RESUMEN

ELABORACIN Y VALIDACIN DE UN MODELO PREDICTIVO DE RIESGO

DE RUPTURA EN EL ANEURISMA ARTICO ABDOMINAL, BASADO EN EL
ANLISIS DE LAS PROPIEDADES MORFOLGICAS Y BIOMECNICAS
INDIVIDUALES ESTIMADAS MEDIANTE TCNICAS DE MODELACIN Y
SIMULACIN NUMRICA A PARTIR IMGENES MDICAS
El Aneurisma Artico Abdominal (AAA) es una enfermedad que se caracteriza por
la dilatacin y deformacin progresiva y permanente de la arteria aorta en su
porcin abdominal, debido a la remodelacin inadecuada de la pared vascular.
Por lo general la enfermedad es asintomtica pero puede llegar a complicaciones
hemodinmicas bastante serias como la ruptura, asociada a una alta mortalidad.
El tratamiento es principalmente quirrgico y existen dos tipos: La ciruga abierta y
la reparacin endovascular (EVAR). La demostrada seguridad y eficacia en el
corto y mediano plazo para EVAR en comparacin a

la ciruga abierta han

postulado a la EVAR como un tratamiento de eleccin en el AAA asintomtico.

La eleccin de tratamiento con ciruga se basa en la estimacin de riesgo de
ruptura dado por el Dimetro Circunferencial Mximo. Sin embargo han surgido
preocupaciones justificadas acerca de este mtodo de estimacin de riesgo de
ruptura y as mismo sobre los beneficios asociados a EVAR en el largo plazo.
Estas discrepancias hacen que la decisin sobre el tratamiento en los AAA
asintomticos sea de una gran complejidad con mltiples factores que se deben
considerar y cierto grado de incertidumbre frente al resultado del tratamiento. De
acuerdo con esto, se hace necesario el desarrollo de mtodos ms precisos y
eficientes que puedan ser utilizados para la estimacin y prediccin de riesgo, y
que sirvan de soporte a la decisin clnica en favor o en contra de uno u otro
tratamiento. En este trabajo se propone elaborar y validar un modelo predictivo de
riesgo de ruptura en el AAA basado en el anlisis de las propiedades morfolgicas
y

biomecnicas

individuales

estimadas

modelacin y simulacin numrica a partir

cohorte de pacientes

mediante

diferentes

tcnicas

de

de las imgenes mdicas de una

Proposal Description for a DAAD

Research Short-Term Grant
Development and validation of a predictive model of
risk of rupture of Abdominal Aortic Aneurysm based on
morphological and biomechanical individual analysis by
geometrical modeling and numerical simulation from
medical imaging data
Andrs H. Gamboa Higuera

Figure used under Creative Commons Attribution-ShareAlike 3.0 Serbia License.

Content

1.

General Information

2.

Problem Statement

3.

Literature Review and State-of-art

4.

Theorical and Methodological Framework

5.

Hypothesis and Objectives

6.

Methods

7.

References

General Information
Information of the Applicant
Name Andrs H. Gamboa Higuera
Degree M.D; MSc Biomedical Engineering
Position Phd Candidate Biomedical Engineering
Birthday 9th June 1982
Place of Birth Bucaramanga, Santander (Colombia)
Nationality Colombian
Identification C.C 91509883
Address

Carrera 55 N 73-03 Casa 14

Phone Number 057 6314266

Mobile 057 3002174112
Email angamhi@posgrado.upv.es

Information of the Project

Title Development and validation of a predictive model of risk of
rupture of Abdominal Aortic Aneurysm based on morphological
and biomechanical individual analysis by geometrical modeling
and numerical simulation from medical imaging data
Field Medical Imaging, Numerical modeling and simulation
Director David Moratal PhD. Polytechnic University of Valencia
Advisors Dr. Ing Christian Cyron (Head of Emmy Noether Group);
Roland Aydin; M.D; MSc ; Post Doc; Vascular Growth a
Remodeling research Group, Technische Universitt Mnchen
University Polytechnic University of Valencia
Time Frame November 2014-November 2017

1. Problem Statement
Abdominal aortic aneurysm (AAA) is a disease characterized by dilation and
progressive and permanent deformation of the abdominal aorta due to impaired
vessel wall biomechanics caused by improper and unbalanced remodeling (1,2). The
disease is mostly asymptomatic, but its rupture can lead to serious hemodynamic
complications associated with high mortality (3). Diagnosis is usually incidental and
takes place in the study of other diseases (4-6). However, early diagnosis without
symptoms or complications has increased in the last years due to screening activities
(4). Treatment is primarily surgical, although small and stable aneurysms are suitable
for conservative treatment with medical supervision (7). Surgical treatment could be
either by Open Aneurysm Repair (OAR) or Endovascular Repair (EVAR) (7). Lower
morbidity and mortality are reported in the short and medium term for EVAR than for
OAR (8). These benefits have postulated EVAR as elective treatment modality for
asymptomatic AAA (8-11). Nevertheless, recent studies have shown that the rate of
rupture is higher in patients treated with EVAR than with OAR in the long term (12).
The decision of surgical treatment in asymptomatic AAA is based on the risk of
rupture, estimated from morphological characteristics obtained from medical imaging
(13). The most used is the Maximum Circumferential Diameter (MCD), with a cutoff of
5.5 cm associated to annual risk of rupture greater than average risk of perioperative
mortality of the elective therapy (13). However, aneurysms below the limit of 5.5 cms
also exhibit rupture with considerable frequency, and likewise, aneurysms of large
diameter can be maintained without rupture (14, 15). Surgeons have to balance the
risk of rupture with the inherent risk of elective therapy in AAA, but there are concerns
about current methods for AAA rupture risk estimation and the higher morbidity and
mortality associated to EVAR in the long term. More accurate methods that serve as
support for clinical decision, for or against one or other treatment are needed.

2. Literature review and state of art

A recent study of 8 years of follow up, reported higher mortality and morbidity
associated with EVAR than with OAR (12). Aneurysm rupture occurred in 5.4% of
patients with EVAR therapy against 1.4% of cases in patients with OAR (P <0.001).
4

Another study evaluating quality of life, found that results in physical function were
greater at six months in patients with EVAR therapy, but this advantage was lost at 12
months of follow up. (16). At one point it seemed that the benefits seen with EVAR
treatment in the short and medium term would be extended to long term, but today it
have raised concerns about complications associated with EVAR in long term. On
the other hand, discrepancies in MCD predictive ability have been reported in
literature. Scott et al. (17) reported a high rate of potential rupture of 2.1% per year for
the AAA with a diameter between 3.0 cm and 4.4 cm and a maximum potential
rupture rate of 10.2% in the AAA case with a MCD between 4.5 cm and 5.9 cm.
Moreover, in an autopsy study of four hundred seventy-three aneurysms without
intervention, it was observed that 13% of aneurysms with MCD less than 5.0 cms
ruptured, and 60% with MCD greater than 5 cms. remained intact (18). Although there
is a correlation between the MDC and rupture, the criterion does not adequately
predict the rupture in all cases because it does not consider other important aspects
that could be related to variations in the composition, remodeling or stability of
vascular wall, specifically for each patient, which are associated with the formation of
AAA (19). In the last decade a very promising method for estimating the risk of
rupture has appeared. It is based on the biomechanical analysis of the vessel wall, as
stress and strength distribution. In this regard, appear methods such as Finite
Element Analysis (FEA), applied to the specific reconstructed geometry of the AAA
from medical images of the patient, to calculate the stresses acting on the vessel wall
(20). This method allows analyzing specific and complex morphologies and their
influence in vessel wall biomechanics (20). Recently, studies have reported that some
biomechanical parameters are better predictors of rupture that the MCD (21). Vorp et
al. (22) reported that Peak Wall Stress (PWS) predicts rupture more accurately than
the MCD alone. Vande Geest et al. (23) reported d the Risk of Wall Rupture Index
(RWRI), which is the ratio between the PWS and Strength of the Wall (SW) to be
more reliable than the PWS parameter, since it was able to estimate the risk of
rupture locally and can discriminate the areas of greatest risk (24). It is a very
interesting tool that could help to the clinical decision in asymptomatic AAA.

3. Theorical and methodological framework

Clinical decision, in the case of AAA, is highly complex and not always easy to define,
since many factors are involved and there is also some uncertainty over the outcome.
Researchers and public health professionals use predictive analytics and inference
from clinical data to determine risk of developing certain events and to support clinical
decisions. But in the case of AAA there is no consensus on the best model for
predicting risk of rupture. The methods proposed today using biomechanical
parameters as PWS and RWRI allow very individualized risk analysis of rupture in
AAA, integrating several known risk factors and patients characteristics (gender,
family history, hypertension etc.) (25). Recently, a novel index,

Risk of Rupture

Equivalent Diameter (RRED)(26) have been described as the expression resulting

from the correlation of the individual RWRI with the AAA average diameter calculated
for a particular population that have the same RWRI, and the same biomechanical
risk of rupture. RRED facilitates clinical interpretation of biomechanical analysis and is
in connection with the state of art in estimating risk of rupture for AAA and decision of
surgical repair. RRED is postulated as an additional diagnostic parameter that can
provide more accurate clinical data to estimate the risk of rupture and decide surgery
in asymptomatic AAA (25, 26)). However, the role of these indexes predicting the risk
of rupture of AAA on individuals has not been sufficiently validated (27, 28). This
project aims to develop and validate a predictive model of risk of rupture in the AAA
based on analysis of individual morphology and biomechanics using different
modeling techniques and numerical simulation from medical images of a cohort of
patients.

4. Hypothesis and objectives

Null hypothesis: Biomechanical parameters of the vascular wall in AAA, specifically
Peak Wall Rupture Risk Index (PWRI) Rupture Risk Equivalent Diameter (RRED)
analyzed by computational methods are NOT predictive of risk of rupture.
Alternative hypothesis biomechanical parameters of the vascular wall in AAA,
specifically Peak Wall Rupture Risk Index (PWRI) Rupture Risk Equivalent Diameter
(RRED) analyzed by computational methods are predictive of risk of rupture
6

GENERAL OBJETIVE
Development and validation of a predictive model of risk of rupture in the abdominal
aortic aneurysm based on the analysis of individual morphological and biomechanical
properties using computational modeling techniques and numerical simulation
SPECIFIC OBJECTIVES
Development of a method for individualized mechanical and morphological analysis of
AAA using numerical modeling and simulations techniques applied to 3D geometric
representations of patients anatomy, obtained from medical imaging data sets.
Developing a dynamic and real-time database of AAA patients

5. Methods
STUDY DESIGN
The study is observational, analytical, and retrospective cohort from a single center.
The reference population is patients diagnosed with AAA treated in a Hospital in the
city of Bucaramanga, Colombia. The following variables are planned to be collected:
Variable

Type

Domain/Units/Formula

Death

Dichotomus

Yes=1; No=0

Surgical Treatment

Dichotomus

Yes=1; No=0

Surgical Technic

Dichotomus

Endovascular=1;

Open S= 2;

Hybrid: 3
Re internvention

Dichotomus

Yes=1; No=0

Rupture or complications

Dichotomus

Yes=1; No=0

Demographic
Variable

Type

Domain/Units/Formula

Age

Quantitative Continuous

18 - 110

Age by decade

Quantitative Ordinal

1= 18-30; 2=31-40; 3= 41-50;

4=51-60;

5=61-70;6=71-

80;7=Above 80
Height

Quantitative Continuous

140-210; centimeter(cms)

Weight

Quantitative Continuous

30-150 Kg

Body Max Index (IMC)

Quantitative Continuous

Weight/Height2

Morphological
Maximun

Circumferencial Quantitative Continuous

mm

Diameter (MCD)
Volume

Quantitative Continuous

mm3

Growth Rate

Quantitative Continuous

mm/year

Configuration

Dichotomus

1=Fusiforme; 2=Sacular

Quantitative continuos

N/cm2

Mechanical
Peak Wall Stress (PWS)

Risk of Wall Rupture Index Ratio Variable

PWS/WS

(RWRI)
Rupture

Risk

Equivalent Interval Variable

According to Curve

Diameter (RRED)

DATA COLLECTION AND PROCESSING: For data collection we will use electronic
medical records of the Information System from a single center, including information
from PACS (Picture Archieving and communication system). Data will be obtained
with different techniques for analysis, processing and modeling from medical imaging
performed in three steps: 1) Segmentation (mesh generation) 2) Analysis of
morphological characteristics (diameter and

volume) and

3) biomechanical

parameters.
STATISTIC ANALYSIS: Multivariate logistic regression analysis is proposed to
identify risk factors in a dynamic database of a Healthcare organization in Colombia.
VALIDATION: The study of the predictive ability of the morphological and
biomechanical properties will be held by AUC. The degree of prediction is determined
according to the classification of Swets for AUC.

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