Variation of disease extent at follow-up MDCT in a 53 years-old man suffering from idiopathic pulmonary fibrosis (IPF) not treated with pirfenidone.

<p>Axial MDCT image at level 5 (1 cm above the right hemi-diaphragm as described in the text) of the initial examination shows mild reticular opacities and minimal honeycombing (arrowheads) in a sub-pleural distribution (a). The 80^th percentile of the initial MDCT attenuation histogram corresponded to -730 HU (b). Follow-up MDCT scan at the same axial level after 17 months shows a predominant increase of reticulations (visual score = +22%) and unmodified honeycombing extent (arrowhead) (c). An increase of 86 HU in the density of the 80^th percentile was seen between initial and follow-up MDCT attenuation histograms (d). (Prob. = probability; HU = Hounsfield units; MDCT = multidetector computed tomography).</p

Correlation analysis of pulmonary function tests (PFTs) with visual scores (VSs) and selected percentiles obtained from multidetector computed tomography (MDCT) attenuation histogram.

<p>Summary of correlation analysis between pulmonary function tests (PFTs), visual scores (VSs), and selected percentiles (PERC) obtained from multidetector computed tomography (MDCT) attenuation histogram at initial MDCT and at 1-year follow-up. Pearson r coefficients were calculated for overall extent of abnormalities (OE), ground-glass opacities extent (GGO), reticulations extent (RET), honeycombing extent (HC) [all expressed as percentage of parenchyma involved (%)], and the density, expressed as Hounsfield Unit (HU), of selected percentiles obtained from the MDCT attenuation histogram with the percent predicted (%) of vital capacity (VC) and of diffusing capacity of the lung for carbon monoxide (DLCO) at baseline. The same coefficients were obtained for both longitudinal changes at 1-year (Δ) in VSs, expressed as percent per year (%/y), and in the density, expressed as Hounsfield Unit per year (HU/y), of selected percentiles obtained from the MDCT attenuation histogram with the variation, expressed as percent predicted per year (%/y), of VC% and of DLCO%. In bold <i>p</i> values statistically significant (<i>p</i><0.05).</p><p>Correlation analysis of pulmonary function tests (PFTs) with visual scores (VSs) and selected percentiles obtained from multidetector computed tomography (MDCT) attenuation histogram.</p

Distribution of the density changes at 1-year in the selected percentiles from the MDCT attenuation histogram of patients suffering from idiopathic pulmonary fibrosis (IPF) treated and untreated with pirfenidone.

<p>Box and Whisker plots represent the 40^th percentile (a) and the 80^th percentile distributions (b) of lung density histogram as observed in patients treated with pirfenidone and in patients not treated with pirfenidone. The central line represents the median, the yellow box encompasses the 25^th-75^th percentiles, whiskers show the 10^th-90^th percentile, and the empty circles represent individual outliers. (HU/y = Hounsfield units per year; Δ 40^th percentile = changes at 1-year in the 40^th percentile of the attenuation histogram; Δ 80^th percentile = changes at 1-year in the 80^th percentile of the attenuation histogram; MDCT = multidetector computed tomography).</p

Visualization of the fully automatic lung parenchyma segmentation as obtained by in-house YACTA software.

<p>Sagittal reconstruction image of a non-enhanced MDCT scan obtained from a patient suffering from idiopathic pulmonary fibrosis (IPF) not included in the current trial. YACTA software automatically segmented lung parenchyma and trachea-bronchial tree, emphasized as green and orange overlay respectively (window width: 1600 HU; level: -600 HU). Note that the segmentation algorithm fails to segment portions of the lung parenchyma in the sub-pleural space of the recessus, due to its similar density to the chest wall. (MDCT = multidetector computed tomography).</p

Correlation analysis between selected percentiles of multidetector computed tomography (MDCT) attenuation histogram and visual scores (VSs).

<p>Summary of correlation analysis between visual scores (VSs) and selected percentiles obtained from multidetector computed tomography (MDCT) attenuation histogram at initial MDCT and at 1-year follow-up. Pearson r coefficients were calculated for overall extent of abnormalities (OE), ground-glass opacities extent (GGO), reticulations extent (RET), and honeycombing extent (HC), expressed as percent of parenchyma involved (%), with the density, expressed as Hounsfield Unit (HU), of both the 40^th and the 80^th percentiles obtained from the MDCT attenuation histogram at baseline. The same coefficients were obtained for longitudinal changes at 1-year (Δ) in VSs, expressed as percent per year (%/y), with the variation in density, expressed as Hounsfield Unit per year (HU/y), of both the 40^th and the 80^th percentiles obtained from the MDCT attenuation histogram. In bold <i>p</i> values statistically significant (<i>p</i><0.05).</p><p>Correlation analysis between selected percentiles of multidetector computed tomography (MDCT) attenuation histogram and visual scores (VSs).</p

Median density changes at 1-year follow-up in the range of 10^th-90^th percentile of the MDCT attenuation histogram for patients suffering from idiopathic pulmonary fibrosis (IPF) treated and untreated with pirfenidone.

<p>The largest difference with the lowest overlap between treated and untreated patients in longitudinal HU changes of the attenuation histogram was detected in the 40th and in the 80th percentiles. Black squares = median increase of each 5^th percentile step included in the 10^th-90^th range of the lung density histogram for patients treated with pirfenidone; black triangles and circles = interquartile range of the increase in each 5^th percentile step included in the 10^th-90^th range of the lung density histogram for patients treated with pirfenidone; grey squares = median increase of each 5^th percentile step included in the 10^th-90^th range of the lung density histogram for patients not treated with pirfenidone; grey triangles and circles = interquartile range of the increase in each 5^th percentile step included in the 10^th-90^th range of the lung density histogram for patients not treated with pirfenidone. (Δ HU/y = changes in Hounsfield units per year; MDCT = multidetector computed tomography).</p

Correlations between changes at 1-year in selected percentiles of MDCT attenuation histogram and visual scores.

<p>Dot plots with linear regression curves for changes in overall extent of parenchymal abnormalities plotted against density variation in the 40^th percentile of the MDCT attenuation histogram (r = 0.69, <i>p</i> < 0.001) (a), for the changes in ground-glass opacity extent plotted against density variation in the 40^th percentile of the MDCT attenuation histogram (r = 0.66, <i>p</i> < 0.001) (b), and for changes in reticulations extent plotted against density variation in 80^th percentile of the MDCT attenuation histogram (r = 0.56, <i>p</i> < 0.001) (c). (%/y = percent per year; HU/y = Hounsfield units per year; MDCT = multidetector computed tomography).</p

Study population (n = 40) characteristics.

<p>Summary of gender, age, body mass index (BMI), smoking history, comorbidities, diagnostic procedures, pulmonary function tests [including vital capacity (VC), total lung capacity (TLC), diffusing capacity of the lung for carbon monoxide (DLCO), and arterial pressure of oxygen (PaO₂)], therapy prior and after initial multidetector computed tomography (MDCT), and interval between initial and follow-up MDCT data of the idiopathic pulmonary fibrosis (IPF) patients that constituted the study population. Data are presented as absolute number of patients (n) or median and interquartile range (in brackets).</p><p>^aWas considered the presence or absence of emphysema additionally to fibrosis.</p><p>^bOne value is missing due to patient inability to perform pulmonary function tests.</p><p>^cSeven values are missing due to patient inability to perform the DLCO test.</p><p>^dImmunomodulator indicates azathioprine and\or cyclophosphamide at a dosage clinically indicated.</p><p>Study population (n = 40) characteristics.</p

Visual scores obtained at multidetector computed tomography (MDCT).

<p>Summary of the visual scores, expressed as percent of parenchyma involved (%), obtained at initial multidetector computed tomography (MDCT) and their longitudinal changes at 1-year (Δ), expressed as percent per year (%/y). Ground-glass opacities, reticular opacities, honeycombing, consolidations, and emphysema were defined according to the recommendations suggested by the Fleischner Society nomenclature committee [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130653#pone.0130653.ref010" target="_blank">10</a>]. Data are expressed as median and interquartile ranges (in brackets).</p><p>Visual scores obtained at multidetector computed tomography (MDCT).</p