title: [(123)I]-IBVM SPECT imaging of cholinergic systems in multiple system atrophy: A specific alteration of the ponto-thalamic cholinergic pathways (Ch5-Ch6).
abstract: We evaluated in vivo the integrity of brain cholinergic pathways in Multiple System Atrophy (MSA) and the relationship between cholinergic dysfunction and motor disturbances, by measuring the vesicular acetylcholine transporter (VAChT) expression using Single Photon Emission Computed Tomography (SPECT) and [(123)I]-iodobenzovesamicol ([(123)I]-IBVM).
  
  
  METHODS
  Nine patients with probable MSA and 12 healthy volunteers underwent a dynamic [(123)I]-IBVM SPECT-CT scan and a magnetic resonance imaging (MRI) scan. All patients were examined with the Unified MSA Rating Scale (UMSARS; subscale I = activities of daily living (ADL), II = motor and IV = disability). CT and MRI images were used to register the dynamic SPECT image to the Montreal Neurological Institute brain template, which includes the regions of interest (ROI) of striatum and Ch1 (medial septum nucleus-hippocampus), Ch4 (nucleus basalis of Meynert-cortex) and Ch5-Ch6 (pedunculopontine and laterodorsal tegmental nuclei-thalamus) cholinergic pathways. For each ROI, pharmacokinetic modeling of regional time activity curves led to the calculation of [(123)I]-IBVM to VAChT binding potential (BPND) value, proportional to VAChT expression.
  
  
  RESULTS
  When compared to controls, BPND values for MSA in Ch5-Ch6 were significantly decreased in both the pedunculopontine-laterodorsal nuclei and the thalamus (p = 0.004 and p = 0.006, respectively). Additionally, thalamus BPND values were correlated with UMSARS ADL (p = 0.006), motor (p = 0.002) and disability (p = 0.02) sub-scores. UMSARS motor subscale items 13 (postural instability) and 14 (gait) were also correlated with thalamus BPND values (p = 0.04).
  
  
  CONCLUSIONS
  Ch5-Ch6 are the most affected cholinergic pathways in MSA at both cell bodies and thalamic cholinergic terminals. These results underscore the relevant role of [(123)I]-IBVM SPECT for improving our understanding of the pathophysiology in MSA.
authors.affiliation: Univ. Bordeaux, INCIA, UMR 5287, F-33400 Talence, France ; CNRS, INCIA, UMR 5287, F-33400 Talence, France ; CHU de Bordeaux, Service de Médecine Nucléaire, Bordeaux, France.
authors.forename: Joachim
authors.initials: J
authors.lastname: Mazere
authors.forename: Wassilios G
authors.initials: WG
authors.lastname: Meissner
authors.forename: Igor
authors.initials: I
authors.lastname: Sibon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamare
authors.forename: François
authors.initials: F
authors.lastname: Tison
authors.forename: Michèle
authors.initials: M
authors.lastname: Allard
authors.forename: Willy
authors.initials: W
authors.lastname: Mayo
keywords: Multiple System Atrophy; Pharmacokinetic modeling; Single Photon Emission Computed Tomography; Vesicular acetylcholine transporter; [123I]-iodobenzovesamicol