Johanna Rotta1, Valentina Perosa2, Renat Yakupov1, Hugo J Kuijf1, Frank Schreiber1, Laura Dobisch1, Jan Oltmer1, Anne Assmann1, Oliver Speck1, Hans-Jochen Heinze1, Julio Acosta-Cabronero1, Emrah Duzel1, Stefanie Schreiber1. 1. From the Department of Neurology (J.R., V.P., F.S., A.A., H.-J.H., S.S.) and Institute of Physics (O.S.), Otto-von-Guericke University; Institute of Cognitive Neurology and Dementia Research (IKND) (V.P., R.Y., J.O., H.-J.H., E.D.), Magdeburg, Germany; J. Philip Kistler Stroke Research Center (V.P.), Massachusetts General Hospital, Boston; German Center for Neurodegenerative Diseases (DZNE) (R.Y., F.S., L.D., O.S., H.-J.H., E.D., S.S.), Magdeburg, Germany; Image Sciences Institute (H.J.K.), University Medical Center Utrecht, the Netherlands; Leibniz-Institute for Neurobiology (LIN) (O.S., H.-J.H., E.D.); Center for Behavioral Brain Sciences (CBBS) (O.S., H.-J.H., E.D., S.S.), Magdeburg, Germany; Tenoke Limited (J.A.-C.), Cambridge, UK; and Institute of Cognitive Neuroscience (E.D.), University College London, UK. 2. From the Department of Neurology (J.R., V.P., F.S., A.A., H.-J.H., S.S.) and Institute of Physics (O.S.), Otto-von-Guericke University; Institute of Cognitive Neurology and Dementia Research (IKND) (V.P., R.Y., J.O., H.-J.H., E.D.), Magdeburg, Germany; J. Philip Kistler Stroke Research Center (V.P.), Massachusetts General Hospital, Boston; German Center for Neurodegenerative Diseases (DZNE) (R.Y., F.S., L.D., O.S., H.-J.H., E.D., S.S.), Magdeburg, Germany; Image Sciences Institute (H.J.K.), University Medical Center Utrecht, the Netherlands; Leibniz-Institute for Neurobiology (LIN) (O.S., H.-J.H., E.D.); Center for Behavioral Brain Sciences (CBBS) (O.S., H.-J.H., E.D., S.S.), Magdeburg, Germany; Tenoke Limited (J.A.-C.), Cambridge, UK; and Institute of Cognitive Neuroscience (E.D.), University College London, UK. VPEROSA@mgh.harvard.edu.
Abstract
OBJECTIVE: Cerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein. METHODS: 7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein. RESULTS: A total of 51 people (mean age [SD] 70.5 [8.6] years, 37% female) participated in the study: 20 had CSVD (cerebral amyloid angiopathy [CAA] with strictly lobar MBs [n = 8], hypertensive arteriopathy [HA] with strictly deep MBs [n = 5], or mixed lobar and deep MBs [n = 7], 72.4 [6.1] years, 30% female) and 31 were healthy controls (69.4 [9.9] years, 42% female). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. Patients with CAA showed the highest ratio of venous to total MBs (19%) (HA = 9%, mixed = 18%, controls = 5%). CONCLUSION: Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathologic studies are needed to confirm our observations.
OBJECTIVE: Cerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein. METHODS: 7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein. RESULTS: A total of 51 people (mean age [SD] 70.5 [8.6] years, 37% female) participated in the study: 20 had CSVD (cerebral amyloid angiopathy [CAA] with strictly lobar MBs [n = 8], hypertensive arteriopathy [HA] with strictly deep MBs [n = 5], or mixed lobar and deep MBs [n = 7], 72.4 [6.1] years, 30% female) and 31 were healthy controls (69.4 [9.9] years, 42% female). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. Patients with CAA showed the highest ratio of venous to total MBs (19%) (HA = 9%, mixed = 18%, controls = 5%). CONCLUSION: Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathologic studies are needed to confirm our observations.
Authors: Adam Nyul-Toth; Gabor A Fulop; Stefano Tarantini; Tamas Kiss; Chetan Ahire; Janet A Faakye; Anna Ungvari; Peter Toth; Attila Toth; Anna Csiszar; Zoltan Ungvari Journal: Geroscience Date: 2022-01-06 Impact factor: 7.581