Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology. Accurate detection of COPD subtypes by image biomarkers are urgently needed to enable individualized treatment thus improving patient outcome. We adapted the Parametric Response Map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype. We analyzed whole lung CT scans of 194 COPD individuals acquired at inspiration and expiration from the COPDGene Study. PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity. PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype, while providing detailed spatial information of disease distribution and location. PRMs ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients complementing standard clinical techniques.

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An automated retrospective image registration based on mutual information is adapted to a multislice functional magnetic resonance imaging (fMRI) acquisition protocol to provide accurate motion correction. Motion correction is performed by mapping each slice to an anatomic volume data set acquired in the same fMRI session to accommodate inter-slice head motion. Accuracy of the registration parameters was assessed by registration of simulated MR data of the known truth. The widely used rigid body volume registration approach based on stacked slices from the time series data may hinder statistical accuracy by introducing inaccurate assumptions of no motion between slices for multislice fMRI data. Improved sensitivity and specificity of the fMRI signal from mapping-each-slice-to-volume method is demonstrated in comparison with a stacked-slice correction method by examining functional data from two normal volunteers. The data presented in a standard anatomical coordinate system suggest the reliability of the mapping-each-slice-tovolume method to detect the activation signals consistent between the two subjects. Magn Reson Med 41:964

The management of bronchiolitis obliterans syndrome (BOS) following hematopoietic cell transplantation (HCT) presents many challenges, both diagnostically and therapeutically. We have developed a computed tomography (CT) voxel-wise methodology termed Parametric Response Mapping (PRM) that quantifies normal parenchyma (PRMNormal), functional small airway disease (PRMfSAD), emphysema (PRMEmph) and parenchymal disease (PRMPD) as relative lung volumes. We now investigate the use of PRM as an imaging biomarker in the diagnosis of BOS. PRM was applied to CT data from four patient cohorts: acute infection (n=11), BOS at onset (n=34), BOS plus infection (n=9), and age-matched, non-transplant controls (n=23). Pulmonary function tests and broncho-alveolar lavage (BAL) were used for group classification. Mean values for PRMfSAD were significantly greater in patients with BOS (38±2%) when compared to those with infection alone (17±4%, p<0.0001) and age-matched controls (8.4±1%, p<0.0001). Patients with BOS had similar PRMfSAD profiles, whether a concurrent infection was present or not. An optimal cut-point for PRMfSAD of 28% of the total lung volume was identified, with values >28% highly indicative of BOS occurrence. PRM may provide a major advance in our ability to identify the small airway obstruction that characterizes BOS, even in the presence of concurrent infection.

Rationale and Objectives The longitudinal relationship between regional air trapping and emphysema remains unexplored. We have sought to demonstrate the utility of parametric response mapping (PRM), a computed tomography (CT) based biomarker, for monitoring regional disease progression in COPD patients, linking expiratory and inspiratory-based CT metrics over time. Materials and Methods Inspiratory and expiratory lung CT scans were acquired from 89 COPD subjects with varying GOLD status at 30 day (n=13) or one year (n=76) from baseline as part of the SPIROMICS clinical trial. PRMs of CT data were used to quantify the relative volumes of normal parenchyma (PRMNormal), emphysema (PRMEmph), and functional small airways disease (PRMfSAD). PRM measurement variability was assessed using the 30-day interval data. Changes in PRM metrics over a one-year period were correlated to pulmonary function (FEV1). A theoretical model that simulates PRM changes from COPD was compared to experimental findings. Results PRM metrics varied by ~6.5% of total lung volume for PRMNormal and PRMfSAD and 1% for PRMEmph when testing 30-day repeatability. Over a one-year interval, only PRMEmph in severe COPD subjects produced significant change (19% to 21%). However, 11 of 76 subjects showed changes in PRMfSAD greater than variations observed from analysis of 30 day data. Mathematical model simulations agreed with experimental PRM results, suggesting fSAD is a transitional phase from normal parenchyma to emphysema. Conclusions PRM of lung CT scans in COPD patients provides an opportunity to more precisely characterize underlying disease phenotypes, with the potential to monitor disease status and therapy response.