U.S. patent application number 14/658930 was filed with the patent office on 2015-07-02 for methods and devices for providing information useful in the diagnosis of abnormalities of the gastrointestinal tract.
This patent application is currently assigned to TEL HASHOMER MEDICAL RESEARCH INFRASTRUCTURE AND SERVICES, LTD.. The applicant listed for this patent is TEL HASHOMER MEDICAL RESEARCH INFRASTRUCTURE AND SERVICES, LTD.. Invention is credited to Genady KOSTENICH, Arie ORENSTEIN.
Application Number | 20150182169 14/658930 |
Document ID | / |
Family ID | 45592767 |
Filed Date | 2015-07-02 |
United States Patent
Application |
20150182169 |
Kind Code |
A1 |
KOSTENICH; Genady ; et
al. |
July 2, 2015 |
METHODS AND DEVICES FOR PROVIDING INFORMATION USEFUL IN THE
DIAGNOSIS OF ABNORMALITIES OF THE GASTROINTESTINAL TRACT
Abstract
Disclosed are methods useful for providing information useful in
the diagnosis of gastrointestinal abnormalities as well as
ingestible devices useful for providing information useful in the
diagnosis of gastrointestinal abnormalities.
Inventors: |
KOSTENICH; Genady; (Ramat
Gan, IL) ; ORENSTEIN; Arie; (Tel Aviv, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
TEL HASHOMER MEDICAL RESEARCH INFRASTRUCTURE AND SERVICES,
LTD. |
Ramat Gan |
|
IL |
|
|
Assignee: |
TEL HASHOMER MEDICAL RESEARCH
INFRASTRUCTURE AND SERVICES, LTD.
Ramat Gan
IL
|
Family ID: |
45592767 |
Appl. No.: |
14/658930 |
Filed: |
March 16, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13979863 |
Jan 14, 2014 |
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PCT/IB2012/050264 |
Jan 19, 2012 |
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14658930 |
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61434566 |
Jan 20, 2011 |
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61440932 |
Feb 9, 2011 |
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Current U.S.
Class: |
600/476 |
Current CPC
Class: |
A61B 5/4255 20130101;
A61B 5/42 20130101; A61B 5/6861 20130101; A61B 1/041 20130101; A61B
5/0059 20130101; A61B 5/0084 20130101 |
International
Class: |
A61B 5/00 20060101
A61B005/00 |
Claims
1.-12. (canceled)
13. An ingestible device useful for providing information useful
for diagnosis of gastrointestinal abnormalities, comprising: a) an
ingestible casing having a device axis, a body section, a distal
end and a proximal end; b) inside said casing, an illuminator
configured to project light radially outwards through an
illuminator window of said casing substantially simultaneously in a
substantially 360.degree. circumferential section around said
device axis; and c) inside said casing, at least one
light-detection assembly configured to determine total intensity of
at least one specified wavelength of light projected by said
illuminator and passing through an associated detector window
substantially simultaneously in a substantially 360.degree.
circumferential section around said device axis, after reflection
from a substantially 360.degree. circumferential section of a
gastrointestinal tract, without acquiring an image.
14. The device of claim 13, wherein said at least one
light-detection assembly and said associated detector window
comprise at least one wavelength filter configured to pass only
light having a said specified wavelength of light.
15. The device of claim 13, wherein said at least one
light-detection assembly comprises a single said light-detection
assembly.
16. The device of claim 13, wherein said at least one
light-detection assembly comprises at least two said light
detection assemblies.
17. The device of claim 13, wherein at least one said
light-detection assembly is configured to determine intensity of
one said specified wavelength of light.
18. The device of claim 13, wherein at least one said
light-detection assembly is configured to determine intensity of at
least two said specified wavelengths of light.
19. The device of claim 13, wherein said device is configured to
determine intensity of at least two specified wavelengths of light
each at a substantially different location in the device.
20. The device of claim 13, wherein said device is configured to
determine intensity of at least two specified wavelengths of light
each with a substantially different light-detection assembly.
21. A method for providing information useful for diagnosis of
gastrointestinal abnormalities, comprising: a) illuminating an area
of an in vivo gastrointestinal tract of a living mammal with light,
wherein said illuminating is outwards from inside a lumen of the
gastrointestinal tract; b) without acquiring an image of said area,
determining total intensity of at least one specified wavelength of
light after said light is reflected from said area of said
gastrointestinal tract; and c) providing information related to
said intensity of light indicative of a potential gastrointestinal
abnormality in said area, wherein said area constitutes a
360.degree. circumferential section of said gastrointestinal
tract
22. The method of claim 21, wherein said reflected light is
substantially diffusely reflected light.
23. The method of claim 21, wherein said information provided is a
comparison of at least two respective said intensities of at least
two different specified wavelengths of light reflected from the
same said area.
24. The method of claim 21, wherein said information provided is
said intensity of at least one specified wavelength of light after
said light is reflected from said area of said gastrointestinal
tract compared to an intensity of light of a same specified
wavelength after said light has been reflected from a different
said area of said gastrointestinal tract.
Description
RELATED APPLICATION
[0001] The present application gains priority from U.S. Provisional
Patent Application No. 61/434,566 filed 20 Jan. 2011 and U.S.
61/440,932 filed 9 Feb. 2011. The present application is also
related to PCT/IB2010/053539 having an international filing date of
4 Aug. 2010 that gains priority from U.S. Provisional Patent
Application No. 61/231,350 filed 5 Aug. 2009, both which are
included by reference as if fully set forth herein.
FIELD AND BACKGROUND OF THE INVENTION
[0002] The invention, in some embodiments, relates to the field of
medical diagnosis, and more particularly but not exclusively, to
methods and devices for providing information useful in the
diagnosis of abnormalities of the gastrointestinal tract
(gastrointestinal abnormalities).
[0003] Ingestible imaging devices for inspecting the
gastrointestinal tract are known, for example the Pillcam.TM.
available from Given Imaging (Yokneam, Israel). Such capsule-shaped
devices generally include an illumination source and an imaging
component (a digital camera) at one or both (distal and proximal)
ends. As known in the art of digital photography, the
image-acquisition portion of such a camera is a planar array of
light sensitive sensors (e.g., CCD, CMOS). For use, such an imaging
device is swallowed by a subject and the device is propelled
through the gastrointestinal tract by peristalsis. While passing
through the gastrointestinal tract, the camera acquires images of
the gastrointestinal tract and wirelessly transmits the images to a
recording device. The images of the gastrointestinal tract are
subsequently inspected by a health care professional, as a lengthy
video, for evidence of gastrointestinal abnormalities such as
bleeding, polyps, cancers and lesions.
[0004] Such ingestible imaging devices have disadvantages.
Ingestible imaging devices are expensive, requiring complex and
expensive cameras and often requiring small moving parts such as
lenses in order to acquire diagnostically-useful images. Ingestible
imaging devices have high power requirements for operating the
camera and an illumination source bright enough to allow
acquisition of the images. The camera of such imaging devices is
necessarily directed parallel to the lumen but has limited field of
view of the intestinal wall where gastrointestinal abnormalities
are located. Furthermore, ingestible imaging devices produce large
amounts of image (video) data. As a result, data acquisition and
transmission is not trivial, must be performed continuously and
requires a significant amount of power. The large amount of data
cannot be reviewed automatically and instead requires a
time-consuming review by a skilled health-care professional, a
factor that raises the cost of using such devices. Even the most
highly skilled health-care professional is only able to identify
relatively large abnormalities that are visible under the poor
intraluminal lighting conditions so that small abnormalities and
abnormalities that have certain colors often remain undetected.
[0005] It would be useful to have methods and ingestible devices
that provide information useful for the diagnosis of
gastrointestinal abnormalities that are devoid of at least some of
the disadvantages of known ingestible imaging devices.
SUMMARY OF THE INVENTION
[0006] Some embodiments of the invention relate to methods and
devices for providing information useful for the diagnosis of
gastrointestinal abnormalities by determining the intensity of at
least one specified wavelength of light reflected, in some
embodiments diffusely reflected light, from a portion of an
intestinal wall, that in some embodiments are devoid of at least
some of the disadvantages of known ingestible imaging devices.
[0007] In some embodiments, the relative intensity of at least two
specified wavelengths of light (diffusely) reflected from a portion
of the intestinal wall is determined and provides information
useful for the diagnosis of gastrointestinal abnormalities.
[0008] According to an aspect of some embodiments of the invention
there is provided an ingestible device useful for providing
information useful for the diagnosis of gastrointestinal
abnormalities, comprising:
a) an ingestible casing having a device axis, a body section, a
distal end and a proximal end; b) inside the casing, an illuminator
configured to project light radially outwards through an
illuminator window of the casing substantially simultaneously in a
substantially 360.degree. circumferential section around the device
axis; and c) inside the casing, at least one light-detection
assembly configured to determine the total intensity of at least
one specified wavelength of light projected by the illuminator and
passing through an associated detector window substantially
simultaneously in a substantially 360.degree. circumferential
section around the device axis, after reflection from a
substantially 360.degree. circumferential section of a
gastrointestinal tract, without acquiring an image.
[0009] According to an aspect of some embodiments of the invention
there is provided a method for providing information useful for the
diagnosis of gastrointestinal abnormalities, comprising:
a) illuminating an area of an in vivo gastrointestinal tract of a
living mammal with light, wherein the illuminating is outwards from
inside the gastrointestinal tract lumen; b) without acquiring an
image of the area, determining the total intensity of at least one
specified wavelength of light after the light is reflected from the
area of the gastrointestinal tract; and c) providing information
related to the intensity of light indicative of a potential
gastrointestinal abnormality in the area, wherein the area is
constitutes a 360.degree. circumferential section of the
gastrointestinal tract.
[0010] Unless otherwise defined, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which the invention pertains. In case
of conflict, the specification, including definitions, will
control.
[0011] As used herein, the terms "comprising", "including",
"having" and grammatical variants thereof are to be taken as
specifying the stated features, integers, steps or components but
do not preclude the addition of one or more additional features,
integers, steps, components or groups thereof. These terms
encompass the terms "consisting of and "consisting essentially
of`.
[0012] As used herein, the indefinite articles "a" and "an" mean
"at least one" or "one or more" unless the context clearly dictates
otherwise.
BRIEF DESCRIPTION OF THE FIGURES
[0013] Some embodiments of the invention are herein described with
reference to the accompanying figures. The description, together
with the figures, makes apparent to a person having ordinary skill
in the art how some embodiments of the invention may be practiced.
The figures are for the purpose of illustrative discussion and no
attempt is made to show details of an embodiment in more detail
than is necessary for a fundamental understanding of the invention.
For the sake of clarity, some objects depicted in the figures are
not to scale.
[0014] In the Figures:
[0015] FIGS. 1A-1C depict results of experimentally-acquired
spectra of normal and abnormal gastrointestinal tissue,
demonstrating aspects of the teachings herein;
[0016] FIGS. 2A-2C are schematic depictions of an embodiment of a
device as described herein configured for determining the intensity
of only one specified wavelength of light;
[0017] FIG. 2D depicts typical information acquired using a device
depicted in FIG. 2A;
[0018] FIG. 3 is a schematic depiction of the device of FIG. 2 in
use inside a gastrointestinal tract;
[0019] FIGS. 4A-4B are schematic depictions of embodiments of a
device as described herein configured for determining the intensity
of three specified wavelength of light with 10 three
light-detection assemblies;
[0020] FIG. 4C depicts typical information acquired using a device
depicted in FIG. 4A;
[0021] FIGS. 5A and 5B are schematic depictions of an embodiment of
a device as described herein configured for determining the
intensity of three specified wavelength of light with a single
light-detection assembly; and
[0022] FIGS. 6A and 6B are schematic depictions of an embodiment of
a device as described herein configured for determining the
intensity of three specified wavelengths of light with a single
light-detection assembly.
DESCRIPTION OF SOME EMBODIMENTS OF THE INVENTION
[0023] Some embodiments of the invention relate to methods and
devices for providing information useful for the diagnosis of
gastrointestinal abnormalities by determining the total intensity
of at least one specified wavelength of light (diffusely) reflected
from an area of the gastrointestinal tract without acquiring an
image of the area, where the area constitutes a substantially
360.degree. circumferential section of the gastrointestinal tract.
The area of a gastrointestinal tract is, depending on the
embodiment, any portion of a gastrointestinal tract that is
downstream of the pylorus, e.g., the duodenum, small intestine or
large intestine.
[0024] The principles, uses and implementations of the teachings of
the invention may be better understood with reference to the
accompanying description and figures. Upon perusal of the
description and figures present herein, one skilled in the art is
able to implement the teachings of the invention without undue
effort or experimentation. In the figures, like reference numerals
refer to like parts throughout.
[0025] Before explaining at least one embodiment of the invention
in detail, it is to be understood that the invention is not
necessarily limited in its application to the details of
construction and the arrangement of the components and/or methods
set forth herein.
[0026] The invention is capable of other embodiments or of being
practiced or carried out in various ways. The phraseology and
terminology employed herein are for descriptive purpose and should
not be regarded as limiting.
[0027] Known ingestible imaging devices for inspection of the
gastrointestinal tract have a 5 number of disadvantages as
discussed in the introduction hereinabove.
[0028] Herein are disclosed methods and devices for providing
information useful for the diagnosis of gastrointestinal
abnormalities by determining the intensity of at least one
specified wavelength of light (diffusely) reflected from an area of
the gastrointestinal tract (e.g., intestinal wall).
[0029] To understand some embodiments of the method, one must
consider the process of reflection, both diffuse reflection and
specular reflection.
[0030] Some light that illuminates an area of intestinal wall
penetrates into the tissue and is absorbed by chromophores in the
tissue. As any given chromophore absorbs different wavelengths of
light with different efficiencies and as the presence, nature and
concentration of chromophores is tissue-type dependent, different
tissue types absorb different wavelengths of light differently.
[0031] Light that penetrates into the tissue is also scattered
inside the tissue, reflected and refracted in many directions from
various features such as cells, organelles and interstitial tissue
where some of the light is ultimately diffusely reflected out of
the tissue back in the general direction of the illumination. The
degree of scattering and diffuse reflection is dependent on the
concentration, size and shape of the reflecting features as well as
the refractive index of the various tissue components. Due to the
ranges of refractive indices, concentrations as well as size of
scattering features in gastrointestinal tissue, the degree of
diffuse reflection of visible light and near-infrared light
(400-800 nm) is wavelength-dependent.
[0032] It has been found and is herein disclosed that the
differences of light absorption, scattering and diffuse reflection
in normal compared to some abnormal gastrointestinal tissue is
sufficient to provide information that can be useful for diagnosis
of gastrointestinal abnormalities.
[0033] Further, for a given light-detector, the detected intensity
of both specular and diffuse reflection from a tissue surface is
dependent on the distance of the detector from the surface: the
further a surface, the lower the intensity of reflected light
independent of wavelength.
[0034] According to an aspect of some embodiments of the invention,
there is provided a method for providing information useful for the
diagnosis of gastrointestinal abnormalities, comprising:
a) illuminating an area of an in vivo gastrointestinal tract of a
living mammal (a human or non-human mammal) with light, wherein the
illuminating is outwards from inside the gastrointestinal tract
lumen; b) without acquiring an image of the area, determining an
intensity of at least one specified wavelength of light after the
light is (diffusely) reflected from the area of the
gastrointestinal tract; and c) providing information related to the
intensity of light indicative of a potential gastrointestinal
abnormality in the area, for example to a person such as a
health-care professional. In some embodiments, the mammal is
unsedated, preferably ambulatory, whether in a clinical or (more
preferably) non-clinical setting.
[0035] In some embodiments, the intensity determined is of
diffusely reflected light. In some embodiments, the intensity
determined is substantially exclusively of diffusely reflected
light. The provided information may then be used, alone or together
with other information regarding the living mammal, to diagnose a
gastrointestinal abnormality, for example bleeding, cancers,
invasive adenocarcinoma, adenomas, adenomatous polyps, benign
polyps and hyperplastic polyps but also other abnormalities.
[0036] In some embodiments, the provided information relates to
wavelength-dependent abnormalities, that is to say, have
characteristics to absorb and scatter different wavelengths of
light differently. In some embodiments, the abnormalities detected
are distance (from an illuminator and to a light-detection
assembly) sensitive, that is to say the intensity of the reflected
light changes with distance, for example polyps and other
abnormalities having an abnormal shape, usually protruding into the
intestinal lumen.
[0037] Thus, in some embodiments, identification of tissue as
potentially abnormal is by wavelength-dependent reflection
characteristics and does not require acquisition and analysis of an
image as known in the art. Accordingly, some embodiments of the
method described herein may be considered a form of spectroscopy.
Useful background art for greater understanding some aspects of
some embodiments of the method may be found, for example, in Dhar M
et al, Gastrointestinal Endoscopy 2006, 63(2), 257.
[0038] In some embodiments, when an area of gastrointestinal tissue
is illuminated with light some of the light penetrates into the
tissue and undergoes both absorption and scattering. The intensity
of a specified wavelength of light that is ultimately diffusely
reflected and detected is tissue-type dependent. By determining an
intensity of a specified wavelength of light diffusely reflected
from an area of tissue and comparing the determined intensity to
some reference value (e.g., an absolute value, an intensity of
light having the same wavelength reflected from a different area,
an intensity of light having a different wavelength reflected from
the same area) it is possible to identify the area of tissue as
potentially abnormal.
[0039] In FIGS. 1A-1C results are shown of actual experiments
performed (as detailed in the Example section) on normal and
abnormal gastrointestinal tissue demonstrating the wavelength and
tissue-type dependence of diffuse reflection.
[0040] In a first experiment, the wavelength dependence of diffuse
reflection from intestinal abnormalities relative to normal
intestinal mucosa was examined in a manner simulating the use of an
ingestible device as described herein on excised intestinal tissue.
The results of the experiment are shown in FIG. 1A, where the
relative detected intensities of light diffusely reflected from
normal mucosa (plot `a`), blood (plot `b`) and invasive
adenocarcinoma (plot `c`) normalized relative to light reflected
from normal mucosa at wavelengths between 400 nm and 800 nm are
shown.
[0041] In a second experiment, the wavelength dependence of diffuse
reflection from various intestinal abnormalities related to
invasive adenocarcinoma relative to normal intestinal mucosa was
examined in a manner simulating the use of an ingestible device as
described herein in vivo. The results of the experiment are shown
in FIG. 1B, where the relative detected intensities of light
diffusely reflected from normal mucosa (plot `a`), invasive
adenocarcinoma (plot `c`), a hyperplastic polyp (plot `d`), an
adenomatous polyp (plot `e`) and adenoma (plot `f) normalized
relative to light diffusely reflected from normal mucosa at
wavelengths between 400 nm and 750 nm are shown.
[0042] In a third experiment, the wavelength dependence of diffuse
reflection from various intestinal abnormalities relative to normal
intestinal mucosa was examined in a manner simulating the use of an
ingestible device as described herein on excised intestinal tissue.
The results of the experiment are shown in FIG. 1C, where the
relative detected intensities of light diffusely reflected from
normal mucosa (plot `a`), blood (plot `b`), invasive adenocarcinoma
(plot `c`), a hyperplastic polyp (plot `d`) and adenoma (plot `f)
normalized relative to light diffusely reflected from normal mucosa
at wavelengths between 400 nm and 800 nm are shown.
[0043] As apparent from FIGS. 1A-1C, different tissue types
diffusely reflect light in a characteristic, identifiable and
wavelength-dependent fashion so that information relating to the
intensity of at least one specified wavelength of diffusely
reflected light provided in accordance with the teachings herein
may be useful in assisting diagnosis of some types of
gastrointestinal abnormalities.
[0044] In some embodiments, at least one of the specified
wavelengths is a wavelength having a high tissue-type dependent
diffuse reflection for a gastrointestinal abnormality and can be
considered a diagnostic wavelength for that gastrointestinal
abnormality. In some embodiments, at least one of the specified
wavelengths is a wavelength having a low tissue-type dependent
diffuse reflection for a gastrointestinal abnormality. "Low" and
"high" are qualitative terms that are easily understood by a person
having ordinarily skill in the art, for 10 example, by consulting
FIGS. 1A-1C or through minor, not undue, experimentation.
[0045] For example, from FIGS. 1A-1C, it is seen that various
wavelengths between 450 and 700 nm can be diagnostic wavelengths
for bleeding, invasive adenocarcinomas, adenomas, and adenomatous
polyps when compared to normal tissue.
[0046] In some embodiments, the intensity of at least two different
specified wavelengths of light reflected from the same area is
determined. The relative intensities of the reflections of the two
different wavelengths are compared and, as apparent from FIGS.
1A-1C, may be indicative of abnormal tissue.
[0047] For example, a strong reduction of intensity for wavelengths
between about 430 nm and about 600 nm (relative to normal tissue)
when accompanied by a more moderate reduction, unchanged or
increase of intensity for wavelengths between about 700 nm and
about 800 nm (relative to normal tissue) may be indicative of an
abnormality such as invasive adenocarcinoma but when accompanied by
a strong reduction of intensity for wavelengths between about 700
nm and about 800 nm (relative to normal tissue) may be indicative
of an abnormality such as bleeding.
[0048] In some such embodiments, one of the at least two specified
wavelengths is diagnostic for one or more abnormalities, and
another of the at least two specified wavelengths is diagnostic for
at least one different abnormality.
[0049] In some such embodiments, one of the at least two specified
wavelengths is diagnostic for an abnormality, and another of the at
least two specified wavelengths is diagnostic for the 30 same
abnormality, providing increased confidence in a potential
diagnosis.
[0050] In some such embodiments, the determination of the intensity
of light of at least two specified wavelength allows comparison of
the intensities of the two wavelengths to provide information
useful for diagnosis.
[0051] In some such embodiments, at least one of the at least two
specified wavelengths is a diagnostic wavelength (a wavelength for
which intensity changes are indicative of an abnormality, e.g. 550
nm indicative of invasive adenocarcinoma) and at least one of the
at least two specified wavelengths is a reference wavelength (e.g.,
700 nm). Determination of the intensity of a reference wavelength
allows, in some embodiments, normalization of the determined
intensities of the one or more diagnostic wavelengths and, in some
embodiments, allows separation of diagnostically useful
measurements from not-useful measurements.
[0052] In some such embodiments, the variations in intensities are
wavelength independent and indicative of the lack of contact with
the intestinal wall. In some such embodiments, the intensities of
the diagnostic wavelength determined during contact with the
intestinal wall are separated from the intensities of the
diagnostic wavelength determined with no contact with the
intestinal wall with reference to the determined intensities of a
reference wavelength. For example, in some embodiments, the
intestinal walls physically contact a device only in the contracted
portion of the peristaltic cycle. A similar magnitude of reduction
in intensity of reflection of both 650 nm (reference) and 550 nm
(diagnostic) wavelengths is indicative of no contact with the
intestinal wall during that measurement. In contrast, a reduction
in intensity of reflection of 550 nm while the intensity of
reflection of 650 nm remains substantially constant is indicative
of contact with the intestinal wall during that measurement with
possible detection of a potential invasive adenocarcinoma.
[0053] In some embodiments, the information provided is the
determined intensities. In some embodiments, the information
provided is information calculated from the determined intensities,
for example relative intensities, ratios and the like.
[0054] In some embodiments, the information provided is the
intensity of a specified wavelength of light reflected from an area
of the gastrointestinal tract compared to the intensity of light
having the same specified wavelength reflected from a different
area of the gastrointestinal tract. In some such embodiments,
especially when the intensity of reflected light is determined from
a plurality of discrete areas substantially simultaneously,
differences in the tissue type in the different areas or difference
in the distance to the different areas can be identified. For
example, as seen from FIG. 1A, when comparing the intensity of
reflection from different areas, a reduced intensity of light at
550 nm may be indicative of an abnormality such as bleeding or
invasive adenocarcinoma.
[0055] In some embodiments, the information provided is a
comparison of at least two (in some embodiments, exactly two or
exactly three) respective intensities of at least two different
specified wavelengths reflected from the same area, for example the
ratio of intensities of two different wavelengths is compared,
where a low ratio is indicative of normal tissue and a high ratio
is indicative of abnormal tissue. In some such embodiments, the
comparison reduces the influence of non-wavelength dependent
variations in intensity and emphasizes the influence of
wavelength-dependent variations, and is therefore useful, in some
embodiments, for differentiating between different tissue types.
Such wavelength intensity ratios that are significantly different
(lower or higher) from those of normal tissue may be indicative of
an abnormality. For example, in some embodiments the intensity of
light having a wavelength of 550 nm (1550) reflected from an area
is compared to that of light having a wavelength of 625 nm (1625)
reflected from the same area. Intensities that are similar
(1550=1625) but both lower than those of normal tissue are
indicative of bleeding, a significantly higher intensity of 1625
compared to 1550 (1625>1550) is indicative of invasive
adenocarcinoma or adenoma, while a significantly higher intensity
of 1550 compared to 1625 (1550>1625) is indicative of
adenomatous polyp of hyperplastic polyp.
[0056] In some embodiments, for example when greater detection
confidence is desired (both with regards to selectivity,
specificity, abnormality type) or when it is desired to seek and
potentially detect more than one type of abnormality, the relative
intensities of more than two wavelengths of reflected light are
determined and compared (e.g., three, four, five and even more
wavelengths). In some embodiments, the relative intensities of only
the wavelengths to be compared are acquired. In some embodiments,
the relative intensities of more than only the wavelengths to be
compared are acquired. In some embodiments, the relative
intensities of a plurality of wavelengths are acquired, in some
embodiments constituting a spectrum. In some embodiments, the
method described herein is not applied to only detecting an
abnormality at one specific selected area of a gastrointestinal
tract.
[0057] In some embodiments, the method described herein includes
scanning the surface of the gastrointestinal tract and determining
the intensity of at least one specified wavelength of light
reflected from each one of a plurality of areas in succession.
[0058] In some embodiments, the method described herein includes
simultaneously determining the intensity of at least one specified
wavelength of light reflected from each one of a plurality of
areas.
[0059] In some embodiments, the method described herein includes
substantially simultaneously illuminating a plurality of discrete
areas of the gastrointestinal tract. In some embodiments, the
plurality of discrete areas constitutes a circumferential section
of the gastrointestinal tract, in some embodiments a 360.degree.
circumferential section (a ring) of the gastrointestinal tract. In
some embodiments, determining the intensity of at least one
specified wavelength of reflected light is substantially
simultaneous for the plurality of discrete areas. In some
embodiments, the method comprises sequentially detecting light
reflected from succeeding rings of tissue making up the
gastrointestinal tract.
[0060] In some embodiments, the determined intensities are analyzed
and reacted upon, for example a specific action is undertaken when
potentially abnormal tissue is detected, e.g., an alarm is sounded,
a marker or active pharmaceutical ingredient is administered.
[0061] In some embodiments, the provided information (e.g.,
determined intensities, relative intensities, ratios) is recorded.
In some embodiments, the provided information is transmitted. In
some embodiments, the provided information is transmitted
continuously. In some embodiments, the provided information is
transmitted intermittently (e.g., less frequently than about every
minute, less frequently than about every hour), for example in
order to save power. In some embodiments, a portable relay device
(e.g., a cellular telephone, a personal digital assistant, a
dedicated transceiver) is in proximity to the living mammal and
used as a relay, continuously or intermittently receiving the
provided information and subsequently retransmitting the provided
information, for example to a central location such as hospital or
physician. In some embodiments, the provided information is
converted into an image, for example using pipe-simulation
mathematics. In some embodiments, a portable recording device
(e.g., a cellular telephone, a personal digital assistant, a
dedicated recorder receiver) is in proximity to the living mammal
and used to, continuously or intermittently receive the provided
information and subsequently record the information, for example on
a removable storage medium such as a memory card.
[0062] The method described herein may be implemented using any
suitable device, for example, in some embodiments, a device as
described herein is used to implement the method.
[0063] According to an aspect of some embodiments of the invention,
there is provided an ingestible device for providing information
useful for the diagnosis of gastrointestinal abnormalities, the
device comprising:
a) an ingestible casing having a device axis, a body section, a
distal end and a proximal end; b) inside the casing, an illuminator
configured to project light radially outwards through an
illuminator window of the casing, allowing illumination a region of
a gastrointestinal tract wall (e.g., intestinal wall) in which the
device is passing and contacting; c) inside the casing, at least
one light-detection assembly configured to determine the intensity
of at least one specified wavelength of light passing through an
associated detector window without acquiring an image.
[0064] For use in accordance with some embodiments of the method
discussed hereinabove, the device is ingested. After passing the
pylorus, the illuminator projects light radially through the
associated illuminator window that in some embodiments acts as a
light guide to guide light from the illuminator out of the casing,
illuminating an area of the gastrointestinal wall. The projected
light is reflected back through a detector window that in some
embodiments acts as a light guide to guide reflected light towards
the light-detection assembly where the intensity of the specified
wavelength of the reflected light is determined. As discussed above
with reference to the method described herein, the intensity of at
least one specified wavelength of light reflected from an area in
the illuminated region may be indicative of an abnormality in the
area.
[0065] In the art, ingestible gastrointestinal imaging devices
include an objective, usually an adjustable objective, comprising
one or more lenses and/or mirrors, that form an image of an object
on a two-dimensional detector array located at the focal plane of
the objective. The device described herein is used for inspection
of the gastrointestinal tract without acquiring an image. In some
embodiments, the inspection of the gastrointestinal tract is
performed without a lens. In some embodiments, the device comprises
a fixed lens to concentrate light at a light detector, but not to
form an image.
[0066] It is important to note that in order to acquire an image,
prior art ingestible imaging devices necessarily include a camera.
The camera acquires an image of a relatively large portion of the
intestinal tract, generally in parallel to the intestinal lumen. As
known in the art of digital cameras, each pixel of the camera
detector simultaneously acquires multiple wavelengths of light from
a given area (each pixel corresponding to an area, where the areas
together make up the portion of the intestinal tract of which image
is being acquired). Such imaging devices need relatively long
acquisition time for each image frame.
[0067] In contrast, in some embodiments of the device herein, the
intensity of each specified wavelength from a given area is
determined in a different physical location, e.g., a different
light-detection assembly, a different region of a detector of the
same light-detection assembly. Thus, in some embodiments, the
device is configured to determine the intensity of at least two
specified wavelengths of light each at a substantially different
location. In some embodiments, the device is configured to
determine the intensity of at least two specified wavelengths of
light, each with a substantially different detector. In some
embodiments of the device described herein, a light-detection
assembly includes a simple, one-dimensional array of light sensors.
Such detectors determine the intensity of each specified wavelength
from a relatively small area and need a relatively short
acquisition time at one physical location of the device.
[0068] Some embodiments of the devices described herein are
relatively cheap, requiring simpler and cheaper components than
known ingestible imaging devices.
[0069] Some embodiments of the devices described herein are
relatively mechanically reliable compared to known ingestible
imaging devices, requiring (substantially) no moving parts.
[0070] Some embodiments of the devices described herein have a low
power consumption compared to known ingestible imaging devices
(depending on the embodiment, due to, for example, less intense
illumination requirements, less acquired data, no moving mechanical
parts, fewer pixels per frame), requiring smaller, cheaper and less
toxic power storage units, e.g., batteries.
[0071] Like prior art ingestible imaging devices, the casing of a
device is generally configured for passage, once swallowed by a
mammalian subject and passing the pylorus, for transport through
the gastrointestinal tract for eventual expulsion through the anus
where either the distal or proximal end faces forwards, where the
device axis is substantially parallel to the gastrointestinal tract
lumen and where the gastrointestinal walls physically contacts the
body section to propel the device by peristalsis.
[0072] In some embodiments, the body section includes a
substantially parallel-walled cylindrical portion where the walls
of the body section are parallel to the device axis.
[0073] In some embodiments, the distal end and/or the proximal end
are streamlined for passage of the device through the
gastrointestinal tract.
[0074] In some embodiments, the device comprises inside the casing
a power supply for providing substantially all power for operation
of the device once ingested until expelled. In some embodiments,
when compared to a power supply required for known ingestible
imaging devices, the power supply is relatively modest as the
device has relatively lower power requirement as there is no need
for imaging, no moving parts, less intense illumination, and per
unit time, less data to transmit and/or record.
[0075] In some embodiments, the device comprises inside the casing,
a processor, for example configured to compare the determined
intensities of specified wavelengths of light.
[0076] In some embodiments, the device comprises inside the casing,
a wireless transmitter for transmitting information related to the
determined intensities of the specified wavelengths, such as the
determined intensity of the specified wavelengths or results of
comparison of the determined intensities of the specified
wavelengths. In some embodiments, the wireless transmitter is, like
in known ingestible imaging devices, configured for continuous
transmission of the information. In some embodiments, the wireless
transmitter is configured for non-continuous (e.g., intermittent or
periodic) transmission of the information, in order to reduce
interference potentially caused by transmission, to reduce exposure
of a subject ingesting the device to radiation, and to reduce power
use by the device. In some embodiments, non-continuous transmission
is possible because the device does not acquire images, but only
modest amounts of information. In some embodiments, the information
is transmitted only over a short range (e.g., to a device carried
by the subject such as a dedicated device, a cellular telephone, a
personal digital assistant) and stored and/or retransmitted.
[0077] In some embodiments, the device comprises inside the casing,
a memory for recording information related to the determined
intensities of the specified wavelength, for example, the device
includes a solid-state memory component or a removable solid-state
memory component such as a micro-SD card. In some embodiments, the
recorded information is substantially all the information useful
for the diagnosis of abnormalities in the gastrointestinal tract
determined during passage through a gastrointestinal tract. In some
embodiments, recording of substantially all the useful information
is possible because the device does not acquire images, but only
relatively modest amounts of information.
[0078] An illuminator of a device described herein is configured to
project light including one or more specified wavelengths,
typically between about 400 nm and 800 nm. In some embodiments, an
illuminator is configured to project monochromatic light. In some
embodiments, an illuminator is configured to project polychromatic
or white light that includes the specified wavelengths of
light.
[0079] In some embodiments, the illuminator comprises a light
source for producing light having the specified wavelengths. Any
suitable light source may be used, for example a light-emitting
diode. In some embodiments, such a light source is configured for
producing monochromatic light. In some embodiments, such a light
source is configured for producing polychromatic light. In some
embodiments, such a light source is configured for producing white
light. In some embodiments, the illuminator comprises a light
source for producing light having wavelengths between 400 and 800
nm
[0080] In some embodiments, a light source comprises a radial
diffuser functionally associated with the light source for radially
distributing light produced by the light source.
[0081] The illuminator and the illuminator window are configured
together to project light in any suitable direction. In some
embodiments, the illuminator and illuminator window are configured
together to project light substantially perpendicularly to the
device axis. In some embodiments, the illuminator and illuminator
window are configured together to project light at an angle
different than 90.degree. to the device axis, e.g., in a direction
towards or away from a detector window, in some embodiments not
more than 10.degree. from perpendicular to the device axis and in
some embodiments not more than 5.degree. from perpendicular to the
device axis.
[0082] The illuminator is configured to project light radially
allowing illumination of any shaped region of a gastrointestinal
lumen. In some embodiments, the illuminator is configured to
project light in circumferential section of at least about
90.degree., at least about 120.degree., and even at least about
180.degree. at one time around the device axis, allowing
substantially simultaneous illumination of an equivalent
circumferential section of gastrointestinal lumen. That said, in
preferred embodiments, the illuminator is configured to project
light in a circumferential section that is substantially the entire
360.degree. around the device axis, allowing substantially
simultaneous illumination of substantially a 360.degree.
circumferential section (a ring) of gastrointestinal tissue.
[0083] The illuminator window through which the illuminator
projects light is substantially transparent to at least the
specified wavelengths. An illuminator window is of any suitable
shape and construction, and is generally fashioned of glass or
plastic material as known in the art of ingestible imaging devices.
In some embodiments, an illuminator window is made up of two or
more discrete parts assembled so that the illuminator window is
continuous. In some embodiments, an illuminator window is made up
of two or more discrete parts assembled where at least two of the
parts are separated by a non-transparent component. That said, it
is generally preferred (for reasons of ease of construction as well
as to reduce the chance of leakage of gastrointestinal fluids into
the casing) that the illuminator window comprises substantially a
single discrete component. In some embodiments, a radial diffuser
constitutes the illuminator window.
[0084] In some embodiments, the illuminator and the illuminator
window together are configured that the projected light is
polarized, for example, the illuminator window is a light
polarization component or the illuminator comprises a light
polarization component.
[0085] In some embodiments where the illuminator is configured to
project light in a certain circumferential section (e.g.,
120.degree.), the illuminator window comprises an arc or disk
section of at least the same circumferential section of a material
substantially transparent to light having the specified
wavelengths. In some embodiments, especially where the illuminator
is configured to project light in a substantially 360.degree.
circumferential section, the illuminator window is a ring or a disk
of a material substantially transparent to light having the
specified wavelengths, in some embodiments positioned coaxial with
the device axis.
[0086] A light-detection assembly of a device described herein is
configured to determine the 5 intensity of at least one specified
wavelength of light passing through an associated detector window.
As discussed above, specified wavelengths are typically between
about 400 nm and 800 nm
[0087] In some embodiments, a device is configured to determine the
intensity of at least two specified wavelengths of light each at a
substantially different (physical) location. In some embodiments, a
device is configured to determine the intensity of at least two
specified wavelengths of light each with a substantially different
light-detection assembly. In some embodiments, a device is
configured to determine the intensity of at least two specified
wavelengths of light at substantially different locations of the
same light-detection assembly. In some embodiments, a
light-detection assembly and associated detector window comprise at
least one wavelength filter configured to pass only light having a
specified wavelength of light. In some embodiments, a wavelength
filter is functionally associated with a detector window. In some
embodiments, a wavelength filter is a component of or is a detector
window.
[0088] In some embodiments, a light-detection assembly and an
associated detector window are configured so that light reaching
the light-detection assembly is polarized, for example, the
illuminator window is a light polarization component or the
light-detection assembly comprises another light polarization
component. In some such embodiments, the light polarization
component associated with the light-detection assembly is oriented
perpendicularly to the light polarization component associated with
the illuminator. Such cross polarization reduces specular
reflection and allows more selective acquisition of substantially
only diffusely reflected light.
[0089] In some embodiments, a device comprises a single
light-detection assembly.
[0090] In some embodiments, a device comprises at least two light
detection assemblies. In some such embodiments, the device
comprises at least one detector window associated with at least two
of the detection assemblies. In some such embodiments, each
light-detection assembly is associated with a single dedicated
detector window.
[0091] In some embodiments, at least one light-detection assembly
is configured to determine the intensity of one specified
wavelength of light. In some such embodiments, the light-detection
assembly is functionally associated with a wavelength filter that
limits the wavelengths of light that reach the light-detection
assembly. In some embodiments, the wavelength filter is a component
of or is the detector window.
[0092] In some embodiments, at least one light-detection assembly
is configured to determine the intensity of at least two specified
wavelengths of light.
[0093] In some such embodiments, the light-detection assembly
configured to determine the intensity of at least two specified
wavelengths of light is associated with at least two detector
windows. In some such embodiments, each detector window is
associated with a wavelength filter each passing light having a
different specified wavelength.
[0094] In some such embodiments, the light-detection assembly
configured to determine the intensity of at least two specified
wavelengths of light is associated with a single detector window.
In some such embodiments, the detector window is associated with
the appropriate number of different wavelength filters, each
passing light having a different specified wavelength.
[0095] The rate of determining the intensities of the specified
wavelengths of light is any suitable rate. A higher rate produces
more data (determined intensities) that must be analyzed and/or
transmitted and/or stored but yields greater axial resolution by
determining intensities at a greater rate as the device passes
through the gastrointestinal tract. Considering the speed at which
peristalsis drives an ingested device through the gastrointestinal
tract, it is currently believed that a rate of between 1 Hz and 20
Hz is preferred. Thus, in some embodiments, a light-detection
assembly is configured to determine the intensity of the at least
one specified wavelength of light at a rate of at least about 0.1
Hz, at least about 0.5 Hz and even at least about 1 Hz, preferably
so that during the period of time that a device passes through the
gastrointestinal tract substantially the entire luminal surface of
a portion or the entire gastrointestinal tract downstream of the
pylorus has been scanned.
[0096] Depending on the embodiments, a light-detection assembly can
be configured to determine the intensity of at least one specified
wavelength of light from any suitable direction and from any
suitably-shaped region of a gastrointestinal wall.
[0097] In some embodiments, a light-detection assembly is
configured to determine the intensity of light of at least one
specified wavelength of light passing through an associated
detector window from a circumferential section around the device
axis of at least about 90.degree., at least about 120.degree., and
even at least about 180.degree. around the device axis, allowing
simultaneous determination of intensities from an equivalent
circumferential section (an arc-shaped region) of gastrointestinal
luminal surface. That said, in preferred embodiments, a
light-detection assembly is configured to determine the intensity
of light in a circumferential section that is substantially the
entire 360.degree. around the device axis substantially
simultaneously, allowing simultaneous determination of the
intensity of reflection of substantially a 360.degree.
circumferential section (a ring-shaped region) of gastrointestinal
tissue.
[0098] A detector window associated with a light-detection assembly
allows light reflected from a given region of the gastrointestinal
tract to reach the light-detection assembly. In some embodiments,
the light-detection assembly is configured to determine the
intensity of light from a single area that is substantially the
entire region. For example, in some embodiments a device including
a 360.degree. circular detector window, light is reflected from a
360.degree. ring-shaped region of the intestinal wall which is one
area for which the intensity of reflected light is determined
[0099] That said, in some embodiments, to provide additional
information for diagnosis, for example, the location of an
abnormality, the size of an abnormality or identification of
multiple abnormalities at the same portion of the gastrointestinal
tract, at least one light-detection assembly is configured to
determine the intensity of at least one the specified wavelength of
light passing through the associated detector window from at least
two different areas, at least three, at least four, at least eight,
at least ten, at least 15, at least 30, and even at least 60
different areas, for example, by an arrangement of a required
number of light sensors in appropriate positions across from an
associated detector window. For example, in some embodiments a
device including a 360.degree. circular detector window, a
360.degree. ring-shaped region of the intestinal luminal wall is
divided into two areas corresponding to two 180.degree. sectors
from which the intensity of light is independently determined,
divided into three different areas corresponding to three
120.degree. sectors, divided into four different area corresponding
to four 90.degree. sectors and the so on. In some such embodiments,
the light-detection assembly comprises a pixelated light-detector
array for determining the intensity of light from the different
areas, the detector array comprising at least as many pixels as
different areas. In some embodiments, a plurality of pixels are
combined as a group to determine the intensity of light from one
area. Any suitable technology of pixelated light-detector array may
be used, e.g., monochrome pixelated arrays, CCD (charge-coupled
device) arrays, PD (photo diode) arrays, CMOS (complementary metal
oxide) arrays and LED (light-emitting diode) arrays.
[0100] In this context, it is important to note that to acquire
images having a diagnostically-useful resolution, known ingestible
imaging devices generally acquire a frame made up of at least 10000
discrete areas (pixels), usually at least 1 million discrete areas
(pixels). In contrast, a device as described herein is generally
configured to simultaneously determine the intensity of not more
than 1000, not more than 360 and even not more than 120 discrete
areas at any one time. An advantage of such a seemingly low spatial
resolution is that much less intense illumination light can be used
(saving power), less data is acquired and still allowing detection
of abnormalities.
[0101] In some embodiments, a light-detection assembly comprises a
focusing component to concentrate light entering an associated
detector window onto the pixelated light-detector array. In some
embodiments, a focusing element is a component of or is the
detector window. In some embodiments, the apertures of the light
detecting elements (pixels) of the light-detector array face an
associated detector window. In some embodiments, a pixelated
light-detector array has a circular periphery around which
outwardly-facing light-detecting elements are arranged, in some
such embodiments, so that the apertures of the light-detecting
elements face the associated detector window.
[0102] In some embodiments, a light-detection assembly comprises a
light-director to change the direction of light passing through an
associated detector window towards a light-detector array. In some
such embodiments, the light-detector array is substantially planar.
Any suitable light-director may be used including a reflecting
element (e.g., a mirror such as a substantially conical-section
mirror), a light-guide, a prism, or a reflecting diffraction
grating (e.g., a substantially conical-section diffraction
grating).
[0103] In some embodiments, a light-director also functions as a
wavelength separator (e.g., 20 a prism (e.g., a conical section
prism), a diffraction grating), in order to direct at least one
specified wavelength of light towards a desired location of a
light-detector array.
[0104] A detector window through which light passes to a
light-detection assembly is substantially transparent to at least
one of the specified wavelengths. As noted above, in some
embodiments, a detector window is configured to act as a wavelength
filter, for example is transparent to substantially only a single
specified wavelength. As noted above, in some embodiments, a
detector window is configured to act as a polarization light
filter. A detector window is of any suitable shape and
construction, and is generally fashioned of glass or plastic
material as known in the art of ingestible imaging devices. In some
embodiments, a detector window is made up of two or more discrete
parts assembled so that the detector window is continuous. In some
embodiments, a detector window is made up of two or more discrete
parts assembled where at least two of the parts are separated by a
non-transparent component. That said, it is generally preferred
(for reasons of ease of construction as well as to reduce the
chance of leakage of gastrointestinal fluids into the casing) that
a detector window comprises substantially a single discrete
component.
[0105] In some embodiments where a light-detection assembly is
configured to determine the intensity of light from a certain
circumferential section (e.g., 120.degree.), the associated
detector window comprises an arc or disk section of at least the
same circumferential section of a material substantially
transparent to at least one specified wavelength. In some
embodiments, especially where an associated light-detection
assembly is configured to determine the intensity of light from a
substantially 360.degree. circumferential section, the associated
detector window is a ring or a disk of a material substantially
transparent to at least one specified wavelength, in some
embodiments positioned coaxial with the device axis.
[0106] In some embodiments, it is desired that one or more
light-detection assemblies selectively detect substantially
exclusively diffusely reflected light.
[0107] As noted above, in some such embodiments, the illuminator is
functionally associated with a polarization component oriented in a
first direction and a light-detection assembly is associated with a
polarization component oriented perpendicularly to the first
direction.
[0108] In some embodiments, the angular aperture of an illuminator
in the plane of the device axis is relatively small so that little
if any specular reflected light is detected by a light-detection
assembly. In some embodiments, the angular aperture of the
illuminator in the plane of the device axis is less than about
30.degree., less than about 20.degree., less than about 10.degree.
and even less than about 5.degree.. In some embodiments, the
angular aperture of an illuminator in the plane of the device axis
is limited by a lens (in some embodiments, the lens constituting
the illuminator window) having the desired limited angular
aperture. In some embodiments, the device comprises a narrow slit
substantially perpendicular to the device axis in which the
illuminator and/or the illuminator window are recessed and through
which light must pass, thereby limiting the angular aperture of the
illuminator in the plane of the device axis.
[0109] In some embodiments, the angular aperture of a
light-detection assembly in the plane of the device axis is
relatively small so that little if any specular reflected light is
detected by a light-detection assembly. In some embodiments, the
angular aperture of the light-detection assembly in the plane of
the device axis is less than about 30.degree., less than about
20.degree., less than about 10.degree. and even less than about
5.degree.. In some embodiments, the angular aperture of a
light-detection assembly in the plane of the device axis is limited
by a lens (in some embodiments, the lens constituting the
associated detector window) having the desired limited angular
aperture. In some embodiments, the device comprises a narrow slit
substantially perpendicular to the device axis in which the
light-detection assembly and/or the associated detection window are
recessed and through which light must pass, thereby limiting the
angular aperture of the light-detection assembly in the plane of
the device axis.
[0110] In some embodiments, a light-detection assembly is
functionally associated with a collimator so that light detected by
the light-detection assembly first must pass the collimator,
ensuring that little if any specular reflected light is detected by
the light-detection assembly. In some embodiments, a collimator is
a separate component. In some embodiments, a detector window is
configured to also function as a collimator.
[0111] Design, construction, assembly and use of a device as
described herein are apparent to a person having ordinary skill in
the art upon perusal of the description and figures. Methods,
materials and dimensions are similar to those used in the art of
ingestible imaging devices such as the Pillcam.TM. (Given Imaging,
Yokneam, Israel) and are easily modified to implement the teachings
herein if necessary.
[0112] The dimensions of a device as described herein are any
suitable dimensions, allowing passage through the gastrointestinal
tract with causing excessive discomfort.
[0113] That said, in some typical embodiments, a device has a total
axial length of between about 15 mm and 35 mm, between about 20 mm
and 30 mm, and even 25 mm like the 15 Pillcam.TM..
[0114] In some typical embodiments, a body section of a device has
an axial length of between about 10 mm and 30 mm, between about 10
mm and 20 mm, and even 15 mm like the Pillcam.TM..
[0115] In some typical embodiments, a body section is substantially
cylindrical with a 20 diameter of between about 5 mm and 20 mm,
between about 7 mm and 15 mm, and even 10 mm like the
Pillcam.TM..
[0116] The axial dimensions (axial length) and distance between the
illuminator window and the detector window are any suitable
values.
[0117] An illuminator window is of any suitable axial length, but
typically not more than 25 about 5 mm. Typically, an illuminator
window is not less than about 0.3 mm long not less than about 0.5
mm long, and even not less than about 1 mm long.
[0118] A detector window is of any suitable axial length, but
typically not more than about 4 mm long, not more than about 3 mm,
not more than about 2 mm, and even not more than about 1 mm
long.
[0119] In some embodiments, in order to collect sufficient light
diffusely reflected from gastrointestinal tissue, the distance from
an illuminator window to a detector window is as small as possible
and in some embodiments, not more than about 5 mm, not more than
about 4 mm, not more than about 3 mm, not more than about 2 mm and
even not more than about 1 mm. Accordingly, in embodiments with
multiple detector windows on the same side of an illumination
window, the detector windows tend to have a small axial length
(e.g., less than about 2 mm, less than about 1 mm) and to be close
together, even substantially abutting.
[0120] As discussed above, the specified wavelength or wavelengths
selected for implementing a device of method as discussed herein
are selected to be diagnostic for some 5 abnormality.
[0121] The spectral width of a specified wavelength is any suitable
spectral width.
[0122] As understood from the discussion above (inter alia, FIG.
1), in some embodiments a suitable spectral width is very broad,
for example, in some embodiments a specified wavelength has a
spectral width of: up to about 400 nm (e.g., spans from about 400
nm to about 800 nm diagnostic for bleeding, FIG. 1A);
up to about 250 nm (e.g., spans from about 400 nm to about 650 nm
diagnostic for bleeding, or from about 400 nm to about 625 nm
diagnostic for invasive adenocarcinoma, FIG. 1A); 1 up to about 150
nm (e.g., spans from about 450 nm to about 600 nm diagnostic for
adenomatous polyp or adenoma, FIG. 1B, for invasive adenocarcinoma,
FIG. 1A, or hyperplastic polyp FIG. 1C or spans from about 500 nm
to about 650 nm diagnostic for bleeding, FIG. 1A); up to about 125
nm (e.g., spans from about 450 nm to 575 nm, diagnostic for
invasive adenocarcinoma, or spans from about 500 nm to 625 nm,
diagnostic for bleeding, FIG. 1A); up to about 100 nm (e.g., spans
from about 450 nm to 555 nm, diagnostic for invasive
adenocarcinoma, or spans from about 500 nm to 600 nm, diagnostic
for bleeding, FIG. 1A); up to about 75 nm (e.g., spans from about
500 nm to 575 nm, diagnostic for bleeding, FIG. 1A); or even up to
about 50 nm (e.g., spans from about 525 nm to 575 nm, diagnostic
for invasive adenocarcinoma, FIG. 1A or adenomatous polyp, FIG.
1B)
[0123] An advantage of such broad spectral widths is that the
illuminator can be configured 30 to produce a relatively low
intensity of light, reducing energy use. A disadvantage of such
broad spectral widths is the possibility that extraneous light
(e.g., from external sources) will be detected as well as technical
difficulty in implementing such broad spectral widths.
[0124] Thus, in some embodiments, a suitable spectral width is
narrow, for example not more than about 10 nm FWHM, not more than
about 5 nm FWHM and even not more than about 2 nm FWHM.
[0125] Such narrow spectral widths are technically simple to
implement using commercially-available wavelength filters.
[0126] A device as described herein may include any suitable
illuminator. In some embodiments, it is preferred to use an
illuminator of the invention. According to an aspect of some
embodiments of the invention, there is provided an illuminator
useful for projecting light in a radially-outwards direction in a
360.degree. circumferential section comprising:
a) a light source for projecting light; and b) a radial diffuser
having a diffuser axis, a first face, a second face and a
substantially circular circumferential outer edge coaxial with the
central diffuser axis, wherein the light source is configured to
project the light into the radial diffuser; and wherein at least a
portion of the light projected into the radial diffuser from the
light source radiates radially-outwards through the circumferential
edge of the radial diffuser.
[0127] In some embodiments, the radial diffuser is disk-shaped,
wherein at least a portion of the first face of the radial diffuser
is substantially transparent to light projected by the light
source; and wherein the light source is configured to project light
into the radial diffuser through the transparent portion of the
first face of the radial diffuser. In some such embodiments, the
light source contacts the transparent portion of the first face of
the radial diffuser.
[0128] In some embodiments, the radial diffuser is ring-shaped
including a central hole with an inner rim; at least a portion of
the inner rim is transparent to light projected by the light
source; and wherein the light source is configured to project light
into the radial diffuser through the inner rim. In some such
embodiments, the light source contacts the transparent portion of
the inner rim.
[0129] In some embodiments, the circumferential edge of the radial
diffuser is perpendicular to the diffuser axis so that
radially-outwards radiating light radiates substantially
perpendicularly to the diffuser axis.
[0130] In some embodiments, the circumferential edge is oriented at
an angle to the diffuser axis so that radially-outwards radiating
light radiates at an angle relative to the diffuser axis. In some
embodiments, at least a portion of the first diffuser face is
opaque to light 30 projected by the light source. In some
embodiments, substantially all of the first diffuser face is opaque
to light projected by the light source. In some embodiments, at
least a portion of the first diffuser face is light reflecting
(e.g., mirrored).
[0131] In some embodiments, at least a portion of the second
diffuser face is light reflecting (e.g., mirrored). In some
embodiments, at least a portion of the second diffuser face is
opaque to light projected by the light source. In some embodiments
with a ring-shaped diffuser, substantially all of the second
diffuser face is opaque to light projected by the light source.
[0132] As noted above, in some embodiments a device described
herein comprises a light-detection assembly comprises a
light-director to change the direction of light passing through an
associated detector window towards a light-detector array and also
to function as a wavelength separator. In some such embodiments,
the light-director is a reflecting diffraction grating. In such
embodiments, any suitable reflecting diffraction grating may be
used. In some embodiments, it is preferred to use a diffraction
grating of the invention. According to an aspect of some
embodiments of the invention, there is provided a diffraction
grating, comprising:
[0133] a substantially conical-section surface having an axis; and
on the surface, periodic features wherein the surface and the
periodic features are configured to reflect light impinging
substantially perpendicularly to the axis at a wavelength-dependent
angle in the general direction of the axis so that the diffraction
grating functions as a dispersive element. In some embodiments, the
periodic features comprise ring-shaped features coaxial to the
axis. In some embodiments, the features comprise ring-shaped slits
in the conical surface. In some embodiments, the features comprise
ring-shaped ridges on the conical surface. In some embodiments, the
surface has a substantially conical shape. In some embodiments, the
diffraction grating has a substantially truncated conical
shape.
[0134] In some embodiments, there is provided a method for
providing information useful for the diagnosis of gastrointestinal
abnormalities, comprising:
a) illuminating an area of an in vivo gastrointestinal tract of a
living mammal with light, wherein the illuminating is outwards from
inside the gastrointestinal tract lumen; b) without acquiring an
image of the area, determining the total intensity of at least one
specified wavelength of light after the light is reflected from the
area of the gastrointestinal tract; and c) providing information
related to the intensity of light indicative of a potential
gastrointestinal abnormality in the area, wherein the area
constitutes a substantially 360.degree. circumferential section of
the gastrointestinal tract. As in some embodiments described above,
the reflected light is substantially diffusely reflected light.
Different from some of the embodiments discussed above, such
embodiments are characterized in that for each one of at least one
specified wavelengths of light a total intensity of light reflected
from a substantially 360.degree. circumferential section of the
gastrointestinal tract is determined, that is to say that each
360.degree. circumferential section of the gastrointestinal tract
is examined as a whole without resolving the circumferential
section into individual sectors. Although some such embodiments
potentially provide less information relating to the size and exact
location of a gastrointestinal abnormality, such embodiments
produce an exceptionally modest volume of data and are thus useful
for screening subjects, whether high-risk subjects or just members
of a normal population. In some embodiments, subjects for which the
method provides evidence indicative of a gastrointestinal
abnormality are subject to invasive but accurate examination, such
as with an endoscope.
[0135] In some such embodiments, the information provided is a
comparison of at least two respective intensities of at least two
different specified wavelengths of light reflected from the same
area of the gastrointestinal tract, the substantially 360.degree.
circumferential section of the gastrointestinal tract.
[0136] In some embodiments, the information provided is the
intensity of at least one specified wavelength of light after the
light is reflected from the area (the substantially 360.degree.
circumferential section of the gastrointestinal tract) compared to
an intensity of light of a same specified wavelength after the
light has been reflected from a different area of the
gastrointestinal tract, in some embodiments, a different
substantially 360.degree. circumferential section of the
gastrointestinal tract.
[0137] Any suitable device may be used in implementing the method,
for example some embodiments of devices as described hereinabove.
In some embodiments it is preferred to implement the method using
an exceptionally simple device that does not differentiate between
intensities of light of a specified wavelength coming from
different directions.
[0138] Thus, in some embodiments there is provided an ingestible
device useful for providing information useful for the diagnosis of
gastrointestinal abnormalities, comprising:
a) an ingestible casing having a device axis, a body section, a
distal end and a proximal end (e.g., a casing as described above);
b) inside said casing, an illuminator configured to project light
radially outwards through an illuminator window of said casing
substantially simultaneously in a substantially 360.degree.
circumferential section around said device axis (e.g., an
illuminator as described above); and c) inside said casing, at
least one light-detection assembly configured to determine the
total intensity of at least one specified wavelength of light
projected by said illuminator and passing through an associated
detector window substantially simultaneously in a substantially
360.degree. circumferential section around said device axis, after
reflection from a substantially 360.degree. circumferential section
of a gastrointestinal tract without acquiring an image.
[0139] In some embodiments, at least one said light-detection
assembly and associated said detector window comprises at least one
wavelength filter configured to pass only light having a said
specified wavelength of light.
[0140] In some embodiments, the device comprises a single
light-detection assembly.
[0141] In some embodiments, the device comprises at least two light
detection assemblies.
[0142] In some embodiments, at least one light-detection assembly
is configured to determine the intensity of one specified
wavelength of light.
[0143] In some embodiments, at least one light-detection assembly
is configured to determine the intensity of at least two specified
wavelengths of light.
[0144] In some embodiments, the device is configured to determine
the intensity of at least two specified wavelengths of light each
at a substantially different location in the device, e.g., a
different light-detection assembly or a different location of a
same light-detection assembly. In some embodiments, the device is
configured to determine the intensity of at least two specified
wavelengths of light each with a substantially different
light-detection assembly.
[0145] In FIGS. 2A-2C, an embodiment 106 of an ingestible device is
schematically depicted, in FIG. 2A device 106 in side
cross-section, in FIG. 2B a detailed view of an illuminator of
device 106 and in FIG. 2C a detailed view of a light-detection
assembly of device 106. Device 106 is similar in dimensions and
construction to a commercially available Pillcam.TM. (Given
Imaging, Yoqneam, Israel).
[0146] The casing of device 106 includes a device axis 12,
streamlined distal and proximal ends 14a and 14b and a
parallel-walled cylindrical body section 16. The casing of device
106 is opaque to light except for illuminator window 18 and
detector window 20, both 1 mm long complete rings of polycarbonate
transparent to wavelengths of light between 400 nm and 800 nm,
separated by separator 22, a 0.2 mm disk of opaque reflective foil,
e.g. aluminum.
[0147] Illuminator window 18 is configured to act as a polarizing
component to polarize light in parallel to device axis 12. Detector
window 20 is configured to act as a polarizing component to
polarize light perpendicularly to device axis 12.
[0148] Inside body section 16 are a power supply 24 (e.g., a
battery), a controller 26 (e.g., an integrated circuit also
configured as a processor to process acquired data), a writeable
memory 28 (e.g., a micro-SD card), a wireless transmitter 30 (e.g.,
a Bluetooth.RTM. transceiver), an illuminator 32 and a single
light-detection assembly 34.
[0149] Illuminator 32 is configured to project light radially
outwards through illuminator window 18 simultaneously in a
360.degree. circumferential section around and perpendicular to
axis 12. Illuminator 32, see FIG. 2B, comprises a light source 36
(e.g., in some embodiments an LED for producing white-light, in
some embodiments producing polychromatic light such as a
phosphor-based white LED, in some embodiments producing specified
monochromatic light (e.g., 500 nm, 515 nm, 530 nm, 545 nm light,
available from Super Bright LEDs Inc., St. Louis. Mo., USA) that
receives electrical power for operation from power supply 24
[0150] 10 through controller 26 and a radial diffuser 38, which is
a disk of transparent material including a diffuser axis 40 and
having a circular outer edge 42 parallel to diffuser axis 40.
Radial diffuser 38 is configured to radially distribute light
produced by light source 36 around diffuser axis 40 where the
radially-outwardly radiating light radiates substantially
perpendicularly to axis 40. A portion of a first face 44 of radial
diffuser 38 where light source 36 contacts first face 44 is
transparent to light produced by light source 36 so that light
source 36 projects light into radial diffuser 38 through the
transparent portion. The other portions of first face 44 as well as
an entire surface of a second face 46 of radial diffuser 38 are
completely mirrored (e.g., by deposition of a layer of silver or
aluminum) and therefore opaque to light.
[0151] When activated, for example by controller 26, light source
36 produces light that enters radial diffuser 38 through the
transparent portion of first face 44. The produced light is
reflected inside radial diffuser 38 between the mirrored portions
of first face 44 and second face 46 to emerge perpendicularly to
diffuser axis 40 through outer edge 42 of radial diffuser 38 and
through illuminator window 18, projecting a ring of light around
device 106.
[0152] Light-detection assembly 34 of device 106 is associated with
detector window 20 and is configured to determine the total
intensity of a single specified wavelength of light (e.g., 500 nm)
passing through detector window 20 from an entire 360.degree.
circumferential section around axis 12. Light-detection assembly
34, see FIG. 2C, comprises a single light detecting element 108
(e.g., an LED such as available from Super Bright LEDs Inc., St.
Louis. Mo., USA suitable for detecting light having a wavelength of
500 nm).
[0153] Intimately contacting the inner surface of detector window
20 is a ring of a narrow pass wavelength filter 50 chosen to
selectively pass 500 nm light. Wavelength filter 50 is any suitable
wavelength filter, for example a flexible filter available from Lee
Filters, Andover, Hampshire, England.
[0154] Light-detection assembly 34 is functionally associated with
controller 26, where the output of light detecting element 108
corresponding to the total intensity of light having a wavelength
of 500 nm passing through detector window 20 is input for
controller 26.
[0155] When light produced by illuminator 32 is reflected from
intestinal tissue towards detector window 20, only light having the
specified wavelength of 500 nm passing through detector window 20
passes through wavelength filter 52 to impinge on light-detecting
element 108. At a rate of 10 Hz, controller 26 receives the
intensity of 500 nm determined from light-detecting element
108.
[0156] For use, device 106 is activated and ingested by a subject,
eventually passing the pylorus to enter and pass through the
duodenum, small intestine, large intestine and rectum before being
expelled through the anus. The location of the device in the
gastrointestinal tract at any time is monitored in the usual way.
In some embodiments, the location of the device in the
gastrointestinal tract is not monitored.
[0157] Illuminator 32 projects a ring of polarized light
perpendicularly from illuminator window 18, illuminating a
360.degree. circumferential section of gastrointestinal tissue in
close proximity or touching illuminator window 18, arrow "a" in
FIG. 3.
[0158] Some of the light is reflected from the gastrointestinal
tissue towards detector window 20, arrow "b" in FIG. 3. Light
reflected from a 360.degree. circumferential section of
gastrointestinal tissue of the specified wavelength (500 nm) passes
through wavelength filter 52 to light-detecting element 108. If
present, most specular reflected light is prevented from passing
through detector window 20 due to the cross polarization between
illuminator window 18 and detector window 20 so that primarily
diffusely projected light reaches light-detecting element 108. The
total intensity of reflected light of the specified wavelength is
determined at a rate of 10 Hz. Thus, the total intensity of light
of the specified wavelength passing through wavelength filter 52
that is reflected by a complete ring of tissue encircling device
106 is detected by light-detecting element 108 at a rate of 10 Hz
and is reported to controller 26.
[0159] For each intensity (variable name intensity) received from
light-detecting element 108, controller 26 functions as a processor
to calculate and store the average intensity of detected light as a
variable average in memory 28. For each intensity received from
light-detecting element 108 after the tenth intensity, controller
26 calculates the intensity relative to the average intensity
(relativeintensity=intensity/average). The values of
relativeintensity are stored as a function of time in an array in
memory 28. The determined intensities are received by controller 26
and stored in an array in memory 28. When device 106 is expelled
from the anus, the device 106 is recovered and the recorded
relative intensities constituting information indicative of a
potential gastrointestinal abnormality can be downloaded for review
and analysis to assist a medical professional in deciding whether
there is an abnormality in the gastrointestinal tract of the
subject.
[0160] Concurrently, controller 26 transmits the instantaneously
determined values of average, intensity and relativeintensity that
constitute information indicative of a potential gastrointestinal
abnormality to an appropriately-configured external unit (not
depicted) outside of the body through wireless transmitter 30. An
automatic program (e.g., written in Fortran programming language
and running on a standard general purpose computer) analyzes the
received values of relativeintensity to identify a relative
intensity that is sufficiently low (e.g., less than about 60%, less
than about 50%, less than about 30%) of the average, indicating a
potential abnormality (e.g., bleeding, invasive
adenocarcinoma).
[0161] If no sufficiently low relative intensity value is
identified, a medical professional may decide (optionally, together
with other information) that there is sufficient evidence that the
examined subject is clear of any potential gastrointestinal
abnormality and take no further immediate action.
[0162] If a sufficiently low relative intensity value is
identified, a medical professional may decide (optionally, together
with other information) that there is sufficient evidence that the
examined subject requires further examination and order a more
invasive and/or more expensive procedure such as the use of a
Pillcam.TM. (Given Imaging, Yokneam, Israel) or endoscopy (such as
sigmoidoscopy, colonoscopy, enteroscopy and
esophagogastroduodenoscopy).
[0163] In some embodiments, the transmitted information is analyzed
in real-time, and whenever a sufficiently low relative intensity is
detected, the external unit sounds an audible alarm to warn an
attending health-care professional.
[0164] In FIGS. 2D and 2E exemplary information acquired by a
device such as device 106 is depicted.
[0165] In FIG. 2D, the relative intensity of light (determined as
described above) having a wavelength of 500 nm reflected from
gastrointestinal tissue and detected by a light detector 30 108 is
plotted as a function of time.
[0166] In the upper plot, device 106 passes through normal
gastrointestinal tissue so the determined relative intensity is
substantially constant.
[0167] In the middle plot, device 106 passes through normal
gastrointestinal tissue until encountering a bleeding lesion. At
the bleeding lesion and downstream therefrom for a significant
length of the gastrointestinal tract, the determined relative
intensity is substantially lower than of normal tissue due to the
presence of blood that reduces the intensity of light having a
wavelength of 500 nm that is reflected from the gastrointestinal
tract to be detected by light-detection assembly 34 of device 106
as discussed above with reference to FIG. 1.
[0168] At some point in the intestine, the amount of blood on the
intestinal surface becomes substantially lower and the average
determined relative intensity returns to normal.
[0169] In the lower plot, device 106 passes through normal
gastrointestinal tissue until encountering a localized invasive
adenocarcinoma. The determined relative intensity at the invasive
adenocarcinoma is substantially lower than of normal tissue as
discussed above with reference to FIG. 1. When detector window 20
passes the invasive adenocarcinoma, the determined relative
intensity returns to normal.
[0170] The information such as depicted in FIG. 2D acquired in
accordance with embodiments of the method and device described
herein, when provided to a person such as a physician can be useful
in helping making a diagnosis as to the presence and nature of
gastrointestinal abnormalities. For example, together with other
medical data, whether the subject is likely healthy, has intestinal
bleeding or invasive adenocarcinoma.
[0171] It is important to note that although device 106 is
specifically configured to determine the intensity of a very narrow
selected wavelength (500 nm), other wavelengths can be used (as
seen from FIGS. 1A-1C), as well as much broader selected
wavelengths. For example, in some embodiments for detecting
bleeding, illuminator 32 is configured to project monochromatic
light with specified wavelength bandwidth, polychromatic light at
specified wavelength range or white light and light-detection
assembly 34 is configured to determine the intensity of a selected
wavelength that spans from 400 nm to 800 nm without discrimination
(useful for detecting bleeding). Analogously, some embodiments
useful for detecting bleeding are configured to determine the
intensity of a selected wavelength that spans from 500 nm to 650
nm, and any sub-group of selected wavelengths. Analogously, some
embodiments useful for detecting invasive adenocarcinoma are
configured to determine the intensity of a selected wavelength that
spans from 400 nm to 600 nm, and any sub-group of selected
wavelengths. Analogously, some embodiments useful for detecting
adenomas or adenomatous polyps are configured to determine the
intensity of a selected wavelength that spans from 475 nm to 575
nm, and any sub-group of selected wavelengths.
[0172] In FIGS. 4A-4B, an embodiment 110 of an ingestible device is
schematically depicted: in FIG. 4A in side cross-section and in
FIG. 4B a detailed view of a light detection assembly 34. Device
110 comprises multiple light-detection assemblies each configured
to determine the intensity of a single specified wavelengths of
light.
[0173] Device 110 comprises an illuminator 32 substantially
identical to illuminator 32 of device 106 configured to project
light radially outwards through illuminator window 18 in a 5
360.degree. circumferential section around and perpendicular to
axis 12.
[0174] Device 110 is similar to device 106 discussed above with a
number of notable differences.
[0175] Whereas device 106 comprises a single light-detection
assembly 34, device 110 comprises three independent light-detection
assemblies 34a, 34b and 34c, each associated with a dedicated
detector window 20a, 20b and 20c respectively. Light-detection
assemblies 34 of device 110 are substantially similar to
light-detection assembly 34 of device 106. However, instead of
including a separate wavelength filter 52 as in device 106, each
detector window 20 is fashioned of a colored polycarbonate
material, thereby functioning as a wavelength filter so that each
light-detection assembly 34 is configured to determine the
intensity of a single specified wavelength of light, specifically,
500 nm (34a), 550 nm (34b) and 650 nm (34c). Consequently, device
110 is configured to determine the intensity of three specified
wavelengths of light at substantially different physical locations,
the respective light-detector arrays of the different
light-detection assemblies 34a, 34b and 34c.
[0176] Instead of a single light-detecting diode 108 as in device
106, in device 110 each light-detection assembly 34 includes a
pixelated planar light-detection array (e.g., CCD, PD, CMOS, LED
such as known in the art of digital photography) that in FIG. 4B is
hidden from view by a miniature fish-eye lens 112. Each fish-eye
lens 112 gathers light entering a respective detector window 20 and
focuses the light on a respective light-detection assembly.
Although each pixel of light-detection assembly is able to
determine a detected light intensity independently of the other
pixels, in device 110 the outputs of all the pixels are summed and
sent as a single intensity value as input for controller 26.
[0177] For use, device 110 is activated and ingested by a subject,
eventually passing the pylorus to enter and pass through the
duodenum, small intestine, large intestine and rectum before being
expelled through the anus. The location of the device in the
gastrointestinal tract at any time is monitored in the usual way.
In some embodiments, the location of the device in the
gastrointestinal tract is not monitored.
[0178] Illuminator 32 projects a ring of polarized light
perpendicularly from illuminator window 18, illuminating a
360.degree. circumferential section of gastrointestinal tissue in
close proximity or touching illuminator window 18.
[0179] Some of the projected light is diffusely reflected from
gastrointestinal tissue towards detector windows 20a, 20b and 20c.
Light reflected from a 360.degree. circumferential section of
gastrointestinal tissue of the first specified wavelength (500 nm)
passes through detector window 20a associated with light-detection
assembly 34a. Light reflected from a 360.degree. circumferential
section of gastrointestinal tissue of the second specified
wavelength (550 nm) passes through detector window 20b associated
with light-detection assembly 34b. Light reflected from a
360.degree. circumferential section of gastrointestinal tissue of
the third specified wavelength (650 nm) passes through detector
window 20c associated with light-detection assembly 34c. Specularly
reflected light is prevented from passing through detector windows
20 due to the cross polarization between illuminator window 18 and
detector windows 20 so that primarily diffusely projected light
reaches the light-detector arrays. The total intensity of reflected
light of the three specified wavelengths of light is determined at
a rate of 10 Hz. Thus, the total intensity of light of the three
specified wavelengths passing through detector windows 20 that is
reflected by a complete ring of tissue encircling device 110 is
detected by the light-detectors of light detection assemblies 34 at
a rate of 10 Hz and are all three reported to controller 26.
[0180] The determined intensities are received by controller 26.
Controller 26 functions as a processor to compare the intensities
of the three different specified wavelengths reflected from the
same area of the gastrointestinal tract. Specifically, for each
cycle where the intensities are determined, controller 26 compares
(e.g., by calculating a ratio) the intensities of 500 nm light, 550
nm light and of 650 nm light reflected from the same area. The
comparisons of intensities constituting information indicative of a
potential gastrointestinal abnormality are then transmitted to an
appropriately-configured external unit (not depicted) outside of
the body through wireless transmitter 30. An automatic program
analyzes the received compared intensities (in some embodiments in
real time, in some embodiments not in real time) to identify
information indicative of a potential abnormality.
[0181] By comparing the determined intensities of light at the
different specified wavelengths 500 nm 550 nm and 650 nm reflected
from the same area of an intestinal wall, various gastrointestinal
abnormalities can be potentially identified. For example,
substantially similar intensities of light having wavelengths of
500 nm, 550 nm and/or 650 nm that is significantly lower than that
of normal tissue is indicative of bleeding, while the pattern of an
intensity of 650 nm greater than at 500 nm greater than at 550 nm
is indicative of invasive adenocarcinoma, FIG. 1A. For example,
intensities of 500 nm and 550 nm higher than at 650 nm are
indicative of adenomatous polyp while intensities of 500 nm and 550
nm lower than of 650 nm are indicative of invasive adenocarcinoma,
FIG. 1B.
[0182] A medical professional receives the provided information and
can then (based on the information, optionally together with other
information) choose to do nothing or order a more 5 invasive and/or
more expensive procedure for further examination
[0183] In FIG. 4C exemplary information acquired by a device such
as device 110 is depicted.
[0184] In FIG. 4C, the ratio of the intensity of light having a
wavelength of 550 nm (I.sub.x.sup.55.degree.) to light having a
wavelength of 650 nm (I.sub.x.sup.650) determined by
light-detection assemblies 34b and 34c reflected from the same area
X of gastrointestinal tissue is plotted as a function of time.
[0185] At time t2, a slight increase
of))(I.sub.x.sup.550/(I.sub.x.sup.650) indicates the potential
presence of a hyperplastic polyp (see FIG. 1B). At time t3, a
significant increase of (I.sup.x550)/ox650,) indicates the
potential presence of an adenomatous polyp (see FIG. 1B).
[0186] At time t4, a significant decrease
of)(I.sub.x.sup.55.degree.)/(I.sub.x.sup.650) indicates the
potential presence of a invasive adenocarcinoma (see FIG. 1B).
[0187] The information such as depicted in FIG. 4C acquired in
accordance with embodiments of the method and device described
herein, when provided to a person such as a physician can be useful
in helping making a diagnosis as to the presence and nature of
gastrointestinal abnormalities.
[0188] An embodiment 114 of an ingestible device is schematically
depicted in FIG. 5A in side cross-section and in FIG. 5B a detailed
view of a light-detection assembly 34. Device 114 comprises a
single light-detection assembly configured to determine the
intensity of multiple specified wavelengths of light. Device 114 is
similar to devices 106 and 110 discussed above with a number of
notable differences.
[0189] Device 114 comprises a single light-detection assembly 34
configured to determine the intensity of three selected wavelengths
of light. Light-detection assembly 34 includes three separate
light-detecting elements 108a, 108b and 108c each substantially
similar to light-detecting element 108 of device 110, except that
each element 108 is configured to detect the intensity of a single
wavelength of light (e.g., are LED configured to determine an
intensity of a specific wavelength of light or are covered with a
wavelength filter) and provide a determined intensity to controller
26. Specifically, light-detecting element 108a is configured to
determine the intensity of light having a wavelength of 500 nm,
light-detecting element 108b is configured to determine the
intensity of light having a wavelength of 550 nm and
light-detecting element 108c is configured to determine the
intensity of light having a wavelength of 650 nm. Consequently,
device 114 is configured to determine the intensity of three
specified wavelengths of light at substantially different physical
locations, light-detecting elements 108a, 108b and 108c.
[0190] Device 114 is devoid of a wavelength filter 52 associated
with detector window 20.
[0191] Device 114 comprises an illuminator 32 substantially
identical to illuminator 32 of device 108 configured to project
light radially outwards through illuminator window 18 in a
360.degree. circumferential section around and perpendicular to
axis 12.
[0192] The use of device 114 is substantially as described above
with reference to device 110.
[0193] An embodiment 116 of an ingestible device is schematically
depicted in FIG. 6A in side cross-section and in FIG. 6B, a
detailed view of a light-detection assembly 34. Device 116
comprises a single light-detection assembly configured to determine
the intensity of multiple specified wavelengths of light. Device
116 is similar to devices 106, 110 and 114 discussed above with a
number of notable differences.
[0194] Device 116 comprises a single multicolor light-detection
assembly 34 configured to determine the intensity of three selected
wavelengths of light. Light-detection assembly 34 includes a single
multicolor light-detection array 118 (a 59706 RGB color sensor by
Hamamatsu Photonics K.K. (Hamamatsu, Japan)) including 81
light-sensitive elements arranged in a 9.times.9 array. An on-chip
mosaic wavelength filter renders 27 of the light-sensitive elements
sensitive to red light (615 nm), 27 sensitive to green light (540
nm) and 27 sensitive to blue light (465 nm). Light-detection array
118 is assembled in device 116 so that all the red-light sensitive
elements have a single output 120 to controller 26, all the
green-light sensitive elements have a single output 122 to
controller 26 and all the blue-light sensitive elements have a
single output 124 to controller 26. Consequently, device 116 is
configured to determine the intensity of three specified
wavelengths of light at substantially the same physical location,
the surface of light-detection array 118.
[0195] Device 116 is devoid of a wavelength filter 52 associated
with detector window 20.
[0196] Device 116 comprises an illuminator 32 substantially
identical to illuminator 32 of device 108 configured to project
light radially outwards through illuminator window 18 in a
360.degree. circumferential section around and perpendicular to
axis 12.
[0197] The use of device 116 is substantially as described above
with reference to device 110, with the changes dictated by the
different specified wavelengths of light which intensity is
detected.
[0198] For example, in some embodiments, an increased intensity of
465 nm light compared to both 540 nm light and 615 nm light
relative to normal mucosa is indicative of blood, while a reduced
intensity of 540 nm light compared to both 465 nm and 615 nm light
compared to normal mucosa is indicative of an invasive
adenocarcinoma, see FIG. 1A.
[0199] For example, in some embodiments, a reduced intensity of 465
nm and 540 nm light compared to 615 nm light relative to normal
mucosa is indicative of an invasive adenocarcinoma or adenoma,
while an increased intensity of 465 nm and 540 nm light compared to
615 nm light relative to normal mucosa is indicative of an
adenomatous polyp, see FIG. 1B.
[0200] In device 116, multicolor light-detection array 118 is an
RGB sensor that, due to the low pixel-resolution, is not suitable
for imaging. In related embodiments, other multicolor
light-detection arrays, including light-detection arrays suitable
for imaging, are used in implementing the teachings herein in an
analogous manner, that is to say, is configured to provide a single
intensity output for each of at least two colors that is a
combination (e.g., sum) of the output of multiple discrete
light-sensitive elements of the light-detection array. In such
related embodiments, any suitable light-detection array technology
can be used, e.g., CMOS, CCD or LED arrays.
[0201] In light-detection array 118 of device 116, a special RGB
filter allows detection of discrete and narrow red, green and blue
colors. In related embodiments, any suitable set of colors can be
used. For example, light-detection arrays with other RGB filters,
for example, Bayer filters, or RGB light-detection arrays such as
the Foveon-X3 CMOS light detection array. For example, in some
embodiments, a light-detection array is a CYYM light-detection
array with three separate outputs: a cyan output, a yellow output
and a magenta output. For example, in some embodiments, a
light-detection array is an RGBE light-detection array with four
separate outputs: a red output, a green output, a blue output and
an emerald output. For example, in some embodiments, a
light-detection array is an CYGM light-detection array with four
separate outputs: a cyan output, a yellow output, a green output
and a magenta output. For example, in some embodiments, a
light-detection array is an CMYW light-detection array with four
separate outputs: a cyan output, a magenta output, a yellow output
and a white output (in some embodiments, the white output is not
used). For example, in some embodiments, a light-detection array is
an RGBW light-detection array with four separate outputs: a red
output, a green output, a blue output and a white output (in some
embodiments, the white output is not used). In such embodiments, a
person skilled in the art is able, upon perusal of the description
herein, to decide (for example, with reference to FIGS. 1A, 1B and
1C) which color outputs to compare to provide information
indicative of a gastrointestinal abnormality.
EXAMPLES
Example 1
Wavelength Dependence of Diffuse Reflection from Normal and
Abnormal Tissue
[0202] The wavelength dependence of diffuse reflection from the
intestinal abnormalities of blood and invasive adenocarcinoma
relative to normal intestinal mucosa was examined in a manner
simulating the use of an ingestible device as described herein.
[0203] Two freshly excised samples (about 20 cm by 40 cm) of human
intestinal tissue were provided, one with a bleeding area and one
having an invasive adenocarcinoma, as determined by a
pathologist.
[0204] As an illuminator, a 0.6 mm diameter glass fiber was
connected to an SE NET Model 1-150 fiber optic light source
including a 150 Watt Quartz halogen lamp and the distal tip of the
fiber contacted with an area of intestinal tissue. As a
light-detection assembly, a 0.2 mm diameter glass fiber was
connected to a StellarNet Green Fiberoptic spectrometer
(StellarNet, Inc, Tampa, Fla., USA) and the distal tip contacted
with the intestinal tissue, 0.2 mm from the illuminator glass
fiber. As the distal tip of the light detection glass fiber
contacted the tissue, only diffusely reflected light was guided
into and detected by the spectrometer.
[0205] The distal tips of the glass fibers were contacted with a
bleeding area of the first sample of intestinal tissue and the
spectrometer activated to detect the intensity of light diffusely
reflected from the bleeding area from 400 nm to 800 nm at
increments of 1 nm. The intensity measurements were repeated with
an area of intact mucosa of the same intestinal tissue sample. The
relative detected intensities are depicted in FIG. 1A, normalized
relative to detected intensities of the intact mucosa, of the
intact mucosa (plot `a`) and of the bleeding area (plot `b`).
[0206] The distal tips of the glass fibers were contacted with an
area of the second sample of intestinal tissue having the invasive
adenocarcinoma and the spectrometer activated to detect the
intensity of light diffusely reflected from the invasive
adenocarcinoma from 400 nm to 800 nm at increments of 1 nm. The
intensity measurements were repeated with an area of intact mucosa
of the same intestinal tissue sample. The relative detected
intensities are depicted in FIG. 1A, normalized relative to
detected intensities of the intact mucosa, of the invasive
adenocarcinoma (plot `c`).
[0207] It is apparent from FIG. 1A, that the diffuse reflection of
different tissue types has distinct spectral characteristics, and
that the teachings herein may be used to provide information useful
for assisting in diagnosis of gastrointestinal abnormalities.
Example 2
Wavelength Dependence of Diffuse Reflection from Normal and
Abnormal Tissue
[0208] The wavelength dependence of diffuse reflection from various
intestinal abnormalities related to invasive adenocarcinoma
relative to normal intestinal mucosa were examined in a manner
simulating the use of an ingestible device as described herein.
[0209] Fifty-four in vivo spectral measurements were performed
during standard colonoscopy in patients having various
abnormalities as determined by a physician (endoscopist) and
confirmed by a pathologist.
[0210] As an illuminator, a standard light source (xenon arc lamp)
of endoscopic system (Olympus CV180, Olympus, Japan) was used.
Light was directed at intestinal tissue to illuminate the entire
surface of the tissue. A light-detection assembly includes a 600g
(0.6 mm) diameter glass fiber connected to a StellarNet Green
Fiberoptic spectrometer (StellarNet, Inc, Tampa, Fla., USA) as
described in Example 1. As the distal tip of the light detection
glass fiber contacted the tissue, only diffusely reflected light
was guided into and detected by the spectrometer.
[0211] For each area of tissue, the distal tip of the
light-detection glass fiber was first contacted with an area of an
identified intestinal abnormality and the intensity of diffusely
reflected light determined between 400 nm and 750 nm at 1 nm
increments. The intensity measurements were repeated with an area
of intact mucosa of the same intestinal tissue sample. The
determined intensities of the abnormal tissue were normalized
relative to the determined intensities of the normal tissue.
[0212] The relative detected intensities are depicted in FIG. 1B,
of intact mucosa (plot `a`), invasive adenocarcinoma (plot `c`,
average of 5 samples), hyperplastic polyp (plot `d`, average of 6
samples), adenomatous polyp (plot `e`, average of 20 samples) and
adenoma (plot `f, average of 23 samples).
[0213] It is apparent from FIG. 1B, that the diffuse reflection of
different tissue types has distinct spectral characteristics, and
that the teachings herein may be used to provide information useful
for assisting in diagnosis of gastrointestinal abnormalities.
Example 3
Wavelength Dependence of Diffuse Reflection from Normal and
Abnormal Tissue
[0214] The wavelength dependence of diffuse reflection from various
intestinal abnormalities relative to normal intestinal mucosa was
examined in a manner simulating the use of an ingestible device as
described herein.
[0215] 45 freshly excised samples (about 20 cm by 40 cm) of human
intestinal tissue were provided, having various abnormalities as
determined by a pathologist.
[0216] As an illuminator, a quartz halogen lamp with polarizing
filter was directed at a sample of intestinal tissue to illuminate
the entire surface of the tissue. A spectral camera (SD-300 from
Applied Spectral Imaging, Migdal Haemek, Israel) with a polarizing
filter oriented perpendicularly to the polarizing filter of the
illuminator was used as a light-detection assembly with the
objective lens positioned 10 cm from a tissue sample surface to
acquire spectra using the polarized-gated method between 400 nm and
800 nm at increments of 1 nm of areas of the surface of each of the
samples. As the illuminator and light-detection assembly were
cross-polarized, the light detected was primarily diffusely
reflected light.
[0217] The spectra of areas of abnormal tissue corresponding to
bleeding tissue (11 samples), invasive adenocarcinoma (5 samples),
hyperplastic polyps (6 samples) and adenoma (23 samples) were
normalized relative to the spectra of nearby normal tissue from the
same sample.
[0218] The spectra of each of the abnormal tissue types and the
normal tissue were averaged and displayed in FIG. 1C: normal tissue
(plot `a`, average of 45 spectra), bleeding (plot `b`, average of
11 spectra) invasive adenocarcinoma (plot `c`, average of 5
spectra), hyperplastic polyps (plot `d`, average of 6 spectra) and
adenoma (plot `f, average of 23 spectra).
[0219] It is apparent from FIG. 1C, that the diffuse reflection of
different tissue types has distinct spectral characteristics, and
that the teachings herein may be used to provide information useful
for assisting in diagnosis of gastrointestinal abnormalities.
[0220] Although the invention has been described in conjunction
with specific embodiments thereof, it is evident that many
alternatives, modifications and variations will be apparent to
those skilled in the art. Accordingly, it is intended to embrace
all such alternatives, modifications and variations that fall
within the scope of the appended claims.
[0221] For example, in the embodiments described above, the devices
comprise an illuminator with a radial diffuser giving a homogenous
illumination around the device. In some embodiments, other types of
illuminators are used, for example, illuminating strips or a
circular array of outwardly-facing light sources such as LEDs.
[0222] It is appreciated that certain features of the invention,
which are, for clarity, described in the context of separate
embodiments, may also be provided in combination in a single
embodiment. Conversely, various features of the invention, which
are, for brevity, described in the context of a single embodiment,
may also be provided separately or in any suitable subcombination
or as suitable in any other described embodiment of the invention.
Certain features described in the context of various embodiments
are not to be considered essential features of those embodiments,
unless the embodiment is inoperative without those elements.
Citation or identification of any reference in this application
shall not be construed as an admission that such reference is
available as prior art to the invention.
[0223] Section headings are used herein to ease understanding of
the specification and should not be construed as necessarily
limiting.
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