Safety, efficacy, and survival of different transarterial chemoembolization techniques in the management of unresectable hepatocellular carcinoma: a comparative single-center analysis.

PURPOSE: Transarterial chemoembolization (TACE) has become the standard of care for the treatment of intermediate-stage hepatocellular carcinoma (HCC). However, current clinical practice guidelines lack consensus on the best selection of a specific TACE technique. This study aims to compare safety, tumor response, and progression-free survival (PFS) of conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE), and degradable starch microsphere TACE (DSM-TACE). METHODS: This retrospective study included n = 192 patients with HCC who underwent first TACE with unbiased follow-up at 4-6 weeks at our center between 2008 and 2021. Eligibility for TACE was BCLC intermediate stage B, bridging/down-staging (B/D) to liver transplantation (LT), or any other stage when patients were not suitable for resection, LT, local ablation, or systemic therapy. Patients were grouped into three cohorts (n = 45 cTACE, n = 84 DEB-TACE, n = 63 DSM-TACE), and further categorized by TACE indication (B/D or palliative). Liver function and adverse events, response assessed by the modified response evaluation criteria in solid tumors (mRECIST) 4-6 weeks post-TACE and PFS were analyzed. RESULTS: There were no significant differences in age, gender distribution, BCLC stage, or etiology of liver disease among the three TACE groups, even in the B/D or palliative subgroups. DEB-TACE induced slight increases in bilirubin in the palliative subgroup and in lactate dehydrogenase in the entire cohort 4-6 weeks post-TACE, and more adverse events in the palliative subgroup. DEB-TACE and DSM-TACE showed significantly higher disease control rates (complete and partial response, stable disease) compared to cTACE, especially in the B/D setting (p < 0.05). There was no significant difference in PFS between the groups [median PFS (months): cTACE, 10.0 vs. DEB, 7.0 vs. DSM, 10.0; p = 0.436]. CONCLUSION: Our study provides valuable perspectives in the decision-making for a specific TACE technique: DEB-TACE and DSM-TACE showed improved tumor response. DEB-TACE showed a prolonged impact on liver function and more side effects, so patients with impaired liver function should be more strictly selected, especially in the palliative subgroup.

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.

Radiomics-Based Prediction Model for Outcome of Radioembolization in Metastatic Colorectal Cancer.

PURPOSE: To evaluate the benefit of a contrast-enhanced computed tomography (CT) radiomics-based model for predicting response and survival in patients with colorectal liver metastases treated with transarterial Yttrium-90 radioembolization (TARE). MATERIALS AND METHODS: Fifty-one patients who underwent TARE were included in this single-center retrospective study. Response to treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 3-month follow-up. Patients were stratified as responders (complete/partial response and stable disease, n = 24) or non-responders (progressive disease, n = 27). Radiomic features (RF) were extracted from pre-TARE CT after segmentation of the liver tumor volume. A model was built based on a radiomic signature consisting of reliable RFs that allowed classification of response using multivariate logistic regression. Patients were assigned to high- or low-risk groups for disease progression after TARE according to a cutoff defined in the model. Kaplan-Meier analysis was performed to analyze survival between high- and low-risk groups. RESULTS: Two independent RF [Energy, Maximal Correlation Coefficient (MCC)], reflecting tumor heterogeneity, discriminated well between responders and non-responders. In particular, patients with higher magnitude of voxel values in an image (Energy), and texture complexity (MCC), were more likely to fail TARE. For predicting treatment response, the area under the receiver operating characteristic curve of the radiomics-based model was 0.75 (95% CI 0.48-1). The high-risk group had a shorter overall survival than the low-risk group (3.4 vs. 6.4 months, p < 0.001). CONCLUSION: Our CT radiomics model may predict the response and survival outcome by quantifying tumor heterogeneity in patients treated with TARE for colorectal liver metastases.

Radial compressed sensing imaging improves the velocity detection limit of single cell tracking time-lapse MRI.

PURPOSE: Time-lapse MRI enables tracking of single iron-labeled cells. Yet, due to temporal blurring, only slowly moving cells can be resolved. To study faster cells for example during inflammatory processes, accelerated acquisition is needed. METHODS: A rotating phantom system was developed to quantitatively measure the current maximum detectable speed of cells in time-lapse MRI. For accelerated cell tracking, an interleaved radial acquisition scheme was applied to phantom and murine brain in vivo time-lapse MRI experiments at 9.4 T. Detection of iron-labeled cells was evaluated in fully sampled and undersampled reconstructions with and without compressed sensing. RESULTS: The rotating phantom system enabled ultra-slow rotation of phantoms and a velocity detection limit of full-brain Cartesian time-lapse MRI of up to 172 µm/min was determined. Both phantom and in vivo measurements showed that single cells can be followed dynamically using radial time-lapse MRI. Higher temporal resolution of undersampled reconstructions reduced geometric distortion, the velocity detection limit was increased to 1.1 mm/min in vitro, and previously hidden fast-moving cells were recovered. In the mouse brain after in vivo labeling, a total of 42 ± 4 cells were counted in fully sampled, but only 7 ± 1 in undersampled images due to streaking artifacts. Using compressed sensing 33 ± 4 cells were detected. CONCLUSION: Interleaved radial time-lapse MRI permits retrospective reconstruction of both fully sampled and accelerated images, enables single cell tracking at higher temporal resolution and recovers cells hidden before due to blurring. The velocity detection limit as determined with the rotating phantom system increased two- to three-fold compared to previous results.

Evaluation of effectiveness and safety of the large-format pRESET 6-50 thrombectomy stent-retriever in the endovascular treatment of ischemic stroke: real-world experiences from two tertiary comprehensive stroke centers.

Objective: Mechanical thrombectomy (MT) has become the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO). First-pass (FP) reperfusion of the occluded vessel and fewer passes with stent retrievers show improvement in functional outcomes in stroke patients, while higher numbers of passes are associated with higher complication rates and worse outcomes. Studies indicate that a larger size of the stent-retriever is associated with a higher rate of first-pass reperfusion and improved clinical outcomes. In this retrospective study, we investigated the clinical performance of a recently developed and one of the largest stent-retrievers available in the treatment of LVO (pRESET 6-50, phenox GmbH, Bochum). Materials and methods: All consecutive patients with ischemic stroke due to proximal large vessel occlusion treated with MT using the pRESET 6-50 stent-retriever in two tertiary stroke centers between 09/2021 and 07/2022 were included in this study. The reperfusion rate after MT was quantified by the modified thrombolysis in cerebral infarction (mTICI) score, and functional neurological outcome was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score and the major early neurological recovery (mENR) rate after 24 h. Successful FP reperfusion was defined as mTICI ≥ 2b. Successful and complete reperfusion were defined as mTICI ≥ 2b and mTICI ≥ 2c, respectively. Results: In total, 98 patients (52 men and 46 women) with a median age of 75 (range 25-95 years) were included. A total of 70 (72%) patients presented with an occlusion of the middle cerebral artery (MCA) in the M1 segment, 6 (6%) patients with an occlusion of the M2 segment, 17 (17%) patients with an occlusion of the internal carotid artery (ICA), and 5 (5%) patients with an occlusion of the obstructed basilar artery (BA). Successful FP reperfusion was achieved in 58 patients (62%). Successful and complete reperfusion were achieved in 95 (97%) and 82 (83%) patients, respectively. The median National Institutes of Health Stroke Scale (NIHSS) in all treated patients improved from 17 to 7.5. Major early neurological recovery (mENR) was observed in 34 patients (35.1%). Conclusion: MT with the pRESET 6-50 stent-retriever achieves high successful first-pass and final reperfusion rates in patients with AIS and LVO. The results of this study support the thesis to use large-format stent-retriever in proximal vessel occlusion MT whenever feasible in order to improve high FP and final reperfusion rate, which are known predictors of good clinical outcome.

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.

Evaluation of effectiveness and safety of the multizone NeVaTM stent retriever for mechanical thrombectomy in ischemic stroke.

PURPOSE: This study aimed to evaluate the effectiveness and safety of the NeVaTM stent retriever as first- and second-line device for mechanical thrombectomy in acute ischemic stroke. METHODS: In this retrospective single-center study, all consecutive patients that underwent mechanical thrombectomy with NeVaTM stent retriever as first- or second-line device due to intracranial vessel occlusion with acute ischemic stroke between March and November 2022 were included. RESULTS: Thirty-nine patients (m=18, f=21) with a mean age of 69.9 ± 13.3 years were treated with the NeVaTM stent retriever. NeVaTM stent retriever was used as first-line device in 24 (61.5%) of patients and in 15 (38.5%) as second-line device. First-pass rate (≥mTICI 2c) of NeVaTM stent retriever was both 66.7% when used as first- or second-line device. Final recanalization rate including rescue strategies was 92.3% for ≥mTICI2c and 94.9% for ≥mTICI2b. No device-related minor or major adverse events were observed. A hemorrhage was detected in 33.3% of patients at 24h post-thrombectomy dual-energy CT, of which none was classified as symptomatic intracerebral hemorrhage. NIHSS and mRS improved significantly at discharge compared to admission (p<0.05). CONCLUSION: The NeVaTM stent retriever has a high effectivity and good safety profile as first- and second-line device for mechanical thrombectomy in acute ischemic stroke.

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.

Dynamic cell tracking using time-lapse MRI with variable temporal resolution Cartesian sampling.

PURPOSE: Temporal resolution of time-lapse MRI to track individual iron-labeled cells is limited by the required data-acquisition time to fill k-space and to reach sufficient SNR. Although motion of slowly patrolling monocytes can be resolved, detection of fast-moving immune cells requires improved acquisition and reconstruction strategies. THEORY AND METHODS: For accelerated MRI cell tracking, a Cartesian sampling scheme was designed, in which the fully sampled and undersampled k-space data for different acceleration factors were acquired simultaneously, and multiple undersampling ratios could be chosen retrospectively. Compressed-sensing reconstruction was applied using dictionary learning and low-rank constraints. Detection of iron-labeled monocytes was evaluated with simulations, rotating phantom experiments and in vivo mouse brain measurements at 9.4 T. RESULTS: Fully sampled and 2.4-times and 4.8-times accelerated images were reconstructed and had sufficient contrast-to-noise ratio (CNR) for single cells to be resolved and followed dynamically. The phantom experiments showed an improvement in CNR of 6.1% per µm/s in the 4.8-times undersampled images. Geometric distortion of cells caused by motion was visibly reduced in the accelerated images, which enabled detection of moving cells with velocities of up to 7.0 µm/s. In vivo, additional cells were resolved in the accelerated images due to the improved temporal resolution. CONCLUSION: The easy-to-implement flexible Cartesian sampling scheme with compressed-sensing reconstruction permits simultaneous acquisition of both fully sampled and high temporal resolution images. The CNR of moving cells is effectively improved, enabling the recovery of high velocity cells with sufficient contrast at virtually no cost.

Clinical impact of a celiac axis stenosis in patients undergoing hepatobiliary surgery.

BACKGROUND: Celiac axis stenosis (CAS) often is an incidental finding in terms of diagnostic for hepatobiliary surgery since most cases remain asymptomatic. It remains unclear whether CAS is a risk factor for postoperative complications after hepatobiliary surgery. Therefore, the aim of this study was to evaluate the impact of an asymptomatic CAS on the postoperative morbidity and survival of patients undergoing hepatobiliary surgery. METHODS: We retrospectively analyzed CT scans and clinicopathological data of 250 consecutive patients undergoing hepatobiliary surgery between 2011 and 2018 in our tertiary center. We compared the postoperative course between patients with and without an incidental CAS as well as their overall survival. RESULTS: CAS was caused by atherosclerotic stenosis in 16 (64%) patients, by ligamentous stenosis in 4 (16%) and by combined conditions in 5 cases (20%). Mean age of patients in the CAS group was significantly higher in comparison to patients of the non-CAS group (71.0 vs. 59.1 years, p < 0.001). Major hepatectomy was conducted in 40% of the CAS patients and 19.6% of non-CAS patients, respectively (p = 0.036). Interestingly, no statistically significant differences in postoperative morbidity (40 vs. 46.2%, p = 0.673) or in overall survival between the groups (41.3 vs. 51.9 months, p = 0.611) were observed. CONCLUSION: Our analysis found no correlation between an asymptomatic celiac axis stenosis and postoperative complications or overall survival after hepatobiliary surgery. Which impact the incidental CAS may have in highly complex cases remains unclear. Further studies are needed to identify patients who benefit from CAS treatment before hepatobiliary surgery.

Radiomics of Tumor Heterogeneity in 18F-FDG-PET-CT for Predicting Response to Immune Checkpoint Inhibition in Therapy-Naïve Patients with Advanced Non-Small-Cell Lung Cancer.

We aimed to evaluate the predictive and prognostic value of baseline 18F-FDG-PET-CT (PET-CT) radiomic features (RFs) for immune checkpoint-inhibitor (CKI)-based first-line therapy in advanced non-small-cell lung cancer (NSCLC) patients. In this retrospective study 44 patients were included. Patients were treated with either CKI-monotherapy or combined CKI-based immunotherapy-chemotherapy as first-line treatment. Treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). After a median follow-up of 6.4 months patients were stratified into "responder" (n = 33) and "non-responder" (n = 11). RFs were extracted from baseline PET and CT data after segmenting PET-positive tumor volume of all lesions. A Radiomics-based model was developed based on a Radiomics signature consisting of reliable RFs that allow classification of response and overall progression using multivariate logistic regression. These RF were additionally tested for their prognostic value in all patients by applying a model-derived threshold. Two independent PET-based RFs differentiated well between responders and non-responders. For predicting response, the area under the curve (AUC) was 0.69 for "PET-Skewness" and 0.75 predicting overall progression for "PET-Median". In terms of progression-free survival analysis, patients with a lower value of PET-Skewness (threshold < 0.2014; hazard ratio (HR) 0.17, 95% CI 0.06-0.46; p < 0.001) and higher value of PET-Median (threshold > 0.5233; HR 0.23, 95% CI 0.11-0.49; p < 0.001) had a significantly lower probability of disease progression or death. Our Radiomics-based model might be able to predict response in advanced NSCLC patients treated with CKI-based first-line therapy.

Detection of Early Endothelial Dysfunction by Optoacoustic Tomography.

Variations in vascular wall shear stress are often presumed to result in the formation of atherosclerotic lesions at specific arterial regions, where continuous laminar flow is disturbed. The influences of altered blood flow dynamics and oscillations on the integrity of endothelial cells and the endothelial layer have been extensively studied in vitro and in vivo. Under pathological conditions, the Arg-Gly-Asp (RGD) motif binding integrin αvß3 has been identified as a relevant target, as it induces endothelial cell activation. Animal models for in vivo imaging of endothelial dysfunction (ED) mainly rely on genetically modified knockout models that develop endothelial damage and atherosclerotic plaques upon hypercholesterolemia (ApoE-/- and LDLR-/-), thereby depicting late-stage pathophysiology. The visualization of early ED, however, remains a challenge. Therefore, a carotid artery cuff model of low and oscillating shear stress was applied in CD-1 wild-type mice, which should be able to show the effects of altered shear stress on a healthy endothelium, thus revealing alterations in early ED. Multispectral optoacoustic tomography (MSOT) was assessed as a non-invasive and highly sensitive imaging technique for the detection of an intravenously injected RGD-mimetic fluorescent probe in a longitudinal (2-12 weeks) study after surgical cuff intervention of the right common carotid artery (RCCA). Images were analyzed concerning the signal distribution upstream and downstream of the implanted cuff, as well as on the contralateral side as a control. Subsequent histological analysis was applied to delineate the distribution of relevant factors within the carotid vessel walls. Analysis revealed a significantly enhanced fluorescent signal intensity in the RCCA upstream of the cuff compared to the contralateral healthy side and the downstream region at all time points post-surgery. The most obvious differences were recorded at 6 and 8 weeks after implantation. Immunohistochemistry revealed a high degree of αv-positivity in this region of the RCCA, but not in the left common carotid artery (LCCA) or downstream of the cuff. In addition, macrophages could be detected by CD68 immunohistochemistry in the RCCA, showing ongoing inflammatory processes. In conclusion, MSOT is capable of delineating alterations in endothelial cell integrity in vivo in the applied model of early ED, where an elevated expression of integrin αvß3 was detected within vascular structures.

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.

Medical imaging training with eye movement modeling examples: A randomized controlled study.

PURPOSE: To determine whether ultrasound training in which the expert's eye movements are superimposed to the underlying ultrasound video (eye movement modeling examples; EMMEs) leads to better learner outcomes than traditional eye movement-free instructions. MATERIALS AND METHODS: 106 undergraduate medical students were randomized in two groups; 51 students in the EMME group watched 5-min ultrasound examination videos combined with the eye movements of an expert performing the task. The identical videos without the eye movements were shown to 55 students in the control group. Performance and behavioral parameters were compared prepost interventional using ANOVAs. Additionally, cognitive load, and prior knowledge in anatomy were surveyed. RESULTS: After training, the EMME group identified more sonoanatomical structures correctly, and completed the tasks faster than the control group. This effect was partly mediated by a reduction of extraneous cognitive load. Participants with greater prior anatomical knowledge benefited the most from the EMME training. CONCLUSION: Displaying experts' eye movements in medical imaging training appears to be an effective way to foster medical interpretation skills of undergraduate medical students. One underlying mechanism might be that practicing with eye movements reduces cognitive load and helps learners activate their prior knowledge.

Clinical Outcome and Quality of Life of Multimodal Treatment of Extracranial Arteriovenous Malformations: The APOLLON Study Protocol.

PURPOSE: Arteriovenous malformations (AVMs) as rare diseases are diagnostically and therapeutically challenging. Due to the limited evidence regarding treatment outcome, prospective data are needed on how different treatment regimens affect outcome. The aims of this prospective trial are to determine effectiveness, safety, and clinical outcome of multimodal treatment in patients with extracranial AVMs. MATERIALS AND METHODS: After clinical and magnetic resonance imaging (MRI)-based diagnosis and informed consent, 146 patients (> 4 years and < 70 years) undergoing multimodal therapy in tertiary care vascular anomalies centers will be included in this prospective observational trial. Treatment options include conservative management, medical therapy, minimally invasive image-guided procedures (embolization, sclerotherapy) and surgery as well as combinations of the latter. The primary outcome is the patient-reported QoL 6 months after completion of treatment using the short form-36 health survey version 2 (SF-36v2) and the corresponding short form-10 health survey (SF-10) for children. In addition, clinical presentation (physician-reported signs), MRI imaging (radiological assessment of devascularization), recurrence rate, and therapeutic safety will be analyzed. Further follow-up will be performed after 12, 24, and 36 months. Moreover, liquid biopsies are being obtained from peripheral blood at multiple time points to investigate potential biomarkers for therapy response and disease progression. DISCUSSION: The APOLLON trial is a prospective, multicenter, observational open-label trial with unequal study groups to generate prospective evidence for multimodal treatment of AVMs. A multicenter design with the potential to assess larger populations will provide an increased understanding of multimodal therapy outcome in this orphan disease. TRIAL REGISTRATION: German Clinical Trials Register (identification number: DRKS00021019) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021019 .

Multicentered analysis of percutaneous sclerotherapies in venous malformations of the face.

Objectives: To evaluate the safety and outcome of image-guided sclerotherapy for treating venous malformations (VMs) of the face. Materials and methods: A multicenter cohort of 68 patients with VMs primarily affecting the face was retrospectively investigated. In total, 142 image-guided sclerotherapies were performed using gelified ethanol and/or polidocanol. Clinical and imaging findings were assessed to evaluate clinical response, lesion size reduction, and complication rates. Sub-analyses of complication rates depending on type and injected volume of the sclerosant as well as of pediatric versus adult patient groups were conducted. Results: Mean number of procedures per patient was 2.1 (±1.7) and mean follow-up consisted of 8.7 months (±6.8 months). Clinical response (n = 58) revealed a partial relief of symptoms in 70.7% (41/58), 13/58 patients (22.4%) presented symptom-free while only 4/58 patients (6.9%) reported no improvement. Post-treatment imaging (n = 52) revealed an overall objective response rate of 86.5% (45/52). The total complication rate was 10.6% (15/142) including 4.2% (7/142) major complications, mostly (14/15, 93.3%) resolved by conservative means. In one case, a mild facial palsy persisted over time. The complication rate in the gelified ethanol subgroup was significantly higher compared to polidocanol and to the combination of both sclerosants (23.5 vs. 6.0 vs. 8.3%, p = 0.01). No significant differences in complications between the pediatric and the adult subgroup were observed (12.1 vs. 9.2%, p = 0.57). Clinical response did not correlate with lesion size reduction on magnetic resonance imaging (MRI). Conclusion: Image-guided sclerotherapy is effective for treating VMs of the face. Clinical response is not necessarily associated with size reduction on imaging. Despite the complex anatomy of this location, the procedures are safe for both adults and children.

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.

Image-guided embolization of arteriovenous malformations of the hand using Ethylene-vinyl Alcohol Copolymer.

PURPOSE This study aimed to evaluate the safety and outcome of image-guided embolization for treating arteriovenous malformations (AVMs) of the hand using ethylene-vinyl alcohol copolymer (EVOH). METHODS A retrospective, multicenter cohort of 15 patients with AVMs of the hand treated with 35 imageguided embolotherapies using EVOH was investigated. Clinical history, symptomatology, and imaging findings were assessed to evaluate clinical outcome (symptom-free, partial relief of pain, no improvement of pain, and clinical progression despite embolization), lesion devascularization (total, 100%; near-total, 90%-99%; substantial, 70%-90%; partial, 30%-70%; and failure, 0%-30%), and peri- and postprocedural complication rates (major complications classified according to CIRSE guidelines). Substratification analysis was performed with respect to the involvement of different anatomical compartments and the injected volume of the embolic agent. RESULTS Patients were treated for pain (93.3%), skin ulceration (46.7%), and local bleeding (33.3%). The mean number of embolotherapies was 2.3 (±1.1) in 3 patients, a planned surgical resection was conducted after embolization. Clinical outcome after a median follow-up of 18 months revealed an overall response of 11/15 patients (73.3%). Imaging at last follow-up revealed 70%- 99% reduced vascularization in 12/15 patients (80%) including 2 patients (13.3%) with a neartotal devascularization of 90%-99%. Peri- and postprocedural complications occurred in 8.5% and 31.5%, respectively, including 17.1% major complications, in 1 case requiring a previously unplanned resection. Involvement of the finger was associated with increased rates of persistent symptoms compared to the other groups (P=.049). No significant difference between the embolic agent volume injected and complication rates was found (P=.372). CONCLUSION Image-guided embolization using EVOH-based liquid embolic agents is effective for treating AVMs of the hand in the mid-term.

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.