## 4 Discussion
In particular in 21 out of 25 cases (84%) HRCT scans showed properly normal or near normal conditions with poor fibrotic changes (grade 1, <10% of fibrotic changes). On the contrary, LUS pattern 3 in 100% of cases was indicative of severe to massive fibrotic alterations. An acoustic map of the peripheral lung is already possible based on these considerations. Echographic scans with a pattern of SIS displaying vertical artifacts prevailing on horizontal phenomena and altered pleural line is in fact indicative of important fibrotic alterations in the peripheral parenchyma [22; 23]. Moreover, if, in correspondence of a specific landmark, a LUS pattern 1 changes towards a LUS pattern 3 in a subsequent evaluation over time, this could be indicative of a progression of the diseases in that specific point, and guide the timing of HRCT scan re-evaluation. This was not the aim of this work, but it might be extremely interesting to evaluate in further studies. As far as LUS pattern 2 is concerned, agreement with HRCT grade 2 has been reported in 24 out of 30 cases (77%). It is really important to focus on the 4 cases in which a LUS pattern 2 was associated with HRCT grade 4 related to peripheral large honeycomb cysts (massive fibrosis subversion) (Figure 3). Large cysts honeycomb could represent a limit for LUS, as in this case the air content is greater than in a healthy condition [24]. Figure 3: Upper right and left: large cysts honeycomb and severe fibrotic changes (red circle) with corresponding LUS pattern 2. Bottom right and left: ground glass opacities and moderate fibrotic alterations (red circle) with corresponding LUS pattern 4. Standard ultrasound imaging evaluation could thus underestimate the degree of alteration in this context. The development of dedicated ultrasound imaging solutions designed around the properties of lungs may play an important role in mitigating these effects. In particular, the characterization of the response of bubbly aggregates when exposed to ultrasound waves centered at different insonating frequencies has already proven to be able to discriminate between bubbly aggregates formed by bubbles of different diameters [19; 25]. Further studies deserve to focus specifically with ultrasound beam behavior in presence of honeycomb. LUS pattern 4 presented a heterogeneous distribution of corresponding HRCT grades. These could be affected by the low number of cases studied. In five cases out of six, HRCT pattern was however indicative of severe to massive fibrotic changes. Instead, in one case, LUS pattern 4 corresponded to a HRCT grade 1. This misleading case, in which fibrotic changes were moderate but ground glass opacity (GGO) was reported, corresponded to an early phase of acute exacerbation of IPF (Figure 3). The physical origin of white lung artefact (LUS pattern 4) is not yet completely known. It would be very interesting to demonstrate in further studies how GGOs can influence ultrasound assessment and why. Ground glass opacities in CT scans are indicative of areas of increased lung density with poor air content, which are however not consolidating and not obscuring the visibility of the underlying vasculature. This can be indicative of inflammatory changes, pulmonary edema, pulmonary hemorrhage, fine fibrotic alterations, etc. [26]. The hypothesis is that fibrotic GGOs can be caused by the presence of multiple layers of randomly distributed small-sized airspaces. In this case, it is reasonable to expect the visualization of a granular white texture of speckle-like appearances (i.e., white lung), when investigating such an area with standard ultrasound imaging [21]. Finally, it is worth addressing the limits and methodological issues of this preliminary work. The first limitation is the impossibility to provide information about basal posterior areas, usually the more involved and more informative in case of IPF patients. Echographic assessment of these areas needs the patients to be seated.