Conquering the Cobb Angle: A Deep Learning Algorithm for Automated, Hardware-Invariant Measurement of Cobb Angle on Radiographs in Patients with Scoliosis.

Scoliosis is a disease estimated to affect more than 8% of adults in the United States. It is diagnosed with use of radiography by means of manual measurement of the angle between maximally tilted vertebrae on a radiograph (ie, the Cobb angle). However, these measurements are time-consuming, limiting their use in scoliosis surgical planning and postoperative monitoring. In this retrospective study, a pipeline (using the SpineTK architecture) was developed that was trained, validated, and tested on 1310 anterior-posterior images obtained with a low-dose stereoradiographic scanning system and radiographs obtained in patients with suspected scoliosis to automatically measure Cobb angles. The images were obtained at six centers (2005-2020). The algorithm measured Cobb angles on hold-out internal (n = 460) and external (n = 161) test sets with less than 2° error (intraclass correlation coefficient, 0.96) compared with ground truth measurements by two experienced radiologists. Measurements, produced in less than 0.5 second, did not differ significantly (P = .05 cutoff) from ground truth measurements, regardless of the presence or absence of surgical hardware (P = .80), age (P = .58), sex (P = .83), body mass index (P = .63), scoliosis severity (P = .44), or image type (low-dose stereoradiographic image vs radiograph; P = .51) in the patient. These findings suggest that the algorithm is highly robust across different clinical characteristics. Given its automated, rapid, and accurate measurements, this network may be used for monitoring scoliosis progression in patients. Keywords: Cobb Angle, Convolutional Neural Network, Deep Learning Algorithms, Pediatrics, Machine Learning Algorithms, Scoliosis, Spine Supplemental material is available for this article. © RSNA, 2023.

Atherogenic Indices as a Predictor of Aortic Calcification in Prostate Cancer Patients Assessed Using 18F-Sodium Fluoride PET/CT.

A major pathophysiological cause of cardiovascular disease is vascular plaque calcification. Fluorine 18−Sodium Fluoride (18F-NaF) PET/CT can be used as a sensitive imaging modality for detection of vascular calcification. The aim of this study was to find a non-invasive, cost-efficient, and readily available metric for predicting vascular calcification severity. This retrospective study was performed on 36 participants who underwent 18F-NaF fused PET/CT scans. The mean standard uptake values (SUVs) were calculated from manually sectioned axial sections over the aortic arch and thoracic aorta. Correlation analyses were performed between SUVs and calculated atherogenic indices (AIs). Castelli's Risk Index I (r = 0.63, p < 0.0001), Castelli's Risk Index II (r = 0.64, p < 0.0001), Atherogenic Coefficient (r = 0.63, p < 0.0001), Atherogenic Index of Plasma (r = 0.51, p = 0.00152), and standalone high-density lipoprotein (HDL) cholesterol (r = −0.53, p = 0.000786) were associated with aortic calcification. AIs show strong association with aortic arch and thoracic aorta calcifications. AIs are better predictors of vascular calcification compared to standalone lipid metrics, with the exception of HDL cholesterol. Clinical application of AIs provides a holistic metric beneficial for enhancing screening and treatment protocols.

Combining concurrent radiotherapy and immunotherapy for synergistic effects in recurrent endometrial cancer - A case report.

Endometrial cancer, also known as uterine cancer, is the second most common cancer affecting women globally and the fourth most prevalent in the United States (US). Treatment often involves a combination of surgery, radiotherapy and chemotherapy depending on the severity. In this case report, we present two patients with relapsed endometrial carcinomas, who responded positively to combined radiotherapy and immunotherapy followed by maintenance immunotherapy. Given the worsening prognoses associated with recurrent endometrial cancers, these two cases warrant the further exploration of the concurrent administration of immunotherapy and radiation therapy in the context of clinical trials.

Design, Synthesis, and Antisickling Investigation of a Nitric Oxide-Releasing Prodrug of 5HMF for the Treatment of Sickle Cell Disease.

5-hydroxyfurfural (5HMF), an allosteric effector of hemoglobin (Hb) with an ability to increase Hb affinity for oxygen has been studied extensively for its antisickling effect in vitro and in vivo, and in humans for the treatment of sickle cell disease (SCD). One of the downstream pathophysiologies of SCD is nitric oxide (NO) deficiency, therefore increasing NO (bio)availability is known to mitigate the severity of SCD symptoms. We report the synthesis of an NO-releasing prodrug of 5HMF (5HMF-NO), which in vivo, is expected to be bio-transformed into 5HMF and NO, with concomitant therapeutic activities. In vitro studies showed that when incubated with whole blood, 5HMF-NO releases NO, as anticipated. When incubated with sickle blood, 5HMF-NO formed Schiff base adduct with Hb, increased Hb affinity for oxygen, and prevented hypoxia-induced erythrocyte sickling, which at 1 mM concentration were 16%, 10% and 27%, respectively, compared to 21%, 18% and 21% for 5HMF. Crystal structures of 5HMF-NO with Hb showed 5HMF-NO bound to unliganded (deoxygenated) Hb, while the hydrolyzed product, 5HMF bound to liganded (carbonmonoxy-ligated) Hb. Our findings from this proof-of-concept study suggest that the incorporation of NO donor group to 5HMF and analogous molecules could be a novel beneficial strategy to treat SCD and warrants further detailed in vivo studies.

Impact of the Early COVID-19 Pandemic on Gender Participation in Academic Publishing in Radiation Oncology.

PURPOSE: There is a known gender gap in oncology publishing with worse disparities within specialty fields such as radiation oncology. There has been a significant increase in the number of articles submitted to academic journals during the pandemic. Several analyses have suggested that the pandemic has had a disproportionate effect on academic productivity of women in academia, as measured by article publication rates. MATERIALS AND METHODS: The gender of first/co-first and corresponding/co-corresponding authors, as well as nonsenior versus senior status and manuscript type, for all articles published by Advances from its inception in December 2015 to the end of February 2020 was compared with those published between March 1, 2020, and May 31, 2020: the months during which the onset of the COVID-19 pandemic in North America began. RESULTS: This examination of papers published during COVID-19 did not indicate a statistically significant decrease in the overall proportion of women publishing in Advances (P = .76). For nonsenior female authors, this proportion fell just short of statistical significance (39% vs 19%, P = .051). When only scientific manuscripts were considered, there was a statistically significant decrease in publications by nonsenior female first authors during the early months of the pandemic (37% vs 11%, P = .02). CONCLUSIONS: During the early months of the COVID-19 pandemic, nonsenior female researchers participated less in article publishing in radiation oncology.

Vertebral Deformity Measurements at MRI, CT, and Radiography Using Deep Learning.

PURPOSE: To construct and evaluate the efficacy of a deep learning system to rapidly and automatically locate six vertebral landmarks, which are used to measure vertebral body heights, and to output spine angle measurements (lumbar lordosis angles [LLAs]) across multiple modalities. MATERIALS AND METHODS: In this retrospective study, MR (n = 1123), CT (n = 137), and radiographic (n = 484) images were used from a wide variety of patient populations, ages, disease stages, bone densities, and interventions (n = 1744 total patients, 64 years ± 8, 76.8% women; images acquired 2005-2020). Trained annotators assessed images and generated data necessary for deformity analysis and for model development. A neural network model was then trained to output vertebral body landmarks for vertebral height measurement. The network was trained and validated on 898 MR, 110 CT, and 387 radiographic images and was then evaluated or tested on the remaining images for measuring deformities and LLAs. The Pearson correlation coefficient was used in reporting LLA measurements. RESULTS: On the holdout testing dataset (225 MR, 27 CT, and 97 radiographic images), the network was able to measure vertebral heights (mean height percentage of error ± 1 standard deviation: MR images, 1.5% ± 0.3; CT scans, 1.9% ± 0.2; radiographs, 1.7% ± 0.4) and produce other measures such as the LLA (mean absolute error: MR images, 2.90°; CT scans, 2.26°; radiographs, 3.60°) in less than 1.7 seconds across MR, CT, and radiographic imaging studies. CONCLUSION: The developed network was able to rapidly measure morphometric quantities in vertebral bodies and output LLAs across multiple modalities.Keywords: Computer Aided Diagnosis (CAD), MRI, CT, Spine, Demineralization-Bone, Feature Detection Supplemental material is available for this article. © RSNA, 2021.

A deep learning system for automated, multi-modality 2D segmentation of vertebral bodies and intervertebral discs.

PURPOSE: Fractures in vertebral bodies are among the most common complications of osteoporosis and other bone diseases. However, studies that aim to predict future fractures and assess general spine health must manually delineate vertebral bodies and intervertebral discs in imaging studies for further radiomic analysis. This study aims to develop a deep learning system that can automatically and rapidly segment (delineate) vertebrae and discs in MR, CT, and X-ray imaging studies. RESULTS: We constructed a neural network to output 2D segmentations for MR, CT, and X-ray imaging studies. We trained the network on 4490 MR, 550 CT, and 1935 X-ray imaging studies (post-data augmentation) spanning a wide variety of patient populations, bone disease statuses, and ages from 2005 to 2020. Evaluated using 5-fold cross validation, the network was able to produce median Dice scores > 0.95 across all modalities for vertebral bodies and intervertebral discs (on the most central slice for MR/CT and on image for X-ray). Furthermore, radiomic features (skewness, kurtosis, mean of positive value pixels, and entropy) calculated from predicted segmentation masks were highly accurate (r ≥ 0.96 across all radiomic features when compared to ground truth). Mean time to produce outputs was <1.7 s across all modalities. CONCLUSIONS: Our network was able to rapidly produce segmentations for vertebral bodies and intervertebral discs for MR, CT, and X-ray imaging studies. Furthermore, radiomic quantities derived from these segmentations were highly accurate. Since this network produced outputs rapidly for these modalities which are commonly used, it can be put to immediate use for radiomic and clinical imaging studies assessing spine health.

Inhibition of the Aquaporin-1 Cation Conductance by Selected Furan Compounds Reduces Red Blood Cell Sickling.

In sickle cell disease (SCD), the pathological shift of red blood cells (RBCs) into distorted morphologies under hypoxic conditions follows activation of a cationic leak current (Psickle) and cell dehydration. Prior work showed sickling was reduced by 5-hydroxylmethyl-2-furfural (5-HMF), which stabilized mutant hemoglobin and also blocked the Psickle current in RBCs, though the molecular basis of this 5-HMF-sensitive cation current remained a mystery. Work here is the first to test the hypothesis that Aquaporin-1 (AQP1) cation channels contribute to the monovalent component of Psickle. Human AQP1 channels expressed in Xenopus oocytes were evaluated for sensitivity to 5-HMF and four derivatives known to have differential efficacies in preventing RBC sickling. Ion conductances were measured by two-electrode voltage clamp, and osmotic water permeability by optical swelling assays. Compounds tested were: 5-HMF; 5-PMFC (5-(phenoxymethyl)furan-2-carbaldehyde); 5-CMFC (5-(4-chlorophenoxymethyl)furan-2-carbaldehyde); 5-NMFC (5-(2-nitrophenoxymethyl)-furan-2-carbaldehyde); and VZHE006 (tert-butyl (5-formylfuran-2-yl)methyl carbonate). The most effective anti-sickling agent, 5-PMFC, was the most potent inhibitor of the AQP1 ion conductance (98% block at 100 µM). The order of sensitivity of the AQP1 conductance to inhibition was 5-PMFC > VZHE006 > 5-CMFC ≥ 5-NMFC, which corresponded with effectiveness in protecting RBCs from sickling. None of the compounds altered AQP1 water channel activity. Combined application of a selective AQP1 ion channel blocker AqB011 (80 µM) with a selective hemoglobin modifying agent 5-NMFC (2.5 mM) increased anti-sickling effectiveness in red blood cells from human SCD patients. Another non-selective cation channel known to be expressed in RBCs, Piezo1, was unaffected by 2 mM 5-HMF. Results suggest that inhibition of AQP1 ion channels and capacity to modify hemoglobin are combined features of the most effective anti-sickling agents. Future therapeutics aimed at both targets could hold promise for improved treatments for SCD.

VZHE-039, a novel antisickling agent that prevents erythrocyte sickling under both hypoxic and anoxic conditions.

Sickle cell disease (SCD) results from a hemoglobin (Hb) mutation ßGlu6 → ßVal6 that changes normal Hb (HbA) into sickle Hb (HbS). Under hypoxia, HbS polymerizes into rigid fibers, causing red blood cells (RBCs) to sickle; leading to numerous adverse pathological effects. The RBC sickling is made worse by the low oxygen (O2) affinity of HbS, due to elevated intra-RBC concentrations of the natural Hb effector, 2,3-diphosphoglycerate. This has prompted the development of Hb modifiers, such as aromatic aldehydes, with the intent of increasing Hb affinity for O2 with subsequent prevention of RBC sickling. One such molecule, Voxelotor was recently approved by U.S. FDA to treat SCD. Here we report results of a novel aromatic aldehyde, VZHE-039, that mimics both the O2-dependent and O2-independent antisickling properties of fetal hemoglobin. The latter mechanism of action-as elucidated through crystallographic and biological studies-is likely due to disruption of key intermolecular contacts necessary for stable HbS polymer formation. This dual antisickling mechanism, in addition to VZHE-039 metabolic stability, has translated into significantly enhanced and sustained pharmacologic activities. Finally, VZHE-039 showed no significant inhibition of several CYPs, demonstrated efficient RBC partitioning and high membrane permeability, and is not an efflux transporter (P-gp) substrate.