Breast density effect on the sensitivity of digital screening mammography in a UK cohort.

OBJECTIVES: To assess the performance of breast cancer screening by category of breast density and age in a UK screening cohort. METHODS: Raw full-field digital mammography data from a single site in the UK, forming a consecutive 3-year cohort of women aged 50 to 70 years from 2016 to 2018, were obtained retrospectively. Breast density was assessed using Volpara software. Examinations were grouped by density category and age group (50-60 and 61-70 years) to analyse screening performance. Statistical analysis was performed to determine the association between density categories and age groups. Volumetric breast density was assessed as a binary classifier of interval cancers (ICs) to find an optimal density threshold. RESULTS: Forty-nine thousand nine-hundred forty-eight screening examinations (409 screen-detected cancers (SDCs) and 205 ICs) were included in the analysis. Mammographic sensitivity, SDC/(SDC + IC), decreased with increasing breast density from 75.0% for density a (p = 0.839, comparisons made to category b), to 73.5%, 59.8% (p = 0.001), and 51.3% (p < 0.001) in categories b, c, and d, respectively. IC rates were highest in the densest categories with rates of 1.8 (p = 0.039), 3.2, 5.7 (p < 0.001), and 7.9 (p < 0.001) per thousand for categories a, b, c, and d, respectively. The recall rate increased with breast density, leading to more false positive recalls, especially in the younger age group. There was no significant difference between the optimal density threshold found, 6.85, and that Volpara defined as the b/c boundary, 7.5. CONCLUSIONS: The performance of screening is significantly reduced with increasing density with IC rates in the densest category four times higher than in women with fatty breasts. False positives are a particular issue for the younger subgroup without prior examinations. CLINICAL RELEVANCE STATEMENT: In women attending screening there is significant underdiagnosis of breast cancer in those with dense breasts, most marked in the highest density category but still three times higher than in women with fatty breasts in the second highest category. KEY POINTS: Breast density can mask cancers leading to underdiagnosis on mammography. Interval cancer rate increased with breast density categories 'a' to 'd'; 1.8 to 7.9 per thousand. Recall rates increased with increasing breast density, leading to more false positive recalls.

ESR Essentials: diagnostic work-up in patients with symptomatic breast disease-practice recommendations by the European Society of Breast Imaging.

Breast complaints are frequent reasons for consultations in primary care or breast clinics. Breast pain, breast lumps, and nipple discharge are the most common complaints. Less common symptoms such as skin changes and axillary abnormalities also require specific diagnostic approaches. Imaging the symptomatic breast should be performed by appropriately trained breast radiologists following the best practice guidelines and quality standards. Full-field digital mammography (FFDM), digital breast tomosynthesis (DBT), and breast ultrasound (US) are the main modalities used in this primary setting. The choice depends on the patient's age and symptoms. Women younger than 30-years-old are first imaged by US, whereas women over 40-years-old usually require both FFDM or DBT and US. For women between 30-years-old and 40-years-old, the US is the modality of choice, whereas FFDM or DBT might also be performed if needed. Pregnant or lactating women with palpable lesions or nipple discharge are imaged with US as the first method; FFDM or DBT can also be performed depending on the degree of suspicion as the dose to the fetus is minimal, and shielding may even further reduce the dose. More advanced techniques such as breast magnetic resonance imaging or contrast-enhanced mammography are not indicated in this first diagnostic setting and are reserved for cases of established malignancy (local staging) or rare cases of equivocal findings not otherwise resolved or inflammatory breast cancer. Last, but not least, male breast symptoms should also be addressed with US and/or FFDM. CLINICAL RELEVANCE STATEMENT: It is equally important to correctly diagnose an underlying malignancy and to avoid false positives that would lead to unnecessary biopsies, increased costs, and anxiety for the patient. Proper use of imaging modalities ensures optimal diagnostic approach and minimizes false negatives. KEY POINTS: Ultrasound, full-field digital mammography, or digital breast tomosynthesis are the main imaging modalities in the diagnostic setting, while MRI or contrast-enhanced mammography should be reserved to selected cases. Initial imaging modality includes ultrasound combined with mammography or digital breast tomosynthesis depending on women's age and the presence (or not) of inconclusive findings. A negative imaging evaluation should not deter biopsy when a highly suspicious finding is found on physical examination.

23Na MRI: inter-reader reproducibility of normal fibroglandular sodium concentration measurements at 3 T.

BACKGROUND: To study the reproducibility of 23Na magnetic resonance imaging (MRI) measurements from breast tissue in healthy volunteers. METHODS: Using a dual-tuned bilateral 23Na/1H breast coil at 3-T MRI, high-resolution 23Na MRI three-dimensional cones sequences were used to quantify total sodium concentration (TSC) and fluid-attenuated sodium concentration (FASC). B1-corrected TSC and FASC maps were created. Two readers manually measured mean, minimum and maximum TSC and mean FASC values using two sampling methods: large regions of interest (LROIs) and small regions of interest (SROIs) encompassing fibroglandular tissue (FGT) and the highest signal area at the level of the nipple, respectively. The reproducibility of the measurements and correlations between density, age and FGT apparent diffusion coefficient (ADC) values were evaluatedss. RESULTS: Nine healthy volunteers were included. The inter-reader reproducibility of TSC and FASC using SROIs and LROIs was excellent (intraclass coefficient range 0.945-0.979, p < 0.001), except for the minimum TSC LROI measurements (p = 0.369). The mean/minimum LROI TSC and mean LROI FASC values were lower than the respective SROI values (p < 0.001); the maximum LROI TSC values were higher than the SROI TSC values (p = 0.009). TSC correlated inversely with age but not with FGT ADCs. The mean and maximum FGT TSC and FASC values were higher in dense breasts in comparison to non-dense breasts (p < 0.020). CONCLUSIONS: The chosen sampling method and the selected descriptive value affect the measured TSC and FASC values, although the inter-reader reproducibility of the measurements is in general excellent. RELEVANCE STATEMENT: 23Na MRI at 3 T allows the quantification of TSC and FASC sodium concentrations. The sodium measurements should be obtained consistently in a uniform manner. KEY POINTS: • 23Na MRI allows the quantification of total and fluid-attenuated sodium concentrations (TSC/FASC). • Sampling method (large/small region of interest) affects the TSC and FASC values. • Dense breasts have higher TSC and FASC values than non-dense breasts. • The inter-reader reproducibility of TSC and FASC measurements was, in general, excellent. • The results suggest the importance of stratifying the sodium measurements protocol.

The paradox of MRI for breast cancer screening: high-risk and dense breasts-available evidence and current practice.

In the mid-1990s, the identification of BRCA1/2 genes for breast cancer susceptibility led to testing breast MRI accuracy in screening women at increased risk. From 2000 onwards, ten intraindividual comparative studies showed the marked superiority of MRI: the sensitivity ranged 25-58% for mammography, 33-52% for ultrasound, 48-67% for mammography plus ultrasound, and 71-100% for MRI; specificity 93-100%, 91-98%, 89-98%, and 81-98%, respectively. Based on the available evidence, in 2006-2007, the UK National Institute for Clinical Excellence and the American Cancer Society recommended MRI screening of high-risk women, followed by other international guidelines. Despite evidence-based medicine ideally requiring randomised controlled trials (RCTs) for policy changes regarding screening procedures, breast MRI for high-risk screening was adopted in many countries worldwide. In 2019, the results of the "DENSE" RCT were published in favour of breast MRI screening of women with extremely dense breasts compared to mammography alone, showing a reduction of more than 80% of the interval cancer rate in women who attended MRI screening. Even though international recommendations in favour of this practice were issued, substantial obstacles still prevent health systems from adopting breast MRI for screening women with extremely dense breasts. A paradox is evident: we adopted a screening procedure without evidence from RCTs, and now that we have this level-1 evidence for the same procedure, we fail to do so. This critical review tries to explain the differences between the two cases, as examples of the complex pathways of translating radiological research into everyday practice.Critical relevance statement The high-level evidence in favour of breast MRI screening of women with extremely dense breasts is failing to persuade policy makers to translate this into clinical practice.Key points• Breast MRI screening of high-risk women was adopted on basis of the evidence provided by test accuracy comparative studies showing an MRI performance greatly superior to that of mammography.• Breast MRI screening of women with extremely dense breasts has not been adopted although the evidence of a large reduction in interval cancer rate from a RCT.• We illustrate the differences between the two cases, as an example of the complex ways of translation of radiological research in clinical practice according to the EBM theory.

European guidelines for the diagnosis, treatment and follow-up of breast lesions with uncertain malignant potential (B3 lesions) developed jointly by EUSOMA, EUSOBI, ESP (BWG) and ESSO.

INTRODUCTION: Breast lesions of uncertain malignant potential (B3) include atypical ductal and lobular hyperplasias, lobular carcinoma in situ, flat epithelial atypia, papillary lesions, radial scars and fibroepithelial lesions as well as other rare miscellaneous lesions. They are challenging to categorise histologically, requiring specialist training and multidisciplinary input. They may coexist with in situ or invasive breast cancer (BC) and increase the risk of subsequent BC development. Management should focus on adequate classification and management whilst avoiding overtreatment. The aim of these guidelines is to provide updated information regarding the diagnosis and management of B3 lesions, according to updated literature review evidence. METHODS: These guidelines provide practical recommendations which can be applied in clinical practice which include recommendation grade and level of evidence. All sections were written according to an updated literature review and discussed at a consensus meeting. Critical appraisal by the expert writing committee adhered to the 23 items in the international Appraisal of Guidelines, Research and Evaluation (AGREE) tool. RESULTS: Recommendations for further management after core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB) diagnosis of a B3 lesion reported in this guideline, vary depending on the presence of atypia, size of lesion, sampling size, and patient preferences. After CNB or VAB, the option of vacuum-assisted excision or surgical excision should be evaluated by a multidisciplinary team and shared decision-making with the patient is crucial for personalizing further treatment. De-escalation of surgical intervention for B3 breast lesions is ongoing, and the inclusion of vacuum-assisted excision (VAE) will decrease the need for surgical intervention in further approaches. Communication with patients may be different according to histological diagnosis, presence or absence of atypia, or risk of upgrade due to discordant imaging. Written information resources to help patients understand these issues alongside with verbal communication is recommended. Lifestyle interventions have a significant impact on BC incidence so lifestyle interventions need to be suggested to women at increased BC risk as a result of a diagnosis of a B3 lesion. CONCLUSIONS: These guidelines provide a state-of-the-art overview of the diagnosis, management and prognosis of B3 lesions in modern multidisciplinary breast practice.

Mammography Breast Cancer Screening Triage Using Deep Learning: A UK Retrospective Study.

Background Breast screening enables early detection of cancers; however, most women have normal mammograms, resulting in repetitive and resource-intensive reading tasks. Purpose To investigate if deep learning (DL) algorithms can be used to triage mammograms by identifying normal results to reduce workload or flag cancers that may be overlooked. Materials and Methods In this retrospective study, three commercial DL algorithms were investigated using consecutive mammograms from two UK Breast Screening Program sites from January 2015 to December 2017 and January 2017 to December 2018 on devices from two mammography vendors. Normal mammograms with a 3-year follow-up and histopathologically proven cancer detected at screening, the subsequent round, or in the 3-year interval were included. Two algorithm thresholds were set: in scenario A, 99.0% sensitivity for rule-out triage to a lone reader, and in scenario B, approximately 1.0% additional recall providing a rule-in triage for further assessment. Both thresholds were then applied to the screening workflow in scenario C. The sensitivity and specificity were used to assess the overall predictive performance of each DL algorithm. Results The data set comprised 78 849 patients (median age, 59 years [IQR, 53-63 years]) and 887 screening-detected, 439 interval, and 688 subsequent screening round-detected cancers. In scenario A (rule-out triage), models DL-1, DL-2, and DL-3 triaged 35.0% (27 565 of 78 849), 53.2% (41 937 of 78 849), and 55.6% (43 869 of 78 849) of mammograms, respectively, with 0.0% (0 of 887) to 0.1% (one of 887) of screening-detected cancers undetected. In scenario B, DL algorithms triaged in 4.6% (20 of 439) to 8.2% (36 of 439) of interval and 5.2% (36 of 688) to 6.1% (42 of 688) of subsequent-round cancers when applied after the routine double-reading workflow. Combining both approaches in scenario C resulted in an overall noninferior specificity (difference, -0.9%; P < .001) and superior sensitivity (difference, 2.7%; P < .001) for the adaptive workflow compared with routine double reading for all three algorithms. Conclusion Rule-out and rule-in DL-adapted triage workflows can improve the efficiency and efficacy of mammography breast cancer screening. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Nishikawa and Lu in this issue.

Preoperative breast MRI positively impacts surgical outcomes of needle biopsy-diagnosed pure DCIS: a patient-matched analysis from the MIPA study.

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

Accelerating artificial intelligence: How federated learning can protect privacy, facilitate collaboration, and improve outcomes.

Cross-institution collaborations are constrained by data-sharing challenges. These challenges hamper innovation, particularly in artificial intelligence, where models require diverse data to ensure strong performance. Federated learning (FL) solves data-sharing challenges. In typical collaborations, data is sent to a central repository where models are trained. With FL, models are sent to participating sites, trained locally, and model weights aggregated to create a master model with improved performance. At the 2021 Radiology Society of North America's (RSNA) conference, a panel was conducted titled "Accelerating AI: How Federated Learning Can Protect Privacy, Facilitate Collaboration and Improve Outcomes." Two groups shared insights: researchers from the EXAM study (EMC CXR AI Model) and members of the National Cancer Institute's Early Detection Research Network's (EDRN) pancreatic cancer working group. EXAM brought together 20 institutions to create a model to predict oxygen requirements of patients seen in the emergency department with COVID-19 symptoms. The EDRN collaboration is focused on improving outcomes for pancreatic cancer patients through earlier detection. This paper describes major insights from the panel, including direct quotes. The panelists described the impetus for FL, the long-term potential vision of FL, challenges faced in FL, and the immediate path forward for FL.

A review of a strategic roadmapping exercise to advance clinical translation of photoacoustic imaging: From current barriers to future adoption.

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of the barriers that were identified, along with short-, medium- and long-term community efforts required to overcome them, both within and beyond the IPASC group.

A survey by the European Society of Breast Imaging on radiologists' preferences regarding quality assurance measures of image interpretation in screening and diagnostic mammography.

OBJECTIVES: Quality assurance (QA) of image interpretation plays a key role in screening and diagnostic mammography, maintaining minimum standards and supporting continuous improvement in interpreting images. However, the QA structure across Europe shows considerable variation. The European Society of Breast Imaging (EUSOBI) conducted a survey among the members to collect information on radiologists' preferences regarding QA measures in mammography. MATERIALS AND METHODS: An anonymous online survey consisting of 25 questions was distributed to all EUSOBI members and national breast radiology bodies in Europe. The questions were designed to collect demographic characteristics, information on responders' mammography workload and data about QA measures currently used in their country. Data was analysed using descriptive statistical analysis, the χ2 test, linear regression, and Durbin-Watson statistic test. RESULTS: In total, 251 breast radiologists from 34 countries completed the survey. Most respondents were providing both screening and symptomatic services (137/251, 54.6%), working in an academic hospital (85/251, 33.9%) and reading 1000-4999 cases per year (109/251, 43.4%). More than half of them (133/251, 53%) had established QA measures in their workplace. Although less than one-third (71/251, 28.3%) had to participate in regular performance testing, the vast majority (190/251, 75.7%) agreed that a mandatory test would be helpful to improve their skills. CONCLUSION: QA measures were in place for more than half of the respondents working in screening and diagnostic mammography to evaluate their breast imaging performance. Although there were substantial differences between countries, the importance of having QA in the workplace and implemented was widely acknowledged by radiologists. CLINICAL RELEVANCE STATEMENT: Although several quality assurance (QA) measures of image interpretation are recommended by European bodies or national organisations, the QA in mammography is quite heterogenous between countries and reporting settings, and not always actively implemented across Europe. KEY POINTS: The first survey that presents radiologists' preferences regarding QA measures of image interpretation in mammography. Quality assurance measures in the workplace are better-established for breast screening compared to diagnostic mammography. Radiologists consider that performance tests would help to improve their mammography interpretation skills.

European Society of Breast Imaging (EUSOBI) guidelines on the management of axillary lymphadenopathy after COVID-19 vaccination: 2023 revision.

Axillary lymphadenopathy is a common side effect of COVID-19 vaccination, leading to increased imaging-detected asymptomatic and symptomatic unilateral axillary lymphadenopathy. This has threatened to negatively impact the workflow of breast imaging services, leading to the release of ten recommendations by the European Society of Breast Imaging (EUSOBI) in August 2021. Considering the rapidly changing scenario and data scarcity, these initial recommendations kept a highly conservative approach. As of 2023, according to newly acquired evidence, EUSOBI proposes the following updates, in order to reduce unnecessary examinations and avoid delaying necessary examinations. First, recommendation n. 3 has been revised to state that breast examinations should not be delayed or rescheduled because of COVID-19 vaccination, as evidence from the first pandemic waves highlights how delayed or missed screening tests have a negative effect on breast cancer morbidity and mortality, and that there is a near-zero risk of subsequent malignant findings in asymptomatic patients who have unilateral lymphadenopathy and no suspicious breast findings. Second, recommendation n. 7 has been revised to simplify follow-up strategies: in patients without breast cancer history and no imaging findings suspicious for cancer, symptomatic and asymptomatic imaging-detected unilateral lymphadenopathy on the same side of recent COVID-19 vaccination (within 12 weeks) should be classified as a benign finding (BI-RADS 2) and no further work-up should be pursued. All other recommendations issued by EUSOBI in 2021 remain valid.

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study.

OBJECTIVES: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. METHODS: The MIPA observational study enrolled women aged 18-80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. RESULTS: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. CONCLUSIONS: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. KEY POINTS: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups.

PET/MRI of hypoxia and vascular function in ER-positive breast cancer: correlations with immunohistochemistry.

OBJECTIVES: To explore the relationship between indices of hypoxia and vascular function from 18F-fluoromisonidazole ([18F]-FMISO)-PET/MRI with immunohistochemical markers of hypoxia and vascularity in oestrogen receptor-positive (ER +) breast cancer. METHODS: Women aged > 18 years with biopsy-confirmed, treatment-naïve primary ER + breast cancer underwent [18F]-FMISO-PET/MRI prior to surgery. Parameters of vascular function were derived from DCE-MRI using the extended Tofts model, whilst hypoxia was assessed using the [18F]-FMISO influx rate constant, Ki. Histological tumour sections were stained with CD31, hypoxia-inducible factor (HIF)-1α, and carbonic anhydrase IX (CAIX). The number of tumour microvessels, median vessel diameter, and microvessel density (MVD) were obtained from CD31 immunohistochemistry. HIF-1α and CAIX expression were assessed using histoscores obtained by multiplying the percentage of positive cells stained by the staining intensity. Regression analysis was used to study associations between imaging and immunohistochemistry variables. RESULTS: Of the lesions examined, 14/22 (64%) were ductal cancers, grade 2 or 3 (19/22; 86%), with 17/22 (77%) HER2-negative. [18F]-FMISO Ki associated negatively with vessel diameter (p = 0.03), MVD (p = 0.02), and CAIX expression (p = 0.002), whilst no significant relationships were found between DCE-MRI pharmacokinetic parameters and immunohistochemical variables. HIF-1α did not significantly associate with any PET/MR imaging indices. CONCLUSION: Hypoxia measured by [18F]-FMISO-PET was associated with increased CAIX expression, low MVD, and smaller vessel diameters in ER + breast cancer, further corroborating the link between inadequate vascularity and hypoxia in ER + breast cancer. KEY POINTS: • Hypoxia, measured by [18F]-FMISO-PET, was associated with low microvessel density and small vessel diameters, corroborating the link between inadequate vascularity and hypoxia in ER + breast cancer. • Increased CAIX expression was associated with higher levels of hypoxia measured by [18F]-FMISO-PET. • Morphologic and functional abnormalities of the tumour microvasculature are the major determinants of hypoxia in cancers and support the previously reported perfusion-driven character of hypoxia in breast carcinomas.

Standalone AI for Breast Cancer Detection at Screening Digital Mammography and Digital Breast Tomosynthesis: A Systematic Review and Meta-Analysis.

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.

Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.

BACKGROUND: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-ßAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. CONCLUSIONS: SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).

Diagnostic Accuracy of a Convolutional Neural Network Assessment of Solitary Pulmonary Nodules Compared With PET With CT Imaging and Dynamic Contrast-Enhanced CT Imaging Using Unenhanced and Contrast-Enhanced CT Imaging.

BACKGROUND: Solitary pulmonary nodules (SPNs) measuring 8 to 30 mm in diameter require further workup to determine the likelihood of malignancy. RESEARCH QUESTION: What is the diagnostic performance of a lung cancer prediction convolutional neural network (LCP-CNN) in SPNs using unenhanced and contrast-enhanced CT imaging compared with the current clinical workup? STUDY DESIGN AND METHODS: This was a post hoc analysis of the Single Pulmonary Nodule Investigation: Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography in the Characterisation of Solitary Pulmonary Nodules trial, a prospective multicenter study comparing the diagnostic accuracy of dynamic contrast-enhanced (DCE) CT imaging with PET imaging in SPNs. The LCP-CNN was designed and validated in an external cohort. LCP-CNN-generated risk scores were created from the noncontrast and contrast-enhanced CT scan images from the DCE CT imaging. The gold standard was histologic analysis or 2 years of follow-up. The area under the receiver operating characteristic curves (AUC) were calculated using LCP-CNN score, maximum standardized uptake value, and DCE CT scan maximum enhancement and were compared using the DeLong test. RESULTS: Two hundred seventy participants (mean ± SD age, 68.3 ± 8.8 years; 49% women) underwent PET with CT scan imaging and DCE CT imaging with CT scan data available centrally for LCP-CNN analysis. The accuracy of the LCP-CNN on the noncontrast images (AUC, 0.83; 95% CI, 0.79-0.88) was superior to that of DCE CT imaging (AUC, 0.76; 95% CI, 0.69-0.82; P = .03) and equal to that of PET with CT scan imaging (AUC, 0.86; 95% CI, 0.81-0.90; P = .35). The presence of contrast resulted in a small reduction in diagnostic accuracy, with the AUC falling from 0.83 (95% CI, 0.79-0.88) on the noncontrast images to 0.80 to 0.83 after contrast (P < .05 for 240 s after contrast only). INTERPRETATION: An LCP-CNN algorithm provides an AUC equivalent to PET with CT scan imaging in the diagnosis of solitary pulmonary nodules. TRIAL REGISTRATION: ClinicalTrials.gov Identifier; No.: NCT02013063.

Evaluation of pretreatment ADC values as predictors of treatment response to neoadjuvant chemotherapy in patients with breast cancer - a multicenter study.

BACKGROUND: Magnetic resonance imaging (MRI) can be used to diagnose breast cancer. Diffusion weighted imaging (DWI) and the apparent diffusion coefficient (ADC) can reflect tumor microstructure in a non-invasive manner. The correct prediction of response of neoadjuvant chemotherapy (NAC) is crucial for clinical routine. Our aim was to compare ADC values between patients with pathological complete response (pCR) and non-responders based upon a multi-center design to improve the correct patient selection, which patient would more benefit from NAC and which patient would not. METHODS: For this study, data from 4 centers (from Japan, Brazil, Spain and United Kingdom) were retrospectively acquired. The time period was overall 2003-2019. The patient sample comprises 250 patients (all female; median age, 50.5). In every case, pretreatment breast MRI with DWI was performed. pCR was assessed by experienced pathologists in every center using the surgical specimen in the clinical routine work up. pCR was defined as no residual invasive disease in either breast or axillary lymph nodes after NAC. ADC values between the group with pCR and those with no pCR were compared using the Mann-Whitney U test (two-group comparisons). Univariable and multivariabe logistic regression analysis was performed to predict pCR status. RESULTS: Overall, 83 patients (33.2%) achieved pCR. The ADC values of the patient group with pCR were lower compared with patients without pCR (0.98 ± 0.23 × 10- 3 mm2/s versus 1.07 ± 0.24 × 10- 3 mm2/s, p = 0.02). The ADC value achieved an odds ratio of 4.65 (95% CI 1.40-15.49) in univariable analysis and of 3.0 (95% CI 0.85-10.63) in multivariable analysis (overall sample) to be associated with pCR status. The odds ratios differed in the subgroup analyses in accordance with the molecular subtype. CONCLUSIONS: The pretreatment ADC-value is associated with pathological complete response after NAC in breast cancer patients. This could aid in clinical routine to reduce treatment toxicity for patients, who would not benefit from NAC. However, this must be tested in further studies, as the overlap of the ADC values in both groups is too high for clinical prediction.