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Osteoarthritis and Cartilage Mar 2020To date, the pathophysiology of the meniscus has not been fully elucidated. Due to the tissue's limited vascularization, nutrients and other molecular signals spread...
OBJECTIVE
To date, the pathophysiology of the meniscus has not been fully elucidated. Due to the tissue's limited vascularization, nutrients and other molecular signals spread through the extracellular matrix via diffusion or convection (interstitial fluid flow). Understanding transport mechanisms is crucial to elucidating meniscal pathophysiology, and to designing treatments for repair and restoration of the tissue. Similar to other fibrocartilaginous structures, meniscal morphology and composition may affect its diffusive properties. The objective of this study was to investigate the role of solute size, and tissue structure and composition on molecular diffusion in meniscus tissue.
DESIGN
Using a custom FRAP technique developed in our lab, we measured the direction-dependent diffusivity in human meniscus of six different molecular probes of size ranging from ∼300Da to 150,000Da. Diffusivity measurements were related to sample water content. SEM images were used to investigate collagen structure in relation to transport mechanisms.
RESULTS
Diffusivity was anisotropic, being significantly faster in the direction parallel to collagen fibers when compared the orthogonal direction. This was likely due to the unique structural organization of the tissue presenting pores aligned with the fibers, as observed in SEM images. Diffusion coefficients decreased as the molecular size increased, following the Ogston model. No significant correlations were found among diffusion coefficients and water content of the tissue.
CONCLUSIONS
This study provides new knowledge on the mechanisms of molecular transport in meniscal tissue. The reported results can be leveraged to further investigate tissue pathophysiology and to design treatments for tissue restoration or replacement.
Topics: Aged; Anisotropy; Biological Transport; Collagen; Dextrans; Diffusion; Extracellular Fluid; Extracellular Matrix; Female; Fluorescein; Fluorescence Recovery After Photobleaching; Humans; Hydrodynamics; Insulin; Male; Menisci, Tibial; Microscopy, Electron, Scanning; Serum Albumin, Bovine
PubMed: 31917232
DOI: 10.1016/j.joca.2019.12.006 -
Pediatric Radiology Jul 2021Diffusion tensor imaging is a widely used imaging method of brain white matter, but it is prone to imaging artifacts. The data corrections can affect the measured values.
BACKGROUND
Diffusion tensor imaging is a widely used imaging method of brain white matter, but it is prone to imaging artifacts. The data corrections can affect the measured values.
OBJECTIVE
To explore the impact of susceptibility correction on diffusion metrics.
MATERIALS AND METHODS
A cohort of 27 healthy adolescents (18 boys, 9 girls, mean age 12.7 years) underwent 3-T MRI, and we collected two diffusion data sets (anterior-posterior). The data were processed both with and without susceptibility artifact correction. We derived fractional anisotropy, mean diffusivity and histogram data of fiber length distribution from both the corrected and uncorrected data, which were collected from the corpus callosum, corticospinal tract and cingulum bilaterally.
RESULTS
Fractional anisotropy and mean diffusivity values significantly differed when comparing the pathways in all measured tracts. The fractional anisotropy values were lower and the mean diffusivity values higher in the susceptibility-corrected data than in the uncorrected data. We found a significant difference in total tract length in the corpus callosum and the corticospinal tract.
CONCLUSION
This study indicates that susceptibility correction has a significant effect on measured fractional anisotropy, and on mean diffusivity values and tract lengths. To receive reliable and comparable results, the correction should be used systematically.
Topics: Adolescent; Anisotropy; Benchmarking; Child; Corpus Callosum; Diffusion Tensor Imaging; Female; Humans; Male; White Matter
PubMed: 33893847
DOI: 10.1007/s00247-021-05000-3 -
Medicine Feb 2021MR tractography of the lumbosacral plexus (LSP) is challenging due to the difficulty of acquiring high quality data and accurately estimating the neuronal tracts. We... (Comparative Study)
Comparative Study
MR tractography of the lumbosacral plexus (LSP) is challenging due to the difficulty of acquiring high quality data and accurately estimating the neuronal tracts. We proposed an algorithm for an accurate visualization and assessment of the major LSP bundles using the segmentation of the cauda equina as seed points for the initial starting area for the fiber tracking algorithm.Twenty-six healthy volunteers underwent MRI examinations on a 3T MR scanner using the phased array coils with optimized measurement protocols for diffusion-weighted images and coronal T2 weighted 3D short-term inversion recovery sampling perfection with application optimized contrast using varying flip angle evaluation sequences used for LSP fiber reconstruction and MR neurography (MRN).The fiber bundles reconstruction was optimized in terms of eliminating the muscle fibers contamination using the segmentation of cauda equina, the effects of the normalized quantitative anisotropy (NQA) and angular threshold on reconstruction of the LSP. In this study, the NQA parameter has been used for fiber tracking instead of fractional anisotropy (FA) and the regions of interest positioning was precisely adjusted bilaterally and symmetrically in each individual subject.The diffusion data were processed in individual L3-S2 nerve fibers using the generalized Q-sampling imaging algorithm. Data (mean FA, mean diffusivity, axial diffusivity and radial diffusivity, and normalized quantitative anisotropy) were statistically analyzed using the linear mixed-effects model. The MR neurography was performed in MedINRIA and post-processed using the maximum intensity projection method to demonstrate LSP tracts in multiple planes.FA values significantly decreased towards the sacral region (P < .001); by contrast, mean diffusivity, axial diffusivity, radial diffusivity and NQA values significantly increased towards the sacral region (P < .001).Fiber tractography of the LSP was feasible in all examined subjects and closely corresponded with the nerves visible in the maximum intensity projection images of MR neurography. Usage of NQA instead of FA in the proposed algorithm enabled better separation of muscle and nerve fibers.The presented algorithm yields a high quality reconstruction of the LSP bundles that may be helpful both in research and clinical practice.
Topics: Adult; Algorithms; Anisotropy; Cauda Equina; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Female; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Lumbosacral Plexus; Lumbosacral Region; Magnetic Resonance Imaging; Male; Spinal Nerves
PubMed: 33578590
DOI: 10.1097/MD.0000000000024646 -
Journal of Neuroscience Methods Jan 2021Diffusion encoding along multiple spatial directions per signal acquisition can be described in terms of a b-tensor. The benefit of tensor-valued diffusion encoding is... (Review)
Review
Diffusion encoding along multiple spatial directions per signal acquisition can be described in terms of a b-tensor. The benefit of tensor-valued diffusion encoding is that it unlocks the 'shape of the b-tensor' as a new encoding dimension. By modulating the b-tensor shape, we can control the sensitivity to microscopic diffusion anisotropy which can be used as a contrast mechanism; a feature that is inaccessible by conventional diffusion encoding. Since imaging methods based on tensor-valued diffusion encoding are finding an increasing number of applications we are prompted to highlight the challenge of designing the optimal gradient waveforms for any given application. In this review, we first establish the basic design objectives in creating field gradient waveforms for tensor-valued diffusion MRI. We also survey additional design considerations related to limitations imposed by hardware and physiology, potential confounding effects that cannot be captured by the b-tensor, and artifacts related to the diffusion encoding waveform. Throughout, we discuss the expected compromises and tradeoffs with an aim to establish a more complete understanding of gradient waveform design and its impact on accurate measurements and interpretations of data.
Topics: Anisotropy; Artifacts; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging
PubMed: 33242529
DOI: 10.1016/j.jneumeth.2020.109007 -
Molecular Biology of the Cell May 2022Chromatin organization and dynamics are critical for gene regulation. In this work we present a methodology for fast and parallel three-dimensional (3D) tracking of...
Chromatin organization and dynamics are critical for gene regulation. In this work we present a methodology for fast and parallel three-dimensional (3D) tracking of multiple chromosomal loci of choice over many thousands of frames on various timescales. We achieved this by developing and combining fluorogenic and replenishable nanobody arrays, engineered point spread functions, and light sheet illumination. The result is gentle live-cell 3D tracking with excellent spatiotemporal resolution throughout the mammalian cell nucleus. Correction for both sample drift and nuclear translation facilitated accurate long-term tracking of the chromatin dynamics. We demonstrate tracking both of fast dynamics (50 Hz) and over timescales extending to several hours, and we find both large heterogeneity between cells and apparent anisotropy in the dynamics in the axial direction. We further quantify the effect of inhibiting actin polymerization on the dynamics and find an overall increase in both the apparent diffusion coefficient D* and anomalous diffusion exponent α and a transition to more-isotropic dynamics in 3D after such treatment. We think that in the future our methodology will allow researchers to obtain a better fundamental understanding of chromatin dynamics and how it is altered during disease progression and after perturbations of cellular function.
Topics: Animals; Anisotropy; Chromatin; Chromosomes; Diffusion; Gene Expression Regulation; Mammals
PubMed: 35352962
DOI: 10.1091/mbc.E21-10-0514 -
Scientific Reports Mar 2021Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA),...
Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA), axial/radial diffusivities (AxD/RD), and mode of anisotropy (MA). Standard DTI is susceptible to the effects of extracellular free water (FW), which can be removed using an advanced free-water DTI (FW-DTI) model. The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer's disease (AD). Data were obtained from the Open Access Series of Imaging Studies (OASIS-3) database and included both healthy controls (HC) and mild-to-moderate AD. With both standard and FW-DTI, decreased FA was found in AD, mainly in the corpus callosum and fornix, consistent with neurodegenerative mechanisms. Widespread higher AxD and RD were observed with standard DTI; however, the FW index, indicative of AD-associated neurodegeneration, was significantly elevated in these regions in AD, highlighting the potential impact of free water contributions on standard DTI in neurodegenerative pathologies. Using FW-DTI, improved consistency was observed in FA, AxD, and RD, and the complementary FW index was higher in the AD group as expected. With both standard and FW-DTI, higher values of MA coupled with higher values of FA in AD were found in the anterior thalamic radiation and cortico-spinal tract, most likely arising from a loss of crossing fibers. In conclusion, FW-DTI better reflects the underlying pathology of AD and improves the accuracy of DTI metrics related to WM integrity in Alzheimer's disease.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anisotropy; Biomarkers; Cognitive Dysfunction; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Humans; Middle Aged; White Matter
PubMed: 33772083
DOI: 10.1038/s41598-021-86505-7 -
AJNR. American Journal of Neuroradiology Oct 2019
Review
Topics: Algorithms; Anisotropy; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Humans; Neuroimaging
PubMed: 31558496
DOI: 10.3174/ajnr.A6235 -
Journal of Biomedical Optics Dec 2022Mueller matrix polarimetry (MMP) and spatial frequency domain imaging (SFDI) are wide-field optical imaging modalities that differentiate tissue primarily by structure...
SIGNIFICANCE
Mueller matrix polarimetry (MMP) and spatial frequency domain imaging (SFDI) are wide-field optical imaging modalities that differentiate tissue primarily by structure alignment and photon transport coefficient, respectively. Because these effects can be related, combining MMP and SFDI may enhance tissue differentiation beyond the capability of each modality alone.
AIM
An instrument was developed to combine MMP and SFDI with the goal of testing whether it enhances contrast of features in reflection mode.
APPROACH
The instrument was constructed using liquid crystal elements for polarization control, a digital light processing projector for generating sinusoidal illumination patterns, and a digital camera for imaging. A theoretical analysis shows that the SFD Mueller matrix is complex-valued and does not follow the same behavior as a regular Mueller matrix. Images were acquired from an anisotropic tissue phantom, an optical fiber bundle, and cerebellum, thalamus, and cerebrum tissues.
RESULTS
The measurement results suggest that singly scattered, few scattered, and diffusely scattered photon paths can be distinguished in some of the samples investigated. The combined imaging modality yields additional spatial frequency phase information, which highlights paths having only a few scattering events.
CONCLUSIONS
The combination of MMP and SFDI offers contrast mechanisms inaccessible by each modality used alone.
Topics: Phantoms, Imaging; Optical Imaging; Anisotropy; Spectrum Analysis
PubMed: 36530345
DOI: 10.1117/1.JBO.27.12.126003 -
NeuroImage Feb 2022Noninvasively detecting and characterizing modulations in cellular scale micro-architecture remains a desideratum for contemporary neuroimaging. Diffusion MRI (dMRI) has...
Noninvasively detecting and characterizing modulations in cellular scale micro-architecture remains a desideratum for contemporary neuroimaging. Diffusion MRI (dMRI) has become the mainstay methodology for probing microstructure, and, in ischemia, its contrasts have revolutionized stroke management. Diffusion kurtosis imaging (DKI) has been shown to significantly enhance the sensitivity of stroke detection compared to its diffusion tensor imaging (DTI) counterparts. However, the interpretation of DKI remains ambiguous as its contrast may arise from competing kurtosis sources related to the anisotropy of tissue components, diffusivity variance across components, and microscopic kurtosis (e.g., arising from cross-sectional variance, structural disorder, and restriction). Resolving these sources may be fundamental for developing more specific imaging techniques for stroke management, prognosis, and understanding its pathophysiology. In this study, we apply Correlation Tensor MRI (CTI) - a double diffusion encoding (DDE) methodology recently introduced for deciphering kurtosis sources based on the unique information captured in DDE's diffusion correlation tensors - to investigate the underpinnings of kurtosis measurements in acute ischemic lesions. Simulations for the different kurtosis sources revealed specific signatures for cross-sectional variance (representing neurite beading), edema, and cell swelling. Ex vivo CTI experiments at 16.4 T were then performed in an experimental photothrombotic stroke model 3 h post-stroke (N = 10), and successfully separated anisotropic, isotropic, and microscopic non-Gaussian diffusion sources in the ischemic lesions. Each of these kurtosis sources provided unique contrasts in the stroked area. Particularly, microscopic kurtosis was shown to be a primary "driver" of total kurtosis upon ischemia; its large increases, coupled with decreases in anisotropic kurtosis, are consistent with the expected elevation in cross-sectional variance, likely linked to beading effects in small objects such as neurites. In vivo experiments at 9.4 T at the same time point (3 h post ischemia, N = 5) demonstrated the stability and relevance of the findings and showed that fixation is not a dominant confounder in our findings. In future studies, the different CTI contrasts may be useful to address current limitations of stroke imaging, e.g., penumbra characterization, distinguishing lesion progression form tissue recovery, and elucidating pathophysiological correlates.
Topics: Animals; Anisotropy; Diffusion Tensor Imaging; Image Interpretation, Computer-Assisted; Male; Mice; Mice, Inbred C57BL; Monte Carlo Method; Stroke
PubMed: 34929382
DOI: 10.1016/j.neuroimage.2021.118833 -
Journal of Alzheimer's Disease : JAD 2022Imaging biomarkers are increasingly used in Alzheimer's disease (AD), and the identification of sex differences using neuroimaging may provide insight into disease...
BACKGROUND
Imaging biomarkers are increasingly used in Alzheimer's disease (AD), and the identification of sex differences using neuroimaging may provide insight into disease heterogeneity, progression, and therapeutic targets.
OBJECTIVE
The purpose of this study was to investigate differences in grey matter (GM) volume and white matter (WM) microstructural disorganization between males and females with AD using voxel-based morphometry (VBM) and free-water-corrected diffusion tensor imaging (FW-DTI).
METHODS
Data were downloaded from the OASIS-3 database, including 158 healthy control (HC; 86 females) and 46 mild AD subjects (24 females). VBM and FW-DTI metrics (fractional anisotropy (FA), axial and radial diffusivities (AxD and RD, respectively), and FW index) were compared using effect size for the main effects of group, sex, and their interaction.
RESULTS
Significant group and sex differences were observed, with no significant interaction. Post-hoc comparisons showed that AD is associated with reduced GM volume, reduced FW-FA, and higher FW-RD/FW-index, consistent with neurodegeneration. Females in both groups exhibited higher GM volume than males, while FW-DTI metrics showed sex differences only in the AD group. Lower FW, lower FW-FA and higher FW-RD were observed in females relative to males in the AD group.
CONCLUSION
The combination of VBM and DTI may reveal complementary sex-specific changes in GM and WM associated with AD and aging. Sex differences in GM volume were observed for both groups, while FW-DTI metrics only showed significant sex differences in the AD group, suggesting that WM tract disorganization may play a differential role in AD pathophysiology between females and males.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Anisotropy; Biomarkers; Case-Control Studies; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Sex Characteristics; White Matter
PubMed: 34842185
DOI: 10.3233/JAD-210406