Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

BACKGROUND: Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. STUDY DESIGN AND METHODS: A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. RESULTS: Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). CONCLUSIONS: Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults.

BACKGROUND AND OBJECTIVE: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults. METHODS: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed. RESULTS: We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52-72]) and DLco was 44% ([35-50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground-glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DLCO declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DLCO , p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow-up in the ABCA3 group. CONCLUSION: SFTPC and ABCA3-associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground-glass opacities and/or cysts is frequently found in these rare conditions.

Silent myocardial infarction fatty scars detected by coronary calcium score CT scan in diabetic patients without history of coronary heart disease.

OBJECTIVES: To evaluate the prevalence of intra-myocardial fatty scars (IMFS) most likely indicating previous silent myocardial infarction (SMI), as detected on coronary artery calcium (CAC) computed tomography (CT) scans in diabetic patients without history of coronary heart disease (CHD). METHODS: Diabetic patients screened for silent coronary insufficiency in a tertiary-care, university hospital between Jan-2015 and Dec-2016 were categorized according to their CAC score in two groups comprising 242 patients with CACS = 0 and 145 patients with CACS ≥ 300. CAC-CT scans were retrospectively evaluated for subendorcardial and transmural IMFS of the left ventricle. Adipose remodeling, patients' characteristics, cardiovascular risk factors and metabolic profile were compared between groups. RESULTS: Eighty-three (21%) patients with IMFS were identified, 55 (37.9%) in the group CACS ≥ 300 and 28 (11.6%) in the CACS = 0 (OR = 4.67; 95% CI = 2.78-7.84; p < 0.001). Total and average surface of IMFS and their number per patient were similar in both groups (p = 0.55; p = 0.29; p = 0.61, respectively). In the group CACS ≥ 300, patients with IMFS were older (p = 0.03) and had longer-lasting diabetes (p = 0.04). Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, more coronary calcifications (all p < 0.05), and higher prevalence of carotid plaques (OR = 3.03; 95% CI = 1.43-6.39, p = 0.004). After correction for other variables, only a CACS ≥ 300 (OR = 5.12; 95% CI = 2.66-9.85; p < 0.001) was associated with an increased risk of having IMFS. CONCLUSIONS: In diabetic patients without known CHD, IMFSs were found in patients without coronary calcifications, although not as frequently as in patients with heavily calcified coronary arteries. It remains to be established if this marker translates in an upwards cardiovascular risk restratification especially in diabetic patients with CACS = 0. CLINICAL RELEVANCE STATEMENT: In diabetic patients without history of coronary heart disease, intramyocardial fatty scars, presumably of post-infarction origin, can be detected on coronary artery calcium CT scans more frequently, but not exclusively, if the coronary arteries are heavily calcified as compared to those without calcifications. KEY POINTS: • Intramyocardial fatty scars (IMFS), presumably of post-infarction origin, can be detected on coronary artery calcium (CAC) CT scans more frequently, but not exclusively, in diabetic patients with CACS ≥ 300 as compared to patients CACS = 0. • Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, and more coronary calcifications. • Carotid plaques and CACS ≥ 300 were associated with an increased risk of having IMFS, about three and five folds respectively.

Quantification of cartilage and subchondral bone cysts on knee specimens based on a spectral photon-counting computed tomography.

Spectral photon-counting computed tomography (SPCCT) is a new technique with the capability to provide mono-energetic (monoE) images with high signal to noise ratio. We demonstrate the feasibility of SPCCT to characterize at the same time cartilage and subchondral bone cysts (SBCs) without contrast agent in osteoarthritis (OA). To achieve this goal, 10 human knee specimens (6 normal and 4 with OA) were imaged with a clinical prototype SPCCT. The monoE images at 60 keV with isotropic voxels of 250 × 250 × 250 µm3 were compared with monoE synchrotron radiation CT (SR micro-CT) images at 55 keV with isotropic voxels of 45 × 45 × 45 µm3 used as benchmark for cartilage segmentation. In the two OA knees with SBCs, the volume and density of SBCs were evaluated in SPCCT images. In 25 compartments (lateral tibial (LT), medial tibial, (MT), lateral femoral (LF), medial femoral and patella), the mean bias between SPCCT and SR micro-CT analyses were 101 ± 272 mm3 for cartilage volume and 0.33 mm ± 0.18 for mean cartilage thickness. Between normal and OA knees, mean cartilage thicknesses were found statistically different (0.005 < p < 0.04) for LT, MT and LF compartments. The 2 OA knees displayed different SBCs profiles in terms of volume, density, and distribution according to size and location. SPCCT with fast acquisitions is able to characterize cartilage morphology and SBCs. SPCCT can be used potentially as a new tool in clinical studies in OA.

French recommendations for the diagnosis and management of lymphangioleiomyomatosis.

BACKGROUND: The present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France. METHODS: Practical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases. RESULTS: Lymphangioleiomyomatosis is a rare lung disease characterised by a proliferation of smooth muscle cells that leads to the formation of multiple lung cysts. It occurs sporadically or as part of a genetic disease called tuberous sclerosis complex (TSC). The document addresses multiple aspects of the disease, to guide the clinicians regarding when to suspect a diagnosis of lymphangioleiomyomatosis, what to do in case of recurrent pneumothorax or angiomyolipomas, what investigations are needed to make the diagnosis of lymphangioleiomyomatosis, what the diagnostic criteria are for lymphangioleiomyomatosis, what the principles of management are, and how follow-up can be organised. Recommendations are made regarding the use of pharmaceutical specialties and treatment other than medications. CONCLUSION: These recommendations are intended to guide the diagnosis and practical management of pulmonary lymphangioleiomyomatosis.

French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2021 update. Full-length version.

BACKGROUND: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS: Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.

Improved image quality and dose reduction in abdominal CT with deep-learning reconstruction algorithm: a phantom study.

OBJECTIVES: To assess the impact of a new artificial intelligence deep-learning reconstruction (Precise Image; AI-DLR) algorithm on image quality against a hybrid iterative reconstruction (IR) algorithm in abdominal CT for different clinical indications. METHODS: Acquisitions on phantoms were performed at 5 dose levels (CTDIvol: 13/11/9/6/1.8 mGy). Raw data were reconstructed using level 4 of iDose4 (i4) and 3 levels of AI-DLR (Smoother/Smooth/Standard). Noise power spectrum (NPS), task-based transfer function (TTF) and detectability index (d') were computed: d' modelled detection of a liver metastasis (LM) and hepatocellular carcinoma at portal (HCCp) and arterial (HCCa) phases. Image quality was subjectively assessed on an anthropomorphic phantom by 2 radiologists. RESULTS: From Standard to Smoother levels, noise magnitude and average NPS spatial frequency decreased and the detectability (d') of all simulated lesions increased. For both inserts, TTF values were similar for all three AI-DLR levels from 13 to 6 mGy but decreased from Standard to Smoother levels at 1.8 mGy. Compared to the i4 used in clinical practice, d' values were higher using the Smoother and Smooth levels and close for the Standard level. For all dose levels, except at 1.8 mGy, radiologists considered images satisfactory for clinical use for the 3 levels of AI-DLR, but rated images too smooth using the Smoother level. CONCLUSION: Use of the Smooth and Smoother levels of AI-DLR reduces the image noise and improves the detectability of lesions and spatial resolution for standard and low-dose levels. Using the Smooth level is apparently the best compromise between the lowest dose level and adequate image quality. KEY POINTS: • Evaluation of the impact of a new artificial intelligence deep-learning reconstruction (AI-DLR) on image quality and dose compared to a hybrid iterative reconstruction (IR) algorithm. • The Smooth and Smoother levels of AI-DLR reduced the image noise and improved the detectability of lesions and spatial resolution for standard and low-dose levels. • The Smooth level seems the best compromise between the lowest dose level and adequate image quality.

Role of the occupational disease consultant in the multidisciplinary discussion of interstitial lung diseases.

BACKGROUND: Diffuse interstitial lung diseases (ILD) constitute a heterogeneous group of conditions with complex etiological diagnoses requiring a multidisciplinary approach. Much is still unknown about them, particularly their relationship with occupational exposures. The primary objective of this study was to investigate the distribution of occupational exposures according to type of ILD. The secondary objectives were to estimate the proportion of ILDs possibly related to occupational exposure and to evaluate the added value of the participation of an occupational disease consultant in ILD multidisciplinary discussions (MDD). METHODS: From May to December 2020, all consecutive patients with ILD whose cases were reviewed during a MDD in a referral centre for ILD were prospectively offered a consultation with an occupational disease consultant. RESULTS: Of the 156 patients with ILD whose cases were reviewed in MDD during the study period, 141 patients attended an occupational exposure consultation. Occupational exposure was identified in 97 patients. Occupational exposure to asbestos was found in 12/31 (38.7%) patients with idiopathic pulmonary fibrosis (IPF) and in 9/18 (50.0%) patients with unclassifiable fibrosis. Occupational exposure to metal dust was found in 13/31 (41.9%) patients with IPFs and 10/18 (55.6%) patients with unclassifiable fibrosis. Silica exposure was found in 12/50 (24.0%) patients with autoimmune ILD. The link between occupational exposure and ILD was confirmed for 41 patients after the specialist occupational consultation. The occupational origin had not been considered (n = 9) or had been excluded or neglected (n = 4) by the MDD before the specialised consultation. A total of 24 (17%) patients were advised to apply for occupational disease compensation, including 22 (15.6%) following the consultation. In addition, a diagnosis different from the one proposed by the MDD was proposed for 18/141 (12.8%) patients. CONCLUSIONS: In our study, we found a high prevalence of occupational respiratory exposure with a potential causal link in patients with ILD. We suggest that a systematic specialised consultation in occupational medicine could be beneficial in the ILD diagnostic approach.

Embolization of Recurrent Pulmonary Arteriovenous Malformations by Ethylene Vinyl Alcohol Copolymer (Onyx®) in Hereditary Hemorrhagic Telangiectasia: Safety and Efficacy.

OBJECTIVES: To evaluate short- and long-term safety and efficacy of embolization with Onyx® for recurrent pulmonary arteriovenous malformations (PAVMs) in hereditary hemorrhagic telangiectasia (HHT). METHODS: In total, 45 consecutive patients (51% women, mean (SD) age 53 (18) years) with HHT referred to a reference center for treatment of recurrent PAVM were retrospectively included from April 2014 to July 2021. Inclusion criteria included evidence of PAVM recurrence on CT or angiography, embolization using Onyx® and a minimal 1-year-follow-up CT or angiography. Success was defined based on the standard of reference criteria on unenhanced CT or pulmonary angiography if a recurrence was suspected. PAVMs were analyzed in consensus by two radiologists. The absence of safety distance, as defined by a too-short distance for coil/plug deployment, i.e., between 0.5 and 1 cm, between the proximal extremity of the primary embolic material used and a healthy upstream artery branch, was reported. RESULTS: In total, 70 PAVM were analyzed. Mean (SD) follow-up was 3 (1.3) years. Safety distance criteria were missing in 33 (47%) PAVMs. All procedures were technically successful, with a short-term occlusion rate of 100% using a mean (SD) of 0.6 (0.5) mL of Onyx®. The long-term occlusion rate was 60%. No immediate complication directly related to embolization was reported, nor was any severe long-term complication such as strokes or cerebral abscesses. CONCLUSIONS: In HHT, treatment of recurrent PAVM with Onyx® showed satisfactory safety and efficacy, with an immediate occlusion rate of 100% and a long-term rate of 60%.

Pleuroparenchymal fibroelastosis.

PURPOSE OF REVIEW: Pleuroparenchymal fibroelastosis (PPFE) is a clinico-radiologic-pathologic interstitial lung disease (ILD) characterized by fibrosis that has upper lobe and subpleural predominance, involving both the visceral pleura and the subjacent subpleural lung parenchyma, and comprises dense fibroelastic changes with prominent elastosis of the alveolar walls together with fibrous thickening of the visceral pleura. The goal of this review is to summarize the state-of-the-art understanding in PPFE. RECENT FINDINGS: PPFE was described in an increasing number of conditions. The course of disease is heterogeneous. Idiopathic PPFE, cases associated with telomerase-related gene mutations, cases related to a history of chemotherapy, and cases combining PPFE with a pattern of usual interstitial pneumonia, may have a particularly poor prognosis. Well-conducted retrospective studies identified marked PPFE features in approximately 10% of patients with idiopathic pulmonary fibrosis, 11% of patients with systemic sclerosis-associated ILD, 6.5% of patients with rheumatoid arthritis-associated ILD, and 23% of patients with hypersensitivity pneumonitis. Drug therapy has not been evaluated prospectively. A small retrospective study suggests that nintedanib may slow disease progression. However, whether the efficacy of antifibrotics is comparable in PPFE and in other forms of progressive pulmonary fibrosis warrants further evaluation. SUMMARY: Accumulating data indicate that PPFE features are associated with poor prognosis in fibrosing ILDs. Further research on the management of PPFE is warranted.

Effect of contrast material injection protocol on first-pass myocardial perfusion assessed by dual-energy dual-layer computed tomography.

Background: Dual-energy dual-layer computed tomography (CT) scanners can provide useful tools, such as iodine maps and virtual monochromatic images (VMI), for the evaluation of myocardial perfusion defects. Data about the influence of acquisition protocols and normal values are still lacking. Methods: Clinically indicated coronary CT-angiographies performed between January-October 2018 in a single university hospital with dual-energy dual-layer CT (DE-DLCT) and different injection protocols were retrospectively evaluated. The two protocols were: 35 mL in patients <80 kg and 0.5 mL/kg in patients >80 kg at 2.5 mL/s (group A) or double contrast dose at 5 mL/s (group B). Patients with coronary stenosis >50% were excluded. Regions of interest were manually drawn on 16 myocardial segments and iodine concentration was measured in mg/mL. Signal-to-noise, contrast-to-noise ratios (CNR) and image noise were measured on conventional images and VMI. Results: A total of 30 patients were included for each protocol. With iodine concentrations of 1.38±0.41 mg/mL for protocol A and 2.07±0.73 mg/mL for protocol B, the two groups were significantly different (P<0.001). No significant iodine concentration differences were found between the 16 segments (P=0.47 and P=0.09 for group A and B respectively), between basal, mid and apical segments for group A and B (P=0.28 and P=0.12 for group A and B respectively) and between wall regions for group A (P=0.06 on normalised data). In group B, iodine concentration was significantly different between three wall regions [highest values for the lateral wall, median =2.03 (1.06) mg/mL]. Post-hoc analysis showed highest contrast-to-noise and signal-to-noise in VMI at 40 eV (P<0.05). Conclusions: Iodine concentration in left ventricular myocardium of patients without significant coronary artery stenosis varied depending on the injection protocol and appeared more heterogeneous in different wall regions at faster injection rate and greater iodine load. Signal-to-noise and contrast-to-noise gradually improved when decreasing VMI energy, although at the expenses of higher noise, demonstrating the potential of DE-DLCT to enhance objective image quality.

Comparison of virtual monoenergetic imaging between a rapid kilovoltage switching dual-energy computed tomography with deep-learning and four dual-energy CTs with iterative reconstruction.

BACKGROUND: To assess the spectral performance of rapid kV switching dual-energy CT (KVSCT-Canon) equipped with a Deep-Learning spectral reconstruction algorithm on virtual-monoenergetic images at low-energy levels and to compare its performances with four other dual-energy CT (DECT) platforms equipped with iterative reconstruction algorithms. METHODS: Two CT phantoms were scanned on five DECT platforms: KVSCT-Canon, fast kV-switching CT (KVSCT-GE), split filter CT, dual-source CT (DSCT), and dual-layer CT (DLCT). The classical parameters of abdomen-pelvic examinations were used for all phantom acquisitions, and a CTDIvol close to 10 mGy. For KVSCT-Canon, virtual-monoenergetic images were reconstructed with a clinical slice thickness of 0.5 and 1.5 mm to be close to other platforms. Noise power spectrum (NPS) and task-based transfer function (TTF) were evaluated from 40 to 80 keV of virtual-monoenergetic images. A detectability index (d') was computed to model the detection task of two contrast-enhanced lesions as function of keV. RESULTS: For KVSCT-Canon, the noise magnitude and average NPS spatial frequency (fav) decreased from 40 to 70 keV and increased thereafter. Similar noise magnitude outcomes were found for KVSCT-GE but the opposite for fav. For the other DECT platforms, the noise magnitude decreased as the keV increased. For split filter CT, DSCT and DLCT, the fav values increased from 40 to 80 keV. For all DECT platforms, TTF at 50% (f50) decreased as the keV increased, decreasing spatial resolution. For KVSCT-Canon, d' values peaked at 60 and 70 keV for both simulated lesions and from 50 to 70 keV for KVSCT-GE. d' decreased between 40 and 70 keV for DSCT, DLCT and split filter CT. For KVSCT-Canon, the increase in slice thickness decreases noise magnitude, fav and f50 and increases d' values. The highest d' values were found for DLCT at 40 and 50 keV and for KVSCT-Canon at 1.5 mm for other keV. CONCLUSIONS: For KVSCT-Canon, the detectability of contrast-enhanced lesions was highest at 60 keV. The highest d' values were found for DLCT at 40 and 50 keV and for KVSCT-Canon at 1.5 mm for other keV.

Virtual monoenergetic images from photon-counting spectral computed tomography to assess knee osteoarthritis.

BACKGROUND: Dual-energy computed tomography has shown a great interest for musculoskeletal pathologies. Photon-counting spectral computed tomography (PCSCT) can acquire data in multiple energy bins with the potential to increase contrast, especially for soft tissues. Our objectives were to assess the value of PCSST to characterise cartilage and to extract quantitative measures of subchondral bone integrity. METHODS: Seven excised human knees (3 males and 4 females; 4 normal and 3 with osteoarthritis; age 80.6 ± 14 years, mean ± standard deviation) were scanned using a clinical PCSCT prototype scanner. Tomographic image reconstruction was performed after Compton/photoelectric decomposition. Virtual monoenergetic images were generated from 40 keV to 110 keV every 10 keV (cubic voxel size 250 × 250 × 250 µm3). After selecting an optimal virtual monoenergetic image, we analysed the grey level histograms of different tissues and extracted quantitative measurements on bone cysts. RESULTS: The optimal monoenergetic images were obtained for 60 keV and 70 keV. Visual inspection revealed that these images provide sufficient spatial resolution and soft-tissue contrast to characterise surfaces, disruption, calcification of cartilage, bone osteophytes, and bone cysts. Analysis of attenuation versus energy revealed different energy fingerprint according to tissues. The volumes and numbers of bone cyst were quantified. CONCLUSIONS: Virtual monoenergetic images may provide direct visualisation of both cartilage and bone details. Thus, unenhanced PCSCT appears to be a new modality for characterising the knee joint with the potential to increase the diagnostic capability of computed tomography for joint diseases and osteoarthritis.

Automatic quantitative computed tomography measurement of longitudinal lung volume loss in interstitial lung diseases.

OBJECTIVES: To compare the lung CT volume (CTvol) and pulmonary function tests in an interstitial lung disease (ILD) population. Then to evaluate the CTvol loss between idiopathic pulmonary fibrosis (IPF) and non-IPF and explore a prognostic value of annual CTvol loss in IPF. METHODS: We conducted in an expert center a retrospective study between 2005 and 2018 on consecutive patients with ILD. CTvol was measured automatically using commercial software based on a deep learning algorithm. In the first group, Spearman correlation coefficients (r) between forced vital capacity (FVC), total lung capacity (TLC), and CTvol were calculated. In a second group, annual CTvol loss was calculated using linear regression analysis and compared with the Mann-Whitney test. In a last group of IPF patients, annual CTvol loss was calculated between baseline and 1-year CTs for investigating with the Youden index a prognostic value of major adverse event at 3 years. Univariate and log-rank tests were calculated. RESULTS: In total, 560 patients (4610 CTs) were analyzed. For 1171 CTs, CTvol was correlated with FVC (r: 0.86) and TLC (r: 0.84) (p < 0.0001). In 408 patients (3332 CT), median annual CTvol loss was 155.7 mL in IPF versus 50.7 mL in non-IPF (p < 0.0001) over 5.03 years. In 73 IPF patients, a relative annual CTvol loss of 7.9% was associated with major adverse events (log-rank, p < 0.0001) in univariate analysis (p < 0.001). CONCLUSIONS: Automated lung CT volume may be an alternative or a complementary biomarker to pulmonary function tests for the assessment of lung volume loss in ILD. KEY POINTS: • There is a good correlation between lung CT volume and forced vital capacity, as well as for with total lung capacity measurements (r of 0.86 and 0.84 respectively, p < 0.0001). • Median annual CT volume loss is significantly higher in patients with idiopathic pulmonary fibrosis than in patients with other fibrotic interstitial lung diseases (155.7 versus 50.7 mL, p < 0.0001). • In idiopathic pulmonary fibrosis, a relative annual CT volume loss higher than 9.4% is associated with a significantly reduced mean survival time at 2.0 years versus 2.8 years (log-rank, p < 0.0001).

Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI.

BACKGROUND: Previous studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using 18F-sodium fluoride (18F-NaF) to check simultaneously 18F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability. METHODS AND RESULTS: We included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent 18F-NaF PET/MRI. 18F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. 18F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between 18F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. 18F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients. CONCLUSIONS: 18F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.

Nintedanib in idiopathic and secondary pleuroparenchymal fibroelastosis.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has a variable disease course with dismal prognosis in the majority of patients with no validated drug therapy. This study is to evaluate the effect of nintedanib in patients with idiopathic and secondary PPFE. Patients admitted to a tertiary care center (2010-2019) were included into this retrospective analysis if they had a multidisciplinary diagnosis of PPFE, had been followed-up for 3 months or more, and had lung function tests and chest CTs available for review. Changes in pulmonary function tests were assessed using non-parametric tests and linear mixed effect model. Lung volumes were measured with lobar segmentation using chest CT. RESULTS: Out of 21 patients with PPFE, nine had received nintedanib, six had received another treatment and another six patients were monitored without drug therapy. Annual FVC (% of predicted) relative decline was - 13.6 ± 13.4%/year before nintedanib and - 1.6 ± 6.02%/year during nintedanib treatment (p = 0.014), whereas no significant change in FVC% relative decline was found in patients receiving another treatment (- 13.25 ± 34 before vs - 16.61 ± 36.2%/year during treatment; p = 0.343). Using linear mixed effect model, the slope in FVC was - 0.97%/month (95% CI: - 1.42; - 0.52) before treatment and - 0.50%/month (95% CI: - 0.88; 0.13) on nintedanib, with a difference between groups of + 0.47%/month (95% CI: 0.16; 0.78), p = 0.004. The decline in the upper lung volumes measured by CT was - 233 mL/year ± 387 mL/year before nintedanib and - 149 mL/year ± 173 mL/year on nintedanib (p = 0.327). Nintedanib tolerability was unremarkable. CONCLUSION: In patients with PPFE, nintedanib treatment might be associated with slower decline in lung function, paving the way for prospective, controlled studies.

In Vivo Molecular K-Edge Imaging of Atherosclerotic Plaque Using Photon-counting CT.

Background Macrophage burden is a major factor in the risk of atherosclerotic plaque rupture, and its evaluation remains challenging with molecular noninvasive imaging approaches. Photon-counting CT (PCCT) with k-edge imaging aims to allow for the specific detection of macrophages using gold nanoparticles. Purpose To perform k-edge imaging in combination with gold nanoparticles to detect and quantify the macrophage burden within the atherosclerotic aortas of rabbits. Materials and Methods Atherosclerotic and control New Zealand white rabbits were imaged before and at several time points up to 2 days after intravenous injection of gold nanoparticles (3.5 mL/kg, 65 mg gold per milliliter). Aortic CT angiography was performed at the end of the follow-up using an intravenous injection of an iodinated contrast material. Gold k-edge and conventional CT images were reconstructed for qualitative and quantitative assessment of the macrophage burden. PCCT imaging results were compared with findings at histologic examination, quantitative histomorphometry, transmission electron microscopy, and quantitative inductively coupled plasma optical emission spectrometry. Pearson correlations between the macrophage area measured in immunostained sections and the concentration of gold and attenuation measured in the corresponding PCCT sections were calculated. Results Seven rabbits with atherosclerosis and four control rabbits without atherosclerosis were analyzed. In atherosclerotic rabbits, calcifications were observed along the aortic wall before injection. At 2 days after injection of gold nanoparticles, only gold k-edge images allowed for the distinction of plaque enhancement within calcifications and for lumen enhancement during angiography. A good correlation was observed between the gold concentration measured within the wall and the macrophage area in 35 plaques (five per rabbit) (r = 0.82; 95% CI: 0.67, 0.91; P < .001), which was higher than that observed on conventional CT images (r = 0.41; 95% CI: 0.09, 0.65; P = .01). Transmission electron microscopy and inductively coupled plasma optical emission spectrometry analyses confirmed the gold k-edge imaging findings. Conclusion Photon-counting CT with gold nanoparticles allowed for the noninvasive evaluation of both molecular and anatomic information in vivo in rabbits with atherosclerotic plaques. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Leiner in this issue.

Progressive fibrosing interstitial lung disease: a clinical cohort (the PROGRESS study).

In patients with chronic fibrosing interstitial lung disease (ILD), a progressive fibrosing phenotype (PF-ILD) may develop, but information on the frequency and characteristics of this population outside clinical trials is lacking.We assessed the characteristics and outcomes of patients with PF-ILD other than idiopathic pulmonary fibrosis (IPF) in a real-world, single-centre clinical cohort. The files of all consecutive adult patients with fibrosing ILD (2010-2017) were examined retrospectively for pre-defined criteria of ≥10% fibrosis on high-resolution computed tomography and progressive disease during overlapping windows of 2 years. Baseline was defined as the date disease progression was identified. Patients receiving nintedanib or pirfenidone were censored from survival and progression analyses.In total, 1395 patients were screened; 617 had ILD other than IPF or combined pulmonary fibrosis and emphysema, and 168 had progressive fibrosing phenotypes. In 165 evaluable patients, median age was 61 years; 57% were female. Baseline mean forced vital capacity (FVC) was 74±22% predicted. Median duration of follow-up was 46.2 months. Annualised FVC decline during the first year was estimated at 136±328 mL using a linear mixed model. Overall survival was 83% at 3 years and 72% at 5 years. Using multivariate Cox regression analysis, mortality was significantly associated with relative FVC decline ≥10% in the previous 24 months (p<0.05), age ≥50 years (p<0.01) and diagnosis subgroup (p<0.01).In this cohort of patients with PF-ILD not receiving antifibrotic therapy, the disease followed a course characterised by continued decline in lung function, which predicted mortality.

Unexpected Vertebral Bodies Trapping of 99mTc-Macroaggregated Albumin During Lung Perfusion Scintigraphy in a Patient With Collateral Paravertebral Venous System.

ABSTRACT: A 35-year-old woman was referred to our nuclear medicine center for a ventilation and perfusion (VQ) pulmonary scintigraphy to detect pulmonary embolism. She was treated with low-molecular-weight heparin following a proximal venous thrombosis of the right upper limb and had a previous history of an infiltrating ductal carcinoma of the right breast. Surprisingly, the VQ scintigraphy showed uptake of 99mTc-MAA in several superior vertebrae. A contrast-enhanced CT scan revealed a dilated collateral paravertebral venous system due to the deep vein thrombosis extended from superior vena cava to brachiocephalic trunk. 99mTc-MAA was trapped through the dilated vertebral venous system.