Medical Physicist and Radiologists, a winning team: definition of a new biomarker for the assessment of small

aortic aneurysm rapid growth risk

Ramiro Moreno 1,5, Olivier Meyrignac 1,2, Charline Zadro 1,2, Anou Sewonu 1,5, Hervé Rousseau 1,2 , Alexis Jacquier 4, Laurence Bal 5(1) Institute of Cardiovascular and Metabolic Diseases, Toulouse, France (2) Toulouse Rangueil University Hospital (CHU), Radiology, Toulouse, France (3)Hospital La Timone of Marseille, Vascular medecine and surgery, aortic center, Marseille, France (4) Hospital La Timone of Marseille, Radiology, Marseille,France , (5) ALARA Expertise, Strasbourg, France.

Abstract:Purpose: Abdominal Aortic Aneurysm (AAA) is a common pathology which surgical intervention decision is mostly made upon measurement of maximaldiameter, despite known limitations. The purpose of this study was to identify volumetric and computational fluid dynamics (CFD) parameters to predictAAAs rapid growth risk.Material and methods: In our multi-centric and prospective study, we included 82 patients with an AAA from September 2012 to June 2014. Patientsunderwent two CT examinations separated by a one-year interval to assess aneurysms growth. Fifty patients were eligible for CFD analysis. Based on a 10ml threshold of total volume growth, we classified patients into slow and rapid growth groups. Aneurysms initial morphological and functionalparameters were analyzed including: maximal diameter and surface, thrombus and lumen volumes, maximal wall pressure and wall shear stress (WSS).Results: There was a significant difference between the two groups regarding aneurysm lumen volume (P=0.0051) and mean WSS variation (P=0.0240)unlike maximal diameter (P=0.71). We found significant correlation of aneurysm volume growth with lumen volume and reduction of the mean WSSvariation value (respectively R=0.47, P=0.0015 and R=-0.42, P=0.0062) and total aneurysm volume growth. Combining these parameters, we computedan AAAs growth-predicting model which featured better area under ROC than the only measurement of maximal diameter (0.78 vs 0.52, P=0.0031).Depending on the threshold, our model yields either excellent sensitivity (95.00% [IC95% 75.1, 99.9]) or specificity (90.00% [IC95% 73.5, 97.9]).Conclusion: Combined analysis of lumen volume and WSS provides better information than maximal diameter to assess rapid volume growth risk.

Introduction: Abdominal aortic aneurysm (AAA) is a serious and common pathology which development goes alongwith aging. The high overall mortality from ruptured AAAs makes growth and subsequent rupture risk assessment crucial forAAA management. Since the 70’s many works proved that AAA diameter is correlated with the rate of rupture. However, soleuse of maximal diameter measurement seems insufficient to predict rapid growth rate among this heterogeneouspopulation. Therefore, we need different prognostic tools to assess rapid growth risk of small AAAs, especially since they arehighly prevalent compared to larger AAAs leading to non negligible rupture events. Volumetric analysis seems promising forrupture risk and growth rate assessment. Besides, it allows detection of morphological changes that do not affect maximaldiameters. Also, over the last decade, we have seen the rise of functional vascular analysis based on computational fluiddynamics (CFD), studying many hemodynamics parameters. The purpose of this prospective study was to identifymorphological and functional parameters to assess small AAA growth risk, based on volumetric and CFD analysis comparedwith maximal diameter measurement.

Two major findings arise from thisstudy. First, high WSS withinaneurysm appears as a protectivefactor regarding aneurysmal growthrate. Second, increased lumenvolume is correlated with theaneurysmal volumetric growth.Previous studies found significantcorrelation of AAA and ILT volumeswith aneurysmal growth rate.However, we did not find suchsignificant differences consideringAAA and ILT volumes between theslow and rapid growth groups.Conversely, we found a significantdifference regarding lumen volumein favor of the rapid growth group.This could imply that even if lumenis slightly enlarged, it may have astronger impact than ILT volume onaneurysmal growth).Since the beginning of CFD-basedhemodynamic analysis, authors havediscussed WSS impact on abdominalaortic aneurysm pathogenesis and itremains controversial. Our resultsand previous findings suggest aprotective role of high WSS valuesfrom aneurysmal growth , afterhaving played a role in the initiationof the disease, reaching anequilibrium.Finally, combined analysis oflumen volume and WSS mayprovide better information thanmaximal diameter to assess smallAAAs rapid growth risk.

Discussion & conclusion:

Material & methods:

Patients were considered for inclusion in the prospective registry ifthey were addressed in vascular surgery for the discovery of an infra-renal AAA.Exclusion criteria were acute aortic disease symptomatology, aorticdissection, previous procedures for aortic aneurysm either thoracic orabdominal, personal or family medical history of bicuspid aortic valve,aortitis, aorta connective tissue diseases, as well as age < 18 years old,pregnancy, contraindications to CT contrast enhanced imaging.From September 2012 to June 2014, 297 consecutive patients wereprospectively included.Patients underwent two CT examinations separated by a one-yearinterval to assess aneurysms evolution. All CT examinations werecontrast-enhanced.We used a 10 ml threshold to classify patients into rapid or slowgrowth groups

Study design

We gathered on both CT scans: saccular or fusiformaneurysm morphology, maximal aneurysm diameterand surface measured perpendicular to the centerlineaxis, total aneurysm, thrombus, and lumen volumes.Upper and lower limits of an AAA were defined by theloss of parallelism of the aortic walls to the end of theaortic dilatation or to the iliac bifurcation dependingon AAA extent.The volume of the aneurysm was measured withsemi-automatic segmentation, using a custom OsiriXplug-in (based on CMIV_CTA_CT plugin, ChungliangWang, Linköping University).

Morphological analysis

Functional CFD analysis

The native volume acquired by CT scan including the whole aorta and the primitive iliac arteries wassegmented using our custom Osirix plug-in (A). Then, we used a commercial CFD mesh generator(Amira 4.1, TGS, Mercury Computer Systems, USA) to reconstruct the full aortic morphology (B). Thefinal geometry was reconstructed through a triangular surface mesh discretization to obtain a three-dimensional volume grid based on tetrahedral native mesh using Gambit (2.4, ANSYS, Canonsburg,Pennsylvania, USA)(C). The flow simulations were performed using YALES2BIO numerical tool, designedto resolve the incompressible Navier-Stokes equations based on a massively parallel-unstructured finitevolume flow solver (IMAG, CNRS and Université Montpellier, France) (D). For each aneurysm, on thefirst CT scan, we gathered the following hemodynamic parameters: maximal wall pressure (MWP), andaverage wall shear stress (WSS) (E). To allow easier comparison of these hemodynamic parameters, weused ratios between non-aneurysmal and aneurysmal aorta, referred as mean indexed parameters.

Results :Populat ion caracterist icsBaseline demographic and clinical characteristics of our population analysis.

Parameters Datum

Patient characteristics

• Age in years (mean ± SD) 74 ± 6.76

• Sex ratio (F/M) 0.02 (1/49)

• Cardiovascular risk factors

o Hypertension 40 (80)

o Diabetes 15 (30)

o Dyslipidemia 43 (86)

o Ever smoked 44 (88)

• Coronary heart diseases 12 (24)

• Intermittent claudication 4 (8)

• Anticoagulant treatment 1 (2)

• BMI (value ± SD) 27,3 ± 3.96

• Arterial pressure (mmHg ± SD) 133/77 ± 16/9

• Left ventricular ejection fraction (% ± SD) 61 ± 7

Aneurysm characteristics

• Metrics

o Maximal diameter (mm ± SD) 46.5 ± 5.6

< 40 mm 5 (10)

40 – 54 mm 41 (82)

≥ 55 mm 4 (8)

o Volume (ml ± SD) 91.4 ± 34.7

• Morphology

o Saccular 12 (24)

o Fusiform 38 (76)

• Presence of ILT 45 (90)

Morphological analysis

o Lumen 46.2 ± 18.1 60.4 ± 14.3 *0.0051

Tableau 1

evovoltot vollumt1 rwssav

0,35 40,25 -0,432633293

1,3 50,12 -0,525982972

1,45 25,72 -0,608974505

1,57 42,02 0,374909284

2,14 18,76 -0,506094612

2,74 43,44 -0,506943993

2,75 37,42 -0,385081111

2,76 30,22 -0,408837557

3,74 69,83 -0,577183681

3,77 33,18 -0,656157548

4,27 62,85 -0,766268565

4,82 43,17 -0,717690694

6,13 23,77 -0,300140079

6,37 57,15 -0,658425017

6,5 18,86 -0,105163704

6,98 48,33 -0,658635021

7,42 34,85 -0,645438058

9,1 74,4 -0,804954946

9,23 38,92 -0,774917474

9,56 35,23 -0,472662223

9,95 63,7 -0,510113766

9,95 50,97 -0,406208756

10,15 66,72 -0,733104481

10,64 77,61 -0,768755813

10,64 58,08 -0,648240407

0,1

1

10

100

0 20 40 60 80 100

1

10

100

significant correlat ionbetween lumen volume and total aneurysmvolume growth

Funct ional CFD analysis6,37 57,15 -0,658425017

6,5 18,86 -0,105163704

6,98 48,33 -0,658635021

7,42 34,85 -0,645438058

9,1 74,4 -0,804954946

9,23 38,92 -0,774917474

9,56 35,23 -0,472662223

9,95 63,7 -0,510113766

9,95 50,97 -0,406208756

10,15 66,72 -0,733104481

10,64 77,61 -0,768755813

10,64 58,08 -0,648240407

10,84 58,06 -0,669409079

11,43 51,69 -0,622030525

11,84 59,33 -0,537167477

12,19 50,33 -0,69650542

12,85 32,81 -0,313101864

0 20 40 60 80 100

0,1

1

10

100

-0,9 -0,75 -0,6 -0,45 -0,3 -0,15 0 0,15 0,3 0,45

(A)(B)

significant correlat ion between the mean indexed WSS and totalaneurysm volume growth

Threshold Sensit ivity % Specifici ty % PPV NPV DOR

Maximal

diameter

(mm)

Model based

on WSS and

lumen

volume

Combined analysisstat ist ical model combining the lumen volume and

the mean indexed WSS

stat ist ical difference in favor of our model