Quantitative validation of a nonlinear histology-MRI coregistration method using generalized Q-sampling imaging in complex human cortical white matter

Abstract

Advanced diffusion MRI methods have recently been proposed for detection of pathologies such as traumatic axonal injury and chronic traumatic encephalopathy which commonly affect complex cortical brain regions. However, radiological-pathological correlations in human brain tissue that detail the relationship between the multi-component diffusion signal and underlying pathology are lacking. We present a nonlinear voxel based two dimensional coregistration method that is useful for matching diffusion signals to quantitative metrics of high resolution histological images. When validated in ex vivo human cortical tissue at a 250 × 250 × 500 micron spatial resolution, the method proved robust in correlations between generalized q-sampling imaging and histologically based white matter fiber orientations, with r = 0.94 for the primary fiber direction and r = 0.88 for secondary fiber direction in each voxel. Importantly, however, the correlation was substantially worse with reduced spatial resolution or with fiber orientations derived using a diffusion tensor model. Furthermore, we have detailed a quantitative histological metric of white matter fiber integrity termed power coherence capable of distinguishing between architecturally complex but intact white matter from disrupted white matter regions. These methods may allow for more sensitive and specific radiological-pathological correlations of neurodegenerative diseases affecting complex gray and white matter.

Design and Validation of Diffusion MRI Models of White Matter

“…Among the first examples to conduct direct validation studies, manual segmentation of axons in stained tissue white matter sections were compared to DTI and DSI (Diffusion Spectrum Imaging) estimates (Leergaard et al, 2010). A variety of automated image processing techniques have been used to derive the angular orientation profiles of stained tissues, permitting large-scale automated analysis of tissue specimens (Budde and Annese, 2013b; Budde and Frank, 2012; Choe et al, 2012; Gangolli et al, 2017; Grussu et al, 2016; Hansen et al, 2011; Mitter et al, 2015; Mollink et al, 2017; Nazaran et al, 2016; Seehaus et al, 2015). These methods generally fall into classes of algorithms that use pattern-matching, Fourier analysis, or edge detection.…”

Systematic review on the characterization of chronic traumatic encephalopathy by MRI and MRS

“…Ten studies based on chronic TBI individuals examined a mixed gender experimental group and one did not provide information on the sex of study participants . All studies focusing on contact sports athletes investigated solely male experimental groups, and the two ex vivo studies did not provide any information on gender . Contact sports athletes included soccer players, boxers, American football players, baseball players, and wrestlers.…”

“…The systematic search resulted in only two articles using ex vivo samples of patients with confirmed CTE (for more details, refer to Table ).…”

“…Twenty‐one studies applied structural MRI, including T 1 ‐weighted (T 1 ‐w), T 2 ‐weighted (T 2 ‐w), fluid attenuated inversion recovery (FLAIR), susceptibility weighted imaging (SWI), and proton‐density weighted (PD‐w) imaging . Thirteen studies used diffusion MRI, specifically diffusion tensor imaging (DTI), generalized q‐sampling imaging (GQI), diffusion kurtosis imaging (DKI), and diffusion weighted imaging (DWI) . Six studies acquired functional MRI (fMRI) with either blood oxygenation level‐dependent (BOLD) or arterial spin labeling (ASL) sequences .…”

“…The two ex vivo studies focused on advanced diffusion modeling and examined brain regions (Brodmann Area [BA] 8/9) of deceased patients with a confirmed neuropathological diagnosis of CTE . By correlating histological power coherence and the diffusion MRI parameters, it was found that WM power coherence and FA were significantly correlated .…”