Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension: A review

Table 1 Characteristics of included studies

Ref.	Study design	Patients (n)	Demographics	Aims	Methodology	Analysis	Results (95%CI)
Amundsen et al[31], 1997	Prospective, qualitative	7	7 patients with suspected PE	To evaluate the feasibility of perfusion MRI for detection of perfusion defects distal to suspected pulmonary embolism compared to V/Q	Rapid acquisition of two sets of dynamic images in coronal and trans axial plane	Qualitative analysis (MRI Vs V/Q)	Perfusion MRI correctly identified 16/18 lung segments with perfusion defects
Amundsen et al[32], 2002	Prospective, qualitative	42	20 suspected PE, 11 Pneumonias, 11 COPD	To compare perfusion MRI and V/Q for the perfusion defects detection	Rapid acquisition of two sets of dynamic images in coronal and trans axial plane with an inversion recovery gradient MRI sequence	Qualitative analysis (MRI Vs V/Q)	For PE: Intra-modality kappa = 0.77, Inter-observer kappa = 0.92
Ohno et al[33], 2004	Prospective, qualitative	40	Controls=15, (Mean age 42 yr), PH patients=25, (Mean age 61 yr)	To assess regional differences in quantitative pulmonary perfusion parameters using MRI	Three dimensional ultrafast DCE-MRI was performed and PBF, PBV & MTT measured by signal intensity time course curve	MATLAB, For PBF, MTT, PBV, Mean, SD, ANOVA, Fisher’s PLSD test	PBF, PBV & MTT showed significant differences between normal volunteers and patients with PH (P < 0.05)
Nikolaou et al[34], 2005	Prospective, qualitative	29	16 females (mean age 54 ± 17 yr), 13 males (Mean age 57 ± 15 yr)	Pulmonary hypertension & CTEPH differentiation by perfusion MRI and pulmonary angiography	Turbo fast low angle shot gradient echo MRI sequence was performed by using generalized auto calibrating partially parallel technique or GRAPPA	Student t test for significance, ROC using SPSS software	ROC: MRA = 0.85, MRI = 0.82, MRA, MRI combined0.90
Kluge et al[35], 2005	Prospective, qualitative	31	15 females, 18 males, (Mean age 59.4 yr) with acute PE	To compare the feasibility of perfusion MRI with CT for follow up examination in acute PE	Contrast enhanced 3-dimensional fast low angle shot or FLASH sequence was used for perfusion MRI and time to peak and peak enhancement was measured	T test for paired samples using SPSS	Follow up examination using MRI were feasible compared to CT for all patients
Kluge et al[36], 2006	Prospective, qualitative	41	41 patients with suspected PE	To assess the agreement of perfusion MRI with SPECT for identifying perfusion defects	Contrast enhanced 3-dimensional fast low angle shot or FLASH sequence was used for perfusion MRI	Not given	MRI and SPECT agreement kappa Lobar = 0.98, Segmental = 0.98, Subsegmental = 0.69
Ohno et al[37], 2007	Prospective, qualitative	28	Controls=14, (Mean age 34 yr), PH patients=14, (Mean age 41 yr)	To measure diagnostic potential of DCE-MRI for pulmonary hypertension	Three dimensional ultrafast DCE-MRI was performed and PBF, PBV & MTT measured by signal intensity time course curve	MATLAB, For PBF, MTT, PBV, MathWorks, Mean, SD, T test	Difference for study groups: PBF: P < 0.0001, PBV: P < 0.0001, MTT: P < 0.0001
Ley et al[38], 2007	Prospective, qualitative	25	Controls=5, PH patients=20	To measure diagnostic potential of DCE-MRI for pulmonary hypertension	Contrast enhanced 3-dimensional fast low angle shot or FLASH sequence was used for perfusion MRI	Quantitative analysis of PBF, PBV and MTT, Mann-Whitney U-test	PBF, PBV & MTT showed significant differences between normal volunteers and patients with PH (P < 0.05)
Ohno et al[39], 2008	Prospective, qualitative	27	Controls = 9, 18 gender and age matched CTD patients	To measure diagnostic potential of DCE-MRI for PAH	PBF, MTT and PBV measured by DCE-MRI and correlated by %DL(CO) measured by pulmonary function test and mPAP, sPAP measured by doppler echo	MATLAB, MathWorks, Mean, SD, T test, Correlation test	PBF, MTT, PBV correlated positively with %DL(CO) & sPAP (P < 0.05), PBF& PBV correlated positively with mPAP& moderately with PVR (P < 0.05)
Ohno et al[40], 2010	Prospective, qualitative	50	50 PE patients with acute pulmonary thromboembolism (APTE)	To measure diagnostic potential of DCE-MRI for acute pulmonary thromboembolism (APTE)	PBF, PBV, MTT & APTE index measured by DCE-MRI using 3-dimensional spoiled gradient sequence, MPAP, PVR measured by RHC. RV/LV diameter ratio, APTE index measured by CT & MRA	ROC curve, Logistic regression	PBF and MTT significantly lower for APTE segments to non-APTE segments (P < 0.05), APTE indexes from all modalities proved significant predictors for differentiating APTE patients
Stein et al[41], 2010	Prospective, qualitative	371	371 adults with diagnosed or excluded pulmonary embolism- (PIOPED III)	To assess performance of MRA and venography for pulmonary embolism detection	MRA was compared with CTPA, V/Q scan, venous ultrasonography, D-dimer assay, and clinical assessment, Qualitative assessment by expert reader only	Chi-square test ANOVA	Technically adequate images for MRA: SE: 78%, SP: 99%
Kang et al[42], 2011	Prospective, qualitative	35	35 PAH patients (Mean age 44 yr)	To assess if Cardiac MRI based pulmonary artery distensibility index correlates with RHC estimates for PAH	Pulmonary artery distensibility indices were derived from transverse view MRI and compared with PVR using RHC	Correlation	Non-invasive MRI based pulmonary artery distensibility index correlates with RHC based estimates P < 0.001
Ohno et al[43], 2012	Prospective, qualitative	24	Response group=13, Non-response group=11, 12 females & 12 males mean age 68 yr ± 8.6	CTPA, MRA & DCE-MRI comparison for treatment response in inoperable CTEPH patients	PBF, PBV, MTT measured by DCE-MRI using 3-dimensional spoiled gradient sequence, RV/LV diameter ratio and embolic burden measured by CTPA & MRA	Mean of student T test, Correlation, ROC curve analysis, McNemar’s test	DCE-MRI SP = 90%, AC = 95%, CTPA SP = 36%, AC = 70%, MRA SP = 54%, AC = 79%
Ley et al[44], 2013	Prospective, qualitative	20 PAH or CTEPH patients	Controls 10, Training group 10	To evaluate if training improves pulmonary perfusion in PH as assessed by MR perfusion imaging	Training group received in hospital exercise training while control group received conventional rehabilitation. 6 min walk test, PBF, PBV, MTT & peak flow velocity measured by MR perfusion were assessed for both groups from baseline to 3 wk	Mann-Whitney-Wilcoxon test, Spearman correlation coefficient	Training group had significantly improved 6-min walk test, MR flow and MR perfusion
Rajaram et al[45], 2013	Prospective, qualitative	132	78 CTEPH patients	To compare the diagnostic accuracy of perfusion MRI for CTEPH Vs. CTPA and V/Q	Pulmonary perfusion MRI using time resolved 3-Dimensional spoiled gradient and pulmonary MRA were compared with CTPA and V/Q	Not given	SE, SP in %, MRI: 97, 92, V/Q: 96, 90, CTPA: 94, 98
Revel et al[46], 2013	Prospective, qualitative	274	274 suspected PE patients	To evaluate unenhanced, enhanced perfusion and MR angiography for PE detection	Unenhanced steady state free precession or SSFP, fast spoiled gradient echo for perfusion MRI and MR angiography were compared with CTPA	Chi-squared Kappa statistics	Kappa agreement MRA = 0.77, Perfusion MRI = 0.51, Unenhanced MRI = 0.62
Sugimoto et al[47], 2013	Prospective, qualitative	34	34 congenital heart disease patients	To assess if velocity encoded cine imaging can measure pulmonary artery pressure in children with congenital heart disease	Pulmonary blood flow (QP), systemic blood flow (QS), acceleration time, ejection time, peak velocity, and maximal change in flow rate during ejection (MCFR) were measured by velocity encoded MRI and RHC		Velocity encoded MRI correlated strongly with RHC for QS, right to left QP ratio and QP/QS. Suggesting usefulness of MRI for pulmonary artery pressure measurement
Schoenfeld et al[48], 2015	Prospective, qualitative	64	64 ruled out or confirmed PE patients	To compare perfusion weighted Fourier decomposition or PW-FD to DCE-MRI for PE detection	Time resolved angiography with stochastic trajectories or TWIST for DCE-MRI was used and compared with PW-FD	Qualitative only, Kappa statistics	For PW-FD per patient basis, SE = 100%, SP = 95%, PPV = 98%, NPV = 98%, Intraobserver k = 0.96, Interobserver k = 0.96
Ingrisch et al[49], 2016	Prospective, qualitative	18	8 acute PE, 10 controls	DCE-MRI evaluation for acute PE detection compared with CTPA	Qualitative assessment of presence and absence of perfusion defects using DCE-MRI using TWIST sequence	Cohen’s kappa, Fisher’s exact test	SE: 87-93%, SP: 90-95%, PPV: 87-93%, NPV: 90-95%, Inter-reader agreement: k = 0.77, Intra-modality agreement: P < 0.001
Johns et al[50], 2017	Prospective, qualitative	74	20 male, 26 female, Mean age 62 ± 14 yr	DCE-MRI, SPECT & CTPA comparison for CTEPH diagnosis	Qualitative comparison of presence/absence of perfusion defects on DCE-MRI using fast spoiled gradient echo, perfusion, SPECT and CTPA	2*2 predictive table, Kappa (k) for inter-observer agreement	SE: 100%, SP: 81%, PPV: 90%, NPV: 100%, Inter-observer agreement for DCE-MRI: k = 0.88, SPECT: (k = 0.80)
Voskrebenzev et al[51], 2018	Prospective, qualitative	5	2 controls, 1 CTEPH patient 1 CF patient, 1 obstructive pulmonary disease patient	To assess the feasibility of phase resolved functional lung MRI (PREFUL) for quantitative reginal ventilation and perfusion	Time to peak, V/Q maps and fractional ventilation flow volume were calculated using PREFUL MRI	Full Cardiac and respiratory cycle were sorted using PREFUL	Post endarterectomy, CTEPH patient showed increased perfusion time to peak in visual agreement with DCE-MRI
Agoston-Coldea et al[52], 2018	Prospective, qualitative	30	30 consecutive patients with COPD and suspected secondary pulmonary hypertension	To evaluate ability of CMR right ventricular parameters and pulmonary artery stiffness to identify pulmonary hypertension	Clinical examination. 6-min walk test, echocardiography, RHC and cardiac functions and late gadolinium CMR imaging with phase contrast flow imaging of pulmonary artery. Followed up for a mean period of 16 mo	ROC curve analysis, Kolmogorov-Smirnov test, ANOVA test. Fischer’s exact test	Pulse wave velocity: SE = 93.5%, SP = 92.8%
Schoenfeld et al[53], 2019	Prospective, qualitative	29	20 CTEPH patients	Cardiopulmonary evaluation of treatment response after BPA in CTEPH patients	PBF and first pass bolus kinetic parameters and biventricular mass and functions were evaluated using MRI	Paired two sides Wilcoxon rank sum test, Spearman p correlation, Multiple linear regression	Post BPA, PBF changes in treated lobes were significantly higher than non-treated lobes P < 0.05, MRI derived pulmonary artery pressure ejection fraction, RV stroke volume, CO, ventricular mass index & PBF in non-treated lobes correlated with PBF changes in treated lobes P < 0.05
Ray et al[54], 2019	Prospective, qualitative	51	20 mild PH, 31 moderate to severe PAH	Utility of pulmonary artery pulsatility by cardiac MRI as an early marker of pulmonary hypertension	Standards steady state free precession or cine SSFP for pulmonary artery pulsatility and phased contrast MRI imaging for pulmonary flow assessment	Wilcoxon rank sum test, Roc analysis	Pulmonary artery pulsatility declined from normal (53%), mild (22%) and moderate to severe PAH (17%)
Alsady et al[55], 2021	Prospective, qualitative	20	20 CTEPH patients	To compare DCE-MRI and computed tomography for lung perfusion defects before and after pulmonary endarterectomy	Lobe based analysis of perfusion defects using DCE-MRI and PBF and PBV measurement, comparison with dual energy computed tomography	Pearson product-moment correlation, Paired t test using MATLAB	Correlation between CT and MRI based perfusion defects (r > 0.78; P < 0.001)
Torres et al[56], 2022	Prospective, qualitative	41	20 IPF patients	DCE-MRI for the evaluation of lung perfusion in IPF	PBF CV, FVC% predicted %DL(CO) and LCI% were evaluated using DCE-MRI	Regression analysis, Spearman rank correlation	DCE-MRI identified regional perfusion defects between controls and IPF (P < 0.05). Correlation observed between PBF CV and %DL(CO) (r = 0.48, P < 0.001)

AC: Diagnostic accuracy; APTE: Acute pulmonary thromboembolism; BPA: Balloon pulmonary angioplasty; CI: Confidence interval; COPD: Chronic obstructive pulmonary disease; CTEPH: Chronic thromboembolic pulmonary hypertension; CTPA: computed tomography pulmonary angiography; CO: Cardiac output; CV: Coefficient of variation; DCE-MRI: Dynamic contrast enhanced magnetic resonance imaging; %DL(CO): Diffusing capacity of carbon monoxide; LV: Left ventricle; LCI: %(lung clearance index), MRA: Magnetic resonance angiography; MTT: Mean transit time; NPV: Negative predictive value; PAP: pulmonary artery pressure; PBF: Pulmonary blood flow; PBV: Pulmonary blood volume; PE: Pulmonary embolism; FVC: % Percent predicted forced vital capacity; PPV: positive predictive value; PVR: Pulmonary venous resistance; ROC: Receiver operating curve; SE: Sensitivity; SP: Specificity; sPAP: Systolic pulmonary artery pressure; SPECT: Single photon emission Computed tomography; SPSS: Statistical package for social sciences; RV: Right ventricle; V/Q: Ventilation perfusion scan.