Distortions in brain MRI caused by gradient nonlinearities may reach several millimeters, thus distortion correction is strongly recommended for radiotherapy treatment planning. However, the significance of MRI distortion correction on actual clinical outcomes has not been described yet. Therefore, we investigated the impact of planning MRI distortion correction on subsequent local control in a historic series of 419 brain metastases in 189 patients treated with stereotactic radiotherapy between 01/2003 and 04/2015. Local control was evaluated using a volumetric extension of the RANO-BM criteria. The predictive significance of distortion correction was assessed using competing risk analysis. In this cohort, 2D distortion-corrected MRIs had been used for treatment planning in 52.5% (220/419) of lesions, while uncorrected MRIs had been employed in 47.5% (199/419) of metastases. 2D distortion correction was associated with improved local control (Cumulative incidence of local progression at 12 months: 14.3% vs. 21.2% and at 24 months: 18.7% vs. 28.6%, p = 0.038). In multivariate analysis, adjusting for histology, baseline tumor volume, interval between MRI and treatment delivery, year of planning MRI, biologically effective dose and adjuvant Whole-brain radiotherapy, use of distortion correction remained significantly associated with improved local control (HR 0.55, p = 0.020). This is the first study to clinically evaluate the impact of MRI gradient nonlinearity distortion correction on local control in stereotactic radiotherapy for brain metastases. In this historic series, we found significantly higher local control when using 2D corrected vs. uncorrected MRI studies for treatment planning. These results stress the importance of assuring that MR images used for radiotherapy treatment planning are properly distortion-corrected.

Recurrent glioblastoma has a poor prognosis, and its optimal management remains unclear. Reirradiation (re-RT) is a promising treatment option, but long-term outcomes and optimal patient selection criteria are not well established. This study analyzed 71 patients with recurrent CNS WHO grade 4, IDHwt glioblastoma (GBM) who underwent re-RT at the University of Erlangen-Nuremberg between January 2009 and June 2019. Imaging follow-ups were conducted every 3 months. Progression-free survival (PFS) was defined using RANO criteria. Outcomes, feasibility, and toxicity of re-RT were evaluated. Contrast-enhancing tumor volume was measured using a deep learning auto-segmentation pipeline with expert validation and jointly evaluated with clinical and molecular-pathologic factors. Most patients were prescribed conventionally fractionated re-RT (84.5

Background/Objectives: Diffusion-weighted imaging (DWI) of the liver is prone to cardiac motion-induced signal dropout, which can be reduced using flow-compensated (FloCo) instead of monopolar (MP) diffusion encodings. This study examined differences in lesion detection capabilities between FloCo and MP DWI and whether visibility depends on lesion size and position. Methods: Forty patients with at least one known or suspected focal liver lesion (FLL) underwent FloCo and MP DWI. For both sequences, b = 800 s/mm2 images were used to manually segment FLLs, which were then sorted by size and location (liver segment). The number of detected lesions, the sensitivity, and the contrast-to-noise ratio (CNR) were calculated and compared across sequences, sizes, and locations. Results: Significantly more lesions were detected using FloCo DWI compared to MP DWI (1211 vs. 1154; p < 0.001). In total, 1258 unique lesions were detected, 104 of which were identified only by FloCo DWI, and 47 of which only by MP DWI. The sensitivities of FloCo DWI and MP DWI were 96.3% (95% CI: 95.1–97.2%) and 91.7% (95% CI: 90.1–93.2%), respectively. The largest additional lesion found with only one of the two sequences measured 10.9 mm in FloCo DWI and 8.2 mm in MP DWI. In relative numbers, more additional FloCo lesions were found in the left liver lobe than in the right liver lobe (6.4% vs. 3.5%). The lesion CNR was significantly higher for FloCo DWI than for MP DWI (p < 0.05) for all evaluated size intervals and liver segments. Conclusions: FloCo DWI appears to enhance the detectability of FLLs compared to MP DWI, particularly for small liver lesions and lesions in the left liver lobe.

PURPOSE:This research aims to develop a feature-guided deep learning approach and compare it with an optimized conventional post-processing algorithm in order to enhance the image quality of diffusion-weighted liver images and, in particular, to reduce the pulsation-induced signal loss occurring predominantly in the left liver lobe.METHODS:Data from 40 patients with liver lesions were used. For the conventional approach, the best-suited out of five examined algorithms was chosen. For the deep learning approach, a U-Net was trained. Instead of learning "gold-standard" target images, the network was trained to optimize four image features (lesion CNR, vessel darkness, data consistency, and pulsation artifact reduction), which could be assessed quantitatively using manually drawn ROIs. A quality score was calculated from these four features. As an additional quality assessment, three radiologists rated different features of the resulting images.RESULTS:The conventional approach could substantially increase the lesion CNR and reduce the pulsation-induced signal loss. However, the vessel darkness was reduced. The deep learning approach increased the lesion CNR and reduced the signal loss to a slightly lower extent, but it could additionally increase the vessel darkness. According to the image quality score, the quality of the deep-learning images was higher than that of the images obtained using the conventional approach. The radiologist ratings were mostly consistent with the quantitative scores, but the overall quality ratings differed among the readers.CONCLUSION:Unlike the conventional algorithm, the deep-learning algorithm increased the vessel darkness. Therefore, it may be a viable alternative to conventional algorithms.

The purpose of this study was to investigate the relevance of focal liver lesions (FLL) size for lesion detection comparing navigator triggering (TRIG) to free breathing (FB) liver Diffusion-weighted magnetic resonance imaging (DWI). Patients with known or suspected FLL were prospectively (registry number 276_19 B) included from October to December 2019 in this study, out of which 32 had liver lesions. Echo planar spin-echo DWI data both with TRIG and FB were with approximately constant acquisition times acquired at 1.5 T. Lesions were segmented in the b = 800 s/mm² images in both the TRIG and FB images. The lesion size, location (liver segment), liver lesion visibility, as well as contrast-to-noise ratio (CNR) were recorded. The CNR was assessed with the Wilcoxon–Mann–Whitney test and the number of visible lesions with the Fisher test. Data from 43 patients (22 female) were analyzed. The mean patient age was 58 ± 14 years. A total of 885 FLL (Ntotal) were segmented. Among these, 811 lesions (Nboth) were detected with TRIG and FB, 65 lesions exclusively with TRIG (NTRIG_Only), and nine exclusively in FB (NFB_Only). The largest additional lesion in TRIG/FB had a diameter of 10.4 mm/7.6 mm. The number of additional lesions detected with TRIG decreased with size. Among all lesions ≤ 4.7 mm, the relative number of additional lesions was 15.6

The purpose of this study was to assess morphological and quantitative changes of the anterior cruciate ligament (ACL) and cartilage after ACL repair. 7T MRI of the knee was acquired in 31 patients 1.5 years after ACL repair and in 13 controls. Proton density-weighted images with fat saturation (PD-fs) were acquired to assess ACL width, signal intensity, elongation, and fraying. T2/T2* mapping was performed for assessment of ACL and cartilage. Segmentation of the ACL, femoral, and tibial cartilage was carried out at 12 ROIs. The outcome evaluation consisted of the Lysholm Knee Score and International Knee Documentation Committee (IKDC) subjective score and clinical examination. ACL showed a normal signal intensity in 96.8

Introduction: The development of an intestinal stricture in patients with Crohn’s disease represents an important and frequent complication, reflecting the progressive nature of the disease. Depending on the inflammatory and fibrotic composition of the stricture, intensified medical therapy, interventional endoscopy, or surgical intervention is required. However, currently available diagnostic approaches can only assess the level of inflammation, but not the degree of fibrosis, limiting rational therapeutic management of Crohn’s disease patients. Recently, prolyl endopeptidase fibroblast activating protein (FAP) has been functionally implicated in fibrotic tissue remodelling, indicating it as a promising target for detection of sites of fibrotic tissue remodelling. Thus, intestinal fibrosis might be visualized using Gallium-68 labelled inhibitors of FAP (FAPI). While F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT is a standard diagnostic tool for visualizing inflammatory processes, we combined Ga-68-FAPI-46-PET/CT and F-18-FDG-PET/CT to differentiate predominantly fibrotic or inflammatory areas in Crohn’s disease patients with ileo-colonic strictures. Methods: In our study, we analysed three Crohn’s disease patients with anastomotic ileo-colonic strictures who underwent both dynamic Ga-68-FAPI-46-PET/CT and static F-18-FDG-PET/CT imaging to assess the level of visualized fibrotic areas within the stricture and differentiate it from inflammatory ones. PET images were analysed both visually and quantitatively. Furthermore, conventional MR enterography and endoscopy were performed in parallel to correlate observed findings. Two of the included patients underwent surgery and the histological specimen were analysed for the level of inflammation and fibrosis, which results were similarly compared to the findings of the PET imaging procedures. Results: Different uptake patterns of Ga-68-FAPI-46 could be observed in the anastomotic ileo-colonic strictures of the examined Crohn’s disease patients, respectively. Immunohistochemical analyses demonstrated that there was a correlation between the level of Ga-68-FAPI-46 uptake and severity of fibrosis, while FDG uptake correlated with the inflammatory activity in the analysed strictures. Discussion: The combination with F-18-FDG-PET/CT represents a promising imaging modality to distinguish inflammation from fibrosis and guide subsequent therapy in stricturing Crohn’s disease patients, warranting further studies.

Zielsetzung Bei der Bildung von Knochenmetastasen spielen Mikroumgebung des Knochenmarks und Adipozyten als Wachstumsmediatoren eine wichtige Rolle. In dieser Studie haben wir das Wachstum von Knochenmetastasen und den zugrundeliegenden pathophysiologischen Prozessen mittels multiparametrischer Magnetresonanztomographie (MRT) und Positronen-Emissions-Tomographie/Computertomographie (PET/CT) bei adipösen Versuchstieren evaluiert.

Purpose The study aims to develop easy-to-implement concomitant field-compensated gradient waveforms with varying velocity-weighting ( M 1 ) and acceleration-weighting ( M 2 ) levels and to evaluate their efficacy in correcting signal dropouts and preserving the black-blood state in liver diffusion-weighted imaging. Additionally, we seek to determine an optimal degree of compensation that minimizes signal dropouts while maintaining blood signal suppression. Methods Numerically optimized gradient waveforms were adapted using a novel method that allows for the simultaneous tuning of M 1 - and M 2 -weighting by changing only one timing variable. Seven healthy volunteers underwent diffusion-weighted magnetic resonance imaging (DWI) with five diffusion encoding schemes (monopolar, velocity-compensated ( M 1 = 0), acceleration-compensated ( M 1 = M 2 = 0), 84%- M 1 – M 2 -compensated, 67%- M 1 – M 2 -compensated) at b-values of 50 and 800 s/mm 2 at a constant echo time of 70 ms. Signal dropout correction and apparent diffusion coefficients (ADCs) were quantified using regions of interest in the left and right liver lobe. The blood appearance was evaluated using two five-point Likert scales. Results Signal dropout was more pronounced in the left lobe (19%-42% less signal than in the right lobe with monopolar scheme) and best corrected by acceleration-compensation (8%-10% less signal than in the right lobe). The black-blood state was best with monopolar encodings and decreased significantly (p < 0.001) with velocity- and/or acceleration-compensation. The partially M 1 – M 2 -compensated encoding schemes could restore the black-blood state again. Strongest ADC bias occurred for monopolar encodings (difference between left/right lobe of 0.41 μm 2 /ms for monopolar vs. < 0.12 μm 2 /ms for the other encodings). Conclusion All of the diffusion encodings used in this study demonstrated suitability for routine DWI application. The results indicate that a perfect value for the level of M 1 – M 2 -compensation does not exist. However, among the examined encodings, the 84%- M 1 – M 2 -compensated encodings provided a suitable tradeoff.

Einleitung Die alveoläre Echinokokkose ist durch eine Infektion mit Echinococcus multilocularis bedingt und befällt bevorzugt die Leber [1]. Das morphologische Erscheinungsbild ist vielgestaltig, in vielen Fällen erfolgt die Diagnose daher erst verspätet [2]. Eine kurative Therapie ist in der Regel nur chirurgisch möglich [3].

Journal Article VEXAS syndrome mimicking lupus-like disease Get access Larissa Valor-Méndez, Larissa Valor-Méndez Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, GermanyDeutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany https://orcid.org/0000-0002-4872-3502 Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Sticherling, Michael Sticherling Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Nuclear Medicine, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin Zeschick, Martin Zeschick Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Nuclear Medicine, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Raja Atreya, Raja Atreya Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar F Daniela Schmidt, F Daniela Schmidt Medical Clinic 1, Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank Waldfahrer, Frank Waldfahrer Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Marc Saake, Marc Saake Department of Radiology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Ulrike Hüffmeier, Ulrike Hüffmeier Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany https://orcid.org/0000-0001-6448-4671 Search for other works by this author on: Oxford Academic PubMed Google Scholar Georg Schett, Georg Schett Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, GermanyDeutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Jürgen Rech Jürgen Rech Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, GermanyDeutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany Correspondence to: Jürgen Rech, Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany. E-mail: juergen.rech@uk-erlangen.de Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, Volume 62, Issue 9, September 2023, Pages e271–e272, https://doi.org/10.1093/rheumatology/kead076 Published: 16 February 2023 Article history Accepted: 24 December 2022 Published: 16 February 2023 Corrected and typeset: 21 February 2023

Purpose: Studies on intravoxel incoherent motion (IVIM) imaging in the liver have been carried out with different acquisition protocols. The number of acquired slices and the distances between slices can influence IVIM measurements due to saturation effects, but these effects have often been disregarded. This study investigated differences in biexponential IVIM parameters between two slice settings. Methods: Fifteen healthy volunteers (21-30 years) were examined at a field strength of 3 T. Diffusion-weighted images of the abdomen were acquired with 16 b values (0-800 s/mm(2)), with four slices for the few slices setting and 24-27 slices for the many slices setting. Regions of interest were manually drawn in the liver. The data were fitted with a monoexponential signal curve and a biexponential IVIM curve, and biexponential IVIM parameters were determined. The dependence on the slice setting was assessed with Student's t test for paired samples (normally distributed IVIM parameters) and the Wilcoxon signed-rank test (non-normally distributed parameters). Results: None of the parameters were significantly different between the settings. For few slices and many slices, respectively, the mean values (SDs) for D were 1.21 mu m(2)/ms (0.19 mu m(2)/ms) and 1.20 mu m(2)/ms (0.11 mu m(2)/ms); for f they were 29.7% (6.2%) and 27.7% (3.6%); and for D* they were 8.76 center dot 10(-2) mm(2)/s (4.54 center dot 10(-2) mm(2)/s) and 8.71 center dot 10(-2) mm(2/)s (4.06 center dot 10(-2) mm(2)/s). Conclusion: Biexponential IVIM parameters in the liver are comparable among IVIM studies that use different slice settings, with mostly negligible saturation effects. However, this may not hold for studies that use much shorter TR.

Diffusion-weighted imaging of the liver is prone to the cardiac pulsation artifact, which can lead to reduced lesion visibility. We addressed this problem with a two-fold approach. First, flow-compensated diffusion weightings were used, which are known to reduce this artifact. Using a dataset of 40 patients suffering from focal liver lesions, we addressed the remaining signal voids with different postprocessing techniques, namely weighted averaging, the p-mean approach, and an outlier exclusion algorithm. The algorithms substantially increased the lesion visibility and further reduced the pulsation artifact. An evaluation of CNR and calculation time showed that weighted averaging was suited best.

(1) Background: For the peripheral zone of the prostate, diffusion weighted imaging (DWI) is the most important MRI technique; however, a high b-value image (hbDWI) must always be evaluated in conjunction with an apparent diffusion coefficient (ADC) map. We aimed to unify the important contrast features of both a hbDWI and ADC in one single image, termed multichannel computed diffusion images (mcDI), and evaluate the values of these images in a retrospective clinical study; (2) Methods: Based on the 2D histograms of hbDWI and ADC images of 70 patients with histologically proven prostate cancer (PCa) in the peripheral zone, an algorithm was designed to generate the mcDI. Then, three radiologists evaluated the data of 56 other patients twice in three settings (T2w images +): (1) hbDWI and ADC; (2) mcDI; and (3) mcDI, hbDWI, and ADC. The sensitivity, specificity, and inter-reader variability were evaluated; (3) Results: The overall sensitivity/specificity were 0.91/0.78 (hbDWI + ADC), 0.85/0.88 (mcDI), and 0.97/0.88 (mcDI + hbDWI + ADC). The kappa-values for the inter-reader variability were 0.732 (hbDWI + ADC), 0.800 (mcDI), and 0.853 (mcDI + hbDWI + ADC). (4) Conclusions: By using mcDI, the specificity of the MRI detection of PCa was increased at the expense of the sensitivity. By combining the conventional diffusion data with the mcDI data, both the sensitivity and specificity were improved.

PurposeTo enhance image quality of flow‐compensated diffusion‐weighted liver MRI data by increasing the lesion conspicuity and reducing the cardiac pulsation artifact using postprocessing algorithms.MethodsDiffusion‐weighted image data of 40 patients with liver lesions had been acquired at 1.5 T. These data were postprocessed with 5 different algorithms (weighted averaging, p‐mean, percentile, outlier exclusion, and exception set). Four image properties of the postprocessed data were evaluated for optimizing the algorithm parameters. These properties were the lesion to tissue contrast‐to‐noise ratio (CNR), the reduction of the cardiac pulsation artifact, the data consistency, and the vessel darkness. They were combined into a total quality score ( set to 1 for the trace‐weighted reference image), which was used to rate the image quality objectively.ResultsThe weighted averaging algorithm performed best according to the total quality score (). The further ranking was outlier exclusion algorithm (), p‐mean algorithm (), percentile algorithm (), and exception set algorithm (). All optimized algorithms except for the exception set algorithm corrected the pulsation artifact and increased the lesion CNR. Changes in were significant for all optimized algorithms except for the percentile algorithm. Liver ADC was significantly reduced (except for the exception set algorithm), particularly in the left lobe.ConclusionPostprocessing algorithms should be used for flow‐compensated liver DWI. The proposed weighted averaging algorithm seems to be suited best to increase the image quality of artifact‐corrupted flow‐compensated diffusion‐weighted liver data.

Purpose: To develop an algorithm for the retrospective correction of signal dropout artifacts in abdominal diffusion-weighted imaging (DWI) resulting from cardiac motion. Methods: Given a set of image repetitions for a slice, a locally adaptive weighted averaging is proposed which aims to suppress the contribution of image regions affected by signal dropouts. Corresponding weight maps were estimated by a sliding-window algorithm which analyzed signal deviations from a patch-wise reference. In order to ensure the computation of a robust reference, repetitions were filtered by a classifier that was trained to detect images corrupted by signal dropouts. The proposed method, termed Deep Learning-guided Adaptive Weighted Averaging (DLAWA), was evaluated in terms of dropout suppression capability, bias reduction in the Apparent Diffusion Coefficient (ADC) and noise characteristics. Results: In the case of uniform averaging, motion-related dropouts caused signal attenuation and ADC overestimation in parts of the liver with the left lobe being affected particularly. Both effects could be substantially mitigated by DLAWA while preventing global penalties with respect to signal-to-noise ratio (SNR) due to local signal suppression. Performing evaluations on patient data, the capability to recover lesions concealed by signal dropouts was demonstrated as well. Further, DLAWA allowed for transparent control of the trade-off between SNR and signal dropout suppression by means of a few hyperparameters. Conclusion: This work presents an effective and flexible method for the local compensation of signal dropouts resulting from motion and pulsation. Since DLAWA follows a retrospective approach, no changes to the acquisition are required.

Magnetic resonance (MR) diffusion-weighted imaging (DWI) is often used to detect focal liver lesions (FLLs), though DWI image quality can be limited in the left liver lobe owing to the pulsatile motion of the nearby heart. Flow-compensated (FloCo) diffusion encoding has been shown to reduce this pulsation artifact. The purpose of this prospective study was to intra-individually compare DWI of the liver acquired with conventional monopolar and FloCo diffusion encoding for assessing metastatic FLLs in non-cirrhotic patients. Forty patients with known or suspected multiple metastatic FLLs were included and measured at 1.5 T field strength with a conventional (monopolar) and a FloCo diffusion encoding EPI sequence (single refocused; b-values, 50 and 800 s/mm2). Two board-certified radiologists analyzed the DWI images independently. They issued Likert-scale ratings (1 = worst, 5 = best) for pulsation artifact severity and counted the difference of lesions visible at b = 800 s/mm² separately for small and large FLLs (i.e., < 1 cm or > 1 cm) and separately for left and right liver lobe. Differences between the two diffusion encodings were assessed with the Wilcoxon signed-rank test. Both readers found a reduction in pulsation artifact in the liver with FloCo encoding (p < 0.001 for both liver lobes). More small lesions were detected with FloCo diffusion encoding in both liver lobes (left lobe: six and seven additional lesions by readers 1 and 2, respectively; right lobe: five and seven additional lesions for readers 1 and 2, respectively). Both readers found one additional large lesion in the left liver lobe. Thus, flow-compensated diffusion encoding appears more effective than monopolar diffusion encoding for the detection of liver metastases.

The growth of primary tumors and metastases is associated with excess body fat. In bone metastasis formation, the bone marrow microenvironment, and particularly adipocytes, play a pivotal role as growth mediators of disseminated tumor cells in the bone marrow. The aim of the present study is to non-invasively characterize the pathophysiologic processes in experimental bone metastasis resulting from accelerated tumor progression within adipocyte-rich bone marrow using multimodal imaging from magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). To achieve this, we have employed small animal models after the administration of MDA-MB 231 breast cancer and B16F10 melanoma cells into the bone of nude rats or C57BL/6 mice, respectively. After tumor cell inoculation, ultra-high field MRI and µPET/CT were used to assess functional and metabolic parameters in the bone marrow of control animals (normal diet, ND), following a high-fat diet (HFD), and/or treated with the peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist bisphenol-A-diglycidylether (BADGE), respectively. In the bone marrow of nude rats, dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI), as well as [18F]fluorodeoxyglucose-PET/CT([18F]FDG-PET/CT), was performed 10, 20, and 30 days after tumor cell inoculation, followed by immunohistochemistry. DCE-MRI parameters associated with blood volume, such as area under the curve (AUC), were significantly increased in bone metastases in the HFD group 30 days after tumor cell inoculation as compared to controls (p < 0.05), while the DWI parameter apparent diffusion coefficient (ADC) was not significantly different between the groups. [18F]FDG-PET/CT showed an enhanced glucose metabolism due to increased standardized uptake value (SUV) at day 30 after tumor cell inoculation in animals that received HFD (p < 0.05). BADGE treatment resulted in the inversion of quantitative DCE-MRI and [18F]FDG-PET/CT data, namely a significant decrease in AUC and SUV in HFD-fed animals as compared to ND-fed controls (p < 0.05). Finally, immunohistochemistry and qPCR confirmed the HFD-induced stimulation in vascularization and glucose activity in murine bone metastases. In conclusion, multimodal and multiparametric MRI and [18F]FDG-PET/CT were able to derive quantitative parameters in bone metastases, revealing an increase in vascularization and glucose metabolism following HFD. Thus, non-invasive imaging may serve as a biomarker for assessing the pathophysiology of bone metastasis in obesity, opening novel options for therapy and treatment monitoring by MRI and [18F]FDG-PET/CT.

Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.