DESCRIPTION
ESTIMATING APPARATUS AND ESTIMATING METHOD
Technical Field
5 [0001] The present invention relates to an
estimating apparatus and an estimating method that
estimate process of therapy using a laser catheter.
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 lj 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
1
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 apatient,
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
2
3
Problem to be solved by the Invention
[0006] As a method of estimating whether a tissue of
an excitation-light-irradiated site is broken, whether
an electric-conduction block is formed, and the like,.
5 there is known a method of leading a device such as a
catheter having a detection means such as an electrode
to an excitation-light-irradiated site, and performing
estimation by using the catheter. However, because an
irradiated site does not coincide with a potential-
10 measured site precisely in therapy using a light, it is
desired to provide means for estimating therapeutic
effects more accurately in real time.
[0007] In view of the above-mentioned circumstances,
an object of the present invention is to provide an
15 estimating apparatus and an estimating method capable
of estimating process of therapy using a laser catheter
accurately in real time.
Means for solving the Problem
[0008] To attain the above-mentioned object, an
20 estimating apparatus according to an embodiment of the
present invention is an apparatus for irradiating a
tissue having absorbed photo-sensitive pharmaceutical,
the photo-sensitive pharmaceutical absorbing an
excitation light and emitting fluorescence, with the
25 excitation light emitted from a tip portion of a laser
catheter, including a connector, a light source, and a
detection unit.
The laser catheter is capable of being
attached/detached to/from the connector.
The light source outputs the excitation light to
5 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 estimate whether
the tissue has changed because of reaction between the
10 excitation light emitted from the tip portion of the
laser catheter and the photo-sensitive pharmaceutical
absorbed in the tissue.
[0009] By detecting the intensity of the
fluorescence entered from the laser catheter, it is
15 possible to estimate whether the tissue has changed
because of the reaction between the excitation light
and the photo-sensitive pharmaceutical in real time. As
a result, it is possible to estimate process of Cherapy
using a laser catheter. Further, by using a laser
20 - catheter used for therapy, operability is improved.
Note that the phrase "tissue is changed" means, for
example, insult to a tissue such as a cytocidal effect
and an electric-conduction block, damage, thermal
denaturation, and the like.
25 [0010] The detection unit may detect intensity of
the fluorescence, the fluorescence being entered from
4
the laser catheter via the connector, to simultaneously
estimate whether the tissue has changed because of
reaction between an excitation light emitted from the
tip portion of the laser catheter and the photos
sensitive pharmaceutical absorbed in the tissue, and
whether a contact state of the tip portion of the laser
catheter with respect to the tissue has changed.
[0011] specifically in intracardiac therapy using a
laser catheter, the laser catheter moves affected by
10 breathing or heartbeat, and the contact state with
respect to a therapy-target tissue may change.
According to this embodiment, the change of a cardiacmuscle
tissue and the contact state of the tip portion
of the laser catheter are monitored in real time, and
15 an irradiation condition may be set/changed according
to the situation.
[0012] The estimating apparatus may further include
a controller for simultaneously estimating whether the
tissue has changed because of reaction between an
20 excitation light emitted from the tip portion of the
laser catheter and the photo-sensitive pharmaceutical
absorbed in the tissue, and a contact state of the tip
portion of the laser catheter with respect to the
tissue, based on the detected intensity of the
25 fluorescence.
[0013] By detecting the intensity of fluorescence
5
6
entered from the laser catheter, the change of the
tissue because of reaction between the excitation light
and the photo-sensitive pharmaceutical, and the contact
state of the tip portion of the laser catheter with
5 respect to a tissue may be estimated in real time.
[0019] The controller may visually reflect a
current-estimated-result of the change of the tissue in
a peak-estimated-result of the change of the tissue,
and output a signal for simultaneously informing of the
10 estimated result of the change of the tissue and the
estimated result of the contact state.
[0015] Here, to "output a signal" means, for example,
to output a display instruction including display
information to a display unit. As a result, a
15 practitioner_ may recognize the current-estimated-result
of the change of the tissue and the contact state of
the tip portion of the laser catheter simultaneously
and intuitively. As a result, during therapeutic-light
irradiation, a practitioner may recognize, in real time,
20 that the tip portion of the laser catheter is displaced
affected by heartbeat or breathing, and may control the
posture promptly. Simultaneously, a practitioner may
understand the estimated result of the change of the
tissue, which may vary according to individual
25 variability and therapy-target sites, accurately in
real time, and perform the operation. A practitioner
6
needs to determine everything with reference to a
plurality of screens during an operation. So it is
helpful fora trouble-free operation by a practitioner
to displaythe current-estimated-result of the change
5 of the tissue and the contact state of the tip portion
of the laser catheter in an intuitively-recognizable
mode.
[0016] The estimating apparatus may further include
storage for storing the peak-estimated-result of the
10 change of the tissue.
The controller may record the current-estimatedresult
of the change of the tissue in the storage,
updates, in a case where the current-estimated-result
of the change of the tissue is equal to or larger than
15 the peak-estimated-result of the change of the. tissue
recorded in the storage, the peak-estimated-result of
the change of the tissue recorded in the storage with
the current-estimated-result of the change of the
tissue, and output a signal for simultaneously
20 -- informing of the estimated result of the change of the
tissue and the estimated result of the contact state,
by displaying the current-estimated-result of the
change of the tissue on the updated peak-estimatedresult
of the change of the tissue in an overlapped
25 manner.
[0017] By displaying the current-estimated-result of
8
the change of the tissue on the peak-estimated-result
of the change of the tissue in an overlapped manner, a
practitioner may recognize the difference between the
peak-estimated-result and the current-estimated-result
5 intuitively as the change of the contact state of the
tip portion of the laser catheter. For example, a
practitioner may intuitively recognize that the contact
state of the tip portion of the laser catheter has
changed from the identical contact state, and that the
10 tip portion of the laser catheter is removed from a
tissue and drifts in blood.
[0018] The estimating apparatus may further include
a controller for estimating whether the tissue has
changed because of reaction between the excitation
15 light emitted from the tip portion of the laser
catheter and the photo-sensitive pharmaceutical
absorbed in the tissue, based on intensity of the
detected fluorescence.
[0019] By detecting the intensity of the
20 --- fluorescence entered from the laser catheter, it is
possible to estimate whether the tissue has changed
because of the reaction between the excitation light
and the photo-sensitive pharmaceutical in real time.
[0020] The controller may output a signal for
25 informing whether the tissue has changed, based on the
estimated result.
8
9
[0021] As a result, it is possible to inform a
practitioner whether a tissue has changed in real time,
based on the intensity of the fluorescence entered from
the laser catheter. Note that to "output a signal"
5 means to output a display instruction including display
information to a display unit, or to output a sound
output instruction to a speaker unit.
[0022] The controller may output a signal to prompt
to change an irradiation condition of the excitation
10 light, based on the estimated result.
[0023] As a result, it is possible to prompt a
practitioner to change an irradiation condition. of the
excitation light in real time, based on the intensity
of the fluorescence entered from the laser catheter.
15 [0024] The controller may obtain an
electrocardiographic signal, and estimates whether the
tissue has changed, based on a correlation between the
electrocardiographic signal and the intensity of the
fluorescence.
20 -- [0025] By calculating the correlation between the
electrocardiographic signal and the intensity of the
fluorescence, it is possible to determine whether a
tissue haschanged in real time.
[0026] An estimating apparatus for therapy for
25 atrial fibrillation according to an embodiment of the
present invention is an apparatus for irradiating a
9
10
cardiac-muscle 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
5 a laser catheter, including a connector, a light source,
and a-detection unit.
The laser catheter is capable of being
attached/detached to/from the connector.
The light source outputs the excitation light to
10 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 estimate whether
the cardiac-muscle tissue is changed because of
15 reaction between the excitation light emitted from the
tip portion of the laser catheter and the photosensitive
pharmaceutical absorbed in the cardiac-muscle
tissue.
[0027] By detecting the intensity of the
20 fluorescence entered from the laser catheter, it is
possible to estimate whether the tissue has changed
because of the reaction between the excitation light
and the photo-sensitive pharmaceutical in real time. As
a result, it is possible to estimate process of therapy
25 for atrial fibrillation using a laser catheter. Further,
by using a laser catheter used for therapy, operability
10
1 1
is improved.
[0028] The detection unit may detect intensity of
the fluorescence, the fluorescence being entered from
the laser catheter via the connector, to simultaneously
5 estimate whether the cardiac-muscle tissue has changed
because of reaction between an excitation light emitted
from the tip portion of the laser catheter and the
photo-sensitive pharmaceutical absorbed in the cardiacmuscle
tissue, and whether a contact state of the tip
10 portion of the laser catheter with respect to the
cardiac-muscle tissue has changed.
[0029] The estimating apparatus may further include
a controller for simultaneously estimating whether the
cardiac-muscle tissue has changed because of reaction
15 between an excitation light emitted from the tip
portion of the laser catheter and the photo-sensitive
pharmaceutical absorbed in the cardiac-muscle tissue,
and a contract state of the tip portion of the laser
catheter with respect to the cardiac-muscle tissue,
20 based on the detected intensity of the fluorescence.
[0030] The controller may visually reflect a peakestimated-
result of the change of the cardiac-muscle
tissue in a current-estimated-result of the change of
the cardiac-muscle tissue, and outputs a signal for
25 simultaneously informing of the estimated result of the
change of the cardiac-muscle tissue and the estimated
11
12
result of the contact state.
[0031] The estimating apparatus may further include
storage forstoring the peak-estimated-result of the
change of the cardiac-muscle tissue.
5 The controller may record the current-estimatedresult
of the change of the cardiac-muscle tissue in
the storage, update, in a case where the currentestimated-
result of the change of the cardiac-muscle
tissue is equal to or larger than the peak-estimated-
10 result of the change of the cardiac-muscle tissue
recorded in the storage, the peak-estimated-result of
the change of the cardiac-muscle tissue recorded in the
storage with the current-estimated-result of the change
of the cardiac-muscle tissue, and output a signal for
15 simultaneously informing of the estimated result of the
change of the cardiac-muscle tissue and the estimated
result of the contact state, by displaying the currentestimatedresult
of the change of the cardiac-mu_cle
tissue on the updated peak-estimated-result of the
20 change of the cardiac-muscle tissue in an overlapped
manner.
[00321 An estimating method according to an
embodiment of the present invention includes
irradiating a tissue having absorbed photo-sensitive
25 pharmaceutical, the photo-sensitive pharmaceutical
absorbing an excitation light and emitting fluorescence,
12
with the excitation light emitted from a tip portion of
a laser catheter.
The fluorescence corresponding to the irradiated
excitation light is extracted via the laser catheter.
5 Whether the tissue has changed because of reaction
between the excitation light emitted from the tip
portion of the laser catheter and the photo-sensitive
pharmaceutical absorbed in the tissue is estimated,
based on intensity of the extracted fluorescence.
10 [0033] By detecting the intensity of the
fluorescence entered from the laser catheter, it is
possible to estimate whether the tissue has changed
because of the reaction between the excitation light
and the photo-sensitive pharmaceutical in real time. As
15 a result, it is possible to estimate process of therapy
using a laser catheter.
[0034] They estimating method may further include
simultaneously estimating whether the tissue has
changed because of reaction between an excitation light
20 emitted from the tip portion of the laser catheter and
the photo-sensitive pharmaceutical absorbed in the
tissue, and a contact state of the tip portion of the
laser catheter with respect to the tissue, based on the
extracted intensity of the fluorescence:
25 [0035] The estimating method may further include
visually reflecting a current-estimated-result of the
13
14
change of the tissue in a peak-estimated-result of the
change of the tissue, and outputting a signal for
simultaneously informing of the estimated result of the
change of the tissue and the estimated result of the
5 contact state.
[0036] The estimating method may further include
recording the current-estimated-result of the change of
the tissue in storage, updating, in a case where the
current-estimated-result of the change of the tissue is
10 equal to or larger than the peak-estimated-result of
the change of the tissue recorded in the storage, the
peak-estimated-result of the change of the tissue
recorded in the storage with the current-estimatedresult
of the change of the tissue, and outputting a
15 signal for simultaneously informing of the estimated
result of the change of the tissue and the estimated
result of the contact state, by displaying the currentestimated-
result of the change of the tissue on Lhe
updated peak-estimated-result of the change of the
20 tissue in an overlapped manner.
[.0037] The estimating method may further include
obtaining an electrocardiographic signal, and
estimating whether the tissue has changed, based on a
correlation between the electrocardiographic signal and
25 the intensity of the fluorescence.
By calculating the correlation between the
14
electrocardiographic signal and the intensity of the
fluorescence, it is possible to determine whether the
tissue has changed because of reaction between the
excitation light and the photo-sensitive pharmaceutical
5 in real time.
[0038] An estimating method according to an
embodiment of the present invention is an estimating
method using photo-sensitive pharmaceutical absorbing
an excitation light and emitting a fluorescence, a
10 laser catheter capable of emitting the excitation light
from a tip portion, and an estimating apparatus
including a connector to/from which the laser catheter
is capable of being attached/detached and a light
source for outputting the excitation light to the laser
15 catheter via the connector.
In a tissue, the photo-sensitive pharmaceutical is
absorbed.
The tip portion of the laser catheter is led to
the tissue having absorbed the photo-sensitive
20 pharmaceutical, the laser catheter being attached to
the connector.
The tissue having absorbed the photo-sensitive
pharmaceutical is irradiated with the excitation light
emitted from the tip portion ofthe laser catheter, the
25 excitation light being output from the light source.
The fluorescence corresponding to the irradiated
15
16
excitation light is extracted via the laser catheter,
Whether the tissue has changed because of reaction
between theexcitation light emitted from the tip
portion of the laser catheter and the photo-sensitive
5 pharmaceutical absorbed in the tissue is estimated,
based on intensity of the extracted fluorescence.
[0039] The estimating method may further include
simultaneously estimating whether the tissue has
changed because of reaction between an excitation light
10 emitted from the tip portion of the laser catheter and
the photo-sensitive pharmaceutical absorbed in the
tissue, and a contact state of the tip portion of the
laser catheter with respect to the tissue, based on the
extracted intensity of the fluorescence.
15 [0040] The estimating method may further include
visually reflecting a current-estimated-result of the
change of the tissue in a peak-estimated-result of the
change of the tissue, and outputting a signal for
simultaneously informing of the estimated result of the
20 -- change of the tissue and the estimated result of the
contact state.
[0041] The estimating method may further include
recording the current-estimated-result of the change of
the tissue in storage, updating, in a case where the
25 current-estimated-result of the change of the tissue is
equal to or larger than the peak-estimated-result of
16
1I
the change of the tissue recorded in the storage, the
peak-estimated-result of the change of the tissue
recorded in the storage with the current-estimatedresult
of the change of the tissue, and outputting a
5 signal for simultaneously informing of the estimated
result of the change of the tissue and the estimated
result of the contact state, by displaying the currentestimated-
result of the change of the tissue on the
updated peak-estimated-result of the change of the
10 tissue in an overlapped manner,
[0042] The estimating method may further include
obtaining an electrocardiographic signal, and
estimating whether the tissue has changed, based on a
correlation between the electrocardiographic signal and
15 the intensity of the fluorescence.
Effect of the Invention
[0043] According to the present invention, it is
possible to estimate process of therapy using a laser
catheter accurately in real time, and to perform the
20 therapy reliably.
Brief Description of Drawings
[0044] [Fig. 1] A schematic diagram showing a PDT
apparatus according to a first embodiment of the
present invention.
25 [Fig. 2] A schematic diagram showing a laser catheter
inserted in a heart.
17
18
[Fig. 3] A block diagram showing a PDT apparatus main
body.
[Fig. 4] A-sectional view showing the tip portion of
the laser catheter.
5 [Fig. 5] A flowchart showing operations of the PDT
apparatus.
[Fig. 6] A schematic diagram showing the laser
catheter inserted in a left atrium.
[Fig. 7] A graph showing the temporal change of
10 fluorescence intensity.
[Fig. 8] A graph showing the correlation between the
fluorescence intensity and pharmaceutical concentration.
[Fig. 9] A graph showing the temporal change of the
pharmaceutical concentration.
15 [Figs. 10]Schematic diagrams each showing a contact
state of the laser catheter.
[Fig. 11] A graph showing the temporal change of the
fluorescence intensity.
[Fig. 12] Another graph showing the temporal change of
20 the fluorescence intensity.
[Fig. 13] A schematic diagram showing a movement track
of the laser catheter.
[Fig. 14] A diagram showing the relation of ECG,
intracardiac pressure, and coronary blood-flow volume,
25 which is dominant in the blood-flow volume in a
cardiac-muscle tissue.
18
19
[Fig. 15].A diagram showing the correlation between
fluorescence intensity and R-wave when the laser
catheter is in the upright-contact state.
[Fig. 16] A diagram showing the correlation between
5 fluorescence intensity and R-wave when the laser
catheter is in the slanting-contact state.
[Fig. 17] A block diagram showing an optical system, a
detection unit, and the like of a second embodiment of
the present invention.
10 [Figs. 18]Schematic diagrams each showing a contact
state of a laser catheter in an intravascular lumen.
[Fig. 19] A graph showing the relation between
wavelength and fluorescence intensity.
[Fig. 20] A flowchart showing operations of the PDT
15 apparatus.
[Fig. 21] A graph showing a temporal change of
fluorescence intensity.
[Fig. 22] A flowchart showing a monitoring operal-ion of
PDT process level and a contact state.
20 -- [Fig. 23] A diagram for explaining formulae for
calculating PDT process level.
[Fig. 241 A diagram for explaining a method of
calculating PDT process level.
[Fig. 25] A diagram for explaining formulae for setting
25 concentration and an irradiation power during
pharmaceutical administration.
19
20
[Fig, 26] A graph showing a PDT process level
calculated based on the formulae of Fig. 23.
[Fig. 27] Agraph showing a modified example of the
graph of Fig. 26.
5 [Fig. 28] A display window displaying the PDT process
level and the contact state of the tip portion of the
laser catheter.
[Fig. 29] Another display window displaying the I'DT
process level and the contact state of the tip portion
10 of the laser catheter.
[Fig. 30] Another display window displaying the PDT
process level and the contact state of the tip portion
of the laser catheter.
[Fig. 31] Another display window displaying the PDT
15 process level and the contact. state of the tip portion
of the laser catheter.
[Fig. 32] Another display window displaying the PDT
process level and the contact state of the tip portion
of the laser catheter.
20 [Fig. 33] A formula for calculating the contact level
of the tip portion of the laser catheter with respect
to an inner wall of a tissue.
[Fig. 34] A diagram for explaining method of
calculating the contact level.
25 [Fig. 35] A display window showing a time-waveform
display and a level-meter display of a contact level.
20
21
[Fig. 36]A schematic diagram showing contact states of
a laser catheter in a plurality of different contact
levels shown in Fig. 35.
Best Modes for Carrying Out the Invention
5 [0045] Hereinafter, embodiments of the present
invention will be described with reference to the
drawings. In the embodiments, the case where a
photodynamic therapy apparatus (hereinafter referred to
as "PDT apparatus".) is used as an estimating apparatus
10 will be described.
[0046]
Fig. 1 is a schematic diagram showing a PDT
apparatus according to a first embodiment of the
present invention.
15 The PDT apparatus 1 includes a PDT apparatus main
body 100, a tube 200 connected to the PDT apparatus
main body 100, and a connector 210 provided on the end
of the tube 200.
The tube 200 is a soft hollow tube, and is capable
20 of transmitting light via an inner apparatus-attached
optical fiber 201 (see Fig. 3.).
A laser the catheter 300 is detachably connected
to the connector 210.
[0047] Photo-sensitive pharmaceutical is
25 administered to a patient 2. In the case of being
administered by intravenous injection, the administered
21
22
photo-sensitive pharmaceutical diffuses in the blood,
and then a tissue such as a cardiac-muscle tissue
absorbs the pharmaceutical. A dose of photo-sensitive
pharmaceutical necessary for therapy may be
5 administered at one time by intravenous injection, may
be administered continuously by intravenous drip, may
be administered at one time or continuously via the
oral route, or may be administered locally. Photosensitive
pharmaceutical is pharmaceutical that absorbs
10 light having a certain wavelength, is photoexcited, and
becomes fluorescent. For example, pharmaceutical called
talaporfin sodium (Laserphyrin (registered trademark),
Meiji Co., Ltd.) is employed. Because the Q-band
absorption wavelength of this pharmaceutical is near
15 664 nm, an excitation light source for this
pharmaceutical with, for example, 600 to 800 nm,
preferably 660 to 680 nm, or more preferably 664 plus
or minus 2 nm is used.
[0048] Fig. 2 is a schematic diagram showing a laser
20 catheter inserted in a heart.
The laser the catheter 300 is inserted in a right
atrium 14 of a heart 10 via a femoral vein or a jugular
vein of the patient 2. The laser the catheter 300,
which has reached the right atrium 14, penetrates a
25 septum, and is led to a left atrium 13.
[0049] [Configuration of PDT apparatus main body]
22
2 3
Fig. 3 is a block diagram showing the PDT
apparatus main body.
The PDT apparatus main body 100 includes a light
source 110, an optical system 120, a detection unit 130,
5 an electrocardiograph 140, a controller 150, storage
160, a display unit 170, and an operating unit 180,
[0050] The light source 110 outputs an excitation
light for photo-sensitive pharmaceutical. The
wavelength of the light output by the light source 110
10 is the same as the Q-band absorption wavelength of the
photo-sensitive pharmaceutical. For example, in the
case where photo-sensitive pharmaceutical whose Q--band
absorption wavelength is near 664 nm is used, a
semiconductor laser with the emission wavelength of 600
15 to 800 nm, preferably 660 to 680 nm, or more preferably
664 plus or minus 2 rim is used as the light source 110.
The excitation light output by the light source 110
enters the laser the catheter 300 via the optical
system 120.
20 [0051] The optical system 120 allows the excitation
light, which is emitted from the light source 110, to
enter the laser the catheter 300, which is connected to
the connector 210 via the apparatus-attached optical
fiber 201. The optical system 120 extracts, from the
25 laser the catheter 300, fluorescence emitted from
photo-sensitive pharmaceutical, which is irradiated
23
24
with the excitation 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
5 "PBS".) 123, a long pass filter 124, and a second lens
125.
The short pass filter 121 is a short-wavelength
transmission filter with a cuton wavelength of 670 nm,
and cuts long-wavelength radiation. The excitation
10 light from the light source 110 has the radiation
component in the fluorescence observation wavelength
range (long-wavelength side of peak wavelength). In
view of this, the radiation component of the excitation
light in the long-wavelength side is cut at the stage
15 prior to collecting the light in the laser the catheter
300. The excitation light, which has passed the short
pass filter 121, enters the first lens 122.
The [first lens 122 collects the excitation light,
which has entered from the short pass filter 121, on
20 one edge of the laser the catheter 300. Further, the
first lens 122 collects fluorescence from the tip
portion of the laser the catheter 300 on the PBS 123.
Note that part of the excitation light from the light
source 110 is reflected off an edge of the apparatus-
25 attached optical fiber 201 at the PDT apparatus main
body 100 side, off the inside of the connector 210, and
24
25
off the tip portion of the laser the catheter 300, and
enters the PBS 123 as specular reflection light. The
specular reflection light is noisy when detecting
fluorescence.
5 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
200, out of the light entered from the first. lerc; 122,
to pass through, does not detect the specular
10 reflection light, reflects fluorescence and the
specular reflection light reflected off the other edges,
and brings them to a detecting device. The fluorescence,
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 the
catheter J00, out of the light entered from the PBS 123,
not to pass through, allows only the fluorescence to
20 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.
The second lens 125 collects the fluorescence,
25 which has entered from the long pass filter 124, on the
detection unit 130.
25
26
[0052] The detection unit 130 is, for example, a
linear image sensor, and spectroscopically detects the
fluorescence. entered from the optical system 120. That
is, the detection unit 130 detects the light having the
5 excitation wavelength, and detects the fluorescence
from the photo-sensitive pharmaceutical, which is a
light having a wavelength longer than the excitation
wavelength. The detection unit 1.30 outputs an
electrical signal, which shows intensity of the
10 detected fluorescence, to the controller 150.
[0053] An electrode pad 141 is connected to the
electrocardiograph 140 via an electrode code (not
shown). The electrocardiograph 140 obtains an
electrocardiographic signal of the patient 2 via the
15 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.
[0054] The controller 150 controls the respective
units of the PDT apparatus 1.
20 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
blood based on the calculated fluorescence intensity
25 (pharmaceutical-concentration-monitoring operation).
The controller 150 determines whether to additionally
26
27
administer the pharmaceutical or not based on the
calculated pharmaceutical concentration.
The controller 150 determines the contact state of
the laser the catheter 300 with respect to the tissue
5 based on the electrical signal obtained from the
detection unit 130 (contact-monitoring operation).
The controller 150 determines, based on change of
the fluorescence intensity during excitation light
irradiation, whether an abnormal situation such as a
10 foreign substance or a breakage occurs or not, and
determines the cytocidal effect (foreignsubstance/
breakage-monitoring operation, and cytocidaleffect-
determining operation). The controller 150
controls the light source 110 to stop irradiating the
15 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
and based on an electrocardiographic signal obtained
20 from the electrocardiograph 140 (electric-conductionblock-
formation determining operation).
The controller 150 outputs, to the display unit
170, display instructions to display the abovementioned
various calculation results, the above-
25 mentioned various determination results, and various
information.
27
28
[0055] The storage 160 is a nonvolatile memory, and
is set in, for example, a flash memory, an HDD (Hard
Disk Drive), or another solid memory. The controller
150 records, in the storage 160, temporal change of
5 fluorescence intensity, in which information on
fluorescence intensity obtained from the detection unit
130 is in relation with time information obtained from
a timing measurement unit (not shown), which measures
the elapsed time after a criterion time such as
10 excitation-light-irradiation start time. The controller
150 records, in the storage 160, electrocardiograms in
which information on an electrocardiographic signal
obtained from the electrocardiograph 140 is in relation
with time information.
15 [0056] 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, tl-,e,
display unit 170 displays, on a display screen, for
20 example, information on fluorescence intensity,
information on an electrocardiographic signal, time
information, and the like, based on display information
in the display instructions.
[0057] The operating unit 180 receives instructions,
25 which are input through operations by a practitioner,
and outputs the received instructions to the controller
28
2.3
150. The instructions include, for example,
instructions to turn on/off the excitation light output
from the light source 110, to change intensity, and the
like. As intensity of the excitation light, it is
5 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
is minimally-invasive with respect to a tissue and
blood, and a second intensity, which has a high power
10 and is approximately 1,000 times higher than the first
intensity. The first intensity is selected when
monitoring the pharmaceutical concentration and the
contact state of the laser the catheter 300 before
therapy. The second intensity is selected when therapy
15 is conducted. Note that the first intensity is a fixed
value, and the second intensity may be variable,
[0058] [Structure of laser catheter] The the laser
the catheter 300 outputs an excitation light from the
tip portion,
20 Fig. 4 is a sectional view showing the tip portion
of the laser catheter.
The laser the catheter 300 includes a catheter
tube 310, a holder 320, an optical fiber 330, and an
optical window 340.
25 [0059] The catheter tube 310 is a soft hollow tube,
and is led to the inner wall of a cardiac-muscle tissue
29
30
of the heart 10 of the patient 2. The catheter tube 310
has the optical fiber 330 therein.
[0060] The holder 320 is fixed to the catheter tube
310. The holder 320 holds the optical fiber 330 and the
5 optical window 340 with respect to the catheter tube
310.
[0061] The optical fiber 330 is, for example, one
quartz step index fiber having a core diameter o[' 133
pm and an outside diameter of 500 pm. The optical fiber
10 330 transmits the excitation light from the PDT
apparatus 1. The optical fiber 330 outputs the
transmitted excitation light, as an irradiation light
301, from the tip to the optical window 340. The beam
diameter of the irradiation light 301 increases at the
15 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 Lber
330 transmits the fluorescence, which is emitted from
20 photo-sensitive pharmaceutical absorbed in a tissue and
irradiated with an excitation light, to the PDT
apparatus 1.
.[0062] The optical window 340 is provided on the
outermost of the tip portion of the laser the catheter
25 300 such that the optical window 340 is optically
connected to the tip of the optical fiber 330. The
30
31
optical window 340 is made from a solid transparent
material, for example, a glass material such as BK7.
The optical window 340 as an irradiation section allows
the irradiation light 301, which is output from the tip
5 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
pharmaceutical, on the tip of the optical fiber 330.
[0063] In order to detect fluorescence with a high
10 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
irradiation and light-reception, to thereby remove
specular reflection light (see Japanese Patent
15 Application Laid-open No. 2009-148550, paragraph
[0037].).
Meanwhile, in the case of performing intracardiac
therapy of diagnosis, in order to increase the
curvature of a laser catheter, it is desirable that the
20 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 extrafinely,
and thus a light having a necessary intensity
may not be transmitted.
25 In view of the above, in diseases requiring
intracardiac approaches such as, specifically, atrial
31
32
fibrillation and ventricular flutter, it is desired
that one optical fiber be in a laser catheter. Further,
because it is necessary to detect fluorescence at
intensity with a low power so as not to affect a living
5 body, it is necessary to form a measurement system with
a high SN (Signal-Noise) ratio by using one optical
fiber.
[0064] In view of the above, according to the PDT
apparatus 1 of this embodiment, the PBS 123 and the
10 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
radiation component of a excitation light. With this
structure, in the laser the catheter 300, while the one
15 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 I::o detect fluorescence with a low powet so as
not to affect a living body. Therefore, in the therapy
20 and diagnosis of circulatory diseases, it is possible
to perform minimally-invasive diagnoses with an extrafine
laser catheter with an increased curvature.
[0065] [Operations of PDT apparatus] Next,
operations of the PDT apparatus _..1 configured as
25 described above will be described.
Fig. 5 is a flowchart showing operations of the
32
33
PDT apparatus.
[0066] The operations of the PDT apparatus 1 will be
described in the following order of (1) to (6).
(1) Preparation for PDT (Step 5101 to Step 5103)
5 (2) Pharmaceutical-concentration-monitoring
operation (Step 5104 to Step S105)
In the pharmaceutical-concentration-monitoring
operation, the light source 110 outputs an excitation
light with a first intensity, and the controller 150
10 constantly calculates the pharmaceutical concentration
based on fluorescence intensity detected by the
detection unit 130, and determines whether to
additionally administer pharmaceutical or not based on
the calculated pharmaceutical concentration.
15 (3) Contact-monitoring operation (Step S106 to
Step 5108)
In the contact-monitoring operation, the light
source 110 outputs the excitation light with the first
intensity, and the controller 150 determines the
20 contact state of the laser the 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, and the like).
25 (4) Foreign-substance/breakage-monitoring
operation (Step 5109 to Step S112)
33
34
In the foreign-substance/breakage-monitoring
operation, the light source 110 outputs the excitation
light with a second intensity, and the controller 150
determines whether a foreign substance adheres to the
5 tip of the laser the catheter 300 for some reason or
not and further determines whether a breakage occurs in
the vicinity of the tip of the laser the catheter 300
or not, during laser-irradiation at appropriate therapy
protocols, based on the fluorescence intensity detected
10 by the detection unit 130.
(5) Cytocidal-effect-determining operation (Step
5113)
In the cytocidal-effect-determining operation, the
light source 110 outputs the excitation light with the
15 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
detection unit 130.
20 (6) Electric-conduction-block-formation
determining operation (Step S114 to Step 5117)
An electric-conduction block is, as described
above, a block in which cardiac-muscle tissues
surrounding a hyperexcited site are necrotized, and in
25 which conduction of electrical pulses from the
hyperexcited site to the left atrium is blocked. Here,
34
35
it is determined whether an electric-conduction block
is formed or not by calculating, by the controller,
temporal-change data of fluorescence intensity used in
the cytocidal-effect-determining operation (Step 5113),
5 and electrocardiographic-wave data. In some cases, the
laser catheter may be relocated in the electricconduction
block, the intensity of the light source 110
may be changed to the first intensity, and the similar
process may be performed, to thereby determine whether
10 an electric-conduction block is formed or not.
[0067] [(1) Preparation for PDT]Fig. 6 is a
schematic diagram showing a laser catheter inserted in
a left atrium.
First, a practitioner such as a doctor inserts the
15 laser the catheter 300 in the heart 10 via a femoral
vein or a jugular vein of the patient 2. The tip
portion of the laser the catheter 300 is disposed in
the vicinity of a pulmonary vein 12 of an inner wall of
a the cardiac-muscle tissue 11 of the left atrium 13
20 (Step 5101).
[0068] Subsequently, with reference to various
referential data (Step 5102), the practitioner
administers photo-sensitive pharmaceutical to the
patient 2 (Step S103). Here, the case where a dose of
25 photo-sensitive pharmaceutical necessary for therapy is
administered to the patient 2 at one time by
35
36
intravenous injection will be described. The
administered photo-sensitive pharmaceutical is diffused
in blood and absorbed in a tissue.
[0069] [(2) Pharmaceutical-concentration-monitoring
S operation]Subsequently, the pharmaceuticalconcentration-
monitoring operation is performed.
First, the practitioner operates the operating
unit 180, and inputs an excitation-light-output
instruction with the low-power first intensity to the
10 controller 150. The controller 150 obtains the
excitation-light-output instruction, and then outputs
the excitation-light-output instruction with the first
intensity, to the light source 110. The light source
110 obtains the excitation-light-output instruction
15 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
and the laser the catheter 300. The photo-sensitive
20 pharmaceutical, which is absorbed in a tissue and blood,
absorbs the excitation light from the laser the
catheter 300, and emits fluorescence. The optical
system 120 extracts the fluorescence emitted from the
photo-sensitive pharmaceutical via the laser the
25 catheter 300, and the fluorescence enters the detection
unit 130. The detection unit 130 detects the entered
36
37
fluorescence, and outputs the detected fluorescence
intensity to the controller 150 as an electrical signal.
[0070] The controller 150 calculates the
fluorescence intensity based on the electrical signal
5 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
the calculated fluorescence intensity is in relation
with time information obtained from a timing
10 measurement unit (not shown.). The controller 150
creates display information of the temporal change of
the fluorescence intensity based on the calculated
fluorescence intensity and elapsed time after a
criterion time such as an intravenous-injection start
15 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 lemporal
change of the fluorescence intensity on a display
20 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.
[0071] Here, an example of the graph showing the
25 temporal change of the fluorescence intensity will be
described.
37
38
Fig. 7 is a graph showing a temporal change of
fluorescence intensity.
Fig. 7 shows the temporal change of fluorescence
intensity in the case where photo-sensitive
5 pharmaceutical (Laserphyrin) is administered to a pig
by intravenous injection (i.v,.), and irradiation is
performed with an excitation light, which is the same
as the Q-band absorption spectrum of the pharmaceutical
(semiconductor laser, emission wavelength with, for
10 example 600 to 800 nm, preferably 660 to 680 nm, or
more preferably 664 plus or minus 2, 400 pW). The tip
portion of the laser the catheter 300 is disposed in
the right atrium of the pig.
The fluorescence intensity in blood monotonically
15 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
decreases. Further, the fluorescence intensity in the
20 blood is higher than the fluorescence intensity in the
cardiac-muscle tissue.
[0072) Here, the relation between fluorescence
intensity and pharmaceutical concentration will be
described.
25 Fig. 8 is a graph showing a correlation between
fluorescence intensity and pharmaceutical concentration.
38
39
Fig. 8 shows a correlation between absolute value
of pharmaceutical concentration (PS concentration)
obtained by a blood collection method, and the
fluorescence intensity in the case where blood is
5 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,
it is possible to monitor pharmaceutical concentration
in real time based on the constantly-calculated
10 fluorescence intensity.
[0073] The controller 150 calculates pharmaceutical
concentration in a tissue and in blood based on
calculated fluorescence intensity (Step 5104). The
controller 150 starts to record, in the storage 160,
15 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 shoon.).
Further, the controller 150 creates display information
20 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
outputs a display instruction including the created
25 display information to the display unit 170. The
display unit 170 obtains the display instruction from
39
40
the controller 150, and then displays the temporal
change of the pharmaceutical concentration on a display
screen based on the display information included in the
display instruction. For example, the display unit 170
5 displays the temporal change of the pharmaceutical
concentration on the display screen in a graph form.
[0074] Here, an example of a graph showing the
temporal change of the pharmaceutical concentration
will be described.
10 Fig. 9 is a graph showing a temporal change of
pharmaceutical concentration.
As described above, the fluorescence intensity in
blood is higher than the fluorescence intensity in a
cardiac-muscle tissue, and, in addition, the
15 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
decreases after the pharmaceutical administration.
20 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,
and then decreases. Further, the pharmaceutical
25 concentration in blood is higher in level than the
pharmaceutical concentration in a tissue.
40
41
[0075] The controller 150 determines whether the
calculated pharmaceutical concentration is equal to or
more than a threshold (Step 5105). If the controller
150 determines that the pharmaceutical concentration is
5 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
operation (Step S105, Yes). Meanwhile, if the
controller 150 determines that the pharmaceutical
10 concentration is less than the threshold, the
controller 150 estimates that the pharmaceutical
concentration fails to reach the necessary value,
creates display information for prompting to
additionally administer the pharmaceutical, and outputs
15 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
information including the display instruction,
20 information prompting the practitioner to additionally
administer the photo-sensitive pharmaceutical (Step
S105, No).
[0076] Note that, because the fluorescence intensity
correlates with the pharmaceutical concentration, if
25 the display unit 170 displays the fluorescence
intensity on the display screen, a practitioner such as
41
42
a doctor may estimate the pharmaceutical concentration
based on the fluorescence intensity, even if the
controller 150 does not calculate the pharmaceutical
concentration.
5 [0077] Meanwhile, in general, as a method of
monitoring the pharmaceutical concentration change in
blood, there is known a method in which absorbance of
blood, which is collected at regular time intervdils
after pharmaceutical administration, is measured.
10 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
concentration in real time.
Alternatively, there is known a method in which a
15 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 he pharmaceutical concentration change
However, it is necessary to pay attention to hygiene in
20 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
into isotope, the isotope is simultaneously
25 administered, and pharmaceutical concentration in each
tissue is monitored based on a radiation quantity
42
(CANCER RESEARCH 50. 3985-3990, July 1, 1990, Tissue
Distribution and Photosensitizing Properties of Mono-Laspartyl
Chlorin e6 in a Mouse Tumor Model, Charles J.
Corner and Angela Ferrario). However, this method
5 involves radiation exposure problems, and involves a
problem in that only a concentration may be monitored
macroscopically.
[0078] To the contrary, according to the
pharmaceutical-concentration-monitoring operation of
10 this embodiment, by calculating the temporal change of
fluorescence intensity, the temporal change of
pharmaceutical concentration, which correlates with
fluorescence intensity, may be calculated. Therefore
the pharmaceutical concentration in a tissue and blood
15 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
temporal changes of pharmaceutical concentration stably
20 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
to additionally provide a pharmaceutical concentration
25 detecting apparatus, to thereby enable a low-cost and
space-saving apparatus. Further, because the
43
44
pharmaceutical concentration may be monitored in real
time, determination of additional pharmaceutical
administration may be assisted in real time,
[0079] Further, the pharmaceutical-concentration-
5 monitoring operation of this embodiment may be
performed not only in PDT but also in therapy or
diagnosis using a pharmaceutical, which absorbs an
excitation light and emits fluorescence. In therapy or
diagnosis using a pharmaceutical, it is important to
10 grasp a pharmaceutical dynamic state (pharmaceutical
delivery). According to the pharmaceuticalconcentration-
monitoring operation of this embodiment,
pharmaceutical concentration in an intended tissue may
be measured microscopically via a catheter in real time,
15 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 advanto,je and
is suitable for practical use. Further, the
20 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
whether pharmaceutical reaches actually and locally.
25 [0080] [(3) Contact-monitoring operation]
Subsequently, the contact-monitoring operation is
44
performed.
[00811 Figs. 10 are schematic diagrams showing
contact states of the laser catheter.
The laser the catheter 300 is preferably disposed
5 such that the tip portion as a light-emitting portion
contacts the inner wall of the the cardiac-muscle
tissue 11 upright (see Fig. 10(a), hereinafter referred
to as "upright-contact state".). This state is
preferable so as to remove intraatrial the blood 15
10 from the tip portion of the laser the catheter 300, and
to prevent activation of photo-sensitive pharmaceutical
in the intraatrial the blood 15 . Further, this state
is preferable so as to selectively activate photosensitive
pharmaceutical absorbed in a tissue when the
15 tip portion of the laser the catheter 300 directly
contacts a tissue.
However, it is difficult to recognize the precise
contact state of the tip portion of the laser tiEc
catheter 300 radiographically or tactually. Because of
20 this, actually, it is not always true that the tip
portion of the laser the catheter 300 is in the
upright-contact state with respect to a tissue. The the
blood 15 may exist between the tip portion of the laser
the catheter 300 and a tissue, and the tip portion may
25 be in the blood (see Fig. 10(c), hereinafter referred
to as "non-contact state".). Alternatively, the tip
45
46
portion of the laser the catheter 300 may contact a
tissue in a slanting direction, and the the blood 15
may partially exist in a gap between the tip portion
and the tissue (see Fig. 10(b), hereinafter referred to
5 as "slanting-contact state".).
In the contact-monitoring operation, such contact
states of the tip portion of the laser the catheter 300,
that is, the contact states and the non-contact state,
are monitored, the contact angle (upright-contact state,
10 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
widely-defined contact angle, in which the contact
15 state of the tip portion of the laser the catheter 300
with respect to a tissue is upright or slanting.
[0082] Continuously, the light source 110 outputs
the excitation light with the first intensity to the
optical system 120, the controller 150 calculates
20 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
25 as a graph,
[0083] Here, an example of a graph showing the
46
47
temporal change of fluorescence intensity will be
described.
Fig. 11 is a graph showing the temporal change of
fluorescence intensity.
5 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,
and the line B fluctuates between the fluorescence
10 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 temporal change of fluorescence
intensity in the case where the tip portion of the
15 laser the catheter 300 is in the upright-contact state,
the temporal change of fluorescence intensity in the
case where the tip portion of the laser the catheter
300 is in the slanting-contact state, and the temporal
change of fluorescence intensity in the case where the
20 tip portion of the laser the 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 the
catheter 300,
25 The line A will be reviewed. Here, as shown in Fig.
7, the fluorescence intensity in a tissue is smaller
47
48
than the fluorescence intensity in blood. Therefore, it
is thought that the line A shows the fluorescence
intensity in the case where the laser the catheter 300
irradiates a tissue with the excitation light. So, in
5 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 the catheter 300
is in the upright-contact state with respect to a
10 tissue.
The line C will be reviewed. Here, as shown in Fig.
7, the fluorescence intensity in blood is larger than
the fluorescence intensity in a tissue. Therefore, it
is thought that the line C shows the fluorescence
15 intensity in the case where the laser the catheter 300
irradiates blood with the excitation light. So, in the
case where the fluorescence intensity of the line C is
calculated, it is thought that the fluorescence
intensity in blood is reflected in the result because
20 the tip portion of the laser the 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
25 that the tip portion of the laser the catheter 300 is
in the slanting-contact state with respect to a tissue.
48
49
Further, because a contact-target object of the tip
portion of the laser the catheter 300 is a moving
cardiac-muscle tissue, the laser the catheter 300
follows the movement of the tissue to thereby move. As
5 a result, in the case where the tip portion of the
laser the catheter 300 contacts a tissue in a slanting
manner, it is likely that the blood volume between the
tip portion of the laser the catheter 300 and a . issue
changes during measurement. In addition, the blood-flow
10 volume in a cardiac-muscle tissue changes and the
intraatrial blood-flow volume changes because of
heartbeat. Affected by them, the fluctuation of the
fluorescence intensity of the line B is larger than the
line A and the line C.
15 Further, in the case where the tip portion of the
laser the catheter 300 contacts a tissue in any state
(upright-contact state, slanting-contact state), the
laser the catheter 300 may be affected by the movement
of the cardiac-muscle tissue. That is, the contact
20 state of the tip portion of the laser the catheter 300
fluctuates between the contact states (upright-contact
state, slanting-contact state) and the non-contact
state. In this case, the fluorescence intensity
fluctuates largely. Therefore, it is determined whether
25 the laser the catheter 300 follows the movement of a
cardiac-muscle tissue or not based on fluctuation of
49
50
the fluorescence intensity shown in a waveform. For
example, in the line A of the graph, the high
fluorescence intensity after four seconds after
pharmaceutical administration and in the vicinity
5 thereof shows that the tip portion of the laser the
catheter 300 momentarily moves from the upright-contact
state to the non-contact state and returns to the -
upright-contact state again.
[0084] Based on the calculated fluorescence
10 intensity, the controller 150 determines the contact
state of the tip portion of the laser the catheter 300
(contact/non-contact states, contact angle in case of
contact state) (Step 5106).
Specifically, in the case where the controller 150
15 determines that the calculated fluorescence intensity
is equal to or larger than a first threshold, the
controller 150 determines the non-contact state (line
C). In the case where the controller 150 determines
that the minimum value of the fluorescence intensity is
20 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
case where the controller 150 determines that the
fluorescence intensity periodically fluctuates between
25 the first threshold and the second threshold, the
controller 150 determines the slanting-contact state
50
i3 1
(line B).
The controller 150 informs the practitioner the
determined contact state by using the display unit 170.
Specifically, when the controller 150 determines the
5 slanting-contact state or the non-contact state, the
controller 150 creates display information for
prompting to change the contact state of the tip
portion of the laser the catheter 300, and outpuls a
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 then displays information for prompting a
practitioner to change the contact state of the tip
portion of the laser the catheter 300 based on the
15 display information in the display instruction (Step
5107). The practitioner operates a handpiece or the
like (not shown.) provided on the laser the catheter
300, to thereby change the contact state of the C_i.p
portion of the laser the catheter 300 with respect to a
20 tissue.
[0085] The controller 150 continuously calculates
fluorescence intensity and pharmaceutical concentration.
The controller 150 refers to fluorescence intensity and
pharmaceutical concentration stored in the storage 160.
25 The controller 150 calculates the blood volume in the
gap between the tip portion of the laser the catheter
51
52
300 and a tissue based on the referred fluorescence
intensity. The controller 150 calculates excitationlight-
irradiation protocols during the therapy, that is,
the second intensity of the excitation light, the
5 irradiation time, and the like, based on the calculated
blood volume and the referred pharmaceutical
concentration (Step 5108).
For example, in the case where the tip portion of
the laser the catheter 300 is in the slanting-contact
10 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 blood volume, and the
excitation-light-irradiation protocols are set, in
15 which the second intensity is high and in which the
irradiation time is long. The controller 150 calculates
the excitation-light-irradiation protocols, creates
display information on the irradiation protocol, and
outputs display instruction including the created
20 _,. display information to the display unit 170. The
display unit 170 obtains the display instruction from
the controller 150, and then displays information on
the excitation-light-irradiation protocols (second
intensity, irradiation time) based on the display
25 information in the display instruction.
As described above, the controller 150 calculates
52
54
movement of the tissue, to reliably perform therapy. In
the past, it is known to determine the contact state of
a catheter by, for example, securing a transparent zone
by removing blood, radioscopy, potential measurement
5 (impedance measurement), potential mapping, temperature
measurement, dynamic measurement (pressure, stress),
reflected light measurement using a polychromatic light
source, and the like. However, in. the field of therapy
and diagnosis via a catheter, it is difficult to
10 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 abovementioned
conventional methods is capable of
determining the contact state roughly, and, in addition,
15 has many problems as follows.
Securing a transparent zone by removing blood is a
method in which a blood flow is temporarily blocked by
using a balloon, saline or the like is flowed from a
catheter tip portion to thereby secure a transparent
20 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
is difficult to determine the distance of a gap between
25 a catheter and a tissue, and the blood volume in the
gap between the catheter and the intended tissue.
54
55
Further, in the case of a moving tissue, it is not
clear that the tip of a catheter follows the movement.
As a result, the tip of a catheter may break blood (in
case of intracardiac therapy) or blood-vessel wall (in
5 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
not be achieved. Further, the biggest problem is that
only a doctor, who has a knowledge of anatomy and is
10 well-experienced (tactile impression when touching),
can make a determination, subjectively (see Japanese
Patent Application Laid-open No. 2007-525263).
Potential measurement (impedance measurement) is a
method in which, since a cardiac-muscle tissue
15 contracts and moves because of potential propagation,
the contact state with respect to a cardiac-muscle
tissue is determined by measuring the potential.
However, in the case of performing an optical therapy,
the tip portion of a catheter (contact portion with
20 °- 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
coincide with a potential-measured site, a diagnosis-
25 target zone does not coincide with a therapy-target
zone, and the therapy may not be performed precisely.
55
56
Further, an electrode area is made smaller, and angle
determination accuracy may thus be decreased. Further,
because electric measurement is performed, there may be
an effect of electromagnetic interference (see Japanese
5 Patent Application Laid-open No. 2008-531170).
Potential mapping is a method in which potential
measurement is three-dimensionally developed. However,
a conventional apparatus lacks a resolution of
determining a contact state in detail. Further, it
10 takes time to perform determination, and an
anthropogenic influence may occur because of an
excessive contact pressure (see Japanese Patent
Application Laid-open No. 2008-531170) . Further, if a
potential measuring catheter is displaced, a mapping
15 imagemay not coincide with an actual position. Further,
because electric measurement is performed, there may be
an effect of electromagnetic interference (see Japanese
Patent Application Laid-open No. 2008-531170).
Temperature measurement is a method in which, with
20 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
occlusions, and is not applicable to diseases including
25 no occlusion zone such as, for example, atrial
fibrillation and ventricular flutter. Further,
56
57
unnecessary heat may be provided on a normal bloodvessel
wall.
Dynamic measurement (pressure, stress) is a method
in which a pressure sensor or a stress sensor is
5 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
Application Laid-open No. 2008/0009750, WIPO
Publication No. 01/33165) However, the tip portion of
10 the catheter may be larger, and there may be an effect
of electromagnetic interference (see Japanese Patent
Application Laid-open No. 2008-531170).
Reflected light measurement by using a
polychromatic light source is a method in which
15 absorption coefficients different from wavelengths are
used. Specifically, by using a polychromatic light
source, a tissue is determined based on reflection
ratio differences of the respective wavelengths (see
Japanese Patent No. 4261101). According to this method,
20 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
sources are provided.
25 [0088] To the contrary, according to the contactmonitoring
operation of this embodiment, by detecting
57
58
fluorescence intensity, it is possible to determine the
contact state with respect to an intended tissue and
following-movements via a catheter in real time. This
method is minimally invasive because it is not
5 necessary to remove blood and the like. Further,
because excitation-light-irradiation protocols may be
calculated based on the determined contact state and
the like, therapy and diagnosis may be assisted safely
and reliably.
10 [0089] [(4) Foreign-substance/breakage-monitoring
operation] During the photodynamic therapy, the foreignsubstance/
breakage-monitoring operation is performed.
First, a practitioner refers to excitation-lightirradiation
protocols displayed on the display unit 170,
15 and operates the operating unit 180 to thereby input an
excitation-light-output instruction with the high-power
second intensity in the controller 150. The controller
150 obtains the excitation-light-output instruction,
and then outputs the excitation-light-output
20 instruction with the second 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
second intensity. A tissue is irradiated with the
25 excitation light output from the light source 110 via
the optical system 120 and the laser the catheter 300,
58
59
and photodynamic therapy is performed (Step 5109).
[0090] Based on an electrical signal obtained from
the detection unit 130, the controller 150 calculates
fluorescence intensity. The controller 150 creates
5 display information of the temporal change of the
fluorescence intensity based on the calculated
fluorescence intensity and elapsed time after a
criterion time such as an intravenous-injection start
time, and outputs a display instruction including the
10 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 fluorescence intensity on a display
screen based on the display information included in the
15 display instruction.
[0091] The controller 150 determines whether the
calculated fluorescence intensity is equal to or more
than a threshold (Step 5110). The threshold is, for
example, a value equal to or more than the multiple of
20 the normal fluorescence intensity.
[0092] Fig. 19 is a graph showing the relation
between wavelength and fluorescence intensity.

Claims
[1] An estimating 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 estimate whether
15 the tissue has changed because of reaction between the
excitation light emitted from the Lip portion of the
laser catheter and the photo-sensitive pharmaceutical
absorbed in the tissue.
[2] The estimating apparatus according to claim 1,
20 wherein
the detection unit detects intensity of the
fluorescence, the fluorescence being entered from the
laser catheter via the connector, to simultaneously
estimate whether the tissue has.... changed because of
25 reaction between an excitation light emitted from the
tip portion of the laser catheter and the photo-
116
117
sensitive pharmaceutical absorbed in the tissue, and
whether a contact state of the tip portion of the laser
catheter with respect to the tissue has changed.
[3] The estimating apparatus according to claim 2,
5 further comprising:
a controller for simultaneously estimating whether
the tissue has changed because of reaction between an
excitation light emitted from the tip portion of the
laser catheter and the photo-sensitive pharmaceutical
10 absorbed in the tissue, and a contact state of the tip
portion of the laser catheter with respect to the
tissue, based on the detected intensity of the
fluorescence.
[4] The estimating apparatus according to claim 3,
15 wherein
the controller visually reflects a currentestimated-
result of the change of the tissue in a pealestimated-
result of the change of the tissue, and
outputs a signal for simultaneously informing of the
20 estimated result of the change of the tissue and the
estimated result of the contact state.
[5] The estimating apparatus according to claim 4,
further comprising
storage for storing the peak-estimated-result of
25 the change of the tissue, wherein
the controller records the current-estimated-
117
118
result of the change of the tissue in the storage,
updates, in a case where the current-estimated-result
of the change of the tissue is equal to or larger than
the peak-estimated-result of the change of the tissue
5 recorded in the storage, the peak-estimated-result of
the change of the tissue recorded in the storage with
the current-estimated-result of the change of the
tissue, and outputs a signal for simultaneously
informing of the estimated result of the change of the
10 tissue and the estimated result of the contact state,
by displaying the current-estimated-result of the
change of the tissue on the updated peals-estimatedresult
of the change of the tissue in an overlapped
manner.
15 [6] The estimating apparatus according to claim 1,
further comprising:
a controller for estimating whether the tissue has
changed because of reaction between the excitation
light emitted from the tip portion of the laser
20 catheter and the photo-sensitive pharmaceutical
absorbed in the tissue, based on intensity of the
detected fluorescence.
[7] The estimating apparatus according to claim 6,
wherein
25 the controller outputs a signal for informing
whether the tissue has changed, based on the estimated
118
119
result.
[8] The estimating apparatus according to claim 6,
wherein
the controller outputs a signal to prompt to
5 change an irradiation condition of the excitation light,
based on the estimated result.
[9] The estimating apparatus according to claim 6,
wherein
the controller obtains an electrocardiographic
10 signal, and estimates whether the tissue has changed,
based on a correlation between the electrocardiographic
signal and the intensity of the fluorescence.
[10] An estimating apparatus for therapy for atrial
fibrillation, for irradiating a cardiac-muscle tissue
15 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,
comprising:
20 -- a connector to/from which the laser catheter is
capable of being attached/detached;
a light source for outputting the excitation light
to the laser catheter via the connector; and
a detection unit for detecting intensity of the
25 fluorescence, the fluorescence being entered from the
laser catheter via the connector, to estimate whether
119
120
the cardiac-muscle tissue is changed because of
reaction between the excitation light emitted from the
tip portion of the laser catheter and the photosensitive
pharmaceutical absorbed in the cardiac-muscle
5 tissue.
[11] The estimating apparatus according to claim 10,
wherein
the detection unit detects intensity of the
fluorescence, the fluorescence being entered from the
10 laser catheter via the connector, to simultaneously
estimate whether the cardiac-muscle tissue has changed
because of reaction between an excitation light emitted
from the tip portion of the laser catheter and the
photo-sensitive pharmaceutical absorbed in the cardiac-
15 muscle tissue, and whether a contact state of the tip
portion of the laser catheter with respect to the
cardiac-muscle tissue has changed.
[12] The estimating apparatus according to claiiu 11,
further comprising:
20 a controller for simultaneously estimating whether
the cardiac-muscle tissue has changed because of
reaction between an excitation light emitted from the
tip portion of the laser catheter and the photosensitive
pharmaceutical absorbed in the cardiac-muscle
25 tissue, and a contact state of the tip portion of the
laser catheter with respect to the cardiac-muscle
120
121
tissue, based on the detected intensity of the
fluorescence.
[13] The estimating apparatus according to claim 12,
wherein
5 the controller visually reflects a peak-estimatedresult
of the change of the cardiac-muscle tissue in a
current-estimated-result of the change of the cardiacmuscle
tissue, and outputs a signal for simultaneously
informing of the estimated result of the change of the
10 cardiac-muscle tissue and the estimated result of the
contact state.
[14] The estimating apparatus according to claim 13,
further comprising
storage for storing the peak-estimated-result of
15 the change of the cardiac-muscle tissue, wherein
the controller records the current-estimatedresult
of the change of the cardiac-muscle tissue in
the storage, updates, in a case where the currentestimated-
result of the change of the cardiac-muscle
20 tissue is equal to or larger than the peak-estimatedresult
of the change of the cardiac-muscle tissue
recorded in the storage, the peak-estimated-result of
the change of the cardiac-muscle tissue recorded in the
storage with the current-estimated-result of the change,
25 of the cardiac-muscle tissue, and outputs a signal for
simultaneously informing of the estimated result of the
121
122
change of the cardiac-muscle tissue and the estimated
result of the contact state, by displaying the currentestimated-
result of the change of the cardiac-muscle
tissue on the updated peak-estimated-result of the
5 change of the cardiac-muscle tissue in an overlapped
manner.
[15] An estimating method, comprising:
irradiating a tissue having absorbed photosensitive
pharmaceutical, the photo-sensitive
10 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
irradiated excitation light via the laser catheter; and
15 estimating whether the tissue has changed because
of reaction between the excitation light emitted from
the tip portion of the laser catheter and the photosensitive
pharmaceutical absorbed in the tissue, based
on intensity of the extracted fluorescence.
20 [16] The estimating method according to claim 15,
further comprising:
simultaneously estimating whether the tissue has
changed because of reaction between an excitation light
emitted from the tip portion ofthe laser catheter and
25 the photo-sensitive pharmaceutical absorbed in the
tissue, and a contact state of the tip portion of the
122
123
laser catheter with respect to the tissue, based on the
extracted intensity of the fluorescence.
[17] The estimating method according to claim 16,
further comprising:
5 visually reflecting a current-estimated-result of
the change of the tissue in a peak-estimated-result of
the change of the tissue, and outputting a signal for
simultaneously informing of the estimated result: of the
change of the tissue and the estimated result of the
10 contact state.
[18] The estimating method according to claim 17,
further comprising:
recording the current-estimated-result of the
change of the tissue in storage, updating, in a case
15 where the current-estimated-result of the change of the
tissue is equal to or larger than the peak-estimatedresult
of the change of the tissue recorded in the
storage, the peak-estimated-result of the change of the
tissue recorded in the storage with the current-
20 -- estimated-result of the change of the tissue, and
outputting a signal for simultaneously informing of the
estimated result of the change of the tissue and the
estimated result of the contact state, by displaying
the current-estimated-result of the change of the
25 tissue on the updated peak-estimated-result of the
change of the tissue in an overlapped manner.
123
124
[19] The estimating method according to claim 15,
further comprising:
obtaining an electrocardiographic signal, and
estimating whether the tissue has changed, based on a
5 correlation between the electrocardiographic signal and
the intensity of the fluorescence.
[20] An estimating method using photo-sensitive
pharmaceutical absorbing an excitation light and
emitting a fluorescence, a laser catheter capable of
10 emitting the excitation light from a tip portion, and
an estimating apparatus including a connector to/from
which the laser catheter is capable of being
attached/detached and a light source for outputting the
excitation light to the laser catheter via the
15 connector, comprising:
absorbing, in a tissue, the photo-sensitive
pharmaceutical;
leading the tip portion of the laser catheter_ to
the tissue having absorbed the photo-sensitive
20 pharmaceutical, the laser catheter being attached to
the connector;
irradiating the tissue having absorbed the photosensitive
pharmaceutical with the excitation light
emitted from the tip portion of the laser catheter, the
25 excitation light being output from the light source;
extracting the fluorescence corresponding to the
124
125
irradiated excitation light via the laser catheter; and
estimating whether the tissue has changed because
of reaction between the excitation light emitted from
the tip portion of the laser catheter and the photo-
5 sensitive pharmaceutical absorbed in the tissue, based
on intensity of the extracted fluorescence.
[21] The estimating method according to claim 20,
further comprising:
simultaneously estimating whether the tissue has
10 changed because of reaction between an excitation light
emitted from the tip portion of the laser catheter and
the photo-sensitive pharmaceutical absorbed in the
tissue, and a contact state of the tip portion of the
laser catheter with respect to the tissue, based on the
15 extracted intensity of the fluorescence.
[22] The estimating method according to claim 21,
further comprising:
visually reflecting a current-estimated-result of
the change of the tissue in a peak-estimated-result of
20 the change of the tissue, and outputting a signal for
simultaneously informing of the estimated result of the
change of the tissue and the estimated result of the
contact state.
[23] The estimating method according to claim 22,
25 further comprising:
recording the current-estimated-result of the
125
126
change of the tissue in storage, updating, in a case
where the current-estimated-result of the change of the
tissue is equal to or larger than the peak-estimatedresult
of the change of the tissue recorded in the
5 storage, the.peak--estimated-result of the change of the
tissue recorded in the storage with the currentestimated-
result of the change of the tissue, and
outputting a signal for simultaneously informing of the
estimated result of the change of the tissue and the
10 estimated result of the contact state, by displaying
the current-estimated-result of the change of the
tissue on the updated peak-estimated-result of the
change of the tissue in an overlapped manner.
[24] The estimating method according to claim 20,
15 further comprising:
obtaining an electrocardiographic signal, and
estimating whether the tissue has changed, based on a
correlation between the electrocardiographic signal and
the intensity of the fluorescence.