DESCRIPTION
CALCULATION APPARATUS AND CALCULATION METHOD
Technical Field
5 [0001] The present invention relates to a
calculation apparatus and a calculation method that
calculate pharmaceutical concentration in a tissue.
Background Art
[0002] Atrial fibrillation is known as a kind of
10 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
and contracts because of the electrical pulse
15 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
"PDT".) (for example, see Patent Document 1.). In PDT,
20 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
oxidizer insults a cardiac-muscle tissue, which
25 surrounds the hyperexcited site, to thereby form an
electric-conduction block, which blocks conduction of
2
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
blocked, and an abnormal vibration and contraction of
5 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
(for example, 8 to 48 hours) passes after photo-
10 sensitive 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
in other tissues and blood is established, that is,
15 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
property of photo-sensitive pharmaceutical is not used
20 - 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.
[0005] Patent Document 1: WIPO Publication No.
25 2008/066126
Disclosure of the Invention
3
Problem to be solved by the invention
[0006] In a therapy, in which pharmaceutical is used,
it is important to monitor pharmaceutical concentration
in a tissue to determine optimum therapeutic protocols.
5 [0007] In view of this, conventionally, as a method
of monitoring pharmaceutical concentration in blood, a
method of measuring absorbance of blood collected every
predetermined time after pharmaceutical administration,
and other methods are known. However, in this method,
10 the plot number is limited because the collectable
blood volume is limited, and in addition, it is not
possible to measure the concentration in real time.
Further, as a method of monitoring pharmaceutical
concentration in a tissue, there is known a method in
15 which part of carbon in pharmaceutical is transformed
into isotope, the isotope is simultaneously
administered, and pharmaceutical concentration in each
tissue is measured based on a radiation quantity.
However, this method involves radiation exposure
20 problems, is not a less-invasive monitoring method, and
is not realistic.
[0008] In view of the above-mentioned circumstances,
an object of the present invention is to provide a
calculation apparatus and a calculation method capable
25 of calculating pharmaceutical concentration in a tissue
in real time.
4
Means for solving the Problem
[0009] To attain the above-mentioned object, a
calculation apparatus according to an embodiment of the
present invention is a calculation apparatus for
5 irradiating a tissue having absorbed photo-sensitive
pharmaceutical, the photo-sensitive pharmaceutical
absorbing an excitation light and emitting fluorescence,
with the excitation light emitted from a tip portion of
a laser catheter, including a connector, a light source,
10 and a detection unit.
Note that, in the specification, the term "tissue"
may sometimes include blood.
The laser catheter is capable of being
attached/detached to/from the connector.
15 The light source outputs the excitation light to
the laser catheter via the connector.
The detection unit detects intensity of the
fluorescence, the fluorescence being entered from the
laser catheter via the connector, to calculate
20 --- concentration of the photo-sensitive pharmaceutical in
a tissue, the tip portion of the laser catheter
contacting the tissue.
[0010] By detecting the intensity of the
fluorescence entered from the laser catheter, it is
25 possible to estimate concentration of the photosensitive
pharmaceutical in a tissue, which the tip
portion of the laser catheter contacts, in real time.
Further, by using a laser catheter used for therapy,
operability is improved.
[0011] The calculation apparatus may further include
5 a calculation unit for calculating the concentration of
the photo-sensitive pharmaceutical in the tissue, the
tip portion of the laser catheter contacting the tissue,
based on intensity of the detected fluorescence.
[0012] By detecting the intensity of the
10 fluorescence entered from the laser catheter, it is
possible to calculate concentration of the photosensitive
pharmaceutical in a tissue, which the tip
portion of the laser catheter contacts, in real time.
[0013] The calculation apparatus may further include
15 a controller for outputting a signal to prompt to
additionally administer the photo-sensitive
pharmaceutical based on the calculated concentration.
[0014] As a result, is possible to prompt u
practitioner to additionally administer the photo-
20 -- sensitive pharmaceutical in real time based on the
intensity of the fluorescence entered from the laser
catheter. Note that to "output a signal" means to
output a display instruction including display
information to a display unit, or to output a sound
25 output instruction to a speaker unit.
[0015] The controller may calculate an excitation6
light-irradiation protocol based on the calculated
concentration, and output a calculation result.
[0016] As a result, it is possible to inform a
practitioner of the excitation-light-irradiation
5 protocol in real time, based on the intensity of the
fluorescence entered from the laser catheter.
[0017] A calculation method according to an
embodiment of the present invention includes
irradiating a tissue having absorbed photo-sensitive
10 pharmaceutical, the photo-sensitive pharmaceutical
absorbing an excitation light and emitting fluorescence,
with the excitation light emitted from a tip portion of
a laser catheter.
The fluorescence corresponding to the irradiated
15 excitation light is extracted via the laser catheter.
Concentration of the photo-sensitive
pharmaceutical in a tissue, the tip portion of the
laser catheter contacting the tissue, is calculal:ed
based on intensity of the extracted fluorescence.
20 [0018] By detecting the intensity of the
fluorescence entered from the laser catheter, it is
possible to estimate concentration of the photosensitive
pharmaceutical in a tissue, which the tip
portion of the laser catheter contacts, in real time.
25 [0019] The calculation method may further include
outputting a signal to prompt to additionally
7
administer the photo-sensitive pharmaceutical based on
the calculated concentration.
[0020] As a result, it is possible to prompt a
practitioner to additionally administer the photo-
5 sensitive pharmaceutical in real time based on the
intensity of the fluorescence entered from the laser
catheter.
[0021] The calculation method may further incLude
calculating an excitation-light-irradiation protocol
10 based on the calculated concentration, and outputs a
calculation result,
[0022] As a result, it is possible to inform a
practitioner of the excitation-light-irradiation
protocol in real time, based on the intensity of the
15 fluorescence entered from the laser catheter.
[0023] A calculation method according to an
embodiment of the present invention is a calculation
method using photo-sensitive pharmaceutical absorbing
an excitation light and emitting a fluorescence, a
20 laser catheter capable of emitting the excitation light
from a tip portion, and a calculation 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
25 catheter via the connector,
In a tissue, the photo-sensitive pharmaceutical is
8
absorbed.
The tip portion of the laser catheter is led to
the tissue having absorbed the photo-sensitive
pharmaceutical, the laser catheter being attached to
5 the connector.
The tissue having absorbed the photo-sensitive
pharmaceutical is irradiated with the excitation light
emitted from the tip portion of the laser catheter, the
excitation light being output from the light source.
10 The fluorescence corresponding to the irradiated
excitation light is extracted via the laser catheter.
Concentration of the photo-sensitive
pharmaceutical in a tissue, the tip portion of the
laser catheter contacting the tissue, is calculated
15. based on intensity of the extracted fluorescence.
.[0024] The calculation method may further include
calculating an excitation-light-irradiation protocol
based on the calculated concentration, and outputs a
calculation result.
20 Effect of the Invention
[0025] According to the present invention, it is
possible to calculate pharmaceutical concentration in a
tissue in real time.
Brief Description of Drawings
25 [0026] [Fig. 1] A schematic diagram showing a PDT
apparatus according to a first embodiment of the
9
present invention.
[Fig. 2] A schematic diagram showing a laser catheter
inserted in a heart.
[Fig. 3] A block diagram showing a PDT apparatus main
5 body.
[Fig. 4] A sectional view showing the tip portion of
the laser catheter.
[Fig. 5] A flowchart showing operationsof the PDT
apparatus.
10 [Fig. 6] A schematic diagram showing the laser
catheter inserted in a left atrium.
[Fig. 7] A graph showing the temporal change of
fluorescence intensity.
[Fig. 8] A graph showing the correlation between the
i5 fluorescence intensity and pharmaceutical concentration.
[Fig. 9] A graph showing the temporal change of the
pharmaceutical concentration.
[Figs. 10] Schematic diagrams each showing a
contact state of the laser catheter.
20 [Fig. Ill A graph showing the temporal change of the
fluorescence intensity.
[Fig. 12] Another graph showing the temporal change of
the fluorescence intensity.
[Fig. 13] A schematic diagram showing a movement track
25 of the laser catheter.
[Fig. 14] A diagram showing the relation of ECG,
10
intracardiac pressure, and coronary blood-flow volume,
which is dominant in the blood-flow volume in a
cardiac-muscle tissue.
[Fig. 15] A diagram showing the correlation between
5 fluorescence intensity and R-wave when the laser
catheter is in the upright-contact state.
[Fig. 16] A diagram showing the correlation between
fluorescence intensity and R-wave when the laser
catheter is in the slanting-contact state.
10 [Fig. 17] A block diagram showing an optical system, a
detection unit, and the like of a second embodiment of
the present invention.
[Figs. 18] Schematic diagrams each showing a
contact state of a laser catheter in an intravascular
15 lumen.
[Fig. 19] A graph showing the relation between
wavelength and fluorescence intensity.
Best Modes for Carrying Out the Invention
[0027] Hereinafter, embodiments of the present
20 -- 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 calculate apparatus
will be described.
25 [0028]
Fig. 1 is a schematic diagram showing a PDT
II
apparatus according to a first embodiment of the
present invention.
The PDT apparatus 1 includes a PDT apparatus main
body 100, a tube 200 connected to the PDT apparatus
5 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
of transmitting light via an inner apparatus-attached
optical fiber 201 (see Fig. 3.).
10 A laser catheter 300 is detachably connected to
the connector 210.
[0029] Photo-sensitive pharmaceutical is
administered to a patient 2. In the case of being
administered by intravenous injection, the administered
15 photo-sensitive pharmaceutical diffuses in the blood,
and then a tissue such as a cardiac-muscle tissue
absorbs the pharmaceutical. Adose of photo-sensitive
pharmaceutical necessary for therapy may be
administered at one time by intravenous injection, may
20 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
light having a certain wavelength, is photoexcited, and
25 becomes fluorescent. For example, pharmaceutical called
talaporfin sodium (Laserphyrin (registered trademark),
12
Meiji Co., Ltd.) is employed. Because the Q-band
absorption wavelength of this pharmaceutical is near
664 nm, an excitation light source for this
pharmaceutical with, for example, 600 to 800 nm,
5 preferably 660 to 680 nm, or more preferably 664 plus
or minus 2 nm is used.
[0030] Fig. 2 is a schematic diagram showing a laser
catheter inserted in a heart.
The laser catheter 300 is inserted in a right
10 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,
and is led to a left atrium 13.
[0031] [Configuration of PDT apparatus main body]
15 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,
an electrocardiograph 140, a controller 150, storage
20 160, a display unit 170, and an operating unit 180,
[0032] The light source 110 outputs an excitation
light for photo-sensitive pharmaceutical. The
wavelength of the light output by the light source 110
is the same as the Q-band absorption wavelength of the
25 photo-sensitive pharmaceutical. For example, in the
case where photo-sensitive pharmaceutical whose Q-band
13
absorption wavelength is near 664 nm is used, a
semiconductor laser with the emission wavelength of 600
to 800 nm, preferably 660 to 680 nm, or more preferably
664 plus or minus 2 nm is used as the light source 110.
5 The excitation light output by the light source 110
enters the laser catheter 300 via the optical system
120.
[0033] The optical system 120 allows the excitation
light, which is emitted from the light source 110, to
10 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
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,
a long pass filter 124, and a second lens 125.
20 -- The short pass filter 121 is a short-wavelength
transmission filter with a cuton wavelength of 670 nm,
and cuts long-wavelength radiation. The excitation
light from the light source 110 has the radiation
component in the fluorescence observation wavelength
25 range (long-wavelength side of peak wavelength). In
view of this, the radiation component of the excitation
14
light in the long-wavelength side is cut at the stage
prior to collecting the light in the laser catheter 300.
The excitation light, which has passed the short pass
filter 121, enters the first lens 1.22.
5 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
lens 122 collects fluorescence from the tip portion of
the laser catheter 300 on the PBS 123. Note that part
10 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
the inside of the connector 210, and off the tip
portion of the laser catheter 300, and enters the PBS
15 123 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
reflected off an edge of the optical fiber in the tube
20 200, 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,
and brings them to a detecting device. The fluorescence,
25 which has passed the PBS 123, enters the long pass
filter 124.
15
The long pass filter 124 causes the specular
reflection light, which has reflected off the inside of
the connector 210 and the tip portion of the laser
catheter 300, out of the light entered from the PBS 123,
5 not to pass through, allows only the fluorescence to
pass through, and brings the fluorescence to the
detecting device. The fluorescence, which has passed
through the long pass filter 124, enters the second
lens 125.
10 The second lens 125 collects the fluorescence,
which has entered from the long pass filter 124, on the
detection unit 130.
[0034] The detection unit 130 is, for example, a
linear image sensor, and spectroscopically detects the
15 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
light having a wavelength longer than the excitation
20 wavelength. The detection unit 130 outputs an
electrical signal, which shows intensity of the
detected fluorescence, to the controller 150.
.[0035] An electrode pad 141 is connected to the
electrocardiograph 140 via an electrode code (not
25 shown) . The electrocardiograph 140 obtains an
electrocardiographic signal of the patient 2 via the
16
electrode pad 141, which is attached to the patient 2,
and via the electrode code, and supplies the obtained
electrocardiographic signal to the controller 150.
[0036] The controller 150 controls the respective
5 units of the PDT apparatus 1.
The controller 150 calculates fluorescence
intensity based on the electrical signal obtained from
the detection unit 130. The controller 150 calculates
pharmaceutical concentration in the tissue or in the
10 blood based on the calculated fluorescence intensity
(pharmaceutical-concentration-monitoring operation).
The controller 150 determines whether to additionally
administer the pharmaceutical or not based on the
calculated pharmaceutical concentration.
15 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).
The controller 150 determines, based on change of
20 -- 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 (foreignsubstance/
breakage-monitoring operation, and cytocidal-
25 effect-determining operation). The controller 150
controls the light source 110 to stop irradiating the
17
excitation light based on determination results.
The controller 150 determines whether an electricconduction
block is formed or not based on an
electrical signal obtained from the detection unit 130
5 and based on an electrocardiographic signal obtained
from the electrocardiograph 140 (electric-conductionblock-
formation determining operation).
The controller 150 outputs, to the display unit
170, display instructions to display the above-
10 mentioned various calculation results, the abovementioned
various determination results, and various
information.
[0037] The storage 160 is a nonvolatile memory, and
is set in, for example, a flash memory, an HDD (Hard
15 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
130 is in relation with time information obtained from
20 -- 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
which information on an electrocardiographic signal
25 obtained from the electrocardiograph 140 is in relation
with time information.
1 s
[0038] The display unit 170 is a display device,
which uses, for example, a liquid-crystal display
device or the like. When the display unit 170 obtains
display instructions from the controller 150, the
5 display unit 170 displays, on a display screen, for
example, information on fluorescence intensity,
information on an electrocardiographic signal, time
information, and the like, based on display information
in the display instructions.
10 [0039] The operating unit 180 receives instructions,
which are input through operations by a practitioner,
and outputs the received instructions to the controller
150. The instructions include, for example,
instructions to turn on/off the excitation light output
15 from the light source 110, to change intensity, and the
like. As intensity of the excitation light, it is
possible to select at least one of two levels of
intensity including a first intensity, which has a low
power (for example, optical output of 1 mW or less) and
20 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
monitoring the pharmaceutical concentration and the
25 contact state of the laser catheter 300 before therapy.
The second intensity is selected when therapy is
19
conducted. Note that the first intensity is a fixed
value, and the second intensity may be variable.
[0040] [Structure of laser catheter]
The the laser catheter 300 outputs an excitation
5 light from the tip portion.
Fig. 4 is a sectional view showing the tip portion
of the laser catheter.
The laser catheter 300 includes a catheter Cube
310, a holder 320, an optical fiber 330, and an optical
10 window 340.
[0041] The catheter tube 310 is a soft hollow tube,
and is led to the inner wall of a cardiac-muscle tissue
of the heart 10 of the patient 2. The catheter tube 310
has the optical fiber 330 therein.
15 [0042] 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.
[0043] The optical fiber 330 is, for example, one
20 --- 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
transmitted excitation light, as an irradiation light
25 301, from the tip to the optical window 340. The beam
diameter of the irradiation light 301 increases at the
20
angle determined by the numerical aperture (NA) of the
optical fiber 330. The tip of the optical fiber 330 is
worked such that the beam diameter of the irradiation
light 301 appropriately increases. The optical fiber
5 330 transmits the fluorescence, which is emitted from
photo-sensitive pharmaceutical absorbed in a tissue and
irradiated with an excitation light, to the PDT
apparatus 1.
[0044] The optical window 340 is provided on the
10 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
340 is made from a solid transparent material, for
example, a glass material such as BK7, The optical
15 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
fluorescence, which is emitted from the photo-sensitive
20 pharmaceutical, on the tip of the optical fiber 330,
[0045] 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
detection fiber in a laser catheter, and performing
25 irradiation and light-reception, to thereby remove
specular reflection light (see Japanese Patent
21
Application Laid-open No, 2009-148550, paragraph
[0037].).
Meanwhile, in the case of performing intracardiac
therapy or diagnosis, in order to increase the
5 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
catheter, each optical fiber should be formed exLrafinely,
and thus a light having a necessary intensity
10 may not be transmitted.
In view of the above, in diseases requiring
intracardiac approaches such as, specifically, atrial
fibrillation and ventricular flutter, it is desired
that one optical fiber be in a laser catheter. Further,
15 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
fiber.
20 [0046] 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
filter 121 further removes a long-wavelength-side
25 radiation component of a excitation light. With this
structure, in the laser catheter 300, while the one
22
optical fiber 330 doubles an irradiation fiber and a
detection fiber, the detection unit 130 can detect
fluorescence with a high SN ratio. As a result, it is
possible to detect fluorescence with a low power so as
5 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 extrafine
laser catheter with an increased curvature.
[0047] [Operations of PDT apparatus]
10 Next, operations of the PDT apparatus 1 configured
as described above will be described.
Fig. 5 is a flowchart showing operations of the
PDT apparatus.
[0048] The operations of the PDT apparatus 1 will be
15 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)
In the pharmaceutical-concentration-monitoring
20 operation, the light source 110 outputs an excitation
light with a first intensity, and the controller 150
constantly calculates the pharmaceutical concentration
based on fluorescence intensity detected by the
detection unit 130, and determines whether to
25 additionally administer pharmaceutical or not based on
the calculated pharmaceutical concentration.
23
(3) Contact-monitoring operation (Step 5106 to
Step S108)
In the contact-monitoring operation, the light
source 110 outputs the excitation light with the first
5 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
detected by the detection unit 130, and calculates
excitation-light-irradiation protocols (intensity, time,
10 and the like).
(4) Foreign-substance/breakage-monitoring
operation (Step S109 to Step 5112)
In the foreign-substance/breakage-monitoring
operation, the light source 110 outputs the excitation
15 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
vicinity of the tip of the laser catheter 300 or not,
20 during laser-irradiation at appropriate therapy
protocols, based on the fluorescence intensity detected
by the detection unit 130.
(5) Cytocidal-effect-determining operation (Step
S113)
25 In the cytocidal-effect-determining operation, the
light source 110 outputs the excitation light with the
24
second intensity, and the controller 150 determines
whether there is a cytocidal effect on a tissue, on
which the excitation light is being irradiated, or not
based on the fluorescence intensity detected by the
5 detection unit 130.
(6) Electric-conduction-block-formation
determining operation (Step 5114 to Step S117)
An electric-conduction block is, as described
above, a block in which cardiac-muscle tissues
10 surrounding a hyperexcited site are necrotized, and in
which conduction of electrical pulses from the
hyperexcited site to the left atrium is blocked. Here,
it is determined whether an electric-conduction block
is formed or not by calculating, by the controller,
15 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 electricconduction
block, the intensity of the light source 110
20 -- 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.
[0049] [(1) Preparation for PDT]
Fig. 6 is a schematic diagram showing a laser
25 catheter inserted in a left atrium.
First, a practitioner such as a doctor inserts the
25
laser catheter 300 in the heart 10 via a femoral vein
or a jugular vein of the patient 2. The tip portion of
the laser catheter 300 is disposed in the vicinity of a
pulmonary vein 12 of an inner wall of a cardiac-muscle
5 tissue 11 of the left atrium 13 (Step S101).
[0050] Subsequently, with reference to various
referential data (Step S102), the practitioner
administers photo-sensitive pharmaceutical to the
patient 2 (Step S103). Here, the case where a dose of
10 photo-sensitive pharmaceutical necessary for therapy is
administered to the patient 2 at one time by
intravenous injection will be described. The
administered photo-sensitive pharmaceutical is diffused
in blood and absorbed in a tissue.
15 [0051] [(2) Pharmaceutical-concentration-monitoring
operation]
Subsequently, the pharmaceutical-concentrationmonitoring
operation is performed.
First, the practitioner operates the operating
20 unit 180, 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
the excitation-light-output instruction with the first
25 intensity, to the light source 110. The light source
110 obtains the excitation-light-output instruction
26
from the controller 150, and then outputs the
excitation light with the first intensity. Tissues and
blood are irradiated with the excitation light output
from the light source 110 via the optical system 120
5 and the laser catheter 300. The photo-sensitive
pharmaceutical, which is absorbed in a tissue and blood,
absorbs the excitation light from the laser catheter
300, and emits fluorescence. The optical system L20
extracts the fluorescence emitted from the photo-
10 sensitive pharmaceutical via the laser catheter 300,
and the fluorescence enters the detection unit 130. The
detection unit 130 detects the entered fluorescence,
and outputs the detected fluorescence intensity to the
controller 150 as an electrical signal.
15 [0052] 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
change of the fluorescence intensity as a log in which
20 - the calculated fluorescence intensity is in relation
with time information obtained from a timing
measurement unit (not shown.). The controller 150
creates display information of the temporal change of
the fluorescence intensity based on the calculated
25 fluorescence intensity and elapsed time after a
criterion time such as an intravenous-injection start
27
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 the controller 150, and then displays the temporal
5 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
displays the temporal change of the fluorescence
intensity on the display screen in a graph form.
10 [0053) Here, an example of the graph showing the
temporal change of the fluorescence intensity will be
described,
Fig. 7 is a-graph showing a temporal change of
fluorescence intensity,
15 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 (i.v.), and irradiation is
performed with an excitation light, which is the same
20 as the Q-band absorption spectrum of the pharmaceutical
(semiconductor laser, emission wavelength with, for
example 600 to.800 rim, preferably 660 to 680 nm, or
more preferably 664 plus or minus 2, 400 pW). The tip
portion of the laser catheter 300 is disposed in the
25 right atrium of the pig.
The fluorescence intensity in blood monotonically
28
decreases. after the pharmaceutical administration.
Meanwhile, the fluorescence intensity in a cardiacmuscle
tissue increases for a predetermined time period
after the pharmaceutical administration, and then
5 decreases. Further, the fluorescence intensity in the
blood is higher than the fluorescence intensity in the
cardiac-muscle tissue.
[0054] Here, the relation between fluorescence
intensity and pharmaceutical concentration will be
10 described.
Fig. 8 is a graph showing a correlation between
fluorescence intensity and pharmaceutical concentration.
Fig.. 8 shows a correlation between absolute value
of pharmaceutical concentration (PS concentration)
15 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
almost the same as the fluorescence intensity. That is,
20 --- it is possible to monitor pharmaceutical concentration
in real time based on the constantly-calculated
fluorescence intensity,
[0055] The controller 150 calculates pharmaceutical
concentration in a tissue and in blood based on
25 calculated fluorescence intensity (Step 5104). The
controller 150 starts to record, in the storage 160,
29
the temporal change of the pharmaceutical concentration
as a log in which the calculated pharmaceutical
concentration is in relation with time information
obtained from a timing measurement unit (not shown.).
5 Further, the controller 150 creates display information
of the temporal change of the pharmaceutical
concentration based on the calculated pharmaceutical
concentration and elapsed time after a criterion time
such as an intravenous-injection start time, and
10 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 displays the temporal
change of the pharmaceutical concentration on a display
15 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.
[0056] Here, an example of a graph showing the
20 temporal change of the pharmaceutical concentration
will be described.
Fig. 9 is a graph showing a temporal change of
pharmaceutical concentration.
As described above, the fluorescence intensity in
25 blood is higher than the fluorescence intensity in a
cardiac-muscle tissue, and, in addition, the
30
fluorescence intensity correlates with the
pharmaceutical concentration. Therefore, similar to the
temporal change of the fluorescence intensity in blood,
the pharmaceutical concentration in blood monotonically
5 decreases after the pharmaceutical administration.
Meanwhile, similar to the temporal change of the
fluorescence intensity in a tissue, the pharmaceutical
concentration in a tissue increases for a predetermined
time period after the pharmaceutical administration,
10 and then decreases. Further, the pharmaceutical
concentration in blood is higher in level than the
pharmaceutical concentration in a tissue.
[0057] The controller 150 determines whether the
calculated pharmaceutical concentration is equal to or
15 more than a threshold (Step S105). If the controller
150 determines that the pharmaceutical concentration is
equal to or more than the threshold, the controller 150
estimates that the pharmaceutical concentration reaches
a necessary value, and moves to the contact-monitoring
20 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
concentration fails to reach the necessary value,
25 creates display information for prompting to
additionally administer the pharmaceutical, and outputs
3l
the 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 displays, based on the display
5 information including the display instruction,
information prompting the practitioner to additionally
administer the photo--sensitive pharmaceutical (Step
5105, No).
[0058] Note that, because the fluorescence intensity
10 correlates with the pharmaceutical concentration, if
the display unit 170 displays the fluorescence
intensity on the display screen, a practitioner such as
a doctor may estimate the pharmaceutical concentration
based on tithe fluorescence intensity, even if the
15 controller 150 does not calculate the pharmaceutical
concentration.
[0059] Meanwhile, in general, as a method of
monitoring the pharmaceutical concentration change in
blood, there is known a method in which absorbance of
20 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
addition, it is not possible to measure the
25 concentration in real time.
Alternatively, there is known a method in which a
32
bypass pathway is prepared outside of a body, blood
passing through the pathway is irradiated with light,
and fluorescence intensity is observed, to thereby
monitor the pharmaceutical concentration change.
5 However, it is necessary to pay attention to hygiene in
this method.
Further, as a method of monitoring pharmaceutical
concentration in a tissue, there is known a method in
which part of carbon in pharmaceutical is transformed
10 into isotope, the isotope is simultaneously
administered, and pharmaceutical concentration in each
tissue is monitored based on a radiation Quantity
(CANCER RESEARCH 50. 3985-3990, July 1, 1990, Tissue
Distribution and Photosensitizing Properties of Mono-L-
15 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
macroscopically.
20 [0060] 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
pharmaceutical concentration,which correlates with
25 fluorescence intensity, may be calculated. Therefore
the pharmaceutical concentration in a tissue and blood
33
may be monitored in real time. Further, the
pharmaceutical-concentration-monitoring operation of
this embodiment is less invasive than the conventional
monitoring method, and is capable of monitoring
5 temporal changes of pharmaceutical concentration stably
and reproducibly. Further, because the temporal change
of pharmaceutical concentration is monitored via a
catheter by using the excitation light from the light
source 110 of the PDT apparatus 1, it is not necessary
10 to additionally provide a pharmaceutical concentration
detecting apparatus, to thereby enable a low-cost and
space-saving apparatus. Further, because the
pharmaceutical concentration may be monitored in real
time, determination of additional pharmaceutical
15 administration may be assisted in real time.
[0061] Further, the pharmaceutical-concentrationmonitoring
operation of this embodiment may be
performed not only in PDT but also in therapy or
diagnosis using a pharmaceutical, which absorbs an
20 -- 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 pharmaceuticalconcentration-
monitoring operation of this embodiment,
25 pharmaceutical concentration in an intended tissue may
be measured microscopically via a catheter in real time,
34
and dynamic states of various pharmaceuticals may be
grasped. Further, because minimally-invasive monitoring
is enabled, the pharmaceutical-concentration-monitoring
operation of this embodiment has a great advantage and
5 is suitable for practical use. Further, the
pharmaceutical-concentration-monitoring operation of
this embodiment may be performed in a system (DDS, Drug
Delivery System) in which pharmaceutical is delivered
to only a certain location, and is useful to estimate
10 whether pharmaceutical reaches actually and locally.
[0062] [(3) Contact-monitoring operation]
Subsequently, the contact-monitoring operation is
performed.
[0063] Figs. 10 are schematic diagrams showing
15 contact states of the laser catheter.
The laser catheter 300 is preferably disposed such
that the tip portion as a light-emitting portion
contacts [,he inner wall of the cardiac-muscle tissue 11
upright (see Fig. l0(a), hereinafter referred to as
20 "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
15. Further, this state is preferable so as to
25 selectively activate photo-sensitive pharmaceutical
absorbed in a tissue when the tip portion of the laser
35
catheter 300 directly contacts a tissue.
However, it is difficult to recognize the precise
contact state of the tip portion of the laser catheter
300 radiographically or tactually. Because of this,
5 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
between the tip portion of the laser catheter 300 and a
tissue, and the tip portion may be in the blood (see
10 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
direction, and the blood 15 may partially exist in a
gap between the tip portion and the tissue (see Fig.
15 10(b), hereinafter referred to as "slanting-contact
state".).
In the contact-monitoring operation, such contact
states of the tip portion of the laser catheter 300,
that is, the contact states and the non-contact state,
20 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
narrowly-defined angular value, but also means a
25 widely-defined contact angle, in which the contact
state of the tip portion of the laser catheter 300 with
36
respect to a tissue is upright or slanting.
[0064] Continuously, the light source 110 outputs
the excitation light with the first intensity to the
optical system 120, the controller 150 calculates
5 fluorescence intensity and pharmaceutical concentration,
and the display unit 170 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
i0 as a graph.
[0065] Here, an example of a graph showing the
temporal change of fluorescence intensity will be
described.
Fig. 11 is a graph showing the temporal change of
15 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
intensity, the line C shows high fluorescence intensity,
20 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
description clear, the temporalchange of fluorescence
25 intensity in the case where the tip portion of the
laser catheter 300 is in the upright-contact state, the
35
temporal change of fluorescence intensity in the case
where the tip portion of the laser catheter 300 is in
the slanting-contact state, and the temporal change of
fluorescence intensity in the case where the tip
5 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
tip portion of the laser catheter 300.
The line A will be reviewed. Here, as shown in Fig.
10 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
intensity in the case where the laser catheter 300
irradiates a tissue with the excitation light. So, in
15 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 30U is in
the upright-contact state with respect to a tissue,
20 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
intensity in the case where the laser catheter 300
25 irradiates blood with the excitation light. So, in the
case where the fluorescence intensity of the line C is
38
5
calculated, it is thought that the fluorescence
intensity in blood is reflected in the result because
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
that the tip portion of the laser catheter 300.-i_sin
the slanting-contact state with respect to a tissue.
10 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
movement of the tissue to thereby move. As a result, in
the case where the tip portion of the laser catheter
15 300 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
cardiac-muscle tissue changes and the intraatrial
20 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 A and
the line C.
Further, in the case where the tip portion of the
25 laser catheter 300 contacts a tissue in any state
(upright-contact state, slanting-contact state), the
39
laser catheter 300 may be affected by the movement of
the cardiac-muscle tissue. That is, the contact state
of the tip portion of the laser catheter 300 fluctuates
between the contact states (upright-contact state,
5 slanting-contact state) and the non-contact state. In
this case, the fluorescence intensity fluctuates
largely. Therefore, it is determined whether the laser
catheter 300 follows the movement of a cardiac-muscle
tissue or not based on fluctuation of the fluorescence
10 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
the vicinity thereof shows that the tip portion of the
laser catheter 300 momentarily moves from the upright-
15 contact state to the non-contact state and returns to
the upright-contact state again.
[0066] Based on the calculated fluorescence
intensity, the controller 150 determines the contact
state of the tip portion of the laser catheter 300
20 - (contact/non-contact states, contact angle in case of
contact state) (Step 5106).
Specifically, in the case where the controller 150
determines that the calculated fluorescence intensity
is equal to or larger than a first threshold, the
25 controller 150 determines the non-contact state (line
C). In the case where the controller 150 determines
40
that the minimum value of the fluorescence intensity is
equal to or smaller than a second threshold, which is
smaller than the first threshold, the controller 150
determines the upright-contact state (line A) In the
5 case where the controller 150 determines that the
fluorescence intensity periodically fluctuates between
the first threshold and the second threshold, the
controller 150 determines the slanting-contact state
(line B),
10 The controller 150 informs the practitioner the
determined contact state by using the display unit 170.
Specifically, when the controller 150 determines the
slanting-contact state or the non-contact state, the
controller 150 creates display information for
15 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
170 obtains the display instruction from the controller
20 - 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 S107). The
practitioner operates a handpiece or the like (not
25 shown.) provided on the laser catheter 300, to thereby
change the contact state of the tip portion of the
41
laser catheter 300 with respect to a tissue.
[0067] The controller 150 continuously calculates
fluorescence intensity and pharmaceutical concentration.
The controller 150 refers to fluorescence intensity and
5 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
and a tissue based on the referred fluorescence
intensity. The controller 150 calculates excitation-
10 light-irradiation protocols during the therapy, that is,
the second intensity of the excitation light, the
irradiation time, and the like, based on the calculated
blood volume and the referred pharmaceutical
concentration (Step S108).
15 For example, in the case where the tip portion of
the laser catheter 300 is in the slanting--contact state
or the non-contact state and where blood exists in the
gap, the loss of the excitation light (excitation light
which does not reach tissue) is considered based on the
20 - 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-lightirradiation
protocols, creates display information on
25 the irradiation protocols, and outputs display
instruction including the created display information
42
to the display unit 1'70. The display unit 170 obtains
the display instruction from the controller 150, and
then displays information on the excitation-lightirradiation
protocols (second intensity, irradiation
5 time) based on the display information in the display
instruction.
As described above, the controller 150 calculates
the pharmaceutical concentration and the blood volume
based on the fluorescence intensity, and calculates the
10 excitation-light-irradiation protocols based on the
calculated pharmaceutical concentration and blood
volume. That is, the controller 150 is capable of
calculating the excitation-light-irradiation protocols
based on the fluorescence intensity.
15 [0068] 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
displayed on the display screen by the display unit 170,
20 it is possible 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.
[0069) Meanwhile, in the field of circulatory
25 disease, it is important to determine, in real time,
the contact state of the tip portion of a catheter with
43
respect to the intended tissue, the blood volume in a
gap, and presence/absence of a foreignsubstance/
breakage in order to ensure safety and
reliability. Further, in the case where the intended
5 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
movement of the tissue, to reliably perform therapy. In
the past, it is known to determine the contact state of
10 a catheter by, for example, securing a transparent zone
by removing blood, radioscopy, potential measurement
(impedance measurement), potential mapping, temperature
measurement, dynamic measurement (pressure, stress),
reflected light measurement using a polychromatic light
15 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
detail has not been developed yet. Each of the above-
20 mentioned 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
method in which a blood flow is temporarily blocked by
25 using a balloon, saline or the like is flowed from a
catheter tip portion to thereby secure a transparent
44
zone, and a contact state is observed by using an
angioscope. However, this method may lead to a
peripheral-vessel-ischemia state.
With radioscopy, because of lacking accuracy, it
5 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.
Further, in the case of a moving tissue, it is not
clear that the tip of a catheter follows the movement.
10 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
energy input in an intended tissue decreases below an
estimated amount, and an enough therapeutic effect may
15 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
Patent Application Laid-open No. 2007-525263).
20 - 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
tissue is determined by measuring the potential.
25 However, in the case of performing an optical therapy,
the tip portion of a catheter (contact portion with
45
respect to cardiac-muscle tissue) is an optical window..
Because of this, a potential-measured site may be
provided on a portion other than the tip portion of the
catheter. As a result, a light-irradiated site does not
5 coincide with a potential-measured site, a diagnosistarget
zone does not coincide with a therapy-target
zone, and the therapy may not be performed precisely.
Further, an electrode area is made smaller, and angle
determination accuracy may thus be decreased. Further,
10 because electric measurement is performed, there may be
an effect of electromagnetic interference (see Japanese
Patent Application Laid-open No. 2008-531170).
Potential mapping is a method in which potential
measurement is three-dimensionally developed. However,
15 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
excessive contact pressure (see Japanese Patent
20 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
an effect of electromagnetic interference (see Japanese
25 Patent Application Laid-open No. 2008-531170).
Temperature measurement is a method in which, with
46
respect to diseases including a vascular occlusion, an
occlusion is determined by measuring temperature (see
Japanese Patent Application Laid-open No. 2007-525263).
However, this is a diagnostic method for only
5 occlusions, and is not applicable to diseases including
no occlusion zone such as, for example, atrial
fibrillation and ventricular flutter. Further,
unnecessary heat may be provided on a normal bloodvessel
wall.
10 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
determined (see Japanese Patent Application Laid-open
No. 2009-542371, US Patent No. 6696808, US Patent
15 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
Application Laid-open No. 2008-531170).
20 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
source, a tissue is determined based on reflection
25 ratio differences of the respective wavelengths (see
Japanese Patent No. 4261101). According to this method,
47
although the blood volume between a catheter and a
tissue may be estimated, an optical system may be
complicated, an apparatus may be made larger, and the
cost may be increased because a plurality of light
5 sources are provided.
[0070] To the contrary, according to the contactmonitoring
operation of this embodiment, by detecting
fluorescence intensity, it is possible to determine the
contact state with respect to an intended tissue and
10 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,
because excitation-light-irradiation protocols may be
calculated based on the determined contact state and
15 the like, therapy and diagnosis may be assisted safely
and reliably.
[0071] [(4) Foreign-substance/breakage-monitoring
operation]
During the photodynamic therapy, the foreign-
20 substance/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
excitation-light-output instruction with the high-power
25 second intensity in the controller 150. The controller
150 obtains the excitation-light-output instruction,
48
and then outputs the excitation-light-output
instruction with the second intensity to the light
source 110. The light source 110 obtains the
excitation-light-output instruction from the controller
5 150, and then outputs the excitation light with the
second intensity. A tissue is irradiated with the
excitation light output from the light source 110 via
the optical system 120 and the laser catheter 300, and
photodynamic therapy is performed (Step 5109).
10 [0072] Based on an electrical signal obtained from
the detection unit 130, the controller 150 calculates
fluorescence intensity. The controller 150 creates
display information of the temporal change of the
fluorescence intensity based on the calculated
15 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 1'70.
The display unit 170 obtains the display instruction
20 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.
[0073] The controller 150 determines whether the
25 calculated fluorescence intensity is equal to or more
than a threshold (Step S110). The threshold is, for
4 9
example, a value equal to or more than the multiple of
the normal fluorescence intensity.
[0074] Fig. 19 is a graph showing the relation
between wavelength and fluorescence intensity.
5 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
of a normal laser catheter. It is understood that, in
the case where the tip portion of a laser catheter
10 contacts a foreign substance other than a living body
tissue or is broken, the fluorescence intensity thereof
is larger than the normal fluorescence intensity.
[0075] The controller 150 determines that the
fluorescence intensity is equal to or more than the
15 threshold, that is, determines that the fluorescence
intensity is increased to equal to or more than the
multiple of the previous fluorescence intensity such
that the current fluorescence intensity ignores the
previous fluorescence intensity, and then the
20 controller 150 estimates that there is a foreign
substance or a breakage (Step 5110, Yes) If the
controller 150 estimates that there is a foreign
substance or a breakage, the controller 150 creates
display information on generation of a foreign-
25 substance/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 foreignsubstance/
breakage includes information to stop the
excitation light irradiation, to reset irradiation time,
5 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
150, based on the display information in the display
instruction, the display unit 170 displays information
10 to stop the excitation light irradiation (Step 5111)
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
15 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
perform the similar processing (Step 5111, Step 5112).
20 [0076] 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
that there is no foreign substance or breakage, and
25 moves to the cytocidal-effect-determining operation
(Step 5110, No).
51
[0077] Note that, because generation of a foreign
substance or a breakage is estimated when the
fluorescence intensity exceeds a predetermined
threshold, if the display unit 170 displays the
5 fluorescence intensity on the display screen, a
practitioner may estimate generation of a foreign
substance or a breakage based on the fluorescence
intensity, even if the controller 150 does not estimate
generation of a foreign substance or a breakage.
10 [0078] 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
contact another catheter. For example, if the laser
catheter 300 emits a light in the state where the laser
15 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
situation of the tip portion of the laser catheter 300,
20 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.
[0079] According to the foreign-substance/breakage-
25 monitoring operation of this embodiment, because a
strong reflected light is measured when the catheter
52
contacts any object other than a living body tissue, it
is possible to estimate generation of a foreignsubstance/
breakage via a catheter in real time. Because
of this, it is possible to prompt a practitioner to
5 check the laser catheter 300, and thus it is possible
to perform the therapy very safely without causing
danger to a patient,
[0080] [(5) Cytocidal-effect-determining operation]
Subsequently, the cytocidal-effect-determining
10 operation is performed.
In photodynamic therapy, photo-sensitive
pharmaceutical absorbed in a tissue absorbs the
excitation light from the laser catheter 300 to gain
energy, and changes from the ground state to the
15 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
emits fluorescence at this time. Further, when photo-
20 -- sensitive 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
tissue, and, in addition, breaks photo-sensitive
25 pharmaceutical (bleaching). If the bleaching occurs,
the effective pharmaceutical amount is decreased, and
53
thus the fluorescence amount is also decreased.
Therefore, decrease of the fluorescence amount
indicates bleaching and a tissue injury amount. The
optical system 120 extracts the fluorescence emitted
5 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 from the optical system 120, and
outputs the intensity of the detected fluorescence to
10 the controller 150 as an electrical signal.
[0081] Continuously, the light source 110 outputs
the excitation light with the second intensity to the
optical system 120, the controller 150 calculates the
fluorescence intensity, and the display unit 170
15 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.
[0082] Here, an example of a graph showing the
20 temporal change of fluorescence intensity will be
described.
Fig. 12 is a graph showing the temporal change of
fluorescence intensity.
Fig. 12 shows the temporal change of fluorescence
25 intensity in the case where the excitation light is
emitted for 20 seconds after 20 minutes pass after
54
photo-sensitive pharmaceutical is administered in a pig
by intravenous-injection. Since decrease of a
fluorescence amount indicates bleaching and a tissue
injury amount as described above, by displaying an
5 attenuation curve of the fluorescence intensity, the
PDT process may be displayed in real time.
[0083] The controller 150 determines whether the
calculated fluorescence intensity is attenuated below a
threshold (Step 5113). If the controller 150 determines
10 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
excitation light (Step S113, Yes). Then, the controller
150 creates display information on an index of a
15 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
displays information on an index of a cytocidal effect
20 for a practitioner 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 electricconduction-
block-formation determining operation.
25 [0084] Meanwhile, if the controller 150 does not
determine that the fluorescence intensity is decreased
55
below the. threshold within a predetermined time period,
the controller 150 creates display information to
prompt to extend the excitation light irradiation and
to reset the light intensity based on the calculated
5 fluorescence intensity, and outputs display instruction
including the created display information to the
display unit 170 (Step 5113, No). When the display unit
170 obtains the display instruction from the controller
150, the display unit 170 displays information to
10 prompt a practitioner to extend the excitation light
irradiation and to reset the light intensity based on
the display information in the display instruction.
After a predetermined time period passes after
outputting the display instruction, the controller 150
15 moves to the operation of Step S108.
[0085] Note that, because generation of a cytocidal
effect is estimated when the fluorescence intensity is
attenuated below a predetermined threshold, if the
display unit 170 displays the fluorescence intensity on
20 - the display screen, a practitioner may estimate whether
there is a cytocidal effect or not based on the
fluorescence intensity, even if the controller 150 does
not estimate whether there is a cytocidal effect or not.
[0086] According to the cytocidal-effect-determining
25 operation of this embodiment, based on fluorescence
intensity correlated with pharmaceutical concentration,
56
is possible to measure injury in a cardiomyocyte,
which progresses in a tissue irradiated with the
excitation light, that is, to measure a therapeutic
effect, via a catheter in real time, and thus the
5 therapy is performed reliably..
[0087] [(6) Electric-conduction-block-formation
determining operation]
Subsequently, the electric-conduction-blockformation
determining operation is performed.
10 In the electric-conduction-block-formation
determining operation, the fluorescence time-waveform
used in the cytocidal effect determination is in
synchronization with electrocardiogram (ECG. ECG
obtaining method will be described later.). The
15 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
cases, the laser catheter 300 may be relocated in an
20 -- 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
synchronization with ECG to thereby perform analysis.
25 The procedure in the case of relocating a laser
catheter for measurement is as follows.
57
[0088] First, a practitioner disposes the tip
portion of the laser catheter 300 in an electricconduction
block (in dashed-dotted line of Fig. 13) or
on an excitation-light-irradiated site. Then, the
5 practitioner operates the operating unit 180 to thereby
input 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 the excitation-light-
10 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. A tissue is irradiated with the
15 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
catheter 300, and emits fluorescence. The optical
20 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
from the optical system 120, and outputs the detected
25 fluorescence intensity to the controller 150 as an
electrical signal. The controller 150 calculates
58
fluorescence intensity based on the obtained electrical
signal.
[0089] Meanwhile, the electrocardiograph 140 obtains
the electrocardiographic signal, and supplies the
5 obtained electrocardiographic signal to the controller
150. The controller 150 creates display information
based on the calculated fluorescence intensity and the
obtained electrocardiographic signal, and outputs
display instruction including the created display
10 information to the display unit 170. The display unit
170 obtains the display instruction from the controller
150, and displays the correlation between the
fluorescence intensity and the electrocardiogram R-wave
on the display screen based on the display information
15 in the display instruction,
[0090] Here, the correlation between fluorescence
intensity and ECG R-wave will be described.
Fig. 14 is a diagram showing the relation o1 ECG,
intracardiac pressure, and coronary blood-flow volume,
20 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
Medical Shujunsha Co., Ltd., 2001), which is effective
25 in the following description.
As shown in Fig. 14, the temporal change of the
59
intracardiac blood-flow volume is different from the
blood-flow volume in a cardiac-muscle tissue. While the
intracardiac blood-flow volume has a peak at the time
when it coincides with R-wave, the blood-flow volume in
5 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 Rwave.
[0091] Fig. 15 is a diagram showing the correlation
10 between fluorescence intensity and R-wave when the
laser catheter is in the upright-contact state.
The correlation between fluorescence intensity
(for example, irradiation power of 900 mW) and R-wave
when the tip portion of the laser catheter 300 is in
15 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
is disposed left-sided, the fluorescence intensity
20 - 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
photo-sensitive pharmaceutical, the fluorescence
25 intensity in a cardiac-muscle tissue is highest when
blood is supplied to blood vessels of a cardiac muscle.
60
As a result, the peak of fluorescence intensity appears
for a predetermined time period after appearance of Rwave.
[0092] Fig. 16 is a diagram showing the correlation
5 between fluorescence intensity and R-wave when the
laser catheter is in the slanting-contact state.
The correlation between fluorescence intensity
(for example, irradiation power of 900 mW) and R--wave
when the tip portion of the laser catheter 300 is in
10 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
fluorescence intensity peak coincides with R-wave.
As described above, the phase difference between
15 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
difference is constant if the contact state is
20 maintained.
[0093] In view of this, the controller 150
determines whether the phase difference between
fluorescence intensity and R-wave is constant based on
the calculated fluorescence intensity and the obtained
25 electrocardiographic signal, to thereby determine
whether an electric-conduction block is formed or not
61
(Step 5114). If the controller 150 determines that the
phase difference between fluorescence intensity and Rwave
is constant, the controller 150 determines that an
electric-conduction block is yet to be formed (Step
5 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
the laser catheter 300 (Step 5117). The practitioner
refers to the information displayed on the display unit
10 170, stops excitation light irradiation once, and moves
the laser catheter 300. Then, the processing of Step
S104 and thereafter are performed again.
[0094] Fig. 13 is a schematic diagram showing a
movement track of the laser catheter.
15 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).
[0095] Meanwhile, if the controller 150 determines
20 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
prompt a practitioner to stop excitation light
25 irradiation and to remove the laser catheter 300, and
outputs a display instruction including the created
62
display information to the display unit 170. When the
display unit 170 obtains the display instruction from
the controller 150, the display unit 170 displays
information to prompt a practitioner to stop excitation
5 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
(Step 5115).
[0096] Here, the principle, in which the controller
10 1.50 determines that an electric-conduction block is
formed when the phase difference between fluorescence
intensity and R-wave is not constant, will be described.
When a cardiomyocyte injury progresses, the
cardiomyocyte fails to conduct electricity, and thus
15 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
the electric-conduction block follows the contraction
20 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
intensity and R-wave becomes unstable. In other words,
25 the correlation between fluorescence intensity and Rwave
moves backward and forward between the correlation
63
shown in Fig. 15 and the correlation shown in Fig. 16,
[0097] In view of this, according to the electricconduction-
block-formation determining operation of
this embodiment, it is possible to determine that an
5 electric-conduction block is formed in real time based
on the phase difference between fluorescence intensity
and electrocardiogram R-wave.
Specifically, in the case where the peak of
fluorescence intensity appears for a predetermined time
10 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
in the upright-contact state. In the case where the
peak of fluorescence intensity and the R-wave appear
15 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
phase difference between the peak of fluorescence
20 intensity and R-wave is not constant, it can be
determined that an electric-conduction block is formed.
[0098] Note that, because it can be determined that
an electric-conduction block is formed in the case
where the phase difference between fluorescence
25 intensity and R-wave is not constant, if the display
unit 170 displays the correlation between fluorescence
64
intensity and R-wave on the display screen, a
practitioner may estimate whether an electricconduction
block is formed or not based on the
correlation between fluorescence intensity and R-wave,
5 even if the controller 150 does not estimate whether an
electric-conduction block is formed or not.
[0099]
Next, a PDT apparatus according to another
embodiment of the present invention will be described.
10 In the following description, descriptions of
configurations, functions, operations, and the like
similar to those of the PDT apparatus 1 of the first
embodiment will be omitted or simplified, and different
points will mainly be described.
15 An optical system and a detection unit according
to the second embodiment will be described.
[0100] [Structures of optical system and detection
unit]
Fig. 17 is a block diagram showing an optical
20 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
dichroic mirror (hereinafter referred to as "DM".) 126,
25 and a second DM 127.
[0101] A detection unit 130a includes a first
65
photodiode (hereinafter referred to as "PD".) 131, and
a second PD 132.
[0102] The first DM 126 reflects light having a
certain wavelength out of the light entered from the
5 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
catheter 300, and allows the fluorescence having the
other wavelengths from the laser catheter 300 and
10 specular reflection light to pass thorough. The
fluorescence, which has reflected off the first DM 126,
enters the first PD 131.
The first PD 131 detects the fluorescence entered
from the first DM 126. The first PD 131 outputs the
15 detected fluorescence intensity to the controller 1.50
as an electrical signal.
[0103] The second DM 127 reflects light having a
certain wavelength out of the light which has passed
through the first DM 126, and causes the light having
20 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
reflection light to pass thorough. The fluorescence,
25 which has reflected off the second DM 127, enters the
second PD 132.
66
The second PD 132 detects the fluorescence entered
from the second DM 127. The second PD 132 outputs the
detected fluorescence intensity to the controller 150
as an electrical signal.
5 [0104] 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
127. In this manner, eventually, the plurality ut DMs
126, 127 ... reflect the fluorescence from the laser
10 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
specular reflection light to pass through.
[0105] Note that, as another embodiment, a pulse
15 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 lung as
length of laser catheter 300).
20 --- [0106]
In the third embodiment, the contact-monitoring
steps are performed based on the phase difference
between the peak of fluorescence intensity, which is in
the interval between R-waves, and R-wave.
25 In the electric-conduction-block-formation
determining operation of the first embodiment, it is
67
determined that an electric-conduction block is formed
based on the phase difference between the peak of
fluorescence intensity, which is in the interval
between R-waves, and R-wave. This principle may be
5 applied to the contact-monitoring operation.
[0107] The light source 110 outputs the excitation
light with the first intensity to the optical system
120. The detection unit 130 detects the fluorescence
entered from the optical system 120. The detection unit
10 130 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.
[0108] Meanwhile, the electrocardiograph 140 obtains
15 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
obtained electrocardiographic signal, and outputs
20 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
intensity and electrocardiogram R-wave on the display
25 screen based on the display information in the display
instruction.
68
[0109] The controller 150 determines the contact
state of the tip portion of the laser catheter 300
based on the calculated fluorescence intensity and the
obtained electrocardiographic signal (Step S106).
5 Specifically, if the controller 150 determines that the
peak of fluorescence intensity appears for a
predetermined time period after appearance of the Rwave,
the controller 150 determines that the tip
portion of the laser catheter 300 is in the upright-
10 contact state. If the controller 150 determines that
the peak of fluorescence intensity and the R-wave
appear simultaneously, the controller 150 determines
that the tip portion of the laser catheter 300 is in
the slanting-contact state. Further, the blood volume
15 between the tip portion of the laser catheter 300 and
the inner wall of a tissue may be estimated based on
fluorescence peak intensity.
[0110]
According to the fourth embodiment, the contact-
20 monitoring 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
pharmaceutical. That is, the fourth embodiment
25 describes a diagnostic method in which no
pharmaceutical is used,
[0111] The light source 110 outputs an excitation
light, with which the difference between the
autofluorescence spectrum property of a cardiac-muscle
tissue and the autofluorescence spectrum property of
5 blood is determined easily. The detection unit 130
detects entered fluorescence. The detection unit 130
outputs the detected fluorescence intensity to the
controller 150 as an electrical signal. The controller
150 calculates the fluorescence spectrum based on the
10 obtained electrical signal. The controller 150
determines whether the calculated fluorescence spectrum
shows the autofluorescence spectrum property of a
cardiac-muscle tissue or the autofluorescence spectrum
property of blood. The controller 150 compares the
15 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
portion of the laser catheter 300 (Step 5106).
20 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
portion of the laser catheter300 is in the upright-
25 contact state. If the controller 150 determines that
the calculated fluorescence spectrum shows the
70
autofluorescence spectrum property of blood, the
controller 150 determines that the tip portion of the
laser catheter 300 is in the non-contact state. if the
controller 150 determines that the calculated
5 fluorescence spectrum does not show the each
autofluorescence spectrum property, the controller 150
determines that the tip portion of the laser catheter
300 is in the slanting-contact state.
[0112] The contact-monitoring using the
10 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
example, arteriosclerotic disease or the like).
Figs. 18 are schematic diagrams each showing a
15 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
portion of the laser catheter 300 contacts a vascular
20 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
occlusion is different from thecomposition ratio of a
25 blood-vessel wall. Specifically, the composition ratio
of a vascular occlusion (arteriosclerosis) is 70% of
71
water, 5% of collagen, 6% of elastin, and 9% of lipid.
The composition ratio of a blood vessel is 73% of water,
6.5% of collagen, 10.5% of elastin, and 1% of lipid.
Because of this, the autofluorescence spectrum property
5 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
excitation light, with which the property difference is
determined easily, and fluorescence is measured, it is
10 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
be determined whether there is an atheromatous plaque
or not based on the composition ratio, the contact-
15 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
not based on the size of the blood vessel diameter,
20 [0113] The embodiments of the present invention are
not limited to the above-mentioned embodiments, and
other various embodiments are conceivable.
[0119] Although in the above-mentioned embodiments,
the laser catheter 300 is detachably connected to the
25 connector 210 of the PDT apparatus 1, the laser
catheter 300 may be provided on the PDT apparatus 1
72
integrally.
Although in the above-mentioned embodiments, the
tube 200 is provided on the PDT apparatus main body 100
and the connector 210 is provided on the end of the
5 tube 200, the connector 210 may be provided on the PDT
apparatus main body 100.
Although in the above-mentioned embodiments, the
PBS 123 is used, a DM may be used instead.
[0115] Although in the above-mentioned embodiments,
10 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.
A speaker unit may be provided on the PDT apparatus 1,
and the controller 150 may create a sound output
15 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
prompt a practitioner to perform the predetermined
20 - controls.
Description of Symbols
[0116] 1 photodynamic therapy (PDT) apparatus
100 PDT apparatus main body
110 light source
25 120, 120a optical system
121 short pass filter
73
122 first lens
123 polarizing beam splitter (PBS)
124 long pass filter
125 second lens
5 126 first dichroic mirror (DM)
127 second dichroic mirror (DM)
130, 130a detection unit
131 first. photodiode (PD)
132 second photodiode (PD)
10 140 electrocardiograph
141 electrode pad
150 controller
160 storage
170 display unit
15 180 controller
200 tube
201 apparatus--attached optical fiber
210 connector
300 laser catheter
20 -- 301 irradiation light
310 catheter tube
320 holder
330 optical fiber
340 optical window
25
74
Claims
[1] A calculation apparatus for irradiating a tissue
having absorbed photo-sensitive pharmaceutical, the
photo-sensitive pharmaceutical absorbing an excitation
5 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
capable of being attached/detached;
10 a light source for outputting the excitation light
to the laser catheter via the connector; and
a detection unit for detecting intensity of the
fluorescence, the fluorescence being entered from the
laser catheter via the connector, to calculate
15 concentration of the photo-sensitive pharmaceutical in
a tissue, the tip portion of the laser catheter
contacting the tissue.
[2] The calculation apparatus according to claim 1,
further comprising:
20 - a controller for calculating the concentration of
the photo-sensitive pharmaceutical in the tissue, the
tip portion of the laser catheter contacting the tissue,
based on intensity of the detected fluorescence.
[3] The calculation apparatus according to claim 2,
25 wherein
the controller outputs a signal to prompt to
additionally administer the photo-sensitive
pharmaceutical based on the calculated concentration.
[4] The calculation apparatus according to claim 2,
wherein
5 the controller calculates an excitation-lightirradiation
protocol based on the calculated
concentration, and outputs a calculation result.
[5] A calculation method, comprising:
irradiating a tissue having absorbed photo-
10 sensitive pharmaceutical, the photo-sensitive
pharmaceutical absorbing an excitation light and
emitting fluorescence, with the excitation light
emitted from a tip portion of a laser catheter;
extracting the fluorescence corresponding to the
15 irradiated excitation light via the laser catheter; and
calculating concentration of the photo-sensitive
pharmaceutical in a tissue, the tip portion of the
laser catheter contacting the tissue, based on
intensity of the extracted fluorescence.
20 -- [6] The calculation method according to claim 5,
further comprising:
calculating an excitation-light-irradiation
protocol based on the calculated concentration, and
outputs a calculation result.
25 [7] A calculation method using photo-sensitive
pharmaceutical absorbing an excitation light and
76
emitting a fluorescence, a laser catheter capable of
emitting the excitation light from a tip portion, and a
calculation apparatus including a connector to/from
which the laser catheter is capable of being
5 attached/detached and a light source for outputting the
excitation light to the laser catheter via the
connector, comprising:
absorbing, in a tissue, the photo-sensitive
pharmaceutical;
10 leading the tip portion of the laser catheter to
the tissue having absorbed the photo-sensitive
pharmaceutical, the laser catheter being attached to
the connector;
irradiating the tissue having absorbed the photo-
15 sensitive pharmaceutical with the excitation light
emitted from the tip portion of the laser catheter, the
excitation light being output from the light source;
extracting the fluorescence corresponding to the
irradiated excitation light via the laser catheter; and
20 - calculating concentration of the photo-sensitive
pharmaceutical in a tissue, the tip portion of the
laser catheter contacting the tissue, based on
intensity of the extracted fluorescence.
[8] The calculation method according to claim 7,
25 further comprising:
calculating an excitation-light-irradiation
77
protocol based on the calculated concentration, and
outputs a calculation result.