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Abstract Background Dark-field radiography imaging exploits the wave character of x-rays to measure small-angle scattering on material interfaces, providing structural information with low radiation exposure. We explored the potential of dark-field imaging of bone microstructure to improve the assessment of bone strength in osteoporosis. Methods We prospectively examined 14 osteoporotic/osteopenic and 21 non-osteoporotic/osteopenic human cadaveric vertebrae (L2–L4) with a clinical dark-field radiography system, micro-computed tomography (CT), and spectral CT. Dark-field images were obtained in both vertical and horizontal sample positions. Bone microstructural parameters (trabecular number, Tb.N; trabecular thickness, Tb.Th; bone volume fraction, BV/TV; degree of anisotropy, DA) were measured using standard ex vivo micro-CT, while hydroxyapatite density was measured using spectral CT. Correlations were assessed using Spearman rank correlation coefficients. Results The measured dark-field signal was lower in osteoporotic/osteopenic vertebrae (vertical position, 0.23 ± 0.05 versus 0.29 ± 0.04, p

Abstract Background The successful integration of artificial intelligence (AI) in healthcare depends on the global perspectives of all stakeholders. This study aims to answer the research question: What are the attitudes of medical, dental, and veterinary students towards AI in education and practice, and what are the regional differences in these perceptions? Methods An anonymous online survey was developed based on a literature review and expert panel discussions. The survey assessed students' AI knowledge, attitudes towards AI in healthcare, current state of AI education, and preferences for AI teaching. It consisted of 16 multiple-choice items, eight demographic queries, and one free-field comment section. Medical, dental, and veterinary students from various countries were invited to participate via faculty newsletters and courses. The survey measured technological literacy, AI knowledge, current state of AI education, preferences for AI teaching, and attitudes towards AI in healthcare using Likert scales. Data were analyzed using descriptive statistics, Mann–Whitney U-test, Kruskal–Wallis test, and Dunn-Bonferroni post hoc test. Results The survey included 4313 medical, 205 dentistry, and 78 veterinary students from 192 faculties and 48 countries. Most participants were from Europe (51.1%), followed by North/South America (23.3%) and Asia (21.3%). Students reported positive attitudes towards AI in healthcare (median: 4, IQR: 3–4) and a desire for more AI teaching (median: 4, IQR: 4–5). However, they had limited AI knowledge (median: 2, IQR: 2–2), lack of AI courses (76.3%), and felt unprepared to use AI in their careers (median: 2, IQR: 1–3). Subgroup analyses revealed significant differences between the Global North and South (r = 0.025 to 0.185, all P

Abstract Background Nowadays, there is no method to quantitatively characterize the material composition of acute ischemic stroke thrombi prior to intervention, but dual-energy CT (DE-CT) offers imaging-based multimaterial decomposition. We retrospectively investigated the material composition of thrombi ex vivo using DE-CT with histological analysis as a reference. Methods Clots of 70 patients with acute ischemic stroke were extracted by mechanical thrombectomy and scanned ex vivo in formalin-filled tubes with DE-CT. Multimaterial decomposition in the three components, i.e., red blood cells (RBC), white blood cells (WBC), and fibrin/platelets (F/P), was performed and compared to histology (hematoxylin/eosin staining) as reference. Attenuation and effective Z values were assessed, and histological composition was compared to stroke etiology according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Results Histological and imaging analysis showed the following correlation coefficients for RBC (r = 0.527, p

Abstract When dealing with a newly emerging disease such as COVID-19, the impact of patient- and disease-specific factors (e.g., body weight or known co-morbidities) on the immediate course of the disease is largely unknown. An accurate prediction of the most likely individual disease progression can improve the planning of limited resources and finding the optimal treatment for patients. In the case of COVID-19, the need for intensive care unit (ICU) admission of pneumonia patients can often only be determined on short notice by acute indicators such as vital signs (e.g., breathing rate, blood oxygen levels), whereas statistical analysis and decision support systems that integrate all of the available data could enable an earlier prognosis. To this end, we propose a holistic, multimodal graph-based approach combining imaging and non-imaging information. Specifically, we introduce a multimodal similarity metric to build a population graph that shows a clustering of patients. For each patient in the graph, we extract radiomic features from a segmentation network that also serves as a latent image feature encoder. Together with clinical patient data like vital signs, demographics, and lab results, these modalities are combined into a multimodal representation of each patient. This feature extraction is trained end-to-end with an image-based Graph Attention Network to process the population graph and predict the COVID-19 patient outcomes: admission to ICU, need for ventilation, and mortality. To combine multiple modalities, radiomic features are extracted from chest CTs using a segmentation neural network. Results on a dataset collected in Klinikum rechts der Isar in Munich, Germany and the publicly available iCTCF dataset show that our approach outperforms single modality and non-graph baselines. Moreover, our clustering and graph attention increases understanding of the patient relationships within the population graph and provides insight into the network’s decision-making process.

Cardiac motion causes unpredictable signal loss in respiratory-triggered diffusion-weighted magnetic resonance imaging (DWI) of the liver, especially inside the left lobe. The left liver lobe may thus be frequently neglected in the clinical evaluation of liver DWI. In this work, a data-driven algorithm that relies on the statistics of the signal in the left liver lobe to mitigate the motion-induced signal loss is presented. The proposed data-driven algorithm utilizes the exclusion of severely corrupted images with subsequent spatially dependent image scaling based on a signal-loss model to correctly combine the multi-average diffusion-weighted images. The signal in the left liver lobe is restored and the liver signal is more homogeneous after applying the proposed algorithm. Furthermore, overestimation of the apparent diffusion coefficient (ADC) in the left liver lobe is reduced. The proposed algorithm can therefore contribute to reduce the motion-induced bias in DWI of the liver and help to increase the diagnostic value of DWI in the left liver lobe.

Abstract Background To determine whether denoised areal bone mineral density (BMD) measurements from scout scans in spectral detector computed tomography (CT) correlate with volumetric trabecular BMD for opportunistic osteoporosis screening. Methods A 64-slice single-source dual-layer spectral CT scanner was used to acquire scout scan data of 228 lumbar vertebral bodies within 57 patients. Scout scans in anterior–posterior (AP) view were performed with a dose of

Frank, Gassert et al. use dark-field chest X-ray imaging to assess COVID-19-pneumonia. Dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and provides an ultralow dose alternative to computed tomography imaging for that purpose.

Abstract Background To investigate the detection capabilities of myocardial perfusion defects of dual-energy computed tomography (CT) technology using time-resolved iodine-based maps for functional assessment of coronary stenosis in a dynamic heart phantom. Methods An anatomical heart model was designed using a three-dimensional (3D) printing technique. The lumen of the right coronary artery was reduced to 25% of the original areal cross-section. Scans were acquired with a 64-slice dual-layer CT equipment using a perfusion protocol with 36 time points. For distinguishing haemodynamically affected from unaffected myocardial regions, conventional and spectral mean transit time (MTT) parameter maps were compared. A dose reduction technique was simulated by using a subset of time points of the time attenuation curves (TACs). Results The tracer kinetic modeling showed decreased errors on fit parameters from conventional to spectral TACs (42% reduction for A and 40% for λ). Three characteristic regions (highly, moderately, and not affected by the simulated stenosis) can be distinguished in all spectral perfusion maps. The best distinction was observed on MTT maps. An area under the curve (AUC) value of 1.00 for the voxel-wise differentiation of haemodynamically affected tissue was achieved versus a 0.89 AUC for conventional MTT maps. By temporal under-sampling, a dose reduction of approximately 78% from 19 to 4.3 mSv was achieved with a 0.96 AUC. Conclusion Dual-energy CT can provide time-resolved iodine density data, which enables the calculation of absolute quantitative perfusion maps with decreased fitting errors, improving the accuracy for poststenotic myocardial ischaemic detection in a 3D-printed heart phantom.

Abstract The separation of mixtures of substances into their individual components plays an important role in many areas of science. In medical imaging, one method is the established analysis using dual-energy computed tomography. However, when analyzing mixtures consisting of more than three individual basis materials, a physical limit is reached that no longer allows this standard analysis. In addition, the X-ray attenuation coefficients of chemically complicated basis materials may not be known and also cannot be determined by other or previous analyses. To address these issues, we developed a novel theoretical approach and algorithm and tested it on samples prepared in the laboratory as well as on ex-vivo medical samples. This method allowed both five-material decomposition and determination or optimization of the X-ray attenuation coefficients of the sample base materials via optimizations of objective functions. After implementation, this new multimodal method was successfully tested on self-mixed samples consisting of the aqueous base solutions iomeprol, eosin Y disodiumsalt, sodium chloride, and pure water. As a first proof of concept of this technique for detailed material decomposition in medicine we analyzed exact percentage composition of ex vivo clots from patients with acute ischemic stroke, using histological analysis as a reference standard.

Background: Dark-field imaging is a novel imaging modality that allows for the assessment of material interfaces by exploiting the wave character of x-ray. While it has been extensively studied in chest imaging, only little is known about the modality for imaging other tissues. Therefore, the purpose of this study was to evaluate whether a clinical X-ray dark-field scanner prototype allows for the assessment of osteoporosis.Materials and methods: In this prospective study we examined human cadaveric lumbar spine specimens (vertebral segments L2 to L4). We used a clinical prototype for dark-field radiography that yields both attenuation and dark-field images. All specimens were scanned in lateral orientation in vertical and horizontal position. All specimens were additionally imaged with CT as reference. Bone mineral density (BMD) values were derived from asynchronously calibrated quantitative CT measurements. Correlations between attenuation signal, dark-field signal and BMD were assessed using Spearman’s rank correlation coefficients. The capability of the dark-field signal for the detection of osteoporosis/osteopenia was evaluated with receiver operating characteristics (ROC) curve analysis.Results: A total of 58 vertebrae from 20 human cadaveric spine specimens (mean age, 73 years ±13 [standard deviation]; 11 women) were studied. The dark-field signal was positively correlated with the BMD, both in vertical (r = 0.56, p < .001) and horizontal position (r = 0.43, p < .001). Also, the dark-field signal ratio was positively correlated with BMD (r = 0.30, p = .02). No correlation was found between the signal ratio of attenuation signal and BMD (r = 0.14, p = .29). For the differentiation between specimens with and without osteoporosis/osteopenia, the area under the ROC curve (AUC) was 0.80 for the dark-field signal in vertical position.Conclusion: Dark-field imaging allows for the differentiation between spine specimens with and without osteoporosis/osteopenia and may therefore be a potential biomarker for bone stability.

New biomarkers are required to improve the assessment of aortic wall integrity and risk of rupture. Here the authors report the development of an imaging probe for ADAMTS4, which they test in an abdominal aortic aneurysm mouse model and show in vivo prediction of aneurysm and rupture.

Abstract Background Spirometry and conventional chest x-ray have limitations in investigating early emphysema, while computed tomography, the reference imaging method in this context, is not part of routine patient care due to its higher radiation dose. In this work, we investigated a novel low-dose imaging modality, dark-field chest x-ray, for the evaluation of emphysema in patients with alpha1-antitrypsin deficiency. Methods By exploiting wave properties of x-rays for contrast formation, dark-field chest x-ray visualises the structural integrity of the alveoli, represented by a high signal over the lungs in the dark-field image. We investigated four patients with alpha1-antitrypsin deficiency with a novel dark-field x-ray prototype and simultaneous conventional chest x-ray. The extent of pulmonary function impairment was assessed by pulmonary function measurement and regional emphysema distribution was compared with CT in one patient. Results We show that dark-field chest x-ray visualises the extent of pulmonary emphysema displaying severity and regional differences. Areas with low dark-field signal correlate with emphysematous changes detected by computed tomography using a threshold of -950 Hounsfield units. The airway parameters obtained by whole-body plethysmography and single breath diffusing capacity of the lungs for carbon monoxide demonstrated typical changes of advanced emphysema. Conclusions Dark-field chest x-ray directly visualised the severity and regional distribution of pulmonary emphysema compared to conventional chest x-ray in patients with alpha1-antitrypsin deficiency. Due to the ultra-low radiation dose in comparison to computed tomography, dark-field chest x-ray could be beneficial for long-term follow-up in these patients.

Abstract Background To evaluate the diagnostic value of MR-derived CT-like images and simulated radiographs compared with conventional radiographs in patients with suspected shoulder pathology. Methods 3 T MRI of the shoulder including a 3D T1-weighted gradient echo sequence was performed in 25 patients (mean age 52.4 ± 18 years, 13 women) with suspected shoulder pathology. Subsequently a cone-beam forward projection algorithm was used to obtain intensity-inverted CT-like images and simulated radiographs. Two radiologists evaluated the simulated images separately and independently using the conventional radiographs as the standard of reference, including measurements of the image quality, acromiohumeral distance, critical shoulder angle, degenerative joint changes and the acromial type. Additionally, the CT-like MR images were evaluated for glenoid defects, subcortical cysts and calcifications. Agreement between the MR-derived simulated radiographs and conventional radiographs was calculated using Cohen’s Kappa. Results Measurements on simulated radiographs and conventional radiographs overall showed a substantial to almost perfect inter- and intra-rater agreement (κ = 0.69–1.00 and κ = 0.65–0.85, respectively). Image quality of the simulated radiographs was rated good to excellent (1.6 ± 0.7 and 1.8 ± 0.6, respectively) by the radiologists. A substantial agreement was found regarding diagnostically relevant features, assessed on Y- and anteroposterior projections (κ = 0.84 and κ = 0.69 for the measurement of the CSA; κ = 0.95 and κ = 0.60 for the measurement of the AHD; κ = 0.77 and κ = 0.77 for grading of the Samilson-Prieto classification; κ = 0.83 and κ = 0.67 for the grading of the Bigliani classification, respectively). Conclusion In this proof-of-concept study, clinically relevant features of the shoulder joint were assessed reliably using MR-derived CT-like images and simulated radiographs with an image quality equivalent to conventional radiographs. MR-derived CT-like images and simulated radiographs may provide useful diagnostic information while reducing the amount of radiation exposure.

The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver’s metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver’s metabolic function in vivo. Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR) and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography–mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into ‘stiff’ and ‘soft’ subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange. In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients.

In the present work, we present a publicly available, expert-segmented representative dataset of 158 3.0 Tesla biparametric MRIs [1]. There is an increasing number of studies investigating prostate and prostate carcinoma segmentation using deep learning (DL) with 3D architectures [2–7]. The development of robust and data-driven DL models for prostate segmentation and assessment is currently limited by the availability of openly available expert-annotated datasets [8–10].The dataset contains 3.0 Tesla MRI images of the prostate of patients with suspected prostate cancer. Patients over 50 years of age who had a 3.0 Tesla MRI scan of the prostate that met PI-RADS version 2.1 technical standards were included. All patients received a subsequent biopsy or surgery so that the MRI diagnosis could be verified/matched with the histopathologic diagnosis. For patients who had undergone multiple MRIs, the last MRI, which was less than six months before biopsy/surgery, was included. All patients were examined at a German university hospital (Charité Universitätsmedizin Berlin) between 02/2016 and 01/2020. All MRI were acquired with two 3.0 Tesla MRI scanners (Siemens VIDA and Skyra, Siemens Healthineers, Erlangen, Germany). Axial T2W sequences and axial diffusion-weighted sequences (DWI) with apparent diffusion coefficient maps (ADC) were included in the data set.T2W sequences and ADC maps were annotated by two board-certified radiologists with 6 and 8 years of experience, respectively. For T2W sequences, the central gland (central zone and transitional zone) and peripheral zone were segmented. If areas of suspected prostate cancer (PIRADS score of ≥ 4) were identified on examination, they were segmented in both the T2W sequences and ADC maps.Because restricted diffusion is best seen in DWI images with high b-values, only these images were selected and all images with low b-values were discarded. Data were then anonymized and converted to NIfTI (Neuroimaging Informatics Technology Initiative) format.

BackgroundQuantitative magnetic resonance imaging (MRI) techniques such as chemical shift encoding-based water-fat separation techniques (CSE-MRI) are increasingly applied as noninvasive biomarkers to assess the biochemical composition of vertebrae. This study aims to investigate the longitudinal change of proton density fat fraction (PDFF) and T2* derived from CSE-MRI of the thoracolumbar vertebral bone marrow in patients that develop incidental vertebral compression fractures (VCFs), and whether PDFF and T2* enable the prediction of an incidental VCF.MethodsIn this study we included 48 patients with CT-derived bone mineral density (BMD) measurements at baseline. Patients that presented an incidental VCF at follow up (N=12, mean age 70.5 ± 7.4 years, 5 female) were compared to controls without incidental VCF at follow up (N=36, mean age 71.1 ± 8.6 years, 15 females). All patients underwent 3T MRI, containing a significant part of the thoracolumbar spine (Th11-L4), at baseline, 6-month and 12 month follow up, including a gradient echo sequence for chemical shift encoding-based water-fat separation, from which PDFF and T2* maps were obtained. Associations between changes in PDFF, T2* and BMD measurements over 12 months and the group (incidental VCF vs. no VCF) were assessed using multivariable regression models. Mixed-effect regression models were used to test if there is a difference in the rate of change in PDFF, T2* and BMD between patients with and without incidental VCF.ResultsPrior to the occurrence of an incidental VCF, PDFF in vertebrae increased in the VCF group (ΔPDFF=6.3 ± 3.1%) and was significantly higher than the change of PDFF in the group without VCF (ΔPDFF=2.1 ± 2.5%, P=0.03). There was no significant change in T2* (ΔT2*=1.7 ± 1.1ms vs. ΔT2*=1.1 ± 1.3ms, P=0.31) and BMD (ΔBMD=-1.2 ± 11.3mg/cm3 vs. ΔBMD=-11.4 ± 24.1mg/cm3, P= 0.37) between the two groups over 12 months. At baseline, no significant differences were detected in the average PDFF, T2* and BMD of all measured vertebrae (Th11-L4) between the VCF group and the group without VCF (P=0.66, P=0.35 and P= 0.21, respectively). When assessing the differences in rates of change, there was a significant change in slope for PDFF (2.32 per 6 months, 95% confidence interval (CI) 0.31-4.32; P=0.03) but not for T2* (0.02 per 6 months, CI -0.98-0.95; P=0.90) or BMD (-4.84 per 6 months, CI -23.4-13.7; P=0.60).ConclusionsIn our study population, the average change of PDFF over 12 months is significantly higher in patients that develop incidental fractures at 12-month follow up compared to patients without incidental VCF, while T2* and BMD show no significant changes prior to the occurrence of the incidental vertebral fractures. Therefore, a longitudinal increase in bone marrow PDFF may be predictive for vertebral compression fractures.

Abstract We present a method to generate synthetic thorax radiographs with realistic nodules from CT scans, and a perfect ground truth knowledge. We evaluated the detection performance of nine radiologists and two convolutional neural networks in a reader study. Nodules were artificially inserted into the lung of a CT volume and synthetic radiographs were obtained by forward-projecting the volume. Hence, our framework allowed for a detailed evaluation of CAD systems’ and radiologists’ performance due to the availability of accurate ground-truth labels for nodules from synthetic data. Radiographs for network training (U-Net and RetinaNet) were generated from 855 CT scans of a public dataset. For the reader study, 201 radiographs were generated from 21 nodule-free CT scans with altering nodule positions, sizes and nodule counts of inserted nodules. Average true positive detections by nine radiologists were 248.8 nodules, 51.7 false positive predicted nodules and 121.2 false negative predicted nodules. The best performing CAD system achieved 268 true positives, 66 false positives and 102 false negatives. Corresponding weighted alternative free response operating characteristic figure-of-merits (wAFROC FOM) for the radiologists range from 0.54 to 0.87 compared to a value of 0.81 (CI 0.75–0.87) for the best performing CNN. The CNN did not perform significantly better against the combined average of the 9 readers (p = 0.49). Paramediastinal nodules accounted for most false positive and false negative detections by readers, which can be explained by the presence of more tissue in this area.

Abstract Purpose In this prospective exploratory study, we evaluated the feasibility of [18F]fluorodeoxyglucose ([18F]FDG) PET/MRI-based chemotherapy response prediction in pancreatic ductal adenocarcinoma at two weeks upon therapy onset. Material and methods In a mixed cohort, seventeen patients treated with chemotherapy in neoadjuvant or palliative intent were enrolled. All patients were imaged by [18F]FDG PET/MRI before and two weeks after onset of chemotherapy. Response per RECIST1.1 was then assessed at 3 months [18F]FDG PET/MRI-derived parameters (MTV50%, TLG50%, MTV2.5, TLG2.5, SUVmax, SUVpeak, ADCmax, ADCmean and ADCmin) were assessed, using multiple t-test, Man–Whitney-U test and Fisher’s exact test for binary features. Results At 72 ± 43 days, twelve patients were classified as responders and five patients as non-responders. An increase in ∆MTV50% and ∆ADC (≥ 20% and 15%, respectively) and a decrease in ∆TLG50% (≤ 20%) at 2 weeks after chemotherapy onset enabled prediction of responders and non-responders, respectively. Parameter combinations (∆TLG50% and ∆ADCmax or ∆MTV50% and ∆ADCmax) further improved discrimination. Conclusion Multiparametric [18F]FDG PET/MRI-derived parameters, in particular indicators of a change in tumor glycolysis and cellularity, may enable very early chemotherapy response prediction. Further prospective studies in larger patient cohorts are recommended to their clinical impact.

Abstract Background Radiographs of the sacroiliac joints are commonly used for the diagnosis and classification of axial spondyloarthritis. The aim of this study was to develop and validate an artificial neural network for the detection of definite radiographic sacroiliitis as a manifestation of axial spondyloarthritis (axSpA). Methods Conventional radiographs of the sacroiliac joints obtained in two independent studies of patients with axSpA were used. The first cohort comprised 1553 radiographs and was split into training (n = 1324) and validation (n = 229) sets. The second cohort comprised 458 radiographs and was used as an independent test dataset. All radiographs were assessed in a central reading session, and the final decision on the presence or absence of definite radiographic sacroiliitis was used as a reference. The performance of the neural network was evaluated by calculating areas under the receiver operating characteristic curves (AUCs) as well as sensitivity and specificity. Cohen’s kappa and the absolute agreement were used to assess the agreement between the neural network and the human readers. Results The neural network achieved an excellent performance in the detection of definite radiographic sacroiliitis with an AUC of 0.97 and 0.94 for the validation and test datasets, respectively. Sensitivity and specificity for the cut-off weighting both measurements equally were 88% and 95% for the validation and 92% and 81% for the test set. The Cohen’s kappa between the neural network and the reference judgements were 0.79 and 0.72 for the validation and test sets with an absolute agreement of 90% and 88%, respectively. Conclusion Deep artificial neural networks enable the accurate detection of definite radiographic sacroiliitis relevant for the diagnosis and classification of axSpA.

Abstract Background In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates with high sensitivity, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR. Methods IgM/IgG chemiluminescent immunoassay was performed for 107 patients with confirmed (group A: PCR + ; CT ±) and 46 patients with suspected (group B: repetitive PCR-; CT +) COVID-19, admitted to a German university hospital during the pandemic’s first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia was used to assess the probability of COVID-19. Results Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p 14 days after symptom onset (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity of SARS-CoV-2 serology was superior to PCR > 17d after symptom onset. Conclusions Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates in PCR negative patients. However, sensitivity of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2nd week following symptom onset.

Abstract To evaluate the diagnostic performance of magnetic resonance imaging (MRI) alone in comparison to positron emission tomography/ magnetic resonance imaging (PET/MRI) in patients with meningiomas. 57 patients with a total of 112 meningiomas of the brain were included. PET/MRI, including a fully diagnostic contrast enhanced MRI and PET, were acquired. PET/MRI was used as reference standard. The size and location of meningiomas was recorded. Likelihood-ratio chi-square tests were used to calculate p-values within logistic regression in order to compare different models. A multi-level logistic regression was applied to comply the hierarchical data structure. Multi-level regression adjusts for clustering in data was performed. The majority (n = 103) of meningiomas could be identified based on standard MRI sequences compared to PET/MRI. MRI alone achieved a sensitivity of 95% (95% CI 0.78, 0.99) and specificity of 88% (95% CI 0.58, 0.98). Based on intensity of contrast medium uptake, 97 meningiomas could be diagnosed with intense uptake (93.75%). Sensitivity was lowest with 74% for meningiomas 2cm3 and highest with 100% for meningiomas 0.5–1.0 cm3. Petroclival meningiomas showed lowest sensitivity with 88% compared to sphenoidal meningiomas with 94% and orbital meningiomas with 100%. Specificity of meningioma diagnostic with MRI was high with 100% for sphenoidal and hemispherical-dural meningiomas and meningiomas with 0.5–1.0 and 1.0–2.0 cm3. Overall MRI enables reliable detection of meningiomas compared to PET/MRI. PET/MRI imaging offers highest sensitivity and specificity for small or difficult located meningiomas.

Abstract Hepatic radiofrequency ablation (RFA) induces a drastic alteration of the biomechanical environment in the peritumoral liver tissue. The resulting increase in matrix stiffness has been shown to significantly influence carcinogenesis and cancer progression after focal RF ablation. To investigate the potential of an elastin-specific MR agent (ESMA) for the assessment of extracellular matrix (ECM) remodeling in the periablational rim following RFA in a VX2 rabbit liver tumor-model, twelve New-Zealand-White-rabbits were implanted in the left liver lobe with VX2 tumor chunks from donor animals. RFA of tumors was performed using a perfused RF needle-applicator with a mean tip temperature of 70 °C. Animals were randomized into four groups for MR imaging and scanned at four different time points following RFA (week 0 [baseline], week 1, week 2 and week 3 after RFA), followed by sacrifice and histopathological analysis. ESMA-enhanced MR imaging was used to assess ECM remodeling. Gadobutrol was used as a third-space control agent. Molecular MR imaging using an elastin-specific probe demonstrated a progressive increase in contrast-to-noise ratio (CNR) (week 3: ESMA: 28.1 ± 6.0; gadobutrol: 3.5 ± 2.0), enabling non-invasive imaging of the peritumoral zone with high spatial-resolution, and accurate assessment of elastin deposition in the periablational rim. In vivo CNR correlated with ex vivo histomorphometry (ElasticaVanGiesson-stain, y = 1.2x − 1.8, R2 = 0.89, p

Abstract Background Small soft tissue masses are often falsely assumed to be benign and resected with failure to achieve tumor-free margins. Therefore, this study retrospectively investigated the distribution of histopathologic diagnosis to be encountered in small soft tissue tumors (≤ 5 cm) in a large series of a tertiary referral center. Methods Patients with a soft tissue mass (STM) with a maximum diameter of 5 cm presenting at our institution over a period of 10 years, who had undergone preoperative Magnetic resonance imaging and consequent biopsy or/and surgical resection, were included in this study. A final histopathological diagnosis was available in all cases. The maximum tumor diameter was determined on MR images by one radiologist. Moreover, tumor localization (head/neck, trunk, upper extremity, lower extremity, hand, foot) and depth (superficial / deep to fascia) were assessed. Results In total, histopathologic results and MR images of 1753 patients were reviewed. Eight hundred seventy patients (49.63%) showed a STM ≤ 5 cm and were therefore included in this study (46.79 +/− 18.08 years, 464 women). Mean maximum diameter of the assessed STMs was 2.88 cm. Of 870 analyzed lesions ≤ 5 cm, 170 (19.54%) were classified as superficial and 700 (80.46%) as deep. The malignancy rate of all lesions ≤ 5 cm was at 22.41% (superficial: 23.53% / deep: 22.14%). The malignancy rate dropped to 16.49% (20.79% / 15.32%) when assessing lesions ≤ 3 cm (p = 0.007) and to 15.0% (18.18% / 13.79%) when assessing lesions ≤ 2 cm (p = 0.006). Overall, lipoma was the most common benign lesion of superficial STMs (29.41%) and tenosynovial giant cell tumor was the most common benign lesion of deep STMs (23.29%). Undifferentiated pleomorphic sarcoma was the most common malignant diagnosis among both, superficial (5.29%) and deep (3.57%) STMs. Conclusions The rate of malignancy decreased significantly with tumor size in both, superficial and deep STMs. The distribution of entities was different between superficial and deep STMs, yet there was no significant difference found in the malignancy rate.

Abstract Purpose This study aimed to calculate an applicable relative ratio threshold value instead of the absolute threshold value for simultaneous 68Ga prostate-specific membrane antigen/positron emission tomography ([68Ga]Ga-PSMA-11 PET) in patients with prostate cancer (PCa). Materials and methods Our study evaluated thirty-two patients and 170 focal prostate lesions. Lesions are classified into groups according to Prostate Imaging Reporting and Data System (PI-RADS). Standardized uptake values maximum (SUVmax), corresponding lesion-to-background ratios (LBRs) of SUVmax, and LBR distributions of each group were measured based on regions of interest (ROI). We examined LBR with receiver operating characteristic analysis to determine threshold values for differentiation between multiparametric magnetic resonance imaging (mpMRI)-positive and mpMRI-negative lesions. Results We analyzed a total of 170 focal prostate lesions. Lesions number of PI-RADS 2 to 5 was 70, 16, 46, and 38. LBR of SUVmax of each PI-RADS scores was 1.5 (0.9, 2.4), 2.5 (1.6, 3.4), 3.7 (2.6, 4.8), and 6.7 (3.5, 12.7). Based on an optimal threshold ratio of 2.5 to be exceeded, lesions could be classified into MRI-positive lesion on [68Ga]Ga-PSMA PET with a sensitivity of 85.2%, a specificity of 72.0%, with the corresponding area under the receiver operating characteristic curve (AUC) of 0.83, p

Abstract Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.

Background: To assess the ability of low-dose dual-energy computed tomography (ld-DECT) virtual non-calcium (VNCa) images for detecting bone marrow pathologies of the sacroiliac joints (SIJs) in patients with axial spondyloarthritis (axSpA). Material and Methods: Sixty-eight patients with suspected or proven axSpA underwent ld-DECT and MRI of the SIJ. VNCa images were reconstructed from DECT data and scored for the presence of osteitis and fatty bone marrow deposition by two readers with different experience (beginner and expert). Diagnostic accuracy and correlation (Kohen’s k) with magnetic resonance imaging (MRI) as the reference standard were calculated for the overall and for each reader separately. Furthermore, quantitative analysis was performed using region-of-interest (ROI) analysis. Results: Twenty-eight patients were classified as positive for osteitis, 31 for fatty bone marrow deposition. DECT’s sensitivity (SE) and specificity (SP) were 73.3% and 44.4% for osteitis and 75% and 67.3% for fatty bone lesions, respectively. The expert reader achieved higher diagnostic accuracy for both osteitis (SE 93.33%; SP: 51.85%) and fatty bone marrow deposition (SE: 65%; SP: 77.55%) than the beginner (SE: 26.67%; SP: 70.37% for osteitis; SE: 60%; SP: 44.9% for fatty bone marrow deposition). Overall correlation with MRI was moderate (r = 0.25, p = 0.04) for osteitis and fatty bone marrow deposition (r = 0.25, p = 0.04). Fatty bone marrow attenuation in VNCa images (mean: −129.58 HU; ±103.61 HU) differed from normal bone marrow (mean: 118.84 HU, ±99.91 HU; p < 0.01) and from osteitis (mean: 172 HU, ±81.02 HU; p < 0.01) while osteitis did not differ significantly from normal bone marrow (p = 0.27). Conclusion: In our study, low-dose DECT failed to detect osteitis or fatty lesions in patients with suspected axSpA. Thus, we conclude that higher radiation might be needed for DECT−based bone marrow analysis.

Background: Proton-density fat fraction (PDFF) and T2* of the vertebrae, as well as the cross-sectional area (CSA) of the paraspinal musculature (PSM), have been suggested as biomarkers for bone fragility. The aim of this study was to longitudinally assess changes in PDFF, T2* and CSA of the PSM over 6 months in patients with and without osteoporosis. Methods: Opportunistic bone mineral density (BMD) measurements (BMD < 120 mg/cm3) were obtained from a CT acquired during the clinical routine work up in osteoporotic/osteopenic patients (n = 29, mean age 72.37 ± 10.12 years, 16 women). These patients were frequency-matched for age and sex to subjects with normal BMD values (n = 29). All study patients underwent 3T MR imaging at baseline and 6-month follow up, including spoiled gradient echo sequences for chemical shift encoding-based water-fat separation, from which T2* and PDFF values of the lumbar spine and the PSM were obtained. Moreover, the CSA of the PSM was assessed longitudinally. Changes in T2*, PDFF and CSA over 6 months were calculated for the vertebrae and PSM and associations with baseline BMD values were assessed. Results: The change in CSA of the PSM over 6 months was significantly lower in the osteoporotic/osteopenic group (−91.5 ± 311.7 mm2), compared to the non-osteoporotic group, in which the CSA increased (29.9 ± 164.0 mm2, p = 0.03). In a further analysis, patients with higher vertebral PDFF at baseline showed a significantly stronger increase in vertebral T2*, compared to those patients with lower vertebral PDFF at baseline (0.9 ± 1.6 ms vs. 0.0 ± 1.8 ms, p = 0.04). Moreover, patients with higher PSM PDFF at baseline showed a significantly stronger increase in vertebral T2*, compared to those patients with lower PSM PDFF at baseline (0.9 ± 2.0 ms vs. 0.0 ± 1.3 ms, p = 0.03). Conclusion: The PSM CSA decreased significantly longitudinally in patients with osteoporosis/osteopenia, compared to those without. Additionally, higher vertebral and PSM PDFF at baseline were associated with stronger changes in vertebral bone marrow T2*. Therefore, longitudinal PDFF and T2* mapping may be useful quantitative radiation-free tools for the assessment and prediction of muscle and bone health in patients with suspected osteoporosis/osteopenia.

Background: Shoulder dislocations represent common injuries and are often combined with rotator cuff tears and potentially damage to the biceps pulley. Purpose: To assess the occurrence and type of biceps pulley lesions in patients after traumatic anterior shoulder dislocation using 3T MRI. Methods: Thirty-three consecutive patients were enrolled between June 2021 and March 2022 (14 women, mean age 48.0 ± 19 years). All patients underwent MR imaging at 3 T within one week. Images were analyzed for the presence and type of pulley tears, subluxation/dislocation of the LHBT, rotator cuff lesions, joint effusion, labral lesions, and osseous defects. Results: Seventeen patients (52%) with traumatic anterior shoulder dislocation demonstrated biceps pulley lesions. Of those, eleven patients (33%) showed a combined tear of the sGHL and CHL. All seventeen patients with lesions of the biceps pulley showed associated partial tearing of the rotator cuff, whereas three patients showed an additional subluxation of the LHBT. Patients with pulley lesions after dislocations were significantly older than those without (mean age 52 ± 12 years vs. 44 ± 14 years, p = 0.023). Conclusion: Our results suggest an increased awareness for lesions of the biceps pulley in acute traumatic shoulder dislocation, particularly in patients over 45 years.

The differentiation between the atypical cartilaginous tumor (ACT) and the enchondromas is crucial as ACTs require a curettage and clinical as well as imaging follow-ups, whereas in the majority of cases enchondromas require neither a treatment nor follow-ups. Differentiating enchondromas from ACTs radiologically remains challenging. Therefore, this study evaluated imaging criteria in a combination of computed tomography (CT) and magnetic resonance (MR) imaging for the differentiation between enchondromas and ACTs in long bones. A total of 82 patients who presented consecutively at our institution with either an ACT (23, age 52.7 ±18.8 years; 14 women) or an enchondroma (59, age 46.0 ± 11.1 years; 37 women) over a period of 10 years, who had undergone preoperative MR and CT imaging and subsequent biopsy or/and surgical removal, were included in this study. A histopathological diagnosis was available in all cases. Two experienced radiologists evaluated several imaging criteria on CT and MR images. Likelihood of an ACT was significantly increased if either edema within the bone (p = 0.049), within the adjacent soft tissue (p = 0.006) or continuous growth pattern (p = 0.077) were present or if the fat entrapment (p = 0.027) was absent on MR images. Analyzing imaging features on CT, the likelihood of the diagnosis of an ACT was significantly increased if endosteal scalloping >2/3 (p < 0.001), cortical penetration (p < 0.001) and expansion of bone (p = 0.002) were present and if matrix calcifications were observed in less than 1/3 of the tumor (p = 0.013). All other imaging criteria evaluated showed no significant influence on likelihood of ACT or enchondroma (p > 0.05). In conclusion, both CT and MR imaging show suggestive signs which can help to adequately differentiate enchondromas from ACTs in long bones and therefore can improve diagnostics and consequently patient management. Nevertheless, these features are rare and a combination of CT and MR imaging features did not improve the diagnostic performance substantially.

Abstract Molecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in atherosclerosis. The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE−/−) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the elastin and iron-oxide-probe were in good agreement with ex-vivo histopathology (Elastica-van-Giesson stain: y = 298.2 + 5.8, R2 = 0.83, p

Abstract We proposed a generic template-derived approach for (semi-) automated brain extraction in animal MRI studies and evaluated our implementation with different animal models (macaque, marmoset, rodent) and MRI protocols (T1, T2). While conventional MR-neuroimaging studies perform brain extraction as an initial step priming subsequent image-registration from subject to template, our proposed approach propagates an anatomical template to (whole-head) individual subjects in reverse order, which is challenging due to the surrounding extracranial tissue, greater differences in contrast pattern and larger areas with field inhomogeneity. As a novel approach, the herein introduced brain extraction algorithm derives whole-brain segmentation using rigid and non-rigid deformation based on unbiased anatomical atlas building with a priori estimates from study-cohort and an initial approximate brain extraction. We evaluated our proposed method in comparison to several other technical approaches including “Marker based watershed scalper”, “Brain-Extraction-Tool”, “3dSkullStrip”, “Primatologist-Toolbox”, “Rapid Automatic Tissue Segmentation” and “Robust automatic rodent brain extraction using 3D pulse-coupled neural networks” with manual skull-stripping as reference standard. ABX demonstrated best performance with accurate (≥92%) and consistent results throughout datasets and across species, age and MRI protocols. ABX was made available to the public with documentation, templates and sample material (https://www.github.com/jlohmeier/atlasBREX).

Abstract The aim was to assess the performance of prostate 3T MRI for pelvic lymph node (LN) staging in prostate cancer (PCa), in comparison to 68Gallium-prostate specific membrane antigen PET-CT (68Ga-PSMA PET-CT) as reference standard for LN detection. 130 patients with PCa underwent non-contrast-enhanced multiparametric prostate 3T MRI and 68Ga-PSMA-PET-CT within 180 days at our institution. Overall, 187 LN metastases (n = 43 patients) detected by 68Ga-PSMA-PET-CT were characterized by calculating maximum standardized uptake value (SUVmax), area, diameter and anatomical location including iliac, obturator, presacral and inguinal region. MRI achieved an overall sensitivity, specificity, positive and negative predictive value of 81.6% (CI 71.1–88.9%), 98.6% (CI 97.6–99.2%), 73.5% (CI 52.1–87.6%) and 99.5% (CI 98.8–99.8%), respectively. On a region-based analysis, detection rates differed non-significantly (ps > 0.12) in the anatomical regions. On a size-dependent analysis, detection of LN > 10 mm did not differ significantly (ps > 0.09) from LN ≤ 10 mm. In comparison to single T1 sequence evaluation, additional use of the T2 weighted sequences did not improve the overall performance significantly (p > 0.05). 3T prostate MRI represented an accurate tool for the detection of LN compared to 68Ga-PSMA-PET-CT. Especially for LN metastases smaller than 10 mm, MRI was less accurate compared to 68Ga-PSMA-PET-CT.

Abstract Background Correct staging and grading of patients with clear cell renal cell carcinoma (cRCC) is of clinical relevance for the prediction of operability and for individualized patient management. As partial or radial resection with postoperative tumor grading currently remain the methods of choice for the classification of cRCC, non-invasive preoperative alternatives to differentiate lower grade from higher grade cRCC would be beneficial. Methods This institutional-review-board approved cross-sectional study included twenty-seven patients (8 women, mean age ± SD, 61.3 ± 14.2) with histopathologically confirmed cRCC, graded according to the International Society of Urological Pathology (ISUP). A native, balanced steady-state free precession T2 mapping sequence (TrueFISP) was performed at 1.5 T. Quantitative T2 values were measured with circular 2D ROIs in the solid tumor portion and also in the normal renal parenchyma (cortex and medulla). To estimate the optimal cut-off T2 value for identifying lower grade cRCC, a Receiver Operating Characteristic Curve (ROC) analysis was performed and sensitivity and specificity were calculated. Students’ t-tests were used to evaluate the differences in mean values for continuous variables, while intergroup differences were tested for significance with two-tailed Mann-Whitney-U tests. Results There were significant differences between the T2 values for lower grade (ISUP 1–2) and higher grade (ISUP 3–4) cRCC (p

Abstract Background The purpose of this study was to evaluate the imaging properties of hepatic metastases in 68Ga-PSMA positron emission tomography (PET) in patients with prostate cancer (PC). Methods 68Ga-PSMA-PET/CT scans of PC patients available in our database were evaluated retrospectively for liver metastases. Metastases were identified using 68Ga-PSMA-PET, CT, MRI and follow-up scans. Different parameters including, maximum standardized uptake values (SUVmax) of the healthy liver and liver metastases were assessed by two- and three-dimensional regions of interest (2D/3D ROI). Results One hundred three liver metastases in 18 of 739 PC patients were identified. In total, 80 PSMA-positive (77.7%) and 23 PSMA-negative (22.3%) metastases were identified. The mean SUVmax of PSMA-positive liver metastases was significantly higher than that of the normal liver tissue in both 2D and 3D ROI (p ≤ 0.05). The mean SUVmax of PSMA-positive metastases was 9.84 ± 4.94 in 2D ROI and 10.27 ± 5.28 in 3D ROI; the mean SUVmax of PSMA-negative metastases was 3.25 ± 1.81 in 2D ROI and 3.40 ± 1.78 in 3D ROI, and significantly lower than that of the normal liver tissue (p ≤ 0.05). A significant (p ≤ 0.05) correlation between SUVmax in PSMA-positive liver metastases and both size (ρSpearman = 0.57) of metastases and PSA serum level (ρSpearman = 0.60) was found. Conclusions In 68Ga-PSMA-PET, the majority of liver metastases highly overexpress PSMA and is therefore directly detectable. For the analysis of PET images, it has to be taken into account that also a significant portion of metastases can only be detected indirectly, as these metastases are PSMA-negative.

Chemical shift encoding-based water–fat MRI (CSE-MRI)-derived proton density fat fraction (PDFF) has been used for non-invasive assessment of regional body fat distributions. More recently, texture analysis (TA) has been proposed to reveal even more detailed information about the vertebral or muscular composition beyond PDFF. The aim of this study was to investigate associations between vertebral bone marrow and paraspinal muscle texture features derived from CSE-MRI-based PDFF maps in a cohort of healthy subjects. In this study, 44 healthy subjects (13 males, 55 ± 30 years; 31 females, 39 ± 17 years) underwent 3T MRI including a six-echo three-dimensional (3D) spoiled gradient echo sequence used for CSE-MRI at the lumbar spine and the paraspinal musculature. The erector spinae muscles (ES), the psoas muscles (PS), and the vertebral bodies L1-4 (LS) were manually segmented. Mean PDFF values and texture features were extracted for each compartment. Features were compared between males and females using logistic regression analysis adjusted for age and body mass index (BMI). All texture features of ES except for Sum Average were significantly (p < 0.05) different between men and women. The three global texture features (Variance, Skewness, Kurtosis) for PS as well as LS showed a significant difference between male and female subjects (p < 0.05). Mean PDFF measured in PS and ES was significantly higher in females, but no difference was found for the vertebral bone marrow’s PDFF. Partial correlation analysis between the texture features of the spine and the paraspinal muscles revealed a highly significant correlation for Variance(global) (r = 0.61 for ES, r = 0.62 for PS; p < 0.001 respectively). Texture analysis using PDFF maps based on CSE-MRI revealed differences between healthy male and female subjects. Global texture features in the lumbar vertebral bone marrow allowed for differentiation between men and women, when the overall PDFF was not significantly different, indicating that PDFF maps may contain detailed and subtle textural information beyond fat fraction. The observed significant correlation of Variance(global) suggests a metabolic interrelationship between vertebral bone marrow and the paraspinal muscles.

BackgroundProstate-specific membrane antigen (PSMA) targeting radioligands have transformed treatment of prostate cancer. Radioligand therapy (RLT) with 177Lu-PSMA in metastasized castration resistant prostate cancer (mCRPC) achieves objective response and disease stabilization in roughly two third of patients, whereas one third of patients progress. This study was performed to assess the role of interim PSMA PET/CT after the 2nd cycle of RLT for early prediction of overall survival in patients undergoing RLT with 177Lu-PSMA.Methods38 mCRPC patients (68.9 ± 8.1 y) treated with at least two cycles of RLT at 8 week intervals and interim 68Ga-PSMA PET/CT (PET) at 8–10 weeks after the 2nd cycle of RLT were included in this study. Prostate-specific antigen (PSA) response was evaluated according to the Prostate Cancer Working Group 3 criteria. Radiographic response assessment of soft tissue, lymph node, and bone lesions was performed according to RECIST 1.1 including the PET component. Patients’ data were collected for follow-up from the local Comprehensive Cancer Center Register.ResultsMedian follow-up was 19.7 months (4.7–45.3). PSA response after the 2nd therapy cycle showed partial remission (PR) in 23.7%, stable disease (SD) in 50%, and progressive disease (PD) in 26.3% of patients. In comparison, 52.6, 23.7, and 23.7% of patients showed PR, SD, and PD respectively on PET/CT. The strength of agreement between PSA response and PET/CT response criteria was only fair (kappa 0.346). Median overall survival (OS) was 22.5 months (95% CI: 15.8–29.2). Median OS stratified to PSA/PET response was 25.6/25.6 months for PR, 21.7/30.6 months for SD and 19.4/13.1 months for PD (p = 0.496 for PSA and 0.013 for PET/CT response).ConclusionsInterim PSMA PET/CT based response evaluation at 8–10 weeks after the 2nd cycle of RLT is predictive of overall survival and PD in patients treated with 177Lu-PSMA. On the contrary, PSA appears to have only limited predictive value.

PurposeTo assess whether volumetric vertebral bone mineral density (BMD) measured with opportunistic quantitative computed tomography (QCT) (i.e., CT acquired for other reasons) can predict osteoporotic fracture occurrence in a prospective clinical cohort and how this performs in comparison to dual-energy X-ray absorptiometry (DXA) measurements.MethodsIn the database of our fracture liaison service, 58 patients (73 ± 11 years, 72% women) were identified that had at least one prevalent low-energy fracture and had undergone CT of the spine. BMD was determined by converting HU using scanner-specific conversion equations. Baseline DXA was available for 31 patients. During a 3-year follow-up, new fractures were diagnosed either by (i) recent in-house imaging or (ii) clinical follow-up with validated external reports. Associations were assessed using logistic regression models, and cut-off values were determined with ROC/Youden analyses.ResultsWithin 3 years, 20 of 58 patients presented new low-energy fractures (34%). Mean QCT BMD of patients with fractures was significantly lower (56 ± 20 vs. 91 ± 38 mg/cm3; p = 0.003) and age was higher (77 ± 10 vs. 71 ± 11 years; p = 0.037). QCT BMD was significantly associated with the occurrence of new fractures, and the OR for developing a new fracture during follow-up was 1.034 (95% CI, 1.010–1.058, p = 0.005), suggesting 3% higher odds for every unit of BMD decrease (1 mg/cm3). Age and sex showed no association. For the differentiation between patients with and without new fractures, ROC showed an AUC of 0.76 and a Youden’s Index of J = 0.48, suggesting an optimal cut-off value of 82 mg/cm3. DXA T-scores showed no significant association with fracture occurrence in analogous regression models.ConclusionIn this use case, opportunistic BMD measurements attained through QCT predicted fractures during a 3-year follow-up. This suggests that opportunistic measurements are useful to reduce the diagnostic gap and evaluate the fracture risk in osteoporotic patients.

Abstract Background The purpose of this study was to investigate the imaging properties of pulmonary metastases and benign opacities in 68Ga-PSMA positron emission tomography (PET) in patients with prostate cancer (PC). Methods 68Ga-PSMA-PET/CT scans of 739 PC patients available in our database were evaluated retrospectively for lung metastases and non-solid focal pulmonary opacities. Maximum standardized uptake values (SUVmax) were assessed by two- and three-dimensional regions of interest (2D/3D ROI). Additionally CT features of the lesions, such as location, morphology and size were identified. Results Ninety-one pulmonary metastases and fourteen opacities were identified in 34 PC patients. In total, 66 PSMA-positive (72.5%) and 25 PSMA-negative (27.5%) metastases were identified. The mean SUVmax of pulmonary opacities was 2.2±0.7 in 2D ROI and 2.4±0.8 in 3D ROI. The mean SUVmax of PSMA-positive pulmonary metastases was 4.5±2.7 in 2D ROI and in 4.7±2.9 in 3D ROI; this was significantly higher than the SUVmax of pulmonary opacities in both 2D and 3D ROI (p

Abstract Background Renal cell carcinoma (RCC) are accompanied by inferior vena cava (IVC) thrombus in up to 10% of the cases, with surgical resection remaining the only curative option. In case of IVC wall invasion, the operative procedure is more challenging and may even require IVC resection. This study aims to determine the diagnostic performance of contrast-enhanced magnetic resonance imaging (MRI) for the assessment of wall invasion by IVC thrombus in patients with RCC, validated with intraoperative findings. Methods Data were collected on 81 patients with RCC and IVC thrombus, who received a radical nephrectomy and vena cava thrombectomy between February 2008 and November 2017. Forty eight patients met the inclusion criteria. Sensitivity and specificity as well as the positive and negative predictive values were calculated for preoperative MRI, based on the assessments of the two readers for visual wall invasion. Furthermore, a logistic regression model was used to determine if there was an association between intraoperative wall adherence and IVC diameter. Results Complete occlusion of the IVC lumen or vessel breach could reliably assess IVC wall invasion with a sensitivity of 92.3% (95%-CI: 0.75–0.99) and a specificity of 86.4% (95%-CI: 0.65–0.97) (Fisher-test: p-value

Human prostate cancer (PCa) is a type of malignancy and one of the most frequently diagnosed cancers in men. Elastin is an important component of the extracellular matrix and is involved in the structure and organization of prostate tissue. The present study examined prostate cancer in a xenograft mouse model using an elastin-specific molecular probe for magnetic resonance molecular imaging. Two different tumor sizes (500 mm3 and 1000 mm3) were compared and analyzed by MRI in vivo and histologically and analytically ex vivo. The T1-weighted sequence was used in a clinical 3-T scanner to calculate the relative contrast enhancement before and after probe administration. Our results show that the use of an elastin-specific probe enables better discrimination between tumors and surrounding healthy tissue. Furthermore, specific binding of the probe to elastin fibers was confirmed by histological examination and laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS). Smaller tumors showed significantly higher signal intensity (p > 0.001), which correlates with the higher proportion of elastin fibers in the histological evaluation than in larger tumors. A strong correlation was seen between relative enhancement (RE) and Elastica–van Gieson staining (R2 = 0.88). RE was related to inductively coupled plasma–mass spectrometry data for Gd and showed a correlation (R2 = 0.78). Thus, molecular MRI could become a novel quantitative tool for the early evaluation and detection of PCa.

Central fat accumulation is a significant determinant of cardio-metabolic health risk, known to differ between ethnically distinct human populations. Despite evidence for preferential central adiposity in Asian populations, the proportional distribution between the subcutaneous and visceral compartments in Chinese postmenopausal women has not been thoroughly investigated. For this analysis, volumetrically quantified subcutaneous and visceral adipose tissue (SAT, VAT) in the pelvic and abdominal regions of postmenopausal Asian (Chinese-Singaporean) and Caucasian (German) women matched for age and Body Mass Index (BMI) was undertaken, to examine such differences between the two groups. Volumes were calculated from segmentations of magnetic resonance imaging datasets of the abdomen and pelvis. Despite SAT, VAT, and the corresponding total adipose tissue (TAT) being similar between the groups, VAT/SAT and VAT/TAT were higher in the Asian group (by 24.5% and 18.2%, respectively, each p = 0.02). Further, VAT/SAT and VAT/TAT were positively correlated with BMI in the Caucasian group only (p = 0.02 and p = 0.01, respectively). We concluded that VAT is proportionally higher in the non-obese Asian women, compared to the Caucasian women of matched age and BMI. This conclusion is in agreement with existing literature showing higher abdominal adiposity in Asian populations. Additionally, in the Asian group, BMI did not correlate with visceral adiposity on a significant level. Further analysis is required to examine the extent to which this increased VAT may impact cardio-metabolic health. There is, however, a need to emphasize healthy lifestyle behaviors in non-obese post-menopausal women of Chinese ancestry.

Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient (ApoE-/-)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE-/--group was treated with pravastatin and received a HFD for 4 months. T1- and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis.

Abstract Background The aim of this study was to evaluate the diagnostic value of the asphericity (ASP) as a novel quantitative parameter, reflecting the spatial heterogeneity of tracer uptake, in the staging process of patients with 68Ga-PSMA-HBED-CC positron emission tomography (PET)-positive prostate cancer (PC). In this study, 37 patients (median age 72 years, range 52–82 years) with newly diagnosed PC, who received a 68Ga-PSMA-HBED-CC PET fused with computed tomography (68Ga-PSMA-PET/CT), a magnetic resonance imaging (MRI) of the prostate, and a core needle biopsy (within 74.2 ± 80.2 days) with an available Gleason score (GSc) were extracted from the local database. The ASP and the viable tumor volume (VTV) was calculated using the rover software (ABX GmbH, Radeberg, Germany), a segmentation tool for automated tumor volume delineation. Additionally, parameters including total lesion binding rate (TLB), maximum, mean and peak standardized uptake value (SUVmax/mean/peak), prostate-specific antigen (PSA), D’Amico classification, and prostate imaging reporting and data system (PI-RADS) were analyzed. Results The ASP mean differed significantly (p ≤ 0.05) between the different GSc groups: GSc 6–7: 11.9 ± 4.8%, GSc 8: 25.5 ± 4.8%, GSc 9–10: 33.3 ± 6.8%. A significant correlation between ASP and GSc (rho = 0.88; CI 0.78–0.94; p 0.05) prediction of the GSc. A moderate correlation was measured between ASP and the D’Amico classification (rho = 0.6; CI 0.32–0.78; p

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The aim of this study is to assess whether perifocal bone marrow edema (BME) in patients with osteoid osteoma (OO) can be accurately detected on dual-layer spectral CT (DLCT) with three-material decomposition. To that end, 18 patients with OO (25.33 ± 12.44 years; 7 females) were pairwise-matched with 18 patients (26.72 ± 9.65 years; 9 females) admitted for suspected pathologies other than OO in the same anatomic location but negative imaging findings. All patients were examined with DLCT and MRI. DLCT data was decomposed into hydroxyapatite and water- and fat-equivalent volume fraction maps. Two radiologists assessed DLCT-based volume fraction maps for the presence of perifocal BME, using a Likert scale (1 = no edema; 2 = likely no edema; 3 = likely edema; 4 = edema). Accuracy, sensitivity, and specificity for the detection of BME on DLCT were analyzed using MR findings as standard of reference. For the detection of BME in patients with OO, DLCT showed a sensitivity of 0.92, a specificity of 0.94, and an accuracy of 0.92 for both radiologists. Interreader agreement for the assessment of BME with DLCT was substantial (weighted κ = 0.78; 95% CI, 0.59, 0.94). DLCT with material-specific volume fraction maps allowed accurate detection of BME in patients with OO. This may spare patients additional examinations and facilitate the diagnosis of OO.

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In this case-control study the value of bone mineral density (BMD) at different vertebral levels, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) to identify patients with incident osteoporotic vertebral fractures in routine multi-detector computed tomography (MDCT) exams was assessed. Material and methods: Seventeen patients who underwent baseline and follow-up routine contrast-enhanced MDCT and had an incident osteoporotic vertebral fracture at follow-up were included. Seventeen age-, sex- and follow-up duration-matched controls were identified. Trabecular BMD (from Th5 to L5) as well as cross-sectional area of SAT and VAT were extracted. Results: BMD performed best to differentiate patients with an incident fracture from controls at the levels of Th5 (area under the curve [AUC] = 0.781, p = 0.014), Th7 (AUC = 0.877, p = 0.001), and Th9 (AUC = 0.818, p = 0.005). Applying multivariate logistic regression BMD at Th7 level remained the only significant predictor of incident vertebral fractures (Th5-L5) with an odds ratio of 1.07 per BMD SD decrease. VAT and SAT did not show significant differences between the fracture and control group (p > 0.05). Conclusion: The local BMD measurement appears to be more suitable than standard mean BMD from L1–L3 for fracture risk assessment.

This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size.

BackgroundThe incidence of abdominal aortic aneurysms (AAAs) will significantly increase during the next decade. Novel biomarkers, besides diameter, are needed for a better characterization of aneurysms and the estimation of the risk of rupture. Fibrin is a key protein in the formation of focal hematoma associated with the dissection of the aortic wall and the development of larger thrombi during the progression of AAAs. This study evaluated the potential of a fibrin‐specific magnetic resonance (MR) probe for the in vivo characterization of the different stages of AAAs. Methods and ResultsAAAs spontaneously developed in ApoE−/− mice following the infusion of angiotensin‐II (Ang‐II, 1 μg/kg−1·per minute). An established fibrin‐specific molecular MR probe (EP2104R, 10 μmol/kg−1) was administered after 1 to 4 weeks following Ang‐II infusion (n=8 per group). All imaging experiments were performed on a clinical 3T Achieva MR system with a microscopy coil (Philips Healthcare, Netherlands). The development of AAA‐associated fibrin‐rich hematoma and thrombi was assessed. The high signal generated by the fibrin probe enabled high‐resolution MR imaging for an accurate assessment and quantification of the relative fibrin composition of focal hematoma and thrombi. Contrast‐to‐noise‐ratios (CNRs) and R1‐relaxation rates following the administration of the fibrin probe were in good agreement with ex vivo immunohistomorphometry (R2=0.83 and 0.85) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy (R2=0.78 and 0.72). ConclusionsThe fibrin‐specific molecular MR probe allowed the delineation and quantification of changes in fibrin content in early and advanced AAAs. Fibrin MRI could provide a novel in vivo biomarker to improve the risk stratification of patients with aortic aneurysms.