulite.
[0115] FIG. 5 is a flow diagram illustrating a method 160 for
improving the appearance of skin by producing one or more freeze
events in accordance with embodiments of the technology. Generally,
a treatment device can be applied to a subject and can cool a
surface of the subject's skin to produce and detect a freeze event.
After detecting the freeze event (or events), operation of the
treatment device can be controlled to keep at least a portion of
the subject's tissue frozen for a sufficient length of time to
improve skin appearance. Details of method 160 are discussed
below.
[0116] At block 162, the treatment device is applied to a subject
by placing its heat-exchanging surface in thermal contact with the
subject's skin. A substance can be applied to the subject's skin
before applying the treatment device and can (a) provide thermal
coupling between the subject's skin and the treatment device to
improve heat transfer therebetween, (b) selectively protect
non-target tissues from freeze damage (e.g., damage due to
crystallization), and/or (c) initiate and/or control freeze events.
The substance may be a fluid, a gel, or a paste and may be
hygroscopic, thermally conductive, and biocompatible. In some
embodiments, the substance can be a cryoprotectant that reduces or
inhibits cell destruction. As used herein, "cryoprotectant,"
"cryoprotectant agent," and "composition" mean substances (e.g.,
compositions, formulations, compounds, etc.) that assist in
preventing freezing of tissue compared to an absence of the
substances(s). In one embodiment, the cryoprotectant allows, for
example, the treatment device to be pre-cooled prior to being
applied to the subject for more efficient treatment. Further, the
cryoprotectant can also enable the treatment device to be
maintained at a desired low temperature while preventing ice
formation on the cooled surface of the treatment device, and thus
reduces the delay in reapplying the treatment device to the
subject. Yet another aspect of the technology is the cryoprotectant
may prevent the treatment device from freezing to the subject's
skin. Certain cryoprotectant can allow microscopic crystals to form
in the tissue but can limit crystal growth that would cause cell
destruction and, in some embodiments, allows for enhanced uptake or
absorption and/or retention in target tissue prior to and during
cooling.
[0117] Some embodiments according to the present technology may use
a cryoprotectant with a freezing point depressant that can assist
in preventing freeze damage that would destroy cells. Suitable
cryoprotectants and processes for implementing cryoprotectants are
described in commonly-assigned U.S. Patent Publication No.
2007/0255362. The cryoprotectant may additionally include a
thickening agent, a pH buffer, a humectant, a surfactant, and/or
other additives and adjuvants as described herein. Freezing point
depressants may include, for example, propylene glycol (PG),
polyethylene glycol (PEG), dimethyl sulfoxide (DMSO), or other
suitable alcohol compounds. In a particular embodiment, a
cryoprotectant may include about 30% propylene glycol, about 30%
glycerin (a humectant), and about 40% ethanol. In another
embodiment, the cryoprotectant may include about 40% propylene
glycol, about 0.8% hydroxyethyl cellulose (a thickening agent), and
about 59.2% water. In a further embodiment, a cryoprotectant may
include about 50% polypropylene glycol, about 40% glycerin, and
about 10% ethanol. The freezing point depressant may also include
ethanol, propanol, iso-propanol, butanol, and/or other suitable
alcohol compounds. Certain freezing point depressants (e.g., PG,
PPG, PEG, etc.) may also be used to improve spreadability of the
cryoprotectant and to provide lubrication. The freezing point
depressant may lower the freezing point of body liquids/lipids to
about 0.degree. C. to -50.degree. C., about 0.degree. C. to
-50.degree. C., or about 0.degree. C. to -30.degree. C. In other
embodiments, the freezing point of the liquid/lipids can be lowered
to about -10.degree. C. to about -40.degree. C., about -10.degree.
C. to about -30.degree. C., or about -10.degree. C. to about
-20.degree. C. In certain embodiments, the freezing point of the
liquid/lipids can be lowered to a temperature below about 0.degree.
C., below about -5.degree. C., below about -10.degree. C., below
about -12.degree. C., below about -15.degree. C., below about
-20.degree. C., below about -30.degree. C., or below about
-35.degree. C. For example, the freezing point depressant may lower
the freezing point of body fluid/lipids to a temperature of between
about -1.degree. C. and -40.degree. C., between about -5.degree. C.
and -40.degree. C., or between about -10 and -40.degree. C.
[0118] Cryoprotectant can be delivered to the surface of the
patient's skin for a period of time which is short enough to not
significantly inhibit the initiation of the freeze event in dermal
tissue but which is long enough to provide substantial protection
to non-targeted tissue (e.g., subcutaneous adipose tissue). The
rate of cryoprotectant delivery can be selected based on the
characteristics of the cryoprotectant and the desired amount of
tissue protection. In one specific treatment process, an interface
member is placed directly over the target area, and the treatment
device with a disposable sleeve or liner is placed in contact with
the interface member. The interface member can be a cotton pad, a
gauze pad, a pouch, or a container with a reservoir containing a
volume of cryoprotectant or other flowable conductive substance.
The interface member can include, for example, a non-woven cotton
fabric pad saturated with cryoprotectant that is delivered at a
desired delivery rate. Suitable pads include Webril.TM. pads
manufactured by Covidien of Mansfield, Mass. Further details
regarding interface members and associated systems and methods of
use are described in commonly-assigned U.S. Patent Publication No.
2010/0280582.
[0119] At block 164, the treatment device can rapidly cool the
surface of the patient's skin to a sufficiently low temperature to
cause a freeze event in targeted tissue. The rapid cooling can
create a thermal gradient with the coldest temperatures near the
applicator (e.g., the upper layers of skin). The resulting thermal
gradient causes the temperature of the upper layer(s) of the skin
to be lower than that of the targeted deeper cells. This allows the
skin to be frozen for a short enough duration to not establish a
temperature equilibrium across the skin and adjacent subcutaneous
tissue. A cryoprotectant and/or warming cycle can be used to
inhibit freezing the uppermost non-targeted layer or layers of
skin.
[0120] A freeze event can include at least some crystallization
(e.g., formation of microscopic ice crystals) in intercellular
material (e.g., fluid, cell components, etc.) and/or extracellular
fluid. By avoiding extensive ice crystal formation that would cause
frostbite or necrosis, partial freeze events can occur without
undesired tissue damage. In some embodiments, the surface of the
patient's skin can be cooled to a temperature no lower than about
-40.degree. C., -30.degree. C., -20.degree. C., -10.degree. C., or
-5.degree. C. to produce a partial or total freeze event without
causing irreversible skin damage. In one example, the treatment
system 100 of FIG. 2 can cool the surface of the skin to from about
-40.degree. C. to about 0.degree. C., from about -30.degree. C. to
about 0.degree. C., from about -20.degree. C. to about 0.degree.
C., or from about -15.degree. C. to about 0.degree. C. or below
about -10.degree. C., -20.degree. C., -20.degree. C., -30.degree.
C., or -40.degree. C. It will be appreciated that the surface of
skin can be cooled to other temperatures based on the mechanism of
action.
[0121] The cooling period can be sufficiently short to minimize,
limit, or substantially eliminate necrosis, or other unwanted
thermal damage, due to the freeze event. In one procedure, the
applicator (e.g., applicator 104 of FIGS. 1B and 2) can produce a
freeze event that begins within a predetermined period of time
after the applicator begins cooling the patient's skin or after the
freeze event begins. The predetermined period of time can be equal
to or shorter than about 30, 60, 90, 120, or 150 seconds and, in
some embodiments, the predetermined period of time can be from
between about 10 seconds to about 150 seconds, between about 30
seconds to about 150 seconds, or between about 60 seconds to about
150 seconds. In some embodiments, the predetermined period of time
can be shorter than about either 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10
minutes. A controller (e.g., controller 114 of FIG. 2) can select
the predetermined period of time based on the treatment
temperatures, treatment sites, and/or cryotherapy to be performed.
Alternatively, an operator can select the period of time for
cooling and can enter it into the controller 114.
[0122] To help initiate the freeze event (e.g., the partial or
total freeze event), energy, pressure, and/or a substance can be
used to aid in the formation of nucleation sites for
crystallization. Energy for promoting nucleation can include,
without limitation, acoustic energy (e.g., ultrasound energy),
mechanical energy (e.g., vibratory motion, massaging, and/or
pulsatile forces), or other suitable energy. The applicators
disclosed herein can include, without limitation, one or more
elements (e.g., elements 171 in FIG. 1B) in the form of actuators
(e.g., motors with eccentric weights), vibratory motors, hydraulic
motors, electric motors, AC electrodes, pneumatic motors,
solenoids, piezoelectric shakers, and so on for providing energy,
pressure, etc. Pressure for promoting nucleation can be applied
uniformly or non-uniformly across the treatment site. Substances
that promote nucleation can be applied topically before and/or
during skin cooling.
[0123] At block 166 of FIG. 5, the treatment device can detect the
freeze event using one or more electrical components. FIG. 1B shows
the applicator 104 with an electronic component in the form of a
sensor 167 that can identify positive (increase) or negative
(decrease) temperature changes. During cooling, targeted tissue can
reach a temperature below the freezing point of its biological
tissue and fluids (e.g., approximately -1.8.degree. C.). As tissue,
fluids, and lipids freeze, crystals can form and energy associated
with the latent heat of crystallization is released. A relatively
small positive change in tissue temperature can indicate a partial
freeze event whereas a relatively large positive change in tissue
temperature can indicate a complete freeze event. The sensor 167
(FIG. 1B) can detect the positive change in tissue temperature, and
the treatment system can identify it as a freeze event. The
treatment system can be programmed so that small temperature
variations do not cause false alarms with respect to false
treatment events. Additionally or alternatively, the treatment
systems disclosed herein may detect changes in the temperature of
its components or changes in power supplied to treatment devices,
or other components, to identify freeze events.
[0124] Referring now to FIG. 2, the system 100 can monitor the
location and/or movement of the applicator 104 and may prevent
false or inaccurate determinations of treatment events based on
such monitoring. The applicator 104 may move during treatment which
may cause the applicator 104 to contact a warmer area of skin, to
no longer contact the skin, and so on. This may cause the system
100 to register a difference in temperature that is inconsistent
with a normal treatment. The controller 114 may be programmed to
differentiate between these types of temperature increases and a
temperature increase associated with freezing. U.S. Pat. No.
8,285,390 discloses techniques for monitoring and detecting freeze
events and applicator movement and is incorporated by reference in
its entirety. Additionally, the treatment system 100 can provide an
indication or alarm to alert the operator to the source of this
temperature increase. In the case of a temperature increase not
associated with a treatment event, the system 100 may also suppress
false indications, while in the case of a temperature increase
associated with freezing, the system 100 take any number of actions
based on that detection as described elsewhere herein.
[0125] The system 100 can use optical techniques to detect events
at block 166 of FIG. 5. For example, the sensor 167 of FIG. 1B can
be an optical sensor capable of detecting changes in the optical
characteristics of tissue caused by freezing. The optical sensor
can include one or more energy emitters (e.g., light sources, light
emitting diodes, etc.), detector elements (e.g., light detectors),
or other components for non-invasively monitoring optical
characteristics of tissue. In place of or in conjunction with
monitoring using optical techniques, tissue can be monitored using
electrical and/or mechanical techniques. In embodiments for
measuring electrical impedance of tissue, the sensor 167 (FIG. 1B)
can include two electrodes that can be placed in electrical
communication with the skin for monitoring electrical energy
traveling between the electrodes via the tissue. In embodiments for
measuring mechanical properties of tissue, the sensor 167 can
comprise one or more mechanical sensors which can include, without
limitation, force sensors, pressure sensors, and so on.
[0126] At block 168 of FIG. 5, the treatment device can be
controlled to maintain the freeze event by continuously or
periodically cooling the patient's tissue to keep a target volume
of skin frozen for a period of time, which can be long enough to
improve skin appearance. In short treatments, the period of time
can be equal to or shorter than about 5, 10, 15, 20, or 25 seconds.
In longer treatments, the period of time can be equal to or longer
than about 25 seconds, 30 seconds, 45 seconds or 1, 2, 3, 4, 5, or
10 minutes. In some procedures, the applicator 104 of FIGS. 1B and
2 can be controlled so that the skin is partially or completely
frozen for no longer than, for example, 5 minutes, 10 minutes, 20
minutes, 30 minutes, 45 minutes, or 1 hour. In some examples, the
skin is frozen for about 1 minute to about 5 minutes, about 5
minutes to about 10 minutes, about 10 minutes to about 20 minutes,
about 20 minutes to about 30 minutes, or about 30 minutes to about
1 hour. The length of time the skin is kept frozen can be selected
based on the severity of the freeze injury.
[0127] At block 168, the treatment system can also control the
applicator so that the partial or total freeze event causes
apoptotic damage to targeted tissue but does not cause such damage
to non-targeted tissue. In one example, the applicator produces a
partial freeze event short enough to prevent establishing
equilibrium temperature gradients in the patient's skin during, for
example, the freeze event. This allows freezing of shallow targeted
tissue without substantially affecting deeper non-targeted tissue.
Moreover, cells in the dermal tissue can be affected to a greater
extent than the cells in the subcutaneous layer. In some
procedures, the subcutaneous layer can be kept at a sufficiently
high temperature (e.g., at or above 0.degree. C.) while the
shallower dermal tissue experiences the partial or total freeze
event. The system can also control operation of the applicator to
thermally injure tissue to cause fibrosis, which increases the
amount of connective tissue in a desired tissue layer (e.g.,
epidermis and/or dermis) to increase the firmness and appearance of
the skin. In other treatments, the system controls the applicator
to supercool and then freeze (e.g., partially or totally freeze) at
least a portion of subcutaneous tissue, such as the fibrous
septae.
[0128] At block 169, the patient's partially or completely frozen
tissue can be thawed by heating it in order to minimize, reduce, or
limit tissue damage. The applicator can thaw the patient's skin, or
other frozen tissue, after the freeze event occurs and after a
period of time has transpired. The period of time can be equal to
or shorter than about 5, 10, 15, 20, or 25 seconds or about 1, 2,
3, 4, 5, 6, 7, 8, 9, or 10 minutes. In one example, the uppermost
skin layer(s) can be periodically heated to a temperature above the
skin's freezing point to provide freeze protection thereto. The
applicator can include one or more thermal elements (e.g.,
resistive heaters, electromagnetic energy emitters, Peltier
devices, etc.) for heating frozen tissue. For example, the element
103 of FIG. 1B can be a Peltier device capable of generating heat
for thawing tissue. Alternatively, the applicator 104 can include
one or more resistive heaters or Peltier devices 171 for thawing
tissue. In some embodiments, the applicator 104 of FIGS. 1B and 2
can have separate and independently controlled cooling elements and
heating elements that can cooperate to provide precise temperature
control for freezing and thawing/warming cycles. In some
embodiments, the applicator may stop cooling tissue to allow cooled
tissue to naturally warm and thaw.
[0129] FIGS. 6 and 7 are flow diagrams illustrating methods for
supercooling tissue in accordance with embodiments of the
technology. Generally, the methods can include treating a human
subject's body to cool a surface of the subject's skin to a
temperature no lower than -40.degree. C. to avoid unwanted skin
damage and so that the temperature of at least a portion of tissue
below the surface is in a supercooled state. The surface of the
skin can be heated to bring shallow non-targeted tissue out of the
supercooled state while deeper targeted tissue remains in the
supercooled state. The supercooled targeted tissue can be nucleated
due to a perturbation that causes at least partial freezing that
destroys or damages targeted cells due to crystallization of
intracellular and/or extracellular fluids. The perturbation can be
vibrations, ultrasound pulses, and/or changes in pressure suitable
for inducing a partial or complete freeze event to disrupt or
destroy targeted lipid-rich cells. The treatment system 100 (FIGS.
2 and 8) can utilize applicators disclosed herein to perform such
supercooling method.
[0130] FIG. 6 is a flow diagram illustrating a method 400 in
accordance with an aspect of the present technology. An early stage
of the method 400 can include cooling a surface of a human
subject's skin to a first temperature (block 402). The first
temperature can be, for example, between about -10.degree. C. and
-40.degree. C. such that a portion of tissue below the surface is
in a supercooled state. In other embodiments, the first temperature
can be a temperature between about -15.degree. C. and -25.degree.
C., a temperature between about -20.degree. C. and about
-30.degree. C., or other temperature below a freezing
temperature.
[0131] In block 404, the surface of the human subject's skin is
heated an amount sufficient to raise the skin surface temperature
from the first temperature to a second temperature, which can be a
non-supercooled temperature, while the targeted tissue remains in
the supercooled state. For example, the treatment system can be
used to heat the surface (e.g., the epidermis) of the skin to a
temperature higher than about 0.degree. C., higher than about
5.degree. C., higher than about 10.degree. C., higher than about
20.degree. C., higher than about 30.degree. C., or higher than
about 35.degree. C. There can be a temperature gradient between the
targeted tissue and the skin surface such that most of the
non-targeted tissue is at a non-supercooled temperature.
[0132] In block 406, the supercooled portion of tissue below the
skin surface can be nucleated to cause at least some fluid and
cells in the supercooled tissue to at least partially freeze. In
one embodiment, nucleation of the supercooled tissue is caused by a
mechanical perturbation. Cells residing at the surface of the human
subject's skin do not freeze, and in certain arrangements,
protection of cells at the surface can be accomplished without the
use of a chemical cryoprotectant.
[0133] In block 408, the supercooled tissue can be maintained in
the at least partially or totally frozen state for a predetermined
period of time longer than, for example, about 10 seconds, 12
seconds, 15 seconds, or 20 seconds. In various arrangements, the
supercooled tissue can be maintained in the at least or totally
frozen state for a duration of time sufficient to improve an
appearance of skin (e.g., by tightening the skin, increasing skin
smoothness, thickening the skin, improving the appearance of
cellulite, etc.), treat acne, improve a quality of hair, improve a
condition associated with hyperhidrosis, etc. In certain
embodiments, the maintaining step can include detecting the
temperatures and controlling the cooling and heating to maintain
targeted tissue in at least a partially or totally frozen state for
the predetermined time (e.g., longer than about 10 seconds, longer
than about 12 seconds, longer than about 15 seconds, or longer than
about 20 seconds).
[0134] In block 409, the patient's partially or completely frozen
tissue can be optionally thawed by heating it in order to minimize,
reduce, or limit tissue damage. The applicator can thaw the
patient's skin, or other frozen tissue, after the freeze event
occurs and after a period of time has transpired. In some
embodiments, the applicator may stop cooling tissue to allow cooled
tissue to naturally warm and thaw.
[0135] The method 400 can be performed to keep the freeze event
localized in the targeted layer. After supercooling tissue,
epidermal tissue can be heated to prevent freeze injuries to the
epidermal cells. In other embodiments, the freeze event can be
centered at the interface between the dermis and the subcutaneous
layer or at any other location. The method 400 can be repeated any
number of times at the same location or different locations along
the subject.
[0136] FIG. 7 illustrates a method 500 for affecting a subcutaneous
layer of a human subject's body in accordance with another
embodiment of the present technology. The method 500 can include
transdermally removing heat from tissue at a target region such
that cells in the target region are cooled to a supercooled
temperature (block 502). The supercooled temperature can be, for
example, below about 0.degree. C. or within a range from about
0.degree. C. to about -20.degree. C., from about -10.degree. C. to
about -30.degree. C., from about -20.degree. C. to about
-40.degree. C., or no lower than about -40.degree. C.
Cryoprotectants can be used to cool tissue to very low
temperatures, including temperatures lower than -40.degree. C.
[0137] In block 504, the method 500 includes applying heat to an
epidermis of the target region to warm epidermal cells in the
target region to a temperature above freezing while lipid-rich
cells in the subcutaneous layer of the target region are at or near
the supercooled temperature. For example, the step of applying heat
can include warming the epidermal cells to a temperature above
about 5.degree. C., about 10.degree. C., about 20.degree. C., about
25.degree. C., or about 32.degree. C.
[0138] In bock 506, a freeze event in the subcutaneous layer of the
target region can selectively affect the lipid-rich cells while
epidermal cells are not affected by the freeze event. The method
500 can include providing at least one of vibration, mechanical
pressure, and ultrasound pulses to the target region to cause such
freeze event. In various arrangements, the freeze event can cause
at least partial crystallization of a plurality of lipid-rich cells
in the target region. Beneficially, the epidermal cells are
protected such that freeze damage to these cells does not occur. In
certain embodiments, freeze damage protection of the epidermal
tissue can occur without applying a cryoprotectant to the surface
of the skin prior to or during the treatment.
[0139] In some embodiments, the dermal layer can be supercooled
while the subcutaneous layer can remain above its freezing point to
avoid affecting the subcutaneous lipid-rich cells. The freeze event
can occur in the dermal layer after non-targeted epidermal tissue
has been warmed such that freeze induced changes at the target
region can be localized in the dermal layer. Thus, dermal cells can
be affected without appreciably affecting epidermal and
subcutaneous cells. The method 500 can also be modified to produce
freeze events in other layers of tissue. For example, a freeze
event can be produced within one or more targeted epidermal layers
by supercooling the targeted epidermal layer(s) and then warming
the non-targeted epidermal layer(s). The supercooled epidermal
layers are then nucleated.
[0140] Various aspects of the methods 400 (FIG. 6) and 500 (FIG. 7)
can include cosmetic treatment methods for treating the target
region of a human subject's body to achieve a cosmetically
beneficial alteration of a portion of tissue within the target
region. Such cosmetic methods can be administered by a
non-medically trained person. The methods disclosed herein can also
be used to (a) improve the appearance of skin by tightening the
skin, improving skin tone and texture, eliminating or reducing
wrinkles, increasing skin smoothness, thickening the skin, (b)
improve the appearance of cellulite, and/or (c) treat sebaceous
glands, hair follicles, and/or sweat glands.
E. Treatment Systems and Treatment Devices
[0141] FIG. 8 is a partially schematic isometric view of the system
100 with a multi-modality applicator 204 positioned along the
subject's waist. The power supply 110 can provide a direct current
voltage to the applicator 204 to remove heat from the subject 101.
The controller 114 can monitor process parameters via sensors
(e.g., sensors of the applicator 204 and/or sensors placed
proximate to the applicator 204) via the control line 116 to, among
other things, adjust the heat removal rate and/or energy delivery
rate based on a custom treatment profile or patient-specific
treatment plan, such as those described, for example, in commonly
assigned U.S. Pat. No. 8,275,442.
[0142] The controller 114 can exchange data with the applicator 204
via an electrical line 112 or, alternatively, via a wireless or an
optical communication link. The control line 116 and electrical
line 112 are shown without any support structure. Alternatively,
control line 116 and electrical line 112 (and other lines
including, but not limited to fluid lines 108a-b and power lines
109a-b) may be bundled into or otherwise accompanied by a conduit
or the like to protect such lines, enhance ergonomic comfort,
minimize unwanted motion (and thus potential inefficient removal of
heat from and/or delivery of energy to subject 101), and to provide
an aesthetic appearance to the system 100. Examples of such a
conduit include a flexible polymeric, fabric, composite sheath, an
adjustable arm, etc. Such a conduit (not shown) may be designed
(via adjustable joints, etc.) to "set" the conduit in place for the
treatment of the subject 101.
[0143] The controller 114 can receive data from an input/output
device 120, transmit data to a remote output device (e.g., a
computer), and/or exchange data with another device. The
input/output device 120 can include a display or touch screen
(shown), a printer, video monitor, a medium reader, an audio device
such as a speaker, any combination thereof, and any other device or
devices suitable for providing user feedback. In the embodiment of
FIG. 8, the input/output device 120 can be a touch screen that
provides both an input and output functionality. The treatment
tower 102 can include visual indicator devices or controls (e.g.,
indicator lights, numerical displays, etc.) and/or audio indicator
devices or controls. These features can be part of a control panel
that may be separate from the input/output device 120, may be
integrated with one or more of the devices, may be partially
integrated with one or more of the devices, may be in another
location, and so on. In alternative examples, input/output device
120 or parts thereof (described herein) may be contained in,
attached to, or integrated with the applicator 204
[0144] The controller 114, power supply 110, chiller unit 106 with
a reservoir 105, and input/output device 120 are carried by a rack
124 with wheels 126 for portability. In alternative embodiments,
the controller 114 can be contained in, attached to, or integrated
with the multi-modality applicator 204 and/or a patient protection
device. In yet other embodiments, the various components can be
fixedly installed at a treatment site. Further details with respect
to components and/or operation of applicators, treatment tower, and
other components may be found in commonly-assigned U.S. Patent
Publication No. 2008/0287839.
[0145] The system 100 can include an energy-generating unit 107 for
applying energy to the target region, for example, to further
interrogate cooled or heated cells via power-lines 109a-b. In one
embodiment, the energy-generating unit 107 can be a pulse
generator, such as a high voltage or low voltage pulse generator,
capable of generating and delivering a high or low voltage current,
respectively, through the power lines 109a, 109b to one or more
electrodes (e.g., cathode, anode, etc.) in the applicator 204. In
other embodiments, the energy-generating unit 107 can include a
variable powered RF generator capable of generating and delivering
RF energy, such as RF pulses, through the power lines 109a, 109b or
to other power lines (not shown). RF energy can be directed to
non-targeted tissue to help isolate cooling. For example, RF energy
can be delivered to non-targeted tissue, such as epidermal tissue,
to inhibit or prevent damage to such non-targeted tissue. In a
further embodiment, the energy-generating unit 107 can include a
microwave pulse generator, an ultrasound pulse laser generator, or
high frequency ultrasound (HIFU) phased signal generator, or other
energy generator suitable for applying energy. In additional
embodiments, the system 100 can include more than one
energy-generating unit 107 such as any one of a combination of the
energy modality generating units described herein. Systems having
energy-generating units and applicators having one or more
electrodes are described in commonly assigned U.S. Patent
Publication No. 2012/0022518 and U.S. patent application Ser. No.
13/830,413.
[0146] The applicator 204 can include one or more heat-exchanging
units. Each heat-exchanging unit can include or be associated with
one or more Peltier-type thermoelectric elements, and the
applicator 204 can have multiple individually controlled
heat-exchanging zones (e.g., between 1 and 50, between 10 and 45;
between 15 and 21, etc.) to create a custom spatial cooling profile
and/or a time-varying cooling profile. Each custom treatment
profile can include one or more segments, and each segment can
include a specified duration, a target temperature, and control
parameters for features such as vibration, massage, vacuum, and
other treatment modes. Applicators having multiple individually
controlled heat-exchanging units are described in commonly assigned
U.S. Patent Publication Nos. 2008/0077211 and 2011/0238051.
[0147] The applicator 204 can be applied with pressure or with a
vacuum type force to the subject's skin. Pressing against the skin
can be advantageous to achieve efficient treatment. In general, the
subject 101 has an internal body temperature of about 37.degree.
C., and the blood circulation is one mechanism for maintaining a
constant body temperature. As a result, blood flow through the
tissue to be treated can be viewed as a heat source that
counteracts the cooling of the desired targeted tissue. As such,
cooling the tissue of interest requires not only removing the heat
from such tissue but also that of the blood circulating through
this tissue. Thus, temporarily reducing or eliminating blood flow
through the treatment region, by means such as, e.g., applying the
applicator with pressure, can improve the efficiency of tissue
cooling (e.g., tissue cooling to reduce cellulite, wrinkles,
sagging skin, loose skin, etc.) and avoid excessive heat loss.
Additionally, a vacuum can pull tissue away from the body which can
assist in cooling targeted tissue.
[0148] FIG. 9 is a schematic cross-sectional view illustrating a
treatment device in the form of an applicator 200 for
non-invasively removing heat from target tissue in accordance with
an embodiment of the present technology. The applicator 200 can
include a cooling device 210 and an interface layer 220. In one
embodiment, the cooling device 210 includes one or more
thermoelectric elements 213 (e.g., Peltier-type TEC elements)
powered by a treatment tower (e.g., treatment tower 102 of FIGS. 2
and 8).
[0149] The applicator 200 can contain a communication component 215
that communicates with the controller 114 to provide a first sensor
reading 242, and a sensor 217 that measures, e.g., temperature of
the cooling device 210, heat flux across a surface of or plane
within the cooling device 210, tissue impedance, application force,
tissue characteristics (e.g., optical characteristics), etc. The
interface layer 220 can be a plate, a film, a covering, a sleeve, a
substance reservoir or other suitable element described herein and,
in some embodiments, may serve as the patient protection device
described herein.
[0150] The interface layer 220 can also contain a similar
communication component 225 that communicates with the controller
114 to provide a second sensor reading 244 and a sensor 227 that
measures, e.g., the skin temperature, temperature of the interface
layer 220, heat flux across a surface of or plane within the
interface layer 220, contact pressure with the skin 230 of the
patient, etc. For example, one or both of the communication
components 215, 225 can receive and transmit information from the
controller 114, such as temperature and/or heat flux information as
determined by one or both of sensors 217, 227. The sensors 217, 227
are configured to measure a parameter of the interface without
substantially impeding heat transfer between the cooling device 210
and the patient's skin 230. The applicator 200 can also contain
components described in connection with FIGS. 2 and 8.
[0151] In certain embodiments, the applicator 200 can include a
sleeve or liner 250 (shown schematically in phantom line) for
contacting the patient's skin 230, for example, to prevent direct
contact between the applicator 200 and the patient's skin 230, and
thereby reduce the likelihood of cross-contamination between
patients, minimize cleaning requirements for the applicator 200,
etc. The sleeve 250 can include a first sleeve portion 252 and a
second sleeve portion 254 extending from the first sleeve portion.
The first sleeve portion 252 can contact and/or facilitate the
contact of the applicator 200 with the patient's skin 230, while
the second sleeve portion 254 can be an isolation layer extending
from the first sleeve portion 252. The second sleeve portion 254
can be constructed from latex, rubber, nylon, Kevlar.RTM., or other
substantially impermeable or semi-permeable material. The second
sleeve portion 254 can prevent contact between the patient's skin
230 and the cooling device 210, among other things. Further details
regarding a patient protection device may be found in U.S. Patent
Publication No. 2008/0077201.
[0152] A device (not shown) can assists in maintaining contact
between the applicator 200 (such as via an interface layer 220) and
the patient's skin 230. The applicator 200 can include a belt or
other retention devices (not shown) for holding the applicator 200
against the skin 230. A belt may be rotatably connected to the
applicator 200 by a plurality of coupling elements that can be, for
example, pins, ball joints, bearings, or other type of rotatable
joints. Alternatively, retention devices can be rigidly affixed to
the end portions of the interface layer 220. Further details
regarding suitable belt devices or retention devices may be found
in U.S. Patent Publication No. 2008/0077211.
[0153] A vacuum can assist in providing contact between the
applicator 200 (such as via the interface layer 220 or sleeve 250)
and the patient's skin 230. The applicator 200 can provide
mechanical energy to a treatment region using the vacuum. Imparting
mechanical vibratory energy to the patient's tissue by repeatedly
applying and releasing (or reducing) the vacuum, for instance,
creates a massage action during treatment. Further details
regarding vacuums and vacuum type devices may be found in U.S.
Patent Application Publication No. 2008/0287839.
[0154] Optionally, the applicator 200 can include one or more
features used with supercooling. For example, the interface layer
220 can include one or more nucleation elements 231, 233 in the
form of positive and negative electrodes for heating the skin using
alternating current heating. For radiofrequency induced nucleation,
the nucleation elements 231, 233 can be RF electrodes. The power
supply 110 (FIG. 8) of the treatment tower 102 can include an RF
generator for driving the nucleation elements 231, 233. The
nucleation elements 231, 233 can also be configured to provide
changes in applied pressure to cause nucleation. Any number of
different types of nucleation elements can be incorporated into the
interface layer 220 or other components of the applicator 200 to
provide the ability to controllably nucleate supercooled
tissue.
[0155] Although the thermoelectric elements 213 can heat tissue,
the applicator 200 can also include dedicated heating elements used
to, for example, thaw tissue. The interface layer 220 or other
components of the applicator 200 can include one or more heaters
235 for generating heat delivered to the surface of the skin 230.
The heaters 235 can be resistive heaters, Peltier devices, or other
thermoelectric elements capable of generating heat. Optionally, the
nucleation elements 231, 233 can also be used to control the
temperature of the skin 230. For example, the nucleation elements
231, 233 can include RF electrodes that cooperate to deliver RF
energy to heat the skin 230 or deeper tissue.
[0156] FIGS. 10A to 10C illustrate treatment devices suitable for
use with the treatment systems in accordance with embodiments of
the technology. FIG. 10A is a schematic, cross-sectional view
illustrating an applicator 260 for non-invasively removing heat
from target areas of a subject 262. The applicator 260 can include
a heat-exchanging unit or cooling device, such as a heat-exchanging
plate 264 (shown in phantom line) and an interface layer 265 (shown
in phantom line). The interface layer 265 can have a rigid or
compliant concave surface 267. When the applicator 260 is held
against the subject, the subject's tissue can be pressed against
the curved surface 267. One or more vacuum ports can be positioned
along the surface 267 to draw the skin 262 against the surface 267.
The configuration (e.g., dimensions, curvature, etc.) of the
applicator 260 can be selected based on the treatment site.
[0157] FIG. 10B is a schematic, cross-sectional view illustrating
an applicator 270 that includes a heat-exchanging unit 274 having a
rigid or compliant convex surface 276 configured to be applied to
concave regions of the subject. Advantageously, the convex surface
276 can spread tissue to reduce the distance between the convex
surface 276 and targeted tissue under the convex surface 276.
[0158] FIG. 10C is a schematic, cross-sectional view illustrating
an applicator 280 including a surface 282 movable between a planar
configuration 284 and a non-planar configuration 285 (shown in
phantom). The surface 282 is capable of conforming to the treatment
site to provide a large contact area. In some embodiments, the
surface 282 can be sufficiently compliant to conform to highly
contoured regions of a subject's face when the applicator 280 is
pressed against facial tissue. In other embodiments, the applicator
280 can include actuators or other devices configured to move the
surface 282 to a concave configuration, a convex configuration, or
the like. The surface 282 can be reconfigured to treat different
treatment sites of the same subject or multiple subjects.
[0159] FIG. 11 is a schematic, cross-sectional view of an
applicator 300 for non-invasively removing heat from target areas
in accordance with another embodiment of the technology. The
applicator 300 includes a housing 301 having a vacuum cup 302 with
a vacuum port 304 disposed in the vacuum cup 302. The housing 301
is coupled to or otherwise supports a first applicator unit 310a on
one side of the cup 302, and a second applicator unit 310b on an
opposing side of the cup 302. Each of the first and second
applicator units 310a, 310b can include a heat-exchanging unit
(e.g., a cooling unit, heating/cooling device, etc.) with a
heat-exchanging plate 312 (shown individually as 312a and 312b),
and an interface layer 314 (shown individually as 314a and 314b).
In one embodiment, the heat-exchanging plate 312 is associated with
one or more Peltier-type TEC elements supplied with coolant and
power from the treatment tower 102 (FIGS. 2 and 6). As such, the
heat-exchanging plates 312a, 312b can be similar to the cooling
device 210 described above with reference to FIG. 9.
[0160] The interface layers 314a and 314b are adjacent to the
heat-exchanging plates 312a and 312b, respectively. Similar to the
interface layer 220 illustrated in FIG. 9, the interface layers
314a and 314b can be plates, films, a covering, a sleeve, a
reservoir or other suitable element located between the
heat-exchanging plates 312a and 312b and the skin (not shown) of a
subject. In one embodiment, the interface layers 314a and 314b can
serve as patient protection devices and can include communication
components (not shown) and sensors (not shown) similar to those
described with respect to the interface layer 220 of FIG. 9 for
communicating with the controller 114. In other embodiments, the
interface layers 314 can be eliminated.
[0161] In operation, a rim 316 of the vacuum cup 302 is placed
against the skin of a subject and a vacuum is drawn within the cup
302. The vacuum pulls the tissue of the subject into the cup 302
and coapts the target area with the interface layers 314a and 314b
of the corresponding first and second applicator units 310a, 310b.
One suitable vacuum cup 302 with cooling units is described in U.S.
Pat. No. 7,367,341. The vacuum can stretch or otherwise
mechanically challenge skin. Applying the applicator 300 with
pressure or with a vacuum type force to the subject's skin or
pressing against the skin can be advantageous to achieve efficient
treatment. The vacuum can be used to damage (e.g., via mechanically
massage) and/or stretch connective tissue, thereby lengthen the
connective tissue. In general, the subject has an internal body
temperature of about 37.degree. C., and the blood circulation is
one mechanism for maintaining a constant body temperature. As a
result, blood flow through the skin and subcutaneous layer of the
region to be treated can be viewed as a heat source that
counteracts the cooling of the desired targeted tissue. As such,
cooling the tissue of interest requires not only removing the heat
from such tissue but also that of the blood circulating through
this tissue. Temporarily reducing or eliminating blood flow through
the treatment region, by means such as, e.g., applying the
applicator with pressure, can improve the efficiency of tissue
cooling and avoid excessive heat loss through the dermis and
epidermis. Additionally, a vacuum can pull skin away from the body
which can assist in cooling targeted tissue.
[0162] The units 310a and 310b can be in communication with a
controller (e.g., controller 114 of FIGS. 2 and 8), and a supply
such that the heat-exchanging plates 312a, 312b can provide cooling
or energy to the target region based on a predetermined or
real-time determined treatment protocol. For example, the
heat-exchanging plates 312a, 312b can first be cooled to cool the
adjacent tissue of the target region to a temperature below
37.degree. C. (e.g., to a temperature in the range of between about
-40.degree. C. to about 20.degree. C.). The heat-exchanging plates
312a, 312b can be cooled using Peltier devices, cooling channels
(e.g., channels through which a chilled fluid flows), cryogenic
fluids, or other similar cooling techniques. In one embodiment, the
heat-exchanging plates 312a, 312b are cooled to a desired treatment
temperature (e.g., -40.degree. C., -30.degree. C., -25.degree. C.,
-20.degree. C., -18.degree. C., -15.degree. C., -10.degree. C.,
-5.degree. C., 0.degree. C., or 5.degree. C.). In this example, the
lipid-rich cells can be maintained at a sufficiently low
temperature to be damaged or destroyed.
F. Suitable Computing Environments
[0163] FIG. 12 is a schematic block diagram illustrating
subcomponents of a computing device 700 suitable for the system 100
of FIGS. 2 and 8 in accordance with an embodiment of the
disclosure. The computing device 700 can include a processor 701, a
memory 702 (e.g., SRAM, DRAM, flash, or other memory devices),
input/output devices 703, and/or subsystems and other components
704. The computing device 700 can perform any of a wide variety of
computing processing, storage, sensing, imaging, and/or other
functions. Components of the computing device 700 may be housed in
a single unit or distributed over multiple, interconnected units
(e.g., though a communications network). The components of the
computing device 700 can accordingly include local and/or remote
memory storage devices and any of a wide variety of
computer-readable media.
[0164] As illustrated in FIG. 12, the processor 701 can include a
plurality of functional modules 706, such as software modules, for
execution by the processor 701. The various implementations of
source code (i.e., in a conventional programming language) can be
stored on a computer-readable storage medium or can be embodied on
a transmission medium in a carrier wave. The modules 706 of the
processor can include an input module 708, a database module 710, a
process module 712, an output module 714, and, optionally, a
display module 716.
[0165] In operation, the input module 708 accepts an operator input
719 via the one or more input/output devices described above with
respect to FIG. 6, and communicates the accepted information or
selections to other components for further processing. The database
module 710 organizes records, including patient records, treatment
data sets, treatment profiles and operating records and other
operator activities, and facilitates storing and retrieving of
these records to and from a data storage device (e.g., internal
memory 702, an external database, etc.). Any type of database
organization can be utilized, including a flat file system,
hierarchical database, relational database, distributed database,
etc.
[0166] In the illustrated example, the process module 712 can
generate control variables based on sensor readings 718 from
sensors (e.g., sensor 167 of FIG. 1B, the temperature measurement
components 217 and 227 of FIG. 9, etc.) and/or other data sources,
and the output module 714 can communicate operator input to
external computing devices and control variables to the controller
114 (FIGS. 2, 8, and 9). The display module 816 can be configured
to convert and transmit processing parameters, sensor readings 818,
output signals 720, input data, treatment profiles and prescribed
operational parameters through one or more connected display
devices, such as a display screen, printer, speaker system, etc. A
suitable display module 716 may include a video driver that enables
the controller 114 to display the sensor readings 718 or other
status of treatment progression (FIGS. 2 and 8).
[0167] In various embodiments, the processor 701 can be a standard
central processing unit or a secure processor. Secure processors
can be special-purpose processors (e.g., reduced instruction set
processor) that can withstand sophisticated attacks that attempt to
extract data or programming logic. The secure processors may not
have debugging pins that enable an external debugger to monitor the
secure processor's execution or registers. In other embodiments,
the system may employ a secure field programmable gate array, a
smartcard, or other secure devices.
[0168] The memory 702 can be standard memory, secure memory, or a
combination of both memory types. By employing a secure processor
and/or secure memory, the system can ensure that data and
instructions are both highly secure and sensitive operations such
as decryption are shielded from observation. The memory 702 can
contain executable instruction for cooling the surface of the
subject's skin to a temperature and controlling treatment devices
in response to, for example, detection of a or total freeze event.
The memory 702 can include thawing instructions that, when
executed, causes the controller to control the applicator to heat
tissue. In some embodiments, the memory 702 stores instructions
that can be executed to control the applicators to perform the
methods disclosed herein without causing undesired effects, such as
significantly lightening or darkening skin one of more days after
the freeze event ends. The instructions and treatment programs can
be modified based on patient information, treatments to be
performed, or other treatment parameters. The instructions can be
executed to perform the methods disclosed herein.
[0169] Suitable computing environments and other computing devices
and user interfaces are described in commonly assigned U.S. Pat.
No. 8,275,442, entitled "TREATMENT PLANNING SYSTEMS AND METHODS FOR
BODY CONTOURING APPLICATIONS," which is incorporated herein in its
entirety by reference.
G. Conclusion
[0170] It will be appreciated that some well-known structures or
functions may not be shown or described in detail, so as to avoid
unnecessarily obscuring the relevant description of the various
embodiments. Although some embodiments may be within the scope of
the technology, they may not be described in detail with respect to
the Figures. Furthermore, features, structures, or characteristics
of various embodiments may be combined in any suitable manner. The
technology disclosed herein can be used for improving the
appearance of skin and to perform the procedures disclosure in U.S.
Provisional Application Ser. No. 61/943,250, filed Feb. 21, 2014,
U.S. Pat. No. 7,367,341 entitled "METHODS AND DEVICES FOR SELECTIVE
DISRUPTION OF FATTY TISSUE BY CONTROLLED COOLING" to Anderson et
al., and U.S. patent Publication No. US 2005/0251120 entitled
"METHODS AND DEVICES FOR DETECTION AND CONTROL OF SELECTIVE
DISRUPTION OF FATTY TISSUE BY CONTROLLED COOLING" to Anderson et
al., the disclosures of which are incorporated herein by reference
in their entireties. The technology disclosed herein can target
tissue for tightening the skin, improving skin tone or texture,
eliminating or reducing wrinkles, increasing skin smoothness as
disclosed in U.S. Provisional Application Ser. No. 61/943,250.
[0171] Unless the context clearly requires otherwise, throughout
the description, the words "comprise," "comprising," and the like
are to be construed in an inclusive sense as opposed to an
exclusive or exhaustive sense; that is to say, in a sense of
"including, but not limited to." Words using the singular or plural
number also include the plural or singular number, respectively.
Use of the word "or" in reference to a list of two or more items
covers all of the following interpretations of the word: any of the
items in the list, all of the items in the list, and any
combination of the items in the list. In those instances where a
convention analogous to "at least one of A, B, and C, etc." is
used, in general such a construction is intended in the sense of
the convention (e.g., "a system having at least one of A, B, and C"
would include but not be limited to systems that have A alone, B
alone, C alone, A and B together, A and C together, B and C
together, and/or A, B, and C together, etc.). In those instances
where a convention analogous to "at least one of A, B, or C, etc."
is used, in general such a construction is intended in the sense of
the convention (e.g., "a system having at least one of A, B, or C"
would include but not be limited to systems that have A alone, B
alone, C alone, A and B together, A and C together, B and C
together, and/or A, B, and C together, etc.).
[0172] Any patents, applications and other references, including
any that may be listed in accompanying filing papers, are
incorporated herein by reference. Aspects of the described
technology can be modified, if necessary, to employ the systems,
functions, and concepts of the various references described above
to provide yet further embodiments. While the above description
details certain embodiments and describes the best mode
contemplated, no matter how detailed, various changes can be made.
Implementation details may vary considerably, while still being
encompassed by the technology disclosed herein. The various aspects
and embodiments disclosed herein are for purposes of illustration
and are not intended to be limiting, with the true scope and spirit
being indicated by the following claims.
* * * * *