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The breasts undergo marked physiologic changes during lactation that can make conventional imaging evaluation with mammography and US challenging. MRI can be a valuable diagnostic aid to differentiate physiologic and benign processes from malignancy in patients who are lactating. In addition, MRI may allow more accurate delineation of disease involvement than does conventional imaging and assists in locoregional staging, screening of the contralateral breast, assessment of response to neoadjuvant chemotherapy, and surgical planning. Although the American College of Radiology recommends against patients undergoing contrast-enhanced MRI during pregnancy because of fetal safety concerns, contrast-enhanced MRI is safe during lactation. As more women delay childbearing, the incidence of pregnancy-associated breast cancer (PABC) and breast cancer in lactating women beyond the 1st year after pregnancy is increasing. Thus, MRI is increasingly being performed in lactating women for diagnostic evaluation and screening of patients at high risk. PABC is associated with a worse prognosis than that of non-PABCs, with delays in diagnosis contributing to an increased likelihood of advanced-stage disease at diagnosis. Familiarity with the MRI features of the lactating breast and the appearance of various pathologic conditions is essential to avoid diagnostic pitfalls and prevent delays in cancer diagnosis and treatment. The authors review clinical indications for breast MRI during lactation, describe characteristic features of the lactating breast at MRI, and compare MRI features of a spectrum of benign and malignant breast abnormalities. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Chikarmane in this issue.

The human GABAB receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction1. A unique GPCR that is known to require heterodimerization for function2-6, the GABAB receptor has two subunits, GABAB1 and GABAB2, that are structurally homologous but perform distinct and complementary functions. GABAB1 recognizes orthosteric ligands7,8, while GABAB2 couples with G proteins9-14. Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail15. Although the VFT heterodimer structure has been resolved16, the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABAB receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.

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Dedicated breast positron emission tomography (dbPET) is an emerging technology with high sensitivity and spatial resolution that enables detection of sub-centimeter lesions and depiction of intratumoral heterogeneity. In this study, we report our initial experience with dbPET using [F-18]fluoroestradiol (FES) in assessing ER+ primary breast cancers. Six patients with >90% ER+ and HER2- breast cancers were imaged with dbPET and breast MRI. Two patients had ILC, three had IDC, and one had an unknown primary tumor. One ILC patient was treated with letrozole, and another patient with IDC was treated with neoadjuvant chemotherapy without endocrine treatment. In this small cohort, we observed FES uptake in ER+ primary breast tumors with specificity to ER demonstrated in a case with tamoxifen blockade. FES uptake in ILC had a diffused pattern compared to the distinct circumscribed pattern in IDC. In evaluating treatment response, the reduction of SUVmax was observed with residual disease in an ILC patient treated with letrozole, and an IDC patient treated with chemotherapy. Future study is critical to understand the change in FES SUVmax after endocrine therapy and to consider other tracer uptake metrics with SUVmax to describe ER-rich breast cancer. Limitations include variations of FES uptake in different ER+ breast cancer diseases and exclusion of posterior tissues and axillary regions. However, FES-dbPET has a high potential for clinical utility, especially in measuring response to neoadjuvant endocrine treatment. Further development to improve the field of view and studies with a larger cohort of ER+ breast cancer patients are warranted.

Purpose To evaluate the effect of background parenchymal enhancement (BPE) on breast magnetic resonance (MR) imaging interpretive performance in a large multi-institutional cohort with independent analysis of screening and diagnostic MR studies. Materials and Methods Analysis of 3770 breast MR studies was conducted. Examinations were performed in 2958 women at six participating facilities in the San Francisco Bay Area from January 2010 to October 2012. Findings were recorded prospectively in the San Francisco Mammography Registry. Performance measures were compared between studies with low BPE (mild or minimal) and those with high BPE (moderate or marked) by using binomial tests of proportions. Results Of 1726 MR imaging studies in the screening group, 1301 were classified as having low BPE and 425 were classified as having high BPE (75% vs 25%, respectively; P < .001). Of 2044 MR imaging studies in the diagnostic group, 1443 were classified as having low BPE and 601 were classified as having high BPE (71% vs 29%, respectively; P < .001). For low versus high BPE groups at screening, abnormal interpretation rate was 157 of 1301 versus 111 of 424 (12% vs 26%, P < .001); biopsy recommendation rate was 85 of 1301 versus 54 of 424 (7% vs 13%, P < .001); and specificity was 89% (95% confidence interval [CI]: 87, 91) versus 75% (95% CI: 71, 80) (P = .01). For the low versus high BPE groups at diagnostic MR imaging, biopsy recommendation rate was 325 of 1443 versus 195 of 601 (23% vs 32%, P < .001); and specificity was 86% (95% CI: 84, 88) versus 75% (95% CI: 74, 82) (P < .001). There were no significant differences between studies with low versus high BPE in sensitivity for screening (76% [95% CI: 55, 91] vs 83% [95% CI: 52, 98]; P = .94) or diagnostic (93% [95% CI: 87, 97] vs 96% [95% CI: 87, 99]; P = .69) MR imaging, nor were there significant differences in cancer detection rate per 1000 patients between the low BPE versus high BPE groups for screening (15 per 1000 vs 24 per 1000, P = .30) or diagnostic (78 per 1000 vs 85 per 1000, P = .64) MR imaging. Conclusion Relative to MR studies with minimal or mild BPE, those with moderate or marked BPE were associated with higher abnormal interpretation and biopsy rates and lower specificity, with no difference in cancer detection rate. © RSNA, 2017 Online supplemental material is available for this article.

ObjectiveThe objective of the present study is to evaluate the effect of comparison with multiple prior mammograms on the outcomes of screening mammography relative to comparison with a single prior mammogram.Materials and methodsWe retrospectively analyzed 46,288 consecutive screening mammograms performed at our institution for 22,792 women. We divided these examinations into three groups: those interpreted without comparison with prior mammograms, those interpreted in comparison with one prior examination, and those interpreted in comparison with two or more prior examinations. For each group, we determined the rate of examination recall. We also calculated the positive predictive value of recall (i.e., positive predictive value level 1 [PPV1]) and the cancer detection rate (CDR) for both the group of examinations compared with a single prior mammogram and the group compared with multiple prior mammograms. Generalized estimating equations with the logistic link function were used to determine the relative odds ratio of recall as a function of the number of comparisons, with adjustment made for age as a confounding variable. The Fisher exact test was performed to compare the PPV1 and the CDR in the different cohorts.ResultsThe recall rate for mammograms interpreted without comparison with prior examinations was 16.6%, whereas that for mammograms compared with one prior examination was 7.8% and that for mammograms compared with two or more prior examinations was 6.3%. After adjustment was made for age, the odds ratio of recall for the group with multiple prior examinations relative to the group with a single prior examination was 0.864 (95% CI, 0.776-0.962; p = 0.0074). Statistically significant increases in the PPV1 of 0.05 (p = 0.0009) and in the CDR of 2.3 cases per 1000 examinations (p = 0.0481) were also noted for mammograms compared with multiple prior examinations relative to those compared with a single prior examination.ConclusionComparison with two or more prior mammograms resulted in a statistically significant reduction in the screening mammography recall rate and increases in the CDR and PPV1 relative to comparison with a single prior mammogram.

The human extracellular calcium-sensing (CaS) receptor controls plasma Ca2+ levels and contributes to nutrient-dependent maintenance and metabolism of diverse organs. Allosteric modulation of the CaS receptor corrects disorders of calcium homeostasis. Here, we report the cryogenic-electron microscopy reconstructions of a near-full-length CaS receptor in the absence and presence of allosteric modulators. Activation of the homodimeric CaS receptor requires a break in the transmembrane 6 (TM6) helix of each subunit, which facilitates the formation of a TM6-mediated homodimer interface and expansion of homodimer interactions. This transformation in TM6 occurs without a positive allosteric modulator. Two modulators with opposite functional roles bind to overlapping sites within the transmembrane domain through common interactions, acting to stabilize distinct rotamer conformations of key residues on the TM6 helix. The positive modulator reinforces TM6 distortion and maximizes subunit contact to enhance receptor activity, while the negative modulator strengthens an intact TM6 to dampen receptor function. In both active and inactive states, the receptor displays symmetrical transmembrane conformations that are consistent with its homodimeric assembly. [ABSTRACT FROM AUTHOR]

Image optimization at digital breast tomosynthesis (DBT) involves a series of trade-offs between multiple variables. Wider sweep angles provide better separation of overlapping tissues, but they result in decreased in-plane resolution as well as increased scan times that may be prone to patient motion. Techniques to reduce scan time, such as continuous tube motion and pixel binning during detector readout, reduce the chances of patient motion but may degrade the in-plane resolution. Image artifacts are inherent to DBT because of the limited angular range of the acquisition. Iterative reconstruction algorithms have been shown to reduce various DBT artifacts. [ABSTRACT FROM AUTHOR]

Purpose To compare quantitative measures of tumor metabolism and perfusion using fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) dedicated breast PET (dbPET) and breast dynamic contrast-enhanced (DCE) MRI during early treatment with neoadjuvant chemotherapy (NAC). Materials and Methods Prospectively collected DCE MRI and 18 F-FDG dbPET examinations were analyzed at baseline (T0) and after 3 weeks (T1) of NAC in 20 participants with 22 invasive breast cancers. FDG dbPET-derived standardized uptake value (SUV), metabolic tumor volume, and total lesion glycolysis (TLG) and MRI-derived percent enhancement (PE), signal enhancement ratio (SER), and functional tumor volume (FTV) were calculated at both time points. Differences between FDG dbPET and MRI parameters were evaluated after stratifying by receptor status, Ki-67 index, and residual cancer burden. Parameters were compared using Wilcoxon signed rank and Mann-Whitney U tests. Results High Ki-67 tumors had higher baseline SUV mean (difference, 5.1; P = .01) and SUV peak (difference, 5.5; P = .04). At T1, decreases were observed in FDG dbPET measures (pseudo-median difference T0 minus T1 value [95% CI]) of SUV max (-6.2 [-10.2, -2.6]; P < .001), SUV mean (-2.6 [-4.9, -1.3]; P < .001), SUV peak (-4.2 [-6.9, -2.3]; P < .001), and TLG (-29.1 mL 3 [-71.4, -6.8]; P = .005) and MRI measures of SER peak (-1.0 [-1.3, -0.2]; P = .02) and FTV (-11.6 mL 3 [-22.2, -1.7]; P = .009). Relative to nonresponsive tumors, responsive tumors showed a difference (95% CI) in percent change in SUV max of -34.3% (-55.9%, 1.5%; P = .06) and in PE peak of -42.4% (95% CI: -110.5%, 8.5%; P = .08). Conclusion 18 F-FDG dbPET was sensitive to early changes during NAC and provided complementary information to DCE MRI that may be useful for treatment response evaluation. Keywords: Breast, PET, Dynamic Contrast-enhanced MRI Clinical trial registration no. NCT01042379 Supplemental material is available for this article. © RSNA, 2024.

The breasts undergo marked physiologic changes during lactation that can make conventional imaging evaluation with mammography and US challenging. MRI can be a valuable diagnostic aid to differentiate physiologic and benign processes from malignancy in patients who are lactating. In addition, MRI may allow more accurate delineation of disease involvement than does conventional imaging and assists in locoregional staging, screening of the contralateral breast, assessment of response to neoadjuvant chemotherapy, and surgical planning. Although the American College of Radiology recommends against patients undergoing contrast-enhanced MRI during pregnancy because of fetal safety concerns, contrast-enhanced MRI is safe during lactation. As more women delay childbearing, the incidence of pregnancy-associated breast cancer (PABC) and breast cancer in lactating women beyond the 1st year after pregnancy is increasing. Thus, MRI is increasingly being performed in lactating women for diagnostic evaluation and screening of patients at high risk. PABC is associated with a worse prognosis than that of non-PABCs, with delays in diagnosis contributing to an increased likelihood of advanced-stage disease at diagnosis. Familiarity with the MRI features of the lactating breast and the appearance of various pathologic conditions is essential to avoid diagnostic pitfalls and prevent delays in cancer diagnosis and treatment. The authors review clinical indications for breast MRI during lactation, describe characteristic features of the lactating breast at MRI, and compare MRI features of a spectrum of benign and malignant breast abnormalities. © RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Chikarmane in this issue.

The human GABA B receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction 1 . A unique GPCR that is known to require heterodimerization for function 2-6 , the GABA B receptor has two subunits, GABA B1 and GABA B2 , that are structurally homologous but perform distinct and complementary functions. GABA B1 recognizes orthosteric ligands 7,8 , while GABA B2 couples with G proteins 9-14 . Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail 15 . Although the VFT heterodimer structure has been resolved 16 , the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABA B receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.