Imaging White Matter in Human Brainstem

Abstract

The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

“…Postmortem diffusion studies of the human brainstem allow considerably higher spatial resolution, superior contrast, and improved tractography. Other groups have used postmortem MRI of human brainstem specimens to investigate complex deep brain white matter anatomy, and even to explore previously uncharacterized white matter connections [Aggarwal et al, 2013; Edlow et al, 2012; Ford et al, 2013; McNab et al, 2009]. Many of these studies have struck a compromise between spatial resolution, angular sampling, and field of view (FOV) in order to keep scan time reasonable.…”

Top-Down Control of Serotonin Systems by the Prefrontal Cortex: A Path toward Restored Socioemotional Function in Depression

“…83, 84 Only with the most recent advances in imaging methods has it become possible to visualize individual raphe nuclei in awake subjects and conduct probabilistic tractographic analyses of major fiber tracts to these brainstem nuclei. 85 This is an important issue as tractography indicates that brainstem nuclei are among key downstream regions likely to mediate the effects of vmPFC neurostimulation for the treatment of MDD. 86 Imaging studies together with postmortem investigations indicate that the distribution of raphe nuclei cell clusters and the architecture of the frontopontine fiber tract are well conserved across mammals.…”

Investigating the human brainstem with structural and functional MRI

“…Yeo et al (2013) use probabilistic fiber tracking on diffusion-weighted images to delineate the ascending reticular activating system. Lastly, by using diffusion tensor imaging at ultra high field strengths, Ford et al (2013) demonstrate precise tractography results of the human brainstem.…”

“…We have assembled articles from a number of scientists who have made important contributions to this evolving field, and continue to shape it. The articles have been divided into a functional (Brooks et al, 2013;Henderson and Macefield, 2013;Ress and Chandrasekaran, 2013;Ritter et al, 2013) and a structural section (Deistung et al, 2013;Ford et al, 2013;Lambert et al, 2013;Yeo et al, 2013;Singleton et al, 2014).The functional section starts with a review by Brooks et al The wealth of methods and applications covered by the authors indicates that functional and structural brainstem-MRI methods have developed to a point where they can be applied to study of a wide range of neuroscientific problems. It is the hope of the editors that the brainstem will soon lose its label of a terra incognita and become a region of major interest in the neuroscience community.…”

“…We have assembled articles from a number of scientists who have made important contributions to this evolving field, and continue to shape it. The articles have been divided into a functional (Brooks et al, 2013;Henderson and Macefield, 2013;Ress and Chandrasekaran, 2013;Ritter et al, 2013) and a structural section (Deistung et al, 2013;Ford et al, 2013;Lambert et al, 2013;Yeo et al, 2013;Singleton et al, 2014).…”