ECR 2019 TOPIC PACKAGE
COPD is a slowly obstructive airway disorder resulting from an exaggerated inflammatory response to cigarette smoking and air pollution that ultimately destroys lung parenchyma and induces an irreversible reduction in calibre and number of small airways. Both phenomena (emphysema and small airway disease [SAD]) are responsible for airflow limitation. Because often SAD precedes lung destruction, patients having equal impairment of lung function may present different morphologic appearances on CT scans. Although quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls and expiratory air trapping, visual assessment of CT scans is important to describe patterns of altered lung structures in COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent and advanced destructive emphysema), panlobular and paraseptal (subclassified as mild or substantial). Airway disease is commonly found with all forms of emphysema but also commonly occurs in the absence of emphysema as a predominant expression of COPD. The CT features of the bronchial disease include thickening of the walls of segmental and subsegmental airways. CT features of SAD include peripheral centrilobular micronodular opacities (inflammatory SAD) and gas trapping on expiratory CT (obstructive SAD). Associated features may be seen on large airway disease (tracheobronchomalacia, sabre sheath trachea, tracheobronchial outpouching/diverticula). Interstitial lung abnormalities include patchy ground-glass abnormality and/or mid subpleural reticular abnormality. Other associated features include pulmonary arterial enlargement suggesting pulmonary hypertension, and bronchiectasis.
A biomarker is defined as an indicator of a biological state that is objectively measured and evaluated. Biological state includes including, normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Imaging modality can also be used to extract biomarkers. In recent studies on COPD, CT has been accepted as one of the important research tools in evaluating disease severity and characteristics. The extent of low attenuation area and bronchial wall thickening at a segmental and distal level on volumetric CT scan acquired at suspended inspiration state are commonly used as useful imaging markers for evaluating the severity of emphysema and airway wall inflammation, respectively. The clinical values of these two imaging biomarkers are as follows: 1) Many recent studies have proved that the extent of emphysema and bronchial wall thickening are independently related with the degree of airflow limitation, 2) The extent of emphysema is correlated with other clinical parameters such as osteoporosis, exercise capacity, respiratory symptoms and most importantly with BODE index, which is known to be one of the best predictors of mortality, 3) Both parameters may be useful in subgrouping/phenotyping of patients, prediction of treatment response, and prediction of disease progression 4) Both parameters are related to frequency of exacerbation. Furthermore, many additional potential imaging biomarkers have been proposed. They include; (1) assessment of air trapping by direct anatomical matching of inspiration and expiration CT, (2) assessment of peripheral vascular changes in COPD, and so on.
Magnetic resonance imaging (MRI) has emerged as a new modality for lung imaging only recently, with airway diseases being the most accepted indications for clinical routine imaging. Beyond being a substitute for X-ray and computed tomography (CT), MRI combines morphologic and functional information more consequently than any other technologies. Morphological sequences for proton MRI suitable for airways disease will be introduced, but the focus will be on functional techniques that have been introduced into clinical routine imaging or are most advanced in scientific studies. These are dynamic contrast-enhanced perfusion MRI, T1-mapping with inhalative oxygen, and non-contrast Fourier-decomposition MRI, which allow for a regional analysis of lung function. Further, noble and fluorinated gas MRI will be discussed as advanced scientific methods to study regional lung ventilation. It has been shown that MRI may sensitively detect changes in lung morphology related to large airways diseases such as airway wall thickening, bronchiectasis, mucus plugging or tracheobronchomalacia with lower resolution than CT, but with similar clinical impact. Ventilation abnormalities attributable to small airways disease are closely linked to subsequent perfusion changes, which can be sensitively detected by dynamic contrast-enhanced perfusion MRI. By a combination of morphological with functional techniques, MRI has the potential to specifically differentiate reversible from irreversible lung changes especially in airway diseases such as COPD and cystic fibrosis. This makes MRI an important modality for non-irradiating regional disease monitoring and therapy follow-up. Subsequently, it has now been used as an endpoint in pioneer clinical trials, which will be presented briefly.
Adenocarcinoma is the most prevalent type of lung cancer, showing a large spectrum of genetics, histologic subtype, CT appearance and prognosis. Activating mutations of EGFR are found in 30%-50% of lung adenocarcinomas in East Asian patients and approximately 15% in Caucasian patients. EGFR mutation status is correlated with nonsmoking status, female sex, lepidic subtype, and a high response rate to EGFR tyrosine kinase inhibitors (TKI). Some CT findings have shown to be associated with EGFR mutation such as nonsolid or mixed ground-glass opacity, air bronchogram, smaller and peripheral tumours. Furthermore, never-smoking patients presenting with diffuse miliary metastatic disease at diagnosis may be diagnosed with adenocarcinoma harbouring EFGR mutation and may show a dramatic response to EGFR-TKI. The most common resistance mechanism to EGFR-TKI is the T790M mutation, against which new irreversible TKIs have been found to be clinically effective, thus increasing demand for rebiopsy in progressive NSCLC to analyse mutational status. Rebiopsies are feasible and informative in most of the patients with acceptable rates of complications. Furthermore, continued EGFR-TKI therapy may be indicated beyond RECIST progression because these tumours grow slowly and some tumour cells remain sensitive to EGFR-TKI. Radiologists should also be aware of the risk of class-effect toxicity of EGFR-TKI, in particular, pneumonitis with an incidence rate of 4-5% in the Japanese population. Finally, European radiologists should keep in mind that a majority of studies dealing with EGFR mutations in adenocarcinomas arise from Asian countries with results that might not be transposable to Caucasian populations.
Immune checkpoint inhibitors are effective in the treatment of many cancers, de-blocking immune pathways; they play an increasing role in the first-line treatment of lung-cancers. This is particularly true when there is evidence for a significant pretreatment tumour lymphocytic infiltration and/or the tumour shows a high expression for PD-L1. As checkpoint inhibitors work through a different mode of action compared to cytotoxic agents, there is a good reason to use therapy response criteria other than RECIST. In contrast to classical chemotherapies anti-tumour response in immunotherapy may take longer, and in the initial phase the response to immune therapies can manifest in a morphologic “progressive disease”, therefore, called “pseudoprogression”. In this situation, early discontinuation of the treatment could be inappropriate, unless PD is confirmed. An initially tolerable PD may even include the detection of new lesions ("unconfirmed progression", iUPD) that may not lead immediately to a discontinuation of the oncologic regiment and has to be reevaluated (iCPD, iSD). The disinhibition of mechanisms normally protecting from autoimmunity and prolonged immunoreactions leads not only to unusual tumour response patterns but also produces atypical toxicities including a broad spectrum of autoimmune diseases. Imaging characteristics of frequent and serious immune-related adverse events will be discussed.
In the last decade, huge improvements in prognosis and quality of life have been granted by molecular characterisation of non-small cell lung cancer (NSCLC). In particular, Anaplastic Lymphoma Kinase (ALK) and ROS1-positive tumours can now be treated by oral tyrosine kinase inhibitors (TKIs), which allow survival outcomes far beyond it could be expected until a decade ago. Notably, these oncogenes are mostly found in adenocarcinoma histology and in never-smokers (about 60% of all ALK-rearranged NSCLC). Target therapy by TKI improves progression-free survival (PFS) compared with previous reference chemotherapy. In the face of a better disease control by TKI, however, it happens that ALK-positive tumours are prone to driver mutation with resistance to first-line TKI, in the first months of therapy. In clinical practice, diagnostic imaging, notably computed tomography (CT), has a high yield in the management of patients under target therapy. The CT evidence of disease progression, either local or systemic (note: brain metastases are relatively common because first-line TKIs have low trespassing coefficient through the hematoencephalic barrier) is paramount for timely adaptation of therapy. Rapid radiologic progression demands prompt TKI swap towards second-line (e.g. ceritinib, brigatinib, or alectinib) or third-line target therapy (e.g. lorlatinib) or otherwise. Re-biopsy is suggested to pitch the optimal second (or further) line therapy by continuous molecular testing. Adverse events occur in a minority of patients under TKI (1% incidence of lung toxicity). Therapy discontinuation is usually sufficient to reduce toxic effects, with only 3-6% of cases lingering after therapy withdrawal.
Cardiomyopathies are a heterogeneous, important group of diseases with significant morbidity and mortality, and can be classified into five major subtypes based on morphology (hypertrophic, dilated, restrictive, arrhythmogenic and unclassified). Diagnosis is based on a composite of clinical history and examination, laboratory and genetic testing, electrocardiography and cardiac imaging. Echocardiography is the first-line imaging test for the evaluation of cardiac structure and function, with cardiac magnetic resonance imaging (CMR) the gold standard. The computerised tomography (CT) has a growing role in this area. ECG-gated cardiac CT is a well-established test for coronary artery imaging, but it also allows an excellent opportunity to assess for structural cardiac abnormalities, such as asymmetric septal hypertrophy in hypertrophic cardiomyopathy, or left ventricular dilatation in dilated cardiomyopathy. The CT features of the common cardiomyopathies will be reviewed with a comparison to CMR, along with a revision of normal cardiac chamber anatomy. The improved temporal resolution of modern CT scanners has reduced the deleterious effect of cardiac motion artefact on routine non-ECG gated chest CT, allowing an opportunity for the detection of cardiac structural abnormalities. Standard non-ECG gated chest CT has a reported sensitivity of 68% in the detection of cardiomyopathies, and the most reliable imaging features of cardiomyopathies on standard chest CT, as well as potential pitfalls, will be reviewed.
The heart and coronary arteries can be identified on imaging performed specifically to assess the heart and also on imaging of the chest performed for other reasons. Normal imaging coronary artery anatomy will be reviewed. Coronary artery calcification (CAC) is a marker of atherosclerotic plaque burden. CAC identified on electrocardiogram-gated computed tomography (CT) is associated with an increased risk of cardiovascular morbidity and mortality. Randomised controlled trials have shown that management guided by CT coronary angiography can improve outcomes for patients with suspected coronary artery disease. CAC can also be identified on non-gated CT performed for other reasons. Calcium scoring or ordinal assessment of CAC on non- gated CT correlates with results from gated imaging. CAC on non-gated CT is associated with increased mortality in a variety of diseases, including patients with respiratory diseases. Evidence of previous myocardial infarction can also be identified on non-gated CT with features including mural thinning, fatty infiltration and complications such as aneurysms.
Population ageing and other risk factors are not only associated with calcification of coronary arteries but are also likely to induce changes in the cardiac structure. These changes can be evaluated on a standard chest CT without cardiac synchronisation. Calcifications of the cardiac valves may be a sign of valvulopathy. Aortic valve calcium scoring by CT is useful to estimate aortic stenosis severity when echocardiography is not feasible or not conclusive. Myocardial calcification may be due to abnormalities of calcium homeostasis or calcium accumulation in necrotised cardiac myocytes. Pericardial calcification is a sign of constrictive pericarditis. Physiological age-related fat deposits within the myocardium or the atrial septum are frequent and must not be misreported as pathological. Benign or more rarely malignant cardiac tumours may present fatty component. More recently epicardial adipose tissue seems to be a new cardiac risk factor quantifiable by imaging.
Malignant pleural mesothelioma (MPM) is the most common primary malignant tumour of the pleura and the second most common pleural malignancy after metastatic disease. MPM has a poor prognosis and limited treatment options. Imaging plays a central role in the detection, diagnosis, staging, and response assessment of MPM. Although multimodality imaging, especially PET/CT, is increasingly used, contrast-enhanced CT alone is often sufficient. MPM has a unique morphology and growth pattern, making the image interpretation frequently a challenge. The aim of the presentation is to provide an overview of the most common and less frequent imaging findings of MPM, staging of MPM according to the 8th TNM classification, the role of PET/CT in the management of MPM, and the revised, modified RECIST 1.1 guidelines for MPM response assessment.
Pleural metastases are the most common malignant pleural tumours, usually originating from an adenocarcinoma of the lung, breast, ovary, and stomach. Pleural malignancy may also be related to lymphoma, a thymoma or may be of unknown origin. Typical features of malignancy include circumferential thickening, nodular thickening, thickness greater than 1 cm, and involvement of the mediastinal pleura. A pleural effusion is commonly seen, sometimes without any associated pleural thickening. Multiple pleural-based nodules or focal pleural thickenings, as well as a solitary mass, may also be observed. Focal pleural thickenings (PT) should not be confused with normal structures, typical pleural plaques, PT related to previous tuberculosis, silicosis, or other rarer conditions. Importantly, in case of known or suspected malignancy, the presence of postero-basal PT in supine examination requires an additional low dose acquisition on prone position. Indeed, such thickenings may be reversible, therefore excluding pleural metastasis. Any atypical shape, location or change of a PT should suggest a pleural metastasis in a context of malignancy. In all cases, a careful analysis of other CT findings, previous imaging studies and clinical history are determinant for the final diagnosis of pleural metastasis. Beside contrast-enhanced MDCT, the major imaging modality in this setting, there is an undeniable role of PET imaging. In particular, by using the latest equipment allowing a spatial resolution of 3 mm, a high metabolic activity in the absence of prior thoracocentesis may help to strongly suggest malignancy faced with minor or subtle anomalies. Illustrative cases will be reviewed.
Pleural malignancies, other than mesothelioma and metastases, are very rare. According to the latest World Health Organization Classification, these tumours can be further divided into lymphoproliferative disorders and mesenchymal tumours. The latter includes malignant solitary fibrous tumour, desmoid-type fibromatosis, sarcomas, desmoplastic round cell tumour,... .Pleural lymphoma can be primary or secondary. Primary lymphoma is a very rare entity that can be seen in the setting of HIV with primary effusion lymphoma or associated with pyothorax. Imaging findings are nonspecific, but an isolated pleural lesion is unlikely to represent lymphoma. Secondary pleural lymphoma is most commonly non-Hodgkin lymphoma and mainly seen in association with other types of thoracic involvement. Pleural solitary fibrous tumours are malignant in up to one-third of cases. On CT these well circumscribed pedunculated large masses are heterogeneous. Calcifications and associated pleural effusion are less common. Desmoid tumours appear as well-defined isodense to hypodense masses on CT. Contrast enhancement is variable and central necrosis is usually absent. Whereas chest radiographs can be the initial study for detection, Computed Tomography remains the imaging modality of choice for primary assessment of pleural masses. Magnetic Resonance Imaging and Positron emission tomography may have a role in further characterisation, defining local tumour extension and staging.
A cavity is defined as “a gas-filled space, seen as a lucency or low-attenuation area, within pulmonary consolidation, a mass, or a nodule”. The wall thickness may vary considerably. There is a continuous transition from cavities to cysts. Cysts are usually thin-walled (i.e., < 2 mm). A wall thickness < 7 mm is highly specific for the benign disease, a thickness >24 mm is highly specific for malignant disease. However, this is not absolute, as thin-walled carcinomas do exist. An additional indicator for malignancy is the lack of perilesional centrilobular nodules around a cavity. The cavity content is unhelpful in differentiating benign and malignant lesions. Wall rim enhancement on contrast-enhanced CT is common in abscesses. A connecting pulmonary artery may be seen in smaller metastases, but not in larger ones, as the larger nodules tend to compress the vessels, so no feeding artery does not always imply benign nodules. The acute onset of symptoms is sometimes helpful to distinguish malignant and non-malignant disease. Hemoptysis is not a useful symptom to differentiate between benign and malignant cavities. Benign diseases may also cause fatigue and weight loss similar to malignancies. Acute onset of fever is usually helpful to distinguish benign disorders from malignant, but pulmonary cancer may cause a super-infection secondary to the tumour. However, the combination of symptoms, laboratory results, past clinical history, and imaging findings leads to recognition of the correct diagnosis. This presentation will guide you through the most commonly encountered cavitary lung in adults.
The presentation will review the typical and atypical features of Langerhans cell histiocytosis (LCH) on HRCT, and the differential diagnosis when faced with cystic lung disease on CT. The evolution of CT appearances of LCH over time, the complications of LCH, as well as the pathological correlates will be discussed.
Lymphangiomyomatosis (LAM) is a rare cystic lung disease caused by infiltration of the lung with smooth muscle cells. It occurs in patients with tuberous sclerosis complex (TSC-LAM) and in a “sporadic” form in patients without tuberous sclerosis (S-LAM). S-LAM is seen exclusively in women of reproductive age while TSC-LAM may also be seen in men. Parenchymal lesions in LAM include cysts, which are thin-walled, well-defined, rounded, usually small in size up to 2 cm and may reach large numbers. They have no zonal lung predominance. Nodules are extremely rare in S-LAM and are more commonly seen in TSC-LAM. They may either be solid or ground-glass and usually tiny. They represent multifocal micronodular pneumocyte hyperplasia. Pleural manifestations include chylothorax and pneumothorax. Chylous pericardial effusions may be seen. Recent guidelines for LAM from the European Respiratory Society LAM task force classify LAM as definite, probable and possible. LAM is differentiated by other cystic lung diseases such as Langerhans histiocytosis (PLCH), Birt-Hogg-Dubbe (BHD), lymphocytic interstitial pneumonia (LIP) and amyloidosis. In PLCH the cysts have a bizarre shape, are variable in number and are upper and middle lobe predominant. In LIP the cysts are round and variable in size but usually small and random in distribution surrounded by ground glass opacity. In BHD the cysts are elliptical in shape and have a subpleural, lower zone predominance adjacent to vessels. In amyloid, the cysts are variable in size but usually large and diffusely distributed. Nodules are seen in PLCH and amyloid.
Pulmonary hypertension (PH) typically presents insidiously with non-specific symptoms and is usually progressive with poor outcome independent of aetiology. CT plays a vital role both in suggesting the possibility of pulmonary hypertension, whether initially clinically suspected or not, and in identifying a specific cause of pulmonary hypertension. The causes of pulmonary hypertension can be broadly divided into those affecting primarily the small vessels, PH secondary to left heart disease or chronic lung disease/hypoxia (the most common causes), chronic thromboembolic PH, and multifactorial causes. CT is widely available, inexpensive, and permits a comprehensive assessment of the heart, pulmonary vasculature and lung parenchyma. CT signs such as dilatation of the proximal pulmonary arteries and right heart chambers can be considered as generic features associated with PH of any cause. Signs of a specific cause may lie in the mediastinum (left heart disease, shunt, oesophageal varices, oesophageal dilatation), vasculature (signs of CTEPH, tumour, large vessel vasculitis, fibrosing mediastinitis) or lungs (parenchymal lung disease, mosaic perfusion in CTEPH, signs of a small vessel vasculopathy). CTEPH is a not uncommon sequela of previous acute embolism. If the distribution is proximal, it is potentially cured by surgical pulmonary endarterectomy or by balloon pulmonary angioplasty. Imaging in general and CT in particular play fundamental roles in both identification of CTEPH, its differentiation from acute PE, and in characterising its distribution. Imaging signs in CTEPH can be a subtle and systematic evaluation of a CTPA is essential.
We will emphasise the importance of combine CT signs with the clinical features and laboratory results, as vasculitis may mimic other disorders and sometimes the clinical features are the clue. We will describe the findings in granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis, highlighting the differences. Diffuse alveolar haemorrhage (DAH) is one of the manifestations of primary pulmonary vasculitis, among other entities (idiopathic alveolar haemorrhage, collagen vascular diseases, drug reactions, anticoagulation disorders). GPA and microscopic polyangiitis are the most common causes of DAH. Radiologic signs of DAH are nonspecific and variable but must be considered in patients with otherwise unexplained alveolar infiltrates, particularly when seen with new-onset renal insufficiency or a connective tissue disease. Finally, we will mention the association between interstitial lung disease and ANCA associated vasculitis.
Behçet disease is a rare multisystem condition associated with HLA-B51 positivity. Arterial involvement in Behçet's disease (BD) is less common than venous lesions. The most commonly affected arteries are: the aorta, lower extremity arteries, mesenteric, femoral, coronary, renal, subclavian and pulmonary arteries. Behçet-related pulmonary vasculitis is an uncommon and heterogeneous group of conditions, often with associated pulmonary artery thrombus formation. These microthrombi can result in a misdiagnosis of acute pulmonary embolism. Hereditary hemorrhagic telangiectasia also known as Osler-Weber-Rendu syndrome is an autosomal dominant disease that occurs due to vascular dysplasia associated with the disorder in the signalling pathway of transforming growth factor β(TGF-β). The clinical consequence is a disorder of blood vessels in multiple organ systems with the existence of telangiectasia which causes dilation of capillaries and veins, are present from birth and are localised on the skin and mouth, respiratory, gastrointestinal and urinary tract. Many patients with gastrointestinal and other organ manifestations are frequently clinically asymptomatic; therefore, organ screening is essential to avoid later complications and should be performed in centres with particular expertise. Hemoptysis is a life-threatening complication that is likely related to pulmonary artery aneurysm (PAA). Diagnostic imaging is the key to success in the management of these patients pulmonary vasculature. CT is the tool with some known advantages and drawbacks. Vascular interventional radiology may offer effective emergency and or elective therapeutic option. Transcatheter embolotherapy should be considered as the first-line emergency treatment for PAA-related hemoptysis, in association with the immunosuppressive regimen.