Free induction decay navigator motion metrics for prediction of diagnostic image quality in pediatric MRI.

PURPOSE: To investigate the ability of free induction decay navigator (FIDnav)-based motion monitoring to predict diagnostic utility and reduce the time and cost associated with acquiring diagnostically useful images in a pediatric patient cohort. METHODS: A study was carried out in 102 pediatric patients (aged 0-18 years) at 3T using a 32-channel head coil array. Subjects were scanned with an FID-navigated MPRAGE sequence and images were graded by two radiologists using a five-point scale to evaluate the impact of motion artifacts on diagnostic image quality. The correlation between image quality and four integrated FIDnav motion metrics was investigated, as well as the sensitivity and specificity of each FIDnav-based metric to detect different levels of motion corruption in the images. Potential time and cost savings were also assessed by retrospectively applying an optimal detection threshold to FIDnav motion scores. RESULTS: A total of 12% of images were rated as non-diagnostic, while a further 12% had compromised diagnostic value due to motion artifacts. FID-navigated metrics exhibited a moderately strong correlation with image grade (Spearman's rho ≥ 0.56). Integrating the cross-correlation between FIDnav signal vectors achieved the highest sensitivity and specificity for detecting non-diagnostic images, yielding total time savings of 7% across all scans. This corresponded to a financial benefit of $2080 in this study. CONCLUSIONS: Our results indicate that integrated motion metrics from FIDnavs embedded in structural MRI are a useful predictor of diagnostic image quality, which translates to substantial time and cost savings when applied to pediatric MRI examinations.

Mutant IDH1 and thrombosis in gliomas.

Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II-IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26-30 % of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0 %). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85-90 % in wild-type versus 2-6 % in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE.

Coordinate regulation of mature dopaminergic axon morphology by macroautophagy and the PTEN signaling pathway.

Macroautophagy is a conserved mechanism for the bulk degradation of proteins and organelles. Pathological studies have implicated defective macroautophagy in neurodegeneration, but physiological functions of macroautophagy in adult neurons remain unclear. Here we show that Atg7, an essential macroautophagy component, regulates dopaminergic axon terminal morphology. Mature Atg7-deficient midbrain dopamine (DA) neurons harbored selectively enlarged axonal terminals. This contrasted with the phenotype of DA neurons deficient in Pten - a key negative regulator of the mTOR kinase signaling pathway and neuron size - that displayed enlarged soma but unaltered axon terminals. Surprisingly, concomitant deficiency of both Atg7 and Pten led to a dramatic enhancement of axon terminal enlargement relative to Atg7 deletion alone. Similar genetic interactions between Atg7 and Pten were observed in the context of DA turnover and DA-dependent locomotor behaviors. These data suggest a model for morphological regulation of mature dopaminergic axon terminals whereby the impact of mTOR pathway is suppressed by macroautophagy.

What Is the Appropriate Use of Renal Sonography in an Inner-City Population With New-Onset Acute Kidney Injury?

OBJECTIVES: We aimed to determine the prevalence of hydronephrosis in patients who underwent renal sonography for new-onset acute kidney injury (AKI) and to identify clinical factors predictive of hydronephrosis. In patients with hydronephrosis, we sought to investigate how routine renal sonography affects patient treatment, including performance of interventional procedures. METHODS: A retrospective chart review identified 274 adults with AKI who underwent renal sonography at an urban teaching hospital from January through July 2011. The prevalence of hydronephrosis was determined. Electronic medical records were reviewed for comorbidities, including risk factors for hydronephrosis such as a pelvic mass, prior renal or pelvic surgery, and neurogenic bladder, and for subsequent interventions and outcomes. RESULTS: Sonography showed hydronephrosis in 28 patients (10%); 5 (18%) had subsequent interventions. In a multivariable logistic regression model with the outcome being hydronephrosis, all considered risk factors (pelvic mass, prior renal or pelvic surgery, and neurogenic bladder) were significantly associated with hydronephrosis (odds ratio, 6.4; 95% confidence interval, 2.7-15.4; P < .001) when adjusting for age and diabetes mellitus. Diabetes had a negative predictive value for hydronephrosis. No diabetic patients younger than 85 years and without clinical risk factors had hydronephrosis. CONCLUSIONS: Hydronephrosis is infrequently seen on sonograms in hospitalized patients with AKI who lack risk factors for urinary tract obstruction. Deferral of sonography pending a trial of medical treatment is safe and will reduce medical costs. Adoption of clinical guidelines to assess patients' risk levels for hydronephrosis is critical to avoid unnecessary imaging.

Neuroimaging considerations in abusive head trauma.

This focused review on abusive head trauma describes the injuries to the head, brain and/or spine of an infant or young child from inflicted trauma and their neuroimaging correlates. Accurate recognition and diagnosis of abusive head trauma is paramount to prevent repeated injury, provide timely treatment, and ensure that accidental or underlying medical contributors have been considered. In this article, we aim to discuss the various findings on neuroimaging that have been associated with AHT, compared to those that are more consistent with accidental injuries or with underlying medical causes that may also be on the differential.

Multisystem inflammatory syndrome in children (MIS-C) and retropharyngeal edema: A case series.

Multisystem inflammatory syndrome in children (MIS-C) is thought to follow SARS-CoV-2 infection and presents with fever and multisystem dysfunction. We report three children with suspected MIS-C found to have retropharyngeal edema without evidence of a bacterial etiology. We raise the possibility that an association between MIS-C and retropharyngeal edema exists.

Assessing the impact of an orientation week on acclimation to radiology residency.

PURPOSE: Acclimating residents to radiology residency requires attention to new responsibilities, educational material, and social cohesion. To this end, we instituted a structured orientation week for incoming residents and assessed its impact. PROCEDURES: During the first weeks of July 2016 and 2017, first year residents attended a five day orientation free of clinical duties, consisting of didactics, hands-on training sessions, and social events. After two orientation cohorts, residents who completed orientation week, and two cohorts who had not, were given a voluntary, anonymous survey using Likert scale questions (1 [worst] to 5 [best]) regarding preparedness for responsibilities, learning, and social cohesion. Residents were asked which components were or would have been helpful. Independent samples t-tests were performed to evaluate differences between the two groups (two-tailed p < 0.05). FINDINGS: 21/37 (57%) residents participated. Higher percentages of residents who participated in the orientation week gave scores ≥4 when asked about preparedness for rotations (70% vs. 36%), learning new material (80% vs. 36%), and class cohesiveness (90% vs. 70%). Mean scores on these questions were also higher for these residents with regards to: preparedness for new responsibilities (3.7 vs. 2.9), learning new material (3.8 vs. 2.9), and class cohesiveness (4.5 vs. 3.8), with differences approaching significance (p = 0.09-0.15). Individual components receiving most votes of ≥4 were social outings, resident lunches, didactic lectures, and PACS training. CONCLUSION: A weeklong orientation program free of clinical duties was valued by residents and contributed to acclimation to new responsibilities, education, and social cohesion.

Clinical utility for diffusion MRI sequence in emergency and inpatient spine protocols.

Diffusion imaging of the spine has the potential to change clinical management, but is challenging due to the small size of the cord and susceptibility artifacts from adjacent structures. Reduced field-of-view (rFOV) diffusion can improve image quality by decreasing the echo train length. Over the past 2 years, we have acquired a rFOV diffusion sequence for MRI spine protocols on most inpatients and emergency room patients. We provide selected imaging diagnoses to illustrate the utility of including diffusion spine MRI in clinical practice. Our experiences support using diffusion MRI to improve diagnostic certainty and facilitate prompt treatment or clinical management.

Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway.

BACKGROUND: Macroautophagy is an evolutionarily conserved mechanism for bulk intracellular degradation of proteins and organelles. Pathological studies have implicated macroautophagy defects in human neurodegenerative disorders of aging including Alzheimer's disease and tauopathies. Neuronal deficiency of macroautophagy throughout mouse embryonic development results in neurodevelopmental defects and early postnatal mortality. However, the role of macroautophagy in mature CNS neurons, and the relationship with human disease neuropathology, remains unclear. Here we describe mice deficient in an essential macroautophagy component, Atg7, specifically within postnatal CNS neurons. RESULTS: Postnatal forebrain-specific Atg7 conditional knockout (cKO) mice displayed age-dependent neurodegeneration and ubiquitin- and p62-positive inclusions. Phosphorylated tau was significantly accumulated in Atg7 cKO brains, but neurofibrillary tangles that typify end-stage human tauopathy were not apparent. A major tau kinase, glycogen synthase kinase 3ß (GSK3ß), was also accumulated in Atg7 cKO brains. Chronic pharmacological inhibition of tau phosphorylation, or genetic deletion of tau, significantly rescued Atg7-deficiency-mediated neurodegeneration, but did not suppress inclusion formation. CONCLUSIONS: These data elucidate a role for macroautophagy in the long-term survival and physiological function of adult CNS neurons. Neurodegeneration in the context of macroautophagy deficiency is mediated through a phospho-tau pathway.