cerning lung ultrasonography is largely growing and opening new diagnostic opportunities. The clinical value of the ultrasonographic interstitio- alveolar syndrome, based on artifactual (lung comets or B-lines) rather than real images, in the detection of lung contusion, pneumonia and pulmonary edema, is clearly demonstrated. As clinical echographists, though, we are living the paradox of relying our experience in lung pathology on images whose biophysical and ge- netic nature is not fully understood. Objective and Perspectives: A detailed re- view of the ultimate findings with an analysis of recent and past literature regarding the forma- tion of ultrasonographic artifacts was undertak- en with the aim of clarifying what we know and where we are heading in this field. It is important for us to underline how lung ultrasonography is not morphological, as this, along with the study of artifact formation, will be the base for the de- velopment of a novel view able to take us from artifact to reality in terms of quantification of lung disease and damage. Conclusions: Lung ultrasonographic artifacts need to be read in a new light which will privilege biophysical knowledge and research. In this field a gap of basic knowledge clearly exists. A greater understanding of the formation of acoustic arti- facts from ultrasound interference on discretely aerated tissues of variable density, would place the practice of lung ultrasonography in the cor- rect technological and clinical position. Key Words: Ultrasound, Sonography, Artifacts, Lung, Diagnosis. Introduction Study of the lung through ultrasound (US) is a relatively recent acquisition 1 . In the last few years, the use of lung US has received growing attention in clinical research in intensive care pa- European Review for Medical and Pharmacological Sciences Lung and ultrasound: time to reflect G. SOLDATI 1 , S. SHER 2 , A. TESTA 3 1 Emergency Department, Valle del Serchio General Hospital, Lucca (Italy) 2 Pediatric Intensive Care Unit, IRCCS Foundation, CaGranda Hospital, Milan (Italy) 3 Emergency Department, Policlinico Abano Terme, Padova (Italy) Corresponding Author: Gino Soldati, MD; e-mail: soldatigino@yahoo.it 223 tients and trauma settings, in patients with heart failure, adult respiratory distress syndrome, pneumonia and pneumothorax 2-5 . More precisely, what is recent, is the study of the partially aerat- ed lung, as both the chest wall and the pathologic pleural cavity have received attention ever since echography began to be used as a diagnostic tool. Although steps ahead have been made, we pay today a cultural debt towards an organ which has always been considered hostile to US 6 . This concept has important biophysical impli- cations as air is a barrier to the progression of ul- trasound. An air collection larger than the ultra- sound wave lenght used for scanning will specu- larly reflect the acoustic energy it receives and thus impede an anatomic scan of underlying structures. Smaller and contiguous air collections instead, produce complex phenomenons of re- flection generating artefactual images 7 . Different lung diseases, collectively included in the gener- ic term of interstitio-alveolar syndrome, are de- scribed not anatomically but through the analysis of these phenomenons. Real US Lung Imaging Normal lung, as well as pathologic lung that is not completely collapsed, does not offer an echo- graphic morphologic representation with usual clinical frequencies (3.5-15 MHz). The presence of air in the normal lung (about 80-85% of its to- tal volume), and that in the pathologic lung up to a density of 0.8-0.9 g/ml, constitutes an acoustic barrier which is inidoneous to the formation of a morphologic echostructure 7 . The normal pleura acts as an almost complete specular reflector (about 85% of incident acoustic energy does not penetrate the pleural plane). Due to the high acoustic impedance of an elevated air to soft tis- sue gradient, US energy cannot penetrate lung tis- sue and it is sent back to the tranducer producing horizontal reverberation phenomena (Figure 1) 2011; 15: 223-227 Figure 1. Normal lung sonographic appearance (10 MHz linear probe). Pleural surface acts as a specular reflector inducing transversal deep reverberations (thin arrows). Figure 2. Multiple comet tails (B-Lines) arising from the pleural line in a case of acute pulmonary edema (5 MHz convex probe). seen each time one tries to explore an air collec- tion whether in the pleural cavity, in the ab- domen or in a phantom 8,9 . Table I summarizes examples of impedent interfaces pertinent to lung sonography. Morphologic lung ultrasonography is, there- fore, a real echography of defined acoustic enti- ties, as a critical lung mass (with a density close to that of water), pleural thickenings or a pleural effusion. The possibility of seeing these entities through echography is part of radiologists, pneumologists and emergency medicine physi- cians culture and they have long been able to study the thoracic wall, the pleural cavity, pneu- monias, superficial lung tumors as well as parts of the mediastinum 10,11 . Only in the last 10 years 12 has it been observed that a specific, sub- compacting lung pathology is able to generate US images which do not actually represent real structures but artifacts (Figure 2). Artefactual US Lung Imaging Most of new diagnostic opportunities in the in- terstitial pathology of the lung (extravascular lung water expansion, edema, interstitial inflam- mation, interstitial fibrosis) are based on sono- graphic visual artifacts. An artifact is defined as an erroneous interpretation of a signal by the ma- chine. Artifacts are produced in echography when the machine creates acoustic interference signals as images which are not correlated to a real morphologic entity 13 . An interesting family of these artifacts is formed by so called ring down artifacts, also known as lung comets or B-lines (Figure 2). These are defined, in lung US, as linear vertical signals that emerge from the pleural line and extend through the entire lung field 12,14,15 . Although well known to all those who use and study lung US in cases of interstitial pathology, their characterization in terms of acoustic interactions has not been fully de- scribed. To date, no scientific evidence exists re- garding their genesis and whether they are simi- lar in different types of lung pathology, or if in- stead they may be discerned in terms of number, density, homogeneity, spared areas and so on. Although their presence in actual US lung im- ages is inequivocably evident, their biophysical G. Soldati, S. Sher, A. Testa 224 Reflection Interfacies coefficients* Fat/muscle 0,13 Muscle/atelectatic lung -0.01 Muscle/consolidated lung (pneumonia) -0.61 Muscle/deflated lung -0.72 Muscle/inflated lung -0.88 Muscle/air -0.99 Water/air -0.99 Table I. Reflective properties of acoustic discontinuities in human chest 18,21 . *Acoustic energy reflected back from anatomic interfa- cies (1 = maximal reflection, 0 = maximal acoustic per- meability). Lung and ultrasound: time to reflect 225 reflect on this thesis and comprehend the real and complex nature of ultrasound lung artifacts. Moreover, in order to see and acquire these in- terference phenomena, we are using machines that paradoxically consider them as errors and that technology is working to adjust. We are studying phenomena that appear to those who design and build echographic machines as para- sites on which to carry out a sort of electronic cosmesis 21 . What occurs is not a purely theoretical or tech- nical problem, it would be so if these effects were only encountered in the laboratory, but ac- tually several clinical studies are based on data regarding pathologic lungs that appear as non- structured fields of B-lines 12,22-25 . And how can we deny the value of being able to use these im- ages clinically, for the detection and differentia- tion of lung disease? How can we deplore the formulation of the echographic interstitial syn- drome based on the presence of few to coalescent B-lines 12,22 ? No doubt exists regarding the value of the echographic interstitial syndrome in the detection of lung pathology, what is missing is a thorough understanding of the formation of US artifacts both in terms of biophysical phenomena but especially of anatomic and structural lung al- terations. The interstitial, or interstitio-alveolar syn- drome, is an anatomo-pathological entity but, un- like the alveolar syndrome which has its respec- tive echographic anatomy (a lung consolidation), it creates artifacts instead of real images. Evi- dence shows that what is tagged as echographic interstitial syndrome does not topographically go characterization is not so clear at all. We are in the paradoxical situation of being able to under- stand certain subatomic interactions and at the same time not know what simple acoustic inter- actions as B-lines or the white lung stand for 7 . The few Authors who have intended to study the formation of these artifacts on biologic and non-biologic substrates have been able to classify US artifacts as reverberation and/or resonance phenomena based on limited past scientific evi- dence 7,14 . In fact, historically, the only study ad- dressing these artifacts formation was the one carried out by Avruch et al. 14 on the concept of US induced resonance between small air bubbles arranged in tetrahedrons 7 . Although this study leaves several perplexities as a pure in vivo phe- nomenon, numerous subsequent ones refer to Avruchs resonant tetrahedrons as the paradigm of a diffuse acoustic phenomenon described prevalently, but confusedly, as ring down arti- facts 14,16,17 . As often happens in science, we may find with surprise that several decades ago certain physi- cists, and not physicians, had described the acoustic behavior of the lung, not in terms of im- ages but of acoustic interactions and permeability, first admitting and later denying productive inter- ference as all that goes beyond acoustic reverber- ations on multiple and discrete air collections 18 . What seems to emerge is that lung tissue per- meability to US is correlated to its density or its porosity, in other words to its increase in weight or, furthermore, to its loss of air content or defla- tion (deflated lung with same weight, isobaric, with no intrinsic pathology) 19 . In this context, the B-lines in their variable arrangements (but are they really all arrangements of different B-lines?) appear to the machine as signals that indicate a physical event corresponding to a physiopatho- logic lung alteration 20 . And if it is so, the image we create through echography is actually redun- dant and a simple display showing numbers, per- haps a color map, or Cartesian axes as the results of complex equations and algorithms solved, could be enough for diagnostic purposes. The Interstitio-Alveolar Syndrome Sonographic interstitio-alveolar syndrome was first described in 1997 12 . To date, the vast majori- ty of Authors refer to the classical Lichtensteins interpretation. This vision emphasizes the role of subpleural interlobular septa for the genesis of lung comets (B-Lines). We believe it is time to Figure 3. Synthetic comet tails arising from a 10 10 7 mm porous wet polyurethane scaffold insonated with a 6,6 MHz linear probe. 226 beyond the first two millimeters of subpleural lung tissue, although what is seen inequivocally fills the entire display. In this view, we are building whole chapters of echographic imaging regarding different lung en- tities, based on signs we do not fully know and which are characterized by an intrinsic elusive- ness. This uncertainty derives from the fact that these vertical artifacts, contrary to current opin- ion, do not appear to correlate with a specific anatomical structure. A recent work on this topic 7 and rare preexisting studies 14,16 have demonstrat- ed how similar artifacts may be created in proper bubble systems both in vitro and in vivo. There is evidence that analogous signals are produced in jelly systems, in foam systems or on a polyurethane scaffold (Figure 3) (personal un- published data) independent of a tetrahedric or definite anatomic structure (as interlobular lung septa) 7,12,26 . It appears ever clearer how signals analogous to B-lines are seen each time the in- sonated substrate increases its permeability to US due to geometric alterations in its porosity (i.e. density). Perspectives and Conclusions Lung sonography is an interesting diagnostic method, with a high sensitivity in cases of inter- stitial lung pathology, in particular located in near subpleural parenchyma 2,3,12,23,24,26 . However, we believe that lung US artifacts need to be read in a new perspective which will privilege bio- physical research and clarify how this type of echography is not morphological. Although we have demonstrated the link between echographic syndromes and certain lung pathology it does not mean we should still be talking, in these specific cases, of echography. It may seem provocative but if we believe in lung US we should at this point plan a future that considers the relationship between artifactual lung images and lung density. Density will be isobaric when what varies is air extension and relatively isovolumetric when what varies is the interstitial space (or organ weight). Will it be a radiant future? No data yet allows us to affirm this. If we think, though, about the applications of Computerized Tomography 27,28 in the quantitative evaluation of subpleural lung density and to the clinical implications this had in terms of pulmonary edema, acute lung injury and adult respiratory distress syndrome, even if the close ideal of lung echography was only a discrete, strictly cortical, densitometric model, we could consider ourselves satisfied. References 1) SOLDATI G, SHER S. Bedside lung ultrasound in criti- cal care practice. Minerva Anestesiol 2009; 75: 509-517. 2) PICANO E, GARGANI L, GHEORGHIADE M. Why, when, and how to assess pulmonary congestion in heart failure: pathophysiological, clinical, and method- ological implications. Heart Fail Rev 2010; 15: 63- 72. 3) COPETTI R, SOLDATI G, COPETTI P. Chest sonography: A useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome. Cardiovasc Ultrasound 2008; 6: 16. 4) PARLAMENTO S, COPETTI R, DI BARTOLOMEO S. Evalua- tion of lung ultrasound for the diagnosis of pneu- monia in the ED. Am J Emerg Med 2009; 27: 379-384. 5) SOLDATI G, TESTA A, SHER S, PIGNATARO G, LA SALA M, GENTILONI SILVERI N. Occult traumatic pneumotho- rax: diagnostic accuracy of lung ultrasonography in the emergency department. Chest 2008; 133: 204-211. 6) DRAZEN JM, WEINBERGER SA. APPROACH TO THE PATIENT WITH DISEASE OF RESPIRATORY SYSTEM. IN: KASPER DL, FAUCI AS, LONGO DL, BRAUNWALD E, HAUSER SL, JAMESON JL (EDS). Harrisons principles of internal medicine. 16th ed. New York, Mc Graw Hill, 2005: p. 1506. 7) SOLDATI G, COPETTI R, SHER S. Sonographic intersti- tial syndrome: The sound of lung water. J Ultra- sound Med 2009; 28: 163-174. 8) KREMKAU FW, TAYLOR KJW. Artifacts in ultrasound imaging. J Ultrasound Med 1986; 5: 227-237. 9) SOLDATI G. Sonographic findings in pulmonary dis- eases. Radiol Med 2006; 111: 507-515. 10) MATHIS G. Thorax sonography - Part I: Chest wall and pleura. Ultrasound Med Biol 1997; 23: 1131- 1139. 11) MATHIS G. Thorax sonography - Part II: Peripheral pulmonary consolidations. Ultrasound Med Biol 1997; 23: 1141-1153. 12) LICHTENSTEIN D, MEZIRE G, BIDERMAN P, GEPNER A, BARR O. The comet-tail artifact: An ultrasound sign of alveolar-interstitial syndrome. Am J Respir Crit Care Med 1997; 156: 1640-1646. 13) SKOLNICK ML, MEIRE HB, LECKY JW. Common arti- facts in ultrasound scanning. J Clin Ultrasound 1975; 3: 273-280. G. Soldati, S. Sher, A. Testa 14) AVRUCH L, COOPERBERG PL. The ring down artifact. J Ultrasound Med 1985; 4: 8-14. 15) KOHZAKI S, TSURUSAKI K, UETANI M, NAKANISHI K, HAYASHI K. The aurora sign: An ultrasonographic sign suggesting parenchymal lung disease. Br J Radiol 2003; 76: 437-443. 16) FELDMAN MK, KATYAL S, BLACKWOOD MS. US arti- facts. Radiographics 2009; 29: 1179-1189. 17) LIM JH, LEE KS, KIM TS, CHUNG MP. Ring-down arti- facts posterior to the right hemidiaphragm on ab- domi nal sonography: si gn of pul monary parenchymal abnormalities. J Ultrasound Med 1999; 18: 403-410. 18) DUNN F, FRY WJ. Ultrasonic absorption and reflection by lung tissue. Phys Med Biol 1961; 5: 401-410. 19) DUNN F. Attenuation and speed of ultrasound in lung. J Acoustic Soc Am 1974; 56: 1638-1639. 20) REISSIG A, KROEGEL C. Transthoracic sonography of diffuse parenchymal lung disease. J Ultrasound Med 2003; 22: 173-180. 21) SZABO TL. Diagnostic ultrasound imaging. Amster- dam, Elsevier Academic Press, 2004. 22) LICHTENSTEIN D, MEZIERE G. A lung ultrasound sign allowing bedside distinction between pulmonary edema and COPD: the comet-tail artifact. Inten- sive Care Med 1998; 24: 1331-1334. 23) JAMBRIK Z, MONTI S, COPPOLA V et al. Usefulness of ultrasound lung comets as non radiologic sign of extravascular lung water. Am J Cardiol 2004; 93: 1265-1270. 24) GARGANI L, FRASSI F, SOLDATI G, TESORIO P, GHEORGHI- ADE M, PICANO E. Ultrasound lung cometsfor differ- ential diagnosis of acute cardiogenic dipnoea: A comparison with natriuretic peptides. Eur J Heart Fail 2008; 10:70-77. 25) WILSON SR, BURNS PN, WILKINSON LM, SIMPSON DH, MURADALI D. Gas at abdominal US: Appearance, relevance, and analysis of artifacts. Radiology 1999; 210: 113-123. 26) FRASSI F, GARGANI L, GLIGOROVA S, CIAMPI Q, MOTTOLA G, PICANO E. Clinical and echocardiographic de- terminants of ultrasound lung comets. Eur J Echocardiogr 2007; 8: 474-479. 27) GATTINONI L, CAIRONI P, CRESSONI M, CHIUMELLO D, RANIERI VM, QUINTEL M, RUSSO S, PATRONITI N, CORNE- JO R, BUGEDO G. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 2006; 354: 1775-1786. 28) GATTINONI L, CAIRONI P, VALENZA F, CARLESSO E. The role of CT-scan studies for the diagnosis and therapy of acute respiratory distress syndrome. Clin Chest Med 2006; 27: 559-570. 227 Lung and ultrasound: time to reflect