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Our rationale was to investigate whether 18 F-FDG PET/MRI in addition to (guideline-recommended) conventional staging leads to changes in therapeutic management in patients with newly diagnosed breast cancer and compare the diagnostic accuracy of 18 F-FDG PET/MRI with that of conventional staging for determining the Union for International Cancer Control (UICC) stage. Methods: In this prospective, double-center study, 208 women with newly diagnosed, therapy-naïve invasive breast cancer were enrolled in accordance with the inclusion criteria. All patients underwent guideline-recommended conventional staging and whole-body 18 F-FDG PET/MRI with a dedicated breast examination. A multidisciplinary tumor board served to determine 2 different therapy recommendations for each patient, one based on conventional staging alone and another based on combined assessment of conventional staging and 18 F-FDG PET/MRI examinations. Major changes in therapy recommendations and differences between the conventional staging algorithm and 18 F-FDG PET/MRI for determining the correct UICC stage were reported and evaluated. Results: Major changes in therapeutic management based on combined assessment of conventional staging and 18 F-FDG PET/MRI were detected in 5 of 208 patients, amounting to changes in therapeutic management in 2.4% (95% CI, 0.78%-5.2%) of the study population. In determining the UICC stage, the guideline-based staging algorithm and 18 F-FDG PET/MRI were concordant in 135 of 208 (64.9%; 95% CI, 58%-71.4%) patients. The conventional guideline algorithm correctly determined the UICC stage in 130 of 208 (62.5%; 95% CI, 55.5%-69.1%) patients, and 18 F-FDG PET/MRI correctly determined the UICC stage in 170 of 208 (81.9%; 95% CI, 75.8%-86.7%) patients. Conclusion: Despite the diagnostic superiority of 18 F-FDG PET/MRI over conventional staging in determining the correct UICC stage, the current (guideline-recommended) conventional staging algorithm is sufficient for adequate therapeutic management of patients with newly diagnosed breast cancer, and 18 F-FDG PET/MRI does not have an impact on patient management., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: To investigate the specific strengths of MRI and PET components in 68 Ga-PSMA-11 PET/MRI for staging of patients with biochemically recurrent prostate cancer (PCa)., Methods: Patients with biochemical recurrence of PCa and contrast-enhanced whole-body 68 Ga-PSMA-11 PET/MRI including a dedicated pelvic multiparametric MRI were included in this retrospective study. Imaging datasets of MRI and PET were evaluated separately regarding local PCa recurrence (Tr), pelvic lymph node metastases (N1), distant lymph node metastases (M1a), bone metastases (M1b), and soft tissue metastases (M1c) according to PROMISE version 1. Data evaluation was performed patient- and region-/lesion-based. Cox regression revealed a PSA of 1.69 ng/mL as a cut-off for subgroup analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were evaluated for each image component. Differences in staging accuracy were assessed using the Wilcoxon and McNemar test., Results: Altogether 102 patients (mean aged 68 ± 8 years, median PSA 1.33 ng/mL) were included. PCa was found in 70/102 (68%) patients. Accuracy of MRI in the detection of Tr, N1, M + , M1a, and M1b was 100%, 79%, 90%, 97%, and 95% for PSA < 1.69 ng/mL and 100%, 87%, 87%, 91%, and 96% for PSA > 1.69 ng/mL. Accuracy of 68 Ga-PSMA-11 PET was 93%, 97%, 93%, 98%, and 100% for PSA < 1.69 ng/mL and 87%, 91%, 96%, 100%, and 96% for PSA > 1.69 ng/mL., Conclusions: Combined assessment of 68 Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence. The MRI detected local recurrence of PCa more often whereas 68  Ga-PSMA-11 PET detected lymph node metastases more often, especially for PSA < 1.69 ng/mL., Clinical Relevance Statement: This study gives a scientific baseline to improve the understanding and reading of 68 Ga-PSMA-11 PET/MRI imaging in patients with biochemically recurrent PCa by showing the specific strength of each imaging component., Key Points: • Combining the individual modality strengths of 68 Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence of prostate cancer. • MRI component of 68  Ga-PSMA-11 PET/MRI shows its strength in detecting local recurrence of prostate cancer, especially at PSA < 1.69 ng/mL. • 68  Ga-PSMA-11 PET component shows its strength in detecting local and distant lymph node metastases, especially at PSA < 1.69 ng/mL., (© 2023. The Author(s).)

Purpose: To evaluate if a machine learning prediction model based on clinical and easily assessable imaging features derived from baseline breast [ 18 F]FDG-PET/MRI staging can predict pathologic complete response (pCR) in patients with newly diagnosed breast cancer prior to neoadjuvant system therapy (NAST)., Methods: Altogether 143 women with newly diagnosed breast cancer (54 ± 12 years) were retrospectively enrolled. All women underwent a breast [ 18 F]FDG-PET/MRI, a histopathological workup of their breast cancer lesions and evaluation of clinical data. Fifty-six features derived from positron emission tomography (PET), magnetic resonance imaging (MRI), sociodemographic / anthropometric, histopathologic as well as clinical data were generated and used as input for an extreme Gradient Boosting model (XGBoost) to predict pCR. The model was evaluated in a five-fold nested-cross-validation incorporating independent hyper-parameter tuning within the inner loops to reduce the risk of overoptimistic estimations. Diagnostic model-performance was assessed by determining the area under the curve of the receiver operating characteristics curve (ROC-AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Furthermore, feature importances of the XGBoost model were evaluated to assess which features contributed most to distinguish between pCR and non-pCR., Results: Nested-cross-validation yielded a mean ROC-AUC of 80.4 ± 6.0% for prediction of pCR. Mean sensitivity, specificity, PPV, and NPV of 54.5 ± 21.3%, 83.6 ± 4.2%, 63.6 ± 8.5%, and 77.6 ± 8.1% could be achieved. Histopathological data were the most important features for classification of the XGBoost model followed by PET, MRI, and sociodemographic/anthropometric features., Conclusion: The evaluated multi-source XGBoost model shows promising results for reliably predicting pathological complete response in breast cancer patients prior to NAST. However, yielded performance is yet insufficient to be implemented in the clinical decision-making process., (© 2023. The Author(s).)

Purpose: Residual glandular tissue (RGT) after risk reducing mastectomy (RRME) is associated with a risk of developing breast cancer for women with a familial predisposition. We aim to examine various surgery-related variables to make risk more easily assessable and to aid in decision-making., Materials and Methods: Pre- and postoperative breast MRI scans from 2006 to 2021 of patients with proven pathogenic mutation were included. The postoperative remaining skin flap was recorded using distance measurements at 8 equally distributed clockwise points and retromamillary. Each breast was volumetrized, as well as existing RGT. Patient-related covariates were further recorded and their influence on RGT was investigated uni- and multivariately., Results: 81 patients (49 with BRCA1, 24 with BRCA2, 9 with other mutations), who were on average 39 years old, had 117 breasts analyzed. The mean follow-up was 71 months. In multivariate analysis, the independent variable skin flap thickness had a positive effect (p ≤ 0.01), while surgeon experience negatively affected RGT (p ≤ 0.05). The incision type was found to impact RGT as well, with nipple-sparing mastectomy (NSM) with inframammary fold incision leading to more RGT (p ≤ 0.01 - p ≤ 0.05), and skin-sparing mastectomy (SSM) with an inverted T incision leading to less (p ≤ 0.01)., Conclusion: Different surgical variables have an impact on postoperative RGT, which is an important tool to quantify the risk of developing breast cancer after RRME. In order to effectively consider these variables in future preoperative/intraoperative management, they must be carefully taken into account., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (© 2023 Published by Elsevier Ltd.)

Objectives: Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [ 18 F]FDG PET/MRI to avoid adverse effects and save time and costs during examination., Methods: A total of 105 [ 18 F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [ 18 F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin's Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests., Results: In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2., Conclusions: The use of MRI contrast agents in [ 18 F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent-free [ 18 F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients., Clinical Relevance Statement: This study gives a scientific baseline switching to a contrast agent-free [ 18 F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients., Key Points: • No additional diagnostic benefit of MRI contrast agents at [ 18 F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging • Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast-free [ 18 F]FDG PET/MRI., (© 2023. The Author(s).)

Objectives: To investigate the diagnostic feasibility of a shortened breast PET/MRI protocol in breast cancer patients., Methods: Altogether 90 women with newly diagnosed T1 tumor-staged (T1 ts ) and T2 tumor-staged (T2 ts ) breast cancer were included in this retrospective study. All underwent a dedicated comprehensive breast [ 18 F]FDG-PET/MRI. List-mode PET data were retrospectively reconstructed with 20, 15, 10, and 5 min for each patient to simulate the effect of reduced PET acquisition times. The SUV max/mean of all malign breast lesions was measured. Furthermore, breast PET data reconstructions were analyzed regarding image quality, lesion detectability, signal-to-noise ratio (SNR), and image noise (IN). The simultaneously acquired comprehensive MRI protocol was then shortened by retrospectively removing sequences from the protocol. Differences in malignant breast lesion detectability between the original and the fast breast MRI protocol were evaluated lesion-based. The 20-min PET reconstructions and the original MRI protocol served as reference., Results: In all PET reconstructions, 127 congruent breast lesions could be detected. Group comparison and T1 ts vs. T2 ts subgroup comparison revealed no significant difference of subjective image quality between 20, 15, 10, and 5 min acquisition times. SNR of qualitative image evaluation revealed no significant difference between different PET acquisition times. A slight but significant increase of IN with decreasing PET acquisition times could be detected. Lesion SUV max group comparison between all PET acquisition times revealed no significant differences. Lesion-based evaluation revealed no significant difference in breast lesion detectability between original and fast breast MRI protocols., Conclusions: Breast [ 18 F]FDG-PET/MRI protocols can be shortened from 20 to below 10 min without losing essential diagnostic information., Key Points: • A highly accurate breast cancer evaluation is possible by the shortened breast [ 18 F]FDG-PET/MRI examination protocol. • Significant time saving at breast [ 18 F]FDG-PET/MRI protocol could increase patient satisfaction and patient throughput for breast cancer patients at PET/MRI., (© 2023. The Author(s).)

Background: This study compares the diagnostic potential of conventional staging (computed tomography (CT), axillary sonography and bone scintigraphy), whole-body magnetic resonance imaging (MRI) and whole-body 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET/)MRI for N and M staging in newly diagnosed breast cancer. Methods: A total of 208 patients with newly diagnosed breast cancer were prospectively included in this study and underwent contrast-enhanced thoracoabdominal CT, bone scintigraphy and axillary sonography as well as contrast-enhanced whole-body 18 F-FDG PET/MRI. The datasets were analyzed with respect to lesion localization and characterization. Histopathology and follow-up imaging served as the reference standard. A McNemar test was used to compare the diagnostic performance of conventional staging, MRI and 18 F-FDG PET/MRI and a Wilcoxon test was used to compare differences in true positive findings for nodal staging. Results: Conventional staging determined the N stage with a sensitivity of 80.9%, a specificity of 99.2%, a PPV (positive predictive value) of 98.6% and a NPV (negative predictive value) of 87.4%. The corresponding results for MRI were 79.6%, 100%, 100% and 87.0%, and were 86.5%, 94.1%, 91.7% and 90.3% for 18 F-FDG PET/MRI. 18 F-FDG PET/MRI was significantly more sensitive in determining malignant lymph nodes than conventional imaging and MRI ( p < 0.0001 and p = 0.0005). Furthermore, 18 F-FDG PET/MRI accurately estimated the clinical lymph node stage in significantly more cases than conventional imaging and MRI (each p < 0.05). Sensitivity, specificity, PPV and NPV for the M stage in conventional staging were 83.3%, 98.5%, 76.9% and 98.9%, respectively. The corresponding results for both MRI and 18 F-FDG PET/MRI were 100.0%, 98.5%, 80.0% and 100.0%. No significant differences between the imaging modalities were seen for the staging of distant metastases. Conclusions: 18 F-FDG PET/MRI detects lymph node metastases in significantly more patients and estimates clinical lymph node stage more accurately than conventional imaging and MRI. No significant differences were found between imaging modalities with respect to the detection of distant metastases.

Locoregional therapy options for CCA are used, in particular, for non-resectable tumors and aim to reduce tumor viability or delay tumor growth and ultimately prolong overall survival. In addition to local ablative procedures such as radiofrequency- or microwave-ablation, transarterial procedures such as transarterial embolization (TAE), transarterial chemoembolization (TACE), or selective internal radiotherapy (SIRT) play a major role. In particular, in combination with advances in molecular medicine and immunotherapy, there has been a further development in the therapy of primary malignant liver tumors in recent years. In this review, we analyze data from recent studies and examine the implications for therapy of CCA, particularly with regard to the combination of locoregional therapies with modern systemic therapies.

Purpose: Evaluate the diagnostic potential of [ 18 F]FDG-PET/MRI data compared with invasive acquired biomarkers in newly diagnosed early breast cancer (BC)., Methods: Altogether 169 women with newly diagnosed BC were included. All underwent a breast- and whole-body [ 18 F]FDG-PET/MRI for initial staging. A tumor-adapted volume of interest was placed in the primaries and defined bone regions on each standard uptake value (SUV)/apparent diffusion coefficient (ADC) dataset. Immunohistochemical markers, molecular subtype, tumor grading, and disseminated tumor cells (DTCs) of each patient were assessed after ultrasound-guided biopsy of the primaries and bone marrow (BM) aspiration. Correlation analysis and group comparisons were assessed., Results: A significant inverse correlation of estrogen-receptor (ER) expression and progesterone-receptor (PR) expression towards SUV max was found (ER: r = 0.27, p < 0.01; PR: r = 0.19, p < 0.05). HER2-receptor expression showed no significant correlation towards SUV and ADC values. A significant positive correlation between Ki67 and SUVmax and SUV mean ( r = 0.42 p < 0.01; r = 0.19 p < 0.05) was shown. Tumor grading significantly correlated with SUV max and SUV mean (ρ = 0.36 and ρ = 0.39, both p 's < 0.01). There were no group differences between SUV/ADC values of DTC-positive/-negative patients., Conclusions: [ 18 F]FDG-PET/MRI may give a first impression of BC-receptor status and BC-tumor biology during initial staging by measuring glucose metabolism but cannot distinguish between DTC-positive/-negative patients and replace biopsy.

In addition to its high prognostic value, the involvement of axillary lymph nodes in breast cancer patients also plays an important role in therapy planning. Therefore, an imaging modality that can determine nodal status with high accuracy in patients with primary breast cancer is desirable. Our purpose was to investigate whether, in newly diagnosed breast cancer patients, machine-learning prediction models based on simple assessable imaging features on MRI or PET/MRI are able to determine nodal status with performance comparable to that of experienced radiologists; whether such models can be adjusted to achieve low rates of false-negatives such that invasive procedures might potentially be omitted; and whether a clinical framework for decision support based on simple imaging features can be derived from these models. Methods: Between August 2017 and September 2020, 303 participants from 3 centers prospectively underwent dedicated whole-body 18 F-FDG PET/MRI. Imaging datasets were evaluated for axillary lymph node metastases based on morphologic and metabolic features. Predictive models were developed for MRI and PET/MRI separately using random forest classifiers on data from 2 centers and were tested on data from the third center. Results: The diagnostic accuracy for MRI features was 87.5% both for radiologists and for the machine-learning algorithm. For PET/MRI, the diagnostic accuracy was 89.3% for the radiologists and 91.2% for the machine-learning algorithm, with no significant differences in diagnostic performance between radiologists and the machine-learning algorithm for MRI ( P = 0.671) or PET/MRI ( P = 0.683). The most important lymph node feature was tracer uptake, followed by lymph node size. With an adjusted threshold, a sensitivity of 96.2% was achieved by the random forest classifier, whereas specificity, positive predictive value, negative predictive value, and accuracy were 68.2%, 78.1%, 93.8%, and 83.3%, respectively. A decision tree based on 3 simple imaging features could be established for MRI and PET/MRI. Conclusion: Applying a high-sensitivity threshold to the random forest results might potentially avoid invasive procedures such as sentinel lymph node biopsy in 68.2% of the patients., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: This study seeks to evaluate MR imaging morphological factors and other covariates that influence the presence of residual glandular tissue after risk-reducing mastectomy in patients with a familial predisposition., Methods: We analyzed women of a high-risk collective with pathogenic mutation (BRCA1 (n = 49), BRCA2 (n = 24), or further mutation (n = 9)). A total of 117 breasts were analyzed, 63 left and 54 right, from a cohort of 81 patients, who were on average 40 years old. The mean follow-up was 63 months (range 12-180 months, SD = 39.67). Retrospective analysis of MR imaging data from 2006-2022 of patients of a high-risk collective (all carriers of a pathogenic mutation) with contralateral (RRCM) or bilateral risk-reducing mastectomy (RRBM) was performed. In the image data the remaining skin flap thickness by distance measurements at eight equally distributed, clockwise points and the retromamillary area, as well as by volumetry of each breast, was elected. Residual glandular tissue was also volumetrized. In addition, patient-related covariates were recorded and their influence on postoperative residual glandular tissue and skin flap thickness was analyzed by uni- and multivariate regressions., Results: A significant association with postoperative residual glandular tissue was shown in multivariate analysis for the independent variables breast density, skin flap mean, and surgical method (all p -values < 0.01). A negatively significant association could be seen for the variables preoperative breast volume ( p -values < 0.01) and surgeon experience (most p -values < 0.05-<0.1)., Conclusion: Postoperative residual glandular tissue is an important tool for quantifying the risk of developing breast cancer after risk-reducing mastectomy. Different effects on residual glandular tissue were shown for the independent variables breast density, skin flap, surgical method, preoperative breast volume, and surgeon experience, so these should be considered in future surgical procedures preoperatively as well as postoperatively. Breast MRI has proven to be a suitable method to analyze the skin flap as well as the RGT.

Objective: Proof-of-concept trial to determine the effects of tumor necrosis factor inhibitor (TNFi) therapy on osteoblastic activity at sites of inflammatory and structural lesions in patients with radiographic axial spondyloarthritis (SpA), using fluorine 18-labeled NaF ( 18 F-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI)., Methods: Sixteen patients with clinically active radiographic axial SpA were prospectively enrolled to receive TNFi treatment and undergo 18 F-NaF PET/MRI of the sacroiliac (SI) joints and spine at baseline and at a follow-up visit 3-6 months after treatment initiation. Three readers (1 for PET/MRI and 2 for conventional MRI) evaluated all images, blinded to time point. Bone marrow edema, structural lesions (i.e., fat lesions, sclerosis, erosions, and ankylosis), and 18 F-NaF uptake at SI joint quadrants and vertebral corners (VCs) were recorded., Results: Overall, 11 male and 5 female patients (mean age ± SD 38.6 ± 12.0 years) were followed up for a mean duration of 4.6 months (range 3-6). 18 F-NaF PET/MRI was conducted on SI joints for 16 patients and the spine for 10; 128 SI joint quadrants and 920 VCs were analyzed at each time point. At baseline, 18 F-NaF uptake was demonstrated in 96.0% of SI joint quadrants with bone marrow edema, 94.2% with sclerosis, and 88.3% with fat lesions. At follow-up, 65.3% of SI joint quadrants with bone marrow edema (P < 0.001), 33.8% with sclerosis (P = 0.23), and 24.5% with fat lesions (P = 0.01) had less 18 F-NaF uptake, compared with baseline. For VCs, 18 F-NaF uptake at baseline was found in 81.5% of edges with sclerosis, 41.9% with fat lesions, and 33.7% with bone marrow edema. At follow-up, 73.5% of VCs with bone marrow edema (P = 0.01), 53.3% with fat lesions (P = 0.03), and 55.6% with sclerosis (P = 0.16) showed less 18 F-NaF uptake, compared with baseline., Conclusion: Anti-TNF antibody treatment led to a significant decrease in osteoblastic activity within 3-6 months, especially, but not solely, at sites of inflammation. Larger data sets are needed for confirmation of the antiosteoblastic effects of TNFi for the prevention of radiographic progression in axial SpA., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

PET/MRI has been available since 2010, representing the newest of the hybrid imaging modalities. It combines functional as well as morphologic high-resolution MRI data with metabolic information from PET, providing image data sets with complementary information. Especially in the field of oncology, PET/MRI is a promising imaging modality with diverse applications. Since its introduction there has already been a large quantity of studies indicating a high diagnostic value of PET/MRI for whole-body cancer staging. The simultaneous acquisition of metabolic PET and MRI data is expected to have a major impact in the assessment of breast cancer due to the superior resolution of MRI in breast tissue compared to CT. While there is an ongoing debate if the added value of breast 18 F-FDG PET/MRI in the primary diagnosis of breast cancer has clinical impact compared to breast MRI, a large number of studies have proven that 18 F-FDG PET/MRI is extremely valuable for whole-body breast cancer staging and especially for treatment monitoring. Besides molecular markers, distant metastases and axillary lymph node involvement are the most important predictors for overall survival and recurrence in breast cancer patients. Due to the high soft tissue contrast, functional imaging from MRI and metabolic information from PET, distant metastases in organs and in particular in the bones are detected better compared to the conventional staging algorithm with CT and bone scan and can significantly influence the therapy regime. Instead of mastectomy and extensive axillary dissection being performed in many patients, the improved imaging and diagnostic confidence also has helped that local therapy control can be achieved with reduced invasiveness. A future role of 18 F-FDG PET/MRI could therefore become treatment response evaluation under neoadjuvant treatment before or instead of operative therapy. In addition to reduced radiation exposure compared to conventional staging examinations, hybrid 18 F-FDG PET/MRI might serve as a comprehensive "all-in-one" breast cancer staging tool, providing precise local and whole-body staging including MRI of the head in one procedure, which save patients a diagnostic marathon., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The evaluation of the clinical relevance of missed lung nodules at initial staging of breast cancer patients in [ 18 F]FDG-PET/MRI compared with CT., Methods: A total of 152 patients underwent an initial whole-body [ 18 F]FDG-PET/MRI and a thoracoabdominal CT for staging. Presence, size, shape and location for each lung nodule in [ 18 F]FDG-PET/MRI was noted. The reference standard was established by taking initial CT and follow-up imaging into account (a two-step approach) to identify clinically-relevant lung nodules. Patient-based and lesion-based data analysis was performed., Results: No patient with clinically-relevant lung nodules was missed on a patient-based analysis with MRI VIBE, while 1/84 females was missed with MRI HASTE (1%). Lesion-based analysis revealed 4/96 (4%, VIBE) and 8/138 (6%, HASTE) missed clinically-relevant lung nodules. The average size of missed lung nodules was 3.2 mm ± 1.2 mm (VIBE) and 3.6 mm ± 1.4 mm (HASTE) and the predominant location was in the left lower quadrant and close to the hilum., Conclusion: All patients with newly-diagnosed breast cancer and clinically-relevant lung nodules were detected at initial [ 18 F]FDG-PET/MRI staging. However, due to the lower sensitivity in detecting lung nodules, a small proportion of clinically-relevant lung nodules were missed. Thus, supplemental low-dose chest CT after neoadjuvant therapy should be considered for backup.

Purpose: The aim of this study was to compare and evaluate three different bilinear conversion curves for attenuation correction (AC) of a 16-channel radiofrequency (RF) coil in positron emission tomography/magnetic resonance (PET/MR) breast cancer imaging., Methods: The quantitative impact of three different bilinear conversions of computed tomography (CT) data for the AC of a 16-channel RF breast coil was systematically evaluated in phantom measurements and on n = 20 PET/MR patients with breast cancer. PET data were reconstructed four times: (1) no coil AC (C-NAC) serving as a reference, (2) established bilinear conversion by Carney et al., (3) bilinear conversion by Paulus et al., and (4) bilinear conversion by Oehmigen et al. Relative differences in PET data were calculated., Results: Independent of the choice of bilinear conversion, significant gains in PET signal, compared to C-NAC, were measurable in all phantom and patient measurements. Mean relative differences of ca. 10% in SUVmean (i.e., standardized uptake value; maximal relative differences up to 30%) due to the integration of the coil AC were calculated, compared to C-NAC in phantom and patient measurements. Relative difference images depict that the quantitative impact of coil AC is highest in regions close to the RF coil when compared to no AC data. Bilinear conversion by Carney et al. shows a slightly overcorrection (2.9%), whereas the conversion by Paulus et al. provides a slight undercorrection of the PET images (-1.6%) in comparison to the no-coil measurement. The bilinear conversion proposed by Oehmigen et al. provides the most appropriate AC for the breast coil in this phantom experiment (-0.2%). A total of 23 congruent lesions could be detected in all patients. All lesions could be detected in all reconstructions., Conclusions: For the best possible PET image quality and accurate PET quantification in breast PET/MRI, the AC of MR hardware components is important. The bilinear conversion proposed by Oehmigen et al. provides the most appropriate AC for the breast coil in this study., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: The aim of this study was to assess whether multiparametric 18 F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification., Methods: A total of 73 female patients (mean age 49 years; range 27-77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18 F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model., Results: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2- group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets., Conclusion: 18 F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2- receptor status.

Background: The free-breathing T1-weighted 3D Stack of Stars GRE (StarVIBE) MR sequence potentially reduces artifacts in chest MRI. The purpose of this study was to evaluate StarVIBE for the detection of pulmonary nodules in 18 F-FDG PET/MRI., Material and Methods: In this retrospective analysis, conducted on a prospective clinical trial cohort, 88 consecutive women with newly diagnosed breast cancer underwent both contrast-enhanced whole-body 18 F-FDG PET/MRI and computed tomography (CT). Patients' chests were examined on CT as well as on StarVIBE and conventional T1-weighted VIBE and T2-weighted HASTE MR sequences, with CT serving as the reference standard. Presence, size, and location of all detectable lung nodules were assessed. Wilcoxon test was applied to compare nodule features and Pearson's, and Spearman's correlation coefficients were calculated., Results: Out of 65 lung nodules detected in 36 patients with CT (3.7 ± 1.4 mm), StarVIBE was able to detect 31 (47.7%), VIBE 26 (40%) and HASTE 11 (16.8%), respectively. Overall, CT showed a significantly higher detectability than all MRI sequences combined (65 vs. 36, difference 44.6%, p < 0.001). The VIBE showed a significantly better detection rate than the HASTE (23.1%, p = 0.001). Detection rates between StarVIBE and VIBE did not significantly differ (7.7%, p = 0.27), but the StarVIBE showed a significant advantage detecting centrally located pulmonary nodules (66.7% vs. 16.7%, p = 0.031). There was a strong correlation in nodule size between CT and MRI sequences (HASTE: ρ = 0.80, p = 0.003; VIBE: ρ = 0.77, p < 0.001; StarVIBE: ρ = 0.78, p < 0.001). Mean image quality was rated as good to excellent for CT and MRI sequences., Conclusion: The overall lung nodule detection rate of StarVIBE was slightly, but not significantly, higher than conventional T1w VIBE and significantly higher than T2w HASTE. Detectability of centrally located nodules is better with StarVIBE than with VIBE. Nevertheless, all MRI analyses demonstrated considerably lower detection rates for small lung nodules, when compared to CT., (© 2022. The Author(s).)

Purpose: To compare CT, MRI, and [ 18 F]-fluorodeoxyglucose positron emission tomography ([ 18 F]-FDG PET/MRI) for nodal status, regarding quantity and location of metastatic locoregional lymph nodes in patients with newly diagnosed breast cancer., Materials and Methods: One hundred eighty-two patients (mean age 52.7 ± 11.9 years) were included in this prospective double-center study. Patients underwent dedicated contrast-enhanced chest/abdomen/pelvis computed tomography (CT) and whole-body ([ 18 F]-FDG PET/) magnet resonance imaging (MRI). Thoracal datasets were evaluated separately regarding quantity, lymph node station (axillary levels I-III, supraclavicular, internal mammary chain), and lesion character (benign vs. malign). Histopathology served as reference standard for patient-based analysis. Patient-based and lesion-based analyses were compared by a McNemar test. Sensitivity, specificity, positive and negative predictive values, and accuracy were assessed for all three imaging modalities., Results: On a patient-based analysis, PET/MRI correctly detected significantly more nodal positive patients than MRI (p < 0.0001) and CT (p < 0.0001). No statistically significant difference was seen between CT and MRI. PET/MRI detected 193 lesions in 75 patients (41.2%), while MRI detected 123 lesions in 56 patients (30.8%) and CT detected 104 lesions in 50 patients, respectively. Differences were statistically significant on a lesion-based analysis (PET/MRI vs. MRI, p < 0.0001; PET/MRI vs. CT, p < 0.0001; MRI vs. CT, p = 0.015). Subgroup analysis for different lymph node stations showed that PET/MRI detected significantly more lymph node metastases than MRI and CT in each location (axillary levels I-III, supraclavicular, mammary internal chain). MRI was superior to CT only in axillary level I (p = 0.0291)., Conclusion: [ 18 F]-FDG PET/MRI outperforms CT or MRI in detecting nodal involvement on a patient-based analysis and on a lesion-based analysis. Furthermore, PET/MRI was superior to CT or MRI in detecting lymph node metastases in all lymph node stations. Of all the tested imaging modalities, PET/MRI showed the highest sensitivity, whereas CT showed the lowest sensitivity, but was most specific., (© 2021. The Author(s).)

Objectives: To compare the diagnostic accuracy of contrast-enhanced thoraco-abdominal computed tomography and whole-body 18F-FDG PET/MRI in N and M staging in newly diagnosed, histopathological proven breast cancer., Material and Methods: A total of 80 consecutive women with newly diagnosed and histopathologically confirmed breast cancer were enrolled in this prospective study. Following inclusion criteria had to be fulfilled: (1) newly diagnosed, treatment-naive T2-tumor or higher T-stage or (2) newly diagnosed, treatment-naive triple-negative tumor of every size or (3) newly diagnosed, treatment-naive tumor with molecular high risk (T1c, Ki67 >14%, HER2neu over-expression, G3). All patients underwent a thoraco-abdominal ceCT and a whole-body 18F-FDG PET/MRI. All datasets were evaluated by two experienced radiologists in hybrid imaging regarding suspect lesion count, localization, categorization and diagnostic confidence. Images were interpreted in random order with a reading gap of at least 4 weeks to avoid recognition bias. Histopathological results as well as follow-up imaging served as reference standard. Differences in staging accuracy were assessed using Mc Nemars chi2 test., Results: CT rated the N stage correctly in 64 of 80 (80%, 95% CI:70.0-87.3) patients with a sensitivity of 61.5% (CI:45.9-75.1), a specificity of 97.6% (CI:87.4-99.6), a PPV of 96% (CI:80.5-99.3), and a NPV of 72.7% (CI:59.8-82.7). Compared to this, 18F-FDG PET/MRI determined the N stage correctly in 71 of 80 (88.75%, CI:80.0-94.0) patients with a sensitivity of 82.1% (CI:67.3-91.0), a specificity of 95.1% (CI:83.9-98.7), a PPV of 94.1% (CI:80.9-98.4) and a NPV of 84.8% (CI:71.8-92.4). Differences in sensitivities were statistically significant (difference 20.6%, CI:-0.02-40.9; p = 0.008). Distant metastases were present in 7/80 patients (8.75%). 18 F-FDG PET/MRI detected all of the histopathological proven metastases without any false-positive findings, while 3 patients with bone metastases were missed in CT (sensitivity 57.1%, specificity 95.9%). Additionally, CT presented false-positive findings in 3 patients., Conclusion: 18F-FDG PET/MRI has a high diagnostic potential and outperforms CT in assessing the N and M stage in patients with primary breast cancer., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Aim of this study was to evaluate the use of computer-aided design (CAD) models for attenuation correction (AC) of hardware components in positron emission tomography/magnetic resonance (PET/MR) imaging., Methods: The technical feasibility and quantitative impact of CAD-AC compared to computer tomography (CT)-based AC (reference) was investigated on a modular phantom consisting of 19 different material samples (plastics and metals arranged around a cylindrical emission phantom) typically used in phantoms, patient tables, and radiofrequency (RF) coils in PET/MR. The clinical applicability of the CAD-AC method was then evaluated on a 16-channel RF breast coil in a PET/MR patient study. The RF breast coil in this study was specifically designed PET compatible. Using this RF breast coil, the impact on clinical PET/MR breast imaging was systematically evaluated in breast phantom measurements and, furthermore, in n = 10 PET/MR patients with breast cancer. PET data were reconstructed three times: (1) no AC (NAC), (2) established CT-AC, and (3) CAD-AC. For both phantom measurements, a scan without attenuating hardware components (material probes or RF breast coil) was acquired serving as reference. Relative differences in PET data were calculated for all experiments., Results: In all phantom and patient measurements, significant gains in PET signal compared to NAC data were measurable with CT and CAD-AC. In initial phantom experiments, mean relative differences of -0.2% for CT-AC and 0.2% for CAD-AC were calculated compared to reference measurements without the material probes. The application to a RF breast coil depicts that CAD-AC results in significant gains compared to NAC data (10%) and a slight underestimation in PET signal of -1.3% in comparison to the no-coil reference measurement. In the patient study, a total of 15 congruent lesions in all 10 patients with a mean relative difference of 14% (CT and CAD-AC) in standardized uptake value compared to NAC data could be detected., Conclusions: To ensure best possible PET image quality and accurate PET quantification in PET/MR imaging, the AC of hardware components such as phantoms and RF coils is important. In initial phantom experiments and in clinical application to an RF breast coil, it was found that CAD-based AC results in significant gains in PET signal compared to NAC data and provides comparably good results to the established method of CT-based AC., (© 2021 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Objectives: To compare the diagnostic performance of [ 18 F]FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients., Material and Methods: A cohort of 154 therapy-naive patients with newly diagnosed, histopathologically proven breast cancer was enrolled in this study prospectively. All patients underwent a whole-body [ 18 F]FDG PET/MRI, computed tomography (CT) scan, and a bone scintigraphy prior to therapy. All datasets were evaluated regarding the presence of bone metastases. McNemar χ 2 test was performed to compare sensitivity and specificity between the modalities., Results: Forty-one bone metastases were present in 7/154 patients (4.5%). Both [ 18 F]FDG PET/MRI and MRI alone were able to detect all of the patients with histopathologically proven bone metastases (sensitivity 100%; specificity 100%) and did not miss any of the 41 malignant lesions (sensitivity 100%). CT detected 5/7 patients (sensitivity 71.4%; specificity 98.6%) and 23/41 lesions (sensitivity 56.1%). Bone scintigraphy detected only 2/7 patients (sensitivity 28.6%) and 15/41 lesions (sensitivity 36.6%). Furthermore, CT and scintigraphy led to false-positive findings of bone metastases in 2 patients and in 1 patient, respectively. The sensitivity of PET/MRI and MRI alone was significantly better compared with CT (p < 0.01, difference 43.9%) and bone scintigraphy (p < 0.01, difference 63.4%)., Conclusion: [ 18 F]FDG PET/MRI and MRI are significantly better than CT or bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. Both CT and bone scintigraphy show a substantially limited sensitivity in detection of bone metastases., Key Points: • [ 18 F]FDG PET/MRI and MRI alone are significantly superior to CT and bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. • Radiation-free whole-body MRI might serve as modality of choice in detection of bone metastases in breast cancer patients., (© 2021. The Author(s).)

Background: This study investigated the performance of simultaneous 18 F-FDG PET/MRI of the breast as a platform for comprehensive radiomics analysis for breast cancer subtype analysis, hormone receptor status, proliferation rate and lymphonodular and distant metastatic spread., Methods: One hundred and twenty-four patients underwent simultaneous 18 F-FDG PET/MRI. Breast tumors were segmented and radiomic features were extracted utilizing CERR software following the IBSI guidelines. LASSO regression was employed to select the most important radiomics features prior to model development. Five-fold cross validation was then utilized alongside support vector machines, resulting in predictive models for various combinations of imaging data series., Results: The highest AUC and accuracy for differentiation between luminal A and B was achieved by all MR sequences (AUC 0.98; accuracy 97.3). The best results in AUC for prediction of hormone receptor status and proliferation rate were found based on all MR and PET data (ER AUC 0.87, PR AUC 0.88, Ki-67 AUC 0.997). PET provided the best determination of grading (AUC 0.71), while all MR and PET analyses yielded the best results for lymphonodular and distant metastatic spread (0.81 and 0.99, respectively)., Conclusion: 18 F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for breast cancer phenotyping and tumor decoding, utilizing the perks of simultaneously acquired morphologic, functional and metabolic data.

Objectives: To investigate the influence of contrast agent administration on attenuation correction (AC) based on a CAIPIRINHA (CAIPI)-accelerated T1-weighted Dixon 3D-VIBE sequence in 68 Ga-DOTATOC PET/MRI., Material and Methods: Fifty-one patients with neuroendocrine tumors underwent whole-body 68 Ga-DOTATOC PET/MRI for tumor staging. Two PET reconstructions were performed using AC-maps that were created using a high-resolution CAIPI-accelerated Dixon-VIBE sequence with an additional bone atlas and truncation correction using the HUGE (B0 homogenization using gradient enhancement) method before and after application of Gadolinium (Gd)-based contrast agent. Standardized uptake values (SUVs) of 21 volumes of interest (VOIs) were compared between in both PET data sets per patient. A student's t-test for paired samples was performed to test for potential differences between both AC-maps and both reconstructed PET data sets. Bonferroni correction was performed to prevent α-error accumulation, p < 0.0024 was considered to indicate statistical significance., Results: Significant quantitative differences between SUVmax were found in the perirenal fat (19.65 ± 48.03 %, p < 0.0001), in the axillary fat (17.46 ± 63.67 %, p < 0.0001) and in the dorsal subcutaneous fat on level of lumbar vertebral body L4 (10.26 ± 25.29 %, p < 0.0001). Significant differences were also evident in the lungs apical (5.80 ± 10.53 %, p < 0.0001), dorsal at the level of the pulmonary trunk (15.04 ± 19.09 %, p < 0.0001) and dorsal in the basal lung (51.27 ± 147.61 %, p < 0.0001)., Conclusion: The administration of (Gd)-contrast agents in this study has shown a considerable influence on the AC-maps in PET/MRI and, consequently impacted quantification in the reconstructed PET data. Therefore, dedicated PET/MRI staging protocols have to be adjusted so that AC-map acquisition is performed prior to contrast agent administration., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To compare breast magnetic resonance imaging (MRI), thoracal MRI, thoracal 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET)/MRI and axillary sonography for the detection of axillary lymph node metastases in women with newly diagnosed breast cancer. Materials and Methods: This prospective double-center study included patients with newly diagnosed breast cancer between March 2018 and December 2019. Patients underwent thoracal ( 18 F-FDG PET/)MRI, axillary sonography, and dedicated prone breast MRI. Datasets were evaluated separately regarding nodal status (nodal+ vs. nodal-). Histopathology served as reference standard in all patients. The diagnostic performance of breast MRI, thoracal MRI, thoracal PET/MRI and axillary sonography in detecting nodal positive patients was tested by creating receiver-operating-characteristic curves (ROC) with a calculated area under the curve (AUC). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all four modalities. A McNemar test was used to assess differences. Results: 112 female patients (mean age 53.04 ± 12.6 years) were evaluated. Thoracal PET/MRI showed the highest ROC-AUC with a value of 0.892. The AUC for breast MRI, thoracal MRI and sonography were 0.782, 0.814 and 0.834, respectively. Differences between thoracal PET/MRI and axillary sonography, thoracal MRI and breast MRI were statistically significant (PET/MRI vs. axillary sonography, P = 0.01; PET/MRI vs. thoracal MRI, P = 0.02; PET/MRI vs. breast MRI, P = 0.03). PET/MRI showed the highest sensitivity (81.8%, 36/44) (95%-CI: 67.29-91.81%) while axillary sonography had the highest specificity (98.5%, 65/66), 95%-CI: 91.84-99.96%). Conclusion: 18 F-FDG PET/MRI outperforms axillary sonography, breast MRI and thoracal MRI in determining the axillary lymph node status. In a clinical setting, the combination of 18 F-FDG PET/MRI and axillary sonography might be considered to provide even more accuracy in diagnosis., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objectives: To investigate a correlation between 68 Ga-DOTATOC PET/MR imaging parameters such as arterial and venous contrast enhancement, diffusion restriction, and maximum standardized uptake value (SUVmax) with histopathological tumor grading in patients with neuroendocrine neoplasms (NEN)., Material and Methods: A total of 26 patients with newly diagnosed, therapy-naive neuroendocrine neoplasms (NEN) were enrolled in this prospective study and underwent 68 Ga-DOTATOC PET/MRI. Images were evaluated regarding NEN lesion number and location, predominant tumor signal intensity on precontrast T1w and T2w images and on postcontrast arterial and portal venous phase T1w images, apparent diffusion coefficient (ADC) and SUVmax. Histopathological tumor grading was assessed and related to PET/MRI features using Pearson's correlation coefficient and Fisher's exact t-test. A binary logistic regression analysis was performed to evaluate a potential relation with an aggressive tumor biology and odds ratios (OR) were calculated., Results: There was a moderate negative correlation between arterial contrast enhancement and tumor grading (r=-0.35, p = 0.005), while portal venous enhancement showed a weak positive correlation with the Ki-67 index (r = 0.28, p = 0.008) and a non-significant positive correlation with tumor grading (r = 0.19, p = 0.063). Features that were significantly associated with an aggressive tumor biology were the presence of liver metastases (OR 2.6, p = 0.042), T1w hyperintensity in comparison to muscle (OR 12.7, p = 0.0001), arterial phase hyperenhancement (OR 1.4, p = 0.001), diffusion restriction (OR 2.8, p = 0.02) and SUVmax above the hepatic level (OR 7.0, p = 0.001)., Conclusion: The study reveals that PET/MRI features might be useful for prediction of NEN grading and thus provide a preliminary assessment of tumor aggressiveness., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Our purpose was to evaluate and compare the clinical utility of simultaneously obtained quantitative 18 F-FDG PET and diffusion-weighted MRI datasets for predicting the histopathologic response of soft-tissue sarcoma (STS) to neoadjuvant isolated limb perfusion (ILP). Methods: In total, 37 patients with a confirmed STS of the extremities underwent 18 F-FDG PET/MRI before and after ILP with melphalan and tumor necrosis factor-α. For each patient, the maximum tumor size, metabolic activity (SUV), and diffusion restriction (apparent diffusion coefficient, ADC) were determined in pre- and posttherapeutic examinations, and percentage changes during treatment were calculated. Mann-Whitney U testing and receiver-operating-characteristic analysis were used to compare the results of the different quantitative parameters to predict the histopathologic response to therapy. Results from histopathologic analysis after tumor resection served as the reference standard, and patients were defined as responders or nonresponders based on the grading scale by Salzer-Kuntschik. Results: Histopathologic analysis categorized 22 (59%) patients as responders (grades I-III) and 15 (41%) as nonresponders (grades IV-VI). Under treatment, tumors in responders showed a mean reduction in size (-9.7%) and metabolic activity (SUV peak , -51.9%; SUV mean , -43.8%), as well as an increase of the ADC values (ADC min , +29.4%; ADC mean , +32.8%). The percentage changes in nonresponders were -6.2% in tumor size, -17.3% in SUV peak , -13.9% in SUV mean , +15.3% in ADC min , and +14.6% in ADC mean Changes in SUV and ADC mean significantly differed between responders and nonresponders (<0.01), whereas differences in tumor size and ADC min did not (>0.05). The corresponding AUCs were 0.63 for tumor size, 0.87 for SUV peak , 0.82 for SUV mean , 0.63 for ADC min , 0.84 for ADC mean , and 0.89 for ratio of ADC mean to SUV peak Conclusion: PET- and MRI-derived quantitative parameters (SUV and ADC mean ) and their combination performed well in predicting the histopathologic therapy response of STS to neoadjuvant ILP. Therefore, integrated PET/MRI could serve as a valuable tool for pretherapeutic assessment as well as monitoring of neoadjuvant treatment strategies of STS., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: The aim of this study was to correlate prognostically relevant immunohistochemical parameters of breast cancer with simultaneously acquired SUVs and apparent diffusion coefficient (ADC) values derived from hybrid breast PET/MRI., Patients and Methods: Fifty-six women with newly diagnosed, therapy-naive, histologically proven breast cancer (mean age, 54.1 ± 12.0 years) underwent dedicated prone 18F-FDG breast PET/MRI. Diffusion-weighted imaging (b-values: 0, 500, 1000 s/mm2) was performed simultaneously with the PET acquisition. A region of interest encompassing the entire primary tumor on each patient's PET/MRI scan was used to determine the glucose metabolism represented by maximum and mean SUV as well as into corresponding ADC maps to assess tumor cellularity represented by mean and minimum ADC values. Histopathological tumor grading and prognostically relevant immunohistochemical markers, that is, Ki67, progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2 (HER2), were assessed. Pearson correlation coefficients were calculated to compare SUV and ADC values as well as the immunohistochemically markers and molecular subtype. For the comparison with the tumor grading, a Wilcoxon test was used., Results: A significant inverse correlation between SUV and ADC values derived from breast PET/MRI (r = -0.49 for SUVmean vs ADCmean; r = -0.43 for SUVmax vs ADCmin; both P's < 0.001) was found. Tumor grading and Ki67 both showed a positive correlation with SUVmean from breast PET/MRI (r = 0.37 and r = 0.32, P < 0.01). For immunohistochemical markers, HER2 showed an inverse correlation with ADC values from breast PET/MRI (r = -0.35, P < 0.01). Molecular subtypes significantly correlate with SUVmax and SUVmean (r = 0.52 and r = 0.42, both P's < 0.05). In addition, estrogen receptor expression showed an inverse correlation with SUVmax and SUVmean from breast PET/MRI (r = -0.45 and r = -0.42, P < 0.001)., Conclusions: The present data show a correlation between increased glucose metabolism, cellularity, tumor grading, estrogen and HER2 expression, as well as molecular subtype of breast cancer primaries. Hence, simultaneous 18F-FDG PET and diffusion-weighted imaging from hybrid breast PET/MRI may serve as a predictive tool for identifying high-risk breast cancer patients in initial staging and guide-targeted therapy., Competing Interests: Conflicts of interest and sources of funding: The authors declare no conflict of interest. The study is funded by Deutsche Forschungsgemeinschaft, a German research foundation (BU3075/2-1). The funding foundation was not involved in the trial design, patient recruitment, data collection, analysis, interpretation or presentation, writing or editing of the reports, or the decision to submit for publication. The corresponding author had full access to all data in the study and had all the responsibility for the decision to submit for publication., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To compare prostate specific membrane antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) and computed tomography (CT) alone for the detection of biochemical recurrence of prostate cancer (PCa) and effect on treatment., Methods: This retrospective study included 59 patients with recently recorded biochemical recurrence of PCa (mean PSA 1.96 ± 1.64 ng/mL) after radical prostatectomy. Patients received PET/CT with either 68 Ga-PSMA-11 (n = 36) or 18 F-PSMA-1007 (n = 23). PET/CT and CT images were evaluated separately in regard to PCa lesion count, type, and localisation by two physicians. Histopathology, follow-up imaging and PSA levels after salvage irradiation served as reference standard. A McNemar test was used to compare detection rates. Changes in therapeutic approaches based on staging differences between CT alone and PET/CT were assessed in a virtual multidisciplinary tumour board., Results: There were 142 lesions in 50 of 59 patients. PSMA PET/CT detected 141 lesions (99.3 %) in 50 patients (84.7 %), while CT detected 72 lesions (50.7 %) in 29 patients (49.2 %). A significantly higher detection rate of PSMA PET/CT was observed on a lesion-based analysis (p < 0.0001) and on a patient based analysis (p < 0.0001). Herein, both 68 Ga- and 18 F-PSMA PET/CT performed significantly better than CT alone (p < 0.0001, respectively). In 9 patients (15.3 %) no relapse was detectable by either modality. All lesions detected by CT were also detected by PSMA PET/CT. In 38 patients PSMA PET/CT detected more lesions than CT alone, altering the treatment approach in 22 of these patients., Conclusion: PSMA PET/CT is superior to CT alone in detecting biochemical recurrence in PCa patients after radical prostatectomy and offered additional therapeutic options in a substantial number of patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To investigate if the combined analysis of the apparent diffusion coefficient (ADC) and standardized uptake values (SUV) measured in 18 F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging ( 18 F-FDG PET/MRI) examinations correlates with overall survival in non-small cell lung cancer (NSCLC)., Material and Methods: A total of 92 patients with newly diagnosed, histopathologically proven NSCLC (44 women and 48 men, mean age 63.1 ± 9.9y) underwent a dedicated thoracic 18 F-FDG PET/MRI examination. A manually drawn polygonal region of interest (ROI), encompassing the entire primary tumor mass, was placed over the primary tumor on fused PET/MR images to determine the maximum and mean standardized uptake values (SUV max ; SUV mean ) as well as on the ADC maps to quantify the mean and minimum ADC values (ADC mean , ADC min ). The impact of these parameters to predict patient's overall survival was tested using hazard ratios (HR). Pearson's correlation coefficients were calculated to assess dependencies between the different values. A p-value < 0.05 indicated statistical significance., Results: In all 92 patients (n = 59 dead at time of retrospective data collection, mean time till death: 19 ± 16 month, n = 33 alive, mean time to last follow-up: 56 ± 22 month) the Hazard ratios (HR) as independent predictors for overall survival (OS) of SUV max were 2.37 (95 % CI: 1.23-4.59, p = 0.008) and for SUV mean 1.85 (95 % CI: 1.05-3.26, p = 0.03) while ADC min showed a HR of 0.95 (95 % CI: 0.57-1.59, p = 0.842) and ADC mean a HR of 2.01 (95 % CI: 1.2-3.38, p = 0.007). Furthermore, a combined analysis for SUV max /ADC mean , SUV max / ADC min and SUV mean /ADC mean revealed a HR of 2.01 (95 % CI: 1.10-3.67, p = 0.02), 1.75 (95 % CI: 0.97-3.15, p = 0.058) and 1.78 (95 % CI: 1.02-3.10, p = 0.04)., Conclusion: SUV max and SUV mean of the primary tumor are predictors for OS in therapy-naive NSCLC patients, whereas the combined analysis of SUV and ADC values does not improve these results. Therefore, ADC values do not further enhance the diagnostic value of SUV as a prognostic biomarker in NSCLC., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: To correlate tumour grading and prognostic immunohistochemical markers of lung cancer with simultaneously acquired standardised uptake values (SUV) and apparent diffusion coefficient (ADC) derived from hybrid PET/MRI., Methods: In this retrospective study, 55 consecutive patients (mean age 62.5 ± 9.2 years) with therapy-naïve, histologically proven lung cancer were included. All patients underwent whole-body PET/MRI using 18F-flourdeoxyglucose (18F-FDG) as a radiotracer. Diffusion-weighted imaging of the chest (DWI, b-values: 0, 500, 1000 s/mm 2 ) was performed simultaneously with PET acquisition. Histopathological tumour grading was available in 43/55 patients. In 15/55 patients, immunohistochemical markers, that is, phospho-AKT Ser473 (pAKTS473), phosphorylated extracellular signal-regulated kinase (pERK), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (erbB2) were available., Results: The average SUVmax, SUVmean, ADCmin and ADCmean in lung cancer primaries were 12.6 ± 5.9, 7.7 ± 4.6, 569.9 ± 96.1 s/mm 2 and 825.8 ± 93.2 s/mm 2 , respectively. We found a significant inverse correlation between the ADCmin and SUVmax (r = -0.58, P < 0.001) as well as between the ADCmin and SUVmean (r = -0.44, P < 0.001). Tumour grading showed a significant positive correlation with SUVmax and SUVmean (R = 0.34 and R = 0.31, both P < 0.05) and a significant inverse correlation with ADCmin and ADCmean (r = -0.30 and r = -0.40, both P < 0.05). In addition, erbB2 showed a significant inverse correlation with SUVmax and SUVmean (r = -0.50 and r = -0.49, both P < 0.05). The other immunohistochemical markers did not show any significant correlation., Conclusion: 18F-FDG-PET/MRI showed weak to moderate correlations between SUV, ADC, tumour grading and erbB2-expression of lung cancer. Hence, 18F-FDG-PET/MRI may, to some extent, offer complementary information to the histopathology of lung cancer, for the evaluation of tumour aggressiveness and treatment response., (© 2020 The Royal Australian and New Zealand College of Radiologists.)

Objectives: To evaluate and compare the diagnostic potential of whole-body MRI and whole-body 18 F-FDG PET/MRI for N and M staging in newly diagnosed, histopathologically proven breast cancer., Material and Methods: A total of 104 patients (age 53.4 ± 12.5) with newly diagnosed, histopathologically proven breast cancer were enrolled in this study prospectively. All patients underwent a whole-body 18 F-FDG PET/MRI. MRI and 18 F-FDG PET/MRI datasets were evaluated separately regarding lesion count, lesion localization, and lesion characterization (malignant/benign) as well as the diagnostic confidence (5-point ordinal scale, 1-5). The N and M stages were assessed according to the eighth edition of the American Joint Committee on Cancer staging manual in MRI datasets alone and in 18 F-FDG PET/MRI datasets, respectively. In the majority of lesions histopathology served as the reference standard. The remaining lesions were followed-up by imaging and clinical examination. Separately for nodal-positive and nodal-negative women, a McNemar chi 2 test was performed to compare sensitivity and specificity of the N and M stages between 18 F-FDG PET/MRI and MRI. Differences in diagnostic confidence scores were assessed by Wilcoxon signed rank test., Results: MRI determined the N stage correctly in 78 of 104 (75%) patients with a sensitivity of 62.3% (95% CI: 0.48-0.75), a specificity of 88.2% (95% CI: 0.76-0.96), a PPV (positive predictive value) of 84.6% % (95% CI: 69.5-0.94), and a NPV (negative predictive value) of 69.2% (95% CI: 0.57-0.8). Corresponding results for 18 F-FDG PET/MRI were 87/104 (83.7%), 75.5% (95% CI: 0.62-0.86), 92.2% (0.81-0.98), 90% (0.78-0.97), and 78.3% (0.66-0.88), showing a significantly better sensitivity of 18 F-FDG PET/MRI determining malignant lymph nodes (p = 0.008). The M stage was identified correctly in MRI and 18 F-FDG PET/MRI in 100 of 104 patients (96.2%). Both modalities correctly staged all 7 patients with distant metastases, leading to false-positive findings in 4 patients in each modality (3.8%). In a lesion-based analysis, 18 F-FDG PET/MRI showed a significantly better performance in correctly determining malignant lesions (85.8% vs. 67.1%, difference 18.7% (95% CI: 0.13-0.26), p < 0.0001) and offered a superior diagnostic confidence compared with MRI alone (4.1 ± 0.7 vs. 3.4 ± 0.7, p < 0.0001)., Conclusion: 18 F-FDG PET/MRI has a better diagnostic accuracy for N staging in primary breast cancer patients and provides a significantly higher diagnostic confidence in lesion characterization than MRI alone. But both modalities bear the risk to overestimate the M stage.

Background: To investigate the diagnostic performance of simultaneous 18 F-fluoro-deoxyglucose ([ 18 F]-FDG) PET/MR enterography in assessing and grading endoscopically active inflammation in patients with ulcerative colitis. Methods: 50 patients underwent PET/MR 24 h before ileocolonoscopy. Inflammatory activities of bowel segments were evaluated with both Mayo endoscopic subscore and Nancy histologic index. MR, DWI (Diffusion-weighted imaging) and PET were utilized as qualitative parameters for detecting endoscopically active inflammation. SUVmaxQuot in each segment (maximum of standard uptake value relative to liver) was calculated to quantify inflammation. Results: In the study arm without bowel purgation, combined reading of PET and MR resulted in significantly increased specificity against each submodality alone (0.944 vs. 0.82 for MR and 0.843 for PET, p < 0.05) and highest overall accuracy. In the study arm with bowel purgation, the significantly lower specificity of PET (0.595) could be markedly improved by a combined reading of PET and MR. Metabolic conditions in bowel segments with both endoscopic and histological remission were significantly lower than in segments with endoscopic remission but persistent microscopic inflammation (SUVmaxQuot 0.719 vs. 0.947, p < 0.001). SUVmaxQuot correlated highly with Mayo endoscopic subscore (ρ = 0.718 and 0.606) and enabled grading of inflammatory activity. Conclusions: Simultaneous [ 18 F]-FDG PET/MR may be considered as an alternative to endoscopy in clinical trials.

Objective: To compare the diagnostic performance of fecal biomarkers and 18 F-fludeoxyglucose ( 18 F-FDG) positron emmision tomography-MR (PET-MR) in the assessment of disease activity in patients with ulcerative colitis., Methods: This study was conducted under the framework of a single-center clinical trial (clinicaltrials.gov [NCT03781284]). N = 50 participants were enrolled. Fecal samples were collected before bowel preparation. All patients underwent whole-body 18 F-FDG PET-MR followed by ileocolonoscopy within 24 h. Diagnostic performance of five fecal biomarkers (calprotectin, lactoferrin, polymorphonuclear leukocyte elastase, S100A12 and eosinophil-derived neurotoxin), MR morphological parameters (MRmorph), diffusion-weighted imaging and PET in detecting active disease determined by Rachmilewitz endoscopic activity index (EAI) were evaluated and compared with each other. Correlations between fecal biomarkers, PET and endoscopy were calculated., Results: According to EAI, n = 38 patients presented with endoscopically active disease (16 mild, 19 moderate and 3 severe). All five biomarkers, PET and MRmorph could differentiate endoscopically active disease from endoscopic remission without significant difference regarding their operating characteristics (accuracies between 0.673 for calprotectin and 0.898 for lactoferrin). In predicting endoscopically moderate to severe disease, PET showed the highest diagnostic performance (accuracy = 0.857) compared to calprotectin and lactoferrin (accuracy = 0.633 and 0.735). PET had also the strongest correlation with endoscopy (ρ = 0.685, p < 0.001), while within fecal biomarkers the levels of lactoferrin and eosinophil-derived neurotoxin correlated significantly with EAI (ρ = 0.423 and 0.528, both p < 0.05)., Conclusion: Both fecal biomarkers and PET-MR were excellent non-invasive diagnostic tools in the assessment of disease activity in ulcerative colitis., Advances in Knowledge: Both fecal biomarkers and PET-MR parameters are able to predict endoscopically active disease with comparable diagnostic performance. PET had the highest correlation with endoscopy and outperformed fecal biomarkers in differentiating moderate to severe from mild disease.

Objective: To analyze why numerous acute stroke treatments were successful in the laboratory but failed in large clinical trials., Methods: We searched all phase 3 trials of medical treatments for acute ischemic stroke and corresponding early clinical and experimental studies. We compared the overall efficacy and assessed the impact of publication bias and study design on the efficacy. Furthermore, we estimated power and true report probability of experimental studies., Results: We identified 50 phase 3 trials with 46,008 subjects, 75 early clinical trials with 12,391 subjects, and 209 experimental studies with >7,141 subjects. Three (6%) phase 3, 24 (32%) early clinical, and 143 (69.08%) experimental studies were positive. The mean treatment effect was 0.76 (95% confidence interval [CI] = 0.70-0.83) in experimental studies, 0.87 (95% CI = 0.71-1.06) in early clinical trials, and 1.00 (95% CI = 0.95-1.06) in phase 3 trials. Funnel plot asymmetry and trim-and-fill revealed a clear publication bias in experimental studies and early clinical trials. Study design and adherence to quality criteria had a considerable impact on estimated effect sizes. The mean power of experimental studies was 17%. Assuming a bias of 30% and pre-study odds of 0.5 to 0.7, this leads to a true report probability of <50%., Interpretation: Pivotal study design differences between experimental studies and clinical trials, including different primary end points and time to treatment, publication bias, neglected quality criteria and low power, contribute to the stepwise efficacy decline of stroke treatments from experimental studies to phase 3 clinical trials. Even under conservative estimates, less than half of published positive experimental stroke studies are truly positive. ANN NEUROL 2020;87:40-51., (© 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Background and Purpose: Peripheral immune cell infiltration contributes to neural injury after ischemic stroke. However, in contrast to lymphocytes and neutrophils, the role of different monocyte/macrophage subsets remains to be clarified. Therefore, we evaluated the effects of selective and unselective monocyte/macrophage depletion and proinflammatory (M1-) and anti-inflammatory (M2-) macrophage transfer on the outcome after experimental cerebral ischemia., Methods: To assess short-term effects of monocytes/macrophages in acute ischemic stroke, mice underwent transient middle cerebral artery occlusion and received either clodronate liposomes for unselective macrophage depletion, MC-21-antibody for selective depletion of proinflammatory Ly-6C high monocytes, or proinflammatory (M1-) or anti-inflammatory (M2-) macrophage transfer. In addition, the impact of MC-21-antibody administration and M2-macrophage transfer on long-term neural recovery was investigated after photothrombotic stroke. Neurobehavioral tests were used to analyze functional outcomes, infarct volumes were determined, and immunohistochemical analyses were performed to characterize the postischemic inflammatory reaction., Results: Selective and unselective monocyte/macrophage depletion and M1- and M2-macrophage transfer did not influence tissue damage and neurobehavioral outcomes in the acute phase after middle cerebral artery occlusion. Beyond, selective depletion of Ly-6C high monocytes and M2-macrophage transfer did not have an impact on neural recovery after photothrombotic stroke., Conclusions: Targeting different monocyte/macrophage subsets has no impact on outcome after ischemic stroke in mice. Altogether, our study could not identify monocytes/macrophages as relevant therapeutic targets in acute ischemic stroke., (© 2017 American Heart Association, Inc.)