Day 1 :
Keynote Forum
Harish C Pant
National Institute of Neurological Disease and Stroke, USA
Keynote: A novel therapeutic approach to ameliorate the Parkinsion’s and Alzheimer’s Disease phenotypes
Time : 9:30 - 10:10
Biography:
Pant received his M.A. and Ph.D. degrees in Physics from Agra University, Agra, India. His postdoctoral studies were conducted on the mechanisms of electron and ion transport in model membrane systems at the Department of Biophysics at Michigan State University. He joined the Laboratory of Neurobiology in the NIMH as a senior staff fellow in 1974 with Dr. Ichiji Tasaki where he studied the function of the axonal cytoskeleton in the squid giant axon. In 1979 he moved to the NIAAA extending his studies on the neuronal cytoskeleton and the effects of alcohol on its regulation. Dr. Pant moved to the NINDS, Laboratory of Neurochemistry in 1987 where he is presently chief of the section on Cytoskeleton Regulation. His laboratory is studying the mechanisms of topographic regulation of neuronal cytoskeleton proteins by post-translational modification, including the role of kinase cascades in normal brain and during neurodegeneration.
Abstract:
The phosphorylation activity is tightly regulated under physiological conditions in the nervous system. Under neuropathological conditions, however, it is deregulated and induces pathology resembling that seen in many neurodegenerative diseases such as Alzheimer’s, (AD), Parkinsion’s (PD) , Amyotrophic Lateral Sclerosis (ALS). During the course of our studies to understand the molecular and cellular basis of the regulation of the cytoskeleton phosphorylation we identified a neuronal cell cycle like kinase , cyclin dependent kinase 5 (Cdk5), together with its activator p35, as a major kinase regulating the topographic neuronal cytoskeleton phosphorylation. However, it is hyperactivated and caused deregulated by neuronal insults (A-beta, glutamate, oxidative stress, mutations and other). Cdk5 is hyperactivated as a stable complex with p25 (a truncated fragment of p35) and induces hyperphosphorylated tau, synuclein and NFPs as seen in AD, PD and ALS. At autopsy, AD, PD and ALS brains display hyperactive Cdk5 (Cdk5/p25) and have confirmed that Cdk5/p25 induces neuroinflammation, tau and NF hyperphorylation along with cell death. A p25-overexpressing (P25Tg) AD model mouse displays the typical AD phenotypes. Accordingly, hyperactive Cdk5/p25 has been identified as a possible therapeutic target for these neurodegenerative diseases. All the therapeutic approaches inhibiting activities of kinases have been by interfering with ATP binding domains of the kinases that turned out to be non-specific and highly toxic. To modulate the Cdk5 activity instead of using the analogs of ATP we decided to study the effect of different truncated fragments of p35 on the regulation of Cdk5 activity. We identified a small peptide p5 (24 aa) bind with Cdk5 with higher affinity than p25 and selectively inhibited Cdk5/p25 hyperactivity in culture, reduced tau, NFP hyperphosphorylation and cell death without toxicity and affecting endogenous Cdk5/p35 activity. The question arose will p5 be non toxic in vivo, in animals as in cell cultures and may prevent the phenotypes of an AD, PD and ALS transgenic mice models? Consistent with the model, we succeeded in showing that pathological and behavioral phenotypes in PD (MPTP) and AD (P25Tg) model mice can be reduced after treatment with modified p5 (TFP5) . We propose that TFP5 is novel therapeutic candidate to prevent PD and AD phenotypes and pathologies.
Keynote Forum
Jesse Weinberger
Mount Sinai School of Medicine, USA
Keynote: Mechanism of carotid stroke
Time : 10:10-10:50
Biography:
Jesse Weinberger has completed his MD at the age of 23 years from The Johns Hopkins University School of Medicine, Neurology Residency at The Mount Sinai Hospital and Postdoctoral studies at the University of Pennsylvania School of Medicine. He is a Professor of Neurology and Director of the Neurovascular Laboratory at the Icahn School of Medicine at Mount Sinai. He has published more than 130 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Extra cranial internal carotid stenosis is a significant cause of stroke. However most patients with carotid stenosis remain a symptomatic even with high grade stenosis. Ultrasound studies of plaque morphology have been used to identify vulnerable plaque prone to rupture and embolization. Heterogeneous plaques with lucent areas are associated with a higher incidence of stroke and TIA. These lucencies correlate with thrombus and lipid on pathology. Sequential studies indicate that plaque growth is associated with stroke events. Further studies with black blood MRI document regression and solidification of plaque with staton medication. Ultrasound imaging of carotid plaque morphology provides a useful tool for identifying patients with a symptomatic carotid stenosis who may benefit most from interventional procedures to prevent stroke.
Keynote Forum
Fahad AlKherayf
University of Ottawa, Canada
Keynote: Timing of Anticoagulant Re-Initiation following Intracerebral Hemorrhage in Patients with Mechanical Heart Valves: Meta Analysis and survey for current practice
Time : 11:10-11:50
Biography:
AlKherayf is an Associate Professor and a Neurosurgeon at University of Ottawa. He is also a neuroscientist at the Ottawa Hospital Research Institute (OHRI) with a cross appointment to the Clinical Epidemiology Program. He is the Director of the Clinical Research Program at the Division of Neurosurgery at the Ottawa Hospital, and the Director of Spine Fellowship Program at University of Ottawa. After graduating from medical school he completed his neurosurgery training at University of Ottawa in 2010. He also completed two fellowships in complex spine surgery and minimally invasive skull base surgery. Additionally, he has training in clinical epidemiology and biostatistics (MSc, Epidemiology and Biostatistics 2011) and has completed the Clinician Investigator Program certified by the Royall College of Physician and Surgeons of Canada (RCPSC). His clinical practice is focused on complex spine surgery, minimally invasive cranial surgery and complex cranio-cervical reconstruction. His clinical research interests lie on translational primary brain tumor research, clinical trials, and spinal cord injury. He has authored and co-authored many research papers and abstracts, and spoken at many international conferences. He has special interest in neurosurgery and spine education by directing many training courses. He also has been serving as an editorial board member of many journals.
Abstract:
Background: While oral anticoagulation (OAC) is universally indicated for patients with mechanical heart valves (MHVs), the time for OAC reinitiation following anticoagulant-associated intracerebral hemorrhage (ICH) is uncertain. We sought to determine the optimal timing for restarting the OAC and the associated clinical outcomes in patients with MHVs following ICH. Furthermore, we surveyed the practice preferences of North American neurosurgeons and thrombosis experts on optimal timing of restarting the OAC in this particular group of patients.
Methods: We performed a systematic review and a meta-analysis of studies published from January 1950 to April 2014. Medline (Ovid), Embase, Scopus, the Cochrane Library, the Cochrane Controlled Trials Register, LILACS, Web of Science and Global Health were searched for studies reporting the time for re-initiation of OAC in patients with MHV following ICH. Extracted data was on the type of initial ICH, use of cranial surgery, presence of atrial fi brillation, type of MHV, position of MHV, number of MHVs, and timing of OAC re-initiation. In addition, the criteria for study selection included data on valve thrombosis, thromboembolic events or ICH recurrence data, calculated absolute risks, and assessing the eff ect. of anticoagulant resumption timing on ICH recurrence via meta-regression. A cross-sectional survey was disseminated to North American members of the American Association of Neurological Surgeons and the International Society for Thrombosis and Haemostasis. Demographic factors, as well as a clinical scenario with 14 modifiable clinical risk factors were included in the survey.
Results: 23 case-series and case-reports were identified and meta-regression was done. Overall proportion of ICH recurrence was 13% (95% confidence interval [CI], 7% – 25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3% - 17%) and 12% (95% CI, 5% - 23%), respectively. A trend towards lower ICH recurrence was observed with delayed OAC re-initiation (slope estimate -0.2154, p=0.10). Recurrence rate ranged from 50% with OAC re-initiation at 3 days to 0% with re-initiation at 16 days. 504 physicians completed our survey (response rate= 34.3%). Majority of participants were affiliated with academic centers, and managed ≤ 10 ICH patients with MHV per year. There was wide distribution in response on optimal timing for OAC re-initiation following an ICH: 59% and 60% preferred to re-start OAC between 3 and 14 days following the hemorrhagic event (median = 6-7 days). Smaller hemorrhages (<30cm2), CHADS2 score ≥2, concomitant venous thromboembolism, mitral valve prosthesis, caged-ball valves and multiple valves prompted earlier OAC re-initiation.
Conclusion: From our meta-analysis restarting OAC in day 4 seems to be associated with low risk of recurrent ICH or valve thrombosis, however this conclusion is limited by the quality of the studies. We support the urgent need for high-quality randomized studies in this population. Moreover, based on our collected survey data, there is a wide variation in the current practice of neurosurgeons and thrombosis specialists when they encounter patients with ICH and MHV, though decisions were influenced by patient- and valve-related factors. As our observed variation likely reflects the immense gap in current evidence, prospective randomized trials in this population are therefore urgently needed.
Keynote Forum
Evelyn M. Garcia
Virginia Tech Carilion School of Medicine, USA
Keynote: Cardioembolic stroke; Sources of embolic material with related distribution, imaging for trans-vascular interventions, and associated embolic complications
Time : 11:50-12:30
Biography:
Evelyn Garcia completed her M.D. from University of New Mexico School of Medicine, Diagnostic Radiology residency from the University of New Mexico Medical Center and Body Imaging fellowship from University of Utah Medical Center. She is board certified in Diagnostic Radiology and Cardiovascular Computed Tomography. She is the Chairman and Medical Director of Radiology at Virginia Tech Carilion School of Medicine and of Carilion Clinic
Abstract:
As societies around the world age and lifespans increase, we are challenged by the increasing incidence of cardioembolic stroke and the associated human and resource related impact on society. This has led to the development of trans-vascular procedures to address disease states in this fragile patient cohort in whom surgery is frequently contraindicated based on comorbidities. Atrial Fibrillation, the leading cause of cardioembolic disease, valvular sources, and cardiac chamber sources with typical end vessel distribution will be discussed. Pre-procedure imaging, identifiable sources of potential embolic complications, and intra-procedure prophylaxis will be presented.
Keynote Forum
Alok Sharma
NeuroGen Brain & Spine Institute, India
Keynote: Clinical results of Stem Cell Therapy in Neurological Disorders
Time : 12:30-13:10
Biography:
Alok Sharma is a Neurosurgeon and presently Professor & Head of Department of Neurosurgery at the LTMG Hospital & LTM Medical College and the Director of the NeuroGen Brain & Spine Institute and Consultant Neurosurgeon at the Fortis Hospital in Mumbai, India. He has authored 12 books, edited 2 books, contributed chapters to 8 other books and has 83 scientific publications in medical journals. He has made 146 scientific c presentations all over the world & has conducted several national and international trials and has been conferred with numerous honors and awards in his distinguished career. He has organized many international and national conferences and regularly conducts hands-on training workshops on Micro vascular Surgery, Neuro endoscopy and Spinal fixations. He has been committed to both basic as well as clinical research in attempting to find an answer to the problems of paralysis and neurological deficits that occur following injury and diseases of the nervous system. Is the pioneer of Stem cell therapy in India and has setup the Stem cell and Genetic research laboratory at the LTMG hospital & LTM Medical College. He has also created the NeuroGen Brain and Spine institute which is India’s first dedicated Stem Cell Therapy and Neurorehabilitation Hospital. He has published path breaking results of Stem Cell therapy in Pediatric Neuro developmental disorders such as Autism and Cerebral palsy as well as in other conditions such as Muscular dystrophy and Spinal cord injury. He is the founder of the “Indian Journal of Stem Cell Therapy” and on the editorial board of 4 other journals. He is the Founding President of the “Stem Cell Society of India” and the Vice President of the “International Association of Neurorestoratology”. His other special interests include Revascularization surgery for cerebral ischemia, Psychosurgery, Stereotactic surgery, Neuroendoscopy, Spinal surgery and Neurotrauma.
Abstract:
Background: While oral anticoagulation (OAC) is universally indicated for patients with mechanical heart valves (MHVs), the time for OAC reinitiation following anticoagulant-associated intracerebral hemorrhage (ICH) is uncertain. We sought to determine the optimal timing for restarting the OAC and the associated clinical outcomes in patients with MHVs following ICH. Furthermore, we surveyed the practice preferences of North American neurosurgeons and thrombosis experts on optimal timing of restarting the OAC in this particular group of patients.
Methods: We performed a systematic review and a meta-analysis of studies published from January 1950 to April 2014. Medline (Ovid), Embase, Scopus, the Cochrane Library, the Cochrane Controlled Trials Register, LILACS, Web of Science and Global Health were searched for studies reporting the time for re-initiation of OAC in patients with MHV following ICH. Extracted data was on the type of initial ICH, use of cranial surgery, presence of atrial fi brillation, type of MHV, position of MHV, number of MHVs, and timing of OAC re-initiation. In addition, the criteria for study selection included data on valve thrombosis, thromboembolic events or ICH recurrence data, calculated absolute risks, and assessing the eff ect. of anticoagulant resumption timing on ICH recurrence via meta-regression. A cross-sectional survey was disseminated to North American members of the American Association of Neurological Surgeons and the International Society for Thrombosis and Haemostasis. Demographic factors, as well as a clinical scenario with 14 modifiable clinical risk factors were included in the survey.
Results: 23 case-series and case-reports were identifi ed and meta-regression was done. Overall proportion of ICH recurrence was 13% (95% confi dence interval [CI], 7% – 25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3% - 17%) and 12% (95% CI, 5% - 23%), respectively. A trend towards lower ICH recurrence was observed with delayed OAC re-initiation (slope estimate -0.2154, p=0.10). Recurrence rate ranged from 50% with OAC re-initiation at 3 days to 0% with re-initiation at 16 days. 504 physicians completed our survey (response rate= 34.3%). Majority of participants were affi liated with academic centers, and managed ≤ 10 ICH patients with MHV per year. Th ere was wide distribution in response on optimal timing for OAC re-initiation following an ICH: 59% and 60% preferred to re-start OAC between 3 and 14 days following the hemorrhagic event (median = 6-7 days). Smaller hemorrhages (<30cm2), CHADS2 score ≥2, concomitant venous thromboembolism, mitral valve prosthesis, caged-ball valves and multiple valves prompted earlier OAC re-initiation.
Conclusion: From our meta-analysis restarting OAC in day 4 seems to be associated with low risk of recurrent ICH or valve thrombosis, however this conclusion is limited by the quality of the studies. We support the urgent need for high-quality randomized studies in this population. Moreover, based on our collected survey data, there is a wide variation in the current practice of neurosurgeons and thrombosis specialists when they encounter patients with ICH and MHV, though decisions were influenced by patient- and valve-related factors. As our observed variation likely reflects the immense gap in current evidence, prospective randomized trials in this population are therefore urgently needed.
Biography
Stem cell therapy has shown great potential as a treatment strategy for neurological disorders. Autologous bone marrow mononuclear cells have shown a positive outcome in these disorders due to their obtainability, safety and effi cacy. In autism, out of 32, 92% cases showed improved social interaction, emotional response, speech and communication, behavior, cognition and sensory aspect on ISAA, CGI and FIM/WeeFIM. In cerebral palsy, 95% out of 40 patients showed improvements in oromotor activities, neck control, sitting balance, standing, walking balance and speech. Th ese improvements correlated with improved brain metabolism recorded in the PET CT scan. In spinal cord injury, 91% out of 110 patients in thoracolumbar SCI and 74% out of 56 patients with cervical SCI showed improvement in spasticity, sensation, trunk control, bladder management, standing and sitting balance, ambulation and ADLs. Changes were recorded in ASIA, FIM scale and electrophysiological studies. In head injury, 93% out of 14 cases showed improvement in balance, voluntary control, muscle tone, memory, oromotor activities, cognition, coordination, speech, communication, ambulation and ADLs. In muscular dystrophy, 86.67% out of 150 showed improved strength in trunk, upper and lower limbs alongwith gait. 6 patients demonstrated muscle regeneration on musculoskeletal MRI and 9 showed improvement in EMG. In ALS, as compared to the control population (n=20), the survival duration of the treated population (n=37) increased by 30.38 months. In Stroke, improvements were observed in ambulation, hand function and standing and walking balance with ischemic stroke demonstrating better recovery than hemorrhagic stroke.
No major adverse events were reported.
Keynote Forum
Zang-Hee Cho
Seoul National University, Korea
Keynote: Recent Advances in Ultra High Field MRI and PET-MRI Fusion Imaging-Applications to Neuroradiology
Time : 9:40 - 10:20
Biography:
Professor Cho received Ph.D, in physics, from Univ. of Uppsala, Sweden. Since then he has been faculty of UCLA, Columbia University, and University of California, Irvine. Last ten years, he served as a Director of the Neuroscience Research Institute, Gachon University and established one of the leading PET-MRI brain imaging centers in the world.
Abstract:
Recent progresses on new imaging and system developments, especially on the Brain dedicated PET-MRI, using High resolution HRRT-PET and Ultra High Field 7.0T Magnetic Resonance Imaging (MRI) and their applications to basic and clinical neuroradiology will be discussed. With high field MRI, such as the 7.0T MRI, one can now visualize the subfields of the hippocampus and brainstem in-vivo as well as tractography hitherto unable to do with existing MRI systems. Together with molecular imaging using Positron Emission Tomography(PET), now, it is possible to visualize metabolic functional changes quantitatively in human brain in-vivo as well as connectivity through the tractography. Another new development is the Ultra-high field MRI super-resolution tractographic imaging which able to delineate the fine fiber structures such as the sub-components of the superior longitudinal fasciculus (SLF) and arcuate fasciculus (FA), among others, suggesting future applications of these fiber track information, for example, to the deep brain stimulation (DBS). One of the most exciting discovery with the PET-MRI fusion imaging is the ability to delineate the individually resolved raphe nuclei in the brainstem suggesting possibility of studying serotonergic activities and related psychiatric and other neurological disorders hitherto unable to do quantitatively in human in-vivo.rnIn short, some recent results of brain PET-MRI fusion system as well as the new tractographic images obtained with 7.0T that can the applicable to the treatment of the neurological disorders will be discussed and highlighted.rn
Keynote Forum
Sudhakar R Satti
Christiana Care Health System, USA
Keynote: Mechanical Thrombectomy for Pediatric Acute Ischemic Stroke: Review of the Literature and Treatment Algorithm
Time : 10:20 - 11:00
Biography:
Sudhakar R. Satti, MD, earned his medical degree from MCP-Hahnemann School and completed a residency in diagnostic radiology at Hahnemann University Hospital in Philadelphia. During the following two years, he completed fellowships in diagnostic neuroradiology and interventional neuroradiology/endovascular neurosurgery at the Hospital of the University of Pennsylvania. He was also an instructor in interventional neuroradiology during his fellowship. Dr. Satti then served as Director of NeuroInterventional Radiology at Albert Einstein Medical Center Philadelphia until 2010, when he accepted his current position at Christiana Care.rnDr. Satti has been at Christiana Care for 5 years. He serves as the Associate Chief of Neurointerventional Surgery in the Department of Neurointerventional Surgery, which is currently part of the Neuroscience service line. rnHis clinical interests include acute stroke treatment, brain aneurysms, interventional pain/spine procedures, carotid artery stenting, dural arteriovenous malformations, and venous sinus stenting. rnDr. Satti has been the PI or Sub-PI in over 10 clinical trials at Christiana, authored approximately 15 articles, and serves as a reviewer for peer reviewed journals including: the Journal of Neurointerventional Surgery and the American Journal of Neuroradiology.rnHis professional memberships include the Societies of NeuroInterventional Surgery, AANS-Cerbrovascular section, and the American Society of Neuroradiology.rn
Abstract:
In light of the recent strongly positive randomized controlled adult mechanical thrombectomy trials, we sought to review the available literature and perform a meta-analysis on intra-arterial pediatric stroke intervention, with a focus on modern mechanical devices. rnMethods rnA Pubmed search was performed for pediatric patients undergoing intra-arterial treatment of acute ischemic stroke using modern devices between 2008 and 2015. A total of 29 patients were included in this retrospective meta-analysis. rnResults: rnThe average age was 10.3 years old, 74.1% were male, the middle cerebral and basilar arteries accounted for 89.6% of 36 occluded vessels, and the average pediatric stroke scale score was 18.1. The average time from symptom onset to intervention was 8.8 hours, and 13.8% of patients received IV tPA prior to mechanical thrombectomy. Stent retrievers were used in 58.6% of cases, the Penumbra system in 34.5%, and the Merci device in 27.6%. TICI 2b/3 recanalization was achieved in 75.9% of cases. There were no major adverse events related to intervention, although 1 procedure was associated with device malfunction, without definite change in long term outcome. The average rnmRS was <1 (0.86) at the longest available follow-up period, based on clinical description or provided modified Rankin scale score. rnConclusions: rnThis study suggests mechanical thrombectomy in pediatric patients presenting with high pediatric NIHSS scores and proximal large vessel occlusion is associated with high recanalization rates and excellent clinical outcome, although this is a retrospective review and sample size is too small to make any definitivern
- Neurology & Neuro Immunology
Chair
Fahad AlKherayf
University of Ottawa, Canada
Session Introduction
Sarah Crawford
Southern Connecticut State University, USA
Title: Autism risk linked to abnormal brain development resulting from Neuroimmunological dysfunction: Quantitative threshold exposure model
Time : 13:50-14:10
Biography:
Sarah Crawford received the Master’s Degree in Biochemistry from Princeton University in 1982 and a Ph.D. Degree from the Department of Biochemistry and Biophysics, Columbia University College of Physicians and Surgeons in 1987. I have been affiliated with Southern Connecticut State University for over 20 years, currently Full Professor in the Department of Biology where I teach Genetics and Medical Genetics, and direct a research laboratory in cancer biology. In 2013 I was awarded a patent by the US Patent Office for a novel cancer treatment for the brain cancer, glioblastoma.
Abstract:
The Quantitative Threshold Exposure (QTE) hypothesis is a multifactorial threshold model that accounts for the cumulative effects of risk factor exposure in both the causation of autism spectrum disorder (ASD) and its dramatic increase over the past 30 years. The QTE hypothesis proposes that ASD is triggered by the cumulative effects of high-level exposure to endogenous and environmental factors that act as antigens to impair normal immune system (IS) and associated central nervous system (CNS) functions during critical developmental stages. The quantitative threshold parameters that comprise a cumulative risk for the development of ASD are identified by the assessment of documented epidemiological factors that, in sum, determine the likelihood that ASD will occur as a result of their effects on critically integrated IS and CNS pathways active during prenatal, neo-natal and early childhood brain maturation. The model proposes an explanation for the relationship between critical developmental stages of brain/immune system development in conjunction with the quantitative effects of genetic and environmental risk factors that may interface with these critical developmental windows. This model may be useful even when the individual contributions of specific risk factors cannot be quantified, as it proposes that the combined quantitative level of exposure to risk factors for ASD rather than exposure to any one risk factor per se defines threshold occurrence rates.
Czeslawa Kowal
The Feinstein Institute for Medical Research, USA
Title: Anti-NMDA receptor antibodies and CNS lupus
Time : 14:10-14:30
Biography:
Czeslawa Kowal completed her PhD in the Institute of Organic Chemistry of the Polish Academy of Sciences, Warsaw, Poland, and her postdoctoral training in molecular biology and in immunology at Columbia University and at the Albert Einstein College of Medicine New York. She has published 45 peer reviewed papers and book chapters in reputed journals. She is a member of the American Association of Immunologists.
Abstract:
Lupus is an autoimmune disease affecting primarily women in child bearing age. It is a multiorgan involvement disease, with frequent central nervous system (CNS) manifestation, most particularly, cognitive impairment. Lupus is characterized by the production of antinuclear autoantibodies and in particular, anti-dsDNA antibodies. We have created an animal model of CNS lupus in which autoantibodies cross-reactive with dsDNA and with the NMDA receptor (NMDAR) lead to an enhanced NMDAR activation and, at higher concentration to neuronal death when present in the brain parenchyma. We have shown that this requires breaching of the blood brain barrier. We have further demonstrated in the mouse model that the impact of these antibodies on neurons was concentration dependent and that at higher concentration, these antibodies promote neuronal excitotoxicity through enhanced mitochondrial permeability transition. In the model spatial recognition deficits are caused by the presence of these antibodies in the hippocampus. Structural analysis revealed a substantial reduction in dendritic processes and spines accompanied by a significant expansion of a place field size of surviving CA1 pyramidal.
We and others have shown that the presence of these antibodies in the cerebrospinal fluid of lupus patients correlates with diff use manifestations of CNS lupus.
Recent studies of lupus patients harboring dsDNA and NMDAR reactive antibodies demonstrate an association with an impairment in spatial memory. This observation is in striking similarity to the mouse model.
António Pais de Lacerda
Hospital de Santa Maria, Portugal
Title: Atherosclerotic burden in patients infected with human immunodefi ciency virus: a carotid ultrasound and transcranial Doppler study
Time : 14:30-14:50
Biography:
António Pais de Lacerda was graduated in medicine at the Medical School of the University of Lisbon (Portugal), and he has a master’s degree in Medical Education. His current position is as intensive care consultant in an Intensive Care Unit (Hospital de Santa Maria); He is Assistant Professor of the Disciplines of “Introduction to Medicine”, “Electrocardiography” and “Intensive Care Medicine”. His main interests are on “pre- and post-graduate medical education “, “Medicine in the movies”, “Sepsis” and “HIV /AIDS medicine.” He has about 80 published papers, and two books on AIDS.
Abstract:
Human immunodeficiency virus (HIV) infection has been associated to premature atherosclerosis. Carotid intima-media thickness (CIMT) and pulsatility index (PI) accessed by carotid duplex ultrasonography (CDU) and transcranial Doppler (TCD), may be useful markers. Carotid and Cerebral circulation were evaluated by CDU and TCD in forty HIV-infected Caucasian men (mean age 49,4±5,9 years). CD4+ T-cell current and nadir counts, current and zenith viral load and duration of antiretroviral therapy (ART) were registered and cardiovascular risk scores were assessed. Multivariate regression analysis and Pearson’s correlation coefficient were used. All men received ART and presented mean CD4+ count of 817±369 cells/mm3, (mean nadir: 242,8 ±158,2 cells/mm3), 95% had non-detectable viral load (mean zenith: 381.416±858.881 copies/mm3), 35% of men had history of high blood pressure, 35% dyslipidaemia, 7,5% diabetes, 80% tobacco consumption. Mean Framingham Risk Score was 8,5±6,6%; 35% presented low risk by SCORE, 55% moderate risk and 7,5% high risk. Mean ASCVD score was 7±4% at 10 years and 49±12% lifetime. 67.5% men had increased CIMT (mean 0,92±0,13mm), but none presented increased PI. No correlation was found between duration of infection, ART or cardiovascular risk scores with CDU or TCD data. However, a significantly positive association between a CD4+ nadir count <400 cells/mm3 and an increase of 0,12 in PI, was confirmed by regression analysis where CD4 categories showed significant effect over PI (p=.04). In this series, HIV infection showed an association with premature cerebral atherosclerosis, even at low cardiovascular risk scores. PI may be an early marker of atherosclerosis in HIV-infected people with CD4+ nadir <400 cells/mm3
Zhengqin Zhai
Peking Union Medical College, China
Title: Median nerve modulation markedly diminishes ventricular arrhythmias after myocardial infarction in rabbits
Time : 14:50-15:10
Biography:
Zhengqin Zhai has completed her Bachelor’s degree from Shandong University and now has been working for her Master’s degree in Peking Union Medical College.
Abstract:
Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the occurrence of ventricular arrhythmias after myocardial infarction. Here, we hypothesize that a novel pathway nerve stimulation - median nerve stimulation inhibit the occurrence of ventricular arrhythmias after myocardial infarction in rabbits. Two weeks after the ligation of the left coronary artery, 11 surviving New Zealand rabbits were randomized to median nerve stimulated (MI-MNS, n = 5) group and sham-stimulated (MI-SS, n = 6) group. Using an implantable electrical stimulator, we stimulated the bilateral median nerve for 2 weeks with the frequency of 5 HZ, width of 200ms, cycle of 10s on and 30s off, and the intensity of electrical stimulation was adjusted to the threshold of not resulting in the tremble of upper limbs. A holter was implanted to record the types and frequencies of arrhythmias. The treated rabbits had significantly lower percentage of ventricular arrhythmias (3.67% ± 1.73% vs. 6.69% ± 2.50%, p< 0.001) and lower norepinephrine (NE) level in blood (7.88 ± 2.34 pg/ml vs. 17.57 pg/ml± 11.72pg/ml, p = 0.01) than the untreated rabbits. Median nerve modulation markedly decreased the incidence of ventricular arrhythmias after myocardial infarction in rabbits through reducing the NE level in blood.
Giovanni Antioco Putzu
Casa di Cura Sant’Elena, Italy
Title: Tumor Necrosis Factor alpha (TNF-alpha) and pro-infl ammatory cytokines in vaculitis of Peripheral Nervous System
Time : 15:10-15:30
Biography:
Giovanni Antioco Putzu is working as professor in Neurology and Clinical Neurophysiology in Casa di Cura Sant’Elena, Italy. He has published more than 15 papers in reputed journals and has been serving as an editorial board member of repute
Abstract:
We demonstrated, by the means of double immunochemistry technique, that TNF-alpha was localized in both axons and Schwann Cells, leading to demyelination and axonal in the peripheral nerve of patients with Guillain-Barré Syndrome (GBS, Putzu G.A. et al, J. Neurol. Sci, 2000). The pivotal role of pro-inflammatory cytokines such as IL-1Beta in GBS was also investigated.
We present an original immunochemistry study with a panel of antibodies directed against TNF-alpha, INF-gamma, IL-1Beta, CD68, CD11, CD3 and C5b9 in the peripheral nerve of seventy-five patients affected by vasculitis. Sixty patients (27 males and 23 females, mean age 63 years) were classified as systemic vasculitic neuropathy (SVN) where as 15 patients (7 males and 8 females, mean age 52 years) had non systemic vasculitic neuropathy (NSVN).
Results suggested a prevalent Th 1 immune response in both SVN e NSVN. The presence of great amounts of TNF alpha and IL-1Beta into the vasculature determines a pro-coagulant effect with thrombosis of the vasa nervorum and hypoxia of the nervous fascicules. TNF-alpha was localized in axons as well, suggesting that it may be responsible for an axonal degeneration per se. Peripheral nerves of SNV e NSVN were immunoreactive to INF-gamma antibodies. This finding indirectly confirms the presence in the vasculature of IL-28A, a powerful pro-inflammatory cytokines. CD11, an antibody reacting with leucocytes and ICAM (Intercellular Adhesion Molecule) was also detected in the peripheral nerve of SVN and NSVN. Immunoreactivity to CD68 (macrophage antigen) and C5b9 (activated complement fraction) were also easily detected.
In conclusion, immune response in SVN and NSVN is of Th 1 type (cellular). The role of TNF-alpha and cytokines is crucial in vascular thrombosis. Axonal degeneration may be the consequence of both hypoxia and direct toxic effect of TNF-alpha on axons. Moreover, pattern of immune response is not specific in SVN and NSVN.
Weimin Yang
First Affi liated Hospital of Zhengzhou University, China
Title: Intracerebral haemorrhage growth is infl uenced by anticoagulation intensity
Time : 15:30-15:50
Biography:
Weimin Yang has completed his PhD from Sichuan University and visitor scholor studies from Melbourne University. He is the professor in Dept. of Neurology, First Affiliated Hospital of Zhengzhou University, master tutor, innovative talents of Henan Province Health Sciences and Technology. His research work mainly related to clinical features of Chinese stroke patients, stroke register, dementia, and systematic reviews of therapies from China. He has published more than 25 papers in reputed journals.
Abstract:
Background: Intracerebral hemorrhage (ICH) is a significant contributor to global health-related morbidity and mortality. Due to improved recognition and treatment of atrial fibrillation by antithrombotics, there is an increase in proportion of ICH caused by warfarin and novel oral anticoagulants. However, the relationship between anticoagulation intensity and hematoma expansion remains unclear. We aimed to investigate the effects of INR on hematoma expansion post ICH.
Methods: We conducted a retrospective study of all patients hospitalized for ICH at a single institution from January 1, 2008 and August 1, 2014. Hematoma volumes on initial CT scans and repeat CT scans were analyzed by the AxBxC/2 method. Univariate analysis was used to compare baseline characteristics and median regression analysis was performed to estimate the effects of INR and hematoma volume changes.
Results: We included 224 consecutive ICH patients. Median age (IQR) was 68.5 years (17.0), 60.3% were male, median presentation Glasgow Coma Scale (GCS) (IQR) was 14.0 (4.0), median volume (IQR) of the first CT was 11.7ml (25.6), median INR (IQR) was 1.1 (0.2). We showed that INR and time lapsed between first CT and second CT were independent risk factors to hematoma volume change, adjusting for baseline hematoma volume and time. For each 1.0 increase in INR was associated with hematoma volume increased by 2.4ml (p = 0.015).
Conclusions: We showed that high INR was associated with hematoma growth post ICH. However, the effects of reversal anticoagulation in the attenuation of hematoma growth remain uncertain and require confirmation in future randomized controlled studies.
Lenka Maruscakova
Comenius University, Slovakia
Title: Immunological aspects of glioma tumorigenesis
Time : 15:50-16:10
Biography:
Lenka Maruscakova, MD. was graduated in General Medicine at the School of Medicine, Comenius University Bratislava, Slovakia. She does her post gradual studies at Institute of Immunology School of Medicine, Comenius University Bratislava, Slovakia. Her PhD. thesis is devoted to the inflammatory markers in brain tumors. Her scientific work is multidisciplinary approach connecting field of immunology, oncology and neurology.
Abstract:
Immune cells and molecules in tumor microenvironment are crucial in tumorigenesis. Inflammation is known as one of hallmarks of cancer and is considered as an protumorigenic factor. Glioma tumor microenvironment glioma still needs deeper insight into its immunological characteristics. Both local and systemic chronic low grade inflammatory response are operative for correlation with gliomas grading and their prognosis. Complex network of immune signals and pathways is in intricate background of most of cancer hallmarks. This concept is an intersection of three huge research fields: immunology, oncology and neurology. Cancer immunology has a perspective in complex approach to diagnosis of gliomas. There is an appealing importance of establishing immune molecules in gliomas. TREM-1 (Triggering receptor expressed on myelocytes) is an inflammation amplifier, hovewer its role in glioma remains still unclear. The aim of our study is to establish the expression of TREM-1 in glioma tissues and to correlate it with staging, grading and other laboratory parameters. Establishing of TREM-1 expression could have a promising role in pathophysiology of gliomas. Our preliminary results show densely infiltrating TREM-1+ immune cells in tumor tissue. At signal pathways level, inflammation is interconnect with molecules related to hypoxia. Cross-talk of inflammation and hypoxia becomes more obvious in glioma as well. Consideration of relations dynamics is also necessary. But, deep understanding of their signal network in glioma tumorigenesis is challenging. Our aim is to provide critical view on our pivotal results in framework of data from literature and discuss their significance for deep understanding of glioma tumorigenesis.
Biography:
Teena Shetty is a Fulbright scholar who received her medical degree and bachelor’s degree with honours from Brown University and her master of philosophy degree in medicine from the University of Cambridge. Her residency was completed at Weill Cornell Medical College, New York-Presbyterian Hospital. Dr. Shetty received her fellowship training in neuromuscular diseases at Harvard Medical School, Brigham and Women’s Hospital and in neuromuscular diseases and intraoperative monitoring at Hospital for Special Surgery. Dr. Teena Shetty is now a neurologist at Hospital for Special Surgery and is triple board-certified in neurology, neuromuscular medicine, and electro diagnostic medicine. Her research interests include concussion, post-operative neuropathies, muscle diseases, and intraoperative monitoring, and she has authored more than 30 publications on these topics.
Abstract:
Historically, routine types of neurological imaging for mTBI include CT and Conventional MRI, both of which are usually normal in mild TBI (mTBI). Newer MRI methods may demonstrate more abnormalities following mTBI than just CT or Conventional MRI alone (Brody et al 2015). These include, but are not limited to, SWI, DTI, rs-fMRI, ASL and Volumetry. Susceptibility Weighted Imaging (SWI) uses contrast to highlight differences between tissues that can show changes in blood products in the brain. Diffusion Tensor Imaging (DTI) can detect brain abnormalities in white matter through its sensitivity to microstructural axonal injury. Resting State Functional MRI (rs-fMRI) measures changes in blood perfusion to determine if pathways of communication within the brain have been disrupted. ASL (arterial spin labelling) uses spatially selective inversion of inflowing arterial blood as a method to label blood flow and measure perfusion. Lastly, volumetric MRI measures the volume and structure of regions in the brain and can detect changes in the volume of gray matter that may result from mTBI. These specific types of imaging can be incorporated into research in order to learn more about concussions, their diagnosis, and their prognosis. This is the case for the GE-NFL Study on Advanced MRI Applications for mild TBI. By utilizing a research pack for neurological imaging that includes SWI, DTI, Volumetric T1, ASL, and rs-fMRI, researchers have been able to detect abnormalities, including white matter lesions, in the brains of several patients who have suffered from mTBI. Overall, neuroimaging is evolving such that white matter abnormalities, changes in gray matter volume, and blood perfusion in the brains of mTBI patients may be visualized. However, these scans cannot be used conclusively and these techniques are limited to research tools at this time. Therefore, continued study is necessary to further validate these software techniques.
- Worksop on Quantitative medical imaging for precision medicine
Chair
Yun Zhou
Johns Hopkins University School of Medicine, USA
Co-Chair
Jianhua Zhang
Peking University First Hospital, China
Session Introduction
Yun Zhou
Johns Hopkins University School of Medicine, USA
Title: Quantitative PET from Brain to Whole-body
Time : 16:50-17:10
Biography:
Dr. Yun Zhou is Assistant Professor at the Russell H. Morgan Department of Radiology and Radiological Science, and Guest Professor of Peking University First Hospital. He obtained his M.S. in Biomathematics and Ph.D. in Biomedical Physics from University of California at Los Angeles.
Abstract:
Brain PET is a well-established quantitative functional imaging technique to measure physiological and biochemical process. As recent advances in hybrid imaging technology, such as PET-CT and PET-MRI, for whole-body PET imaging, there are urgent needs to develop and validate technologies for quantitative whole-body PET from data acquisition to quantification. The fundamentals of quantitative PET developed in last three decades which include kinetic modeling approach and parametric imaging algorithms will be briefly reviewed. Recent developments in quantitative PET imaging on dopamine and serotonin receptors and transporters will be highlighted. Tremendous efforts have been made to extend quantitative brain or organ-specific PET to dynamic whole-body PET in last few years. We investigated the feasibility of quantitative dynamic whole-body PET via multi-bed multi-pass technology. Optimization in data acquisition and quantification were studied by both computer simulation and an ongoing multi-center multi-tracer dynamic whole-body PET project. The potentials and challenges in quantitative whole-body PET in clinical diagnosis, monitoring disease progression, responses to treatments or psychological/pharmacological stimulations will be discussed with our promising results.
Jianhua Zhang
Peking University First Hospital, China
Title: Application of Quantitative Dynamic Whole-Body 18FDG-PET/CT in the differential Diagnosis of Pulmonary Nodules
Time : 17:10-17:30
Biography:
Jianhua Zhang has completed his M.S. in 2004 and M.D. studies in 2012 from Peking University, majoring in Radiology and Nuclear Medicine. He joined the faculty of nuclear medicine at Peking University First Hospital.in 2004 and now is the associate professor. He has published more than 20 papers in journals and 20 chapters in proceedings and medical textbooks. The research interests of Dr. Zhang include application of positron emission tomography (PET) in studies of tumors, especially the lymphoma, and quantitve analysis. He has mentored 1 doctoral student and has been involved in teaching of more than 30 residents.
Abstract:
18F-FDG PET/CT imaging has become a crucial component of oncological management for a wide variety of malignancies and is routinely used in staging, restaging and treatment response assessment tasks. Compared to qualitative method and semi-quantitative method, quantitative method is more accurate and can overcome the limitations of the routine methods, but it is more complicated on the management of many cancer patients. As for the quantitative method, plasma input function and FDG influx rate constant (Ki) are indispensable. An emphasis in the present work is to develop non-invasive plasma input function estimation techniques in order to facilitate clinical acceptance. Image derived input function method will be studied and validated in the novel context of whole body dynamically-acquired images to facilitate parametric imaging. The present work is expected to significantly enhance the capability of dynamic whole body FDG PET/CT imaging to quantify the kinetics of FDG, and in turn, has the long-term potential to significantly enhance diagnostic, prognostic and treatment response monitoring capabilities of the FDG PET imaging modality and to fundamentally alter routine clinical practice.
Rong Fu Wang
Peking University Health Science Center, China
Title: Generalization and optimization of a population-based input function estimation and approach for quantification of sparsely sampled dynamic 18F-FDG PET/CT data
Time : 17:30-17:50
Biography:
Prof. & Dr. Rong Fu Wang has completed his MD at the age of 27 years from Fujian Medical University in 1982, postdoctoral studies from Paris V University School of Medicine in 1993 and his PhD at the age of 40 years from Toulous IIl University in 1995. He is the director of Department of Nuclear Medicine, Peking University Health Science Center. The research interests of Dr. Wang include experimental study and clinical application of molecular and clinical nuclear medicine. He has published more than 400 papers in reputed journals and has been serving as many editorial board member of reputed journals at home and abroad. He has published 3 monographs, and has got 3 patents of invention and 3 provincial and ministerial Awards
Abstract:
18F-FDG uptake rate constant Ki is a most interested and commonly used parameter for absolute quantification of 18F-FDG PET/CT. Ki is usually estimated by fitting a kinetic model with plasma input function (PIF) to the measured dynamic PET data. The need for arterial blood sampling to measure PIF (mPIF) is a main barrier to estimate Ki for clinical 18F-FDG PET. Two existing noninvasive PIF estimation methods, image derived PIF and simultaneous fitting method with kinetic model and parametric PIF, require image data to be acquired continuously and immediately post tracer injection. The objective of the study is to validate and optimize a generalized population-based PIF estimation method for noninvasive quantification of dynamic 18F-FDG PET for sparsely sampled PIF. Eight 60-min 27-frame monkey dynamic 18F-FDG PET studies were collected from a Philips Gemini GXL PET/CT with 3D data acquisition mode. Total 34 arterial blood samples were taken during PET scan as: 22 samples for the first 4 min, and followed by sampling at 5, 6, 8, 10, 12, 15, 20, 25, 30, 40, 50 and 60 min. Time activity curves (TACs) of 7 cerebral regions of interests (ROIs) were generated from each study. A generalized population-based approach to recover full kinetics of the PIF from sparsely sampled blood data is proposed. The estimated PIF (ePIF) from the incomplete PIF sampling data was determined by interpolation and extrapolation using scale-calibrated population mean of normalized PIFs. The optimal blood sampling scheme with given sample size m was determined by maximizing coefficient coefficients of Ki estimates between the Kis from measured PIF (mPIF) and estimated PIF (ePIF). The leave-two-out cross validation was performed. The linear correlations between the Ki estimates from the ePIF (with optimal sampling scheme) and those from the mPIF were: Ki(ePIF; 1 sample at 40 min) = 1.015Ki(mPIF) -0.000, R2 = 0.974; Ki(ePIF; 2 samples at 25 and 50 min) = 1.029Ki(mPIF) - 0.000, R2 = 0.985; Ki(ePIF; 3 samples at 8, 20, and 50 min) = 1.039Ki(mPIF) - 0.001, R2= 0.993; and Ki(ePIF; 4 samples at 8,12, 25, 40, and 55 min) = 1.02Ki(mPIF)-0.000, R2=0.997. The correlations of R2 from leave-2-out validation study were 0.978±0.007, 0.990±0.006, and 0.996±0.003 (mean ±SD) for 1, 2, and 3 samples of optimal sampling scheme, respectively. The generalized population-based PIF estimation method is a reliable method to estimate PIFs from incomplete blood sampling data for quantification of dynamic 18F-FDG PET using the Gjedde-Patlak plot.
Zhoulei Li
Helmholtz Center Munich, Germany
Title: Early prediction of response to anti-cancer therapy using molecular Imaging PET/CT
Time : 17:50-18:10
Biography:
Dr. Zhoulei Li has completed her PhD in 2013 from Ludwig-Maximilians-University of Munich and postdoctoral studies from technical university Munich. She has published more than 10 papers in reputed journals. She is a research leader, managing a pharmaceutical project from Helmholtz Center Munich. Before that, She was a postdoc researcher, managed the clinical research lab at nuclear medicine of technical university Munich, supervised research staff and graduate students. She has extensive hands on experience on molecular imaging. Her research focuses on monitoring progress of cancer therapy and developing biomarker for cancer therapy.
Abstract:
The prognosis of relapsed or refractory aggressive lymphoma is poor. The huge variety of currently evolving targeted treatment approaches would benefit from tools for early prediction of response or resistance. Molecular imaging is recently recognized as a tool that can improve every facet of cancer care. PET images biochemical or physiologic phenomena in comparison with computed tomography (CT) or magnetic resonance imaging (MRI), which show anatomic details. PET imaging would predict areas of abnormal metabolic behaviour of cancers in vivo, and the addition of CT imaging underlines the site of malignancy. More accurate andprecise interpretation of cancer lesions can therefore be performed by PET/CT imaging than PET or CT imaging alone. We used various lymphoma cell lines (ALCL, DLBCL, MCL, Myc-induced murine lymphoma etc.) to evaluate therapeutic effect of different anti-cancer drugs in vitro by molecular biological and biochemical methods. Micro-FDG- and/or FLT-positron emission tomography (PET) or PET/CT imaging studies were carried out with the suitable xenograft or transgenic mouse models to assess early treatment response to anti-cancer therapy in vivo. Interestingly, we detected a significant reduction of FLT-uptake in ALCL bearing animals using targeted drug therapy compared with baseline as early as 2 days after initiation of targeted therapy. Immunostaining showed a decrease in Ki-67 and an increase in cleaved caspase-3 staining. Additionally, the detection of therapeutic response of other aggressive cancer was proved to be highly correlated with other in vito and in vivo data, suggests that PET/CT is a suitable method for detection of therapeutic respons on cancer.
Rong Tang
Massachusetts General Hospital, USA
Title: A New Method for Intraoperative Breast Specimen Imaging at Massachusetts General Hospital-- Micro-computed Tomography (Micro-CT)
Time : 18:10-18:30
Biography:
Dr. Tang graduated from University of South China and received her master’s degree in plastic and reconstruction surgery form Peking Union Medical College. She finished her surgical residency training and became a breast surgery specialist in 2011. After that, she has been working as a postdoctoral fellow at Surgical Oncology of Massachusetts General Hospital.She has published 20 peer reviewed journal papers. Her interests include oncoplastic breast procedures, breast cancer shaved cavity margins, nipple sparing mastectomy, and novel breast imaging methods.
Abstract:
Intraoperative specimen imaging is commonly performed to confirm complete excision breast lesions, but has false positive and false negative rates that lead to incorrect specimen assessment in 21-44% of cases. Micro-CT provides non-invasive, highly quantitative imaging in small specimens within a few minutes. We explored the use of micro-CT for intraoperative assessment of a variety of breast specimens. Excised breast specimens, including lumpectomy specimens, shaved cavity margins(SCM), mastectomy specimens and axillary lymph nodes, were evaluated with a table top micro-CT scanner, Skyscan 1173 (Skyscan, Belgium), with a 40-130kV,8W X-ray source. Scanning for 7 minutes and reconstruction for another 7 minutes provided desired resolution in breast specimens. In lumpectomy specimens, micro-CT could clearly visualize orienting sutures and see the location of tumor masses and associated calcifications relative to specimen margins. In separately excised cavity margin specimens, micro-CT visualized tumor masses and calcifications that indicated the need for additional tissue excision. Micro-CT provided detailed images of axillary lymph nodes and their vessels’ 3D structure. 103 SCM from 26 lumpectomies were scanned and compaired with histopathology results. Margin status by micro-CT was concordant with histopathology in 86/103 (83%) SCM. Micro-CT had 73% sensitivity, 85% specificity, 46% positive predictive value, and 95% negative predictive value of SCM. 5/26(19%) case required a re-excision based on the final margin status, micro-CT could identify 3 out of these 5 cases intraoperatively. Micro-CT is a potentially useful tool for assessment of breast cancer specimens, allowing real-time analysis of breast lumpectomy specimens or cavity shaved margins.