Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation

Miku Oda, Kentaro Yamaura, Haruyuki Ishii, Nobutaka Kitamura, Ryushi Tazawa, Mitsuhiro Abe, Koichiro Tatsumi, Ryosuke Eda, Shotaro Kondoh, Konosuke Morimoto, Takeshi Tanaka, Etsuro Yamaguchi, Ayumu Takahashi, Shinyu Izumi, Haruhito Sugiyama, Atsushi Nakagawa, Keisuke Tomii, Masaru Suzuki, Satoshi Konno, Shinya OhkouchiNaoki Tode, Tomohiro Handa, Toyohiro Hirai, Yoshikazu Inoue, Toru Arai, Katsuaki Asakawa, Takahiro Tanaka, Toshinori Takada, Hirofumi Nonaka, Koh Nakata

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Background: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. Methods: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from -1,000 to 0 HU. Results: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from -1,000 to -857 and -143 to 0 HU. Conclusion: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
Issue number2
Publication statusPublished - 2023 Feb 1


  • Granulocyte-macrophage colony-stimulating factor
  • High-resolution computed tomography
  • Hounsfield unit
  • Pulmonary alveolar proteinosis


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