B‐mode ultrasound and contrast‐enhanced ultrasound for evaluation of pneumonia: A pictorial essay

Abstract Due to their often peripheral pleural‐based location, pneumonias can be visualised by B‐mode ultrasound. Therefore, sonography can be used as an alternative imaging modality to chest X‐ray in suspected cases of pneumonia. Depending on the clinical background of the patient, and various underlying pathological mechanisms, a heterogeneous pattern of pneumonia is seen in both B‐mode lung ultrasound and contrast‐enhanced ultrasound. Here, we describe the spectrum of sonographic manifestations of pneumonic/inflammatory consolidation on B‐mode lung ultrasound and contrast‐enhanced ultrasound.


Introduction
Radiological examination, including chest X-ray and computed tomography, are the conventional imaging techniques for the evaluation of pulmonary pathology. [1][2][3][4] Despite known limitations, such as high interobserver variability, interdevice variability, absence of overview, and inability to visualise the central lung areas, transcutaneous lung ultrasound (LUS) can be used in clinical practice as point-of-care sonography for the evaluation of pleural-based lung pathologies in the emergency department, 5,6 in intensive care units, 6,7 in palliative care units, 8 in paediatrics, 9 in ambulance settings 10 and generally in outpatient care. 11 Here, the LUS functions as the physician's new "stethoscope". 12,13 Indeed, LUS is currently the standard procedure in the detection of pleural effusion. [14][15][16][17][18] The diagnosis of pneumonia is made clinically, taking into account the patient's medical history and possible underlying risk factors. 19 The imaging method is only of secondary importance for diagnostic verification. For the imaging diagnosis of community-acquired pneumonia (CAP), LUS has a diagnostic accuracy at least equal to conventional chest X-ray and is recommended in guidelines as an alternative procedure for the diagnosis of pneumonia. [20][21][22][23] Pneumonia is present in 38% of cases where the patient presents with dyspnoea and can be diagnosed by ultrasound. 24 A distinction must be made between CAP and the heterogeneous clinical picture of hospital-acquired pneumonia (HAP). In the clinical inpatient setting, LUS can be used at the bedside in both CAP and HAP in addition to standard imaging for short-term follow-up, predominantly in cases where the course of the disease is atypical, there are complications, clinically absent regression, and possibly needing diagnostic confirmation by ultrasoundguided biopsy. 25,26 Ehsan Safai Zadeh and Amjad Alhyari contributed equally to this work. Correspondence to email ehsan_sz@yahoo.de doi: 10.1002/ajum.12332 B-mode LUS patterns of pneumonia have been adequately described. 27 CEUS enables the additional evaluation of perfusion patterns of pneumonia in terms of type of enhancement (pulmonary arterial vs. bronchial arterial), extent of enhancement (EE; isoechogenic vs. hypoechogenic vs. absent), homogeneity of enhancement (HE; homogeneous vs. inhomogeneous), and decrease of enhancement (DE; early washout [<120 s] vs. late washout [>120 s]). [28][29][30] In this regard, contrast-enhanced ultrasound (CEUS) can provide valuable information in addition to B-mode LUS. 30,32 The aim of this Pictorial Essay is to present to the clinical practitioner the different B-mode LUS and CEUS patterns of pneumonia according to the clinical background of the patients. The basic assessment criteria of CEUS in pulmonary pathologies in general are explained with accompanying illustrations (Figures 1-4).   Typical perfusion patterns of pneumonia on CEUS The diagnosis of pneumonia is based on the clinical symptoms of the patient (fever, cough, or dyspnea) and pathological changes in laboratory parameters (increase in inflammation parameters). 33 Pneumonia can be differentiated into intra-alveolar pneumonia (pleuropneumonia, lobar pneumonia) 34,35 ( Figures 5 and 6) and interstitial pneumonia ( Figure 7).
Patients with pleuropneumoniafocal peripheral pneumonia with simultaneous pleurisy -present with respiratory localised pleural pain. 34 Pleuropneumonia is characterised by a     peripheral pleura-based consolidation on B-mode LUS, with homogeneous pulmonary-arterial enhancement on CEUS ( Figure 5). 34 Patients with lobar pneumonia usually have a poor general state. Lobar pneumonia is characterised by a diffuse consolidation with or without air bronchogram on B-mode LUS and homogeneous pulmonary-arterial enhancement on CEUS ( Figure 6). 30,31 Interstitial pneumonias are caused by viruses (e.g. coronavirus SARS-CoV-2) or by bacteria (e.g. mycoplasma, chlamydiae, coxiellae). 36,37 Furthermore, in patients with pneumonia symptoms, the presence of an irregular pleural line with multiple B-lines (interstitial syndrome) on B-mode LUS may indicate interstitial pneumonia (Figure 7). 36 Due to the absence of consolidations, CEUS examination is not indicated.  , a hypoechoic consolidation with an oval, pleural, nearly anechoic area (arrows) is seen (AO = aorta, S = spleen); on contrast-enhanced ultrasound (c), the consolidation shows a homogeneous perfusion pattern of enhancement after 16 seconds. Furthermore, a pleural-based oval area with absent enhancement and marked wall enhancement is present, consistent with community-acquired pneumonia with pleural empyema (E). A diagnostic/therapeutic thoracentesis of the empyema was performed.   Uncomplicated pneumonia shows a characteristic CEUS pattern with homogeneous pulmonary-arterial enhancement (Figure 6) and is characterised by a corresponding rapid regression under therapy (Figure 8). A parainfectious effusion (Figure 9), pleural empyema (Figure 10), or pulmonary abscess ( Figure 11) indicates a complicated course and can be detected in CEUS examinations. Pleural empyema is characterised by pleural thickening with marked enhancement on CEUS ( Figure 10). 18 In the case of lung abscess, the lung consolidation shows central areas with absent enhancement (Figure 11). 26 In CEUS, further various pulmonary-arterial perfusion disturbances associated with pneumonia can be observed (Figures 12-15). The lesions may show an early and marked washout ( Figure 12). Furthermore, the lesions may reveal areas shows an inhomogeneous, hypoechoic consolidation with signs of an air bronchogram (arrows); on contrast-enhanced ultrasound, the consolidation shows an inhomogeneous, pulmonary arterial pattern of enhancement after 3 seconds (c), with areas showing no pulmonary arterial perfusion (NPA = non-perfused area); after 9 seconds (d), the primary NPA tissue of the lung shows a secondary bronchial arterial perfusion, which is still demarked as a hypoechoic area after 3 minutes (arrows) (e), indicating a community-acquired pneumonia with primary partial absence of pulmonary arterial perfusion. B-mode ultrasound shows an inhomogeneous, hypoechoic consolidation (L = liver); on contrast-enhanced ultrasound, after 2 minutes, the consolidation reveals a peripheral, moth-like pleural area without contrast enhancement in overview and magnification (arrows); Series (c) after 2 days, there is regression of the consolidation with a mild air bronchogram (arrow); furthermore, a complete reperfusion of the peripheral nonperfused areas can be observed, indicating a community-acquired pneumonia with primarily disturbed, peripheral, pulmonary arterial and bronchial arterial perfusion. Final diagnosis was pneumonia due to Mycoplasma pneumoniae. of absent perfusion during the pulmonary-arterial phase with present ( Figures 13 and 14) or absent perfusion (Figure 15) during the bronchial-arterial phase. These patterns may be hypoxemia-related due to the Euler-Liljestand mechanism. 38 In patients with pneumonia, local hypoxia may cause reflex vasoconstriction of pulmonary-arterial vessels, with an increase of local flow resistance. 39 In the event of adequate systemic bronchial-arterial supply (in patients with sufficient cardiac function), pneumonic consolidation can be perfused by the bronchial artery (Figures 13 and 14). In the case of inadequate systemic bronchial-arterial supply (in patients with inadequate cardiac function), the absence of pulmonary-arterial supply cannot be compensated by the bronchial artery ( Figure 15). 38 However, the definite underlying pathogenesis and clinical relevance of these perfusion disturbances is still unclear.

Contrast-enhanced ultrasound pattern of pneumonia with specific pathogenesis
The sonographic appearance of pneumonia depends on the underlying aetiology. Therefore, tuberculous pleuropneumonia shows a bronchial-arterial hypoenhancement with areas of absent enhancement due to avascular areas (granulomas) and a rapid washout (Figure 16). 40 In patients with a clinical or radiological suspicion of tuberculosis, this pattern may be suggestive of tuberculous pneumonia. 40 Pulmonary candidiasis ( Figure 17) and pulmonary aspergilloma ( Figure 18) can also demonstrate areas of absent perfusion due to avascular areas (abscess, necrosis, haemorrhage). The patients frequently have immune suppression due to an underlying malignant disease or systemic inflammatory disease. However, the definitive diagnosis can be made only by histological confirmation. 41 Various underlying pathomechanisms may lead to radiation pneumonitis (Figure 19), aspiration pneumonitis (Figure 20), or obstructive pneumonitis ( Figure 21). The diagnosis can be made only based on the clinical background of the patient.
Disturbance of the pulmonary-arterial supply can result in pneumonic infarct ( Figure 22) and is not unusual in pneumonia caused by sickle cell crisis ( Figure 23). 42 However, perfusion disturbances can also be seen in COVID-19 pneumonia ( Figure 24). 37 The variable perfusion patterns of these specific pneumonias can be explained by the underlying pathomechanism.
Pitfalls in the use of perfusion patterns on CEUS in the diagnosis of pneumonia On CEUS, chronic organising pneumonia 41 ( Figure 25            bronchial-arterial pattern of enhancement with rapid washout similar to the pattern of malignancy and are considered to be pitfalls in the diagnosis of pneumonia. The definitive diagnosis is made histologically. 40,41 Another important obstacle to diagnosis is lepidic growth adenocarcinoma, which can mimic pneumonia clinically, on B-mode LUS and on CEUS ( Figure 27). 43

Conclusion
In summary, pneumonias show a heterogeneous pattern on Bmode LUS and CEUS. Type of enhancement, extent of enhancement, homogeneity of enhancement, and decrease of enhancement are used to evaluate CEUS according to the guidelines. 28,30 Sonographic evaluation of findings is based on clinical background of patients, sonographic follow-up, and in some cases on ultrasound-guided histological confirmation ( Figure 28). In patients with suspected pneumonia, sonography provides indicative findings for the final diagnosis.

Funding
No funding information is provided.

Acknowledgement
Open Access funding enabled and organized by Projekt DEAL.
Conflict of interest C. G€ org received funding from Bracco Imaging. Bracco Imaging supported CEUS workshops at the University Hospital Marburg.