Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure (mPAP) ≥25mmHg at rest. A clinical classification is established in order to individualize different groups of PH sharing similar pathological findings¹. Among them, both pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) show pre-capillary PH. However, their image findings such as ventilation/perfusion scintigraphy implies difference of occluded vasculatures and pulmonary circulation between the two diseases. Past study demonstrated the presence of vortex flow visualized by 4D flow MR imaging in the pulmonary trunk in PH². However, there have been sparse data showing differences of PA flow patterns between PAH and CTEPH. We aimed to evaluate whether PA flow patterns imaged with 4D flow MR imaging are different between PAH and CTEPH.

This retrospective study included 64 consecutive patients with pulmonary hypertension (PAH, 25, CTEPH, 39). All patients were imaged with a 3.0T whole-body scanner (Magnetom Trio A Tim System, Siemens Healthcare, Erlangen, Germany). Scan protocols included standard cardiac cine MR imaging and prototype 4D flow MR imaging of the pulmonary trunk. 4D flow MR imaging was acquired using the following parameters: 3 dimensional phase-contrast MR imaging with 3-directional velocity encoding in transverse slab orientation; ECG gating; respiratory gating using a navigator; TR/TE, 52.4ms/3.43ms; flip angle, 15 degrees; VENC, 50-110cm/sec; voxel size, 2.4mm x 1.8mm x 3.5mm; the number of slices, 30.

Using cine MR images, we measured left-ventricular ejection fraction (LVEF), LV stroke volume, LV cardiac index, right-ventricular ejection fraction (RVEF), RV stroke volume, RV cardiac index, RV end-diastolic and end-systolic volume index (RVEDVI and RVESVI) and pulmonary trunk diameter to ascending aortic diameter ratio (PA/AA ratio). 4D flow images were analyzed with a standalone prototype software (4D Flow Demonstrator ver. 2.3, Siemens Healthcare, Erlangen, Germany). On 4D flow MR imaging, two parameters indicating the degree of vortex flow in the pulmonary trunk were measured in the end-systolic phase. 1) Backward flow ratio: a cross-section that contained the largest vortex flow was extracted; a ratio of area with backward flow to total cross-sectional area was calculated (backward flow ratio). 2) Forward flow eccentricity: on the same cross-section with the largest vortex flow, a distance between the center of gravity of forward flow and the center of gravity of total flow was calculated; the distance was divided by the mean of long and short axis diameters of the cross-section (forward flow eccentricity).

MRI parameters, mPAP as assessed by right heart catheterization and patients’ demographics were compared between the two groups with PAH and CTEPH using unpaired t-test. Multivariable logistic regression analysis using a stepwise backward selection method (p>0.10 for removal from model) was used to evaluate significant difference of PA flow patterns controlling for potential confounding factors. P < 0.05 was used to designate statistical significance.

The mean age in the PAH group was significantly lower than that in the CTEPH group (39.4±13.7 years vs. 66.1±13.0 years, p<0.01). The mean of mPAP was not significantly different between the two groups (42.5±12.3 mmHg vs. 37.6±9.5 mmHg, p<0.08).

Vortex flow in the pulmonary trunk was observed in all patients on 4D flow MR imaging. Significant differences between the PAH and CTEPH groups were observed in the following MR parameters: LVEF (56.6±9.8% vs. 63.4±9.7%, p<0.01), RVEDVI (124.4±59.9 ml/m² vs. 96.9±30.0 ml/m², p=0.01), RVESVI (79.2.4±55.3ml/m² vs. 57.24±23.9ml/m², p=0.03), PA/AA ratio (1.4±0.3 vs, 1.1 ± 0.2, p<0.01), backward flow ratio (0.31±0.12 vs. 0.22±0.09, p<0.01) and forward flow eccentricity (0.28±0.10 vs. 0.20±0.13, p=0.01).

In a multivariable logistic regression analysis controlling for age and mPAP as potential confounders, only backward flow ratio remained significant; when CTEPH was used as the reference, the adjusted odds ratio for 0.1 increase of backward flow ratio was 1.1 (95% confidence interval, 1.04, 8.37, p=0.04). The other MR parameters were removed by the backward stepwise selection.

Vortex flow in the pulmonary trunk may be a characteristic finding of PH. Among various parameters derived by cardiac MR imaging, backward flow ratio was the strongest differentiator between PAH and CTEPH after controlling for age and mPAP. CTEPH mainly differs from PAH by the proximal location of pulmonary artery obstruction. Occlusion in the proximal portion may lead to production of pressure wave reflections and decrease vascular compliance³. These factors may induce difference of flow patterns in the pulmonary trunk between CTEPH and PAH as identified by 4D flow MR imaging. Backward flow area ratio was the strongest differentiator between PAH and CTEPH. 4D flow MR imaging has a potential to visualize the difference of PA hemodynamics according to etiologies of PH.