Reduction in O-15-labeled-water lung uptake rate in patients with chronic thromboembolic pulmonary hypertension reflects pulmonary blood flow rather than blood volume

Objectives: Evaluating pulmonary blood flow (PBF) may be useful in assessing pulmonary perfusion abnormality in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The rate of O-15-labeled-water uptake as obtained using a mathematical model may be associated with PBF rather than with pulmonary blood volume. However, this possibility has not been studied. The purpose of the present study was to evaluate, using O-15-labeled water PET, whether there was a difference in lung uptake rate between patients with CTEPH and those with pulmonary arterial hypertension (PAH). In addition, for each group, we aim to quantify the uptake rate and to compare it to cardiac output (CO).

Methods: Eleven CTEPH and 16 PAH patients with WHO functional class II or III pulmonary hypertension (PH) prospectively underwent dynamic O-15-labeled-water PET at rest and during right heart catheterization. Seven healthy individuals also had dynamic O-15-labeled-water PET as controls. All CTEPH patients showed multiple perfusion defects in both lungs based on a Tc-99m macroaggregated human serum albumin lung scan. Dynamic O-15-labeled-water PET was used to measure whole and bilateral pulmonary perfusion. A single-tissue compartment model was used to estimate lung perfusion. Regions of interest were created on the whole and bilateral lung using transmission scan data. Thermodilution was used to measure CO (L/min).

Results: CTEPH and PAH showed similar mean pulmonary arterial pressure (mPAP) (CTEPH 36.7±11.6 mmHg vs. PAH 42.3±14.4 mmHg, P=0.30). CTEPH patients showed significantly lower whole lung uptake than did either PAH patients (145.9±21.6 mL/100mL of lung/min vs.182.4±33.0 mL/100mL of lung/min, P=0.0036) or controls (145.9±21.6 mL/100mL of lung/min vs.188.5±34.5 mL/100mL of lung/min, P=0.0052). CTEPH patients also showed significantly lower left (P=0.0043) and right (P=0.0029) lung uptake than did PAH patients. CTEPH showed CO (4.5±1.1 L/min vs. 4.7±1.1 L/min, P=0.66) and cardiac index (CI) (2.8±0.7 L/min/m² vs. 3.0±0.7 L/min/m², P=0.43) values similar to those for PAH. Uptake for the whole O-15-labeled-water lung did not correlate with CO (R=-0.05, P=0.81) or CI (R=0.10, P=0.62).

Conclusion: CTEPH patients had significantly lower bilateral lung uptake rate than did PAH patients even with similar mPAP. The quantitative O-15-labeled-water lung uptake rate did not correlate with cardiac output. This may indicate that quantitative lung uptake rate may be associated with pulmonary blood flow rather than with lung blood volume. Therefore, quantitative lung perfusion assessment using O-15-labeled-water PET may be useful in evaluating pathophysiological severity or therapeutic response for CTEPH. Research Support: