Progressive Supranuclear Palsy: In Vivo SPECT Imaging of Presynaptic Vesicular Acetylcholine Transporter with [123I]-Iodobenzovesamicol

Published Online:https://doi.org/10.1148/radiol.12112650

We found that cholinergic pathways are differentially affected in patients with progressive supranuclear palsy, with a significant alteration of the ponto-thalamic cholinergic pathway that is correlated with disease duration.

Purpose

To evaluate the integrity of brain cholinergic pathways in vivo in patients with progressive supranuclear palsy (PSP) by measuring the vesicular acetylcholine transporter expression at single photon emission computed tomography (SPECT) with [123I]-iodobenzovesamicol.

Materials and Methods

All participants provided informed written consent according to institutional human ethics committee guidelines. Ten patients with PSP and 12 healthy volunteers underwent dynamic [123I]-iodobenzovesamicol SPECT and magnetic resonance (MR) imaging. CT and MR images were used to register the dynamic SPECT image to the Montreal Neurologic Institute brain template, which includes the regions of interest of the striatum and the septo-hippocampal, innominato-cortical, and ponto-thalamic cholinergic pathways. For each region of interest, pharmacokinetic modeling of regional time activity curves was used to calculate [123I]-iodobenzovesamicol to vesicular acetylcholine transporter binding potential value, proportional to vesicular acetylcholine transporter expression.

Results

When compared with control participants, patients with PSP had binding potential values that were unchanged in the striatum and septohippocampal pathway, significantly lower in the anterior cingulate cortex (P = .017) in the innominatocortical pathway, and significantly decreased in the thalamus (P = .014) in the pontothalamic cholinergic pathway. In addition, binding potential values in the thalamus were positively correlated with those in the pedunculopontine nucleus (ρ = 0.81, P < .004) and binding potential values in both the thalamus (ρ = −0.88, P < .001) and pedunculopontine nucleus (ρ = −0.80, P < .010) were inversely correlated with disease duration.

Conclusion

Cholinergic pathways were differentially affected in the PSP group, with a significant alteration of pontothalamic pathways that increased with disease progression at both cell body and terminal levels, while the innominatocortical pathway was only mildly affected, and the septohippocampal pathway and the striatum were both preserved.

© RSNA, 2012

References

  • 1 Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 2009;8(3):270–279.
  • 2 Ruberg M, Javoy-Agid F, Hirsch E, et al.. Dopaminergic and cholinergic lesions in progressive supranuclear palsy. Ann Neurol 1985;18(5):523–529.
  • 3 Kish SJ, Chang LJ, Mirchandani L, Shannak K, Hornykiewicz O. Progressive supranuclear palsy: relationship between extrapyramidal disturbances, dementia, and brain neurotransmitter markers. Ann Neurol 1985;18(5):530–536.
  • 4 Suzuki M, Desmond TJ, Albin RL, Frey KA. Cholinergic vesicular transporters in progressive supranuclear palsy. Neurology 2002;58(7):1013–1018.
  • 5 Gilman S, Koeppe RA, Nan B, et al.. Cerebral cortical and subcortical cholinergic deficits in parkinsonian syndromes. Neurology 2010;74(18):1416–1423.
  • 6 Asahina M, Suhara T, Shinotoh H, Inoue O, Suzuki K, Hattori T. Brain muscarinic receptors in progressive supranuclear palsy and Parkinson’s disease: a positron emission tomographic study. J Neurol Neurosurg Psychiatry 1998;65(2):155–163.
  • 7 Kuhl DE, Koeppe RA, Fessler JA, et al.. In vivo mapping of cholinergic neurons in the human brain using SPECT and IBVM. J Nucl Med 1994;35(3):405–410.
  • 8 Wevers A. Localisation of pre- and postsynaptic cholinergic markers in the human brain. Behav Brain Res 2011;221(2):341–355.
  • 9 Litvan I, Agid Y, Calne D, et al.. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996;47(1):1–9.
  • 10 Mazère J, Prunier C, Barret O, et al.. In vivo SPECT imaging of vesicular acetylcholine transporter using [(123)I]-IBVM in early Alzheimer’s disease. Neuroimage 2008;40(1):280–288.
  • 11 Giovacchini G, Lerner A, Toczek MT, et al.. Brain incorporation of 11C-arachidonic acid, blood volume, and blood flow in healthy aging: a study with partial-volume correction. J Nucl Med 2004;45(9):1471–1479.
  • 12 Meltzer CC, Kinahan PE, Greer PJ, et al.. Comparative evaluation of MR-based partial-volume correction schemes for PET. J Nucl Med 1999;40(12):2053–2065.
  • 13 Tzourio-Mazoyer N, Landeau B, Papathanassiou D, et al.. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 2002;15(1):273–289.
  • 14 Barret O, Mazère J, Seibyl J, Allard M. Comparison of noninvasive quantification methods of in vivo vesicular acetylcholine transporter using [123I]-IBVM SPECT imaging. J Cereb Blood Flow Metab 2008;28(9):1624–1634.
  • 15 McGeer PLES, McGeer EG. Molecular neurobiology of the mammalian brain. New York, NY: Plenum, 1980.
  • 16 Araujo DM, Lapchak PA, Robitaille Y, Gauthier S, Quirion R. Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer’s disease. J Neurochem 1988;50(6):1914–1923.
  • 17 Erickson JD, Varoqui H, Schäfer MK, et al.. Functional identification of a vesicular acetylcholine transporter and its expression from a “cholinergic” gene locus. J Biol Chem 1994;269(35):21929–21932.
  • 18 Kuhl DE, Minoshima S, Fessler JA, et al.. In vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol 1996;40(3):399–410.
  • 19 Bohnen NI, Frey KA. Imaging of cholinergic and monoaminergic neurochemical changes in neurodegenerative disorders. Mol Imaging Biol 2007;9(4):243–257.
  • 20 Bird TD, Stranahan S, Sumi SM, Raskind M. Alzheimer’s disease: choline acetyltransferase activity in brain tissue from clinical and pathological subgroups. Ann Neurol 1983;14(3):284–293.
  • 21 Perry RH, Candy JM, Perry EK, Thompson J, Oakley AE. The substantia innominata and adjacent regions in the human brain: histochemical and biochemical observations. J Anat 1984;138(Pt 4):713–732.
  • 22 Gilman S, Koeppe RA, Chervin RD, et al.. REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA. Neurology 2003;61(1):29–34.
  • 23 Shinotoh H, Namba H, Yamaguchi M, et al.. Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson’s disease and progressive supranuclear palsy. Ann Neurol 1999;46(1):62–69.
  • 24 Hirano S, Shinotoh H, Shimada H, et al.. Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia. Brain 2010;133(Pt 7):2058–2068.
  • 25 Jenkinson N, Nandi D, Muthusamy K, et al.. Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus. Mov Disord 2009;24(3):319–328.
  • 26 Tagliavini F, Pilleri G, Bouras C, Constantinidis J. The basal nucleus of Meynert in patients with progressive supranuclear palsy. Neurosci Lett 1984;44(1):37–42.

Article History

Received December 30, 2011; revision requested February 22, 2012; revision received April 19; accepted May 1; final version accepted May 24.
Published online: Nov 2012
Published in print: Nov 2012