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Intravascular
Ultrasound
From Acquisition to Advanced
Quantitative Analysis
Intravascular
Ultrasound
From Acquisition to Advanced
Quantitative Analysis
EDITED BY

SIMONE BALOCCO
Elsevier
Radarweg 29, PO Box 211, 1000 AE Amsterdam, Netherlands
The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom
50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States

© 2020 Elsevier Ltd. All rights reserved.

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This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted
herein).

Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in
research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods,
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ISBN: 978-0-12-818833-0

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Typeset by SPi Global, India

Contributors

The editor would like to acknowledge and offer grateful thanks for the input of all contributors,
without whom this first edition would not have been possible.
Simone Balocco Josep Lluís Gómez-Huertas
Department of Mathematics and Informatics, University InspireMD, Tel-Aviv, Israel
of Barcelona, Barcelona; Computer Vision Center,
Bellaterra, Spain Akira Iguchi
Terumo Corporation, Tokyo, Japan
R. Pawel Banys
Department of Radiology, John Paul II Hospital; Tomas Kovarnik
Department of Physics and Applied Informatics, AGH Second Department of Internal Medicine, Charles
University of Science and Technology, Krakow, Poland University, Prague, Czech Republic

 phane Carlier
Ste Su-Lin Lee
UMONS & CHU Ambroise Pare, Mons, Belgium EPSRC Center for Interventional and Surgical Sciences,
University College London, London, United Kingdom
Xavier Carrillo
Jurgen M.R. Ligthart
University Hospital Germans Trias i Pujol, Badalona,
Erasmus MC, Rotterdam, The Netherlands
Spain
John J. Lopez
Maria Elena de Ceglia
Stritch School of Medicine, Loyola University,
InspireMD, Tel-Aviv, Israel Maywood, IL, United States
Zhi Chen Josepa Mauri
Electrical and Computer Engineering; Iowa Institute for University Hospital Germans Trias i Pujol, Badalona,
Biomedical Imaging, University of Iowa, Iowa City, IA, Spain
United States
Adam Mazurek
Francesco Ciompi Jagiellonian University, Department of Cardiac &
Diagnostic Image Analysis Group, Pathology Vascular Diseases, John Paul II Hospital, Krakow,
Department, Radboud University Medical Center, Poland
Nijmegen, The Netherlands
Piotr Musialek
Wladyslaw Dabrowski Jagiellonian University, Department of Cardiac &
Jagiellonian University, Department of Cardiac & Vascular Diseases, John Paul II Hospital, Krakow,
Vascular Diseases, Department of Radiology, John Paul Poland
II Hospital, Krakow, Poland
Ricardo Ñanculef
Stamatia Giannarou Federico Santa María Technical University, Valparaíso,
Hamlyn Center for Robotic Surgery, Imperial College Chile
London, London, United Kingdom
Eric A. Osborn
Joan Antoni Gomez-Hospital Cardiovascular Division, Beth Israel Deaconess Medical
Interventional Cardiology Unit, Hospital de Bellvitge, Center, Harvard Medical School, Boston, MA,
Barcelona, Spain United States

ix
x CONTRIBUTORS

Lukasz Partyka Lukasz Tekieli

InspireMD, Tel-Aviv, Israel Jagiellonian University, Department of Cardiac &
Vascular Diseases; Department of Interventional
Petia Radeva Cardiology, John Paul II Hospital, Krakow, Poland
Department of Mathematics and Informatics, University
of Barcelona, Barcelona; Computer Vision Center, Giovanni J. Ughi
Bellaterra, Spain New England Center for Stroke Research, Department of
Radiology, University of Massachusetts Medical School,
Fernando Ramos Worcester, MA, United States
Department of Mathematics and Informatics, University
of Barcelona, Barcelona, Spain Beatriz Vaquerizo
Interventional Cardiology Unit, Hospital del Mar,
Josep Rigla Barcelona, Spain
Department of Mathematics and Informatics, University
of Barcelona, Barcelona, Spain Andreas Wahle
Electrical and Computer Engineering; Iowa Institute for
Juan Rigla Biomedical Imaging, University of Iowa, Iowa City, IA,
InspireMD, Tel-Aviv, Israel; Department of Mathematics United States
and Informatics, University of Barcelona, Barcelona,
Spain; InspireMD, Boston, MA, United States Karen Th. Witberg
Erasmus MC, Rotterdam, The Netherlands
Yuki Sakaguchi
Terumo Corporation, Tokyo, Japan Guang-Zhong Yang
Institute of Medical Robotics, Shanghai Jiao Tong
Elias Sanidas University, Shanghai, China
Department of Cardiology, LAIKO General Hospital,
Athens, Greece Honghai Zhang
Electrical and Computer Engineering; Iowa Institute for
Yusuke Seki Biomedical Imaging, University of Iowa, Iowa City,
Terumo Corporation, Tokyo, Japan IA, United States

Milan Sonka Ling Zhang

Electrical and Computer Engineering; Iowa Institute for Electrical and Computer Engineering; Iowa Institute for
Biomedical Imaging, University of Iowa, Iowa City, IA, Biomedical Imaging, University of Iowa, Iowa City,
United States IA, United States

Justyna Stefaniak Liang Zhao

Data Management and Statistical Analysis (DMSA), Center for Autonomous Systems, University of
Krakow, Poland Technology Sydney, Ultimo, NSW, Australia
Editor Biography

Dr. Balocco Simone is an associate professor in the

Department of Mathematics and Informatics at the Uni-
versity of Barcelona, and a senior researcher at the Com-
puter Vision Center, Bellaterra. He earned his PhD in
acoustics from the CREATIS Laboratory, Lyon and in
Electronic and Telecommunication from MSD Labora-
tory, University of Florence (Italy). He conducted a post-
doctoral research at the CISTIB Laboratory, Pompeu
Fabra University. Dr. Balocco’s main research interests
include pattern recognition and computer vision
methods for the computer-aided detection of clinical
pathologies. In particular, his research focuses on ultra-
sound and magnetic imaging applications and vascular
modeling.

xi
Acknowledgments

I am deeply grateful to “Captain” Juan Rigla, PhD, MD, a My heartfelt thanks to uncles Carlo Gatta and Fran-
great friend who coordinated the clinical part of the cesco Ciompi for being true brothers.
manuscript. Without his help, this book would not be Thanks go to Phillippe Delachartre, who transferred
possible. to me his passion for the research in IVUS so many years
I would like to thank all the contributors of this book ago. Thanks are due to Piero Tortoli, Christian Cachard,
for making possible this legacy for the new generation. and Olivier Basset, my mentors now and forever.
Thanks go to those who participated and those who I would also like to thank my family, Sara,
wanted but couldn’t. Some of them have been working Giampiero, and Gaetano, for encourage me all along
day and night, stealing time from their personal life, and this long journey.
putting aside work, family duties, patients for delivering
“⋯Tell me and I forget, teach me and I may remember,
the best result ever.
involve me and I will learn⋯.”
My special thanks go to Petia Radeva, the founder of
this research line in IVUS, for letting me complete the
BENJAMIN FRANKLIN
work that she started so many years ago.
Thanks are due to Fina Mauri and Xavier Carrillo,
who were the true motivators of most of this research.

xv
CHAPTER 1

Introduction
SIMONE BALOCCOa,b
a
Department of Mathematics and Informatics, University of Barcelona, Barcelona, Spain, bComputer
Vision Center, Bellaterra, Spain

Atherosclerosis, a disease of the vessel walls that causes boundaries, including cerebral, coronary, and cardiac
vessel narrowing and obstruction, is the major cause of interventions. In particular, an introduction for the non-
cardiovascular diseases such as heart attack or stroke. expert readers recalls the basics of this image modality.
Intravascular ultrasound (IVUS) is an intraoperative Special care was taken to describe the relevance of these
imaging tool that allows visualizing internal vessel problems, and to identify the locks that currently hinder
structures, quantifying and characterizing coronary pla- their realization.
que, and is useful for diagnostic purposes and image- The second section provides a deep overview of
guided intervention. intravascular ultrasound imaging systems analysis. It
The book focuses on imaging, treatment, and includes topics of the whole imaging pipeline, ranging
computer-assisted technological advances in diagnostic from the definition of the clinical problem and image
and intraoperative vascular imaging and stenting in acquisition systems, to the image processing and analy-
IVUS. Such techniques offer increasingly useful informa- sis, including the assisted clinical decision-making pro-
tion regarding vascular anatomy and function and are cedures and the treatment planning (stent deployment
poised to have dramatic impact on the diagnosis, analy- and follow-up). The book will conclude with new
sis, modeling, and treatment of vascular diseases. Com- research horizons and open questions.
putational vision techniques designed to analyze images The context of the book is transversal to several dis-
for modeling, simulating, and visualizing anatomy and ciplines, and specifically it covers several technological
medical devices such as stents as well as the assessment fields such as clinical intervention, catheter and IVUS
of interventional procedures therefore play an important system design, biomechanics, 3D visualization, tissue
role and are currently receiving significant interest. characterization, segmentation, plaque evolution and
The book brings together the advanced knowledge of rupture analysis, stent deployment, and planning.
scientific researchers, medical experts, and industry part- For these reasons, the book will be a compendium of
ners working in the field of IVUS in different anatomical the current state of the art in this research field and will
regions. be a perfect resource to get updated on the advances of
The book is organized into two sections: the first one the intravascular ultrasound and stent analysis topics.
includes a clinical perspective of the vascular disease, the Finally, our sincerest thanks go to the authors of all
current clinical workflow, and the main challenges chapters for their dedication to this project and to Else-
faced by the research community across anatomical vier for their support.

Intravascular Ultrasound. https://doi.org/10.1016/B978-0-12-818833-0.00001-1

© 2020 Elsevier Ltd. All rights reserved. 1
 SECTION I CLINICAL IVUS

CHAPTER 2

Clinical Utility of Intravascular

Ultrasound
a


ELIAS SANIDASa

STEPHANE CARLIERb

,
Department of Cardiology, LAIKO General Hospital, Athens, Greece, bUMONS & CHU Ambroise Pare
Mons, Belgium

1. INTRODUCTION 3 mm. However, the first transluminal images of human

Coronary angiography remains the gold standard imag- arteries were recorded by Paul Yock in 1988.2–4
ing method for the detection of coronary artery disease IVUS is considered a diagnostic imaging method that
(CAD) and its widespread clinical application has delivers real-time, high-resolution images of the coro-
steered patients to a host of beneficial interventional nary arteries and provides a precise depiction of the
medical therapies. Nonetheless, this approach only pro- morphology of atherosclerotic plaque.5 Its role begins
vides a two-dimensional image of the contrast-filled with pre-PCI imaging targeted to (1) measure the diam-
arterial lumen and does not visualize the arterial wall eter and the area of the lesion/reference segment, (2)
where largest atherosclerotic plaques are located. Conse- measure the length of the lesion, (3) evaluate the distri-
quently, angiography often underestimates the degree bution of plaque and presence of calcification, and (4)
of intraluminal stenosis and does not gauge the size estimate in vivo plaque composition and burden, iden-
of the plaque burden itself.1 tifying plaque characteristics associated with increased
Currently, intravascular ultrasound (IVUS) provides vulnerability.6 In order to further guide percutaneous
a more detailed assessment of CAD and has emerged procedures, IVUS will also be performed poststenting
as an essential diagnostic tool for understanding in order to (1) evaluate stent expansion, (2) assess side
coronary lesion morphology, deploying stents, and branch compromise, (3) assess the presence of coronary
solving postpercutaneous coronary intervention (PCI) dissection, and (4) determine the mechanism or stent
complications. restenosis or thrombosis (i.e., underexpansion).7–9
Historically, the first medical ultrasound application Notably, 2018 ESC/EACTS Guidelines on myocar-
was described in 1953 by Inge Edler and Carl Hertz, who dial revascularization recommend the use of IVUS to
introduced the recording of the motion pattern of car- detect stent-related mechanical problems in left main
diac structures along a single sound beam. This tech- coronary artery (LMCA) as class IIa with level of evi-
nique, known as supersonic reflectoscope, used short dence B.10 IVUS has also been shown to be an adjunctive
supersonic sound pulses that were generated by an elec- imaging technique for the crossing of coronary chronic
trically excited quartz crystal and delivered to the heart. total occlusions (CTO), the performance of complex
Part of the sound was reflected back to the quartz crystal aortic, carotid, and peripheral artery endovascular pro-
and the time difference between the emanation of the cedures without excluding even vein intervention.
sound pulse and the reception of the echo was a mea-
sure of the distance between the crystal and the reflect- 2. BASIC PRINCIPLES OF IMAGING
ing material. In 1971, the first true IVUS system was ACQUISITION
designed by Nicolaas Bom and Charles Lanc
ee in Rotter- In summary, the function of IVUS is based on the fol-
dam. It was conceived as an improved technique for the lowing general principles:
continuous visualization of cardiac chambers and valves • conversion of electrical energy into sound waves via
by a catheter with 32 elements with an outer diameter of piezoelectric crystals;

Intravascular Ultrasound. https://doi.org/10.1016/B978-0-12-818833-0.00002-3

© 2020 Elsevier Ltd. All rights reserved. 3
4 SECTION I Clinical IVUS

• transmission and detection of sound waves reflected the classical three-layer appearance of a normal coro-
by tissues using the same piezoelectric crystals, the nary artery by IVUS. Intimal thickening is the first path-
transducer, and converting back the received sound ophysiological change related to atherosclerosis. With
waves into an electrical signal; the accumulation of plaque, intima and IEL tend to
• amplification and processing of this electrical signal merge and the separation from the media is difficult
and conversion to an image; to assess.13,14
• projection of that image on the device’s computer The definitions of “reference segment” along with the
screen from where it can be analyzed or stored.5 most common measurements using IVUS are presented
There are two types of IVUS catheters: the mechani- in Table 2.15
cally rotated single-element transducer and the synthetic
steered phased array system (Fig. 1). The mechanical
catheter has a piezoelectric transducer placed at the edge 3. IVUS IN CLINICAL PRACTICE
of a flexible shaft that is rotated and advanced or with- Atherosclerosis, from the Greek ἀθ
ηρα, ath^era, meaning
drawn in order to scan the artery within a protective “gruel” and σκλ
ηρωσις, sclerosis or “hardening,” is by
sheath. The systems that have been used lately are essence a disease of the arterial wall while the lumen will
high-definition devices running at frequencies between only lately be compromised.16–18 Thus, an atheroscle-
40 and 60 MHz. The 20-MHz synthetic aperture array rotic lesion can evolve during years without any clinical
catheter has 64 tiny transducers permanently embedded symptom or flow limitation. Previous studies have
around the circumference of the catheter edge. Cross- reported that a coronary angiography performed weeks
sectional images are produced using an electronically before an acute myocardial infarction revealed that at
phased-array rotating beam forming without any neces- the culprit lesion there was only a mild to moderate
sary mechanical rotation of the catheter while advanced degree of stenosis in more than half of the patients
or withdrawn within the artery.11,12 The main features and as such an angiogram does not provide adequate
of the IVUS catheters are summarized in Table 1. prognostic information concerning future ischemic
A gray-scale IVUS image is formed from a codifica- events.19 Such conclusions have given rise to the notion
tion of the level of echogenicity of the radiofrequency that acute ischemic syndromes are the result of how
signal that is reflected by the tissues. Signals with low “vulnerable” an atherosclerotic plaque is to rupture
echogenicity are coded as dark gray or black, while and are less dependent on the degree of luminal steno-
highly echogenic signals are coded as light gray or white. sis.20 Several attempts of IVUS signal postprocessing
The strongest reflection of ultrasound comes from colla- have been reported to detect such vulnerable pla-
gen and calcium. The adventitia of the coronary arteries ques21–24; however, it is seldom used nowadays in a
is very rich in collagen and appears as the brightest struc- clinical setting. On the other side, numerous studies
ture in a noncalcified segment. The external elastic lam- and metaanalyses compared the clinical outcomes
ina (EEL) is lies between the adventitia and the media, between IVUS-guided and angiography-guided stent
mostly muscular, and typically echolucent (dark). In implantation with the latest results supporting the util-
normal, nonatherosclerotic arteries, the thickness of ity of IVUS to guide complex PCI procedures, yet
the media is typically 200 μm. The internal elastic lam- remaining underused25 (Table 3).
ina (IEL) separates the media from the most inner struc-
ture of the artery, the intima, covered by a single layer of 3.1. IVUS in Percutaneous Transluminal
endothelial cells. Intimal thickness increases with age Coronary Angioplasty
and it is typically 200 μm at 40 years of age producing IVUS could improve angiographic results by safely
upsizing the largest balloon for angioplasty once vessel
remodeling was taken into account, as demonstrated in
the CLOUT trial.26 Using balloons sized to the EEL
diameter, some advocated aggressive percutaneous
transluminal coronary angioplasty (PTCA) instead of
systematic stent implantation.27 Nowadays, with the
FIG. 1 Two types of IVUS imaging systems. (A) Mechanical
advent of DES that solved the issues of (1) late lumen
system with a rotating element; (a) cross-sectional image
provided by a mechanical system (Atlantis SR Pro Catheter
loss secondary to negative remodeling post balloon
iLab Ultrasound Imaging System). (B) Electronic system with angioplasty,28 and (2) in-stent restenosis process, such
a multielement array; (b) cross-sectional image given by an provisional angioplasty strategies based on IVUS or
electronic system (Eagle Eye Gold Catheter S5 System). physiological measurements29 are no more considered.
TABLE 1
Main Features of Available IVUS Catheters.
Eagle Eye Eagle Eye OPTICROSS OPTICROSS
Platinum Platinum ST Revolution Refinity ST Kodama AltaView (Boston HD (Boston
(Philips) (Philips) (Philips) (Philips) (ACIST) (Terumo) Scientific) Scientific)
Frequency 20 MHz 20 MHz 45 MHz 45 MHz 40–60 MHz 40–60 MHz 40 MHz 60 MHz
Maximum imaging 20 mm 20 mm 14 mm 14 mm 12 mm 12 mm 12 mm 12 mm
diameter
Diameter at 3.5F 3.5F 3.2F 3F 3.6F 3F 2.6F 2.6F
transducer 1.17 mm 1.17 mm 1.07 mm 1 mm 1.2 mm 1 mm
Tip entry profile 1.5F 1.5F 1.7F 1.9F 3.2F 2.6F 2F 2F
0.5 mm 0.5 mm 0.56 mm 0.64 mm 1.07 mm 0.86 mm 0.66 mm 0.66 mm
Tip-to-transducer 10 mm 2.5 mm 29 mm 20.5 mm 20 mm 20 mm 20 mm 20 mm
length
Working length 150 cm 150 cm 135 mm 135 mm 120 mm 155 mm 135 mm 135 mm
Wire lumen length 24 cm 24 cm 23 mm 15 mm 15 mm 15 mm 16 mm 16 mm
Maximum guide 0.01400 0.01400 0.01400 0.01400 0.01400 0.01400 0.01400 0.01400
wire
Minimum guide 5F 5F (ID  0.05600 ) 6F 5F 6F 5F 5F (ID  0.05800 ) 5F (ID  0.05800 )
catheter (ID  0.05600 ) (ID  0.06400 ) (ID  0.05600 ) (ID  0.06400 ) (ID  0.05600 )
Maximum Manual Manual 1 mm/s 1 mm/s 10 mm/s 1 mm/s 1 mm/s 1 mm/s
pullback speed
Flushing No No Yes Yes Yes Yes Yes Yes
necessary
6 SECTION I Clinical IVUS

3.2. IVUS in the Bare Metal Stent Era

TABLE 2 Intimal hyperplasia is the major underlying mechanism
Definitions of “Reference Segment” and of bare metal stent (BMS) restenosis. In BMS, percentage
Measurements by the Use of IVUS. of intimal hyperplasia volume averages 30% of stent
Reference volume and is consistently greater in diabetics than in
segment Definitions nondiabetics. In BMS that do not restenose, initial stud-
Proximal The site with the largest lumen ies showed that intimal hyperplasia remains stable or
reference proximal to the stenosis and within regresses slightly after 6 months for a period of up to
the same segment 2–3 years. Nevertheless, more recent quantitative angio-
Distal reference The site with the largest lumen distal
graphic data indicate a triphasic BMS luminal response
to the stenosis and within the same characterized by early restenosis, intermediate-term
segment neointima regression (from 6 months to 3 years), and
late re-narrowing (beyond 4 years).32
Largest reference The largest site of distal or proximal
reference
Most of the clinical trials from the BMS era (such as
CRUISE,33 TULIP,34 DIPOL,35 AVID36) showed a bene-
Average The average value of lumen at distal ficial effect of IVUS in BM stenting, mainly by achieving
reference lumen and proximal reference
larger acute lumen dimensions while avoiding increased
size
complications.32 The MUSIC trial37 was the first study,
Measurements followed by a sequence of many others later, that estab-
Lumen CSA The area bounded by lumen border lished IVUS criteria for optimal stent implantation.
Minimum lumen The shortest diameter of the lumen According to the proposed MUSIC criteria, excellent
diameter expansion is evident when the minimum lumen area
(MLA) in the stent is >90% of the average reference
Maximum lumen The longest diameter of the lumen
diameter
lumen area. All the proposed criteria for IVUS optimiza-
tion used in different studies have relied on distal
Lumen area (Reference lumen CSA minus reference or on mean reference vessel for stent or post-
stenosis minimum lumen CSA)/reference
dilatation balloon sizing. However, this fact reduces
lumen CSA
the potential to optimally increase the lumen size partic-
Plaque plus EEL CSA minus lumen CSA ularly in long lesions with overlapping stents and in ves-
media CSA sels with distal tapering.
Plaque burden Plaque plus media CSA divided by A metaanalysis of randomized trials comparing IVUS
EEL CSA with angiographic-guided BMS implantation (n ¼ 2193
Superficial The leading edge of the acoustic patients) showed that IVUS guidance was associated
calcium shadowing appears within the most with a significantly lower rate of angiographic resteno-
shallow 50% of plaque plus media sis, repeat revascularization, and overall major adverse
thickness cardiac events (MACE), but had no significant effect
Deep calcium The leading edge of the acoustic on myocardial infarction.38 Conversely, the results of
shadowing appears within the the OPTICUS trial did not show a significant difference
deepest 50% of plaque plus media between the angiographic- and IVUS-guided groups not
thickness supporting the routine use of ultrasound guidance for
Stent CSA The area bounded by stent border coronary stenting.39 Likewise, a large metaanalysis that
included five randomized trials and four registries with a
CSA, cross-sectional area; EEL, external elastic lamina.
total of 2972 patients found that the primary endpoint
(occurrence of death or nonfatal myocardial infarction)
was similar for both strategies at 6 months. Pooled data
On the other side, the importance of optimal lesion of individual cardiac endpoints showed a 38% reduced
preparation before stenting, using rotational atherect- probability of target lesion revascularization (TLR) in
omy, cutting balloons, or newer devices, has been iden- favor of IVUS-guided stenting, while death, nonfatal
tified and IVUS is a very important guidance tool to myocardial infarction, or coronary artery bypass graft
assess the results of these techniques.30,31 were equally distributed in both groups.40
 TABLE 3
Clinical End Points of Studies and Metaanalyses That Compared IVUS With Angiography Guidance in PCI.
MYOCARDIAL
RESTENOSIS RATE MACE INFARCTION MORTALITY RATE
IVUS Angio P- IVUS Angio P- IVUS Angio P- IVUS Angio P-
Study Year Patients Follow-up group group Value group group Value group group Value group group Value
Parise et al. 2011 2193 6–30 months 22% 29% .02 19% 23% .03 35% 44% .51 25% 17% .18
Mudra et al. 2001 550 6–12 months 24.5% 22.8% .68 NA NA NA NA NA NS NA NA .12
Casella et al. 2003 2972 6 months 0.6% 1% .2 15% 18.7% .03 4.1% 3.7% .5 0.6% 0.6% 1
Zhang et al. 2012 19,619 20.7  11.5 NA NA <.001 NA NA .008 NA NA .126 NA NA <.001
months
Hong et al. 2015 1323 12 months NA NA NA 2.9% 5.8% .007 NA NA NA 0.4% 0.7% .48
Steinvil et al. 2016 31,283 9–48 months NA NA <.001 NA NA <.001 NA NA <.001 NA NA <.001
Elgendy et al. 2016 3192 12–24 months 0.6% 1.3% .04 6.5% 10.3% <.0001 0.8% 1.5% .06 0.5% 1.2% .05
Bavishi et al. 2017 3276 1.4  0.5 years 0.6% 1.3% .15 6.5% 10.5% .0001 2% 2.4% .65 0.5% 1.2% .09
Shin et al. 2016 1170 12 months 0.3% 0.5% .32 0.4% 1.2% .04 0 0.4% .02 0.3% 0.7% .134
Witzenbichler 2014 8583 12 months 0.6% 1% .003 3.1% 4.7% .002 2.5% 3.7% .004 0.8% 1.2% .12
et al.
Maehara et al. 2018 8586 24 months 0.55% 1.16% .003 4.9% 7.5% .003 3.5% 5.6% .0006 1.7% 2.4% .03
Zhang et al. 2018 1448 12 months 1.5% 2.9% .07 2.9% 5.4% .02 1% 1.5% .34 0.7 1.4 .19
NA, nonavailable; NS, no significant.
8 SECTION I Clinical IVUS

3.3. IVUS in the Drug-Eluting Stent Era as compared with angiography-guidance alone was
Drug-eluting stent (DES) implantation is commonly associated with a reduced incidence of death, MACE,
associated with very few clinical events. IVUS predictors and stent thrombosis.47 The IVUS-XPL study demon-
associated with PCI failures and increased adverse out- strated that IVUS-guided DES implantation resulted in
comes with DES include stent underexpansion, nonuni- lower rate of MACE (2.8%, HR, 0.47 [95% CI,
form strut distribution, edge-related problems such as 0.27–0.82]; P ¼ .007, per protocol analysis) compared
residual reference disease (geographic miss) and dissec- to angiography-guided stent implantation (5.9%) at
tions, as well as acute and, especially, late incomplete 1-year follow-up among 1323 patients with long coro-
stent apposition (malapposition).9,41–45 nary lesions, primarily due to lower risk of TLR. In the
Stent underexpansion results from poor expansion post hoc analysis of the patients of the IVUS-guided
during implantation rather than from chronic stent group, those who did not meet the IVUS criteria had a
recoil and may be undetectable angiographically in significantly higher incidence of MACE compared with
many cases; suspicion may be raised in an area of fluo- those meeting the IVUS criteria for stent optimization
roscopically underexpanded stent struts (compared (4.6% vs 1.5%; HR 0.31 [95% CI, 0.11–0.86],
with the rest of struts) in the context of a calcified lesion P ¼ .02). These data support strongly IVUS guidance in
or an inability to fully expand the balloon inside the such lesions.48
stent. Nevertheless, the use of IVUS can be instrumental An updated metaanalysis of 7 randomized control
to detect underexpansion; despite good apposition of trials and 18 observational studies confirmed the above
the stent struts to the vessel wall, the underexpanded site data and found that IVUS-guided PCI was associated
would be evident by a stent cross-sectional area signifi- with better clinical outcomes including MACE, mortal-
cantly smaller than the vessel cross-sectional area in the ity, stent thrombosis, TLR, and target vessel revasculari-
same site, smaller than the stent cross-sectional area in zation than angiography-guided DES implantation.
other sites, and smaller than the reference lumen area. However, in a separate analysis that included only the
According to proposed strict criteria, excellent expan- randomized control trials, the observed benefit for
sion is evident when the MLA in the stent is 90% of MACE was driven only by reduced rates of revasculariza-
the average reference lumen area.44 tions.49 Similarly, a metaanalysis of seven randomized
A condition that needs to be differentiated from trials (n ¼ 3192) showed that IVUS-guided PCI was
underexpansion is stent malapposition; unlike underex- not inferior to angiography-guided PCI in reducing
pansion, there are stent struts not apposed to the vessel the risk of MACE (6.5% vs 10.3%) mainly due to the
wall (i.e., space occupied by blood can be detected reduction in the risk of TLR (4.1% vs 6.6%). The risk
between the stent struts and the arterial intima). Malap- of cardiovascular mortality (0.5% vs 1.2%) and stent
position cannot be judged angiographically (except in thrombosis (0.6% vs 1.3%) were also lower in the
very few extreme cases), typically occurs with use of IVUS-guided group.50
undersized stents or in arteries that have significant tor- ADAPT-DES was a prospective, multicenter,
tuosity and fluctuations of reference arterial lumen real-world study of 8583 consecutive patients at 11 inter-
diameter within the treated segment and is thought to national centers undergoing DES implantation that
predispose to stent thrombosis. However, no associa- investigated the frequency, timing, and correlation
tion was found between early or late incomplete stent between stent thrombosis and adverse clinical outcomes
apposition and stent thrombosis in 1580 patients post-PCI. During the index procedure, IVUS was used in
enrolled in IVUS substudies of various TAXUS clinical 3349 patients. IVUS performance resulted in longer stent
trials. Because both malapposition and underexpansion length and larger stent size without increasing periproce-
affect selected regions of a stent, it is entirely possible dural myocardial infarction. It was shown that IVUS guid-
that they coexist in two separate sites of the same stent ance led to less stent thrombosis (0.6% vs 1%) beginning
(i.e., proximal struts can be malapposed owing to large at the time of implantation, as well as fewer myocardial
and tortuous proximal reference sites, whereas the mid infarction (2.5% vs 3.7%) within the first year.51 The ben-
stent area at the original lesion site can be efits of IVUS guidance further increased with long-term
underexpanded).44,46 follow-up of up to 2 years.52
Whether IVUS compared to angiography guidance Currently, the ULTIMATE trial that included 1448
reduces stent thrombosis and improves clinical out- all-comer patients who were randomly assigned (1:1
comes associated with DES treatment has been investi- ratio) to either IVUS guidance or angiography guidance
gated over the years. In a metaanalysis of 11 clinical before DES implantation indicated a significant reduc-
studies (n ¼ 19,619), IVUS-guided DES implantation tion in MACE at 12-month follow-up in IVUS-guided
 CHAPTER 2 Clinical Utility of Intravascular Ultrasound 9

compared to angiography-guided group (2.9% vs 5.4%, States). IB-IVUS was applied to 18 samples of coronary
respectively, HR: 0.530; 95% CI: 0.312–0.901; artery and the results were compared with the corre-
P ¼ .019). In the IVUS group, TVF was 1.6% for patients sponding histological findings. The resulting IB-IVUS
with successful procedures versus 4.4% in patients who values were divided into five categories so that coded
failed to achieve all optimal criteria (HR: 0.349; 95% CI: color maps could be constructed: thrombus, intimal
0.135–0.898; P ¼ .029), namely MLA in the stented seg- hyperplasia or lipid core, fibrous tissue, mixed lesions,
ment >5.0 mm2 or >90% of the MLA at the distal refer- and calcification. The initial comparisons between angi-
ence segments, plaque burden 5 mm proximal or distal ography and IB-IVUS showed that the angioscopically
to the stent edge is <50%, and no edge dissection colored surface of the plaque reflected the thickness of
involving the media with a length >3 mm.53 In the the fibrous cap more than the size of the lipid core.59 Ini-
all-comers, open-label, single-arm SYNTAX II study that tially developed with the Boston Scientific Clearview
investigated the impact of a state-of-the-art PCI strategy system, IB-IVUS (IB-IVUS, YD Co, Ltd., Nara, Japan) is
on clinical outcomes in patients with triple vessel dis- now used with the VISIWAVE platform from Terumo
ease, final minimal stent area measured by IVUS was (Tokyo, Japan). With the ViewIT 40-MHz catheter
available in 819 lesions in 367 patients (53% of lesions, (Terumo, Tokyo, Japan), a comparison of IB-IVUS with
81% of patients). The single postprocedural MSA value histopathology shows that the sensitivity in the classifi-
that best separated lesions with TLR from those with no cation of calcification, fibrous tissue, and lipids was
TLR was 5.2 mm2.54 90%, 84%, and 90%, while specificity was 97%, 96%,
A large registry of more than 6000 patients undergo- and 86%, respectively.60
ing PCI with DES for complex lesions (defined as bifur-
cation, chronic total occlusion, left main disease, long 4.2. VH-IVUS
lesion, multivessel PCI, multiple stent implantation, VH-IVUS allows tissue characterization of vascular
in-stent restenosis, or heavily calcified lesion) reported lesions and is based on the spectral analysis of the pri-
recently that IVUS guidance lead to a significantly lower mary raw backscattered ultrasound wave
risk of cardiac death during 64 months of median (radiofrequency-based signal). This method has an esti-
follow-up (10.2% vs 16.9% with angiography-guided mated axial resolution (based on the resolution of the
PCI; HR: 0.573; 95% CI: 0.460–0.714; P < .001).55 With 20-MHz IVUS catheter) of approximately 200 μm
IVUS, the implanted stents had a significantly larger (Table 4). The spectral signatures of four tissue types
mean diameter (3.2  0.4 vs 3.0  0.4; P < .001) and (fibrous tissue, fibrofatty tissue, necrotic core, and dense
were more frequently postdilatated (49.0% vs 17.9%; calcium) were determined in vitro.21 These signatures
P < .001). are programmed in the software of the IVUS console
or on a stand-alone software package for off-line analy-
4. IVUS APPLICATIONS sis of patient data. Radiofrequency-IVUS plaque compo-
Gray-scale IVUS offers only a limited characterization of nents are color coded as dense calcium (white), necrotic
the atherosclerotic plaque composition and is unable to core (red), fibrofatty (light green), and fibrous tissue
detect the specific histomorphological features that are (dark green).61,62 Correlation between gray-scale and
associated with the rupture of vulnerable plaques, namely VH-IVUS imaging is shown in Fig. 2.
a large and lipid-rich necrotic core; a thin and inflamed Ex vivo validation of VH images directly with the his-
fibrous cap, rich in macrophages, that covers the necrotic topathology sections provided accuracies of up to 97%.
core; and neovascularization.56,57 For these reasons, Independent studies have demonstrated in vivo a rela-
novel IVUS techniques such as integrated backscatter tively high level of accuracy and reproducibility of
IVUS (IB-IVUS), VH-IVUS, iMap-IVUS, near-infrared VH-IVUS in human arteries utilizing directional coro-
spectroscopy-IVUS (NIRS-IVUS), and contrast-enhanced nary atherectomy specimens, yielding predictive accura-
IVUS (CE-IVUS) have been developed.5,11 cies of up to 95% in nonacute coronary syndrome (ACS)
patients.61 Of note, such a sequential assessment is
4.1. IB-IVUS impacted by precise co-registration of the histologic tis-
A tissue classification scheme based only on the analysis sue sample and the imaging. In adult atherosclerosis-
of the integrated backscattered (IB) signal, using a sim- prone minipigs, no correlation was observed between
ple surface scanner on carotid samples was primarily the size of the necrotic core determined by VH-IVUS
described in 2001.58 This methodology was developed and histology.63
with the integrated, rotating, 40-MHz IVUS catheter The PROSPECT trial tried to assess the natural history
from Boston Scientific (Fremont, California, United of atherosclerosis by studying 697 patients with ACS
10 SECTION I Clinical IVUS

after successful PCI of a culprit lesion under optimal

TABLE 4
medical therapy using angiography plus three-vessel
Detection and Technical Parameters of IVUS
imaging including gray scale and VH-IVUS. In patients
and VH-IVUS.
with ACS, both culprit and nonculprit lesions were
IVUS VH-IVUS equally likely to spur subsequent adverse events such
Detection as cardiac death, cardiac arrest, myocardial infarction,
or rehospitalization due to unstable or progressive
Lipid/necrotic core + ++
angina over 3 years. Independent predictors of a future
Fibrous cap + +++ cardiovascular event were plaques classified as
Thrombus + No VH-TCFAs (fibroatheroma without evidence of a fibrous
Calcium +++ +++ cap: >10% confluent NC with >30° NC abutting the
lumen in at least three consecutive frames) with a pla-
Plaque rupture ++ No
que burden >70% and an MLA <4 mm2.64
Attenuated plaque +++ No Similarly, the VIVA study was a prospective analysis
TCFA (thin-cap fibroatheroma) No ++ of 170 patients with stable angina or ACS who under-
went three-vessel VH-IVUS before and after PCI. At a
Dissection ++ No
median of 1.7 years, 19 lesions (13 nonculprit and 6 cul-
Stent expansion/apposition ++ No prit) resulted in major adverse cardiac events (MACE
Stent strut coverage + + including death, myocardial infarction, unplanned
Technical parameters revascularization). Nonculprit lesion factors associated
with nonrestenotic MACE were VH-IVUS thin-capped
Frequency (MHz) 20–45 20–45
fibroatheroma (TCFA), plaque burden >70%, and
Frame rate 10–30 10–30 MLA <4 mm2 suggesting that VH-IVUS can identify pla-
Pullback speed (mm/s) 0.5–1 0.5–1 ques at an increased risk of subsequent events.65 More
Axial resolution (μm) 70–200 70–200 recently, after a mean follow-up of 51  6 months of
86 patients with 89 intermediate lesions defined as
Tissue penetration (mm) >5 >5
30%–70% stenosis in coronary angiography, MACE
Ease of use +++ ++ were found to be significantly related to angiographic
Need for contrast No No diameter stenosis, fibrofatty area (FFA) but not necrotic
core, IVUS plaque burden 70%, and area stenosis
Notes: +: Limited possibilities only; ++: well suited; +++: excellent.

Fibro-fatty tissue
Calcium Fibro-fatty tissue

Lumen

Lumen
Calcium

Catheter

Fibrous tissue Necrotic core Fibrous tissue

Necrotic core

FIG. 2 Correlation between gray-scale IVUS and VH-IVUS imaging. These two cross-sectional frames depict
the same arterial location and allow visualization of a significant eccentric atherosclerotic plaque. Gray-scale
IVUS (left) can easily identify lumen and plaque borders, but VH-IVUS (right) provides additional information
regarding the compositional plaque characteristics.
 CHAPTER 2 Clinical Utility of Intravascular Ultrasound 11

50%. In a multivariable analysis, only FFA was inde-

pendently associated with the occurrence of MACE
(HR 1.36, 95% CI 1.05–1.77, P ¼ .019).66 The differen-
tial predictive value of the IVUS-VH-derived necrotic
core or fibrofatty components among different studies
illustrates the challenges of IVUS-derived tissue charac-
terization, from the reliability of the training dataset to
the complexity of the recognition algorithms67 with
underestimated issues initially such as the lack of
enough ultrasound signal for any spectral analysis
behind calcified lesions.68

4.3. iMap-IVUS
With this software, results are presented in a way similar
to the VH-IVUS system. However, there are differences:
it is based on a full spectrum analysis and the applied
color scheme shows (i) fibrous tissue in light green,
(ii) lipid tissue in yellow, (iii) necrotic core in pink,
and (iv) calcium in blue.23 Furthermore, the applied
IVUS catheter is a 40-MHz rotating single-element cath-
FIG. 3 Multimodality assessment in the catheterization
eter instead of the 20-MHz mechanical one used in
laboratory.An intermediate angiographic lesion located at the
VH-IVUS. Ex vivo validation demonstrated accuracies distal LCX (A). The MLA measured by IVUS was 4.0 mm2 and
at the highest level of confidence (97%, 98%, 95%, the plaque burden 63% (B). The related chemogram shows
and 98% for necrotic, lipid, fibrotic, and calcified yellow areas indicating lipid core plaque (C). Physiologic
regions, respectively).69,70 In a study of 87 patients, lesion assessment after intravenous administration of
iMap analysis showed that the ACS lesions had larger adenosine demonstrated a fractional flow reserve (FFR) of
lipidic and necrotic components compared to non- 0.80. The lesion was finally treated with a drug-eluting stent
ACS lesions.71 Among 63 patients with ST-segment (DES).
myocardial infarction (STEMI), iMap-IVUS detected a
higher percentage of necrotic tissue in culprit lesions 1000 measurements/12.5 mm and each measurement
that remained high after 10 months whereas the propor- interrogates 1–2 mm2 of lumen. The available LipiScan
tion of lipidic tissue decreased.72 It can also predict slow IVUS (InfraReDx, Inc., Burlington, Massachusetts,
flow, a serious complication of PCI that is correlated United States) combines a 40-MHz rotational IVUS
with poor prognosis.73 Finally, iMap evaluates the imaging system along with the NIRS advanced technol-
neointimal tissue after stent placement providing addi- ogy. This allows a complete visualization of coronary
tional insights.74 structure and plaque morphology together with a
detailed chemical map of the vessel for the simulta-
4.4. NIRS-IVUS neous detection and localization of LCP.61
Infrared region is the most reliable for the documenta- NIRS-IVUS is highly accurate in detecting LCP in
tion of complex molecules because each bond vibration human coronary arteries and show the existence and
contributes to a fingerprint of the molecule. Identifica- distribution of necrotic core, but not the amount or
tion of a lipid core plaque (LCP) is based on the distinc- the fibrous cap thickness. Increasing evidence is linking
tion of cholesterol spectral features differentiating LCP to vulnerable plaque, lesions at risk for emboliza-
cholesterol from the other chemicals present and espe- tion, and stent thrombosis. As part of a continuing goal
cially collagen. The NIRS-IVUS system provides real- to understand the linkage between NIR signals indicat-
time chemical measurements in the coronaries. It ing the presence of a lipid-rich plaque and subsequent
includes a console, a pullback motor unit, a rotation coronary events, the COLOR registry showed that the
device, and a catheter that automatically scans the artery absence of a lipid-rich plaque is associated with good
like IVUS. Spectra are processed by a specific algorithm prognosis. In particular, PCI performed in lesions with
trained in vitro75 and displayed as a chemical image of large lipid core was correlated with a 50% risk of peri-
lipid-rich plaque probability (called the “chemogram”), procedural myocardial infarction compared with only
which is depicted as yellow (Fig. 3). The system acquires a 4.2% risk in lesions without large lipid core.76
12 SECTION I Clinical IVUS

The CANARY study aimed to evaluate criteria for The implementation of this method in ACS patients
defining LCP that is at high risk of rupturing during demonstrated that CE-IVUS images could shed light on
standard-of-care therapy and causing intraprocedural the neovascularization of the adventitia and within the
complications such as distal embolization. According atherosclerotic plaque region. Hence, CE-IVUS can pro-
to this study, plaques responsible for periprocedural vide important information concerning the presence of
myonecrosis were lipid rich and had a large plaque bur- a vulnerable plaque and cardiovascular risk
den and a small MLA. However, nonlipid rich plaques stratification.81
could evoke a substantial proportion of myocardial
infarction.77
Finally, the LRP study is a prospective, multicenter 5. IVUS ASSESSMENT OF PLAQUE
trial that was designed to investigate the correlation PROGRESSION
between LCP and the occurrence of MACE. It included
Ultrasound waves from IVUS catheters can travel deep
1563 patients with suspected CAD (46.3% stable
enough to image completely the thickened atheroscle-
angina) that underwent angiography and possibly PCI
rotic vessel wall and study atherosclerosis progression.1
for an index event. All the patients were evaluated with
Several studies have indicated the value of IVUS in eval-
IVUS-NIRS to assess the vessel structure and the plaque
uating plaque volume regression over time using differ-
composition and were followed for 2 years. According to
ent treatment. The IVUS-derived rate of progression of
this trial, the risk for a nonculprit or unstented MACE
atherosclerotic burden is a surrogate end point that
event was 18% higher with each 100 unit increase in
could reflect the beneficial clinical impact of the inves-
maxLCBI4 mm (maximum lipid burden in any 4 mm
tigated therapies.
subsegment). However, the risk in case of a vulnerable
Early reports have described a reduction in the lipoid
coronary segment was 45% higher with each 100 unit
components and an increase in fibrous tissue after statin
increase in maxLCBI4 mm. Of note, the risk in a coro-
therapy.85 The REVERSAL trial was the first double-
nary segment with a maxLCBI4 mm >400 was 422%
blind randomized multicenter study that demonstrated
higher than a segment with a lesser maxLCBI4 mm.78
a difference in the effects of two statins (atorvastatin vs
pravastatin) administered for 18 months.86 The IVUS-
4.5. Contrast-Enhanced IVUS derived change in atheroma volume showed a signifi-
Neovascularization in an atherosclerotic plaque has cantly lower coronary plaque progression rate in the
been linked to plaque growth and instability and atorvastatin group. The ESTABLISH trial that included
contrast-enhanced IVUS (CE-IVUS) is a proposed ACS patients showed that aggressive lipid-lowering ator-
method for the detection of vasa vasorum (VV), the vastatin therapy decreased significantly the plaque vol-
microvessels that nourish the vessel walls. CE-IVUS is ume after 6-month follow-up, positively correlated
based on the infusion of contrast microbubbles, which with the LDL level.87 The most important changes in
can cause an increase in the echogenicity of selected IVUS measurements (progression and regression) were
regions on the IVUS images that include atheromatous seen in the ASTEROID trial. Among patients with an
plaques. It is able to record qualitatively and quantita- ACS or stable CAD who received intensive therapy with
tively the flow (presence) of microbubbles in human rosuvastatin, LDL level decreased by 53% while mean
atherosclerotic plaques, mainly within the microvessels percentage atheroma volume for the entire vessel was
and neovasculature using specially developed software lower by 1%  3%.88
for this purpose (Fig. 4).79–82 IVUS plaque regression has been also investigated
The perivascular network was examined using with other therapies such as ezetimibe and PCSK9
CE-IVUS in an animal study that aimed to detect blood inhibitors. The PRECISE-IVUS study revealed a greater
flow into the coronary lumen and perivascular flow. plaque regression combining ezetimibe with statins
A statistically significant enhancement was found in probably due to the most aggressive lipid-lowering
the echogenicity of the total perivascular space (adven- effect because of the inhibition of cholesterol absorp-
titial region and perivascular vessels), as indicated by an tion by ezetimibe.89
increase in gray level intensity after microbubble injec- Additionally, the GLAGOV trial showed that among
tion.83 A recently published study also showed that 868 patients with CAD, the addition of evolocumab to
CE-IVUS images could detect aortic wall neovasculariza- statin therapy resulted in a significant decrease in LDL-C
tion in rabbits being in agreement with histological levels (93.0 vs 36.6 mg/dL) and the primary efficacy
data.84 parameter, the nominal change in percent atheroma
Another random document with
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 Ja päästä vuoden,
Jos Luoja suo sen,
Hän saapuu tänne hääsanan tuoden.
Mut siihen asti
Mun ahkerasti
Kutoa täytyvi joutuisasti.
NUOR' ASTRI

Nuor' Astri astuvi nurmea,

Käy tuuli vallaton lehdosta.
»Ah terve, tyttöni herttainen!
Suo suortuvillas mun leikkiä,
Hajalleen hiuksesi viskellä,
Kai sallit sen?
Nyt olet soma,
Kenen lietkään oma?»

Nuor' Astri kulkevi hyräillen,

Kedon kukkaset nyökkivät tuoksuen.
»Hyv' iltaa, neitinen suloisin!
Kai saavut seppelen solmintaan,
Käy siskojas kainoja poimimaan!
Voi kuitenkin,
Kuin sorja, soma!
Kenen lietkään oma?»

Nuor' Astri kietovi kiehkuraa,

Mies uljas metsästä ratsastaa.
»Yks kukka suokaa — ma rukoilen
Olette ruusunen itsekin,
Sen poimisin kyllä, jos tohtisin,
Ah neitinen!
Sa armas, soma,
Mun ollos oma!»
AMOR

Keväällä herää Amor,

Levittää kultasiivet,
Olalle heittää jousen
Ja selkään nuolilaukun.
Näin lähtee maailmalle
Sydänten pyydäntähän.

Voi, väisty, tyttö kulta!

Pakohon pian juokse,
Kun Amor saapuu luokse!

Vaan varotus on turha,

Sä sokkosilmin kuljet,
Et huomaakaan, kun Amor
Jo jousen jännittääpi
Ja hymyhuulin tähtää — —

Nyt sattui jo. Sä huudat,

Poveesi kättäs painat
Ja pakoon joutuin juokset.
Se myöhäistä vaan ompi,
Sydämeen nuoli painui —
Voi sua, kaunis kevät!
Voi sua, häijy Amor!
SYDÄMENI HALTIA

On sydämessäni mulla
Pien' haltia herttainen.
»Minut irti päästä jo, tyttö!»
Hän pyytävi kolkuttaen.

»Voi, Amor, kylmä on talvi,

Lumen helmassa lepää maa.» —
»Vähät siitä! Kun hankeen hengin,
Kevät kerkeä taas palajaa.» —

»En lempeä leikkiä taida,

On synkeä mieleni mun.» —
»Ah, unhota pois, ma onneen,
Elon riemuhun kutsun sun.» —

»Voi, Amor, jo kuihtui tyttös,

Katos ruususet poskiltain.» —
»Elä huoli, ne kukkivat jälleen,
Minut irti päästähän vain!»
KEVÄÄN LAPSET

Kaks lasta on kevähällä,

Nuor poika ja neitonen.
He yhdessä kulkevat mailmaa,
Käsi kädessä astellen.

Kuin kuohuva koski on poika,

Raju, hurja ja vallaton,
Joka jänne uhkuvi voimaa,
Ja säihkyä silmissä on.

Meren kahleet jäiset hän murtaa,

Puron vilkkaan hyppiä suo,
Kevätmyrskynä myllertääpi,
Vapautta luontohon luo.

Vaan tyttö on hentonen, hieno,

Kuin henkäys läntisen,
Siro, kaino ja hellämieli
Kuin kukkiva kielonen.

Hän veljensä jäljissä hiipii,

Puut lehtihin suutelee,
Kevätruohoa maasta nostaa
Ja umpuja aukaisee.

On voiton varmuutta heissä,

Keväthenkeä lämmintä,
Sitä talven jää ei kestä,
Sen pakko on väistyä.
SEITSENTOISTAVUOTIAS

Olet hento ruusunen keväimen,

Viel' uinuva ummussaan,
Säde päivän lehtiä suutelee
Ja kutsuvi puhkeemaan.

Olet lintunen viel' emon suojissa,

Mut mieli on lentohon,
Oma siipi jo taitaisi kannattaa,
Pesä ahtahaks käynyt on.
LÄPI VERHOJEN

Hän ikkunalaudalla istuu

Mun tyttöni vallaton.
Ja valkea ikkunaverho
Hänet puoliks peittänyt on.
Väliin sieltä vaan kurkistaapi
Tuo pienonen kutripää,
Hän veitikkamaisesti katsoo
Ja nauraa ja hymyää.

Voi, veitikka on hän suuri

Ja viistoista vuotinen.
Hän mailmaa vielä katsoo
Kuin lävitse verhojen.
On ruusunväriä verhot,
Ja siksipä kaikki muu
Myös hänelle ruusuiseksi
Ja kaunihiks kuvastuu.

Vaan kuulehan tyttiseni,

Jos verhot nuo poistetaan
Kenties ei jäljelle jääkään
Kuin mustaa ja harmaata vaan?
Hän nauraa ja päätään puistaa. —
Kai turhaa väitellä on.
Ei uskois hän sitä sentään,
Tuo tyttönen vallaton!
ELÄMÄ ON IHANA

Huoneessa ahkerasti
Ompelet, neitinen,
Poskilla kukkii ruusut
Raittihit nuoruuden.

Valoisa mieles ompi,

Lämmin ja hehkuva,
Elämä armas lienee,
Ihanaa maailma.

Hetkeksi heität työsi,

Kadulle katsahdat, —
Hautajaissaatto kulkee,
Suruisna saattajat.

Valkoinen, kaunis arkku,

Vihreät seppeleet,
Kellojen soitto kaikuu,
Tulvivat kyyneleet.

Hetkeksi hymy häipyy,

Huuliltas, neitinen.
Mutta jo kohta jälleen
Ompelet hyräillen.

Kuinkapa voiskaan nuorna

Muistella kuolemaa?
Lempeä sydän sykkii,
Eloa aaltoaa.
SINIKELLO

Sinikellonen kasvaa
Lomassa louhikon,
Louhia laine huuhtoo,
Virta käy vallaton.

Puhdasna, viatonna
Taistelun telmeessä,
Kohoat kuvastellen
Taivahan sineä.

Uneksit auringosta
Kallion suojassa,
Kuilu kuin lähell' ompi
Sitä et aavista.
ILTA TUNTUREILLA

On hehkua täynnä taivas,

Kuin tulessa tunturit.
Kun tietäis, tuoko se poudan,
Vai vinheät vihurit?

Myös mulla on hehkua mieli

Ja tunnetta tulvillaan.
Kun tietäis, viekö se onneen,
Vai suruhun katkeraan?
LIEDEN ÄÄRESSÄ

Takassa tuli palavi,

Räiskyellen, riemuellen.
Minä katson kaihomielin,
Tuijotan tulen kisahan.
Sydämessä lemmen liekki,
Tuli polttava povessa.

Kyselen tulelta tuolta,

Arastellen, aavistellen:
»Mitä tuonetkin minulle?»
Viluiselle voinetkohan
Luoda lämpöä, valoa,
Surujen tytönkin tehdä
Onnesta osalliseksi? —
Vai tuli tuhosa lienet,
Kalvava, kiduttavainen,
Rauhan ryöstätkin minulta?

Takassa tuli palavi,

Räiskyellen, riemuellen.
Sen voin kyllä sammutella,
Mut en liekkiä sydämen,
Polttoa oman poveni.
PIKKU VÄINÖ

Pikku Väinö, hetkiseksi

Lakkaa leikeistäsi,
Tule tänne! Otsalleni
Paina lämmin käsi.

Sydän mulla sairas ompi,

Päätä pakoittaapi,
Mutta hellä hyväilysi
Haihtumaan sen saapi.

Kirkas, avoin, lapsellinen,

Viel on katse sulla,
Tylyn mailman monet murheet
Ei voi luokses tulla.

Pikku Väinö, kulta Väinö,

Istu polvellani!
Paljon, paljon parantuupi
Sua katsoissani.
LINNOJA LAATIESSA

Kivestä linnaa laadin

Huviksi lapsosen,
Korskana kohoo torni,
Taivasta tavaten.

Linna on hetken työtä,

Kaatuvi piankin,
Korkeat tornit, muurit,
Sortuvat pirstoihin.

Suretko, lapsi, sitä? —

Elähän kuitenkaan.
Linna jos särkyy, voihan
Rakentaa uudestaan.

Toista on sitten kerran

Suureksi tultua,
Linnoja laitellessa
Haaveista, onnesta.

Särkyvät nekin linnat,

Mailmassa murtuvat,
Vaan ovat ehjiks saada,
Korjata vaikeat.