DESCRIPTION
DETERMINING APPARATUS AND DETERMINING METHOD
Technical Field
5 [0001] The present invention relates to a
determining apparatus and a determining method that
determine a contact state of a tip portion of a laser
catheter with respect to a therapy-target tissue.
Background Art
10 [0002] Atrial fibrillation is known as a kind of
tachyarrhythmia. A hyperexcited site, which generates
an electrical pulse, appears in the vicinity of a root
portion, in which a pulmonary vein and a left atrium
are connected, and the left atrium minutely vibrates
15 and contracts because of the electrical pulse
stimulation, to thereby cause an atrial fibrillation.
[0003] As an atrial fibrillation therapeutic method,
the inventors have been proposed application of
photodynamic therapy (hereinafter, referred to as
20. "PDT".) (for example, see Patent Document 1.) In PDT,
a cardiac-muscle tissue, which has absorbed photosensitive
pharmaceutical, is irradiated with an
excitation light by using a laser catheter, to thereby
generate singlet oxygen. The singlet oxygen as a strong
25 oxidizer insults a cardiac-muscle tissue, which
surrounds the hyperexcited site, to thereby form an
2
electric-conduction block, which blocks conduction of
the electrical pulse from the hyperexcited site to the
left atrium. As a result, an electric conduction
between the hyperexcited site and the left atrium is
5 blocked, and an abnormal vibration and contraction of
the left atrium is inhibited.
[0004] Photo-sensitive pharmaceutical has a property
of selectively accumulating in a certain tissue. In
view of this, in general, after a predetermined time
10 (for example, 8 to 48 hours) passes after photosensitive
pharmaceutical is administered in a patient,
when the state where the photo-sensitive pharmaceutical
concentration is high in a therapy-target tissue and
the photo-sensitive pharmaceutical concentration is low
15 in other tissues and blood is established, that is,
when the state where a so-called photo-sensitive
pharmaceutical contrast is high is established,
irradiation with the excitation light is started..
Further, recently, PDT, in which the accumulating
20 property of photo-sensitive pharmaceutical is not used
and in which irradiation with the excitation light is
started when photo-sensitive pharmaceutical is
delivered to a therapy-target tissue by blood, is
proposed.
25 [0005] Patent Document 1: WIPO Publication No.
2008/066126
3
Disclosure of the Invention
Problem to be solved by the Invention
[0006] In the field of circulatory disease therapy,.
in order to ensure safety and reliability, it is
5 important to determine, in real time, the contact state
of a tip portion of a laser catheter, which outputs an
excitation light, with respect to a tissue. Further, in
the case where an intended tissue is a movable target
such as a cardiac-muscle tissue, in order to attain
10 reliable therapy, it is necessary to determine the.
contact state in detail, that is, whether the catheter
follows the movement of the tissue. However, it is
difficult to determine the contact state of a tip
portion of a catheter in blood in detail.
15 [0007] In view of this, in the past, there is known,
for example, a method in which a balloon provided
around a catheter blocks a blood vessel to thereby
temporarily block a blood flow, in which saline ur the
like is flowed from a catheter tip portion to thereby
20 _- secure a transparent zone, and in which the catheter
dontact state is observed by using an angioscope.
However, this method may lead to a peripheral-vesselischemia
state. Because of this, by using this method,
it is not possible to observe, in real time, the
25 contact state of the tip portion of the catheter for a
long time.
4
[0008] In view of the above-mentioned circumstances,
an object of the present invention is to provide a
determining. apparatus and a determining method capable
of safely determine the contact state of a tip portion
5 of a catheter with respect to a tissue in real time.
Meansfor solving the Problem
[0009] To attain the above-mentioned object, a
determining apparatus according to an embodiment.: of the
present invention is a determining apparatus for
10 irradiating a tissue having absorbed photo-sensitive
pharmaceutical, the photo-sensitive pharmaceutical
absorbing an excitation light and emitting fluorescence,
or a tissue absorbing the excitation light and emitting
fluorescence, with the excitation light emitted from a
15 tip portion of a laser catheter, including a connector,
a light source, and a detection unit.
The laser catheter is capable of being
attached/detached to/from the connector.
The light source outputs the excitation light to
20 the laser catheter via the connector.
The detection unit detects intensity or a spectrum
of the fluorescence, the fluorescence being entered
from the laser catheter via the connector, to determine
whether the tip portion of the -laser catheter contacts
25 the tissue or not.
[0010] By detecting the intensity or the spectrum of
5
the fluorescence entered from the laser catheter, it is
possible to measure whether the tip portion of the
laser catheter contacts a tissue or not in real time.
Further, by using a laser catheter used for therapy,
5 operability is improved.
[0011] The determining apparatus may further include
a controller for determining whether the tip portion of
the laser catheter contacts the tissue or not, tried on
intensity or a spectrum of the detected fluorescence.
10 [0012] By detecting the intensity or spectrum of the
fluorescence entered from the laser catheter, it is
possible to determine whether the tip portion of the
laser catheter contacts the tissue or not in real time.
[0013] The determining apparatus may further include
15 a controller for determining a contact angle in a state
where the tip portion of the laser catheter contacts
the tissue or determining that the tip portion of the
laser catheter fails to contact the tissue, based on
intensity or a spectrum of the detected fluorescence.
20 „. [0014] By detecting the intensity or spectrum of the
fluorescence entered from the laser catheter, it is
possible to determine, in real time, a contact angle in
the state where the tip portion of the laser catheter
contacts the tissue or determine that the tip portion
25 of the laser catheter fails to contact the tissue.
[0015] The controller may output a signal to prompt
S
to change _a contact state of the tip portion of the
laser catheter with respect to the tissue, based on the
determination result.
[0016] As a result, it is possible to prompt a
5 practitioner to change the contact state of the laser
catheter in real time, based on the intensity or
spectrum of the fluorescence entered from the laser
catheter. Note that to ''output a signal" means Co.
output a display instruction including display
10 information to a display unit, or to output a sound
output instruction to a speaker unite.
[0017] The controller may calculate an excitationlight-
irradiation protocol based on the intensity or
the spectrum of the detected fluorescence, and output a
15 calculation result.
[0018] As a result, it. is possible to inform a
practitioner of the excitation-light-irradiation
protocol in real time, based on the intensity or
spectrum of the fluorescence entered from the laser
20 catheter.
[0019] The light source may output the excitation
light with a first intensity when determining whether
the tip portion of the laser catheter contacts the
tissue or not, and output the excitation light with a
25 second intensity when performing a photodynamic therapy
with respect to the tissue, the second intensity being
7
larger than the first intensity.
[0020] Because it is possible to measure whether the
tip portion of the laser catheter contacts a tissue or
not with the low-power excitation light, the method is
5 minimally-invasive.
[0021} The controller may obtain an
electrocardiographic signal, and determine a contact
angle in a state where the laser catheter contacts the
tissue or determines that the laser catheter fails to
10 contact the tissue, based on a correlation between the
electrocardiographic signal and the intensity of the
fluorescence.
[0022] By calculating the correlation between an
electrocardiographic signal and fluorescence intensity,
15 it is possible to determine, in real time, whether the
tip portion of the laser catheter contacts the tissue
or not.
[0023] The controller may determine an abnormal
situation of the tip portion of the laser catheter,
20 based on the intensity or the spectrum of the detected
fluorescence.
[0024] By detecting the intensity or spectrum of the
fluorescence entered from the laser catheter, it is
possible to determine, in real time, an abnormal
25 situation-in which the tip portion of the laser
catheter contacts a foreign substance, in which the tip
S
portion of the laser catheter is broken, or the like.
[0025] A determining method according to an
embodiment of the present invention includes
irradiating a tissue having absorbed photo-sensitive
5 pharmaceutical, the photo-sensitive pharmaceutical
absorbing an excitation light and emitting fluorescence,
or a tissue absorbing the excitation light and emitting
fluorescence, with the excitation light emitted from a
tip portion of a laser catheter.
10 The fluorescence corresponding to the irradiated
excitation light is extracted via the laser catheter.
Whether the tip portion of the laser catheter
contacts the tissue or not is determined, based on
intensity or a spectrum of the extracted fluorescence.
15 [0026] By detecting the intensity or spectrum of the
fluorescence entered from the laser catheter, it is
possible to determine whether the tip portion of the
laser catheter contacts the tissue or not in rent. time.
[0027] The determining method may further include
20 calculating an excitation-light-irradiation protocol
based on the intensity or the spectrum of the extracted
fluorescence, and outputting a calculation result.
[0028] As a result, it is possible to inform a
practitioner of an excitation-light-irradiation
25 protocol in real time, based on the intensity or
spectrum of the fluorescence extracted via the laser
9
catheter
[0029] A determining method according to an
embodiment of the present invention is a determining
method using photo-sensitive pharmaceutical absorbing
5 an excitation light and emitting a fluorescence, a
laser catheter capable of emitting the excitation light
from a tip portion, and an estimating apparatus
including a connector to/fromwhich the laser catheter
is capable of being attached/detached and a light
10 source for outputting the excitation light to the laser
catheter via the connector.
In a tissue, the photo-sensitive pharmaceutical is
absorbed.
The tip portion of the laser catheter is led to
15 the tissue having absorbed the photo-sensitive
pharmaceutical, the laser. catheter being attached to
the connector..
The tissue having absorbed the photo-sensitive
pharmaceutical is irradiated with the excitation light
20 emitted from the tip portion of the laser catheter, the
excitation light being output from the light sources
The fluorescence corresponding to the irradiated
excitation light is extracted via the laser catheter.
Whether the tip portion of the laser catheter
25 contacts the tissue or not is determined, based on
intensity or a spectrum of the extracted fluorescence.
10
[0030] The determining method may further. include
calculating an excitation-light-irradiation protocol
based on the intensity or the spectrum of the extracted
fluorescence, and outputting a calculation result.
5 Effect of the Invention
[0031] According to the present invention, it is
possible to safely determine the contact state of a tip
portion of a catheter with respect to a tissue in real
time.
10 Brief Description of Drawings
[0032] [Fig. 1] A schematic diagram showing a PDT
apparatus according to a first embodiment of the
present invention,
[Fig. 2] A schematic diagram showing a laser catheter
15 inserted in a heart.
[Fig. 3] A block diagram showing a PDT apparatus main
body.
[Fig. 4] A sectional view showing the tip portion of
the laser catheter.
20 [Fig. 5] A flowchart showing operations of the PDT
apparatus.
[Fig. '6] A schematic diagram showing the laser
catheter inserted in a left atrium.
[Fig, 7] A graph showing the temporal change of
25 fluorescence intensity.
[Fig. 8] A graph showing the correlation between the
11
fluorescence intensity and pharmaceutical concentration.
[Fig. 9] A graph showing the temporal change of the
pharmaceutical concentration.
[Figs. 10] Schematic diagrams each showing a
5 contact state of the laser catheter.
[Fig. Ill A graph showing the temporal change of the
fluorescence intensity.
[Fig. 12] Another graph showing the temporal change of
the fluorescence intensity.
10 [Fig. 13] A schematic diagram showing a movement track
of the laser catheter.
[Fig. 14] A diagram showing the relation of ECG,
intracardiac pressure, and coronary blood-flow volume,
which is dominant in the blood-flow volume in a
15 cardiac-muscle tissue.
[Fig. 15] A diagram showing the correlation between
fluorescence intensity and R-wave when the laser
catheter is in the upright-contact state.
[Fig. 16] A diagram showing the correlation between
20 fluorescence intensity and R-wave when the laser
catheter is in the slanting-contact state.
[Fig. 17] A block diagram showing an optical system, a
detection unit, and the like of a second embodiment of
the present invention.
25 [Figs. 18] Schematic diagrams each showing a
contact state of a laser catheter in an intravascular
12
lumen.
[Fig. 19] A graph showing the relation between
wavelength and fluorescence intensity.
Best Modes for Carrying Out the Invention
5 [0033] Hereinafter, embodiments of the present
invention will be described with reference to the
drawings. In the embodiments, the case where a
photodynamic therapy apparatus (hereinafter referred to
as "PDT apparatus".) is used as a determining apparatus
10 will be described.
[0039]
Fig. 1 is a schematic diagram showing a PDT
apparatus according to a first embodiment of the
present invention.
15 The PDT apparatus 1 includes a PDT apparatus main
body 100, a tube 200 connected to the PDT apparatus
main body 100, and a connector 210 provided on the end
of the tube 200.
The tube 200 is a soft hollow tube, and is capable
20 of transmitting light via an inner apparatus-attached
optical fiber 201 (see Fig. 3.).
A laser catheter 300 is detachably connected to
the connector 210.
[0035] Photo-sensitive pharmaceutical is
25 administered to a patient 2. In the case of being
administered by intravenous injection, the administered
13
photo-sensitive pharmaceutical diffuses in the blood,
and then a tissue such as a cardiac-muscle tissue
absorbs the pharmaceutical. A dose of photo-sensitive
pharmaceutical necessary for therapy may be
5 administered at one time by intravenous injection, may
be administered continuously by intravenous drip, may
be administered at one time or continuously via the
oral route, or may be administered locally. Photosensitive
pharmaceutical is pharmaceutical that absorbs
10 light having a certain wavelength, is photoexcited, and
becomes fluorescent. For example, pharmaceutical called
talaporfin sodium (Laserphyrin (registered trademark),
Meiji Co., Ltd.) is employed. Because the 0-band
absorption wavelength of this pharmaceutical is near
15 664 nm, an excitation light source for this
pharmaceutical with, for example, 600 to 800 nm,
preferably 660 to 680 nm, or more preferably 664 plus
or minus 2 nm is used.
[0036] Fig. 2 is a schematic diagram showing a laser
20 catheter inserted in a heart.
The laser catheter 300 is inserted in a right
atrium 14 of a heart 10 via a femoral vein or a jugular
vein of the patient 2. The laser catheter 300, which
has reached the right atrium 14, penetrates a septum,
25 and is led to a left atrium 13.
[0037] [Configuration of PDT apparatus main body]
14
Fig. 3 is a block diagram showing the PDT
apparatus main body.
The PDT apparatus main body 100 includes a light
source 110, an optical system 120, a detection unit 130,
5 an electrocardiograph 140, a controller 150, storage
160, a display unit 170, and an operating unit 180.
[0038] The light source 110 outputs an excitation
light for photo-sensitive pharmaceutical. The
wavelength of the light output by the light source 110
10 is the same as the Q-band absorption wavelength of the
photo-sensitive pharmaceutical. For example, in the
case where photo-sensitive pharmaceutical whose Q--band
absorption wavelength is near 664 nm is used, a
semiconductor laser with the emission wavelength of 600
15 to 800 nm, preferably 660 to 680 nm, or more preferably
664 plus or minus 2 nm is used as the light source 110.
The excitation light output by the light source 110
enters the laser catheter 300 via the optical system
120.
20 [0039]
light,
The optical system 120 allows the excitation
which is emitted from the light source 110, to
enter the laser catheter 300, which is connected to the
connector 210 via the apparatus-attached optical fiber
201. The optical system 120 extracts, from the laser
25 catheter 300, fluorescence emitted from photo-sensitive
pharmaceutical, which is irradiated with the excitation
15
light, and allows the fluorescence to enter the
detection unit 130. The optical system 120 includes a
short pass filter 121, a first lens 122, a polarizing
beam splitter (hereinafter referred to as "PBS".) 123,
5 a long pass filter 124, and a second lens 125.
The short pass filter 121 is a short-wavelength
transmission filter with a cuton wavelength of 670 rim,
and cuts long-wavelength radiation. The excitation
light from the light source 110 has the radiation
10 component in the fluorescence observation wavelength
range (long-wavelength side of peak wavelength). In
view of this, the radiation component of the excitation
light in the long-wavelength side is cut at the stage
prior to collecting the light in the laser catheter 300.
15 The excitation light, which has passed the short pass
filter 121, enters the first lens 122.
The first lens 122 collects the excitation light,
which has entered from the short pass filter 121, on
one edge of the laser catheter 300. Further, the first
20 lens 122 collects fluorescence from the tip portion of
the laser catheter 300 on the PBS 123. Note that part
of the excitation light from the light source 110 is
reflected off an edge of the apparatus-attached optical
fiber 201 at the PDT apparatus main body 100 side, off
25 the inside of the connector 210, and off the tip
portion of the laser catheter 300, and enters the PBS
10
123 as specular reflection light. The specular
reflection light is noisy when detecting fluorescence.
By using polarization differences , the PBS 123
allows the specular reflection light, which has
5 reflected off an edge of the optical fiber in the tube
200, out of the light entered from the first lens 122,
to pass through , does not detect the specular
reflection light, reflects fluorescence and the
specular reflection light reflected off the other edges,
10 and brings them to a detecting device. The fluorescence,
which has passed the PBS 123, enters the long pass
filter 124.
The long pass filter 124 causes the specular
reflection light, which has reflected off the inside of
15 the connector 210 and the tip portion of the laser
catheter 300, out of the light entered from the PBS 123,
not to pass through, allows only the fluorescence to
pass through , and brings the fluorescence to thu
detecting device. The fluorescence, which has passed
20 through the long pass filter 124 , enters the second
lens 125.
The second lens 125 collects the fluorescence,
which has entered from the long pass filter 124, on the
detection unit 130.
25 [0040] The detection unit 130 is, for example, a
linear image sensor, and spectroscopically detects the
fluorescence entered from the optical system 120. That
is, the detection unit 130 detects the light having the
excitation wavelength, and detects the fluorescence
from the photo-sensitive pharmaceutical, which is a
5 light having a wavelength longer than the excitation
wavelength. The detection unit 130 outputs an
electrical signal, which shows intensity of the
detected fluorescence, to the controller 150
[0041] An electrode pad 141 is connected to the
10 electrocardiograph 140 via an electrode code (not
shown). The electrocardiograph 140 obtains an
electrocardiographic signal of the patient 2 via the
electrode pad 141, which is attached to the patient 2,
and via the electrode code, and supplies the obtained
15 electrocardiographic signal to the controller 150.
[0042] The controller 150 controls the respective
units of the PDT apparatus 1.
The controller 150 calculates fluorescence
intensity based on the electrical signal obtained from
20 the detection unit 130. The controller 150 calculates
pharmaceutical concentration in the tissue or in the
blood based on the calculated fluorescence intensity
(pharmaceutical-concentration-monitoring operation).
The controller 150 determines whether to additionally
25 administer the pharmaceutical or not based on the
calculated pharmaceutical concentration.
18
The controller 150 determines the contact state of
the laser catheter 300 with respect to the tissue based
on the electrical signal obtained from the detection
unit 130 (contact-monitoring operation).
5 The controller 150 determines, based on change of
the fluorescence intensity during excitation light
irradiation, whether an abnormal situation such as a
foreign substance or a breakage occurs or not, and
determines the cytocidal effect (foreign-
10 substance/breakage-monitoring operation, and cytocidaleffect-
determining operation) . The controller 150
controls the light source 110 to stop irradiating the
excitation light based on determination results.
The controller 150 determines whether an electric-
15 conduction block is formed or not based on an
electrical signal obtained from the detection unit 130
and based on an electrocardiographic signal obtained
from the electrocardiograph 140 (electric-conductionblock-
formation determining operation).
20 - The controller 150 outputs, to the display unit
170, display instructions to display the abovementioned
various calculation results, the abovementioned
various determination results, and various
information.
25 [00431 The storage 160 is a nonvolatile memory, and
is set in, for example, a flash memory, an HDD (Hard
19
Disk Drive), or another solid memory. The controller
150 records, in the storage 160, temporal change of
fluorescence intensity, in which information on
fluorescence intensity obtained from the detection unit
5 130 is in relation with time information obtained from
a timing measurement unit (not shown), which measures
the elapsed time after a criterion time such as
excitation-light-irradiation start time. The controller
150 records, in the storage 160, electrocardiograms in
10 which information on an electrocardiographic signal
obtained from the electrocardiograph 140 is in relation
with time information.
[0044] The display unit 170 is a display device,
which uses, for example, a liquid-crystal display
15 device or the like. When the display unit 170 obtains
display instructions from the controller 150, the
display unit 170 displays, on a display screen, for
example, information on fluorescence intensity,
information on an electrocardiographic signal, time
20 information, and the like, based on display information
in the display instructions.
[0045] The operating unit 180 receives instructions,
which are input through operations by a practitioner,
and outputs the received instructions to the controller
25 150. The instructions include, for example,
instructions to turn on/off the excitation light output
20
from the light source 110, to change intensity, and the
like. As intensity of the excitation light, it is
possible toselect at least one of two levels of
intensity including a first intensity, which has a low
5 power (for example, optical output of 1 mW or less) and
is minimally-invasive with respect to a tissue and
blood, and a second intensity, which has a high power
and is approximately 1,000 times higher than the first
intensity. The first intensity is selected when
10 monitoring the pharmaceutical concentration and the
contact state of the laser catheter 300 before therapy.
The second intensity is selected when therapy is
conducted. Note that the first intensity is a fixed
value, and the second intensity may be variable.
15 [0046] [Structure of laser catheter]
The the laser catheter 300 outputs an excitation
light from tha tip portion.
Fig. 4 is a sectional view showing the tip portion
of the laser catheter.
The laser catheter 300 includes a catheter tube
310, a holder 320, an optical fiber 330, and an optical
window 340.
[0047] The catheter tube 310 is a soft hollow tube,
and is led to the inner wall of a cardiac-muscle tissue
25 of the heart 10 of the patient 2. The catheter tube 310
has the optical fiber 330 therein.
21
[0048] The holder 320 is fixed to the catheter tube
310. The holder 320 holds the optical fiber 330 and the
optical window 340 with respect to the catheter tube
310.
5 [0049] The optical fiber 330 is, for example, one
quartz step index fiber having a core diameter of 133
pm and an outside diameter of 500 pm. The optical fiber
330 transmits the excitation light from the PDT
apparatus 1. The optical fiber 330 outputs the
10 transmitted excitation light, as an irradiation light
301, from the tip to the optical window 340. The beam
diameter of the irradiation light 301 increases at the
angle determined by the numerical aperture (NA) of the
optical fiber 330. The tip of the optical fiber 330 is
15 worked such that the beam diameter of the irradiation
light 301 appropriately increases. The optical fiber
330 transmits the fluorescence, which is emitted from
photo-sensitive pharmaceutical absorbed in a tissue and
irradiated with an excitation light, to the PDT
20 apparatus 1,
[0050] The optical window 340 is provided on the
outermost of the tip portion of the laser catheter 300
such that the optical window 340 is optically connected
to the tip of the optical fiber 330. The optical window
25 340 is made from a solid transparent material, for
example, a glass material such as BK7. The optical
22
window 340 as an irradiation section allows the
irradiation light 301, which is output from the tip of
the optical fiber 330, to pass through. The optical
window 340 as a light-receiving section collects the
5 fluorescence, which is emitted from the photo-sensitive
pharmaceutical, on the tip of the optical fiber 330.
[0051] In order to detect fluorescence with a high
SN (Signal-Noise) ratio, there is known a method of
separately providing an irradiation fiber and a
10 detection fiber in a laser catheter, and performing
irradiation and light-reception, to thereby remove
specular reflection light (see Japanese Patent
Application Laid-open No. 2009-148550, paragraph
[0037].).
15 Meanwhile, in the case of performing intracardiac
therapy or diagnosis, in order to increase the
curvature of a laser catheter, it is desirable that the
diameter of a laser catheter be small. In the case of
providing a plurality of optical fibers in a laser
20 catheter, each optical fiber should be formed extrafinely,
and thus a light having a necessary intensity
may not be transmitted.
In view of the above, in diseases requiring
intracardiac approaches such as., specifically, atrial
25 fibrillation and ventricular flutter, it is desired
that one optical fiber be in a laser catheter. Further,
23
because it is necessary to detect fluorescence at
intensity with a low power so as not to affect a living
body, it is necessary to form a measurement system with
a high SN (Signal-Noise) ratio by using one optical
5 fiber.
[0052] In view of the above, according to the PDT
apparatus 1 of this embodiment, the PBS 123 and the
long pass filter 124 removes a specular reflection
light on the fiber entrance edge, and the short pass
10 filter 121 further removes a long-wavelength-side
radiation component of a excitation light. With this
structure, in the laser catheter 300, while the one
optical fiber 330 doubles an irradiation fiber and a
detection fiber, the detection unit 130 can detect
15 fluorescence with a high SN ratio. As a result, it is
possible to detect fluorescence with a low power so as
not to affect a living body. Therefore, in the therapy
and diagnosis of circulatory diseases, it is possible
to perform minimally-invasive diagnoses with an extra-
20 fine laser catheter with an increased curvature.
[0053] [Operations of PDT apparatus]
Next, operations of the PDT apparatus 1 configured
as described above will be described.
Fig. 5 is a flowchart showing operations of the
25 PDT apparatus.
[0054] The operations of the PDT apparatus 1 will be
24
described in the following order of (1) to (6).
(1) Preparation for PDT (Step 5101 to Step 5103)
(2) Pharmaceutical-concentration-monitoring
operation (Step S104 to Step 5105)
5 In the pharmaceutical-concentration-monitoring
operation, the light source 110 outputs an excitation
light with a first intensity, and the controller 150
constantly calculates the pharmaceutical concentrration
based on fluorescence intensity detected by the
10 detection unit 130, and determines whether to
additionally administer pharmaceutical or not based on
the calculated pharmaceutical concentration.
(3) Contact-monitoring operation (Step 5106 to
Step S108)
15 In the contact-monitoring operation, the light
source 110 outputs the excitation light with the first
intensity, and the controller 150 determines the
contact state of the laser catheter 300 with respect to
a tissue inner wall based on fluorescence intensity
20 detected by the detection unit 130, and calculates
excitation-light-irradiation protocols (intensity, time,
and the like)
(4) Foreign-substance/breakage-monitoring
operation (Step S109 to Step S112)
25 In the foreign-substance/breakage-monitoring
operation, the light source 110 outputs the excitation
25
light with a second intensity, and the controller 150
determines whether a foreign substance adheres to the
tip of the laser catheter 300 for some reason or not
and further determines whether a breakage occurs in the
5 vicinity of the tip of the laser catheter 300 or not,
during laser-irradiation at appropriate therapy
protocols, based on the fluorescence intensity detected
by the detection unit 130.
(5) Cytocidal-effect-determining operation (Step
10 S113)
In the cytocidal-effect-determining operation, the
light source 110 outputs the excitation light with the
second intensity, and the controller 150 determines
whether there is a cytocidal effect on a tissue, on
15 which the excitation light is being irradiated, or not
based on the fluorescence intensity detected by the
detection unit 130,
(6) Electric-conduction-bloc]- formation
determining operation (Step S114 to Step 5117)
20 An electric-conduction block is, as described
above, a block in which cardiac-muscle tissues
surrounding a hyperexcited site are necrotized, and in
which conduction of electrical pulses from the
hyperexcited site to the left atrium is blocked. Here,
25 it is determined whether an electric-conduction block
is formed or not by calculating, by the controller,
26
temporal-change data of fluorescence intensity used in
the cytocidal-effect-determining operation (Step S113),
and electrocardiographic-wave data. In some cases, the
laser catheter may be relocated in the electric-
5 conduction block, the intensity of the light source 110
may be changed to the first intensity, and the similar
process may be performed, to thereby determine whether
an electric-conduction block is formed or not.
[0055] [(1) Preparation for PDT]
10 Fig. 6 is a schematic diagram showing a laser
catheter inserted in a left atrium.
First, a practitioner such as a doctor inserts the
laser catheter 300 in the heart 10 via a femoral vein
or a jugular vein of the patient 2. The tip portion of
15 the laser catheter 300 is disposed in the vicinity of a
pulmonary vein 12 of an inner wall of a cardiac-muscle
tissue 11 of the left atrium 13 (Step S101).
[0056] Subsequently, with reference to various
referential data (Step S102), the practitioner
20 administers photo-sensitive pharmaceutical to the
patient 2 (Step S103). Here, the case where a dose of
photo-sensitive pharmaceutical necessary for therapy is
administered to the patient 2 at one time by
intravenous injection will be described. The
25 administered photo-sensitive pharmaceutical is diffused
in blood and absorbed in a tissue.
27
[0057] [(2) Pharmaceutical-concentration-monitoring
operation]
Subsequently, the pharmaceutical-concentrationmonitoring
operation is performed.
5 First, the practitioner operates the operating
unit 1,80, and inputs an excitation-light-output
instruction with the low-power first intensity to the
controller 150. The controller 150 obtains the
excitation-light-output instruction, and then outputs
10 the excitation-light-output instruction with the first
intensity, to the light source 110. The light source
110 obtains the excitation-light-output instruction
from the controller 150, and then outputs the
excitation light with the first intensity. Tissues and
15 blood are irradiated with the excitation light output
from the light source 110 via the optical system 120
and the laser catheter 300. The photo-sensitive
pharmaceutical, which is absorbed in a tissue amd blood,
absorbs the excitation light from the laser catheter
20 300, and emits fluorescence. The optical system 120
extracts the fluorescence emitted from the photosensitive
pharmaceutical via the laser catheter 300,
and the fluorescence enters the detection unit 130. The
detection unit 130 detects the entered fluorescence,
25 and outputs the detected fluorescence intensity to the
controller 150 as an electrical signal.
2.8
[0058] The controller 150 calculates the
fluorescence intensity based on the electrical signal
obtained from the detection unit 130. The controller
150 starts to record, in the storage 160, the temporal
5 change of the fluorescence intensity as a log in which
the calculated fluorescence intensity is in relation
with time information obtained from a timing
measurement unit (not shown.). The controller 1.50
creates display information of the temporal change of
10 the fluorescence intensity based on the calculated
fluorescence intensity and elapsed time after a
criterion time such as an intravenous-injection start
time, and outputs a display instruction including the
created display information to the display unit 170.
15 The display unit 170 obtains the display instruction
from the controller 150, and then displays the temporal
change of the fluorescence intensity on a display
screen based on the display information included in the
display instruction. For example, the display unit 170
20 displays the temporal change of the fluorescence
intensity on the display screen in a graph form.
[0059] Here, an example of the graph showing the
temporal change of the fluorescence intensity will be
described,
25 Fig. 7 is a graph showing a temporal change of
fluorescence intensity.
29
Fig. 7 shows the temporal change of fluorescence
intensity in the case where photo-sensitive
pharmaceutical (Laserphyrin) is administered to a pig
by intravenous injection and irradiation is
5 performed with an excitation light, which is the same
as the Q-band absorption spectrum of the pharmaceutical
(semiconductor laser, emission wavelength with, for
example 600 to 800 nm, preferably 660 to 680 nm, or
more preferably 664 plus or minus 2, 400 1W). The tip
10 portion of the laser catheter 300 is disposed in the
right atrium of the pig.
The fluorescence intensity in blood monotonically
decreases after the pharmaceutical administration.
Meanwhile, the fluorescence intensity in a cardiac-
15 muscle tissue increases for a predetermined time period
after the pharmaceutical administration, and then
decreases. Further, the fluorescence intensity in the
blood is higher than the fluorescence intensity in the
cardiac-muscle tissue.
20 [0060] Here, the relation between fluorescence
intensity and pharmaceutical concentration will be
described.
Fig. 8 is a graph showing a correlation between
fluorescence intensity and pharmaceutical concentration.
25 Fig. 8 shows a correlation between absolute value
of pharmaceutical concentration (PS concentration)
30
obtained by a blood collection method, and the
fluorescence intensity in the case where blood is
irradiated with the excitation light as shown in Fig. 7.
The absolute value of pharmaceutical concentration is
5 almost the same as the fluorescence intensity. That is,
it is possible to monitor pharmaceutical concentration
in real time based on the constantly-calculated
fluorescence intensity,
[0061] The controller 150 calculates pharmaceutical
10 concentration in a tissue and in blood based on
calculated fluorescence intensity (Step S104). The
controller 150 starts to record, in the storage 160,
the temporal change of the pharmaceutical concentration
as a log in which the calculated pharmaceutical
15 concentration is in relation with time information
obtained from a timing measurement unit (not shown.).
Further, the controller 150 creates display information
of the temporal change of the pharmaceutical
concentration based on the calculated pharmaceutical
20 concentration and elapsed time after a criterion time
such as an intravenous-injection start time, and
outputs a display instruction including the created
display information to the display unit 170. The
display unit 170 obtains the display instruction from
25 the controller 150, and then displays the temporal
change of the pharmaceutical concentration on a display
31
screen based on the display information included in the
display instruction. For example, the display unit 170
displays the temporal change of the pharmaceutical
concentration on the display screen in a graph form.
5 [0062] Here, an example of a graph showing the
temporal change of the pharmaceutical concentration
will be described.
Fig. 9 is a graph showing a temporal change of
pharmaceutical concentration.
10 As described above, the fluorescence intensity in
blood is higher than the fluorescence intensity in a
cardiac-muscle tissue, and, in addition, the
fluorescence intensity correlates with the
pharmaceutical concentration. Therefore, similar to the
15 temporal change of the fluorescence intensity in blood,
the pharmaceutical concentration in blood monotonically
decreases after the pharmaceutical administration.
Meanwhile, similar to the temporal change of the
fluorescence intensity in a tissue, the pharmaceutical
20 concentration in a tissue increases for a predetermined
time period after the pharmaceutical administration,
and then decreases. Further, the pharmaceutical
concentration in blood is higher in level than the
pharmaceutical concentration in ._.a tissue.
25 [0063] The controller 150 determines whether the
calculated pharmaceutical concentration is equal to or
32
more than a threshold (Step 5105). If the controller
150 determines that the pharmaceutical concentration is
equal to ormore than the threshold, the controller 150
estimates that the pharmaceutical concentration reaches
5 a necessary value, and moves to the contact-monitoring
operation (Step 5105, Yes). Meanwhile, if the
controller 150 determines that the pharmaceutical
concentration is less than the threshold, the
controller 150 estimates that the pharmaceutical
10 concentration fails to reach the necessary value,
creates display information for prompting to
additionally administer the pharmaceutical, and outputs
the display instruction including the created display
information to the display unit 170. The display unit
15 170 obtains the display instruction from the controller
150, and then displays, based on the display
information including the display instruction,
information prompting the practitioner to addita_unally
administer the photo-sensitive pharmaceutical (Step
20 5105, No).
[0064] Note that, because the fluorescence intensity
correlates with the pharmaceutical concentration, if
the display unit 170 displays the fluorescence
intensity on the display screen, a practitioner such as
25 a doctor may estimate the pharmaceutical concentration
based on the fluorescence intensity, even if the
33
controller 150 does not calculate the pharmaceutical
concentration.
]0065] Meanwhile, in general, as a method of
monitoring the pharmaceutical concentration change in
5 blood, there is known a method in which absorbance of
blood, which is collected at regular time intervals
after pharmaceutical administration, is measured.
However, in this method, the plot number is limited
because the collectable blood volume is limited, and in
10 addition, it is not possible to measure the
concentration in real time.
Alternatively, there is known a method in which a
bypass pathway is prepared outside of a body, blood
passing through the pathway is irradiated with light,
15 and fluorescence intensity is observed, to thereby
monitor the pharmaceutical concentration change.
However, it is necessary to pay attention to hygiene in
this method.
Further, as a method of monitoring pharmaceutical
20 concentration in a tissue, there is known a method in
which part of carbon in pharmaceutical is transformed
into isotope, the isotope is simultaneously
administered, and pharmaceutical concentration in each
tissue is monitored based on a radiation quantity
25 (CANCER RESEARCH 50. 3985-3990, July 1, 1990, Tissue
Distribution and Photosensitizing Properties of Mono-L34
aspartyl Chlorin e6 in a Mouse Tumor Model, Charles J.
Corner and Angela Ferrario) . However, this method
involves radiation exposure problems, and involves a
problem in that only a concentration may be monitored
5 macroscopically.
[0066] To the contrary, according to the
pharmaceutical-concentration-monitoring operation of
this embodiment, by calculating the temporal change of
fluorescence intensity, the temporal change of
10 pharmaceutical concentration, which correlates with
fluorescence intensity, may be calculated. Therefore
the pharmaceutical concentration in a tissue and blood
may be monitored in real time. Further, the
pharmaceutical-concentration-monitoring operation of
15 this embodiment is less invasive than the conventional
monitoring method, and is capable of monitoring
temporal changes of pharmaceutical concentration stably
and reproducibly. Further, because the temporal change
of pharmaceutical concentration is monitored via a
20 catheter by using the excitation light from the light
source 110 of the PDT apparatus 1, it is not necessary
to additionally provide a pharmaceutical concentration
detecting apparatus, to thereby enable a low-cost and
space-saving apparatus. Further, because the
25 pharmaceutical concentration may be monitored in real
time, determination of additional pharmaceutical
35
administration may be assisted in real time.
[0067] Further, the pharmaceutical-concentrationmonitoring
operation of this embodiment may be
performed not only in PDT but also in therapy or
5 diagnosis using a pharmaceutical, which absorbs an
excitation light and emits fluorescence. In therapy or
diagnosis using a pharmaceutical, it is important to
grasp a pharmaceutical dynamic state (pharmaceutical
delivery). According to the pharmaceutical-
10 concentration-monitoring operation of this embodiment,
pharmaceutical concentration in an intended tissue may
be measured microscopically via a catheter in real time,
and dynamic states of various pharmaceuticals may be
grasped. Further, because minimally-invasive monitoring
15 is enabled, the pharmaceutical-concentration-monitoring
operation of this embodiment has a great advantage and
is suitable for practical use. Further, the
pharmaceutical-concentration-monitoring operation of
this embodiment may be performed in a system (DDS, Drug
20 Delivery System) in which pharmaceutical is delivered
to only a certain location, and is useful to estimate
whether pharmaceutical reaches actually and locally.
[0068] [(3) Contact-monitoring operation]
Subsequently, the contact-monitoring operation is
25 performed.
[0069) Figs. 10 are schematic diagrams showing
36
contact states of the laser catheter.
The laser catheter 300 is preferably disposed such
that the tip portion as a light-emitting portion
contacts the inner wall of the cardiac-muscle tissue 11
5 upright (see Fig. 10(a), hereinafter referred to as
"upright-contact state".). This state is preferable so
as to remove intraatrial blood 15 from the tip portion
of the laser catheter 300, and to prevent activation of
photo-sensitive pharmaceutical in the intraatrial blood
10 15. Further, this state is preferable so as to
selectively activate photo-sensitive pharmaceutical
absorbed in a tissue when the tip portion of the laser
catheter 300 directly contacts a tissue.
However, it is difficult to recognize the precise
15 contact state of the tip portion of the laser catheter
300 radiographically or tactually. Because of this,
actually, it is not always true that the tip portion of
the laser catheter 300 is in the upright-contact state
with respect to a tissue. The blood 15 may exist
20 between the tip portion of the laser catheter 300 and a
tissue, and the tip portion may be in the blood (see
Fig. 10(c), hereinafter referred to as "non-contact
state".). Alternatively, the tip portion of the laser
catheter 300 may contact a tissue in a slanting
25 direction, and the blood 15 may partially exist in a
gap between the tip portion and the tissue (see Fig.
37
10(b), hereinafter referred to as "slanting-contact
state".).
In thecontact-monitoring operation, such contact
states of the tip portion of the laser catheter 300,
5 that is, the contact states and the non-contact state,
are monitored, the contact angle (upright-contact state,
slanting-contact state) in the case of the contact
states is monitored, and the like. Note that, in this
specification, the "contact angle" not only means a
10 narrowly-defined angular value, but also means a
widely-defined contact angle, in which the contact
state of the tip portion of the laser catheter 300 with
respect to a tissue is upright or slanting.
[0070] Continuously, the light source 110 outputs
15 the excitation light with the first intensity to the
optical system 120, the controller 150 calculates
fluorescence intensity and pharmaceutical concentration,
and the display unit 170 displays the temporal change
of fluorescence intensity on the display screen. For
20 example, the display unit 170 displays the temporal
change of fluorescence intensity on the display screen
as a graph.
.[0071] Here, an example of a graph showing the
temporal change of fluorescence intensity will be
25 described.
Fig. 11 is a graph showing the temporal change of
38
fluorescence intensity.
Fig. 11 is a graph showing the temporal change of
fluorescence intensity under the condition same as Fig.
7. In the graph, the line A shows low fluorescence
5 intensity , the line C shows high fluorescence intensity,
and the line B fluctuates between the fluorescence
intensity of the line A and the fluorescence intensity
of the line C.
Note that , in Fig. 11, in order to make the
10 description clear, the temporal change of fluorescence
intensity in the case where the tip portion of the
laser catheter 300 is in the upright-contact state, the
temporal change of fluorescence intensity in the case
where the tip portion of the laser catheter 300 is in
15 the slanting-contact state, and the temporal change of
fluorescence intensity in the case where the tip
portion of the laser catheter 300 is in the non-contact
state are shown in one graph. However, actually, one of
them is displayed according to the contact state of the
20 tip portion of the laser catheter 300.
The line A will be reviewed . Here, as shown in Fig.
7, the fluorescence intensity in a tissue is smaller
than the fluorescence intensity in blood. Therefore, it
is thought that the line A shows the fluorescence
25 intensity in the case where the laser catheter 300
irradiates a tissue with the excitation light. So, in
39
the case where the fluorescence intensity of the line A
is calculated, it is thought that the fluorescence
intensity in a tissue is reflected in the result
because the tip portion of the laser catheter 300 is in
5 the upright-contact state with respect to a tissue.
The line C will be reviewed. Here, as shown in Fig.
7, the fluorescence intensity in blood is larger than
the fluorescence intensity in a tissue. Therefore, it
is thought that the line C shows the fluorescence
10 intensity in the case where the laser catheter 300
irradiates blood with the excitation light. So, in the
case where the fluorescence intensity of the line C is
calculated, it is thought that the fluorescence
intensity in blood is reflected in the result because
15 the tip portion of the laser catheter 300 is in the
non-contact state with respect to a tissue.
The line B will be reviewed. Because the line B is
between the fluorescence intensity of the line A and
the fluorescence intensity of the line C, it is thought
20 that the tip portion of the laser catheter 300 is in
the slanting-contact state with respect to a tissue.
Further, because a contact-target object of the tip
portion of the laser catheter 300 is a moving cardiacmuscle
tissue, the laser catheter 300 follows the
25 movement of the tissue to thereby move. As a result, in
the case where the tip portion of the laser catheter
40
300 contacts a tissue in a slanting manner, it is
likely that the blood volume between the tip portion of
the laser catheter 300 and a tissue changes during
measurement. In addition, the blood-flow volume in a
5 cardiac-muscle tissue changes and the intraatrial
blood-flow volume changes because of heartbeat.
Affected by them, the fluctuation of the fluorescence
intensity of the line B is larger than the line h and
the line C.
10 Further, in the case where the tip portion of the
laser catheter 300 contacts a tissue in any state
(upright-contact state, slanting-contact state), the
laser catheter 300 may be affected by the movement of
the cardiac-muscle tissue. That is, the contact state
15 of the tip portion of the laser catheter 300 fluctuates
between the contact states (upright-contact state,
slanting-contact state) and the non-contact state. In
this case, the fluorescence intensity fluctuates
largely. Therefore, it is determined whether the laser
20 catheter 300 follows the movement of a cardiac-muscle
tissue or not based on fluctuation of the fluorescence
intensity shown in a waveform. For example, in the line
A of the graph, the high fluorescence intensity after
four seconds after pharmaceutical administration and in
25 the vicinity thereof shows that the tip portion of the
laser catheter 300 momentarily moves from the upright41
contact state to the non--contact state and returns to
the upright-contact state again.
[0072] Based on the calculated fluorescence
intensity, the controller 150 determines the contact
5 state of the tip portion of the laser catheter 300
(contact/non-contact states, contact angle in case of
contact state) (Step S106).
Specifically, in the case where the controller 150
determines that the calculated fluorescence intensity
10 is equal to or larger than a first threshold, the
controller 150 determines the non-contact state (line
C). In the case where the controller 150 determines
that the minimum value of the fluorescence intensity is
equal to or smaller than a second threshold, which is
15 smaller than the first threshold, the controller 150
determines the upright-contact state (line A) In the
case where the controller 150 determines that the
fluorescence intensity periodically fluctuates between
the first threshold and the second threshold, the
20 controller 150 determines the slanting-contact state
(line B).
The controller 150 informs the practitioner the
determined contact state by using the display unit 170.
Specifically, when the controller 150 determines the
25 slanting-contact state or the non-contact state, the
controller 150 creates display information for
42
prompting to change the contact state of the tip
portion of the laser catheter 300, and outputs a
display instruction including the created display
information to the display unit 170. The display unit
5 170 obtains the display instruction from the controller
150, and then displays information for prompting a
practitioner to change the contact state of the tip
portion of the laser catheter 300 based on the display
information in the display instruction (Step 5107). The
10 practitioner operates a handpiece or the like (not
shown.) provided on the laser catheter 300, to thereby
change the contact state of the tip portion of the
laser catheter 300 with respect to a tissue.
[0073] The controller 150 continuously calculates
15 fluorescence intensity and pharmaceutical concentration.
The controller 150 refers to fluorescence intensity and
pharmaceutical concentration stored in the storage 160.
The controller 150 calculates the blood volume in the
gap between the tip portion of the laser catheter 300
20 --- and a tissue based on the referred fluorescence
intensity. The controller 150 calculates excitationlight-
irradiation protocols during the therapy, that is,
the second intensity of the excitation light, the
irradiation time, and the like, based on the calculated
25 blood volume and the referred pharmaceutical
concentration (Step 5108).
43
For example, in the case where the tip portion of
the laser catheter 300 is in the slanting-contact state
or thenon-contact state and where blood exists in the
gap, the loss of the excitation light (excitation. light
5 which does not reach tissue) is considered based on the
blood volume, and the excitation-light-irradiation
protocols are set, in which the second intensity is
high and in which the irradiation time is long. The
controller 150 calculates the excitation-light-
10 irradiation protocols, creates display information on
the irradiation protocols, and outputs display
instruction including the created display information
to the display unit 170. The display unit 170 obtains
the display instruction from the controller 150, and
15 then displays information on the excitation-lightirradiation
protocols (second intensity, irradiation
time) based on the display information in the display
instruction.
As described above, the controller 150 calculates
20 the pharmaceutical concentration and the blood volume
based on the fluorescence intensity, and calculates the
excitation-light-irradiation protocols based on the
calculated pharmaceutical concentration and blood
volume. That is, the controller 150 is capable of
25 calculating the excitation-light-irradiation protocols
based on the fluorescence intensity.
4 4
[0074] Note that, because the temporal change of
fluorescence intensity differs depending on the contact
state of the tip portion of the laser catheter 300, if
the temporal change of fluorescence intensity is
5 displayed on the display screen by the display unit 170,
it ispossible for a practitioner to estimate a contact
state based on the temporal change of fluorescence
intensity even if the controller 150 does not determine
the contact state.
10 [0075] Meanwhile, in the field of circulatory
disease, it is important to determine, in real time,
the contact state of the tip portion of a catheter with
respect to the intended tissue, the blood volume in a
gap, and presence/absence of a foreign-
15 substance/breakage in order to ensure safety and
reliability. Further, in the case where the intended
tissue is a movable target such as a cardiac-muscle
tissue, it is necessary to determine the contact: state
in detail, in which a laser catheter follows the
20 - movement of the tissue, to reliably perform therapy. In
the past, it is known to determine the contact state of
a catheter by, for example, securing a transparent zone
by removing blood, radioscopy, potential measurement
(impedance measurement), potential mapping, temperature
25 measurement, dynamic measurement (pressure, stress),
reflected light measurement using a polychromatic light
45
source, and the like. However, in the field of therapy
and diagnosis via a catheter, it is difficult to
determine the tip state of the catheter in blood, and a
technique capable of determining the contact state in
5 detail has not been developed yet. Each of the abovementioned
conventional methods is capable of
determining the contact state roughly, and, in addition,
has many problems as follows.
Securing a transparent zone by removing blood is a
10 method in which a blood flow is temporarily blocked by
using a balloon, saline or the like is flowed from a
catheter tip portion to thereby secure a transparent
zone, and a contact state is observed by using an
angioscope. However, this method may lead to a
15 peripheral-vessel-ischemia state.
With radioscopy, because of lacking accuracy, it
is difficult to determine the distance of a gap between
a catheter and a tissue, and the blood volume in the
gap between the catheter and the intended tissue.
20 Further, in the case of a moving tissue, it is not
clear that the tip of a catheter follows the movement.
As a result, the tip of a catheter may break blood (in
case of intracardiac therapy) or blood-vessel wall (in
case of intravascular therapy), Further, the amount of
25 energy input in an intended tissue decreases below an
estimated amount, and an enough therapeutic effect may
not be achieved. Further, the biggest problem is that
only a doctor, who has a knowledge of anatomy and is
well-experienced (tactile impression when touching),
can make a determination, subjectively (see Japanese
5 Patent Application Laid-open No. 2007-525263).
Potential measurement (impedance measurement) is a
method in which, since a cardiac-muscle tissue
contracts and moves because of potential propagation,
the contact state with respect to a cardiac-muscle
10 tissue is determined by measuring the potential.
However, in the case of performing an optical therapy,
the tip portion of a catheter (contact portion with
respect to cardiac-muscle tissue) is an optical window.
Because of this, a potential-measured site may be
15 provided on a portion other than the tip portion of the
catheter. As a result, a light-.irradiated site does not
coincide with -a potential-measured site, a diagnosis--
target zone does not coincide with a therapy-target
zone, and the therapy may not be performed precisely.
20 Further, an electrode area is made smaller, and angle
determination accuracy may thus be decreased. Further,
because electric measurement is performed, there may be
an effect of electromagnetic interference (see Japanese
Patent Application Laid-open No. 2008-531170).
25 Potential mapping is a method in which potential
measurement is three-dimensionally developed. However,
}7
a conventional apparatus lacks a resolution of
determining a contact state in detail, Further, it
takes time to perform determination, and an
anthropogenic influence may occur because of an
5 excessive contact pressure (see Japanese Patent
Application Laid-open No. 2008-531170). Further, if a
potential measuring catheter is displaced, a mapping
image may not coincide with an actual. position. Further,
because electric measurement is performed, there may be
10 an effect of electromagnetic interference (see Japanese
Patent Application Laid-open No. 2008-531170).
Temperature measurement is a method in which, with
respect to diseases including a vascular occlusion, an
occlusion is determined by measuring temperature (see
15 Japanese Patent Application Laid-open No. 2007-525263).
However, this is a diagnostic method for only
occlusions, and. is not applicable to diseases including
no occlusion zone such as, for example, atrial
fibrillation and ventricular flutter. Further,
20 unnecessary heat may be provided on a normal bloodvessel
wall.
Dynamic measurement (pressure, stress) is a method
in which a pressure sensor or a stress sensor is
mounted on a catheter, and a contact-target object is
25 determined (see Japanese Patent Application Laid-open
No. 2009-542371, US Patent No, 6696808, US Patent
48
Application Laid-open No.. 2008/0009750, WIPO
Publication No. 01/33165) However, the tip portion of
the catheter may be larger, and there may be an effect
of electromagnetic interference (see Japanese Patent
5 Application Laid-open No. 2008-531170).
Reflected light measurement by using a
polychromatic light source is a method in which
absorption coefficients different from wavelengths are
used. Specifically, by using a polychromatic light
10 source, a tissue is determined based on reflection
ratio differences of the respective wavelengths (see
Japanese Patent No. 4261101). According to this method,
although the blood volume between a catheter and a
tissue may be estimated, an optical system may be
15 complicated, an apparatus may be made larger, and the
cost may be increased because a plurality of light
sources are provided.
[0076] To the contrary, according to the contactmonitoring
operation of this embodiment, by detecting
20 fluorescence intensity, it is possible to determine the
contact state with respect to an intended tissue and
following-movements via a catheter in real time. This
method is minimally invasive because it is not
necessary to remove blood and the like. Further,
25 because excitation-light-irradiation protocols may be
calculated based on the determined contact state and
49
the like, therapy and diagnosis may be assisted safely
and reliably.
[0077] [(4) Foreign-substance/breakage-monitoring
operation]
5 During the photodynamic therapy, the foreignsubstance/
breakage-monitoring operation is performed.
First, a practitioner refers to excitation-lightirradiation
protocols displayed on the display unit 170,
and operates the operating unit 180 to thereby input an
10 excitation-light-output instruction with the high-power
second intensity in the controller 150. The controller
150 obtains the excitation-light-output instruction,
and then outputs the excitation-light-output
instruction with the second intensity to the light
15 source 110. The light source 110 obtains the
excitation-light-output instruction from the controller
150, and then outputs the excitation light with the
second intensity. A tissue is irradiated with Lhe
excitation light output from the light source 110 via
20 the optical system 120 and the laser catheter 300, and
photodynamic therapy is performed (Step S109).
[0078] Based on an electrical signal obtained from
the detection unit 130, the controller 150 calculates
fluorescence intensity. The controller 150 creates
25 display information of the temporal change of the
fluorescence intensity based on the calculated
J0
fluorescence intensity and elapsed time after a
criterion time such as an intravenous-injection start
time, and outputs a display instruction including the
created display information to the display unit 170.
5 The display unit 170 obtains the display instruction
from the controller 150, and then displays the temporal
change of the fluorescence intensity on a display
screen based on the display information included in the
display instruction.
10 [0079] The controller 150 determines whether the
calculated fluorescence intensity is equal to or more
than a threshold (Step 5110). The threshold is, for
example, a value equal to or more than the multiple of
the normal fluorescence intensity.
15 [0080] Fig. 19 is a graph showing the relation
between wavelength and fluorescence intensity.
Fig. 19 shows the relation between wavelength and
fluorescence intensity of a laser catheter, which may
contact a foreign substance or may be broken, and those
20 of a normal laser catheter. It is understood that, in
the case where the tip portion of a laser catheter
contacts a foreign substance other than a living body
tissue or is broken, the fluorescence intensity thereof
is larger than the normal fluorescence intensity.
25 [0081] The controller 150 determines that the
fluorescence intensity is equal to or more than the
51
threshold, that is, determines that the fluorescence
intensity is increased to equal to or more than the
multiple ofthe previous fluorescence intensity such
that the current fluorescence intensity ignores the
5 previous fluorescence intensity, and then the
controller 150 estimates that there is a foreign
substance or a breakage (Step S110, Yes) If the
controller 150 estimates that there is a foreign
substance or a breakage, the controller 150 creates
10 display information on generation of a foreignsubstance/
breakage to stop the excitation light
irradiation, and outputs display instruction including
the created display information to the display unit 170.
The display information on generation of a foreign-
15 substance/breakage includes information to stop the
excitation light irradiation, to reset irradiation time,
to reset an irradiation power, to prompt to check the
laser catheter 300, and the like. When the display unit
170 obtains the display instruction from the controller
20 150, based on the display information in the display
25
instruction, the display unit 170 displays information
to stop the excitation light irradiation (Step Sill)
and information on generation of a foreignsubstance/
breakage (Step S112) to a practitioner.
Note that, in the case where the controller 150
detects abnormal intensity increase of an arbitrary
52
wavelength other than the fluorescence wavelength
(excitation light wavelength or the like), the
controller 150 estimates that there is a foreign
substance or a breakage (Step 5110, Yes), and may
5 perform the similar processing (Step S111, Step 5112).
[0082]- Meanwhile, in the case where the controller
150 does not determine that the fluorescence intensity
is equal to or more than the threshold within a
predetermined time period, the controller 150 estimates
10 that there is no foreign substance or breakage, and
moves to the cytocidal-effect-determining operation
(Step S110, No).
[0083] Note that, because generation of a foreign
substance or a breakage is estimated when the
15 fluorescence intensity exceeds a predetermined
threshold, if the display unit 170 displays the
fluorescence intensity on the display screen, a
practitioner may estimate generation of a foreign
substance or a breakage based on the fluorescence
20 intensity, even if the controller 150 does not estimate
generation of a foreign substance or a breakage.
[0084] Further, in the case where a plurality of
catheters are disposed in a cardiac cavity in addition
to the laser catheter 300, the laser catheter 300 may
25 contact another catheter. For example, if the laser
catheter 300 emits a light in the state where the laser
53
catheter 300 contacts another catheter disposed in a
cardiac cavity, both of the catheters may lose their
functions. If a practitioner is keep on emitting an
excitation light without noticing the abnormal
5 situation of the tip portion of the laser catheter 300,
the tip portion of the laser catheter 300 may generate
heat to thereby be in danger of thermally damaging a
living body. Further, a catheter being contacted may
lose its function.
10 [0085] According to the foreign-substance/breakagemonitoring
operation of this embodiment, because a
strong reflected light is measured when the catheter
contacts any object other than a living body tissue, it
is possible to estimate generation of a foreign-
15 substance /breakage via a catheter in real time, Because
of this, it is possible to prompt a practitioner to
check the laser catheter 300, and thus it is possible
to perform the therapy very safely without causing
danger to a patient.
20 [0086] [(5) Cytocidal-effect-determining operation]
Subsequently, the cytocidal-effect-determining
operation is performed.
In photodynamic therapy, photo-sensitive
pharmaceutical absorbed in a tissue absorbs the
25 excitation light from the laser catheter 300 to gain
energy, and changes from the ground state to the
54
singlet excited state. Most of the energy changes from
the singlet excited state to the triplet excited state
because of intersystem crossing, but the rest part
returns from the singlet state to the ground state, and
5 emits fluorescence at this time. Further, when photosensitive
pharmaceutical in the triplet excited state
clashes triplet oxygen, the photo-sensitive
pharmaceutical transfers energy to oxygen, and creates
strong oxidizer singlet oxygen. The oxidizer breaks a
10 tissue, and, in addition, breaks photo-sensitive
pharmaceutical (bleaching). If the bleaching occurs,
the effective pharmaceutical amount is decreased, and
thus the fluorescence amount is also decreased.
Therefore, decrease of the fluorescence amount
15 indicates bleaching and a tissue injury amount. The
optical system 120 extracts the fluorescence emitted
from the photo--sensitive pharmaceutical via the laser
catheter 300, and the fluorescence enters the detection
unit 130. The detection unit 130 detects the
20 --- fluorescence entered from the optical system 120, and
outputs the intensity of the detected fluorescence to
the controller 150 as an electrical signal.
[0087] Continuously, the light source 110 outputs
the excitation light with the second intensity to the
25 optical system 120, the controller 150 calculates the
fluorescence intensity, and the display unit 170
55
displays the temporal change of fluorescence intensity
on the display screen. For example, the display unit
170 displays the temporal change of fluorescence
intensity on the display screen as a graph.
5 [0088] Here, an example of a graph showing the
temporal change of fluorescence intensity will be
described.
Fig. 12 is a graph showing the temporal change of
fluorescence intensity.
10 Fig. 12 shows the temporal change of fluorescence
intensity in the case where the excitation light is
emitted for 20 seconds after 20 minutes pass after
photo-sensitive pharmaceutical is administered in a pig
by intravenous-injection. Since decrease of a
15 fluorescence amount indicates bleaching and a tissue
injury amount as described above, by displaying an
attenuation curve of the fluorescence intensity, the
PDT process may be displayed in real time.
[0089] The controller 150 determines whether the
20 calculated fluorescence intensity is attenuated below a
threshold (Step S113). If the controller 150 determines
that the fluorescence intensity is attenuated below the
threshold, the controller 150 estimates that there is a
cytocidal effect on a tissue irradiated with the
25 excitation light (Step 0113, Yes). Then, the controller
150 creates display information on an index of a
56
cytocidal.effect, and outputs a display instruction
including the created display information to the
display unit 170. The display unit 170 obtains the
display instruction from the controller 150, and then
5 displays information on an index of a cytocidal effect
for apractitioner based on the display information in
the display instruction. The practitioner refers to the
information on an index of a cytocidal effect displayed
on the display unit 170, and moves to the electric-
10 conduction-block-formation determining operation.
[0090] Meanwhile, if the controller 150 does not
determine that the fluorescence intensity is decreased
below the threshold within a predetermined time period,
the controller 150 creates display information to
15 prompt to extend the excitation light irradiation and
to reset the light intensity based on the calculated
fluorescence intensity, and outputs display instruction
including the created display information to the
display unit 170 (Step S113, No). When the display unit
20 170 obtains the display instruction from the controller
150, the display unit 170 displays information to
prompt a practitioner to extend the excitation light
irradiation and to reset the light intensity based on
the display information in the display instruction.
25 After a predetermined time period passes after
outputting the display instruction, the controller 150
Y/
moves to the operation of Step 5108.
[0091) Note that, because generation of a cytocidal
effect is estimated when the fluorescence intensity is
attenuated below a predetermined threshold, if the
5 display unit 170 displays the fluorescence intensity on
the display screen, a practitioner may estimate whether
there is a cytocidal effect or not based on the
fluorescence intensity, even if the controller 1.50 does
not estimate whether there is a cytocidal effect or not.
10 [0092] According to the cytocidal-effect-determining
operation of this embodiment, based on fluorescence
intensity correlated with pharmaceutical concentration,
it is possible to measure injury in a cardiomyocyte,
which progresses in a tissue irradiated with the
15 excitation light, that is, to measure a therapeutic
effect, via a catheter in real time, and thus the
therapy is performed reliably.
[0093] [(6) Electric-conduction-block-formation
determining operation]
20 Subsequently, the electric-conduction-blockformation
determining operation is performed.
In the electric-conduction-block-formation
determining operation, the fluorescence time-waveform
used in the cytocidal effect determination is in
25 synchronization with electrocardiogram (ECG. ECG
obtaining method will be described later.). The
58
controller 150 analyzes the phase difference between
the ECG R-wave and the fluorescence peak intensity in
the interval between R-waves to thereby determine
whether an electric-conduction block is formed. In some
5 cases, the laser catheter 300 may be relocated in an
electric-conduction block (in dashed-dotted line of Fig.
13), the excitation light output may be changed to the
first intensity, and the fluorescence time-waveform,
which is measured in low power, may be in
10 synchronization with ECG to thereby perform analysis.
The procedure in the case of relocating a laser
catheter for measurement is as follows.
[0099] First, a practitioner disposes the tip
portion of the laser catheter 300 in an electric-
15 conduction block (in dashed-dotted line of Fig. 13) or
on an excitation-light-irradiated site. Then, the
practitioner operates the operating unit 180 to thereby
input an excitation-light-output instruction wiLb the
low-power first intensity to the controller 150. The
20 controller 150 obtains the excitation-light-output
instruction, and then outputs the excitation-lightoutput
instruction with the first intensity to the
light source 110. The light source 110 obtains the
excitation-light-output instruction from the controller
25 150, and then outputs the excitation light with the
first intensity. A tissue is irradiated with the
59
excitation light output from the light source 110 via
the optical system 120 and the laser catheter 300.
Photo-sensitive pharmaceutical, which is absorbed in a
tissue, absorbs the excitation light from the laser
5 catheter 300, and emits fluorescence. The optical
system 120 extracts the fluorescence emitted from the
photo-sensitive pharmaceutical via the laser catheter
300, and the fluorescence enters the detection unit 130.
The detection unit 130 detects the fluorescence entered
10 from the optical system 120, and outputs the detected
fluorescence intensity to the controller 150 as an
electrical signal. The controller 150 calculates
fluorescence intensity based on the obtained electrical
signal.
15 [0095] Meanwhile, the electrocardiograph 140 obtains
the electrocardiographic signal, and supplies the
obtained electrocardiographic signal to the controller
150. The controller 150 creates display informal-ion
based on the calculated fluorescence intensity and the
20 obtained electrocardiographic signal, and outputs
display instruction including the created display
information to the display unit 170. The display unit
170 obtains the display instruction from the controller
150, and displays the correlation between the
25 fluorescence intensity and the electrocardiogram R-wave
on the display screen based on the display information
60
in the display instruction,
[00961 Here, the correlation between fluorescence
intensity and ECG R-wave will be described.
Fig. 14 is a diagram showing the relation of ECG,
5 intracardiac pressure, and coronary blood-flow volume,
which is dominant in the blood-flow volume in a
cardiac-muscle tissue, and being a prerequisite
knowledge described in "Essential Anatomy and
Physiology (Essensharu Kaibo Seirigaku)" (Gakken
10 Medical Shujunsha Co., Ltd., 2001), which is effective
in the following description.
As shown in Fig. 14, the temporal change of the
intracardiac blood-flow volume is different from the
blood-flow volume in a cardiac-muscle tissue. While the
15 intracardiac blood-flow volume has a peak at the time
when it coincides with R-wave, the blood-flow volume in
a right-sided cardiac-muscle tissue has a first peak at
the time when about 200 ms pass after R-wave, and a
second peak at the time when about 400 ms pass after R-
20 wave.
[0097] Fig. 15 is a diagram showing the correlation
between fluorescence intensity and R-wave when the
laser catheter is in the upright-contact state.
The correlation between fluorescence intensity
25 (for example, irradiation power of 900 mW) and R-wave
when the tip portion of the laser catheter 300 is in
61
the upright-contact state will be described. In the
upright-contact state, fluorescence peaks are observed
after 100 ms pass after R-wave and after 400 ms pass
after R-wave. Note that, in the case where the catheter
5 is disposed left-sided, the fluorescence intensity
changes in proportion to the left coronary blood-flow
volume of Fig. 14. A ventricle contracts when R-wave
appears, and blood is supplied to a whole body
(including cardiac-muscle tissue). Since blood includes
10 photo-sensitive pharmaceutical, the fluorescence
intensity in a cardiac-muscle tissue is highest when
blood is supplied to blood vessels of a cardiac muscle.
As a result, the peak of fluorescence intensity appears
for a predetermined time period after appearance of R-
15 wave.
[0098] Fig. 16 is a diagram showing the correlation
between fluorescence intensity and R-wave when the
laser cat.fieter is in the slanting-contact state.
The correlation between fluorescence intensity
20 (for example, irradiation power of 900 mW) and R-wave
when the tip portion of the laser catheter 300 is in
the slanting-contact state will be described. In the
slanting-contact state, because blood exists in a gap
and the intracardiac blood-flow.. volume is dominant, the
25 fluorescence intensity peak coincides with R-wave.
As described above, the phase difference between
6>_
R-wave and fluorescence intensity peak in the uprightcontact
state is obviously different from the phase
difference between R-wave and fluorescence intensity
peak in the slanting-contact state, and the phase
5 difference is constant if the contact state is
maintained.
[0099] In view of this, the controller 150
determines whether the phase difference between
fluorescence intensity and R-wave is constant based on
10 the calculated fluorescence intensity and the obtained
electrocardiographic signal, to thereby determine
whether an electric-conduction block is formed or not
(Step 5114). If the controller 150 determines that the
phase difference between fluorescence intensity and R-
15 wave is constant, the controller 150 determines that an
electric-conduction block is yet to be formed (Step
5114, No), and causes the display unit 170 to display
information to prompt a practitioner to stop the
excitation light irradiation (Step 5116) and to move
20 the laser catheter 300 (Step 5117). The practitioner
refers to the information displayed on the display unit
170, stops excitation light irradiation once, and moves
the laser catheter 300. Then, the processing of Step
5104 and thereafter are performed again.
25 [0100] Fig. 13 is a schematic diagram showing a
movement track of the laser catheter.
63
A practitioner moves the tip portion of the laser
catheter 300 so as to surround a hyperexcited site in
pulmonary veins (PV) (dashed-dotted line or dashed line
in Fig. 13).
5 [0101] Meanwhile, if the controller 150 determines
that the phase difference between fluorescence
intensity is R-wave is not constant, the controller 150
determines that an electric-conduction block is formed
(Step 5114, Yes), creates a display instruction to
10 prompt a practitioner to stop excitation light
irradiation and to remove the laser catheter 300, and
outputs a display instruction including the created
display information to the display unit 170. When the
display unit 170 obtains the display instruction from
15 the controller 150, the display unit 170 displays
information to prompt a practitioner to stop excitation
light irradiation and to remove the laser catheter 300
on the display screen based on the display information
in the display instruction, and stops the processing
20 (Step S115).
[0102] Here, the principle, in which the controller
150 determines that an electric-conduction block is
formed when the phase difference between fluorescence
intensity and R-wave is not constant, will be described.
25 When a cardiomyocyte injury progresses, the
cardiomyocyte fails to conduct electricity, and thus
64
the cardiomyocyte fails to contract by itself at time
of heartbeat. An electric-conduction block, which is
formed by the injured cardiomyocytes and has a box
shape, fails to contract by itself, and moves such that
5 the electric-conduction block follows the contraction
movement of the adjacent cardiac-muscle tissue. As a
result, the contact state of the tip portion of the
laser catheter 300 is unstable and changes every second.
As a result, the phase difference between fluorescence
10 intensity and R-wave becomes unstable. In other words,
the correlation between fluorescence intensity and Rwave
moves backward and forward between the correlation
shown in Fig. 15 and the correlation shown in Fig. 16.
[0103] In view of this, according to the electric-
15 conduction-block-formation determining operation of
this embodiment, it is possible to determine that an
electric-conduction block is formed in real time based
on the phase difference between fluorescence intensity
and electrocardiogram R-wave.
20 -- Specifically, in the case where the peak of
fluorescence intensity appears for a predetermined time
period after appearance of R-wave, it can be determined
that an electric-conduction block is yet to be formed,
and that the tip portion of the laser catheter 300 is
25 in the upright-contact state. In the case where the
peak of fluorescence intensity and the R-wave appear
65
substantially simultaneously, it can be determined that
an electric-conduction block is yet to be formed, and
that the tip portion of the the laser catheter 300 is
in the slanting-contact state. In the case where the
5 phase difference between the peak of fluorescence
intensity and R-wave is not constant, it can be
determined that an electric-conduction block is formed.
[0104] Note that, because it can be determined that
an electric-conduction block is formed in the case
10 where the phase difference between fluorescence
intensity and R-wave is not constant, if the display
unit 170 displays the correlation between fluorescence
intensity and R-wave on the display screen, a
practitioner may estimate whether an electric-
15 conduction block is formed or not based on the
correlation between fluorescence intensity and R-wave,
even if the controller 150 does not estimate whether an
electric-conduction block is formed or not.
[0105]
20 Next, a PDT apparatus according to another
embodiment of the present invention will be described.
In the following description, descriptions of
configurations, functions, operations, and the like
similar to those of the PDT apparatus 1 of the first
25 embodiment will be omitted or simplified, and different
points will mainly be described.
6 6
An optical system and a detection unit according
to the second embodiment will be described.
[0106] [Structures of optical system and detection
unit]
5 Fig. 17 is a block diagram showing an optical
system, a detection unit, and the like of the second
embodiment of the present invention.
An optical system 120a includes the short pass
filter 121, the first lens 122, the PBS 123, a first
10 dichroic mirror (hereinafter referred to as "DM".) 126,
and a second DM 127.
[0107] A detection unit 130a includes a first
photodiode (hereinafter referred to as "PD".) 131, and
a second PD 132.
15 [0108] The first DM 126 reflects light having a
certain wavelength out of the light entered from the
PBS 123, and causes the light having the other
wavelengths to pass through. In this manner, the first
DM 126 reflects part of fluorescence from the laser
20 catheter 300, and allows the fluorescence having the
other wavelengths from the laser catheter 300 and
specular reflection light to pass thorough. The
fluorescence, which has reflected off the first DM 126,
enters the first PD 131.
25 The first PD 131 detects the fluorescence entered
from the first DM 126. The first PD 131 outputs the
67
detected fluorescence intensity to the controller 150
as an electrical signal.
[0109] The second DM 127 reflects light having a
certain wavelength out of the light which has passed
5 through the first DM 126, and causes the light having
the other wavelengths to pass through. In this manner,
the second DM 127 reflects part of fluorescence, which
has passed through the first DM 126, and allows the
fluorescence having the other wavelengths and specular
10 reflection light to pass thorough. The fluorescence,
which has reflected off the second DM 127, enters the
second PD 132.
The second PD 132 detects the fluorescence entered
from the second DM 127. The second PD 132 outputs the
15 detected fluorescence intensity to the controller 150
as an electrical signal.
[0110] Note that the optical system 120a may further
include DMs each having a structure similar to the
structure of each of the first DM 126 and the second DM
20 127. In this manner, eventually, the plurality of DMs
126, 127 ... reflect the fluorescence from the laser
catheter 300, and the plurality of PDs 131, 132 ...
detect the fluorescence from the laser catheter 300.
Then, the plurality of DMs 126,127 ... causes the
25 specular reflection light to pass through.
[0111] Note that, as another embodiment, a pulse
68
light source may be used as the light source 110, and
the specular reflection light reflected off the fiber
entrance edge may be temporally separated based on
optical path length difference (about twice as long as
5 length of laser catheter 300).
[0112]-
In the third embodiment, the contact-monitoring
steps are performed based on the phase difference
between the peak of fluorescence intensity, which is in
10 the interval between R-waves, and R-wave.
In the electric-conduction-block-formation
determining operation of the first embodiment, it is
determined that an electric-conduction block is formed
based on the phase difference between the peak of
15 fluorescence intensity, which is in the interval
between R-waves, and R-wave. This principle may be
applied to the contact-monitoring operation.
[0113] The light source 110 outputs the excitation
light with the first intensity to the optical system
20 - 120. The detection unit 130 detects the fluorescence
entered from the optical system 120. The detection unit
130 outputs the detected fluorescence intensity to the
controller 150 as an electrical signal. The controller
150 calculates fluorescence intensity based on the
25 obtained electrical signal.
[0114] Meanwhile, the electrocardiograph 140 obtains
69
an electrocardiographic signal, and supplies the
obtained electrocardiographic signal to the controller
150. The controller 150 creates display information
based on the calculated fluorescence intensity and the
5 obtained electrocardiographic signal, and outputs
display instruction including the created display
information to the display unit 170. The display unit
170 obtains the display instruction from the controller
150, and displays the correlation between fluorescence
10 intensity and electrocardiogram R-wave on the display
screen based on the display information in the display
instruction.
[0115] The controller 150 determines the contact
state of the tip portion of the laser catheter 300
15 based on the calculated fluorescence intensity and the
obtained electrocardiographic signal (Step 5106).
Specifically, if the controller 150 determines that the
peak of fluorescence intensity appears for a
predetermined time period after appearance of the R-
20 --- wave, the controller 150 determines that the tip
portion of the laser catheter 300 is in the uprightcontact
state. If the controller 150 determines that
the peak of fluorescence intensity and the R-wave
appear simultaneously, the controller 150 determines
25 that the tip portion of the laser catheter 300 is in
the slanting-contact state. Further, the blood volume
70
between the tip portion of the laser catheter 300 and
the inner wall of a tissue may be estimated based on
fluorescence peak intensity.
[0116]
5 According to the fourth embodiment, the contactmonitoring
steps are performed by using
autofluorescence spectrum differences. Note that,
autofluorescence indicates light emitted from a tissue
by itself, and does not mean fluorescence from a
10 pharmaceutical. That is, the fourth embodiment
describes a diagnostic method in which no
pharmaceutical is used.
[0117] The light source 110 outputs an excitation
light, with which the difference between the
15 autofluorescence spectrum property of a cardiac-muscle
tissue and the autofluorescence spectrum property of
blood is determined easily. The detection unit 130
detects entered fluorescence. The detection unit 130
outputs the detected fluorescence intensity to the
20 controller 150 as an electrical signal. The controller
150 calculates the fluorescence spectrum based on the
obtained electrical signal. The controller 150
determines whether the calculated fluorescence spectrum
shows the autofluorescence spectrum property of a
25 cardiac-muscle tissue or the autofluorescence spectrum
property of blood. The controller 150 compares the
'71
calculated fluorescence spectrum with the
autofluorescence spectrum property of a cardiac-muscle
tissue and the autofluorescence spectrum property of
blood, and determines the contact state of the tip
5 portion of the laser catheter 300 (Step 5106).
Specifically, if the controller 150 determines that the
calculated fluorescence spectrum shows the
autofluorescence spectrum property of a cardiac-muscle
tissue, the controller 150 determines that the tip
10 portion of the laser catheter 300 is in the uprightcontact
state. If the controller 150 determines that
the calculated fluorescence spectrum shows the
autofluorescence spectrum property of blood, the
controller 150 determines that the tip portion of the
15 laser catheter 300 is in the non-contact state. If the
controller 150 determines that the calculated
fluorescence spectrum does not show the each
autofluorescence spectrum property, the controller 150
determines that the tip portion of the laser catheter
20 - 300 is in the slanting-contact state.
[0118] The contact-monitoring using the
autofluorescence spectrum difference is also useful for
laser-catheter contact-monitoring in the case of a
therapy for a disease with a vascular occlusion (for
25 example, arteriosclerotic disease or the like).
Figs. 18 are schematic diagrams each showing a
72
contact state of a laser catheter in an intravascular
lumen.
In a therapy for a disease with a vascular
occlusion, it is desired to determine whether the tip
5 portion of the laser catheter 300 contacts a vascular
occlusion (atheromatous plaque) 21 in a blood vessel 20
(see Fig. 18(a)) or contacts a blood-vessel wall 22
(see Fig. 18(b)). Here, the composition ratio of
collagen, elastin, lipid, and the like of a vascular
10 occlusion is different from the composition ratio of a
blood-vessel wall. Specifically, the composition ratio
of a vascular occlusion (arteriosclerosis) is 70% of
water, 5% of collagen, 6% of elastin, and 9% of lipid.
The composition ratio of a blood vessel is 73% of water,
15 6.5% of collagen, 10.5% of elastin, and 1% of lipid.
Because of this, the autofluorescence spectrum property
of a vascular occlusion is different from the
autofluorescence spectrum property of a blood-vessel
wall. If a therapy-target site is irradiated with an
20 excitation light, with which the property difference is
determined easily, and fluorescence is measured, it is
possible to determine whether the tip portion of the
laser catheter 300 contacts the vascular occlusion 21
or the blood-vessel wall 22. Note that, because it can
25 be determined whether there is an atheromatous plaque
or not based on the composition ratio, the contact73
monitoring using the autofluorescence spectrum
difference can perform diagnosis more precisely than
IVUS (intravascular ultrasound), with which it is
determined whether there is an atheromatous plaque or
5 not based on the size of the blood vessel diameter.
[0119]. The embodiments of the present invention are
not limited to the above-mentioned embodiments, and
other various embodiments are conceivable.
[0120] Although in the above-mentioned embodiments,
10 the laser catheter 300 is detachably connected to the
connector 210 of the PDT apparatus 1, the laser
catheter 300 may be provided on the PDT apparatus 1
integrally.
Although in the above-mentioned embodiments, the
15 tube 200 is provided on the PDT apparatus main body 100
and the connector 210 is provided on the end of the
tube 200, the connector 210 may be provided on the PDT
apparatus main body 100.
Although in the above-mentioned embodiments, the
20 PBS 123 is used, a DM may be used instead.
[0121] Although in the above-mentioned embodiments,
the controller 150 informs a practitioner of
information to prompt the predetermined controls by
using the display unit 170, but.... is not limited to this.
25 A speaker unit may be provided on the PDT apparatus 1,
and the controller 150 may create a sound output
74
instruction when prompting a practitioner to perform
the predetermined controls, may output the created
sound output instruction to the speaker unit, and may
cause the speaker unit to output sounds, to thereby
5 prompt a practitioner to perform the predetermined
controls.
Description of Symbols
[0122] 1 photodynamic therapy (PDT) apparatus
100 PDT apparatus main body
10 110 light source
120, 120a optical system
121 short pass filter
122 first lens
123 polarizing beam splitter (PBS)
15 124 long pass filter
125 second lens
126 first dichroic mirror (DM)
127 second dichroic mirror (DM)
130, 130a detection unit
20 131 first photodiode (PD)
132 second photodiode (PD)
140 electrocardiograph
141 electrode pad
150 controller
25 160 storage
170 display unit
75
180 controller
200 tube
201 apparatus-attached optical fiber
210 connector
5 300 laser catheter
301 irradiation light
310 catheter tube
320 holder
330 optical fiber
10 340 optical window
76
Claims
[1] A determining apparatus for irradiating a tissue
having absorbed photo-sensitive pharmaceutical, the
photo-sensitive pharmaceutical absorbing an excitation
5 light and emitting fluorescence, or a tissue absorbing
the excitation light and emitting fluorescence, with
the excitation light emitted from a tip portion of a
laser catheter, comprising:
a connector to/from which the laser catheter is
10 capable of being attached/detached;
a light source for outputting the excitation light
to the laser catheter via the connector; and
a detection unit for detecting intensity or a
spectrum of the fluorescence, the fluorescence being
15 entered from the laser catheter via the connector, to
determine whether the tip portion of the laser catheter
contacts the tissue or not.
[2] The determining apparatus according to claim 1,
further comprising:
20 a controller for determining whether the tip
portion of the laser catheter contacts the tissue or
not, based on intensity or a spectrum of the detected
fluorescence.
[3] The determining apparatus according to claim 1,
25 further comprising:
a controller for determining a contact angle in a
77
state where the tip portion of the laser catheter
contacts the tissue or determining that the tip portion
of the laser catheter fails to contact the tissue,
based on intensity or a spectrum of the detected
5 fluorescence.
[4] The determining apparatus according to claim 3,
wherein
the controller outputs a signal to prompt to
change a contact state of the tip portion of the laser
10 catheter with respect to the tissue, based on the
determination result.
[5] The determining apparatus according to claim 3,
wherein
the controller calculates an excitation-light-
15 irradiation protocol based on the intensity or the
spectrum of the detected fluorescence, and outputs a
calculation result.
[6] The determining apparatus according to claim 4,
wherein
20 the light source outputs the excitation light with
a first intensity when determining whether the tip
portion of the laser catheter contacts the tissue or
not, and outputs the excitation light with a second
intensity when performing a photodynamic therapy with
25 respect to the tissue, the second intensity being
larger than the first intensity.
78
[7] The determining apparatus according to claim 4,
wherein
the controller obtains an electrocardiographic
signal, and determines a contact angle in a state where
5 the laser catheter contacts the tissue or determines
that the laser catheter fails to contact the tissue,
based on a correlation between the electrocardiographic
signal and the intensity of the fluorescence.
[8] The determining apparatus according to claim 3,
10 wherein
the controller determines an abnormal situation of
the tip portion of the laser catheter, based on the
intensity or the spectrum of the detected fluorescence.
[9] A determining method, comprising:
15 irradiating a tissue having absorbed photosensitive
pharmaceutical, the photo-sensitive
pharmaceutical absorbing an excitation light and
emitting fluorescence, or a tissue absorbing the
excitation light and emitting fluorescence, with the
20 -- excitation light emitted from a tip portion of a laser
catheter;
extracting the fluorescence corresponding to the
irradiated excitation light via the laser catheter; and
determining whether the tip portion of the laser
25 catheter contacts the tissue or not, based on intensity
or a spectrum of the extracted fluorescence.
79
[10] The determining method according to claim 9,
further comprising:
calculating an excitation-light-irradiation
protocol based on the intensity or the spectrum of the
5 extracted fluorescence, and outputting a calculation
result.
[11] A determining method using photo-sensitive
pharmaceutical absorbing an excitation light and
emitting a fluorescence, a laser catheter capable of
10 emitting the excitation light from a tip portion, and
an estimating apparatus including a connector to/from
which the laser catheter is capable of being
attached/detached and a light source for outputting the
excitation light to the laser catheter via the
15 connector, comprising:
absorbing, in a tissue, the photo-sensitive
pharmaceutical;
leading the tip portion of the laser catheter to
the tissue having absorbed the photo-sensitive
20 ". pharmaceutical, the laser catheter being attached to
the connector;
irradiating the tissue having absorbed the photosensitive
pharmaceutical with the excitation light
emitted from the tip portion of the laser catheter, the
25 excitation light being output from the light source;
extracting the fluorescence corresponding to the
80
irradiated excitation light via the laser catheter; and
determining whether the tip portion of the laser
catheter contacts the tissue or not, based on intensity
or a spectrum of the extracted fluorescence.
5 [12] The determining method according to claim 11,
further comprising:
calculating an excitation-light-irradiation
protocol based on the intensity or the spectrum of the
extracted fluorescence, and outputting a calculation
10 result.