Improving Prognostication in Pulmonary Hypertension Using AI-quantified Fibrosis and Radiologic Severity Scoring at Baseline CT.

Background There is clinical need to better quantify lung disease severity in pulmonary hypertension (PH), particularly in idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-LD). Purpose To quantify fibrosis on CT pulmonary angiograms using an artificial intelligence (AI) model and to assess whether this approach can be used in combination with radiologic scoring to predict survival. Materials and Methods This retrospective multicenter study included adult patients with IPAH or PH-LD who underwent incidental CT imaging between February 2007 and January 2019. Patients were divided into training and test cohorts based on the institution of imaging. The test cohort included imaging examinations performed in 37 external hospitals. Fibrosis was quantified using an established AI model and radiologically scored by radiologists. Multivariable Cox regression adjusted for age, sex, World Health Organization functional class, pulmonary vascular resistance, and diffusing capacity of the lungs for carbon monoxide was performed. The performance of predictive models with or without AI-quantified fibrosis was assessed using the concordance index (C index). Results The training and test cohorts included 275 (median age, 68 years [IQR, 60-75 years]; 128 women) and 246 (median age, 65 years [IQR, 51-72 years]; 142 women) patients, respectively. Multivariable analysis showed that AI-quantified percentage of fibrosis was associated with an increased risk of patient mortality in the training cohort (hazard ratio, 1.01 [95% CI: 1.00, 1.02]; P = .04). This finding was validated in the external test cohort (C index, 0.76). The model combining AI-quantified fibrosis and radiologic scoring showed improved performance for predicting patient mortality compared with a model including radiologic scoring alone (C index, 0.67 vs 0.61; P < .001). Conclusion Percentage of lung fibrosis quantified on CT pulmonary angiograms by an AI model was associated with increased risk of mortality and showed improved performance for predicting patient survival when used in combination with radiologic severity scoring compared with radiologic scoring alone. © RSNA, 2024 Supplemental material is available for this article.

Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry.

BACKGROUND: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined. METHODS: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included. RESULTS: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents. CONCLUSIONS: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH.

External validation, radiological evaluation, and development of deep learning automatic lung segmentation in contrast-enhanced chest CT.

OBJECTIVES: There is a need for CT pulmonary angiography (CTPA) lung segmentation models. Clinical translation requires radiological evaluation of model outputs, understanding of limitations, and identification of failure points. This multicentre study aims to develop an accurate CTPA lung segmentation model, with evaluation of outputs in two diverse patient cohorts with pulmonary hypertension (PH) and interstitial lung disease (ILD). METHODS: This retrospective study develops an nnU-Net-based segmentation model using data from two specialist centres (UK and USA). Model was trained (n = 37), tested (n = 12), and clinically evaluated (n = 176) on a diverse 'real-world' cohort of 225 PH patients with volumetric CTPAs. Dice score coefficient (DSC) and normalised surface distance (NSD) were used for testing. Clinical evaluation of outputs was performed by two radiologists who assessed clinical significance of errors. External validation was performed on heterogenous contrast and non-contrast scans from 28 ILD patients. RESULTS: A total of 225 PH and 28 ILD patients with diverse demographic and clinical characteristics were evaluated. Mean accuracy, DSC, and NSD scores were 0.998 (95% CI 0.9976, 0.9989), 0.990 (0.9840, 0.9962), and 0.983 (0.9686, 0.9972) respectively. There were no segmentation failures. On radiological review, 82% and 71% of internal and external cases respectively had no errors. Eighteen percent and 25% respectively had clinically insignificant errors. Peripheral atelectasis and consolidation were common causes for suboptimal segmentation. One external case (0.5%) with patulous oesophagus had a clinically significant error. CONCLUSION: State-of-the-art CTPA lung segmentation model provides accurate outputs with minimal clinical errors on evaluation across two diverse cohorts with PH and ILD. CLINICAL RELEVANCE: Clinical translation of artificial intelligence models requires radiological review and understanding of model limitations. This study develops an externally validated state-of-the-art model with robust radiological review. Intended clinical use is in techniques such as lung volume or parenchymal disease quantification. KEY POINTS: • Accurate, externally validated CT pulmonary angiography (CTPA) lung segmentation model tested in two large heterogeneous clinical cohorts (pulmonary hypertension and interstitial lung disease). • No segmentation failures and robust review of model outputs by radiologists found 1 (0.5%) clinically significant segmentation error. • Intended clinical use of this model is a necessary step in techniques such as lung volume, parenchymal disease quantification, or pulmonary vessel analysis.

Establishing minimally important differences for cardiac MRI end-points in pulmonary arterial hypertension.

BACKGROUND: Cardiac magnetic resonance (CMR) is the gold standard technique to assess biventricular volumes and function, and is increasingly being considered as an end-point in clinical studies. Currently, with the exception of right ventricular (RV) stroke volume and RV end-diastolic volume, there is only limited data on minimally important differences (MIDs) reported for CMR metrics. Our study aimed to identify MIDs for CMR metrics based on US Food and Drug Administration recommendations for a clinical outcome measure that should reflect how a patient "feels, functions or survives". METHODS: Consecutive treatment-naïve patients with pulmonary arterial hypertension (PAH) between 2010 and 2022 who had two CMR scans (at baseline prior to treatment and 12 months following treatment) were identified from the ASPIRE registry. All patients were followed up for 1 additional year after the second scan. For both scans, cardiac measurements were obtained from a validated fully automated segmentation tool. The MID in CMR metrics was determined using two distribution-based (0.5sd and minimal detectable change) and two anchor-based (change difference and generalised linear model regression) methods benchmarked to how a patient "feels" (emPHasis-10 quality of life questionnaire), "functions" (incremental shuttle walk test) or "survives" for 1-year mortality to changes in CMR measurements. RESULTS: 254 patients with PAH were included (mean±sd age 53±16 years, 79% female and 66% categorised as intermediate risk based on the 2022 European Society of Cardiology/European Respiratory Society risk score). We identified a 5% absolute increase in RV ejection fraction and a 17 mL decrease in RV end-diastolic or end-systolic volumes as the MIDs for improvement. Conversely, a 5% decrease in RV ejection fraction and a 10 mL increase in RV volumes were associated with worsening. CONCLUSIONS: This study establishes clinically relevant CMR MIDs for how a patient "feels, functions or survives" in response to PAH treatment. These findings provide further support for the use of CMR as a clinically relevant clinical outcome measure and will aid trial size calculations for studies using CMR.

Plain language summaryPulmonary arterial hypertension (PAH) is a disease of the vessels of the lung that causes their narrowing and stiffening. As a result, the heart pumping blood into these diseased lung vessels has to work harder and eventually gets worn out. PAH can affect patients' ability to function in daily activities and impact their quality of life. It also reduces their life expectancy dramatically. Patients are, therefore, often monitored and undergo several investigations to adapt treatment according to their situation. These investigations include a survey of how a patient feels (the emPHasis-10 questionnaire), functions (walking test) and how well the heart is coping with the disease (MRI of the heart). Until now, it is unclear how changes on MRI of the heart reflect changes in how a patient feels and functions. Our study identified patients that had the emPHasis-10 questionnaire, walking test and MRI of the heart at both the time of PAH diagnosis and one year later. This allowed us to compare how the changes in the different tests relate to each other. And because previous research identified thresholds for important changes in the emPHasis-10 questionnaire and the walking tests, we were able to use these tests as a benchmark for changes in the MRI of the heart. Our study identified thresholds for change on heart MRI that might indicate whether a patient has improved or worsened. This finding might have implications for how patients are monitored in clinical practice and future research on PAH treatments.

Validation of Artificial Intelligence Cardiac MRI Measurements: Relationship to Heart Catheterization and Mortality Prediction.

Background Cardiac MRI measurements have diagnostic and prognostic value in the evaluation of cardiopulmonary disease. Artificial intelligence approaches to automate cardiac MRI segmentation are emerging but require clinical testing. Purpose To develop and evaluate a deep learning tool for quantitative evaluation of cardiac MRI functional studies and assess its use for prognosis in patients suspected of having pulmonary hypertension. Materials and Methods A retrospective multicenter and multivendor data set was used to develop a deep learning-based cardiac MRI contouring model using a cohort of patients suspected of having cardiopulmonary disease from multiple pathologic causes. Correlation with same-day right heart catheterization (RHC) and scan-rescan repeatability was assessed in prospectively recruited participants. Prognostic impact was assessed using Cox proportional hazard regression analysis of 3487 patients from the ASPIRE (Assessing the Severity of Pulmonary Hypertension In a Pulmonary Hypertension Referral Centre) registry, including a subset of 920 patients with pulmonary arterial hypertension. The generalizability of the automatic assessment was evaluated in 40 multivendor studies from 32 centers. Results The training data set included 539 patients (mean age, 54 years ± 20 [SD]; 315 women). Automatic cardiac MRI measurements were better correlated with RHC parameters than were manual measurements, including left ventricular stroke volume (r = 0.72 vs 0.68; P = .03). Interstudy repeatability of cardiac MRI measurements was high for all automatic measurements (intraclass correlation coefficient range, 0.79-0.99) and similarly repeatable to manual measurements (all paired t test P > .05). Automated right ventricle and left ventricle cardiac MRI measurements were associated with mortality in patients suspected of having pulmonary hypertension. Conclusion An automatic cardiac MRI measurement approach was developed and tested in a large cohort of patients, including a broad spectrum of right ventricular and left ventricular conditions, with internal and external testing. Fully automatic cardiac MRI assessment correlated strongly with invasive hemodynamics, had prognostic value, were highly repeatable, and showed excellent generalizability. Clinical trial registration no. NCT03841344 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Ambale-Venkatesh and Lima in this issue. An earlier incorrect version appeared online. This article was corrected on June 27, 2022.

Training and clinical testing of artificial intelligence derived right atrial cardiovascular magnetic resonance measurements.

BACKGROUND: Right atrial (RA) area predicts mortality in patients with pulmonary hypertension, and is recommended by the European Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines. The advent of deep learning may allow more reliable measurement of RA areas to improve clinical assessments. The aim of this study was to automate cardiovascular magnetic resonance (CMR) RA area measurements and evaluate the clinical utility by assessing repeatability, correlation with invasive haemodynamics and prognostic value. METHODS: A deep learning RA area CMR contouring model was trained in a multicentre cohort of 365 patients with pulmonary hypertension, left ventricular pathology and healthy subjects. Inter-study repeatability (intraclass correlation coefficient (ICC)) and agreement of contours (DICE similarity coefficient (DSC)) were assessed in a prospective cohort (n = 36). Clinical testing and mortality prediction was performed in n = 400 patients that were not used in the training nor prospective cohort, and the correlation of automatic and manual RA measurements with invasive haemodynamics assessed in n = 212/400. Radiologist quality control (QC) was performed in the ASPIRE registry, n = 3795 patients. The primary QC observer evaluated all the segmentations and recorded them as satisfactory, suboptimal or failure. A second QC observer analysed a random subcohort to assess QC agreement (n = 1018). RESULTS: All deep learning RA measurements showed higher interstudy repeatability (ICC 0.91 to 0.95) compared to manual RA measurements (1st observer ICC 0.82 to 0.88, 2nd observer ICC 0.88 to 0.91). DSC showed high agreement comparing automatic artificial intelligence and manual CMR readers. Maximal RA area mean and standard deviation (SD) DSC metric for observer 1 vs observer 2, automatic measurements vs observer 1 and automatic measurements vs observer 2 is 92.4 ± 3.5 cm2, 91.2 ± 4.5 cm2 and 93.2 ± 3.2 cm2, respectively. Minimal RA area mean and SD DSC metric for observer 1 vs observer 2, automatic measurements vs observer 1 and automatic measurements vs observer 2 was 89.8 ± 3.9 cm2, 87.0 ± 5.8 cm2 and 91.8 ± 4.8 cm2. Automatic RA area measurements all showed moderate correlation with invasive parameters (r = 0.45 to 0.66), manual (r = 0.36 to 0.57). Maximal RA area could accurately predict elevated mean RA pressure low and high-risk thresholds (area under the receiver operating characteristic curve artificial intelligence = 0.82/0.87 vs manual = 0.78/0.83), and predicted mortality similar to manual measurements, both p < 0.01. In the QC evaluation, artificial intelligence segmentations were suboptimal at 108/3795 and a low failure rate of 16/3795. In a subcohort (n = 1018), agreement by two QC observers was excellent, kappa 0.84. CONCLUSION: Automatic artificial intelligence CMR derived RA size and function are accurate, have excellent repeatability, moderate associations with invasive haemodynamics and predict mortality.

Diagnostic accuracy of CT pulmonary angiography in suspected pulmonary hypertension.

OBJECTIVES: Computed tomography (CT) pulmonary angiography is widely used in patients with suspected pulmonary hypertension (PH). However, the diagnostic and prognostic significance remains unclear. The aim of this study was to (a) build a diagnostic CT model and (b) test its prognostic significance. METHODS: Consecutive patients with suspected PH undergoing routine CT pulmonary angiography and right heart catheterisation (RHC) were identified. Axial and reconstructed images were used to derive CT metrics. Multivariate regression analysis was performed in the derivation cohort to identify a diagnostic CT model to predict mPAP ≥ 25 mmHg (the existing ESC guideline definition of PH) and > 20 mmHg (the new threshold proposed at the 6th World Symposium on PH). In the validation cohort, sensitivity, specificity and compromise CT thresholds were identified with receiver operating characteristic (ROC) analysis. The prognostic value of the CT model was assessed using Kaplan-Meier analysis. RESULTS: Between 2012 and 2016, 491 patients were identified. In the derivation cohort (n = 247), a CT model was identified including pulmonary artery diameter, right ventricular outflow tract thickness, septal angle and left ventricular area. In the validation cohort (n = 244), the model was diagnostic, with an area under the ROC curve of 0.94/0.91 for mPAP ≥ 25/> 20 mmHg respectively. In the validation cohort, 93 patients died; mean follow-up was 42 months. The diagnostic thresholds for the CT model were prognostic, log rank, all p < 0.01. DISCUSSION: In suspected PH, a diagnostic CT model had diagnostic and prognostic utility. KEY POINTS: • Diagnostic CT models have high diagnostic accuracy in a tertiary referral population of with suspected PH. • Diagnostic CT models stratify patients by mortality in suspected PH.

From coeliac disease to noncoeliac gluten sensitivity; should everyone be gluten free?

PURPOSE OF REVIEW: Gluten-free diets (GFDs) have seen a disproportional rise in use and popularity relative to the prevalence of established gluten-related disorders such as coeliac disease or immunoglobulin E wheat allergy. This entity has been termed noncoeliac gluten sensitivity (NCGS). This review aims to provide a current perspective on the emerging evidence for and against NCGS, along with the associated need for a GFD. RECENT FINDINGS: NCGS and the benefits of a GFD are reported amongst patients with irritable bowel syndrome, inflammatory bowel disease, and nonintestinal disorders such as neuropsychiatric diseases and fibromyalgia. However, no reliable biomarkers currently exist to diagnose NCGS and hence confirmatory testing can only be performed using double-blind placebo-controlled gluten-based challenges. Unfortunately, such tests are not available in routine clinical practice. Furthermore, recent novel studies have highlighted the role of other gluten-based components in contributing to the symptoms of self-reported NCGS. These include fermentable oligo, di, mono-saccharides and polyols, amylase trypsin inhibitors, and wheat germ agglutinins. Therefore, NCGS is now seen as a spectrum encompassing several biological responses and terms such as 'noncoeliac wheat sensitivity' have been suggested as a wider label to define the condition. SUMMARY: Despite the rising use of a GFD further studies are required to clearly establish the extent and exclusivity of gluten in NCGS.

Advancements in cardiac structures segmentation: a comprehensive systematic review of deep learning in CT imaging.

Background: Segmentation of cardiac structures is an important step in evaluation of the heart on imaging. There has been growing interest in how artificial intelligence (AI) methods-particularly deep learning (DL)-can be used to automate this process. Existing AI approaches to cardiac segmentation have mostly focused on cardiac MRI. This systematic review aimed to appraise the performance and quality of supervised DL tools for the segmentation of cardiac structures on CT. Methods: Embase and Medline databases were searched to identify related studies from January 1, 2013 to December 4, 2023. Original research studies published in peer-reviewed journals after January 1, 2013 were eligible for inclusion if they presented supervised DL-based tools for the segmentation of cardiac structures and non-coronary great vessels on CT. The data extracted from eligible studies included information about cardiac structure(s) being segmented, study location, DL architectures and reported performance metrics such as the Dice similarity coefficient (DSC). The quality of the included studies was assessed using the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Results: 18 studies published after 2020 were included. The DSC scores median achieved for the most commonly segmented structures were left atrium (0.88, IQR 0.83-0.91), left ventricle (0.91, IQR 0.89-0.94), left ventricle myocardium (0.83, IQR 0.82-0.92), right atrium (0.88, IQR 0.83-0.90), right ventricle (0.91, IQR 0.85-0.92), and pulmonary artery (0.92, IQR 0.87-0.93). Compliance of studies with CLAIM was variable. In particular, only 58% of studies showed compliance with dataset description criteria and most of the studies did not test or validate their models on external data (81%). Conclusion: Supervised DL has been applied to the segmentation of various cardiac structures on CT. Most showed similar performance as measured by DSC values. Existing studies have been limited by the size and nature of the training datasets, inconsistent descriptions of ground truth annotations and lack of testing in external data or clinical settings. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], PROSPERO [CRD42023431113].

A systematic review of artificial intelligence tools for chronic pulmonary embolism on CT pulmonary angiography.

Background: Chronic pulmonary embolism (PE) may result in pulmonary hypertension (CTEPH). Automated CT pulmonary angiography (CTPA) interpretation using artificial intelligence (AI) tools has the potential for improving diagnostic accuracy, reducing delays to diagnosis and yielding novel information of clinical value in CTEPH. This systematic review aimed to identify and appraise existing studies presenting AI tools for CTPA in the context of chronic PE and CTEPH. Methods: MEDLINE and EMBASE databases were searched on 11 September 2023. Journal publications presenting AI tools for CTPA in patients with chronic PE or CTEPH were eligible for inclusion. Information about model design, training and testing was extracted. Study quality was assessed using compliance with the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Results: Five studies were eligible for inclusion, all of which presented deep learning AI models to evaluate PE. First study evaluated the lung parenchymal changes in chronic PE and two studies used an AI model to classify PE, with none directly assessing the pulmonary arteries. In addition, a separate study developed a CNN tool to distinguish chronic PE using 2D maximum intensity projection reconstructions. While another study assessed a novel automated approach to quantify hypoperfusion to help in the severity assessment of CTEPH. While descriptions of model design and training were reliable, descriptions of the datasets used in training and testing were more inconsistent. Conclusion: In contrast to AI tools for evaluation of acute PE, there has been limited investigation of AI-based approaches to characterising chronic PE and CTEPH on CTPA. Existing studies are limited by inconsistent reporting of the data used to train and test their models. This systematic review highlights an area of potential expansion for the field of AI in medical image interpretation.There is limited knowledge of A systematic review of artificial intelligence tools for chronic pulmonary embolism in CT. This systematic review provides an assessment on research that examined deep learning algorithms in detecting CTEPH on CTPA images, the number of studies assessing the utility of deep learning on CTPA in CTEPH was unclear and should be highlighted.

Clinical assessment of an AI tool for measuring biventricular parameters on cardiac MR.

Introduction: Cardiac magnetic resonance (CMR) is of diagnostic and prognostic value in a range of cardiopulmonary conditions. Current methods for evaluating CMR studies are laborious and time-consuming, contributing to delays for patients. As the demand for CMR increases, there is a growing need to automate this process. The application of artificial intelligence (AI) to CMR is promising, but the evaluation of these tools in clinical practice has been limited. This study assessed the clinical viability of an automatic tool for measuring cardiac volumes on CMR. Methods: Consecutive patients who underwent CMR for any indication between January 2022 and October 2022 at a single tertiary centre were included prospectively. For each case, short-axis CMR images were segmented by the AI tool and manually to yield volume, mass and ejection fraction measurements for both ventricles. Automated and manual measurements were compared for agreement and the quality of the automated contours was assessed visually by cardiac radiologists. Results: 462 CMR studies were included. No statistically significant difference was demonstrated between any automated and manual measurements (p > 0.05; independent T-test). Intraclass correlation coefficient and Bland-Altman analysis showed excellent agreement across all metrics (ICC > 0.85). The automated contours were evaluated visually in 251 cases, with agreement or minor disagreement in 229 cases (91.2%) and failed segmentation in only a single case (0.4%). The AI tool was able to provide automated contours in under 90 s. Conclusions: Automated segmentation of both ventricles on CMR by an automatic tool shows excellent agreement with manual segmentation performed by CMR experts in a retrospective real-world clinical cohort. Implementation of the tool could improve the efficiency of CMR reporting and reduce delays between imaging and diagnosis.

A transparent artificial intelligence framework to assess lung disease in pulmonary hypertension.

Recent studies have recognized the importance of characterizing the extent of lung disease in pulmonary hypertension patients by using Computed Tomography. The trustworthiness of an artificial intelligence system is linked with the depth of the evaluation in functional, operational, usability, safety and validation dimensions. The safety and validation of an artificial tool is linked to the uncertainty estimation of the model's prediction. On the other hand, the functionality, operation and usability can be achieved by explainable deep learning approaches which can verify the learning patterns and use of the network from a generalized point of view. We developed an artificial intelligence framework to map the 3D anatomical models of patients with lung disease in pulmonary hypertension. To verify the trustworthiness of the framework we studied the uncertainty estimation of the network's prediction, and we explained the learning patterns of the network. Therefore, a new generalized technique combining local explainable and interpretable dimensionality reduction approaches (PCA-GradCam, PCA-Shape) was developed. Our open-source software framework was evaluated in unbiased validation datasets achieving accurate, robust and generalized results.

Non-invasive detection of severe PH in lung disease using magnetic resonance imaging.

Introduction: Severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg) in chronic lung disease (PH-CLD) is associated with high mortality and morbidity. Data suggesting potential response to vasodilator therapy in patients with PH-CLD is emerging. The current diagnostic strategy utilises transthoracic Echocardiography (TTE), which can be technically challenging in some patients with advanced CLD. The aim of this study was to evaluate the diagnostic role of MRI models to diagnose severe PH in CLD. Methods: 167 patients with CLD referred for suspected PH who underwent baseline cardiac MRI, pulmonary function tests and right heart catheterisation were identified. In a derivation cohort (n = 67) a bi-logistic regression model was developed to identify severe PH and compared to a previously published multiparameter model (Whitfield model), which is based on interventricular septal angle, ventricular mass index and diastolic pulmonary artery area. The model was evaluated in a test cohort. Results: The CLD-PH MRI model [= (-13.104) + (13.059 * VMI)-(0.237 * PA RAC) + (0.083 * Systolic Septal Angle)], had high accuracy in the test cohort (area under the ROC curve (0.91) (p < 0.0001), sensitivity 92.3%, specificity 70.2%, PPV 77.4%, and NPV 89.2%. The Whitfield model also had high accuracy in the test cohort (area under the ROC curve (0.92) (p < 0.0001), sensitivity 80.8%, specificity 87.2%, PPV 87.5%, and NPV 80.4%. Conclusion: The CLD-PH MRI model and Whitfield model have high accuracy to detect severe PH in CLD, and have strong prognostic value.

Evaluating the performance of artificial intelligence software for lung nodule detection on chest radiographs in a retrospective real-world UK population.

OBJECTIVES: Early identification of lung cancer on chest radiographs improves patient outcomes. Artificial intelligence (AI) tools may increase diagnostic accuracy and streamline this pathway. This study evaluated the performance of commercially available AI-based software trained to identify cancerous lung nodules on chest radiographs. DESIGN: This retrospective study included primary care chest radiographs acquired in a UK centre. The software evaluated each radiograph independently and outputs were compared with two reference standards: (1) the radiologist report and (2) the diagnosis of cancer by multidisciplinary team decision. Failure analysis was performed by interrogating the software marker locations on radiographs. PARTICIPANTS: 5722 consecutive chest radiographs were included from 5592 patients (median age 59 years, 53.8% women, 1.6% prevalence of cancer). RESULTS: Compared with radiologist reports for nodule detection, the software demonstrated sensitivity 54.5% (95% CI 44.2% to 64.4%), specificity 83.2% (82.2% to 84.1%), positive predictive value (PPV) 5.5% (4.6% to 6.6%) and negative predictive value (NPV) 99.0% (98.8% to 99.2%). Compared with cancer diagnosis, the software demonstrated sensitivity 60.9% (50.1% to 70.9%), specificity 83.3% (82.3% to 84.2%), PPV 5.6% (4.8% to 6.6%) and NPV 99.2% (99.0% to 99.4%). Normal or variant anatomy was misidentified as an abnormality in 69.9% of the 943 false positive cases. CONCLUSIONS: The software demonstrated considerable underperformance in this real-world patient cohort. Failure analysis suggested a lack of generalisability in the training and testing datasets as a potential factor. The low PPV carries the risk of over-investigation and limits the translation of the software to clinical practice. Our findings highlight the importance of training and testing software in representative datasets, with broader implications for the implementation of AI tools in imaging.

The reproducibility of manual RV/LV ratio measurement on CT pulmonary angiography.

Objectives: Right ventricular (RV) dysfunction carries elevated risk in acute pulmonary embolism (PE). An increased ratio between the size of the right and left ventricles (RV/LV ratio) is a biomarker of RV dysfunction. This study evaluated the reproducibility of RV/LV ratio measurement on CT pulmonary angiography (CTPA). Methods: 20 inpatient CTPA scans performed to assess for acute PE were retrospectively identified from a tertiary UK centre. Each scan was evaluated by 14 radiologists who provided a qualitative overall opinion on the presence of RV dysfunction and measured the RV/LV ratio. Using a threshold of 1.0, the RV/LV ratio measurements were classified as positive (≥1.0) or negative (<1.0) for RV dysfunction. Interobserver agreement was quantified using the Fleiss κ and intraclass correlation coefficient (ICC). Results: Qualitative opinion of RV dysfunction showed weak agreement (κ = 0.42, 95% CI 0.37-0.46). The mean RV/LV ratio measurement for all cases was 1.28 ± 0.68 with significant variation between reporters (p < 0.001). Although agreement for RV/LV measurement was good (ICC = 0.83, 95% CI 0.73-0.91), categorisation of RV dysfunction according to RV/LV ratio measurements showed weak agreement (κ = 0.46, 95% CI 0.41-0.50). Conclusion: Both qualitative opinion and quantitative manual RV/LV ratio measurement show poor agreement for identifying RV dysfunction on CTPA. Advances in knowledge: Caution should be exerted if using manual RV/LV ratio measurements to inform clinical risk stratification and management decisions.

Computed tomography lung parenchymal descriptions in routine radiological reporting have diagnostic and prognostic utility in patients with idiopathic pulmonary arterial hypertension and pulmonary hypertension associated with lung disease.

BACKGROUND: Patients with pulmonary hypertension (PH) and lung disease may pose a diagnostic dilemma between idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-CLD). The prognostic impact of common computed tomography (CT) parenchymal features is unknown. METHODS: 660 IPAH and PH-CLD patients assessed between 2001 and 2019 were included. Reports for all CT scans 1 year prior to diagnosis were analysed for common lung parenchymal patterns. Cox regression and Kaplan-Meier analysis were performed. RESULTS: At univariate analysis of the whole cohort, centrilobular ground-glass (CGG) changes (hazard ratio, HR 0.29) and ground-glass opacification (HR 0.53) predicted improved survival, while honeycombing (HR 2.79), emphysema (HR 2.09) and fibrosis (HR 2.38) predicted worse survival (all p<0.001). Fibrosis was an independent predictor after adjusting for baseline demographics, PH severity and diffusing capacity of the lung for carbon monoxide (HR 1.37, p<0.05). Patients with a clinical diagnosis of IPAH who had an absence of reported parenchymal lung disease (IPAH-noLD) demonstrated superior survival to patients diagnosed with either IPAH who had coexistent CT lung disease or PH-CLD (2-year survival of 85%, 60% and 46%, respectively, p<0.05). CGG changes were present in 23.3% of IPAH-noLD and 5.8% of PH-CLD patients. There was no significant difference in survival between IPAH-noLD patients with or without CGG changes. PH-CLD patients with fibrosis had worse survival than those with emphysema. INTERPRETATION: Routine clinical reports of CT lung parenchymal disease identify groups of patients with IPAH and PH-CLD with significantly different prognoses. Isolated CGG changes are not uncommon in IPAH but are not associated with worse survival.

Semi-automatic thresholding of RV trabeculation improves repeatability and diagnostic value in suspected pulmonary hypertension.

Objectives: Right ventricle (RV) mass is an imaging biomarker of mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR). Some methods of RV mass measurement on cardiac MRI (CMR) exclude RV trabeculation. This study assessed the reproducibility of measurement methods and evaluated whether the inclusion of trabeculation in RV mass affects diagnostic accuracy in suspected pulmonary hypertension (PH). Materials and methods: Two populations were enrolled prospectively. (i) A total of 144 patients with suspected PH who underwent CMR followed by right heart catheterization (RHC). Total RV mass (including trabeculation) and compacted RV mass (excluding trabeculation) were measured on the end-diastolic CMR images using both semi-automated pixel-intensity-based thresholding and manual contouring techniques. (ii) A total of 15 healthy volunteers and 15 patients with known PH. Interobserver agreement and scan-scan reproducibility were evaluated for RV mass measurements using the semi-automated thresholding and manual contouring techniques. Results: Total RV mass correlated more strongly with MPAP and PVR (r = 0.59 and 0.63) than compacted RV mass (r = 0.25 and 0.38). Using a diagnostic threshold of MPAP ≥ 25 mmHg, ROC analysis showed better performance for total RV mass (AUC 0.77 and 0.81) compared to compacted RV mass (AUC 0.61 and 0.66) when both parameters were indexed for LV mass. Semi-automated thresholding was twice as fast as manual contouring (p < 0.001). Conclusion: Using a semi-automated thresholding technique, inclusion of trabecular mass and indexing RV mass for LV mass (ventricular mass index), improves the diagnostic accuracy of CMR measurements in suspected PH.

Severe pulmonary hypertension associated with lung disease is characterised by a loss of small pulmonary vessels on quantitative computed tomography.

Background: Pulmonary hypertension (PH) in patients with chronic lung disease (CLD) predicts reduced functional status, clinical worsening and increased mortality, with patients with severe PH-CLD (≥35 mmHg) having a significantly worse prognosis than mild to moderate PH-CLD (21-34 mmHg). The aim of this cross-sectional study was to assess the association between computed tomography (CT)-derived quantitative pulmonary vessel volume, PH severity and disease aetiology in CLD. Methods: Treatment-naïve patients with CLD who underwent CT pulmonary angiography, lung function testing and right heart catheterisation were identified from the ASPIRE registry between October 2012 and July 2018. Quantitative assessments of total pulmonary vessel and small pulmonary vessel volume were performed. Results: 90 patients had PH-CLD including 44 associated with COPD/emphysema and 46 with interstitial lung disease (ILD). Patients with severe PH-CLD (n=40) had lower small pulmonary vessel volume compared to patients with mild to moderate PH-CLD (n=50). Patients with PH-ILD had significantly reduced small pulmonary blood vessel volume, compared to PH-COPD/emphysema. Higher mortality was identified in patients with lower small pulmonary vessel volume. Conclusion: Patients with severe PH-CLD, regardless of aetiology, have lower small pulmonary vessel volume compared to patients with mild-moderate PH-CLD, and this is associated with a higher mortality. Whether pulmonary vessel changes quantified by CT are a marker of remodelling of the distal pulmonary vasculature requires further study.

Fully automatic cardiac four chamber and great vessel segmentation on CT pulmonary angiography using deep learning.

Introduction: Computed tomography pulmonary angiography (CTPA) is an essential test in the work-up of suspected pulmonary vascular disease including pulmonary hypertension and pulmonary embolism. Cardiac and great vessel assessments on CTPA are based on visual assessment and manual measurements which are known to have poor reproducibility. The primary aim of this study was to develop an automated whole heart segmentation (four chamber and great vessels) model for CTPA. Methods: A nine structure semantic segmentation model of the heart and great vessels was developed using 200 patients (80/20/100 training/validation/internal testing) with testing in 20 external patients. Ground truth segmentations were performed by consultant cardiothoracic radiologists. Failure analysis was conducted in 1,333 patients with mixed pulmonary vascular disease. Segmentation was achieved using deep learning via a convolutional neural network. Volumetric imaging biomarkers were correlated with invasive haemodynamics in the test cohort. Results: Dice similarity coefficients (DSC) for segmented structures were in the range 0.58-0.93 for both the internal and external test cohorts. The left and right ventricle myocardium segmentations had lower DSC of 0.83 and 0.58 respectively while all other structures had DSC >0.89 in the internal test cohort and >0.87 in the external test cohort. Interobserver comparison found that the left and right ventricle myocardium segmentations showed the most variation between observers: mean DSC (range) of 0.795 (0.785-0.801) and 0.520 (0.482-0.542) respectively. Right ventricle myocardial volume had strong correlation with mean pulmonary artery pressure (Spearman's correlation coefficient = 0.7). The volume of segmented cardiac structures by deep learning had higher or equivalent correlation with invasive haemodynamics than by manual segmentations. The model demonstrated good generalisability to different vendors and hospitals with similar performance in the external test cohort. The failure rates in mixed pulmonary vascular disease were low (<3.9%) indicating good generalisability of the model to different diseases. Conclusion: Fully automated segmentation of the four cardiac chambers and great vessels has been achieved in CTPA with high accuracy and low rates of failure. DL volumetric biomarkers can potentially improve CTPA cardiac assessment and invasive haemodynamic prediction.