Intra-arterial catheter-directed CT angiography for assessment of endovascular aortic aneurysm repair.

ObjectiveTo compare the efficacy and safety as well as associated image quality of catheter-directed CT angiography (CCTA) with a low dose of iodine contrast agent compared to intravenous CTA in patients undergoing endovascular aortic aneurysm repair (EVAR).MethodsRetrospective data analysis of 92 patients undergoing EVAR between January 2009 and December 2017 was performed. Patients were divided in two groups; those receiving CTA (n = 59) after intravenous contrast agent application and those receiving CCTA (n = 33) via an intraarterial catheter placed in the descending aorta. Demographic and cardiovascular risk factors as well as renal function parameters before, immediately after and 6-60 months after EVAR were evaluated. As primary endpoint, changes in serum creatinine levels in the two groups were evaluated. Secondary endpoints encompassed complications associated with intraarterial catheter placement. Objective (signal-to-noise ratios) and subjective image quality (5-point Likert scale) were compared.ResultsAmount of contrast medium was significantly lower in CCTA compared to i.v. CTA (23 ± 7 ml vs. 119 ± 15 ml, pConclusionsCatheter-directed CTA is safe and provides comparable image quality with a substantial retrenchment of the needed amount of iodine-based contrast medium. However, no benefit of the reduced contrast medium protocol with respect to renal function was observed

Multispectral Optoacoustic Tomography: Intra- and Interobserver Variability Using a Clinical Hybrid Approach

Multispectral optoacoustic tomography (MSOT) represents a new imaging approach revealing functional tissue information without extrinsic contrast agents. Using a clinical combined ultrasound (US)/MSOT device, we investigated the interindividual robustness and impact of intra- and interobserver variability of MSOT values in soft tissue (muscle and subcutaneous fat) of healthy volunteers. Semiquantitative MSOT values for deoxygenated (Hb), oxygenated (HbO2) and total hemoglobin (HbT), as well as oxygen saturation (sO2), were calculated for both forearms in transversal and longitudinal probe orientation (n = 3, 8 measurements per subject). For intraobserver reproducibility, the same examiner investigated three subjects twice. Mean values of left vs. right forearm and transversal vs. longitudinal probe orientation were compared using an unpaired Student’s t test. Bland Altmann plots with 95% limits of agreement for absolute averages and differences were calculated. Intraclass correlation coefficients (ICC 2,k) were computed for three different examiners. We obtained reproducible and consistent MSOT values with small-to-moderate deviation for muscle and subcutaneous fat tissue. Probe orientation and body side had no impact on calculated MSOT values (p > 0.05 each). Intraobserver reproducibility revealed equable mean values with small-to-moderate deviation. For muscular tissue, good ICC was obtained for sO2. Measurements of subcutaneous tissue revealed good-to-excellent ICCs for all calculated values. Thus, in this preliminary study on healthy individuals, clinical MSOT provided consistent and reproducible functional soft tissue characterization, independent on the investigating personnel

Interventional recanalization therapy in patients with non-cirrhotic, non-malignant portal vein thrombosis: comparison between transjugular versus transhepatic access

Purpose To compare the safety and outcome of transjugular versus percutaneous technique in recanalization of non-cirrhotic, non-malignant portal vein thrombosis. Methods We present a retrospective bicentric analysis of 21 patients with non-cirrhotic, non-malignant PVT, who were treated between 2016 and 2021 by interventional recanalization via different access routes (percutaneous [PT] vs. transjugular in transhepatic portosystemic shunt [TIPS] technique). Complication rates with a focus on periprocedural bleeding and patency as well as outcome were compared. Results Of the 21 patients treated (median age 48 years, range of 19-78), seven (33%) patients had an underlying prothrombotic condition. While 14 (57%) patients were treated for acute PVT, seven (43%) patients had progressive thrombosis with known chronic PVT. Nine patients underwent initial recanalization via PT access and twelve via TIPS technique. There was no significant difference in complete technical success rate according to initial access route (55.5% in PT group vs. 83.3% in TIPS group, p = 0.331). However, creation of an actual TIPS was associated with higher technical success in restoring portal venous flow (86.6% vs. 33.3%, p = 0.030). 13 (61.9%) patients received thrombolysis. Nine (42.8%) patients experienced hemorrhagic complications. In a multivariate analysis, thrombolysis (p = 0.049) and PT access as the first procedure (p = 0.045) were significant risk factors for bleeding. Conclusion Invasive recanalization of the portal vein in patients with PVT and absence of cirrhosis and malignancy offers a good therapeutic option with high recanalization and patency rates. Bleeding complications result predominantly from a percutaneous access and high amounts of thrombolytics used;therefore, recanalization via TIPS technique should be favored

Intra-arterial catheter-directed CT angiography for assessment of endovascular aortic aneurysm repair

OBJECTIVE: To compare the efficacy and safety as well as associated image quality of catheter-directed CT angiography (CCTA) with a low dose of iodine contrast agent compared to intravenous CTA in patients undergoing endovascular aortic aneurysm repair (EVAR). METHODS: Retrospective data analysis of 92 patients undergoing EVAR between January 2009 and December 2017 was performed. Patients were divided in two groups; those receiving CTA (n = 59) after intravenous contrast agent application and those receiving CCTA (n = 33) via an intraarterial catheter placed in the descending aorta. Demographic and cardiovascular risk factors as well as renal function parameters before, immediately after and 6–60 months after EVAR were evaluated. As primary endpoint, changes in serum creatinine levels in the two groups were evaluated. Secondary endpoints encompassed complications associated with intraarterial catheter placement. Objective (signal-to-noise ratios) and subjective image quality (5-point Likert scale) were compared. RESULTS: Amount of contrast medium was significantly lower in CCTA compared to i.v. CTA (23 ± 7 ml vs. 119 ± 15 ml, p<0.0001). Patients undergoing catheter-directed CTA had higher baseline creatinine values compared to the group with intravenous iodine application (1.9 ± 0.6 mg/dl vs. 1.3 ± 0.5 mg/dl; p<0.0001). Follow-up serum creatinine levels however did not show significant alterations between the two groups (1.9 ± 0.4 mg/dl vs. 1.3 ± 0.5 mg/dl). No major complications were detected in the CCTA group. Signal-to-noise ratio (SNR) was comparable between i.v. CTA and CCTA (8.5 ± 4.6 vs. 7.7 ± 4.0; p = 0.37) and subjective image similarly revealed no differences with a good interobserver agreement (ICC = 0.647). CONCLUSIONS: Catheter-directed CTA is safe and provides comparable image quality with a substantial retrenchment of the needed amount of iodine-based contrast medium. However, no benefit of the reduced contrast medium protocol with respect to renal function was observed

Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease

Early assessment of target hit in anti-cancer therapies is a major task in oncologic imaging. In this study, immediate target hit and effectiveness of CD13-targeted tissue factor tTF-NGR in patients with advanced malignant disease enrolled in a phase I trial was assessed using a multiparametric MRI protocol. Seventeen patients with advanced solid malignancies were enrolled in the trial and received tTF-NGR for at least one cycle of five daily infusions. Tumor target lesions were imaged with multiparametric MRI before therapy initiation, five hours after the first infusion and after five days. The imaging protocol comprised ADC, calculated from DWI, and DCE imaging and vascular volume fraction (VVF) assessment. DCE and VVF values decreased within 5 h after therapy initiation, indicating early target hit with a subsequent decrease in tumor perfusion due to selective tumor vessel occlusion and thrombosis induced by tTF-NGR. Simultaneously, ADC values increased at five hours after tTF-NGR administration. In four patients, treatment had to be stopped due to an increase in troponin T hs, with subsequent anticoagulation. In these patients, a reversed effect, with DCE and VVF values increasing and ADC values decreasing, was observed after anticoagulation. Changes in imaging parameters were independent of the mean vessel density determined by immunohistochemistry. By using a multiparametric imaging approach, changes in tumor perfusion after initiation of a tumor vessel occluding therapy can be evaluated as early as five hours after therapy initiation, enabling early assessment of target hit

Tracking of Tumor Cell–Derived Extracellular Vesicles In Vivo Reveals a Specific Distribution Pattern with Consecutive Biological Effects on Target Sites of Metastasis

Purpose!#!Extracellular vesicles, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators of intercellular communication. The purpose of this study was to assess the distribution of extracellular vesicles from highly malignant breast cancer and their subsequent effect on the immune cell infiltrate in target organs of metastasis.!##!Procedures!#!Extracellular vesicles were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthy BALB/c mice. The purity of the isolate was verified by electron microscopy and western blotting. Extracellular vesicles were additionally subjected to proteome analysis. After labeling with the fluorescent dye DiR, extracellular vesicles were injected into healthy BALB/c mice and their in vivo distribution was assessed using fluorescence reflectance imaging (FRI). Following ex vivo imaging of the organs, lung tissue samples were analyzed for extracellular vesicle-mediated changes of myeloid cells and T cell numbers, using flow cytometry. Proteome analysis revealed major differences in the cargo of tumor cell-derived versus extracellular vesicles from healthy serum.!##!Results!#!In contrast to control extracellular vesicles, DiR-labeled extracellular vesicles from tumor cells preferentially accumulated in lung, liver, and spine. Subsequent flow cytometry of the immune cell composition of lung tissue samples revealed an increase of cytotoxic CD8+ T cells and a decrease of CD4+ T-helper cells as well as an increase in mature macrophages in response to tumor cell EV.!##!Conclusions!#!In conclusion, distribution of tumor cell-derived extracellular vesicles follows a specific pattern and can be monitored, using dedicated imaging. Extracellular vesicles alter the immune cell composition in target organs of metastasis, using a specific proteome cargo

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

Abstract 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

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 3 106 to 20 3 106 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 FcgRIIIA/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

Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology

Zusammenfassung Ziel Vergleich der Punktionsabweichung und -dauer zwischen Computertomografie (CT) - und C-Arm-CT (CACT) -gesteuertem Punktionsverfahren bei Anwendung durch Assistenzarzte in Weiterbildung (AiW). Material und Methode In einer Kohorte von 25 AiW, die Teil einer wissenschaftlichen Forderung waren, wurden entweder CT- oder CACT-gesteuerte Punktionen an einem Phantom durchgefuhrt. Vor Beginn wurden der Weiterbildungsstand, die Erfahrung mit Spielen eines Musikinstruments, mit Videospielen und mit Ballsportarten und die Selbsteinschatzung von manueller Geschicklichkeit und raumlichem Denkvermogen abgefragt. Jede/r AiW fuhrte 2 Punktionen durch, wobei die 1. Punktion mit einem transaxialen bzw. einfach angulierten Nadelpfad und die 2. Punktion mit einem einfach bzw. doppelt angulierten Nadelpfad erfolgte. Punktionsabweichung und -dauer wurden zwischen den Verfahren verglichen und mit den Selbsteinschatzungen korreliert. Ergebnisse Die beiden Gruppen der AiW zeigten keine Unterschiede in der Erfahrung in der Radiologie (p = 1), in der Angiografie (p = 0.415) und in der Anzahl bereits durchgefuhrter Punktionen gesteuert durch Ultraschall (p = 0,483), CT (p = 0,934) und CACT (p = 0,466). In der CT (ohne Navigationssoftware) war die Punktionsdauer signifikant langer als mit der CACT-Bildsteuerung mit Navigationssoftware (p < 0,001). Bei der Punktionsdauer zeigten sich keine signifikanten Unterschiede zwischen der 1. und 2. Punktion im CT (p = 0,719), wahrend die 2. Punktion mit CACT schneller durchgefuhrt werden konnte (p = 0,006). Die Punktionsabweichung war weder signifikant zwischen CT- und CACT-Bildsteuerung (p = 0,337), noch zwischen der 1. und 2. Punktion der jeweiligen Verfahren (CT: p = 0,130; CACT: p = 0,391). Die Selbsteinschatzung der manuellen Geschicklichkeit korrelierte nicht mit der Punktionsabweichung (p = 0,059) und -dauer (p = 0,158). Das subjektive raumliche Denkvermogen zeigte eine moderate positive Korrelation zur Punktionsabweichung (p = 0,011), aber nicht zur -dauer (p = 0,541). Schlussfolgerung Die AiW erreichten eine dem Ausbildungsstand entsprechende, klinisch adaquate Punktionsabweichung unter CT- und CACT-Bildsteuerung. Die CACT-gesteuerten Punktionen mit Unterstutzung durch Navigationssoftware wurden schneller durchgefuhrt, und auch die Lernkurve war mit CACT-Bildsteuerung steiler. Raumliches Denkvermogen kann moglicherweise das Erlernen bildgesteuerter Punktionen beschleunigen. Kernaussagen: Die Erfahrung mit Punktionen war in einer Gruppe von AiW, die im Rahmen des Programms der Deutschen Rontgengesellschaft e. V. Forscher-fur-die-Zukunft ausgesucht wurden, dem Weiterbildungsstand entsprechend. Trotz kollektiv geringerer Erfahrung der radiologischen AiW mit der CACT-gesteuerten Punktion mit Navigationssoftwareunterstutzung ist die Lernkurve gegenuber der einfachen CT-Punktion moglicherweise steiler. Bei schwierigen Punktionswegen konnte die CACT-Bildsteuerung mit Softwareunterstutzung einen Vorteil in der Durchfuhrung gegenuber der konventionellen CT-Bildsteuerung haben. Zitierweise Meine TC, Hinrichs JB, Werncke T et al. Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology. Fortschr Rontgenstr 2021; DOI: 10. 1055/a-1586-273