Towards Direct Mapping of the Human Pallido-Subthalamic Pathway with 3T Diffusion MRI

Poster No:

1918 

Submission Type:

Abstract Submission 

Authors:

Nicolas Tempier1, Mélanie Didier2, Christophe Destrieux3, Mathieu Santin2, Carine Karachi1, Eric Bardinet2

Institutions:

1Paris Brain Institute, Paris, Paris, 2CENIR, Paris, Paris, 3UMR Inserm U1253, Université de Tours, Tours, France

First Author:

Nicolas Tempier  
Paris Brain Institute
Paris, Paris

Co-Author(s):

Mélanie Didier  
CENIR
Paris, Paris
Christophe Destrieux  
UMR Inserm U1253, Université de Tours
Tours, France
Mathieu Santin  
CENIR
Paris, Paris
Carine Karachi  
Paris Brain Institute
Paris, Paris
Eric Bardinet  
CENIR
Paris, Paris

Introduction:

The subthalamic nucleus (STN) integrates motor, cognitive, and limbic functions (Nambu 2011; Hamani 2004), yet its pallido-subthalamic pathway remains poorly understood. Ex vivo 11.7T DWI and histology revealed a complex, topographically organized projection, but translating these insights to in vivo 3T conditions is hampered by coarser spatial resolution and crossing fibers (Coenen 2021). Here, we leverage ex vivo findings to guide 3T tractography, moving toward direct mapping of the human pallido-subthalamic pathway for clinical applications such as DBS.

Methods:

In vivo MR images were acquired on a 3T MAGNETOM Cima.X with ultra intense Gemini Gradients operating at Gmax of 200 mT/m with a slew rate of 200 T/m/s (Siemens Healthineers) with a 64-channel head coil at CENIR.
Acquisition consisted of 3D-T1-weighted MPRAGE and diffusion-weighted imaging. Diffusion Images were acquired using CMRR 2D EPI MultiBand sequence (TE=53 ms, TR=2600 ms, multi-band acceleration factor=4, iPAT=2, phase partial Fourier=6/8, flip angle=90°, EPI factor=104, bmax=6000 s/mm2, voxel size 2mm3 isotropic, 6 b=0 s/mm2, 32 b=500 s/mm2, 40 b=1000 s/mm2, 40 b=2000 s/mm2, 40 b=3000 s/mm2, 40 b=4000 s/mm2, 40 b=6000 s/mm2) and three b=0 s/mm2 with reversed phase encoding, total acquisition time for the DWI part was 12:04min.
The postmortem human brain (F/78y) was cut to fit inside the MRI bore. Then immersion-fixed in 4% PFA for 8 days at 4°C and scanned with CENIR 11.7T Bruker BioSpec with a 72 mm transceiver coil. A T2*-weighted image at 110 μm isotropic resolution was acquired. Subsequently, multi-shell diffusion MRI (7 b=1000; 29 b=4000; and 64 b=10000 s/mm²) at 0.22 mm isotropic resolution with TR/TE= 250/25.2ms, total acquisition time of 61 hours.
3T and 11.7T diffusion preprocessing included Gibbs ringing artifact removal, Eddy and motion denoising, for the 3T dataset, phase and magnitude were reconstructed, allowing us to apply the NORDIC algorithm for data denoising (Moeller 2021)
Bidirectional STN-GPe tractography (iFOD2; FA>0.07; length=1.1–25 mm), excluding internal capsule edges. Tractograms filtered by GPe functional territories (Bardinet 2009) were mapped to STN (Tournier 2019).

Results:

Projections from the GPe follow an ascending path, bypassing the GPi and heading towards the STN. The STN is organized into three anatomo-functional territories, limbic projections projecting to the anterior pole, motor projections central, ventral and posterior, and associative projections rather central, although covering almost the entire nucleus.
The fiber orientation densities (FODs) reveal the presence of complex directional information within the internal capsule. Using MSMT-CSD, the FODs display multiple peaks indicative of crossing or bending fibers. This configuration is prominent in regions where the pallido-subthalamic pathway passes through the densely packed internal capsule.
For the 3T dataset, the associative territory has a central-posterior density peak, the sensory-motor territoryhas a central-inferior peak, and the limbic territory has an anterior peak. For the 11.7T dataset, the distribution of the territories was similar with wider sensorimotor territory.
Supporting Image: Fig1.png
   ·Figure 1: Pallido Subthalamic projections in Human, from 3T dataset (A&B) and 11.7T dataset (C&D)
Supporting Image: Fig2.png
   ·Figure 2: Fiber Orientation Density Functions in the internal capsule showing crossing fibers
 

Conclusions:

We reproduced ex vivo-level details of the pallido-subthalamic pathway at 3T in clinically feasible times. Despite lower resolution and complex fiber crossings, the STN's functional territories were preserved. This may improve neurosurgical targeting and patient-specific interventions (DBS, HIFU).

Brain Stimulation:

Deep Brain Stimulation

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Anatomy and Functional Systems 2
Subcortical Structures
Neuroanatomy Other

Novel Imaging Acquisition Methods:

Diffusion MRI 1

Keywords:

Acquisition
Basal Ganglia
HIGH FIELD MR
STRUCTURAL MRI
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Diffusion MRI

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

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Was this research conducted in the United States?

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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

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Please indicate which methods were used in your research:

Structural MRI
Diffusion MRI
Postmortem anatomy

For human MRI, what field strength scanner do you use?

3.0T
If Other, please list  -   11.7T

Which processing packages did you use for your study?

Other, Please list  -   Mrtrix3 FSL Yeb Atlas

Provide references using APA citation style.

Nambu, A. (2011). Somatotopic organization of the primate basal ganglia. Frontiers in Neuroanatomy, 5(26), 1–9.

Tournier, J.-D., Smith, R., Raffelt, D., Tabbara, R., Dhollander, T., Pietsch, M., Christiaens, D., Jeurissen, B., Yeh, C.-H., & Connelly, A. (2019). MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation. NeuroImage, 202, 116137.

Bardinet, E., Bhattacharjee, M., Dormont, D., Pidoux, B., Malandain, G., Schüpbach, M., Ayache, N., Cornu, P., Agid, Y., & Yelnik, J. (2009). A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease. Journal of Neurosurgery, 110(2), 208–219.

Moeller, S., Pisharady, P. K., Ramanna, S., Lenglet, C., Wu, X., Dowdle, L., Yacoub, E., Uğurbil, K., & Akçakaya, M. (2021). NOise reduction with DIstribution Corrected (NORDIC) PCA in dMRI with complex-valued parameter-free locally low-rank processing. NeuroImage, 226, 117539.

Hamani, C., Saint-Cyr, J., Fraser, J., Kaplitt, M., & Lozano, A. (2004). The subthalamic nucleus in the context of movement disorders. Brain, 127(1), 4–20.

Coenen, V. A., Döbrössy, M. D., Teo, S. J., Wessolleck, J., Sajonz, B. E. A., Reinacher, P. C., Thierauf-Emberger, A., Spittau, B., Leupold, J., von Elverfeldt, D., Schlaepfer, T. E., & Reisert, M. (2022). Diverging prefrontal cortex fiber connection routes to the subthalamic nucleus and the mesencephalic ventral tegmentum investigated with long range (normative) and short range (ex-vivo high resolution) 7T DTI. Brain Structure and Function, 227(1), 23–47.

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