OBJECTIVES: The objective of this work was to compare quantification techniques for CEST imaging that specifically separate APT and NOE effects for application in the clinical setting. Towards this end a methodological comparison of different CEST quantification techniques was undertaken in healthy subjects, and around clinical endpoints in a cohort of acute stroke patients.
METHODS: MRI data from 12 patients presenting with ischaemic stroke were retrospectively analysed. Six APT quantification techniques, comprising model-based and model-free techniques, were compared for repeatability and ability for APT to distinguish pathological tissue in acute stroke.
RESULTS: Robustness analysis of six quantification techniques indicated that the multi-pool model-based technique had the smallest contrast between grey and white matter (2%), whereas model-free techniques exhibited the highest contrast (>30%). Model-based techniques also exhibited the lowest spatial variability, of which 4-pool APTR∗ was by far the most uniform (10% coefficient of variation, CoV), followed by 3-pool analysis (20%). Four-pool analysis yielded the highest ischaemic core contrast-to-noise ratio (0.74). Four-pool modelling of APT effects was more repeatable (3.2% CoV) than 3-pool modelling (4.6% CoV), but this appears to come at the cost of reduced contrast between infarct growth tissue and normal tissue.
CONCLUSION: The multi-pool measures performed best across the analyses of repeatability, spatial variability, contrast-to-noise ratio, and grey matter-white matter contrast, and might therefore be more suitable for use in clinical imaging of acute stroke. Addition of a fourth pool that separates NOEs and semisolid effects appeared to be more biophysically accurate and provided better separation of the APT signal compared to the 3-pool equivalent, but this improvement appeared be accompanied by reduced contrast between infarct growth tissue and normal tissue.
METHODS: Two consecutive cohorts of patients with IPF were accessed from the Open Source Imaging Consortium database. Automated computed tomography (CT) biomarkers of disease severity incorporating fibrotic and pulmonary vascular features (the reticulovascular score and weighted reticulovascular score (WRVS)) were studied. Relationships between imaging biomarkers, lung function and survival were analysed.
RESULTS: In separate test and validation cohorts, 168 and 176 patients with IPF respectively (median survival 2.6 years) were studied. A threshold of WRVS ≥15% at baseline CT was most strongly associated with transplant-free survival (HR 3.00, 95% CI 1.47-6.10, p=0.002) when adjusted for baseline forced vital capacity (FVC) and age. In patients with 12-month follow-up CT and lung function tests (n=89) an increase in 3% of WRVS (the minimal clinically important difference) was also significantly associated with reduced survival independent of FVC, and outperformed visual evaluation of progressive fibrosis.
CONCLUSIONS: WRVS is an automated CT biomarker which can identify patients with IPF at increased risk of progression and is able to reliably capture disease progression over time.