In Vivo Quantification of Ascending Thoracic Aortic Aneurysm Wall Stretch Using MRI: Relationship to Repair Threshold Diameter and Ex Vivo Wall Failure Behavior

Abstract

Ascending thoracic aortic aneurysms (aTAAs) can lead to life-threatening dissection and rupture. Recent studies have highlighted aTAA mechanical properties as relevant factors associated with progression. The aim of this study was to quantify in vivo aortic wall stretch in healthy participants and aTAA patients using displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging. Moreover, aTAA wall stretch between surgical and nonsurgical patients was investigated. Finally, DENSE measurements were compared to reference-standard mechanical testing on aTAA specimens from surgical repairs. In total, 18 subjects were recruited, six healthy participants and 12 aTAA patients, for this prospective study. Electrocardiogram-gated DENSE imaging was performed to measure systole–diastole wall stretch, as well as the ratio of aTAA stretch to unaffected descending thoracic aorta stretch. Free-breathing and breath-hold DENSE protocols were used. Uniaxial tensile testing-measured indices were correlated to DENSE measurements in five harvested specimens. in vivo aortic wall stretch was significantly lower in aTAA compared to healthy subjects (1.75 $\pm$1.44% versus 5.28 $\pm$1.92%, respectively, P = 0.0004). There was no correlation between stretch and maximum aTAA diameter (P = 0.56). The ratio of aTAA to unaffected thoracic aorta wall stretch was significantly lower in surgical candidates compared to nonsurgical candidates (0.993 $\pm$0.011 versus 1.017 $\pm$0.016, respectively, P = 0.0442). Finally, in vivo aTAA wall stretch correlated to wall failure stress and peak modulus of the intima (P = 0.017 and P = 0.034, respectively), while the stretch ratio correlated to whole-wall thickness failure stretch and stress (P = 0.013 and P = 0.040, respectively). Aortic DENSE has the potential to assess differences in aTAA mechanical properties and progressions.

1 Introduction

Ascending thoracic aortic aneurysm (aTAA) predisposes to mechanical failure of the aortic wall, including dissection and frank mural rupture, both associated with significant morbidity and mortality. The risk of these often-catastrophic aortic injuries generally increases with increasing aTAA diameter. Management guidelines thus recommend surgical intervention for aTAA with a diameter ≥5.5 cm in patients with tricuspid (TAV) and ≥5.0 cm in patients with bicuspid (BAV) aortic valves [1]. Unfortunately, diameter is an imperfect predictor of aortic dissection and rupture [2]; in the International Registry of Acute Aortic Dissection, the majority of acute type A dissections occurred in aTAA that did not meet the threshold for surgical repair.

Aneurysm development and progression is associated with extracellular matrix (ECM) degradation in the vessel wall [3,4]. Mural ECM composition dynamically modulates aortic stiffness. This suggests wall stiffness as a new measure to assess aneurysm progression [5,6]. Clinically, few noninvasive techniques can measure aortic stiffness in vivo. Pulse wave velocity, the established reference standard, can only measure global stiffness over a long aortic segment and cannot reflect the properties of aTAA that typically affect only short segments [7,8].

Displacement encoding with stimulated echoes (DENSE) is a noninvasive phase-contrast magnetic resonance imaging (MRI) technique that measures true tissue displacement. Local tissue stretch can be derived from the measured displacements, thereby yielding a quantitative measure of tissue stiffness [9,10]. One of the advantages of DENSE is that both in-plane and through-plane tissue displacement can be measured using the respective displacement encoding gradients, allowing more accurate quantification of tissue stretch using the displacement information obtained from all three orthogonal directions.

Displacement encoding with stimulated echoes was initially developed and validated for imaging the myocardium [11]. Pilot work has shown that it can also be used to measure aortic wall stretch in vivo [7,12,13]. However, the relationship of DENSE-based stretch measurements and ground-truth mechanical properties of aortic wall tissue is unknown. Also unknown is how DENSE-derived aTAA wall stretch compares in aTAA categorized according to current guideline-recommended repair thresholds.

The aims of this study were twofold. First, to compare DENSE-derived wall stretch between healthy controls and aTAA patients who did and did not meet the guideline-recommended surgical thresholds. Second, we sought to compare DENSE-derived aneurysm wall stretch to uniaxial tensile mechanical testing performed on aTAA specimens obtained from patients who underwent surgery.

2 Methods

2.1 Study Population.

This Health Insurance Portability and Accountability Act compliant and Institutional Review Board-approved study included 18 participants: six healthy participants and 12 patients with aTAA. Informed consent was obtained from all participants. For aTAA patients, the inclusion criteria were consecutive patients undergoing MRI evaluation of aTAA for whom a technically successful DENSE acquisition was obtained. Patients with a history of aortic vascular injury and vasculitis, connective tissue disorder, prior aortic repair, and contradiction to MRI were excluded. Of the 12 aTAA patients, seven underwent aortic repair surgery. The clinical decision to proceed to surgery adhered to clinical management guidelines, considering multiple factors including maximum aTAA diameter, valve morphology, growth rate, and symptoms. No data or results from this study were used in the decision to proceed to surgery.

2.2 Data Acquisition.

Imaging was performed at 1.5 T or 3 T (Avanto or Skyra platforms, Siemens Healthcare, Erlangen, Germany). For participants with aTAA, DENSE was acquired at a single slice orthogonal to the vessel centerline at the level of maximum aTAA diameter in the tubular portion of the ascending aorta (see Fig. 1(a)). A similar level was used for DENSE acquisitions in healthy participants. For all participants, a steady-state free precession electrocardiogram (ECG)-gated cine series was acquired first to determine the time in the cardiac cycle at which the ascending aorta reached its maximum distension. Cine imaging parameters were echo time (TE) = 1.27–2.47 ms, repetition time (TR) = 3–5.1 ms, flip angle = 12 deg, field of view (FOV) = 340–360 mm², generalized autocalibrating partial parallel acquisition acceleration factor 2, pixel size = 1.4–1.8 mm, slice thickness = 6–7 mm, and 25 cardiac phases were reconstructed from the data by rebinning (temporal resolution 22–44 ms depending on heart rate). Subsequently, an ECG-triggered DENSE spiral acquisition was performed with gradients encoding tissue displacement in all three spatial dimensions [10]. The DENSE displacement encoding gradients were applied at the time of maximum aortic distension during systole, as determined using the cine images described above. The DENSE readout was then performed in end-diastole, at approximately 80–90% of the cardiac cycle. This was achieved using a delay of 250–450 ms between DENSE encoding and readout depending on heart rate, again chosen based on the cine imaging. This approach thus allowed DENSE to quantify the wall displacement between systolic and diastolic loading conditions (see Fig. 1(d)). The DENSE phase images contain phase values for each of the three encoding directions and are linearly converted to the displacement in mm at a voxel level. This measured displacement is that which occurred from systole to diastole of the tissue contained in that voxel. For aTAA patients, a free-breathing DENSE protocol with diaphragmatic navigators was used, while for healthy participants a breath-hold protocol was used. Imaging parameters are summarized in Table 1. With these parameters, a maximum displacement of 26–50 mm could be encoded for each of the three spatial dimensions, with a resolution of approximately 0.006–0.012 mm.

Fig. 1.

(a) DENSE and cine data were acquired at the level of the aTAA. The slice was selected to capture both the aTAA and descending thoracic aorta. (b) Markings of the four quadrants from which specimens for mechanical testing were obtained. (c)DENSE produces one magnitude and three phase images. Phase images encode the displacement of tissue in each of the x/y/z directions that the tissue in each voxel underwent between DENSE encoding and readout. For the parameters used in this work, displacement up to 2.6–5 cm could be resolved in each direction with a resolution of 0.006–0.012 mm. (d) DENSE encoding was applied to coincide with maximum aortic distension as determined by the cine MRI acquisition, and readout was performed 250–450 ms later depending on heart rate to coincide with diastole (80–90% of the cardiac cycle). Voxels in the center of the aortic wall were delineated on the acquired DENSE magnitude image (panel (d), the aortic wall outline overlaid in the magnitude image), and displacements of the tissue in those voxels were calculated from the DENSE phase data, thereby yielding the full three-dimensional displacement of the aortic wall between systole and diastole. Note that in panel (d) three-dimensional displacements have been projected to the image plane for clarity.

Table 1.

Imaging parameters for free-breathing and breath-hold DENSE

	Free-breathing	Breath-hold
TE/TR (ms)	1.14/22.00	1.00/17.00
Flip angle (deg)	90	65
FOV (mm2)	320 × 320	180 × 180
Slice thickness (mm)	8–12	12
No. of spiral interleaves per heartbeat	1	2
No. of spiral interleaves per image	10	8
Displacement encoding (cycles/mm)	0.04–0.08	0.04–0.08
Anti-echo suppression	Two-point CSPAMM	Two-point CSPAMM
Reduced field-of-view via intersecting slabs for DENSE encoding	No	Yes
	Free-breathing	Breath-hold
TE/TR (ms)	1.14/22.00	1.00/17.00
Flip angle (deg)	90	65
FOV (mm2)	320 × 320	180 × 180
Slice thickness (mm)	8–12	12
No. of spiral interleaves per heartbeat	1	2
No. of spiral interleaves per image	10	8
Displacement encoding (cycles/mm)	0.04–0.08	0.04–0.08
Anti-echo suppression	Two-point CSPAMM	Two-point CSPAMM
Reduced field-of-view via intersecting slabs for DENSE encoding	No	Yes

CSPAMM: complementary spatial modulation of magnetization.

2.3 Aortic Wall Stretch Analysis.

Displacement encoding with stimulated echoes phase data encoding the displacement of each image voxel between systole and diastole as described above were first unwrapped using a previously described Poisson solver when needed [14]. A purpose-built postprocessing pipeline implemented in matlab (MathWorks, Inc., Natick, MA) was then used to calculate the displacement of the vessel wall as follows: first, 100 points were automatically distributed equidistantly along a spline curve delineating the center of the aortic wall in the DENSE images (Fig. 1(d), left spline). The displacement field for each of these points was then extracted from the unwrapped DENSE phase data. The encoded displacements were then subtracted from the position of the points, thereby yielding the locations of those same points at systole (Fig. 1(d), right spline). Finally, wall stretch $\lambda$ was calculated by comparing the distance between every pair of adjacent points on the displaced (systolic) spline to the distance of the same set of points on the initially drawn (diastolic) spline

$${\lambda }_{\mathrm{DENSE}}=\hspace{0.17em}{\mathrm{Mean}(\mathrm{Pairwise}\hspace{0.17em}\mathrm{Distance}}_{\mathrm{Systole}}/{\mathrm{Pairwise}\hspace{0.17em}\mathrm{Distance}}_{\mathrm{Diastole}})$$ (1)

where ${\mathrm{Pairwise}\hspace{0.17em}\mathrm{Distance}}_{\mathrm{systole}}$ and ${\mathrm{Pairwise}\hspace{0.17em}\mathrm{Distance}}_{\mathrm{Diastole}}$ are the distance between two adjacent points on the spline at systole and diastole, respectively.

For aTAA patients, we similarly calculated the stretch of the unaffected descending thoracic aorta that was included in the large FOV possible with the free-breathing protocol. Below, ${\lambda }_{\mathrm{DENSE},\hspace{0.17em}\mathrm{aTAA}}$ and ${\lambda }_{\mathrm{DENSE},\mathrm{DA}}$ are used to denote the aTAA and descending aorta stretch, respectively. Finally, we calculated the aTAA to descending aortic wall stretch ratio as

$${\gamma }_{\mathrm{DENSE}}=\hspace{0.17em}{\lambda }_{\mathrm{DENSE},\hspace{0.17em}\mathrm{aTAA}}/{\lambda }_{\mathrm{DENSE},\mathrm{DA}}$$ (2)

In one patient, calculation of the stretch ratio was not possible as the descending aorta was not fully included in the FOV.

2.4 Mechanical Testing.

Whole specimens were harvested from all seven patients who underwent surgical repair. Testing was not performed on two patients' specimens due to technical issues. From each specimen, tissue strips aligned with the circumferential axes of physiologic deformation were harvested from the anterior, posterior, medial, and lateral segments (Fig. 1(b)). Tensile testing measurements described below were averaged across each specimen's four segments for comparison to the DENSE measurements.

Uniaxial tensile testing was performed using an established displacement-controlled protocol on a planar stretching system [15,16]. The load cell capacity was 22.25 N with 1% accuracy and 0.1% precision. Tissue strips were prepared into dog-bone shape with area for failure testing of 10 mm × 2.5 mm rectangle. The strips were then attached to the two linear arms of the stretcher and immersed in a water bath with Dulbecco's phosphate buffered saline at 37 °C (Fig. 2). The stretch rate was 0.05 mm/s after ten preconditioning cycles. The preconditioning cycles had a maximum of 10% of the length along the loading direction. For each tested strip, we recorded the stretch at failure, ${\lambda }_{\mathrm{MT}}$, stress at failure, ${\sigma }_{\mathrm{MT}}$, and peak elastic modulus in the linear portion of the stress–stretch curve before failure, ${\epsilon }_{\mathrm{MT}}$. Tests were performed for strips of the entire aortic wall thickness, as well as peeled strips of the intima and adventitia only, using a similar protocol for sample preparation and testing process as in our previous studies [17,18]. The failure stretch, failure stress, and peak tangent modulus were measured along the circumferential direction of the aTAA to match the in vivo DENSE measurements.

Fig. 2.

Uniaxial tensile testing was performed on surgical aTAA specimens using a custom-built planar stretching system with two linear arms. Circumferential failure stretch and stress were recorded as the specimen deformation and load at failure with respect to its original length, and peak elastic modulus was recorded as the slope of the linear portion of the stress–stretch curve just prior to failure.

2.5 Statistical Analysis.

Measurements were recorded as mean $\pm$standard deviation. To compare DENSE-derived stretch between groups, we used the unpaired two-sample t-test or Mann–Whitney U test depending on data normality. The Shapiro–Wilk test was used to establish data normality. Equality of variance was tested via a two-tailed F-test. Pearson's correlation was used to associate the DENSE-derived stretch ${\lambda }_{\mathrm{DENSE}}$ and stretch ratio ${\gamma }_{\mathrm{DENSE}}$ with the aTAA maximum diameter and each of the mechanical testing-measurements (i.e., failure stretch, stress and peak modulus of the entire wall, the intimal layer, and the adventitial layer). A P value <0.05 was considered statistically significant.

3 Results

3.1 Participant Characteristics.

Three and nine patients were imaged at 1.5 T and 3 T, respectively. All six healthy participants were imaged at 3 T. Characteristics of the 12 aTAA patients (all male, mean age 64 $\pm$8 yr) categorized by leaflet morphology and management guidelines are provided in Table 2. Two patients with BAV and five with TAV underwent surgery as recommended by management guidelines, while five patients, all with TAV, continued imaging surveillance. For the seven patients undergoing surgery, DENSE imaging was performed within two days prior to the surgery. Six healthy volunteers were also enrolled in this study (all male, mean age 38 $\pm$7 yr, mean maximum aortic diameter 2.98 $\pm$0.36 cm).

Table 2.

Demographics of participants with aTAA

	BAV surgical (n = 2)	TAV surgical (n = 5)	Nonsurgical (n = 5, all TAV)
Age (yr)	66±10	65±2	61±10
Height (cm)	190±10	174±9	182±5
Weight (kg)	97±17	84±26	83±12
Sex	All males	All males	All males
Systolic blood pressure (mm Hg)	143±6	119±7	130±9
Diastolic blood pressure (mm Hg)	89±2	73±9	82±7
BMI (kg/m2)	27±4.4	28±6.0	25±3.0
Maximum aTAA diameter (cm)	4.9±0.2	5.8±0.5	4.7±0.1
Diameter/height ratio	0.0268±0.0016	0.0318±0.0021	0.0254±0.0040
Smoking	1	1	2
Diabetes**	0	0	1
Hypertension**	2	2	3
Hyperlipidemia**	1	2	3

Note: Data are means $\pm$standard deviations; BAV = bicuspid aortic valve; TAV = tricuspid aortic valve; BMI = body to mass index; and **diabetes, hypertension, and hyperlipidemia were defined according to American Heart Association guidelines.

3.2 Displacement Encoding With Stimulated Echoes-Derived Stretch and Stretch Ratio Association With Diameter.

The mean aortic wall stretch ${\lambda }_{\mathrm{DENSE}}$ significantly differed between healthy participants (5.28 $\pm$1.92%, n = 6) and all aTAA patients pooled together (1.75 $\pm$1.44%, n = 12, P = 0.0004, Fig. 3).

Fig. 3.

DENSE-derived aortic wall stretch in healthy participants and aTAA patients. * = statistically significant difference.

Figure 4(a) compares aTAA measurements between the three guideline-defined groups of patients, aneurysm diameter differed between TAV surgical and nonsurgical candidates (P = 0.0031, Fig. 5(a)).

Fig. 4.

(a) Correlation between DENSE-derived aTAA wall stretch and aTAA diameter and (b) correlation between DENSE-derived stretch ratio and aTAA diameter

Fig. 5.

Diameter (a) DENSE-derived wall stretch (b) and stretch ratio (c) in aTAA patients categorized by management guidelines. * = statistically significant difference.

Wall stretch was generally lower in surgical candidates (1.56 $\pm$0.62% for BAV, 1.33 $\pm$1.40% for TAV, and 1.39 $\pm$1.18% for pooled BAV/TAV surgical candidates) than in TAV nonsurgical candidates (2.24 $\pm$1.76%), but none of the differences were statistically significant (Fig. 5(b)).

Similarly, the wall stretch ratio was lower for surgical candidates (1.00 $\pm$0.005 for BAV, 0.99 $\pm$0.011 for TAV, and 0.993 $\pm$0.011 for pooled surgical candidates) than for TAV nonsurgical candidates (1.017 $\pm$0.016), with statistically significant differences observed between TAV surgical and nonsurgical candidates, and between the pooled surgical and TAV nonsurgical candidates (P = 0.0277 and P = 0.0442, respectively, Fig. 5(c)).

There was no significant correlation between ${\lambda }_{\mathrm{DENSE}}$ and aTAA diameter (P = 0.56, Fig. 4(a)) or between ${\gamma }_{\mathrm{DENSE}}$ and aTAA diameter (P = 0.11, Fig. 4(b)).

3.3 Association of Displacement Encoding With Stimulated Echoes-Derived Stretch and Mechanical Testing.

Of the 60 strips planned to undergo uniaxial testing (five patients × four quadrants each, × whole wall, intima, and adventitia strips), data were unavailable for two whole wall strips and one intimal strip due to insufficient tissue in the inner curvature of the aorta. Table 3 provides the stress/stretch of individual samples at failure.

Table 3.

Failure stress and stretch

	Intima		Adventitia		Whole
Specimen	Failure stretch	Failure stress (kPa)	Failure stretch	Failure stress (kPa)	Failure stretch	Failure stress (kPa)
1	1.6242	978.0	1.6779	977.7	1.7634	1475.0
2	1.6347	729.4	1.6590	1609.6	1.8383	1534.0
3	1.6922	2462.3	1.8512	2394.9	1.5907	3392.4
4	1.8464	2266.8	2.0920	3064.5	1.9058	1837.6
5	2.0551	1550.1	2.2043	1902.0	1.8048	992.7

Statistically significant correlations were observed between the DENSE stretch ratio ${\gamma }_{\mathrm{DENSE}}$ and the circumferential whole-wall failure stretch ${\lambda }_{\mathrm{MT}}^{\mathrm{wall}}$ and whole-wall failure stress ${\sigma }_{\mathrm{MT}}^{\mathrm{wall}}$ measured by uniaxial tensile testing (P = 0.013 and P = 0.040, respectively, Figs. 6(a) and 6(b), respectively) and between DENSE stretch ${\lambda }_{\mathrm{DENSE}}$ and intimal layer circumferential failure stress ${\sigma }_{\mathrm{MT}}^{\mathrm{intima}}$ (P = 0.017, Fig. 6(c)) and intimal layer circumferential peak elastic modulus ${\epsilon }_{\mathrm{MT}}^{\mathrm{intima}}$ (P = 0.034, Fig. 6(d)). The complete set of correlation results including those not shown in Fig. 7 are provided in Figs. 1 and 2 available in the Supplemental Materials on the ASME Digital Collection. Figure 7 demonstrates the stretch–stress curves from one patient.

Fig. 6.

(a) Correlation between DENSE-derived stretch ratio and failure stretch of the whole wall, (b)correlation between DENSE-derived stretch ratio and failure stress of the whole wall, (c) correlation between DENSE-derived stretch and failure stress of the intima, and (d) correlation between DENSE-derived stretch and peak modulus of the intima

Fig. 7.

Stretch–strain curves from the aTAA specimens of one patient

4 Discussion

In this proof-of-concept study, we sought to investigate aTAA wall mechanical properties using in vivo DENSE MRI, a technique initially developed and validated for measuring myocardial deformation under cardiac load [19]. We first compared aortic DENSE measurements between aTAA and healthy ascending aortas. We then investigated the wall stretch and stretch ratio in aTAA above versus below the guideline-recommended diameter thresholds for surgery. Finally, we compared DENSE measurements to reference-standard uniaxial tensile testing of surgical specimens.

No correlation was observed between aTAA wall stretch or stretch ratio and aTAA diameter. This adds to the evidence, including by MR elastography [20–22] and patient-specific finite element analysis correlating poorly to aneurysm diameter [23], that aneurysm mechanical properties may potentially offer independent information to standard risk factors. The International Registry of Acute Aortic Dissection study in which ∼60% of patients presenting with acute type A dissection had aTAA diameters smaller than guideline-recommended repair thresholds, highlighting the need to identify additional independent predictors of risk.

Our work extends several earlier studies that assessed healthy arterial wall tissue stretch using DENSE [7,12,13], providing initial information regarding aTAA wall stretch across different disease stages, thereby relating them to standard-of-care risk stratification. In this context, our results confirm a prior report that DENSE-derived wall stretch is significantly lower in aTAA than healthy ascending thoracic aortas [7]. We furthermore found that aTAA wall stretch did not differ significantly between high-risk aTAA and those below the repair thresholds as categorized by current guideline diameter thresholds. However, the ratio between aTAA wall stretch and that of the unaffected descending thoracic aorta significantly differed between surgical and nonsurgical patients, lending a mechanical interpretation of current management guidelines. Specifically, a stretch ratio value lower than one for aTAA patients meeting repair thresholds suggests that the aTAAs are stiffer than the unaffected descending thoracic aorta. Conversely, in aTAA patients with TAV and less advanced disease, we observed a ratio greater than one, suggesting the aTAA is more compliant than the unaffected thoracic aorta. ECM remodeling can play a critical role in determining aTAA wall stiffness as well as its integrity. Previous studies observed pathological change of the ECM fiber waviness and dispersion in aortic dissection flaps associated with tissue mechanical parameters related to stiffness [24] and found correlation between vessel structural stress and local degradation of elastin and aortic media degeneration in BAV [25]. Decreased elastin density and increased collagen content are often observed in advanced aTAAs as well, resulting in a reduction of wall compliance [5,16], which is in agreement with our findings.

The stretch ratio is also potentially advantageous compared to studying stretch as the biomechanical properties of the aorta are dependent not only of the disease state but also on other patient-specific factors such as blood pressure and age [26], and potentially differences in imaging protocols or pulse sequences. The normalization inherent in normalizing aTAA to descending aortic wall stretch may help reduce the effect of such confounding factors, helping elucidate differences among different patients.

Furthermore, this initial investigation of the association of aTAA in vivo DENSE measurements to ground-truth tissue mechanical properties measured via tensile testing showed that aTAA wall stretch ratio correlated to the ultimate failure stretch and stress of the whole wall, while the aTAA wall stretch positively correlated to the ultimate failure stress and peak modulus of the intima, which can be potentially resulted by the layer-dependence of vessel wall material properties [27]. This may be relevant to predicting dissection which begins with the tear of the intima. The observed correlation between DENSE-derived stretch and intima wall strength, as indicated by the failure stress, suggests DENSE could be potentially investigated for risk stratification for dissection. Our findings regarding the tandem correlation between DENSE-derived stretch and peak modulus in addition to failure stress of the intima is in agreement with the work of Khanafer et al. who reported that failure stress was positively correlated to peak modulus [28].

There are several limitations of this study including a small sample size and lack of validation to histopathology. Due to the small number of patients, it is possible that some of the associations observed are potentially driven by outliers, for example, those shown in Figs. 6(a) and 6(b). Further investigation in a larger patient cohort is needed to determine if aortic DENSE offers clinical value for aTAA management. Additionally, healthy subjects across all ages should be studied to establish baseline values of ascending thoracic aortic DENSE stretch and ratio for different age groups for comparison to aTAA measurements. Furthermore, validation of DENSE-measured wall properties with respect to aTAA ECM content measured from histopathology would be needed to inform its use for monitoring ECM degradation that is presumably reflected by wall stiffness. It is also important to note that DENSE-derived stretch is an average value over a slice thickness 6–7 mm and may suppress local variations in mechanical properties. We have not thoroughly evaluated this effect as the primary goal of this study was to investigate whether DENSE-derived aTAA wall stretch is associated with failure parameters, which were measured for strips of similar thickness. Nonetheless, our previous study has demonstrated the feasibility of measuring asymmetric local stretch in the ascending aorta using DENSE [7], and this should be further explored in the future. Another limitation is that the stretch during mechanical testing was measured through the applied displacement, which may overestimate the stretch ratio compared to measuring the strain in the center area. However, the system error may not impact the conclusion of the correlation study concerning the failure stretch. Finally, we note that DENSE of the ascending aorta presents several technical challenges. DENSE is technically challenging. These include limited signal-to-noise ratio, the need to carefully manage cardiac and respiratory motion, and long scan times necessitated by a large field-of-view to avoid wrap-around artifacts. The yield of a successful free-breathing DENSE acquisition of the ascending thoracic aorta in this study was just over 50%. Nonetheless, breath-hold DENSE protocols are being developed to address the primary issues in aortic DENSE imaging, namely, motion artifact due to breathing, cardiac motion during the spiral acquisition window, and image wrapping artifact due to the chest and arms exceeding the size of the FOV that can be acquired in reasonable scan time. In the present study, the breath-hold protocol with outer volume suppression applied to healthy participants helped reduce breathing motion and wraparound artifacts. In a recent preliminary study [29], we found aortic DENSE interscan reproducibility limits of agreement to be 0.12 $\pm$0.25% for the breath-hold protocol and 0.14 $\pm$0.25% between the breath-hold and free-breathing protocols, which compare favorably with the differences in stretch observed between different patients and groups in this study.

5 Conclusion

Aortic DENSE in aTAA may be able to assess differences in aneurysmal wall mechanical properties between different disease stages. It potentially offers a noninvasive approach to risk-stratify aTAA and elucidate their progression.

Funding Data

• Veterans Affairs Office of Research and Development (Grant No. I01-CX002071; Funder ID: 10.13039/100006379).

• National Institutes of Health (Grant Nos. R01-HL119857 and K25-HL150408; Funder ID: 10.13039/100000002).

• American Heart Association (Grant No. 20POST35211107; Funder ID: 10.13039/100000968).

• Marfan Foundation (Funder ID: 10.13039/100010258).

Data Availability Statement

The datasets generated and supporting the findings of this article are obtainable from the corresponding author upon reasonable request.

Supplementary Material

Supplementary Material

Supplementary PDF

Nomenclature

aTAA =

ascending thoracic aortic aneurysm

BAV =

bicuspid aortic valves

DA =

descending aorta

DENSE =

displacement encoding with stimulated echoes

ECM =

extracellular matrix

MT =

mechanical testing

TAV =

tricuspid aortic valves