Multi-Parametric Radiomic Model to Predict 1p/19q Co-Deletion in Patients with IDH-1 Mutant Glioma: Added Value to the T2-FLAIR Mismatch Sign.

PURPOSE: The T2-FLAIR mismatch sign has shown promise in determining IDH mutant 1p/19q non-co-deleted gliomas with a high specificity and modest sensitivity. To develop a multi-parametric radiomic model using MRI to predict 1p/19q co-deletion status in patients with newly diagnosed IDH1 mutant glioma and to perform a comparative analysis to T2-FLAIR mismatch sign+. METHODS: In this retrospective study, patients with diagnosis of IDH1 mutant gliomas with known 1p/19q status who had preoperative MRI were included. T2-FLAIR mismatch was evaluated independently by two board-certified neuroradiologists. Texture features were extracted from glioma segmentation of FLAIR images. eXtremeGradient Boosting (XGboost) classifiers were used for model development. Leave-one-out-cross-validation (LOOCV) and external validation performances were reported for both the training and external validation sets. RESULTS: A total of 103 patients were included for model development and 18 patients for external testing validation. The diagnostic performance (sensitivity/specificity/accuracy) in the determination of the 1p/19q co-deletion status was 59%/83%/67% (training) and 62.5%/70.0%/66.3% (testing) for the T2-FLAIR mismatch sign. This was significantly improved (p = 0.04) using the radiomics model to 77.9%/82.8%/80.3% (training) and 87.5%/89.9%/88.8% (testing), respectively. The addition of radiomics as a computer-assisted tool resulted in significant (p = 0.02) improvement in the performance of the neuroradiologist with 13 additional corrected cases in comparison to just using the T2-FLAIR mismatch sign. CONCLUSION: The proposed radiomic model provides much needed sensitivity to the highly specific T2-FLAIR mismatch sign in the determination of the 1p/19q non-co-deletion status and improves the overall diagnostic performance of neuroradiologists when used as an assistive tool.

Evaluating the Utilization of a Perioperative Hyperglycemic Protocol: A Quality Improvement Project.

PURPOSE: The purpose of this project to evaluate adherence to the perioperative hyperglycemic protocol among Certified Registered Nurse Anesthetists (CRNAs) at a large academic hospital. A secondary objective of this project is CRNAs' perceptions of barriers to point-of-care (POC) testing and the protocol. DESIGN: A quality improvement project. METHODS: Using Donabedian's conceptual framework, a Phase 1 retrospective chart analysis of 297 patients with diabetes undergoing noncardiac surgery before and after implementing POC testing for intraoperative glucose control was performed. Only patients with preoperative BG ≥ 180 mg/dL were included in this phase of the project, which involved a comparison of the protocol utilization before and after implementation of POC testing. Phase 2 included an assessment of CRNA's perceptions of the protocol. FINDINGS: The final sample included 91 (37 preimplementation; 54 postimplementation) participants. There were no significant demographic differences between the groups. Overall, 52.7% of patients had intraoperative glucose checks, and only 16.5% received insulin. Preoperative BG levels decreased 11.4-points, and postoperative BG levels increased 20.4 points when comparing pre- and postimplementation groups. However, there were significant differences in postoperative glucose levels, pre- and postimplementation. The survey showed that the majority (65.5%) of CRNAs identified difficulty locating the protocol as the primary barrier to utilization. CONCLUSIONS: Although all patients included in this project qualified for an intraoperative glucose check, findings revealed that only half of the patients had a glucose check and less than one fifth of the patients received insulin treatment, indicating poor adherence to the protocol. Thus, while implementing protocols is essential, utilization and adherence to the protocol are critical to improving patient outcomes. Recommendations for continued improvement include increasing protocol accessibility, staff training, compliance monitoring, and a more simple protocol structure.

High-Resolution CT Imaging of the Temporal Bone: A Cadaveric Specimen Study.

Objective Super-high and ultra-high spatial resolution computed tomography (CT) imaging can be advantageous for detecting temporal bone pathology and guiding treatment strategies. Methods Six temporal bone cadaveric specimens were used to evaluate the temporal bone microanatomic structures utilizing the following CT reconstruction modes: normal resolution (NR, 0.5-mm slice thickness, 512 2 matrix), high resolution (HR, 0.5-mm slice thickness, 1,024 2 matrix), super-high resolution (SHR, 0.25-mm slice thickness, 1,024 2 matrix), and ultra-high resolution (UHR, 0.25-mm slice thickness, 2,048 2 matrix). Noise and signal-to-noise ratio (SNR) for bone and air were measured at each reconstruction mode. Two observers assessed visualization of seven small anatomic structures using a 4-point scale at each reconstruction mode. Results Noise was significantly higher and SNR significantly lower with increases in spatial resolution (NR, HR, and SHR). There was no statistical difference between SHR and UHR imaging with regard to noise and SNR. There was significantly improved visibility of all temporal bone osseous structures of interest with SHR and UHR imaging relative to NR imaging ( p < 0.001) and most of the temporal bone osseous structures relative to HR imaging. There was no statistical difference in the subjective image quality between SHR and UHR imaging of the temporal bone ( p ≥ 0.085). Conclusion Super-high-resolution and ultra-high-resolution CT imaging results in significant improvement in image quality compared with normal-resolution and high-resolution CT imaging of the temporal bone. This preliminary study also demonstrates equivalency between super-high and ultra-high spatial resolution temporal bone CT imaging protocols for clinical use.

Artificial Intelligence in Head and Neck Imaging.

Artificial intelligence (AI) can be applied to head and neck imaging to augment image quality and various clinical tasks including segmentation of tumor volumes, tumor characterization, tumor prognostication and treatment response, and prediction of metastatic lymph node disease. Head and neck oncology care is well positioned for the application of AI since treatment is guided by a wealth of information derived from CT, MRI, and PET imaging data. AI-based methods can integrate complex imaging, histologic, molecular, and clinical data to model tumor biology and behavior, and potentially identify associations, far beyond what conventional qualitative imaging can provide alone.

Cochlear Meniere's: A Distinct Clinical Entity With Isolated Cochlear Hydrops on High-Resolution MRI?

Objective: Describe the clinical characteristics of patients with isolated cochlear endolymphatic hydrops (EH). Study design: Clinical case series. Setting: Tertiary Neurotology referral clinic. Patients: All subjects presenting to a University Neurotology clinic during a 1-year period from July 2015 until August 2016 who had isolated cochlear EH on MRI. Patients with a history of temporal bone surgery prior to the MRI were excluded. Intervention: High-resolution delayed-intravenous contrast MRI. Main outcome measures: Audiometric and vestibular testing, clinical history analysis. Results: 10 subjects demonstrated isolated, unilateral cochlear hydrops on MRI. None of these patients met the criteria for Meniere's disease. Mean age of the group was 66.4 years and most were males (70%). Unilateral aural fullness (70%), tinnitus (80%), and hearing loss (90%) were frequently observed. Only one patient presented with unsteadiness (10%) and one patient had a single isolated spell of positional vertigo 1 month prior to the MRI (10%) but no further vertigo spells in the 4 years following the MRI. The mean PTA was 37.8 dB which was significantly decreased from the non-affected ear with PTA of 17.9 (p < 0.001). One patient developed vertiginous spells and unsteadiness 4 years after initial presentation and a repeat MRI revealed progression to utricular, saccular and cochlear hydrops. Vestibular testing was obtained in five patients with one patient presenting with 50% caloric paresis and all others normal. The most common treatment tried was acetazolamide in seven patients with 86% reporting subjective clinical improvement. Two out of the 10 patients had a history of migraine (20%). Conclusions: Patients with MRI exhibiting isolated cochlear EH present with predominantly auditory symptoms: mild to moderate low-frequency hearing loss, aural fullness, tinnitus without significant vertigo. Isolated cochlear hydrops is more common in males, average age in mid-60's and there is a low comorbidity of migraine headaches. This contrasts significantly with patients with isolated saccular hydrops on MRI from our prior studies. We believe that isolated cochlear EH with hearing loss but no vertigo is distinct from Meniere's disease or its variant delayed endolymphatic hydrops. We propose that cochlear Meniere's disease represents a distinct clinical entity that could be a variant of Meniere's disease.

Neuroimaging findings and pathophysiology of dorsal spinal arachnoid webs: illustrative case.

BACKGROUND: Spinal arachnoid webs are uncommon and difficult to diagnose, especially because causative intradural transverse bands of arachnoid tissue are radiographically occult. Left untreated, arachnoid webs may cause progressive, debilitating, and permanent neurological dysfunction. Conversely, more than 90% of patients may experience rapid neurological recovery after resection, even with a prolonged duration of presenting symptoms. Indirect imaging signs such as spinal cord indentation and compression with cerebrospinal fluid (CSF) flow alteration provide crucial diagnostic clues that are critical in guiding appropriate management of such patients. OBSERVATIONS: The authors reported a patient with no significant medical history who presented with back pain, progressive lower extremity weakness, gait ataxia, and bowel and bladder incontinence. They discussed multimodality imaging for determining the presence of arachnoid webs, including magnetic resonance imaging, phase-contrast CSF flow study, computed tomography myelography, and intraoperative ultrasound. They also discussed the detailed anatomy of the spinal subarachnoid space and a plausible pathophysiological mechanism for dorsal arachnoid webs. LESSONS: The authors report on a patient who underwent comprehensive imaging evaluation detailing the arachnoid web and whose subsequent anatomical localization and surgical treatment resulted in a full neurological recovery.

A Comprehensive Review of Cross-Sectional Imaging of the Nasolacrimal Drainage Apparatus: What Radiologists Need to Know.

OBJECTIVE. The purpose of this study is to provide a comprehensive review of the radiographic anatomy and cross-sectional imaging findings of the full gamut of nasolacrimal drainage apparatus diseases, highlighting imaging findings from the different nasolacrimal drainage apparatus surgeries, posttreatment complications, and potential imaging pitfalls. CONCLUSION. Radiologists play a critical role in guiding the management of nasolacrimal drainage apparatus diseases and should be familiar with the anatomy and characteristic imaging findings of commonly encountered nasolacrimal drainage apparatus abnormalities and surgeries.

Identification of quinones as novel PIM1 kinase inhibitors.

PIM1 is a proto-oncogene encoding the serine/threonine PIM1 kinase. PIM1 kinase plays important roles in regulating aspects of cell cycle progression, apoptosis resistance, and has been implicated in the development of such malignancies as prostate cancer and acute myeloid leukemia among others. Knockout of PIM1 kinase in mice has been shown to be non-lethal without any obvious phenotypic changes, making it an attractive therapeutic target. Our investigation of anthraquinones as kinase inhibitors revealed a series of quinone analogs showing high selectivity for inhibition of the PIM kinases. Molecular modeling studies were used to identify key interactions and binding poses of these compounds within the PIM1 binding pocket. Compounds 1, 4, 7 and 9 inhibited the growth of DU-145 prostate cancer cell lines with a potency of 8.21µM, 4.06µM, 3.21µM and 2.02µM.

Complications of aortic valve surgery: manifestations at CT and MR imaging.

Aortic valve replacement accounts for a significant portion of cardiac surgeries in the United States. Despite advances in prosthetic heart valve design, surgical technique, and postoperative care, complications after aortic valve replacement remain a leading cause of morbidity and mortality. Routine surveillance of prosthetic heart valves with transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and fluoroscopy is important, as these techniques allow accurate detection of prosthetic valve dysfunction. However, echocardiography and fluoroscopy may not allow identification of the specific underlying cause, including paravalvular leak, dehiscence, endocarditis, obstruction, structural failure, pseudoaneurysm formation, aortic dissection, and hemolysis. Magnetic resonance (MR) imaging and computed tomography (CT) have an emerging role as diagnostic tools complementary to conventional imaging for detection and monitoring of complications after aortic valve replacement. The choice between CT and MR imaging depends on individual patient characteristics, the type of prosthetic valve, and the acuity of the clinical situation. In general, screening with TTE followed by TEE is recommended. When results of TTE and TEE are inconclusive, cardiac CT and MR imaging should be considered. The choice between these imaging techniques depends on the presence of patient-specific contraindications to CT or MR imaging.

Particle embolization of the bilateral superior and inferior alveolar arteries for life threatening dental socket hemorrhage.

Particle embolization for epistaxis and intra-oral hemorrhage are performed on an as needed basis by neurointerventionalists. A case is presented of massive oral hemorrhage associated with end stage liver disease coagulopathy after tooth extraction of bilateral maxillary and mandibular molars. A man in his fifties with end stage liver disease who presented for evaluation of a syncopal episode was determined to be in hemorrhagic shock from 2 days of persistent oral bleeding after elective tooth extractions. Conservative management with multiple blood transfusion products, packing and vasoconstrictive spray was ineffective. Microcatheter angiograms of the alveolar arteries demonstrated blood and contrast pooling within the sockets of the extracted teeth. Selection of the bilateral supplying alveolar and inferior alveolar artery branches was achieved followed by polyvinyl alcohol particle embolization (250-355 µm). Polyvinyl alcohol particle embolization of dental socket hemorrhages is technically feasible and effective.

Extracranial sources of S100B do not affect serum levels.

S100B, established as prevalent protein of the central nervous system, is a peripheral biomarker for blood-brain barrier disruption and often also a marker of brain injury. However, reports of extracranial sources of S100B, especially from adipose tissue, may confound its interpretation in the clinical setting. The objective of this study was to characterize the tissue specificity of S100B and assess how extracranial sources of S100B affect serum levels. The extracranial sources of S100B were determined by analyzing nine different types of human tissues by ELISA and Western blot. In addition, brain and adipose tissue were further analyzed by mass spectrometry. A study of 200 subjects was undertaken to determine the relationship between body mass index (BMI) and S100B serum levels. We also measured the levels of S100B homo- and heterodimers in serum quantitatively after blood-brain barrier disruption. Analysis of human tissues by ELISA and Western blot revealed variable levels of S100B expression. By ELISA, brain tissue expressed the highest S100B levels. Similarly, Western blot measurements revealed that brain tissue expressed high levels of S100B but comparable levels were found in skeletal muscle. Mass spectrometry of brain and adipose tissue confirmed the presence of S100B but also revealed the presence of S100A1. The analysis of 200 subjects revealed no statistically significant relationship between BMI and S100B levels. The main species of S100B released from the brain was the B-B homodimer. Our results show that extracranial sources of S100B do not affect serum levels. Thus, the diagnostic value of S100B and its negative predictive value in neurological diseases in intact subjects (without traumatic brain or bodily injury from accident or surgery) are not compromised in the clinical setting.

HLA-DR3 transgenic mice immunized with adenovirus encoding the thyrotropin receptor: T cell epitopes and functional analysis of the CD40 Graves' polymorphism.

The major histocompatibility (MHC) molecule HLA-DR3 is a susceptibility gene for Graves' disease (GD) in Caucasians. Mice lacking murine MHC and expressing human HLA-DR3 develop thyrotropin receptor (TSHR) antibodies and sometimes hyperthyroidism after vaccination with TSHR-DNA. MHC molecules present peptides processed from antigens to T cells. Therefore, we used DR3-transgenic mice to investigate recognition of TSHR ectodomain peptides. After immunization with TSHR A-subunit adenovirus (A-subunit-Ad) but not control-adenovirus (Control-Ad), splenocytes from DR3 mice responded to A-subunit protein in culture by producing interferon-gamma (IFN-gamma). When challenged with 29 overlapping TSHR peptides, splenocytes from A-subunit-Ad- or Control-Ad-immunized mice responded to several peptides. However, in splenocytes from A-subunit-Ad but not Control-Ad mice, a peptide containing TSHR residues 142-161 induced significantly more IFN-gamma than the same splenocytes in medium alone. Immunized DR3 mice also permitted testing the TSHR-specific function of the CD40 single nucleotide polymorphism (C vs. T) associated with GD. Of three human DR3 human Epstein-Barr virus lines (EBVL), two had C in both alleles (CC) and one was CT. However, these EBVL presented peptides poorly and there was no difference between CC vs. CT EBVL in peptide presentation to splenocytes from immunized mice. A peptide corresponding to residues 145-163 is one of seven suggested to be important in GD based on HLA-binding affinities, T-epitope algorithms, and human studies. Consequently, as in human GD, TSHR amino acids 142-161 appear to include a major T cell epitope in HLA-DR3 transgenic mice immunized with A-subunit-Ad.

Targeted expression of the human thyrotropin receptor A-subunit to the mouse thyroid: insight into overcoming the lack of response to A-subunit adenovirus immunization.

The thyrotropin receptor (TSHR), the major autoantigen in Graves' disease, is posttranslationally modified by intramolecular cleavage to form disulfide-linked A- and B-subunits. Because Graves' hyperthyroidism is preferentially induced in BALB/c mice using adenovirus encoding the free A-subunit rather than full-length human TSHR, the shed A-subunit appears to drive the disease-associated autoimmune response. To further investigate this phenomenon, we generated transgenic mice with the human A-subunit targeted to the thyroid. Founder transgenic mice had normal thyroid function and were backcrossed to BALB/c. The A-subunit mRNA expression was confirmed in thyroid tissue. Unlike wild-type littermates, transgenic mice immunized with low-dose A-subunit adenovirus failed to develop TSHR Abs, hyperthyroidism, or splenocyte responses to TSHR Ag. Conventional immunization with A-subunit protein and adjuvants induced TSHR Abs lacking the characteristics of human autoantibodies. Unresponsiveness was partially overcome using high-dose, full-length human TSHR adenovirus. Although of low titer, these induced Abs recognized the N terminus of the A-subunit, and splenocytes responded to A-subunit peptides. Therefore, "non-self" regions in the B-subunit did not contribute to inducing responses. Indeed, transgenic mice immunized with high-dose A-subunit adenovirus developed TSHR Abs with thyrotropin-binding inhibitory activity, although at lower titers than wild-type littermates, suggesting down-regulation in the transgenic mice. In conclusion, in mice expressing a human A-subunit transgene in the thyroid, non-self human B-subunit epitopes are not necessary to induce responses to the A-subunit. Our findings raise the possibility that autoimmunity to the TSHR in humans may not involve epitopes on a cross-reacting protein, but rather, strong adjuvant signals provided in bystander immune responses.

Relationship between thyroid peroxidase T cell epitope restriction and antibody recognition of the autoantibody immunodominant region in human leukocyte antigen DR3 transgenic mice.

We investigated the relationship between thyroid peroxidase (TPO) antibody and T lymphocyte epitopes in TPO-adenovirus (TPO-Ad) immunized BALB/c mice and mice transgenic for the human class II molecule DR3 associated with human thyroid autoimmunity. TPO autoantibodies are largely restricted to an immunodominant region (IDR). BALB/c mice immunized with fewer (10(7) vs. 10(9)) TPO-Ad particles developed TPO antibodies with lower titers that displayed greater restriction to the IDR. However, as with higher-dose TPO-Ad immunization, T cell epitopes (assessed by splenocyte interferon-gamma response to TPO in vitro) were highly diverse and variable in different animals. In contrast, DR3 mice immunized the higher TPO-Ad dose (10(9) particles) had high TPO antibody levels that showed relative focus on the IDR. Moreover, T cell epitopes recognized by splenocytes from DR3 mice showed greater restriction than BALB/c mice. Antibody affinities for TPO were higher in DR3 than in BALB/c mice. The present study indicates that weak TPO-Ad immunization of BALB/c mice (with consequent low TPO antibody titers) is required for enhanced IDR focus yet is not associated with T cell epitopic restriction. Humanized DR3 transgenic mice, despite stronger TPO-Ad immunization, develop higher titer TPO antibodies that do focus on the autoantibody IDR with T cells that recognize a more limited range of TPO peptides. These data suggest a relationship between major histocompatibility complex class II molecules and the development of antibodies to the IDR, a feature of human thyroid autoimmunity.