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Atypical Parkinsonian syndromes are a subset of progressive neurodegenerative disorders that present with signs of Parkinson's disease. However, due to multisystem degeneration, the atypical Parkinsonian syndromes have additional symptoms that are often referred to as Parkinson-plus syndromes. The most well-studied subsets include progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and Lewy body dementia. Specifically, progressive supranuclear palsy is a tauopathy neurodegenerative disorder that presents with parkinsonism symptoms along with postural instability, vertical saccade, and vertical gaze palsy. Here, we present a case of PSP and provide a brief review of the literature., (© 2023 Published by Elsevier Inc. on behalf of University of Washington.)

Surgical resection of brain tumors is challenging because of the delicate balance between maximizing tumor removal and preserving vital brain functions. Functional MRI (fMRI) offers noninvasive preoperative mapping of widely distributed brain areas and is increasingly used in presurgical functional mapping. However, its impact on survival and functional outcomes is still not well-supported by evidence. Task-based fMRI (tb-fMRI) maps blood oxygen level-dependent (BOLD) signal changes during specific tasks, while resting-state fMRI (rs-fMRI) examines spontaneous brain activity. rs-fMRI may be useful for patients who cannot perform tasks, but its reliability is affected by tumor-induced changes, challenges in data processing, and noise. Validation studies comparing fMRI with direct cortical stimulation (DCS) show variable concordance, particularly for cognitive functions such as language; however, concordance for tb-fMRI is generally greater than that for rs-fMRI. Preoperative fMRI, in combination with MRI tractography and intraoperative DCS, may result in improved survival and extent of resection and reduced functional deficits. fMRI has the potential to guide surgical planning and help identify targets for intraoperative mapping, but there is currently limited prospective evidence of its impact on patient outcomes. This review describes the current state of fMRI for preoperative assessment in patients undergoing brain tumor resection. Keywords: MR-Functional Imaging, CNS, Brain/Brain Stem, Anatomy, Oncology, Functional MRI, Functional Anatomy, Task-based, Resting State, Surgical Planning, Brain Tumor © RSNA, 2023.

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a rare autosomal recessive disorder characterized by a decrease in creatine synthesis, resulting in cerebral creatine deficiency syndrome (CCDS). GAMT deficiency is caused by mutations in the GAMT gene located on chromosome 19, which impairs the conversion of guanidinoacetic acid (GAA) to creatine. The resulting accumulation of the toxic metabolite GAA and the lack of creatine lead to various symptoms, including global developmental delays, behavioral issues, and epilepsy. The gold standard for diagnosis of GAMT deficiency is genetic testing. Treatment options for GAMT deficiency include creatine supplementation, ornithine supplementation, arginine restriction, and sodium benzoate supplementation. These treatment options have been shown to improve movement disorders and epileptic symptoms, but their impact on intellectual and speech development is limited. Early intervention has shown promising results in normalizing neurological development in a minor subgroup of patients. Therefore, there is a growing need for newborn screening techniques to detect GAMT deficiency early and prevent permanent neurological delays. Here we report a case of GAMT deficiency with emphasis on imaging presentation. Our case showed reduced brain parenchyma creatine stores on MR Spectroscopy, which may provide an avenue to aid in early diagnosis., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Neurodegenerative disorders are classified as a group of diseases with progressive loss of neurons secondary to aggregation of misfolded proteins. A few of these neurodegenerative diseases have been associated with degeneration of the transverse pontocerebellar tracts and median pontine raphe nuclei. This specific neuron degeneration results in the radiologic hot cross bun sign (HCBS) on MRI T2 imaging and helps narrow down the differential diagnosis. While multiple system atrophy has a higher prevalence of the HCBS than other neurodegenerative diseases, the sign has also been described with other neurodegenerative disorders such as spinocerebellar ataxia (SCA), and variant Creutzfeldt-Jakob disease. Here, we present a case of spinocerebellar ataxia type 34 with a characteristic hot-cross bun sign and provide a brief review of the literature., (© 2023 The Authors.)

A deep learning model (LCP CNN) for the stratification of indeterminate pulmonary nodules (IPNs) demonstrated better discrimination than commonly used clinical prediction models. However, the LCP CNN score is based on a single timepoint that ignores longitudinal information when prior imaging studies are available. Clinically, IPNs are often followed over time and temporal trends in nodule size or morphology inform management. In this study we investigated whether the change in LCP CNN scores over time was different between benign and malignant nodules. This study used a prospective-specimen collection, retrospective-blinded-evaluation (PRoBE) design. Subjects with incidentally or screening detected IPNs 6-30 mm in diameter with at least 3 consecutive CT scans prior to diagnosis (slice thickness ≤ 1.5 mm) with the same nodule present were included. Disease outcome was adjudicated by biopsy-proven malignancy, biopsy-proven benign disease and absence of growth on at least 2-year imaging follow-up. Lung nodules were analyzed using the Optellum LCP CNN model. Investigators performing image analysis were blinded to all clinical data. The LCP CNN score was determined for 48 benign and 32 malignant nodules. There was no significant difference in the initial LCP CNN score between benign and malignant nodules. Overall, the LCP CNN scores of benign nodules remained relatively stable over time while that of malignant nodules continued to increase over time. The difference in these two trends was statistically significant. We also developed a joint model that incorporates longitudinal LCP CNN scores to predict future probability of cancer. Malignant and benign nodules appear to have distinctive trends in LCP CNN score over time. This suggests that longitudinal modeling may improve radiomic prediction of lung cancer over current models. Additional studies are needed to validate these early findings., (© 2023. The Author(s).)

Transient ischemic attack (TIA) has gained significant attention recently due to the increased incidence of subsequent stroke. However, there are many nonvascular clinical mimics of TIA, creating a need for improved biomarkers to identify a vascular origin. Following the recent approval of ultra-high field (UHF) 7T MRI in clinical practice, several clinical studies have highlighted its added utility in neuroimaging compared to lower-field 1.5T and 3T MRI, particularly in epilepsy and multiple sclerosis. Our case series of three patients with TIA illustrates that 7T MRI can depict small areas of intracortical microhemorrhages and microinfarctions, which could not be resolved with 3T or 1.5T MRI. There are currently no reports of intracortical localization of microhemorrhages in patients with TIA. This discovery may enhance our understanding and characterization of cerebrovascular abnormalities in TIAs. In addition, UHF imaging could potentially be utilized to distinguish transient neurological episodes secondary to cerebrovascular events from other differential considerations. Our cases highlight the underestimation of imaging abnormalities in cases of TIA and support the potential expanded application of clinical 7T to assess patients with TIA. Future studies are necessary at 7T redundant to determine the true incidence of such lesions in TIA and to examine the correlation between cortical microhemorrhages and subsequent ischemic stroke, hemorrhagic events, and neurocognitive impairment.

Wide variation exists in research training, experience, opportunities, and exposure across various radiology residency training programs, ranging from having a dedicated research track to no exposure to hypothesis driven projects. Studies conducted at different residency training programs with varied resources and National Institutes of Health funding have shown that resident-driven research initiatives and mentorship programs have the potential to improve research experience during residency training, engage more medical students in research, increase departmental peer-reviewed publications and increase peer-reviewed publications of early-career faculty physicians. In an attempt to standardize the research training during radiology residency, we propose a standardized resident-led program which institutions may adapt, as well as resources that the American Alliance of Academic Chief Residents in Radiology (A 3 CR 2 ) might compile in collaboration with other national organizations to improve trainee's research experience during their radiology residency training., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes., Methods: We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis: 1-3 days of antibiotics, 4-6 days of antibiotics and 7 days or more of antibiotics. Rates of infection diagnosis within 30 days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall-Wallace tests. Multivariable analysis was conducted to evaluate independent risk factors for infection., Results: Medical charts of 980 patients with cirrhosis and upper GI bleeding during the study period were reviewed. A total of 303 with upper gastrointestinal bleeding were included in the final sample, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4-6 days, and 97 patients longer than 6 days. The three groups were well matched in demographic and clinical variables. Twenty-seven patients developed infections within 30 days of bleeding. MELD-Na score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the three antibiotic groups (p = 0.78). In the thirty days following the GI bleed, pneumonia was the most diagnosed infection (eleven patients) followed by urinary tract infections (eight patients). Four patients developed spontaneous bacterial peritonitis and three were diagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection., Conclusion: Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adenocarcinomas of the distal bile duct are traditionally classified as either pancreatobiliary or intestinal type, with pancreatic adenocarcinoma and cholangiocarcinoma included within the former classification. Cholangiocarcinoma is a rare and deadly malignancy that occurs within three clinically defined regions: intrahepatic, perihilar, and in the distal bile duct. We present a 68-year-old male with a past medical history of human immunodeficiency virus, hepatitis B, hypertension, and hyperlipidemia who presented to the emergency department with a 3-week history of diarrhea, diffuse abdominal pain, malaise, and nausea. Contrast enhanced CT of the abdomen and pelvis revealed a periampullary mass. Endoscopic ultrasound biopsy was performed, with histopathology suggestive of distal cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography was utilized for palliative stent placement until patient received pancreaticoduodenectomy (ie, Whipple procedure). In this case, we highlight the imaging presentation and histopathology of a distal cholangiocarcinoma., (© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Lingual thyroid is by far the most common presentation of ectopic thyroid. Though mostly asymptomatic it is associated with congenital hypothyroidism and importantly, absence of orthotopic thyroid making it the only functional thyroid tissue a patient has in many cases. It appears indistinguishable to orthotopic thyroid tissue on imaging, with avid homogeneous enhancement on contrast computed tomography. Here we report clinical presentation and imaging findings of lingual thyroid in a 38-year-old man., (© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Eosinophilic myocarditis (EM) is a cardiac manifestation of hypereosinophilic syndrome with a high mortality rate. EM shares imaging features similar to other restrictive cardiopathies, and include patchy intramural late gadolinium enhancement on cardiac magnetic resonance with or without presence of biventricular thrombus. Diagnosis is confirmed on histopathology, and is the current gold standard. Here we report clinical presentation and imaging findings of EM in a 70-year-old woman who presented with fever and chills., (© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Rationale and Objectives: Cinematic Rendering (CR) incorporates a complex lightning model that creates photorealistic models from isotropic 3D imaging data. The utility of CR in depicting volumetric MRI data for pre-therapeutic planning is discussed, with intracranial tumors as a demonstrative example., Materials and Methods: We present a series of Cinematically Rendered intracranial tumors and discuss their utility in multidisciplinary pre-therapeutic evaluation. Isotropic, high-resolution, volumetric MRI data was collected, and CR was performed utilizing a proprietary application, "Anatomy Education" Siemens, Munich, Germany., Results: Discrimination of cortex to white matter, brain surface to vessels, subarachnoid space to cortex and skull to intracranial structures was achieved and optimized by using various display settings on the Anatomy education application. Progressive removal of tissue layers allowed for a comprehensive assessment of the entire region of interest. Complex, small structures were demonstrated in very high detail. The depth and architecture of the sulci was appreciated in a format that more closely mimicked gross pathology than traditional imaging modalities. With appropriate display settings, the relationship of the cortical surface to the adjacent vasculature was also delineated., Conclusion: CR depicts the anatomic location of brain tumors in a format that depicts the relative proximity of adjacent structures in all dimensions and degrees of freedom. This allows for better conceptualization of the pathology and greater ease of communication between radiologists and other clinical teams, especially in the context of pretherapeutic planning., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Engaging medical students and radiology residents in research during clinically focused training in residency can be challenging. We investigated extending a substantial degree of supervised autonomy to qualified residents to engage, mentor, and manage teams of medical students and other residents in research projects, fostering a system of laddered mentoring, referred to as "Resident Managed Peer Mentoring Program." The structure is as follows: a resident with research experience (preceptor) first identifies small-scale hypothesis driven projects which different novice learner-researchers at different levels of research background and training can undertake. The learner and preceptor then outline the learner's deliverables and set deadlines for outcomes, with regular faculty check-ins and oversight., Materials and Methods: This observational study assessed the outcomes of our "Resident Managed Peer Mentoring Program" beginning November 2019. Primary outcomes were numbers of peer-reviewed publications credited to individual radiology physicians. Secondary outcomes were: numbers of radiology physicians who participated in publication and academic rank-based analysis of publication numbers for attending radiologists before and after the intervention., Results: Number of peer-reviewed PubMed publications increased after our intervention (47.8%, in year-1; 167.4% in year-2). Increases also occurred in the number of radiology physicians who authored publications. The effect was largest for early career physicians., Conclusion: The "Resident managed peer-mentoring program" was a productive method that proved especially beneficial for students, residents, and early career physicians in our clinically focused training program. This approach may be transferable to other programs where an increase in research participation and productivity are valued., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Celiac disease (CD) is associated with an increased risk for respiratory infections and severe outcomes. No data have been reported in the scientific literature regarding the outcomes of COVID-19 in this population. The aim of this study was to report matched clinical outcomes in a large cohort of 930 patients with COVID-19 in the setting of known CD., Methods: Analysis of a multicenter research network TriNETX was performed, including COVID-19 patients aged more than 16 years. Outcomes of COVID-19-positive patients with concurrent CD were compared with a propensity-matched cohort of patients without CD., Results: A total of 341,499 patients with SARS-CoV-2 infection were identified on the research network: 930 (0.27%) with CD and 340,569 (99.73%) without CD. In the 30- and 60-day periods post SARS-CoV-2 infection, 12 (1.29%) and 13 (1.40%) deaths, respectively, were reported in the CD group. Fewer patients in the CD group reached the composite outcome of either mechanical ventilation or mortality at 60 days (risk ratio 0.58, 95% confidence interval 0.36-0.95). After propensity matching, no difference in clinical outcomes was observed., Conclusion: Our data suggest that patients with CD are not at increased risk of COVID-19-related morbidity or mortality., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Congenital adrenal hyperplasia is an autosomal recessive disease most commonly associated with 21-hydroxylase deficiency, an enzyme integral in the biosynthesis of mineralocorticoids and glucocorticoids. We present a case of a 49-year-old male with congenital adrenal hyperplasia and commonly associated findings of adrenal myelolipoma, testicular adrenal rest tumors, as well as primary pigmented nodular adrenocortical disease. Adrenal myelolipoma is a rare, benign disease process associated with exogenous steroid treatment noncompliance in the setting of congenital adrenal hyperplasia. Testicular adrenal rest tumors are benign testicular tumors associated with congenital adrenal hyperplasia. Primary pigmented nodular adrenocortical disease is an ACTH-independent cortisol producing lesion. Our case emphasizes the association of congenital adrenal hyperplasia with adrenal myelolipoma and testicular adrenal rest tumors as well as the importance of familiarity with these associations to guide patient management., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Primary nodular chest wall amyloidoma, in which a solitary mass of amyloid is deposited in and around the lungs with no evidence of systemic amyloidosis, is extremely rare, most often asymptomatic, and may resemble primary bronchogenic carcinoma. As a result, there are fewer than 100 cases published in the literature and no controlled clinical trials. Primary nodular chest wall amyloidoma is typically diagnosed either as an incidental radiological finding or after very serious and destructive mass growth at which point late-stage respiratory and pain symptoms finally develop, most often in elderly patients. We present imaging studies of a 61-year-old male patient with an unusually massive and destructive chest wall mass, originating in the chest wall, diagnosed as chest wall amyloidoma by histopathology analysis. Our CT, MRI, and PET scan findings are consistent with and contribute to the developing pattern of imaging characteristics seen in other case studies, which can be used to identify amyloidoma before it becomes destructive using non-invasive imaging analyses., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The crista terminalis is a normal anatomical structure, characterized by a smooth muscular ridge along the superior aspect of the right atrium. It is derived from resorption of the right valve of the sinus venosus and it divides the right atrium into smooth posteromedial and trabeculated anterolateral portions. Crista terminalis is not normally detected in the standard views of transthoracic echocardiogram and non-gated CT of the chest. In rare circumstances, the crista terminalis may be prominent and could lead to misdiagnosis as a malignant process, such as in our case. A comprehensive understanding of the crista terminalis anatomy, and its characteristic appearance on transthoracic echocardiogram, CT and PET/CT will minimize the risk of misdiagnosis and will avoid patient anxiety with more extensive examinations. Here, we present a case of a 78-year-old male with newly diagnosed high-grade invasive urinary bladder urothelial carcinoma. Pre-operative transthoracic echocardiogram reported as 2 cm right atrial mass concerning a metastasis lesion. Subsequent evaluation with MRI cardiac morphology confirmed the diagnosis of benign prominent crista terminalis, a normal anatomical structure., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant multiorgan systemic disorder manifesting as cutaneous fibrofolliculomas, lung cysts with or without spontaneous pneumothorax, and renal tumors. It results from mutation of the gene located on the short arm of chromosome 17 (17p11.2). The gene codes for the protein folliculin, which is believed to be an oncogene suppressor protein. This syndrome is often underdiagnosed. Presence of lung cysts on chest CT should prompt inclusion of BHDS in the differential diagnosis, since these findings may develop earlier than other manifestations. There are key imaging characteristics of pulmonary cysts on CT of the chest which can suggest the diagnosis of BHDS and help in early detection and prompt screening for renal tumors. The main concern with BHDS is the increased risk of renal carcinoma. Here, we report a case of a 59-year-old male who was suspected to have the diagnosis of BHDS based on characteristic features of lung cysts on the Chest CT, subsequently confirmed by genetic testing., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: In this study, we report clinical outcomes in COVID-19 infection in a large cohort of people with cystic fibrosis (pwCF) and compare these outcomes to a propensity score matched cohort of people without CF., Methods: Analysis of a multicenter research network TriNETX was performed including patients more than 16 years of age diagnosed with COVID-19. Outcomes in COVID-19 positive pwCF were compared with a propensity-matched cohort of people without CF., Results: A total of 507,810 patients with COVID-19 were included (422 patients, 0.08% with CF; 507,388 patients, 99.92% without CF. Mean age at COVID-19 diagnosis in CF cohort was 46.6 ± 19.3 years, with female predominance (n = 225, 53.32%). Majority of the participants were Caucasian (n = 309, 73.22%). In the crude, unmatched analysis, mortality, hospitalization, critical care need, mechanical ventilation, acute kidney injury and composite (combination of intubation and mortality) outcome at 30 days was higher in the pwCF. Following robust propensity matching, pwCF had higher hospitalization rate (RR 1.56, 95% CI 1.20-2.04), critical care need (RR 1.78, 95% CI 1.13-2.79), and acute renal injury (RR 1.60, 95% CI 1.07-2.39) as compared to patients without CF., Conclusion: People with CF are at risk of poor outcomes with COVID-19.5.2% of these patients died within one month of COVID-19 diagnosis, and more than one in 10 patients required critical care. Therefore, the relatively young median age of cystic fibrosis patients, and lower prevalence of obesity do not protect these patients from severe disease contrary to prior reports., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Analyses of COVID-19 infection outcomes in patients with preexisting pulmonary sarcoidosis are lacking and are limited to case reports or small case series with the largest study reporting outcomes of 37 patients., Research Question: Retrospective cohort study to assess clinical outcomes of 945 patients with pulmonary sarcoidosis, presenting with COVID 19, compared to a propensity matched cohort of patients without sarcoidosis., Study Design and Methods: Analysis of a multi-center research network TriNETX was performed including patients more than 16 years of age diagnosed with COVID-19. Outcomes in COVID-19 positive patients with concurrent pulmonary sarcoidosis were compared with a propensity score matched cohort of patients without pulmonary sarcoidosis., Results: A total of 278,271 patients with COVID-19 on the research network were identified, 954 patients (0.34 %) carried a diagnosis of pulmonary sarcoidosis. Mean age of patients with sarcoidosis was 56.3 ± 13.2 years, with female predominance (n = 619, 64.89 %). 49.69 % of the participants were African American (n = 474). Co-morbidities including hypertension, chronic lower respiratory diseases, diabetes mellitus, ischemic heart disease, nicotine dependence, and chronic kidney disease were more common in patients with pulmonary sarcoidosis when compared to the non-pulmonary sarcoidosis cohort (all p values < 0.01). In unmatched analysis, pulmonary sarcoidosis group had higher mortality, increased risk for hospitalization, intubation and need for renal replacement therapy. After propensity score matching, no difference in any of the outcome measures was observed., Interpretation: Crude COVID-19 mortality and other clinical outcome measures are poor in pulmonary sarcoidosis cohort; however, propensity-matched analyses revealed no difference in outcomes, showing that higher mortality is driven by higher burden of comorbidities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Axonal injury is the primary source of irreversible neurological decline in persons with multiple sclerosis (pwMS). Identifying and quantifying myelin and axonal loss in lesional and perilesional tissue in vivo is fundamental for a better understanding of multiple sclerosis (MS) outcomes and patient impairment. Using advanced magnetic resonance imaging (MRI) methods, consisting of selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT) and multi-compartment diffusion MRI with the spherical mean technique (SMT), we conducted a cross-sectional pilot study to assess myelin and axonal damage in the normal appearing white matter (NAWM) surrounding chronic black holes (cBHs) and how this pathology correlates with disability in vivo. We hypothesized that lesional axonal transection propagates tissue injury in the surrounding NAWM and that the degree of this injury is related to patient disability., Methods: Eighteen pwMS underwent a 3.0 Tesla conventional clinical MRI, inclusive of T1 and T2 weighted protocols, as well as SIR-qMT and SMT. Regions of interests (ROIs) were manually delineated in cBHs, NAWM neighboring cBHs (perilesional NAWM), distant ipsilateral NAWM and contra-lateral distant NAWM. SIR-qMT-derived macromolecular-to-free pool size ratio (PSR) and SMT-derived apparent axonal volume fraction (V ax ) were extracted to infer on myelin and axonal content, respectively. Group differences were assessed using mixed-effects regression models and correlation analyses were obtained by bootstrapping 95% confidence interval., Results: In comparison to perilesional NAWM, both PSR and V ax values were reduced in cBHs (p < 0.0001) and increased in distant contra-lateral NAWM ROIs (p < 0.001 for PSR and p < 0.0001 for V ax ) but not ipsilateral NAWM (p = 0.176 for PSR and p = 0.549 for V ax ). V ax values measured in cBHs correlated with those in perilesional NAWM (Pearson rho = 0.63, p < 0.001). No statistically relevant associations were seen between PSR/V ax values and clinical and/or MRI metrics of the disease with the exception of cBH PSR values, which correlated with the Expanded Disability Status Scale (Pearson rho = -0.63, p = 0.03)., Conclusions: Our results show that myelin and axonal content, detected by PSR and V ax , are reduced in perilesional NAWM, as a function of the degree of focal cBH axonal injury. This finding is indicative of an ongoing anterograde/retrograde degeneration and suggests that treatment prevention of cBH development is a key factor for preserving NAWM integrity in surrounding tissue. It also suggests that measuring changes in perilesional areas over time may be a useful measure of outcome for proof-of-concept clinical trials on neuroprotection and repair. PSR and V ax largely failed to capture associations with clinical and MRI characteristics, likely as a result of the small sample size and cross-sectional design, however, longitudinal assessment of a larger cohort may unravel the impact of this pathology on disease progression., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Implementation of low-dose chest computed tomography (CT) lung cancer screening and the ever-increasing use of cross-sectional imaging are resulting in the identification of many screen- and incidentally detected indeterminate pulmonary nodules. While the management of nodules with low or high pre-test probability of malignancy is relatively straightforward, those with intermediate pre-test probability commonly require advanced imaging or biopsy. Noninvasive risk stratification tools are highly desirable., Methods: We previously developed the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a conventional predictive radiomic model based on eight imaging features capturing nodule location, shape, size, texture and surface characteristics. Herein we report its external validation using a dataset of incidentally identified lung nodules (Vanderbilt University Lung Nodule Registry) in comparison to the Brock model. Area under the curve (AUC), as well as sensitivity, specificity, negative and positive predictive values were calculated., Results: For the entire Vanderbilt validation set (n=170, 54% malignant), the AUC was 0.87 (95% CI 0.81-0.92) for the Brock model and 0.90 (95% CI 0.85-0.94) for the BRODERS model. Using the optimal cut-off determined by Youden's index, the sensitivity was 92.3%, the specificity was 62.0%, the positive (PPV) and negative predictive values (NPV) were 73.7% and 87.5%, respectively. For nodules with intermediate pre-test probability of malignancy, Brock score of 5-65% (n=97), the sensitivity and specificity were 94% and 46%, respectively, the PPV was 78.4% and the NPV was 79.2%., Conclusions: The BRODERS radiomic predictive model performs well on an independent dataset and may facilitate the management of indeterminate pulmonary nodules., Competing Interests: Conflict of interest: F. Maldonado reports grants from Department of Defense (Lung Cancer Research Program under award number W81XWH-15-1-0110), during the conduct of the study; and holds intellectual property rights as an inventor of the CANARY software and BRODERS classifier, but does not receive any financial relationships regarding this software. Conflict of interest: C. Varghese has nothing to disclose. Conflict of interest: S. Rajagopalan reports grants from Department of Defense (Lung Cancer Research Program under award number W81XWH-15-1-0110 to F. Maldonado), during the conduct of the study; CALIPER software is licensed to Imbio, LLC, from whom The Mayo Clinic and B.J. Bartholmai receive royalties related to CALIPER (also known as Imbio Lung Texture Analysis, LTA); and S. Rajagoplan holds intellectual property rights as an inventor of the CANARY software and BRODERS classifier, but does not receive any financial relationships regarding this software. Conflict of interest: F. Duan reports grants from Department of Defense (Lung Cancer Research Program under award number W81XWH-15-1-0110 to F. Maldonado), during the conduct of the study. Conflict of interest: A.B. Balar has nothing to disclose. Conflict of interest: D.A. Lakhani has nothing to disclose. Conflict of interest: S.L. Antic has nothing to disclose. Conflict of interest: P.P. Massion has nothing to disclose. Conflict of interest: T.F. Johnson reports grants from Department of Defense, during the conduct of the study. Conflict of interest: R.A. Karwoski reports grants from Department of Defense (Lung Cancer Research Program under award number W81XWH-15-1-0110 to F. Maldonado), during the conduct of the study; CALIPER software is licensed to Imbio, LLC, from whom The Mayo Clinic and B.J. Bartholmai receive royalties related to CALIPER (also known as Imbio Lung Texture Analysis, LTA); and R.A. Karwoski holds intellectual property rights as an inventor of the CANARY software and BRODERS classifier, but does not receive any financial relationships regarding this software. Conflict of interest: R.A. Robb reports grants from Department of Defense (Lung Cancer Research Program under award number W81XWH-15-1-0110 to F. Maldonado), during the conduct of the study; CALIPER software is licensed to Imbio, LLC, from whom The Mayo Clinic and B.J. Bartholmai receive royalties related to CALIPER (also known as Imbio Lung Texture Analysis, LTA); and R.A. Robb holds intellectual property rights as an inventor of the CANARY software and BRODERS classifier, but does not receive any financial relationships regarding this software. Conflict of interest: B.J. Bartholmai reports grants from Department of Defense (Lung Cancer Research Program under award number W81XWH-15-1-0110 to F. Maldonado), during the conduct of the study; personal fees for advisory board work from Promedior, LLC, outside the submitted work; CALIPER software is licensed to Imbio, LLC, from whom The Mayo Clinic and B.J. Bartholmai receive royalties related to CALIPER (also known as Imbio Lung Texture Analysis, LTA); and B.J. Bartholmai holds intellectual property rights as an inventor of the CANARY software and BRODERS classifier, but does not receive any financial relationships regarding this software. Conflict of interest: T. Peikert reports grants from Department of Defense (Lung Cancer Research Program under award number W81XWH-15-1-0110 to F. Maldonado), during the conduct of the study; fees paid to institution for advisory board work from AstraZeneca and Novocure, outside the submitted work; and holds intellectual property rights as an inventor of the CANARY software and BRODERS classifier, but does not receive any financial relationships regarding this software., (Copyright ©ERS 2021.)