Magnetic resonance diffusion tensor imaging for the pedunculopontine nucleus: proof of concept and histological correlation
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The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ post-mortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.
KeywordsPedunculopontine nucleus Deep brain stimulation Diffusion tensor imaging Histology
We are grateful to the volunteers who participated and family members who donated the brain for this study. We would also like to thank all the members of the Brain Bank of the Brazilian Aging Brain Study Group. Funding sources: Brazilian National Council for Scientific and Technological Development (CNPq), Institute for Education and Research of Albert Einstein Hospital, São Paulo Research Foundation (FAPESP), LIM-22 and LIM-44 (HC-FMUSP) for research financial and technical support in Brazil, and the National Institutes of Health, USA (R01AG040311).
Brazilian National Council for Scientific and Technological Development (CNPq), Institute for Education and Research of Albert Einstein Hospital, São Paulo Research Foundation (FAPESP), LIM-44 and LIM-22 (HC-FMUSP) for research financial and technical support in Brazil, and the National Institutes of Health, USA (R01AG040311).
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest.
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