MRI assessment of aortic flow in patients with pulmonary hypertension in response to exercise
Jacob Macdonald1, Omid Forouzan2, Naomi Chesler2, Christopher Francois3, and Oliver Wieben1,3

1Medical Physics, University of Wisconsin - Madison, Madison, WI, United States, 2Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, United States, 3Radiology, University of Wisconsin - Madison, Madison, WI, United States

Synopsis

Cardiopulmonary exercise testing is gaining increased recognition as a useful tool for assessing pulmonary hypertension (PH). Using an MRI-compatible exercise device that allows subjects to exercise in the bore of the magnet, we investigated the effects of exercise stress on blood flow in the ascending aorta in healthy controls and patients with PH. The measurements we obtained demonstrated a decreased exercise capacity in PH subjects and in older controls. Some parameters, such as cardiac output, demonstrated statistically significant changes between rest and stress, while others were unclear due to the relatively low exercise power tolerated by the PH patients.

Purpose

Cardiopulmonary exercise testing is gaining increased recognition as a useful tool for assessing pulmonary hypertension (PH)1. The increased pulmonary artery pressure associated with the disease can shift the ventricular septum, resulting in decreased left ventricular (LV) filling and aortic flow. This response becomes more pronounced when stressed through exercise. Due to its increased accuracy in measuring cardiopulmonary function, MRI is preferred to echocardiography for assessing such physiologic responses. Traditionally, however, MRI relies on pharmacologically induced stress due to inherent constraints within the MRI bore. Previously we demonstrated the use of MRI-compatible exercise equipment2 to assess aortic flow and LV function in healthy subjects3,4. In this study, we aim to determine if changes to aortic flow caused by PH are detectable using MRI following exercise stress.

Methods

Three subject cohorts were imaged: 20 young, healthy controls (26±4 years,8M,12F), 8 older, age-matched controls (58±10 years,1M,7F), and 6 PH patients (60±9 years,1M,5F). Imaging was performed on a clinical 1.5 T system (HDx/Discovery 450w, GE Healthcare, Waukesha, WI). A custom-built MRI-compatible stepping device was used which allowed subjects to exercise in a supine position in the scanner bore (Figure 1). Figure 2 shows the exercise/scanning protocol for each cohort. A low power of 30W was targeted for the PH patients whose exercise capacity can be greatly compromised. The control groups exercised at slightly higher powers to induce measurable responses. Each exercise stage was followed immediately by an ECG-gated 2D cine PC acquisition (TR/TE=6.1/3.7ms; FA=30o; ASSET=2; VENC=200cm/s; resolution=256x256) with 20 cardiac phases in the ascending aorta across a 15s breath hold. Changes in heart rate, stroke volume, cardiac output, peak systolic velocity and flow, relative aorta area change, and pulse wave velocity (using the QA method5) were analyzed with CV Flow (Version 3.3, Medis, Leiden, Netherlands) and MATLAB (Mathworks,Natick,NJ). A paired t-test and 1-way ANOVA with Tukey’s HSD test were used to determine the statistical significance (p<0.05) of intra-group and inter-group changes respectively between exercise and baseline. To reduce the effect of varying exercise power between subjects, the exercise stage measuring closest to 30 W was analyzed for each subject.

Results

The average exercise powers were 36±8 W, 33±6 W, and 30±9 W with an average increase in heart rate of 35%, 39%, and 65% (Figure 3) for the young controls, older controls, and PH subjects respectively, all of which were statistically significant. Figure 4 displays boxplots comparing the results for each group for the remaining parameters investigated. A bracket between two boxplots indicates the two groups have a statistically significant difference.

Discussion

The increase in heart rate was much higher for the PH subjects than the control groups, indicating a higher stress level for this modest exercise. The results for stroke volume and cardiac output indicated that younger, healthy subjects showed a greater ability to increase blood supply in response to exercise stress. For many of the parameters measured at stress the older controls and PH groups showed a wider range of values than the younger controls. We hypothesize this is due to a greater perceived difficulty for each exercise challenge to these groups, resulting in higher respiratory and cardiac motion compromising image quality, making ROI measurements more difficult. Differing degrees of PH and age-related loss of CV function could also be responsible for the spread found in these subjects. Many of the parameters investigated did not show strong intra-group statistical significance between rest and stress. This may be a result of low statistical power from the small sample size for the PH subjects, and work-rates that were too low to elicit a strong cardiopulmonary response, as evidenced by the lower heart rates, in the healthy controls. Future studies may benefit from standardizing comparisons based on heart rate instead of exercise power. The implementation of improved motion-correction and real-time imaging would also allow for more accurate measurements, possibly allowing us to detect more subtle hemodynamic changes brought on by exercise.

Conclusion

This study demonstrates the use of MRI to measure the effect of modest exercise stress on aortic flow in both healthy controls and patients with pulmonary hypertension. The PH patients showed a good response to the exercise challenge (an average 65% increase in heart rate), yet their response was heterogeneous for measures of cardiac output and stroke volume, likely reflecting different stages of loss of CV function. The response to the exercise challenge was less pronounced for the control groups due to the low exercise power. Future studies comparing larger cohorts of subjects based off of heart-rate instead of work-rate may provide comparisons with more statistical power.

Acknowledgements

We gratefully acknowledge funding by NIH grant R01HL105598 and GE Healthcare for their research support.

References

1. Arena R, Lavie CJ, Milani RV, et al. Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension: An evidence-based review. The Journal of Heart and Lung Transplantation. 2010; 29(2).

2. Forouzan O, Flink E, Warczytowa J, et al. Low Cost Magnetic Resonance Imaging-Compatible Stepper Exercise Device for Use in Cardiac Stress Tests. Journal of Medical Devices. 2014;8(4).

3. Macdonald J, Forouzan O, Warczytowa J, et al. MRI assessment of aortic flow and pulse wave velocity in response to exercise. Journal of Cardiovascular Magnetic Resonance. 2015; 17(Suppl 1): M2.

4. Macdonald J, Forouzan O, Warczytowa J, et al. MRI assessment of cardiac function in response to exercise. Proceedings of the 23rd ISMRM annual meeting. 2015.

5. Ibrahim EH, Johnson KR, Miller AB, et al. Measuring aortic pulse wave velocity using high-field cardiovascular magnetic resonance: comparison of techniques. Journal of Cardiovascular Magnetic Resonance. 2012; 26(12).

Figures

Figure 1: MRI-compatible exercise device. The subject exercises via a dynamic stepping motion to the beat of a metronome. The resistance is controlled by removable weights at the end of each lever. Power is calculated with readings from an optical displacement sensor on the levers and frequency of the motion.

Figure 2: Exercise and scanning protocols for the three cohorts of interest. The younger controls exercised in three incremental stages of 50, 60, 70 W. The older controls and PH patients exercised at two lower stages of 35 W or 30 W due to limitations in their capacity for exercise.

Figure 3: Heart rate response for the three cohorts of interest. The two control groups showed similar responses to their exercise protocol, while the PH subjects showed a stronger exercise response. A bracket indicates statistical significance between two groups.

Figure 4: Comparison of stroke volume, cardiac output, peak systolic velocity and flow, relative area change, and pulse wave velocity among the three cohorts at rest and following exercise stress. A bracket between two boxes indicates a statistically significant difference.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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