Abstract Rationale Pulmonary sarcoidosis is a granulomatous inflammatory disease with variable rates of persistence, progression, and response to therapy. Identifying vulnerable patients and proactively guiding treatment decisions regarding immunosuppressive medications remains a challenge. Identifying vulnerable patients to proactively guide immunosuppressive treatment decisions remains a challenge. Current radiographic tools lack the sensitivity and specificity to predict fibrotic progression, and increase risk of radiation with serial imaging. Alternatively, xenon gas (129Xe) MRI can be used to evaluate regional ventilation and gas exchange without risks associated with repeated radiation dose. These biomarkers may provide quantitative regional information early in the disease process, advance mechanistic understanding, and provide insight into potential future interventional and therapeutic strategies. Methods Patients with varying severity of pulmonary sarcoidosis were recruited across three sites. All underwent consortium-standardized gas exchange xenon MRI to map ventilation, membrane uptake, and red blood cell (RBC) transfer. Data were centrally processed using publicly available pipelines. Quantitative outputs included ventilation defect percent (VDP - impaired ventilation), membrane defect (MDP - no membrane uptake) and membrane high percent (MHP - inflammation/membrane thickening), and RBC defect percent (RDP - no RBC transfer). Results Data from twenty patients (12F/8M; 59.6 ± 12.6 years) were included. Subjects demonstrated significant variability in functional 129Xe metrics (see Figure 1 for functional maps from 5 subjects). Airflow obstruction is variable in sarcoidosis, and our cohort exhibited a range of ventilation impairments, from minimal to extensive. Mean (SD) VDP was 16.4% (14.5%) (range:2.1% - 47.4%). Membrane uptake was similarly widely variable, with some patients exhibiting elevated membrane signal similar to common signatures in interstitial lung disease, while others exhibited reduced membrane signal as is commonly seen in COPD. Mean (SD) MDP was 19.66% (25.44%) (range:0% - 77.80%), while mean MHP was 7.23% (21.10%) (range:0% - 92.37%). Mean (SD) RDP was 10.87% (8.93) (range:0.03 - 28.65). Mean RBC:Membrane ratio was 0.34 (0.10), compared to published healthy reference distributions (0.49 - 0.55), indicating impaired gas exchange in this population. Conclusions Xenon MRI reveals significant heterogeneity in regional pulmonary function, suggesting that functional 129Xe imaging has the potential for personalized assessment of the underlying pathophysiology in pulmonary sarcoidosis. Such non-invasive imaging further expands potential for longitudinal evaluation of the disease course and/or impact of therapy. These imaging-based biomarkers may help clinicians identify subclinical manifestations of pulmonary impairment that are likely to go undetected via other tools, thereby aiding in early management of this variable and often unpredictable disease. This abstract is funded by: NIH/NHLBI R01 HL126771; RSNA Research Seed Grant RSD24-338
Puliyakote et al. (Fri,) studied this question.