Elena Herranz1, Céline Louapre1, Constantina Andrada Treaba1, Sindhuja T Govindarajan2, Russell Ouellette2, Gabriel Mangeat3, Marco L Loggia1, Julien Cohen-Adad4, Eric C Klawiter5, Jacob A Sloane6, Caterina Mainero1. 1. Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA/ Harvard Medical School, Boston, MA, USA. 2. Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA. 3. Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA/ Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada. 4. Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada. 5. Harvard Medical School, Boston, MA, USA/ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. 6. Harvard Medical School, Boston, MA, USA/ Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Abstract
BACKGROUND: Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis. OBJECTIVE: Using 11C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing-remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity. METHODS: Mean 11C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T2* (q-T2*) abnormalities, and normal-appearing cortex. The relative difference in cortical 11C-PBR28 uptake between patients and 14 controls was used to classify cortical lesions as either active or inactive. Disease burden was investigated according to cortical lesion inflammatory profiles. The relation between q-T2* and 11C-PBR28 uptake along the cortex was assessed. RESULTS: 11C-PBR28 uptake was abnormally high in cortical lesions in RRMS and SPMS; in SPMS, tracer uptake was significantly increased also in normal-appearing cortex. 11C-PBR28 uptake and q-T2* correlated positively in many cortical areas, negatively in some regions. Patients with high cortical lesion inflammation had worse clinical outcome and higher intracortical lesion burden than patients with low inflammation. CONCLUSION: 11C-PBR28 and 7T imaging reveal distinct profiles of cortical inflammation in MS, which are related to disease burden.
BACKGROUND: Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis. OBJECTIVE: Using 11C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing-remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity. METHODS: Mean 11C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T2* (q-T2*) abnormalities, and normal-appearing cortex. The relative difference in cortical 11C-PBR28 uptake between patients and 14 controls was used to classify cortical lesions as either active or inactive. Disease burden was investigated according to cortical lesion inflammatory profiles. The relation between q-T2* and 11C-PBR28 uptake along the cortex was assessed. RESULTS: 11C-PBR28 uptake was abnormally high in cortical lesions in RRMS and SPMS; in SPMS, tracer uptake was significantly increased also in normal-appearing cortex. 11C-PBR28 uptake and q-T2* correlated positively in many cortical areas, negatively in some regions. Patients with high cortical lesion inflammation had worse clinical outcome and higher intracortical lesion burden than patients with low inflammation. CONCLUSION: 11C-PBR28 and 7T imaging reveal distinct profiles of cortical inflammation in MS, which are related to disease burden.
Authors: Roberta Magliozzi; Owain W Howell; Cheryl Reeves; Federico Roncaroli; Richard Nicholas; Barbara Serafini; Francesca Aloisi; Richard Reynolds Journal: Ann Neurol Date: 2010-10 Impact factor: 10.422
Authors: Roberta Magliozzi; Owain W Howell; Richard Nicholas; Carolina Cruciani; Marco Castellaro; Chiara Romualdi; Stefania Rossi; Marco Pitteri; Maria Donata Benedetti; Alberto Gajofatto; Francesca B Pizzini; Stefania Montemezzi; Sarah Rasia; Ruggero Capra; Alessandra Bertoldo; Francesco Facchiano; Salvatore Monaco; Richard Reynolds; Massimiliano Calabrese Journal: Ann Neurol Date: 2018-04 Impact factor: 10.422
Authors: Céline Louapre; Sindhuja T Govindarajan; Costanza Giannì; Christian Langkammer; Jacob A Sloane; Revere P Kinkel; Caterina Mainero Journal: Neurology Date: 2015-10-14 Impact factor: 9.910
Authors: Armin Kolb; Hans F Wehrl; Matthias Hofmann; Martin S Judenhofer; Lars Eriksson; Ralf Ladebeck; Matthias P Lichy; Larry Byars; Christian Michel; Heinz-Peter Schlemmer; Matthias Schmand; Claus D Claussen; Vesna Sossi; Bernd J Pichler Journal: Eur Radiol Date: 2012-03-27 Impact factor: 5.315
Authors: Alexandra Kutzelnigg; Claudia F Lucchinetti; Christine Stadelmann; Wolfgang Brück; Helmut Rauschka; Markus Bergmann; Manfred Schmidbauer; Joseph E Parisi; Hans Lassmann Journal: Brain Date: 2005-10-17 Impact factor: 13.501
Authors: Douglas N Greve; Claus Svarer; Patrick M Fisher; Ling Feng; Adam E Hansen; William Baare; Bruce Rosen; Bruce Fischl; Gitte M Knudsen Journal: Neuroimage Date: 2013-12-19 Impact factor: 6.556
Authors: Elena Herranz; Costanza Giannì; Céline Louapre; Constantina A Treaba; Sindhuja T Govindarajan; Russell Ouellette; Marco L Loggia; Jacob A Sloane; Nancy Madigan; David Izquierdo-Garcia; Noreen Ward; Gabriel Mangeat; Tobias Granberg; Eric C Klawiter; Ciprian Catana; Jacob M Hooker; Norman Taylor; Carolina Ionete; Revere P Kinkel; Caterina Mainero Journal: Ann Neurol Date: 2016-10-25 Impact factor: 10.422
Authors: Assunta Dal-Bianco; Günther Grabner; Claudia Kronnerwetter; Michael Weber; Romana Höftberger; Thomas Berger; Eduard Auff; Fritz Leutmezer; Siegfried Trattnig; Hans Lassmann; Francesca Bagnato; Simon Hametner Journal: Acta Neuropathol Date: 2016-10-27 Impact factor: 17.088
Authors: Marios Politis; Paolo Giannetti; Paul Su; Federico Turkheimer; Shiva Keihaninejad; Kit Wu; Adam Waldman; Omar Malik; Paul M Matthews; Richard Reynolds; Richard Nicholas; Paola Piccini Journal: Neurology Date: 2012-07-03 Impact factor: 9.910
Authors: Jennifer Orthmann-Murphy; Cody L Call; Gian C Molina-Castro; Yu Chen Hsieh; Matthew N Rasband; Peter A Calabresi; Dwight E Bergles Journal: Elife Date: 2020-05-27 Impact factor: 8.140
Authors: Tammy T Hshieh; Sarinnapha M Vasunilashorn; Madeline L D'Aquila; Steven E Arnold; Bradford C Dickerson; Tamara G Fong; Richard N Jones; Edward R Marcantonio; Eva M Schmitt; Guoquan Xu; Yun Gou; Fan Chen; Lisa J Kunze; Kamen V Vlassakov; Ayesha R Abdeen; Jeffrey K Lange; Brandon E Earp; Alexandra Touroutoglou; Becky C Carlyle; Pia Kivisakk-Webb; Thomas G Travison; Simon T Dillon; Towia A Libermann; Sharon K Inouye Journal: Alzheimers Dement (Amst) Date: 2019-11-06