Heterogeneous PSMA ligand uptake inside parotid glands.

The purpose of this investigation is to quantify the spatial heterogeneity of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) uptake within parotid glands. We aim to quantify patterns in well-defined regions to facilitate further investigations. Furthermore, we investigate whether uptake is correlated with computed tomography (CT) texture features. METHODS: Parotid glands from [18F]DCFPyL PSMA PET/CT images of 30 prostate cancer patients were analyzed. Uptake patterns were assessed with various segmentation schemes. Spearman's rank correlation coefficient was calculated between PSMA PET uptake and feature values of a Grey Level Run Length Matrix using a long and short run length emphasis (GLRLML and GLRLMS) in subregions of the parotid gland. RESULTS: PSMA PET uptake was significantly higher (p < 0.001) in lateral/posterior regions of the glands than anterior/medial regions. Maximum uptake was found in the lateral half of parotid glands in 50 out of 60 glands. The difference in SUVmean between parotid halves is greatest when parotids are divided by a plane separating the anterior/medial and posterior/lateral halves symmetrically (out of 120 bisections tested). PSMA PET uptake was significantly correlated with CT GLRLML (p < 0.001), and anti-correlated with CT GLRLMS (p < 0.001). CONCLUSION: Uptake of PSMA PET is heterogeneous within parotid glands, with uptake biased towards lateral/posterior regions. Uptake within parotid glands was strongly correlated with CT texture feature maps.

Image denoising and model-independent parameterization for IVIM MRI.

Objective. To improve intravoxel incoherent motion imaging (IVIM) magnetic resonance Imaging quality using a new image denoising technique and model-independent parameterization of the signal versusb-value curve.Approach. IVIM images were acquired for 13 head-and-neck patients prior to radiotherapy. Post-radiotherapy scans were also acquired for five of these patients. Images were denoised prior to parameter fitting using neural blind deconvolution, a method of solving the ill-posed mathematical problem of blind deconvolution using neural networks. The signal decay curve was then quantified in terms of several area under the curve (AUC) parameters. Improvements in image quality were assessed using blind image quality metrics, total variation (TV), and the correlations between parameter changes in parotid glands with radiotherapy dose levels. The validity of blur kernel predictions was assessed by the testing the method's ability to recover artificial 'pseudokernels'. AUC parameters were compared with monoexponential, biexponential, and triexponential model parameters in terms of their correlations with dose, contrast-to-noise (CNR) around parotid glands, and relative importance via principal component analysis.Main results. Image denoising improved blind image quality metrics, smoothed the signal versusb-value curve, and strengthened correlations between IVIM parameters and dose levels. Image TV was reduced and parameter CNRs generally increased following denoising.AUCparameters were more correlated with dose and had higher relative importance than exponential model parameters.Significance. IVIM parameters have high variability in the literature and perfusion-related parameters are difficult to interpret. Describing the signal versusb-value curve with model-independent parameters like theAUCand preprocessing images with denoising techniques could potentially benefit IVIM image parameterization in terms of reproducibility and functional utility.

Neural blind deconvolution for deblurring and supersampling PSMA PET.

Objective. To simultaneously deblur and supersample prostate specific membrane antigen (PSMA) positron emission tomography (PET) images using neural blind deconvolution.Approach. Blind deconvolution is a method of estimating the hypothetical 'deblurred' image along with the blur kernel (related to the point spread function) simultaneously. Traditionalmaximum a posterioriblind deconvolution methods require stringent assumptions and suffer from convergence to a trivial solution. A method of modelling the deblurred image and kernel with independent neural networks, called 'neural blind deconvolution' had demonstrated success for deblurring 2D natural images in 2020. In this work, we adapt neural blind deconvolution to deblur PSMA PET images while simultaneous supersampling to double the original resolution. We compare this methodology with several interpolation methods in terms of resultant blind image quality metrics and test the model's ability to predict accurate kernels by re-running the model after applying artificial 'pseudokernels' to deblurred images. The methodology was tested on a retrospective set of 30 prostate patients as well as phantom images containing spherical lesions of various volumes.Main results. Neural blind deconvolution led to improvements in image quality over other interpolation methods in terms of blind image quality metrics, recovery coefficients, and visual assessment. Predicted kernels were similar between patients, and the model accurately predicted several artificially-applied pseudokernels. Localization of activity in phantom spheres was improved after deblurring, allowing small lesions to be more accurately defined.Significance. The intrinsically low spatial resolution of PSMA PET leads to partial volume effects (PVEs) which negatively impact uptake quantification in small regions. The proposed method can be used to mitigate this issue, and can be straightforwardly adapted for other imaging modalities.

Analysis of left ventricle regional myocardial motion for cardiac radioablation: Left ventricular motion analysis.

PURPOSE: Left ventricle (LV) regional myocardial displacement due to cardiac motion was assessed using cardiovascular magnetic resonance (CMR) cine images to establish region-specific margins for cardiac radioablation treatments. METHODS: CMR breath-hold cine images and LV myocardial tissue contour points were analyzed for 200 subjects, including controls (n = 50) and heart failure (HF) patients with preserved ejection fraction (HFpEF, n = 50), mid-range ejection fraction (HFmrEF, n = 50), and reduced ejection fraction (HFrEF, n = 50). Contour points were divided into segments according to the 17-segment model. For each patient, contour point displacements were determined for the long-axis (all 17 segments) and short-axis (segments 1-12) directions. Mean overall, tangential (longitudinal or circumferential), and normal (radial) displacements were calculated for the 17 segments and for each segment level. RESULTS: The greatest overall motion was observed in the control group-long axis: 4.5 ± 1.2 mm (segment 13 [apical anterior] epicardium) to 13.8 ± 3.0 mm (segment 6 [basal anterolateral] endocardium), short axis: 4.3 ± 0.8 mm (segment 9 [mid inferoseptal] epicardium) to 11.5 ± 2.3 mm (segment 1 [basal anterior] endocardium). HF patients exhibited lesser motion, with the smallest overall displacements observed in the HFrEF group-long axis: 4.3 ± 1.7 mm (segment 13 [apical anterior] epicardium) to 10.6 ± 3.4 mm (segment 6 [basal anterolateral] endocardium), short axis: 3.9 ± 1.3 mm (segment 8 [mid anteroseptal] epicardium) to 7.4 ± 2.8 mm (segment 1 [basal anterior] endocardium). CONCLUSIONS: This analysis provides an estimate of epicardial and endocardial displacement for the 17 segments of the LV for patients with normal and impaired LV function. This reference data can be used to establish treatment planning margin guidelines for cardiac radioablation. Smaller margins may be used for patients with higher degree of impaired heart function, depending on the LV segment.

Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET.

BACKGROUND: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. METHODS: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. DISCUSSION: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

PSMA PET/CT as a predictive tool for subregional importance estimates in the parotid gland.

Objective. Xerostomia and radiation-induced salivary gland dysfunction remain a common side effect for head-and-neck radiotherapy patients, and attempts have been made to quantify the heterogeneity of the dose response within parotid glands. Prostate Specific Membrane Antigen (PSMA) ligands have demonstrated high uptake in salivary glands, which has been shown to correlate with gland functionality. Here we compare several models of parotid gland subregional relative importance with PSMA positron emission tomography (PET) uptake. We then develop a predictive model for Clarket al's relative importance estimates using PSMA PET and CT radiomic features, and demonstrate a methodology for predicting patient-specific importance deviations from the population.Approach. Intra-parotid gland uptake was compared with four regional importance models using 30 [18F]DCFPyL PSMA PET images. The correlation of uptake and importance was ascertained when numerous non-overlapping subregions were defined, while a paired t-test was used to compare binary region pairs. A radiomics-based predictive model of population importance was developed using a double cross-validation methodology. A model was then devised for supplementing population-level subregional importance estimates for each patient using patient-specific radiomic features.Main Results. Anticorrelative relationships were found to exist between PSMA PET uptake and four independent models of subregional parotid gland importance from the literature. Kernel Ridge Regression with principal component analysis feature selection performed best over test sets (Mean Absolute Error = 0.08), with gray level co-occurrence matrix (GLCM) features being particularly important. Deblurring PSMA PET images with neural blind deconvolution strengthened correlations and improved model performance.Significance. This study suggests that regions of relatively low PSMA PET uptake in parotid glands may exhibit relatively high dose-sensitivity. We've demonstrated the utility of PSMA PET radiomic features for predicting relative importance within subregions of parotid glands. PSMA PET appears to be a promising quantitative imaging modality for analyzing salivary gland functionality.

Neural network and spline-based regression for the prediction of salivary hypofunction in patients undergoing radiation therapy.

BACKGROUND: This study leverages a large retrospective cohort of head and neck cancer patients in order to develop machine learning models to predict radiation induced hyposalivation from dose-volume histograms of the parotid glands. METHODS: The pre and post-radiotherapy salivary flow rates of 510 head and neck cancer patients were used to fit three predictive models of salivary hypofunction, (1) the Lyman-Kutcher-Burman (LKB) model, (2) a spline-based model, (3) a neural network. A fourth LKB-type model using literature reported parameter values was included for reference. Predictive performance was evaluated using a cut-off dependent AUC analysis. RESULTS: The neural network model dominated the LKB models demonstrating better predictive performance at every cutoff with AUCs ranging from 0.75 to 0.83 depending on the cutoff selected. The spline-based model nearly dominated the LKB models with the fitted LKB model only performing better at the 0.55 cutoff. The AUCs for the spline model ranged from 0.75 to 0.84 depending on the cutoff chosen. The LKB models had the lowest predictive ability with AUCs ranging from 0.70 to 0.80 (fitted) and 0.67 to 0.77 (literature reported). CONCLUSION: Our neural network model showed improved performance over the LKB and alternative machine learning approaches and provided clinically useful predictions of salivary hypofunction without relying on summary measures.

Development of a CT-Based Auto-Segmentation Model for Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography-Delineated Tubarial Glands.

Modern inverse planning radiotherapy techniques allow for organs at risk (OARs) to evade radiation doses that they would have been subjected to with earlier techniques. The extent to which patient outcomes may be improved using these techniques depends on the delineation accuracy of target volumes and OARs on medical images as well as clinical dose constraints applied to regions of interest (ROIs). The recent discovery of bilateral "tubarial" salivary glands, which were found in the nasopharynx using prostate-specific membrane antigen (PSMA) positron emission tomography (PET), raises concerns over how dose to this region might affect patient outcomes. The dose response of the major salivary glands is known to be variable, and it is possible that the dose in tubarial glands constitutes a missing variable in the optimization of head and neck (HN) radiotherapy plans. A necessary first step toward conducting clinical studies that include the tubarial glands in plan optimization is to develop methods for delineating these glands without the use of PSMA PET images, as their acquisition is not considered a part of the standard of care for HN patients. In this study, we develop an open-source program, Organogenesis, for the auto-segmentation of tubarial glands using only computed tomography (CT) images. A predictive model is trained using contours derived from PSMA PET images, allowing for accurate delineation of tubarial glands, which cannot be manually contoured using CT only. Organogenesis provides a predictive model for tubarial glands that can be iteratively improved on with additional data, creating a viable pathway to clinical studies that can assess the importance of incorporating tubarial glands into HN radiotherapy plan optimization.

Radiomics-guided radiation therapy: opportunities and challenges.

Radiomics is an advanced image-processing framework, which extracts image features and considers them as biomarkers towards personalized medicine. Applications include disease detection, diagnosis, prognosis, and therapy response assessment/prediction. As radiation therapy aims for further individualized treatments, radiomics could play a critical role in various steps before, during and after treatment. Elucidation of the concept of radiomics-guided radiation therapy (RGRT) is the aim of this review, attempting to highlight opportunities and challenges underlying the use of radiomics to guide clinicians and physicists towards more effective radiation treatments. This work identifies the value of RGRT in various steps of radiotherapy from patient selection to follow-up, and subsequently provides recommendations to improve future radiotherapy using quantitative imaging features.

The association of multidimensional schizotypy with symptoms and impairment across racial groups.

The assessment of schizotypy and schizophrenia-spectrum psychopathology has historically been adversely impacted by multiple forms of measurement bias, including racial bias. The Multidimensional Schizotypy Scale (MSS) was developed using modern scale construction methods to minimize measurement bias in the assessment of schizotypic traits. However, studies have not examined the validity of the measurement across different racial groups. The present study examined whether the associations of MSS positive, negative, and disorganized schizotypy subscales with interview-assessed ratings of functioning, schizophrenia-spectrum personality traits, and depressive disorders were generally comparable across nonclinically ascertained samples of Black (n = 46), Asian (n = 87), and White (n = 116) young adults. Consistent with previous findings, all three schizotypy subscales were associated with impairment and schizotypal and paranoid traits. Negative schizotypy was associated with schizoid traits, and disorganized schizotypy was associated with depressive disorders. These associations were comparable across the racial groups, supporting the use of the MSS in these groups. Culturally and empirically valid assessments are essential for providing accurate assessments across racial/ethnic groups and reducing the risk of overpathologizing people of color. The present findings support the cross-cultural validity of the MSS; however, future studies should expand upon these findings by including more diverse samples and longitudinal designs.

Association of positive, negative, and disorganized schizotypy with cluster a, borderline, and avoidant personality disorders and traits.

The present study examined the associations of positive, negative, and disorganized schizotypy dimensions assessed by the Multidimensional Schizotypy Scale with 5 interview-rated personality disorder diagnoses and traits in 151 young adults. As hypothesized, all 3 schizotypy dimensions were associated with impaired functioning. Positive schizotypy was associated with schizotypal and borderline personality traits; negative schizotypy was associated with schizotypal, schizoid, paranoid, and avoidant personality traits; and disorganized schizotypy was associated with paranoid, borderline, and avoidant personality disorder traits. Negative schizotypy predicted broad diagnoses of Cluster A personality disorders. Both negative and disorganized schizotypy predicted the broad diagnosis of any of the 5 personality disorders. The study further examined the association of the schizotypy dimensions with the individual personality disorder criteria to better understand the overall associations. Given the common origins and high comorbidity, we examined whether the schizotypy dimensions explained the association of borderline and schizotypal personality disorder traits. Positive and disorganized schizotypy fully mediated the association between borderline and schizotypal traits. In summary, the study replicated and extended previous findings that the schizotypy dimensions are uniquely associated with personality disorders and traits, as well as impaired functioning, in young adults. The study also provided additional support for the construct validity of the Multidimensional Schizotypy Scale and for the use of psychometric assessment of schizotypy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Incorporating parotid gland inhomogeneity into head-and-neck treatment optimization through the use of artificial base plans.

Despite a great improvement in target volume dose conformality made possible in recent years by modulated therapies, xerostomia remains a common and severe side effect for head-and-neck radiotherapy patients. It is known that parotid glands exhibit a spatially varying dose response; however, the relative importance of subregions throughout the entire gland has yet to be incorporated into treatment plan optimization, with the current standard being to minimize the mean dose to whole parotid glands. The relative importance of regions within contralateral parotid glands has been recently quantified, creating an opportunity for the development of a method for including this data in plan optimization. We present a universal and straightforward approach for imposing varying sub-parotid gland dose constraints during inverse treatment planning by using patient-specific artificial base plans to penalize dose deposited in sensitive regions. In this work, the proposed method of optimization is demonstrated to reduce dose to regions of high relative importance throughout contralateral parotids and improve predictions for stimulated saliva output at 1-year post-radiotherapy. This method may also be applied to impose varying dose constraints to other organs-at-risk for which regional importance data exists.

MDR-1 function protects oocyte mitochondria against the transgenerational effects of nitrogen mustard exposure.

Oocytes are vulnerable to alkylating agents like nitrogen mustard (NM), which can cause mitochondrial dysfunction associated with increased oxidative stress. Because mitochondria are maternally inherited, NM exposure affects oocyte mitochondrial physiology and compromises future progeny. Multidrug resistance transporters (MDRs) are transmembrane proteins that efflux such cytotoxic substances; MDR-1 is expressed in oocyte plasma and mitochondrial membranes and protects against oxidative stress. Our objective was to investigate how loss of MDR-1 can modulate oocyte response to NM transgenerationally. Wild Type (WT) and Mdr1a mutant female mice were injected intraperitoneally with sterile saline (control) or 0.1 mg/kg NM. 48 h post-injection, females were either sacrificed for F0 studies or mated with control males to yield F1 pups. After weaning, F1 females were sacrificed or mated to yield F2 pups. Germinal vesicle oocytes were assessed for mitochondrial membrane potential and reactive oxygen species (ROS) levels. NM exposed oocytes of both genotypes exhibited significantly higher ROS than controls in F0 and F1. NM F2 oocytes of neither genotype exhibited significantly higher ROS, though variation in Mdr1a mutants led to an upward trend. NM oocytes of both genotypes exhibited significantly disrupted mitochondrial membrane potential in F0. WT regained normalcy by F1 whereas Mdr1a mutants were unable to by F2. Our data suggest that Mdr1a mutants exhibit transgenerational mitochondrial dysfunction following toxic challenge that persists, implying that MDR-1 protects against toxicant-induced mitochondrial stress. Women without functional MDR-1 exposed to environmental toxicants could therefore be at risk for passing on compromised mitochondria to future offspring.

Use of Fetal Magnetic Resonance Imaging After Sonographic Identification of Major Structural Anomalies.

OBJECTIVES: To characterize population-based use of fetal magnetic resonance imaging (MRI) incorporating recent American College of Radiology (ACR)-Society of Perinatal Radiologists (SPR) guidelines about fetal anomalies for which MRI may provide valuable additional information when sonography is limited. METHODS: We conducted a retrospective review of nonreferred singleton pregnancies that received prenatal care and had prenatal sonographic diagnosis of 1 or more major structural anomalies at our hospital between January 2010 and May 2018. Detailed sonography was performed in all anomaly cases. Fetal anomaly information was obtained from a prospectively maintained database, and medical records were reviewed to determine the rationale for why MRI was or was not performed, according to the indication. RESULTS: A total of 104,597 singleton pregnancies underwent sonographic assessments of anatomy at our institution during the study period. Major structural anomalies were identified in 1650 (1.6%) of these pregnancies. Potential indications for fetal MRI per ACR-SPR guidelines were identified in 339 cases. However, fetal MRI was performed in only 253 cases, 15% of those with major anomalies and 75% with a potential indication. Magnetic resonance imaging was not performed in 41 (20%) of identified pregnancies because of an improved prognosis on serial sonography (36), because of a poor prognosis (3), or because it would not alter management (2). CONCLUSIONS: Fetal MRI was used in 15% of those pregnancies with prenatal diagnosis of a major structural anomaly. This amounted to fewer than 0.3% of singleton deliveries. Judicious application of ACR-SPR guidelines in the context of serial sonography results in a relatively small number of fetal MRI examinations in a nonreferred population.

Placenta Accreta Spectrum: Correlation of MRI Parameters With Pathologic and Surgical Outcomes of High-Risk Pregnancies.

OBJECTIVE. The purpose of this study is to determine whether MRI parameters of placenta accreta spectrum correlate with pathologic and surgical outcomes in high-risk pregnancies. MATERIALS AND METHODS. This retrospective study evaluated second- and third-trimester pregnancies assessed by MRI from 2007 to the present. Women were included in the study if placental invasion was suspected on the basis of a clinical history of cesarean delivery, ultrasound findings, or both. MR images were reviewed by an experienced radiologist who was blinded to the clinical outcomes. Eighteen MRI parameters were assessed and compared with four clinical outcomes: surgical impression of invasion, need for cesarean hysterectomy, pathologic findings, and need for blood transfusion. RESULTS. Of 64 women, 43 required cesarean hysterectomy, 20 underwent cesarean delivery, and one delivered vaginally. There was no statistical difference among the women in terms of maternal age, gestational age, or the number of prior cesarean deliveries. Eight of the 18 MRI parameters assessed showed statistical significance. The five variables with the highest odds ratios were bulge (7.432), placenta previa (7.283), low-attenuation T2 linear bands (5.985), placental heterogeneity near the scar (4.384), and fibrin deposition (4.322), with additional significant variables including interruption of the bladder-serosa interface, the radiologist's interpretation of invasion, and the largest dimension of invasion. Some previously described parameters, such as the degree of maternal pelvic vascularity, were not statistically significant. CONCLUSION. MRI parameters are associated with placental invasion and correlate with the need for cesarean hysterectomy, as well as pathologic and surgical impressions of invasion. From these parameters, an organized template can be created to standardize reporting of placental invasion.

Inflammaging is associated with shifted macrophage ontogeny and polarization in the aging mouse ovary.

The fertility of women declines sharply after age 35 and is essentially lost upon menopause at age 51. The ovary plays an important part in aging-associated changes in women's physiology since it is an essential component of both the reproductive and endocrine systems. Several previous studies in mice have shown that the ovarian tissue goes through drastic changes over the course of aging and exhibits signs of aging-associated chronic inflammation (inflammaging), which may contribute to the marked decline of oocyte quality in aged individuals. To further examine aging-associated gene expression changes in the ovary and to characterize the development of inflammaging, we performed detailed transcriptomic analysis of whole ovaries from mice of six different age groups over the mouse reproductive lifespan and identified more than 5000 genes with significant expression change over the course of aging. Intriguingly, we found aging-associated changes in the expression of several markers that indicate alterations in the composition of ovarian macrophages, which are known to be central players of inflammaging. Using flow cytometry, we analyzed and compared macrophage populations and polarization in young and old ovaries and found a significant increase in monocyte recruitment and macrophage alternative activation (M2) in the old ovaries compared to those in young. Our results are consistent with previous findings of aging-associated increase of fibrosis in the ovarian stromal extracellular matrix, and they provide new clues about the development of inflammaging in the mammalian ovary.

Breast Lesions in Women Aged Younger than 30 Years: Clinical Presentation, Diagnosis, and Management.

Women aged younger than 30 years frequently present with palpable breast lesions, breast pain, and nipple discharge. Diagnostic work-up often results in benign findings, including a variety of benign solid masses, infectious or inflammatory conditions, pregnancy- or lactation-related abnormalities, and normal variants. While rare, breast cancer can occur within this demographic, and it is often more advanced and aggressive than in older women. Other rare tumors can present within this patient demographic, including primary sarcoma of the breast and granular cell tumors. A knowledge of the clinical presentation, diagnostic approach, and management of this spectrum of pathologic entities is crucial to ensure optimal and cost-effective care within this patient demographic.

Dysfunctional MDR-1 disrupts mitochondrial homeostasis in the oocyte and ovary.

Multidrug resistance transporters (MDRs) are best known for their pathological role in neoplastic evasion of chemotherapeutics and antibiotics. Here we show that MDR-1 is present in the oocyte mitochondrial membrane, and it protects the female gamete from oxidative stress. Female mdr1a mutant mice have no significant difference in ovarian follicular counts and stages, nor in reproductively functioning hormone levels, yet these mice are significantly more vulnerable to gonadotoxic chemotherapy, have chronically elevated reactive oxygen species in immature germinal vesicle oocytes, exhibit a significant over-accumulation of metabolites involved in the tricarboxylic acid cycle (TCA), and have abnormal mitochondrial membrane potential. The mdr1a mutant ovaries have a dramatically different transcriptomic profile with upregulation of genes involved in metabolism. Our findings indicate that functionality of MDR-1 reveals a critical intersection of metabolite regulation, oxidative stress, and mitochondrial dysfunction that has direct implications for human infertility, premature reproductive aging due to oxidative stress, and gonadoprotection.

A Practical Radiotherapy Treatment Planning Technique for Second-Incidence Cancers That Incorporates Complete Organ-At-Risk Dose History.

INTRODUCTION: Patients requiring treatment for second cancer incidences present unique radiotherapy plan development challenges. Historical dose delivered to organs at risk must be accounted for to properly estimate lifetime toxicity risks, but historical dose delivered to the region now occupied by tumours does not contribute to the prescription dose. Treatment planning systems permit inclusion of a base plan but do not provide the ability to manipulate it. We present a technique, dose cropping, which incorporates organ-at-risk dose history into the base plan while selectively excising dose history to diseased tissues now occupied by tumours. A retrospective plan comparison is performed to assess the effectiveness of dose cropping. METHODS AND MATERIALS: Nine patients who received a second course of radiotherapy for cancers of the head-and-neck were replanned using the proposed technique. Clinical second courses and replans were compared on the basis of conformity index, heterogeneity index, maximum point dose, tissue control probability (TCP), normal tissue complication probability (NTCP), and whether the planning guidelines could be met by the treatment planning system. Replan constraints and guidelines followed the clinical treatment. In addition, a tissue recovery model was incorporated, applied to both clinical and replan courses, and compared to estimate the relevance of the dose cropping technique in such regimes. RESULTS AND DISCUSSION: Replans had reduced organ-at-risk maximum point doses (5 Gy for spinal cord, 4 Gy for brainstem), NTCP (2.9% median reduction), and were able to more consistently achieve the V95% > 98% coverage target regardless of the tissue recovery model. At the same time, replans using the dose cropping technique were statistically indistinguishable from clinical second courses on the basis of plan conformity, heterogeneity, or TCP (P > .31 in all cases). CONCLUSIONS: Dosimetric history cropping is a valuable and widely applicable technique for second cancer radiotherapy planning. It also provides a natural means to incorporate tissue recovery models, biologically effective dose conversion, and NTCP and TCP model evaluation.

Breast ultrasound utilization in a safety net emergency department.

PURPOSE: The purpose of this study is to (1) assess the diagnostic yield of ultrasounds performed in the emergency department for suspected breast abscess and determine the rates of reimaging, discordance, and emergent intervention in a large, busy safety net hospital and (2) determine clinical factors significantly associated with abscess as a way to improve patient selection for emergent breast ultrasounds. METHODS: A total of 581 consecutive breast ultrasounds performed in the emergency department for suspected abscess over 15 months were retrospectively reviewed for imaging, demographics, laboratory data, and physical exam findings. Breast abscess was confirmed by combining imaging, clinical, and laboratory data. Linear logistic regression analysis estimated the likelihood of abscess, and the cross-validated area under the receiver operating characteristic curve (AUC) evaluated diagnostic performance. RESULTS: Final diagnoses included abscess (153/581, 26%), cancer (29/581, 5%), granulomatous mastitis (41/581, 7%), normal (120/581, 21%), and other/indeterminate (238/581, 41%). Factors associated with abscess included induration, fluctuance, erythema, drainage, smoking, diabetes, and Black race. Based on these factors, the AUC of the characteristics predictive of abscess was 0.77 (CI, 0.72-0.81). Six breast cancers were not diagnosed on ultrasound. 40% of ultrasounds (231/581) were considered incomplete/inadequate. CONCLUSION: 74% (428/581) of emergent breast ultrasounds in our population were negative for abscess, while 21% (6/29) of cancers were not diagnosed, and 40% (231/581) of exams were incomplete/inadequate. Patient selection for emergent ultrasounds can be improved, allowing patients with a low likelihood of abscess to be imaged in a more optimal setting.