Poster No:
1746
Submission Type:
Abstract Submission
Authors:
Kadharbatcha Saleem1, Alexandru Avram1, Daniel Glen2, Cecil Yen2, Peter Basser1
Institutions:
1Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, 2National Institute of Mental Health (NIMH), NIH, Bethesda, MD
First Author:
Kadharbatcha Saleem
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH
Bethesda, MD
Co-Author(s):
Alexandru Avram
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH
Bethesda, MD
Daniel Glen
National Institute of Mental Health (NIMH), NIH
Bethesda, MD
Cecil Yen
National Institute of Mental Health (NIMH), NIH
Bethesda, MD
Peter Basser
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH
Bethesda, MD
Introduction:
The subcortical areas are important targets for neuromodulation devices in the development of new treatments for motor and cognitive-related symptoms [1]. However, detailed parcellation of the subcortical regions using multimodal MRI is limited. Here, we generated a comprehensive Subcortical Atlas of the Human Brain in MNI coordinates using nine microstructural parameters derived from ex vivo ultrahigh-resolution mean apparent propagator (MAP) MRI [2-5], a powerful diffusion MRI framework. We also generated a gray and white matter atlas of the cerebellum derived from the in vivo MNI template and a whole brain connectome dMRI dataset. Tracing and validating these atlas-based deep brain regions is imperative for neurosurgical planning, navigation of deep brain stimulation probes, localization of functional activation regions in fMRI, cross-species comparison, and establishing brain structure-function relationships.
Methods:
We dissected the entire human brainstem, including the thalamus and the basal ganglia, but not the cerebellum, from a postmortem formalin-fixed adult female brain (age: 24 years old; PMI: 34 hr; fixation time: ~6 months). We placed the specimen inside the custom-made mold and container assembly (Fig. 1A-B) and scanned it on a 7T MRI scanner and a MAP-MRI acquisition with 250 μm resolution. We acquired 104 DWIs with multiple b-values (bmax=10000 s/mm2), and pulse duration, and separation of δ=8 ms and Δ=28 ms, respectively. In each voxel, we estimated the MAP and computed microstructural DTI/MAP parameters: fractional anisotropy (FA); mean, axial, and radial diffusivities (MD, AD, and RD, respectively); propagator anisotropy (PA), non-gaussianity (NG), return-to-origin probability (RTOP), return-to-axis probability (RTAP), and return-to-plane probability (RTPP), along with the fiber orientation distribution (FOD) [6] functions. We computed the MT ratio (MTR) from 3D gradient echo images acquired with and without MT preparation. The total duration of the MAP-MRI scan was 62 h and 25 min, and the MT scan was 13 h and 7 min.
We registered the microstructural parameters derived from the ex vivo MAP-MRI dataset to the in vivo MNI_icbm152 template [7]. We also registered the direction-encoded color (DEC) volume derived from the in vivo human whole-brain connectome diffusion MRI and the BigBrain dataset to the same MNI volume [8,9]. All these volumes registered well to the standard MNI space (Fig. 1C), helping us delineate different subcortical nuclei and white matter fiber tracts directly in the MNI template space.
Results:
We identified and segmented the subregions of the basal ganglia, thalamus, brainstem, amygdala, cerebellum, etc., directly in the coordinates of the in vivo MNI template using the warped ex vivo MAP-MRI, T2W, and MTR images (Fig. 1D; e.g., thalamus). In addition, we also segmented the cerebellar lobules and fiber bundles using the MAP-MRI and FOD-derived DEC map [8,10] (Fig. 1E). These novel brain segmentation are called the Subcortical Atlas of the Human Brain (SAHB) and the Human Cerebellar Atlas (HCA). Figure 2A-B shows two atlases in 2D axial, sagittal, or coronal MRI and 3D.
We also validated the atlas-based areal boundaries of segmented subcortical and cerebellar areas by registering these in vivo SAHB and HCA templates to individual in vivo T1W MRI volumes of control human subjects of different age groups and genders, using a sequence of affine and nonlinear registration steps. This procedure resulted in both SAHB and HCA atlases registered to the individual subject space (Fig. 2C; specific to cerebellar or HCA atlas). These results demonstrate that affine and nonlinear warpings are sufficient to distinguish and provide atlas-based estimates of areal boundaries in control subjects in vivo.


Conclusions:
The MAP-MRI enabled noninvasive segmentation of subcortical regions in the human brain. The 3D atlas provides a readily usable standard for region definition, while the template provides a standard reference and space.
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures 1
White Matter Anatomy, Fiber Pathways and Connectivity
Neuroinformatics and Data Sharing:
Brain Atlases 2
Novel Imaging Acquisition Methods:
Diffusion MRI
Multi-Modal Imaging
Keywords:
Brainstem
Cerebellum
CHEMOARCHITECTURE
Data Registration
HIGH FIELD MR
MRI
Open-Source Software
Sub-Cortical
Thalamus
White Matter
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Other
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Healthy subjects
Was this research conducted in the United States?
Yes
Are you Internal Review Board (IRB) certified?
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Not applicable
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Not applicable
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
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?
7T
Which processing packages did you use for your study?
AFNI
Provide references using APA citation style.
1. Davidson B, Bhattacharya A, Sarica C, Darmani G, Raies N, Chen R, Lozano AM (2024). Neuromodulation techniques – From non-invasive brain stimulation to deep brain stimulation. Neurotherapeutics 21: e00330.
2. Özarslan E, Koay CG, Shepherd TM, Komlosh ME, İrfanoğlu MO, Pierpaoli C, Basser PJ (2013). Mean apparent propagator (MAP) MRI: a novel diffusion imaging method for mapping tissue microstructure. Neuroimage 78:16-32.
3. Avram A, Sarlls JE, Barnett AS, Özarslan E, Thomas C, Irfanoglu MO, Hutchinson E, Pierpaoli C, Basser PJ (2016). Clinical feasibility of using mean apparent propagator (MAP) MRI to characterize brain tissue microstructure. Neuroimage 127:422-434.
4. Saleem KS, Avram AV, Glen D, Yen CC, Ye FQ, Komlosh M, Basser PJ. High-resolution mapping and digital atlas of subcortical regions in the macaque monkey based on matched MAP-MRI and histology. Neuroimage. 2021; 245:118759. https://doi.org/10.1016/j.neuroimage.2021.118759
5. Saleem KS, Avram AV, Yen CC, Magdoom KN, Schram V, Basser PJ (2023). Multimodal anatomical mapping of subcortical regions in Marmoset monkeys using high-resolution MRI and matched histology with multiple stains. Neuroimage 281: 120311. http://dx.doi.org/10.1016/j.neuroimage.2023.120311
6. Tournier JD, Calamante F, Connelly, A (2012). MRtrix: diffusion tractography in crossing fiber regions. International journal of imaging systems and technology 22:53-66.
7. Fonov V, Evans AC, Botteron K, Almli CR, McKinstry RC, Collins DL, et al. (2011). Unbiased average age-appropriate atlases for pediatric studies. Neuroimage 54, 313–327.
8. Wang F, Dong Z, Tian Q, Liao C, Fan Q, Hoge WS, Keil B, Polimeni JR, Wald LL, Huang SY, Setsompop K (2021). In vivo human whole-brain Connectom diffusion MRI dataset at 760 μm isotropic resolution.
Scientific Data 8:1-12.
9. Amunts K, Lepage C, Borgeat L, Mohlberg H, Dickscheid T, Rousseau M, Bludau S, Bazin P, Lewis LB, Oros-Peusquens A, Shah NJ, Lippert T, Zilles K, Evans AC (2013). BigBrain: An Ultrahigh-Resolution 3D Human Brain Model. Science 340: 1472-1475.
10. Pajevic S, Pierpaoli C (1999). Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: application to white matter fiber tract mapping in the human brain. Magn Reson Med 42:526-540.
No