In vivo dopaminergic imaging strongly correlates with brain pathology

By Joanna Lyford, Senior medwireNews Reporter

Striatal dopamine transporter binding, assessed using single-photon emission computed tomography (SPECT), is strongly correlated with substantia nigra cell counts assessed at postmortem, say the authors of a study.

Writing in Movement Disorders, the researchers say that their findings validate this imaging modality as an in vivo marker of nigrostriatal dopaminergic degeneration in patients with Parkinson’s disease and related disorders.

Walter Pirker (Medical University of Vienna, Austria) and colleagues used their hospital database to identify deceased individuals who, when alive, had undergone single-photon emission computed tomography (SPECT) imaging using [123I]β-CIT, a ligand with high affinity for the striatal dopamine transporter, and for whom postmortem brain pathology data were available.

Nine individuals were included in the study, of whom seven had neurodegenerative parkinsonism. Diagnoses included Parkinson’s disease (n=1), dementia with lewy bodies (n=2), atypical parkinsonism with multiple pathology (n=1), multisystem atrophy (n=1), corticobasal degeneration (n=2), Alzheimer’s disease (n=1) and Creutzfeld-Jakob disease (n=1).

[123I]β-CIT imaging was performed at a mean disease duration of 2.3 years and at a mean age of 72.2 years. The mean interval between imaging and death was 29.3 months.

Analysis of SPECT images revealed bilaterally reduced striatal dopamine transporter binding. There was more severe involvement of the putamen than the caudate nucleus in all seven patients with neurodegenerative parkinsonism, whereas overall binding was normal in patients with Alzheimer’s disease and CJD. The specific striatal binding ratio ranged from markedly reduced to normal in individual patients.

The average number of cells that stained positive for neuromelanin and tyrosine hydroxylase (TH) over both hemispheres strongly correlated with striatal dopamine transporter binding, with r-values of 0.98 and 0.96, respectively.

Similarly strong correlations were found for striatal binding when analysed separately for the right and left hemispheres, as well as in the seven patients with neurodegenerative parkinsonism.

Also, the right–left asymmetry of striatal binding moderately correlated with the asymmetry of dopaminergic degeneration in the substantia nigra, based on the number of neuromelanin-containing cells, with an r-value of 0.76.

Taken together, these data support a high correlation of striatal dopamine transporter binding with dopaminergic cell counts in the substantia nigra, say the study authors.

“To our knowledge, this is only the third human study to validate imaging techniques for the nigrostriatal dopaminergic system by correlating in vivo imaging data with dopaminergic cell counts at autopsy”, they remark.

The researchers add that their findings “are in good agreement with other human studies” and “further validate [dopamine transporter] imaging as a surrogate marker of dopaminergic cell loss in [Parkinson’s disease] and related disorders.”

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