Functional imaging of regional pulmonary perfusion using arterial spin labeling proton MRI (ASL-FAIRER) has the potential to provide increased sensitivity to early pulmonary vascular disease because of the ability to detect locally impaired function that is obscured by otherwise normal lung. We hypothesized that pulmonary arterial hypertension (PAH, WHO group I) manifests as a progressive alteration in the pulmonary circulation with: increases in the volume of un-perfused regions as vessels succumb to remodeling (volume of absent perfusion, VAP, =% of lung ROI with signal characteristics indistinguishable from noise), increases in the spatial heterogeneity of perfusion (relative dispersion, =SD/mean), and increases in the spatial heterogeneity of the fluctuations in perfusion over time (fluctuation dispersion, calculated as the SD of the change in perfusion from baseline in a time series) reflecting a failure of local pressure regulation.
As a first step to developing early PAH biomarkers, we evaluated these metrics in patients with PAH (9F,Age=51±11y, height=161±9cm, weight=62±12kg) and controls (7F,2M Age=40±16y, height=165±12cm, weight=72±12kg). ASL-FAIRER was used to measure regional pulmonary perfusion in a single sagittal slice in the right lung. Subjects were imaged supine in a 1.5T GE MR scanner. There were no significant differences between PAH and controls for age (p=0.11), height (p=0.43), or weight (p=0.08), however FEV1%pred (p=0.02) and FVC%pred (p=0.01) were significantly reduced in PAH. VAP was significantly increased in PAH (9.1±0.07% PAH, 2.8±0.04% controls, p=0.02) as was relative dispersion (1.28±0.28 PAH, 0.93±0.11 controls, p=0.003) and fluctuation dispersion (0.38±0.11 PAH, 0.17±0.04 controls, p<0.0001). Combined, the two spatial metrics, VAH and relative dispersion, perfectly distinguished the groups (area under the ROC curve =1.0) as did the fluctuation dispersion (area under the ROC curve =1.0). Proton MRI perfusion biomarkers provide a high degree of sensitivity and specificity for PAH and may provide useful noninvasive screening tools.