Multi-modal, multi-scale imaging shows that long-association systems are made of short relay fibers

2200 

Abstract Submission 

Chiara Maffei¹, Evan Dann¹, Marina Celestine², Robert Jones¹, Julia Lehman³, Hui Wang¹, Suzanne Haber^3,2, Anastasia Yendiki¹

¹Massachusetts General Hospital and Harvard Medical School, Boston, MA, ²Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, ³Department of Pharmacology & Physiology, University of Rochester, Rochester, NY

Chiara Maffei  
Massachusetts General Hospital and Harvard Medical School
Boston, MA

Evan Dann  
Massachusetts General Hospital and Harvard Medical School
Boston, MA

Marina Celestine  
Department of Psychiatry, McLean Hospital, Harvard Medical School
Belmont, MA

Robert Jones  
Massachusetts General Hospital and Harvard Medical School
Boston, MA

Julia Lehman  
Department of Pharmacology & Physiology, University of Rochester
Rochester, NY

Hui Wang  
Massachusetts General Hospital and Harvard Medical School
Boston, MA

Suzanne Haber  
Department of Pharmacology & Physiology, University of Rochester|Department of Psychiatry, McLean Hospital, Harvard Medical School
Rochester, NY|Belmont, MA

Anastasia Yendiki  
Massachusetts General Hospital and Harvard Medical School
Boston, MA

Obtaining accurate connectional neuroanatomy across scales and modalities ex vivo is crucial to inform the interpretation of in-vivo diffusion MRI (dMRI) findings and advance our understanding of brain circuitry. Here we combine data across multiple modalities, scales, and species to show that low spatial resolution may result in artifactual long-range connections. We focus on the dorsal superior longitudinal fasciculus (SLF-I), a major fiber association system running within the superior frontal gyrus (SFG). Tracing studies in monkeys describe the SLF-I as connecting the postero-medial parietal regions (PGm, PE, PEc) to different frontal regions (6D, 8B, 9)[1]. Due to the complexity of the SFG, with shorter, superficial fibers running parallel to longer, association fibers, the morphology of the human SLF-I remains controversial. Tractography and post-mortem dissections have yielded conflicting results, some supporting direct, long connections, and others supporting shorter or no SLF-I fibers [2,3]. Here, we combine multi-scale, multi-species, multi-modality data to investigate the mesoscopic organization within the SLF-I fiber system.

The datasets used in this work are presented in Figure 1A and acquisition details are listed below.
Human data:
1) In vivo 1.5 mm dMRI: 3T, 2D EPI, 552 volumes (40 b=0, 64 b=1000, 64 b=3000; 128 b=5000; 256 b=10000 s/mm²)[4].
2) In vivo 760 μm dMRI: 3T, gSlider-SMS, 2808 volumes (144 b=0, 420 b=1000, 840 b=2500 s/mm²)[5].
3) Ex vivo 750 μm dMRI: 3T, 3D DW SSFP, 68 volumes (TR=30.21 ms, TE=25.12 ms, 8 b=0, 60 b=4,000 s/mm²).
4) Ex vivo 250 μm dMRI: 4 small blocks (roughly 2x2x1cm) cut from dataset 3 (9.4T, 3D EPI, 515 volumes, TR=75ms, TE=43ms, max b=40,000 s/mm²).
5) Ex vivo 10 μm polarization-sensitive optical coherence tomography (PS-OCT)[6].
Macaque data:
6) Ex vivo 700 μm dMRI: 4.7T, 3D EPI, 514 volumes (max b=40,000 s/mm²).
7) Tracer data: 3 male macaques received an injection in the frontal pole, in 9M, and in 6A (cases 1, 2, 3 respectively)[7].
Pre-processing: All dMRI data were denoised and corrected for motion/eddy current distortions. For each dataset, fiber orientation distributions were estimated using constrained spherical deconvolution and connectivity matrices were generated in MRtrix3. PS-OCT data were processed as described in [8] and tractography was performed using an in-house algorithm developed in Julia. Datasets 2,3 and 6 were downsampled to 1.5 mm to investigate the effect of spatial resolution.

Higher resolution tractography in humans (<750 μm) shows that the medial SFG white matter mainly comprises short-range connections that come in and out the cortex, rather than long-range direct connections as observed in in vivo lower resolution dMRI (Figure 1B, top row). Anatomic tracing and dMRI tractography in macaques support these findings, showing direct connections only between 6M and Pe/Pec and shorter relay fibers rostral to 6M (Figure 1B, bottom row). Most of the longer, direct connections between parietal and frontal regions course within the cingulum bundle (Figure 2B), in accordance with the literature [9]. White-matter fibers originating in parietal regions and coursing withing the SFG white matter mainly terminate in areas 4, 6, and 8B, as previously reported [2]. The number of direct, long connections coursing within the SFG white matter is greater at 1.5 mm resolution than at higher resolutions (Figure 2C-D).

By comparing data across multiple modalities, scales, and species, we provide preliminary novel evidence that the SLF-I is composed of a succession of shorter relay fibers, which, in lower-resolution dMRI tractography result in a long, direct association bundle. These results point to the fact that each large white matter pathways like the SLF should not be thought of as monolithic structures, connecting a pair of remote cortical regions, but as conduits for connections between multiple pairs of regions.

Connectivity (eg. functional, effective, structural)

Diffusion MRI Modeling and Analysis ²

Anatomy and Functional Systems

White Matter Anatomy, Fiber Pathways and Connectivity ¹

Diffusion MRI

MRI

Tractography

White Matter

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC

Other - Fiber Pathways