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Objectives To demonstrate the feasibility of an automated, non-invasive approach to estimate bone marrow (BM) infiltration of multiple myeloma (MM) by dual-energy computed tomography (DECT) after virtual non-calcium (VNCa) post-processing. Methods Individuals with MM and monoclonal gammopathy of unknown significance (MGUS) with concurrent DECT and BM biopsy between May 2018 and July 2020 were included in this retrospective observational study. Two pathologists and three radiologists reported BM infiltration and presence of osteolytic bone lesions, respectively. Bone mineral density (BMD) was quantified CT-based by a CE-certified software. Automated spine segmentation was implemented by a pre-trained convolutional neural network. The non-fatty portion of BM was defined as voxels > 0 HU in VNCa. For statistical assessment, multivariate regression and receiver operating characteristic (ROC) were conducted. Results Thirty-five patients (mean age 65 ± 12 years; 18 female) were evaluated. The non-fatty portion of BM significantly predicted BM infiltration after adjusting for the covariable BMD ( p  = 0.007, r  = 0.46). A non-fatty portion of BM > 0.93% could anticipate osteolytic lesions and the clinical diagnosis of MM with an area under the ROC curve of 0.70 [0.49–0.90] and 0.71 [0.54–0.89], respectively. Our approach identified MM-patients without osteolytic lesions on conventional CT with a sensitivity and specificity of 0.63 and 0.71, respectively. Conclusions Automated, AI-supported attenuation assessment of the spine in DECT VNCa is feasible to predict BM infiltration in MM. Further, the proposed method might allow for pre-selecting patients with higher pre-test probability of osteolytic bone lesions and support the clinical diagnosis of MM without pathognomonic lesions on conventional CT. Key Points • The retrospective study provides an automated approach for quantification of the non-fatty portion of bone marrow, based on AI-supported spine segmentation and virtual non-calcium dual-energy CT data. • An increasing non-fatty portion of bone marrow is associated with a higher infiltration determined by invasive biopsy after adjusting for bone mineral density as a control variable (p  =  0.007, r  =  0.46). • The non-fatty portion of bone marrow might support the clinical diagnosis of multiple myeloma when conventional CT images are negative (sensitivity 0.63, specificity 0.71).

The presented work explores the regulatory influence of upstream open reading frames (uORFs) on gene expression in Trypanosoma congolense. More than 31,000 uORFs in total were identified and characterized here. We found evidence for the uORFs' appearance in the transcriptome to be correlated with proteomic expression data, clearly indicating their repressive potential in T. congolense, which has to rely on post-transcriptional gene expression regulation due to its unique genomic organization. Our data show that uORF's translation repressive potential does not only correlate with elemental sequence features such as length, position and quantity, but involves more subtle components, in particular the codon and amino acid profiles. This corresponds with the popular mechanistic model of a ribosome shedding initiation factors during the translation of a uORF, which can prevent reinitiation at the downstream start codon of the actual protein-coding sequence, due to the former extensive consumption of crucial translation components. We suggest that uORFs with uncommon codon and amino acid usage can slow down the translation elongation process in T. congolense, systematically deplete the limited factors, and restrict downstream reinitiation, setting up a bottleneck for subsequent translation of the protein-coding sequence. Additionally we conclude that uORFs dynamically influence the T. congolense life cycle. We found evidence that transition to epimastigote form could be supported by gain of uORFs due to alternative trans-splicing, which down-regulate housekeeping genes' expression and render the trypanosome in a metabolically reduced state of endurance.

To evaluate the association between the coronavirus disease 2019 (COVID-19) and post-inflammatory emphysematous lung alterations on follow-up low-dose CT scans. Consecutive patients with proven COVID-19 infection and a follow-up CT were retrospectively reviewed. The severity of pulmonary involvement was classified as mild, moderate and severe. Total lung volume, emphysema volume and the ratio of emphysema/-to-lung volume were quantified semi-automatically and compared inter-individually between initial and follow-up CT and to a control group of healthy, age- and sex-matched patients. Lung density was further assessed by drawing circular regions of interest (ROIs) into non-affected regions of the upper lobes. A total of 32 individuals (mean age: 64 ± 13 years, 12 females) with at least one follow-up CT (mean: 52 ± 66 days, range: 5-259) were included. In the overall cohort, total lung volume, emphysema volume and the ratio of lung-to-emphysema volume did not differ significantly between the initial and follow-up scans. In the subgroup of COVID-19 patients with > 30 days of follow-up, the emphysema volume was significantly larger as compared to the subgroup with a follow-up < 30 days (p = 0.045). Manually measured single ROIs generally yielded lower attenuation values prior to COVID-19 pneumonia, but the difference was not significant between groups (all p > 0.05). COVID-19 patients with a follow-up CT >30 days showed significant emphysematous lung alterations. These findings may help to explain the long-term effect of COVID-19 on pulmonary function and warrant validation by further studies.

The latest advancement of artificial intelligence (AI) is generative pretrained transformer large language models (LLMs). They have been trained on massive amounts of text, enabling humanlike and semantical responses to text-based inputs and requests. Foreshadowing numerous possible applications in various fields, the potential of such tools for medical data integration and clinical decision-making is not yet clear. In this study, we investigate the potential of LLMs in report-based medical decision-making on the example of acute ischemic stroke (AIS), where clinical and image-based information may indicate an immediate need for mechanical thrombectomy (MT). The purpose was to elucidate the feasibility of integrating radiology report data and other clinical information in the context of therapy decision-making using LLMs. A hundred patients with AIS were retrospectively included, for which 50% (50/100) was indicated for MT, whereas the other 50% (50/100) was not. The LLM was provided with the computed tomography report, information on neurological symptoms and onset, and patients' age. The performance of the AI decision-making model was compared with an expert consensus regarding the binary determination of MT indication, for which sensitivity, specificity, and accuracy were calculated. The AI model had an overall accuracy of 88%, with a specificity of 96% and a sensitivity of 80%. The area under the curve for the report-based MT decision was 0.92. The LLM achieved promising accuracy in determining the eligibility of patients with AIS for MT based on radiology reports and clinical information. Our results underscore the potential of LLMs for radiological and medical data integration. This investigation should serve as a stimulus for further clinical applications of LLMs, in which this AI should be used as an augmented supporting system for human decision-making.

Cardiovascular comorbidity anticipates poor prognosis of SARS-CoV-2 disease (COVID-19) and correlates with the systemic atherosclerotic transformation of the arterial vessels. The amount of aortic wall calcification (AWC) can be estimated on low-dose chest CT. We suggest quantification of AWC on the low-dose chest CT, which is initially performed for the diagnosis of COVID-19, to screen for patients at risk of severe COVID-19. Seventy consecutive patients (46 in center 1, 24 in center 2) with parallel low-dose chest CT and positive RT-PCR for SARS-CoV-2 were included in our multi-center, multi-vendor study. The outcome was rated moderate (no hospitalization, hospitalization) and severe (ICU, tracheal intubation, death), the latter implying a requirement for intensive care treatment. The amount of AWC was quantified with the CT vendor's software. Of 70 included patients, 38 developed a moderate, and 32 a severe COVID-19. The average volume of AWC was significantly higher throughout the subgroup with severe COVID-19, when compared to moderate cases (771.7 mm3 (Q1 = 49.8 mm3, Q3 = 3065.5 mm3) vs. 0 mm3 (Q1 = 0 mm3, Q3 = 57.3 mm3)). Within multivariate regression analysis, including AWC, patient age and sex, as well as a cardiovascular comorbidity score, the volume of AWC was the only significant regressor for severe COVID-19 (p = 0.004). For AWC > 3000 mm3, the logistic regression predicts risk for a severe progression of 0.78. If there are no visually detectable AWC risk for severe progression is 0.13, only. AWC seems to be an independent biomarker for the prediction of severe progression and intensive care treatment of COVID-19 already at the time of patient admission to the hospital; verification in a larger multi-center, multi-vendor study is desired.

Compressed sensing accelerates magnetic resonance imaging (MRI) acquisition by undersampling of the k-space. Yet, excessive undersampling impairs image quality when using conventional reconstruction techniques. Deep-learning-based reconstruction methods might allow for stronger undersampling and thus faster MRI scans without loss of crucial image quality. We compared imaging approaches using parallel imaging (SENSE), a combination of parallel imaging and compressed sensing (COMPRESSED SENSE, CS), and a combination of CS and a deep-learning-based reconstruction (CS AI) on raw k-space data acquired at different undersampling factors. 3D T2-weighted images of the lumbar spine were obtained from 20 volunteers, including a 3D sequence (standard SENSE), as provided by the manufacturer, as well as accelerated 3D sequences (undersampling factors 4.5, 8, and 11) reconstructed with CS and CS AI. Subjective rating was performed using a 5-point Likert scale to evaluate anatomical structures and overall image impression. Objective rating was performed using apparent signal-to-noise and contrast-to-noise ratio (aSNR and aCNR) as well as root mean square error (RMSE) and structural-similarity index (SSIM). The CS AI 4.5 sequence was subjectively rated better than the standard in several categories and deep-learning-based reconstructions were subjectively rated better than conventional reconstructions in several categories for acceleration factors 8 and 11. In the objective rating, only aSNR of the bone showed a significant tendency towards better results of the deep-learning-based reconstructions. We conclude that CS in combination with deep-learning-based image reconstruction allows for stronger undersampling of k-space data without loss of image quality, and thus has potential for further scan time reduction.

Cardiovascular comorbidity anticipates severe progression of COVID-19 and becomes evident by coronary artery calcification (CAC) on low-dose chest computed tomography (LDCT). The purpose of this study was to predict a patient's obligation of intensive care treatment by evaluating the coronary calcium burden on the initial diagnostic LDCT. Eighty-nine consecutive patients with parallel LDCT and positive RT-PCR for SARS-CoV-2 were included from three centers. The primary endpoint was admission to ICU, tracheal intubation, or death in the 22-day follow-up period. CAC burden was represented by the Agatston score. Multivariate logistic regression was modeled for prediction of the primary endpoint by the independent variables \"Agatston score > 0\", as well as the CT lung involvement score, patient sex, age, clinical predictors of severe COVID-19 progression (history of hypertension, diabetes, prior cardiovascular event, active smoking, or hyperlipidemia), and laboratory parameters (creatinine, C-reactive protein, leucocyte, as well as thrombocyte counts, relative lymphocyte count, d-dimer, and lactate dehydrogenase levels). After excluding multicollinearity, \"Agatston score >0\" was an independent regressor within multivariate analysis for prediction of the primary endpoint (p<0.01). Further independent regressors were creatinine (p = 0.02) and leucocyte count (p = 0.04). The Agatston score was significantly higher for COVID-19 cases which completed the primary endpoint (64.2 [interquartile range 1.7-409.4] vs. 0 [interquartile range 0-0]). CAC scoring on LDCT might help to predict future obligation of intensive care treatment at the day of patient admission to the hospital.

The multi-dimensional RACOON Viral Pneumonia Score (RVPS) was developed to compensate for the main weaknesses of the established one-dimensional chest computed tomography (CT) scores. It aimed to quantify the severity of pneumonia and qualitatively monitor infectious lung disease from the acute stage to post-pneumonic sequelae. This research focuses on the original development and evaluation of applicability and inter-reader reliability of the RVPS. Within the Radiological Cooperative Network (RACOON), the scoring system was developed after several expert meetings and tested in this proof-of-concept study with 8,525 observations. In the subset of inter-reader validation (7,800 observations), eight blinded radiologists applied the RVPS and evaluated the following CT findings for each lung lobe individually: (I) pure ground glass opacities (GGO), (II) GGO and interstitial thickening, (III) consolidations, (IV) linear opacities and reticulations, and (V) fibrotic-like changes. The extent of each pathology was scored on a scale of 0-5 points, and the total involvement was calculated. Inter-reader variability was assessed using Kendall's W. Overall inter-reader reliability of the RVPS was excellent (Kendalls' W 0.95). CT findings associated with acute pneumonia were scored with good agreement (W 0.81-0.87). Moderate uncertainty was introduced when separating category IV vs. category V findings (W 0.55-0.69). The overall extent of post-infectious findings was assessed with good agreement (W 0.79). The longitudinal distribution of subscores allowed for differentiation between acute pneumonia and post-pneumonic sequelae. This study presents the RVPS as a comprehensive tool for inter-reader reliable evaluation, longitudinal monitoring, and structured documentation of the extent as well as quality of chest CT findings in infectious lung disease.

Virtual non-calcium (VNCa) images from dual-energy computed tomography (DECT) have shown high potential to diagnose bone marrow disease of the spine, which is frequently disguised by dense trabecular bone on conventional CT. In this study, we aimed to define reference values for VNCa bone marrow images of the spine in a large-scale cohort of healthy individuals. DECT was performed after resection of a malignant skin tumor without evidence of metastatic disease. Image analysis was fully automated and did not require specific user interaction. The thoracolumbar spine was segmented by a pretrained convolutional neuronal network. Volumetric VNCa data of the spine’s bone marrow space were processed using the maximum, medium, and low calcium suppression indices. Histograms of VNCa attenuation were created for each exam and suppression setting. We included 500 exams of 168 individuals (88 female, patient age 61.0 ± 15.9). A total of 8298 vertebrae were segmented. The attenuation histograms’ overlap of two consecutive exams, as a measure for intraindividual consistency, yielded a median of 0.93 (IQR: 0.88–0.96). As our main result, we provide the age- and sex-specific bone marrow attenuation profiles of a large-scale cohort of individuals with healthy trabecular bone structure as a reference for future studies. We conclude that artificial-intelligence-supported, fully automated volumetric assessment is an intraindividually robust method to image the spine’s bone marrow using VNCa data from DECT.

Background: in magnetic resonance imaging (MRI), automated detection of brain metastases with convolutional neural networks (CNN) represents an extraordinary challenge due to small lesions sometimes posing as brain vessels as well as other confounders. Literature reporting high false positive rates when using conventional contrast enhanced (CE) T1 sequences questions their usefulness in clinical routine. CE black blood (BB) sequences may overcome these limitations by suppressing contrast-enhanced structures, thus facilitating lesion detection. This study compared CNN performance in conventional CE T1 and BB sequences and tested for objective improvement of brain lesion detection. Methods: we included a subgroup of 127 consecutive patients, receiving both CE T1 and BB sequences, referred for MRI concerning metastatic spread to the brain. A pretrained CNN was retrained with a customized monolayer classifier using either T1 or BB scans of brain lesions. Results: CE T1 imaging-based training resulted in an internal validation accuracy of 85.5% vs. 92.3% in BB imaging (p < 0.01). In holdout validation analysis, T1 image-based prediction presented poor specificity and sensitivity with an AUC of 0.53 compared to 0.87 in BB-imaging-based prediction. Conclusions: detection of brain lesions with CNN, BB-MRI imaging represents a highly effective input type when compared to conventional CE T1-MRI imaging. Use of BB-MRI can overcome the current limitations for automated brain lesion detection and the objectively excellent performance of our CNN suggests routine usage of BB sequences for radiological analysis.