Multiparametric MRI for characterization of the tumour microenvironment.

Our understanding of tumour biology has evolved over the past decades and cancer is now viewed as a complex ecosystem with interactions between various cellular and non-cellular components within the tumour microenvironment (TME) at multiple scales. However, morphological imaging remains the mainstay of tumour staging and assessment of response to therapy, and the characterization of the TME with non-invasive imaging has not yet entered routine clinical practice. By combining multiple MRI sequences, each providing different but complementary information about the TME, multiparametric MRI (mpMRI) enables non-invasive assessment of molecular and cellular features within the TME, including their spatial and temporal heterogeneity. With an increasing number of advanced MRI techniques bridging the gap between preclinical and clinical applications, mpMRI could ultimately guide the selection of treatment approaches, precisely tailored to each individual patient, tumour and therapeutic modality. In this Review, we describe the evolving role of mpMRI in the non-invasive characterization of the TME, outline its applications for cancer detection, staging and assessment of response to therapy, and discuss considerations and challenges for its use in future medical applications, including personalized integrated diagnostics.

Standardization of a CT Protocol for Imaging Patients with Suspected COVID-19-A RACOON Project.

CT protocols that diagnose COVID-19 vary in regard to the associated radiation exposure and the desired image quality (IQ). This study aims to evaluate CT protocols of hospitals participating in the RACOON (Radiological Cooperative Network) project, consolidating CT protocols to provide recommendations and strategies for future pandemics. In this retrospective study, CT acquisitions of COVID-19 patients scanned between March 2020 and October 2020 (RACOON phase 1) were included, and all non-contrast protocols were evaluated. For this purpose, CT protocol parameters, IQ ratings, radiation exposure (CTDIvol), and central patient diameters were sampled. Eventually, the data from 14 sites and 534 CT acquisitions were analyzed. IQ was rated good for 81% of the evaluated examinations. Motion, beam-hardening artefacts, or image noise were reasons for a suboptimal IQ. The tube potential ranged between 80 and 140 kVp, with the majority between 100 and 120 kVp. CTDIvol was 3.7 ± 3.4 mGy. Most healthcare facilities included did not have a specific non-contrast CT protocol. Furthermore, CT protocols for chest imaging varied in their settings and radiation exposure. In future, it will be necessary to make recommendations regarding the required IQ and protocol parameters for the majority of CT scanners to enable comparable IQ as well as radiation exposure for different sites but identical diagnostic questions.

The anteromedial retinaculum in ACL-injured knees: An overlooked injury?

PURPOSE: The purpose of this study was to retrospectively analyse the pattern of injury to the medial knee structures in anterior cruciate ligament (ACL) injured patients. It was hypothesised that anteromedial injuries would be more common than posteromedial lesions. METHODS: One hundred and twenty subjects aged 18-25 years with a primary ACL injury were included. Patients were excluded if the time between injury and magnetic resonance imaging (MRI) was more than 28 days or if a knee dislocation or fracture was present. The MRIs were analysed with particular emphasis on injuries to the medial knee structures, menisci and bone bruise patterns. Injuries to the ligaments and anteromedial retinaculum (AMR) were graded according to severity, ranging from periligamentous oedema (grade I), partial fibre disruption of less or more than 50% (grade IIa or IIb) to complete tears (grade III). RESULTS: AMR injury was seen in 87 subjects (72.5%) on the coronal plane and in 88 (73.3%) on the axial plane, with grade III lesions observed in 27 (22.5%) and 29 knees (24.2%). Injuries to the superficial medial collateral ligament (sMCL), deep MCL (dMCL) and posterior oblique ligament (POL) were detected in 60 patients (50%), 93 patients (77.5%) and 38 patients (31.6%). However, grade III injuries to the POL were observed in only seven knees (5.8%). Medial meniscus injuries were associated with lesions of the sMCL and AMR (p < 0.05), while lateral meniscus injuries were significantly more common in patients with dMCL rupture (p < 0.05). CONCLUSION: Data from this study suggest that injuries to the AMR are much more common than posteromedial lesions in subjects with ACL injuries. LEVEL OF EVIDENCE: Level IV.

[Emergency diagnoses in the gastrointestinal tract]. / Notfalldiagnosen im Gastrointestinaltrakt.

Gastrointestinal emergencies are a frequent reason for presentation in the emergency department and involve patients of all ages. The patients must undergo an immediate cross-sectional imaging as in many cases the underlying pathology is a life-threatening condition, which often needs surgical or in some cases also interventional radiological treatment. In this overview, the most important differential diagnoses and their characteristics on cross-sectional imaging are presented.

Utility of Coronary Computed Tomography Angiography in Patients Undergoing Transcatheter Aortic Valve Implantation: A Meta-Analysis and Meta-Regression Based on Published Data from 7458 Patients.

BACKGROUND: Coronary CT angiography (CCTA) may detect coronary artery disease (CAD) in transcatheter aortic valve implantation (TAVI) patients and may obviate invasive coronary angiography (ICA) in selected patients. We assessed the diagnostic accuracy of CCTA for detecting CAD in TAVI patients based on published data. METHODS: Meta-analysis and meta-regression were performed based on a comprehensive electronic search, including relevant studies assessing the diagnostic accuracy of CCTA in the setting of TAVI patients compared to ICA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated on a patient and per segment level. RESULTS: Overall, 27 studies (total of 7458 patients) were included. On the patient level, the CCTA's pooled sensitivity and NPV were 95% (95% CI: 93-97%) and 97% (95% CI: 95-98%), respectively, while the specificity and PPV were at 73% (95% CI: 62-82%) and 64% (95% CI: 57-71%), respectively. On the segmental coronary vessel level, the sensitivity and NPV were 90% (95% CI: 79-96%) and 98% (95% CI: 97-99%). CONCLUSIONS: This meta-analysis highlights CCTA's potential as a first-line diagnostic tool although its limited PPV and specificity may pose challenges when interpreting heavily calcified arteries. This study underscores the need for further research and protocol standardization in this area.

Imaging-Derived Biomarkers Integrated with Clinical and Laboratory Values Predict Recurrence of Hepatocellular Carcinoma After Liver Transplantation.

Purpose: To investigate the prognostic value of computed tomography (CT) derived imaging biomarkers in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and develop a predictive nomogram model. Patients and Methods: This retrospective study included 178 patients with histopathologically confirmed HCC who underwent liver transplantation between 2007 and 2021 at the two academic liver centers. We evaluated dedicated imaging features from baseline multiphase contrast-enhanced CT supplemented by several clinical findings and laboratory parameters. Time-to-recurrence was estimated by Kaplan-Meier analysis. Univariable Cox proportional hazard regression and multivariable Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent prognostic factors for recurrence. A nomogram model was then built based on the independent factors selected through LASSO regression, to predict the probabilities of HCC recurrence at one, three, and five years. Results: The rate of HCC recurrence after LT was 17.4% (31 of 178). The LASSO analysis revealed six independent predictors associated with an elevated risk of tumor recurrence. These predictors included the presence of peritumoral enhancement, the presence of over three tumor lesions, the largest tumor diameter greater than 3 cm, serum alpha-fetoprotein (AFP) levels exceeding 400 ng/mL, and the presence of a tumor capsule. Conversely, a history of bridging therapies was found to be correlated with a reduced risk of HCC recurrence. In addition, Kaplan-Meier curves showed patients with irregular margin, satellite nodules, or small lesions displayed shorter time-to-recurrence. Our nomogram demonstrated good performance, yielding a C-index of 0.835 and AUC values of 0.86, 0.88, and 0.85 for the predictions of 1-year, 3-year, and 5-year TTR, respectively. Conclusion: Imaging parameters derived from baseline contrast-enhanced CT showing malignant behavior and aggressive growth patterns, along with serum AFP and history of bridging therapies, show potential as biomarkers for predicting HCC recurrence after transplantation.

Diagnostic approach to splenic lesions.

BACKGROUND: Splenic lesions are rare and mostly incidental findings on cross-sectional imaging. Most lesions are of benign nature and can be correctly identified based on imaging characteristics. Further, invasive evaluation is only necessary in cases of splenic lesions with uncertain or potentially malignant etiology. METHOD: While in most cases a correct diagnosis can be made from computed tomography (CT), (additional) magnetic resonance imaging (MRI) can aid in the identification of lesions. As these lesions are rare, only a few of the differential diagnoses are regularly diagnosed in the clinical routine. RESULT AND CONCLUSION: This review presents the differential diagnoses of splenic lesions, including imaging characteristics and a flowchart to determine the right diagnosis. In conjunction with laboratory results and clinical symptoms, histological workup is necessary only in a few cases, especially in incidental findings. In these cases, image-guided biopsies should be preferred over splenectomy, if possible. KEY POINTS: · Splenic lesions are rare and are usually incidental findings on abdominal imaging. · CT imaging and MRI imaging are the diagnostic tools of choice for the further workup of splenic lesions. · Based on their image morphological characteristics, a large number of splenic lesions can be assigned to one entity and do not need histological analysis.

Multi-organ Radiomics-Based Prediction of Future Remnant Liver Hypertrophy Following Portal Vein Embolization.

BACKGROUND: Portal vein embolization (PVE) is used to induce remnant liver hypertrophy prior to major hepatectomy. The purpose of this study was to evaluate the predictive value of baseline computed tomography (CT) data for future remnant liver (FRL) hypertrophy after PVE. METHODS: In this retrospective study, all consecutive patients undergoing right-sided PVE with or without hepatic vein embolization between 2018 and 2021 were included. CT volumetry was performed before and after PVE to assess standardized FRL volume (sFRLV). Radiomic features were extracted from baseline CT after segmenting liver (without tumor), spleen and bone marrow. For selecting features that allow classification of response (hypertrophy ≥ 1.33), a stepwise dimension reduction was performed. Logistic regression models were fitted and selected features were tested for their predictive value. Decision curve analysis was performed on the test dataset. RESULTS: A total of 53 patients with liver tumor were included in this study. sFRLV increased significantly after PVE, with a mean hypertrophy of FRL of 1.5 ± 0.3-fold. sFRLV hypertrophy ≥ 1.33 was reached in 35 (66%) patients. Three independent radiomic features, i.e. liver-, spleen- and bone marrow-associated, differentiated well between responders and non-responders. A logistic regression model revealed the highest accuracy (area under the curve 0.875) for the prediction of response, with sensitivity of 1.0 and specificity of 0.5. Decision curve analysis revealed a positive net benefit when applying the model. CONCLUSIONS: This proof-of-concept study provides first evidence of a potential predictive value of baseline multi-organ radiomics CT data for FRL hypertrophy after PVE.

Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy.

BACKGROUND: With metabolic alterations of the tumor microenvironment (TME) contributing to cancer progression, metastatic spread and response to targeted therapies, non-invasive and repetitive imaging of tumor metabolism is of major importance. The purpose of this study was to investigate whether multiparametric chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) allows to detect differences in the metabolic profiles of the TME in murine breast cancer models with divergent degrees of malignancy and to assess their response to immunotherapy. METHODS: Tumor characteristics of highly malignant 4T1 and low malignant 67NR murine breast cancer models were investigated, and their changes during tumor progression and immune checkpoint inhibitor (ICI) treatment were evaluated. For simultaneous analysis of different metabolites, multiparametric CEST-MRI with calculation of asymmetric magnetization transfer ratio (MTRasym) at 1.2 to 2.0 ppm for glucose-weighted, 2.0 ppm for creatine-weighted and 3.2 to 3.6 ppm for amide proton transfer- (APT-) weighted CEST contrast was conducted. Ex vivo validation of MRI results was achieved by 1H nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry imaging with laser postionization and immunohistochemistry. RESULTS: During tumor progression, the two tumor models showed divergent trends for all examined CEST contrasts: While glucose- and APT-weighted CEST contrast decreased and creatine-weighted CEST contrast increased over time in the 4T1 model, 67NR tumors exhibited increased glucose- and APT-weighted CEST contrast during disease progression, accompanied by decreased creatine-weighted CEST contrast. Already three days after treatment initiation, CEST contrasts captured response to ICI therapy in both tumor models. CONCLUSION: Multiparametric CEST-MRI enables non-invasive assessment of metabolic signatures of the TME, allowing both for estimation of the degree of tumor malignancy and for assessment of early response to immune checkpoint inhibition.

Extracellular vesicle-associated tyrosine kinase-like orphan receptors ROR1 and ROR2 promote breast cancer progression.

BACKGROUND: Extracellular vesicles (EVs) harbor a plethora of different biomolecules, which they can transport across cells. In cancer, tumor-derived EVs thereby support the creation of a favorable tumor microenvironment. So far, EV uptake and cargo delivery into target cells have been regarded as the main mechanisms for the pro-tumoral function of EVs. To test this hypothesis, we investigated the fate of the oncogenic transmembrane Wnt tyrosine kinase-like orphan receptor 1 and 2 (ROR1, ROR2) delivered via distinct EV subpopulations to breast cancer cells and aimed to unravel their impact on tumor progression. METHODS: EVs were isolated by differential ultracentrifugation from cell culture supernatant as well as plasma samples from healthy individuals (n = 27) and breast cancer patients (n = 41). EVs were thoroughly characterized by electron microscopy, nanoparticle tracking analysis, immunoblot, and flow cytometry. ROR transfer to target cells was observed using microscopy-based assays and biodistribution experiments were conducted in syngeneic mice. EV impact on cancer cell migration and invasion was tested in functional assays. RESULTS: We observed that the supernatant of ROR-overexpressing cells was sufficient for transferring the receptors to ROR-negative cells. Analyzing the secretome of the ROR-overexpressing cells, we detected a high enrichment of ROR1/2 on large and small EVs, but not on large oncosomes. Interestingly, the majority of ROR-positive EVs remained attached to the target cell surface after 24 h of stimulation and was quickly removed by treatment with trypsin. Nonetheless, ROR-positive EVs increased migration and invasion of breast cancer cells, even after chemically inhibiting EV uptake, in dependence of RhoA downstream signaling. In vivo, ROR-depleted EVs tended to distribute less into organs prone for the formation of breast cancer metastases. ROR-positive EVs were also significantly elevated in the plasma of breast cancer patients and allowed to separate them from healthy controls. CONCLUSIONS: The oncogenic Wnt receptors ROR1/2 are transferred via EVs to the surface of ROR-negative cancer cells, in which they induce an aggressive phenotype supporting tumor progression. Video Abstract.

Vascular response patterns to targeted therapies in murine breast cancer models with divergent degrees of malignancy.

BACKGROUND: Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy. METHODS: Low malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry. RESULTS: Therapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage. CONCLUSION: DCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy.

Profiling specific cell populations within the inflammatory tumor microenvironment by oscillating-gradient diffusion-weighted MRI.

BACKGROUND: The inflammatory tumor microenvironment (TME) is formed by various immune cells, being closely associated with tumorigenesis. Especially, the interaction between tumor-infiltrating T-cells and macrophages has a crucial impact on tumor progression and metastatic spread. The purpose of this study was to investigate whether oscillating-gradient diffusion-weighted MRI (OGSE-DWI) enables a cell size-based discrimination between different cell populations of the TME. METHODS: Sine-shaped OGSE-DWI was combined with the Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion (IMPULSED) approach to measure microscale diffusion distances, here relating to cell sizes. The accuracy of IMPULSED-derived cell radii was evaluated using in vitro spheroid models, consisting of either pure cancer cells, macrophages, or T-cells. Subsequently, in vivo experiments aimed to assess changes within the TME and its specific immune cell composition in syngeneic murine breast cancer models with divergent degrees of malignancy (4T1, 67NR) during tumor progression, clodronate liposome-mediated depletion of macrophages, and immune checkpoint inhibitor (ICI) treatment. Ex vivo analysis of IMPULSED-derived cell radii was conducted by immunohistochemical wheat germ agglutinin staining of cell membranes, while intratumoral immune cell composition was analyzed by CD3 and F4/80 co-staining. RESULTS: OGSE-DWI detected mean cell radii of 8.8±1.3 µm for 4T1, 8.2±1.4 µm for 67NR, 13.0±1.7 for macrophage, and 3.8±1.8 µm for T-cell spheroids. While T-cell infiltration during progression of 4T1 tumors was observed by decreasing mean cell radii from 9.7±1.0 to 5.0±1.5 µm, increasing amount of intratumoral macrophages during progression of 67NR tumors resulted in increasing mean cell radii from 8.9±1.2 to 12.5±1.1 µm. After macrophage depletion, mean cell radii decreased from 6.3±1.7 to 4.4±0.5 µm. T-cell infiltration after ICI treatment was captured by decreasing mean cell radii in both tumor models, with more pronounced effects in the 67NR tumor model. CONCLUSIONS: OGSE-DWI provides a versatile tool for non-invasive profiling of the inflammatory TME by assessing the dominating cell type T-cells or macrophages.

Work expectations, their fulfillment, and exhaustion among radiologists of all career levels: what can be learned from the example of Germany.

OBJECTIVES: To evaluate work expectations of radiologists at different career levels, their fulfillment, prevalence of exhaustion, and exhaustion-associated factors. METHODS: A standardized digital questionnaire was distributed internationally to radiologists of all career levels in the hospital and in ambulatory care via radiological societies and sent manually to 4500 radiologists of the largest German hospitals between December 2020 and April 2021. Statistics were based on age- and gender-adjusted regression analyses of respondents working in Germany (510 out of 594 total respondents). RESULTS: The most frequent expectations were "joy at work" (97%) and a "good working atmosphere" (97%), which were considered fulfilled by at least 78%. The expectation of a "structured residency within the regular time interval" (79%) was more frequently judged fulfilled by senior physicians (83%, odds ratio (OR) 4.31 [95% confidence interval (95% CI) 1.95-9.52]), chief physicians (85%, 6.81 [95% CI 1.91-24.29]), and radiologists outside the hospital (88%, 7.59 [95% CI 2.40-24.03]) than by residents (68%). Exhaustion was most common among residents (physical exhaustion: 38%; emotional exhaustion: 36%), in-hospital specialists (29%; 38%), and senior physicians (30%; 29%). In contrast to paid extra hours, unpaid extra hours were associated with physical exhaustion (5-10 extra hours: OR 2.54 [95% CI 1.54-4.19]). Fewer opportunities to shape the work environment were related to a higher probability of physical (2.03 [95% CI 1.32-3.13]) and emotional (2.15 [95% CI 1.39-3.33]) exhaustion. CONCLUSIONS: While most radiologists enjoy their work, residents wish for more training structure. Ensuring payment of extra hours and employee empowerment may help preventing burnout in high-risk groups. KEY POINTS: • Most important work expectations of radiologists who work in Germany are "joy at work," a "good working atmosphere," "support for further qualification," and a "structured residency within the regular time interval," with the latter containing potential for improvement according to residents. • Physical and emotional exhaustion are common at all career levels except for chief physicians and for radiologists who work outside the hospital in ambulatory care. • Exhaustion as a major burnout criterion is associated with unpaid extra hours and reduced opportunities to shape the work environment.

Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer.

Objective: The objective of this study was to non-invasively differentiate the degree of malignancy in two murine breast cancer models based on identification of distinct tissue characteristics in a metastatic and non-metastatic tumor model using a multiparametric Magnetic Resonance Imaging (MRI) approach. Methods: The highly metastatic 4T1 breast cancer model was compared to the non-metastatic 67NR model. Imaging was conducted on a 9.4 T small animal MRI. The protocol was used to characterize tumors regarding their structural composition, including heterogeneity, intratumoral edema and hemorrhage, as well as endothelial permeability using apparent diffusion coefficient (ADC), T1/T2 mapping and dynamic contrast-enhanced (DCE) imaging. Mice were assessed on either day three, six or nine, with an i.v. injection of the albumin-binding contrast agent gadofosveset. Ex vivo validation of the results was performed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), histology, immunhistochemistry and electron microscopy. Results: Significant differences in tumor composition were observed over time and between 4T1 and 67NR tumors. 4T1 tumors showed distorted blood vessels with a thin endothelial layer, resulting in a slower increase in signal intensity after injection of the contrast agent. Higher permeability was further reflected in higher Ktrans values, with consecutive retention of gadolinium in the tumor interstitium visible in MRI. 67NR tumors exhibited blood vessels with a thicker and more intact endothelial layer, resulting in higher peak enhancement, as well as higher maximum slope and area under the curve, but also a visible wash-out of the contrast agent and thus lower Ktrans values. A decreasing accumulation of gadolinium during tumor progression was also visible in both models in LA-ICP-MS. Tissue composition of 4T1 tumors was more heterogeneous, with intratumoral hemorrhage and necrosis and corresponding higher T1 and T2 relaxation times, while 67NR tumors mainly consisted of densely packed tumor cells. Histogram analysis of ADC showed higher values of mean ADC, histogram kurtosis, range and the 90th percentile (p90), as markers for the heterogenous structural composition of 4T1 tumors. Principal component analysis (PCA) discriminated well between the two tumor models. Conclusions: Multiparametric MRI as presented in this study enables for the estimation of malignant potential in the two studied tumor models via the assessment of certain tumor features over time.

Work and Training Conditions of German Residents and Young Radiologists in Interventional Radiology - A Nationwide Survey.

With the increasing need for minimally invasive procedures based on lower complication rates, higher patient acceptance, and technical developments, there is a growing focus on the sound interventional training of young radiologists. This survey aimed to analyze the current situation in interventional radiology (IR) training in Germany to detect shortcomings and identify areas for improvement.From November 1-30, 2020, an online questionnaire was distributed to representative radiological associations and societies with the request to forward it to radiology residents and radiologists < 40 years. The 44 questions covered six distinct areas from personal working conditions to the characterization of the IR department, training conditions, role of women in IR, and attendance at congresses/external training.A total of 330 participants completed the questionnaire. 77 % of participants expressed a high interest in IR, and 47 % could even imagine subspecializing in interventional radiology. Most institutions provided the necessary learning conditions and infrastructure. The rate of overall satisfaction with IR training conditions was 45 % (vs. a dissatisfaction rate of 39 %). However, females showed a lower satisfaction rate with their training environment than male participants (28 % vs. 51 %; P = 0.06). Positive correlations with work satisfaction were found for the presence and duration of the IR rotation, the number of partly independently/mentored performed interventions, and structured feedback. Moreover, the need for a structured training curriculum was expressed by 67 % of participants.Radiological residents and young radiologists expressed a high interest in interventional radiology, and they rate the infrastructure of German hospitals regarding IR as sufficient. However, they expressed the need for consistent IR rotations and better-structured resident and postgraduate education (curricula & interviews).Interest in interventional radiology among radiological residents and young radiologists in Germany is high, but satisfaction with interventional radiology training leaves room for improvement. The most frequently mentioned aspects that can improve IR training were · organized rotations of at least 6 months. · structured curriculums with face-to-face feedback. · structured guidance by senior interventionists during procedures. CITATION FORMAT: · Sieren M, Katoh M, Mahnken AH et al. Work and Training Conditions of German Residents and Young Radiologists in Interventional Radiology - A Nationwide Survey. Fortschr Röntgenstr 2022; 194: 1346 - 1357.

Diffusion-Weighted Imaging Prior to Percutaneous Sclerotherapy of Venous Malformations-Proof of Concept Study for Prediction of Clinical Outcome.

Prediction of response to percutaneous sclerotherapy in patients with venous malformations (VM) is currently not possible with baseline clinical or imaging characteristics. This prospective single-center study aimed to predict treatment outcome of percutaneous sclerotherapy as measured by quality of life (QoL) by using radiomic analysis of diffusion-weighted (dw) magnetic resonance imaging (MRI) before and after first percutaneous sclerotherapy. In all patients (n = 16) pre-interventional (PRE-) and delta (DELTA-) radiomic features (RF) were extracted from dw-MRI before and after first percutaneous sclerotherapy with ethanol gel or polidocanol foam, while QoL was assessed using the Toronto Extremity Salvage Score (TESS) and the 36-Item Short Form Survey (SF-36) health questionnaire. For selecting features that allow differentiation of clinical response, a stepwise dimension reduction was performed. Logistic regression models were fitted and selected PRE-/DELTA-RF were tested for their predictive value. QoL improved significantly after percutaneous sclerotherapy. While no common baseline patient characteristics were able to predict response to percutaneous sclerotherapy, the radiomics signature of VMs (independent PRE/DELTA-RF) revealed high potential for the prediction of clinical response after percutaneous sclerotherapy. This proof-of-concept study provides first evidence on the potential predictive value of (delta) radiomic analysis from diffusion-weighted MRI for Quality-of-Life outcome after percutaneous sclerotherapy in patients with venous malformations.

Using stroma-anchoring cytokines to augment ADCC: a phase 1 trial of F16IL2 and BI 836858 for posttransplant AML relapse.

Natural killer (NK) cells are key effectors in cancer immunosurveillance and posttransplant immunity, but deficiency of environmental signals and insufficient tumor recognition may limit their activity. We hypothesized that the antibody-mediated anchoring of interleukin-2 (IL-2) to a spliced isoform of the extracellular matrix (ECM) glycoprotein tenascin-C would potentiate NK-cell-mediated antibody-dependent cellular cytotoxicity against leukemic blasts. In this novel-novel combination, dose-escalation, phase 1 trial, we enrolled patients with posttransplant acute myeloid leukemia (AML) relapse to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of the antibody-cytokine fusion F16IL2 (10 × 106 to 20 × 106 IU IV; days 1, 8, 15, and 22 of each 28-day cycle) in combination with the anti-CD33 antibody BI 836858 (10-40 mg IV, 2 days after each F16IL2 infusion). Among the 15 patients (median [range] age, 50 [20-68] years) treated across 4 dose levels (DLs), 6 (40%) had received 2 or 3 prior transplantations. The most frequent adverse events were pyrexia, chills, and infusion-related reactions, which were manageable, transient and of grade ≤2. One dose-limiting toxicity occurred at each of DLs 3 (pulmonary edema) and 4 (graft-versus-host disease). Three objective responses were observed among 7 patients treated at the 2 higher DLs, whereas no responses occurred at the 2 starting DLs. Combination therapy stimulated the expansion and activation of NK cells, including those expressing the FcγRIIIA/CD16 receptor. ECM-targeted IL-2 combined with anti-CD33 immunotherapy represents an innovative approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. This trial was registered at EudraCT as 2015-004763-37.

In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker.

PURPOSE: As a promotor of tumor invasion and tumor microenvironment (TME) formation, the protein complex S100A8/S100A9 is associated with poor prognosis. Our aim was to further evaluate its origin and regulatory effects, and to establish an imaging biomarker for TME activity. METHODS: S100A9-/-cells (ko) were created from syngeneic murine breast cancer 4T1 (high malignancy) and 67NR (low malignancy) wildtype (wt) cell lines and implanted into either female BALB/c wildtype or S100A9-/- mice (n = 10 each). Anti-S100A9-Cy5.5-targeted fluorescence reflectance imaging was performed at 0 h and 24 h after injection. Potential early changes of S100A9-presence under immune checkpoint inhibition (anti-PD-L1, n = 7 vs. rat IgG2b as isotype control, n = 3) were evaluated. RESULTS: In S100A9-/-mice contrast-to-noise-ratios were significantly reduced for wt and S100A9-/-tumors. No significant differences were detected for 4T1 ko and 67NR ko cells as compared to wildtype cells. Under anti-PD-L1 treatment S100A9 presence significantly decreased compared with the control group. CONCLUSION: Our results confirm a secretion of S100A8/S100A9 by the TME, while tumor cells do not apparently release the protein. Under immune checkpoint inhibition S100A9-imaging reports an early decrease of TME activity. Therefore, S100A9-specific imaging may serve as an imaging biomarker for TME formation and activity.