Publications by authors named "Thomas H Helbich"

150 Publications

Breast Tumor Characterization Using [F]FDG-PET/CT Imaging Combined with Data Preprocessing and Radiomics.

Cancers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

Division of Molecular and Gender Imaging, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria.

: This study investigated the performance of ensemble learning holomic models for the detection of breast cancer, receptor status, proliferation rate, and molecular subtypes from [F]FDG-PET/CT images with and without incorporating data pre-processing algorithms. Additionally, machine learning (ML) models were compared with conventional data analysis using standard uptake value lesion classification. : A cohort of 170 patients with 173 breast cancer tumors (132 malignant, 38 benign) was examined with [F]FDG-PET/CT. Breast tumors were segmented and radiomic features were extracted following the imaging biomarker standardization initiative (IBSI) guidelines combined with optimized feature extraction. Ensemble learning including five supervised ML algorithms was utilized in a 100-fold Monte Carlo (MC) cross-validation scheme. Data pre-processing methods were incorporated prior to machine learning, including outlier and borderline noisy sample detection, feature selection, and class imbalance correction. Feature importance in each model was assessed by calculating feature occurrence by the R-squared method across MC folds. : Cross validation demonstrated high performance of the cancer detection model (80% sensitivity, 78% specificity, 80% accuracy, 0.81 area under the curve (AUC)), and of the triple negative tumor identification model (85% sensitivity, 78% specificity, 82% accuracy, 0.82 AUC). The individual receptor status and luminal A/B subtype models yielded low performance (0.46-0.68 AUC). SUV model yielded 0.76 AUC in cancer detection and 0.70 AUC in predicting triple negative subtype. : Predictive models based on [F]FDG-PET/CT images in combination with advanced data pre-processing steps aid in breast cancer diagnosis and in ML-based prediction of the aggressive triple negative breast cancer subtype.
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http://dx.doi.org/10.3390/cancers13061249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000810PMC
March 2021

Correct determination of the enhancement curve is critical to ensure accurate diagnosis using the Kaiser score as a clinical decision rule for breast MRI.

Eur J Radiol 2021 May 5;138:109630. Epub 2021 Mar 5.

Department of Biomedical Imaging and Image-Guided Therapy, Medical University and General Hospital of Vienna, Austria. Electronic address:

Objectives: the Kaiser score is increasingly recognized as a valuable tool to improve breast MRI interpretation. Contrast enhancement kinetics are the second most important diagnostic criterion, thus defining the curve type plays a crucial role in Kaiser score assessment. We investigate whether the timepoint used to determine the initial enhancement (earlyor peak) for the signal-intensity time curve analysis affects the diagnostic performance of the Kaiser score.

Methods: This IRB-approved, retrospective, single-center study included 70 consecutives histologically verified breast MRI cases. Two off-site breast radiologists independently read all examinations using the Kaiser score, assessing the initial enhancement using three approaches: -first (1 st), second (2nd) and peak (maximum) of either 1 st or 2nd post-contrast timepoints. The initial enhancement was then compared to the last timepoint (delayed enhancement) to determine the curve type. Visual assessment of curve types was used for this study. Diagnostic performance was evaluated by receiver operating characteristics (ROC) analysis.

Results: Kaiser score reading results using the peak enhancement of either the first or second timepoint performed significantly better than the other approaches (P < 0.05, respectively) and specifically achieved higher sensitivity. Diagnostic accuracy (AUC area under the curve) ranged between 85.4 % and 91.6 %, without significant differences between the two readers (P < 0.5).

Conclusions: Diagnostic performance of the Kaiser score is significantly influenced by how the initial enhancement timepoint is determined. Peak enhancement should be used as initial timepoint to avoid pitfalls due to timing or physiological differences.
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http://dx.doi.org/10.1016/j.ejrad.2021.109630DOI Listing
May 2021

Can supplementary contrast-enhanced MRI of the breast avoid needle biopsies in suspicious microcalcifications seen on mammography? A systematic review and meta-analysis.

Breast 2021 Apr 15;56:53-60. Epub 2021 Feb 15.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria. Electronic address:

Purpose: To analyze the rate of potentially avoidable needle biopsies in mammographically suspicious calcifications if supplementary Contrast-Enhanced MRI (CE-MRI) is negative.

Methods: Using predefined criteria, a systematic review was performed. Studies investigating the use of supplemental CE-MRI in the setting of mammographically suspicious calcifications undergoing stereotactic biopsy and published between 2000 and 2020 were eligible. Two reviewers extracted study characteristics and true positives (TP), false positives, true negatives and false negatives (FN). Specificity, in this setting equaling the number of avoidable biopsies and FN rates were calculated. The maximum pre-test probability at which post-test probabilities of a negative CE-MRI met with BI-RADS benchmarks was determined by a Fagan nomogram. Random-effects models, I-statistics, Deek's funnel plot testing and meta-regression were employed. P-values <0.05 were considered significant.

Results: Thirteen studies investigating 1414 lesions with a cancer prevalence of 43.6% (range: 22.7-66.9%) were included. No publication bias was found (P = 0.91). CE-MRI performed better in pure microcalcification studies compared to those also including associate findings (P < 0.001). In the first group, the pooled rate of avoidable biopsies was 80.6% (95%-CI: 64.6-90.5%) while the overall and invasive cancer FN rates were 3.7% (95%-CI: 1.2-6.2%) and 1.6% (95%-CI 0-3.6%), respectively. Up to a pre-test probability of 22%, the post-test probability did not exceed 2%.

Conclusion: A negative supplementary CE-MRI could potentially avoid 80.6% of unnecessary stereotactic biopsies in BI-RADS 4 microcalcifications at a cost of 3.7% missed breast cancers, 1.6% invasive. BI-RADS benchmarks for downgrading mammographic calcifications would be met up to a pretest probability of 22%.
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http://dx.doi.org/10.1016/j.breast.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907894PMC
April 2021

Diffusion-weighted Imaging Allows for Downgrading MR BI-RADS 4 Lesions in Contrast-enhanced MRI of the Breast to Avoid Unnecessary Biopsy.

Clin Cancer Res 2021 Apr 14;27(7):1941-1948. Epub 2021 Jan 14.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Purpose: Diffusion-weighted imaging with the calculation of an apparent diffusion coefficient (ADC) has been proposed as a quantitative biomarker on contrast-enhanced MRI (CE-MRI) of the breast. There is a need to approve a generalizable ADC cutoff. The purpose of this study was to evaluate whether a predefined ADC cutoff allows downgrading of BI-RADS 4 lesions on CE-MRI, avoiding unnecessary biopsies.

Experimental Design: This was a retrospective, multicentric, cross-sectional study. Data from five centers were pooled on the individual lesion level. Eligible patients had a BI-RADS 4 rating on CE-MRI. For each center, two breast radiologists evaluated the images. Data on lesion morphology (mass, non-mass), size, and ADC were collected. Histology was the standard of reference. A previously suggested ADC cutoff (≥1.5 × 10 mm/second) was applied. A negative likelihood ratio of 0.1 or lower was considered as a rule-out criterion for breast cancer. Diagnostic performance indices were calculated by ROC analysis.

Results: There were 657 female patients (mean age, 42; SD, 14.1) with 696 BI-RADS 4 lesions included. Disease prevalence was 59.5% (414/696). The area under the ROC curve was 0.784. Applying the investigated ADC cutoff, sensitivity was 96.6% (400/414). The potential reduction of unnecessary biopsies was 32.6% (92/282).

Conclusions: An ADC cutoff of ≥1.5 × 10 mm/second allows downgrading of lesions classified as BI-RADS 4 on breast CE-MRI. One-third of unnecessary biopsies could thus be avoided.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3037DOI Listing
April 2021

MR Imaging of Peripheral Nerves Using Targeted Application of Contrast Agents: An Experimental Proof-of-Concept Study.

Front Med (Lausanne) 2020 11;7:613138. Epub 2020 Dec 11.

Clinical Laboratory for Bionic Extremity Reconstruction, Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.

Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported. We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS). All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mMs. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in e MRI. measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg). In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.
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http://dx.doi.org/10.3389/fmed.2020.613138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759654PMC
December 2020

Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging at 7T for Breast Cancer Diagnosis and Characterization.

Cancers (Basel) 2020 Dec 14;12(12). Epub 2020 Dec 14.

Breast Imaging Service, Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY 10065, USA.

The purpose of this study was to investigate whether ultra-high-field dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast at 7T using quantitative pharmacokinetic (PK) analysis can differentiate between benign and malignant breast tumors for improved breast cancer diagnosis and to predict molecular subtypes, histologic grade, and proliferation rate in breast cancer. In this prospective study, 37 patients with 43 lesions suspicious on mammography or ultrasound underwent bilateral DCE-MRI of the breast at 7T. PK parameters (K, k, V) were evaluated with two region of interest (ROI) approaches (2D whole-tumor ROI or 2D 10 mm standardized ROI) manually drawn by two readers (senior reader, R1, and R2) independently. Histopathology served as the reference standard. PK parameters differentiated benign and malignant lesions (n = 16, 27, respectively) with good accuracy (AUCs = 0.655-0.762). The addition of quantitative PK analysis to subjective BI-RADS classification improved breast cancer detection from 88.4% to 97.7% for R1 and 86.04% to 97.67% for R2. Different ROI approaches did not influence diagnostic accuracy for both readers. Except for K for whole-tumor ROI for R2, none of the PK parameters were valuable to predict molecular subtypes, histologic grade, or proliferation rate in breast cancer. In conclusion, PK-enhanced BI-RADS is promising for the noninvasive differentiation of benign and malignant breast tumors.
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http://dx.doi.org/10.3390/cancers12123763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765071PMC
December 2020

Ameliorative effects of deferiprone and tetraethylammonium salt of salinomycinic acid on lead-induced toxicity in mouse testes.

Environ Sci Pollut Res Int 2021 Feb 2;28(6):6784-6795. Epub 2020 Oct 2.

Faculty of Medicine, Sofia University "St. Kliment Ohridski", Kozjak Str., 1, 1407, Sofia, Bulgaria.

In this study, we compare the effects of deferiprone (Def) and tetraethylammonium salt of salinomycinic acid (Sal) on lead (Pb)-induced toxicity in testes of Pb-exposed mice. Mature male ICR mice were allocated into four groups as follows: untreated control mice (ctrl)-received distilled water for 4 weeks; Pb-exposed mice (Pb)-subjected to 14-day Pb (II) nitrate administration at dose 80 mg/kg body weight (b.w.); Pb + Def group-Pb-exposed mice, treated with 20 mg/kg b.w. Def for 2 weeks; and Pb + Sal group-Pb-intoxicated mice, treated with 16 mg/kg b.w. Sal for 14 days. The results demonstrated that Pb exposure significantly increased blood and testicular Pb concentrations, decreased testicular calcium (Ca) content, significantly elevated testicular levels of magnesium (Mg), zinc (Zn), and selenium (Se) but did not significantly affect the endogenous contents of phosphorous (P) and iron (Fe) compared with untreated controls. Pb intoxication induced disorganization of the seminiferous epithelium. Def or Sal administration reduced blood Pb and testicular Pb concentrations in Pb-exposed mice compared with the Pb-intoxicated group. Mg, Zn, and Se concentrations in testes of Pb-exposed mice, treated with Def or Sal, remained higher compared with the untreated controls. Sal significantly increased testicular P concentration compared with untreated controls and significantly elevated the testicular Ca and Fe concentrations compared with the toxic control group. Both chelating agents improved testicular morphology to a great extent. The results demonstrate the potential of both compounds as antidotes for treatment of Pb-induced impairment of male reproductive function.
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http://dx.doi.org/10.1007/s11356-020-10960-4DOI Listing
February 2021

Non-Invasive Assessment of Hypoxia and Neovascularization with MRI for Identification of Aggressive Breast Cancer.

Cancers (Basel) 2020 Jul 24;12(8). Epub 2020 Jul 24.

Department of Neurosurgery, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.

The aim of this study was to investigate the potential of magnetic resonance imaging (MRI) for a non-invasive synergistic assessment of tumor microenvironment (TME) hypoxia and induced neovascularization for the identification of aggressive breast cancer. Fifty-three female patients with breast cancer underwent multiparametric breast MRI including quantitative blood-oxygen-level-dependent (qBOLD) imaging for hypoxia and vascular architecture mapping for neovascularization. Quantitative MRI biomarker maps of oxygen extraction fraction (OEF), metabolic rate of oxygen (MRO2), mitochondrial oxygen tension (mitoPO2), microvessel radius (VSI), microvessel density (MVD), and microvessel type indicator (MTI) were calculated. Histopathology was the standard of reference. Histopathological markers (vascular endothelial growth factor receptor 1 (FLT1), podoplanin, hypoxia-inducible factor 1-alpha (HIF-1alpha), carbonic anhydrase 9 (CA IX), vascular endothelial growth factor C (VEGF-C)) were used to confirm imaging biomarker findings. Univariate and multivariate regression analyses were performed to differentiate less aggressive luminal from aggressive non-luminal (HER2-positive, triple negative) malignancies and assess the interplay between hypoxia and neoangiogenesis markers. Aggressive non-luminal cancers ( = 40) presented with significantly higher MRO2 (i.e., oxygen consumption), lower mitoPO2 values (i.e., hypoxia), lower MTI, and higher MVD than less aggressive cancers ( = 13). Data suggest that a model derived from OEF, mitoPO2, and MVD can predict tumor proliferation rate. This novel MRI approach, which can be easily implemented in routine breast MRI exams, aids in the non-invasive identification of aggressive breast cancer.
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http://dx.doi.org/10.3390/cancers12082024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464174PMC
July 2020

The Kaiser score reliably excludes malignancy in benign contrast-enhancing lesions classified as BI-RADS 4 on breast MRI high-risk screening exams.

Eur Radiol 2020 Nov 6;30(11):6052-6061. Epub 2020 Jun 6.

Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.

Objectives: MRI is an integral part of breast cancer screening in high-risk patients. We investigated whether the application of the Kaiser score, a clinical decision-support tool, may be used to exclude malignancy in contrast-enhancing lesions classified as BI-RADS 4 on breast MRI screening exams.

Methods: This retrospective study included 183 consecutive, histologically proven, suspicious (MR BI-RADS 4) lesions detected within our local high-risk screening program. All lesions were evaluated according to the Kaiser score for breast MRI by three readers blinded to the final histopathological diagnosis. The Kaiser score ranges from 1 (lowest, cancer very unlikely) to 11 (highest, cancer very likely) and reflects increasing probabilities of malignancy, with scores greater than 4 requiring biopsy. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic accuracy.

Results: There were 142 benign and 41 malignant lesions, diagnosed in 159 patients (mean age, 43.6 years). Median Kaiser scores ranged between 2 and 5 in benign and 7 and 8 in malignant lesions. For all lesions, the Kaiser score's accuracy, represented by the area under the curve (AUC), ranged between 86.5 and 90.2. The sensitivity of the Kaiser score was high, between 95.1 and 97.6% for all lesions, and was best in mass lesions. Application of the Kaiser score threshold for malignancy (≤ 4) could have potentially avoided 64 (45.1%) to 103 (72.5%) unnecessary biopsies in 142 benign lesions previously classified as BI-RADS 4.

Conclusions: The use of Kaiser score in high-risk MRI screening reliably excludes malignancy in more than 45% of contrast-enhancing lesions classified as BI-RADS 4.

Key Points: • The Kaiser score shows high diagnostic accuracy in identifying malignancy in contrast-enhancing lesions in patients undergoing high-risk screening for breast cancer. • The application of the Kaiser score may avoid > 45% of unnecessary breast biopsies in high-risk patients. • The Kaiser score aids decision-making in high-risk breast cancer MRI screening programs.
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http://dx.doi.org/10.1007/s00330-020-06945-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553895PMC
November 2020

A closer look into ECR 2020 on hybrid, molecular, and translational imaging.

Authors:
Thomas H Helbich

Eur Radiol 2020 10 18;30(10):5536-5538. Epub 2020 May 18.

Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna & General Hospital, Waehringer Guertel 18-20, Floor 7F, 1090, Vienna, Austria.

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http://dx.doi.org/10.1007/s00330-020-06938-yDOI Listing
October 2020

Factors influencing agreement of breast cancer luminal molecular subtype by Ki67 labeling index between core needle biopsy and surgical resection specimens.

Virchows Arch 2020 Oct 7;477(4):545-555. Epub 2020 May 7.

Department of Pathology and Comprehensive Cancer Center, Medical University of Vienna, 18-20 Waehringer Guertel, A-1090, Vienna, Austria.

Reliable determination of Ki67 labeling index (Ki67-LI) on core needle biopsy (CNB) is essential for determining breast cancer molecular subtype for therapy planning. However, studies on agreement between molecular subtype and Ki67-LI between CNB and surgical resection (SR) specimens are conflicting. The present study analyzed the influence of clinicopathological and sampling-associated factors on agreement. Molecular subtype was determined visually by Ki67-LI in 484 pairs of CNB and SR specimens of invasive estrogen receptor (ER)-positive, human epidermal growth factor (HER2)-negative breast cancer. Luminal B disease was defined by Ki67-LI > 20% in SR. Correlation of molecular subtype agreement with age, menopausal status, CNB method, Breast Imaging Reporting and Data System imaging category, time between biopsies, type of surgery, and pathological tumor parameters was analyzed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. CNB had a sensitivity of 77.95% and a specificity of 80.97% for identifying luminal B tumors in CNB, compared with the final molecular subtype determination after surgery. The correlation of Ki67-LI between CNB and SR was moderate (ROC-AUC 0.8333). Specificity and sensitivity for CNB to correctly define molecular subtype of tumors according to SR were significantly associated with tumor grade, immunohistochemical progesterone receptor (PR) and p53 expression (p < 0.05). Agreement of molecular subtype did not significantly impact RFS and OS (p = 0.22 for both). The identified factors likely mirror intratumoral heterogeneity that might compromise obtaining a representative CNB. Our results challenge the robustness of a single CNB-driven measurement of Ki67-LI to identify luminal B breast cancer of low (G1) or intermediate (G2) grade.
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http://dx.doi.org/10.1007/s00428-020-02818-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508960PMC
October 2020

Solving the preoperative breast MRI conundrum: design and protocol of the MIPA study.

Eur Radiol 2020 Oct 6;30(10):5427-5436. Epub 2020 May 6.

Unit of Radiology, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Italy.

Despite its high diagnostic performance, the use of breast MRI in the preoperative setting is controversial. It has the potential for personalized surgical management in breast cancer patients, but two of three randomized controlled trials did not show results in favor of its introduction for assessing the disease extent before surgery. Meta-analyses showed a higher mastectomy rate in women undergoing preoperative MRI compared to those who do not. Nevertheless, preoperative breast MRI is increasingly used and a survey from the American Society of Breast Surgeons showed that 41% of respondents ask for it in daily practice. In this context, a large-scale observational multicenter international prospective analysis (MIPA study) was proposed under the guidance of the European Network for the Assessment of Imaging in Medicine (EuroAIM). The aims were (1) to prospectively and systematically collect data on consecutive women with a newly diagnosed breast cancer, not candidates for neoadjuvant therapy, who are offered or not offered breast MRI before surgery according to local practice; (2) to compare these two groups in terms of surgical and clinical endpoints, adjusting for covariates. The underlying hypotheses are that MRI does not cause additional mastectomies compared to conventional imaging, while reducing the reoperation rate in all or in subgroups of patients. Ninety-six centers applied to a web-based call; 36 were initially selected based on volume and quality standards; 27 were active for enrollment. On November 2018, the target of 7000 enrolled patients was reached. The MIPA study is presently at the analytic phase. Key Points • Breast MRI has a high diagnostic performance but its utility in the preoperative setting is controversial. • A large-scale observational multicenter prospective study was launched to compare women receiving with those not receiving preoperative MRI. • Twenty-seven centers enrolled more than 7000 patients. The study is presently at the analytic phase.
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http://dx.doi.org/10.1007/s00330-020-06824-7DOI Listing
October 2020

Can second-look ultrasound downgrade MRI-detected lesions? A retrospective study.

Eur J Radiol 2020 Jun 11;127:108976. Epub 2020 Apr 11.

Department of Biomedical Imaging and Image-Guided Therapy, General and Pediatric Radiology, Allgemeines Krankenhaus, Medical University of Vienna, Austria. Electronic address:

Purpose: To determine whether MRI-detected suspicious (BIRADS 4 & 5) breast lesions can be downgraded using second-look ultrasound (SLU) and thus reduce unnecessarily performed breast biopsies.

Materials Methods: A retrospective single-center review of consecutive patients, who underwent breast MRI studies during a 12-month time period was performed. 94 patients with 103 lesions undergoing SLU of incidentally detected MRI BI-RADS 4&5 lesions which were not identified on previous ultrasound were included in the study. The SLU detection rate and SLU features of the lesions were assessed. Histology (91/103) or two year follow up (n = 12) were defined as the reference standard for lesion diagnosis.

Results: 57 (55.3 %) of the 103 lesions were identified on SLU. 17 of the identified lesions were malignant (29.8 %). Lesions detected on ultrasound presented on MRI as masses in 66.7 % (38/57) and non-mass in 33.3 % (19/57). Our findings showed that it is possible to distinguish between malignant and benign lesions with SLU. The results were significant (p < 0.05) for the following morphological features: shape, orientation, margins, architectural distortion, hyperechoic rim/ edema. All lesions classified as SLU BI-RADS 2 in our study were benign and thus, 30 % of all unnecessary biopsies could potentially have been avoided. Including SLU BI-RADS 3 lesions, this rate increased to 60 %, while yielding one (of 17, 5.8 %) false negative result. All three BI-RADS 5 lesions detected by SLU presented as malignant on ultrasound.

Conclusion: SLU can potentially downgrade incidental MRI BIRADS 4 lesions. This may reduce the number of unnecessarily performed biopsies by 30-60 %, thus simplifying patient management.
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http://dx.doi.org/10.1016/j.ejrad.2020.108976DOI Listing
June 2020

Impact of osteopontin on the development of non-alcoholic liver disease and related hepatocellular carcinoma.

Liver Int 2020 07 30;40(7):1620-1633. Epub 2020 May 30.

Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Background & Aims: Osteopontin, a multifunctional protein and inflammatory cytokine, is overexpressed in adipose tissue and liver in obesity and contributes to the induction of adipose tissue inflammation and non-alcoholic fatty liver (NAFL). Studies performed in both mice and humans also point to a potential role for OPN in malignant transformation and tumour growth. To fully understand the role of OPN on the development of NAFL-derived hepatocellular carcinoma (HCC), we applied a non-alcoholic steatohepatitis (NASH)-HCC mouse model on osteopontin-deficient (Spp1 ) mice analysing time points of NASH, fibrosis and HCC compared to wild-type mice.

Methods: Two-day-old wild-type and Spp1 mice received a low-dose streptozotocin injection in order to induce diabetes, and were fed a high-fat diet starting from week 4. Different cohorts of mice of both genotypes were sacrificed at 8, 12 and 19 weeks of age to evaluate the NASH, fibrosis and HCC phenotypes respectively.

Results: Spp1 animals showed enhanced hepatic lipid accumulation and aggravated NASH, as also increased hepatocellular apoptosis and accelerated fibrosis. The worse steatotic and fibrotic phenotypes observed in Spp1 mice might be driven by enhanced hepatic fatty acid influx through CD36 overexpression and by a pathological accumulation of specific diacylglycerol species during NAFL. Lack of osteopontin lowered systemic inflammation, prevented HCC progression to less differentiated tumours and improved overall survival.

Conclusions: Lack of osteopontin dissociates NASH-fibrosis severity from overall survival and HCC malignant transformation in NAFLD, and is therefore a putative therapeutic target only for advanced chronic liver disease.
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http://dx.doi.org/10.1111/liv.14464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384114PMC
July 2020

Clinical relevance of total choline (tCho) quantification in suspicious lesions on multiparametric breast MRI.

Eur Radiol 2020 Jun 17;30(6):3371-3382. Epub 2020 Feb 17.

Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender, Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.

Purpose: To assess the additional value of quantitative tCho evaluation to diagnose malignancy and lymph node metastases in suspicious lesions on multiparametric breast MRI (mpMRI, BI-RADS 4, and BI-RADS 5).

Methods: One hundred twenty-one patients that demonstrated suspicious multiparametric breast MRI lesions using DCE, T2w, and diffusion-weighted (DW) images were prospectively enrolled in this IRB-approved study. All underwent single-voxel proton MR spectroscopy (H-MRS, point-resolved spectroscopy sequence, TR 2000 ms, TE 272 ms) with and without water suppression. The total choline (tCho) amplitude was measured and normalized to millimoles/liter according to established methodology by two independent readers (R1, R2). ROC-analysis was employed to predict malignancy and lymph node status by tCho results.

Results: One hundred three patients with 74 malignant and 29 benign lesions had full H-MRS data. The area under the ROC curve (AUC) for prediction of malignancy was 0.816 (R1) and 0.809 (R2). A cutoff of 0.8 mmol/l tCho could diagnose malignancy with a sensitivity of > 95%. For prediction of lymph node metastases, tCho measurements achieved an AUC of 0.760 (R1) and 0.788 (R2). At tCho levels < 2.4 mmol/l, no metastatic lymph nodes were found.

Conclusion: Quantitative tCho evaluation from H-MRS allowed diagnose malignancy and lymph node status in breast lesions suspicious on multiparametric breast MRI. tCho therefore demonstrated the potential to downgrade suspicious mpMRI lesions and stratify the risk of lymph node metastases for improved patient management.

Key Points: • Quantitative tCho evaluation can distinguish benign from malignant breast lesions suspicious after multiparametric MRI assessment. • Quantitative tCho levels are associated with lymph node status in breast cancer. • Quantitative tCho levels are higher in hormonal receptor positive compared to hormonal receptor negative lesions.
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http://dx.doi.org/10.1007/s00330-020-06678-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248046PMC
June 2020

Low-Dose, Contrast-Enhanced Mammography Compared to Contrast-Enhanced Breast MRI: A Feasibility Study.

J Magn Reson Imaging 2020 08 14;52(2):589-595. Epub 2020 Feb 14.

Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.

Contrast-enhanced MRI (CE-MRI) is the most sensitive technique for breast cancer detection. Contrast-enhanced mammography (CEM) is emerging as a possible alternative to CE-MRI.

Purpose: To evaluate the diagnostic performance of a low radiation dose contrast-enhanced mammography (L-CEM) in women with suspicious findings on conventional imaging compared to CE-MRI of the breast.

Study Type: Prospective, single center.

Population: Women with suspicious findings on mammography, tomosynthesis, or ultrasound, and no contraindications for L-CEM or CE-MRI. Eighty women were included.

Field Strength/sequence: 1.5 and 3T CE-MRI, standard protocol for breast, with dedicated coils, according to international guidelines. L-CEM was performed using a dedicated prototype.

Assessment: Three, off-site, blinded readers evaluated the images according to the BI-RADS lexicon in a randomized order, each in two separate reading sessions. Histology served as a gold standard.

Statistical Test: Lesion detection rate, sensitivity, specificity, and negative and positive predictive values (NPV, PPV) were calculated and compared with multivariate statistics.

Results: Included were 80 women (mean age, 54.3 years ±11.2 standard deviation) with 93 lesions (32 benign, 61 malignant). The detection rate was significantly higher with CE-MRI (92.5-94.6%; L-CEM 79.6-91.4%, P = 0.014). Sensitivity (L-CEM 65.6-90.2%; CE-MRI 83.6-93.4%, P = 0.086) and NPV (L-CEM 59.6-71.4%; CE-MRI 63.0-76.5%, P = 0.780) did not differ between the modalities. Specificity (L-CEM 46.9-96.9%; CE-MRI 37.5-53.1%, P = 0.001) and PPV (L-CEM 76.4-97.6%; CE-MRI 73.3-77.3%, P = 0.007) were significantly higher with L-CEM. Variations between readers were significant for sensitivity and NPV. The accuracy of L-CEM was as good as CE-MRI (75.3-76.3% vs. 72.0-75.3%, P = 0.514).

Data Conclusion: L-CEM showed a high sensitivity and accuracy in women with suspicious findings on conventional imaging. Compared to CE-MRI, L-CEM has the potential to increase specificity and PPV. L-CEM might help to reduce false-positive biopsies while obtaining sensitivity comparable to that of CE-MRI LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:589-595.
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http://dx.doi.org/10.1002/jmri.27079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496227PMC
August 2020

Image-guided breast biopsy and localisation: recommendations for information to women and referring physicians by the European Society of Breast Imaging.

Insights Imaging 2020 Feb 5;11(1):12. Epub 2020 Feb 5.

Unit of Radiology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.

We summarise here the information to be provided to women and referring physicians about percutaneous breast biopsy and lesion localisation under imaging guidance. After explaining why a preoperative diagnosis with a percutaneous biopsy is preferred to surgical biopsy, we illustrate the criteria used by radiologists for choosing the most appropriate combination of device type for sampling and imaging technique for guidance. Then, we describe the commonly used devices, from fine-needle sampling to tissue biopsy with larger needles, namely core needle biopsy and vacuum-assisted biopsy, and how mammography, digital breast tomosynthesis, ultrasound, or magnetic resonance imaging work for targeting the lesion for sampling or localisation. The differences among the techniques available for localisation (carbon marking, metallic wire, radiotracer injection, radioactive seed, and magnetic seed localisation) are illustrated. Type and rate of possible complications are described and the issue of concomitant antiplatelet or anticoagulant therapy is also addressed. The importance of pathological-radiological correlation is highlighted: when evaluating the results of any needle sampling, the radiologist must check the concordance between the cytology/pathology report of the sample and the radiological appearance of the biopsied lesion. We recommend that special attention is paid to a proper and tactful approach when communicating to the woman the need for tissue sampling as well as the possibility of cancer diagnosis, repeat tissue sampling, and or even surgery when tissue sampling shows a lesion with uncertain malignant potential (also referred to as "high-risk" or B3 lesions). Finally, seven frequently asked questions are answered.
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http://dx.doi.org/10.1186/s13244-019-0803-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002629PMC
February 2020

Substantial radiation dose reduction with consistent image quality using a novel low-dose stone composition protocol.

World J Urol 2020 Nov 28;38(11):2971-2979. Epub 2020 Jan 28.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Purpose: To assess a novel low-dose CT-protocol, combining a 150 kV spectral filtration unenhanced protocol (Sn150 kVp) and a stone-targeted dual-energy CT (DECT) in patients with urolithiasis.

Methods: 232 (151 male, 49 ± 16.4 years) patients with urolithiasis received a low-dose non-contrast enhanced CT (NCCT) for suspected urinary stones either on a third-generation dual-source CT system (DSCT) using Sn150 kVp (n = 116, group 1), or on a second-generation DSCT (n = 116 group 2) using single energy (SE) 120 kVp. For group 1, a subsequent dual-energy CT (DECT) with a short stone-targeted scan range was performed. Objective and subjective image qualities were assessed. Radiation metrics were compared.

Results: 534 stones (group 1: n = 242 stones; group 2: n = 292 stones) were found. In group 1, all 215 stones within the stone-targeted DECT-scan range were identified. DE analysis was able to distinguish between UA and non-UA calculi in all collected stones. 11 calculi (5.12%) were labeled as uric acid (UA) while 204 (94.88%) were labeled as non-UA calculi. There was no significant difference in overall Signal-to-noise-ratio between group 1 and group 2 (p = 0.819). On subjective analysis both protocols achieved a median Likert rating of 2 (p = 0.171). Mean effective dose was significantly lower for combined Sn150 kVp and stone-targeted DECT (3.34 ± 1.84 mSv) compared to single energy 120 kVp NCCT (4.45 ± 2.89 mSv) (p < 0.001), equaling a 24.9% dose reduction.

Conclusion: The evaluated novel low-dose stone composition protocol allows substantial radiation dose reduction with consistent high diagnostic image quality.
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http://dx.doi.org/10.1007/s00345-020-03082-6DOI Listing
November 2020

4D perfusion CT of prostate cancer for image-guided radiotherapy planning: A proof of concept study.

PLoS One 2019 19;14(12):e0225673. Epub 2019 Dec 19.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Purpose: Advanced forms of prostate cancer (PCa) radiotherapy with either external beam therapy or brachytherapy delivery techniques aim for a focal boost and thus require accurate lesion localization and lesion segmentation for subsequent treatment planning. This study prospectively evaluated dynamic contrast-enhanced computed tomography (DCE-CT) for the detection of prostate cancer lesions in the peripheral zone (PZ) using qualitative and quantitative image analysis compared to multiparametric magnet resonance imaging (mpMRI) of the prostate.

Methods: With local ethics committee approval, 14 patients (mean age, 67 years; range, 57-78 years; PSA, mean 8.1 ng/ml; range, 3.5-26.0) underwent DCE-CT, as well as mpMRI of the prostate, including standard T2, diffusion-weighted imaging (DWI), and DCE-MRI sequences followed by transrectal in-bore MRI-guided prostate biopsy. Maximum intensity projections (MIP) and DCE-CT perfusion parameters (CTP) were compared between healthy and malignant tissue. Two radiologists independently rated image quality and the tumor lesion delineation quality of PCa using a five-point ordinal scale. MIP and CTP were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis.

Results: The PCa detection rate ranged between 57 to 79% for the two readers for DCE-CT and was 92% for DCE-MRI. DCE-CT perfusion parameters in PCa tissue in the PZ were significantly different compared to regular prostate tissue and benign lesions. Image quality and lesion visibility were comparable between DCE-CT and DCE-MRI (VGC: AUC 0.612 and 0.651, p>0.05).

Conclusion: Our preliminary results suggest that it is feasible to use DCE-CT for identification and visualization, and subsequent segmentation for focal radiotherapy approaches to PCa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922381PMC
April 2020

Intestinal bacterial indicator phylotypes associate with impaired DNA double-stranded break sensors but augmented skeletal bone micro-structure.

Carcinogenesis 2020 06;41(4):483-489

Department of Environmental Health Sciences, Fielding School of Public Health, University of California, Los Angeles 650 Charles E. Young Dr. South, Los Angeles, CA, USA.

Intestinal microbiota are considered a sensor for molecular pathways, which orchestrate energy balance, immune responses, and cell regeneration. We previously reported that microbiota restriction promoted higher levels of systemic radiation-induced genotoxicity, proliferative lymphocyte activation, and apoptotic polarization of metabolic pathways. Restricted intestinal microbiota (RM) that harbors increased abundance of Lactobacillus johnsonii (LBJ) has been investigated for bacterial communities that correlated radiation-induced genotoxicity. Indicator phylotypes were more abundant in RM mice and increased in prevalence after whole body irradiation in conventional microbiota (CM) mice, while none of the same ten most abundant phylotypes were different in abundance between CM mice before and after heavy ion irradiation. Muribaculum intestinale was detected highest in female small intestines in RM mice, which were lacking Ureaplasma felinum compared with males, and thus these bacteria could be contributing to the differential amounts of radiation-induced systemic genotoxicity between the CM and RM groups. Helicobacter rodentium and M.intestinale were found in colons in the radiation-resistant CM phenotype. While the expression of interferon-γ was elevated in the small intestine, and lower in blood in CM mice, high-linear energy transfer radiation reduced transforming growth factor-β with peripheral interleukin (IL)-17 in RM mice, particularly in females. We found that female RM mice showed improved micro-architectural bone structure and anti-inflammatory radiation response compared with CM mice at a delayed phase 6 weeks postexposure to particle radiation. However, microbiota restriction reduced inflammatory markers of tumor necrosis factor in marrow, when IL-17 was reduced by intraperitoneal injection of IL-17 neutralizing antibody.
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http://dx.doi.org/10.1093/carcin/bgz204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456343PMC
June 2020

Limited role of DWI with apparent diffusion coefficient mapping in breast lesions presenting as non-mass enhancement on dynamic contrast-enhanced MRI.

Breast Cancer Res 2019 12 4;21(1):136. Epub 2019 Dec 4.

Department of Radiology, Breast Imaging Service, Memorial Sloan Kettering Cancer Center, Suite 705, 300 E 66th Street, New York, NY, 10065, USA.

Background: Available data proving the value of DWI for breast cancer diagnosis is mainly for enhancing masses; DWI may be less sensitive and specific in non-mass enhancement (NME) lesions. The objective of this study was to assess the diagnostic accuracy of DWI using different ROI measurement approaches and ADC metrics in breast lesions presenting as NME lesions on dynamic contrast-enhanced (DCE) MRI.

Methods: In this retrospective study, 95 patients who underwent multiparametric MRI with DCE and DWI from September 2007 to July 2013 and who were diagnosed with a suspicious NME (BI-RADS 4/5) were included. Twenty-nine patients were excluded for lesion non-visibility on DWI (n = 24: 12 benign and 12 malignant) and poor DWI quality (n = 5: 1 benign and 4 malignant). Two readers independently assessed DWI and DCE-MRI findings in two separate randomized readings using different ADC metrics and ROI approaches. NME lesions were classified as either benign (> 1.3 × 10 mm/s) or malignant (≤ 1.3 × 10 mm/s). Histopathology was the standard of reference. ROC curves were plotted, and AUCs were determined. Concordance correlation coefficient (CCC) was measured.

Results: There were 39 malignant (59%) and 27 benign (41%) lesions in 66 (65 women, 1 man) patients (mean age, 51.8 years). The mean ADC value of the darkest part of the tumor (Dptu) achieved the highest diagnostic accuracy, with AUCs of up to 0.71. Inter-reader agreement was highest with Dptu ADC max (CCC 0.42) and lowest with the point tumor (Ptu) ADC min (CCC = - 0.01). Intra-reader agreement was highest with Wtu ADC mean (CCC = 0.44 for reader 1, 0.41 for reader 2), but this was not associated with the highest diagnostic accuracy.

Conclusions: Diagnostic accuracy of DWI with ADC mapping is limited in NME lesions. Thirty-one percent of lesions presenting as NME on DCE-MRI could not be evaluated with DWI, and therefore, DCE-MRI remains indispensable. Best results were achieved using Dptu 2D ROI measurement and ADC mean.
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http://dx.doi.org/10.1186/s13058-019-1208-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894318PMC
December 2019

Consensus Meeting of Breast Imaging: BI-RADS® and Beyond.

Breast Care (Basel) 2019 Oct 2;14(5):308-314. Epub 2019 Oct 2.

Institute of Clinical Radiology, Medical Faculty and University Hospital Münster, Münster, Germany.

Organizers of medical educational courses are often confronted with questions that are clinically relevant yet trespassing the frontiers of scientifically proven, evidence-based medicine at the point of care. Therefore, since 2007 organizers of breast teaching courses in German language met biannually to find a consensus in clinically relevant questions that have not been definitely answered by science. The questions were prepared during the 3 months before the meeting according to a structured process and finally agreed upon the day before the consensus meeting. At the consensus meeting, the open questions concerning 2D/3D mammography, breast ultrasound, MR mammography, interventions as well as risk-based imaging of the breast were presented first for electronic anonymized voting, and then the results of the audience were separately displayed from the expert votes. Thereafter, an introductory statement of the moderator was followed by pros/cons of two experts, and subsequently the final voting was performed. With ≥75% of votes of the expert panel, an answer qualified as a consensus statement. Seventeen consensus statements were gained, addressing for instance the use of 2D/3D mammography, breast ultrasound in screening, MR mammography in women with intermediate breast cancer risk, markers for localization of pathologic axillary lymph nodes, and standards in risk-based imaging of the breast. After the evaluation, comments from the experts on each field were gathered supplementarily. Methodology, transparency, and soundness of statements achieve a unique yield for all course organizers and provide solid pathways for decision making in breast imaging.
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http://dx.doi.org/10.1159/000503412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883472PMC
October 2019

Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth.

Nucleic Acids Res 2019 12;47(22):11807-11825

Department of Biotechnology, Institute of Molecular Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190 Vienna, Austria.

Modifications of ribosomal RNA expand the nucleotide repertoire and thereby contribute to ribosome heterogeneity and translational regulation of gene expression. One particular m5C modification of 25S ribosomal RNA, which is introduced by Rcm1p, was previously shown to modulate stress responses and lifespan in yeast and other small organisms. Here, we report that NSUN5 is the functional orthologue of Rcm1p, introducing m5C3782 into human and m5C3438 into mouse 28S ribosomal RNA. Haploinsufficiency of the NSUN5 gene in fibroblasts from William Beuren syndrome patients causes partial loss of this modification. The N-terminal domain of NSUN5 is required for targeting to nucleoli, while two evolutionary highly conserved cysteines mediate catalysis. Phenotypic consequences of NSUN5 deficiency in mammalian cells include decreased proliferation and size, which can be attributed to a reduction in total protein synthesis by altered ribosomes. Strikingly, Nsun5 knockout in mice causes decreased body weight and lean mass without alterations in food intake, as well as a trend towards reduced protein synthesis in several tissues. Together, our findings emphasize the importance of single RNA modifications for ribosome function and normal cellular and organismal physiology.
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http://dx.doi.org/10.1093/nar/gkz1043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145617PMC
December 2019

Evaluation of 3.0-T MRI Brain Signal after Exposure to Gadoterate Meglumine in Women with High Breast Cancer Risk and Screening Breast MRI.

Radiology 2019 12 22;293(3):523-530. Epub 2019 Oct 22.

From the Department of Biomedical Imaging and Image-guided Therapy, Divisions of General and Pediatric Radiology (B.B.B., T.H.H., P.A.T.B.) and Neurology and Musculoskeletal Radiology (S.B.), Allgemeines Krankenhaus, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; and Department of Radiology (B.K., D.G.) and Department of Medical Statistics and Bioinformatics (M.H.), University Hospital Cologne, Cologne, Germany.

Background Otherwise healthy women at high risk for breast cancer undergo annual contrast agent-enhanced breast MRI screening examinations, resulting in high cumulative doses of gadolinium-based contrast agents (GBCAs). Whereas the majority of studies showed no T1 signal ratio increase in deep brain nuclei after more than six doses of macrocyclic GBCA, this has not been explored in a healthy study population. Purpose To assess whether women who are administered large cumulative doses of macrocyclic GBCA with breast MRI at high-risk breast cancer screening exhibit T1 alterations in deep brain nuclei. Materials and Methods In this prospective study from November 2017 to March 2018, healthy women who were either exposed (because of high-risk breast cancer screening) or unexposed to only gadoterate meglumine underwent 3.0-T brain MRI with a dedicated head coil, including T1 mapping and magnetization-prepared rapid gradient-echo sequences. T1 times and T1 signal intensities were measured in the dentate nucleus (DN), globus pallidus (GP), crus anterior of capsula interna (CA), and pons. Ratios of DN to pons and GP to CA were calculated, and univariable Pearson correlation coefficients were calculated. Multivariable analysis included partial regression analysis. Results This study evaluated 25 women (mean age, 51 years ± 11 [standard deviation]) who were exposed to a mean GBCA dose of 129 mL (median 112 mL; range, 70-302 mL) and 16 women (mean age, 37 years ± 10) who were never exposed to any GBCA. Infratentorially, no correlation between cumulative GBCA dose and T1 times or signal intensity ratios was detected ( = .66 and .55, respectively). In partial correlation analysis by considering age as a confounder, there was a moderate negative correlation between GP-to-CA ratio and GBCA dose ( = -0.40; = .01) but not for GP T1 times ( = 0.19; = .24). Conclusion After administration of relatively large cumulative doses of gadoterate dimeglumine, healthy women at high risk for breast cancer who underwent annual contrast-enhanced breast MRI screening did not exhibit T1 signal increase in deep brain nuclei at 3.0-T MRI. © RSNA, 2019.
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http://dx.doi.org/10.1148/radiol.2019190847DOI Listing
December 2019

Maternal immune activation during pregnancy impacts on brain structure and function in the adult offspring.

Brain Behav Immun 2020 01 14;83:56-67. Epub 2019 Sep 14.

Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Austria. Electronic address:

Gestational infection constitutes a risk factor for the occurrence of psychiatric disorders in the offspring. Activation of the maternal immune system (MIA) with subsequent impact on the development of the fetal brain is considered to form the neurobiological basis for aberrant neural wiring and the psychiatric manifestations later in offspring life. The examination of validated animal models constitutes a premier resource for the investigation of the neural underpinnings. Here we used a mouse model of MIA based upon systemic treatment of pregnant mice with Poly(I:C) (polyriboinosinic-polyribocytidilic acid), for the unbiased and comprehensive analysis of the impact of MIA on adult offspring brain activity, morphometry, connectivity and function by a magnetic resonance imaging (MRI) approach. Overall lower neural activity, smaller brain regions and less effective fiber structure were observed for Poly(I:C) offspring compared to the control group. The corpus callosum was significantly smaller and presented with a disruption in myelin/ fiber structure in the MIA progeny. Subsequent resting-state functional MRI experiments demonstrated a paralleling dysfunctional interhemispheric connectivity. Additionally, while the overall flow of information was intact, cortico-limbic connectivity was hampered and limbic circuits revealed hyperconnectivity in Poly(I:C) offspring. Our study sheds new light on the impact of maternal infection during pregnancy on the offspring brain and identifies aberrant resting-state functional connectivity patterns as possible correlates of the behavioral phenotype with relevance for psychiatric disorders.
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http://dx.doi.org/10.1016/j.bbi.2019.09.011DOI Listing
January 2020

Subarachnoid hemorrhage in rats - Visualizing blood distribution in vivo using gadolinium-enhanced magnetic resonance imaging: Technical note.

J Neurosci Methods 2019 09 19;325:108370. Epub 2019 Jul 19.

Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria. Electronic address:

Background: The aims of this study were to assess the feasibility of magnetic resonance imaging (MRI) to track the in vivo distribution of autologous, injected blood in a subarachnoid hemorrhage model (SAH), and to evaluate whether this technique results in observable morphological detriment.

New Method: We used an SAH model of stereotactic injection of autologous blood into the prechiasmatic cistern in Sprague Dawley rats. To visualize its in vivo distribution, a gadolinium-containing contrast agent was added to the autologous blood prior to injection. MRI was performed on a 9.4 T Bruker Biospec scanner preoperatively, as well as at variable time points between 30 min to 23 days after SAH. T1-weighted and diffusion-weighted images were acquired. The morphological examination was completed by a histopathological work-up.

Results: Upon injection of contrast agent-enriched autologous blood, enhancement was observed in the entire subarachnoid space within 30 min of injection. Total clearance was noted at the first postoperative day. SAH induction did not result in changes in clinical scores or on histopathological or radiological images.

Comparison With Existing Methods: We modified an established method to allow in vivo MRI monitoring of subarachnoid blood distribution in an SAH model.

Conclusion: This technique could be used to evaluate the distribution of blood components during the development of novel SAH models. Since no additional morphological detriment was observed, this technique could be used as a validation tool to verify correct application and induction in preclinical SAH models.
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http://dx.doi.org/10.1016/j.jneumeth.2019.108370DOI Listing
September 2019

Multiparametric F-FDG PET/MRI of the Breast: Are There Differences in Imaging Biomarkers of Contralateral Healthy Tissue Between Patients With and Without Breast Cancer?

J Nucl Med 2020 01 28;61(1):20-25. Epub 2019 Jun 28.

Department of Radiology, Breast Imaging Service, Memorial Sloan Kettering Cancer Center, New York, New York

The rationale was to assess whether there are differences in multiparametric F-FDG PET/MRI biomarkers of contralateral healthy breast tissue in patients with benign and malignant breast tumors. In this institutional review board-approved prospective single-institution study, 141 women with imaging abnormalities on mammography or sonography (BI-RADS 4/5) underwent combined F-FDG PET/MRI of the breast at 3T with dynamic contrast-enhanced MRI, diffusion-weighted imaging, and the radiotracer F-FDG. In all patients, the following imaging biomarkers were recorded for the contralateral (tumor-free) breast: breast parenchymal uptake (BPU) (from F-FDG PET), mean apparent diffusion coefficient (from diffusion-weighted imaging), background parenchymal enhancement (BPE), and amount of fibroglandular tissue (FGT) (from MRI). Appropriate statistical tests were used to assess differences in F-FDG PET/MRI biomarkers between patients with benign and malignant lesions. There were 100 malignant and 41 benign lesions. BPE was minimal in 61 patients, mild in 56, moderate in 19, and marked in 5. BPE differed significantly ( < 0.001) between patients with benign and malignant lesions, with patients with cancer demonstrating decreased BPE in the contralateral tumor-free breast. FGT approached but did not reach significance ( = 0.055). BPU was 1.5 for patients with minimal BPE, 1.9 for mild BPE, 2.2 for moderate BPE, and 1.9 for marked BPE. BPU differed significantly between patients with benign lesions (mean, 1.9) and patients with malignant lesions (mean, 1.8) ( < 0.001). Mean apparent diffusion coefficient did not differ between groups ( = 0.19). Differences in multiparametric F-FDG PET/MRI biomarkers, obtained from contralateral tumor-free breast tissue, exist between patients with benign and patients with malignant breast tumors. Contralateral BPE, BPU, and FGT are decreased in breast cancer patients and may potentially serve as imaging biomarkers for the presence of malignancy.
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http://dx.doi.org/10.2967/jnumed.119.230003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954464PMC
January 2020

Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis.

Nat Commun 2019 06 20;10(1):2717. Epub 2019 Jun 20.

Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.

Hepatic steatosis develops when lipid influx and production exceed the liver's ability to utilize/export triglycerides. Obesity promotes steatosis and is characterized by leptin resistance. A role of leptin in hepatic lipid handling is highlighted by the observation that recombinant leptin reverses steatosis of hypoleptinemic patients with lipodystrophy by an unknown mechanism. Since leptin mainly functions via CNS signaling, we here examine in rats whether leptin regulates hepatic lipid flux via the brain in a series of stereotaxic infusion experiments. We demonstrate that brain leptin protects from steatosis by promoting hepatic triglyceride export and decreasing de novo lipogenesis independently of caloric intake. Leptin's anti-steatotic effects are generated in the dorsal vagal complex, require hepatic vagal innervation, and are preserved in high-fat-diet-fed rats when the blood brain barrier is bypassed. Thus, CNS leptin protects from ectopic lipid accumulation via a brain-vagus-liver axis and may be a therapeutic strategy to ameliorate obesity-related steatosis.
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http://dx.doi.org/10.1038/s41467-019-10684-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586634PMC
June 2019

A multiparametric [F]FDG PET/MRI diagnostic model including imaging biomarkers of the tumor and contralateral healthy breast tissue aids breast cancer diagnosis.

Eur J Nucl Med Mol Imaging 2019 Aug 13;46(9):1878-1888. Epub 2019 Jun 13.

Department of Radiology, Breast Imaging Service, Memorial Sloan Kettering Cancer Center, 300 E 66th St, 7th Floor, New York, NY, 10065, USA.

Purpose: To develop a multiparametric [F]FDG positron emission tomography/magnetic resonance imaging (PET/MRI) model for breast cancer diagnosis incorporating imaging biomarkers of breast tumors and contralateral healthy breast tissue.

Methods: In this prospective study and retrospective data analysis, 141 patients (mean 57 years) with an imaging abnormality detected on mammography and/or ultrasound (BI-RADS 4/5) underwent combined multiparametric [F]FDG PET/MRI with PET/computed tomography and multiparametric MRI of the breast at 3 T. Images were evaluated and the following were recorded: for the tumor, BI-RADS descriptors on dynamic contrast-enhanced (DCE)-MRI, mean apparent diffusion co-efficient (ADCmean) on diffusion-weighted imaging (DWI), and maximum standard uptake value (SUVmax) on [F]FDG-PET; and for the contralateral healthy breast, background parenchymal enhancement (BPE) and amount of fibroglandular tissue (FGT) on DCE-MRI, ADCmean on DWI, and SUVmax. Histopathology served as standard of reference. Uni-, bi-, and multivariate logistic regression analyses were performed to assess the relationships between malignancy and imaging features. Predictive discrimination of benign and malignant breast lesions was examined using area under the receiver operating characteristic curve (AUC).

Results: There were 100 malignant and 41 benign lesions (size: median 1.9, range 0.5-10 cm). The multivariate regression model incorporating significant univariate predictors identified tumor enhancement kinetics (P = 0.0003), tumor ADCmean (P < 0.001), and BPE of the contralateral healthy breast (P = 0.0019) as independent predictors for breast cancer diagnosis. Other biomarkers did not reach significance. Combination of the three significant biomarkers achieved an AUC value of 0.98 for breast cancer diagnosis.

Conclusion: A multiparametric [F]FDG PET/MRI diagnostic model incorporating both qualitative and quantitative parameters of the tumor and the healthy contralateral tissue aids breast cancer diagnosis.
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http://dx.doi.org/10.1007/s00259-019-04331-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647078PMC
August 2019