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To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel

The kidney is the most common solid organ transplant globally and rates continue to climb, driven by the increasing prevalence of end stage renal disease (ESRD). Compounded by advancements in surgical techniques and immunosuppression leading to longer graft survival, radiologists evermore commonly evaluate kidney transplant patients and candidates, underscoring their role along the transplant process. Multiphase computed tomography (CT) with multiplanar and 3D reformatting is the primary method for evaluating renal donor candidates, detailing renal size, vascular/collecting system anatomy, and identifying significant pathologies such as renal vascular diseases and nephrolithiasis. Ultrasound is the preferred initial postoperative imaging modality for graft evaluation due to its low cost, accessibility, noninvasiveness, and lack of radiation. CT and magnetic resonance imaging (MRI) may be useful adjunctive imaging techniques in diagnosing transplant pathology when ultrasound alone is not diagnostic. Kidney transplant complications are categorized by an approximate timeline framework, aiding in differential diagnosis based on onset, duration, and severity and include perinephric fluid collections, graft compression, iatrogenic injuries, vascular compromise, graft rejection, and neoplastic processes. This review discusses imaging strategies and important findings along the transplant timeline, from donor assessment to long-term recipient complications., Competing Interests: Declarations. Conflict of interest: RJG, JD, and LAD, have no financial or other disclosures. AK- Research Grant – GE Healthcare, PanCAN, Bayer; Consultant- Bayer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUND. The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations for small gallbladder polyps support management that is less aggressive than earlier approaches and may help standardize evaluation of polyps by radiologists. OBJECTIVE. The purpose of the present study was to assess the interreader agreement of radiologists in applying SRU recommendations for management of incidental gallbladder polyps on ultrasound. METHODS. This retrospective study included 105 patients (75 women and 30 men; median age, 51 years) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003, and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using the SRU recommendations, assessed one polyp per patient to assign risk category (extremely low risk, low risk, or indeterminate risk) and make a possible recommendation for surgical consultation. Five radiologists were considered less experienced (< 5 years of experience), and five were considered more experienced (≥ 5 years of experience). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. RESULTS. For risk category assignments, interreader agreement was substantial among all readers (k = 0.710), less-experienced readers (k = 0.705), and more-experienced readers (k = 0.692). For surgical consultation recommendations, inter-reader agreement was substantial among all readers (k = 0.795) and more-experienced readers (k = 0.740) and was almost perfect among less-experienced readers (k = 0.811). Of 10 readers, a median of 5.0 (IQR, 2.0-8.0), 4.0 (IQR, 2.0-7.0), and 0.0 (IQR, 0.0-0.0) readers classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the percentage of polyps classified as extremely low risk ranged from 32% to 72%; as low risk, from 24% to 65%; and as indeterminate risk, from 0% to 8%. Of 10 readers, a median of zero change to 0 (IQR, 0.0-1.0) readers recommended surgical consultation; the percentage of polyps receiving a recommendation for surgical consultation ranged from 4% to 22%. Of a total of 105 polyps, 102 were nonneo-plastic and three were neoplastic (all benign). Based on readers' most common assessments for nonneoplastic polyps, the risk category was extremely low risk for 53 polyps, low risk for 48 polyps, and indeterminate risk for one polyp; surgical consultation was recommended for 16 polyps. CONCLUSION. Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. CLINICAL IMPACT. The findings support the overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.

Purpose This special report outlines a retrospective observational study of CT fractional flow reserve (CT-FFR) analysis using dual-source coronary CT angiography (CTA) scans performed without heart rate control and its impact on clinical outcomes. Materials and Methods All patients who underwent clinically indicated coronary CTA between August 2020 and August 2021 were included in this retrospective observational study. Scans were performed in the late systolic to early diastolic period without heart rate control and analyzed at the interpreting physician's discretion. Demographics, coronary CTA features, and rates of invasive coronary angiography (ICA), percutaneous coronary intervention (PCI), myocardial infarction, and all-cause death at 3 months were assessed by chart review. Results During the study period, 3098 patients underwent coronary CTA, of whom 113 with coronary bypass grafting were excluded. Of the remaining 2985 patients, 292 (9.7%) were referred for CT-FFR analysis. Two studies (0.7%) were rejected from CT-FFR analysis, and six (2.1%) analyses did not evaluate the lesion of concern. A total of 160 patients (56.3%) had CT-FFR greater than 0.80. Among patients with significant stenosis at coronary CTA, patients who underwent CT-FFR analysis presented with lower rates of ICA (74.5% vs 25.5%, P = .04) and PCI (78.9% vs 21.1%, P = .05). Conclusion CT-FFR was implemented in patients not requiring heart rate control by using dual-source coronary CTA acquisition and showed the potential to decrease rates of ICA and PCI without compromising safety in patients with significant stenosis and an average heart rate of 65 beats per minute. Keywords: Angiography, CT, CT-Angiography, Fractional Flow Reserve, Cardiac, Heart, Arteriosclerosis Supplemental material is available for this article. © RSNA, 2024.

Hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) is highly suited for abdominal pathologies. A precise co-registration of anatomic and metabolic data is possible thanks to the simultaneous acquisition, leading to accurate imaging. The literature shows that PET/MRI is at least as good as PET/CT and even superior for some indications, such as primary hepatic tumors, distant metastasis evaluation, and inflammatory bowel disease. PET/MRI allows whole-body staging in a single session, improving health care efficiency and patient comfort., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Incidentally detected gallbladder polyps are commonly encountered when performing upper abdominal ultrasound. Our purpose was to estimate the life expectancy (LE) benefit of ultrasound-based gallbladder surveillance in patients with small (6-7 to <10 mm), incidentally detected gallbladder polyps, accounting for patient sex, age, and comorbidity level., Methods: We developed a decision-analytic Markov model to evaluate hypothetical cohorts of women and men with small gallbladder polyps, with varying age (66-80 years) and comorbidity level (none, mild, moderate, severe). Drawing from current evidence, in the base case, we assumed no increased risk of gallbladder cancer in patients with small gallbladder polyps. To estimate maximal possible LE gains from surveillance, we assumed perfect cancer control consequent to 5 years of surveillance. We varied key assumptions including cancer risk and test performance characteristics in sensitivity analysis., Results: Projected LE gains from surveillance were <3 days across most cohorts and scenarios evaluated. For 66- and 80-year-olds with no comorbidities, LE gains were 1.46 and 1.45 days, respectively, for women, and 0.67 and 0.75 days for men. With 10 years of surveillance, LE gains increased to 2.94 days for 66-year-old women with no comorbidities (men: 1.35 days). If we assumed a 10% increase in gallbladder cancer risk among individuals with polyps, LE gains increased slightly to 1.60 days for 66-year-old women with no comorbidities (men: 0.74 days). Results were sensitive to test performance and surgical mortality., Discussion: Even under unrealistic, optimistic assumptions of cancer control, ultrasound surveillance of incidentally detected small gallbladder polyps provided limited benefit., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Deceased liver donor transplantation is increasing in prevalence resulting in larger volumes of posttransplant imaging studies. Radiologists should familiarize themselves with the spectrum of normal posttransplant anatomy. The key findings can be categorized into 4 systems reconstructed during surgery: hepatic venous, portal venous, hepatic arterial, and biliary ductal systems. Here we discuss the imaging findings seen with the most common surgical techniques, those that can be misidentified as complications, and some less common variations resulting from different surgical techniques., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The COVID-19 pandemic disrupted the delivery of preventative care and management of acute diseases. This study assesses the effect of the COVID-19 pandemic on coronary calcium score and coronary CT angiography imaging volume., Materials and Methods: A single institution retrospective review of consecutive patients presenting for coronary calcium score or coronary CT angiography examinations between January 1, 2020 to January 4, 2022 was performed. The weekly volume of calcium score and coronary CT angiogram exams were compared., Results: In total, 1,817 coronary calcium score CT and 5,895 coronary CT angiogram examinations were performed. The average weekly volume of coronary CTA and coronary calcium score CT exams decreased by up to 83% and 100%, respectively, during the COVID-19 peak period compared to baseline (P < 0.0001). The post-COVID recovery through 2020 saw weekly coronary CTA volumes rebound to 86% of baseline (P = 0.024), while coronary calcium score CT volumes remained muted at only a 53% recovery (P < 0.001). In 2021, coronary CTA imaging eclipsed pre-COVID rates (P = 0.012), however coronary calcium score CT volume only reached 67% of baseline (P < 0.001)., Conclusions: A significant decrease in both coronary CTA and coronary calcium score CT volume occurred during the peak-COVID-19 period. In 2020 and 2021, coronary CTA imaging eventually superseded baseline rates, while coronary calcium score CT volumes only reached two thirds of baseline. These findings highlight the importance of resumption of screening exams and should prompt clinicians to be aware of potential undertreatment of patients with coronary artery disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: This learning opportunity was designed to provide an interactive, virtual, educational anesthesiology program for interested medical students and to offer an opportunity to learn more about an institutional culture through a question and answer (Q&A) with program faculty preceptors for the 2020-2021 anesthesiology residency application cycle. We sought to identify if this virtual learning program was a valuable educational tool through a survey., Methods: A short Likert-scale survey was sent to medical students before and after participation in a session using REDCap electronic data capture tool. We designed the survey to assess the program's self-reported effect on participants' anesthesiology knowledge, and whether the program design was successful in creating a collaborative experience while also providing a forum to explore residency programs., Results: All respondents found the call useful in building anesthesiology knowledge and networking, and 42 (86%) found the call helpful in deciding where to apply for residency. Overall, 100% of respondents found the call useful, collaborative, engaging, and important to define critical thinking skills., Conclusions: The framework used for this program-virtual asynchronous and synchronous problem-based learning-can be applied broadly with potential benefit to medical student participants challenged by the cancellation of clinical rotations., Competing Interests: Conflicts of Interest: None.

Importance: Lung cancer screening with chest computed tomography (CT) prevents lung cancer death; however, fewer than 5% of eligible Americans are screened. CXR-LC, an open-source deep learning tool that estimates lung cancer risk from existing chest radiograph images and commonly available electronic medical record (EMR) data, may enable automated identification of high-risk patients as a step toward improving lung cancer screening participation., Objective: To validate CXR-LC using EMR data to identify individuals at high-risk for lung cancer to complement 2022 US Centers for Medicare & Medicaid Services (CMS) lung cancer screening eligibility guidelines., Design, Setting, and Participants: This prognostic study compared CXR-LC estimates with CMS screening guidelines using patient data from a large US hospital system. Included participants were persons who currently or formerly smoked cigarettes with an outpatient posterior-anterior chest radiograph between January 1, 2013, and December 31, 2014, with no history of lung cancer or screening CT. Data analysis was performed between May 2021 and June 2022., Exposures: CXR-LC lung cancer screening eligibility (previously defined as having a 3.297% or greater 12-year risk) based on inputs (chest radiograph image, age, sex, and whether currently smoking) extracted from the EMR., Main Outcomes and Measures: 6-year incident lung cancer., Results: A total of 14 737 persons were included in the study population (mean [SD] age, 62.6 [6.8] years; 7154 [48.5%] male; 204 [1.4%] Asian, 1051 [7.3%] Black, 432 [2.9%] Hispanic, 12 330 [85.2%] White) with a 2.4% rate of incident lung cancer over 6 years (361 patients with cancer). CMS eligibility could be determined in 6277 patients (42.6%) using smoking pack-year and quit-date from the EMR. Patients eligible by both CXR-LC and 2022 CMS criteria had a high rate of lung cancer (83 of 974 patients [8.5%]), higher than those eligible by 2022 CMS criteria alone (5 of 177 patients [2.8%]; P < .001). Patients eligible by CXR-LC but not 2022 CMS criteria also had a high 6-year incidence of lung cancer (121 of 3703 [3.3%]). In the 8460 cases (57.4%) where CMS eligibility was unknown, CXR-LC eligible patients had a 5-fold higher rate of lung cancer than ineligible (127 of 5177 [2.5%] vs 18 of 2283 [0.5%]; P < .001). Similar results were found in subgroups, including female patients and Black persons., Conclusions and Relevance: Using routine chest radiographs and other data automatically extracted from the EMR, CXR-LC identified high-risk individuals who may benefit from lung cancer screening CT.

Hemorrhagic cholecystitis is a rare disorder associated with considerable morbidity and mortality. The clinical presentation of hemorrhagic cholecystitis is non-specific and imaging findings can be difficult to accurately interpret without a high level of suspicion. Most recent reports of hemorrhagic cholecystitis have been associated with concurrent therapeutic anticoagulation. Here, we report imaging findings of a case of acute, spontaneous hemorrhagic cholecystitis in a 67-year-old male patient admitted for hypoxic respiratory failure secondary to COVID-19 pneumonia., (© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Numerous abdominal manifestations have been reported in patients with coronavirus disease 2019 (COVID-19), including involvement of the luminal gastrointestinal (GI) tract, hepatobiliary system, pancreas, kidneys, spleen, and blood vessels. Although most of the associated radiological abnormalities are nonspecific without distinguishing imaging features to suggest COVID-19, unique presentations such as findings of bowel ischemia preceding gross findings of bowel necrosis have been reported. Awareness of the spectrum of abdominal manifestations of COVID-19 allows radiologists to optimize their search pattern and to raise the possibility of this etiology when appropriate. Awareness of the possible abdominal manifestations of COVID-19 should enhance detection by radiologists and improve patient care. This review provides a comprehensive overview with illustrative imaging examples of COVID-19 in the abdomen., (© 2022 Elsevier Inc. All rights reserved.)

Aim: To evaluate the change in diagnosis rates, disease severity at presentation, and treatment of acute appendicitis and diverticulitis during the COVID-19 shutdown., Materials and Methods: Following institutional review board approval, 6,002 CT examinations performed at five hospitals for suspected acute appendicitis and/or diverticulitis over the 12 weeks preceding and following the shutdown were reviewed retrospectively. Semi-automated language analysis (SALA) of the report classified 3,676 CT examinations as negative. Images of the remaining 2,326 CT examinations were reviewed manually and classified as positive or negative. Positive cases were graded as non-perforated; perforated, contained; and perforated, free., Results: CT examinations performed for suspected appendicitis and/or diverticulitis decreased from 3,558 to 2,200 following the shutdown. The rates of positive diagnoses before and after shutdown were 4% (144) and 4% (100) for appendicitis and 8% (284) and 7% (159) for diverticulitis (p>0.2 for both). For positive CT examinations, the rates of perforation, hospitalisation, surgery, and catheter drainage changed by -2%, -3%, -2%, and -3% for appendicitis (n=244, p>0.3 for all) and +6% (p=0.2) +9% (p=0.06), +4% (p=0.01) and +1% (p=0.6) for diverticulitis (n=443)., Conclusion: CT examinations performed for suspected appendicitis or diverticulitis declined after the shutdown, likely reflecting patients leaving urban centres and altered triage of non-COVID-19 patients. The diagnosis rates, disease severity at presentation, and treatment approach otherwise remained mostly unchanged., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Structured reports offer overall improvement in quality and safety, largely centered upon more effective communication. Structured reporting is helpful to trainees as a method to develop organized search patterns and include pertinent positive and negative findings. However, limitations of structured report use include lack of development of individualized search patterns and failure to recognize key elements of the report to be formulated in the impression. Instruction on the value of a structured reporting approach, its impact on patient care and clinical service, and compliance with billing requirements must be balanced with early and consistent feedback on appropriate use and reporting errors. It is incumbent upon radiology educators to integrate and optimize structured reporting in the learning environment. This manuscript addresses the impact of structured reporting on radiology education, reviewing quality and safety considerations, detailing benefits and drawbacks for trainees, and offering strategies for optimizing the use of structured reporting/templates in the training environment., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

We sought to determine relative utilization of abdominal imaging modalities in coronavirus disease 2019 (COVID-19) patients at a single institution during the first surge and evaluate whether abdominal magnetic resonance imaging (MRI) changed diagnosis and management. 1107 COVID-19 patients who had abdominal imaging were analyzed for modality and imaging setting. Patients who underwent abdominal MRI were reviewed to determine impact on management. Of 2259 examinations, 80% were inpatient, 14% were emergency, and 6% were outpatient consisting of 55% radiograph (XR), 31% computed tomography (CT), 13% ultrasound (US), and 0.6% MRI. Among 1107 patients, abdominal MRI was performed in 12 within 100 days of positive SARS-CoV-2 PCR. Indications were unrelated to COVID-19 in 75% while MRI was performed for workup of acute liver dysfunction in 25%. In 1 of 12 patients, MRI resulted in change to management unrelated to COVID-19 diagnosis. During the first surge of COVID-19 at one institution, the most common abdominal imaging examinations were radiographs and CT followed by ultrasound with the majority being performed as inpatients. Future COVID-19 surges may place disproportionate demands on inpatient abdominal radiography and CT resources. Abdominal MRI was rarely performed and did not lead to change in diagnosis or management related to COVID-19 but needs higher patient numbers for accurate assessment of utility.

The role of imaging in clinically staging colorectal cancer has grown substantially in the 21 st century with more widespread availability of multi-row detector computed tomography (CT), high-resolution magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI), and integrated positron-emission tomography (PET)/CT. In contrast to staging many other cancers, increasing colorectal cancer stage does not highly correlate with survival. As has been the case previously, clinical practice incorporates advances in staging and it is used to guide therapy before adoption into international staging guidelines. Emerging imaging techniques show promise to become part of future staging standards., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the effect on procedure time and patient radiation indices of replacing helical acquisitions for needle guidance during thoracic needle biopsy (TNB) with intermittent single-rotation axial acquisitions., Materials and Methods: This retrospective intervention study included 215 consecutive TNBs performed by a single operator from 2014 to 2018. Characteristics of patients, lesions, and procedures were compared between TNBs guided only by helical acquisitions initiated in the control room (helical group, n=141) and TNBs guided in part by intermittent single-rotation axial computed tomography controlled by foot pedal (single-rotation group, n=74). Procedure time and patient radiation indices were primary outcomes, complications, and radiologist radiation dose were secondary outcomes., Results: Patient, lesion, and procedural characteristics did not differ between helical and single-rotation groups. Use of single-rotation axial acquisitions decreased procedure time by 10.5 minutes (95% confidence interval [CI]: 8.2-12.8 min) or 27% (95% CI: 22%-32%; P<0.001). Patient dose in cumulative volume computed tomography dose index decreased by 23% (95% CI: 12%-33%) or 8 mGy (95% CI: 4.3-31.6 mGy; P=0.01). Dose-length product decreased by 50% (95% CI: 40%-60%) or 270 mGy cm (95% CI: 195-345 mGy cm; P<0.001). No operator radiation exposure was detected. Rate of diagnostic result, pneumothorax, hemoptysis, and hemorrhage did not differ between groups., Conclusions: Replacing helical acquisitions with intermittent single-rotation axial acquisitions significantly decreases TNB procedure time and patient radiation indices without adversely affecting diagnostic rate, procedural complications, or operator radiation dose., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To perform a retrospective review of Coronary Artery Disease Reporting and Data System (CAD-RADS) adoption at a high-volume cardiac CT service., Materials and Methods: In this retrospective study, the adoption of CAD-RADS in 6562 coronary CT angiography (CTA) reports from January 1, 2017, to February 13, 2020, was evaluated. Reports without CAD-RADS were classified as opt-outs or exceptions to CAD-RADS. CAD-RADS classifications were retrospectively assigned to the opt-outs and the clinical indications for coronary CTA., Results: CAD-RADS scores were reported in 95% (6264 of 6562) of cases. Among the 5% ( n = 298) of reports not reported according to CAD-RADS, 58% ( n = 172) were considered opt-outs and 42% ( n = 126) were exceptions. Cases with higher degree of stenosis, stents, and coronary artery bypass grafts (CABGs) occurred more often in opt-outs versus reports with CAD-RADS (odds ratio [OR], 8.3 [95% CI: 1.6, 42.1]; P < .001). The quarterly opt-out rate decreased over consecutive quarters in the 1st year (OR, 0.77 [95% CI: 0.61, 0.96]; P = .01), then stabilized. Quarterly opt-out rate for patients with stents decreased over time (OR, 0.82 [95% CI: 0.73, 0.92]; P = .008), as did the opt-out rates in patients with CABG (OR, 0.83 [95% CI: 0.76, 0.91]; P < .001). Exceptions ( n = 126) included coronary dissections (44%), anomalous coronary arteries (41%), coronary artery aneurysms or pseudoaneurysms (10%), vasculitis (2%), stent complications (2%), and extrinsic compression of grafts (2%)., Conclusion: CAD-RADS was adopted rapidly and widely. Readers opted out of its use most often in complex cases of CAD, and the most common exceptions were coronary dissections and anomalous coronary artery. Keywords: Coronary Arteries, CT Angiography© RSNA, 2021., Competing Interests: Disclosures of Conflicts of Interest: A.K.T. disclosed no relevant relationships. V.T. disclosed no relevant relationships. R.J.G. disclosed no relevant relationships. J.D. disclosed no relevant relationships. S. Gupta disclosed no relevant relationships. S. Garrana Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author receives author royalties from Elsevier, unrelated to this study. Other relationships: disclosed no relevant relationships. V.K. disclosed no relevant relationships. A.T.R. disclosed no relevant relationships. M.T.L. disclosed no relevant relationships. N.M. disclosed no relevant relationships. U.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author received consultancy fees from Recor and Duke University; author’s institution has grants/grants pending from KOWA, Astra Zeneca, Medimmune, and HeartFlow. Other relationships: disclosed no relevant relationships. S.H. disclosed no relevant relationships. B.G. Activities related to the present article: author’s institution has grant support from Siemens Healthineers for cardiac CT research unrelated to this work; author is on the editorial board of Radiology: Cardiothoracic Imaging (not involved in handling of the article). Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Myeloperoxidase (MPO) is a circulating cardiovascular disease (CVD) biomarker used to estimate clinical risk and patient prognosis. Current enzyme-linked immunosorbent assays (ELISA) for MPO concentration are costly and time-intensive. Here we report a novel bioluminescence assay, designated MPO activity on a polymer surface (MAPS), for measuring MPO activity in human plasma samples using the bioluminescent substrate L-012. The method delivers a result in under an hour and is resistant to confounding effects from endogenous MPO inhibitors. In a pilot clinical study, we compared MAPS and two clinical ELISAs using 72 plasma samples from cardiac catheterization patients. Results from parallel MAPS and ELISAs were concordant within 2±11 μg l(-1) MPO with similar uncertainty and reproducibility. Results between parallel MAPS and ELISA were in better agreement than those between independent ELISAs. MAPS may provide an inexpensive and rapid assay for determining MPO activity in plasma samples from patients with CVD or potentially other immune and inflammatory disorders.

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.

Patients with triple-negative breast cancer (TNBC) - defined by lack of estrogen receptor and progesterone receptor expression as well as lack of human epidermal growth factor receptor 2 (HER2) amplification - have a poor prognosis. There is a need for targeted therapies to treat this condition. TNBCs frequently harbor mutations in TP53, resulting in loss of the G1 checkpoint and reliance on checkpoint kinase 1 (Chk1) to arrest cells in response to DNA damage. Previous studies have shown that inhibition of Chk1 in a p53-deficient background results in apoptosis [corrected] in response to DNA damage. We therefore tested whether inhibition of Chk1 could potentiate the cytotoxicity of the DNA damaging agent irinotecan in TNBC using xenotransplant tumor models. Tumor specimens from patients with TNBC were engrafted into humanized mammary fat pads of immunodeficient mice to create 3 independent human-in-mouse TNBC lines: 1 WT (WU-BC3) and 2 mutant for TP53 (WU-BC4 and WU-BC5). These lines were tested for their response to irinotecan and a Chk1 inhibitor (either UCN-01 or AZD7762), either as single agents or in combination. The combination therapy induced checkpoint bypass and apoptosis in WU-BC4 and WU-BC5, but not WU-BC3, tumors. Moreover, combination therapy inhibited tumor growth and prolonged survival of mice bearing the WU-BC4 line, but not the WU-BC3 line. In addition, knockdown of p53 sensitized WU-BC3 tumors to the combination therapy. These results demonstrate that p53 is a major determinant of how TNBCs respond to therapies that combine DNA damage with Chk1 inhibition.

Background: Positron emission tomography (PET) allows sensitive, non-invasive analysis of the distribution of radiopharmaceutical tracers labeled with positron (β(+))-emitting radionuclides in small animals and humans. Upon β(+) decay, the initial velocity of high-energy β(+) particles can momentarily exceed the speed of light in tissue, producing Cerenkov radiation that is detectable by optical imaging, but is highly absorbed in living organisms., Principal Findings: To improve optical imaging of Cerenkov radiation in biological systems, we demonstrate that Cerenkov radiation from decay of the PET isotopes (64)Cu and (18)F can be spectrally coupled by energy transfer to high Stokes-shift quantum nanoparticles (Qtracker705) to produce highly red-shifted photonic emissions. Efficient energy transfer was not detected with (99m)Tc, a predominantly γ-emitting isotope. Similar to bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), herein we define the Cerenkov radiation energy transfer (CRET) ratio as the normalized quotient of light detected within a spectral window centered on the fluorophore emission divided by light detected within a spectral window of the Cerenkov radiation emission to quantify imaging signals. Optical images of solutions containing Qtracker705 nanoparticles and [(18)F]FDG showed CRET ratios in vitro as high as 8.8±1.1, while images of mice with subcutaneous pseudotumors impregnated with Qtracker705 following intravenous injection of [(18)F]FDG showed CRET ratios in vivo as high as 3.5±0.3., Conclusions: Quantitative CRET imaging may afford a variety of novel optical imaging applications and activation strategies for PET radiopharmaceuticals and other isotopes in biomaterials, tissues and live animals.

We have generated extreme ionizing radiation resistance in a relatively sensitive bacterial species, Escherichia coli, by directed evolution. Four populations of Escherichia coli K-12 were derived independently from strain MG1655, with each specifically adapted to survive exposure to high doses of ionizing radiation. D(37) values for strains isolated from two of the populations approached that exhibited by Deinococcus radiodurans. Complete genomic sequencing was carried out on nine purified strains derived from these populations. Clear mutational patterns were observed that both pointed to key underlying mechanisms and guided further characterization of the strains. In these evolved populations, passive genomic protection is not in evidence. Instead, enhanced recombinational DNA repair makes a prominent but probably not exclusive contribution to genome reconstitution. Multiple genes, multiple alleles of some genes, multiple mechanisms, and multiple evolutionary pathways all play a role in the evolutionary acquisition of extreme radiation resistance. Several mutations in the recA gene and a deletion of the e14 prophage both demonstrably contribute to and partially explain the new phenotype. Mutations in additional components of the bacterial recombinational repair system and the replication restart primosome are also prominent, as are mutations in genes involved in cell division, protein turnover, and glutamate transport. At least some evolutionary pathways to extreme radiation resistance are constrained by the temporally ordered appearance of specific alleles.

The excited state of an organic molecule is a crossroads which can lead to many directions, such as non-radiative emission as heat, fluorescence, intersystem crossing and phosphorescence. Due to the unpredictable nature of the excited molecular structure, manipulation of this represents significant challenges for physicists and chemists. However, the successful management of the excited state provides a number of benefits with innumerable applications to fields like photonics and medicine. One such property of the excited state with powerful ramifications in medical diagnostics is fluorescence lifetime.