## 2 Perfluorocarbon (PFC) Filling
### Discussion  
Lung filling with PFC is safe, with a low complication rate, and represents an accepted modality that experienced pneumological centers are used to handling. Limiting long recovery time due to their biological inertness requires complete vaporization of intrapulmonary liquid [20]. Sonography of PFC filled lung has been inadequately studied thus far. The underlying assumption of complete gas exchange has not been proven. It is important to notice that PFC has a much lower speed of sound than solid tissue (Table 1). Images based on time of flight (TOF) assumption would be falsified and require adoption for image reconstruction. Such a correction algorithm would need to distinguish normal tissue with typical water-like speed of sound and PFC filled lung to derive realistic images representing anatomic \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Paper** & **Year** & **Method/Model/Liquid** & \multicolumn{2}{c}{**Findings**} \\ \hline \multirow{6}{*}{[PERSON] et al.} & \multirow{6}{*}{2004} & \multirow{6}{*}{TLV—sheep PFC—Perflubron} & - & trans pulmonary cardiac visualization \\  & & & - & maximum penetration depth 2–4 cm \\  & & & - & bright echogenicity of \\  & & & - & lung/white lung \\  & & & - & no bronchial and vascularity detected \\ \hline \multirow{2}{*}{[PERSON] et al.} & \multirow{2}{*}{2018} & \multirow{2}{*}{PLV—Infants PF—Perflubron} & - & bright echogenicity of \\  & & & - & lung/white lung \\  & & & - & no bronchial and vascularity detected \\ \hline \multirow{2}{*}{[PERSON] et al.} & \multirow{2}{*}{1998} & \multirow{2}{*}{OLF—porcine model PFC—PF77} & - & bright echogenicity of \\  & & & - & lung/white lung \\  & & & - & no bronchial and vascularity detected \\ \hline \multirow{2}{*}{[PERSON] et al.} & \multirow{2}{*}{1999} & \multirow{2}{*}{OLF—porcine model Saline 0.9\%} & - & unimpaired lung ultrasound \\  & & & - & visualization of simulated nodules \\ \hline \multirow{2}{*}{[PERSON] at al.} & \multirow{2}{*}{2013} & \multirow{2}{*}{OLF—porcine model and ex vivo human lung saline 0.9\%} & - & complete lung imaging \\  & & & - & hypoechoic lung tumors \\  & & & - & demarcation of adjacent organs \\  & & & - & hypoechoic bronchial and vasculature \\ \hline \multirow{2}{*}{[PERSON] et al.} & \multirow{2}{*}{2014} & \multirow{2}{*}{OLF—human cadaver saline 0.9\%} & - & limited lung imaging \\  & & & - & residual gas \\  & & & - & sub-centimeter imaging of a forceps \\ \hline \multirow{2}{*}{[PERSON] et al.} & \multirow{2}{*}{2018} & \multirow{2}{*}{OLF—porcine model and ex vivo human lung saline 0.9\%} & - & unimpaired lung imaging \\  & & & - & visualization of simulated nodules \\  & & & - & hypoechoic lung tumors \\  & & & - & bright echogenicity of \\  & & & - & puncture needle \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Summary of literature related to sonographic imaging of lung during liquid instillation. dimensions. In addition, the reported visualization depth of 2-4 cm in PFC filled sheep lung [17] was estimated using such general sonography. Therefore, a realistic penetration depth of only 1-3 cm can be assumed. All authors reported a bright echogenic character of PFC lung, similar to white lung syndrome. The sonographic impairment cannot be explained by PFC attenuation, which is in range of 0.3-0.4 dB/cm/MHz [17,21], slightly lower than solid tissue (0.5-0.8 dB/cm/MHz). When imaging liquid PFC the medium appears hypoechoic similar to water with clear visualization of backstop structures [19]. This indicates multiple reflections of ultrasound waves due to the impedance mismatch in flooded lung as a PFC-tissue compound. Given an impedance of 1.7 MRayl and an attenuation of 0.2 dB/cm MHz of atelectatic lung [22], the reflection coefficients for ultrasound intensities at a PFC interface varies between 1%-13% (Table 1). Theoretically, multiple reflections of ultrasound waves would lead to a 10-130 dB intensity loss within 1 cm of lung penetration (0100 \(\upmu\)m alveoli) and therefore impair sonographic imaging.