Subthalamic nucleus volumes are highly consistent but decrease age-dependently-a combined magnetic resonance imaging and stereology approach in humans

Abstract

The subthalamic nucleus (STN) is a main target structure of deep brain stimulation (DBS) in idiopathic Parkinson's disease. Nevertheless, there is an ongoing discussion regarding human STN volumes and neuron count, which could potentially have an impact on STN-DBS. Moreover, a suspected functional subdivision forms the basis of the tripartite hypothesis, which has not yet been morphologically substantiated. In this study, it was aimed to investigate the human STN by means of combined magnetic resonance imaging (MRI) and stereology. STN volumes were obtained from 14 individuals (ranging from 65 to 96 years, 25 hemispheres) in 3 T MRI and in luxol-stained histology slices. Neuron number and cell densities were investigated stereologically over the entire STN and in pre-defined subregions in anti-human neuronal protein HuC/D-stained slices. STN volumes measured with MRI were smaller than in stereology but appeared to be highly consistent, measuring on average 99 ± 6 mm (MRI) and 132 ± 20 mm (stereology). The neuron count was 431,088 ± 72,172. Both STN volumes and cell count decreased age-dependently. Neuron density was different for the dorsal, medial and ventral subregion with significantly higher values ventrally than dorsally. Small variations in STN volumes in both MRI and stereology contradict previous findings of large variations in STN size. Age-dependent decreases in STN volumes and neuron numbers might influence the efficacy of STN-DBS in a geriatric population. Though the study is limited in sample size, site-dependent differences for the STN subregions form a morphological basis for the tripartite theory. Hum Brain Mapp 38:909-922, 2017. © 2016 Wiley Periodicals, Inc.

Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy

“…Our results are in line with previous studies showing volume decreases in PSP, but not in PD subjects. Given the small size of the structure, only a few MRI studies have investigated the STN volume in humans, mostly using 7T MRI in healthy volunteers, finding a correlation between volume reduction and age . In PSP, elevated free water diffusion, increased iron content using R2* relaxometry, and elevated tau tracer binding using PET were reported.…”

Anatomy and Connectivity of the Subthalamic Nucleus in Humans and Non-human Primates

“…Few authors have approached the human STh from a morphometrical perspective and through the aid of unbiased stereology (Lange et al, 1976;Hardman et al, 2002;Levesque and Parent, 2005;Salvesen et al, 2015;Zwirner et al, 2017). We have reported stereology based studies on subjects with no clinical or pathological evidence in Table 1.…”

Comparing functional MRI protocols for small, iron‐rich basal ganglia nuclei such as the subthalamic nucleus at 7 T and 3 T

“…However, in the BG the anatomical specificity of traditional functional Magnetic Resonance Imaging (fMRI) techniques is limited, because the nuclei in the BG are very small compared with the voxel size of most functional MRI protocols. For example, with a voxel size of 3 mm isotropic, a commonly used voxel size in 3 T fMRI studies, the entire STN can be covered in 4–5 voxels, assuming only small partial volume effects [the STN has a volume of approximately 100 mm 3 ; de Hollander et al, ; Keuken et al, ; Zwirner et al, ]. This is especially problematic because a related nucleus, the SN, lies directly adjacent to the STN (and also other related nuclei, such as the red nucleus, RN, are only a few millimeters away).…”