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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3721_Библиотеки_им_академика_М_И_Перельмана
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1 Clinically Available Fluorescent Reagents
https://t.me/medicina_free
5
Point
• Fluorescence imaging using 5-aminolevulinic acid for
identication of liver cancer
For this purpose, we orally administered 5-ALA hydrochloride (1g) 3hours before surgery. Care must be taken in
hepatic dysfunction, which has been reported as an adverse
event associated with 5-ALA [3].
4 Expected Future Applications
The current applications of uorescence imaging include (1)
angiography and evaluation of blood ow, (2) lymph node
mapping and lymphography, (3) visualization of anatomical
structures, and (4) cancer localization. The applications will
be expanded to various elds of surgery by adjusting uores-
a
cent reagents and administration methods according to surgical situations.
For example, Mitsuhashi etal. reported that intraoperative
ICG uorescence imaging in hepatobiliary surgery is useful
for understanding the anatomy of the hepatic artery, portal
vein, and bile ducts [4]. We also reported that uorescence
cholangiography using uorescence signals emitted from
ICG bounded with bile proteins [5] was effective for detecting the origins of bile leaks, which could not be identied by
conventional methods [6]. Furthermore, Uchiyama et al.
have applied ICG uorescence imaging to intraoperative
navigation during hepatectomy for liver cancer [7].
We have also reported that the combined use of ICG and
5-ALA uorescence imaging is useful for intraoperative
identication of small hepatic lesions (Fig.1.1) and disseminated nodules (Fig.1.2), which can provide essential information for surgical planning in patients with liver cancer [8].
d
b
c
Fig. 1.1 Hepatocellular carcinoma identied by uorescence imaging.
(a) Two supercial malignant liver tumors with serosa (arrows) under
conventional white light illumination. (b) Indocyanine green uorescence imaging of the same liver tumors; insets show the incised lesions,
which were diagnosed as hepatocellular carcinoma. (c) Indocyanine
green uorescence imaging of the same liver tumors using color mode;
e
f
insets show the incised lesions. (d) The same liver tumors show 5-ALA
uorescence under blue light through an optical lter. (e)
5- aminolevulinic acid uorescence imaging of one of the same liver
tumors; inset shows the incised lesion. (f) 5-aminolevulinic acid uorescence imaging of the other liver tumor; inset shows the incised lesion

6
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K. Matsui and M. Kaibori
a
b
c
d
Fig. 1.2 Disseminated lesions identied by uorescence imaging. (a)
Ovarian and peritoneal metastasis from hepatocellular carcinoma,
under conventional white light illumination. (b) Indocyanine green uorescence imaging of peritoneal metastasis of hepatocellular carci-
Based on the experiences in liver surgery, we believe that
uorescence imaging can be applied to accurately determine
the extent of tumor invasion and dissemination in various
cancer surgeries.
Point
• It is important to understand the characteristics of uorescent reagents for using intraoperative uorescence imaging effectively.
The uorescence imaging technique can be applied to
intraoperative navigation.
5 Conclusions
The insurance coverage and dosage/administration of ICG
and 5-ALA are summarized in this chapter. Intraoperative
uorescence imaging will be applied more widely with the
development of uorescence reagents and imaging
techniques.
noma. (c) 5-aminolevulinic acid uorescence imaging of colon ① and
peritoneal ② metastases of intrahepatic cholangiocellular carcinoma.
(d) 5-aminolevulinic acid uorescence imaging of omental metastasis
of hepatocellular carcinoma
References
1. Makuuchi M, Kosuge T, Takayama T, etal. Surgery for small liver
cancers. Semin Surg Oncol. 1993;9:298–304.
2. Ishizawa T, Hasegawa K, Aoki T, etal. Neither multiple tumors nor
portal hypertension are surgical contraindications for hepatocellular
carcinoma. Gastroenterology. 2008;134:1908–16.
3. Stummer W, Stocker S, Wagner S, etal. Intraoperative detection
of malignant gliomas by 5-aminolevulinic acid-induced porphyrin
uorescence. Neurosurgery. 1998;42:518–26.
4. Mitsuhashi N, Kimura F, Shimizu H, etal. Usefulness of intraoperative uorescence imaging to evaluate local anatomy in hepatobiliary
surgery. Hepatobiliary Pancreat Surg. 2008;15:508–14.
5. Mulllock BM, Shaw LJ, Fitzharris B, etal. Sources of proteins in
the human bile. Gut. 1985;26:500–9.
6. Kaibori M, Ishizaki M, Matsui K, et al. Intraoperative indocyanine green uorescent imaging for prevention of bile leakage after
hepatic resection. Surgery. 2011;150:91–8.
7. Uchiyama K, Ueno M, Ozawa S, etal. Combined intraoperative use
of contrast-enhanced ultrasonography imaging using a sonazoid and
uorescence navigation system with indocyanine green during anatomical hepatectomy. Langenbeck's Arch Surg. 2011;396:1101–7.
8. Kaibori M, Matsui K, Ishizaki M, etal. Intraoperative detection of
supercial liver tumors by Fluorescence Imaging Using Indocyanine
Green and 5-aminolevulinic Acid. Anticancer Res. 2016;36:1841–9.

Indocyanine Green Fluorescence
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Imaging System forOpen Surgery
NobuyukiTakemura andNorihiroKokudo
2
Summary
Currently in Japan, the following ICG uorescence imaging
systems are commercially available for laparotomy and body
surface surgery.
• pde-neo® (Hamamatsu Photonics K.K.)
• SPY-PHI (Stryker)
• LIGHTVISION (Shimadzu Corporation)
• HyperEyeMedicalSystem Plus+ (Mizuho Corporation)
• VISIONSENSE system (Medtronic)
• LUOBEAM® (Fluoptics)
• MIPS (Mitaka Kohki Co., Ltd.)
1 Introduction
The development of indocyanine green (ICG) uorescence
imaging systems began with the identication of sentinel
lymph nodes during breast cancer surgery by Dr. Kitai, with
the use of a prototype of the Photo Dynamic Eye (PDE,
Hamamatsu Photonics K.K.) [1]. Herein, we describe the
features of the ICG uorescence imaging systems for open
surgery (laparotomy and body surface surgery) that are currently available for clinical use in Japan (Table2.1).
N. Takemura (*)
Hepato-Biliary Pancreatic Surgery Division, Department of
Surgery, National Center for Global Health and Medicine,
Shinjuku, Tokyo, Japan
e-mail: takemuranobu-tky@umin.ac.jp
N. Kokudo
National Center for Global Health and Medicine,
Shinjuku, Tokyo, Japan
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
T. Ishizawa (ed.), Fluorescence-Guided Surgery, https://doi.org/10.1007/978-981-19-7372-7_2
7

8
(Hamamatsu Photonics K.K.)
pde-neo
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N. Takemura and N. Kokudo
Table 2.1
Product
pde-neo®
Sales started: Aug. 2010~
Country of manufacture: Japan
Price: 4800 Yen(net)
SPY-PHI
Sales started: Jan. 2015~
Country of manufacture: Canada
Price: 7000–9000 Yen (actual
price including display, etc.)
LIGHTVISION
Sales started: Aug. 2016~
Country of manufacture: Japan
Price: 24,000 Yen
HyperEyeMedicalSystem Plus+
Sales started: Aug. 2019~
Country of manufacture: Japan
Price: 9000 Yen
EleVision™
Sales started: Dec. 2015~
Country of manufacture: Israel,
USA
Price: 10,000–12,000 Yen
FLUOBEAM
Sales started: Apr. 2019~
Country of manufacture: France
Price: Open (10,000–12,000
Yen)
MIPS
Sales started: Feb. 2020~
Country of manufacture: Japan
Price: 24,000 Yen
Note: Prices are for the minimum conguration (e.g., rigid mirror, camera head, light guide, imaging system, and display)
Characteristics of ICG uorescence imaging system for open surgery commercially available in Japan (as of August 2020)
Characteristics
Excitation light
and trend signal
Image
quality
Non-HD N/A Available External Stored image
Full-HD Available N/A Yes N/A Stryker Japan KK
Full-HD Available Available Yes N/A Shimadzu Corporation
Full-HD Available Available Yes N/A Mizuho Corporation
Full-HD Available Available Built-in Available
Full-HD N/A N/A Yes Available (relative
Full-HD Available
Superimposed
uorescence
(projection
mapping directly
on the affected area
and display on the
monitor)
intensity
adjustment
Available Yes
Recording
device
Fluorescence
intensity analysis
analysis software
available
(numerical value
relative to maximum
uorescence
intensity)
evaluation of
uorescence
intensity in the
captured area)
Available (multivalued display
according to
uorescence
intensity)
Manufacturer/
distributor
Manufactured by
Hamamatsu Photonics
K.K., and distributed
by IMI Co., Ltd.
Manufactured by
Medtronic and
distributed by Heiwa
Medical Instruments
Co., Ltd.
Manufactured by
Fluoptics and
distributed by Vital
Corporation
Mitaka Kohki Co.,
Ltd.
2 pde-neo® (Hamamatsu Photonics
K.K.)
The pde-neo® (Fig.2.1) was developed based on the concept
of measuring uorescence with high sensitivity and is
equipped with a uorescence mapping function that displays
the uorescence intensity in color for clearer observation of
uorescence images.
Fig. 2.1 pde-neo® (Hamamatsu Photonics K.K.)

(Stryker)
SPY-PHI
(Shimadzu Corporation)
LIGHTVISION
2 Indocyanine Green Fluorescence Imaging System forOpen Surgery
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9
3 SPY-PHI (Stryker)
The main body of this device (Fig.2.2) is the same as that for
laparoscopic surgery manufactured by Stryker. The features
of SPY-PHI include “ICG black and white mode (SPY
mode)” for clearer conrmation of the uorescent area,
“overlay mode (PINPOINT mode)” for displaying the uorescent image obtained by uorescence imaging superimposed in green on the white-light high-denition image, and
“colorized mode (CSF mode)” for demonstrating trends of
uorescence intensity in a blue-red gradation. The surgeon
can switch between the three modes at hand.
a
4 LIGHTVISION (Shimadzu Corporation)
LIGHTVISION (Fig.2.3) is capable of high-denition imaging. Because it is an arm-type device, there is no need to hold
the camera by hand during imaging, enabling surgeons to
continue surgical procedures freely during uorescence
imaging. It is also equipped with a 10× zoom lens, which
enables image magnication.
b
Fig. 2.3 LIGHTVISION (Shimadzu Corporation)
Fig. 2.2 SPY-PHI (Stryker): main body of the device (a) and handheld
imager (b)

10
(MIZUHO Corporation)
HyperEyeMedicalSystem Plus+
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N. Takemura and N. Kokudo
5 HyperEyeMedicalSystem Plus+
(Mizuho Corporation)
The HyperEyeMedicalSystem Plus+ (Fig.2.4) is capable of
high-denition imaging, and the uorescence color can be
selected between green and white. LEDs for auxiliary illumi-
nation are placed in the irradiation unit of the camera unit so
that the near-infrared light can be captured with a bright eld
of view even in an environment where the illumination is
turned off. Furthermore, as new functions, excitation LEDs
for uorescein uorescence and also for 5-albuminate uorescence are equipped.
Fig. 2.4 HyperEyeMedicalSystem Plus+ (Mizuho Corporation)

(Medtronic)
EleVision
TM
(Fluoptics)
FLUOBEAM
®
2 Indocyanine Green Fluorescence Imaging System forOpen Surgery
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11
6 EleVision™ IR Platform (Medtronic) (in
Japan, Distributed asVISIONSENSE by
Heiwa Medical Instruments Co., Ltd.)
The EleVision™ IR Platform (Fig.2.5) is also capable of full
high-denition imaging, and except for the lens part, everything including the camera can also be used for endoscopic
surgery. The greatest feature of this device is its high sensitivity to detect uorescence at a depth of up to 7mm with a
dual sensor and its ability to display uorescence intensity
numerically.
IR Platform
7 FLUOBEAM® (Fluoptics)
In addition to the conventional functions for uorescence
imaging using ICG, FLUOBEAM® (Fig.2.6) has a mode
optimized for highly sensitive visualization of tissue autouorescence under infrared irradiation, which can be used
for the identication of parathyroid glands.
Fig. 2.5 EleVision™ IR platform (Medtronic)
Fig. 2.6 FLUOBEAM® (Fluoptics)

12
(Mitaka Kohki Co., Ltd.)
MIPS
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N. Takemura and N. Kokudo
8 MIPS (Mitaka Kohki Co., Ltd.)
MIPS (Fig.2.7) applies the projection mapping technology
that has been widely used in the entertainment industry and
projects the ICG uorescence image directly onto the
patient’s organ in real time, eliminating the need for eye
movement between the surgical eld and the monitor.
Another important feature of this system is that it uses an
algorithm that converts non-uorescent areas to white, which
can provide a bright surgical eld even when the surgical
lights are turned off during uorescence imaging.
9 Conclusions
Now that various uorescence imaging systems for open surgery have become commercially available, it is essential to
select the best device considering the characteristics of each
system and the purpose of uorescence imaging. With the
advance in technology, image quality and functions of uorescence imaging systems for open surgery will be further
improved and expanded.
Reference
1. Kitai T, Inomoto T, Miwa M, etal. Fluorescence navigation with
indocyanine green for detecting sentinel lymph nodes in breast cancer. Breast Cancer. 2005;12:211–5.
Fig. 2.7 MIPS (Mitaka Kohki Co., Ltd.)

Indocyanine Green Fluorescence
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Imaging System forEndoscopic
andRobot-Assisted Surgeries
ShuichiWatanabe, ToshiroOgura, HironobuBaba,
YusukeKinugasa, andMinoruTanabe
3
Summary
• Fluorescence imaging has become widely used during
endoscopic surgery as the introduction of a variety of
near-infrared endoscopic systems into clinical settings.
• The current models of the robot-assisted surgery system
are also equipped with a near-infrared imaging system,
which makes it even easier to use in clinical practice.
1 Introduction
In the early days of the indocyanine green (ICG) uorescence imaging techniques, the types of near-infrared imaging devices that could be used for surgery, especially for
endoscopic surgery, were quite limited, but nowadays, dedicated imaging devices have become commercially available
from various manufacturers. In this chapter, we will outline
the functions of the endoscopic uorescence imaging system
and show the features and practical applications of intraoperative uorescence imaging in our department.
2 Basis ofNear-Infrared Camera
Systems
rescence wavelengths, near-infrared light, which is often
used clinically, is characterized by its excellent tissue permeability and properties of the uorescence reagent. For example, ICG has the property of emitting uorescence in a
similar band by absorbing near-infrared light with 805nm as
the maximum absorption wavelength, and by observing it
with an infrared imaging system, it is possible to detect the
area where ICG exists (such as bile ducts where bile exists or
tumors where ICG accumulates) with a penetration of about
1cm.
The near-infrared laparoscopic systems designed for
detecting weak uorescence signals can have drawbacks in
the brightness and resolutions of white-light color images,
although these limitations are being improved in the latest
models of laparoscopic imaging systems. When selecting a
near-infrared laparoscopic imaging system, it is necessary to
be familiar with the characteristics of uorescence imaging
as described above and to consider the situations in which
the system will be used instead of normal observation based
on white-light color imaging.
3 Characteristics oftheNear-Infrared
Laparoscopic Imaging System
A near-infrared imaging system is designed to detect light
(uorescence) generated by irradiating an object with excitation light through a specic imaging lter. Among the uo-
S. Watanabe (*) · M. Tanabe
Department of Hepatobiliary and Pancreatic Surgery, Tokyo
Medical and Dental University, Bunkyo-ku, Tokyo, Japan
e-mail: shumsrg@tmd.ac.jp
T. Ogura
Department of Gastrointestinal Surgery, Saitama Cancer Center,
Ina, Kitaadachi District, Saitama, Japan
H. Baba · Y. Kinugasa
Department of Gastrointestinal Surgery, Tokyo Medical and Dental
University, Bunkyo-ku, Tokyo, Japan
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
T. Ishizawa (ed.), Fluorescence-Guided Surgery, https://doi.org/10.1007/978-981-19-7372-7_3
Table 3.1 summarizes the infrared imaging systems for laparoscopic/thoracoscopic surgery and robot-assisted surgery
that are currently available for clinical use in Japan. All of
these systems allow observation in full HD, support scope
diameters of 10mm and 5mm, and allow the use of oblique
views in addition to direct views. At present, only rigid
scopes are available for uorescence observation. Therefore,
in a situation where a exible scope is often used (e.g., laparoscopic hepatectomy), surgeons may have to adjust port
placement and scope manipulation. In addition, please note
that only a few imaging systems support adjustment and
measurement of uorescence signal intensity in the eld of
laparoscopic surgery.
13

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Table 3.1 Characteristics of near-infrared uorescence imaging systems for laparoscopic and robotic surgery, available in Japan
IMAGE1
S™ NIR/
Product
(manufacturer)
Image quality Hull HD Hull HD 4K UHD
Scope diameter 5mm,
Rigid/soft mirror Rigid Rigid Rigid Rigid Rigid Rigid Rigid
View direction 0° / 30° /
Superimposition n/a
Fluorescence
signal intensity
adjustment
Recording device Built-in n/a n/a n/a Built-in n/a n/a
Fluorescence
intensity analysis
Sales started Dec 2013~ Jan 2018~ Jan 2020~ Mar 2017~ Oct 2018~ Mar 2016~ Apr 2014~
Country of
manufacture
Price JPY
Note: Prices are for the minimum conguration (e.g., rigid mirror, camera head, light guide, imaging system, and display)
ICG (KARL
STORZ)
10mm
45°
n/a n/a Available n/a Available Available Available
n/a n/a n/a n/a Available n/a n/a
Germany Canada USA Japan Israel, USA USA Japan
12,000k
PINPOINT
(Stryker)
5.5mm, 10mm 10mm, 5.5mm,
0° / 30° / 45° 0° / 30° / 45° 0° / 30° 0° / 30° 0° / 30° 0° / 30°
◎ ◎
JPY
15,000~18,000k
1688 AIM4K
(Stryker)
(3840×2160)
5.4mm
JPY
12,000~15,000k
VISERA
ELITE II
(Olympus)
Hull HD Hull HD 3D HD
10mm,
5.4mm
〇
JPY
11,500k
VISIONSENSE
Iridium
(Medtronic)
5mm, 10mm 8mm 10mm, 5.4mm
◎
JPY 11,500k Standard in
da Vinci
Xi/X
(Intuitive
Surgical)
(SXGA)
Black and
white
display
(standard
mode)
the system
S. Watanabe et al.
CNOS-SK-1057
(Shinko Optical
Co., Ltd.)
Full HD
n/a
JPY 9400k
4 Clinical Experiences ofUsing
Laparoscopic Imaging Systems inOur
Center
In our department, we have tried four near-infrared imaging
systems for laparoscopy and conrmed their characteristics
(Figs.3.1 and 3.2).
Olympus and KARL STORZ install imaging systems that
enable observation with the same light source and camera as
their own conventional white-light endoscope systems, and it
is possible to change from the eld of view during normal
white-light imaging to uorescent imaging with one-touch
action. On the other hand, uorescence signals are displayed
on a dark background without full-color information, which
makes it difcult for surgeons to understand the spatial relationships with surrounding organs and the position of forceps during uorescence imaging.
The Stryker and EleVision™ IR Platform (sold as
VISIONSENSE in Japan) are especially focused on uorescence imaging, and the visualizability of near-infrared uorescence signals seemed to be very high. One of the features
of these two systems is that they enable superimposition of
uorescence images onto white-light full-color images,
which makes it easy for surgeons to go on surgical procedures using information obtained by uorescence imaging.
In conclusion from our clinical experiences, it would be
better to select a laparoscopic imaging system prioritizing
the quality of white-light color imaging in surgical procedures where the time and frequency of near-infrared imaging
are limited. In contrast, laparoscopic imaging systems with
advantages in near-infrared uorescence imaging (e.g.,
superimposition on full-color imaging) can be a promising
option when uorescence imaging is essential for assuring
the efcacy of surgery.
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