Biology subjects

Reddick, W. E.

Publications and source records attributed to Reddick, W. E..

4 recordsLinked to original sources

bioRxiv2025

Comparing Orientation-Dependent Transverse Relaxation at 3T and 7T: Deciphering Anisotropic Relaxation Mechanisms in White Matter

Purpose: This work aims to elucidate the mechanisms underlying orientation-dependent transverse relaxation in human brain white matter (WM), which have long been ambiguous. Methods: We analyzed publicly available 3T and 7T DTI datasets (b-values = 1000 and 2000 s/mm2) from 25 young adults participating in the Human Connectome Project. Orientation-dependent transverse relaxation R2 profiles from whole brain WM were generated from T2-weighted images (b-value = 0) and characterized using a previously developed cone model based on the generalized magic angle effect (MAE). Derived anisotropic R2 or R2a values were compared between different magnetic fields. Similar comparisons were also conducted for the derived R2a values from whole brain WM and two fiber tracts, based on gradient-echo signals reported in the literature. Classical relaxation theories predict that the ratio of (R2a (7T))/R2a (3T)) will be unity or (7/3)^2 (i.e., approximately 5.4) if the measured orientation-dependent R2 arises exclusively from MAE or from the previously proposed susceptibility effect, respectively. Results: Fitted model parameters were comparable for DTI datasets with b-values of 1000 and 2000 (s/mm2). The fitted R2a increased, on average, from 3.6{+/-}1.1 (1/s) at 3T to 5.4{+/-}1.5 (1/s) at 7T for DTI datasets with a b-value=1000 s/mm2. The measured ratio of (R2a (7T))/(R2a (3T)) was thus approximately 1.5. However, based on gradient-echo signals, this ratio essentially became unity within the measurement precision. Conclusion: This study suggests that MAE is the primary mechanism for the observed orientation-dependent transverse relaxation at 3T in human brain WM, offering a different perspective from previous literature.

biophysics↗

bioRxiv2025

Unifying Orientation-Dependent Relaxation and Diffusion Around Axonal Fibers from DTI: Characterizing Fiber-Tract-Specific Anisotropic R2 Profiles of the Corpus Callosum

This work aims to characterize fiber-tract-specific orientation-dependent R2 from the seven callosal segments (CC1-CC7) based on human brain Connectome high-resolution DTI datasets. WM voxels from each segment were masked by the thresholds of FA and mode of anisotropy. Encoded in T2W images (b-value = 0), an orientation-dependent R2 profile was constructed based on voxel-wise fiber orientations and characterized by a "cone" model. This allowed [Formula], an orientation-dependent or anisotropic R2, to be separated from its orientation-independent or isotropic counterpart. Except for [Formula], no discernible differences were found for the fits between the two b-values. On average, [Formula] increased from 2.4{+/-}0.2 (1/s) to 3.2{+/-}0.3 (1/s) as the b-value increased. Furthermore, [Formula] showed an increasing trend from CC1 to CC7 and the open angle of the cone fluctuated around 65{degrees}. As usual, FA was found increasing from CC1 to CC7 and from a higher to a lower b-value. In conclusion, we have shown that fiber-tract-specific Anisotropic R2 profiles from the callosal segments can be characterized by a cone model. The proposed method offers a unique opportunity to reevaluate existing clinical DTI studies and optimize new ones for characterizing specific WM tracts in both healthy and diseased subjects.

biophysics↗

bioRxiv2024

High-Dimensional Mediation Analysis with Network Mediators: Applications to Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with survivors frequently experiencing long-term neurocognitive morbidities. Here, we utilize the TOTXVI clinical trial data to elucidate the mechanisms underlying treatment-related neurocognitive side effects in pediatric ALL patients by incorporating brain connectivity network data. To enable such analysis, we propose a high-dimensional mediation analysis method with a novel network mediation structural shrinkage (NMSS) prior, which is particularly suited for analyzing high-dimensional brain structural connectivity network data that serve as mediators. Our method is capable of addressing the structural dependencies of brain connectivity networks including sparsity, effective degrees of nodes, and modularity, yielding accurate estimates of the high-dimensional coefficients and mediation effects. We demonstrate the effectiveness and superiority of the proposed NMSS method through simulation studies and apply it to the TOTXVI data, revealing significant mediation effects of brain connectivity on visual processing speed directed by IT intensity. The findings shed light on the potential of targeted interventions to mitigate neurocognitive deficits in pediatric ALL survivors.

cancer biology↗

bioRxiv2016

Tractography-based connectomes are dominated by false-positive connections

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

neuroscience↗