Pulmonary Hypertension in Chronic Lung Diseases: What Role Do Radiologists Play?

Pulmonary hypertension (PH) is a pathophysiological disorder, defined by a mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, as assessed by right heart catheterization (RHC). PH is not a specific disease, as it may be observed in multiple clinical conditions and may complicate a variety of thoracic diseases. Conditions associated with the risk of developing PH are categorized into five different groups, according to similar clinical presentations, pathological findings, hemodynamic characteristics, and treatment strategy. Most chronic lung diseases that may be complicated by PH belong to group 3 (interstitial lung diseases, chronic obstructive pulmonary disease, combined pulmonary fibrosis, and emphysema) and are associated with the lowest overall survival among all groups. However, some of the chronic pulmonary diseases may develop PH with unclear/multifactorial mechanisms and are included in group 5 PH (sarcoidosis, pulmonary Langerhans' cell histiocytosis, and neurofibromatosis type 1). This paper focuses on PH associated with chronic lung diseases, in which radiological imaging-particularly computed tomography (CT)-plays a crucial role in diagnosis and classification. Radiologists should become familiar with the hemodynamical, physiological, and radiological aspects of PH and chronic lung diseases in patients at risk of developing PH, whose prognosis and treatment depend on the underlying disease.

Extension of Lung Damage at Chest Computed Tomography in Severely Ill COVID-19 Patients Treated with Interleukin-6 Receptor Blockers Correlates with Inflammatory Cytokines Production and Prognosis.

Elevated inflammatory markers are associated with severe coronavirus disease 2019 (COVID-19), and some patients benefit from Interleukin (IL)-6 pathway inhibitors. Different chest computed tomography (CT) scoring systems have shown a prognostic value in COVID-19, but not specifically in anti-IL-6-treated patients at high risk of respiratory failure. We aimed to explore the relationship between baseline CT findings and inflammatory conditions and to evaluate the prognostic value of chest CT scores and laboratory findings in COVID-19 patients specifically treated with anti-IL-6. Baseline CT lung involvement was assessed in 51 hospitalized COVID-19 patients naive to glucocorticoids and other immunosuppressants using four CT scoring systems. CT data were correlated with systemic inflammation and 30-day prognosis after anti-IL-6 treatment. All the considered CT scores showed a negative correlation with pulmonary function and a positive one with C-reactive protein (CRP), IL-6, IL-8, and Tumor Necrosis Factor α (TNF-α) serum levels. All the performed scores were prognostic factors, but the disease extension assessed by the six-lung-zone CT score (S24) was the only independently associated with intensive care unit (ICU) admission (p = 0.04). In conclusion, CT involvement correlates with laboratory inflammation markers and is an independent prognostic factor in COVID-19 patients representing a further tool to implement prognostic stratification in hospitalized patients.

Delta radiomics: a systematic review.

BACKGROUND: Radiomics can provide quantitative features from medical imaging that can be correlated with various biological features and clinical endpoints. Delta radiomics, on the other hand, consists in the analysis of feature variation at different acquisition time points, usually before and after therapy. The aim of this study was to provide a systematic review of the different delta radiomics approaches. METHODS: Eligible articles were searched in Embase, PubMed, and ScienceDirect using a search string that included free text and/or Medical Subject Headings (MeSH) with three key search terms: "radiomics", "texture", and "delta". Studies were analysed using QUADAS-2 and the RQS tool. RESULTS: Forty-eight studies were finally included. The studies were divided into preclinical/methodological (five studies, 10.4%); rectal cancer (six studies, 12.5%); lung cancer (twelve studies, 25%); sarcoma (five studies, 10.4%); prostate cancer (three studies, 6.3%), head and neck cancer (six studies, 12.5%); gastrointestinal malignancies excluding rectum (seven studies, 14.6%), and other disease sites (four studies, 8.3%). The median RQS of all studies was 25% (mean 21% ± 12%), with 13 studies (30.2%) achieving a quality score < 10% and 22 studies (51.2%) < 25%. CONCLUSIONS: Delta radiomics shows potential benefit for several clinical endpoints in oncology (differential diagnosis, prognosis and prediction of treatment response, and evaluation of side effects). Nevertheless, the studies included in this systematic review suffer from the bias of overall low quality, so that the conclusions are currently heterogeneous, not robust, and not replicable. Further research with prospective and multicentre studies is needed for the clinical validation of delta radiomics approaches.

Role of delayed phase contrast-enhanced CT in the intra-thoracic staging of non-small cell lung cancer (NSCLC): What does it add?

PURPOSE: The aim of the study was to investigate differences in non-small cell lung cancer (NSCLC) intra-thoracic staging by using contrast-enhanced computed tomography (ce-CT) at the arterial phase (AP), at the arterial plus delayed phases (AP + DEP), and at the delayed phase (DEP), and to evaluate their potential impact on disease staging. MATERIALS AND METHODS: Two chest radiologists with different level of expertise and a general radiologist independently reviewed the chest CT exams of 150 patients with NSCLC; CT scans were performed 40 s (AP) and 60 s (DEP) after contrast material injection. Image assessment included three reading sessions: session A (AP), session B (AP + DEP) and session C (DEP). CT descriptors for the primary tumour (T), regional nodal involvement (N), and intra-thoracic metastases (M) were evaluated in each reading session. Readers had to assign a confidence level (CL) for the assessment of each descriptor and define the TNM stage. Friedman and Cochran Q test was used to compare the assessments of the 3 reading sessions; inter-reader agreement was determined (Intraclass Correlation Coefficient - ICC). RESULTS: The CL was significantly higher in sessions B and C than in session A for all descriptors, with the exception of pulmonary arterial invasion. Primary tumour inner necrosis and regional nodal involvement were detected in a significantly higher number of cases in sessions B and C as compared to session A (p ≤ 0.001). DEP significantly changed N stage determination (p < 0.001), particularly N3, and excluded chest wall invasion (p = 0.05) and venous invasion (p = 0.001). The agreement was good among the 3 readers (ICC = 0.761) and excellent between the 2 chest radiologists (ICC ≥ 0.940), regardless of the contrast phase. CONCLUSIONS: The 60-second DEP ce-CT for staging NSCLC significantly increased the readers' CL, changed the N stage determination, and helped excluding chest wall invasion and venous invasion.

Impact of the COVID-19 pandemic on the selection of chest imaging modalities and reporting systems: a survey of Italian radiologists.

PURPOSE: Chest imaging modalities play a key role for the management of patient with coronavirus disease (COVID-19). Unfortunately, there is no consensus on the optimal chest imaging approach in the evaluation of patients with COVID-19 pneumonia, and radiology departments tend to use different approaches. Thus, the main objective of this survey was to assess how chest imaging modalities have been used during the different phases of the first COVID-19 wave in Italy, and which diagnostic technique and reporting system would have been preferred based on the experience gained during the pandemic. MATERIAL AND METHODS: The questionnaire of the survey consisted of 26 questions. The link to participate in the survey was sent to all members of the Italian Society of Medical and Interventional Radiology (SIRM). RESULTS: The survey gathered responses from 716 SIRM members. The most notable result was that the most used and preferred chest imaging modality to assess/exclude/monitor COVID-19 pneumonia during the different phases of the first COVID-19 wave was computed tomography (51.8% to 77.1% of participants). Additionally, while the narrative report was the most used reporting system (55.6% of respondents), one-third of participants would have preferred to utilize structured reporting systems. CONCLUSION: This survey shows that the participants' responses did not properly align with the imaging guidelines for managing COVID-19 that have been made by several scientific, including SIRM. Therefore, there is a need for continuing education to keep radiologists up to date and aware of the advantages and limitations of the chest imaging modalities and reporting systems.

Novelties in Imaging of Thoracic Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease affecting various organs, and the lungs are the most commonly involved. According to guidelines, diagnosis relies on a consistent clinical picture, histological demonstration of non-caseating granulomas, and exclusion of other diseases with similar histological or clinical picture. Nevertheless, chest imaging plays an important role in both diagnostic assessment, allowing to avoid biopsy in some situations, and prognostic evaluation. Despite the demonstrated lower sensitivity of chest X-ray (CXR) in the evaluation of chest findings compared to high-resolution computed tomography (HRCT), CXR still retains a pivotal role in both diagnostic and prognostic assessment in sarcoidosis. Moreover, despite the huge progress made in the field of radiation dose reduction, chest magnetic resonance (MR), and quantitative imaging, very little research has focused on their application in sarcoidosis. In this review, we aim to describe the latest novelties in diagnostic and prognostic assessment of thoracic sarcoidosis and to identify the fields of research that require investigation.

Mediastinal lymph node enlargement in idiopathic pulmonary fibrosis: relationships with disease progression and pulmonary function trends.

BACKGROUND AND OBJECTIVES: Evidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients. METHODS: This retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models. RESULTS: The study population consisted of 152 IPF patients, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86-13.62, p ≤ 0.001) and significant disease progression (HR 2.99, 95% CI 1.22-7.33, p = 0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time. CONCLUSIONS: Diffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.

Multimodality imaging of COVID-19 pneumonia: from diagnosis to follow-up. A comprehensive review.

Due to its pandemic diffusion, SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection represents a global threat. Despite a multiorgan involvement has been described, pneumonia is the most common manifestation of COVID-19 (Coronavirus disease 2019) and it is associated with a high morbidity and a considerable mortality. Especially in the areas with high disease burden, chest imaging plays a crucial role to speed up the diagnostic process and to aid the patient management. The purpose of this comprehensive review is to understand the diagnostic capabilities and limitations of chest X-ray (CXR) and high-resolution computed tomography (HRCT) in defining the common imaging features of COVID-19 pneumonia and correlating them with the underlying pathogenic mechanisms. The evolution of lung abnormalities over time, the uncommon findings, the possible complications, and the main differential diagnosis occurring in the pandemic phase of SARS-CoV-2 infection are also discussed.

Exploring technical issues in personalized medicine: NSCLC survival prediction by quantitative image analysis-usefulness of density correction of volumetric CT data.

The aim of this study was to apply density correction method to the quantitative image analysis of non-small cell lung cancer (NSCLC) computed tomography (CT) images, determining its influence on overall survival (OS) prediction of surgically treated patients. Clinicopathological (CP) data and preoperative CT scans, pre- and post-contrast medium (CM) administration, of 57 surgically treated NSCLC patients, were retrospectively collected. After CT volumetric density measurement of primary gross tumour volume (GTV), aorta and tracheal air, density correction was conducted on GTV (reference values: aortic blood and tracheal air). For each resulting data set (combining CM administration and normalization), first-order statistical and textural features were extracted. CP and imaging data were correlated with patients 1-, 3- and 5-year OS, alone and combined (uni-/multivariate logistic regression and Akaike information criterion). Predictive performance was evaluated using the ROC curves and AUC values and compared among non-normalized/normalized data sets (DeLong test). The best predictive values were obtained when combining CP and imaging parameters (AUC values: 1 year 0.72; 3 years 0.82; 5 years 0.78). After normalization resulted an improvement in predicting 1-year OS for some of the grey level size zonebased features (large zone low grey level emphasis) and for the combined CP-imaging model, a worse performance for grey level co-occurrence matrix (cluster prominence and shade) and first-order statistical (range) parameters for 1- and 5-year OS, respectively. The negative performance of cluster prominence in predicting 1-year OS was the only statistically significant result (p value 0.05). Density corrections of volumetric CT data showed an opposite influence on the performance of imaging quantitative features in predicting OS of surgically treated NSCLC patients, even if no statistically significant for almost all predictors.

CT Radiomics Signature of Tumor and Peritumoral Lung Parenchyma to Predict Nonsmall Cell Lung Cancer Postsurgical Recurrence Risk.

RATIONALE AND OBJECTIVES: To estimate recurrence risk after surgery in nonsmall cell lung cancer (NSCLC) patients by employing tumoral and peritumoral radiomics analysis. MATERIALS AND METHODS: One-hundred twenty-four surgically treated stage IA-IIB NSCLC patients' data from 2008 to 2013 were retrospectively collected. Patient outcome was defined as local recurrence (LR), distant metastasis (DM), and (sum of LR and DM) total recurrence (TR) at follow-up. Volumetric region of interests (ROIs) were drawn for the tumor, peritumoral lung parenchyma (2 cm around the tumor) and involved lobe on CT images. Ninety-four (morphological, first-order, textural, fractal-based) radiomics features were extracted from the ROIs and datasets were created from single or combined ROIs. Predictive models were built with radiomics signature (RS) and clinicopathological data, and the area under the curve (AUC) was used to evaluate the performance. Radiomics score was calculated with the best models' feature coefficients, low- and high-risk groups of patients defined accordingly. Kaplan-Meier curves were built, and the log-rank test was used for comparison among low- and high-risk groups. Differences in recurrence risk among the two risk groups were calculated (chi-square test). RESULTS: Fifty-six patients developed TR (25 LR, 31 DM). The tumor-node-metastasis (TNM) stage recurrence predictability (AUCTR 0.680; AUCDM 0.672; AUCLR 0.580) was substantially improved when RS was added to the predictive model (AUCTR 0.760; AUCDM 0.759; AUCLR 0.750). Seventy-five percent of high-risk patients developed TR. Recurrence risk of the high-risk group was 16-fold higher than that of the low-risk group (p < 0.001). CONCLUSION: Combination of the tumoral and peritumoral RS with TNM staging system outperformed TNM staging alone in individualized recurrence risk estimation of patients with surgically treated NSCLC.

Management of incidental pulmonary nodule in CT: a survey by the Italian College of Chest Radiology.

OBJECTIVES: The aim of this study is to present the results of the Italian survey on the management of pulmonary nodules incidentally identified at computed tomography (CT). MATERIALS AND METHODS: An online electronic survey, consisting of 23 multiple-choice questions, was created using the SurveyMonkey web-based tool. The questionnaire was developed by the Board of the Italian College of Chest Radiology of the Italian Society of Medical and Interventional Radiology (SIRM) and by an experienced group of Italian Academic Chest Radiologists. The link to the online electronic survey was submitted by email to all the SIRM members. RESULTS: A total of 767 radiologists, corresponding to 7.5% of all the SIRM members, participated in the online survey. The majority of participants (92%) routinely describe the attenuation of pulmonary nodules in the report, and 84.1% recommend the further follow-up, with 92.7% of respondents taking CT nodule morphological features into consideration. The 57.7% of participants adhere to the Fleischner Society guidelines for the management of incidental pulmonary nodules. However, 56.6% and 75.6% of respondents have a more cautious approach than that recommended by the guidelines and tend to use a shorter follow-up for both solid and ground-glass nodules, respectively. Finally, 94.5% of participants favor congresses and refresher courses dedicated to insights on lung nodule diagnosis and management. CONCLUSIONS: This survey demonstrates that the management of pulmonary nodules incidentally detected on CT is still complex and controversial. The majority of SIRM members express a need for an update on this topic.

Towards a modular decision support system for radiomics: A case study on rectal cancer.

Following the personalized medicine paradigm, there is a growing interest in medical agents capable of predicting the effect of therapies on patients, by exploiting the amount of data that is now available for each patient. In disciplines like oncology, where images and scans are available, the exploitation of medical images can provide an additional source of potentially useful information. The study and analysis of features extracted by medical images, exploited for predictive purposes, is termed radiomics. A number of tools are available for supporting some of the steps of the radiomics process, but there is a lack of approaches which are able to deal with all the steps of the process. In this paper, we introduce a medical agent-based decision support system capable of handling the whole radiomics process. The proposed system is tested on two independent data sets of patients treated for rectal cancer. Experimental results indicate that the system is able to generate highly performant centre-specific predictive model, and show the issues related to differences in data sets collected by different centres, and how such issues can affect the performance of the generated predictive models.

Pulmonary fibrolysis in a patient with idiopathic pulmonary fibrosis: improvement of clinical and radiological pattern after treatment with pirfenidone.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia associated with the histologic and/or radiologic pattern of usual interstitial pneumonia (UIP). Nowadays, the high-resolution computed tomography pattern of "definite UIP" is enough to define a diagnosis of UIP without histological proof. This is pivotal especially in elderly patients with comorbidities. Early recognition of IPF is relevant for its prognostic implication. Some pharmacological strategies have been proposing novel molecules that tend to slow lung function decline, even though without healing fibrosis. We report a case of ex-heavy smoker male with IPF showing clinical and radiological improvement after 11 months of treatment with Pirfenidone. The definite diagnosis was challenging and it was reached by a multidisciplinary approach.

Lung nodules: size still matters.

The incidence of indeterminate pulmonary nodules has risen constantly over the past few years. Determination of lung nodule malignancy is pivotal, because the early diagnosis of lung cancer could lead to a definitive intervention. According to the current international guidelines, size and growth rate represent the main indicators to determine the nature of a pulmonary nodule. However, there are some limitations in evaluating and characterising nodules when only their dimensions are taken into account. There is no single method for measuring nodules, and intrinsic errors, which can determine variations in nodule measurement and in growth assessment, do exist when performing measurements either manually or with automated or semi-automated methods. When considering subsolid nodules the presence and size of a solid component is the major determinant of malignancy and nodule management, as reported in the latest guidelines. Nevertheless, other nodule morphological characteristics have been associated with an increased risk of malignancy. In addition, the clinical context should not be overlooked in determining the probability of malignancy. Predictive models have been proposed as a potential means to overcome the limitations of a sized-based assessment of the malignancy risk for indeterminate pulmonary nodules.

Evaluation of the Added Value of Diffusion-Weighted Imaging to Conventional Magnetic Resonance Imaging in Pancreatic Neuroendocrine Tumors and Comparison With 68Ga-DOTANOC Positron Emission Tomography/Computed Tomography.

OBJECTIVES: The aims of this study were to investigate the added value of diffusion-weighted imaging (DWI) in pancreatic neuroendocrine tumor (pNET) evaluation and to compare magnetic resonance imaging (MRI) to Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) results. METHODS: Morphological MRI (T2-weighted [T2-w] + contrast-enhanced [CE] T1-w) and DWI (T2-w + DWI) and Ga-DOTANOC PET/CT in 25 patients/30 pNETs were retrospectively evaluated. Per-patient and per-lesion detection rates (pDR and lDR, respectively) were calculated. Apparent diffusion coefficient values were compared among pNET and surrounding and normal pancreas (control group, 18 patients). Apparent diffusion coefficient and standardized uptake value (SUV) values were compared among different grading and staging groups. RESULTS: No statistically significant differences in PET/CT and MRI session detection rates were found (morphological MRI and DW-MRI, 88% pDR and 87% lDR; combined evaluation, 92% pDR and 90% lDR; Ga-DOTANOC PET/CT, 88% pDR and 80% lDR). Consensus reading (morphological/DW-MRI + PET/CT) improved pDR and lDR (100%). Apparent diffusion coefficient mean value was significantly lower compared with surrounding and normal parenchyma (P < 0.01). The apparent diffusion coefficient and SUV values of pNETs among different grading and staging groups were not statistically different. CONCLUSIONS: Conventional MRI, DW-MRI + T2-w sequences, and Ga-DOTANOC PET/CT can be alternative tools in pNET detection. Diffusion-weighted MRI could be valuable in patients with clinical suspicion but negative conventional imaging findings. However, the consensus reading of the 3 techniques seems the best approach.

Normal hepatic parenchyma visibility and ADC quantification on diffusion-weighted MRI at 3 T: influence of age, gender, and iron content.

OBJECTIVES: To investigate how normal liver parenchyma visibility on 3 T diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) quantification are influenced by age, gender, and iron content. METHODS: Between February 2011 and April 2013, 86 patients (52 women) with normal livers who underwent respiratory-triggered abdominal 3 T DWI (b = 0, 150, 600, 1,000 s/mm(2)) were retrospectively included. Normal liver and spleen parenchyma visibility was scored independently by two readers. Correlations between visibility scores or ADC with age, gender, T2*, or recent serum ferritin (SF) were investigated. RESULTS: Liver visibility scores in b = 1,000 s/mm(2) images correlated with the age (Spearman R = -0.56 in women, -0.45 in men), T2* (R = 0.75) and SF (R = -0.64) and were significantly higher in women (P < 0.01). SF and T2* were within normal values (T2*: 13 - 31 ms, SF: 14 - 230 µg/L). Liver ADC correlated with visibility scores (R = 0.69) and T2* (R = 0.64) and was age- and gender-dependent. ADC ROI standard deviation negatively correlated with visibility scores (R = -0.65) and T2* (R = -0.62). The spleen visibility did not depend on age or gender. CONCLUSIONS: Normal liver parenchyma visibility in DWI is age- and gender-dependent, according to the iron content. Visibility scores and iron content significantly affect ADC quantification in the normal liver. KEY POINTS: Normal DWI liver visibility is gender-dependent and superior in women. In women, normal DWI liver visibility is superior before age 50 years. Normal DWI liver visibility negatively correlates with normal range iron content markers. Liver ADC quantification depends on liver iron content even within normal range. Normal liver T2* is age- and gender-dependent.

Unilocular macrocystic serous cystadenoma of the pancreas--atypical features: a case report.

The authors report and discuss an exceedingly rare case of a unilocular macrocystic serous cystadenomas diagnosed in a 63-year-old female patient, which was preoperatively misdiagnosed as a mucinous cystic neoplasm, due to the atypical magnetic resonance (MR) imaging features shown at presentation and the misleading results obtained through cystic fluid analysis. This manuscript overviews the typical and atypical manifestations of this entity and highlights the advantages, potential limitations and pitfalls of both MR imaging and cystic fluid analysis.