Exercise lung water MRI in a clinical cohort

Background: Imaging pulmonary edema is an important clinical diagnostic capability when assessing dyspnea and suspected heart failure (HF).¹ While multiple 2D modalities are used clinically, including chest X-ray and echocardiography, cardiovascular magnetic resonance (CMR)-based proton density weighted methods allow 3D quantification of lung water density (LWD).^2,3 Recent developments allow time-resolved LWD imaging during exercise. However, dynamic imaging of cardiogenic exercise-induced cardiogenic increase in LWD has not been previously studied in a clinical cohort.³ We aimed to characterize the global, regional, and temporal behavior of CMR-determined LWD during exercise in a broad cohort of patients with and without HF.

Methods: We included 34 patients who underwent a clinical CMR-exam at Karolinska University Hospital, Stockholm, Sweden, or Medstar Washington Hospital Center, Washington DC, USA between (February 2024 – June 2025). Patients were scanned at 1.5T (MAGNETOM Sola, Siemens) during an exercise protocol (3-minutes rest, 3-minute exercise, 4 minutes rest) using a CMR-compatible pedal ergometer (CardioStep, Ergospect). Lung images were continuously acquired using a free-breathing gradient echo sequence (TE/TR/ θ =0.7ms/5ms/1°, 1.5ms readout, 3.5x3.5x3.5mm resolution, FOV 450x450x252mm, 10-min acquisition time). Dynamic LWD-maps were derived using previously described sliding window image reconstruction and automated image analysis, with manual lung segmentation corrections³. Global and regional anteroposterior LWD dynamics⁴ were compared across HF groups.

Results: Patient characteristics are summarized in Table 1. Across the entire cohort, there was a consistent increase in LWD during exercise (median [inter-quartile range, IQR]: 2.9 [1.9-3.6] %, p< 0.001), followed by a clearance of LWD buildup. We did not observe any differences in global (Figure 1) or regional (Figure 2) LWD dynamics across groups (No HF, median [IQR]: 18.2 [15.4-19.8] %, HF and EF≥50%: 19.5 [16.3-22.0] %, HF and EF< 50%: 18.6 [15.4-21.8] %, p >0.05). There was also a similar pattern with median peak increase in global LWD (No HF: 2.4 [1.0-3.6] %, HF and EF≥50%: 3.4 [1.7-4.6] %, HF and EF< 50%: 3.1 [2.3-3.5]% LWD increase). Visualization of LWD-curves during exercise are shown in Figures 1E and 1F. Baseline global LWD was not correlated with body mass index (R²=0.11, P=0.058). Peak global LWD increase was not correlated with exercise-induced increase in heart rate (R²=0.08, p=0.11).

Conclusion: Dynamic CMR-measured LWD during exercise is feasible, showing a consistent exercise-induced increase in LWD, although we found no clear association with HF diagnosis, LVEF or NYHA classification. The accumulation of lung water during exercise may have been mitigated by HF medical treatment, moderate exercise intensity and heterogeneity in adaptation mechanisms such as lung lymph drainage capacity. Our sample size was limited, particularly the HFpEF and NYHA III-IV subgroups.

Table 1. Cohort Characteristics

 

 

Characteristics	All patients	Non-HF	HF with EF ≥50 %	HF with EF < 50 %	NYHA I-II	NYHA III-IV	P-value (HF vs non-HF)
N	34	11	5	18	19	4
Basic characteristics
Age – years	59.5 ±12.9	58.5 ±16.7	54.6 ± 12.6	61.5 ± 11.3	59.4 ± 11.7	62.5 ± 12.7	n.s.
Sex – female (%)	18 (51)	9 (82)	4 (80)	5 (28)	7 (37)	2 (50)	0.03
BMI – kg/m2	29.7 ± 6.9	29.1 ± 6.1	29.8 ± 9.8	30.0 ± 6.8	30.1 ± 7.9	29.3 ± 4.1	n.s.
BSA – m2	2.03 ± 0.26	1.95 ± 0.26	2.05 ± 0.23	2.07 ± 0.27	2.08 ± 0.26	2.03 ± 0.24	n.s.
Height – cm	172 ± 8	168 ± 5	174 ± 6	174 ± 9	174 ± 8	172 ± 11	n.s.
Weight – kg	87 ± 21	83 ± 19	89 ± 23	90 ± 21	90 ± 22	87 ± 16	n.s.
Disease history
Atrial fibrillation at CMR - n (%)	1 (3)	0 (0)	0 (0)	1 (6)	1 (5)	0 (0)	n.s.
Diabetes – n (%)	12 (359	3 (37)	0 (0)	9 (50)	7 (37)	2 (50)	n.s.
Hypertension – n (%)	21 (62)	7 (64)	2 (40)	12 (67)	11 (58)	3 (75)	n.s.
Hyperlipidemia – n (%)	21 (62)	8 (73)	2 (40)	11 (61)	11 (58)	2 (50)	n.s.
History of smoking – n (%)	3 (9)	1 (9)	1 (20)	1 (6)	2 (11)	0 (0)	n.s.
Heart failure diagnosis – n (%)	23 (38)	0 (0)	5 (100)	18 (100)	19 (100)	4 (100)
Medications
ACEi/ARB – n (%)	21 (62)	3 (27)	2 (40)	16 (89)	14 (74)	4 (100)	0.008
ARNI – n (%)	15 (44)	1 (9)	0 (0)	14 (78)	10 (53)	4 (100)	0.008
Beta blocker – n (%)	22 (65)	5 (45)	2 (40)	15 (83)	13 (68)	4 (100)	n.s.
Loop diuretic – n (%)	10 (29)	2 (18)	0 (0)	8 (44)	5 (26)	3 (75)	n.s.
Other diuretic – n (%)	8 (24)	3 (27)	0 (0)	5 (28)	4 (21)	1 (25)	n.s.
SGLT2-inhibitor – n (%)	13 (38)	1 (9)	0 (0)	12 (67)	10 (53)	2 (50)	0.023
CMR findings
LVEF	49 (35-60)	63 (60-66)	56 (52-58)	35 (29-41)	41 (33-50)	30 (23-36)	< 0.001
Ischemic LGE	6 (18)	0 (0)	0 (0)	6 (33)	4 (21)	2 (50)	n.s
Primary CMR diagnosis
-Ischemic cardiomyopathy	4 (12)	0 (0)	0 (0)	4 (22)	3 (16)	1 (25)	n.s
-Nonischemic cardiomyopathy	15 (44)	0 (0)	3 (60)	12 (67)	13 (68)	2 (50)	< 0.001
-Storage or infiltrative disease	1 (3)	0 (0)	0 (0)	1 (6)	1 (5)	0 (0)	n.s
-Hypertrophic cardiomyopathy	2 (6)	1 (9)	0 (0)	1 (6)	0 (0)	1 (25)	n.s
-CMR findings within normal ranges	11 (32)	9 (82)	2 (40)	0 (0)	2 (11)	0 (0)	< 0.001
-Other	1 (3)	1 (9)	0 (0)	0 (0)	0 (0)	0 (0)	n.s.

Abbreviations: ACEi - Angiotensin-Converting Enzyme inhibitor. ARB - Angiotensin II Receptor Blocker. ARNI - Angiotensin Receptor-Neprilysin Inhibitor. BMI - Body Mass Index. BSA - Body Surface Area. CMR - Cardiac Magnetic Resonance. LGE - Late Gadolinium Enhancement. LVEF - Left Ventricular Ejection Fraction. n.s. – not significant.The top row (panels A and B) shows the lung water density (LWD) measured at baseline, by ejection fraction (EF) and New York Heart Association (NYHA) class symptom severity. The middle row (panels C and D) shows the peak LWD increase during exercise, reported in percentage points. The bottom row (panels E an F) shows the dynamic LWD over time during the exercise protocol according to EF (panel E) and NYHA class (panel F), respectively. Transparent lines represent individual data points, whereas thick lines represent the group median LWD at each respective timeframe. Statistical comparisons were made using Student’s T-test or Mann Whitney U-test, as appropriate.
The top row shows the difference between resting posterior and anterior lung water density (LWD) (Panel A) with comparisons according to ejection fraction (EF) (Panel B) and New York Heart Association (NYHA) class (Panel C), respectively. The middle row shows the peak increase of LWD in the anterior third of the lungs (Panel D) by EF (Panel E) and NYHA (Panel F), respectively. The bottom row shows the difference between posterior and anterior LWD (Panel G) at the time of peak global LWD increase by EF (Panel H) and NYHA class (Panel I), respectively. Statistical comparisons were made using Student’s T-test or Mann Whitney U-test, as appropriate.