Decrease In Radial Diffusivity Research Articles

Assessment of Mechanically Induced Changes in Helical Fiber Microstructure Using Diffusion Tensor Imaging.

Noninvasive methods to detect microstructural changes in collagen-based fibrous tissues are necessary to differentiate healthy from damaged tissues in vivo but are sparse. Diffusion Tensor Imaging (DTI) is a noninvasive imaging technique used to quantitatively infer tissue microstructure with previous work primarily focused in neuroimaging applications. Yet, it is still unclear how DTI metrics relate to fiber microstructure and function in musculoskeletal tissues such as ligament and tendon, in part because of the high heterogeneity inherent to such tissues. To address this limitation, we assessed the ability of DTI to detect microstructural changes caused by mechanical loading in tissue-mimicking helical fiber constructs of known structure. Using high-resolution optical and micro-computed tomography imaging, we found that static and fatigue loading resulted in decreased sample diameter and a re-alignment of the macro-scale fiber twist angle similar with the direction of loading. However, DTI and micro-computed tomography measurements suggest microstructural differences in the effect of static versus fatigue loading that were not apparent at the bulk level. Specifically, static load resulted in an increase in diffusion anisotropy and a decrease in radial diffusivity suggesting radially uniform fiber compaction. In contrast, fatigue loads resulted in increased diffusivity in all directions and a change in the alignment of the principal diffusion direction away from the constructs' main axis suggesting fiber compaction and microstructural disruptions in fiber architecture. These results provide quantitative evidence of the ability of DTI to detect mechanically induced changes in tissue microstructure that are not apparent at the bulk level, thus confirming its potential as a noninvasive measure of microstructure in helically architected collagen-based tissues, such as ligaments and tendons.

White Matter Microstructure Alterations Associated With Paroxetine Treatment Response in Major Depression.

More than one-third of depressive patients do not achieve remission after the first antidepressant treatment. The “watch and wait” approach used to find the most effective antidepressant leads to an increased personal, social, and economic burden in society. In order to overcome this challenge, there has been a focus on studying neural biomarkers associated with antidepressant response. Diffusion tensor imaging measures have shown a promising role as predictors of antidepressant response by pointing to pretreatment differences in the white matter microstructural integrity between future responders and non-responders to different pharmacotherapies. Therefore, the aim of the present study was to explore whether response to paroxetine treatment was associated with differences in the white matter microstructure at baseline. Twenty drug-naive patients diagnosed with major depressive disorder followed a 6- to 12-week treatment with paroxetine. All patients completed magnetic resonance brain imaging and a clinical assessment at baseline and 6–12 weeks after treatment. Whole-brain tract-based spatial statistics was used to explore differences in white matter microstructural properties estimated from diffusion magnetic resonance imaging. Voxel-wise statistical analysis revealed a significant increase in fractional anisotropy and a decrease in radial diffusivity in forceps minor and superior longitudinal fasciculus in responders compared to non-responders. Thus, alterations in white matter integrity, specifically in forceps minor and the superior longitudinal fasciculus, are associated with paroxetine treatment response. These findings pave the way for personalized treatment strategies in major depression.

Met5]-enkephalin preserves diffusion metrics in EAE mice

Multiple sclerosis is a chronic progressive neurological disorder that has few distinctive biomarkers associated with disease progression or response to therapy. This research investigated whether non-invasive imaging correlated with animal behavior and morphological indicators of disease in response to serum levels of [Met5]-enkephalin. Using the experimental autoimmune encephalomyelitis (EAE) model, adult female C57BL/6 J mice were randomized to receive daily injections of 0.1 mg/kg naltrexone (NTX) (= low dose naltrexone, LDN), 10 mg/kg Opioid Growth Factor (OGF) (chemically termed [Met5]-enkephalin) or saline beginning at the time of disease induction. Daily composite behavior scores were recorded over a 30-day period based on tail tone, gait, righting reflex, and limb strength. Prior to disease onset (day 7), and at peak disease (day 18), mice were imaged and tissues (blood and spinal cord) collected at day 30 for serum analyses of OGF and morphology. Serum OGF levels of EAE mice treated with saline were significantly reduced from baseline and from normal mice. Longitudinal cohort data demonstrated an increase in fractional anisotropy in all cohorts by day 18. There was a significant decrease in radial diffusivity in the saline group seen at day 18 whereas the axial diffusivity was not altered amongst treatment groups. Treatment with OGF or LDN resulted in mean diffusivity rates that were comparable to baseline (normal) levels at days 7 and 18. Luxol fast blue staining of the lumbar spinal cords demonstrated a 16 % reduction in myelin staining in saline treated EAE animals when compared to OGF and LDN treated EAE mice. Immunohistochemistry with Olig2 (pan-oligodendrocyte marker) and myelin basic protein (MBP) revealed that OGF and LDN treatment restored the area (%) of MBP and number of oligodendrocytes to that of normal spinal cord (∼75 %). Saline treated EAE mice had more demyelination and fewer oligodendrocytes than normal mice. Collectively, these data suggest that a panel of biomarkers including imaging, serum biomarker levels, and behavior correlate with progression of disease, and may begin to validate use of specific non-invasive markers for MS.

Increased tumour burden alters skeletal muscle properties in the KPC mouse model of pancreatic cancer.

Cancer cachexia is a multifactorial wasting syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. We address these issues in a novel transgenic mouse model Kras, Trp53 and Pdx-1-Cre (KPC) of pancreatic ductal adenocarcinoma (PDA) using multi-parametric magnetic resonance (mp-MR) measures. KPC mice (n = 10) were divided equally into two groups (n = 5/group) depending on the size of the tumor i.e. tumor size <250 mm3 and >250 mm3. Using mp-MR measures, we demonstrated the changes in the gastrocnemius muscle at the microstructural level. In addition, we evaluated skeletal muscle contractile function in KPC mice using an in vivo approach. Increase in tumor size resulted in decrease in gastrocnemius maximum cross sectional area, decrease in T2 relaxation time, increase in magnetization transfer ratio, decrease in mean diffusivity, and decrease in radial diffusivity of water across the muscle fibers. Finally, we detected significant decrease in absolute and specific force production of gastrocnemius muscle with increase in tumor size. Our findings indicate that increase in tumor size may cause alterations in structural and functional parameters of skeletal muscles and that MR parameters may be used as sensitive biomarkers to noninvasively detect structural changes in cachectic muscles.

Third-trimester in utero fetal brain diffusion tensor imaging fiber tractography: a prospective longitudinal characterization of normal white matter tract development.

White matter is responsible for inter-neuronal connections throughout the brain that are a driving force in cognitive development. Diffusion tensor imaging (DTI) fiber tractography has been used to evaluate white matter development in the fetal brain; however, longitudinal studies of DTI fiber tractography to assess white matter development in the third trimester are lacking. To characterize in utero longitudinal changes in the fetal brain DTI fiber tracts of normal third-trimester fetuses. For this single-center prospective longitudinal observational pilot study, we recruited 28 pregnant females with normal third-trimester pregnancies who had routine prenatal ultrasound. MRI of the in utero fetal brain was performed with a Siemens 1.5-tesla (T) Espree scanner at 31weeks, 33weeks and 36weeks of gestation, with 14 DTI tractography parameters quantified in 7 brain regions using DTI-studio version 2.4 (Johns Hopkins University, Baltimore, MD; n=98 measurements). We used multilevel mixed models to examine the relationship between longitudinal changes in DTI measurements and between 98 DTI measurements at 31weeks and 4 routine fetal brain anatomical biometrics (n=392 assessments). We observed statistically significant decreases in radial diffusivity and apparent diffusion coefficient in 13 of 14 brain regions from 31weeks to 36weeks of gestation (P<0.001 for all regions except the genu of the corpus callosum). Significant decreases in radial diffusivity from weeks 33 to 36 and weeks 31 to 36 were seen in the corticospinal tracts, centrum semiovale, posterior limb of the internal capsule, and crus cerebri (P<0.001 for all). When considering all possible combinations of DTI fiber tract measurements and the routine morphological fetal brain biometrics, only 6% (24/392) had a significant association (P<0.05), indicating relative independence of the DTI fiber tract measurements from anatomical biometrics. In utero longitudinal changes in fetal brain DTI fiber tractography are quantifiable in normal third-trimester fetuses and are largely independent of morphological brain changes.

A preliminary examination of the relationship between biomechanical measures and structural changes in the brain

Introduction Currently, biomechanics has not been able to effectively predict when a mild traumatic brain injury may occur as a result of head impact. To improve prediction of brain trauma and the development of protective innovations, it is important to create an understanding of the relationship between the biomechanics of the head impact event and the structural damage incurred by the brain as a result of that event. The purpose of this research was to examine the relationship between diffusion tensor imaging measures and biomechanical characteristics of a head impact. Methods Diffusion tensor imaging was conducted on concussed subjects to identify regions of white matter structural differences. The injury event was reconstructed using physical and finite element methods to identify the biomechanical parameters of the impact as well as strain to the regions of the brain. Results A significant relationship was found between shear strain, rotational acceleration, and impact velocity on increases in radial diffusivity and mean diffusivity in the fornix. Linear acceleration was also found to have a weaker but significant relationship with a decrease in radial diffusivity in the cingulum hippocampus. Conclusion These results demonstrate that impacts resulting in high shear strains may affect radial diffusivity and mean diffusivity measures, and that impact mechanics likely have an important role in what regions may present differences in diffusion tensor imaging measures.

Evidence for wakefulness-related changes to extracellular space in human brain white matter from diffusion-weighted MRI

Recently, several magnetic resonance imaging (MRI) studies have reported time-of-day effects on brain structure and function. Due to the possibility that time-of-day effects reflect mechanisms of circadian regulation, the aim of this prospective study was to assess these effects while under strict experimental control of variables that might influence biological clocks, such as caffeine intake and exposure to blue-emitting light. In addition, the current study assessed whether time-of-day effects were driven by changes to extracellular space, by including estimations of non-Gaussian diffusion metrics obtained from diffusion kurtosis imaging, white matter tract integrity and the spherical mean technique, in addition to conventional diffusion tensor imaging -derived parameters. Participants were 47 healthy adults who underwent diffusion-weighted imaging in the morning and evening of the same day. Morning and evening scans were compared using voxel-wise tract based spatial statistics and permutation testing. A day of wakefulness was associated with widespread increases in fractional anisotropy, indices of kurtosis and indices of the axonal water fraction. In addition, wakefulness was associated with widespread decreases in radial diffusivity, both in the single compartment and in extra-axonal space. These results suggest that an increase in the intra-axonal space relative to the extra-axonal volume underlies time-of-day effects in human white matter, which is in line with activity-induced reductions to the extracellular volume. These findings provide important insight into possible mechanisms driving time-of-day effects in MRI.

A preliminary analysis of biomechanics and saccadic responses for concussion

Background Concussion is an injury that occurs in non-sporting and sporting environments. To determine improved clinical methods for identifying this injury, it is important to develop and understand how the impact event results in quantifiable differences in brain functioning—functioning that has been quantified in the past using saccadic measures. The purpose of this research was to examine the relationships between oculomotor deficits, specifically antisaccade responses, and the biomechanics of impact for a concussion. Methods Participants underwent a diffusion tensor imaging protocol as well as saccadic testing to determine differences in brain functioning in comparison to controls. The injury event was then reconstructed in laboratory using physical and finite element models to determine the biomechanics of the impact and brain tissue strain. Relationships between the biomechanical variables and antisaccade responses were then examined. Results The diffusion tensor imaging analyses found that there was a decrease in radial diffusivity and axial diffusivity found in the cerebral peduncle (p &lt; 0.05) and cingulum hippocampus (p &lt; 0.05), respectively. There was an increase in the axial diffusivity for the corona radiata (p &lt; 0.05). The saccadic testing found an increase in mean latency for the concussed group (p &lt; 0.05). The results indicated no significant relationship between mean latency, duration, amplitude and peak velocity antisaccade measures and the biomechanical variables. This may have been influenced not only by a lack of sensitivity in biomechanical variable to antisaccade responses, but also to these responses being affected by factors other than injury such as attentiveness and wakefulness. Conclusion While the sample of this research was small, this research suggests that to improve the understanding of the relationship between impact biomechanics and concussion, methods that can quantify the damage to brain structures through imaging, such as diffusion tensor imaging, may be more appropriate.

Reduced brain glutamine in female varsity rugby athletes after concussion and in non-concussed athletes after a season of play.

The purpose of this study was to use non-invasive proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) to monitor changes in prefrontal white matter metabolite levels and tissue microstructure in female rugby players with and without concussion (ages 18-23, n = 64). Evaluations including clinical tests and 3 T MRI were performed at the beginning of a season (in-season) and followed up at the end of the season (off-season). Concussed athletes were additionally evaluated 24-72 hr (n = 14), three months (n = 11), and six months (n = 8) post-concussion. Reduced glutamine at 24-72 hr and three months post-concussion, and reduced glutamine/creatine at three months post-concussion were observed. In non-concussed athletes (n = 46) both glutamine and glutamine/creatine were lower in the off-season compared to in-season. Within the MRS voxel, an increase in fractional anisotropy (FA) and decrease in radial diffusivity (RD) were also observed in the non-concussed athletes, and correlated with changes in glutamine and glutamine/creatine. Decreases in glutamine and glutamine/creatine suggest reduced oxidative metabolism. Changes in FA and RD may indicate neuroinflammation or re-myelination. The observed changes did not correlate with clinical test scores suggesting these imaging metrics may be more sensitive to brain injury and could aid in assessing recovery of brain injury from concussion.

Dynamic Diffusion Tensor Imaging Reveals Structural Changes in the Bilateral Pyramidal Tracts after Brain Stem Hemorrhage in Rats.

Background and Purpose: Few studies have concentrated on pyramidal tract (PY) changes after brain stem hemorrhage (BSH). In this study, we used a diffusion tensor imaging (DTI) technique and histologic identification to investigate longitudinal PY changes on both the contralateral and ipsilateral sides after experimental BSH.Methods: BSH was induced in 61 Sprague-Dawley rats by infusing 30 μl of autogenous tail blood into each rat’s right pons. DTI and motor function examinations were performed repeatedly on days 1, 3, 7, 14, and 28 after surgery. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity were measured in the bilateral PYs. The axon and myelin injury in the PY were evaluated by histologic study.Results: As compared with normal controls, the bilateral PYs in rats with induced BSH showed an early decrease and a late increase in FA and an early increase and a late decrease in MD. A progressive decrease in axial diffusivity with dramatic axon loss from day 1 to day 28 after BSH was found bilaterally. The bilateral PYs showed an early increase and a late decrease in radial diffusivity. Early myelin injury and late repair were also detected pathologically in the bilateral PYs of rats with BSH. Thus, the early motor function deficits of rats with BSH began to improve on day 14 and had almost completely disappeared by day 28.Conclusions: DTI revealed dynamic changes in the bilateral PYs after BSH, which was confirmed by histologic findings and which correlated with motor function alteration. These findings support the idea that quantitative DTI can track structural changes in the bilateral PYs and that DTI may serve as a noninvasive tool to predict the prognoses of patients with BSH.

Analysis of Corpus Callosum Diffusion Tensor Imaging Parameters in Infants

Radial diffusivity is a diffusion tensor imaging (DTI) metric that has received increased attention in recent studies as a parameter that may better reflect myelination than the more commonly-used fractional anisotropy (FA). This study compared rates of radial diffusivity decrease against FA increase and axial diffusivity decrease on DTI maps in the corpus callosum of normal infants during the first postnatal year. Fifty-three normal infants (range: 0-52 weeks adjusted for gestational age) underwent six-direction DTI on a 1.5 Tesla scanner (b= 1,000 s/mm(2), one excitation). A single individual placed regions of interest on FA maps in the genu 1) and radial diffusivity (i.e., λ and splenium to obtain axial (i.e., 3)/2]), FA and ADC. We calculated mean and median values for FA, λ 2+λ[ ADC, radial diffusivity and axial diffusivity in each of four 13-week epochs and measured the percent change over the first year of life. Within the genu, radial diffusivity decreased 36%, FA increased 25%, ADC decreased 22% and axial diffusivity decreased 10%. Within the splenium, radial diffusivity decreased 53%, FA increased 43%, ADC decreased 38%, and axial diffusivity decreased 23%. For both genu and splenium, the greatest difference was seen in radial diffusivity values, followed in order by FA, ADC and axial diffusivity. Furthermore, decreases in radial diffusivity were on the order of two to threefold greater than those in axial diffusivity. The high rate of radial diffusivity decrease compared to axial diffusivity decrease is consistent with myelination. Decreases in radial diffusivity were greater than increases in FA values. This finding is further support of the concept that radial diffusivity and FA values represent two different types of microstructural change during development of white matter.

Everolimus alters white matter diffusion in tuberous sclerosis complex

Diffusion tensor imaging (DTI) analysis was performed on patients with tuberous sclerosis complex (TSC) to investigate potential changes in normal-appearing white matter after treatment with everolimus, a mammalian target of rapamycin (mTOR) inhibitor. Recently, a phase I/II trial of everolimus demonstrated significant reductions in subependymal giant cell astrocytoma (SEGA) volume and decreased seizure frequency. Subgroup analysis was performed on DTI data available from this study. TSC patients with SEGA received everolimus, titrated to tolerability to achieve target trough concentrations of 5-15 ng/mL. DTI (1.5 T, 15 directions) was used to calculate fractional anisotropy (FA) and axial, radial, and mean diffusivity within regions of interest (ROIs). Baseline scans were compared to 12-18 months post-treatment and compared to a TSC age- and gender-matched nontreatment control cohort. Of 28 enrolled patients, 20 had sufficient DTI data. Comparing baseline values with those acquired 12-18 months after treatment, a significant change in FA was observed in the corpus callosum, internal capsule, and geniculo-calcarine region (p < 0.05). Mean change in FA was 0.04 (p < 0.01), driven primarily by a significant decrease in radial diffusivity. Mean diffusivity of the combined ROIs decreased slightly (p < 0.05), axial diffusivity remained stable. The control group showed no change over time. Significant changes in FA and radial diffusivity were observed after treatment with everolimus in patients with TSC, suggesting that the genetic defect of TSC in the brain may be modified pharmacologically, even in normal-appearing white matter.

Experience-dependent plasticity in white matter microstructure: reasoning training alters structural connectivity

Diffusion tensor imaging (DTI) techniques have made it possible to investigate white matter plasticity in humans. Changes in DTI measures, principally increases in fractional anisotropy (FA), have been observed following training programs as diverse as juggling, meditation, and working memory. Here, we sought to test whether three months of reasoning training could alter white matter microstructure. We recruited participants (n = 23) who were enrolled in a course to prepare for the Law School Admission Test (LSAT), a test that places strong demands on reasoning skills, as well as age- and IQ-matched controls planning to take the LSAT in the future (n = 22). DTI data were collected at two scan sessions scheduled three months apart. In trained participants but not controls, we observed decreases in radial diffusivity (RD) in white matter connecting frontal cortices, and in mean diffusivity (MD) within frontal and parietal lobe white matter. Further, participants exhibiting larger gains on the LSAT exhibited greater decreases in MD in the right internal capsule. In summary, reasoning training altered multiple measures of white matter structure in young adults. While the cellular underpinnings are unknown, these results provide evidence of experience-dependent white matter changes that may not be limited to myelination.

A mouse model of blast-induced mild traumatic brain injury

Improvised explosive devices (IEDs) are one of the main causes for casualties among civilians and military personnel in the present war against terror. Mild traumatic brain injury from IEDs induces various degrees of cognitive, emotional and behavioral disturbances but knowledge of the exact brain pathophysiology following exposure to blast is poorly understood. The study was aimed at establishing a murine model for a mild BI-TBI that isolates low-level blast pressure effects to the brain without systemic injuries. An open-field explosives detonation was used to replicate, as closely as possible, low-level blast trauma in the battlefield or at a terror-attack site. No alterations in basic neurological assessment or brain gross pathology were found acutely in the blast-exposed mice. At 7days post blast, cognitive and behavioral tests revealed significantly decreased performance at both 4 and 7m distance from the blast (5.5 and 2.5PSI, respectively). At 30days post-blast, clear differences were found in animals at both distances in the object recognition test, and in the 7m group in the Y maze test. Using MRI, T1 weighted images showed an increased BBB permeability 1month post-blast. DTI analysis showed an increase in fractional anisotropy (FA) and a decrease in radial diffusivity. These changes correlated with sites of up-regulation of manganese superoxide dismutase 2 in neurons and CXC-motif chemokine receptor 3 around blood vessels in fiber tracts. These results may represent brain axonal and myelin abnormalities. Cellular and biochemical studies are underway in order to further correlate the blast-induced cognitive and behavioral changes and to identify possible underlying mechanisms that may help develop treatment- and neuroprotective modalities.

Memory training impacts short‐term changes in aging white matter: A Longitudinal Diffusion Tensor Imaging Study

A growing body of research indicates benefits of cognitive training in older adults, but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored. Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our understanding of both aging- and training-related neuronal plasticity. Specifically, studies using diffusion tensor imaging (DTI) suggest substantial changes in white matter (WM) in aging, but it is not known whether cognitive training might modulate these structural alterations. We used tract-based spatial statistics (TBSS) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure. 41 participants (mean age 61 years) matched for age, sex and education were randomly assigned to an intervention or control group. All participants underwent MRI-scanning and neuropsychological assessments at the beginning and end of the study. Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity (MD), indicating that DTI is sensitive to WM structural alterations over a 10-week interval. Further, group analysis demonstrated positive effects of training on the short-term changes. Participants in the training group showed a relative increase in fractional anisotropy (FA) compared with controls. Further, a significant relationship between memory improvement and change in FA was found, suggesting a possible functional significance of the reported changes. The training effect on FA seemed to be driven by a relative decrease in radial diffusivity, which might indicate a role for myelin-related processes in WM plasticity.

Modeling the Electrochemical Impedance Spectra of Electroactive Pseudocapacitor Materials

Measured electrochemical impedance spectra of porous electrodes comprised of redox-active ruthenium oxide and inert niobium hydroxide are compared with the results of structurally consistent mathematical models describing coupled processes of electron transport in the solid matrix, ion transport in the electrolyte, proton transport within the ruthenium oxide particles, and redox reaction on particle surfaces. Addition of moderate amounts of niobium to crystalline ruthenium oxide is found to improve the frequency response due to enhanced intraparticle proton transport. However, excessive niobium reduces ion and electron transport through the electrode thickness, reducing the available capacitance. Thus, an optimum composition is needed to achieve the best balance in transport properties. Near this optimum, the intraparticle proton transport undergoes a transition from a constant phase element (CPE) response for Ru-rich materials to a classical Warburg diffusion response for Nb-rich compositions. The CPE regime is analyzed in detail to identify fractal-like structures as well as alternative radial distributions of intraparticle proton diffusivity consistent with measured response. The models involving variations in radial diffusivity appear most probable and have nearly exponential decreases in radial diffusivity with distance from particle surfaces similar to a Debye distribution of charge carriers in an electric double layer.

Abnormal white matter integrity in young children with autism

This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty-two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract-based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS-VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid-body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism.

Ex Vivo Diffusion Tensor Imaging and Neuropathological Correlation in a Murine Model of Hypoxia–Ischemia-Induced Thrombotic Stroke

Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia-ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24 hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.

Age-related variations in white matter anisotropy in school-age children

Determination of diffusion tensor metrics in typically developing school-age children shows that maturational increases in fractional anisotropy (FA) vary across the brain and that age effects on FA are to increases in axial diffusivity in some regions, to decreases in radial diffusivity in some, and to both increases in axial and decreases in radial diffusivity in others. When studying developing white matter (WM) using diffusion tensor imaging (DTI), knowledge of age-related normative tensor metrics is important, as normal variations can mask or mimic disease effects. Right-handed English-speaking children (n = 32) 6-18 years old (mean 11.0) were studied over 31 months, 7 longitudinally. Anisotropy data were analyzed using tract-based spatial statistics; 43 regions showing significant (P < 0.05) age effects on fractional anisotropy (FA) were analyzed for age effects (r), coefficient of variability (CV), and FA, axial and radial diffusivity. This study was IRB-approved. The callosal genu and splenium showed the highest FA values, smallest age effects, and lowest between-subject variability. Mean FA was lower and age effects were greatest in the dorsal callosal body. The highest age effects on FA were in the cingulum, centrum semiovale, right corticospinal tract, and right temporal WM. The dorsal callosal body, calcarine WM, superior frontal and temporal gyri, and right corticospinal tract showed the highest CV. Radial diffusivity decreased while axial diffusivity increased in the cingulum, decreased in the optic tracts, and showed minimal or no age effects in most other regions. Age effects on FA and variability in FA are location-dependant in developing WM.

Myelin water weighted diffusion tensor imaging

In this study we describe our development and implementation of a magnetization transfer (MT) prepared stimulated-echo diffusion tensor imaging (DTI) technique that can be made sensitive to the microanatomy of myelin tissue. The short echo time (TE) enabled by the stimulated-echo acquisition preserves significant signal from the short T2 component (myelin water), and the MT preparation further provides differentiating sensitization to this signal. It was found that this combined strategy could provide sufficient sensitivity in our first attempt to image myelin microstructure. Compared to the diffusion tensor derived from the conventional DTI technique, the myelin water weighted (MWW) tensor has the same principal diffusion direction but exhibits a significant increase in fractional anisotropy (FA), which is mainly due to a decrease in radial diffusivity. These findings are consistent with the microstructural organization of the myelin sheaths that wrap around the axons in the white matter and therefore hinder radial diffusion. Given that many white matter diseases (e.g. multiple sclerosis) begin with a degradation of myelin microanatomy but not a loss of myelin content (e.g. loosening of the myelin sheaths), our newly implemented MWW DTI has the potential to lead to improved assessment of myelin pathology and early detection of demyelination.