Systemic sclerosis (scleroderma, SSc) is a complex life-threatening autoimmune disease that affects multiple organ systems. Lung involvement is the leading cause of morbidity and mortality. The aim is to quantify the changes for monitoring the progression or improvement in interstitial lung disease (ILD) over time using voxel-by-voxel transitional scores.
METHOD AND MATERIALSWe report transitional scores using volumetric HRCT scans obtained from participants in SLSII who received either cyclophosphamide (CYC) (n=47) or mycophenolate mofetil (MMF)(n=50). The steps in this process include (1) lobar segmentation and classification of ILD patterns of quantitative lung fibrosis (QLF), quantitative ground glass (QGG), quantitative honeycomb (QHC), and quantitative normal lung (QNL); (2) registration of lobes between two paired scans; (3) mapping each voxel (<27mm3) using a nearest neighbor algorithm; (4) summarizing the transitional patterns into a ratio, where the ratio expresses the counts of changes from one pattern to the other to the counts of patterns at baseline; (5) integrating the transitional net-improvement into a matrix across all patterns. Mixed effect models were used to compare the differences.
RESULTSMeans of the differences in the transitional proportions in the most severe lobe were as follows: CYC group 16% from fibrotic reticulation to GG, 21% from reticulation to normal pattern, and 31% from GG to normal pattern; MMF group 12%, 17%, and 28%, respectively. Similar means were found in whole lung. Mean transitional net improvement from GG or fibrotic pattern to normal patterns and from fibrotic pattern to GG were significant in the two arms (all p<0.001).
CONCLUSIONUsing voxel-by-voxel transitional scores on paired HRCT scans 24 months apart, we found obvious changes in extent of ILD patterns, indicating significant transitions from ground glass opacity or fibrotic reticulation to normal patterns and regionally dependent changes between fibrotic patterns and ground glass opacity in patients with SSc-ILD treated with either CYC or MMF. These findings demonstrate the utility of serial HRCT scans and quantitative technique in monitoring the response to treatment in SSc-ILD, and provide insights into the nature of the therapeutic effects
CLINICAL RELEVANCE/APPLICATIONRegistration-based transitional texture-based CT scores are effective in characterizing structural changes to therapy at each neighboring voxel level.