Biology subjects

Basser, P.

Publications and source records attributed to Basser, P..

7 recordsLinked to original sources

bioRxiv2026

Towards Mesoscopic Human Brain Imaging Using Non-Parametric Diffusion Tensor Distribution (DTD) MRI

The majority of MR-based brain imaging methods provides macroscopic information averaged over the entire imaging voxel. Yet tissue composition and microstructure are heterogeneous within the cubic millimeter-sized MRI voxel that contains numerous distinct water pools at mesoscopic, microscopic, and nanoscopic length scales. Accurately measuring their individual characteristics in live human brain has the potential to reveal hidden salient meso/micro-structural features and uncover subtle changes that may occur in development, neurological disorders, trauma, etc. Nevertheless, because of many technical and scientific challenges, there is a dearth of robust, quantitative methods to probe tissue water dynamics at these subvoxel length scales. Here we present a novel empirical spectroscopic diffusion MRI method that estimates the probability density function (pdf) of diffusion tensors, i.e., the diffusion tensor distribution (DTD) in the human brain in-vivo. Our method entails performing a multi-dimensional Inverse Laplace Transform (ILT) which is generally an ill-posed and ill-conditioned problem. However, we overcome these obstacles using a hierarchy of lower-dimensional marginal distributions of the DTD estimated from diffusion weighted (DW) signals obtained from single, double, and triple pulsed-field gradient (PFG) experiments. Iteratively applying this hierarchy of marginal distribution progressively shrinks the space of admissible solutions. We extensively vet this framework with simulated DWI data obtained from realistic DTD motifs that mimic different cell and tissue properties seen in the brain. We then experimentally test our approach in vivo in brains of healthy normal human subjects. We segment the reconstructed DTD within a voxel to identify signatures of different tissue and cell types, and cluster these DTDs to identify various water pools. We use the high dimensional spectrum to robustly remove the free water compartment that often confounds tissue microstructure. We take ensemble averages of invariants of the micro-diffusion tensors, and measure and map their distributions to visualize salient intrinsic mesoscopic features. Since DTD MRI subsumes DTI, we also compute the family of DTI-derived quantitative imaging biomarkers from the moments of the distributions of the mean diffusivity and FA derived from the DTD. Our approach has great translational potential, revealing new microstructural features not observed previously observed in in vivo MRI.

bioengineering↗

bioRxiv2026

Nonuniform scaling of cerebellar cortical-nuclear architecture across primates revealed by cross-species atlases

The cerebellum shapes distributed motor and association networks through precisely organized pathways linking the cerebellar cortex to the deep cerebellar nuclei (DCN), its principal output structures. Whether these cortical and nuclear compartments scale proportionally across primates and how their relative expansion influences large-scale brain organization remains unclear. We generated multimodal, high-resolution cross-species 3D cerebellar atlases in marmoset, macaque, and human, integrating iron-sensitive magnetic resonance contrast with complementary histological markers to delineate DCN subdivisions in detail. Comparative volumetric analyses reveal nonuniform scaling of cerebellar cortical-nuclear architecture: cortical expansion markedly outpaces enlargement of the DCN, indicating disproportionate growth of input relative to output structures. This divergence parallels preferential expansion of posterior hemispheric territories, particularly lobules VI-IX and Crus I/II linked to higher-order association networks, whereas DCN subdivisions show selective rather than uniform scaling. Together, these findings establish nonuniform cortical-nuclear scaling as a systems-level organizational principle that reshapes cerebellar contributions to distributed brain networks.

neuroscience↗

bioRxiv2024

The Diffusion Exchange Ratio (DEXR): A minimal sampling of diffusion exchange spectroscopy to probe exchange, restriction, and time-dependence

Water exchange is increasingly recognized as an important biological process that can affect the study of biological tissue using diffusion MR. Methods to measure exchange, however, remain immature as opposed to those used to characterize restriction, with no consensus on the optimal pulse sequence(s) or signal model(s). In general, the trend has been towards data-intensive fitting of highly parameterized models. We take the opposite approach and show that a judicious sub-sample of diffusion exchange spectroscopy (DEXSY) data can be used to robustly quantify exchange, as well as restriction, in a data-efficient manner. This sampling produces a ratio of two points per mixing time: (i) one point with equal diffusion weighting in both encoding periods, which gives maximal exchange contrast, and (ii) one point with the same total diffusion weighting in just the first encoding period, for normalization. We call this quotient the Diffusion EXchange Ratio (DEXR). Furthermore, we show that it can be used to probe time-dependent diffusion by estimating the velocity autocorrelation function (VACF) over intermediate to long times ([~] 2 - 500 ms). We provide a comprehensive theoretical framework for the design of DEXR experiments in the case of static or constant gradients. Data from Monte Carlo simulations and experiments acquired in fixed and viable ex vivo neonatal mouse spinal cord using a permanent magnet system are presented to test and validate this approach. In viable spinal cord, we report the following apparent parameters from just 6 data points:{tau} k = 17 {+/-} 4 ms, fNG = 0.71 {+/-} 0.01, Reff = 1.10 {+/-} 0.01 m, and keff = 0.21 {+/-} 0.06 m/ms, which correspond to the exchange time, restricted or non-Gaussian signal fraction, an effective spherical radius, and permeability, respectively. For the VACF, we report a long-time, power-law scaling with {approx} t- 2.4, which is approximately consistent with disordered domains in 3-D. Overall, the DEXR method is shown to be highly efficient, capable of providing valuable quantitative diffusion metrics using minimal MR data.

biophysics↗

bioRxiv2022

Novel Pore Size-Controlled, Susceptibility Matched, 3D-Printed MRI Phantoms

Diffusion magnetic resonance imaging (dMRI) methods are commonly employed to infer changes in tissue microstructure. Quantities like the apparent diffusion coefficient (mADC), and the fractional anisotropy (FA), derived from diffusion tensor imaging (DTI) data, characterize voxel-averaged diffusion properties, whereas double pulse field gradient (dPFG) or double diffusion encoded (DDE) MR methods can be used to characterize heterogeneous diffusion processes occurring within the voxel. Owing to its unique modular design, our novel 3D-printed dMRI phantom exhibits both macroscopic and microscopic anisotropy and can serve to calibrate measures of them. Our phantom susceptibility is close to that of waters, enabling fast diffusion weighted echo-planar image (DW-EPI) acquisitions to be used to scan it. 3D printed microstructures offer a new medium with which to vet and validate theoretical models of diffusion and pipelines used to estimate it. HighlightsO_LIResearch highlight 1: We report the design concept and fabrication of dimensionally stable, uniformly oriented blocks or modules that can be assembled into large-scale MRI phantoms. Waffle-like structures containing blocks of aligned microcapillaries can be stacked into even larger arrays to construct diameter distribution phantoms, or fractured, to create a "powder-averaged" emulsion of randomly oriented blocks. C_LIO_LIResearch highlight 2: This phantom can be used to vet and calibrate various MRI methods, such as DTI, AxCaliber MRI, MAP-MRI, and various multiple pulsed field gradient (PFG) or multiple diffusion-encoded microstructure imaging methods. C_LI Graphical Abstract

biophysics↗

bioRxiv2022

Water exchange rates measure active transport and homeostasis in neural tissue

For its size, the brain is the most metabolically active organ in the body. Most of its energy demand is used to maintain stable homeostatic physiological conditions. Altered homeostasis and active states are hallmarks of many diseases and disorders. Yet there is currently no reliable method to assess homeostasis and absolute basal activity or activity-dependent changes non-invasively. We propose a novel, high temporal resolution low-field, high-gradient diffusion exchange NMR method capable of directly measuring cellular metabolic activity via the rate constant for water exchange across cell membranes. Using viable ex vivo neonatal mouse spinal cords, we measure a component of the water exchange rate which is active, i.e., coupled to metabolic activity. We show that this water exchange rate is sensitive primarily to tissue homeostasis and viability and provides distinct functional information in contrast to the Apparent Diffusion Coefficient (ADC), which is sensitive primarily to tissue microstructure but not activity. SIGNIFICANCE STATEMENTDespite what physiology text-books may report, water transport across membranes is not only a passive process. However, current understanding is limited because standard techniques can only measure net flux (the difference between water moving in and water moving out). Even so, water is constantly exchanging between the inside and outside of cells and organelles without net flux during homeostasis. We developed a Magnetic Resonance method able to "see" water molecules exchanging on shorter timescales than could be observed before. In neural tissue we find most water exchange is active, that is, linked to ATP-driven processes. This method may one day be translated to clinical MRI applications for measuring cellular function and activity in the human brain and body.

neuroscience↗

bioRxiv2021

Multidimensional MRI for characterization of subtle axonal injury accelerated using an adaptive nonlocal multispectral filter

Multidimensional MRI is an emerging approach that simultaneously encodes water relaxation (T1 and T2) and mobility (diffusion) and replaces voxel-averaged values with subvoxel distributions of those MR properties. While conventional (i.e., voxel-averaged) MRI methods cannot adequately quantify the microscopic heterogeneity of biological tissue, using subvoxel information allows to selectively map a specific T1-T2-diffusion spectral range that corresponds to a group of tissue elements. The major obstacle to the adoption of rich, multidimensional MRI protocols for diagnostic or monitoring purposes is the prolonged scan time. Our main goal in the present study is to evaluate the performance of a nonlocal estimation of multispectral magnitudes (NESMA) filter on reduced datasets to limit the total acquisition time required for reliable multidimensional MRI characterization of the brain. Here we focused and reprocessed results from a recent study that identified potential imaging biomarkers of axonal injury pathology from the joint analysis of multidimensional MRI, in particular voxelwise T1-T2 and diffusion-T2 spectra in human Corpus Callosum, and histopathological data. We tested the performance of NESMA and its effect on the accuracy of the injury biomarker maps, relative to the co-registered histological reference. Noise reduction improved the accuracy of the resulting injury biomarker maps, while permitting data reduction of 35.7% and 59.6% from the full dataset for T1-T2 and diffusion-T2 cases, respectively. As successful clinical proof-of-concept applications of multidimensional MRI are continuously being introduced, reliable and robust noise removal and consequent acquisition acceleration would advance the field towards clinically-feasible diagnostic multidimensional MRI protocols.

neuroscience↗

bioRxiv2019

Magnetic Resonance measurements of sub-cellular membrane structures in live and fixed neural tissue

We develop magnetic resonance (MR) methods for measuring real-time changes of tissue microstructure and membrane permeability of live and fixed neural tissue. Diffusion and exchange MR measurements are performed using the large static gradient produced by a single-sided permanent magnet. Using tissue delipidation methods, we show that water diffusion is restricted solely by lipid membranes. Most of the diffusion signal can be assigned to water in tissue which is far from membranes. The remaining 25% can be assigned to water restricted on length scales of roughly a micron or less, near or within membrane structures at the cellular, organelle, and vesicle levels. Diffusion exchange spectroscopy measures water exchanging between membrane structures and free environments at 100 s-1.

biophysics↗