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PAPAVER
Perspectief CARISMA 11630
PAPAVER
Progression in image Analysis for Percutaneous Aortic ValvE Replacement
Applicants
Dr. H.A. Marquering
Dr. Ir. H.C van Assen
J. Baan MD PhD
AMC, Biomedical Engineering & Physics, Radiology
PO Box 22700, 1100 DE Amsterdam; +31 (0)20 566 51 82
[email protected]
TU/e, Dept of Biomedical Engineering
PO Box 513 NL, 5600 MB Eindhoven; +31 (0)40 247 25 16
[email protected]
AMC, Cardiology
PO Box 22660, 1100 DD Amsterdam; +31 (0)20 566 91 11
[email protected]
No support has been applied elsewhere for the research described in this proposal
1. Summaries
Research Summary
Transcatheter Aortic Valve Implantation (TAVI) is a valuable alternative therapy for patients with severe
aortic valve stenosis and high operative risk: It provides sustained clinical and hemodynamic benefits in
1,2
selected high-risk patients declined for conventional aortic valve replacement . However, the TAVI
procedure is associated with potential adverse effects, such as paravalvular leakage, coronary
obstruction, and conduction disorders. Yet, with the recent clinical procedural advances in catheter
systems and prosthetic valves, imaging and image analysis support for TAVI is lagging behind. Imaging
and image analysis are needed to reduce these adverse effects, facilitating optimized patient selection,
and efficiently define image based prognostic values. Furthermore, a standardized sizing of the aortic root
dimensions is lacking. As a result, only few automated tools supporting TAVI image measurements exist.
We propose to study, develop, and validate novel quantitative image analysis methods providing the clinic
with quantitative numbers on risk factors to optimize patient treatment and limit adverse outcome. In
specific, we will study new methods for automated sizing, quantify aortic valve calcium providing new
prognostic imaging biomarkers, optimize fluoroscopy angulation, and analyzing LV dynamic parameters
focusing on local dynamics in particular.
At the end of the project we expect to have (1) software prototypes for a standardized and automated
sizing of the aortic root dimensions; (2) methods to determine and predict pre- and postprocedural LV
dynamic parameters to that can be used for prognostic analysis; (3) quantitative measurement tooling for
the amount and pre- and postprocedural distribution of valve leaflet calcifications. These tools will result in
an optimization of various stages of the TAVI procedure, improved patient and treatment selection,
eventually leading to improved patient outcome.
Utilization Summary
Transcatheter aortic valve implantation has proven to be a valuable therapy for high risk patients. In view
of the growing cohort of aging patients with degenerative valvular disease, this novel treatment is
increasingly applied. To date, over 20,000 patients have been treated worldwide with this novel therapy
and promising results have been reported. We aim to come with automated and validated analysis
methods to analyze the pre-, peri- and postprocedural imaging providing the clinic with novel approaches
to support the TAVI procedure and generate novel prognostic image biomarkers.
We have formed a consortium with multiple industrial partners, multiple clinical departments, and three
image research groups from two academic institutes. The strong involvement of the cardiology
department and the cardiothoracal surgery department ensures that imaging research subjects are
clinically relevant and are continuously evaluated by potential users. Our consortium includes two imaging
companies: 3mensio offers the state-of-art solution for CT-based TAVI patient selection and manual
sizing. Pie Medical Imaging has imaging solutions for perioperative procedures with extensive experience
in bringing high-tech solutions to the interventional catheterization room. Furthermore, with its experience
in cardiovascular hemodynamics, HemoLab provides the possibility to perform controlled experiments
with the valve placement under high resolution imaging in ex-vivo beating heart experiments as well as
validation of software prototypes using phantom models and in-vitro equipment. Within this field new
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Perspectief CARISMA 11630
knowledge and technology will be directly utilized by HemoLab in performing contract R&D. Medtronic is
one of the two manufacturers of transcatheter valve prosthesis and has a strong Dutch involvement.
During the project, we will develop multiple prototypes. These prototypes ensure industrial and clinical
feedback at an early phase to evaluate the functionality. Furthermore, they allow our clinical partners to
conduct research with cutting edge image analysis methods. The results of this applied clinical research
will be published allowing the establishment of a new standard in the image analysis TAVI support. These
prototypes will also be used to start validation studies during the course of the project. Finally, novel
academic algorithms will be presented as libraries that can be integrated in current commercial products
facilitating a commercial introduction. Concluding, our proposal has a large utilization potential with a
continuous involvement of clinical partners, multiple industry partners, and academic applicants with
proven track records in transferring high-technology methods to commercial clinical products.
2. Composition of the group
Academic Partners
Department
University
Fte
Dr. H.A. Marquering
Dr. G.J. Streekstra
Dr. Ir. M. Siebes
Prof. Dr. Ir. C.A. Grimbergen*
Dr. Ir. H.C. van Assen
Prof. Dr. Ir. B. ter Haar Romeny*
Prof. Dr. L.M.J. Florack
Clinical Partners
Dr J. Baan
Dr. Z.-Y. Yong
Dr. M Groenink
Prof. Dr. Mr. B.A.J.M. de Mol*
Dr. K. Lam
Industrial Partners
F. Wessels
L. Verstraeten
J.-P. Aben
Dr. J. de Hart
H. van Heusden
Biomedical Engineering & Physics, Radiology
Biomedical Engineering & Physics, Radiology
Biomedical Engineering & Physics
Biomedical Engineering & Physics
Biomedical Engineering
Biomedical Engineering
Mathematics and Computer Science
Department
Cardiology
Cardiology
Cardiology, Radiology
Cardiothoracal Surgery
Cardiothoracal Surgery
Company
3mensio
3mensio
Pie Medical Imaging
HemoLab
Medtronic
AMC
AMC
AMC
AMC
TU/e
TU/e
TU/e
University
AMC
AMC
AMC
AMC
AMC
City
Bilthoven
Bilthoven
Maastricht
Eindhoven
Heerlen
0.2
0.1
0.05
0.05
0.2
0.05
0.1
0.1
0.05
0.05
0.05
0.05
* Promotor
The PAPAVER consortium has strong academic, clinical and industrial expertise. Within the research
team we expertise in all relevant research areas: cardiovascular image processing (Marquering, van
Assen), mathematical image processing (Florack, ter Haar Romeny), medical physics (Streekstra,
Grimbergen), cardiovascular hemodynamics (Siebes), and radiology (Groenink). The applicants
Marquering en Van Assen have a strong background in combining applied academic and industrial
research. At the AMC the focus is on applied image processing. The TU/e has an extensive expertise in
research on fundamental image processing issues, in particular on cardiac dynamics analysis.
The clinical partners have already a comprehensive experience in the aortic valve replacement
procedure, both in clinical practice as in fundamental research. This consortium has a firm industrial
component: 3mensio has the state-of-art preprocedural image analysis tool, Pie Medical Imaging
provides periprocedural imaging support and tools for cardiac segmentation for functional analysis
support, and HemoLab is expert in the field of the hemodynamics of the aortic valve prosthesis. Medtronic
is one of the two manufactures of medical approved transcatheter aortic valve implants.
Available infrastructure
The AMC is one of the 5 Dutch medical centers that is certified for TAVI by the Dutch Health Care
Inspectorate. As a result, there is a large patient population indicated for this specific procedure. We
have the special situation that valve replacements are performed transfemoral as well as
transapical. As a result, all patients are carefully considered in a large multidisciplinary team. Image
analysis has here an essential role to determine the patient specific optimum trajectory;
At the AMC, a valuable cooperation has been established between technological and clinical
researchers and physicians;
For all patients that are eligible for TAVI, dynamic CT scanning is performed resulting in 10 multi
phase dynamic 3D images of the heart and large vessels per patient. The AMC is equipped with
state-of-art 64 slice CT scanners from both Siemens and Philips, and a 3.0 Tesla MRI scanner;
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The Biomedical engineering departments both at the TU/e ad at the AMC have an extensive library of
specialized image processing tooling. The TU/e has libraries of specialized mathematical image
processing tooling and prototypes for the analysis of local cardiac dynamics from 3D and 4D MRI.
The AMC has functionality for the analysis of cardiac and vascular anatomy and morphology in 3D
and 4D CTA images;
The BMIA group has joined a TU/e cross-divisional research consortium: Image Science &
Technology Eindhoven (IST/e) headed by Luc Florack, which combines strengths of four imagerelated research groups at the departments of BME and Mathematics and Computer Science.
Together these groups cover the spectrum of MR acquisition, biomedical and mathematical image
analysis, algorithms and visualization.
HemoLab has developed extensive expertise and infrastructure in performing ex-vivo beating heart
experiments for various valve replacement studies.
3. Scientific Description
Medical Background
Aortic valve stenosis (AS) is a leading cause of morbidity and mortality worldwide. Up to 30-40% of the
patients with severe AS are denied for surgery because of high operative morbidity and mortality risk and
3,4
subsequently have a poor prognosis . Recently, the minimally invasive transcatheter aortic valve
implantation (TAVI) has proven to be a valuable alternative to surgical procedures for patients in this highrisk category and is increasingly performed on the population of patients with severe comorbidities. The
first exploratory procedures have proven to be successful and this procedure has passed the early stage
of clinical application.
Despite the early indications that TAVI provides sustained clinical benefits, the procedure is associated
with a number of adverse effects:
1. A clinically relevant potential side effect of TAVI is the development of leaking of the aortic valve,
known as aortic regurgitation (AR). In 5% - 10% severe AR may occur immediately after valve
5
implantation and may lead to serious, life-threatening problems .
2. An infrequent but lethal acute complication is the coronary ostium occlusion by a native calcified
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valve leaflet requiring emergency coronary intervention . The reasons for this complication are related
to procedural events or patient anatomy such as bulky calcifications on aortic valve cusps, low lying
coronary arteries, and narrow and short sinus of Valsava.
3. TAVI is commonly associated with electrophysiological defects resulting in a need for permanent
pacing or even in perioperative mortality;
4. Incorrect sizing may result in implant migration and even aortic root rupture.
The native aortic valve of most patients eligible for TAVI suffers from severe calcifications. There is
growing evidence that the presence of extensive calcification is associated with multiple adverse
7
8
outcomes such as increased likelihood of paravalvular regurgitation and conduction disorder . Moreover,
severely calcified valves can pose an increased resistance during the deployment and it can prevent a
7
sufficient apposition of the transcatheter prosthesis . However, there is currently little knowledge on the
exact mechanisms of these defects. In the proposed research, the evaluation of distribution and amount
of aortic valve calcifications and its impact on the adverse effects is of special interest.
Much more than in the surgical approach, imaging plays a pivotal role at multiple stages of TAVI, starting
from the patient selection up to the follow-up imaging for the postprocedural evaluation. Without a direct
access of the aortic root, image-based positioning with respect to the aortic valve annulus is a crucial step
because once deployed it is not possible to adjust the valve implantation. Surprisingly, despite its utmost
importance, the imaging and automated image analysis has received relatively little attention to date and
is subject to significant improvements.
Main Goals of the Project
Research Objective
Currently, TAVI related image analysis is lagging behind relative to clinically advances, lacking
functionality for a state-of-art automated risk analysis, planning, and on-site imaging of this procedure.
We aim to research and develop quantitative image analysis methods for the advancement of multiple
stages of the TAVI procedure (See figure 1). Furthermore, special attention will be given to the analysis of
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Figure 1: Schematic overview of the role of imaging and image analysis for the TAVI procedure
aortic valve calcifications, providing quantitative tooling to explore its role in adverse post-procedural
effects and incomplete valve deployment in particular.
Preprocedural image analysis
Patients that are eligible for TAVI have a high-risk of perioperative complications. Therefore, it is
mandatory to accurately select candidates to optimize the TAVI results and minimize the procedural
complications. Also, sizing is of utmost importance for TAVI: Stability of the prosthesis with optimal
coverage and the least paravalvular regurgitation relies on
the choice of the appropriate valve size and accurate
"Compared to the transcatheter valve
implantation height. Current (manual) sizing approaches
replacement procedure, the actual
are laborious, tedious and prone to significant
patient selection is a much more difficult
interobserver variability. Therefore, we aim to develop
automated segmentation techniques for patient and
task" Cardiothoracal surgeon AMC
technique selection, risk stratification, and sizing.
Accurate sizing is not straightforward: The aortic root has a complex 3-dimensional structure (Fig. 2 and
3). The diameter at the base of the aortic root, also known as the aortic annulus is the most common
10
measure for sizing . The aortic annulus is not a true anatomical entity; it is defined as the virtual ring
connecting the nadir of the aortic leaflets. Furthermore, the aortic annulus and its connected Left Ventricle
Outflow Tract (LVOT) are non-circular but rather oval shaped. Because of its complex crown-like
11,12
anatomical structure, true 3D imaging and sizing is mandatory
. It has been demonstrated that the
minimum and maximum diameter of the annulus differ between 5 to 8 mm. Therefore, a 2D measurement
13
may have a substantial bias on the chosen prosthesis size . It has even been shown that sizing on 3D
13
instead of 2D increases the number of patients that are eligible for TAVI .
Fig 2: Opened and spread aortic root. The valvular
leaflets have been removed showing the semilunar
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nature of the attachments .
Fig 3: Schematic overview of aortic root illustrating
how the attachment of the valve leaflets incorporates
aortic wall and ventricular tissue.
The manual alignment of the annulus plane is the most tedious task in current 3D sizing approaches. We
plan to come up with automated methods to present the physician with a well-defined annulus plane as a
starting point for the aortic root measurements. Subsequently we will determine methods for the
automatic measurements of aortic root and LVOT dimensions and eccentricity, sinus height, and
ascending aorta diameters. We will also study and develop methods for automatic determination of the
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Figure 4: Illustration of a proof of concept manual tool to
quantify and classify aortic valve calcifications.
Figure 5: A "bull's eye" representation of the density and
size of aortic valve calcifications. The calcifications are
labeled by their leaflet (NC, LC, RC) and distance to the
aortic wall.
leaflet length to coronary ostium ratio to rule out that a bulky calcified cup exceeds the distance between
its base and ostium. The automatic determination of the annulus plane also anticipates on the
periprocedural fluoroscopy projection angle to reduce preparation time for fluoroscopy and reduce the
amount of iodinated contrast volume, which is all for the patient's benefit.
14
Statistics have shown that severe native valve calcification is strongly related to adverse outcomes and
can thus be considered as an important biomarker for risk stratification. However, the exact mechanisms
of how the calcifications cause these problems are unknown. Furthermore, the current quantitative valve
calcification measurement is very coarse (scale from 0 to 4), performed by "eyeballing" and ignores the
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calcification distribution . In this research we are planning to focus on the quantification of aortic valve
calcifications. A manual tool has already been developed for an initial proof of concept to quantify and
label the aortic valve calcifications (Fig. 4 and 5). We will use this approach as a head start to develop
automated aortic valve quantification and position labeling. The quantitative numbers on the calcium
amount and distribution will be related to peri- and postprocedural success in subsequent clinical studies.
Periprocedural imaging and image analysis
The TAVI procedure is performed in the catheterization lab with supporting capabilities such as mobile
fluoroscopy and transesophageal echocardiography. The actual positioning of the aortic valve prosthesis
is guided by bi- or mono-plane fluoroscopy. The optimal projection angle of the angiographic system is
difficult but crucial: it should be chosen such that all three sinuses are visualized (Fig. 6). We propose to
register pre- and periprocedural images to predict optimal angles to visualize all three valve leaflet cusps:
The detection of the annulus plane in preprocedural CT allows the determination of the optimal projection
angle. Additionally, the optimal projection can be extracted based on 3D reconstruction of the aortic root
obtained from two angiographic projections. Figure 6 shows some results of a proof of concept as
developed by Pie Medical Imaging.
Figure 6. The left shows an illustration of the optimal projection in which all three sinuses are aligned. In the middle
and on the right, the proof of concept is shown in which the optimal projection angle is extracted during the
intervention procedure.
Postprocedural imaging and image analysis
Because there is currently no valve specific surgical risk score, risk assessment for TAVI is a complex
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and suboptimal task . Prognostic factors to predict symptomatic improvement are not known. There is a
great need for novel validated and quantitative risk prognostic values. However, prognostic analysis is
difficult without knowledge of long-term successes because TAVI is a recently introduced procedure and
treated patients generally have comorbidities limiting life expectancy
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To improve prognosis estimation and patient selection, we propose to perform functional assessment of
the LV to quantify patient improvements due to TAVI. LV dynamics are generally considered a predictor
of long-term postprocedural outcome. We will use MR to assess ventricular and valvular function and
myocardial perfusion. We will develop tooling to monitor the midterm and long-term response to the TAVI
procedure by comparing pre- with postprocedural MR yielding additional indications based on the preoperative status of the global and local function of the LV.
It is hypothesized that the postprocedural calcium distribution
has a strong effect on adverse effects. Unfortunately, it is
difficult to predict the postprocedural position of the calcified
native valve after implantation of the prosthesis. We will use
follow-up CT scanning assess the calcium distribution after
valve
implantation.
Straightforward
evaluation
of
postprocedural calcification distribution is hampered by
blooming artifacts of the valve stent obscuring the calcified
plaques (Fig. 7). We will study and develop methods for
postprocedural visualization and quantification of the
calcification distribution. This distribution allows prognostic
analysis of calcification distribution as a predictor for TAVI
adverse effects.
Methods
Figure 7. Postprocedural CT image
displaying native calcifications after TAVI.
The beam hardening artifacts hinder the
straightforward evaluation of the native
calcifications.
Current mathematic morphological methods to segment the
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ascending aorta and LVOT will be used as a starting point for
quantitative image analysis for sizing of the aortic dimensions.
Mathematical anatomical models of the aortic root will be developed to facilitate the automatic analysis of
a segmented aortic root in 3D and 4D CT images. These models make will be developed using the large
data base of available CT images. The automated analysis will generate:
The position of the leaflets by matching using a crown-like leaflet model in the aortic root;
The orientation of the annulus plane using the detection of the three aortic leaflet bases;
The distance to the ostia by making use of the typical anatomy of the aortic sinus.
The orientation of the detected annulus plane is subsequently used to determine optimal angulation of the
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angiographic viewing angles . With the segmented aortic root and detected position of the native valve,
the calcifications can be detected using straightforward thresholding techniques in combination with
information of the position. Multiple features from the calcium distribution will be extracted such as its
size, its density distribution, and the distance to the aortic wall.
For the postprocedural calcium visualization and quantification, we will apply a combination of stent
19
20
modeling and image subtraction . We will develop subtraction techniques in which an analytical model
of the valve stent including CT related artifacts is matched with the images and subsequently subtracted.
The analytical stent model will developed based upon multiple CT images of standalone stents.
We will study the placement of the aortic valves with various degrees of calcified plaques using beating
heart models. These placements will be performed under high resolution 2D and 3D imaging to follow the
deformation of the native aortic valves. We will come up with calcium detection algorithms and methods to
label the shape, size and distribution in the aortic root area.
To monitor TAVI success, we will assess functional imaging parameters and effects of altered flow across
the valve prosthesis on LV hemodynamics and perfusion on MR. Functional imaging, LV segmentation
and quantitative flow analysis will be performed with current available Pie Medical Imaging's CAAS MR
software. In addition, development and evaluation of an advanced image analysis toolkit to determine
21-23
improvement of LV diameters and systolic and diastolic function imaging methods will be developed
.
22,23
A prototype for myocardial motion and strain analysis has recently been developed
, which will be
used as a point of departure for the further exploration of LV functional analysis. This toolkit will involve
detailed and high-resolution cardiac LV motion and deformation analysis from MR images (e.g. cine,
tagging, and phase contrast) including confidence measures. In addition to MR, a feasibility study using
the LV dynamics analysis for echocardiography image data will be performed.
Initial visual inspection of postprocedural MR scans does not seem to reveal serious data compromise.
However, should postprocedural MR image data be compromised by the implanted valve prosthesis, the
echocardiology route will be pursued in more detail. Well-known biomarkers will be investigated, such as
global wall-thickening, ejection fraction, myocardial mass, stroke volume. In addition, novel local
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biomarkers related to perfusion, contraction, strain rotation will be developed. These biomarkers will be
evaluated in relation to the functional response to the valve replacement intervention.
Prototypes and validation
24
HemoLab's PhysioHeart platform plays a substantial role in this project. The PhysioHeart platform is a
working heart model based on isolating slaughterhouse pig hearts and resuscitating the hearts up to
physiological performance levels, allowing the TAVI procedure to be performed under high-resolution 2D
and 3D imaging. During the beating heart experiments cardiac output, LV pressures, coronary flow,
myocardial perfusion, and P-V loops will be recorded to assess LV dynamics and electrophysiological
defects. The ex-vivo beating heart experiments allows acquisition with multiple imaging modalities and
will be used for (1) pre-procedural morphological and dynamic analysis validation, (2) implantations
carried out under different conditions enabling to visualise and study the effect of AV calcifications, and
(3) validation of cardiac functional performance assessments. For this goal, the PhysioHeart model will be
made MR compatible. Because pig heart valves are rarely calcified, human calcification simulations shall
be performed and postmortem calcified aortic valves will be implanted in the heart models.
The validation of the algorithms is an important issue in this project. CT size and MR dynamics
measurements will be validated using (1) in-vitro phantoms developed by HemoLab, (2) ex-vivo beating
heart models, (3) comparisons with manual measurements, and (4) inter- and intra- observer variability
studies. During the project we will generate approximately dynamic CT scans of 300 patients, and MR
scans of 100 patients. To this end we will create multiple prototypes within the 3mensio Valves
workstation environment to generate clinical feedback and to evaluate the success of our approach. With
these multiple prototypes, clinical validations will be carried out during the running of this project.
Furthermore, LV dynamics will be evaluated using both digital and physical phantoms.
Aortic root phantoms models will be developed for basic image protocol development and large scale
technical validation. To this end, casts from the aortic roots will be developed. These models will be
applied for high-resolution imaging regarding anatomical characterization for type and size of valve
selection and for assessing possible adverse effects and risks with e.g. coronary ostium occlusions.
Allocation of tasks
The research will carried out in close collaboration of the AMC and TU/e. The AMC will focus mainly on
CTA image analysis. Research on MR image analysis shall be performed by our team at the TU/e. two
months. At the end of every year milestones have been defined resulting in prototypes. These prototypes
will be used by the physician scientist for validation and prognostic analysis. Throughout the project, the
scientific programmer will develop libraries based upon the researched algorithms. We plan to have
regular meetings with the entire research group every two months, while the PhD students and the direct
supervisors will have meetings more frequently to exchange of findings throughout the project.
Publications are expected in years 2, 3, and 4.
Connection with other research
This research is embedded in the AMC programs "Cardiovascular Diseases" and "Diagnosis and
Treatment of Coronary Syndromes".
A clinical AMC research program on aortic valves has been approved by the medical ethical
committee and subsequently started.
A close collaboration exists with Dr. Jean Claude Laborde (Toulouse, France). He was one of the
inventors of the CoreValve and has extensive preclinical and clinical experience with percutaneous
implantation, having performed over 200 percutaneous valve procedures.
This study is related to the long-term CTA-based neurovascular research that is carried out at the
AMC in cooperation with the radiology and biomedical engineering & physics departments.
This research is embedded in the recently formed Imaging Science and Technology Eindhoven group
(IST/e), which is a collaboration of the imaging related groups at the TU/e departments of Biomedical
Engineering and Mathematics & Computer Science.
This project perfectly fits in the cardiovascular research line at BMIA (TU/e) which is built on
segmentation and dynamics analysis for pathology detection and localization, treatment selection,
treatment guidance and –response, jointly coined “clinical decision support”. TU/e is currently setting
up a TU/e broad Health Institute. Cardiovascular research will have a prominent place in this institute.
4. Fit within the research topics of the program
This project focuses is related to three CARISMA themes. The proposed research has a strong focus on
analysis of preprocedural images to support the surgical procedure, thus fitting theme 4: Improved
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guidance in image guided interventions. The automated image analysis will be performed on 3D and
4D CT and MR image data and therefore fits in research theme 2: 3D & 4D cardiovascular image
analysis. Furthermore, the postprocedural imaging and calcification quantification is applied to determine
new prognostic indicators to predict the expected procedural success and therefore fits in theme 3.
5. Utilization plan
Valvular heart disease is an important cause of morbidity and mortality worldwide. Symptomatic severe
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aortic stenosis has a bad prognosis with a mortality rate of 25% per year . Because of high operative
morbidity and mortality risk, the high-risk up to 30-40% patients are rejected for surgery. Transcatheter
aortic valve implantation procedures have been among the main therapeutic breakthroughs of the last
decade providing a feasible alternative therapy to patients with severe symptomatic aortic stenosis and
high operative risk. Currently, TAVI is a rapidly evolving field with almost exponentially increasing
numbers of treated patients. The first exploratory procedures have proven to be successful and this
procedure has passed the early stage of clinical application: To date up to 20,000 patients have been
treated with this novel. TAVI has the potential to create a paradigm shift similar to introduction of
26
percutaneous coronary angioplasty in the early eighties .
Although imaging has a pivotal role in the TAVI procedure, there is a lack of image analysis support.
Automated, standardized and validated quantification is very valuable to improve patient selection and
sizing. We believe that we have the fortunate position to develop standard automated solutions which will
be adopted by the clinic and industry.
Full involvement of our clinical partners ensures an early utilization of researched and developed
methods. At the AMC we have the fortunate situation that we have medical staff software engineers and
physics researchers working together. Prototypes based upon 3mensio Valves workstation will be
developed. These prototypes can be used by our clinical partners for research purposes and for clinical
practice. This ensures early feedback, assessment of feasibility, and the availability of automated
methods to be used in clinical research leading to publications. The publication of clinical research
studies may help to set the standard for future analysis enabling a speed up market introduction.
Validated algorithms will be documented and described in detail. Dynamic linked libraries will be provided
to the industrial partners for evaluation and/or integration in the partner's products. Multiple beta versions
of the analysis algorithms will be created for the evaluation by our clinical partners. These will be used for
validation studies and results will be published in clinical journals. Dr L. van Garsse is a cardiothoracal
surgeon at the MUCM has agreed to join our user committee. Both the AMC and the MUMC are one of
the 5 Dutch hospitals that is licensed to perform TAVI. Her presence in the users committee will facilitate
the widespread knowledge transfer in the Netherlands.
Pie Medical Imaging is dedicated to the development and sales of quantitative analysis software to
support medical professionals with the diagnostic process and applied treatment and to facilitate research
to study the efficacy of modern interventions. Pie Medical Imaging will provide us with their current state
of the art analysis system for quantitative analysis support during the interventional TAVI procedure. The
result of this project provides important information about optimizing patient treatment, novel validated
analysis methods and novel prognostics image biomarkers. Pie Medical Imaging sees this as important
addition to provide the optimum software solution during the interventional TAVI procedure.
3mensio and Pie Medical Imaging will provide us with their current state-of-art analyses systems for
advanced image analysis. Developed methods will be integrated in their current systems to create
prototypes with novel analysis functionality. HemoLab will contribute their expertise, infrastructure, and
hardware for the beating heart experiments. The close contacts that we have with the commercial
partners guarantees a natural route from prototypes to validated commercial products.
3mensio has recently established a co-marketing agreement with Medtronic such that the 3mensio
workstation will be used in the TAVI training for cardiologists. In this way we can introduce new
functionality to the clinical environment in an early stage, also enabling an early acceptance in the clinical
environment. Furthermore, Medtronic therapy development specialists will be equipped with a 3mensio
Valves workstation in which new developed functionality can smoothly be integrated. Medtronic, which
manufactures one of the two commercially available valve prostheses, will use the results in the training
of cardiologists and cardiothoracal surgeons to optimize the treatment and patient selection.
Past performance
27-29
Dr. Henk Marquering
is assistant professor cardiovascular image analysis at the department
Biomedical Engineering & Physics and the Radiology department at the AMC. With a background as a
researcher in large industry, SME and academics, Dr Henk Marquering has an extensive experience in
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the utilization of research algorithms in commercial environments. He has headed a research group on
image analysis and pattern recognition for Océ research, he has set up the CTA group at the LKEB
(LUMC), was the lead developer and researcher at 3mensio for the development of CTA applications for
surgery planning, including the 3mensio valves workstation. He has developed algorithms and software
that has been integrated in multiple commercial image analysis applications. Furthermore, as an
academic researcher he has lead the team to develop a specific arterial in-stent restenosis software
application for Core Lab research, utilizing methods and algorithms researched and developed in
academic projects. He was project leader of the SENTER-IS project ADVANCE (Automatic diagnostic
vascular analysis of CTA Examinations) and initiated the awarded project CADASTR (Computer aided
diagnosis for coronary CT angiography and risk stratification: an image fusion approach, STW 2008).
30,31
Dr Hans van Assen
is assistant professor cardiovascular image analysis within the Biomedical Image
Analysis (BMIA) group at the department of Biomedical Engineering of Eindhoven University of
Technology. His focus is on segmentation, motion and deformation quantification, and statistical
modelling for computer aided detection of cardiac pathology. He did his PhD working on statistical
modelling for cardiac LV image segmentation. He publishes in the major conferences and journals.
Currently, he supervises, a.o., a PhD project on cardiac left atrium segmentation, which is a joint effort
between TU/e and Philips Healthcare, and specifically aims at utilization by inclusion of the resulting tools
in existing Philips Healthcare software. Hans van Assen has experience with thorough validation of
developed methods and transfer of knowledge to industry. He developed peripheral vascular analysis
algorithms, now part of QAngio® XA software package currently marketed by Medis.
8,16,32-35
Dr. Jan Baan
is staff interventional cardiologist at the AMC, who has performed over 2000
percutaneous coronary interventions. He set up and leads the transcatheter heart valves program in the
AMC, incorporating a research protocol which was approved by the Medical Ethical Committee. He has
performed a total of 125 transfemoral and transapical aortic valve implantations and mitral valve clips. He
is the supervisor of two PhD students who perform basic and clinical research in this research. He was
organizer of the Percutaneous Valve Symposium, including performance of live cases (October 2009). He
is teacher at the Dutch CardioVascular Research Institute. Dr. Jan Baan has experience in measurement
of left ventricular and coronary hemodynamics in animal studies and in patients.
The biomedical engineering and physics group of the AMC have generated numerous successful
applications in the biomedical field of which we will describe a few:
Localization of electrical activity in the heart by combination of radiography, catheter mapping and
body-surface mapping (STW, Prof.dr.ir. C.A. Grimbergen). This project has resulted in a system for
the reconstruction of 3D electrical activity distribution in the heart using multichannel intracardial and
body surface electrocardiograms. The software that was developed during this program is currently
used in multiple laboratories all over the world and is at the stage that commercialization is feasible.
Closed chest coronary surgery on the beating heart: technical development of an automated bypass
grafting methods (STW, Prof.dr. C. Borst, Dr.Ir. G.J. Streekstra et al). During this project an end-toside coronary artery bypass grafting method was studied. Devices have been developed which have
been patented. A start up is created to develop and produce these automated grafting devices.
Automated systems for red blood-cell deformability measurement (Prof. Dr.Ir. C.A. Grimbergen, Dr. Ir.
G.J.Streekstra et al). Within this program equipment was developed to measure the deformation an
aggregation of red blood cells in flow. A system based on light scattering by blood suspensions (the
LORRCA system) is commercialized and by a Dutch company (Mechatronics Instruments BV).
The Biomedical Image Analysis group has numerous previous experiences in bringing research results
into industrial practice together with Philips Healthcare, e.g., in the analysis of abdominal aorta
aneurysms and pulmonary emboli detection. At the BMIA continuously a number of PhD students have
worked in collaborative projects between Philips Healthcare and BMIA. The recent QANU (Quality
Assurance Netherlands Universities) assessment report of the Department of Biomedical Engineering of
Eindhoven University of Technology evaluated the BMIA group in 2010 as excellent, with an evaluation
score of 19.5 out of 20.
6. Contracts and patents
A provisional patent search has not revealed any patents that obstruct our approach. In the course of the
project, it will become apparent if results will be patentable. All project members do not have any
contracts with any industry that may hinder this research.
PAPAVER
Perspectief CARISMA 11630
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PAPAVER
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33
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effective orifice area. Submitted for publication.
9. Key words, abbreviations and acronyms
AMC
AR
AS
AVC
AVR
BMIA
CT
CVD
Academic Medical Center (Amsterdam)
Aortic Regurgitation
Aortic Valve Stenosis
Aortic Valve Calcification
Aortic Valve Replacement
Biomedical Image Analysis
Computed Tomography
Cardiovascular Disease
LV
LVOT
MRI
PCA
TAVI
TEE
TTE
TU/e
Left Ventricle
Left Ventricle Outflow Tract
Magnetic Resonance Imaging
Percutaneous Coronary Angioplasty
Transcatheter Aortic Valve Implantation
Transesophageal Echocardiography
Transthoracic Echocardiography
Technical University Eindhoven
Keywords: Transcatheter aorta valve implantation, CTA, MRI, quantitative image analysis, treatment
support, cardiovascular imaging, image guided interventions, local cardiac dynamics, aortic valve
calcifications.