Hypoxia and perfusion in breast cancer: simultaneous assessment using PET/MR imaging.

OBJECTIVES: Hypoxia is associated with poor prognosis and treatment resistance in breast cancer. However, the temporally variant nature of hypoxia can complicate interpretation of imaging findings. We explored the relationship between hypoxia and vascular function in breast tumours through combined 18F-fluoromisonidazole (18 F-FMISO) PET/MRI, with simultaneous assessment circumventing the effect of temporal variation in hypoxia and perfusion. METHODS: Women with histologically confirmed, primary breast cancer underwent a simultaneous 18F-FMISO-PET/MR examination. Tumour hypoxia was assessed using influx rate constant Ki and hypoxic fractions (%HF), while parameters of vascular function (Ktrans, kep, ve, vp) and cellularity (ADC) were derived from dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI, respectively. Additional correlates included histological subtype, grade and size. Relationships between imaging variables were assessed using Pearson correlation (r). RESULTS: Twenty-nine women with 32 lesions were assessed. Hypoxic fractions > 1% were observed in 6/32 (19%) cancers, while 18/32 (56%) tumours showed a %HF of zero. The presence of hypoxia in lesions was independent of histological subtype or grade. Mean tumour Ktrans correlated negatively with Ki (r = - 0.38, p = 0.04) and %HF (r = - 0.33, p = 0.04), though parametric maps exhibited intratumoural heterogeneity with hypoxic regions colocalising with both hypo- and hyperperfused areas. No correlation was observed between ADC and DCE-MRI or PET parameters. %HF correlated positively with lesion size (r = 0.63, p = 0.001). CONCLUSION: Hypoxia measured by 18F-FMISO-PET correlated negatively with Ktrans from DCE-MRI, supporting the hypothesis of perfusion-driven hypoxia in breast cancer. Intratumoural hypoxia-perfusion relationships were heterogeneous, suggesting that combined assessment may be needed for disease characterisation, which could be achieved using simultaneous multimodality imaging. KEY POINTS: • At the tumour level, hypoxia measured by 18F-FMISO-PET was negatively correlated with perfusion measured by DCE-MRI, which supports the hypothesis of perfusion-driven hypoxia in breast cancer. • No associations were observed between 18F-FMISO-PET parameters and tumour histology or grade, but tumour hypoxic fractions increased with lesion size. • Intratumoural hypoxia-perfusion relationships were heterogeneous, suggesting that the combined hypoxia-perfusion status of tumours may need to be considered for disease characterisation, which can be achieved via simultaneous multimodality imaging as reported here.

A Coronavirus Disease 2019 Pandemic Pivot: Development of the American Board of Anesthesiology's Virtual APPLIED Examination.

In 2020, the coronavirus disease 2019 (COVID-19) pandemic interrupted the administration of the APPLIED Examination, the final part of the American Board of Anesthesiology (ABA) staged examination system for initial certification. In response, the ABA developed, piloted, and implemented an Internet-based "virtual" form of the examination to allow administration of both components of the APPLIED Exam (Standardized Oral Examination and Objective Structured Clinical Examination) when it was impractical and unsafe for candidates and examiners to travel and have in-person interactions. This article describes the development of the ABA virtual APPLIED Examination, including its rationale, examination format, technology infrastructure, candidate communication, and examiner training. Although the logistics are formidable, we report a methodology for successfully introducing a large-scale, high-stakes, 2-element, remote examination that replicates previously validated assessments.

Evaluation of dyspnea of unknown etiology in HIV patients with cardiopulmonary exercise testing and cardiovascular magnetic resonance imaging.

AIM: Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. METHODS AND RESULTS: Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). CONCLUSION: Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.

A Meta-analysis of the Diagnostic Performance of Diffusion MRI for Breast Lesion Characterization.

Background Various techniques are available to assess diffusion properties of breast lesions as a marker of malignancy at MRI. The diagnostic performance of these diffusion markers has not been comprehensively assessed. Purpose To compare by meta-analysis the diagnostic performance of parameters from diffusion-weighted imaging (DWI), diffusion-tensor imaging (DTI), and intravoxel incoherent motion (IVIM) in the differential diagnosis of malignant and benign breast lesions. Materials and Methods PubMed and Embase databases were searched from January to March 2018 for studies in English that assessed the diagnostic performance of DWI, DTI, and IVIM in the breast. Studies were reviewed according to eligibility and exclusion criteria. Publication bias and heterogeneity between studies were assessed. Pooled summary estimates for sensitivity, specificity, and area under the curve were obtained for each parameter by using a bivariate model. A subanalysis investigated the effect of MRI parameters on diagnostic performance by using a Student t test or a one-way analysis of variance. Results From 73 eligible studies, 6791 lesions (3930 malignant and 2861 benign) were included. Publication bias was evident for studies that evaluated apparent diffusion coefficient (ADC). Significant heterogeneity (P < .05) was present for all parameters except the perfusion fraction (f). The pooled sensitivity, specificity, and area under the curve for ADC was 89%, 82%, and 0.92, respectively. The highest performing parameter for DTI was the prime diffusion coefficient (λ1), and pooled sensitivity, specificity, and area under the curve was 93%, 90%, and 0.94, respectively. The highest performing parameter for IVIM was tissue diffusivity (D), and the pooled sensitivity, specificity, and area under the curve was 88%, 79%, and 0.90. Choice of MRI parameters had no significant effect on diagnostic performance. Conclusion Diffusion-weighted imaging, diffusion-tensor imaging, and intravoxel incoherent motion have comparable diagnostic accuracy with high sensitivity and specificity. Intravoxel incoherent motion is comparable to apparent diffusion coefficient. Diffusion-tensor imaging is potentially promising but to date the number of studies is limited. © RSNA, 2019 Online supplemental material is available for this article.

Maternal high-fat diet alters angiotensin II receptors and causes changes in fetal and neonatal rats†.

Maternal high-fat diet (HFD) during pregnancy is linked to cardiovascular diseases in postnatal life. The current study tested the hypothesis that maternal HFD causes myocardial changes through angiotensin II receptor (AGTR) expression modulation in fetal and neonatal rat hearts. The control group of pregnant rats was fed a normal diet and the treatment group of pregnant rats was on a HFD (60% kcal fat). Hearts were isolated from embryonic day 21 fetuses (E21) and postnatal day 7 pups (PD7). Maternal HFD decreased the body weight of the offspring in both E21 and PD7. The ratio of heart weight to body weight was increased in E21, but not PD7, when compared to the control group. Transmission electron microscopy revealed disorganized myofibrils and effacement of mitochondria cristae in the treatment group. Maternal HFD decreased S-phase and increased G1-phase of the cellular cycle for fetal and neonatal cardiac cells. Molecular markers of cardiac hypertrophy, such as Nppa and Myh7, were found to be increased in the treatment group. There was an associated increase in Agtr2 mRNA and protein, whereas Agtr1a mRNA and AGTR1 protein were decreased in HFD fetal and neonatal hearts. Furthermore, maternal HFD decreased glucocorticoid receptors (GRs) binding to glucocorticoid response elements at the Agtr1a and Agtr2 promoter, which correlated with downregulation of GR in fetal and neonatal hearts. These findings suggest that maternal HFD may promote premature termination of fetal and neonatal cardiomyocyte proliferation and compensatory hypertrophy through intrauterine modulation of AGTR1 and AGTR2 expression via GR dependent mechanism.

The American Board of Anesthesiology's Standardized Oral Examination for Initial Board Certification.

The American Board of Anesthesiology (ABA) has been administering an oral examination as part of its initial certification process since 1939. Among the 24 member boards of the American Board of Medical Specialties, 13 other boards also require passing an oral examination for physicians to become certified in their specialties. However, the methods used to develop, administer, and score these examinations have not been published. The purpose of this report is to describe the history and evolution of the anesthesiology Standardized Oral Examination, its current examination development and administration, the psychometric model and scoring, physician examiner training and auditing, and validity evidence. The many-facet Rasch model is the analytic method used to convert examiner ratings into scaled scores for candidates and takes into account how difficult grader examiners are and the difficulty of the examination tasks. Validity evidence of the oral examination includes that it measures aspects of clinical performance not accounted for by written certifying examinations, and that passing the oral examination is associated with a decreased risk of subsequent license actions against the anesthesiologist. Explaining the details of the Standardized Oral Examination provides transparency about this component of initial certification in anesthesiology.

Association Between Participation and Performance in MOCA Minute and Actions Against the Medical Licenses of Anesthesiologists.

BACKGROUND: In January 2016, as part of the Maintenance of Certification in Anesthesiology (MOCA) program, the American Board of Anesthesiology launched MOCA Minute, a web-based longitudinal assessment, to supplant the former cognitive examination. We investigated the association between participation and performance in MOCA Minute and disciplinary actions against medical licenses of anesthesiologists. METHODS: All anesthesiologists with time-limited certificates (ie, certified in 2000 or after) who were required to register for MOCA Minute in 2016 were followed up through December 31, 2016. The incidence of postcertification prejudicial license actions was compared between those who did and did not register and compared between registrants who did and did not meet the MOCA Minute performance standard. RESULTS: The cumulative incidence of license actions was 1.2% (245/20,006) in anesthesiologists required to register for MOCA Minute. Nonregistration was associated with a higher incidence of license actions (hazard ratio, 2.93 [95% confidence interval {CI}, 2.15-4.00]). For the 18,534 (92.6%) who registered, later registration (after June 30, 2016) was associated with a higher incidence of license actions. In 2016, 16,308 (88.0%) anesthesiologists met the MOCA Minute performance standard. Of those not meeting the standard (n = 2226), most (n = 2093, 94.0%) failed because they did not complete the required 120 questions. Not meeting the standard was associated with a higher incidence of license actions (hazard ratio, 1.92 [95% CI, 1.36-2.72]). CONCLUSIONS: Both timely participation and meeting performance standard in MOCA Minute are associated with a lower likelihood of being disciplined by a state medical board.

A Machine Learning-Based Triage Tool for Children With Acute Infection in a Low Resource Setting.

OBJECTIVES: To deploy machine learning tools (random forests) to develop a model that reliably predicts hospital mortality in children with acute infections residing in low- and middle-income countries, using age and other variables collected at hospital admission. DESIGN: Post hoc analysis of a single-center, prospective, before-and-after feasibility trial. SETTING: Rural district hospital in Rwanda, a low-income country in Sub-Sahara Africa. PATIENTS: Infants and children greater than 28 days and less than 18 years of life hospitalized because of an acute infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age, vital signs (heart rate, respiratory rate, and temperature) capillary refill time, altered mental state collected at hospital admission, as well as survival status at hospital discharge were extracted from the trial database. This information was collected for 1,579 adult and pediatric patients admitted to a regional referral hospital with an acute infection in rural Rwanda. Nine-hundred forty-nine children were included in this analysis. We predicted survival in study subjects using random forests, a machine learning algorithm. Five prediction models, all including age plus two to five other variables, were tested. Three distinct optimization criteria of the algorithm were then compared. The in-hospital mortality was 1.5% (n = 14). All five models could predict in-hospital mortality with an area under the receiver operating characteristic curve ranging between 0.69 and 0.8. The model including age, respiratory rate, capillary refill time, altered mental state exhibited the highest predictive value area under the receiver operating characteristic curve 0.8 (95% CI, 0.78-0.8) with the lowest possible number of variables. CONCLUSIONS: A machine learning-based algorithm could reliably predict hospital mortality in a Sub-Sahara African population of 949 children with an acute infection using easily collected information at admission which includes age, respiratory rate, capillary refill time, and altered mental state. Future studies need to evaluate and strengthen this algorithm in larger pediatric populations, both in high- and low-/middle-income countries.

Increasing Evidence-Based Interventions in Patients with Acute Infections in a Resource-Limited Setting: A Before-and-After Feasibility Trial in Gitwe, Rwanda.

OBJECTIVE: To evaluate whether a focused education program and implementation of a treatment bundle increases the rate of early evidence-based interventions in patients with acute infections. DESIGN: Single-center, prospective, before-and-after feasibility trial. SETTING: Emergency department of a sub-Saharan African district hospital. PATIENTS: Patients > 28 days of life admitted to the study hospital for an acute infection. INTERVENTIONS: The trial had three phases (each of four months). Interventions took place during the second (educational program followed by implementation of the treatment bundle) and third (provision of resources to implement treatment bundle) phases. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data were collected at study enrollment; 24, 48, and 72 hours after hospital admission; and at discharge. A total of 1,594 patients were enrolled (pre-intervention, n = 661; intervention I, n = 531; intervention II, n = 402). The rate of early evidence-based interventions per patient during Intervention Phase I was greater than during the pre-intervention phase (74 ± 17 vs. 79 ± 15%, p < 0.001). No difference was detected when data were compared between Intervention Phases I and II (79 ± 15 vs. 80 ± 15%, p = 0.58). No differences in the incidence of blood transfusion (pre-intervention, 6%; intervention I, 7%; intervention II, 7%) or severe adverse events in the first 24 hours (allergic reactions: pre-intervention, 0.2%; intervention I, 0%; intervention II, 0%; respiratory failure: pre-intervention, 2%; intervention I, 2%; intervention II, 2%; acute renal failure: pre-intervention, 2%; intervention I, 2%; intervention II, 1%) were observed. CONCLUSIONS: Our results indicate that a focused education program and implementation of an infection treatment bundle in clinical practice increased the rate of early evidence-based interventions in patients with acute infections (mostly malaria) admitted to a sub-Saharan African district hospital. Provision of material resources did not further increase this rate. While no safety issues were detected, this could be related to the very low disease severity of the enrolled patient population (www.clinicaltrials.gov: NCT02697513).

Association between Performance in a Maintenance of Certification Program and Disciplinary Actions against the Medical Licenses of Anesthesiologists.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: In 2000, the American Board of Anesthesiology (Raleigh, North Carolina) began issuing time-limited certificates requiring renewal every 10 yr through a maintenance of certification program. This study investigated the association between performance in this program and disciplinary actions against medical licenses. METHODS: The incidence of postcertification prejudicial license actions was compared (1) between anesthesiologists certified between 1994 and 1999 (non-time-limited certificates not requiring maintenance of certification) and those certified between 2000 and 2005 (time-limited certificates requiring maintenance of certification); (2) within the non-time-limited cohort, between those who did and did not voluntarily participate in maintenance of certification; and (3) within the time-limited cohort, between those who did and did not complete maintenance of certification requirements within 10 yr. RESULTS: The cumulative incidence of license actions was 3.8% (587 of 15,486). The incidence did not significantly differ after time-limited certificates were introduced (hazard ratio = 1.15; 95% CI, 0.95 to 1.39; for non-time-limited cohort compared with time-limited cohort). In the non-time-limited cohort, 10% (n = 953) voluntarily participated in maintenance of certification. Maintenance of certification participation was associated with a lower incidence of license actions (hazard ratio = 0.60; 95% CI, 0.38 to 0.94). In the time-limited cohort, 90% (n = 5,329) completed maintenance of certification requirements within 10 yr of certificate issuance. Not completing maintenance of certification requirements (n = 588) was associated with a higher incidence of license actions (hazard ratio = 4.61; 95% CI, 3.27 to 6.51). CONCLUSIONS: These findings suggest that meeting maintenance of certification requirements is associated with a lower likelihood of being disciplined by a state licensing agency. The introduction of time-limited certificates in 2000 was not associated with a significant change in the rate of license actions.

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population.

OBJECTIVE: To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population. METHODS: Thirty-patients were imaged at 3 T including DKI (Kapp and Dapp) with b-values 150/450/800/1150/1500 s/mm2 and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics. RESULTS: Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and Dapp were significantly lower and the Kapp and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and Dapp and higher Kapp and MTR compared to normal PZ. MTR showed a moderate correlation to Kapp (r = 0.570) and Dapp (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825). CONCLUSION: ADC, Dapp, Kapp and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease. KEY POINTS: • MTR was significantly higher in PZ and TZ tumours versus normal tissue • K app was significantly lower and D app higher for PZ and TZ tumours • There was no incremental value for DKI/MTI over mono-exponential ADC parameters • No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease • Divergent MTR/DKI values in TZ tumours suggests they offer different functional information.

Three-dimensional black-blood multi-contrast carotid imaging using compressed sensing: a repeatability study.

OBJECTIVE: The purpose of this work is to evaluate the repeatability of a compressed sensing (CS) accelerated multi-contrast carotid protocol at 3 T. MATERIALS AND METHODS: Twelve volunteers and eight patients with carotid disease were scanned on a 3 T MRI scanner using a CS accelerated 3-D black-blood multi-contrast protocol which comprises T 1w, T 2w and PDw without CS, and with a CS factor of 1.5 and 2.0. The volunteers were scanned twice, the lumen/wall area and wall thickness were measured for each scan. Eight patients were scanned once, the inter/intra-observer reproducibility of the measurements was calculated. RESULTS: In the repeated volunteer scans, the interclass correlation coefficient (ICC) for the wall area measurement using a CS factor of 1.5 in PDw, T 1w and T 2w were 0.95, 0.81, and 0.97, respectively. The ICC for lumen area measurement using a CS factor of 1.5 in PDw, T 1w and T 2w were 0.96, 0.92, and 0.96, respectively. In patients, the ICC for inter/intra-observer measurements of lumen/wall area, and wall thickness were all above 0.81 in all sequences. CONCLUSION: The results show a CS accelerated 3-D black-blood multi-contrast protocol is a robust and reproducible method for carotid imaging. Future protocol design could use CS to reduce the scanning time.

Gadofosveset-enhanced thoracic MR venography: a comparative study evaluating steady state imaging versus conventional first-pass time-resolved dynamic imaging.

Background Dedicated blood-pool contrast agents combined with optimal angiographic protocols could improve the diagnostic accuracy of thoracic magnetic resonance angiography (MRA). Purpose To assess the clinical utility of Gadofesveset-enhanced imaging and compare an optimized steady-state (SS) sequence against conventional first-pass dynamic multi-phase (DMP) imaging. Material and Methods Twenty-nine patients (17 men, 12 women; mean age = 42.7, age range = 18-72 years) referred for MR thoracic venography were recruited. Imaging was performed on a 1.5T MRI system. A blood-pool contrast agent (Gadofesveset) was administered intravenously. Thirty temporal phases were acquired using DMP. This was immediately followed by a high-resolution SS sequence. Three radiologists in consensus reviewed seven thoracic vascular segments after randomizing the acquisition order. Image quality, stenoses, thromboses, and artifacts were graded using a categorical scoring system. The image quality for both approaches was compared using Wilcoxon's signed-rank test. McNemar's test was used to compare the proportions of stenosis grades, thrombus and artifacts. Results SS had significantly better image quality than DMP (3.14 ± 0.73 and 2.92 ± 0.60, respectively; P < 0.001). SS identified fewer stenoses (>50%) than DMP; the differences in stenosis categorizations was statistically significant ( P = 0.013). There was no significant difference in the proportions of vessels with thromboses ( P = 0.617). DMP produced more artifacts than SS (101 versus 85); however, the difference was not statistically significant ( P = 0.073). Conclusion Gadofesveset-enhanced thoracic angiography is clinically feasible. SS imaging produces better image quality and fewer artifacts than conventional DMP imaging.

Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) Score With Excess Hospital Mortality in Adults With Suspected Infection in Low- and Middle-Income Countries.

Importance: The quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score has not been well-evaluated in low- and middle-income countries (LMICs). Objective: To assess the association of qSOFA with excess hospital death among patients with suspected infection in LMICs and to compare qSOFA with the systemic inflammatory response syndrome (SIRS) criteria. Design, Settings, and Participants: Retrospective secondary analysis of 8 cohort studies and 1 randomized clinical trial from 2003 to 2017. This study included 6569 hospitalized adults with suspected infection in emergency departments, inpatient wards, and intensive care units of 17 hospitals in 10 LMICs across sub-Saharan Africa, Asia, and the Americas. Exposures: Low (0), moderate (1), or high (≥2) qSOFA score (range, 0 [best] to 3 [worst]) or SIRS criteria (range, 0 [best] to 4 [worst]) within 24 hours of presentation to study hospital. Main Outcomes and Measures: Predictive validity (measured as incremental hospital mortality beyond that predicted by baseline risk factors, as a marker of sepsis or analogous severe infectious course) of the qSOFA score (primary) and SIRS criteria (secondary). Results: The cohorts were diverse in enrollment criteria, demographics (median ages, 29-54 years; males range, 36%-76%), HIV prevalence (range, 2%-43%), cause of infection, and hospital mortality (range, 1%-39%). Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. Compared with a low or moderate score, a high qSOFA score was associated with increased risk of death overall (19% vs 6%; difference, 13% [95% CI, 11%-14%]; odds ratio, 3.6 [95% CI, 3.0-4.2]) and across cohorts (P < .05 for 8 of 9 cohorts). Compared with a low qSOFA score, a moderate qSOFA score was also associated with increased risk of death overall (8% vs 3%; difference, 5% [95% CI, 4%-6%]; odds ratio, 2.8 [95% CI, 2.0-3.9]), but not in every cohort (P < .05 in 2 of 7 cohorts). High, vs low or moderate, SIRS criteria were associated with a smaller increase in risk of death overall (13% vs 8%; difference, 5% [95% CI, 3%-6%]; odds ratio, 1.7 [95% CI, 1.4-2.0]) and across cohorts (P < .05 for 4 of 9 cohorts). qSOFA discrimination (area under the receiver operating characteristic curve [AUROC], 0.70 [95% CI, 0.68-0.72]) was superior to that of both the baseline model (AUROC, 0.56 [95% CI, 0.53-0.58; P < .001) and SIRS (AUROC, 0.59 [95% CI, 0.57-0.62]; P < .001). Conclusions and Relevance: When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.

Neovascularization in Vertebral Artery Atheroma-A Dynamic Contrast-Enhanced Magnetic Resonance Imaging-Based Comparative Study in Patients with Symptomatic and Asymptomatic Carotid Artery Disease.

BACKGROUND: Atherosclerosis is a systemic inflammatory disease intertwined with neovascularization. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables the assessment of plaque neovascularization. This study aimed to explore the systemic nature of atherosclerosis by assessing difference in severity of neovascularization as quantified by DCE-MRI of vertebral arteries (VAs) between patients with symptomatic and asymptomatic carotid artery disease. METHODS: Ten consecutive patients with asymptomatic VA stenosis and concomitant symptomatic carotid artery disease (group 1) and 10 consecutive patients with asymptomatic VA stenosis and concomitant asymptomatic carotid artery disease (group 2) underwent 3-dimensional DCE-MRI of their cervical segment of VAs. A previously validated pharmacokinetic modeling approach was used for DCE-MRI analysis. Ktrans was calculated in the adventitia and plaque as a measure of neovessel permeability. RESULTS: Both patient groups were comparable for demographics and comorbidities. Mean luminal stenosis was comparable for both groups (54.4% versus 52.27%, P = .32). Group 1 had higher adventitial Ktrans and plaque Ktrans (.08 ± .01 min-1, .07 ± .01 min-1) compared with Group 2 (.06 ± .01 min-1, .06 ± .01 min-1) (P = .004 and .03, respectively). Good correlation was present among the two image analysts (intraclass correlation coefficient = .78). CONCLUSIONS: Vertebral Artery atheroma of patients with symptomatic carotid artery disease had increased neovessel permeability compared with the patients with asymptomatic carotid artery disease. These findings are consistent with the hypothesis that atherosclerosis is a systemic inflammatory disease. The VA atherosclerosis is likely to have increased severity of neovascularization if another arterial territory is symptomatic in the same patient cohort.

Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations.

OBJECTIVES: To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. METHODS: Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm2). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D t), vascular fraction (ƒ), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. RESULTS: All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. CONCLUSION: DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes. KEY POINTS: • Baseline diffusion coefficients demonstrated significant differences between complete pathological responders and non-responders. • Increase in ADC and DDC at mid-treatment can discriminate responders and non-responders. • The ƒ fraction at mid-treatment decreased in responders whereas increased in non-responders. • The mono- and stretched-exponential models showed excellent inter- and intrarater repeatability. • Treatment effects can potentially be assessed by non-mono-exponential diffusion models.

Assessment of Carotid Plaque Inflammation in Diabetic and Nondiabetic Patients-An Exploratory Ultrasmall Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging Study.

BACKGROUND: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging enables the identification of inflammation within the atheroma, predominantly by USPIO uptake by macrophages present in atherosclerotic tissue. Diabetic patients, however, may have dysfunctional macrophage activity, which may affect utilization of USPIO in identifying plaque inflammation in this patient cohort. METHODS: Fifteen diabetic and fifteen nondiabetic patients underwent USPIO-enhanced carotid MR imaging using 1.5T MR system. Pre- and post-USPIO carotid MR images were manually coregistered. The percentage decrease in the signal intensity after USPIO administration was calculated as a relative measure of the USPIO uptake. RESULTS: Diabetic and nondiabetic patients had comparable demographics and comorbidities. The mean global, maximum quadrant, and maximum slice changes showing change in relative signal intensity as a result of USPIO administration were comparable for the two patient cohorts (P > .05). CONCLUSIONS: USPIO can identify inflammatory burden with carotid atheroma in both diabetic and nondiabetic patients.

Effect of Radiofrequency Transmit Field Correction on Quantitative Dynamic Contrast-enhanced MR Imaging of the Breast at 3.0 T.

PURPOSE: To investigate the effects of radiofrequency transmit field (B1(+)) correction on (a) the measured T1 relaxation times of normal breast tissue and malignant lesions and (b) the pharmacokinetically derived parameters of malignant breast lesions at 3 T. MATERIALS AND METHODS: Ethics approval and informed consent were obtained. Between May 2013 and January 2014, 30 women (median age, 58 years; range, 32-83 years) with invasive ductal carcinoma of at least 10 mm were recruited to undergo dynamic contrast material-enhanced magnetic resonance (MR) imaging before surgery. B1(+) and T1 mapping sequences were performed to determine the effect of B1(+) correction on the native tissue relaxation time (T10) of fat, parenchyma, and malignant lesions in both breasts. Pharmacokinetic parameters were calculated before and after correction for B1(+) variations. Results were correlated with histologic grade by using the Kruskal-Wallis test. RESULTS: Measurements showed a mean 37% flip angle difference between the right and left breast, which resulted in a 61% T10 difference in fat and a 41.5% difference in parenchyma between the two breasts. The T1 of lesions in the right breast increased by 58%, whereas that of lesions in the left breast decreased by 30% after B1(+) correction. The whole-tumor transendothelial permeability across the vascular compartment(K(trans)) of lesions in the right breast decreased by 41%, and that of lesions in the left breast increased by 46% after correction. A systematic increase in K(trans) was observed, with significant differences found across the histologic grades (P < .001). The effect size of B1(+) correction on K(trans) calculation was large for lesions in the right breast and moderate for lesions in the left breast (Cohen effect size, d = 0.86 and d = 0.59, respectively). CONCLUSION: B1(+) correction demonstrates a substantial effect on the results of quantitative dynamic contrast-enhanced analysis of breast tissue at 3 T, which propagates into the pharmacokinetic analysis of tumors that is dependent on whether the tumor is located in the right or left breast.

Detecting gas-induced vasomotor changes via blood oxygenation level-dependent contrast in healthy breast parenchyma and breast carcinoma.

PURPOSE: To evaluate blood oxygenation level-dependent (BOLD) contrast changes in healthy breast parenchyma and breast carcinoma during administration of vasoactive gas stimuli. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) was performed at 3T in 19 healthy premenopausal female volunteers using a single-shot fast spin echo sequence to acquire dynamic T2 -weighted images. 2% (n = 9) and 5% (n = 10) carbogen gas mixtures were interleaved with either medical air or oxygen in 2-minute blocks, for four complete cycles. A 12-minute medical air breathing period was used to determine background physiological modulation. Pixel-wise correlation analysis was applied to evaluate response to the stimuli in breast parenchyma and these results were compared to the all-air control. The relative BOLD effect size was compared between two groups of volunteers scanned in different phases of the menstrual cycle. The optimal stimulus design was evaluated in five breast cancer patients. RESULTS: Of the four stimulus combinations tested, oxygen vs. 5% carbogen produced a response that was significantly stronger (P < 0.05) than air-only breathing in volunteers. Subjects imaged during the follicular phase of their cycle when estrogen levels typically peak exhibited a significantly smaller BOLD response (P = 0.01). Results in malignant tissue were variable, with three out of five lesions exhibiting a diminished response to the gas stimulus. CONCLUSION: Oxygen vs. 5% carbogen is the most robust stimulus for inducing BOLD contrast, consistent with the opposing vasomotor effects of these two gases. Measurements may be confounded by background physiological fluctuations and menstrual cycle changes. J. Magn. Reson. Imaging 2016;44:335-345.

Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge.

PURPOSE: To evaluate the utility of oxygen challenge and report on temporal changes in blood oxygenation level-dependent (BOLD) contrast in normal liver, hepatocellular carcinoma (HCC) and background fibrosis. MATERIALS AND METHODS: Eleven volunteers (nine male and two female, mean age 33.5, range 27-41 years) and 10 patients (nine male and one female, mean age 68.9, range 56-87 years) with hepatocellular carcinoma on a background of diffuse liver disease were recruited. Imaging was performed on a 3T system using a multiphase, multiecho, fast gradient echo sequence. Oxygen was administered via a Hudson mask after 2 minutes of free-breathing. Paired t-tests were performed to determine if the mean pre- and post-O2 differences were statistically significant. RESULTS: In patients with liver fibrosis (n = 8) the change in T2* following O2 administration was elevated (0.88 ± 0.582 msec, range 0.03-1.69 msec) and the difference was significant (P = 0.004). The magnitude of the BOLD response in patients with HCC (n = 10) was larger, however the response was more variable (1.07 ± 1.458 msec, range -0.93-3.26 msec), and the difference was borderline significant (P = 0.046). The BOLD response in the volunteer cohort was not significant (P = 0.121, 0.59 ± 1.162 msec, range -0.81-2.44 msec). CONCLUSION: This work demonstrates that the BOLD response following oxygen challenge within cirrhotic liver is consistent with a breakdown in vascular autoregulatory mechanisms. Similarly, the elevated BOLD response within HCC is consistent with the abnormal capillary vasculature within tumors and the arterialization of the blood supply. Our results suggest that oxygen challenge may prove a viable BOLD contrast mechanism in the liver. J. Magn. Reson. Imaging 2016;44:739-744.