Frank J. Minja

Vessel wall magnetic resonance imaging identifies the site of rupture in patients with multiple intracranial aneurysms: proof of principle.

BACKGROUND High-resolution magnetic resonance vessel wall imaging (MR-VWI) is increasingly used to study steno-occlusive cerebrovascular disease, but has not yet been applied to patients with aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE To study the ability of high-resolution MR-VWI to determine the site of rupture in patients with aneurysmal SAH. METHODS Medical records of patients admitted with aneurysmal SAH between December 2011 and May 2012 were reviewed. MR-VWI was routinely performed for patients treated in the IMRIS Neurovascular Suite immediately before definitive treatment of the ruptured aneurysm. RESULTS We report for the first time high-resolution MR-VWI in 5 patients with aneurysmal SAH. Three patients harbored multiple intracranial aneurysms. The ruptured aneurysms demonstrated thick vessel wall enhancement in all cases. None of the associated unruptured aneurysms demonstrated this MR imaging finding. CONCLUSION High-resolution MR-VWI identified the site of rupture in patients with aneurysmal SAH, including those patients harboring multiple intracranial aneurysms. It may represent a useful tool in the investigation of aneurysmal SAH.

Ocular anatomy and cross-sectional imaging of the eye.

Ocular cross-sectional imaging is usually obtained as an adjunct to clinical ophthalmologic examination and ocular ultrasound. Computed tomography/magnetic resonance imaging (CT/MRI) are complimentary for ocular imaging and are performed for evaluation of the vitreous cavity, choroid, retina, sclera, and potential spaces and for the assessment of extension of disease beyond the globe into the orbit or brain. CT has superior spatial resolution aided by the natural contrast between bone, soft tissues, air, and fat. The short scanning time is advantageous to reduce motion effects and the need for sedation. CT is also the modality of choice for evaluation of traumatic injury and for visualization of foreign bodies. Potential clinical indications for MRI include staging of retinoblastoma and other causes of leukocoria, assessment of retinal or choroidal detachments for underlying retinal mass or hemorrhage, uveal melanoma, ocular metastases, choroidal hemangioma, and buphthalmus, staphyloma, and coloboma. Last, but not least, MRI has the advantage of no ionizing radiation.

Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors

Exome sequencing analysis of over 2,000 children with complex malformations of cortical development identified five independent (four homozygous and one compound heterozygous) deleterious mutations in KATNB1, encoding the regulatory subunit of the microtubule-severing enzyme Katanin. Mitotic spindle formation is defective in patient-derived fibroblasts, a consequence of disrupted interactions of mutant KATNB1 with KATNA1, the catalytic subunit of Katanin, and other microtubule-associated proteins. Loss of KATNB1 orthologs in zebrafish (katnb1) and flies (kat80) results in microcephaly, recapitulating the human phenotype. In the developing Drosophila optic lobe, kat80 loss specifically affects the asymmetrically dividing neuroblasts, which display supernumerary centrosomes and spindle abnormalities during mitosis, leading to cell cycle progression delays and reduced cell numbers. Furthermore, kat80 depletion results in dendritic arborization defects in sensory and motor neurons, affecting neural architecture. Taken together, we provide insight into the mechanisms by which KATNB1 mutations cause human cerebral cortical malformations, demonstrating its fundamental role during brain development.

Brain Malformations Associated With Knobloch Syndrome—Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations

BACKGROUND Knobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, and cutis aplasia). Although there is clear heterogeneity in clinical presentation, central nervous system malformations, aside from the characteristic encephalocele, have not typically been considered a component of the disease phenotype. METHODS Four patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, we investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database. RESULTS We identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, we found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. Our data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII. CONCLUSIONS This case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology-allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. We suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1 mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele.

Verification of supraselective drug delivery for retinoblastoma using intra-arterial gadolinium

We present a description of retinoblastoma treated with supraselective intra-arterial chemotherapy, demonstrating selective delivery of the infused chemotherapeutic agent into the tumor bed by MRI. A 7-month-old presented with group E (international classification) unilateral retinoblastoma. We treated the patient with several rounds of intra-ophthalmic artery melphalan. Gadolinium was infused along with melphalan to visualize the distribution of this chemotherapeutic drug. Intraoperative MRI was obtained within 15 min after treatment and showed increased enhancement of the tumor and subretinal space. We demonstrate here that supraselective administration of chemotherapy into the ophthalmic artery appears to result in drug delivery to the tumor and subretinal space.

High-resolution Vessel Wall Magnetic Resonance Imaging in Intracranial Aneurysms and Brain Arteriovenous Malformations.

Abstract Over the last several years, the advent of intracranial high-resolution vessel wall magnetic resonance imaging (VW-MRI) has provided a new lens with which to view cerebrovascular disease that has not previously been available with conventional imaging. It has already fundamentally changed the way that steno-occlusive diseases are evaluated at many academic centers. This review focuses on current and emerging applications of intracranial high-resolution VW-MRI in the clinical evaluation of intracranial aneurysms and brain arteriovenous malformations. Examples are provided from our clinical practice.

Erratum to Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors[Neuron, 84, 1226-1239, 2014]

Ketu Mishra-Gorur,1,2,3,4,19 Ahmet Okay Ça glayan,1,2,3,4,19 Ashleigh E. Schaffer,5 Chiswili Chabu,2,6 Octavian Henegariu,1,2,3,4 Fernando Vonhoff,7 Gözde Tu gce Akgümüsx,1,2,3,4 Sayoko Nishimura,1,4 Wenqi Han,3,8 Shu Tu,9 Burçin Baran,1,2,3,4 Hakan Gümüsx,10 Cengiz Dilber,11 Maha S. Zaki,12 Heba A.A. Hossni,13 Jean-Baptiste Rivière,14 Hülya Kayserili,15 Emily G. Spencer,5 Rasim Ö. Rosti,5 Jana Schroth,5 Hüseyin Per,10 Caner Ça glar,1,2,3,4 Ça gri Ça glar,1,2,3,4 Duygu Dölen,1,2,3,4 Jacob F. Baranoski,1,2,3,4 Sefer Kumandasx,10 Frank J. Minja,16 E. Zeynep Erson-Omay,1,2,3,4 ShrikantM.Mane,2,17 Richard P. Lifton,2,6 Tian Xu,2,6 Haig Keshishian,7WilliamB. Dobyns,18 Neil C. Chi,9 Nenad Sestan,3,4,8 Angeliki Louvi,1,3,4 Kaya Bilgüvar,2,17 Katsuhito Yasuno,1,2,3,4 Joseph G. Gleeson,5,* and Murat Günel1,2,3,4,* 1Department of Neurosurgery 2Department of Genetics 3Department of Neurobiology 4Yale Program on Neurogenetics Yale School of Medicine, New Haven, CT 06510, USA 5Neurogenetics Laboratory, Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA 6Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06510, USA 7Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA 8Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA 9Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA 10Division of Pediatric Neurology, Department of Pediatrics, Erciyes University Medical Faculty, Kayseri 38039, Turkey 11Division of Pediatric Neurology, Department of Pediatrics, Sütcü Imam University Medical Faculty, Kahramanmarasx 46100, Turkey 12Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Center, Cairo 12311, Egypt 13Department of Neurology, National Institute of Neuromotor System, Cairo 12311, Egypt 14Equipe Génétique des Anomalies du Développement, EA 4271, Université de Bourgogne, 21078 Dijon, France 15Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey 16Department of Radiology 17Yale Center for Genome Analysis Yale School of Medicine, New Haven, CT 06510, USA 18Departments of Pediatrics and Neurology, University of Washington and Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, Washington 98105, USA 19Co-first author *Correspondence: jogleeson@rockefeller.edu (J.G.G.), murat.gunel@yale.edu (M.G.) http://dx.doi.org/10.1016/j.neuron.2014.12.014

Successful Implementation of a PACS in Tanzania

INTRODUCTION TO THE PROBLEM Muhimbili Orthopaedic Institute (MOI) is a public, academic tertiary care referral center in Dar es Salaam, Tanzania, East Africa. MOI is the main referral center for orthopedic and neurosurgical patients in Tanzania. In July 2014, the Radiology Department at MOI consisted of two attending radiologists, 10 technologists, and three IT staff with imaging capabilities of radiography, fluoroscopy, and ultrasound. MOI is affiliated with and located on the same campus as Muhimbili National Hospital, the main national referral hospital, which had one four-slice CT scanner, one 1.5-T MRI scanner, four ultrasound units, and one analog radiography/fluoroscopy unit. MOI patients were often transported to Muhimbili National Hospital for cross-sectional imaging. X-ray images acquired at MOI were first converted into the DICOM format by a computed radiography (CR) system. From theCR system, the DICOM data were sent to a laser printer for hard-copy films or a CDROM burner. Each hard-copy film cost approximatelyUS

A Comprehensive Review of MR Imaging Changes following Radiosurgery to 500 Brain Metastases

2.50, resulting in a total of over US

Radiologic and histologic consequences of radiosurgery for brain tumors

5,000 for an average of 2,000 radiology studies per month at MOI. Hard-copy film was a prohibitive recurrent expense forMOI, resulting in frequent film shortages and disruption of imaging services.