Letter to the Editor Regarding the Article: “Vascularization of Primary, Peripheral Lung Carcinoma in CEUS – A Retrospective Study (n = 89 Patients)” by Findeisen H et al.

Dear Editor, The article entitled “Vascularization of Primary, Peripheral Lung Carcinoma in CEUS – A Retrospective Study (n = 89 Patients)” by Findeisen H et al. [1] described the vascularization of peripheral lung carcinoma in contrast-enhanced ultrasound (CEUS) and concluded that “lung carcinomas are predominantly supplied by bronchial arteries (BA), whereas a part of adenocarcinomas and non-adenocarcinomas show pulmonary artery (PA) enhancement”. The premise of the authors is that “due to dual pulmonary blood vascularization, more precisely the nutritive bronchial artery system and functional role of the pulmonary arteries, analogous to the hepatic vasculature, CEUS is of particular interest for the examination of peripheral lung consolidations regarding the type of arterial blood supply”. On this basis, they found that the time to enhancement (TE) was fast in the PA group (8 ± 3.7 s), while it was delayed in the BA group (17.6 ± 6.2 s). The first indication for CEUS use in Europe was for Doppler echocardiography and the assessment of lesions of the liver, where it is possible to recognize arterial (10–20 s), portal-venous (30/45–120 s) and late vascular (> 120 s-4/6min) phases [2]. However, as we well know from the study of anatomy, lungs have a dual blood supply that is different from that of the liver. The pulmonary circulation receives mixed venous blood from the right ventricle, carries it to the alveolar capillary system to be oxygenated and reintroduces it to the systemic circulation. The bronchial circulation arises from the aorta, perfuses and feeds the entire lung parenchyma (with the exception of the alveoli) and, finally, drains in part into the veins of the systemic circle (to the right heart) and to a lesser degree into the pulmonary veins (to the left heart), as a component of the physiological right-left shunt. In addition, along their course, bronchial arteries form a broad network with preand postcapillary anastomoses to the pulmonary system which allows them to increase their flow by up to 300% in ventilated areas under hypoxic conditions (pathologic rightleft shunt) [3]. In the normal lung, only 6–7 seconds after the infusion of contrast, the 4 cardiac chambers will be completely perfused (i. e., both the venous and arterial circulation will be perfused). Therefore, the contrast-enhanced evaluation of lung subpleural lesions, after 7 seconds, will reveal only the presence of vascularization but won’t allow differentiation of the arterial phase from the venous one [4]. Nevertheless, variations in transit time can be influenced by anastomoses between the two lung circulation systems (shunts opening in the course of pathology) as well as by the specific neovascularization characteristics of various types of lung tumors and the potential effects on pulmonary vascularization of concomitant cardiac or lung diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary hypertension, cardiopathy, atherosclerosis, hypertension, pneumoconiosis etc. [5]. The tumor itself can act as a hypoxic stimulus that leads to a vascular reflex of constriction with the opening of anastomoses and redistribution of blood flow to better ventilated areas of the lung. In addition, variations in lung contrast-medium transit times can thus depend on the patient’s position during the examination. In the upright human lung, blood flow increases almost linearly from top to bottom, while, when the subject is lying supine, blood flow in the posterior regions of the lung exceeds flow in the anterior parts, due to the intrapleural pressure gradient and gravity-related hydrostatic pressure differences [3]. The authors did not specify the position in which their patients were examined (supine or seated). This seems important for the standardization of early and late phases of enhancement in CEUS studies of lung tumors. In conclusion, in our opinion it is very important to emphasize the concept that, because of the particular/peculiar and exclusive pulmonary circulation, CEUS cannot be used to differentiate malignant lesions, unless the lesion is evaluated in the first 6–7 seconds. Moreover, with regard to the authors’ assessment that air bronchograms could indicate local air-filled areas of necrosis in lepidic adenocarcinomas, we would like to state that no study or meta-analysis demonstrated that linear/arborescent hyperechoic images on TUS really correspond to the CT imaging of the air bronchogram [6]. They may also be due to the interposition of air microns between the lesion and pleural surface, areas of fibrosis and/or vascular interfacing. It remains to be demonstrated with compared studies if and in what way CEUS could aid in the discrimination of necrosis from vital tissue in order to increase the diagnostic accuracy of ultrasoundguided biopsy.