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Perfusion Imaging During NO Inhalation Can Identify Patients With Pulmonary Arterial Hypertension

Key findings

  • In this study, combined positron emission tomography and high-resolution CT was used to characterize the spatial distributions of pulmonary perfusion and ventilation in four patients with pulmonary arterial hypertension (PAH) and five controls
  • Compared with breathing air during imaging, breathing oxygen plus nitric oxide produced significant differences in the regional distribution of perfusion between patients with PAH and controls
  • Changes in regional perfusion in response to oxygen plus nitric oxide were noted in all patients with PAH, including the two who had been non-responders on acute vasoreactivity testing
  • A parameter designated CV2Qvgrad (spatial heterogeneity of perfusion in the vertical direction) had the largest effect size in distinguishing PAH patients from controls
  • CV2Qvgrad measured during oxygen and nitric oxide inhalation may be a suitable biomarker for PAH and allow earlier detection that might improve survival

Only about 10% of patients with idiopathic pulmonary arterial hypertension (PAH) meet the European Society of Cardiology and European Respiratory Society (ESC/ERS) joint criteria for response to acute vasodilation during cardiac catheterization. Because the response to vasodilators at diagnosis affects therapeutic options and prognosis, a precise method is needed to identify patients with PAH.

Massachusetts General Hospital physicians have observed differences in pulmonary perfusion images acquired at baseline and during vasodilation that distinguished patients with PAH from healthy individuals. Puja Kohli, MD, MSSc, a physician–researcher previously in the Division of Pulmonary and Critical Care Medicine, Tilo Winkler, PhD, associate investigator in the Department of Anesthesia, Critical Care and Pain Medicine, R. Scott Harris, MD, also previously of the Division of Pulmonary and Critical Care Medicine, and colleagues report in Respiratory Research.


The team studied four patients with PAH and five controls using combined positron emission tomographic and high-resolution CT imaging of pulmonary perfusion and ventilation.

Four primary parameters were measured while the participants were breathing air and, separately, while they were breathing both oxygen and inhaled nitric oxide (O2+iNO):

  • The total spatial heterogeneity of perfusion (CV2Qtotal)
  • Component of CV2Qtotal in the vertical direction (CV2Qvgrad)
  • Residual heterogeneity (CV2Qr)
  • Vertical gradient in perfusion (Qvgrad)

Perfusion Heterogeneity

Breathing O2+iNO significantly enhanced differences in perfusion distribution between controls and patients with PAH. During O2+iNO:

  • CV2Qvgrad was significantly higher in controls than in patients, 0.08 vs. 6.7 × 10–3 (P<0.001), effect size 4.30 (95% CI, 1.42–7.17)
  • Qvgrad was −7.3 vs. −2.5 (P=0.002), effect size −3.25 (95% CI, −5.65 to −0.84)
  • CV2Qtotal was 0.12 vs. 0.06 (P=0.01), effect size 2.23 (95% CI, 0.22–4.25)
  • CV2Qr and its length scale spectrum were similar in controls and patients

There were no significant differences between patients and controls in ventilation-perfusion distributions while breathing air.

An Unexpected Finding

Two patients with PAH had been non-responders to acute vasodilation according to the ESC/ERS guidelines. Their mean absolute changes in voxel-by-voxel perfusion during exposure to O2+iNO were similar to controls, even though they showed no change in their vertical gradient in perfusion.

There's clinical evidence that patients with a ≥30% decrease in pulmonary vascular resistance in response to O2+iNO can benefit from vasodilator therapy, even if they don't meet ESC/ERS criteria for response during vasoreactivity testing.

The Potential to Improve Care

This study suggests the potential for CV2Qvgrad measured during O2+iNO inhalation to serve as a biomarker for PAH. Earlier detection of PAH with perfusion imaging might improve survival.

Explore research in the Division of Pulmonary and Critical Care Medicine

View research in the Department of Anesthesia, Critical Care and Pain Medicine

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