Probabilistic versus deterministic tractography for delineation of the cortico-subthalamic hyperdirect pathway in patients with Parkinson disease selected for deep brain stimulation

Abstract

OBJECTIVE Diffusion-weighted MRI (DWI) and tractography allows noninvasive mapping of the structural connections of the brain, and may provide important information for neurosurgical planning. The hyperdirect pathway, connecting the subthalamic nucleus (STN) with the motor cortex, is assumed to play a key role in mediating the effects of deep brain stimulation (DBS), which is an effective but poorly understood treatment for Parkinson disease. This study aimed to apply recent methodological advances in DWI acquisition and analysis to the delineation of the hyperdirect pathway in patients with Parkinson disease selected for surgery. METHODS High spatial and angular resolution DWI data were acquired preoperatively from 5 patients with Parkinson disease undergoing DBS. The authors compared the delineated hyperdirect pathways and associated STN target maps generated by 2 different tractography methods: a tensor-based deterministic method, typically available in clinical settings, and an advanced probabilistic method based on constrained spherical deconvolution. In addition, 10 high-resolution data sets with the same scanning parameters were acquired from a healthy control participant to assess the robustness of the tractography results. RESULTS Both tractography approaches identified connections between the ipsilateral motor cortex and the STN. However, the 2 methods provided substantially different target regions in the STN, with the target center of gravity differing by > 1.4 mm on average. The probabilistic method (based on constrained spherical deconvolution) plausibly reconstructed a continuous set of connections from the motor cortex, terminating in the dorsolateral region of the STN. In contrast, the tensor-based method reconstructed a comparatively sparser and more variable subset of connections. Furthermore, across the control scans, the probabilistic method identified considerably more consistent targeting regions within the STN compared with the deterministic tensor-based method, which demonstrated a 1.9-2.4 times higher variation. CONCLUSIONS These data provide a strong impetus for the use of a robust probabilistic tractography framework based on constrained spherical deconvolution, or similar advanced DWI models, in clinical settings. The inherent limitations and demonstrated inaccuracy of the tensor-based method leave it questionable for use in high-precision stereotactic DBS surgery. The authors have also described a straightforward method for importing tractography-derived information into any clinical neuronavigation system, based on the generation of track-density images.

Deep Brain Stimulation and L-DOPA Therapy: Concepts of Action and Clinical Applications in Parkinson's Disease

“…In addition, the modulation of the hyperdirect pathway between the STN and cortical regions was postulated (115). A recent study using diffusion MRI-based tractography (both deterministic and probabilistic) showed that the connections from ipsilateral motor cortex primarily terminated in the dorsolateral STN, further highlighting a key role of hyperdirect pathways in mediating the effects of DBS (116). A diffusion tensor imaging (DTI) analysis investigating the connectivity map of GPi revealed the anterior part to be mainly connected to the prefrontal cortex, the middle section to the brainstem and GPe and the dorsal GPi mainly to the thalamus and GPe (117).…”

Using probabilistic tractography to target the subcallosal cingulate cortex in patients with treatment resistant depression

“…While the probabilistic approach is time intensive, the data-driven nature may be more practical and provide advantages over a manual iterative approach. Moreover, probabilistic tractography provides more consistent and plausible tractography results that deterministic tractography (Petersen et al, 2016). Still, there are studies that controvert the reliability of diffusion tractography, whether using deterministic or probabilistic methods, for reproducing known anatomy, with results highly dependent on data quality, the algorithm selected, and the parameter settings (Thomas et al, 2014; Knösche et al, 2015).…”

Neuromagnetic investigations of mechanisms and effects of STN-DBS and medication in Parkinson's disease

“…Such a pathway has now also been shown in humans (Fernandez-Miranda et al, 2012;Petersen et al, 2017). Dopamine effects, on the other hand, could be driven via nigro-striatal input going into the basal ganglia structures at the subcortical level while also affecting the oscillatory dynamics between the inhibitory interneurons and the excitatory pyramidal neurons at the cortical level and thus affecting the corticospinal drive.…”

“…Striatum is the main input nucleus in the BG system receiving glutamatergic (excitatory) inputs from several parts of the cerebral cortex (Bolam et al, 2000;Hammond et al, 2007;Utter and Basso, 2008). Recent evidence also shows that the STN receives wide excitatory connections from the cortical areas including the motor cortex via the so-called hyperdirect pathway (Nambu et al, 2000;Fernandez-Miranda et al, 2012;Petersen et al, 2017). Striatum receives dopaminergic innervation from substantia nigra pars compacta (SNc) while the ventral tegmental area (VTA) projects to limbic and frontal cortex, both nuclei with a large proportion of dopaminergic neuronal populations.…”

“…The GPi along with the SNr are the main output nuclei of the BG system with inhibitory projections to several nuclei of the thalamus (ventrolateral, ventroanterior), which in turn project back to the cortex (Wichmann and DeLong, 2006;DeLong and Wichmann, 2007;Hammond et al, 2007;Obeso et al, 2008;Utter and Basso, 2008;Nambu, 2011). furthermore receives profuse glutamatergic inputs from the cortical areas (motor, premotor) evidenced from anatomical (Monakow et al, 1978;Kitai and Deniau, 1981;Nambu et al, 2002) and tractography studies (Lambert et al, 2012;Petersen et al, 2017), these connections are referred to as the "hyperdirect" pathway. Moreover, STN is the only nucleus in the BG circuitry with an excitatory output drive (Kitai and Deniau, 1981) and it exerts a direct influence on the main output nucleus of the BG circuit (GPi).…”