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result(s) for
"Herr, Felix L."
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Contrast-enhanced ultrasound with VEGFR2-targeted microbubbles for monitoring combined anti-PD-L1/anti-CTLA-4 immunotherapy effects in a murine melanoma model with immunohistochemical validation
by
Clevert, Dirk-Andre
,
Kloiber-Langhorst, Sandra
,
Burkard, Tanja
in
Allografts
,
Anesthesia
,
Angiogenesis
2025
Immune checkpoint inhibitors (ICIs) have emerged as a highly effective treatment option for patients with metastatic melanoma. As not all patients respond to ICI immunotherapy, imaging biomarkers are required to accurately monitor early response to therapy. Therefore, the aim of this study was to evaluate contrast-enhanced ultrasound (CEUS) with VEGFR2-targeted microbubbles for monitoring the effects of combined anti-PD-L1/anti-CTLA-4 immunotherapy in a murine melanoma model.
Murine melanoma allografts (B16-F10) were implanted subcutaneously in n = 10 therapy and n = 10 control female C57BL/6 mice. CEUS with VEGFR2-targeted microbubbles was performed on day 7 and 12. The therapy group received 3 intraperitoneal injections on days 7, 9, 11 of combined anti-PD-L1/anti-CTLA-4 immunotherapy, the control group received a placebo. CEUS assessed tumour perfusion during an early vascular phase (wash-in area under the curve = WiAUC) and VEGFR2-specific binding during a late molecular phase (signal intensity at 8 minutes (SI8min) and 10 minutes (SI10min)). For pathophysiological validation immunohistochemistry was performed.
At follow-up, the CEUS perfusion parameter WiAUC demonstrated a significantly higher decrease in the therapy than in the control group (p = 0.021). At follow-up, the signal enhancement in the late phase was significantly lower in the therapy than in the control group (SI8min p = 0.003; SI10min p = 0.002). Immunohistochemistry revealed significantly more apoptotic tumour cells (p = 0.001), more tumour infiltrating lymphocytes (p = 0.049), lower tumour cell proliferation (p = 0.001), lower microvascular density (p = 0.003) and lower VEGFR2 expression (p = 0.003) in the therapy than in the control group.
CEUS with VEGFR2-targeted microbubbles allowed for monitoring early treatment effects of a combined anti-PD-L1/anti-CTLA-4 immunotherapy on melanoma allografts with significantly lower tumour perfusion and significantly lower binding of VEGFR2-targeted microbubbles in the therapy than in the control group.
Journal Article
Structured reporting of B-mode, color Doppler, and CEUS in testicular tumor assessment: a reader study with urologist ratings
by
Waldbillig, Frank
,
Clevert, Dirk-Andre
,
Frölich, Matthias Frank
in
Adult
,
CEUS
,
Classification systems
2026
Purpose
Structured reporting (SR) offers standardized radiological documentation, enhancing clarity and reproducibility. However, its role in contrast-enhanced ultrasound (CEUS) for testicular tumors remains underexplored. This study evaluates urologist-perceived clarity, completeness, and clinical usefulness of SR compared to free-text reporting (FTR).
Methods and materials
In this retrospective, single-center study, 65 male patients with suspected testicular tumors underwent CEUS at LMU University Hospital. Reports were initially documented as FTRs by an experienced radiologist and later converted into SRs using Smart Reporting software. Four board-certified urologists independently assessed both formats using a structured questionnaire. Completeness, readability, trust, and impact on clinical decision-making were evaluated. Statistical analysis included McNemar’s test and the Wilcoxon signed-rank test, with α = 0.05.
Results
SRs significantly improved readability (97.3% vs. 10.0%,
p
< 0.001) and information extraction (98.8% vs. 91.9%,
p
< 0.001). However, completeness (56.9% vs. 60.8%,
p
= 0.427) and clinical decision support (85.7% vs. 84.9%,
p
= 0.152) were comparable. Trust in SRs was lower than in FTRs (4.92 vs. 5.22,
p
< 0.001), likely due to missing diagnostic parameters and retrospective SR generation.
Conclusions
SR was associated with improved reporting clarity and consistency but did not outperform FTR in completeness or clinical decision-making. Interdisciplinary collaboration in template development and the integration of classification systems could improve SR’s diagnostic value. Future prospective, multicenter studies should assess real-time SR implementation and its potential impact on reporting quality, communication, and outcome-based endpoints in prospective settings.
Clinical relevance/application
Structured reporting in multiparametric testicular ultrasound including CEUS improved perceived readability and facilitated information access for referring clinicians. However, SR showed no clear advantage over free-text reporting regarding completeness or clinical decision-making. The lower clinician trust in SR highlights the need for clinically tailored templates developed in interdisciplinary collaboration. The broader clinical value of SR in testicular imaging should be confirmed in prospective real-time studies incorporating outcome-based and workflow-related endpoints.
Journal Article
Impact of ischemia duration on MRI-derived perfusion parameters in a mouse kidney transplant model
2026
Objectives
Cold ischemia during kidney transplantation induces ischemia-reperfusion injury with endothelial dysfunction, capillary leak, and impaired perfusion. Its duration critically determines graft outcome. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables noninvasive assessment of renal microcirculation and may indicate ischemic injury. We evaluated the impact of ischemia duration on DCE-MRI-derived perfusion parameters in renal transplants in mice.
Materials and methods
Procedures were approved by the local institutional animal care and use committee. A total of 15 C57BL/6 mice underwent kidney transplantation and were assigned to a short or prolonged cold ischemia group. DCE-MRI was performed to assess renal perfusion. Imaging was conducted at a mean of 268 ± 30 days (mean ± standard deviation) after transplantation. Perfusion parameters were calculated using the Patlak model, which provides the plasma volume fraction (v
p
), reflecting renal blood volume and perfusion, and the volume transfer constant (K
trans
), characterizing the rate of contrast agent extravasation from capillaries into the extravascular extracellular space.
Results
Significant differences were observed in the K
trans
parameter of transplanted kidneys between groups. The median K
trans
(mL/100 mL/min) was significantly higher in the 16-h group (2.87, interquartile range 2.45–3.03)
versus
the 30-min group (0.91, 0.90–1.42;
p
= 0.008). Median v
p
(mL/100 mL/min) was non-significantly lower in the 16-h group (21.89, 17.28–23.22)
versus
the 30-min group (29.02, 24.99–37.15;
p
= 0.151).
Conclusion
Cold ischemia with 16-h duration was associated with significantly higher K
trans
values in kidney transplants, reflecting significantly increased vascular permeability. DCE-MRI provides a sensitive tool for detecting ischemia-induced microvascular dysfunction.
Relevance statement
Quantitative DCE-MRI detects microvascular injury after 16-h cold ischemia in kidney transplants in mice, supporting its potential as a noninvasive tool to assess graft integrity and guide interventions aimed at improving long-term transplant outcomes.
Key Points
The duration of ischemia critically affects endothelial integrity and perfusion characteristics in a mouse kidney transplant model.
Prolonged 16-h ischemia leads to increased vascular permeability, indicating more severe endothelial and microcirculatory injury in transplanted kidneys.
DCE-MRI enables sensitive detection of subtle ischemia-related microvascular alterations, supporting its value for noninvasive graft assessment.
Graphical Abstract
Journal Article
3D isotropic FastView MRI localizer allows reliable torsion measurements of the lower limb
2025
Computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used to assess femoral and tibial torsion. While CT offers high spatial resolution, it involves ionizing radiation. MRI avoids radiation but requires multiple sequences and extended acquisition time. We retrospectively evaluated whether a three-dimensional isotropic MRI localizer (FastView) could serve as a reliable and faster alternative. In this retrospective single-center study, 60 lower limbs from 30 patients, aged 27.1 ± 11.5 years (mean ± standard deviation), 19 females and 11 males, were assessed using both FastView and a dedicated MRI protocol. FastView (5 × 5 × 5 mm
3
voxels) imaged the entire lower limb in 17.4 s compared to nearly 7 min for the dedicated protocol. Torsion angles were measured independently by two readers. Agreement between methods was evaluated using intraclass correlation coefficients (ICCs), Bland–Altman plots, and Pearson
R
². No significant differences in torsion values were found (all
p
> 0.305). Femoral (ICC: 0.91–0.96) and tibial (ICC: 0.91–0.94) torsion showed excellent inter-modality agreement. Inter-reader reliability was also high (ICC: 0.95–0.99). Correlation values confirmed strong agreement (
R
²: 0.891–0.963). FastView demonstrated accuracy comparable to the dedicated protocol, offering a fast, efficient, and radiation-free option for routine torsion assessment.
Relevance statement
FastView MRI localizer offers a fast and resource-efficient method for assessing lower limb torsion, potentially replacing standard multisequence protocols in routine clinical practice.
Key Points
FastView MRI enables lower limb torsion measurements with full-limb coverage in under 20 s.
Torsion angles from FastView and dedicated MRI showed no significant differences.
Femoral and tibial ICCs between 0.91 and 0.96 confirm excellent inter-protocol agreement.
Inter-reader agreement was consistently high across both protocols.
FastView may replace multisequence MRI protocols in routine clinical torsion assessment.
Graphical Abstract
Journal Article
Predictors of renal function decline in patients with gastroenteropancreatic neuroendocrine tumors undergoing 177LuLu-DOTA-TATE therapy
by
Smith, Caroline
,
Ebner, Ricarda
,
Sheikh, Gabriel T.
in
[177Lu]Lu-DOTA-TATE
,
Cardiac Imaging
,
Cohort analysis
2025
Background
Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE is an established treatment for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). While overall renal safety is high, the kidneys remain an organ at risk. This study aimed to determine whether clinical parameters can predict the risk of PRRT-associated renal function decline.
Results
This retrospective single-center study included 178 patients with well-differentiated GEP-NETs (Grade 1 or 2) who completed four cycles of [
177
Lu]Lu-DOTA-TATE between 2012 and 2023. Mean baseline eGFR was 81.1 ± 16.3 mL/min/1.73 m² and remained stable at follow-up (81.1 ± 17.8 mL/min/1.73 m²,
p
= 0.989). A KDIGO-defined renal function decline (eGFR follow-up to baseline ratio < 0.8) was observed in 15 patients (8.9%). Higher age at baseline was significantly associated with increased risk (OR: 1.07, 95% CI: 1.01–1.14,
p
= 0.023), while baseline eGFR (OR: 1.03, 95% CI: 0.99–1.06,
p
= 0.1) and estimated renal radiation dose (eRRD) (OR: 1.06, 95% CI: 0.89–1.21,
p
= 0.456) were not significant predictors. No significant associations were found for preexisting renal disease, arterial hypertension, diabetes mellitus, or nephrotoxic drugs. ROC analysis yielded an AUC of 0.683 for age, identifying 68.77 years as the optimal threshold for risk stratification of CKD-progression free survival.
Conclusions
While the overall risk of renal function decline following [
177
Lu]Lu-DOTA-TATE therapy of GEP-NET patients is low, age at baseline emerged as a simple yet clinically meaningful predictor of renal function decline in this cohort.
Journal Article
Diagnostic performance and reader confidence of MRI-derived CT-like images in patients with femoral head necrosis
2026
Femoral head necrosis (FHN) requires accurate imaging for staging and treatment planning. While MRI is sensitive, conventional sequences may miss subchondral fractures. A CT-like MRI sequence combines CT-like structural detail with soft-tissue contrast. We evaluated its performance for Association Research Circulation Osseous (ARCO) staging compared with MRI and radiography. In this retrospective study, 21 patients (33 hips) with confirmed FHN underwent radiography and MRI, including T1- and T2-weighted sequences and a T1-weighted gradient-echo CT-like sequence. Two musculoskeletal imaging specialists assessed ARCO stage, reader confidence, and image quality. Interrater reliability was evaluated using the intraclass correlation coefficient, intermodality agreement with weighted Cohen’s
κ
, and modality comparisons with Wilcoxon signed-rank tests. CT-like MRI demonstrated higher ARCO staging than radiography (
p
= 0.004), T1-weighted (
p
= 0.031), and T2-weighted MRI (
p
= 0.046). Upstaging compared with conventional modalities occurred in 6 of 33 hips (18.2%). Reader confidence was highest for CT-like MRI (all
p
≤ 0.003), and image quality was superior compared with T1- and T2-weighted MRI (both
p
< 0.001). Agreement in ARCO staging was excellent with T1-weighted and T2-weighted images and substantial with radiography. CT-like MRI improved image quality and diagnostic confidence, enabling more accurate FHN assessment and detection of subchondral collapse missed by conventional MRI.
Relevance statement
CT-like MRI improves detection of early femoral head collapse, enabling more accurate staging and treatment planning.
Key Points
Femoral head necrosis requires precise imaging to accurately stage the disease.
Conventional MRI may miss early subchondral femoral head fractures.
CT-like MRI enhances visualization of bone microstructure, diagnostic confidence and image quality.
Improved staging with CT-like MRI may influence clinical management.
Graphical Abstract
Journal Article
Quantitative response assessment of combined immunotherapy in a murine melanoma model using multiparametric MRI
by
Kloiber-Langhorst, Sandra
,
Herr, Felix L.
,
Antons, Melissa J.
in
Animals
,
Diagnostic Radiology
,
Disease Models, Animal
2025
Background
We assessed immunotherapy response in a murine melanoma model using multiparametric magnetic resonance imaging (mpMRI) features with
ex vivo
immunohistochemical validation.
Methods
Murine melanoma cells (B16-F10) were inoculated into the subcutaneous flank of
n
= 28 C57BL/6 mice (
n
= 14 therapy;
n
= 14 control). Baseline mpMRI was acquired on day 7 at 3 T. The immunotherapy group received three intraperitoneal injections of anti-PD-L1 and anti-CTLA-4 antibodies on days 7, 9, and 11 after inoculation. Controls received a volume equivalent placebo. Follow-up mpMRI was performed on day 12. We assessed tumor volume, diffusion-weighted imaging parameters, including the apparent diffusion coefficient (ADC), and dynamic-contrast-enhanced metrics, including plasma volume and plasma flow. Tumor-infiltrating lymphocytes (TIL; CD8+), cell proliferation (Ki-67), apoptosis (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling, TUNEL), and microvascular density (CD31+) were assessed in a validation cohort of
n
= 24 animals for time-matched
ex vivo
validation.
Results
An increase in tumor volume was observed in both groups (
p
≤ 0.004) without difference at follow-up (
p
= 0.630). A lower ADC value was observed in the immunotherapy group at follow-up (
p
= 0.001). Immunohistochemistry revealed higher TUNEL values (
p
< 0.001) and CD8+ TILs (
p
= 0.048) following immunotherapy, as well as lower tumor cell Ki-67 values (
p
< 0.001) and microvascular density/CD31+ (
p
< 0.001).
Conclusion
Lower tumor ADC, paired with higher intratumoral expression of CD8+ TIL, was observed five days after immunotherapy, suggestive of early immunological response.
Ex vivo
immunohistochemistry confirmed the antitumoral efficacy of immunotherapy.
Relevance statement
Compared to tumor size, diffusion-weighted MRI demonstrated potential for early response assessment to immunotherapy in a murine melanoma model, which could reflect changes in the tumor microenvironment and immune cell infiltration.
Key Points
No difference in tumor volume was observed between groups before and after therapy.
Lower ADC values paired with increased CD8+ TILs were observed following immunotherapy.
Ex vivo
immunohistochemistry confirmed antitumoral efficacy of anti-PD-L1 and anti-CTLA-4 immunotherapy.
Graphical Abstract
Journal Article
Software-assisted structured reporting and semi-automated TNM classification for NSCLC staging in a multicenter proof of concept study
by
Tufman, Amanda
,
Ingrisch, Michael
,
Cyran, Clemens C
in
Annotations
,
Automation
,
Classification
2024
ObjectivesIn this multi-center study, we proposed a structured reporting (SR) framework for non-small cell lung cancer (NSCLC) and developed a software-assisted tool to automatically translate image-based findings and annotations into TNM classifications. The aim of this study was to validate the software-assisted SR tool for NSCLC, assess its potential clinical impact in a proof-of-concept study, and evaluate current reporting standards in participating institutions.MethodsA framework for SR and staging of NSCLC was developed in a multi-center collaboration. SR annotations and descriptions were used to generate semi-automated TNM classification. The SR and TNM classification tools were evaluated by nine radiologists on n = 20 representative [18F]FDG PET/CT studies and compared to the free text reporting (FTR) strategy. Results were compared to a multidisciplinary team reference using a generalized linear mixed model (GLMM). Additionally, participants were surveyed on their experience with SR and TNM classification.ResultsOverall, GLMM analysis revealed that readers using SR were 1.707 (CI: 1.137–2.585) times more likely to correctly classify TNM status compared to FTR strategy (p = 0.01) resulting in increased overall TNM correctness in 71.9% (128/178) of cases compared to 62.8% (113/180) FTR. The primary source of variation in classification accuracy was explained by case complexity. Participants rated the potential impact of SR and semi-automated TNM classification as positive across all categories with improved scores after template validation.ConclusionThis multi-center study yielded an effective software-assisted SR framework for NSCLC. The SR and semi-automated classification tool improved TNM classification and were perceived as valuable.Critical relevance statementSoftware-assisted SR provides robust input for semi-automated rule-based TNM classification in non-small-cell lung carcinoma (NSCLC), improves TNM correctness compared to FTR, and was perceived as valuable by radiology physicians.Key PointsSR and TNM classification are underutilized across participating centers for NSCLC staging.Software-assisted SR has emerged as a promising strategy for oncologic assessment.Software-assisted SR facilitates semi-automated TNM classification with improved staging accuracy compared to free-text reports in NSCLC.
Journal Article
Neutropenic Enterocolitis in Acute Myeloid Leukemia and Morbus Behcet: Pivotal Role of Medical Imaging and Multidisciplinary Management in a Complex Clinical Case
2025
Neutropenic enterocolitis (NE), also known as typhlitis, is a life-threatening gastrointestinal complication primarily affecting immunocompromised patients undergoing intensive chemotherapy. Its management becomes particularly challenging when compounded by comorbidities such as Behçet's disease with gastrointestinal involvement.
We report the case of a 44-year-old male with acute myeloid leukemia (AML) and intestinal Behçet's disease who developed severe NE during induction chemotherapy. Initial conservative management was guided by serial cross-sectional imaging, which revealed progressive bowel wall thickening, pneumatosis intestinalis, and signs of ileus. The clinical course was complicated by septic shock, multiorgan dysfunction, and later, acute gastrointestinal hemorrhage. Active arterial bleeding was identified via computed tomography angiography and successfully treated with interventional radiological coil embolization. Surgical intervention was avoided. Multidisciplinary collaboration, including hematology, radiology, rheumatology, intensive care, and pain management, was essential in navigating this complex clinical scenario.
This case highlights the pivotal role of radiological imaging in diagnosing and monitoring NE and demonstrates the value of interventional radiology as a minimally invasive alternative to surgery. In patients with overlapping autoimmune and oncological pathologies, individualized, multidisciplinary management is crucial for optimizing outcomes.
Journal Article
Association of integrated biomarkers and progression-free survival prediction in patients with gastroenteropancreatic neuroendocrine tumors undergoing 177LuLu-DOTA-TATE therapy
2025
Integrated biomarkers that predict survival in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) receiving peptide receptor radionuclide therapy (PRRT) are still limited. This study aims to identify predictors of progression-free survival (PFS) in patients with GEP-NET undergoing two cycles of PRRT.
This single-center retrospective study included 178 patients with GEP-NET (G1 and G2) who received at least two consecutive cycles of PRRT with [177Lu]Lu-DOTA-TATE and underwent somatostatin receptor (SSTR)-PET/CT before and after therapy. At baseline, Krenning score (KS) > 2, clinical, pathological and laboratory parameters were collected and correlated to PFS. Survival predictors were analyzed using univariate and multivariate models. For goodness-of-fit analysis, the Akaike information criterion and Harrell concordance index were determined. To determine the impact on the regression model the Wald-Test was performed.
In univariate analysis, KS 3 (vs. KS 4; HR, 2.02; 95% CI, 1.27-3.22; p = 0.012), Ki-67 > 5 % (HR, 2.00; 95% CI, 1.31-3.04; p = 0.008), CgA > 200 ng/mL (HR, 1.77; 95% CI, 1.14-2.76; p = 0.027) and NSE > 35 ng/mL (HR, 2.37; 95% CI, 1.44-3.89; p < 0.008) were significantly associated with shorter PFS, with CgA providing the highest C-index (0.6). In multivariate analysis , KS 3 (vs. KS 4; HR, 1.94; 95% CI, 1.17-3.21; p = 0.01), CgA > 200 ng/mL (HR, 1.76; CI, 1.08-2.87; p = 0.024), NSE > 35 ng/mL (HR, 1.98; 95% CI, 1.17-3.36; p = 0.011), and Ki-67 > 5 % (HR, 1.89; 95% CI, 1.18-3.02; p = 0.008) were significantly associated with reduced PFS. Including KS into multivariate analysis significantly improved the Cox regression model performance, as shown by a reduction in Akaike Information Criterion (592/596) and an increase in concordance index (0.66/0.65). The Wald test for individual variables supported the significance of both Ki-67 (7.1) and KS (6.7) as independent predictors of PFS.
NSE, CgA, KS and Ki-67 emerged as independent predictors of PFS in GEP-NET patients scheduled for two cycles of PRRT, thereby emphasizing the importance of integrated diagnostics including in- and ex-vivo biomarkers to identify high-risk individuals prone to disease progression.
Journal Article