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Abstract Background Severe asthma is a heterogeneous disease and the relationship between airway inflammation and airway remodelling is poorly understood. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts. Methods In a single centre cross-sectional observational study we recruited 59 subjects with severe asthma that underwent sputum induction and thoracic CT. Quantitative CT analysis of the apical segment of the right upper lobe (RB1) was performed. Forty-one mediators in sputum samples were measured of which 21 mediators that were assessable in >50% of samples were included in the analyses. Results Independent of airway geometry, sputum MMP9 and IL-1β were elevated in those groups with a high sputum neutrophil count while sputum ICAM was elevated in those subjects with a low sputum neutrophil count. In contrast, sputum CCL11, IL-1α and fibrinogen were different in groups stratified by both sputum neutrophil count and airway geometry. Sputum CCL11 concentration was elevated in subjects with a low sputum neutrophil count and high luminal and total RB1 area, whereas sputum IL1α was increased in subjects with a high sputum neutrophil count and low total RB1 area. Sputum fibrinogen was elevated in those subjects with RB1 luminal narrowing and in those subjects with neutrophilic inflammation without luminal narrowing. Conclusions We have demonstrated that sputum mediator profiling reveals a number of associations with airway geometry. Whether these findings reflect important biological phenotypes that might inform stratified medicine approaches requires further investigation.

Abstract: An 84-year-old man with a genetically confirmed diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome treated with tocilizumab reported with a 3-day history of left eye pain, conjunctival chemosis and injection, and horizontal binocular diplopia. Examination revealed restriction of left eye ductions in all directions with mild unilateral proptosis. MRI of his brain and orbits demonstrated abnormal enhancement of the left posterior sclera and intraorbital optic nerve sheath, without involvement of the extraocular muscles, cavernous sinus, or optic nerve parenchyma. B-scan ultrasonography heralded a positive "T-sign." Empiric treatment with high-dose intravenous methylprednisolone led to rapid clinical improvement. Workup for alternative causes was unremarkable. Oral prednisone dose and tocilizumab ultimately resulted in complete resolution after 4 weeks. The final diagnosis was consistent with orbital inflammatory manifestations of VEXAS syndrome., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.)

The analysis of cell-free tumor DNA (ctDNA) and proteins in the blood of patients with cancer potentiates a new generation of non-invasive diagnostic approaches. However, confident detection of tumor-originating markers is challenging, especially in the context of brain tumors, where these analytes in plasma are extremely scarce. Here, we apply a sensitive single-molecule technology to profile multiple histone modifications on individual nucleosomes from the plasma of patients with diffuse midline glioma (DMG). The system reveals epigenetic patterns unique to DMG, significantly differentiating this group of patients from healthy subjects or individuals diagnosed with other cancer types. We further develop a method to directly quantify the tumor-originating oncoproteins, lysine 27 to methionine substitution in histone H3 (H3-K27M) and mutant p53, from <1 mL of plasma, allowing for the accurate molecular classification of patients with DMG. We show that our strategy correlates with MRI and droplet-digital PCR (ddPCR) measurements of ctDNA, highlighting the clinical potential of single-molecule-based, multi-parametric assays for DMG diagnosis and treatment monitoring., Competing Interests: Declaration of interests Yeda Research and Development Co., Ltd. have filed a provisional patent application related to aspects of this publication, and E.S. is named as an inventor. E.S. is also an inventor on an additional patent application related to this work (US2016/047747) and serves as a consultant for the company SeqLL, Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Objective: Benign expansion of the subarachnoid spaces (BESS) is a condition seen in macrocephalic infants. BESS is associated with mild developmental delays which tend to resolve within a few years. It is accepted that patients with BESS are at increased risk of spontaneous subdural hematomas (SDHs), although the exact pathophysiology is not well understood. The prevalence of spontaneous SDH in BESS patients is poorly defined, with only a few large single-center series published. In this study the authors aimed to better define BESS prevalence and developmental outcomes through the longitudinal review of a large cohort of BESS patients., Methods: A large retrospective review was performed at a single institution from 1995 to 2020 for patients 2 years of age or younger with a diagnosis of BESS by neurology or neurosurgery and head circumference > 85th percentile. Demographic data, head circumference, presence of developmental delay, occurrence of SDH, and need for surgery were extracted from patient charts. The subarachnoid space (SAS) size was measured from the available MR images, and the sizes of those who did and did not develop SDH were compared., Results: Free text search revealed BESS mentioned within the medical records of 1410 of 2.6 million patients. After exclusion criteria, 480 patients remained eligible for the study. Thirty-two percent (n = 154) of patients were diagnosed with developmental delay, most commonly gross motor delay (53%). Gross motor delay resolved in 86% of patients at a mean age of 22.2 months. The prevalence of spontaneous SDH in this BESS population over a period of 25 years was 8.1%. There was no significant association between SAS size and SDH formation., Conclusions: This study represents results for one of the largest cohorts of patients with BESS at a single institution. Gross motor delay was the most common developmental delay diagnosed, and a majority of patients had resolution of their delay. These data support that children with BESS have a higher prevalence of SDH than the general pediatric population, although SAS size was not significantly associated with SDH development.

Background: Pituitary adenomas and nonadenomatous lesions in the sellar region may be difficult to distinguish by imaging yet that distinction is critical in guiding management. The nature of the diagnostic errors in this setting has not been well documented., Methods: Two neurosurgeons and 2 neuroradiologists of differing experience levels viewed deidentified MRIs of 18 nonadenomatous sellar lesions and 21 adenomas. They recorded their diagnoses, the imaging features they used to make those diagnoses, and their confidence in making those diagnoses., Results: Among the 18 nonadenoma cases, 11 (61%) were incorrectly diagnosed as adenoma by at least 1 reader, including Rathke cleft cyst, plasmacytoma, aneurysm, craniopharyngioma, chordoma, Langerhans cell histiocytosis, metastasis, and undifferentiated sinonasal carcinoma. Among the 21 adenoma cases, 8 (38%) were incorrectly diagnosed by at least 1 reader as craniopharyngioma, Rathke cleft cyst, sinonasal carcinoma, hemangioblastoma, and pituitary hyperplasia. Incorrect imaging diagnoses were made with high confidence in 13% of readings. Avoidable errors among the nonadenomatous cases occurred when readers failed to appreciate that the lesion was separate from the pituitary gland. Unavoidable errors in those cases occurred when the lesions were so large that the pituitary gland had been obliterated or the imaging features of a nonadenomatous lesion resembled those of a cystic pituitary adenoma. Avoidable errors in misdiagnosis of adenomas as nonadenomas occurred when readers failed to appreciate features highly characteristic of adenomas. An unavoidable error occurred because a cystic adenoma had features correctly associated with craniopharyngioma., Conclusions: Errors in imaging differentiation of pituitary adenoma from nonadenomatous lesions occurred often and sometimes with high confidence among a small sample of neurosurgeons and neuroradiologists. In the misdiagnosis of nonadenomatous lesions as adenomas, errors occurred largely from failure to appreciate a separate pituitary gland, but unavoidable errors occurred when large lesions had obliterated this distinguishing feature. In the misdiagnosis of adenomas as nonadenomatous lesions, avoidable errors occurred because readers failed to recognize imaging features more characteristic of adenomas and because cystic adenomas share features with craniopharyngiomas and Rathke cleft cysts. Awareness of these errors should lead to improved management of sellar lesions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Background: Neonates and young children require efficacious magnetic resonance imaging (MRI) examinations but are potentially more susceptible to the short- and long-term adverse effects of gadolinium-based contrast agents due to the immaturity of their body functions., Objective: To evaluate the acute safety and diagnostic efficacy of gadoteridol (ProHance) for contrast-enhanced MRI of the central nervous system (CNS) in children ≤2 years of age., Materials and Methods: One hundred twenty-five children ≤2 years old (including 57 children <6 months old) who underwent contrast-enhanced MRI of the CNS with gadoteridol at 0.1 mmol/kg body weight were retrospectively enrolled at five imaging centers. Safety data were assessed for acute/subacute adverse events in the 48 h following gadoteridol administration and, when available, vital signs, electrocardiogram (ECG) and clinical laboratory values obtained from blood samples taken from 48 h before until 48 h following the MRI exam. The efficacy of gadoteridol-enhanced MRI compared to unenhanced MRI for disease diagnosis was evaluated prospectively by three blinded, unaffiliated readers., Results: Thirteen changes of laboratory values (11 mild, 1 moderate, 1 unspecified) were reported as adverse events in 7 (5.6%) patients. A relationship to gadoteridol was deemed possible though doubtful for two of these adverse events in two patients (1.6%). There were no clinical adverse events, no serious adverse events and no clinically meaningful changes in vital signs or ECG recordings. Accurate differentiation of tumor from non-neoplastic disease, and exact matching of specific MRI-determined diagnoses with on-site final diagnoses, was achieved in significantly more patients by each reader following the evaluation of combined pre- and post-contrast images compared to pre-contrast images alone (84.6-88.0% vs. 70.9-76.9%; P≤0.006 and 67.5-79.5% vs. 47.0-66.7%; P≤0.011, respectively)., Conclusion: Gadoteridol at 0.1 mmol/kg body weight is safe, well tolerated and effective for contrast-enhanced MRI of the CNS in children ≤2 years of age., (© 2021. The Author(s).)

Background: Adversely prognostic hypercellular and hyperperfused regions of glioblastoma (GBM) predict progression-free survival, and are a novel target for dose-intensified chemoradiation (chemoRT) recently implemented in a phase II clinical trial. As a secondary aim, we hypothesized that dose-intensified chemoRT would induce greater mid-treatment response of hypercellular/hyperperfused tumor regions vs standard chemoradiation, and that early response would improve overall survival (OS)., Methods: Forty-nine patients with newly diagnosed GBM underwent prospective, multiparametric high b value diffusion-weighted MRI (DW-MRI) and perfusion dynamic contrast-enhanced MRI (DCE-MRI) pre-RT and 3-4 weeks into RT. The hypercellular tumor volume (TVHCV, mean contralateral normal brain + 2SD) and hyperperfused tumor volume (TVCBV, contralateral normal frontal gray matter + 1SD) were generated using automated thresholding. Twenty-six patients were enrolled on a dose-escalation trial targeting TVHCV/TVCBV with 75 Gy in 30 fractions, and 23 non-trial patients comprised the control group. OS was estimated using the Kaplan-Meier method and compared using the log-rank test. The effect of TVHCV/TVCBV and Gd-enhanced tumor volume on OS was assessed using multivariable Cox proportional-hazard regression., Results: Most patients had gross total (47%) or subtotal resection (37%), 25% were MGMT-methylated. Patients treated on the dose-escalation trial had significantly greater reduction in TVHCV/TVCBV (41% reduction, IQR 17%-75%) vs non-trial patients (6% reduction, IQR 6%-22%, P = .002). An increase in TVHCV/TVCBV during chemoRT was associated with worse OS (adjusted hazard ratio [aHR] 1.2, 95%CI 1.0-1.4, P = .02), while pre-treatment tumor volumes (P > .5) and changes in Gd-enhanced volume (P = .9) were not., Conclusions: Multiparametric MRI permits identification of therapeutic resistance during chemoRT and supports adaptive strategies in future trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: We hypothesized that dose-intensified chemoradiation therapy targeting adversely prognostic hypercellular (TV HCV ) and hyperperfused (TV CBV ) tumor volumes would improve outcomes in patients with glioblastoma., Methods and Materials: This single-arm, phase 2 trial enrolled adult patients with newly diagnosed glioblastoma. Patients with a TV HCV /TV CBV >1 cm 3 , identified using high b-value diffusion-weighted magnetic resonance imaging (MRI) and dynamic contrast-enhanced perfusion MRI, were treated over 30 fractions to 75 Gy to the TV HCV /TV CBV with temozolomide. The primary objective was to estimate improvement in 12-month overall survival (OS) versus historical control. Secondary objectives included evaluating the effect of 3-month TV HCV /TV CBV reduction on OS using Cox proportional-hazard regression and characterizing coverage (95% isodose line) of metabolic tumor volumes identified using correlative 11 C-methionine positron emission tomography. Clinically meaningful change was assessed for quality of life by the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30, for symptom burden by the MD Anderson Symptom Inventory for brain tumor, and for neurocognitive function (NCF) by the Controlled Oral Word Association Test, the Trail Making Test, parts A and B, and the Hopkins Verbal Learning Test-Revised., Results: Between 2016 and 2018, 26 patients were enrolled. Initial patients were boosted to TV HCV alone, and 13 patients were boosted to both TV HCV /TV CBV . Gross or subtotal resection was performed in 87% of patients; 22% were O 6 -methylguanine-DNA methyltransferase (MGMT) methylated. With 26-month follow-up (95% CI, 19-not reached), the 12-month OS rate among patients boosted to the combined TV HCV /TV CBV was 92% (95% CI, 78%-100%; P = .03) and the median OS was 20 months (95% CI, 18-not reached); the median OS for the whole study cohort was 20 months (95% CI, 14-29 months). Patients whose 3-month TV HCV /TV CBV decreased to less than the median volume (3 cm 3 ) had superior OS (29 vs 12 months; P = .02). Only 5 patients had central or in-field failures, and 93% (interquartile range, 59%-100%) of the 11 C-methionine metabolic tumor volumes received high-dose coverage. Late grade 3 neurologic toxicity occurred in 2 patients. Among non-progressing patients, 1-month and 7-month deterioration in quality of life, symptoms, and NCF were similar in incidence to standard therapy., Conclusions: Dose intensification against hypercellular/hyperperfused tumor regions in glioblastoma yields promising OS with favorable outcomes for NCF, symptom burden, and quality of life, particularly among patients with greater tumor reduction 3 months after radiation therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The evaluation, treatment, and prognosis of neonatal brachial plexus palsy (NBPP) continues to have many areas of debate, including the use of ancillary testing. Given the continued improvement in imaging, it is important to revisit its utility. Nerve root avulsions have historically been identified by the presence of pseudomeningoceles or visible ruptures. This "all-or-none" definition of nerve root avulsions has many implications for the understanding and management of NBPP, especially as characterization of the proximal nerve root as a potential donor remains critical. This study examined the ability of high-resolution MRI to more specifically define the anatomy of nerve root avulsions by individually examining the ventral and dorsal rootlets as they exit the spinal cord., Methods: This is a retrospective review of patients who had undergone brachial plexus protocol MRI for clinical evaluation of NBPP at a single institution. Each MR image was independently reviewed by a board-certified neuroradiologist, who was blinded to both established diagnosis/surgical findings and laterality. Each dorsal and ventral nerve rootlet bilaterally from C5 to T1 was evaluated from the spinal cord to its exit in the neuroforamen. Each rootlet was classified as avulsed, intact, or undeterminable., Results: Sixty infants underwent brachial plexus protocol MRI from 2010 to 2018. All infants were included in this study. Six hundred individual rootlets were analyzed. There were 49 avulsed nerve rootlets in this cohort. Twenty-nine (59%) combined dorsal/ventral avulsions involved both the ventral and dorsal rootlets, and 20 (41%) were either isolated ventral or isolated dorsal rootlet avulsions. Of the isolated avulsion injuries, 13 (65%) were dorsal only, meaning that the motor rootlets were intact., Conclusions: A closer look at nerve root avulsions with MRI demonstrates a significant prevalence (approximately 41%) of isolated dorsal or ventral nerve rootlet disruptions. This finding implies that nerve roots previously labeled as "avulsed" but with only isolated dorsal (sensory) rootlet avulsion can yet provide donor fascicles in reconstruction strategies. A majority (99%) of the rootlets can be clearly visualized with MRI. These findings may significantly impact the clinical understanding of neonatal brachial plexus injury and its treatment.

Background: Allergic fungal rhinosinusitis (AFRS) is a common condition in which sinusitis develops as an IgE-mediated response to common sinonasal fungal organisms. If that response leads to blockage of sinus ostia, bone expansion and erosion by expansive cysts containing dense inspissated debris may occur with the potential for critical neurovascular compression including damage to the anterior visual pathway., Methods: Review of clinical and imaging features of 2 patients who sustained catastrophic clinical outcomes., Results: The first patient had pansinusitis with massive mucocele-like cysts expanding the sphenoid sinus and cranial base and causing compression of the anterior visual pathway that led to persistent severe vision loss despite extensive sinus surgery. The second patient developed sphenoethmoidal expansion with a marked inflammatory response and presumed conversion to invasive fungal sinusitis that caused anterior visual pathway vision loss, bilateral ocular motor palsies from extension into the cavernous sinuses, and death from a large middle cerebral artery stroke., Conclusions: Although AFRS is most often benign and treatable, it may rarely produce catastrophic outcomes, especially if the sphenoid sinus is involved. Irreversible vision loss may occur from compression, and ocular motor palsies and death from conversion to invasive fungal disease. Close ophthalmologic and imaging monitoring is necessary in patients with expanded sinuses, and prophylactic sinus surgery may be indicated in certain cases.

Purpose: To determine the recommended phase 2 dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases and to assess whether quantitative changes in perfusion magnetic resonance imaging (MRI) after RRx-001 correlate with response., Methods and Materials: Five centers participated in this phase 1/2 trial of RRx-001 given once pre-WBRT and then twice weekly during WBRT. Four dose levels were planned (5 mg/m 2 , 8.4 mg/m 2 , 16.5 mg/m 2 , 27.5 mg/m 2 ). Dose escalation was managed by the time-to-event continual reassessment method algorithm. Linear mixed models were used to correlate change in 24-hour T1, Ktrans (capillary permeability), and fractional plasma volume with change in tumor volume., Results: Between 2015 and 2017, 31 patients were enrolled. Two patients dropped out before any therapy. Median age was 60 years (range, 30-76), and 12 were male. The most common tumor types were melanoma (59%) and non-small cell lung cancer (18%). No dose limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia (6.9%, 2 of 29). The median intracranial response rate was 46% (95% confidence interval, 24-68) and median overall survival was 5.2 months (95% confidence interval, 4.5-9.4). No neurologic deaths occurred. Among 10 patients undergoing dynamic contrast-enhanced MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 and 4 months (P ≤ .01)., Conclusions: The addition of RRx-001 to WBRT is well tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, the recommended phase 2 dose is 10 mg twice weekly. A reduction in fractional plasma volume on dynamic contrast-enhanced MRI 24 hours after RRx-001 suggests antiangiogenic activity associated with longer-term tumor response., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Histiocytosis syndromes (HS) are group of heterogeneous disorders characterized by abnormal accumulation and infiltration of histiocytes, cells derived from hematopoietic cells of monocyte/macrophage lineage. Overall these disorders are rare. When they do occur they involve many organ systems including the central nervous system (CNS). While imaging findings can provide important clues, diagnosis of this disorder is challenging and definitive diagnosis often necessitates pathologic examination. In this review, we describe imaging features of HS involving the CNS, with the aim to increase our understanding of these disorders. The entities discussed in this review will include: Langerhans cell histiocytosis (LCH), Rosai-Dorfman Disease (RDD), Erdheim Chester Disease (ECD), hemophagocytic lymphohistiocytosis (HLH), and crystal-storing histiocytosis (CSH)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: Contrast-enhanced MR imaging provides essential information for pediatric imaging applications. We evaluated gadobenate dimeglumine for contrast-enhanced MR imaging of infants younger than 2 years of age., Materials and Methods: Ninety children younger than 2 years of age (including 55 children younger than 1 year) who underwent enhanced MR imaging of the CNS with gadobenate dimeglumine at 0.1 mmol/kg body weight ± 25% by volume were retrospectively enrolled at 2 imaging centers. Safety data were assessed for adverse events and, when available, vital signs and electrocardiogram and clinical laboratory values obtained from 48 hours before until 48 hours after the MR imaging examination. The efficacy of gadobenate dimeglumine-enhanced MR imaging was evaluated prospectively by 3 blinded, unaffiliated readers in terms of the accuracy of combined pre- and postcontrast images relative to precontrast images alone for differentiation of tumor from non-neoplastic disease and the correct diagnosis of specific disease. Differences were tested using the McNemar test. A possible effect of dose on diagnostic accuracy was assessed using the Fisher exact test., Results: Nine nonserious adverse events were reported for 8 (8.8%) patients. Five adverse events occurred in patients 12 months of age or older. All events occurred at least 24 hours after gadobenate dimeglumine administration, and in each case, the investigating radiologist considered that there was no reasonable possibility of a relationship to gadobenate dimeglumine. No clinically meaningful changes in vital signs, electrocardiogram results, or laboratory parameters were reported. Accurate differentiation of tumor from non-neoplastic disease and exact matching of each specific MR imaging-determined diagnosis with the on-site final diagnosis were achieved in significantly more patients by each reader following evaluation of combined pre- and postcontrast images relative to precontrast images alone (91.0%-94.4% versus 75.3%-87.6%, P  < .04, and 66.3%-73.0% versus 52.8%-58.4%, P  < .02, respectively). No significant differences ( P  > .133) in diagnostic accuracy were noted between patients receiving ≤0.08 mmol/kg of gadobenate dimeglumine and patients receiving >0.08 mmol/kg of gadobenate dimeglumine., Conclusions: Gadobenate dimeglumine is safe and effective for pediatric MR imaging., (© 2019 by American Journal of Neuroradiology.)

Intramedullary cord hyperintensity at T2-weighted MRI is a common imaging feature of disease in the spinal cord, but it is nonspecific. Radiologists play a valuable role in helping narrow the differential diagnosis by integrating patient history and laboratory test results with key imaging characteristics. The authors present an algorithmic approach to evaluating intrinsic abnormality of spinal cord signal intensity (SI), which incorporates clinical evaluation results, time of onset (acute vs nonacute), cord expansion, and pattern of T2 SI abnormality. This diagnostic approach provides a practical framework to aid both trainees and practicing radiologists in workup of myelopathy. © RSNA, 2019.

Quantitative mapping of hyperperfused and hypercellular regions of glioblastoma has been proposed to improve definition of tumor regions at risk for local recurrence following conventional radiation therapy. As the processing of the multiparametric dynamic contrast-enhanced (DCE-) and diffusion-weighted (DW-) magnetic resonance imaging (MRI) data for delineation of these subvolumes requires additional steps that go beyond the standard practices of target definition, we sought to devise a workflow to support the timely planning and treatment of patients. A phase II study implementing a multiparametric imaging biomarker for tumor hyperperfusion and hypercellularity consisting of DCE-MRI and high b-value DW-MRI to guide intensified (75 Gy/30 fractions) radiation therapy (RT) in patients with newly diagnosed glioblastoma was launched. In this report, the workflow and the initial imaging outcomes of the first 12 patients are described. Among all the first 12 patients, treatment was initiated within 6 weeks of surgery and within 2 weeks of simulation. On average, the combined hypercellular volume and high cerebral blood volume/tumor perfusion volume were 1.8 times smaller than the T1 gadolinium abnormality and 10 times smaller than the FLAIR abnormality. Hypercellular volume and high cerebral blood volume/tumor perfusion volume each identified largely distinct regions and showed 57% overlap with the enhancing abnormality, and minimal-to-no extension outside of the FLAIR. These results show the feasibility of implementing a workflow for multiparametric magnetic resonance-guided radiation therapy into clinical trials with a coordinated multidisciplinary team, and the unique and complementary tumor subregions identified by the combination of high b-value DW-MRI and DCE-MRI.

Purpose: Advanced imaging modalities such as high b-value diffusion and dynamic contrast enhancement magnetic resonance imaging have the potential to improve the clinical management of glioblastoma by informing prognosis, predicting sites of progression, and guiding dose-escalated radiation to maximize tumor control and minimize toxicity., Methods and Materials: Fifty-two patients with de novo glioblastoma underwent magnetic resonance imaging before chemoradiation therapy. Enhanced tumor volumes (TVs), excluding the surgical cavity, hypercellularity (TV HCV ) and increased cerebral blood volume (TV CBV ) were defined using conventional gadolinium-enhanced T1-weighted images, high b-value (3000 s/mm 2 ) diffusion-weighted images, and cerebral blood volume maps from T1-weighted dynamic contrast enhancement images, respectively. The image-phenotype TVs were analyzed for prediction of progression-free survival (Cox proportional hazard models), and sites of progression (pattern of failure tumor volume)., Results: The median progression-free survival (PFS) of the cohort was 13 months. The TV CBV and TV HCV were spatially distinct, with a mean overlap of only 21%. Univariate analysis showed that increasing age, decreasing radiation dose, larger TV HCV , and larger overlap of TV HCV and TV CBV were significantly associated with inferior PFS. Multivariate analysis identified that TV HCV was the most adversely prognostic imaging-defined variable. Enhanced TVs, excluding the surgical cavity, and the union of TV HCV and TV CBV showed a high likelihood of containing the pattern of failure tumor volume, and the volume composed of the intersection of TV HCV and TV CBV had an especially high likelihood of progression., Conclusions: TV HCV and the overlap of TV HCV and TV CBV are prognostic for PFS. Combinations of gadolinium-enhanced TVs, TV CBV , and TV HCV could predict tumor progression locations better than could individual subvolumes. Radiation dose escalation to these subvolumes could be a promising therapeutic strategy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: A modern imaging review is necessary to further define the anatomic origin of the juvenile nasopharyngeal angiofibroma., Methods: After institutional review board approval, a search from January 1998 to January 2013 yielded 33 male patients (aged 10-23 years) with pathologically proven juvenile nasopharyngeal angiofibroma lesions, as well as pretreatment computed tomography/magnetic resonance imaging. Juvenile nasopharyngeal angiofibroma involvement was assessed in the following regions: sphenopalatine foramen, pterygopalatine fossa, vidian canal, nasopharynx, nasal cavity, sphenoid sinus, choana, pterygomaxillary fissure/masticator space, orbit, and sphenoid bone., Results: The choana and nasopharynx were involved in all 33 patients. In contrast, only 22 lesions involved the pterygopalatine fossa, 24 lesions involved the sphenopalatine foramen, and 28 lesions involved the vidian canal., Conclusions: Our results suggest that the juvenile nasopharyngeal angiofibroma origin is in the region of the choana and nasopharynx rather than the sphenopalatine foramen or pterygopalatine fossa.

This review article describes advancement of magnetic resonance imaging technologies in radiation therapy planning, guidance, and adaptation of brain tumors. The potential for MR-guided radiation therapy to improve outcomes and the challenges in its adoption are discussed., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The vulnerable brain areas in hypoxic-ischemic encephalopathy (HIE) following systemic hypotension are typically the neocortex, deep cerebral gray nuclei, hippocampus, cerebellum, and the parieto-occipital arterial border zone region. The visual cortex is not commonly recognized as a target in this setting., Methods: Single-institution review from 2007 to 2015 of patients who suffered cortical visual loss as an isolated clinical manifestation following systemic hypotension and whose brain imaging showed abnormalities limited to the occipital lobe., Results: Nine patients met inclusion criteria. Visual loss at outset ranged from hand movements to 20/20, but all patients had homonymous field loss at best. In 1 patient, imaging was initially normal but 4 months later showed encephalomalacia. In 2 patients, imaging was initially subtle enough to be recognized as abnormal only when radiologists were advised that cortical visual loss was present., Conclusions: The occipital lobe may be an isolated target in HIE with cortical visual loss as the only clinical manifestation. Imaging performed in the acute period may appear normal or disclose abnormalities subtle enough to be overlooked. Radiologists informed of the clinical manifestations may be more attune to these abnormalities, which will become more apparent months later when occipital volume loss develops.

Introduction: Despite recent improvements in perinatal care, the incidence of neonatal brachial plexus palsy (NBPP) remains relatively common. CT myelography is currently considered to be the optimal imaging modality for evaluating nerve root integrity. Recent improvements in MRI techniques have made it an attractive alternative to evaluate nerve root avulsions (preganglionic injuries)., Aim: We demonstrate the utility of MRI for the evaluation of normal and avulsed spinal nerve roots. We also show the utility of ultrasound in providing useful preoperative evaluation of the postganglionic brachial plexus in patients with NBPP.

Background: Ultrasound has been utilized in the evaluation of compressive and traumatic peripheral nerve pathology., Objective: To determine whether US can provide comprehensive evaluation of the post-ganglionic brachial plexus in the setting of neonatal brachial plexus palsy and whether this information can be used to guide preoperative nerve reconstruction strategies., Materials and Methods: In this retrospective cohort study, preoperative brachial plexus ultrasonography was performed in 52 children with neonatal brachial plexus palsy who were being considered for surgery. The 33 children who had surgery compose the patient cohort. The presence and location of post-ganglionic neuromas were evaluated by US and compared to the surgical findings. US evaluation of shoulder muscle atrophy was conducted as an indirect way to assess the integrity of nerves. Finally, we correlated glenohumeral joint laxity to surgical and clinical management., Results: Ultrasound correctly identified 21 of 25 cases of upper trunk and middle trunk neuroma involvement (84% sensitivity for each). It was 68% sensitive and 40% specific in detection of lower trunk involvement. US identified shoulder muscle atrophy in 11 of 21 children evaluated; 8 of these 11 went on to nerve transfer procedures based upon the imaging findings. US identified 3 cases of shoulder joint laxity of the 13 children evaluated. All 3 cases were referred for orthopedic evaluation, with 1 child undergoing shoulder surgery and another requiring casting., Conclusion: Ultrasound can provide useful preoperative evaluation of the post-ganglionic brachial plexus in children with neonatal brachial plexus palsy.

Purpose: Use of conventional magnetic resonance imaging (MRI) for target definition may expose glioblastomas (GB) to inadequate radiation dose coverage of the nonenhanced hypercellular subvolume. This study aimed to develop a technique to identify the hypercellular components of GB by using high b-value diffusion-weighted imaging (DWI) and to investigate its relationship with the prescribed 95% isodose volume (PDV) and progression-free survival (PFS)., Methods and Materials: Twenty-one patients with GB underwent chemoradiation therapy post-resection and biopsy. Radiation therapy (RT) treatment planning was based upon conventional MRI. Pre-RT DWIs were acquired in 3 orthogonal directions with b-values of 0, 1000, and 3000 s/mm(2). Hypercellularity volume (HCV) was defined on the high b-value (3000 s/mm(2)) DWI by a threshold method. Nonenhanced signified regions not covered by the Gd-enhanced gross tumor volume (GTV-Gd) on T1-weighted images. The PDV was used to evaluate spatial coverage of the HCV by the dose plan. Association between HCV and PFS or other clinical covariates were assessed using univariate proportional hazards regression models., Results: HCVs and nonenhanced HCVs varied from 0.58 to 67 cm(3) (median: 9.8 cm(3)) and 0.15 to 60 cm(3) (median: 2.5 cm(3)), respectively. Fourteen patients had incomplete dose coverage of the HCV, 6 of whom had >1 cm(3) HCV missed by the 95% PDV (range: 1.01-25.4 cm(3)). Of the 15 patients who progressed, 5 progressed earlier, within 6 months post-RT, and 10 patients afterward. Pre-RT HCVs within recurrent GTVs-Gd were 78% (range: 65%-89%) for the 5 earliest progressions but lower, 53% (range: 0%-85%), for the later progressions. HCV and nonenhanced HCV were significant negative prognostic indicators for PFS (P<.002 and P<.01, respectively). The hypercellularity subvolume not covered by the 95% PDV was a significant negative predictor for PFS (P<.05)., Conclusions: High b-value DWI identifies the hypercellular components of GB and could aid in RT target volume definition. Future studies will allow us to investigate the role of high b-value DWI in identifying radiation boost volumes and diagnosing progression., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Bilateral lateral geniculate nucleus (LGN) injury is a rare cause of vision loss. We describe a patient with pre-eclampsia who developed profound but reversible bilateral vision loss, bilateral serous retinal detachments, and magnetic resonance imaging signs of a variant of posterior reversible encephalopathy syndrome (PRES) that affected both LGNs and spared the retrogeniculate pathways. We provide evidence that the visual loss was not from the chorioretinal lesions but from the LGN lesions. The concurrence of PRES and lesions attributed to choroidal hypoperfusion provides support for the notion that vasoconstriction also underlies the pathogenesis of PRES.

Ultrasonography has previously been reported for use in the evaluation of compressive or traumatic peripheral nerve pathology and for its utility in preoperative mapping. However, these studies were not performed in infants, and they were not focused on the brachial plexus. The authors report a case in which ultrasonography was used to improve operative management of neonatal brachial plexus palsy (NBPP). An infant boy was born at term, complicated by right-sided shoulder dystocia. Initial clinical evaluation revealed proximal arm weakness consistent with an upper trunk injury. Unlike MRI or CT myelography that focus on proximal nerve roots, ultrasonography of the brachial plexus in the supraclavicular fossa was able to demonstrate a small neuroma involving the upper trunk (C-5 and C-6) and no asymmetry in movement of the diaphragm or in the appearance of the rhomboid muscle when compared with the unaffected side. However, the supra- and infraspinatus muscles were significantly asymmetrical and atrophied on the affected side. Importantly, ultrasound examination of the shoulder revealed posterior glenohumeral laxity. Instead of pursuing the primary nerve reconstruction first, timely treatment of the shoulder subluxation prevented formation of joint dysplasia and formation of a false glenoid, which is a common sequela of this condition. Because the muscles innervated by proximal branches of the cervical nerve roots/trunks were radiographically normal, subsequent nerve transfers were performed and good functional results were achieved. The authors believe this to be the first report describing the utility of ultrasonography in the surgical treatment planning in a case of NBPP. Noninvasive imaging, in addition to thorough history and physical examination, reduces the intraoperative time required to determine the extent and severity of nerve injury by allowing improved preoperative planning of the surgical strategy. Inclusion of ultrasonography as a preoperative modality may yield improved outcomes for children with NBPP.

Objective: Inborn errors of metabolism in children can be challenging to interpret because of the similarity of their appearances on imaging. There are important clues to the diagnosis based on clinical history, head circumference (e.g., macrocephaly), geographic distribution of lesions (e.g., subcortical vs deep white matter or frontal vs parietooccipital), and other imaging features (e.g., contrast enhancement, calcification, cysts, and cortical dysplasia)., Conclusion: In this article, we present an algorithm-based approach to diagnosing pediatric metabolic disease with a discussion of key imaging features.

Background: Over the last decade there has been escalating concern regarding the increasing radiation exposure stemming from CT exams, particularly in children. Adaptive statistical iterative reconstruction (ASIR) is a relatively new and promising tool to reduce radiation dose while preserving image quality. While encouraging results have been found in adult head and chest and body imaging, validation of this technique in pediatric population is limited., Objective: The objective of our study was to retrospectively compare the image quality and radiation dose of pediatric head CT examinations obtained with ASIR compared to pediatric head CT examinations without ASIR in a large patient population., Materials and Methods: Retrospective analysis was performed on 82 pediatric head CT examinations. This group included 33 pediatric head CT examinations obtained with ASIR and 49 pediatric head CT examinations without ASIR. Computed tomography dose index (CTDIvol) was recorded on all examinations. Quantitative analysis consisted of standardized measurement of attenuation and the standard deviation at the bilateral centrum semiovale and cerebellar white matter to evaluate objective noise. Qualitative analysis consisted of independent assessment by two radiologists in a blinded manner of gray-white differentiation, sharpness and overall diagnostic quality., Results: The average CTDIvol value of the ASIR group was 21.8 mGy (SD = 4.0) while the average CTDIvol for the non-ASIR group was 29.7 mGy (SD = 13.8), reflecting a statistically significant reduction in CTDIvol in the ASIR group (P < 0.01). There were statistically significant reductions in CTDI for the 3- to 12-year-old ASIR group as compared to the 3- to 12-year-old non-ASIR group (21.5 mGy vs. 30.0 mGy; P = 0.004) as well as statistically significant reductions in CTDI for the >12-year-old ASIR group as compared to the >12-year-old non-ASIR group (29.7 mGy vs. 49.9 mGy; P = 0.0002). Quantitative analysis revealed no significant difference in the homogeneity of variance in the ASIR group compared to the non-ASIR group. Radiologist assessment of gray-white differentiation, sharpness and overall diagnostic quality in ASIR examinations was not substantially different compared to non-ASIR examinations., Conclusion: The use of ASIR in pediatric head CT examinations allows for a 28% CTDIvol reduction in the 3- to 12-year-old age group and a 48% reduction in the >12-year-old age group without substantially affecting image quality.

Over the last two decades, there has been a marked increase in the number of computed tomography (CT) studies performed in the United States, with a resultant increase in the radiation dose delivered to patients. Hence there is an urgent need to optimize CT protocols and to get familiar with the factors affecting the CT radiation dose and with available dose reduction options. This article discusses the basic physics related to CT technique and describes current and future methods of dose reduction. Also briefly described are other CT techniques applicable in the maxillofacial region, such as three-dimensional CT, cone beam CT, and dual-energy CT., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Purpose: Despite recent improvements in perinatal care, the incidence of neonatal brachial plexus palsy remains relatively common. CT myelography is currently considered to be the optimal imaging technique for evaluating nerve root integrity. Recent improvements in MR imaging techniques have made it an attractive alternative to evaluate nerve root avulsions (preganglionic injuries). We aim to demonstrate utility of MR imaging in the evaluation of normal and avulsed spinal nerve roots., Materials and Methods: All study patients with clinically diagnosed neonatal brachial plexus palsy underwent MR imaging by use of a high-resolution, heavily T2-weighted (driven equilibrium) sequence. MR imaging findings were reviewed for presence of nerve root avulsion from C5-T1 and for presence of pseudomeningocele. The intraoperative findings were reviewed and compared with the preoperative MR imaging findings., Results: Thirteen patients (9 male, 4 female) underwent MR imaging; 6 patients underwent nerve reconstruction surgery, during which a total of 19 nerve roots were evaluated. Eight avulsions were noted at surgery and in the remainder, the nerve injury was more distal (rupture/postganglionic injury). Six of the 8 nerve root avulsions identified at surgery were at C5-6 level, whereas 1 nerve root avulsion was identified at C7 and C8 levels, respectively. The overall sensitivity and specificity of MR imaging for nerve root avulsions was 75% and 82%, respectively., Conclusions: Our preliminary results demonstrate that high-resolution MR imaging offers an excellent alternative to CT myelography for the evaluation of neonatal brachial plexus palsy with similar sensitivity compared with CT myelography., (© 2014 by American Journal of Neuroradiology.)

Demyelinating disorders of the central nervous system are characterized by the breakdown of myelin, with or without preservation of the associated axons. Primary demyelinating diseases typically involve loss of myelin with relative sparing of axons. Secondary demyelinating disorders represent a spectrum of white matter disease characterized by damage to neurons or axons with the resultant breakdown of myelin. The pathologic changes seen in secondary demyelinating disorders are varied, ranging from pure demyelination to necrosis with subsequent demyelination. Secondary demyelinating diseases are associated with a wide variety of conditions, including infections/vaccinations, nutritional/vitamin deficiencies, chemical agents, genetic abnormalities, and vascular insult., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Our aim with this study was to develop a user-friendly method for pediatric sonographically guided lumbar punctures so that we can visualize intrathecal anatomy, confirm intrathecal injection at the time of injection, and, most importantly, avoid ionizing radiation to a child's already radiosensitive pelvis. Sonographically guided lumbar puncture was prospectively performed in children aged 7 weeks to 16 years. All attempts (n = 9) were successful. We were able to identify relevant anatomy (including the conus in children 10 years and younger), confirm intrathecal injection, visualize intrathecal hematoma, and avoid radiation. Sonography is a promising modality for image-guided lumbar punctures without radiation in children.

Rosai-Dorfman disease is a rare pathologic entity characterized by massively enlarged painless cervical lymph nodes. Exclusive extranodal disease is much less common than the characteristic presentation with exclusive central nervous system and skull base involvement being quite rare. We present a case of exclusive extranodal Rosai-Dorfman disease of the skull base and briefly discuss the entity., (© 2013 Elsevier Inc. All rights reserved.)

This article provides a summary of how to approach the imaging analysis of lesions of the anterior, central, and posterior skull base. The primary focus is tumors and tumor-mimickers, and representative examples are shown to differentiate the features of lesions that can occur in the same location., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The overwhelming majority of pineal region tumors are malignant germ cell tumors, pineal cell tumors, or glial tumors. To our knowledge we report the first patient with myeloid sarcoma in the pineal region. Myeloid sarcomas are composed of immature granulocytic precursor cells and are associated with acute myelogenous leukemia. Thus, myeloid sarcoma should be considered in the differential diagnosis of pineal region masses in patients with a known history of acute myelogenous leukemia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: To develop an approach for computer-aided detection (CAD) of small brain metastases in post-Gd T1-weighted magnetic resonance imaging (MRI)., Method: A set of unevenly spaced 3D spherical shell templates was optimized to localize brain metastatic lesions by cross-correlation analysis with MRI. Theoretical and simulation analyses of effects of lesion size and shape heterogeneity were performed to optimize the number and size of the templates and the cross-correlation thresholds. Also, effects of image factors of noise and intensity variation on the performance of the CAD system were investigated. A nodule enhancement strategy to improve sensitivity of the system and a set of criteria based upon the size, shape and brightness of lesions were used to reduce false positives. An optimal set of parameters from the FROC curves was selected from a training dataset, and then the system was evaluated on a testing dataset including 186 lesions from 2753 MRI slices. Reading results from two radiologists are also included., Results: Overall, a 93.5% sensitivity with 0.024 of intra-cranial false positive rate (IC-FPR) was achieved in the testing dataset. Our investigation indicated that nodule enhancement was very effective in improving both sensitivity and specificity. The size and shape criteria reduced the IC-FPR from 0.075 to 0.021, and the brightness criterion decreases the extra-cranial FPR from 0.477 to 0.083 in the training dataset. Readings from the two radiologists had sensitivities of 60% and 67% in the training dataset and 70% and 80% in the testing dataset for the metastatic lesions <5 mm in diameter., Conclusion: Our proposed CAD system has high sensitivity and fairly low FPR for detection of the small brain metastatic lesions in MRI compared to the previous work and readings of neuroradiologists. The potential of this method for assisting clinical decision- making warrants further evaluation and improvements., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Gelastic syncope or laughter-induced syncope is a rare disease often misdiagnosed as narcolepsy or cataplexy. We report a 54-year-old man with syncopal episodes. Each episode started after laughter, leading to light-headedness with blurring of vision and loss of consciousness for a few seconds. The episodes resolved spontaneously. The treatment of gelastic syncope is the same as that for neurally mediated syncope., (Copyright 2012, NMJI.)

Brain tumors of the fetus and neonate are uncommon entities, compared with those of the older child and adolescents. They differ from those occurring in the older child and adolescent in several ways, including the tumor histology, tumor location, and overall prognosis. In this article, we review the most common intracranial tumors encountered in very young children, with emphasis on their imaging features., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Congenital cerebral vascular anomalies include a spectrum of conditions that result from perturbation of normal developmental processes. Although some of these conditions are asymptomatic and well compensated by collateral circulation, others can cause significant morbidity or produce a range of complications for affected patients. Knowledge of the underlying developmental etiologies and the associated imaging characteristics helps fully elucidate the morphologic and hemodynamic details of these lesions and determine the necessity for any intervention., (Copyright © 2011. Published by Elsevier Inc.)

This article is a review of vascular tumors and malformations that occur in infancy and childhood. It discusses anomalies of arterial, venous, capillary, lymphatic, and mixed vascular endothelium in terms of their varying forms, clinical course, imaging characteristics, complications, and treatment. The comparative utility of various imaging modalities is simplified., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This article reviews normal embryologic development of the spine and spinal cord and the imaging features of congenital abnormalities of the spine and spinal cord, with particular focus on magnetic resonance imaging. The authors discuss spinal dysraphisms, a heterogeneous group of congenital abnormalities of the spine and spinal cord, and provide information to expand understanding of these complex entities., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Congenital ear or temporal bone malformations are a diagnostic challenge to radiologists and surgeons alike. Newer imaging techniques can detect subtle changes in middle ear and cochlear anatomy. This information is invaluable with increasing use of hearing restoration surgeries and/or cochlear implants in such patients. This article discusses the embryogenesis, classification system, and salient imaging findings of congenital outer, middle ear, and inner ear anomalies in children. Both high-resolution computerized tomography and magnetic resonance imaging scans of the temporal bones are described., (Copyright © 2011 Elsevier Inc. All rights reserved.)