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Nicole Lindenblatt,1 Karem El-Rabadi,2 Thomas H Helbich,2 Heinrich Czembirek,3 Maria Deutinger,4 Heike Benditte-Klepetko5 1Division of Plastic and Hand Surgery, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; 2Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna - General Hospital Vienna, 3Department of Radiology, Hospital Wiener Privatklinik, 4Department of Plastic and Reconstructive Surgery, Hospital Rudolfstiftung, Vienna, Austria; 5Department of Plastic and Reconstructive Surgery, Erasmus Medical Center, Rotterdam, the Netherlands Background: Silicone gel breast implants may silently rupture without detection. This has been the main reason for magnetic resonance imaging (MRI) of the augmented or reconstructed breast. The aim of the present study was to investigate the accuracy of MRI for implant rupture. Methods: Fifty consecutive patients with 85 silicone gel implants were included in the study. The mean age of the patients was 51 (range 21–72) years, with a mean duration of implantation of 3.8 (range 1–28) years. All patients underwent clinical examination and breast MRI. Intraoperative implant rupture was diagnosed by the operating surgeon. Results: Nineteen of the 50 patients suffered from clinical symptoms. An implant rupture was diagnosed by MRI in 22 of 85 implants (26%). In seven of 17 removed implants (41%), the intraoperative diagnosis corresponded with the positive MRI result. However, only 57% of these patients were symptomatic. Ultrasound imaging of the harvested implants showed signs of interrupted inner layers of the implant despite integrity of the outer shell. By microsurgical separation of the different layers of the implant shell, we were able to reproduce this phenomenon and to produce signs of implant rupture on MRI. Conclusion: Our results show that rupture of only the inner layers of the implant shell with integrity of the outer shell leads to a misdiagnosis on MRI. Correlation with clinical symptoms and the specific wishes of the patient should guide the indication for implant removal. Keywords: breast implant, rupture, silicone gel, magnetic resonance imaging, linguine, keyhole

Objective: To identify which breast lesion descriptors in the ACR BI-RADS® MRI lexicon are most strongly associated with the diagnosis of breast cancer when performing breast MR imaging at 3 T.Methods: 150 patients underwent breast MR imaging at 3 T. Lesion size, morphology and enhancement kinetics were assessed according to the BI-RADS® classification. Sensitivity, specificity and diagnostic accuracy were assessed. The effects of the BI-RADS® descriptors on sensitivity and specificity were evaluated. Data were analysed using logistic regression. Histopathological diagnoses were used as the standard of reference.Results: The sensitivity, specificity and diagnostic accuracy of breast MRI at 3 T was 99%, 81% and 93%, respectively. In univariate analysis, the final diagnosis of malignancy was positively associated with irregular shape (p < 0.001), irregular margin (p < 0.001), heterogeneous enhancement (p < 0.001), Type 3 enhancement kinetics (p = 0.02), increasing patient age (p = 0.02) and larger lesion size (p < 0.001). In multivariate analysis, significant associations with malignancy remained for mass shape (p = 0.06), mass margin (p < 0.001), internal enhancement pattern (p = 0.03) and Type 3 enhancement kinetics (p = 0.06).Conclusion: The ACR BI-RADS® breast lesion descriptors that are mostly strongly associated with breast cancer in breast MR imaging at 3 T are lesion shape, lesion margin, internal enhancement pattern and Type 3 enhancement kinetics.Key Points: • 3 Tesla breast MRI allows an accurate diagnosis of breast cancer • The BI-RADS® descriptors help provide a confident diagnosis • The shape, margin, enhancement pattern and kinetics are the most important features • An irregular shape and margin, heterogeneous enhancement and type-3 kinetics indicate malignancy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the frequency of diagnosis of high-risk lesions at MRI-guided vacuum-assisted breast biopsy (MRgVABB) and to determine whether underestimation may be predicted.Methods: Retrospective review of the medical records of 161 patients who underwent MRgVABB was performed. The underestimation rate was defined as an upgrade of a high-risk lesion at MRgVABB to malignancy at surgery. Clinical data, MRI features of the biopsied lesions, and histological diagnosis of cases with and those without underestimation were compared.Results: Of 161 MRgVABB, histology revealed 31 (19%) high-risk lesions. Of 26 excised high-risk lesions, 13 (50%) were upgraded to malignancy. The underestimation rates of lobular neoplasia, atypical apocrine metaplasia, atypical ductal hyperplasia, and flat epithelial atypia were 50% (4/8), 100% (5/5), 50% (3/6) and 50% (1/2) respectively. There was no underestimation in the cases of benign papilloma without atypia (0/3), and radial scar (0/2). No statistically significant differences (p > 0.1) between the cases with and those without underestimation were seen in patient age, indications for breast MRI, size of lesion on MRI, morphological and kinetic features of biopsied lesions.Conclusions: Imaging and clinical features cannot be used reliably to predict underestimation at MRgVABB. All high-risk lesions diagnosed at MRgVABB require surgical excision. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the value of galactography-guided, stereotactic, vacuum-assisted breast biopsy (VABB) for the assessment of intraductal breast lesions and its potential as a therapeutic tool that could eliminate the need for surgical excision. Eighteen patients (median age 64 years, range 37-80) with nipple discharge and galactography-verified intraductal lesions underwent galactography-guided, stereotactic, 11-gauge VABB followed by surgery. Histopathology findings from VABB and subsequent surgery were compared. Underestimation and false-negative rates were assessed. After VABB, histopathology revealed invasive ductal carcinoma (IDC) in three (17%), ductal carcinoma in situ (DCIS) in six (33%), high-risk lesions in six (33%) and benign lesions in three (17%) cases. After surgical biopsy, histopathology confirmed the previously established diagnosis in 11 lesions (61%). The underestimation rate for high-risk lesions and DCIS was 50% (6/12). The false-negative rate was 7% (1/14). Histopathology examination after surgery showed that not a single lesion had been completely removed at VABB. Galactography-guided VABB is a feasible diagnostic tool. However, its value as a therapeutic procedure is limited because of the high number of underestimated and missed lesions and because of the histopathological detection of lesions' remnants in every case. Surgical excision should be the therapeutic gold standard in cases of pathological nipple discharge and galactography abnormalities. [ABSTRACT FROM AUTHOR]

Ultrasound-guided, large-core needle biopsy (US-LCNB) of suspicious breast lesions is acknowledged as less invasive and less expensive and less time consuming than surgical biopsy, and provides a histologic diagnosis with a comparable high degree. US-LCNB has been proven to help reduce the number of unnecessary surgeries for benign disease. Its limitations, however, are false-negative results and underestimation of disease. Thus, the demand for breast teams is to carefully adhere to the principles of triple assessment and imaging-histologic correlation, and follow-up of lesions with a specific benign histology after biopsy. Also, the acceptance of guidelines and rigorous quality controls help to reliably minimize the delay in the diagnosis of breast cancer in patients with false-negative biopsies. This paper aims to summarize the equipment and methods as well as the benefits and limitations of US-LCNB. Also, guidelines of quality assessment are suggested. Finally, recent developments which may help to overcome the limitations of US-LCNB will be discussed, i.e., directional vacuum-assisted biopsy (VAB), three-dimensional (3D) US-guided biopsy, as well as the use of tissue harmonic imaging (THI) and compound imaging (CI) during biopsy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the inter-reader agreement of the breast imaging reporting and data system (BI-RADS) contrast-enhanced mammography (CEM) lexicon., Materials and Methods: In this IRB-approved, single-center, retrospective study, three breast radiologists, each with different levels of experience, reviewed 462 lesions in 421 routine clinical CEM according to the fifth edition of the BI-RADS lexicon for mammography and to the first version of the BI-RADS lexicon for CEM. Readers were blinded to patient outcomes and evaluated breast and lesion features on low-energy (LE) images (breast density, type of lesion, associated architectural distortion), lesion features on recombined (RC) images (type of enhancement, characteristic of mass enhancement, non-mass enhancement or enhancing asymmetry), and provided a final BI-RADS assessment. The inter-reader agreement was calculated for each evaluated feature using Fleiss' kappa coefficient. Sensitivity and specificity were calculated., Results: The inter-reader agreement was moderate to substantial for breast density (ĸ = 0.569), type of lesion on LE images (ĸ = 0.654), and type of enhancement (ĸ = 0.664). There was a moderate to substantial agreement on CEM mass enhancement descriptors. The agreement was fair to moderate for non-mass enhancement and enhancing asymmetry descriptors. Inter-reader agreement for LE and LE with RC BI-RADS assessment was moderate (ĸ = 0.421) and fair (ĸ = 0.364). Diagnostic performance was good and comparable for all readers., Conclusion: Inter-reader agreement of the CEM lexicon was moderate to substantial for most features. There was a low agreement for some RC descriptors, such as non-mass enhancement and enhancing asymmetry, and BI-RADS assessment, but this did not impact the diagnostic performance., Key Points: Question Data on the reproducibility and inter-reader agreement for the first version of the BI-RADS lexicon dedicated to CEM are missing. Finding The inter-reader agreement for the lexicon was overall substantial to moderate, but it was lower for the descriptors for non-mass enhancement and enhancing asymmetry. Clinical relevance A common lexicon simplifies communication between specialists in clinical practice. The good inter-reader agreement confirms the effectiveness of the CEM-BIRADS in ensuring consistent communication. Detailed definitions of some descriptors (non-mass, enhancing asymmetry) are needed to ensure higher agreements., (© 2024. The Author(s).)

Background: Magnetic resonance imaging (MRI) has a superior sensitivity for the diagnosis of breast cancer, leading to lesions primarily detected by MRI. Some of these lesions cannot be identified by targeted second-look ultrasound (SLUS) examinations and are thus referred to as MRI-only lesions. We hypothesize that biologically more aggressive cancers lead to more distinct tissue damage improving visibility on SLUS., Objective: To investigate whether there are differences in cancer subtypes between MRI-only and SLUS-detected malignant lesions., Methods: This retrospective single-center observational study evaluated 435 patients who received breast MRI examinations between January 2017 and December 2022, with at least one lesion primarily detected on MRI and histologically confirmed as malignant. Demographic characteristics, lesion type (mass or non-mass), MRI-assessed lesion size (mm), histological diagnosis, stage, immunohistochemical analysis (ER, PR, HER-2, Ki-67), and lymph node status were assessed and compared between MRI-only and SLUS-detected., Results: Among 435 patients (mean age of 57.4 ± 13.3), 34.02 % (n = 148) were in the MRI-only group, while the remaining 65.98 % (n = 287) were identified by SLUS. MRI-only cases were significantly smaller in size (10 mm vs 20 mm), mostly staged as T1 (66.9 %) and showed features associated with less biological aggressiveness (higher pure ductal carcinoma in situ rates: 30.4 % vs 5.2 %; lower Ki-67, median values: 10 vs 20) compared to SLUS-detected cases (P < 0.001). SLUS-detected cancers had higher ratios of microscopic (4.9 % vs 3.4 %) and macroscopic axillary metastasis (26.8 % vs 7.4 %) compared to MRI-only lesions (P < 0.001)., Conclusion: MRI-only lesions presented histologically and immunohistochemically with less aggressive patterns compared to those detected via SLUS. Clinic Impact: Our data provide evidence that MRI-only lesions are biologically less aggressive and of lower stage, offering the potential of earlier treatment chance since they are visible on MRI before becoming more aggressive and destructive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient - in vitro PDOs - in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns., Results: The main liver metastasis of the CRC patient exhibited high 2-[ 18 F]FDG uptake and moderate and focal [ 68 Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[ 18 F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient's liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient's sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [ 68 Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [ 68 Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking., Conclusions: We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient's tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [ 68 Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[ 18 F]FDG was avidly taken up in the patient's liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients., (© 2024. The Author(s).)

Purpose: Ongoing efforts are focusing on optimizing diffusion-weighted imaging (DWI) as an essential part of breast MRI protocol. Our study aimed to evaluate the effect of contrast media (CM) on the apparent diffusion coefficients (ADC) acquired following current recommendations., Patient and Methods: Patients who underwent 3 T breast MRI with a histologically verified suspicious lesion were included in this IRB-approved, single-center, cross-sectional retrospective study. Breast MRI protocol included a DWI sequence with multiple b-values, which was acquired before and after CM administration. ADC maps were calculated by in-line monoexponential fitting with b-values 0 /800 and 50/800. Two independent readers (R1, R2) reviewed the images in separate sessions for b values 0/800 and 50/800, pre- and post-CM. Bland Altmann plots as well as intraclass correlation coefficients (ICCs) for inter-reader agreement, different b-values, and pre- and post-CM were calculated. Diagnostic accuracy was evaluated and compared by calculating the area under the receiver operating characteristics curve (AUC)., Results: 91 lesions in 89 patients were examined (mean age 50.7 years, standard deviation 13.9). ADC values were significantly (P<0.05) lower post-CM (mean ranging from 1.28 x10 -3 mm 2 /s to 1.30 x10 -3 mm 2 /s) compared to pre-CM (mean ranging from 1.32 x10 -3 mm 2 /s to 1.37 x10 -3 mm 2 /s) for both b-values combinations (0/800 and 50/800 s/mm 2 ). We found an almost perfect inter-reader agreement pre-/post-CM with b values 0/800 and 50/800 (ICC ranging from 0.853 to 0.939). Bland Altman plot demonstrated no systematic difference between readers. ROC analysis revealed good diagnostic performance without significant differences (P>0.05) between b values 0/800 and 50/800 s/mm2 as well as pre- and post-CM with areas under the ROC curve between 0.834 and 0.877., Conclusion: ADC values are slightly lower when acquiring b values 0/800 and post-CM. This effect does not reduce the diagnostic performance but may be relevant in case of definite cut-offs in medical decision making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To create a simple model using standard BI-RADS® descriptors from pre-treatment B-mode ultrasound (US) combined with clinicopathological tumor features, and to assess the potential of the model to predict the presence of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients., Method: 245 female BC patients receiving NAC between January 2017 and December 2019 were included in this retrospective study. Two breast imaging fellows independently evaluated representative B-mode tumor images from baseline US. Additional clinicopathological tumor features were retrieved. The dataset was split into 170 training and 83 validation cases. Logistic regression was used in the training set to identify independent predictors of residual disease post NAC and to create a model, whose performance was evaluated by ROC curve analysis in the validation set. The reference standard was postoperative histology to determine the absence (pathological complete response, pCR) or presence (non-pCR) of residual invasive tumor in the breast or axillary lymph nodes., Results: 100 patients (40.8%) achieved pCR. Logistic regression demonstrated that tumor size, microlobulated margin, spiculated margin, the presence of calcifications, the presence of edema, HER2-positive molecular subtype, and triple-negative molecular subtype were independent predictors of residual disease. A model using these parameters demonstrated an area under the ROC curve of 0.873 in the training and 0.720 in the validation set for the prediction of residual tumor post NAC., Conclusions: A simple model combining standard BI-RADS® descriptors from pre-treatment B-mode breast US with clinicopathological tumor features predicts the presence of residual disease after NAC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cholangiocarcinoma (CCA) is a type of primary liver cancer originating from the biliary tract epithelium, characterized by limited treatment options for advanced cases and low survival rates. This study aimed to establish an orthotopic mouse model for CCA and monitor tumor growth using PET/MR imaging. Murine CCA cells were implanted into the liver lobe of male C57BL/6J mice. The imaging groups included contrast-enhanced (CE) MR, CE-MR with static [ 18 F]FDG-PET, and dynamic [ 18 F]FDG-PET. Tumor volume and FDG uptake were measured weekly over four weeks. Early tumor formation was visible in CE-MR images, with a gradual increase in volume over time. Dynamic FDG-PET revealed an increase in the metabolic glucose rate (MRGlu) over time. Blood analysis showed pathological changes in liver-related parameters. Lung metastases were observed in nearly all animals after four weeks. The study concludes that PET-MR imaging effectively monitors tumor progression in the CCA mouse model, providing insights into CCA development and potential treatment strategies.

Purpose: Gadolinium-based contrast media (GBCM) may affect apparent diffusion coefficient measurements on diffusion-weighted imaging. We aimed at investigating the effect of GBCM and inter-reader variation on intravoxel incoherent motion (IVIM) parameters in breast lesions., Methods: A total of 89 patients referred to 3T breast MRI with at least one histologically verified lesion were included. IVIM data were acquired using a single-shot echo planar imaging sequence before and after GBCM administration. D (true diffusion coefficient), D* (pseudo-diffusion coefficient) and f (perfusion fraction) were calculated and measured by two readers (R1, R2). Inter-reader and intra-reader agreements were assessed by intraclass correlation coefficients (ICCs) and Bland-Altman plots., Results: D was comparable before and after GBCM administration and between readers. D* and f decreased after GBCM administration and showed a lower agreement between readers. Intra-reader agreement before and after GBCM administration was almost perfect for D for both R1 and R2 (ICC 0.955 and 0.887). The intra-reader agreement was substantial to moderate for D* (ICC R1 0.708, R2 0.583) and moderate for f (ICC R1 0.529 and R2 0.425). Inter-reader agreement before GBCM administration was almost perfect for D (ICC 0.905), substantial for D* (ICC 0.733), and moderate for f (ICC 0.404); after contrast media administration, it was almost perfect for D (ICC 0.876) and substantial for D* (ICC 0.654) and f (ICC 0.606). Bland-Altman plots revealed no significant bias., Conclusion: Administration of GBCM seems to have a stronger effect on D* and f values than on D values. This should be considered when applying IVIM in clinical practice.

Objectives: To investigate the influence of preoperative breast MRI on mastectomy and reoperation rates in patients with pure ductal carcinoma in situ (DCIS)., Methods: The MIPA observational study database (7245 patients) was searched for patients aged 18-80 years with pure unilateral DCIS diagnosed at core needle or vacuum-assisted biopsy (CNB/VAB) and planned for primary surgery. Patients who underwent preoperative MRI (MRI group) were matched (1:1) to those who did not receive MRI (noMRI group) according to 8 confounding covariates that drive referral to MRI (age; hormonal status; familial risk; posterior-to-nipple diameter; BI-RADS category; lesion diameter; lesion presentation; surgical planning at conventional imaging). Surgical outcomes were compared between the matched groups with nonparametric statistics after calculating odds ratios (ORs)., Results: Of 1005 women with pure unilateral DCIS at CNB/VAB (507 MRI group, 498 noMRI group), 309 remained in each group after matching. First-line mastectomy rate in the MRI group was 20.1% (62/309 patients, OR 2.03) compared to 11.0% in the noMRI group (34/309 patients, p = 0.003). The reoperation rate was 10.0% in the MRI group (31/309, OR for reoperation 0.40) and 22.0% in the noMRI group (68/309, p < 0.001), with a 2.53 OR of avoiding reoperation in the MRI group. The overall mastectomy rate was 23.3% in the MRI group (72/309, OR 1.40) and 17.8% in the noMRI group (55/309, p = 0.111)., Conclusions: Compared to those going directly to surgery, patients with pure DCIS at CNB/VAB who underwent preoperative MRI had a higher OR for first-line mastectomy but a substantially lower OR for reoperation., Clinical Relevance Statement: When confounding factors behind MRI referral are accounted for in the comparison of patients with CNB/VAB-diagnosed pure unilateral DCIS, preoperative MRI yields a reduction of reoperations that is more than twice as high as the increase in overall mastectomies., Key Points: • Confounding factors cause imbalance when investigating the influence of preoperative MRI on surgical outcomes of pure DCIS. • When patient matching is applied to women with pure unilateral DCIS, reoperation rates are significantly reduced in women who underwent preoperative MRI. • The reduction of reoperations brought about by preoperative MRI is more than double the increase in overall mastectomies., (© 2023. The Author(s).)

Background: One of the main features of several metabolic disorders is dysregulation of hepatic glucose and lipid metabolism. Deuterium metabolic imaging (DMI) allows for assessing the uptake and breakdown of 2 H-labeled substrates, giving specific insight into nutrient processing in healthy and diseased organs. Thus, DMI could be a useful approach for analyzing the differences in liver metabolism of healthy and diseased subjects to gain a deeper understanding of the alterations related to metabolic disorders., Purpose: Evaluating the feasibility of DMI as a tool for the assessment of metabolic differences in rodents with healthy and fatty livers (FLs)., Study Type: Animal Model., Population: 18 male Sprague Dawley rats on standard (SD, n = 9, healthy) and high-fat diet (HFD, n = 9, FL disease)., Field Strength/sequence: Phase-encoded 1D pulse-acquire sequence and anatomy co-registered phase-encoded 3D pulse-acquire chemical shift imaging for 2 H at 9.4T., Assessment: Localized and nonlocalized liver spectroscopy was applied at eight time points over 104 minutes post injection. The obtained spectra were preprocessed and quantified using jMRUI (v7.0) and the resulting amplitudes translated to absolute concentration (mM) according to the 2 H natural abundance water peak., Statistical Tests: Two-way repeated measures ANOVA were employed to assess between-group differences, with statistical significance at P < 0.05., Results: DMI measurements demonstrated no significant difference (P = 0.98) in the uptake of [6,6'- 2 H 2 ]glucose between healthy and impaired animals (AUC SD  = 1966.0 ± 151.5 mM - minutes vs. AUC HFD  = 2027.0 ± 167.6 mM·minutes). In the diseased group, the intrahepatic uptake of palmitic acid d-31 was higher (AUC HFD  = 57.4 ± 17.0 mM·minutes, AUC SD  = 33.3 ± 10.5 mM·minutes), but without statistical significance owing to substantial in-group variation (P = 0.73)., Data Conclusion: DMI revealed higher concentrations of palmitic acid in rats with FL disease and no difference in hepatic glucose concentration between healthy and impaired animals. Thus, DMI appears to be a useful tool for evaluating metabolism in rodents with FL disease., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 3., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

"Hot spot" 19 F magnetic resonance imaging (MRI) has garnered significant attention recently for its ability to image various disease markers quantitatively. Unlike conventional gadolinium-based MRI contrast agents, which rely on proton signal modulation, 19 F-MRI's direct detection has a unique advantage in vivo, as the human body exhibits a negligible background 19 F-signal. However, existing perfluorocarbon (PFC) or PFC-based contrast materials suffer from several limitations, including low longitudinal relaxation rates and relatively low imaging efficiency. Hence, we designed a macromolecular contrast agent featuring a high number of magnetically equivalent 19 F-nuclei in a single macromolecule, adequate fluorine nucleus mobility, and excellent water solubility. This design utilizes superfluorinated polyphosphazene (PPz) polymers as the 19 F-source; these are modified with sodium mercaptoethanesulfonate (MESNa) to achieve water solubility exceeding 360 mg/mL, which is a similar solubility to that of sodium chloride. We observed substantial signal enhancement in MRI with these novel macromolecular carriers compared to non-enhanced surroundings and aqueous trifluoroacetic acid (TFA) used as a positive control. In conclusion, these novel water-soluble macromolecular carriers represent a promising platform for future MRI contrast agents.

Tumor neoangiogenesis is an important hallmark of cancer progression, triggered by alternating selective pressures from the hypoxic tumor microenvironment. Non-invasive, non-contrast-enhanced multiparametric MRI combining blood-oxygen-level-dependent (BOLD) MRI, which depicts blood oxygen saturation, and intravoxel-incoherent-motion (IVIM) MRI, which captures intravascular and extravascular diffusion, can provide insights into tumor oxygenation and neovascularization simultaneously. Our objective was to identify imaging markers that can predict hypoxia-induced angiogenesis and to validate our findings using multiplexed immunohistochemical analyses. We present an in vivo study involving 36 female athymic nude mice inoculated with luminal A, Her2+, and triple-negative breast cancer cells. We used a high-field 9.4-tesla MRI system for imaging and subsequently analyzed the tumors using multiplex immunohistochemistry for CD-31, PDGFR-β, and Hif1-α. We found that the hyperoxic-BOLD-MRI-derived parameter Δ R2* discriminated luminal A from Her2+ and triple-negative breast cancers, while the IVIM-derived parameter fIVIM discriminated luminal A and Her2+ from triple-negative breast cancers. A comprehensive analysis using principal-component analysis of both multiparametric MRI- and mpIHC-derived data highlighted the differences between triple-negative and luminal A breast cancers. We conclude that multiparametric MRI combining hyperoxic BOLD MRI and IVIM MRI, without the need for contrast agents, offers promising non-invasive markers for evaluating hypoxia-induced angiogenesis.

Purpose: We aimed to investigate the effect of using visual or automatic enhancement curve type assessment on the diagnostic performance of the Kaiser Score (KS), a clinical decision rule for breast MRI., Method: This IRB-approved retrospective study analyzed consecutive conventional BI-RADS 0, 4 or 5 patients who underwent biopsy after 1.5T breast MRI according to EUSOBI recommendations between 2013 and 2015. The KS includes five criteria (spiculations; signal intensity (SI)-time curve type; margins of the lesion; internal enhancement; and presence of edema) resulting in scores from 1 (=lowest) to 11 (=highest risk of breast cancer). Enhancement curve types (Persistent, Plateau or Wash-out) were assessed by two radiologists independently visually and using a pixel-wise color-coded computed parametric map of curve types. KS diagnostic performance differences between readings were compared by ROC analysis., Results: In total 220 lesions (147 benign, 73 malignant) including mass (n = 148) and non-mass lesions (n = 72) were analyzed. KS reading performance in distinguishing benign from malignant lesions did not differ between visual analysis and parametric map (P = 0.119; visual: AUC 0.875, sensitivity 95 %, specificity 63 %; and map: AUC 0.901, sensitivity 97 %, specificity 65 %). Additionally, analyzing mass and non-mass lesions separately, showed no difference between parametric map based and visual curve type-based KS analysis as well (P = 0.130 and P = 0.787)., Conclusions: The performance of the Kaiser Score is largely independent of the curve type assessment methodology, confirming its robustness as a clinical decision rule for breast MRI in any type of breast lesion in clinical routine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this prospective study, 117 female patients (mean age = 53 years) with 127 histologically proven breast cancer lesions (lymph node (LN) positive = 85, LN negative = 42) underwent simultaneous 18F-FDG PET/MRI of the breast. Quantitative parameters were calculated from dynamic contrast-enhanced (DCE) imaging (tumor Mean Transit Time, Volume Distribution, Plasma Flow), diffusion-weighted imaging (DWI) (tumor ADCmean), and PET (tumor SUVmax, mean and minimum, SUVmean of ipsilateral breast parenchyma). Manual whole-lesion segmentation was also performed on DCE, T2-weighted, DWI, and PET images, and radiomic features were extracted. The dataset was divided into a training (70%) and a test set (30%). Multi-step feature selection was performed, and a support vector machine classifier was trained and tested for predicting axillary LN status. 13 radiomic features from DCE, DWI, T2-weighted, and PET images were selected for model building. The classifier obtained an accuracy of 79.8 (AUC = 0.798) in the training set and 78.6% (AUC = 0.839), with sensitivity and specificity of 67.9% and 100%, respectively, in the test set. A machine learning-based radiomics model comprising 18F-FDG PET/MRI radiomic features extracted from the primary breast cancer lesions allows high accuracy in non-invasive identification of axillary LN metastasis.

Background and Aims: The worldwide prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) raises concerns about associated risk factors, such as obesity and type 2 Diabetes Mellitus, for leading causes of disability and death. Besides Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS), functional imaging with Positron Emission Tomography (PET) could contribute to a deeper understanding of the pathophysiology of NAFLD. Here we describe a novel approach using the PET tracer [ 18 F]FTHA, which is an analog of long-chain free fatty acids (FFA) and is taken up by tissues to enter mitochondria or to be incorporated into complex lipids for further export as very-low-density lipoprotein (VLDL)., Methods: Male Sprague Dawley rats, after 6 weeks on a high-fat diet (HFD), were used as a model of diet induced NAFLD, while a standard diet (SD) served as a control group. Liver fat was estimated by MR spectroscopy at a 9.4 T system for phenotyping. To measure hepatic FFA uptake, rats underwent 60 min dynamic [ 18 F]FTHA-PET scans after unrestricted access to food (HFD: n = 6; SD: n = 6) or overnight (≤16h) fasting (HFD: n = 6; SD: n = 5). FFA removal was assessed from incorporated 18 F-residual in de novo synthesized VLDL out of plasma., Results: MRS of the liver confirmed the presence of NAFLD (>5.6% fat). Under non-fasting conditions, hepatic [ 18 F]FTHA uptake was significantly increased in NAFLD: SUVmean (p = 0.03) within [0; 60] min interval, SUVmean (p = 0.01) and SUVmax (p = 0.03) within [30; 60] min interval. SUVs for hepatic uptake under fasting conditions were not significantly different between the groups. Analysis of FFA removal demonstrated elevated values of 18 F-residue in the VLDL plasma fraction of the healthy group compared to the NAFLD (p = 0.0569)., Conclusion: Our novel approach for assessing FFA metabolism using [ 18 F]FTHA demonstrated differences in the hepatic FFA uptake and FFA incorporation into VLDL between healthy and NAFLD rats. [ 18 F]FTHA-PET could be used to study metabolic disturbances involved in the progression of NAFLD., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Hyperoxic BOLD-MRI targeting tumor hypoxia may provide imaging biomarkers that represent breast cancer molecular subtypes without the use of injected contrast agents. However, the diagnostic performance of hyperoxic BOLD-MRI using different levels of oxygen remains unclear. We hypothesized that molecular subtype characterization with hyperoxic BOLD-MRI is feasible independently of the amount of oxygen. Twenty-three nude mice that were inoculated into the flank with luminal A ( n = 9), Her2 + ( n = 5), and triple-negative ( n = 9) human breast cancer cells were imaged using a 9.4 T Bruker BioSpin system. During BOLD-MRI, anesthesia was supplemented with four different levels of oxygen (normoxic: 21%; hyperoxic: 41%, 71%, 100%). The change in the spin-spin relaxation rate in relation to the normoxic state, ΔR2*, dependent on the amount of erythrocyte-bound oxygen, was calculated using in-house MATLAB code. ΔR2* was significantly different between luminal A and Her2 + as well as between luminal A and triple-negative breast cancer, reflective of the less aggressive luminal A breast cancer's ability to better deliver oxygen-rich hemoglobin to its tissue. Differences in ΔR2* between subtypes were independent of the amount of oxygen, with robust distinction already achieved with 41% oxygen. In conclusion, hyperoxic BOLD-MRI may be used as a biomarker for luminal A breast cancer identification without the use of exogenous contrast agents.