Volumetric characteristics of idiopathic pulmonary fibrosis lungs: computational analyses of high-resolution computed tomography images of lung lobes

Background Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease involving progressive degeneration of lung capacity. Current diagnosis of IPF heavily relies on visual evaluation of fibrotic features in high-resolution computed tomography (HRCT) images of the lungs. Although the characteristics of this disease have been studied at the molecular and cellular levels, little is known about the mechanical characteristics of IPF lungs inferred from HRCT images. To this end, we performed a pilot study to investigate the radiographic and volumetric characteristics of lungs in subjects with IPF. Methods We collected HRCT images of healthy (N = 13) and IPF (N = 9) lungs acquired at breath-holds after full inspiration (expanded state) and full expiration (contracted state). We performed statistical analyses on Hounsfield unit (HU) histograms, lobar volumes (V: lobe volume normalized by the lung volume), and lobar flows (Q: the difference in lobe volume divided by the difference in lung volume between the expanded and contracted states). Results Parameters characterizing the HU histograms (i.e., mean, median, skewness, and kurtosis) significantly differed between healthy and IPF subjects, for all lobes in both expanded and contracted states. The distribution of V across lobes differed significantly between the groups in both states. The distribution of Q also differed significantly between the groups: Q values of the lower lobes for the IPF group were 33% (right) and 22% (left) smaller than those for the healthy group, consistent with the observation that radiographic scores were highest in the lower lung section in IPF. Notably, the root-mean-squared difference (RMSD) of Q, a measure of distance from the mean value of the healthy group, clearly distinguished the IPF subjects (RMSD of Q > 1.59) from the healthy group (RMSD of Q < 0.67). Conclusion This study shows that lung volume and flow distribution change heterogeneously across the lung lobes of IPF subjects, with reduced capacity in the lower lobes. These volumetric changes may improve our understanding of the pathophysiology in IPF lungs.


Figure S4
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H4. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S5
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H5. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S6
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H6. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S7
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H7. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S8
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H8. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S9
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H9. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S10
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H10. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S11
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H11. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S12
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H12. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S13
High-resolution computed tomography images and Hounsfield unit (HU) histograms of healthy subject H13. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.
High-resolution computed tomography images and Hounsfield unit (HU) histograms of idiopathic pulmonary fibrosis subject D1. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.
High-resolution computed tomography images and Hounsfield unit (HU) histograms of idiopathic pulmonary fibrosis subject D2. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S16
High-resolution computed tomography images and Hounsfield unit (HU) histograms of idiopathic pulmonary fibrosis subject D3. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S17
High-resolution computed tomography images and Hounsfield unit (HU) histograms of idiopathic pulmonary fibrosis subject D4. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S18
High-resolution computed tomography images and Hounsfield unit (HU) histograms of idiopathic pulmonary fibrosis subject D5. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S19
High-resolution computed tomography images and Hounsfield unit (HU) histograms of idiopathic pulmonary fibrosis subject D6. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.
High-resolution computed tomography images and Hounsfield unit (HU) histograms of idiopathic pulmonary fibrosis subject D7. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S21
High-resolution computed tomography images and Hounsfield unit (HU) histograms of idiopathic pulmonary fibrosis subject D8. RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.

Figure S23
The strain of the lung lobes (S; See Eq. 4 in the Methods Section), defined as the difference in lobe volume between the expanded and contracted states normalized by the lobe volume in the expanded state, for the healthy (N = 13) and idiopathic pulmonary fibrosis (IPF) subjects (N = 9). (a) S values of healthy (H1H13) and IPF subjects (D1D9). (b) Mean values of S for the healthy and IPF groups. The error bars denote one standard deviation and the asterisks indicate different levels of statistical significance for differences in the mean values between the two groups. (c) Individual root-mean-squared difference (RMSD) values of S (See Eq. 5 in the Methods Section). The error bars denote one standard deviation computed from 13 iterative leave-one-out validations (See the Methods Section). RU denotes the right upper and right middle lobes combined. RL, LL, and LU denote the right lower, left lower, and left upper lobes, respectively.