OPEN Research Support
head

Professor and Consultant
Jes Sanddal Lindholt
Department of cardiac, thoracic and vascular surgery, Odense University Hospital


Projekt styring
Projekt status    Sampling ongoing
 
Data indsamlingsdatoer
Start 01.09.2016  
Slut 31.01.2023  
 



Individualized prediction of rupture risk of abdominal aortic aneurysms based upon clinical variables and aneurysmal morphology

Short summary

Our aim with this project is to develop a highly individualized risk assessment tool to evaluate AAA's. A risk assessment tool that will encounter new aspects like: Individual risk factors. Relative-to-size risk. Wall shear stress. Wall strength.We want to do that by using existing finite element analysis technology, known from Car Crash simulations and transpose that to 4D-flow-MRI-scans.

Why? Because the only way patients with AAA's are risk assesset for now is by absolute diameter and growth-rate. And we know that if patients with an AAA greater then 55mm are left untreated, only half of them will rupture over time. And from time to time a medium-sized aneurysm rupture.


Rationale

An abdominal aortic aneurysm (AAA) is a permanent and progressive enlargement of the aorta. It is potentially life-threatening and when it progresses, the rupture risk increases. In the case of a ruptured AAA (rAAA), the mortality is close to 90%. When hospitalized and treated surgically, the mortality is still 40-50%.

The 2014 ESC guidelines for an AAA recommend, depending on size, a variation from an annual control to a control every 3rd year, to check for further expansion. Surgical treatment is advised when diameter exceeds 55 mm, performed as open surgery or endovascular treatment of the AAA.

Even when following advised treatment of surgery this is associated with 3-4 % mortality among the patients within 30 days postoperatively. 

Even though a large AAA is a potentially life-threatening enlargement that should be followed over time, left untreated, only half of the large AAA's will rupture over time. Furthermore, medium sized AAA's between 30 mm and 50 mm occasionally rupture unexpectedly.

This shows that further research is highly needed to assess a more individualized risk evaluation of a patient's AAA. Selecting the right patients is important, as the surgical treatment of an AAA is dangerous as well as expensive.

An AAA is usually defined as an abdominal aortic diameter >30mm. This rough estimation of an AAA has no relation to the individual patient, and the relative degree of dilation may be more associated with rupture, than the absolute diameter. If so, the definition of an AAA could easily follow the general definition of an aneurysm as a 50% dilation. This may show to be a much better definition, as the described natural history of cases greater than 30mm is very variable – however this needs to be proven as well as its association to rupture.

Although size matters – absolute or relative – the risk of rupture also relies on the strength of the wall. The last decades, various factors enhancing or decreasing the risk of rupture independently have been exposed: 

1. Demographic and clinical parameters:  Age, gender, BMI, smoking, diabetes, ischemic heart disease, hypertension, previous stroke, renal insufficiency, COPD and PAD 

2. Medication: Use of statins, and perhaps glucocorticoids and warfarin

3. CT based morphological signs: aneurysmal blebs, relative size to 4th lumbal or suprarenal aortic diameter, wall calcification, mural thrombus, and elongation 

4. The stress (force) on the aneurysmal wall – consisting of circumferential, longitudinal and the wall shear stress - all play a role in the stress of the aortic wall.

While the first three parts can be obtained by medical records and stored CT scans, the latter is more difficult as the three components varies individually. This has been challenged by bioengineers since the nineties using finite element analysis (FEA) – a simulation with is based upon splitting an item up in multiple small cubes. It is best known from the car-crash simulation and airplane construction and are based upon predictions of what will happen if a cube with known mechanical properties, is hit with a known force – for instance from the cube in front of it - it can predict what will happen with it, and which force that will hit the cube behind it.

Professor in Bioengineering, Christian Gasser, have developed such one for AAA (A4Vascops), a computational dividing the aneurysm into small squares, that allows calculation of the rupture risk in each square. However, it never obtained sufficient predictability. We believe this might partly be due to a very simple prediction of the strength of the wall and partly by not taking the individual flow pattern into consideration.

This research group has obtained exclusive rights to a software, when installed to a Magnetic Resonance imaging (MRI) scanner, we will be able to perform a 4D-flow scan. Then a non-invasive MRI-scan can provide individual dynamic patient-specific aneurysm geometry and flow data without having to submit the patient to harmful radiation and nephrotoxic contrast agents. With this unique opportunity it will be possible to avoid prediction regarding the individual flow pattern, as we can do an exact measurement.

One thing is the force that effects the wall of the blood vessel, another thing is the actually strange of the wall. The simple physics is; when the force that hits the wall exceeds the strange of the wall a rupture will accrue – that is why the strange of the wall is interesting. We have the equipment to do the tensometric measurements, thereby making it possible for us to obtain tensometric-data from wall samples from open AAA-repairs.

That can provide important data for completing a new and very individualized risk assessment, when every aspect is used in a prediction model.

Consequently, this research project hypotheses and aims to develop a game-changing individualized risk assessment tool by development of a novel multivariate prediction model for the strength of the wall based upon the identified factors associated with rupture, and not only integrate and validate that in A4Vascops FEA, but implement the most novel MRI technology into A4Vascops, assisted by national and international top-experts in MR-technology and FEA.

When validated and tested, we expect this project to provide a tool that can do highly qualified risk assessment of AAAs, thus we can offer a lenient endovascular treatment to high-risk-patients, before the AAA growth, expand and become a lethal threat.


Description of the cohort

Men and women with an abdominal aortic aneurysm or a ruptured abdominal aortic aneurysm.


Data and biological material

Medical Journals.

Measurements from CT-scans.


Collaborating researchers and departments

Department of Cardiothoracic and Vascular Surgery

  • PhD-student, Anders S. Bøvling

Department of Cardiothoracic and Vascular Surgery 

  • Professor in Vascular Surgery, Jes S. Lindholt

KTH Solid Mechanics, KTH Royal Institute of Technology, Stockholm 

  • Professor in bioengineering, PhD, Christian Gasser

Department of Cardiothoracic and Vascular Surgery, OUH 

  • Ph.D. student, MR phycist, Ernst-Torben W. Fruend

Research Centre of Individualized Medicine (CIMA), OUH 

  • Post. Doc, Cand. Scient, Lisette Bjerregaard

Department of Radiology, Viborg Hospital

  • Consultant in MR scanning, Lise Gammelgaard

Department of Vascular Surgery, Viborg Hospital 

  • Registrar Carsten Behr Rasmussen

Department of Vascular Surgery, Kolding Sygehus 

  • Professor in Vascular Surgery Kim Houlind