Early detection of nasopharyngeal carcinoma: performance of a short contrast-free screening magnetic resonance imaging.

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.

The Association Between Transverse Maxillary Deficiency and Septal Deviation in Adults with Obstructive Sleep Apnea.

OBJECTIVES: Recent evidence suggests that environmental factors impact craniofacial development. Specifically, the height and width of the maxilla may impact the degree of septal deviation. We sought to determine the relationship between transverse maxillary deficiency and severity of septal deviation. METHODS: A prospective cohort of adult sleep surgery patients were evaluated by standardized CT imaging. Primary outcomes evaluated the relationship of a narrow, high-arched palate (the palatal height to width ratio) with the degree of septal deviation at the level of the 1st premolar and 1st molar. Secondary outcome evaluated the relationship of the palatal height-to-width ratio and nasal obstruction. Both adjusted and unadjusted linear regression were performed, including correction for multiple hypothesis testing. RESULTS: Ninety-three patients were included. On average, the cohort was middle aged (54.7 ± 12.7 years), obese (BMI 30.1 ± 4.5 kg/m2), predominantly male (74.2%), White (73.1%), and with severe obstructive sleep apnea (OSA) (AHI 30.0 ± 18.7 events/h). A moderate correlation was observed between both the relative and absolute inter-premolar palatal height and the degree of septal deviation at the inter-molar region. No significant correlation was observed between palatal dimensions and NOSE score. CONCLUSION: This study found that transverse maxillary deficiency is moderately associated with greater degree of septal deviation among a sample of OSA patients. This contributes to the concept that craniofacial development impacts the nasal airway, promoting a comprehensive evaluation of both endonasal and extranasal structures. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2464-2470, 2024.

Harmonization of multi-site diffusion tensor imaging data for cervical and thoracic spinal cord at 1.5 T and 3 T using longitudinal ComBat.

MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths. DTI metrics were extracted and averaged for all slices within each vertebral level. Metrics were examined for variability and then harmonized using longitudinal ComBat (longComBat). Four scanners were used: Siemens 3 T Prisma, Siemens 1.5 T Avanto, Philips 3 T Ingenia, Philips 1.5 T Achieva. Average full cord diffusion values/standard deviation for all subjects and scanners were FA: 0.63, σ = 0.10, MD: 1.11, σ = 0.12 × 10-3 mm2/s, AD: 1.98, σ = 0.55 × 10-3 mm2/s, RD: 0.67, σ = 0.31 × 10-3 mm2/s. FA metrics averaged for all subjects by level were relatively consistent across scanners, but large variability was found in diffusivity measures. Coefficients of variation were lowest in the cervical region, and relatively lower for FA than diffusivity measures. Harmonized metrics showed greatly improved agreement between scanners. Variability in DTI of the spinal cord arises from scanner hardware differences, pulse sequence differences, physiological motion, and subject compliance. The use of longComBat resulted in large improvement in agreement of all DTI metrics between scanners. This study shows the importance of harmonization of diffusion data in the spinal cord and potential for longitudinal and multisite clinical research and clinical trials.

Transverse Maxillary Deficiency Predicts Increased Upper Airway Collapsibility during Drug-Induced Sleep Endoscopy.

OBJECTIVE: To examine the relationship between craniofacial skeletal anatomy and objective measures of pharyngeal collapse obtained during drug-induced sleep endoscopy. We hypothesized that transverse maxillary deficiency and an increased pharyngeal length will be associated with higher levels of pharyngeal collapsibility. STUDY DESIGN: Cross-sectional analysis in a prospective cohort. SETTING: University Hospital. METHODS: A cross-sectional analysis was conducted in a cohort of consecutive patients from the positive airway pressure (PAP) alternatives clinic who underwent computed tomography (CT) analysis and drug-induced sleep endoscopy for characterization of upper airway collapsibility. PAP titration was used to determine pharyngeal critical pressure (PCRIT ) and pharyngeal opening pressure (PhOP). CT metrics included: Transverse maxillary dimensions (interpremolar and intermolar distances) and pharyngeal length (posterior nasal spine to hyoid distance). RESULTS: The cohort (n = 103) of severe obstructive sleep apnea (Apnea and Hipopnea Index 32.1 ± 21.3 events/h) was predominantly male (71.8%), Caucasian (81.6%), middle-aged (54.4 ± 14.3 years), and obese (body mass index [BMI] = 30.0 ± 4.9 kg/m2 ). Reduced transverse maxillary dimensions were associated with higher PCRIT (intermolar distance: ß [95% confidence interval, CI] = -.25 [-0.14, -0.36] cmH2 O/mm; p = .03) and PhOP (Interpremolar distance: ß = -.25 [-0.14, -0.36] cmH2 O/mm; p = .02). Longer pharyngeal length was also associated with higher PCRIT (ß = .11 [0.08, 0.14] cmH2 O/mm, p = .04) and PhOP (ß [95% CI] = .06 [0.03, 0.09] cmH2 O/mm, p = .04). These associations persisted after adjustments for sex, age, height, and BMI. CONCLUSION: Our results further the concept that skeletal restriction in the transverse dimension and hyoid descent are associated with elevations in pharyngeal collapsibility during sleep, suggesting a role of transverse deficiency in the pathogenesis of airway obstruction.

Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions.

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.

Plasma Epstein-Barr Virus DNA and Risk of Future Nasopharyngeal Cancer.

BACKGROUND: We previously conducted a prospective study to show that nasopharyngeal cancer (NPC) screening with circulating Epstein­Barr virus (EBV) DNA analysis can improve survival. However, the long-term significance of positive results in individuals without cancer was unclear. METHODS: We conducted a second-round screening at a median of 43 months after the initial screening. Participants with detectable plasma EBV DNA were retested in 4 weeks, and those with persistently positive results were investigated with nasal endoscopy and magnetic resonance imaging. RESULTS: Of the 20,174 volunteers who participated in the first-round screening, 17,838 (88.6%) were rescreened. Among them, 423 (2.37%) had persistently detectable plasma EBV DNA. Twenty-four patients were identified as having NPC. A significantly higher proportion of patients had stage I/II cancer than in a historical cohort (67% vs. 20%; chi-square test, P<0.001), and they had superior 3-year progression-free survival (100% vs. 78.8%). Compared with participants with undetectable plasma EBV DNA in the first round of screening, participants with transiently and persistently positive results in the first round were more likely to have a cancer identified in the second round, with relative risks of 4.4 (95% confidence interval, 1.3 to 15.0) and 16.8 (95% confidence interval, 5.7 to 49.6), respectively. CONCLUSIONS: Individuals with detectable plasma EBV DNA but without an immediately identifiable NPC were more likely to have the cancer identified in another round of screening performed 3 to 5 years later. (Funded by Kadoorie Charitable Foundation and others; ClinicalTrials.gov number, NCT02063399.)

Ipsilateral Carotid Plaque Presence is Inversely Associated with Patent Foramen Ovale in Cryptogenic Stroke: A Multicenter CohortStudy.

BACKGROUND: Embolic stroke of undetermined source (ESUS) accounts for up to 20% of all strokes. Potential contributors to ESUS include patent foramen ovale (PFO) and non-stenotic plaque (<50%, NSP) of the ipsilateral internal carotid artery (ICA). To better differentiate these as unique mechanisms, we explored the prevalence of each in a multicenter observational cohort. METHODS: A retrospective multicenter cohort of consecutive patients with ESUS was queried (2015-2021). Patients with unilateral, anterior circulation ESUS who had a computed tomography angiography neck scan and a transthoracic echocardiogram (TTE) and/or transesophageal echocardiogram (TEE) with adequate visualization of a PFO were included. Patients with prior carotid stent, endarterectomy or alternative etiologies were excluded from the study. Descriptive statistics were used to characterize patients with and without PFO, with multivariable logistic regression used to predict the presence of a PFO based on clinicoradiographic factors as well as degree of luminal stenosis and ipsilateral plaque thickness >3mm, based on previously published thresholds of clinical relevance. RESULTS: Of the 234 included patients with unilateral anterior ESUS and adequate TTE or TEE, 17 (7.3%) had a PFO and 64 (27.4%) had ≥3mm of ipsilateral ICA plaque. Patients with PFO had significantly less NSP and less ipsilateral cervical ICA stenosis (0% [IQR 0-0%] vs. 0% [IQR 0-50%], p=0.03; Table). After adjustment for all predictors of PFO in multivariable regression (p<0.1: Hispanic ethnicity and ipsilateral plaque thickness), ipsilateral NSP was independently associated with a 62% lower odds of harboring a PFO (ORadj per 1cm of plaque 0.48, 95%CI 0.25-0.94). No patients with a PFO had ≥3mm of ipsilateral ICA plaque. CONCLUSION: Ipsilateral NSP is more common in ESUS patients without a PFO. While this study is limited by the small PFO event rate, it supports the notion that NSP and PFO may be independent contributors to ESUS.

Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape.

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.

Sex Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source.

Background We examined sex differences in nonstenotic carotid plaque composition in patients with embolic stroke of undetermined source (ESUS). Methods and Results Patients with anterior circulation ischemic stroke imaged with neck computed tomographic angiography who met criteria for ESUS or had atrial fibrillation were identified. Patients with atrial fibrillation were included as a negative control. Semiautomated plaque quantification software analyzed carotid artery bifurcations. Plaque subcomponent (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core) volumes were compared by sex and in paired analyses of plaque ipsilateral versus contralateral to stroke. Multivariate linear regressions tested for associations. Ninety-four patients with ESUS (55% women) and 95 patients with atrial fibrillation (47% women) were identified. Men with ESUS showed significantly higher volumes of calcified plaque (63.9 versus 19.6 mm3, P<0.001), IPH (9.4 versus 3.3 mm3, P=0.008) and a IPH/lipid rich necrotic core ratio (0.17 versus 0.07, P=0.03) in carotid plaque ipsilateral to stroke side than women. The atrial fibrillation cohort showed no significant sex differences in plaque volumes ipsilateral to stroke. Multivariate analyses of the ESUS cohort showed male sex was associated with IPHipsi (ß=0.49; 95% CI, 0.11-0.87) and calciumipsi (ß=0.78; 95% CI, 0.33-1.23). Paired plaque analyses in men with ESUS showed significantly higher calcified plaque (63.9 versus 34.1 mm3, P=0.03) and a trend of higher IPHipsi (9.4 versus 7.5 mm3, P=0.73) and lipid rich necrotic coreipsi (59.0 versus 48.4 mm3, P=0.94) volumes. Conclusions Sex differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of nonstenosing carotid plaque as a stroke mechanism in men versus women.

Mismatch between automated CTP and ASPECTS score in patients with anterior large vessel occlusion.

OBJECTIVES: To evaluate the relationship between delay to computed tomography perfusion and estimated core infarct volumes in patients with large vessel occlusion (LVO). PATIENTS AND METHODS: A retrospective registry of consecutive adults >18 years old who underwent CTP in clinical practice for suspected LVO within 24 h of LKN at 3 academic hospitals was queried (06/2017 - 12/2017). CT and CTP findings were compared over time as a continuous variable, and dichotomized by ≤6 h or 6-24 h from LKN. RESULTS: Of 410 screened patients, 75 had LVO, of whom 60 (14.6 %) met inclusion criteria (median age 78y [IQR 64-84], 36 were female [60 %]), and 39 (65.0 %) underwent thrombectomy. Thirty (50 %) presented in the extended window (6-24 h) and had lower ASPECTS scores compared to patients in the early window (median 7 vs. 9, p < 0.01). Perfusion core (rCBF <30 %) volumes were similar (median 8 vs. 25, p = 0.10). After adjustment for age, NIHSS, and thrombolysis, there was a trend for lower ASPECTS for every hour after LKN (proportional OR 0.92, 95 %CI 0.84-1.00, p = 0.06), but no change in perfusion core (p = 0.37) or Tmax>6 s volumes (p = 0.29), or mismatch ratios (p = 0.48) after adjusting for age, NIHSS, ASPECTS, and thrombolysis. CONCLUSION: As time progresses in anterior LVO, the unenhanced CT is more sensitive than CTP for detecting irreversibly damaged tissue. These results underscore the importance of carefully reviewing the unenhanced and perfusion CT when considering a patient for thrombectomy.

Frontal inverted papillomas: A 25-year study.

OBJECTIVES/HYPOTHESIS: This study analyzes the treatment outcomes of frontal inverted papillomas (FIPs) in an attempt to provide guidelines for surgery selection. STUDY DESIGN: Retrospective case series. METHODS: The treatment results of 29 FIPs classified into five categories were retrospectively analyzed. The five categories are F1, tumor prolapsed into frontal sinus, tumor origin outside frontal sinus; F2, tumor origin inside frontal sinus, medial to the plane of lamina papyracea; F3, tumor origin inside frontal sinus, lateral to the plane of lamina papyracea; F4, bilateral; and F5, extrasinonasal. RESULTS: Of the 11 F1 cases, 73% had Draf I and 27% had Draf IIA procedures. There was one (9%) frontal recurrence and one (9%) frontal stenosis. Of the 10 F2 cases, 10% had Draf I, 40% had Draf IIA, 40% had Draf IIB, and 10% had Draf III surgery with a trephination. One patient (10%) had a frontal recurrence. Of the five F3 cases, 40% had Draf IIA surgery, 20% had external frontoethmoidectomy, and 40% had external frontal sinusotomy. The recurrence rate was 60%, and frontal stenosis rate was 60%. The two F4 cases had external frontal sinusotomies and Draf III surgery with no frontal recurrence or stenosis. The patient with the F5 had a frontal recurrence after Draf IIA surgery and external frontoethmoidectomy. CONCLUSIONS: Draf I or IIA surgery is adequate for most F1 tumors, and Draf II surgery is adequate for most F2 tumors. F3 and F4 tumors can be managed initially by Draf III surgery with external frontal sinusotomy added when required. F5 tumors probably require combined surgical approaches. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1622-1628, 2020.

Methylation analysis of plasma DNA informs etiologies of Epstein-Barr virus-associated diseases.

Epstein-Barr virus (EBV) is associated with a number of diseases, including malignancies. Currently, it is not known whether patients with different EBV-associated diseases have different methylation profiles of circulating EBV DNA. Through whole-genome methylation analysis of plasma samples from patients with nasopharyngeal carcinoma (NPC), EBV-associated lymphoma and infectious mononucleosis, we demonstrate that EBV DNA methylation profiles exhibit a disease-associated pattern. This observation implies a significant potential for the development of methylation analysis of plasma EBV DNA for NPC diagnostics. We further analyse the plasma EBV DNA methylome of NPC and non-NPC subjects from a prospective screening cohort. Plasma EBV DNA fragments demonstrate differential methylation patterns between NPC and non-NPC subjects. Combining such differential methylation patterns with the fractional concentration (count) and size of plasma EBV DNA, population screening of NPC is performed with an improved positive predictive value of 35.1%, compared to a count- and size-based only protocol.

Prevalence of Nonstenotic Carotid Plaque in Stroke Due to Atrial Fibrillation Compared to Embolic Stroke of Undetermined Source.

BACKGROUND: Embolic stroke of undetermined source (ESUS) accounts for about 20% of strokes. Nonstenotic cervical arterial plaque may be a mechanism of stroke in a subset of these patients. METHODS: A cohort of consecutive patients with ischemic stroke was retrospectively identified from a stroke registry. Patients with unilateral anterior circulation embolic stroke due to atrial fibrillation (AF) or consistent with ESUS who underwent computed tomographic neck angiography were included. The prespecified primary outcome was a comparison of the prevalence of carotid plaque greater than or equal to 3 mm thickness ipsilateral versus contralateral to the infarct side. RESULTS: Of 772 screened patients, 96 patients with ESUS and 99 patients with AF were included. Plaque greater than or equal to 3 mm was more frequently ipsilateral than contralateral to the infarct in patients with ESUS (41% versus 29%, P = .03), and plaque thickness was greater ipsilateral compared to contralateral (median 2.5 versus 2.2 mm, P = .02). No significant differences in plaque characteristics ipsilateral compared to contralateral were found in patients with AF. The prevalence of ipsilateral versus contralateral plaque was greater in ESUS patients less than or equal to 65 years old (48% versus 19%, P < .01), but no different in patients greater than 65 years old (35% versus 39%, P = .57). CONCLUSIONS: Nonstenotic cervical carotid plaque is more common ipislateral to the infarction in patients with ESUS, but not in patients with AF, supporting an underlying atheroembolic mechanism in a subset of ESUS patients. This association might be greater in younger ESUS patients.

Magnetic Resonance Imaging Findings in Pediatric Pseudotumor Cerebri Syndrome.

BACKGROUND: Revised diagnostic criteria for pseudotumor cerebri syndrome require three of four neuroimaging findings in the absence of papilledema. We examined the sensitivity and specificity of three or more of four of these magnetic resonance imaging (MRI) findings for pseudotumor cerebri syndrome in children. METHODS: As part of clinical care, patients in whom there was suspicion for pseudotumor cerebri syndrome underwent neurological and fundoscopic examinations, lumbar puncture, MRI, or magnetic resonance venogram. For this retrospective study, we used this information to classify 119 subjects into definite (n = 66) or probable pseudotumor cerebri syndrome (n = 12), elevated opening pressure without papilledema (n = 23), or controls who had normal opening pressure without papilledema (n = 24). A neuroradiologist, unaware of the clinical findings or original MRI report, reviewed MRIs for pituitary gland flattening, flattening of the posterior sclera, optic nerve sheath distention, and transverse venous sinus stenosis. RESULTS: The presence of three or more MRI findings has a sensitivity of 62% (95% confidence interval: 47% to 75%) and a specificity of 95% (95% confidence interval: 77% to 100%), compared with controls. Two of three (transverse venous sinus stenosis, pituitary gland flattening, flattening of the posterior sclera) had a similar sensitivity and specificity. Transverse venous sinus stenosis alone had a slightly higher sensitivity (74%, 95% confidence interval: 60% to 85%) and specificity (100%, 95% confidence interval: 80% to 100%). CONCLUSIONS: In children, three of four of the proposed neuroimaging criteria and transverse venous sinus stenosis alone have a moderate sensitivity and robust specificity for pseudotumor cerebri syndrome. MRIs should be reviewed for these criteria, and their presence should raise suspicion for pseudotumor cerebri syndrome in children, particularly if the presence of papilledema is uncertain.

Distinguishing early-stage nasopharyngeal carcinoma from benign hyperplasia using intravoxel incoherent motion diffusion-weighted MRI.

OBJECTIVES: MRI can detect early-stage nasopharyngeal carcinoma (NPC), but the detection is more challenging in early-stage NPCs because they must be distinguished from benign hyperplasia in the nasopharynx. This study aimed to determine whether intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) MRI could distinguish between these two entities. METHODS: Thirty-four subjects with early-stage NPC and 30 subjects with benign hyperplasia prospectively underwent IVIM DWI. The mean pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) values were calculated for all subjects and compared between the 2 groups using Student's t test. Receiver operating characteristics with the area under the curve (AUC) was used to identify the optimal threshold for all significant parameters, and the corresponding diagnostic performance was calculated. A p value of < 0.05 was considered statistically significant. RESULTS: Compared with benign hyperplasia, early-stage NPC exhibited a significantly lower D mean (0.64 ± 0.06 vs 0.87 ± 0.11 × 10-3 mm2/s), ADC0-1000 mean (0.77 ± 0.08 vs 1.00 ± 0.13 × 10-3 mm2/s), ADC300-1000 (0.63 ± 0.05 vs 0.86 ± 0.10 × 10-3 mm2/s) and a higher D* mean (32.66 ± 4.79 vs 21.96 ± 5.21 × 10-3 mm2/s) (all p < 0.001). No significant difference in the f mean was observed between the two groups (p = 0.216). The D and ADC300-1000 mean had the highest AUC of 0.985 and 0.988, respectively, and the D mean of < 0.75 × 10-3 mm2/s yielded the highest sensitivity, specificity and accuracy (100%, 93.3% and 96.9%, respectively) in distinguishing early-stage NPC from benign hyperplasia. CONCLUSION: DWI has potential to distinguish early-stage NPC from benign hyperplasia and D and ADC300-1000 mean were the most promising parameters. KEY POINTS: • Diffusion-weighted imaging has potential to distinguish early-stage nasopharyngeal carcinoma from benign hyperplasia in the nasopharynx. • The pure diffusion coefficient, pseudo-diffusion coefficient from intravoxel incoherent motion model and apparent diffusion coefficient from conventional diffusion-weighted imaging were significant parameters for distinguishing these two entities in the nasopharynx. • The pure diffusion coefficient, followed by apparent diffusion coefficient, may be the most promising parameters to be used in screening studies to help detect early-stage nasopharyngeal carcinoma.

Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema.

OBJECTIVE: Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of intracranial hypertension without papilledema (WOP) by using 3 or 4 MRI features of intracranial hypertension when a sixth nerve palsy is absent. This study was undertaken to evaluate the sensitivity and specificity of the MRI criteria and to validate their utility for diagnosing IIH in patients with chronic headaches and elevated opening pressure (CH + EOP), but WOP. METHODS: Brain MRIs from 80 patients with IIH with papilledema (WP), 33 patients with CH + EOP, and 70 control patients with infrequent episodic migraine were assessed in a masked fashion for MRI features of intracranial hypertension. RESULTS: Reduced pituitary gland height was moderately sensitive for IIH WP (80%) but had low specificity (64%). Increased optic nerve sheath diameter was less sensitive (51%) and only moderately specific (83%). Flattening of the posterior globe was highly specific (97%) but had low sensitivity (57%). Transverse venous sinus stenosis was moderately sensitive for IIH WP (78%) but of undetermined specificity. A combination of any 3 of 4 MRI features was nearly 100% specific, while maintaining a sensitivity of 64%. Of patients with CH + EOP, 30% had 3 or more MRI features, suggesting IIH WOP in those patients. CONCLUSION: A combination of any 3 of 4 MRI features is highly specific for intracranial hypertension and suggests IIH WOP when present in patients with chronic headache and no papilledema.

Quality of CT Imaging of Periocular Metallic Foreign Bodies Using Artifact Reduction Software.

PURPOSE: CT is the standard of care for assessment of ocular and orbital trauma; however, artifacts from metallic foreign bodies can limit the utility of CT. The authors hypothesize that implementation of metal artifact reduction techniques can improve image quality and diagnostic confidence for a diverse group of interpreters. METHODS: A case series of ten subjects with retained periocular metallic foreign bodies imaged with CT were identified retrospectively from a large urban trauma center. Postacquisition images were processed with an iterative-based metal streak artifact reduction software. The severity of the metal streak artifact was assessed by clinicians including radiologists (4), ophthalmologists (4), and oculoplastic specialists (3) using a numeric scale to grade images on seven clinically relevant criteria. Each image was also analyzed to measure the size of the artifact and degree of streaking. RESULTS: Overall confidence in diagnosis and severity of metallic streak was improved with metallic artifact reduction (p < 0.001, Wilcoxon signed-rank test). Similarly, confidence in assessing specific features-including extra-ocular muscle, optic nerve, globe rupture, orbital fracture and identification of foreign bodies-was improved after metallic artifact reduction (p < 0.001, Wilcoxon signed-rank test). The standard deviation of pixel intensity for a path surrounding the foreign body as well as the area of the streak artifact decreased in the metallic artifact reduction-processed images (p < 0.001, paired t test). CONCLUSIONS: Metal artifact reduction in CT has potential benefits in improving image quality and reader confidence for periocular trauma cases in real-world settings.

Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma.

Circulating tumor-derived DNA testing for cancer screening has recently been demonstrated in a prospective study on identification of nasopharyngeal carcinoma (NPC) among 20,174 asymptomatic individuals. Plasma EBV DNA, a marker for NPC, was detected using real-time PCR. While plasma EBV DNA was persistently detectable in 97.1% of the NPCs identified, ∼5% of the general population had transiently detectable plasma EBV DNA. We hypothesized that EBV DNA in plasma of subjects with or without NPC may have different molecular characteristics. We performed target-capture sequencing of plasma EBV DNA and identified differences in the abundance and size profiles of EBV DNA molecules within plasma of NPC and non-NPC subjects. NPC patients had significantly higher amounts of plasma EBV DNA, which showed longer fragment lengths. Cutoff values were established from an exploratory dataset and tested in a validation sample set. Adopting an algorithm that required a sample to concurrently pass cutoffs for EBV DNA counting and size measurements, NPCs were detected at a positive predictive value (PPV) of 19.6%. This represented superior performance compared with the PPV of 11.0% in the prospective screening study, which required participants with an initially detectable plasma EBV DNA result to be retested within 4 weeks. The observed differences in the molecular nature of EBV DNA molecules in plasma of subjects with or without NPC were successfully translated into a sequencing-based test that had a high PPV for NPC screening and achievable through single time-point testing.