Search

Objective: To evaluate the effect of menopausal status on the background parenchymal enhancement (BPE) and amount of fibroglandular tissue (FGT) on breast MRI.Methods: Retrospective review identified 1,130 women who underwent screening breast MRI between July and November 2010. In 28 of these women, breast MRI was performed both at one time point while pre- and one time point while post-menopausal (median interval 49 months). Two independent readers blinded to menopausal status used categorical scales to rate BPE (minimal/mild/moderate/marked) and FGT (fatty/scattered/heterogeneously dense/dense). Consensus was reached when there was disagreement. The sign test was used to assess changes in rating categories, and the Spearman rank and Fisher's exact tests were used to measure correlations and associations between variables.Results: Significant proportions of women demonstrated decreases in BPE and FGT on post-menopausal breast MRI (P = 0.0001 and P = 0.0009). BPE category was unchanged in 39 % (11/28) and decreased in 61 % (17/28) of women. FGT category was unchanged in 61 % (17/28) and decreased in 39 % (11/28) of women. Age, reason for menopause, or interval between MRIs had no significant impact on changes in BPE and FGT.Conclusion: On MRI, BPE, and FGT decrease after menopause in significant proportions of women; BPE decreases more than FGT.Key Points: On MRI, background parenchymal enhancement and fibroglandular tissue both decrease after menopause. The reduced postmenopausal enhancement is more marked in parenchyma than fibroglandular tissue. Background enhancement and fibroglandular tissue seen on MRI are under hormonal influence. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Lubricin, also referred to as superficial zone protein and PRG4, is a synovial glycoprotein that supplies a friction-resistant, antiadhesive coating to the surfaces of articular cartilage, thereby protecting against arthritis-associated tissue wear and degradation. This study was undertaken to generate and characterize a novel recombinant lubricin protein construct, LUB:1, and to evaluate its therapeutic efficacy following intraarticular delivery in a rat model of osteoarthritis (OA). METHODS: Binding and localization of LUB:1 to cartilage surfaces was assessed by immunohistochemistry. The cartilage-lubricating properties of LUB:1 were determined using a custom friction testing apparatus. A cell-binding assay was performed to quantify the ability of LUB:1 to prevent cell adhesion. Efficacy studies were conducted in a rat meniscal tear model of OA. One week after the surgical induction of OA, LUB:1 or phosphate buffered saline vehicle was administered by intraarticular injection for 4 weeks, with dosing intervals of either once per week or 3 times per week. OA pathology scores were determined by histologic analysis. RESULTS: LUB:1 was shown to bind effectively to cartilage surfaces, and facilitated both cartilage boundary lubrication and inhibition of synovial cell adhesion. Treatment of rat knee joints with LUB:1 resulted in significant disease-modifying, chondroprotective effects during the progression of OA, by markedly reducing cartilage degeneration and structural damage. CONCLUSION: Our findings demonstrate the potential use of recombinant lubricin molecules in novel biotherapeutic approaches to the treatment of OA and associated cartilage abnormalities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Protein kinase Czeta (PKCzeta), an atypical PKC, has been found to be transcriptionally up-regulated in human osteoarthritic (OA) articular cartilage. This study was undertaken to examine the role of PKCzeta in interleukin-1beta (IL-1beta)-induced NF-kappaB signaling in human OA chondrocytes, and ultimately to better understand its function in the regulation of downstream mediators of cartilage matrix degradation. METHODS: Pharmacologic inhibitors or genetic knockdown techniques were used to investigate the role of PKCzeta. Western blot analysis was used to evaluate phosphorylation of PKCzeta and NF-kappaB. Quantitative polymerase chain reaction (PCR) and activity assays were used to evaluate ADAMTS-4 expression and aggrecanase activity, respectively. Quantitative PCR, biochemical identification, and Western blot analysis were used to evaluate type 2 nitric oxide synthase (NOS2) and NO production. RESULTS: Phosphorylation of PKCzeta and NF-kappaB was induced by IL-1beta treatment in a time-dependent manner, and was specifically inhibited by inhibitors of atypical PKCs. Inhibition of PKCzeta suppressed IL-1beta-induced up-regulation of ADAMTS-4 messenger RNA (mRNA) and aggrecanase activity. Inhibitors of atypical PKCs also inhibited IL-1beta-induced NO production and NOS2 mRNA expression, demonstrating a novel link between PKCzeta and NO production. Furthermore, small interfering RNA- or short hairpin RNA-mediated knockdown of PKCzeta mRNA resulted in significant repression of both ADAMTS-4 and NOS2 mRNA expression. CONCLUSION: Our results show that PKCzeta is involved in the regulation of IL-1beta-induced NF-kappaB signaling in human OA chondrocytes, which in turn regulates downstream expression of ADAMTS-4 and NOS2. Therefore, inhibition of PKCzeta could potentially regulate the production of matrix-degrading enzymes as well as NO production and have a profound effect on disease progression in OA. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify potential molecular mediators and biomarkers for osteoarthritis (OA), through comparative proteomic analysis of articular cartilage tissue obtained from normal donors without OA (n = 7) and patients with OA (n = 7). METHODS: The proteomic analyses comprised extraction of soluble proteins from cartilage, separation of the protein mixtures by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by in-gel digestion, and subsequent nano-liquid chromatography-tandem mass spectrometry analysis in conjunction with a database search for protein identification and semiquantitation. RESULTS: A total of 814 distinct proteins were identified with high confidence from 14 samples; 420 of these proteins were detected with > or = 3 unique peptides in at least 4 samples from the same group. Using stringent criteria, 59 proteins were found to be differentially expressed in OA cartilage. Gene Ontology and Ingenuity pathway analysis tools were used to characterize these proteins into functional categories. One of the up-regulated proteins, HtrA1, a serine protease, was detected at high levels in cartilage. CONCLUSION: Altered protein expression in the disease state is associated with many aspects of the pathogenesis of OA, such as increased proteolysis, lipid metabolism, immune response, and decreased signal transduction. To our knowledge, this is the first time that a large portion of these proteins and their expression patterns were identified in cartilage, thus providing new insights for finding novel pathologic mediators and biomarkers of OA. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the ability of magnetic resonance imaging (MRI) and mammography to determine the presence and extent of ductal carcinoma in situ (DCIS). Retrospective review of medical records of women who underwent MRI and mammographic examination during a 23-month period revealed 39 sites of pure DCIS in 33 breasts of 32 women. No invasive or microinvasive tumor was found. Women ranged in age from 34 to 79 years (mean age 53 years). In these 33 breasts, both MRI and mammography were done before surgery. Reports and images of mammography and MRI were reviewed to determine if each study was positive for the presence of single or multiple sites of DCIS and the imaging patterns associated with these sites. Of 33 breasts involved, DCIS was discovered by MRI alone in 21 (64%), by both MRI and mammography in 8 (24%), and by mammography alone in 1 (3%); in 3 breasts (9%), DCIS was found at mastectomy without findings on mammography or MRI. MRI had significantly higher sensitivity than mammography for DCIS detection (29/33 = 88% versus 9/33 = 27%, p < 0.00001). Multiple sites of disease were present in five breasts; these were better demonstrated with MRI in three, mammography in one, and equally by both in one. The predominant enhancement pattern of DCIS on MRI was linear/ductal in 18 of 29 breasts (62%); mammography found calcifications associated with DCIS in 8 of 9 (89%). The nuclear grade of DCIS found with MRI and mammography was similar; size of lesions was larger on MRI; breast density did not impact results. In this study, MRI was significantly more sensitive than mammography in DCIS detection. In women with known or suspected DCIS, MRI may have an important role to play in assessing the extent of disease in the breast. [ABSTRACT FROM AUTHOR]

This article describes the recent experiments undertaken by the William Blake Archive in preparing a digital edition of Vala, or the Four Zoas, one of Blake’s most materially challenging works. The aim is to provide users with multiple tools for analysing Blake’s messy and mysterious manuscript: a high-quality image of the manuscript page paired with a dynamic transcription that allows readers to choose the level of detail they want for understanding what it is, precisely, they are looking at. However, the existing encoding standards and display were revealed to be totally inadequate by the complexity of The Four Zoas, and early models were almost impossible to read and understand. The article traces the journey towards the latest prototype as the team try to strike a balance between detail and accessibility, description and interpretation, readability and reliability, and established conventions and new approaches.

Rationale and Objectives: To develop and evaluate an AI algorithm that detects breast cancer in MRI scans up to one year before radiologists typically identify it, potentially enhancing early detection in high-risk women., Materials and Methods: A convolutional neural network (CNN) AI model, pre-trained on breast MRI data, was fine-tuned using a retrospective dataset of 3029 MRI scans from 910 patients. These contained 115 cancers that were diagnosed within one year of a negative MRI. The model aimed to identify these cancers, with the goal of predicting cancer development up to one year in advance. The network was fine-tuned and tested with 10-fold cross-validation. Mean age of patients was 52 years (range, 18-88 years), with average follow-up of 4.3 years (range 1-12 years)., Results: The AI detected cancers one year earlier with an area under the ROC curve of 0.72 (0.67-0.76). Retrospective analysis by a radiologist of the top 10% highest risk MRIs as ranked by the AI could have increased early detection by up to 30%. (35/115, CI:22.2-39.7%, 30% sensitivity). A radiologist identified a visual correlate to biopsy-proven cancers in 83 of prior-year MRIs (83/115, CI: 62.1-79.4%). The AI algorithm identified the anatomic region where cancer would be detected in 66 cases (66/115, CI:47.8-66.5%); with both agreeing in 54 cases (54/115, CI:%37.5-56.4%)., Conclusion: This novel AI-aided re-evaluation of "benign" breasts shows promise for improving early breast cancer detection with MRI. As datasets grow and image quality improves, this approach is expected to become even more impactful., Competing Interests: Declaration of Competing Interest All authors declare no financial or non-financial competing interests., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Digital breast tomosynthesis (DBT) has outpaced digital mammography in clinical adoption in the United States; however, substantial technological limitations remain to image quality in DBT, including undersampling from a one-dimensional (1D) scan geometry, x-ray source motion during acquisition, and patient motion artifacts from long exam times., Purpose: A thermionic cathode x-ray system employing two-dimensional (2D, planar) multiple x-ray-source arrays (MXA) is proposed to improve DBT image quality., Methods: A 1D MXA, consisting of a linear array of thermionic cathodes was used to simulate a 2D MXA. The 1D MXA included 11 focal spots separated by a distance of Δ d ${{\Delta}}d$  = 23 mm. The 11 cathodes were paired with 11 molybdenum 50 mm diameter anode disks, mounted on a rotating shaft within a single vacuum enclosure. Image quality was investigated as a function of MXA configuration by integrating the 1D MXA with a 200 × 250 mm 2 flat panel detector at a source-to-detector distance of 630 mm, resulting in a 20° tomographic arc. To simulate a 2D MXA, the detector (with phantom) was translated orthogonally to the linear array by a distance ( δ $\delta $ ) ranging from δ $\delta $  = 0 mm (conventional 1D) to δ $\delta $  = 57 mm. All sources operated at 30 kV with 80 mA and 4.5 mAs/pulse, yielding ∼100 mAs per DBT dataset. DBT reconstructions involved 22 projections and used filtered backprojection with a ramp and Hann apodization filter. Volumetric reconstructions for each source were weighted by sampling differences between sources, and averaged. Image quality was assessed in terms of contrast-to-noise ratio (CNR), background clutter noise and power spectrum, and slice sensitivity profile (SSP) using a set of physical phantoms, including: (i) contrast-detail signals coupled to spherical clutter (PMMA in air); (ii) an SSP phantom; (iii) a commercial "breast" phantom (CIRS BR3D, Sun Nuclear, Norfolk, VA); and (iv) bovine muscle., Results: Background clutter noise amplitude reduced monotonically from the 1D MXA (σ clutter  = 5.9 A.U., δ $\delta $  = 0 mm) and 2D MXA arrays with increasing δ $\delta $ , with statistical significance between the 1D MXA and 2D MXA with δ $\delta $  = 57 mm (σ clutter  = 5.0 A.U., p < 0.001). The contrast-detail/clutter phantom demonstrated CNR from the 2D MXA (δ  = 57 mm) outperforming the 1D MXA in all combinations of contrast and detail. 2D power spectrum analysis of clutter demonstrated a pronounced Fourier domain null cone for the 1D MXA in the anterior field-of-view (away from the 1D MXA position), whereas the 2D MXA geometry (δ = 57 mm) did not exhibit the null cone. The SSP was 15%-50% narrower (FWHM) for the 2D versus the 1D geometry, across all reconstruction setups., Conclusions: The advantages of a 2D source geometry for DBT imaging were demonstrated quantitatively compared to a conventional 1D line of x-ray sources. The improvement in the 2D geometry was attributed both to improved Fourier domain sampling and reduced SSP. We conclude that 2D MXA sources have the potential to substantially improve DBT imaging in comparison to existing commercial DBT systems., (© 2024 American Association of Physicists in Medicine.)

Objectives/hypothesis: To evaluate costs associated with perioperative gastrostomy tube (G-tube) placement for neonates with Robin sequence (PRS) that undergo mandibular distraction osteogenesis (MDO)., Methods: Retrospective chart review was performed to examine the medical records of neonates with RS who received treatment at our institution between 2012 and 2021. Patients under 6 months of age that underwent MDO for RS were included. Billing records of hospital costs over a 2-year period were analyzed., Results: The study included 26 total patients with 11 in the MDO-only group, 9 in G-tube after MDO group, and 6 in G-tube before MDO group. There was a significant difference (p < 0.001) in total hospital costs between groups with MDO-only group averaging $119,532 (SD ± $$ \pm $$ 33,503), the G-tube after MDO group averaging $245,315 (SD ± $$ \pm $$ 102,327), and G-tube before MDO group averaging $252,300 (SD ± $$ \pm $$ 84,990). Multiple linear regression was performed controlling for genetic syndrome and birth weight, which still showed a statistically significant difference in total cost between the MDO-only group and G-tube after MDO (p = 0.006), and between the MDO-only group and G-tube prior to MDO (p = 0.01). There was a significant difference in costs between all three groups for total inpatient/outpatient costs with MDO-only group averaging $78,502 (SD ± $$ \pm $$ 30,953), the G-tube after MDO group averaging $176,125 (SD ± $$ \pm $$ 84,315), and the G-tube prior to MDO group averaging $156,309 (SD ± $$ \pm $$ 95,746)., Conclusions: MDO performed without perioperative G-tube placement may reduce charges by >$100,000. The associated improvement of dysphagia after MDO surgery and potential for avoiding a G-tube has tremendous downstream cost and social benefits for families., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Mycophenolate mofetil (MMF) is an immunosuppressant used to treat rheumatological diseases, including Systemic Sclerosis (SSc). While MMF is an established inhibitor of lymphocyte proliferation, recent evidence suggests MMF also mediates effects on other cell types. The goal of this study was to determine the effect of MMF on monocytes and macrophages, which have been implicated in SSc pathogenesis., Methods: Human monocyte-derived macrophages were cultured with the active MMF metabolite, mycophenolic acid (MPA), and assessed for changes in viability and immuno-phenotype. Guanosine supplementation studies were performed to determine whether MPA-mediated effects were dependent on de novo purine synthesis. The ability of MPA-treated macrophages to induce fibroblast activation was evaluated, and dermal myeloid expression signatures were analyzed in MMF-treated SSc patients., Results: MPA reduced viability and induced apoptosis in monocytes and macrophages at doses (average IC50 = 1.15 µg/ml) within the target serum concentration of MMF patients (1-3µg/ml). These effects were reversed by guanosine supplementation. Low-dose MPA (0.5 µg/ml) attenuated IL-4 or SSc plasma-mediated macrophage activation, and inhibited the ability of SSc plasma-activated macrophages to induce SSc fibroblast activation. Gene expression studies demonstrated significant reductions in dermal myeloid signatures in MMF-responsive SSc patients., Conclusions: For the first time, we demonstrate that MMF inhibits the viability and pro-fibrotic activation of human monocytes and macrophages, which is dependent on de novo purine synthesis. Coupled with myeloid gene expression attenuation following MMF treatment in patients, these results suggest that fibrotic inhibition observed with MMF may be attributable, at least in part, to direct effects on myeloid cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Artificial intelligence (AI) has the potential to improve breast cancer screening; however, prospective evidence of the safe implementation of AI into real clinical practice is limited. A commercially available AI system was implemented as an additional reader to standard double reading to flag cases for further arbitration review among screened women. Performance was assessed prospectively in three phases: a single-center pilot rollout, a wider multicenter pilot rollout and a full live rollout. The results showed that, compared to double reading, implementing the AI-assisted additional-reader process could achieve 0.7-1.6 additional cancer detection per 1,000 cases, with 0.16-0.30% additional recalls, 0-0.23% unnecessary recalls and a 0.1-1.9% increase in positive predictive value (PPV) after 7-11% additional human reads of AI-flagged cases (equating to 4-6% additional overall reading workload). The majority of cancerous cases detected by the AI-assisted additional-reader process were invasive (83.3%) and small-sized (≤10 mm, 47.0%). This evaluation suggests that using AI as an additional reader can improve the early detection of breast cancer with relevant prognostic features, with minimal to no unnecessary recalls. Although the AI-assisted additional-reader workflow requires additional reads, the higher PPV suggests that it can increase screening effectiveness., (© 2023. The Author(s).)

Objective: Congenital Diaphragmatic Hernia (CDH) is diagnosed prenatally in ~60% of cases. Prenatal measures typically guide management and prognostication. Simple postnatal prognosticators are needed when prenatal diagnosis is lacking. We hypothesized that preoperative orogastric tube (OGT) tip position relative to the contralateral diaphragm correlates with defect severity, resource utilization, and clinical outcomes regardless of diagnostic status., Study Design: 150 neonates with left-posterolateral CDH were analyzed. Impact of intrathoracic and intraabdominal preoperative tip position on clinical outcomes was compared., Results: Ninety-nine neonates were prenatally diagnosed. Overall, intrathoracic position significantly correlated with larger diaphragmatic defects, advanced postnatal pulmonary support requirements (HFOV, pulmonary vasodilators, and ECMO), operative complexity, longer hospitalization, and poorer survival to discharge. These observations persisted when analyzing only cases lacking prenatal diagnosis., Conclusions: Preoperative OGT tip position predicts defect severity, resource utilization, and outcomes in CDH. This observation enhances postnatal prognostication and care planning for neonates without a prenatal diagnosis., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background Background parenchymal enhancement (BPE) at breast MRI has been associated with increased breast cancer risk in several independent studies. However, variability of subjective BPE assessments have precluded its use in clinical practice. Purpose To examine the association between fully objective measures of BPE at MRI and odds of breast cancer. Materials and Methods This prospective case-control study included patients who underwent a bilateral breast MRI examination and were receiving care at one of three centers in the United States from November 2010 to July 2017. Breast volume, fibroglandular tissue (FGT) volume, and BPE were quantified using fully automated software. Fat volume was defined as breast volume minus FGT volume. BPE extent was defined as the proportion of FGT voxels with enhancement of 20% or more. Spearman rank correlation between quantitative BPE extent and Breast Imaging Reporting and Data System (BI-RADS) BPE categories assigned by an experienced board-certified breast radiologist was estimated. With use of multivariable logistic regression, breast cancer case-control status was regressed on tertiles (low, moderate, and high) of BPE, FGT volume, and fat volume, with adjustment for covariates. Results In total, 536 case participants with breast cancer (median age, 48 years [IQR, 43-55 years]) and 940 cancer-free controls (median age, 46 years [IQR, 38-55 years]) were included. BPE extent was positively associated with BI-RADS BPE ( r s = 0.54; P < .001). Compared with low BPE extent (range, 2.9%-34.2%), high BPE extent (range, 50.7%-97.3%) was associated with increased odds of breast cancer (odds ratio [OR], 1.74 [95% CI: 1.23, 2.46]; P for trend = .002) in a multivariable model also including FGT volume (OR, 1.39 [95% CI: 0.97, 1.98]) and fat volume (OR, 1.46 [95% CI: 1.04, 2.06]). The association of high BPE extent with increased odds of breast cancer was similar for premenopausal and postmenopausal women (ORs, 1.75 and 1.83, respectively; interaction P = .73). Conclusion Objectively measured BPE at breast MRI is associated with increased breast cancer odds for both premenopausal and postmenopausal women. Clinical trial registration no. NCT02301767 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bokacheva in this issue.

Tamoxifen (TMX), a selective estrogen receptor modulator, is commonly used in the treatment of hormone-responsive cancers. However, the effects of TMX in anabolic tissues harboring estrogen receptors, such as skeletal muscle, are poorly understood. We report a tandem mass-tag approach to TMX-treated myogenesis in C 2 C 12 cells, a well-characterized model of in vitro murine skeletal muscle differentiation. A longitudinal analysis of >10,000 proteins identified in untreated C 2 C 12 myogenesis revealed a novel subset of 1,062 myogenically regulated proteins. These proteins clustered into five distinct longitudinal expression trends which significantly overlap those obtained in similar analyses performed in human myocytes. We document a specific functional enrichment for adiponectin-signaling unique to TMX-treated myogenesis, as well as a subset of 198 proteins that are differentially expressed in TMX-treated cells relative to controls at one or more stages of myogenesis, the majority of which were involved in steroid and lipid metabolism. Further analysis highlights metallothionein-1 as a novel target of TMX treatment at each stage of C 2 C 12 myogenesis. Finally, we present a powerful, self-validating pipeline for analyzing the total proteomic response to in vitro treatment across every stage of muscle cell development which can be easily adapted to study the effects of other drugs on myogenesis.

Congenital hypothyroidism rarely causes a clinically significant neck mass in newborns. We present the case of a newborn with congenital hypothyroidism and significantly enlarged goiter and discuss imaging considerations and medical and surgical management. This infant was prenatally discovered to have a midline neck mass on 28 week ultrasound measuring 6.0 cm × 3.4 cm × 5.8 cm. Diagnostic cordocentesis demonstrated elevated thyroid-stimulating hormone (TSH, 361 µIU/mL). Maternal evaluation for thyroid disease and antithyroid antibodies was negative. A Cesarean section at 38 weeks gestation was recommended due to hyperextension of the fetal neck. The infant was intubated for respiratory distress. Postnatal magnetic resonance imaging revealed a 5.5 cm × 4.4 cm × 7.6 cm goiter and laboratory studies confirmed the diagnosis of primary hypothyroidism (TSH 16.7 µIU/mL). Treatment was initiated with intravenous levothyroxine and transitioned to oral supplementation. Serial ultrasounds showed decreased goiter volume over several weeks, with recent volume per lobe being 22% and 44% of original volume. This case demonstrates the importance of prompt diagnosis and initiation of thyroid hormone replacement, allowing for significant goiter regression without surgical intervention and ensuring normal growth and neurodevelopmental outcome. Surgical management should be considered for those with persistent compressive symptoms despite optimal medical management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Gastroschisis is a challenging neonatal condition often with prolonged hospitalizations, need for parenteral nutrition, infectious complications, and can even result in death. Infection is reported to occur in up to two-thirds of patients with gastroschisis and is a strong risk factor for increased morbidity and mortality. Increased days with a central venous catheter, complex gastroschisis, and delayed abdominal wall closure have been consistently found to be associated with increased risk of infection, whereas sutureless gastroschisis closure has been associated with fewer infections. Although one of the most common complications of gastroschisis is infection, the use of antibiotic agents varies widely with variability in the literature to guide management. Antibiotic usage should be selective and short-term, especially in neonates with simple gastroschisis regardless of method for abdominal wall closure. Conclusions: Future initiatives should focus on development of evidence-based guidelines on the care of these patients with the goal of reducing variability and improve outcomes within and across institutions.

Background There is considerable interest in the potential use of artificial intelligence (AI) systems in mammographic screening. However, it is essential to critically evaluate the performance of AI before it can become a modality used for independent mammographic interpretation. Purpose To evaluate the reported standalone performances of AI for interpretation of digital mammography and digital breast tomosynthesis (DBT). Materials and Methods A systematic search was conducted in PubMed, Google Scholar, Embase (Ovid), and Web of Science databases for studies published from January 2017 to June 2022. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) values were reviewed. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 and Comparative (QUADAS-2 and QUADAS-C, respectively). A random effects meta-analysis and meta-regression analysis were performed for overall studies and for different study types (reader studies vs historic cohort studies) and imaging techniques (digital mammography vs DBT). Results In total, 16 studies that include 1 108 328 examinations in 497 091 women were analyzed (six reader studies, seven historic cohort studies on digital mammography, and four studies on DBT). Pooled AUCs were significantly higher for standalone AI than radiologists in the six reader studies on digital mammography (0.87 vs 0.81, P = .002), but not for historic cohort studies (0.89 vs 0.96, P = .152). Four studies on DBT showed significantly higher AUCs in AI compared with radiologists (0.90 vs 0.79, P < .001). Higher sensitivity and lower specificity were seen for standalone AI compared with radiologists. Conclusion Standalone AI for screening digital mammography performed as well as or better than radiologists. Compared with digital mammography, there is an insufficient number of studies to assess the performance of AI systems in the interpretation of DBT screening examinations. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Scaranelo in this issue.

Imaging of breast cancer is the backbone of breast cancer screening, diagnosis, preoperative/treatment assessment and follow-up. The main modalities are mammography, ultrasound and magnetic resonance imaging, each with its own advantages and disadvantages. New emerging technologies have also enabled each modality to improve on their weaknesses. Imaging-guided biopsies have allowed for accurate diagnosis of breast cancer, with low complication rates. The purpose of this article is to review the common modalities for breast cancer imaging in current practice with emphasis on the strengths and potential weaknesses, discuss the selection of the best imaging modality for the specific clinical question or patient population, and explore new technologies / future directions of breast cancer imaging., 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. Published by Elsevier Inc.)

Contrast-enhanced mammography (CEM) may provide an alternative to magnetic resonance imaging as a diagnostic exam in women with known or suspected breast cancer or as a screening exam in women at increased risk of breast cancer. Women with breast augmentation, either for oncologic or cosmetic reasons, may fall into this increased risk population and need safe and effective screening and diagnostic imaging tools. Here, we present our clinical practice data in order to demonstrate the feasibility of CEM in women with breast implants. An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, retrospective review of our tertiary cancer center's database yielded 104 women with breast implants who underwent 198 CEM exams from November 2014 to March 2020. All 198/198 (100%) exams were successfully completed in 104 women. Exam indications included: 174/198 (88%) screening due to increased risk, 10/198 (5%) to evaluate a palpable abnormality, 9/198 (<5%) to evaluate disease extent following neoadjuvant chemotherapy for a known breast malignancy, and 5/198 (<3%) for a 6-month follow-up. 97/104 (93%) women had dense breasts. Routine and implant-displaced low-energy views were obtained with contrast-enhanced images obtained on displaced views for all patients. 197/198 (99.5%) exams yielded no complications. In one exam, the patient experienced mild vasovagal symptoms following the administration of contrast. In conclusion, it is feasible to utilize CEM in both diagnostic and screening capacities in women with breast implants., Competing Interests: Declaration of competing interest Maxine Jochelson reports honorarium for speaking for GE, and consulting and speaking for Bayer. Elizabeth A. Morris previously received a grant from GRAIL, Inc. for research not related to the present article. Dr. Mango received unrelated research support from Pfizer, Inc. and was a consultant for Bayer Healthcare. The remaining authors declare no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Response to immunotherapy across multiple cancer types is approximately 25%, with some tumor types showing increased response rates compared to others (i.e. response rates in melanoma and non-small cell lung cancer (NSCLC) are typically 30-60%). Patients whose tumors are resistant to immunotherapy often lack high levels of pre-existing inflammation in the tumor microenvironment. Increased tumor glycolysis, acting through glucose deprivation and lactic acid accumulation, has been shown to have pleiotropic immune suppressive effects using in-vitro and in-vivo models of disease. To determine whether the immune suppressive effect of tumor glycolysis is observed across human solid tumors, we analyzed glycolytic and immune gene expression patterns in multiple solid malignancies. We found that increased expression of a glycolytic signature was associated with decreased immune infiltration and a more aggressive disease across multiple tumor types. Radiologic and pathologic analysis of untreated estrogen receptor (ER)-negative breast cancers corroborated these observations, and demonstrated that protein expression of glycolytic enzymes correlates positively with glucose uptake and negatively with infiltration of CD3 + and CD8 + lymphocytes. This study reveals an inverse relationship between tumor glycolysis and immune infiltration in a large cohort of multiple solid tumor types., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cohen, Pareja, Socci, Shen, Doane, Schwartz, Khanin, Morris, Sutton and Blasberg.)

Background: Background parenchymal enhancement (BPE) is assessed on breast MRI reports as mandated by the Breast Imaging Reporting and Data System (BI-RADS) but is prone to inter and intrareader variation. Semiautomated and fully automated BPE assessment tools have been developed but none has surpassed radiologist BPE designations., Purpose: To develop a deep learning model for automated BPE classification and to compare its performance with current standard-of-care radiology report BPE designations., Study Type: Retrospective., Population: Consecutive high-risk patients (i.e. &gt;20% lifetime risk of breast cancer) who underwent contrast-enhanced screening breast MRI from October 2013 to January 2019. The study included 5224 breast MRIs, divided into 3998 training, 444 validation, and 782 testing exams. On radiology reports, 1286 exams were categorized as high BPE (i.e., marked or moderate) and 3938 as low BPE (i.e., mild or minimal)., Field Strength/sequence: A 1.5 T or 3 T system; one precontrast and three postcontrast phases of fat-saturated T1-weighted dynamic contrast-enhanced imaging., Assessment: Breast MRIs were used to develop two deep learning models (Slab artificial intelligence (AI); maximum intensity projection [MIP] AI) for BPE categorization using radiology report BPE labels. Models were tested on a heldout test sets using radiology report BPE and three-reader averaged consensus as the reference standards., Statistical Tests: Model performance was assessed using receiver operating characteristic curve analysis. Associations between high BPE and BI-RADS assessments were evaluated using McNemar's chi-square test (α* = 0.025)., Results: The Slab AI model significantly outperformed the MIP AI model across the full test set (area under the curve of 0.84 vs. 0.79) using the radiology report reference standard. Using three-reader consensus BPE labels reference standard, our AI model significantly outperformed radiology report BPE labels. Finally, the AI model was significantly more likely than the radiologist to assign "high BPE" to suspicious breast MRIs and significantly less likely than the radiologist to assign "high BPE" to negative breast MRIs., Data Conclusion: Fully automated BPE assessments for breast MRIs could be more accurate than BPE assessments from radiology reports., Level of Evidence: 4 TECHNICAL EFFICACY STAGE: 3., (© 2022 International Society for Magnetic Resonance in Medicine.)

Breast tissue enhances on contrast MRI and is called background parenchymal enhancement (BPE). Having high BPE has been associated with an increased risk of breast cancer. We examined the relationship between BPE and the amount of fibroglandular tissue on MRI (MRI-FGT) and breast cancer risk factors. This was a cross-sectional study of 415 women without breast cancer undergoing contrast-enhanced breast MRI at Memorial Sloan Kettering Cancer Center. All women completed a questionnaire assessing exposures at the time of MRI. Prevalence ratios (PR) and 95% confidence intervals (CI) describing the relationship between breast cancer risk factors and BPE and MRI-FGT were generated using modified Poisson regression. In multivariable-adjusted models a positive association between body mass index (BMI) and BPE was observed, with a 5-unit increase in BMI associated with a 14% and 44% increase in prevalence of high BPE in pre- and post-menopausal women, respectively. Conversely, a strong inverse relationship between BMI and MRI-FGT was observed in both pre- (PR = 0.66, 95% CI 0.57, 0.76) and post-menopausal (PR = 0.66, 95% CI 0.56, 0.78) women. Use of preventive medication (e.g., tamoxifen) was associated with having low BPE, while no association was observed for MRI-FGT. BPE is an imaging marker available from standard contrast-enhanced MRI, that is influenced by endogenous and exogenous hormonal exposures in both pre- and post-menopausal women., (© 2022. The Author(s).)

Background: For critically ill congenital diaphragmatic hernia (CDH) patients on high frequency oscillatory ventilation (HFOV), extracorporeal membrane oxygenation (ECMO), and/or inhaled nitric oxide (iNO), operative repair in the neonatal intensive care unit (NICU) has been proposed to avoid complications during transport to an operating room (OR). This study compared neonates with CDH who received herniorrhaphy in the NICU or OR, with a subgroup analysis considering only patients supported with ECMO., Methods: Patients admitted to the NICU in the first 2 weeks of life at a free-standing children's hospital between July 2004 and September 2021 were examined. Patients were categorized according to location of CDH repair, and impact on operative complications and survival was compared., Results: 185 patients were admitted to the NICU with posterolateral CDH and received operative repair. 48 cases were operated on at the bedside in the NICU and 137 in the OR. Patients repaired in the NICU had higher use of HFOV, pulmonary vasodilators, and ECMO (all P < .001). Children repaired in the NICU experienced significantly higher in-hospital death and overall mortality ( P < .001). However, in multivariate analysis, repair location was not a significant predictor of survival to discharge in patients receiving ECMO. No significant difference in surgical site infection was detected for operative location ( P = .773)., Discussion: Congenital diaphragmatic hernia repair in the NICU occurred more frequently among higher risk patients who experienced worse survival. The rate of surgical site infection appeared similar overall and across subgroups suggesting adequate sterility and technique for bedside procedures, when necessary, despite restricted access to advanced operative equipment.

Background: Technology acceptability and usage surveys (TAUS) are brief questionnaires that measure technology comfort, typical daily use, and access in a population. However, current measures are not adapted to low- and middle-income country (LMIC) contexts., Objective: The objective of this pilot study was to develop a TAUS that could be used to inform the implementation of a mobile health (mHealth) intervention in Nigeria., Methods: A literature review of validated technology comfort and usage scales was conducted to identify candidate items. The draft measure was reviewed for face validity by an expert panel comprised of clinicians and researchers with cultural, methodological, and clinical expertise. The measure was piloted by radiologists at an oncology symposium in Nigeria., Results: After expert review, the final measure included 18 items organized into 3 domains: (1) comfort with using mobile applications, (2) reliability of internet or electricity, and (3) attitudes toward using computers or mobile applications in clinical practice. The pilot sample (n=16) reported high levels of comfort and acceptability toward using mHealth applications in the clinical setting but faced numerous infrastructure challenges., Conclusions: Pilot results indicate that the TAUS may be a feasible and appropriate measure for assessing technology usage and acceptability in LMIC clinical contexts. Dedicating a domain to technology infrastructure and access yielded valuable insights for program implementation., (©Kathleen A Lynch, Thomas M Atkinson, Adeleye D Omisore, Olusola Famurewa, Olalekan Olasehinde, Oluwole Odujoko, Olusegun I Alatise, Adedeji Egberongbe, T Peter Kingham, Elizabeth A Morris, Elizabeth Sutton. Originally published in JMIR Formative Research (https://formative.jmir.org), 20.04.2022.)

Purpose: To develop a deep network architecture that would achieve fully automated radiologist-level segmentation of cancers at breast MRI., Materials and Methods: In this retrospective study, 38 229 examinations (composed of 64 063 individual breast scans from 14 475 patients) were performed in female patients (age range, 12-94 years; mean age, 52 years ± 10 [standard deviation]) who presented between 2002 and 2014 at a single clinical site. A total of 2555 breast cancers were selected that had been segmented on two-dimensional (2D) images by radiologists, as well as 60 108 benign breasts that served as examples of noncancerous tissue; all these were used for model training. For testing, an additional 250 breast cancers were segmented independently on 2D images by four radiologists. Authors selected among several three-dimensional (3D) deep convolutional neural network architectures, input modalities, and harmonization methods. The outcome measure was the Dice score for 2D segmentation, which was compared between the network and radiologists by using the Wilcoxon signed rank test and the two one-sided test procedure., Results: The highest-performing network on the training set was a 3D U-Net with dynamic contrast-enhanced MRI as input and with intensity normalized for each examination. In the test set, the median Dice score of this network was 0.77 (interquartile range, 0.26). The performance of the network was equivalent to that of the radiologists (two one-sided test procedures with radiologist performance of 0.69-0.84 as equivalence bounds, P < .001 for both; n = 250)., Conclusion: When trained on a sufficiently large dataset, the developed 3D U-Net performed as well as fellowship-trained radiologists in detailed 2D segmentation of breast cancers at routine clinical MRI. Keywords: MRI, Breast, Segmentation, Supervised Learning, Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning AlgorithmsPublished under a CC BY 4.0 license. Supplemental material is available for this article., Competing Interests: Disclosures of Conflicts of Interest: L.H. Grant from NIBIB and NIMH through the NIH BRAIN Initiative (R01 EB02157); consulting fee from City College of New York. Y.H. Consulting fee from City College of New York. S.L. No relevant relationships. C.R.S. No relevant relationships. R.L.G. No relevant relationships. I.D.N. Grant from Alfonso Martín Escudero Foundation. A.G.V.B. No relevant relationships. N.O. No relevant relationships. E.S.K. No relevant relationships. D.L. No relevant relationships. D.A. Consulting fee AEAD850301RG4. S.E.W. RSNA Research and Education Foundation grant no. RF1905 (content is solely the responsibility of the authors and does not necessarily represent the official views of the RSNA R&E Foundation). M.H. No relevant relationships. D.F.M. No relevant relationships. K.P. Funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 and the Breast Cancer Research Foundation; ongoing research grants include Digital Hybrid Breast PET/MRI for Enhanced Diagnosis of Breast Cancer (HYPMED) H2020 - Research and Innovation Framework Programme PHC-11-2015 #667211-2, A Body Scan for Cancer Detection using Quantum Technology (CANCERSCAN) H2020-FETOPEN-2018-2019-2020-01 # 828978, Multiparametric 18F-Fluoroestradiol PET/MRI coupled with Radiomics Analysis and Machine Learning for Prediction and Assessment of Response to Neoadjuvant Endocrine Therapy in Patients with Hormone Receptor+/HER2− Invasive Breast Cancer Jubiläumsfonds of the Austrian National Bank # Nr: 18207, Deciphering breast cancer heterogeneity and tackling the hypoxic tumor microenvironment challenge with PET/MRI, MSI and radiomics The Vienna Science and Technology Fund LS19-046, MSKCC 2020 Molecularly Targeted Intra-Operative Imaging Award 07/2020-06/2021, Breast Cancer Research Foundation 06/2019 - 05/2021 PI Mark Robson Co-I, NIH R01 Breast Cancer Intravoxel-Incoherent-Motion MRI Multisite (BRIMM) 09/01/2020-08/30/2025 PI Eric Sigmund Co-I, NIH R01 subaward: Abbreviated Non-Contrast-Enhanced MRI for Breast Cancer Screening 09/01/2023-08/31/2025 PI Brian Hargreaves; payment for lectures, service on speakers bureaus and for travel/accommodations/meeting expenses from the European Society of Breast Imaging (MRI educational course, annual scientific meeting) and Siemens Healthcare (lectures). K.J. No relevant relationships. A.E.E. No relevant relationships. P.E. No relevant relationships. E.A.M. No relevant relationships. H.A.M. Grant from NIBIB and NIMH through the NIH BRAIN Initiative (R01 EB028157). L.C.P. Grant from NIH (R01CA247910). E.J.S. Grant from National Institutes of Health/National Cancer Institute (P30 CA008748)., (2022 by the Radiological Society of North America, Inc.)

Objectives: To investigate the association between pre-pregnancy subclinical insulin resistance and cardiovascular dysfunction in healthy nulliparous women, and with hypertension in subsequent pregnancy., Study Design: Secondary analysis of a single center prospective observational study conducted November 2011-June 2014. Healthy nulliparous women underwent detailed cardiovascular and metabolic assessment. Insulin resistance was determined by homeostasis model assessment (HOMA-IR). Associations of HOMA-IR with metabolic and cardiovascular measurements were assessed with Spearman correlations. Charts were reviewed in women who conceived singleton pregnancies., Main Outcome Measures: Metabolic measurements included serum glucose, insulin, creatinine, CRP, and lipids. HOMA-IR was calculated using fasting serum insulin and glucose. Indices of cardiovascular stiffness were determined from pulse wave velocity and response to volume challenge. Pregnancy outcomes included delivery mode and gestational age, birthweight, and hypertension., Results: HOMA-IR was positively associated with BMI (r = 0.462, p < 0.001), body fat percentile (r = 0.463, p < 0.001), CRP (r = 0.364, p = 0.003), and negatively associated with serum HDL (r = -0.38, p = 0.002) and creatinine (r = -0.242, p = 0.049). HOMA-IR was positively associated with blood pressure (r = 0.347, p = 0.004), resting heart rate (r = 0.433, p = <0.001), response to volume challenge (r = 0.325, p < 0.01). Increased HOMA-IR was associated with a faster cardiac ejection time in response to volume challenge (r = -0.415, p < 0.001), which is a marker of decreased cardiac compliance to volume increase, or cardiac stiffness., Conclusion: HOMA-IR is associated with pre-pregnancy cardiac stiffness. Cholesterol was not associated with cardiovascular dysfunction. A non-significant trend was observed between HOMA-IR and hypertension in subsequent pregnancy., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: As neoadjuvant chemotherapy (NAC) for breast cancer has become more widely used, so has nipple-sparing mastectomy. A common criterion for eligibility is a 1 cm tumor-to-nipple distance (TND), but its suitability after NAC is unclear. In this study, we examined factors predictive of negative nipple pathologic status (NS-) in women undergoing total mastectomy after NAC., Methods: Women with invasive breast cancer treated with NAC and total mastectomy from August 2014 to April 2018 at our institution were retrospectively identified. Following review of pre- and post-NAC magnetic resonance imaging (MRI) and mammograms, the association of clinicopathologic and imaging variables with NS- was examined and the accuracy of 1 cm TND on imaging for predicting NS- was determined., Results: Among 175 women undergoing 179 mastectomies, 74% of tumors were cT1-T2 and 67% were cN+ on pre-NAC staging; 10% (18/179) had invasive or in situ carcinoma in the nipple on final pathology. On multivariable analysis, after adjusting for age, grade, and tumor stage, three factors, namely number of positive nodes, pre-NAC nipple-areolar complex retraction, and decreasing TND, were significant predictors of nipple involvement (p < 0.05). The likelihood of NS- was higher with increasing TND on pre- and post-NAC imaging (p < 0.05). TND ≥ 1 cm predicted NS- in 97% and 95% of breasts on pre- and post-NAC imaging, respectively., Conclusions: Increasing TND was associated with a higher likelihood of NS-. A TND ≥ 1 cm on pre- or post-NAC imaging is highly predictive of NS- and could be used to determine eligibility for nipple-sparing mastectomy after NAC., (© 2021. Society of Surgical Oncology.)

BACKGROUND. Targeted ultrasound (US) can be performed to characterize and potentially biopsy areas of enhancement detected on contrast-enhanced mammography (CEM). OBJECTIVE. The purpose of this study was to assess the utility of targeted US in predicting malignancy of lesions with indeterminate or suspicious enhancement on CEM. METHODS. One thousand consecutive CEM examinations with same-day targeted breast US at one institution between October 2013 and May 2018 were retrospectively reviewed. All patients with indeterminate or suspicious enhancement detected on CEM that underwent US evaluation were included. Patients with palpable or symptomatic lesions, those with suspicious findings on low-energy mammograms or images obtained with another modality, and those with less than 1 year of follow-up were excluded. Medical records, imaging, and pathology data were reviewed. Histopathologic analysis was used as the reference standard for biopsied lesions, and follow-up imaging was used for unbiopsied lesions. Associations between pathologic diagnosis, presence of a US correlate, and lesion characteristics were assessed by Fisher exact, chi-square, and Wilcox-on rank sum tests. RESULTS. Among 153 enhancing lesions detected on CEM in 144 patients, 47 (31%) had a US correlate. The frequency of a correlate between CEM and US was significantly higher among enhancing masses (28/43 [65%]) than among lesions exhibiting nonmass enhancement (19/110 [17%]) ( p < .001). The likelihood of malignancy was significantly greater among lesions with a US correlate (12/47 [26%]) than among those without a US correlate (11/106 [10%]) ( p = .03), and among mass lesions (11/43 [26%]) than among nonmass lesions (12/110 [11%]) ( p = .04). The PPV of US-guided biopsy after CEM-directed US was 32%. CONCLUSION. Enhancing CEM-detected lesions that have a US correlate are more likely to be malignant and can be evaluated with US-guided biopsy to obviate additional breast MRI. CLINICAL IMPACT. CEM-directed US of enhancing lesions is useful given that lesions with a US correlate are more likely to be malignant and can be used as targets for US-guided biopsy until a CEM biopsy system becomes commercially available.

OBJECTIVE. The objective of this study was to assess to the role of contrast-enhanced digital mammography (CEDM) as a screening tool in women at intermediate risk for developing breast cancer due to a personal history of lobular neoplasia without additional risk factors. MATERIALS AND METHODS. In this institutional review board-approved, observational, retrospective study, we reviewed our radiology department database to identify patients with a personal history of breast biopsy yielding lobular neoplasia who underwent screening CEDM at our institution between December 2012 and February 2019. A total of 132 women who underwent 306 CEDM examinations were included. All CEDM examinations were interpreted by dedicated breast imaging radiologists in conjunction with a review of the patient's clinical history and available prior breast imaging. In statistical analysis, sensitivity, specificity, NPV, positive likelihood ratio, and accuracy of CEDM in detecting cancer were determined, with pathology or 12-month imaging follow-up serving as the reference standard. RESULTS. CEDM detected cancer in six patients and showed an overall sensitivity of 100%, specificity of 88% (95% CI, 84-92%), NPV of 100%, and accuracy of 88% (95% CI, 84-92%). The positive likelihood ratio of 8.33 suggested that CEDM findings are 8.3 times more likely to be positive in an individual with breast cancer when compared with an individual without the disease. CONCLUSION. CEDM shows promise as a breast cancer screening examination in patients with a personal history of lobular neoplasia. Continued investigation with a larger patient population is needed to determine the true sensitivity and positive predictive value of CEDM for these patients.

Purpose: To investigate whether radiomics features extracted from magnetic resonance imaging (MRI) of patients with biopsy-proven atypical ductal hyperplasia (ADH) coupled with machine learning can differentiate high-risk lesions that will upgrade to malignancy at surgery from those that will not, and to determine if qualitatively and semi-quantitatively assessed imaging features, clinical factors, and image-guided biopsy technical factors are associated with upgrade rate., Methods: This retrospective study included 127 patients with 139 breast lesions yielding ADH at biopsy who were assessed with multiparametric MRI prior to biopsy. Two radiologists assessed all lesions independently and with a third reader in consensus according to the BI-RADS lexicon. Univariate analysis and multivariate modeling were performed to identify significant radiomic features to be included in a machine learning model to discriminate between lesions that upgraded to malignancy on surgery from those that did not., Results: Of 139 lesions, 28 were upgraded to malignancy at surgery, while 111 were not upgraded. Diagnostic accuracy was 53.6%, specificity 79.2%, and sensitivity 15.3% for the model developed from pre-contrast features, and 60.7%, 86%, and 22.8% for the model developed from delta radiomics datasets. No significant associations were found between any radiologist-assessed lesion parameters and upgrade status. There was a significant correlation between the number of specimens sampled during biopsy and upgrade status (p = 0.003)., Conclusion: Radiomics analysis coupled with machine learning did not predict upgrade status of ADH. The only significant result from this analysis is between the number of specimens sampled during biopsy procedure and upgrade status at surgery.

The purpose of this multicenter retrospective study was to evaluate radiomics analysis coupled with machine learning (ML) of dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) radiomics models separately and combined as multiparametric MRI for improved breast cancer detection. Consecutive patients (Memorial Sloan Kettering Cancer Center, January 2018-March 2020; Medical University Vienna, from January 2011-August 2014) with a suspicious enhancing breast tumor on breast MRI categorized as BI-RADS 4 and who subsequently underwent image-guided biopsy were included. In 93 patients (mean age: 49 years ± 12 years; 100% women), there were 104 lesions (mean size: 22.8 mm; range: 7-99 mm), 46 malignant and 58 benign. Radiomics features were calculated. Subsequently, the five most significant features were fitted into multivariable modeling to produce a robust ML model for discriminating between benign and malignant lesions. A medium Gaussian support vector machine (SVM) model with five-fold cross validation was developed for each modality. A model based on DWI-extracted features achieved an AUC of 0.79 (95% CI: 0.70-0.88), whereas a model based on DCE-extracted features yielded an AUC of 0.83 (95% CI: 0.75-0.91). A multiparametric radiomics model combining DCE- and DWI-extracted features showed the best AUC (0.85; 95% CI: 0.77-0.92) and diagnostic accuracy (81.7%; 95% CI: 73.0-88.6). In conclusion, radiomics analysis coupled with ML of multiparametric MRI allows an improved evaluation of suspicious enhancing breast tumors recommended for biopsy on clinical breast MRI, facilitating accurate breast cancer diagnosis while reducing unnecessary benign breast biopsies.

Purpose: To develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer., Methods: ASCO convened an Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy for breast cancer and provide recommended care options., Results: A total of 41 articles met eligibility criteria and form the evidentiary basis for the guideline recommendations., Recommendations: Patients undergoing neoadjuvant therapy should be managed by a multidisciplinary care team. Appropriate candidates for neoadjuvant therapy include patients with inflammatory breast cancer and those in whom residual disease may prompt a change in therapy. Neoadjuvant therapy can also be used to reduce the extent of local therapy or reduce delays in initiating therapy. Although tumor histology, grade, stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) expression should routinely be used to guide clinical decisions, there is insufficient evidence to support the use of other markers or genomic profiles. Patients with triple-negative breast cancer (TNBC) who have clinically node-positive and/or at least T1c disease should be offered an anthracycline- and taxane-containing regimen; those with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy. Carboplatin may be offered to patients with TNBC to increase pathologic complete response. There is currently insufficient evidence to support adding immune checkpoint inhibitors to standard chemotherapy. In patients with hormone receptor (HR)-positive (HR-positive), HER2-negative tumors, neoadjuvant chemotherapy can be used when a treatment decision can be made without surgical information. Among postmenopausal patients with HR-positive, HER2-negative disease, hormone therapy can be used to downstage disease. Patients with node-positive or high-risk node-negative, HER2-positive disease should be offered neoadjuvant therapy in combination with anti-HER2-positive therapy. Patients with T1aN0 and T1bN0, HER2-positive disease should not be routinely offered neoadjuvant therapy.Additional information is available at www.asco.org/breast-cancer-guidelines., Competing Interests: Reprint Requests: 2318 Mill Road, Suite 800, Alexandria, VA 22314; guidelines@asco.org Lisa A. CareyResearch Funding: Innocrin Pharma, Syndax, Immunomedics, Novartis, NanoString Technologies, AbbVie, Seattle GeneticsPatents, Royalties, Other Intellectual Property: Royalty-sharing agreement, investorship interest in licensed IP to startup company, Falcon Therapeutics, that is designing neural stem cell-based therapy for glioblastoma multiforme(OPTIONAL) Uncompensated Relationships: Sanofi, Novartis, G1 Therapeutics, Genentech/Roche, GlaxoSmithKline, Exact Sciences, AstraZeneca/Daiichi Sanyo, Aptitude Health(OPTIONAL) Open Payments Link: https://openpaymentsdata.cms.gov/physician/179671 Neelima DenduluriResearch Funding: Amgen, Novartis, Genentech, Lilly, Pfizer, Daiichi Sankyo, ImmunomedicsTravel, Accommodations, Expenses: Seattle Genetics Sibylle LoiblHonoraria: Chugai PharmaConsulting or Advisory Role: Pfizer, Roche, Novartis, Seattle Genetics, Celgene, Lilly, AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck KGaA, AbbVie, Amgen, prime/Medscape, Daiichi Sankyo, Samsung, Puma Biotechnology, Pierre Fabre, Immunomedics, GlaxoSmithKline, EirGenix, BayerResearch Funding: AbbVie, AstraZeneca, Vifor Pharma, Amgen, Celgene, Novartis, Pfizer, Roche, Cepheid, Myriad Genetics, Immunomedics, Seattle Genetics, Daiichi Sankyo, Pierre FabrePatents, Royalties, Other Intellectual Property: Patent Pending EP14153692.0 Elizabeth A. MorrisResearch Funding: GRAIL Alejandra PerezResearch Funding: Genentech/Roche, Macrogenics, Nektar, Immunomedics, AstraZeneca Meredith M. ReganHonoraria: Bristol-Myers SquibbConsulting or Advisory Role: Ipsen, Tolmar, Bristol-Myers SquibbResearch Funding: Veridex, OncoGenex, Pfizer, Ipsen, Novartis, Merck, Ferring, Celgene, AstraZeneca, Pierre Fabre, Ipsen, Bayer, Bristol-Myers Squibb, Roche, Astellas Pharma, Medivation, Janssen, Millennium Pharamceuticals, Sanofi, Sotio, Dendreon, Pfizer, TerSeraTravel, Accommodations, Expenses: Bristol-Myers Squibb Patricia A. SpearsConsulting or Advisory Role: Pfizer Preeti K. SudheendraHonoraria: Boston ScientificConsulting or Advisory Role: Boston Scientific, Vesper Medical, Sirtex MedicalSpeakers' Bureau: Boston Scientific W. Fraser SymmansStock and Other Ownership Interests: ISIS Pharmaceuticals, Nuvera Biosciences, Delphi Diagnostics, Eiger BioPharmaceuticalsConsulting or Advisory Role: Merck, Almac DiagnosticsPatents, Royalties, Other Intellectual Property: Intellectual propertyTravel, Accommodations, Expenses: Luminex, Merck(OPTIONAL) Uncompensated Relationships: Delphi Diagnostics Rachel L. YungResearch Funding: Novartis, Odonate Therapeutics Dawn L. HershmanConsulting or Advisory Role: AIM Specialty HealthNo other potential conflicts of interest were reported.

Background: In preterm infants who require mechanical ventilation (MV), volume-targeted ventilation (VTV) modes are associated with lower rates of bronchopulmonary dysplasia compared with pressure-limited ventilation. Bronchopulmonary dysplasia rates in our NICU were higher than desired, prompting quality improvement initiatives to improve MV by increasing the use of VTV., Methods: We implemented and tested interventions over a 3-year period. Primary outcomes were the percentage of conventional MV hours when any-VTV mode was used and the percentage of conventional MV hours when an exclusively VTV mode was used. Exclusively VTV modes were modes in which all breaths were volume targeted. We evaluated outcomes during 3 project periods: baseline (May 2016-December 2016); epoch 1 (December 2016-October 2018), increasing the use of any-VTV mode; and epoch 2 (October 2018-November 2019), increasing the use of exclusively VTV modes., Results: Use of any-VTV mode increased from 18 694 of 22 387 (83%) MV hours during baseline to 72 846 of 77 264 (94%) and 58 174 of 60 605 (96%) MV hours during epochs 1 and 2, respectively ( P < .001). Use of exclusively VTV increased from 5967 of 22 387 (27%) during baseline to 47 364 of 77 264 (61%) and 46 091 of 60 605 (76%) of all conventional MV hours during epochs 1 and 2, respectively ( P < .001). In statistical process control analyses, multiple interventions were associated with improvements in primary outcomes. Measured clinical outcomes were unchanged., Conclusions: Quality improvement interventions were associated with improved use of VTV but no change in measured clinical outcomes., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Purpose: To assess the feasibility and diagnostic accuracy of multispectral MRI (MSI) in the detection and localization of biopsy markers during MRI-guided breast biopsy., Methods: This prospective study included 20 patients undergoing MR-guided breast biopsy. In 10 patients (Group 1), MSI was acquired following tissue sampling and biopsy marker deployment. In the other 10 patients (Group 2), MSI was acquired following tissue sampling but before biopsy marker deployment (to simulate deployment failure). All patients received post-procedure mammograms. Group 1 and Group 2 designations, in combination with the post-procedure mammogram, served as the reference standard. The diagnostic performance of MSI for biopsy marker identification was independently evaluated by two readers using two-spectral-bin MR and one-spectral-bin MR. The κ statistic was used to assess inter-rater agreement for biopsy marker identification., Results: The sensitivity, specificity, and accuracy of biopsy marker detection for readers 1 and 2 using 2-bin MSI were 90.0% (9/10) and 90.0% (9/10), 100.0% (10/10) and 100.0% (10/10), 95.0% (19/20) and 95.0% (19/20); and using 1-bin MSI were 70.0% (7/10) and 80.0% (8/10), 100.0% (8/8) and 100.0% (10/10), 85.0% (17/20) and 90.0% (18/20). Positive predictive value was 100% for both readers for all numbers of bins. Inter-rater agreement was excellent: κ was 1.0 for 2-bin MSI and 0.81 for 1-bin MSI., Conclusion: MSI is a feasible, diagnostically accurate technique for identifying metallic biopsy markers during MRI-guided breast biopsy and may eliminate the need for a post-procedure mammogram., Competing Interests: YW and PS are inventors on QSM-related patents issued to Cornell University and hold equity in Medimagemetric LLC. KP received payment for activities not related to the present article including lectures including service on speakers bureaus and for travel/accommodations/meeting expenses unrelated to activities listed from the European Society of Breast Imaging (MRI educational course, annual scientific meeting), and the IDKD 2019 (educational course). EM has received a grant from GRAIL, Inc. for research not related to the present article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Eskreis-Winkler, Simon, Reichman, Spincemaille, Nguyen, Christos, Drotman, Prince, Pinker, Sutton, Morris and Wang.)

Altered metabolism including lipids is an emerging hallmark of breast cancer. The purpose of this study was to investigate if breast cancers exhibit different magnetic resonance spectroscopy (MRS)-based lipid composition than normal fibroglandular tissue (FGT). MRS spectra, using the stimulated echo acquisition mode sequence, were collected with a 3T scanner from patients with suspicious lesions and contralateral normal tissue. Fat peaks at 1.3 + 1.6 ppm (L13 + L16), 2.1 + 2.3 ppm (L21 + L23), 2.8 ppm (L28), 4.1 + 4.3 ppm (L41 + L43), and 5.2 + 5.3 ppm (L52 + L53) were quantified using LCModel software. The saturation index (SI), number of double bods (NBD), mono and polyunsaturated fatty acids (MUFA and PUFA), and mean chain length (MCL) were also computed. Results showed that mean concentrations of all lipid metabolites and PUFA were significantly lower in tumors compared with that of normal FGT ( p ≤ 0.002 and 0.04, respectively). The measure best separating normal and tumor tissues after adjusting with multivariable analysis was L21 + L23, which yielded an area under the curve of 0.87 (95% CI: 0.75-0.98). Similar results were obtained between HER2 positive versus HER2 negative tumors. Hence, MRS-based lipid measurements may serve as independent variables in a multivariate approach to increase the specificity of breast cancer characterization.