U.S. patent application number 17/072020 was filed with the patent office on 2021-02-11 for treatment systems, methods, and apparatuses for improving the appearance of skin and 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 | 20210038278 17/072020 |
Document ID | / |
Family ID | 1000005164296 |
Filed Date | 2021-02-11 |
United States Patent
Application |
20210038278 |
Kind Code |
A1 |
DeBenedictis; Leonard C. ;
et al. |
February 11, 2021 |
TREATMENT SYSTEMS, METHODS, AND APPARATUSES FOR IMPROVING THE
APPEARANCE OF SKIN AND PROVIDING OTHER TREATMENTS
Abstract
Treatment systems, methods, and apparatuses for improving the
appearance of skin or other target regions are described as well as
for providing for other treatments. 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
of cellulite. Treatments can include cooling a surface of a
patient's skin and detecting at least one freeze event in the
cooled skin. The treatment system can continue cooling the
patient's skin after the freeze event(s) are detected so to
maintain at least a partially frozen state of the tissue for a
period of time.
Inventors: |
DeBenedictis; Leonard C.;
(Dublin, CA) ; Frangineas, JR.; George; (Fremont,
CA) ; Tatsutani; Kristine; (Redwood City, CA)
; Pham; Linda; (Kensington, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Zeltiq Aesthetics, Inc. |
Pleasanton |
CA |
US |
|
|
Family ID: |
1000005164296 |
Appl. No.: |
17/072020 |
Filed: |
October 15, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16233951 |
Dec 27, 2018 |
10806500 |
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17072020 |
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14611127 |
Jan 30, 2015 |
10201380 |
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16233951 |
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61934549 |
Jan 31, 2014 |
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61943250 |
Feb 21, 2014 |
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61943257 |
Feb 21, 2014 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2018/00291
20130101; A61F 2007/0052 20130101; A61K 31/045 20130101; A61B
2018/00875 20130101; A61B 2018/00714 20130101; A61B 18/02 20130101;
A61F 2007/0087 20130101; A61F 2007/0003 20130101; A61F 2007/0004
20130101; A61F 2007/0047 20130101; A61B 90/04 20160201; A61F 7/007
20130101; A61B 2090/065 20160201; A61H 1/008 20130101; A61H 1/006
20130101; A61B 2018/0262 20130101; A61F 2007/0096 20130101; A61F
7/00 20130101; A61N 7/00 20130101; A61B 2018/00464 20130101; A61F
2007/0036 20130101; A61F 2007/0045 20130101; A61F 2007/0075
20130101; A61B 2090/0463 20160201; A61F 2007/0019 20130101; A61B
2018/00791 20130101; A61F 2007/0093 20130101; A61K 31/047 20130101;
A61F 2007/0056 20130101; A61B 18/0206 20130101; A61B 2018/0237
20130101; A61B 2018/00994 20130101 |
International
Class: |
A61B 18/02 20060101
A61B018/02; A61F 7/00 20060101 A61F007/00; A61H 1/00 20060101
A61H001/00; A61N 7/00 20060101 A61N007/00; A61K 31/045 20060101
A61K031/045; A61K 31/047 20060101 A61K031/047; A61B 90/00 20060101
A61B090/00 |
Claims
1. A treatment method for improving the appearance of skin, the
treatment method comprising: removing heat from a treatment site of
a subject using a cooling device applied to the subject's skin to
reduce a temperature of the treatment site to no lower than -40
degrees C. to produce a cold shock response for affecting proteins
that improve the appearance of the skin at the treatment site by
tightening the skin, improving skin tone and texture, eliminating
or reducing wrinkles, increasing skin smoothness, or improving the
appearance of cellulite.
2. The method of claim 1, wherein the proteins are heat shock
proteins, cold shock proteins, and/or stress response proteins.
3. The method of claim 1, wherein removing heat from the treatment
site includes cooling the treatment site to a temperature for
increasing a protein synthesis rate of one or more of the
proteins.
4. The method of claim 1, wherein the improvement in the appearance
of skin does not include significant lightening or darkening of a
color of the skin days after stopping removal of heat from the
treatment site using the cooling device.
5. The method of claim 1, further including controlling the cooling
device to remove the heat from the treatment site to at least
partially freeze tissue without causing significant lightening or
darkening of a color of the skin days after the removal of heat
from the treatment site event stops.
6. The method of claim 1, wherein heat is removed from the
treatment site for a period of time less than about 40 minutes.
7. The method of claim 1, further including controlling the cooling
device to remove the heat from the treatment site without causing a
thermal injury to subcutaneous adipose tissue below the treatment
site.
8. A method for improving an appearance of skin, the method
comprising: applying a cooling surface of a cooling device to a
surface of a patient's skin; and cooling the surface of the
patient's skin using the cooling surface to keep dermal tissue of
the patient cool long enough to produce at least one cold shock
response that causes one or more of visible tightening the skin,
visible improvement to skin tone or texture, elimination or
reduction of wrinkles, increase in skin smoothness, or improvement
the appearance of cellulite.
9. The method of claim 8, wherein the cold shock response affects
proteins, the proteins including one or more of heat shock
proteins, cold shock proteins, or stress response proteins.
10. The method of claim 8, wherein cooling of the surface of the
patient's skin does not cause significant lightening or darkening
of a color of the cooled surface of the skin days after the freeze
event ends.
11. The method of claim 8, wherein cooling the surface of the
patient's skin causes a freeze event in the skin that produces the
at least one cold shock response.
12. The method of claim 11, wherein the freeze event does not cause
significant lightening or darkening of a color of the skin days
after the freeze event ends.
13. The method of claim 8, wherein heat is removed from the
treatment site for a period of time less than about 40 minutes.
14. The method of claim 8, further comprising monitoring the
cooling of the surface of the patient's skin using at least one
sensor, and controlling the cooling device based on output from the
at least one sensor.
15. The method of claim 8, further including controlling the
cooling device to remove the heat from the treatment site without
causing a thermal injury to subcutaneous adipose tissue below the
treatment site.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a divisional of U.S. patent
application Ser. No. 16/233,951, filed Dec. 27, 2018, which is a
divisional of U.S. patent application Ser. No. 14/611,127, filed
Jan. 30, 2015, now U.S. Pat. No. 10,201,380, which claims priority
under 35 U.S.C. .sctn. 119(e) to U.S. Provisional Application Ser.
No. 61/943,250, filed Feb. 21, 2014, U.S. Provisional Application
Ser. No. 61/934,549, filed Jan. 31, 2014, and U.S. Provisional
Application Ser. No. 61/943,257, 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. Pat. No. 8,337,539 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. Pat. No. 9,132,031 entitled "COOLING DEVICE HAVING A
PLURALITY OF CONTROLLABLE COOLING ELEMENTS TO PROVIDE A
PREDETERMINED COOLING PROFILE";
[0010] U.S. Patent Publication No. 2009/0118722, 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. Pat. No. 8,523,927 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. Pat. No. 8,603,073 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. Pat. No. 8,702,774 entitled "DEVICE, SYSTEM AND METHOD
FOR REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS";
[0025] U.S. Pat. No. 8,676,338 entitled "COMBINED MODALITY
TREATMENT SYSTEMS, METHODS AND APPARATUS FOR BODY CONTOURING
APPLICATIONS";
[0026] U.S. Pat. No. 9,314,368 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. Pat. No. 9,844,461 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. Pat. No. 9,545,523 entitled "MULTI-MODALITY TREATMENT
SYSTEMS, METHODS AND APPARATUS FOR ALTERING SUBCUTANEOUS LIPID-RICH
TISSUE"; and
[0030] U.S. Pat. No. 9,844,460 entitled "TREATMENT SYSTEMS WITH
FLUID MIXING SYSTEMS AND FLUID-COOLED APPLICATORS AND METHODS OF
USING THE SAME".
TECHNICAL FIELD
[0031] The present disclosure relates generally to treatment
devices, methods, and apparatuses for affecting targeted tissue. In
particular, several embodiments are directed to treatment systems,
methods, and apparatuses for improving the appearance of skin or
for providing for other patient treatments.
BACKGROUND
[0032] Rhytide (e.g., wrinkles) can affect the appearance of skin
on the face and other areas of the body and may be an indicator of
age. For example, wrinkles may be present around the eyes, mouth,
forehead, neck, hands, etc. As the skin naturally ages, cell
division reduces, skin loosens, and skin sags. Age-related
wrinkling of the skin can be promoted and/or exacerbated by
habitual facial expressions or sleeping patterns, as well as poor
hydration. Exposure to ultraviolet radiation and tobacco smoke can
accelerate the skin's aging process and result in premature
wrinkling. Wrinkles, loose sagging skin, poor skin tone or texture,
and other skin abnormalities are often considered to be visually
unappealing and have proved to be difficult and vexing problems to
treat, although the demand for effective treatments has been and
remains quite high. A need exists for more effective treatments of
these conditions and other conditions. Accordingly, it is an
objective of various embodiments of the present invention to
address these and other needs.
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] In the drawings, identical reference numbers identify
similar elements or acts.
[0034] FIG. 1A is a schematic cross-sectional view of tissue with
an undesirable appearance.
[0035] FIG. 1B is a schematic cross-sectional view of the tissue in
FIG. 1A with an improved appearance. An applicator is in thermal
contact with the surface of the skin.
[0036] FIG. 2 is a partially schematic isometric view of a
treatment system for improving the appearance of facial skin in
accordance with an embodiment of the disclosure.
[0037] FIGS. 3 to 5B are flow diagrams illustrating methods for
improving the appearance of skin in accordance with embodiments of
the technology.
[0038] FIG. 6 is a partially schematic isometric view of a
treatment system treating tissue located along a subject's torso in
accordance with an embodiment of the disclosure.
[0039] FIG. 7 is a partial cross-sectional view illustrating a
treatment device in accordance with embodiments of the
technology.
[0040] FIGS. 8A to 8C are schematic cross-sectional views
illustrating treatment devices in accordance with embodiments of
the technology.
[0041] FIG. 9 is a partial cross-sectional view illustrating a
vacuum treatment device in accordance with another embodiment of
the technology.
[0042] FIG. 10 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 an
embodiment of the technology.
DETAILED DESCRIPTION
A. Overview
[0043] The present disclosure describes treatment systems and
methods for improving the appearance of tissue and other
treatments. 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.
[0044] 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. The headings provided herein are
for convenience only and are not intended to limit or interpret the
scope or meaning of the technology.
[0045] At least some embodiments are directed to reducing or
eliminating wrinkles, loose skin, sagging skin, poor skin tone or
texture, and other skin irregularities often considered to be
cosmetically unappealing. Some embodiments are directed to skin
tightening and/or improving the appearance of cellulite. As used
herein, the term "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,
improving the appearance of cellulite, or other similar effects.
What is not included in the term is treating the skin to such an
extent 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. Treatment
systems disclosed herein can improve skin appearance by causing
skin tightening, thickening of tissue (e.g., thickening of the
epidermis, dermis, and/or subcutaneous tissue), and/or inducing a
cold shock response at the cellular level so as to improve skin
tone, skin texture, and/or skin smoothness. In one embodiment, a
treatment system has an applicator configured to be applied to a
subject's face to treat wrinkles around the eyes, mouth, forehead,
etc. The applicator can cool facial tissue to reduce the number of
visible wrinkles, reduce the size of wrinkles (e.g., depths,
lengths, etc.), or the like. Conformable or contoured applicators
can be applied to highly contoured regions around the eyes to
reduce or eliminate, for example, crow's feet wrinkles. Treatment
systems can also have applicators configured to be applied to other
locations along the subject's body. The shape, configuration,
mechanical properties, and cooling capabilities of the applicators
can be selected based on the tissue characteristics at the
treatment site.
[0046] Various aspects of the technology are directed to
non-invasive applicators that cool the epidermis, dermis, and/or
other tissue for a period of time selected to localize thermal
effects in targeted tissue while preventing thermal effects in
deeper non-targeted tissue. Oftentimes, but not always, target
tissue can be intermediate (not surface and not deep) tissue. For
example, when treating the face, it is often undesirable to injure
the subcutaneous layer beneath the skin, which acts as a support
layer for the skin. Additionally, when treating the face and other
body areas, it is desirable to minimize or control injury to the
epidermis. In an extreme case, if the epidermis is overly frozen,
hyperpigmentation (skin darkening) or hypopigmentation (skin
lightening) can result, which is often undesirable. At least some
embodiments are methods and apparatuses for non-invasively cooling
relatively shallow tissue located along the face, neck, hands,
hips, buttock, thighs, etc. Targeted tissue be cooled to a
temperature equal to or below about -40.degree. C., -35.degree. C.,
-30.degree. C., -25.degree. C., -20.degree. C., -10.degree. C., or
-5.degree. C. for a treatment period equal to or longer than 1
second, 2 seconds, 3 seconds, 5 seconds, 30 seconds, 1 minute, a
few minutes, or the like. In some embodiments, targeted epidermal
and/or dermal tissue can be cooled to a temperature between about
-40.degree. C. and about 0.degree. C., between about -35.degree. C.
and about 0.degree. C., between about -30.degree. C. and about
0.degree. C., between about -25.degree. C. and about 0.degree. C.,
or between about -20.degree. C. and about 0.degree. C. In some
embodiments, the treatment period can be exceed about 1 minute, 5
minutes, or 20 minutes, or other periods of time selected based on
the treatment to be performed. In some embodiments, the treatment
period can be shorter than about 1 minute, 5 minutes, 10 minutes,
20 minutes, 30 minutes, or 1 hour. In some procedures, the surface
of the patient's skin is cooled to a temperature equal to or
greater than about -40.degree. C., -35.degree. C., -30.degree. C.
-25.degree. C., -20.degree. C., -10.degree. C., -5.degree. C., or
0.degree. C. Non-targeted tissue may be subcutaneous adipose
tissue, epidermal tissue, or other non-targeted tissue that remains
at a higher temperature or is otherwise protected, such as by use
of one or more cryoprotectants.
[0047] In some embodiments, a thermoelectric applicator can cool
the patient's skin to produce a cooling zone in the epidermal
and/or dermal layers. As such, cooling can be localized in the
epidermis and/or dermis. In some examples, the cooling zone can be
at a maximum depth equal to or less than about 2.5 mm. In one
procedure, a central region of the cooling zone (e.g., a zone where
the most tissue injury is created) can be at a maximum depth of
about 0.25 mm to about 1 mm, about 0.25 mm to about 1.5 mm, about
0.25 mm to about 2 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm
to about 2 mm, about 0.5 mm to about 2.5 mm, or about 0.5 mm to
about 3 mm. In some procedures, the depth of the cooling zone and
depth of the most significant tissue injury can be at a equal to or
less than about 1 mm, 1.5 mm, 2 mm, 2.5 mm, or 3 mm. In some
procedures for treating areas with thin skin (e.g., facial skin
around the eyes), the cooling zone can be located at a depth equal
to or less than about 1 mm, 0.25 mm, 0.5 mm, 1 mm, or 1.5 mm.
[0048] Various aspects of the technology are directed to improving
the appearance of skin by cooling a surface of a patient's skin to
produce at least a cooling event (e.g., a partial freeze event,
total freeze event, etc.). The cooling event can be detected, and a
cooling device 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. In one procedure, the tissue can be kept in
a partially or totally frozen state for longer than about, for
example, about 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.
[0049] In certain embodiments, methods for affecting skin of a
human subject's body include positioning an applicator of a cooling
apparatus on the subject and removing heat from a treatment site to
affect the appearance of the subject's skin without causing an
appreciable reduction of subcutaneous adipose tissue. A sufficient
amount of thermal energy can be removed from the site so as to
reduce wrinkles by, for example, reducing the number of visible
wrinkles and/or sizes of the wrinkles. In other embodiments, a
sufficient amount of thermal energy is removed from the treatment
site so as to tighten skin at the treatment site, or in further
embodiments, to alter the tissue between a surface of the skin and
subcutaneous lipid-rich cells of the subject's body. In a further
embodiment, tissue is cooled to induce fibrosis that increases the
firmness of tissue at the treatment site. Fibrosis can be induced
in the epidermis, dermis, and/or subcutaneous tissue. Vacuum
applicators can stretch or otherwise mechanically alter skin to
increase damage and fibrosis in the skin.
[0050] At least some aspects of the technology are directed to
treatment methods for affecting a target region of a human
subject's body to alter an appearance of a treatment site by
removing heat using a cooling apparatus to alter at least one of
skin tightness, smoothness, or skin surface irregularities. The
methods can include removing a sufficient amount of heat to produce
fibrosis that alters the subject's skin. In certain embodiments,
the fibrosis increases the tightness of the skin and/or increases
the smoothness of the surface of the skin. Other embodiments of the
technology are directed to methods of cooling tissue using a
cooling apparatus to produce a cold shock response for affecting
proteins that alter the appearance of the subject's skin. The
proteins can be heat shock proteins, cold shock proteins, and/or
stress response proteins. In one embodiment, tissue can be cooled
to a temperature for increasing a protein synthesis rate of one or
more of the proteins.
[0051] At least some embodiments of the technology are directed to
freezing skin to induce injury to the skin. An applicator can be
placed at a treatment site on the subject and can remove heat from
the subject's skin to controllably freeze the skin to control the
freeze injury (or trauma) to the skin. The freeze injury can
improve tissue appearance by, for example, tightening of the skin,
thickening of the skin, and/or inducing a cold shock response at
the cellular level. In some procedures, most of the skin located
between the applicator and subcutaneous tissue can experience at
least partial freezing. With or without freezing, at least some
embodiments of the technology are directed to controlling the
cooling device or providing other means for sufficiently protecting
the epidermis from injury to an extent that causes
hyperpigmentation (skin darkening) or hypopigmentation (skin
lightening). The other means can include 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.
[0052] In further embodiments of the technology, damage to tissue
(e.g., dermis and/or subcutaneous tissue) can be reduced or
eliminated by applying a substance to the subject's skin. In other
embodiments, tissue damage can be limited by applying energy to
non-targeted tissue while cooling the treatment site. For example,
electromagnetic energy, infrared energy, microwave energy,
radiofrequency energy, ultrasound energy, electrical energy (e.g.,
AC or DC electric fields), and/or light can be delivered to the
subject's skin to supply energy thereto. In certain arrangements,
the applied energy can inhibit the reduction of subcutaneous
lipid-rich cells while the treatment site is cooled by the
applicator.
[0053] Some aspects of the technology are directed to treatment
methods for affecting tissue of a human subject's body by cooling
tissue to produce a freeze event that affects at least one of skin
tone, thickness of the tissue layers (e.g., 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. 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.
[0054] Devices and systems that enable target tissue supercooling
are also described. 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.
[0055] Tissue can be supercooled by controllably cooling the
surface of the skin for altering and reducing adipose tissue, body
contouring and augmentation, treating of acne, treating
hyperhidrosis, or other cryotherapy applications. Aspects of the
disclosure are further directed to methods and devices that provide
protection of non-targeted cells, such as non-lipid-rich cells
(e.g., 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 for
performing cryotherapy methods can be configured to control thermal
parameters such that body fluids within the treatment site are
supercooled to temperatures below the freezing point without
forming or nucleating ice crystals. The supercooled body fluids can
then be intentionally nucleated to damage, reduce, disrupt, or
otherwise affect the 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.
[0056] Some of the embodiments disclosed herein can be for
cosmetically beneficial alterations of a variety of body regions.
As such, some treatment procedures may be for the sole purpose of
altering the body region to conform to a cosmetically desirable
look, feel, size, shape or other desirable cosmetic characteristic
or feature. Accordingly, at least some embodiments of the cosmetic
procedures can be performed without providing any, or in another
embodiment, providing minimal therapeutic effect. For example, some
treatment procedures may be directed to treatment goals that do not
include restoration of health, physical integrity, or the physical
well-being of a subject. In other embodiments, however, the
cosmetically desirable treatments may have therapeutic outcomes
(whether intended or not), such as, psychological benefits,
alteration of body hormones levels (by the reduction of adipose
tissue), etc. The cosmetic methods can target regions of a
subject's skin to change a subject's appearance. In another
embodiment, the methods can target skin irregularities, wrinkles,
sebaceous glands to treat acne, sweat glands to treat
hyperhidrosis, hair follicles to injure and remove hair, or other
targeted cells to change a subject's appearance or address a
therapeutic condition.
B. Treatment Sites
[0057] FIG. 1A is a schematic cross-sectional view of tissue with
skin 10 having wrinkles 20 (e.g., folds, ridges, or creases) that
may be located, for example, along the face, legs (e.g., thighs,
buttock, etc.), or other locations. The dimensions (e.g., depths,
lengths, etc.) of the wrinkles 20 can vary by body location and
typically increase over time. Wrinkles 20 typically affect the
epidermis 14 and dermis 12 layers of the skin; however, the
subdermal adipose and connective tissue can also play a role in the
appearance of skin irregularities. For example, loss of adipose or
fat cells 18 and/or weakened connective tissue 22 in the
subcutaneous layers (e.g., subdermal tissue 16) can increase the
appearance of wrinkles 20 in the skin 10.
[0058] FIG. 1B is a schematic cross-sectional view of the skin 10
of the subject in FIG. 1A with improved appearance. An illustrated
treatment device in the form of a thermoelectric applicator 104
("applicator 104") has affected tissue (e.g., skin 10, epidermis
14, dermis 12, or other targeted tissue) to reduce or eliminate the
wrinkles, improve skin tone and/or texture, increase skin
smoothness, and/or improve the appearance of cellulite. The
applicator 104 can perform different cryotherapy procedures
designed to make the skin 10 substantially free of visible
irregularities.
[0059] In one example, a heat-exchanging surface 19 of the
applicator 104 can be in thermal contact with a surface of the skin
10. A cooling device 103 of the applicator 104 can cool a treatment
site 15 and affect tissue at a cooling zone 21 (shown in phantom
line). A central region 17 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, or about 0.5 mm
to about 2 mm. The depth of the cooling zone 21 can be selected to
avoid injuring deeper subcutaneous tissue (e.g., subdermal tissue
16). In one procedure, the cooling zone 21 comprises mostly
epidermal tissue. In another procedure, the cooling device 103
cools and affects tissue in the cooling zone 21' (shown in
dashed-dot line) which comprises mostly epidermal and dermal
tissue. Adjacent tissue (e.g., subcutaneous tissue) may also be
cooled but can be at a sufficiently high temperature to avoid
thermal injury. In some procedures, the cooling zone 21' can
comprise most of the tissue located directly between the cooled
heat-exchanging surface 19 and the subcutaneous tissue (e.g.,
dermal tissue 16). For example, at least about 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'.
C. Cryotherapy
[0060] FIG. 2 and the following discussion provide a general
description of an example of a suitable non-invasive treatment
system 100 in which aspects of the technology can be implemented.
The treatment system 100 can be a temperature-controlled cooling
apparatus for cooling tissue at a targeted treatment site to
perform cryotherapy. Tissue characteristics affected by cryotherapy
can include, without limitation, tissue strength, tissue
elasticity, cell size, cell number, and/or tissue layer thickness.
For example, the treatment system 100 can cool the epidermis,
dermis, or other targeted tissue to reduce or eliminate skin
irregularities. Non-targeted tissue, such as subdermal tissue, can
remain generally unaffected. In one embodiment, cryotherapy can
increase the thicknesses of multiple tissue layers. In one example,
cooling can produce a cold shock response to increase the
thicknesses of the epidermis and/or dermis by affecting protein
proliferation and other cellular functions. Those skilled in the
relevant art will appreciate that other examples of the disclosure
can be practiced with other treatment systems and treatment
protocols, including invasive, minimally invasive, and other
non-invasive medical treatments.
[0061] The applicator 104 is suitable for altering a human
subject's skin without affecting subcutaneous tissue (e.g.,
subcutaneous adipose tissue and lipid-rich cells, etc.). The
applicator 104 can be suitable for reducing wrinkles (e.g.,
wrinkles 20 of FIG. 1A), loose skin, sagging skin, or other skin
surface irregularities by cooling the skin without permanently
altering cells of non-targeted tissue (e.g., deep dermal tissue,
subdermal tissue, etc.). Without being bound by theory, the effect
of cooling selected cells (e.g., cells of the skin, layers of
epidermis, etc.) is believed to result in, for example, protein
alteration (e.g., synthesis of heat shock proteins, stress
proteins, etc.), cell size alteration, cell division, wound
remodeling (e.g., thickening of the epidermis, contraction of the
epidermis, etc.), fibrosis, and so forth. By cooling the skin to a
sufficient low temperature, target cells that contribute to the
presence of undesired features can be selectively affected while
non-targeted tissue can be unaffected.
[0062] The applicator 104 can be used to perform a wide range of
different cryotherapy procedures. 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. To avoid destroying skin cells, 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 (including
long-lasting or permanent hyperpigmentation or hypopigmentation).
In another embodiment, destruction of skin cells can be avoided by
applying heat to the surface of the patient's skin to heat the skin
cells above their freezing temperature. The patient's skin can be
warmed to at least about -30.degree. C., -25.degree. C.,
-20.degree. C., -15.degree. C., -10.degree. C., 0.degree. C.,
10.degree. C., 20.degree. C., 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, skin can be cooled to produce partial freeze
events that cause apoptotic damage to skin tissue without causing
significant damage to adjacent subcutaneous tissue. Apoptosis, also
referred to as "programmed cell death", of the skin tissue can be a
genetically-induced death mechanism by which cells slowly
self-destruct without incurring damage to surrounding tissues.
Other cryotherapy procedures may cause non-apoptotic responses.
[0063] In some tissue-freezing procedures, the applicator 104 can
controllably freeze tissue and can optionally detect the freeze
event (or other 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 or
partially 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. 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 treatment, the applicator 104 can produce a
partial or total freeze event that includes, without limitation,
partial or full thickness freezing of the patient's skin for a
relatively short time limit to avoid cooling the adjacent
subcutaneous tissue to a low enough temperature for subcutaneous
cell death or undue injury to the subcutaneous layer. The freezing
process can include forming ice crystals in intracellular and/or
extracellular fluids, and the ice crystals can be small enough to
avoid disrupting membranes so as to 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. In other procedures,
partial freeze events can include freezing mostly intercellular
material without freezing a substantial amount of extracellular
material. The frozen target tissue can remain in the frozen state
long enough to affect the target tissue but short enough to avoid
damaging non-targeted tissue. For example, the duration of the
freeze event can be shorter than about 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 about 20 seconds, 30 seconds, or 45 seconds or about
1, 2, 3, 4, 5, or 10 minutes after initiation of the freeze
event.
[0064] In several embodiments, tissue can be cooled to induce cold
shock cellular responses in the region of the subject being treated
are a desirable outcome for beneficially alter (e.g., smoothing
and/or tightening) the skin. Without being bound by theory, it is
believed that exposure to cold induces a stress response cascade in
the interrogated cells that results in the immediate synthesis of
cytoprotective genes. Among these are genes that code for heat
shock proteins and/or chaperone proteins involved in protein
folding. Heat shock proteins can help alter a cell's phenotype by
either impeding, protecting or promoting protein function both
during the acute response to stress as well as to subsequent
stresses. Cold shock proteins (e.g., cold-inducible RNA-binding
protein (CIRP) that may have roles in cellular proliferation and
inflammation) have also been identified in mammalian cells.
Induction of cold shock cellular responses can dramatically change
a cell's proteome to promote cellular survival under environmental
interrogation and/or following cold-induced tissue injury. It has
been observed in mammalian cells that cold stress can alter the
lipid composition of the cellular membranes, as well as change
rates of protein synthesis and cell proliferation. Without being
bound by theory, the selective effect of cooling on target cells
(e.g., epidermal and/or dermal cells) is believed to result in, for
example, changes in cellular metabolism, proliferation,
survivability, wound healing, wound contraction and other cellular
responses that can improve tissue characteristics at the treatment
site.
[0065] The mechanisms of cold-induced tissue injury in cryotherapy
can also involve direct cellular injury (e.g., damage to the
cellular machinery) and/or vascular injury. For example, cell
injury can be controlled by adjusting thermal parameters, including
(1) cooling rate, (2) end (or minimum) temperature, (3) time held
at the minimum temperature (or hold time), (4) temperature profile,
and (5) thawing rate. In one example, increasing the hold time can
allow the intracellular compartments to equilibrate with the
extracellular space, thereby increasing cellular dehydration.
Another mechanism of cold-induced injury is cold and/or
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.
[0066] During an inflammatory phase of healing following
cold-induced injury, platelets are among the first cells to appear
at the treatment 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. 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, and
collagenase-1 disrupts attachment to fibrillar collagen which
allows for continued migration of keratinocytes into the treatment
site. It is during the proliferative phase that a healing process
following injury can result in a thicker epidermal layer with
increased cellular activity.
[0067] In additional embodiments, induction of fibrosis (e.g., the
formation of fibrous connective tissue) in the region of the
subject being treated is a desirable outcome for beneficially
altering the skin. For example, fibrosis can increase the amount of
connective tissue in a desired tissue layer (e.g., epidermis,
dermis, and/or subcutaneous tissue) to increase a firmness of the
tissue. In some embodiments, increased firmness of the tissue can
increase the tightness and/or the smoothness of the surface of the
skin. Without being bound by theory, cooling temperatures can
result in inflammation of the interrogated tissue. Immune cells,
such as macrophages, release transforming growth factor beta
(TGF-.beta.) which stimulates the proliferation and activation of
fibroblast cells. Migrating and activated fibroblast cells deposit
connective tissue, including collagen and glycosaminoglycans that
can thicken and/or strengthen the affected tissue. Such thickening
and/or firming of the affected tissue can beneficially alter skin
characteristics by reducing the appearance of wrinkles, fine lines,
loose skin, etc.
[0068] The system 100 can also perform treatments to affect
subcutaneous tissue by cooling the subject's skin for a period of
time long enough so that lipid-rich cells in a subcutaneous layer
are substantially affected. This can be desired particularly when
treating non-facial areas, such as the thighs, arms, abdomen etc.,
where a skin tightening effect is desired as well as a volumetric
reduction, which is aided by altering subcutaneous lipid rich
cells. The term "subcutaneous tissue" means tissue lying beneath
the dermis and includes subcutaneous fat, or adipose tissue, which
is composed primarily of lipid-rich cells, or adipocytes. It is
believed that shallow tissue can be cooled to improve skin
appearance while also cooling subcutaneous tissue to cause, for
example, apoptosis. Apoptosis of subcutaneous lipid-rich cells may
be a desirable outcome for beneficially altering (e.g., sculpting
and/or reducing) adipose tissue that may contribute to an
undesirable appearance. Apoptosis of subcutaneous lipid-rich cells
can involve ordered series of biochemical events that 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.
[0069] 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 at temperatures
that may or may 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, targeted adipose tissue 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., electromagnetic, 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.
[0070] 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).
[0071] Without being bound by theory, the 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
destroying the overlying skin cells. In some embodiments,
lipid-rich cells are destroyed while the appearance of overlying
skin is improved.
[0072] Deep hypodermal fat cells are more easily damaged by low
temperatures than the overlying dermal and epidermal layers of
skin, and as such, 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. It is believed that the
temperatures can be controlled to manage damage in the epidermis
and/or dermis via, for example, intracellular and/or extracellular
ice formation. Excessive ice formation may rupture the cell wall
and may also form sharp crystals that locally pierce the cell wall
as well as vital internal organelles. Ice crystal initiation and
growth can be managed to avoid cell death in the skin. 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 to be driven through the
semi-permeable cellular wall by osmosis resulting in cell
dehydration. The applicator 104 can reduce the temperature of the
deep lipid-rich cells such that the deep lipid rich cells are
destroyed while the temperature of the upper and surface skin cells
are maintained at a high enough temperature to produce
non-destructive freeze events in the skin. Cryoprotectants and/or
thermal cycling can prevent destructive freeze events in the skin
and limit injury to the skin cells.
D. Treatment Systems and Methods of Treatment
[0073] 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 components of the treatment system 100 can be selected and
implemented in various embodiments to apply selected treatment
profiles to the subject 101 (e.g., a human or an animal) for
improving the appearance of the treatment site. 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.
[0074] The applicator 104 can have one or more cooling devices
powered by electrical energy delivered via the power-lines 109a-b.
A control line 116 can provide communication between electrical
components of the applicator 104 and a controller 114 of the
treatment tower 102. The cooling devices 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 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 one embodiment, the applicator 104
can be a non-thermoelectric device that is heated/cooled using only
coolant. The applicator 104 can include sensors configured to
measure tissue impedance, treatment application force, and/or
tissue contact. As described herein, sensors can be used to monitor
tissue and, in some embodiments, detect freeze events. Applicators
configured to be applied to facial tissue can have pressure sensors
to monitor applied pressures to maintain a desired level of
comfort. The number and types of sensors can be selected based on
the treatment to be performed.
[0075] 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 that is 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. 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 made of 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. 6.
[0076] FIG. 2 shows the applicator 104 positioned to treat crow's
feet wrinkles near the patient's right eye. 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
partial or total freeze event is detected. Tissue can be monitored
to keep the tissue in the frozen state (e.g., at least partially or
totally 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, force/pressure applied to the subject
101, optical characteristics of tissue, and/or tissue contact
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.
[0077] The applicator 104 can be used at other treatment sites and
can be replaced with other applicators. Applicators can be
configured to treat identified portions of the patient's body, such
as the face, neck, chin, cheeks, arms, pectoral areas, thighs,
calves, buttocks, abdomen, "love handles", back, hands, and so
forth. For example, mask applicators can be used to cover the
subject's face. Conformable applicators can be applied along the
face, neck, or other highly contoured regions. By way of another
example, vacuum applicators may be applied at the back region, and
belt applicators can be applied around the thigh region, either
with or without massage or vibration as discussed in connection
with FIG. 9. Exemplary applicators and their configurations usable
or adaptable for use with the treatment system 100 variously 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.
[0078] In further embodiments, the system 100 of FIG. 2 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.
[0079] 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 that are 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 the 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 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 tissue to perform the methods discussed herein.
[0080] FIG. 3 is a flow diagram illustrating a method 140 for
improving the appearance of a subject's skin in accordance with
embodiments of the disclosure. 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 of the applicator
104. In another embodiment, the heat-exchanging surface 19 can be
the surface of an interface layer or a dielectric layer. Coupling
of the 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 thermally conductive substance can couple the heat-exchanging
surface 19 to the patient's skin and can optionally be a
cryoprotectant. Suitable and preferred cryoprotectants are
described in commonly assigned U.S. Patent Publication No.
2007/0255362.
[0081] At block 144, heat is removed from tissue for a period of
time that may vary depending on the location of the treatment site
and may induce cold shock, freeze tissue, injure tissue, etc.
Thermal injuries can induce fibrosis that increases the firmness
and/or tone of the tissue. In some cold shock procedures, the
subject's skin can be cooled to produce a cold shock response which
affects proteins, such as heat shock proteins, cold shock proteins,
and/or stress response proteins. In some embodiments, the subject's
skin can be cooled to a temperature no lower than about -40.degree.
C., -30.degree. C., -20.degree. C., -10.degree. C. to produce the
cold shock response. Additionally or alternatively, the treatment
site can be cooled to a temperature selected to increase a protein
synthesis rate of one or more of the proteins. Some treatment
protocols can include two or more segments each designed to produce
cold shocks responses, freeze tissue, or injure tissue. For
example, a treatment protocol may alternate between tissue-freeze
segments and tissue-thaw segments. In another example, one
treatment protocol can be designed to reduce wrinkles (e.g.,
age-related wrinkles) via shock proteins and another treatment
protocol can be designed to tighten loose tissue via fibrosis.
Accordingly, different treatment protocols can be used on different
parts of a patient's body. Although the method 140 is described
with reference to the treatment system 100 of FIG. 2, the method
140 may also be performed using other treatment systems with
additional or different applicators, hardware, and/or software
components.
[0082] FIG. 4 is a flow diagram illustrating a method 150 for
improving the appearance of skin in accordance with embodiments of
the disclosure. 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). At block 154,
the method 150 includes cooling the subject's skin to affect tissue
at the target region. In one embodiment, the skin's smoothness,
thickness, texture, tone, and/or elasticity is improved. In one
embodiment, the skin is cooled to induce a freeze-related injury,
and in another embodiment, the skin is cooled to induce a cold
shock response.
[0083] FIG. 5A is a flow diagram illustrating a method 160 for
improving the appearance of skin by producing a freeze event in
accordance with embodiments of the disclosure. Generally, a
treatment device can be applied to a subject and can cool a surface
of a patient'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
the appearance of the skin but not so long as to create undue
injury to tissue. Details of method 160 are discussed below.
[0084] At block 162, the treatment device is applied to a subject
by placing a heat-exchanging surface in thermal contact with the
subject's skin. In some embodiments, a substance is applied to the
subject's skin before applying the treatment device. A substance
can be used to (a) provide thermal coupling between the subject's
skin and cooling devices (e.g., cooling plates of cooling devices)
to improve heat transfer therebetween, (b) selectively protect
non-target tissues from freeze damage (e.g., damage due to
crystallization), and/or (c) promote freeze events by increasing
nucleation sites. 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 from
forming on a surface (e.g., heat-exchanging surface), and thus
reduces the delay in reapplying the treatment device to the
subject. Yet another aspect of the technology is that the
cryoprotectant may prevent the treatment device from freezing to
the skin of the patient or subject. Additionally or alternatively,
the 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
the introduction of cooling.
[0085] 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, a 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 liquids/lipids can be lowered
to about -10.degree. C. to about -40.degree. C., about -10.degree.
C. to about -30.degree. C., or to about -10.degree. C. to about
-20.degree. C. In certain embodiments, the freezing point of the
liquids/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 the liquids/lipids to a temperature of about
-1 .degree. C. to about -40.degree. C., about -5.degree. C. to
about -40.degree. C., or about -10 to about -40.degree. C.
[0086] Cryoprotectant can be intermittently or continuously
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 partial or total freeze event in dermal tissue but 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, 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
the substance that delivers cryoprotectant at a desired delivery
rate. Suitable pads include Webril.TM. pads manufactured by
Covidien of Mansfield, Mass. Further details regarding the
interface member and associated systems and methods are described
in commonly-assigned U.S. Patent Publication No. 2010/0280582.
[0087] In a certain embodiment, the system 100 (FIG. 2) can be used
to perform several treatment methods without using a chemical
cryoprotectant. FIG. 5B is a flow diagram illustrating a method 500
for improving the appearance of skin without any chemical
composition in accordance with embodiments of the disclosure. As
shown in FIG. 5B, an early stage of the method 500 can include
cooling a surface of a human subject's skin to a first temperature
(block 502). The first temperature can be, for example, between
about -5.degree. C. and -40.degree. C. such that a portion of
tissue below the surface is in a supercooled state. The supercooled
tissue can include epidermal tissue, dermal tissue, subcutaneous
tissue, other tissue, and combinations thereof.
[0088] The method 500 can also include heating the surface of the
human subject's skin in an amount sufficient to raise the
temperature of the surface or upper layer of tissue from the first
temperature to a second temperature that is a non-supercooled
temperature. Deeper tissue below the surface can remain in the
supercooled state (block 504). For example, the treatment system
can be used to heat the surface (e.g., an upper portion of the
epidermis) of the skin to a temperature greater than about
0.degree. C. while underlying tissue remains supercooled. In some
embodiments, tissue of the skin at a depth of less than about 0.2
mm, 0.5 mm, or 1 mm are warmed to a non-supercooled state. The
temperature of the skin surface can be increased about 40.degree.
C., 30.degree. C. 20.degree. C., 10.degree. C. during the warming
period (e.g., 0.5 second, 1 second, 2 seconds, 5 seconds, etc.).
The surface of the skin can be periodically heated to minimize or
limit thermal damage while deeper tissue is at or below the
treatment temperature (e.g., a temperature for supercooling).
[0089] In block 506, the method 500 can further include nucleating
the supercooled portion of tissue below warmed tissue to cause at
least some cells in the supercooled tissue to at least partially
freeze. In one embodiment, nucleation of the supercooled tissue is
caused by a mechanical perturbation (e.g., vibration, ultrasound
pulses, etc.) while warmed cells residing at the surface of the
human subject's skin do not freeze. This allows for localized
nucleation and protection of cells at the surface can be
accomplished without the use of a chemical cryoprotectant.
Optionally, a cryoprotectant may also be used to provide further
protection for epidermal tissue to minimize any undue damage
thereto which might result in a hyperpigmentation or
hypopigmentation response sometime after completing treatment. In
various embodiments, the supercooled tissue can comprise some
portion of the epidermal tissue (e.g., a lower region of epidermal
tissue), dermal tissue, connective tissue, subcutaneous tissue, or
other tissue targeted to experience a freeze injury.
[0090] In certain embodiments, the method 500 may further include
maintaining the supercooled tissue in at least a partially or
totally frozen state for a predetermined period of time (block
508). For example, the supercooled tissue can be maintained in the
at least partially or totally frozen state for longer than about 2
seconds, 5 seconds, 10 seconds, 12 seconds, 15 seconds, or 20
seconds. In various arrangements, the supercooled tissue can be
maintained in the at least partially or totally frozen state for a
duration of time sufficient to improve an appearance of skin or
provide for other treatments (e.g., tightening the skin, increasing
skin smoothness, thickening the skin, improving the appearance of
cellulite, improving acne, improving a quality of hair, improving a
condition associated with hyperhidrosis, etc.). In certain
embodiments, the maintaining the freeze event can include detecting
a temperature of the portion of tissue and controlling the cooling
and heating to maintain at least a portion of the tissue in at
least a partially or totally frozen state for the predetermined
time (e.g., greater than about 10 seconds, greater than about 12
seconds, greater than about 15 seconds, or greater than about 20
seconds).
[0091] Referring back to FIG. 5A, and at block 164, the treatment
device can rapidly cool the surface of the patient's skin to a
sufficiently low temperature to cause a partial or total 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 so that temperature equilibrium
is not established across the skin and adjacent subcutaneous
tissue, typically adipose tissue. A cryoprotectant and/or warming
cycle can be used to inhibit freezing the uppermost non-targeted
layer, or layers, of skin, particularly epidermal tissue, so as to
prevent or minimize any chance of creating hyperpigmentation or
hypopigmentation.
[0092] A partial 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 addition, total freeze
events can be created which are maintained for a period of time
which is kept short enough so as to not cause an undesired amount
of 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 in the skin without
causing irreversible skin damage. For example, the treatment system
100 of FIG. 2 can cool the skin to a temperature in a range from
about -40.degree. C. to about 0.degree. C. In another example, the
surface of the patient's skin can be cooled 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 -5.degree.
C., or from about -15.degree. C. to about -5.degree. C. In further
examples, the surface of the patient's skin can be cooled to below
about -10.degree. C., or in yet another embodiment, from about
-25.degree. C. to about -15.degree. C. It will be appreciated that
the skin surface can be cooled to other temperatures based on the
mechanism of action.
[0093] To perform cryotherapy, 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 less than about 30,
60, 90, 120, or 150 seconds and, in some embodiments, the
predetermined period of time can be from about 30 seconds to about
150 seconds. 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.
[0094] To help initiate the freeze event (e.g., the partial or
total freeze event), a substance, energy, and/or pressure can be
used to aid in the formation of nucleation sites for
crystallization. Substances that promote nucleation can be applied
topically before and/or during skin cooling. The 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
energy. The energy can also comprise alternating current electrical
energy. A nucleating substance can also optionally be applied to
the skin. The applicators disclosed herein can include one or more
actuators (e.g., motors with eccentric weights), vibratory motors,
hydraulic motors, electric motors, pneumatic motors, solenoids,
piezoelectric shakers, and so on for providing mechanical energy,
pressure, etc. Pressure for promoting nucleation can be applied
uniformly or non-uniformly across the treatment site. The
applicators can also include AC electrodes. For example, the
applicator 104 of FIG. 1B can include one or more elements 155 in
the form of actuators, motors, solenoids, piezoelectric shakers,
transducers (e.g., ultrasound transducers), electrodes (e.g.,
electrical electrodes, RF electrodes, etc.), or combinations
thereof. Substances that promote nucleation can be applied
topically before and/or during skin cooling.
[0095] At block 166, the treatment device can detect the partial or
total freeze event in the patient's skin 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, lipids, and fluids
freeze, crystals can form and energy associated with the latent
heat of crystallization of the tissue 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 to prevent small variations in
temperature from causing false alarms with respect to false
treatment events. Additionally or alternatively, the treatment
system disclosed herein may detect changes in the temperature of
its components or changes in power supplied to the treatment device
(e.g., treatment devices receive more power from the system to
provide additional cooling). For example, the sensor 167 can detect
changes in temperature of the applicator 104 as the applicator gets
colder in order to cool the tissue warmed by crystallization.
[0096] 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 a treatment event. 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.
[0097] The system 100 can use optical techniques to detect events
at block 166 of FIG. 5A. 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 because changes in
electrical impedance and/or mechanical properties of the tissue can
be detected and may indicate freezing of tissue. In embodiments for
measuring electrical impedance, 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, the sensor 167 can comprise one or
more mechanical sensors which can include, without limitation,
force sensors, pressure sensors, and so on.
[0098] At block 168, the partial or total freeze event can be
maintained 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 affect the skin and thereby 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,
or about 20 minutes to about 30 minutes. The length of time the
skin is kept frozen can be selected based on severity of the freeze
injury.
[0099] At block 168 of FIG. 5A, the treatment system can control
the applicator so that the partial or total freeze event causes
apoptotic damage to the target tissue and does not cause necrotic
damage to non-targeted tissue. The cooling period can be
sufficiently short to avoid or limit permanent tissue damage and,
in some embodiments, can be less than about, for example, 5
minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30
minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55
minutes, or 1 hour. In one example, the applicator produces a
partial freeze event short enough to prevent establishing
equilibrium temperature gradients in the patient's skin. 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. For example, skin cells can be reduced in size
or number to a greater extent than subcutaneous cells, including
lipid-rich cells. In some procedures, the subcutaneous layer can be
kept at a sufficiently high temperature (e.g., at or above
0.degree. C.) to prevent any freeze event in the subcutaneous layer
while the shallower skin tissue experiences the partial or total
freeze event. Cryoprotectant can be used to protect the
subcutaneous layer. Topical cryoprotectants can be absorbed by the
skin and can ultimately reach the subcutaneous layer.
Cryoprotectant can be injected directly into the subcutaneous layer
before performing the cooling cycle.
[0100] In some embodiments, the freeze event can occur in the
epidermal layer to injure, reduce, or disrupt the epidermal cells
without substantially injuring, reducing, or disrupting dermal
cells and/or subcutaneous cells. In other embodiments, the freeze
event can occur in the dermal layer to injure, reduce, or disrupt
dermal cells without substantially injuring, reducing, or
disrupting epidermal cells and/or subcutaneous cells. A
cryoprotectant can be used to protect the epidermal layer to avoid
causing long-lasting or permanent hyperpigmentation or
hypopigmentation. For example, a 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
partial or total freeze event in dermal tissue, but the period of
time can be long enough to provide substantial protection to
epidermal tissue. The cryoprotectant can prevent permanent
hyperpigmentation or hypopigmentation of epidermal tissue due to
tissue cooling, and the cryoprotectant delivery time and rate can
be selected based on the cryoprotectant's ability to protect
tissue. In one embodiment, the cryoprotectant prevents
hyperpigmentation or hypopigmentation of the skin surface and also
prevents damage of the epidermal tissue due to tissue cooling. In
yet other embodiments, the freeze event can occur in the epidermal
and dermal layers to injure, reduce, or disrupt the epidermal and
dermal cells without substantially injuring, reducing, or
disrupting subcutaneous tissue to avoid body contouring. Such
treatments are well suited for improving the appearance of skin
along the face, including wrinkled, loose, and/or sagging skin
around the eyes and mouth.
[0101] Certain treatment protocols can include sequentially
targeting different layers. A first treatment session can target
the epidermal layer and a subsequent additional treatment sessions
can target the other layers. Different layers can be targeted in a
different protocol.
[0102] The treatment system can also control operation of the
applicator to thermally injure the patient's skin 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
treatment system controls the applicator to supercool at least a
portion of tissue below the skin layer. A perturbation (e.g., a
mechanical perturbation) can be used to nucleate the supercooled
tissue to at least partially or totally freeze the tissue.
Alternating electric fields can be used to create nucleation
perturbations. Various substances can be applied to the treatment
site to facilitate nucleation of supercooled tissue.
[0103] At block 169, the patient's partially or completely frozen
skin can be thawed by heating it in order to minimize, reduce, or
limit tissue damage. The applicator (e.g., applicator 104 of FIG.
2) 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, 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 thermal elements can be resistive heaters,
electromagnetic energy emitters, Peltier devices, etc. In some
embodiments, the applicator 104 of FIGS. 1B and 2 can have cooling
elements and separate heating elements that can cooperate to
provide precise temperature control of freezing and thawing/warming
cycles. Alternatively, the applicator 104 may stop or reduce tissue
cooling to allow cooled tissue to naturally warm and thaw. Thus,
tissue can be actively or passively thawed.
[0104] The applicator 104 (FIG. 2) can thaw the patient's skin, or
other frozen tissue, after the freeze event occurs and after the
period of time has transpired to reduce and control freeze damage.
In one example, the uppermost skin layer can be periodically heated
to a temperature above the skin's freezing point to provide freeze
protection thereto. In some procedures, the applicator 104
repeatedly freezes and thaws tissue to control thermal injuries to
that tissue.
[0105] The system 100 can be used to perform several different
cryotherapy procedures. Although specific methods are described in
connection with FIGS. 3-5B, one skilled in the art is capable of
identifying other methods that the system 100 could perform.
Additionally, the treatment system 100 of FIG. 6 can perform the
methods described in connection with FIGS. 3-5B. Applicators are
discussed in connection with FIGS. 7-9 and can be used with the
system 100 (FIGS. 2 and 6) or different treatment systems to
perform the procedures disclosed herein.
[0106] FIG. 6 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.
[0107] 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.
[0108] 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. 6, 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.
[0109] 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.
[0110] 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 subdermal 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-generator 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.
[0111] 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.
[0112] 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.
[0113] FIG. 7 is a schematic cross-sectional view illustrating a
treatment device in the form 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 the treatment tower
(e.g., treatment tower 102 of FIGS. 2 and 6).
[0114] 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.
[0115] 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 heat-exchanging
plate 210 and the patient's skin 230. The applicator 200 can also
contain components described in connection with FIGS. 2 and 6.
[0116] 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 heat-exchanging plates 210, among other things. Further
details regarding a patient protection device may be found in U.S.
Patent Publication No. 2008/0077201.
[0117] 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. The 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 a suitable belt devices or retention devices may be found
in U.S. Patent Publication No. 2008/0077211.
[0118] A vacuum can assist in forming a 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.
[0119] FIGS. 8A to 8C illustrate treatment devices suitable for use
with the system 100 of FIGS. 2 and 6 in accordance with embodiments
of the technology. FIG. 8A 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.
[0120] FIG. 8B is a schematic, cross-sectional view illustrating an
applicator 270 that can include a heat-exchanging unit 274 having a
rigid or compliant convex surface 276 configured to be applied to
concave regions of the subject 272. 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.
[0121] FIG. 8C 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.
[0122] FIG. 9 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
heat-exchanging plate 210 described above with reference to FIG.
7.
[0123] 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. 7, 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. 7 for
communicating with the controller 114. In other embodiments, the
interface layers 314 can be eliminated.
[0124] 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.
[0125] The units 310a and 310b can be in communication with a
controller (e.g., the controller 114 of FIGS. 2 and 6), 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.
E. Suitable Computing Environments
[0126] FIG. 10 is a schematic block diagram illustrating
subcomponents of a computing device 700 suitable for the system 100
of FIGS. 2 and 6 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. In some embodiments, the input/output
device 703 can be the input/output device 120 of FIG. 6.
[0127] As illustrated in FIG. 10, 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.
[0128] 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.
[0129] 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. 6, 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 and 6). 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 on the input/output device 120
(FIG. 6).
[0130] 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.
[0131] 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.
[0132] 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.
F. Conclusion
[0133] 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 to perform the procedures
disclosed in U.S. Provisional Application Ser. Nos. 61/943,257 and
61/943,251, both 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.
[0134] 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.).
[0135] 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.
* * * * *