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Zusammenfassung Klinisches Problem Raucherassoziierte interstitielle Lungenerkrankungen umfassen heterogene pulmonale Pathologien, deren korrekte Diagnostik prognostische und therapeutische Konsequenzen hat. In diesem Artikel werden die gängigsten raucherassoziierten interstitiellen Lungenerkrankungen beschrieben sowie eine strukturierte Herangehensweise präsentiert, welche den diagnostischen Arbeitsprozess erleichtern kann. Empfehlungen für die Praxis Die Computertomographie (CT) besitzt einen hohen Stellenwert in der Diagnose der raucherassoziierten interstitiellen Lungenerkrankungen und kann dazu beitragen, Lungenbiopsien zu verhindern. Um eine hohe diagnostische Genauigkeit zu erreichen, sollten standardisierte Untersuchungsprotokolle sowie eine strukturierte Herangehensweise in der Befundung zur Anwendung kommen. In den entzündlich dominierten Stadien der respiratorischen Bronchiolitis (RB), der respiratorischen Bronchiolitis mit interstitieller Lungenerkrankung (RB-ILD) sowie der desquamativen interstitiellen Pneumonie (DIP) haben die Beendigung des Rauchens sowie Steroide den größten therapeutischen Effekt. Bei fibrotischen Veränderungen (z. B. im Rahmen einer idiopathischen pulmonalen Fibrose [IPF]) können antifibrotische Therapien mit Pirfenidon und Nintedanib zum Einsatz kommen. Patienten mit dem Verdacht auf raucherassoziierte interstitielle Lungenerkrankung sollten in multidisziplinären Boards abgeklärt und behandelt werden.

Supplementary Materials (clean)

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1–13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7–11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5–6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential.Significance:Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7–11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Background Photon-counting detector (PCD) CT allows ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after COVID-19. Purpose To compare PCD CT with energy-integrating detector (EID) CT for noninvasive assessment of post-COVID-19 lung abnormalities. Materials and Methods For this prospective study, adult participants with one or more COVID-19-related persisting symptoms (resting or exertional dyspnea, cough, and fatigue) underwent same-day EID and PCD CT scans between April 2022 and June 2022. EID CT 1.0mm images and, subsequently, 1.0mm, 0.4mm, and 0.2mm PCD CT images were reviewed for the presence of lung abnormalities. Subjective and objective EID and PCD CT image quality was evaluated using a 5-point Likert scale (-2 to 2) and lung signal-to-noise ratios (SNR). Results Twenty participants (mean age, 54 years ±16 [SD], 10 men) were included. EID CT showed post-COVID-19 lung abnormalities in 15 of 20 (75%) participants with a median involvement of 10% of lung volume [IQR 0-45%], and 3.5 lobes [IQR 0-5]. Ground-glass opacities (GGO) and linear bands (both 10 of 20 participants, 50%) were the most frequent findings on EID CT. PCD CT revealed additional lung abnormalities in 10 of 20 (50%) participants, most commonly bronchiolectasis (10 of 20, 50%). Subjective image quality was improved for 1.0mm PCD vs. 1.0mm EID CT images (1 [IQR 1-2]

A wide spectrum of conditions, from life-threatening to non-urgent, can manifest with acute dyspnea, thus presenting major challenges for the treating physician when establishing the diagnosis and severity of the underlying disease. Imaging plays a decisive role in the assessment of acute dyspnea of cardiac and/or pulmonary origin. This article presents an overview of the current imaging modalities used to narrow the differential diagnosis in the assessment of acute dyspnea of cardiac or pulmonary origin. The current indications, findings, accuracy, and limits of each imaging modality are reported. Chest radiography is usually the primary imaging modality applied. There is a low radiation dose associated with this method, and it can assess the presence of fluid in the lung or pleura, consolidations, hyperinflation, pneumothorax, as well as heart enlargement. However, its low sensitivity limits the ability of the chest radiograph to accurately identify the causes of acute dyspnea. CT provides more detailed imaging of the cardiorespiratory system, and therefore, better sensitivity and specificity results, but it is accompanied by higher radiation exposure. Ultrasonography has the advantage of using no radiation, and is fast and feasible as a bedside test and appropriate for the assessment of unstable patients. However, patient-specific factors, such as body habitus, may limit its image quality and interpretability. Advances in knowledge This review provides guidance to the appropriate choice of imaging modalities in the diagnosis of patients with dyspnea of cardiac or pulmonary origin.

PurposeTo determine if pelvic/ovarian and omental lesions of ovarian cancer can be reliably segmented on computed tomography (CT) using fully automated deep learning-based methods.Materials and MethodsA deep learning model for the two most common disease sites of high grade serous ovarian cancer lesions (pelvis/ovaries and omentum) was developed and compared against the well-established “no-new-Net” (nnU-Net) framework and unrevised trainee radiologist segmentations. A total of 451 pre-treatment and post neoadjuvant chemotherapy (NACT) CT scans collected from four different institutions were used for training (n=276), hyper-parameter tuning (n=104) and testing (n=71) of the methods. The performance was evaluated using the Dice similarity coefficient (DSC) and compared using a Wilcoxon test on paired resultsResultsOur model outperforms the nnU-Net framework by a significant margin for both disease (validation: p=1×10-4,1.5×10-6, test: p=0.004, 0.005) and it does not perform significantly different from a trainee radiologist for the pelvic/ovarian lesions (p=0.392). On an independent test set (n=71), the model achieves a performance of 72±19 mean DSC for the pelvic/ovarian and 64±24 for the omental lesions.ConclusionAutomated ovarian cancer segmentation on CT using deep neural networks is feasible and achieves performance close to a trainee-level radiologist for pelvic/ovarian lesions.SummaryDeep learning-based models were used to assess whether fully automated segmentation is feasible for the main two disease sites in high grade serous ovarian cancer.Key PointsFirst automated approach for pelvic/ovarian and omental ovarian cancer lesion segmentation on CT images.Automated segmentation of ovarian cancer lesions can be comparable with manual segmentation of trainee radiologists with three years of experience in oncological and gynecological imaging.Careful hyper-parameter tuning can provide models significantly outperforming strong state-of-the-art baselines.

Following coronavirus disease 2019 (COVID-19), a proportion of patients report prolonged or worsening symptoms and impairments. These symptoms are increasingly referred to as "long COVID" syndrome. They may be associated with radiological changes on computed tomography (CT) and pulmonary function impairment.To discuss the role of long-term assessment of COVID-19 patients to determine which patients may benefit from follow-up.This article presents the current results of clinical, radiological, and pulmonary function follow-up tests after COVID-19 pneumonia.Chronic fatigue and dyspnea are the most common persistent symptoms after COVID-19. Patients also present impaired exercise capacity. On CT, ground-glass opacities and parenchymal bands are the most common residual changes after COVID-19 pneumonia, histologically corresponding to organizing pneumonia. A proportion of patients who had severe COVID-19 pneumonia may show fibrotic-like changes during follow-up. Patients with severe acute infection may present with a restrictive syndrome with lower diffusing capacity for carbon monoxide (DLCO) and total lung capacity (TLC) values. Overall, significant and continuous improvement in all symptoms as well as radiomorphological and functional changes were observed over time.Patients with persistent symptoms after COVID-19 should be evaluated and treated in specialized post-COVID-19 clinics in a multidisciplinary manner.HINTERGRUND: Nach einer Coronavirus-Krankheit-2019 (COVID-19) berichtet ein Teil der Patienten über länger andauernde oder sich verschlechternde Symptome und Beeinträchtigungen. Diese anhaltenden Symptome werden mit dem Begriff „Long-COVID“-Syndrom zusammengefasst. Sie können mit radiologischen Veränderungen in der Computertomographie (CT) und einer Verschlechterung der Lungenfunktion einhergehen.Die Rolle der langfristigen Verlaufskontrollen von COVID-19-Patienten wird erörtert, um festzustellen, welche Patienten davon profitieren können.In diesem Artikel werden die aktuellen Ergebnisse der klinischen, radiologischen und lungenfunktionellen Nachsorgenuntersuchungen nach COVID-19-Pneumonie präsentiert.Chronische Müdigkeit und Dyspnoe sind die häufigsten anhaltenden Symptome nach COVID-19. Außerdem zeigen viele dieser Patienten eine Beeinträchtigung der körperlichen Leistungsfähigkeit. In der CT sind Milchglasareale und strangförmige Verdichtungen die häufigsten residualen Veränderungen nach einer COVID-19-Pneumonie, die histologisch einer organisierenden Pneumonie entsprechen. Ein Teil der Patienten kann nach einer schweren COVID-19-Pneumonie im Verlauf fibroseähnliche Veränderungen aufweisen. Patienten mit einem vormals schwereren Verlauf können ein restriktives Syndrom mit niedriger Kohlenmonoxid-Diffusionskapazität (DLCO) und Gesamt-Lungenkapazität (TLC) zeigen. Im längerfristigen Verlauf zeigen die meisten Patienten eine deutliche und kontinuierliche Verbesserung aller Symptome sowie einen Rückgang der radiologisch-morphologischen und funktionellen Veränderungen.Patienten mit persistierenden Symptomen nach COVID-19 sollten in spezialisierten Post-COVID-19-Ambulanzen multidisziplinär abgeklärt und behandelt werden.

Smoking-related interstitial lung diseases are a heterogeneous group of pulmonary abnormalities. The correct diagnosis has prognostic and therapeutic implications. This article introduces the most common smoking-related interstitial lung diseases and describes a structured approach to support the diagnostic workflow.Computed tomography is pivotal in the diagnostic workflow of smoking-related interstitial lung diseases and may reduce the number of unnecessary lung biopsies. To achieve high diagnostic accuracy, a standardized scanning protocol, and a structured assessment approach should be utilized. During inflammatory stages of respiratory bronchiolitis (RB), respiratory bronchiolitis interstitial lung diseases (RB-ILD), and desquamative interstitial pneumonia (DIP), cessation of smoking as well as the use of steroids are the treatment of choice. In case of fibrotic changes (e.g., in idiopathic pulmonary fibrosis [IPF]), antifibrotic therapy with nintedanib and pirfenidone may be used. Patients with suspected smoking-related interstitial lung disease should be discussed in interdisciplinary board meetings.KLINISCHES PROBLEM: Raucherassoziierte interstitielle Lungenerkrankungen umfassen heterogene pulmonale Pathologien, deren korrekte Diagnostik prognostische und therapeutische Konsequenzen hat. In diesem Artikel werden die gängigsten raucherassoziierten interstitiellen Lungenerkrankungen beschrieben sowie eine strukturierte Herangehensweise präsentiert, welche den diagnostischen Arbeitsprozess erleichtern kann. EMPFEHLUNGEN FüR DIE PRAXIS: Die Computertomographie (CT) besitzt einen hohen Stellenwert in der Diagnose der raucherassoziierten interstitiellen Lungenerkrankungen und kann dazu beitragen, Lungenbiopsien zu verhindern. Um eine hohe diagnostische Genauigkeit zu erreichen, sollten standardisierte Untersuchungsprotokolle sowie eine strukturierte Herangehensweise in der Befundung zur Anwendung kommen. In den entzündlich dominierten Stadien der respiratorischen Bronchiolitis (RB), der respiratorischen Bronchiolitis mit interstitieller Lungenerkrankung (RB-ILD) sowie der desquamativen interstitiellen Pneumonie (DIP) haben die Beendigung des Rauchens sowie Steroide den größten therapeutischen Effekt. Bei fibrotischen Veränderungen (z. B. im Rahmen einer idiopathischen pulmonalen Fibrose [IPF]) können antifibrotische Therapien mit Pirfenidon und Nintedanib zum Einsatz kommen. Patienten mit dem Verdacht auf raucherassoziierte interstitielle Lungenerkrankung sollten in multidisziplinären Boards abgeklärt und behandelt werden.

Background & Aims To explore whether sarcopenia, diagnosed by an abbreviated magnetic resonance imaging (MRI) protocol is a risk factor for hepatic decompensation and mortality in patients with chronic liver disease (CLD). Methods In this retrospective single‐centre study we included 265 patients (164 men, mean age 54 ± 16 years) with CLD who had undergone MRI of the liver between 2010 and 2015. Transverse psoas muscle thickness (TPMT) was measured on unenhanced and contrast‐enhanced T1‐weighted and T2‐weighted axial images. Sarcopenia was defined by height‐adjusted and gender‐specific cut‐offs in women as TPMT

Summary Background Immune checkpoint inhibitors have become a valuable tool in the therapeutic strategy against metastasized non-small cell lung cancer (NSCLC) as they represent an effective and safe treatment option for many patients; however, the treatment response and side effects of this class of drugs can considerably differ compared to classical chemotherapeutics. The aim of this study was to highlight specific radiological pulmonary findings of NSCLC patients treated with immune checkpoint inhibitors. Methods and results Medical records and images of prospectively collected data from 70 patients with advanced NSCLC, treated with immune checkpoint inhibitors, were reviewed. Of the patients two experienced an initial increase in tumor size, followed by a decrease in tumor size that was described as pseudoprogression. Another patient developed a sarcoid-like reaction accompanied by clinical improvements and radiological treatment response. A further two patients developed immune checkpoint-associated pulmonary injury that was clinically and radiologically classified as pneumonitis, which responded well to anti-inflammatory treatment. Conclusion Management of patients with NSCLC using immune checkpoint inhibitors requires a knowledge of specific clinical and radiological findings. Both oncologists and radiologists have to be aware of the most common types, including atypical response patterns, such as a sarcoid-like reaction and pseudoprogression as well as of the pulmonary side effects that can encompass pneumonitis.

Diffuse parenchymal lung diseases include a heterogeneous group of diseases of the lung parenchyma, the alveolar spaces, the vessels and the airways, which can be triggered by various pathomechanisms, such as inflammation and fibrotic changes. Since the therapeutic approaches and prognoses differ significantly between the diseases, the correct diagnosis is of fundamental importance. In routine clinical practice, next to the patients' history, the clinical presentation, the laboratory findings and the bronchoscopy, imaging plays a central role in establishing a diagnosis.The diagnosis of diffuse parenchymal lung diseases is an enormous challenge for clinicians, radiologists as well as pathologists and should therefore preferably be carried out in a multidisciplinary setting. Since patients often present with unspecific, respiratory symptoms, chest radiographs are the first imaging method used. Many patterns of diffuse parenchymal lung diseases (e.g., ground-glass opacities and consolidations), their distribution (e.g., cranial-caudal) and the presence of additional findings (e.g., mediastinal lymphadenopathy) are often already detectable on chest X‑rays. However, the imaging reference standard and thus, an integral part of the assessment of diffuse parenchymal lung disease, is the chest HR-CT. In some cases, the pattern of the HR-CT is pathognomonic, in others it is unspecific for a disease, so that further diagnostic steps are necessary.KLINISCHES PROBLEM: Diffuse parenchymatöse Lungenerkrankungen umfassen eine heterogene Krankheitsgruppe des Lungenparenchyms, der Alveolarräume, der Gefäße sowie Atemwege, welche durch diverse Pathomechanismen, wie Entzündung sowie fibrotische Veränderungen, ausgelöst werden können. Da sich die Therapieansätze sowie Prognosen zwischen den Erkrankungen wesentlich unterscheiden, ist die korrekte Diagnosestellung von grundlegender Bedeutung. In der klinischen Routine spielt neben der Anamnese, der Klinik, den Laborbefunden und der Bronchoskopie die Bildgebung eine zentrale Rolle in der Diagnosefindung. EMPFEHLUNGEN FüR DIE PRAXIS: Die Diagnose diffuser parenchymatöser Lungenerkrankungen stellt eine enorme Herausforderung sowohl für Kliniker, Radiologen als auch Pathologen dar und sollte daher bevorzugt im multidisziplinären Rahmen erfolgen. Da sich die Patienten häufig mit einer unspezifischen, respiratorischen Symptomatik präsentieren, ist das Thorax-Röntgen die erste bildgebende Methode, welche eingesetzt wird. Bereits hier sind oft die verschiedenen Muster diffuser parenchymatöser Lungenerkrankungen (z. B. Milchglasverdichtungen und Konsolidierungen), deren Verteilung (z. B. kranial-kaudal) sowie zusätzliche Befunde, wie mediastinale Lymphadenopathie, bereits erkennbar. Der bildgebende Referenzstandard und somit integraler Bestandteil bei der Beurteilung einer diffusen parenchymatösen Lungenerkrankung ist jedoch die hochauflösende („high resolution“, HR) Computertomographie (CT) des Thorax. In manchen Fällen ist das Muster der HR-CT pathognomonisch, in anderen jedoch unspezifisch für eine Erkrankung, sodass weitere diagnostische Schritte nötig sind.

Radioproteomics is the integration of proteomics, the systematic study of the protein expression of an organism, with radiomics, the extraction and analysis of large numbers of quantitative features from medical images. This article examines this developing field, and it’s application in high grade serous ovarian carcinoma. Seminal proteomic studies in the area of ovarian cancer, such as the PROVAR and CPTA studies are discussed, along side recent research, such as that highlighting the central role of methyltransferase nicotinamide N-methyltransferase as the metabolic regulation of cancer progression in the tumour stroma. Finally, this article considers a novel, hypothesis generating approach to integrate CT-based qualitative and radiomic features with proteomic analysis, and the future direction of the field. Combined advances in radiomic, proteomic and genomic analysis has the potential to signal the age of true precision medicine, where treatment is centered specifically on the molecular profile of the tumour, rather than based on empirical knowledge, thus altering the course of a disease that has the highest mortality of all cancers of the female reproductive system.

Functional liver imaging score (FLIS) - derived from gadoxetic acid-enhanced MRI - correlates with liver function and independently predicts liver-related mortality in patients with chronic liver disease (CLD), while splenic craniocaudal diameter (SCCD) is a marker of portal hypertension. The aim of this study was to investigate the accuracy of a combination of FLIS and SCCD for predicting hepatic decompensation, acute-on-chronic liver failure (ACLF), and mortality in patients with advanced CLD (ACLD).We included 397 patients with CLD who underwent gadoxetic acid-enhanced liver MRI. The FLIS was calculated by summing the points (0-2) of 3 hepatobiliary-phase features: hepatic enhancement, biliary excretion, and portal vein signal intensity. Patients were stratified into 3 groups according to liver fibrosis severity and presence/history of hepatic decompensation: non-ACLD, compensated ACLD (cACLD), and decompensated ACLD (dACLD).SCCD showed excellent intra- and inter-reader agreement. Importantly, SCCD was an independent risk factor for hepatic decompensation in patients with cACLD (per cm; adjusted hazard ratio [aHR] 1.13; 95% CI 1.04-1.23; p = 0.004). Patients with cACLD and a FLIS of 0-3 points and/or a SCCD of13 cm were at increased risk of hepatic decompensation (aHR 3.07; 95% CI 1.43-6.59; p = 0.004). In patients with dACLD, a FLIS of 0-3 was independently associated with an increased risk of ACLF (aHR 2.81; 95% CI 1.16-6.84; p = 0.02), even after adjusting for other prognostic factors. Finally, a FLIS and SCCD-based algorithm was independently predictive of transplant-free mortality and stratified the probability of transplant-free survival (TFS) in ACLD (p0.001): FLIS 4-6 and SCCD ≤13 cm (5-year TFS of 84%) vs. FLIS 4-6 and SCCD13 cm (5-year TFS of 70%) vs. FLIS 0-3 (5-year TFS of 24%).The FLIS and SCCD are simple imaging markers that provide complementary information for risk stratification in patients with compensated and decompensated ACLD.Magnetic resonance imaging (MRI) can be used to assess the state of the liver. Previously the functional liver imaging score, which is based on MRI criteria, was developed as a measure of liver function and to predict the risk of liver-related complications or death. By combining this score with a measurement of spleen diameter, also using MRI, we generated an algorithm that could predict the risk of adverse liver-related outcomes in patients with advanced chronic liver disease.

Background Gadoxetic acid-enhanced MRI enables estimation of liver function in patients with chronic liver disease (CLD). The functional liver imaging score (FLIS), derived from gadoxetic acid-enhanced MRI, has been shown to predict transplant-free survival in liver transplant patients. Purpose To investigate the accuracy of the FLIS for predicting hepatic decompensation and transplant-free survival in patients with CLD. Materials and Methods Patients with CLD who had undergone gadoxetic acid-enhanced liver MRI, including T1-weighted volume-interpolated breath-hold examination sequences with fat suppression, performed between 2011 and 2015 were included. FLIS was assigned on the basis of the sum of three hepatobiliary phase features, each scored on an ordinal 0-2 scale: hepatic enhancement, biliary excretion, and the signal intensity in the portal vein. Patients were stratified into the following three groups according to fibrosis stage and a presence or history of hepatic decompensation: nonadvanced CLD, compensated advanced CLD (CACLD), and decompensated advanced CLD (DACLD). The predictive value of FLIS for first and/or further hepatic decompensation and for transplant-free survival was investigated by using Kaplan-Meier analysis, log-rank tests, and Cox regression analysis. Results This study evaluated 265 patients (53 years ± 14 [standard deviation]; 164 men). Intraobserver (κ = 0.98; 95% confidence interval: 0.97, 0.99) and interobserver (κ = 0.93; 95% confidence interval: 0.90, 0.95) agreement for FLIS were excellent. In patients with CACLD, the FLIS was independently predictive of a first hepatic decompensation (adjusted hazard ratio, 3.7; 95% confidence interval: 1.1, 12.6; P = .04), but not for further hepatic decompensations in patients with DACLD (adjusted hazard ratio, 1.4; 95% confidence interval: 0.9, 1.9; P = .17). The FLIS was an independent risk factor for mortality in both patients with CACLD (adjusted hazard ratio, 7.4; 95% confidence interval: 2.7, 20.2; P < .001) and those with DACLD (adjusted hazard ratio, 3.8; 95% confidence interval: 1.7, 9.5; P = .004). Conclusion The functional liver imaging score derived from gadoxetic acid-enhanced MRI identified patients with advanced chronic liver disease who are at increased risk for a first hepatic decompensation and for mortality. © RSNA, 2019 Online supplemental material is available for this article.

The aim of this study was to compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the immune RECIST (iRECIST) criteria, and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 in patients with advanced non-small cell lung cancer treated with programmed cell death protein 1 (PD-1)/programmed cell death protein 1 ligand (PD-L1) inhibitors.This prospective study of 42 patients treated with a PD-1/PD-L1 inhibitor was approved by our institutional review board, and all patients gave written, informed consent. Tumor burden dynamics were assessed on F-FDG PET/CT before and after treatment initiation. Immunotherapeutic responses were evaluated according to RECIST 1.1, iRECIST, and PERCIST 1.0 for the dichotomous groups, responders versus nonresponders. Cohen κ and Wilcoxon signed rank tests were used to evaluate concordance among these criteria. We assessed progression-free survival and overall survival using the Kaplan-Meier estimator.The RECIST 1.1 and PERCIST 1.0 response classifications were discordant in 6 patients (14.2%; κ = 0.581). RECIST 1.1 and iRECIST were discordant in 2 patients, who evidenced pseudoprogression after treatment initiation. Median progression-free survival, as well as overall survival, was significantly longer for responders compared with nonresponders for all criteria (P0.001), with no significant difference between the 3 criteria (P0.05).RECIST 1.1 and PERCIST 1.0 show only moderate agreement, but both can predict treatment response to PD-1/PD-L1 inhibitor therapy. In case of pseudoprogression, metabolic tumor activity may help to correctly classify treatment response.

High grade serous ovarian cancer (HGSOC) is a highly heterogeneous disease that often presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to measuring response to neoadjuvant chemotherapy (NACT) and understanding its determinants. Here we propose a radiogenomic framework integrating clinical, radiomic, and blood-based biomarkers to measure and predict the response of HGSOC patients to NACT, showing how quantitative imaging data can serve as the backbone of multi-scale data integration. We developed and validated our approach in two independent highly-annotated multi-omic multi-lesion data sets. In a discovery cohort (n=72) we found that different tumour sites present distinct response patterns, and identified volumetric response assessment as a better predictor of overall survival (OS) than RECIST 1.1 status. We trained an ensemble machine learning approach to predict tumour volume response to NACT from data obtained prior to treatment, and validated the model in an internal hold-out cohort (n=20) and an independent external patient cohort (n=42). Benchmarking integrated models against models built on single data types highlighted the importance of comprehensive patient characterisation. Our study sets the foundation for developing new clinical trials of NACT in HGSOC.

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1–13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7–11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5–6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. Significance: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7–11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Funder: Horizon 2020; doi: http://dx.doi.org/10.13039/501100007601, Funder: Cancer Research UK, Funder: Mark Foundation For Cancer Research; doi: http://dx.doi.org/10.13039/100014599, Purpose: To develop a precision tissue sampling technique that uses computed tomography (CT)–based radiomic tumour habitats for ultrasound (US)-guided targeted biopsies that can be integrated in the clinical workflow of patients with high-grade serous ovarian cancer (HGSOC). Methods: Six patients with suspected HGSOC scheduled for US-guided biopsy before starting neoadjuvant chemotherapy were included in this prospective study from September 2019 to February 2020. The tumour segmentation was performed manually on the pre-biopsy contrast-enhanced CT scan. Spatial radiomic maps were used to identify tumour areas with similar or distinct radiomic patterns, and tumour habitats were identified using the Gaussian mixture modelling. CT images with superimposed habitat maps were co-registered with US images by means of a landmark-based rigid registration method for US-guided targeted biopsies. The dice similarity coefficient (DSC) was used to assess the tumour-specific CT/US fusion accuracy. Results: We successfully co-registered CT-based radiomic tumour habitats with US images in all patients. The median time between CT scan and biopsy was 21 days (range 7–30 days). The median DSC for tumour-specific CT/US fusion accuracy was 0.53 (range 0.79 to 0.37). The CT/US fusion accuracy was high for the larger pelvic tumours (DSC: 0.76–0.79) while it was lower for the smaller omental metastases (DSC: 0.37–0.53). Conclusion: We developed a precision tissue sampling technique that uses radiomic habitats to guide in vivo biopsies using CT/US fusion and that can be seamlessly integrated in the clinical routine for patients with HGSOC. Key Points: • We developed a prevision tissue sampling technique that co-registers CT-based radiomics–based tumour habitats with US images. • The CT/US fusion accuracy was high for the larger pelvic tumours (DSC: 0.76–0.79) while it was lower for the smaller omental metastases (DSC: 0.37–0.53).

The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA&ndash, miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1&beta, and INF&gamma, synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions.

Zusammenfassung Klinisches/methodisches Problem Seit dem Auftreten des neuartigen Coronavirus Ende 2019 und der damit verbundenen Erkrankung – Coronavirus Disease 2019 (COVID-19) – kam es zum Ausrufen einer Pandemie durch die Weltgesundheitsorganisation (WHO). Der Referenzstandard für die Diagnose ist der Virusnachweis mittels „reverse transcription polymerase chain reaction“ (RT-PCR). Bei hoher Spezifizität ist die Sensitivität der RT-PCR jedoch stark abhängig von der Symptomdauer, der Viruslast, der Qualität der Probe sowie des verwendeten Tests. Radiologische Standardverfahren Im Rahmen von COVID-19 werden primär Thoraxröntgen und Thorax-Computertomographie(CT) zur Erkennung von Lungenmanifestationen bzw. deren Ausdehnung und von Komplikationen eingesetzt. Leistungsfähigkeit Die Sensitivität und Spezifizität des Thoraxröntgens bei COVID-19 ist gering. Die Thorax-CT weist eine hohe Sensitivität von ungefähr 90 % bei jedoch geringer Spezifizität auf (zwischen 25 und 33 %). Empfehlung für die Praxis Die Indikation für die Durchführung von Bildgebung im Rahmen von COVID-19 sollte immer mit Bedacht gestellt werden, um das Übertragungsrisiko für medizinisches Personal und andere Patienten zu minimieren. Die Bildgebung ist vor allem hilfreich zur Evaluierung des Ausmaßes der Lungenbeteiligung der Erkrankung, zur Abgrenzung von Komplikationen und Differenzialdiagnosen. Typischerweise zeigen sich bilaterale, subpleurale Milchglasverdichtungen mit oder ohne Konsolidierungsareale. Im Verlauf können auch Veränderungen einer organisierenden Pneumonie beobachtet werden. Bei Untersuchungen nach Genesung einer COVID-19-Pneumonie ist auf fibrotische Lungenveränderungen zu achten.

PURPOSE Spatial heterogeneity of tumors is a major challenge in precision oncology. The relationship between molecular and imaging heterogeneity is still poorly understood because it relies on the accurate coregistration of medical images and tissue biopsies. Tumor molds can guide the localization of biopsies, but their creation is time consuming, technologically challenging, and difficult to interface with routine clinical practice. These hurdles have so far hindered the progress in the area of multiscale integration of tumor heterogeneity data. METHODS We have developed an open-source computational framework to automatically produce patient-specific 3-dimensional–printed molds that can be used in the clinical setting. Our approach achieves accurate coregistration of sampling location between tissue and imaging, and integrates seamlessly with clinical, imaging, and pathology workflows. RESULTS We applied our framework to patients with renal cancer undergoing radical nephrectomy. We created personalized molds for 6 patients, obtaining Dice similarity coefficients between imaging and tissue sections ranging from 0.86 to 0.96 for tumor regions and between 0.70 and 0.76 for healthy kidneys. The framework required minimal manual intervention, producing the final mold design in just minutes, while automatically taking into account clinical considerations such as a preference for specific cutting planes. CONCLUSION Our work provides a robust and automated interface between imaging and tissue samples, enabling the development of clinical studies to probe tumor heterogeneity on multiple spatial scales.

WFDC proteins such as peptidase inhibitor 3 and SLPI inhibit proteases in the epidermis and other tissues. In this study, we tested the hypothesis that further WFDC protein family members might contribute to epidermal homeostasis. We found that in addition to peptidase inhibitor 3 and SLPI, WFDC5 and WFDC12 were expressed in human epidermis. In contrast to WFDC5, the expression of WFDC12 was induced during the late differentiation of keratinocytes and was restricted to the outermost layer of live cells. Single-cell RNA sequencing demonstrated that WFDC12-positive keratinocytes were characterized by the upregulation of LCE mRNA expression and downregulated the expression of keratins and claudins. Immunogold-electron microscopy revealed the colocalization of WFDC12 with corneodesmosomes in the lower stratum corneum. WFDC12 was elevated in the affected skin of patients with psoriasis, atopic dermatitis, and Darier disease. By contrast, WFDC12 expression was strongly upregulated not only in the affected but even more so in clinically normal-appearing skin of patients with Netherton syndrome. Finally, functional analysis showed distinct inhibitory activity of WFDC12 on neutrophil elastase and epidermal kallikrein‒related peptidase. Altogether, our study identified WFDC12 as a marker of the last stage of epidermal keratinocyte differentiation and suggests that WFDC12 contributes to the control of protease activity in the stratum corneum.

Lung cancer is the third most common cancer in the UK and is the leading cause of death. Radiology plays a central role in the diagnostic work-up of patients with suspected and known lung cancer. Tumour assessment includes both local staging, as well as distant staging. Local staging objectives include the assessment of technical resectability with regard to the evaluation of tumour size and invasion of surrounding structures. Distant staging objectives aim to identify distant metastasis in lymphatic and extra lymphatic tissues. CT, positron emission tomography/CT, MRI, and ultrasound are routinely used imaging techniques for staging in patients with lung cancer. In this review, we will consider the pitfalls of these examinations that radiologists potentially face during the work-up of patients with lung cancer.

Purpose To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material–enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods In this institutional review board–approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent 13C MRI after injection of hyperpolarized [1–carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The 13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized 13C MRI and the pharmacokinetic parameters transfer constant (Ktrans) and washout parameter (kep) derived from DCE MRI were compared before and after treatment. Results Exchange of the 13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean Ktrans (132%) and mean kep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion Hyperpolarized 13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI. Published under a CC BY 4.0 license.