scholarly journals Probabilistic Assessment of Nerve Regeneration with Diffusion MRI: Validation in Rat Models of Peripheral Nerve Trauma

2019 ◽  
Author(s):  
Isaac V. Manzanera Esteve ◽  
Angel F. Farinas ◽  
Alonda C. Pollins ◽  
Marlieke E. Nussenbaum ◽  
Nancy L. Cardwell ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Diffusion Mri ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Behavioral Data ◽  
Diffusion Kurtosis Imaging ◽  
Partial Recovery ◽  
Limited Information ◽  
Sprague Dawley ◽  
Post Surgery

ABSTRACTNerve regeneration after injury must occur in a timely fashion to restore function. Unfortunately, current methods (e.g., electrophysiology) provide limited information following trauma, resulting in delayed management and suboptimal outcomes. Herein, we evaluated the ability of diffusion MRI to monitor nerve regeneration after injury/repair. Sprague-Dawley rats were divided into three treatment groups (sham=21, crush=23, cut/repair=19) and ex vivo diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was performed 1-12 weeks post-surgery. Behavioral data showed a distinction between crush and cut/repair nerves at 4 weeks. This was consistent with DTI, which found that thresholds based on the ratio of radial and axial diffusivities (RD/AD=0.40±0.02) and fractional anisotropy (FA=0.53±0.01) differentiated crush from cut/repair injuries. By the 12th week, cut/repair nerves whose behavioral data indicated a partial recovery were below the RD/AD threshold (and above the FA threshold), while nerves that did not recover were on the opposite side of each threshold. Additional morphometric analysis indicated that DTI-derived normalized scalar indices report on axon density (RD/AD: r=−0.54, p<1e-3; FA: r=0.56, p<1e-3). Interestingly, higher-order DKI analyses did not improve our ability classify recovery. These findings suggest that DTI can distinguish successful/unsuccessful nerve repairs and potentially identify cases that require reoperation.

scholarly journals Probabilistic Assessment of Nerve Regeneration with Diffusion MRI in Rat Models of Peripheral Nerve Trauma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Isaac V. Manzanera Esteve ◽  
Angel F. Farinas ◽  
Alonda C. Pollins ◽  
Marlieke E. Nussenbaum ◽  
Nancy L. Cardwell ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Diffusion Mri ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Behavioral Data ◽  
Diffusion Kurtosis Imaging ◽  
Partial Recovery ◽  
Limited Information ◽  
Sprague Dawley ◽  
Post Surgery

AbstractNerve regeneration after injury must occur in a timely fashion to restore function. Unfortunately, current methods (e.g., electrophysiology) provide limited information following trauma, resulting in delayed management and suboptimal outcomes. Herein, we evaluated the ability of diffusion MRI to monitor nerve regeneration after injury/repair. Sprague-Dawley rats were divided into three treatment groups (sham = 21, crush = 23, cut/repair = 19) and ex vivo diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was performed 1–12 weeks post-surgery. Behavioral data showed a distinction between crush and cut/repair nerves at 4 weeks. This was consistent with DTI, which found that thresholds based on the ratio of radial and axial diffusivities (RD/AD = 0.40 ± 0.02) and fractional anisotropy (FA = 0.53 ± 0.01) differentiated crush from cut/repair injuries. By the 12th week, cut/repair nerves whose behavioral data indicated a partial recovery were below the RD/AD threshold (and above the FA threshold), while nerves that did not recover were on the opposite side of each threshold. Additional morphometric analysis indicated that DTI-derived normalized scalar indices report on axon density (RD/AD: r = −0.54, p < 1e-3; FA: r = 0.56, p < 1e-3). Interestingly, higher-order DKI analyses did not improve our ability classify recovery. These findings suggest that DTI may provide promising biomarkers for distinguishing successful/unsuccessful nerve repairs and potentially identify cases that require reoperation.

scholarly journals Repeated Mild Traumatic Brain Injury Results in Long-Term White-Matter Disruption

2014 ◽  
Vol 34 (4) ◽  
pp. 715-723 ◽  
Author(s):  
Virginia Donovan ◽  
Claudia Kim ◽  
Ariana K Anugerah ◽  
Jacqueline S Coats ◽  
Udochuwku Oyoyo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Health Concern ◽  
Sprague Dawley ◽  
G Ratio

Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI.

scholarly journals Age, sex, and puberty related development of the corpus callosum: a multi-technique diffusion MRI study

2017 ◽  
Author(s):  
Sila Genc ◽  
Charles B Malpas ◽  
Gareth Ball ◽  
Timothy J Silk ◽  
Marc L Seal
Keyword(s):  
Corpus Callosum ◽  
Diffusion Mri ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Profile Analysis ◽  
Pubertal Development ◽  
Strong Relationship ◽  
Childhood And Adolescence ◽  
Fibre Density ◽  
The Impact

AbstractPurposeThe corpus callosum is integral to the central nervous system, and continually develops with age by virtue of increasing axon diameter and ongoing myelination. Magnetic resonance imaging (MRI) techniques offer a means to disentangle these two aspects of white matter development. We investigate the profile of microstructural metrics across the corpus callosum, and assess the impact of age, sex and pubertal development on these processes.MethodsThis study made use of two independent paediatric populations. Multi-shell diffusion MRI data were analysed to produce a suite of diffusion tensor imaging (DTI), neurite orientation density and dispersion imaging (NODDI), and apparent fibre density (AFD) metrics. A multivariate profile analysis was performed for each diffusion metric across 10 subdivisions of the corpus callosum.ResultsAll diffusion metrics significantly varied across the length of the corpus callosum. AFD exhibited a strong relationship with age across the corpus callosum (partial η2 = .65), particularly in the posterior body of the corpus callosum (partial η2 = .72). In addition, females had significantly higher AFD compared with males, most markedly in the anterior splenium (partial η2 = .14) and posterior genu (partial η2 = .13). Age-matched pubertal group differences were localised to the splenium.ConclusionWe present evidence of a strong relationship between apparent fibre density and age, sex, and puberty during development. These results are consistent with ex vivo studies of fibre morphology, providing insights into the dynamics of axonal development in childhood and adolescence using diffusion MRI.Target journalsBrain Structure & Function; HBM; NeuroImage; Developmental Cognitive Neuroscience

scholarly journals Molecular and cellular correlates of human nerve regeneration: ADCYAP1 encoding PACAP enhances sensory neuron outgrowth

2019 ◽  
Author(s):  
Annina B Schmid ◽  
Georgios Baskozos ◽  
Katherine Windsor ◽  
Pall Karlsson ◽  
Oliver Sandy-Hindmarch ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Sensory Nerve ◽  
Neural Regeneration ◽  
Human Model ◽  
Symptom Improvement ◽  
Decompression Surgery ◽  
Partial Recovery ◽  
Post Surgery ◽  
Human Nerve

AbstractWe only have a rudimentary understanding of the molecular and cellular determinants of human nerve regeneration. Here, we use carpal tunnel syndrome (CTS) as a human model system to prospectively evaluate correlates of neural regeneration and their relationship with clinical recovery after decompression surgery. At 6 months post-surgery, we noted a significant improvement of median nerve neurophysiological and somatosensory function. Serial skin biopsies revealed a partial recovery of intraepidermal innervation, whose extent correlated with symptom improvement. In myelinated afferents, nodal length increased postoperatively. Transcriptional profiling of the skin revealed 23 differentially expressed genes following decompression, with ADCYAP1 (encoding PACAP) being the most strongly upregulated and showing an association with regeneration of intraepidermal nerve fibres. Using human induced pluripotent stem cell-derived sensory neurons, we confirmed that PACAP significantly enhances axon outgrowth in vivo. Since PACAP signals through G-protein receptors, this pathway provides an interesting therapeutic target for human sensory nerve regeneration.

scholarly journals Enabling complex fibre geometries using 3D printed axon-mimetic phantoms

2021 ◽  
Author(s):  
Tristan K. Kuehn ◽  
Farah N. Mushtaha ◽  
Ali R. Khan ◽  
Corey A. Baron
Keyword(s):  
Diffusion Mri ◽  
Volume Fraction ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Ground Truth ◽  
Diffusion Kurtosis Imaging ◽  
Strongly Correlated ◽  
3D Print ◽  
3D Printed ◽  
Stick Model

AbstractPurposeTo introduce a method to create 3D-printed axon-mimetic phantoms with complex fibre orientations to characterize the performance of diffusion MRI models and representations in the presence of orientation dispersion.MethodsAn extension to an open source 3D printing package was created to 3D print a set of five 3D-printed axon-mimetic (3AM) phantoms with various combinations of bending and crossing fibre orientations. A two-shell diffusion MRI scan of the five phantoms in water was performed at 9.4T. Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), the ball and stick model, neurite orientation density and dispersion imaging (NODDI), and Bingham-NODDI were all fit to the resulting diffusion MRI data. A fiducial in each phantom was used to register a ground truth map of that phantom’s crossing angles and/or arc radius to the diffusion-weighted images. Metrics from each model and representation were compared to the ground-truth maps, and a quadratic regression model was fit to each combination of output metric and ground-truth metric.ResultsThe mean diffusivity (MD) metric defined by DTI was insensitive to crossing angle, but increased with fibre curvature. Axial diffusivity (AD) decreased sharply with increasing crossing angle. DKI’s diffusivity metrics replicated the trends seen in DTI, and its mean kurtosis (MK) metric, decreased with fibre curvature, except in regions with high crossing angles. The estimated stick volume fraction in the ball and stick model decreased with increasing fibre curvature and crossing angle. NODDI’s intra-neurite volume fraction was insensitive to crossing angle, and its orientation dispersion index (ODI) was strongly correlated to crossing angle. Bingham-NODDI’s intra-neurite volume fraction was also insensitive to crossing angle, while its primary ODI (ODIP) was also strongly correlated to crossing angle and its secondary ODI (ODIS) was insensitive to crossing angle. For both NODDI models, the volume fractions of the extra-neurite and CSF compartments had low reliability with no clear relationship to crossing angle.ConclusionsThis study demonstrates that inexpensive 3D-printed axon-mimetic phantoms can be used to investigate the effect of fibre curvature and crossings on diffusion MRI representations and models of diffusion signal. As a proof of concept, the dependence of several representations and models on fibre dispersion/crossing were investigated. As expected, Bingham-NODDI was best able to characterize planar fibre dispersion in the phantoms.

scholarly journals MESMERISED: Super-accelerated 7 T STEAM imaging for quantitative multi-contrast and diffusion MRI

2020 ◽  
Author(s):  
F.J. Fritz ◽  
B.A. Poser ◽  
A. Roebroeck
Keyword(s):  
Diffusion Mri ◽  
Diffusion Tensor ◽  
Diffusion Imaging ◽  
B Value ◽  
Diffusion Kurtosis Imaging ◽  
Acquisition Time ◽  
Whole Brain ◽  
B Values ◽  
Isotropic Resolution ◽  
And Diffusion

AbstractThere is an increasing interest in quantitative imaging of T1, T2 and diffusion contrast in the brain due to greater robustness against bias fields and artifacts, as well as better biophysical interpretability in terms of microstructure. However, acquisition time constraints are a challenge, particularly when multiple quantitative contrasts are desired and when extensive sampling of diffusion directions, high b-values or long diffusion times are needed for multi-compartment microstructure modeling. Although ultra-high fields of 7 T and above have desirable properties for many MR modalities, the shortening T2 and the high specific absorption rate (SAR) of inversion and refocusing pulses bring great challenges to quantitative T1, T2 and diffusion imaging. Here, we present the MESMERISED sequence (Multiplexed Echo Shifted Multiband Excited and Recalled Imaging of STEAM Encoded Diffusion). MESMERISED removes the dead time in Stimulated Echo Acquisition Mode (STEAM) imaging by an echo-shifting mechanism. The echo-shift (ES) factor is independent of multiband (MB) acceleration and allows for very high multiplicative (ESxMB) acceleration factors, particularly under moderate and long mixing times. This results in high duty cycle and time efficiency at 7 T, particularly for quantitative T1 and diffusion imaging, while also retaining the capacity to perform quantitative T2 and B1 mapping. We demonstrate the super-acceleration of MESMERISED for whole-brain T1 relaxometry with total acceleration factors up to 36 at 1.8 mm isotropic resolution, and up to 54 at 1.25 mm resolution qT1 imaging, corresponding to a 6x and 9x speed-up, respectively, compared to MB-only accelerated acquisitions. We demonstrate quantitative T2 and B1 mapping to illustrate multi-contrast mapping with the same MESMERISED sequence and the same readout train. Finally, we demonstrate highly efficient diffusion MRI with high b-values and long diffusion times in two separate cases. First, we show that super-accelerated multi-shell diffusion acquisitions with 370 whole-brain diffusion volumes over 8 b-value shells up to b = 7000 s/mm2 can be generated at 2 mm isotropic in under 8 minutes, a data rate of almost a volume per second, or at 1.8 mm isotropic in under 11 minutes. Second, we demonstrate time-efficient sampling of different diffusion times with 1.8 mm isotropic diffusion data acquired at four diffusion times up to 290 ms, which supports both Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI) at each diffusion time. MESMERISED extends possibilities to efficiently probe T1, T2 and diffusion contrast for multi-component modeling of tissue microstructure.

scholarly journals Combination of histochemical analyses and micro-MRI reveals regional changes of the murine cervix in preparation for labor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antara Chatterjee ◽  
Rojan Saghian ◽  
Anna Dorogin ◽  
Lindsay S. Cahill ◽  
John G. Sled ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Muscle Cells ◽  
Pregnant Mouse ◽  
Collagen Fibers ◽  
Muscular Layer ◽  
Tissue Organization ◽  
Picrosirius Red

AbstractThe cervix is responsible for maintaining pregnancy, and its timely remodeling is essential for the proper delivery of a baby. Cervical insufficiency, or “weakness”, may lead to preterm birth, which causes infant morbidities and mortalities worldwide. We used a mouse model of pregnancy and term labor, to examine the cervical structure by histology (Masson Trichome and Picrosirius Red staining), immunohistochemistry (Hyaluronic Acid Binding Protein/HABP), and ex-vivo MRI (T2-weighted and diffusion tensor imaging), focusing on two regions of the cervix (i.e., endocervix and ectocervix). Our results show that mouse endocervix has a higher proportion of smooth muscle cells and collagen fibers per area, with more compact tissue structure, than the ectocervix. With advanced gestation, endocervical changes, indicative of impending delivery, are manifested in fewer smooth muscle cells, expansion of the extracellular space, and lower presence of collagen fibers. MRI detected three distinctive zones in pregnant mouse endocervix: (1) inner collagenous layer, (2) middle circular muscular layer, and (3) outer longitudinal muscular layer. Diffusion MRI images detected changes in tissue organization as gestation progressed suggesting the potential application of this technique to non-invasively monitor cervical changes that precede the onset of labor in women at risk for preterm delivery.

scholarly journals The effect of nano-hydroxyapatite/chitosan scaffolds on rat calvarial defects for bone regeneration

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Emmanouil Chatzipetros ◽  
Spyros Damaskos ◽  
Konstantinos I. Tosios ◽  
Panos Christopoulos ◽  
Catherine Donta ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Mean Value ◽  
Parietal Bone ◽  
Female Rats ◽  
Sprague Dawley ◽  
Post Surgery ◽  
Group A ◽  
The Mean ◽  
Group B ◽  
The Right

Abstract Background This study aims at determining the biological effect of 75/25 w/w nano-hydroxyapatite/chitosan (nHAp/CS) scaffolds on bone regeneration, in terms of fraction of bone regeneration (FBR), total number of osteocytes (Ost), and osteocyte cell density (CD), as well as its biodegradability. Methods Two critical-size defects (CSDs) were bilaterally trephined in the parietal bone of 36 adult Sprague-Dawley rats (18 males and 18 females); the left remained empty (group A), while the right CSD was filled with nHAp/CS scaffold (group B). Two female rats died postoperatively. Twelve, 11, and 11 rats were euthanized at 2, 4, and 8 weeks post-surgery, respectively. Subsequently, 34 specimens were resected containing both CSDs. Histological and histomorphometric analyses were performed to determine the FBR, calculated as [the sum of areas of newly formed bone in lateral and central regions of interest (ROIs)]/area of the original defect, as well as the Ost and the CD (Ost/mm2) in each ROI of both groups (A and B). Moreover, biodegradability of the nHAp/CS scaffolds was estimated via the surface area of the biomaterial (BmA) in the 2nd, 4th, and 8th week post-surgery. Results The FBR of group B increased significantly from 2nd to 8th week compared to group A (P = 0.009). Both the mean CD and the mean Ost values of group B increased compared to group A (P = 0.004 and P < 0.05 respectively). Moreover, the mean value of BmA decreased from 2nd to 8th week (P = 0.001). Conclusions Based on histological and histomorphometric results, we support that 75/25 w/w nHAp/CS scaffolds provide an effective space for new bone formation.

scholarly journals Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

2021 ◽  
Vol 22 (10) ◽  
pp. 5216
Author(s):  
Koji Kamagata ◽  
Christina Andica ◽  
Ayumi Kato ◽  
Yuya Saito ◽  
Wataru Uchida ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Diffusion Tensor Imaging ◽  
Magnetic Resonance ◽  
Neurodegenerative Diseases ◽  
Diffusion Magnetic Resonance Imaging ◽  
New Technologies ◽  
Diffusion Tensor ◽  
Free Water ◽  
Diffusion Kurtosis Imaging ◽  
Resonance Imaging

There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.

In Vivo and ex Vivo Approaches to Studying the Biomechanical Properties of Healing Wounds in Rat Skin

2013 ◽  
Vol 135 (10) ◽  
Author(s):  
Clare Y. L. Chao ◽  
Gabriel Y. F. Ng ◽  
Kwok-Kuen Cheung ◽  
Yong-Ping Zheng ◽  
Li-Ke Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Normal Skin ◽  
Biomechanical Properties ◽  
Skin Wound ◽  
Sprague Dawley ◽  
Rat Skin ◽  
Mechanical Stiffness ◽  
Air Jet

An evaluation of wound mechanics is crucial in reflecting the wound healing status. The present study examined the biomechanical properties of healing rat skin wounds in vivo and ex vivo. Thirty male Sprague-Dawley rats, each with a 6 mm full-thickness circular punch biopsied wound at both posterior hind limbs were used. The mechanical stiffness at both the central and margins of the wound was measured repeatedly in five rats over the same wound sites to monitor the longitudinal changes over time of before wounding, and on days 0, 3, 7, 10, 14, and 21 after wounding in vivo by using an optical coherence tomography-based air-jet indentation system. Five rats were euthanized at each time point, and the biomechanical properties of the wound tissues were assessed ex vivo using a tensiometer. At the central wound bed region, the stiffness measured by the air-jet system increased significantly from day 0 (17.2%), peaked at day 7 (208.3%), and then decreased progressively until day 21 (40.2%) as compared with baseline prewounding status. The biomechanical parameters of the skin wound samples measured by the tensiometer showed a marked reduction upon wounding, then increased with time (all p < 0.05). On day 21, the ultimate tensile strength of the skin wound tissue approached 50% of the normal skin; while the stiffness of tissue recovered at a faster rate, reaching 97% of its prewounded state. Our results suggested that it took less time for healing wound tissues to recover their stiffness than their maximal strength in rat skin. The stiffness of wound tissues measured by air-jet could be an indicator for monitoring wound healing and contraction.

Sign in / Sign up

Export Citation Format

Share Document