Silence of the lungs: comparing measures of slow and non-communicating lung units from pulmonary function tests with computed tomography.

Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of under-ventilated lung units (UVLU). Additionally, we used 2 previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P<0.0001) and sensitivity (79%). Bland-Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (-249ml [95%CI -10796; 580ml] and -203ml [95%CI -997;591ml], respectively). Parameters from both spirometry and body plethysmography were sub-optimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared to the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF.

Idiopathic pulmonary haemosiderosis.

In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent diagnosis of idiopathic pulmonary haemosiderosis (IPH). This is a slowly progressive and life-threatening disorder and is of paramount importance that this is identified early and treated appropriately. His first chest CT was not typical for IPH, and this appearance should be highlighted (small cystic changes alone initially). He also had focal disease, which allowed us to make the diagnosis using CT-guided biopsy. During his treatment, he experienced an uncommon side effect to a commonly prescribed medication (bradycardia with methylprednisolone). Since starting azathioprine as a steroid-sparing agent, he has been doing well.

Left Atrial Appendage Pseudothrombus Is Associated With Stroke History in Patients With Atrial Fibrillation Undergoing Cardiac Computed Tomography.

BACKGROUND: In nonvalvular atrial fibrillation (NVAF), the left atrial appendage (LAA) is the source of thrombus in up to 90% of patients. LAA pseudothrombus (LAAPT), defined as a filling defect on the initial but not the 60-second delayed acquisition on cardiovascular computed tomography scan (CCT), is a recognized phenomenon in NVAF, with unknown clinical relevance. We aimed to determine the relationship between LAAPT and history of stroke in patients with NVAF. METHODS AND RESULTS: The study included 213 consecutive patients with NVAF undergoing CCT who were assessed for LAAPT. LA and LAA dimensions and LAA morphology correlated with clinical demographics including cardiovascular risk factors, history of stroke, thromboembolic stroke, and transient ischemic attack. Mean age (±SD) was 65.1±10.5 years (range 31-89) and 150 of 213 (70.4%) were men. LAAPT was present in 59 of 213 (27.7%) patients. Greater mean LAA ostium area (5.7 versus 4.5, P<0.001), greater mean LAA ostium area:curved length (0.11 versus 0.08, P<0.001), increased LAA volume (14.0 versus 10.2, P<0.001), and lower mean LAA tortuosity index (1.17 versus 1.38, P<0.001) were all associated with the presence of LAAPT. On multivariable analysis, LAAPT on CCT (odds ratio [OR], 3.20 [95% CI, 1.40-7.20]; P<0.006) and higher CHA2DS2-VASc score (OR, 1.65 [95% CI, 1.16-2.35]; P=0.01) were associated with all strokes, with LAAPT remaining a statistically significant risk factor even after adjustment for CHA2DS2-VASc score. CONCLUSIONS: LAAPT on CCT is common in patients with NVAF. It has a strong positive association with stroke prevalence, even after adjustment for CHA2DS2-VASc score. LAAPT on CCT may potentially allow further stratification for stroke risk, additive to the CHA2DS2-VASc score.

Discrepancy Between Achieved and Vendor-Predicted Ablation Zones in the Lung: Contributing Factors.

PURPOSE: Several factors are known to affect lung ablation zones. Questions remain as to why there are discrepancies between achieved and vendor-predicted ablation zones and what contributing factors can be modified to balance therapeutic effects with avoidance of complications. This retrospective study of lung tumour microwave ablation analyses day 1 post-treatment CT to assess the effects of lesion-specific and operator-dependent factors on ablation zones. METHODS AND MATERIALS: Consecutive patients treated at a tertiary centre from 2018 to 2021 were included. All ablations were performed using a single microwave ablation device under lung isolation. The lung tumours were categorised as primary or secondary, and their "resistance" to ablation was graded according to their locations. Intraprocedural pulmonary inflation was assessed as equal to or less than the contralateral non-isolated lung. Ablation energy was categorised as high, medium, or low. Ablation zone dimensions were measured on day 1 CT and compared to vendor reference charts. Ablations with multiple needle positions or indeterminate boundaries were excluded. RESULTS: A total of 47 lesions in 31 patients were analysed. Achieved long axes are longer than predicted by 5 mm or 14% (p < 0.01) without overall short axis discrepancy. Secondary tumours (p = 0.020), low-resistance location (p < 0.01), good lung inflation (p < 0.01), low (p = 0.003) and medium (p = 0.038) total energy produce lengthened long axes by 4-6 mm or 10-19%. High total energy results in shorter than predicated short axes by 6 mm or 18% (p = 0.010). CONCLUSION: We identified several factors affecting ablation zone dimensions which may have implications for ablation planning and the avoidance of complications.

Radiomics-based decision support tool assists radiologists in small lung nodule classification and improves lung cancer early diagnosis.

BACKGROUND: Methods to improve stratification of small (≤15 mm) lung nodules are needed. We aimed to develop a radiomics model to assist lung cancer diagnosis. METHODS: Patients were retrospectively identified using health records from January 2007 to December 2018. The external test set was obtained from the national LIBRA study and a prospective Lung Cancer Screening programme. Radiomics features were extracted from multi-region CT segmentations using TexLab2.0. LASSO regression generated the 5-feature small nodule radiomics-predictive-vector (SN-RPV). K-means clustering was used to split patients into risk groups according to SN-RPV. Model performance was compared to 6 thoracic radiologists. SN-RPV and radiologist risk groups were combined to generate "Safety-Net" and "Early Diagnosis" decision-support tools. RESULTS: In total, 810 patients with 990 nodules were included. The AUC for malignancy prediction was 0.85 (95% CI: 0.82-0.87), 0.78 (95% CI: 0.70-0.85) and 0.78 (95% CI: 0.59-0.92) for the training, test and external test datasets, respectively. The test set accuracy was 73% (95% CI: 65-81%) and resulted in 66.67% improvements in potentially missed [8/12] or delayed [6/9] cancers, compared to the radiologist with performance closest to the mean of six readers. CONCLUSIONS: SN-RPV may provide net-benefit in terms of earlier cancer diagnosis.

Pulmonary hypertension: the hallmark of acute COVID-19 microvascular angiopathy?

In situ pulmonary arterial thrombosis in COVID-19 is not visible on CTPA. However, the presence of CT-measured right heart and pulmonary artery dilatation in COVID-19 is likely attributable to this process and may be a possible surrogate for its detection. https://bit.ly/3g7z5TV.

Dual-energy Computed Tomographic Pulmonary Angiography Accurately Estimates Lobar Perfusion Before Lung Volume Reduction for Severe Emphysema.

PURPOSE: To assess if dual-energy computed tomographic pulmonary angiography (DECTPA) derived lobar iodine quantification can provide an accurate estimate of lobar perfusion in patients with severe emphysema, and offer an adjunct to single-photon emission CT perfusion scintigraphy (SPECT-PS) in assessing suitability for lung volume reduction (LVR). MATERIALS AND METHODS: Patients with severe emphysema (forced expiratory volume in 1 s <49% predicted) undergoing evaluation for LVR between May 2018 and April 2020 imaged with both SPECT-PS and DECTPA were included in this retrospective study. DECTPA perfused blood volume maps were automatically segmented and lobar iodine mass was estimated and compared with lobar technetium (Tc99m) distribution acquired with SPECT-PS. Pearson correlation and Bland-Altman analysis were used for intermodality comparison between DECTPA and SPECT-PS. Univariate and adjusted multivariate linear regression were modelled to ascertain the effect sizes of possible confounders of disease severity, sex, age, and body mass index on the relationship between lobar iodine and Tc99m values. Effective radiation dose and adverse reactions were recorded. RESULTS: In all, 123 patients (64.5±8.8 y, 71 men; mean predicted forced expiratory volume in 1 s 32.1 ±12.7%,) were eligible for inclusion. There was a linear relationship between lobar perfusion values acquired using DECTPA and SPECT-PS with statistical significance ( P <0.001). Lobar relative perfusion values acquired using DECTPA and SPECT-PS had a consistent relationship both by linear regression and Bland-Altman analysis (mean bias, -0.01, mean r2 0.64; P <0.0001). Individual lobar comparisons demonstrated moderate correlation ( r =0.79, 0.78, 0.84, 0.78, 0.8 for the right upper, middle, lower, left upper, and lower lobes, respectively, P <0.0001). The relationship between lobar iodine and Tc99m values was not significantly altered after controlling for confounders including symptom and disease severity, age, sex, and body mass index. CONCLUSIONS: DECTPA provides an accurate estimation of lobar perfusion, showing good agreement with SPECT-PS and could potentially streamline preoperative assessment for LVR.

COVID-protected pathways for image-guided lung cancer intervention during the COVID-19 pandemic: A cohort study.

OBJECTIVES: To compare the experience of COVID-protected and mixed cohort pathways in COVID-19 transmission at a tertiary referral hospital for elective CT-guided lung biopsy and ablation during the COVID-19 pandemic. METHODS: From September 2020 to August 2021, patients admitted for elective thoracic intervention were treated at a tertiary hospital (Site 1). Site 1 received patients for extracorporeal membrane oxygenation (ECMO) and invasive ventilation in the treatment of COVID-19. Shared imaging, theater, and hallway facilities were used.From April 2020 to August 2020, patients admitted for elective thoracic intervention were treated at a COVID-protected hospital (Site 2). No patients with suspected or confirmed COVID-19 were treated at Site 2.Patients were surveyed for clinical and laboratory signs of COVID-19 infection up to 30 days post-procedure. RESULTS: At Sites 1 and 2, patients (2.4%) were tested positive for COVID-19 at 10 and 14 days post-procedure.At Site 2, there were no COVID-19 positive cases within 30 days of undergoing elective thoracic intervention. CONCLUSION: A mixed-site method for infection control could represent a pragmatic approach to the management of elective procedures during the COVID-19 pandemic or for similar illnesses. ADVANCES IN KNOWLEDGE: Mixed-cohort infection control is possible in the prevention of nosocomial COVID-19 infection.

Persistent isolated impairment of gas transfer following COVID-19 pneumonitis relates to perfusion defects on dual-energy computed tomography.

A novel iodine perfusion score correlates with breathlessness and D LCO in patients post-#COVID19 without obvious interstitial disease on CT, suggesting that lung perfusion assessment may be useful in patients without another cause of dyspnoea https://bit.ly/3U6E2f5.

Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression.

We developed a novel lentiviral vector, pseudotyped with the F and HN proteins from Sendai virus (rSIV.F/HN), that produces long-lasting, high-efficiency transduction of the respiratory epithelium. Here we addressed whether this platform technology can secrete sufficient levels of a therapeutic protein into the lungs to ameliorate a fatal pulmonary disease as an example of its translational capability. Pulmonary alveolar proteinosis (PAP) results from alveolar granulocyte-macrophage colony-stimulating factor (GM-CSF) insufficiency, resulting in abnormal surfactant homeostasis and consequent ventilatory problems. Lungs of GM-CSF knockout mice were transduced with a single dose of rSIV.F/HN-expressing murine GM-CSF (mGM-CSF; 1e5-92e7 transduction units [TU]/mouse); mGM-CSF expression was dose related and persisted for at least 11 months. PAP disease biomarkers were rapidly and persistently corrected, but we noted a narrow toxicity/efficacy window. rSIV.F/HN may be a useful platform technology to deliver therapeutic proteins for lung diseases requiring long-lasting and stable expression of secreted proteins.

Extracorporeal membrane oxygenation (ECMO): Radiographic appearances, complications and imaging artefacts for radiologists.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary support primarily used in cardiothoracic and intensive care unit (ICU) settings. The purpose of this review is to familiarise radiologists with the imaging features of ECMO devices, their associated complications and appropriate imaging protocols for contrast-enhanced CT imaging of ECMO patients. This paper will provide a brief introduction to ECMO and the imaging modalities utilised in ECMO patients, followed by a description of the types of ECMO available and cannula positioning. Indications and contraindications for ECMO will be outlined followed by a description of the complications associated with ECMO, which radiologists should recognise. Finally, the imaging protocol and interpretation of contrast-enhanced CT imaging in ECMO patients will be discussed. In the current clinical climate with millions of COVID-19 cases around the world and tens of thousands of critically ill patients, many requiring cardiopulmonary support in intensive care units, the use of ECMO in adults has increased, and thus so has the volume of imaging. Radiologists need to be familiar with the types of ECMO available, the correct positioning of the catheters depending on the type of ECMO being utilised, and the associated complications and imaging artefacts.

Implications of incidental findings from lung screening for primary care: data from a UK pilot.

Regional lung cancer screening (LCS) is underway in England, involving a "lung health check" (LHC) and low-dose CT scan for those at high risk of cancer. Incidental findings from LHCs or CTs are usually referred to primary care. We describe the proportion of participants referred from the West London LCS pilot to primary care, the indications for referral, the number of general practitioner (GP) attendances and consequent changes to patient management, and provide an estimated cost-burden analysis for primary care. A small proportion (163/1542, 10.6%) of LHC attendees were referred to primary care, primarily for suspected undiagnosed chronic obstructive pulmonary disease (55/163, 33.7%) or for QRISK® (63/163, 38.7%) assessment. Ninety one of 159 (57.2%) participants consenting to follow-up attended GP appointments; costs incurred by primary care were estimated at £5.69/LHC participant. Patient management changes occurred in only 36/159 (22.6%) referred participants. LHCs result in a small increase to primary care workload provided a strict referral protocol is adhered to. Changes to patient management arising from incidental findings referrals are infrequent.

Prevalence of Thrombotic Complications in ICU-Treated Patients With Coronavirus Disease 2019 Detected With Systematic CT Scanning.

OBJECTIVES: Severe coronavirus disease 2019 is associated with an extensive pneumonitis and frequent coagulopathy. We sought the true prevalence of thrombotic complications in critically ill patients with severe coronavirus disease 2019 on the ICU, with or without extracorporeal membrane oxygenation. DESIGN: We undertook a single-center, retrospective analysis of 72 critically ill patients with coronavirus disease 2019-associated acute respiratory distress syndrome admitted to ICU. CT angiography of the thorax, abdomen, and pelvis were performed at admission as per routine institution protocols, with further imaging as clinically indicated. The prevalence of thrombotic complications and the relationship with coagulation parameters, other biomarkers, and survival were evaluated. SETTING: Coronavirus disease 2019 ICUs at a specialist cardiorespiratory center. PATIENTS: Seventy-two consecutive patients with coronavirus disease 2019 admitted to ICU during the study period (March 19, 2020, to June 23, 2020). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All but one patient received thromboprophylaxis or therapeutic anticoagulation. Among 72 patients (male:female = 74%; mean age: 52 ± 10; 35 on extracorporeal membrane oxygenation), there were 54 thrombotic complications in 42 patients (58%), comprising 34 pulmonary arterial (47%), 15 peripheral venous (21%), and five (7%) systemic arterial thromboses/end-organ embolic complications. In those with pulmonary arterial thromboses, 93% were identified incidentally on first screening CT with only 7% suspected clinically. Biomarkers of coagulation (e.g., d-dimer, fibrinogen level, and activated partial thromboplastin time) or inflammation (WBC count, C-reactive protein) did not discriminate between patients with or without thrombotic complications. Fifty-one patients (76%) survived to discharge; 17 (24%) patients died. Mortality was significantly greater in patients with detectable thrombus (33% vs 10%; p = 0.022). CONCLUSIONS: There is a high prevalence of thrombotic complications, mainly pulmonary, among coronavirus disease 2019 patients admitted to ICU, despite anticoagulation. Detection of thrombus was usually incidental, not predicted by coagulation or inflammatory biomarkers, and associated with increased risk of death. Systematic CT imaging at admission should be considered in all coronavirus disease 2019 patients requiring ICU.

Baseline Results of the West London lung cancer screening pilot study - Impact of mobile scanners and dual risk model utilisation.

OBJECTIVES: The West London lung screening pilot aimed to identify early-stage lung cancer by targeting low-dose CT (LDCT) to high risk participants. Successful implementation of screening requires maximising participant uptake and identifying those at highest risk. As well as reporting pre-specified baseline screening metrics, additional objectives were to 1) compare participant uptake between a mobile and hospital-based CT scanner and 2) evaluate the impact on cancer detection using two lung cancer risk models. METHODS: From primary care records, ever-smokers aged 60-75 were invited to a lung health check at a hospital or mobile site. Participants with PLCOM2012 6-yr risk ≥1.51 % and/or LLPv2 5-yr risk ≥2.0 % were offered a LDCT. Lung cancer detection rate, stage, and recall rates are reported. Participant uptake was compared at both sites (chi-squared test). LDCT eligibility and cancer detection rate were compared between those recruited under each risk model. RESULTS: Of 8366 potential participants invited, 1047/5135 (20.4 %) invitees responded to an invitation to the hospital site, and 702/3231 (21.7 %) to the mobile site (p = 0.14). The median distance travelled to the hospital site was less than to the mobile site (3.3 km vs 6.4 km, p < 0.01). Of 1159 participants eligible for a scan, 451/1159 (38.9 %) had a LLPv2 ≥2.0 % only, 71/1159 (6.1 %) had a PLCOM2012 ≥1.5 % only; 637/1159 (55.0 %) met both risk thresholds. Recall rate was 15.9 %. Lung cancer was detected in 29/1145 (2.5 %) participants scanned (stage 1, 58.6 %); 5/29 participants with lung cancer did not meet a PLCOM2012 threshold of ≥1.51 %; all had a LLPv2 ≥2.0 %. CONCLUSION: Targeted screening is effective in detecting early-stage lung cancer. Similar levels of participant uptake at a mobile and fixed site scanner were demonstrated, indicating that uptake was driven by factors in addition to scanner location. The LLPv2 model was more permissive; recruitment with PLCOM2012 alone would have missed several cancers.

Pulmonary Angiopathy in Severe COVID-19: Physiologic, Imaging, and Hematologic Observations.

Rationale: Clinical and epidemiologic data in coronavirus disease (COVID-19) have accrued rapidly since the outbreak, but few address the underlying pathophysiology.Objectives: To ascertain the physiologic, hematologic, and imaging basis of lung injury in severe COVID-19 pneumonia.Methods: Clinical, physiologic, and laboratory data were collated. Radiologic (computed tomography (CT) pulmonary angiography [n = 39] and dual-energy CT [DECT, n = 20]) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography.Measurements and Results: In 39 consecutive patients (male:female, 32:7; mean age, 53 ± 10 yr [range, 29-79 yr]; Black and minority ethnic, n = 25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 ± 14.7 ml/cm H2O; Murray lung injury score, 3.14 ± 0.53; mean ventilatory ratios, 2.6 ± 0.8) with evidence of hypercoagulability and fibrinolytic "shutdown". The mean CT extent (±SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 ± 16.7%, 36.3 ± 24.7%, and 42.7 ± 27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 [47.6%] with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 [90%]) were present in all patients (wedge-shaped, n = 3; mottled, n = 9; mixed pattern, n = 6).Conclusions: Physiologic, hematologic, and imaging data show not only the presence of a hypercoagulable phenotype in severe COVID-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.