Comparison of MRI and VQ-SPECT as a Screening Test for Patients With Suspected CTEPH: CHANGE-MRI Study Design and Rationale

Abstract

The diagnostic strategy for chronic thromboembolic pulmonary hypertension (CTEPH) is composed of two components required for a diagnosis of CTEPH: the presence of chronic pulmonary embolism and an elevated pulmonary artery pressure. The current guidelines require that ventilation-perfusion single-photon emission computed tomography (VQ-SPECT) is used for the first step diagnosis of chronic pulmonary embolism. However, VQ-SPECT exposes patients to ionizing radiation in a radiation sensitive population. The prospective, multicenter, comparative phase III diagnostic trial CTEPH diagnosis Europe - MRI (CHANGE-MRI, ClinicalTrials.gov identifier NCT02791282) aims to demonstrate whether functional lung MRI can serve as an equal rights alternative to VQ-SPECT in a diagnostic strategy for patients with suspected CTEPH. Positive findings are verified with catheter pulmonary angiography or computed tomography pulmonary angiography (gold standard). For comparing the imaging methods, a co-primary endpoint is used. (i) the proportion of patients with positive MRI in the group of patients who have a positive SPECT and gold standard diagnosis for chronic pulmonary embolism and (ii) the proportion of patients with positive MRI in the group of patients with negative SPECT and gold standard. The CHANGE-MRI trial will also investigate the performance of functional lung MRI without i.v. contrast agent as an index test and identify cardiac, hemodynamic, and pulmonary MRI-derived parameters to estimate pulmonary artery pressures and predict 6-12 month survival. Ultimately, this study will provide the necessary evidence for the discussion about changes in the recommendations on the diagnostic approach to CTEPH.

Keywords: CTEPH; MRI; PH; VQ-SPECT; diagnostic strategy; pulmonary embolism.

Copyright © 2020 Lasch, Karch, Koch, Derlin, Voskrebenzev, Alsady, Hoeper, Gall, Roller, Harth, Steiner, Krombach, Ghofrani, Rengier, Heußel, Grünig, Beitzke, Hacker, Lang, Behr, Bartenstein, Dinkel, Schmidt, Kreitner, Frauenfelder, Ulrich, Hamer, Pfeifer, Johns, Kiely, Swift, Wild and Vogel-Claussen.

Figures

Figure 1

Diagnostic algorithm for CTEPH based on the 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension with potential change in red (7, 8).

Figure 2

Cardio-pulmonary MRI (A,B,D,E,F,H) and V/Q SPECT (C,G) images of a patient with CTEPH. MRI angiography [coronal maximum intensity projection, (A)] Maximum intensity projection (MIP) depicts pulmonary artery stenosis and irregularities predominantly in the lower lobes as well as in the left upper lobe. Time resolved 4D MRI perfusion DCE angiography (coronal, acquisition time per volume: 1.3 s, voxel size 3 × 4 × 5 mm, B) depicts corresponding parenchymal hypoperfusion, which, matches with the Q-SPECT (coronal, voxel size 5 × 5 × 12 mm, C) findings. V-SPECT (coronal, voxel size 5 × 5 × 12 mm, G) shows relatively homogeneous ventilation. In accordance, neither infiltrates nor atelectasis are seen on T2 weighted Half-Fourier Acquisition Single-shot Turbo spin Echo (HASTE)-MRI (coronal, voxel size 2 × 2 × 6 mm, F), notice the signal in the main pulmonary arteries due to slow flow. V/Q Phase resolved functional lung MRI (PREFUL, coronal, voxel size 4 × 4 × 15 mm, D,H) depicts normal regional ventilation (H) and regions of hypoperfusion matching the V/Q SPECT (C,G) and DCE MRI (B) findings. Short axis cardiac cine MRI shows right ventricular hypertrophy and septal flattening (arrow) in systole due to increased pulmonary vascular resistance.

Figure 3

Detailed description of the MRI protocol.

Figure 4

Integration of the MRI scan in the clinical workflow in the CHANGE-MRI study.