title: Brain venular pattern by 7T MRI correlates with memory and haemoglobin in sickle cell anaemia.
abstract: Sickle cell anaemia (SCA) is a hereditary hemoglobinopathy characterised by extensive vascular dysfunction that stems from inflammation, thrombosis and occlusion of post-capillary venules. Cognitive impairment is a neurological complication of SCA whose pathogenesis is unknown. We hypothesised that cerebral venular abnormalities are linked to cognitive impairment in SCA. Thus, we employed 7T magnetic resonance imaging (MRI) to examine the association between venular density and cognitive function in homozygous SCA. We quantified the density of total, long, and short venules in pre-defined regions of interest between the frontal and occipital cornu on each hemisphere. Cognitive function was assessed using the Hopkins Verbal Learning Test - Revised (HVLT-R) test of learning and memory. Patients (n=11) were compared with race, age and gender-equated controls (n=7). Compared to controls, patients had an overall venular rarefaction, with significantly lower density of long venules and greater density of short venules which was inversely related to HVLT-R performance and haemoglobin. To our knowledge, this is the first 7T MRI study in SCA and first report of associations between cerebral venular patterns and cognitive performance and haemoglobin. Future studies should examine whether these novel neuroimaging markers predict cognitive impairment longitudinally and are mechanistically linked to severity of anaemia.
authors.affiliation: University of Pittsburgh Medical Center (UPMC) and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: novellie@upmc.edu.
authors.forename: Enrico M
authors.initials: EM
authors.lastname: Novelli
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Elizabeth Sarles
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Jay Aizenstein
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Tamer S
authors.initials: TS
authors.lastname: Ibrahim
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Butters
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Connelly Ritter
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Kirk I
authors.initials: KI
authors.lastname: Erickson
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Rosano
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000473:pathology* / Q000523:psychology; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology* / Q000523:psychology; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D014699:Venules / Q000473:pathology*; D014706:Verbal Learning / Q000502:physiology; D055815:Young Adult
chemical_list: D006454:Hemoglobins
keywords: Cerebral small vessel diseases; Cognition; Magnetic resonance spectroscopy