Although increasing used in the preclinical testing of new anti-fibrotic drugs, a thorough validation of micro-computed tomography (CT) in pulmonary fibrosis models has not been performed. Moreover, no attempts have been made so far to define density thresholds to discriminate between aeration levels in lung parenchyma. In the present study, a histogram-based analysis was performed in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis by micro-CT, evaluating longitudinal density changes from 7 to 21 days after BLM challenge, a period representing the progression of fibrosis. Two discriminative densitometric indices (i.e. 40th and 70th percentiles) were extracted from Hounsfield Unit density distributions and selected for lung fibrosis staging. The strong correlation with histological findings (r_Spearman = 0.76, p < 0.01) confirmed that variations in 70th percentile could reflect a pathological lung condition and estimate the effect of antifibrotic treatments. This index was therefore used to define lung aeration levels in mice distinguishing in hyper-inflated, normo-, hypo- and non-aerated pulmonary compartments. A retrospective analysis performed on a large cohort of mice confirmed the correlation between the proposed preclinical density thresholds and the histological outcomes (r_Spearman = 0.6, p < 0.01), strengthening their suitability for tracking disease progression and evaluating antifibrotic drug candidates.

Aims To evaluate the accuracy of echocardiography in conjunction with quantitative high-dose dipyridamole technetium-99m sestamibi tomography (SPECT)

Recently a new iterative reconstruction algorithm named Sinogram Affirmed Iterative Reconstruction (SAFIRE) has been released by Siemens. This algorithm works in the raw data domain with noise reduction as main purpose, providing five different strengths. In this study, the effect of SAFIRE on image quality has been investigated using selected phantoms and a comparison with standard filtered back projection (FBP) has been carried out. The following quantitative parameters have been evaluated: image noise, impact of different reconstruction kernels on noise reduction, noise power spectrum (NPS), contrast‐to‐noise ratio (CNR), spatial resolution, and linearity and accuracy of CT numbers. The influence of strengths on image quality parameters has also been examined. Results show that image noise reduction is independent of reconstruction kernel and strongly related to the strength of SAFIRE applied. The peak of NPS curve for SAFIRE reconstructions is shifted towards low frequencies; this effect is more marked at higher levels of strength. Contrast‐to‐noise ratio is always improved in SAFIRE reconstruction and increases with higher strength. At different dose levels SAFIRE preserves CT number accuracy, linearity, and spatial resolution, both in transversal and coronal planes. These results confirm that SAFIRE allows for image noise reduction with preserved image quality. First clinical data to validate this phantom analysis and confirm that commercially available iterative algorithms can play an effective role in dose containment.PACS number: 87.57.Q

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive degenerative lung disease leading to respiratory failure and death. Although anti-fibrotic drugs are now available for treating IPF, their clinical efficacy is limited and lung transplantation remains the only modality to prolong survival of IPF patients. Despite its limitations, the bleomycin (BLM) animal model remains the best characterized experimental tool for studying disease pathogenesis and assessing efficacy of novel potential drugs. In the present study, the effects of oropharyngeal (OA) and intratracheal (IT) administration of BLM were compared in C57BL/6 mice. The development of lung fibrosis was followed in vivo for 28 days after BLM administration by micro-computed tomography and ex vivo by histological analyses (bronchoalveolar lavage, histology in the left lung to stage fibrosis severity and hydroxyproline determination in the right lung). In a separate study, the antifibrotic effect of Nintedanib was investigated after oral administration (60 mg/kg for two weeks) in the OA BLM model. Lung fibrosis severity and duration after BLM OA and IT administration was comparable. However, a more homogeneous distribution of fibrotic lesions among lung lobes was apparent after OA administration. Quantification of fibrosis by micro-CT based on % of poorly aerated tissue revealed that this readout correlated significantly with the standard histological methods in the OA model. These findings were further confirmed in a second study in the OA model, evaluating Nintedanib anti-fibrotic effects. Indeed, compared to the BLM group, Nintedanib inhibited significantly the increase in % of poorly aerated areas (26%) and reduced ex vivo histological lesions and hydroxyproline levels by 49 and 41%, respectively. This study indicated that micro-computed tomography is a valuable in vivo technology for lung fibrosis quantification, which will be very helpful in the future to better evaluate new anti-fibrotic drug candidates.