A Spatial Interpolation Approach to Assign Magnetic Resonance Imaging-Derived Material Properties for Finite Element Models of Adeno-Associated Virus Infusion Into a Recurrent Brain Tumor.

Adeno-associated virus (AAV) is a clinically useful gene delivery vehicle for treating neurological diseases. To deliver AAV to focal targets, direct infusion into brain tissue by convection-enhanced delivery (CED) is often needed due to AAV's limited penetration across the blood-brain-barrier and its low diffusivity in tissue. In this study, computational models that predict the spatial distribution of AAV in brain tissue during CED were developed to guide future placement of infusion catheters in recurrent brain tumors following primary tumor resection. The brain was modeled as a porous medium, and material property fields that account for magnetic resonance imaging (MRI)-derived anatomical regions were interpolated and directly assigned to an unstructured finite element mesh. By eliminating the need to mesh complex surfaces between fluid regions and tissue, mesh preparation was expedited, increasing the model's clinical feasibility. The infusion model predicted preferential fluid diversion into open fluid regions such as the ventricles and subarachnoid space (SAS). Additionally, a sensitivity analysis of AAV delivery demonstrated that improved AAV distribution in the tumor was achieved at higher tumor hydraulic conductivity or lower tumor porosity. Depending on the tumor infusion site, the AAV distribution covered 3.67-70.25% of the tumor volume (using a 10% AAV concentration threshold), demonstrating the model's potential to inform the selection of infusion sites for maximal tumor coverage.

Pediatric craniosynostosis computed tomography: an institutional experience in reducing radiation dose while maintaining diagnostic image quality.

BACKGROUND: Children with craniosynostosis may undergo multiple computed tomography (CT) examinations for diagnosis and post-treatment follow-up, resulting in cumulative radiation exposure. OBJECTIVE: To reduce the risks associated with radiation exposure, we evaluated the compliance, radiation dose reduction and clinical image quality of a lower-dose CT protocol for pediatric craniosynostosis implemented at our institution. MATERIALS AND METHODS: The standard of care at our institution was modified to replace pediatric head CT protocols with a lower-dose CT protocol utilizing 100 kV, 5 mAs and iterative reconstruction. Study-ordered, protocol-utilized and radiation-dose indices were collected for studies performed with routine pediatric brain protocols (n=22) and with the lower-dose CT protocol (n=135). Two pediatric neuroradiologists evaluated image quality in a subset (n=50) of the lower-dose CT studies by scoring visualization of cranial structures, confidence of diagnosis and the need for more radiation dose. RESULTS: During the 30-month period, the lower-dose CT protocol had high compliance, with 2/137 studies performed with routine brain protocols. With the lower-dose CT protocol, volume CT dose index (CTDIvol) was 1.1 mGy for all patients (0-9 years old) and effective dose ranged from 0.06 to 0.22 mSv, comparable to a 4-view skull radiography examination. CTDIvol was reduced by 98% and effective dose was reduced up to 67-fold. Confidence in diagnosing craniosynostosis was high and more radiation dose was considered unnecessary in all studies (n=50) by both radiologists. CONCLUSION: Replacing the routine pediatric brain CT protocol with a lower-dose CT craniosynostosis protocol substantially reduced radiation exposure without compromising image quality or diagnostic confidence.

A method for pre-operative single-subject thalamic segmentation based on probabilistic tractography for essential tremor deep brain stimulation.

PURPOSE: Deep brain stimulation is a common treatment for medication-refractory essential tremor. Current coordinate-based targeting methods result in variable outcomes due to variation in thalamic structure and the optimal patient-specific functional location. The purpose of this study was to compare the coordinate-based pre-operative targets to patient-specific thalamic segmentation utilizing a probabilistic tractography methodology. METHODS: Using available diffusion MRI of 32 subjects from the Human Connectome Project database, probabilistic tractography was performed. Each thalamic voxel was coded based on one of six predefined cortical targets. The segmentation results were analyzed and compared to a 2-mm spherical target centered at the coordinate-based location of the ventral intermediate thalamic nucleus. RESULTS: The traditional coordinate-based target had maximal overlap with the junction of the region most connected to primary motor cortex (M1) (36.6 ± 25.7% of voxels on left; 58.1 ± 28.5% on right) and the area connected to the supplementary motor area/premotor cortex (SMA/PMC) (44.9 ± 21.7% of voxels on left; 28.9 ± 22.2% on right). There was a within-subject coefficient of variation from right-to-left of 69.4 and 63.1% in the volume of overlap with the SMA/PMC and M1 regions, respectively. CONCLUSION: Thalamic segmentation based on structural connectivity measures is a promising technique that may enhance traditional targeting methods by generating reproducible, patient-specific pre-operative functional targets. Our results highlight the problematic intra- and inter-subject variability of indirect, coordinate-based targets. Future prospective clinical studies will be needed to validate this targeting methodology in essential tremor patients.

Contrast-enhanced CT and MR imaging of renal vessels.

In the evaluation of renal vessels, the accepted diagnostic gold standard digital subtraction angiography is now being challenged by state of the art CT and MR imaging. Currently in many centers, cross-sectional imaging modalities are being used as a first line diagnostic tool to evaluate arterial and venous system of the kidneys and conventional angiography has been reserved only for therapeutic intervention. CT and MR imaging display not only the lumen of the vessel as in conventional angiography, but also allow the visualization of the vessel wall, renal parenchyma, collecting system, and other adjacent soft tissue structures. Therefore, CT and MRI have each become a one-stop shop for a thorough evaluation of kidneys. In this pictorial essay, we reviewed normal anatomical variants and wide range of pathologies involving renal arteries and veins with illustrated contrast-enhanced CT and MR imaging samples.

Intramyelinic edema manifesting as central white matter diffusion restriction associated with brain contusion in pediatric patients.

In traumatic brain injury, white matter diffusion restriction can be an imaging manifestation of non-hemorrhagic axonal injury. In this article, a different pattern of widespread white matter diffusion restriction associated with ipsilateral cortical damage, all noted in pediatric and young adult TBI patients, is presented. Its atypical pattern of distribution and extensive scope on imaging suggest excitotoxicity and intramyelinic edema as possible underlying mechanisms.

Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

For over two centuries, clinicians have been aware of various conditions affecting white matter which had come to be grouped under the umbrella term multiple sclerosis. Within the last 20 years, specific scientific advances have occurred leading to more accurate diagnosis and differentiation of several of these conditions including, neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody disease. This new understanding has been coupled with advances in disease-modifying therapies which must be accurately applied for maximum safety and efficacy.

Brain Dead and Pregnant.

The presence of pregnancy in a brain-dead woman is a rare circumstance. We present a case of a 31-year-old woman who was 22 weeks pregnant at the time of diagnosis of brain death after intracranial and subarachnoid hemorrhage. After a multidisciplinary approach, the decision was made to continue somatic support to maintain the pregnancy until optimal fetus viability. Cesarean section was performed after 11 weeks (33 weeks gestational age) of brain-death diagnosis with a successful delivery of a live infant. Management of brain-death complications during pregnancy is described.

Adeno-associated virus-mediated gene therapy in a patient with Canavan disease using dual routes of administration and immune modulation.

Gene replacement therapy is a rational therapeutic strategy and clinical intervention for neurodegenerative disorders like Canavan disease, a leukodystrophy caused by biallelic mutations in the aspartoacylase (ASPA) gene. We aimed to investigate whether simultaneous intravenous (i.v.) and intracerebroventricular (i.c.v.) administration of rAAV9-CB6-ASPA provides a safe and effective therapeutic strategy in an open-label, individual-patient, expanded-access trial for Canavan disease. Immunomodulation was given prophylactically prior to adeno-associated virus (AAV) treatment to prevent an immune response to ASPA or the vector capsid. The patient served as his own control, and change from baseline was assessed by clinical pathology tests, vector genomes in the blood, antibodies against ASPA and AAV capsids, levels of cerebrospinal fluid (CSF) N-acetylaspartate (NAA), brain water content and morphology, clinical status, and motor function tests. Two years post treatment, the patient's white matter myelination had increased, motor function was improved, and he remained free of typical severe epilepsy. NAA level was reduced at 3 months and remained stable up to 4 years post treatment. Immunomodulation prior to AAV exposure enables repeat dosing and has prevented an anti-transgene immune response. Dual-route administration of gene therapy may improve treatment outcomes.

NS-HGlio: A generalizable and repeatable HGG segmentation and volumetric measurement AI algorithm for the longitudinal MRI assessment to inform RANO in trials and clinics.

Background: Accurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable. Methods: A single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed. Results: IV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed. Conclusion: NS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others.

Detection of bifid mandibular condyle using computed tomography.

OBJECTIVE: To determine the frequency and characteristics of bifid mandibular condyle (BMC) using computed tomography (CT) evaluation. STUDY DESIGN: A retrospective study was carried out using the CT records of 550 patients referred to the Medical School of Erciyes University (Kayseri, Turkey) between 2007 and 2010. T-tests were used to compare frequency of BMC between the left and right sides and between female and male patients. Statistical analysis was performed using SPSS software and a chi-squared test. RESULTS: Of the 550 Patients, 10 patients (1.82%) were found to have BMCs. Five patients were female (50%) and five were male (50%). Of these 10 patients, 7 (70%) had unilateral and 3 (30%) had bilateral BMCs. As a result, a total of 13 BMCs were found in 10 patients. No statistically significant differences were found between either the right- and left-sided BMCs or between female and male patients (p >.05). CONCLUSIONS: To our knowledge, this is the first retrospective study investigating the prevalence and characteristics of BMC using computed tomography. Although BMC is an uncommon anomaly, it may be a more frequent condition in the Turkish population. Further studies and research on the orientation of duplicated condylar heads should be carried out.

A Comparison of Pediatric- and Adult-Onset Aquaporin-4 Immunoglobulin G-Positive Neuromyelitis Optica Spectrum Disorder: A Review of Clinical and Radiographic Characteristics.

BACKGROUND: The identification of immunoglobulin G antibodies against the aquaporin-4 channel (AQP-IgG) in the majority of adult patients differentiates neuromyelitis optica as a distinct disease entity. The high specificity of AQP4-IgG for neuromyelitis optica has allowed the identification of seropositive patients with atypical presentations of this disease. Neuromyelitis optica spectrum disorder has been increasingly recognized in children who demonstrate patterns of clinical involvement beyond the traditional boundaries of the optic pathways and spinal cord. METHODS: This is a single-center, retrospective review comparing demographic, clinical/paraclinical, and laboratory features of children and adults with a serologically confirmed diagnosis of AQP4-IgG-positive neuromyelitis optica spectrum disorder. RESULTS: Of 151 reviewed patient charts, 12 pediatric-onset and 31 adult-onset patients had AQP4-IgG-positive neuromyelitis optica spectrum disorder. The mean age of pediatric-onset neuromyelitis optica spectrum disorder was 12 ± 3.58 years with a female predilection (3:1). Pediatric patients showed more frequent involvement of the brainstem (6/12 [50%]); P = .008) and diencephalon (3/12 [25%]; P = .018). A preceding infection was identifiable in only 3 of 12 (25%) pediatric-onset patients. Moreover, disability as calculated on the expanded disability status scale was less severe in pediatric-onset cases compared to adult-onset cases in their most recent assessment (0 [0-9]) vs 6.5 [0-10]; P = .005). Pediatric-onset patients were also more likely to respond to treatment of acute episodes with corticosteroids ± intravenous immunoglobulin and/or plasmapheresis (Clinical Global Impression-Change scale: 2.5 [1-4] vs 4 [1-6], P = .009). INTERPRETATION: This retrospective study was able to compare and contrast pediatric- and adult-onset neuromyelitis optica spectrum disorder. Relative to their adult counterparts, pediatric-onset neuromyelitis optica spectrum disorder patients were more likely to respond to treatment and less likely to be disabled from their disease at follow-up. Therefore, pediatric-onset disease may represent a less virulent form of neuromyelitis optica spectrum disorder.

Visualization of the perivenous glymphatic efflux in human brain after laser interstitial thermal therapy.

Recent studies have revealed that there is existence of a specific waste clearance pathway in the brain, coined the glymphatic system. This case report demonstrates supportive finding of drainage of Gadolinium and waste products released after Laser Interstitial Thermal Therapy via perivenous routes and a paradural lymphatic system. These findings provide further evidence of interstitial fluid drainage along the perivenous spaces in accordance with a glymphatic system theory.

Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes.

Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Here we show dural lymphatic structures along the dural venous sinuses in dorsal regions and along cranial nerves in the ventral regions in the human brain. 3D T2-Fluid Attenuated Inversion Recovery magnetic resonance imaging relies on internal signals of protein rich lymphatic fluid rather than contrast media and is used in the present study to visualize the major human dural lymphatic structures. Moreover we detect direct connections between lymphatic fluid channels along the cranial nerves and vascular structures and the cervical lymph nodes. We also identify age-related cervical lymph node atrophy and thickening of lymphatics channels in both dorsal and ventral regions, findings which reflect the reduced lymphatic output of the aged brain.

Pituitary Apoplexy (PA): Delayed Diagnosis of a Rare Clinical Syndrome in a Patient With a Known Pituitary Adenoma.

Pituitary apoplexy (PA) is a rare clinical syndrome in which the pituitary gland undergoes infarction or hemorrhage, predominantly in the setting of an underlying tumor. We report on apoplexy of an expanding pituitary macroadenoma that was compressing the optic chiasm in a patient with progressively worsening neurologic deficits. Due to the patient's rapidly declining clinical status and family's goals of care, no neurosurgical intervention took place, and the patient expired a few days following discharge to hospice. This case highlights the importance of early suspicion for apoplexy in a patient with a history of pituitary adenoma and signs of neurologic deficit.

Presumptive Diagnosis of Pallister-Hall Syndrome Using Magnetic Resonance Imaging.

Pallister-Hall syndrome (PHS) is an extremely rare genetic disorder for which the diagnosis is often overlooked. The objective of this case report is to highlight how clinical features used in conjunction with brain MRI findings can lead to an expeditious diagnosis without the need for invasive measures or genetic test results. We present the case of a three-day-old infant delivered at 34 and 4/7 weeks gestation who presented with mild respiratory distress and bilious emesis in the setting of an uncomplicated gestational course and vaginal delivery with no known teratogen exposure. A diagnosis of Pallister-Hall syndrome was made on the basis of physical exam findings, hormonal abnormalities and the identification of a hypothalamic hamartoma on brain MRI. The patient underwent multiple procedures for diagnosis and management of PHS complications, including a diverting jejunostomy for a long-segment Hirschsprung's and a laryngoscopy which identified a bifid epiglottis. The patient tolerated the interventions and did not have seizures on admission. The MRI brain detection of a hypothalamic hamartoma led to an earlier diagnosis of Pallister-Hall syndrome and thus further screening and identification of complications associated with this disorder were performed before genetic analyses or brain biopsies were obtained. Given the unique MRI features of hypothalamic hamartomas, brain MRI can be a useful tool for making an early PHS diagnosis when taken with clinical features concerning possible PHS.

Management of Cavernous Sinus Thrombosis Following Herpes Zoster Ophthalmicus.

Herpes zoster opthalmicus (HZO) is the reactivation of latent varicella zoster virus (VZV) within the ophthalmic branch of the trigeminal ganglion (V1). Common complications are postherpetic neuralgia and vasculopathy. Here, we report a rare case of a 47-year-old female presenting with HZO and aseptic cavernous sinus thrombosis (CST). Early screening for rare and deadly complications such as CST using CT cerebral venography (CTV) and magnetic resonance venography (MRV), as was done, is crucial to detection at earlier stages when intervention is most effective. Anticoagulation therapy was promptly started, and the patient's symptoms continued to improve during the hospital stay.

Gadolinium in tears: Evidence for an alternative cerebrospinal fluid absorption pathway in the setting of ischemia-induced blood brain barrier disruption.

Cerebral ischemia results in disruption of the blood-brain barrier (BBB) allowing leakage of gadolinium-based contrast media (GBCM) into cerebrospinal fluid (CSF) within the craniospinal and perineural subarachnoid spaces (SAS). This phenomenon is well visualized with fluid-attenuated inversion recovery MRI techniques and allows for visualization of CSF flow dynamics. We present a case of ischemia-induced BBB disruption resulting in accumulation of GBCM in the SAS and ocular chambers as well as within the precorneal tear film and nasolacrimal duct. We present imaging evidence for a hypothetical alternate CSF absorption pathway through the ocular structures in keeping with prior experimental evidence.

Glioblastoma with a primitive neuroectodermal component: two cases with implications for glioblastoma cell-of-origin.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain malignancy, but much remains unknown about the histogenesis of these tumors. In the great majority of cases, GBM is a purely glial tumor but in rare cases the classic-appearing high-grade glioma component is admixed with regions of small round blue cells with neuronal immunophenotype, and these tumors have been defined in the WHO 2016 Classification as "glioblastoma with a primitive neuronal component." METHODS: In this paper, we present two cases of GBM-PNC with highly divergent clinical courses, and review current theories for the GBM cell-of-origin. RESULTS AND CONCLUSIONS: GBM-PNC likely arises from a cell type competent to give rise to glial or neuronal lineages. The thesis that GBM recapitulates to some extent normal neurodevelopmental cellular pathways is supported by molecular and clinical features of our two cases of GBM-PNC, but more work is needed to determine which cellular precursor gives rise to specific cases of GBM. GBM-PNC may have a dramatically altered clinical course compared to standard GBM and may benefit from specific lines of treatment.