WashU weekly Neuroscience publications

Allopregnanolone: From molecular pathophysiology to therapeutics. A historical perspective
(2020) Neurobiology of Stress, 12, art. no. 100215, . 

Paul, S.M.^{a b c} , Pinna, G.^d , Guidotti, A.^{d e}

^a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
^b The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States
^c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
^d The Psychiatric Institute, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
^e Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of IIIinois at Chicago, United States

Abstract
Allopregnanolone is synthesized in the central nervous system either de novo from cholesterol or from steroid hormone precursors like progesterone and pregnenolone. Over the past 30 years, direct and rapid, non-genomic actions of allopregnanolone and its derivatives via GABAA receptors have been demonstrated. Changes in brain levels of allopregnanolone during pregnancy and in the postpartum period, or during exposure to protracted stress appear to play a crucial role in the pathophysiology of mood disorders. The discovery that allopregnanolone at low (nanomolar) concentrations elicits marked anxiolytic, anti-stress and antidepressant effects by facilitating allosterically the action of GABA at extrasynaptic GABAA receptors has provided new perspectives for the discovery of novel drugs useful for the treatment of mood disorders. These findings have led to the seminal clinical studies that recently demonstrated that treatment with allopregnanolone (i.e., brexanolone) can dramatically and rapidly improve the symptoms of postpartum depression in many patients. © 2020 The Authors

Author Keywords
Allopregnanolone;  Brexanolone;  GABAA receptors;  Mood disorders;  Neurosteroids;  Postpartum depression;  Zulresso

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

Human iPSC-Derived Neurons and Cerebral Organoids Establish Differential Effects of Germline NF1 Gene Mutations
(2020) Stem Cell Reports, 14 (4), pp. 541-550. 

Anastasaki, C.^a , Wegscheid, M.L.^a , Hartigan, K.^a , Papke, J.B.^a , Kopp, N.D.^{b c} , Chen, J.^b , Cobb, O.^a , Dougherty, J.D.^b , Gutmann, D.H.^a

^a Department of Neurology, Washington University School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States
^b Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
^c David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

Abstract
To critically evaluate NF1 mutational equivalency in human brain cells, Anastasaki and colleagues generated an isogenic series of seven human induced pluripotent stem cell lines harboring different NF1 patient NF1 mutations. Although all mutations increased 2D NPC and astrocyte RAS activity and cell proliferation, distinct NF1 mutations had differential effects on NPC proliferation, apoptosis and neuronal differentiation within 3D cerebral organoids. © 2020 The Authors

Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder caused by a spectrum of distinct germline NF1 gene mutations, traditionally viewed as equivalent loss-of-function alleles. To specifically address the issue of mutational equivalency in a disease with considerable clinical heterogeneity, we engineered seven isogenic human induced pluripotent stem cell lines, each with a different NF1 patient NF1 mutation, to identify potential differential effects of NF1 mutations on human central nervous system cells and tissues. Although all mutations increased proliferation and RAS activity in 2D neural progenitor cells (NPCs) and astrocytes, we observed striking differences between NF1 mutations on 2D NPC dopamine levels, and 3D NPC proliferation, apoptosis, and neuronal differentiation in developing cerebral organoids. Together, these findings demonstrate differential effects of NF1 gene mutations at the cellular and tissue levels, suggesting that the germline NF1 gene mutation is one factor that underlies clinical variability. © 2020 The Authors

Author Keywords
disease modeling;  human iPSCs;  neurodevelopment;  neurofibromatosis type 1

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

A role for CT in COVID-19? What data really tell us so far
(2020) The Lancet, 395 (10231), pp. 1189-1190. 

Hope, M.D.^{a b} , Raptis, C.A.^c , Shah, A.^d , Hammer, M.M.^e , Henry, T.S.^a

^a Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, United States
^b Department of Radiology, San Francisco Veterans Affairs Medical Center, San Francisco, CA, United States
^c Mallinckrodt Institute of Radiology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States
^d Department of Radiology, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, United States
^e Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States

Document Type: Letter
Publication Stage: Final
Source: Scopus
Access Type: Open Access

Project management for developing a spine “enhanced recovery after surgery” program in a large university-affiliated hospital
(2020) Journal of Neurosurgical Sciences, 64 (2), pp. 216-222. 

Hawasli, A.H.^{a b} , Ray, W.Z.^{c d} , Goad, M.A.^e , Frank, T.L.^c , Ellis, E.R.^e , Schmidt, M.^e , Lamartina, P.^e

^a Department of Neurological Surgery, Washington University School of Medicine, MO, Saint Louis, United States
^b Department of Orthopedic Surgery, Washington University School of Medicine, MO, Saint Louis, United States
^c Department of Neurological Surgery, Washington University School of Medicine, MO, Saint Louis, United States
^d Department of Orthopedic Surgery, Washington University School of Medicine, MO, Saint Louis, United States
^e Barnes-Jewish Hospital, MO, Saint Louis, United States

Abstract
Enhanced recovery after surgery (ERAS) programs for spine surgery have been developed throughout Europe and the United States leading to reduced hospital stay lengths, reduced opioid consumption, and faster return to activities of daily living and exercise. Development and execution of an ERAS spine program require commitment from the physician practice and collaborative hospital along with commitments from the entire health care team. Navigating this process can be a daunting task for a surgeon, whose traditional training involves no project management. Here we review our experience in the development of an ERAS program at a major academic medical institution and tertiary-care hospital in the USA from a program management perspective. In this manuscript, we provide the language and an outline to educate a surgeon on the project management processes needed to develop and initiate a pilot spine ERAS program.

Document Type: Article
Publication Stage: Final
Source: Scopus

T cell response kinetics determines neuroinfection outcomes during murine HSV infection
(2020) JCI Insight, 5 (5), art. no. e134258, .

Lee, A.G.^a , Scott, J.M.^a , Fabbrizi, M.R.^{a c} , Jiang, X.^a , Sojka, D.K.^b , Miller, M.J.^a , Baldridge, M.T.^a , Yokoyama, W.M.^b , Shin, H.^a

^a Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
^b Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
^c Department of Molecular and Clinical Cancer Medicine, Northwest Cancer Research Centre, University of Liverpool, Lverpool, United Kingdom

Abstract
Herpes simplex virus-2 (HSV-2) and HSV-1 both can cause genital herpes, a chronic infection that establishes a latent reservoir in the nervous system. Clinically, the recurrence frequency of HSV-1 genital herpes is considerably less than HSV-2 genital herpes, which correlates with reduced neuronal infection. The factors dictating the disparate outcomes of HSV-1 and HSV-2 genital herpes are unclear. In this study, we show that vaginal infection of mice with HSV-1 leads to the rapid appearance of mature DCs in the draining lymph node, which is dependent on an early burst of NK cell-mediated IFN-γ production in the vagina that occurs after HSV-1 infection but not HSV-2 infection. Rapid DC maturation after HSV-1 infection, but not HSV-2 infection, correlates with the accelerated generation of a neuroprotective T cell response and early accumulation of IFN-γ-producing T cells at the site of infection. Depletion of T cells or loss of IFN-γ receptor (IFN-γR) expression in sensory neurons both lead to a marked loss of neuroprotection only during HSV-1, recapitulating a prominent feature of HSV-2 infection. Our experiments reveal key differences in host control of neuronal HSV-1 and HSV-2 infection after genital exposure of mice, and they define parameters of a successful immune response against genital herpes. Copyright: © 2020, American Society for Clinical Investigation.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

Management of Hip Disorders in Patients with Cerebral Palsy
(2020) JBJS Reviews, 8 (3), p. e0148. 

Hosseinzadeh, P.^a , Baldwin, K.^b , Minaie, A.^a , Miller, F.^c

^a Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, United States
^b Department of Orthopaedic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
^c Motion Analysis Laboratory, Alfred I. DuPont Institute, Wilmington, DE, United States

Document Type: Article
Publication Stage: Final
Source: Scopus

Mimickers of Carpal Tunnel Syndrome
(2020) JBJS Reviews, 8 (2), p. e0087. 

Dengler, J.^a , Stephens, J.D.^b , Bamberger, H.B.^b , Moore, A.M.^c

^a Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
^b Kettering Health Network Orthopaedic Surgery Residency, Dayton, OH, United States
^c Washington University in St. Louis, St. Louis, MO, United States

Document Type: Article
Publication Stage: Final
Source: Scopus

Spinal cord infarction with resultant paraplegia after Chiari i decompression: Case report
(2020) Journal of Neurosurgery: Spine, 32 (4), pp. 615-621. 

Shah, A.S.^a , Yahanda, A.T.^a , Athiraman, U.^b , Tempelhoff, R.^b , Chicoine, M.R.^a

^a Departments of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
^b Departments of Anesthesia, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Paraplegia after posterior fossa surgery is a rare and devastating complication. The authors reviewed a case of paraplegia following Chiari decompression and surveyed the literature to identify strategies to reduce the occurrence of such events. An obese 44-year-old woman had progressive left arm pain, weakness, and numbness and tussive headaches. MRI studies revealed a Chiari I malformation and a cervicothoracic syrinx. Immediately postoperatively after Chiari decompression the patient was paraplegic, with a T6 sensory level bilaterally. MRI studies revealed equivocal findings of epidural hematoma at the site of the Chiari decompression and in the upper thoracic region. Surgical exploration of the Chiari decompression site and upper thoracic laminectomies identified possible venous engorgement, but no hematoma. Subsequent imaging suggested a thoracic spinal cord infarction. Possible explanations for the spinal cord deficit included spinal cord ischemia related to venous engorgement from prolonged prone positioning in an obese patient in the chin-tucked position. At 6.5 years after surgery the patient had unchanged fixed motor and sensory deficits. Spinal cord infarction is rare after Chiari decompression, but the risk for this complication may be increased for obese patients positioned prone for extended periods of time. Standard precautions may be insufficient and intraoperative electrophysiological monitoring may need to be considered in these patients. © AANS 2020.

Author Keywords
Chiari malformation;  Complication;  Congenital;  Neuromonitoring;  Paraplegia;  Posterior fossa decompression

Document Type: Article
Publication Stage: Final
Source: Scopus

iTBS to Relieve Depression and Executive Dysfunction in Older Adults: An Open Label Study
(2020) American Journal of Geriatric Psychiatry, . 

Cristancho, P.^a , Kamel, L.^a , Araque, M.^a , Berger, J.^a , Blumberger, D.M.^b , Miller, J.P.^c , Barch, D.M.^d , Lenze, E.J.^a

^a Department of Psychiatry, Healthy Mind Lab, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
^b Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada
^c Division of Biostatistics, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
^d Department of Psychological and Brain Sciences, Washington University Box 1125, St. Louis, MO, United States

Abstract
Background: Executive Function Deficits (EFD) accompany depression and are associated with poor outcomes in older adults. We examined whether Intermittent Theta Burst Stimulation (iTBS) could improve depression with EFD. Methods: Thirteen geriatric patients with depression and EFD were enrolled. Open label iTBS was delivered bilaterally over the dorso-lateral-prefrontal-cortex for four weeks. Results: Montgomery Asberg Depression Scale scores improved significantly from baseline to treatment-end, mean change in score = 11.82 points, 95% CI = 8.3, 15.4. The Flanker Inhibitory control and attention test showed significant improvement in executive function from baseline to treatment-end, mean change in score = −7.73, 95% CI ( −13.54, −1.92). Side effects included twitching in facial muscles (n = 11), headaches (n = 10) and stimulation discomfort (n = 4). Limitations: Small sample size and lack of a sham comparator. Conclusion: iTBS improved depression with EFD in older adults. Side effects appeared higher than in previous iTBS studies. © 2020

Author Keywords
Depression;  executive dysfunction;  executive function;  intermittent theta burst stimulation;  late life depression;  neuromodulation;  older adults;  transcranial magnetic stimulation

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

Cost comparison of surgical management of nonsagittal synostosis: Traditional open versus endoscope-assisted techniques
(2020) Journal of Neurosurgery: Pediatrics, 25 (4), pp. 351-360. 

Zubovic, E.^a , Lapidus, J.B.^b , Skolnick, G.B.^a , Naidoo, S.D.^a , Smyth, M.D.^c , Patel, K.B.^a

^a Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine in St. LouisMO, United States
^b Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, CA, United States
^c Department of Neurosurgery, Washington University School of Medicine in St. LouisMO, United States

Abstract
OBJECTIVE Management of craniosynostosis at an early age is important for mitigating the risk of abnormal cranial development, but treatment can result in significant expenses. Previous research has shown that endoscope-assisted craniectomy (EAC) is less costly than open cranial vault remodeling (CVR) for patients with sagittal synostosis. The aim of this study was to strengthen the existing body of healthcare cost research by elucidating the charges associated with open and endoscopic treatment for patients with nonsagittal synostosis. METHODS The authors performed a retrospective analysis of data obtained in 41 patients who underwent open CVR and 38 who underwent EAC with postoperative helmet therapy for nonsagittal, single-suture craniosynostosis (metopic, coronal, and lambdoid) between 2008 and 2018. All patients were < 1 year of age at the time of surgery and had a minimum 1 year of follow-up. Inpatient charges, physician fees, helmet charges, and outpatient clinic visits in the 1st year were analyzed. RESULTS The mean ages of the children treated with EAC and open CVR were 3.5 months and 8.7 months, respectively. Patients undergoing EAC with postoperative helmet therapy required more outpatient clinic visits in the 1st year than patients undergoing CVR (4 vs 2; p < 0.001). Overall, 13% of patients in the EAC group required 1 helmet, 30% required 2 helmets, 40% required 3 helmets, and 13% required 4 or more helmets; the mean total helmeting charges were $10,072. The total charges of treatment, including inpatient charges, physician fees, outpatient clinic visit costs, and helmet charges, were significantly lower for the EAC group than they were for the open CVR group ($50,840 vs $95,588; p < 0.001). CONCLUSIONS Despite the additional charges for postoperative helmet therapy and the more frequent outpatient visits, EAC is significantly less expensive than open CVR for patients with metopic, coronal, and lambdoid craniosynostosis. In conjunction with the existing literature on clinical outcomes and perioperative resource utilization, these data support EAC as a cost-minimizing treatment for eligible patients with nonsagittal synostosis. © AANS 2020.

Author Keywords
Cost;  Cranial vault remodeling;  Craniofacial;  Craniosynostosis;  Endoscopic;  Fronto-orbital advancement

Document Type: Conference Paper
Publication Stage: Final
Source: Scopus

Tinnitus
(2020) JAMA – Journal of the American Medical Association, . 

Piccirillo, J.F.^{a b} , Rodebaugh, T.L.^c , Lenze, E.J.^d

^a Washington University School of Medicine, Department of Otolaryngology-Head and Neck Surgery, St Louis, MO, United States
^b JAMA Otolaryngology-Head and Neck Surgery
^c Department of Psychology, Washington University, St Louis, MO, United States
^d Department of Psychiatry, Washington University, School of Medicine, St Louis, MO, United States

Document Type: Note
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

The Return of the Mast Cell: New Roles in Neuroimmune Itch Biology
(2020) Journal of Investigative Dermatology, . 

Wang, F.^{a b c} , Yang, T.-L.B.^{a b} , Kim, B.S.^{a b d e}

^a Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
^b Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO, United States
^c Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
^d Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
^e Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
The mast cell–nerve unit classically has represented a fundamental neuroimmune axis in the development of itch because of the traditional prominence of histamine as a pruritogen. However, it is appreciated increasingly that most chronic itch disorders are likely nonhistaminergic in nature, provoking the hypothesis that other novel effector itch mechanisms derived from mast cells are important. In this review, we present an overview of classical mast cell biology and put these concepts into the context of recent advances in our understanding of the regulation and function of the mast cell–nerve unit in itch biology. © 2019 The Authors

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability
(2020) Genetics in Medicine, . 

Malinowski, J.^a , Miller, D.T.^b , Demmer, L.^c , Gannon, J.^{d e} , Pereira, E.M.^f , Schroeder, M.C.^g , Scheuner, M.T.^{h i} , Tsai, A.C.-H.^j , Hickey, S.E.^k , Shen, J.^l , on behalf of the ACMG Professional Practice and Guidelines Committee^m

^a Write Inscite, LLC, Hebron, CT, United States
^b Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, United States
^c Atrium Health’s Levine Children’s Hospital, Charlotte, NC, United States
^d Division of Clinical Genetics, Children’s Mercy Hospital, Kansas City, MO, United States
^e Department of Pediatrics, University of Missouri, Kansas City, MO, United States
^f Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, NY, United States
^g Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
^h Division of Medical Genetics, Department of Pediatrics and Division of Hematology–Oncology, Department of Medicine, University of California, San Francisco, CA, United States
ⁱ San Francisco VA Healthcare System, San Francisco, CA, United States
^j Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Aurora, CO, United States
^k Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States
^l Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
^m American College of Medical Genetics and Genomics, Bethesda, MD, United States

Abstract
Purpose: Exome and genome sequencing (ES/GS) are performed frequently in patients with congenital anomalies, developmental delay, or intellectual disability (CA/DD/ID), but the impact of results from ES/GS on clinical management and patient outcomes is not well characterized. A systematic evidence review (SER) can support future evidence-based guideline development for use of ES/GS in this patient population. Methods: We undertook an SER to identify primary literature from January 2007 to March 2019 describing health, clinical, reproductive, and psychosocial outcomes resulting from ES/GS in patients with CA/DD/ID. A narrative synthesis of results was performed. Results: We retrieved 2654 publications for full-text review from 7178 articles. Only 167 articles met our inclusion criteria, and these were primarily case reports or small case series of fewer than 20 patients. The most frequently reported outcomes from ES/GS were changes to clinical management or reproductive decision-making. Two studies reported on the reduction of mortality or morbidity or impact on quality of life following ES/GS. Conclusion: There is evidence that ES/GS for patients with CA/DD/ID informs clinical and reproductive decision-making, which could lead to improved outcomes for patients and their family members. Further research is needed to generate evidence regarding health outcomes to inform robust guidelines regarding ES/GS in the care of patients with CA/DD/ID. © 2020, American College of Medical Genetics and Genomics.

Author Keywords
clinical genetics;  congenital anomalies;  exome sequencing;  intellectual disability;  systematic evidence review

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

Preprocessing of clinical neuro-oncology MRI studies for big data applications
(2020) Progress in Biomedical Optics and Imaging – Proceedings of SPIE, 11318, art. no. 1131809, . 

Chakrabarty, S.^{a b} , Lamontagne, P.^b , Marcus, D.S.^b , Milchenko, M.^b

^a Department of Electrical and Systems Engineering, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO 63130, United States
^b Neuroinformatics Research Group, Department of Radiology, Washington University, School of Medicine, 4525 Scott Ave, St. Louis, MO 63110, United States

Abstract
Clinically acquired, multimodal and multi-site MRI datasets are widely used for neuro-oncology research. However, manual preprocessing of such data is extremely tedious and error prone due to high intrinsic heterogeneity. Automatic standardization of such datasets is therefore important for data-hungry applications like deep learning. Despite rapid advances in MRI data acquisition and processing algorithms, only limited effort was dedicated to automatic methodologies for standardization of such data. To address this challenge, we augment our previously developed Multimodal Glioma Analysis (MGA) pipeline with automation tools to achieve processing scale suitable for big data applications. This new pipeline implements a natural language processing (NLP) based scan-type classifier, with features constructed from DICOM metadata based on bag-ofwords model. The classifier automatically assigns one of 18 pre-defined scan types to all scans in MRI study. Using the described data model, we trained three types of classifiers: logistic regression, linear SVM, and multi-layer artificial neural network (ANN) on the same dataset. Their performance was validated on four datasets from multiple sources. ANN implementation achieved the highest performance, yielding an average classification accuracy of over 99%. We also built a Jupyter notebook based graphical user interface (GUI) which is used to run MGA in semi-automatic mode for progress tracking purposes and quality control to ensure reproducibility of the analyses based thereof. MGA has been implemented as a Docker container image to ensure portability and easy deployment. The application can run in a single or batch study mode, using either local DICOM data or XNAT cloud storage. © COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only.

Author Keywords
Clinical MRI;  Docker;  Jupyter Notebook;  MRI scan classifier;  Natural Language Processing;  Neuro-oncology imaging;  Translational research

Document Type: Conference Paper
Publication Stage: Final
Source: Scopus

SNIPR: Stroke Neuroimaging Phenotype Repository
(2020) Progress in Biomedical Optics and Imaging – Proceedings of SPIE, 11318, art. no. 113180B, . 

Mohammadian Foroushani, H.^a , Dhar, R.^b , Chen, Y.^c , Gurney, J.^d , Hamzehloo, A.^b , Lee, J.-M.^c , Marcus, D.S.^d

^a Department of Electrical and System Engineering, Washington University, School of Engineering, One Brookings Drive, St. Louis, MO 63130, United States
^b Division of Neurocritical Care, Department of Neurology, Washington University, School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, United States
^c Division of Cerebrovascular Disease, Department of Neurology, Washington University, School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, United States
^d Department of Radiology, Washington University, School of Medicine, 510 S Kingshighway Blvd, St. Louis, MO 63110, United States

Abstract
Understanding of stroke etiology and its genetic pathways is critical for planning, implementation, and evaluation of stroke patient treatments. However, this knowledge discovery requires phenotyping stroke and integration of multiple demographic, clinical, genetic and imaging phynotypes by developing and running sophisticated processing pipelines at massive scale. The Stroke Neuroimaging Phenotype Repository (SNIPR) was developed in 2018 as a large multi-center centralized imaging repository of clinical CT and MRI scans from stroke patients worldwide, based on the Extensible Neuroimaging Archive Toolkit (XNAT). The aims of this repository are to: (i) Create a central retrospective repository to host and provide secure access to data from anonymized acute stroke patients with serial clinical imaging; (ii) Facilitate integration of independent stroke phenotypic studies via data aggregation techniques; and (iii) Expedite the development of containerized deep learning pipelines to perform large-scale analysis of complications after stroke. Currently, SNIPR hosts 8 projects, 1877 subjects and 5281 imaging sessions from Washington University Medical Center’s clinical image archive as well as contributions from collaborators in different countries, including US, Finland, Poland, and Spain. Moreover, we have used XNAT’s standard XML Schema extension mechanism to create data type extensions to support stroke phenotypic studies, including clinical phenotypes like NIHSS and imaging phenotypes like infarct and Cerebrospinal fluid (CSF) volume. We have developed deep learning pipelines to facilitate image processing and analysis and deployed these pipelines through XNAT’s container service. The container service enables these pipelines to execute at large scale with Docker Swarm on an attached compute cluster. Our pipelines include a scan-type classifier which includes a convolutional neural network (CNN) approach and a natural language processing approach to automatically categorize uploaded CT sequences into defined classes to facilitate selection for further analysis. We deployed this containerized classifier within a broader pipeline to facilitate big data analysis of cerebral edema after stroke, and we got 99.4 % test accuracy on 10000 scans. SNIPR enables the developed automatic pipelines to use this automatic scan selection, develop and validate imaging phenotypes and couple them with clinical and genetic data with the overarching aim of enabling a broad understanding of stroke progression and outcomes. © COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only.

Author Keywords
Big data;  Containerized pipeline;  Convolutional neural network (CNN);  Informatics;  Phenotype repository;  Stroke neuroimaging;  XNAT

Document Type: Conference Paper
Publication Stage: Final
Source: Scopus