High-resolution dynamic susceptibility contrast perfusion imaging using higher-order temporal smoothness regularization.

PURPOSE: To improve image quality and resolution of dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) by developing acquisition and reconstruction methods exploiting the temporal regularity property of DSC-PWI signal. THEORY AND METHODS: A novel regularized reconstruction is proposed that recovers DSC-PWI series from interleaved segmented spiral k-space acquisition using higher order temporal smoothness (HOTS) properties of the DSC-PWI signal. The HOTS regularization is designed to tackle representational insufficiency of the standard first-order temporal regularizations for supporting higher accelerations. The higher accelerations allow for k-space coverage with shorter spiral interleaves resulting in improved acquisition point spread function, and acquisition of images at multiple TEs for more accurate DSC-PWI analysis. RESULTS: The methods were evaluated in simulated and in-vivo studies. HOTS regularization provided increasingly more accurate models for DSC-PWI than the standard first-order methods with either quadratic or robust norms at the expense of increased noise. HOTS DSC-PWI optimized for noise and accuracy demonstrated significant advantages over both spiral DSC-PWI without temporal regularization and traditional echo-planar DSC-PWI, improving resolution and mitigating image artifacts associated with long readout, including blurring and geometric distortions. In context of multi-echo DSC-PWI, the novel methods allowed ∼4.3× decrease of voxel volume, providing 2× number of TEs compared to the previously published results. CONCLUSIONS: Proposed HOTS reconstruction combined with dynamic spiral sampling represents a valid mechanism for improving image quality and resolution of DSC-PWI significantly beyond those available with established fast imaging techniques.

Focused Abbreviated Survey MRI Protocols for Brain and Spine Imaging.

There has been extensive growth in both the technical development and the clinical applications of MRI, establishing this modality as one of the most powerful diagnostic imaging tools. However, long examination and image interpretation times still limit the application of MRI, especially in emergent clinical settings. Rapid and abbreviated MRI protocols have been developed as alternatives to standard MRI, with reduced imaging times, and in some cases limited numbers of sequences, to more efficiently answer specific clinical questions. A group of rapid MRI protocols used at the authors' institution, referred to as FAST (focused abbreviated survey techniques), are designed to include or exclude emergent or urgent conditions or screen for specific entities. These FAST protocols provide adequate diagnostic image quality with use of accelerated approaches to produce imaging studies faster than traditional methods. FAST protocols have become critical diagnostic screening tools at the authors' institution, allowing confident and efficient confirmation or exclusion of actionable findings. The techniques commonly used to reduce imaging times, the imaging protocols used at the authors' institution, and future directions in FAST imaging are reviewed to provide a practical and comprehensive overview of FAST MRI for practicing neuroradiologists. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Simultaneous T1 -weighted and T2 -weighted 3D MRI using RF phase-modulated gradient echo imaging.

PURPOSE: T1 -weighted and T2 -weighted (T1w and T2w) imaging are essential sequences in routine clinical practice to detect and characterize a wide variety of pathologies. Many approaches have been proposed to obtain T1w and T2w contrast, although many challenges still remain, including long acquisition time and limitations that favor 2D imaging. In this study, we propose a novel method for simultaneous T1w and T2w imaging using RF phase-modulated 3D gradient-echo imaging. THEORY: Configuration theory is used to derive closed-form equations for the steady state of RF phase-modulated gradient-echo signal. These equations suggest the use of small RF phase increments to provide orthogonal signal contrast with T2w and T1w in the real and imaginary components, respectively. Background phase can be removed using a two-pass acquisition with opposite RF phase increments. METHODS: Simulation and phantom experiments were performed to validate our proposed method. Volunteer images of the brain and knee were acquired to demonstrate the clinical feasibility. The proposed method was compared with T1w and T2w fast spin-echo imaging. RESULTS: The relative signal intensity of images acquired using the proposed method agreed closely with simulations and fast spin-echo imaging in phantoms. Images from volunteer imaging showed very similar contrast compared to conventional fast spin-echo imaging. CONCLUSION: Radiofrequency phase-modulated gradient-echo with small RF phase increments is an alternative method that provides simultaneous T1w and T2w contrast in short scan times with 3D volumetric coverage.

Evoked potentials as a biomarker of remyelination.

Multiple sclerosis (MS) is a common cause of neurologic disease in young adults that is primarily treated with disease-modifying therapies which target the immune and inflammatory responses. Promotion of remyelination has opened a new therapeutic avenue, but how best to determine efficacy of remyelinating drugs remains unresolved. Although prolongation and then shortening of visual evoked potential (VEP) latencies in optic neuritis in MS may identify demyelination and remyelination, this has not been directly confirmed. We recorded VEPs in a model in which there is complete demyelination of the optic nerve, with subsequent remyelination. We examined the optic nerves microscopically during active disease and recovery, and quantitated both demyelination and remyelination along the length of the nerves. Latencies of the main positive component of the control VEP demonstrated around 2-fold prolongation during active disease. VEP waveforms were nonrecordable in a few subjects or exhibited a broadened profile which precluded peak identification. As animals recovered neurologically, the VEP latencies decreased in association with complete remyelination of the optic nerve but remained prolonged relative to controls. Thus, it has been directly confirmed that VEP latencies reflect the myelin status of the optic nerve and will provide a surrogate marker in future remyelination clinical trials.

High-resolution diffusion tensor magnetic resonance imaging of the brainstem safe entry zones.

Operative management of intrinsic brainstem lesions remains challenging despite advances in electrophysiological monitoring, neuroimaging, and neuroanatomical knowledge. Surgical intervention in this region requires detailed knowledge of adjacent critical white matter tracts, brainstem nuclei, brainstem vessels, and risks associated with each surgical approach. Our aim was to systematically verify internal anatomy associated with each brainstem safety entry zone (BSEZ) via neuroimaging modalities commonly used in pre-operative planning, namely high-resolution magnetic resonance imaging (MRI) and diffusion tensor tractography (DTT). Twelve BSEZs were simulated in eight, formalin-fixed, cadaveric brains. Specimens then underwent radiological investigation including T2-weighted imaging and DTT using 4.7 T MRI to verify internal anatomic relationships between simulated BSEZs and adjacent critical white matter tracts and nuclei. The distance between simulated BSEZs and pre-defined, adjacent critical structures was systemically recorded. Entry points and anatomic limits on the surface of the brainstem are described for each BSEZ, along with description of potential neurological sequelae if such limits are violated. With high-resolution imaging, we verified a maximal depth for each BSEZ. The relationship between proposed safe entry corridors and adjacent critical structures within the brainstem is quantified. In combination with tissue dissection, high-resolution MR diffusion tensor imaging allows the surgeon to develop a better understanding of the internal architecture of the brainstem, particularly as related to BSEZs, prior to surgical intervention. Through a careful study of such imaging and use of optimal surgical corridors, a more accurate and safe surgery of brainstem lesions may be achieved.

Conventional and quantitative MRI in a novel feline model of demyelination and endogenous remyelination.

BACKGROUND: The feeding of irradiated food to healthy adult cats results in widespread, noninflammatory demyelination of the central nervous system (CNS); a return to a normal diet results in endogenous remyelination with functional recovery. This recently discovered, reversible disease might provide a compelling clinical neuroimaging model system for the development and testing of myelin-directed MRI methods as well as future remyelination therapies. PURPOSE: Identify the noninvasive imaging characteristics of this new disease model and determine whether it features measurable changes on conventional and quantitative MRI. STUDY TYPE: Pilot study. ANIMAL MODEL: Ten adult cats at various stages of demyelinating disease induced by an irradiated diet (35-55 kGy), and during recovery following a return to a normal diet. FIELD STRENGTH/SEQUENCE: Conventional (T2 -weighted) and quantitative (diffusion tensor, magnetization transfer) at 3T. ASSESSMENT: MRI of the brain, optic nerves, and cervical spinal cord; a subset of diseased cats was euthanized for comparative histopathology. STATISTICAL TESTS: Descriptive statistics. RESULTS: Disease produced T2 prolongation, progressing from patchy to diffuse throughout most of the cerebral white matter (eventually involving U-fibers) and spinal cord (primarily dorsal columns, reminiscent of subacute combined degeneration but without evidence of B12 deficiency). Magnetization transfer parameters decreased by 50-53% in cerebral white matter and by 25-30% in optic nerves and spinal cord dorsal columns. Fractional diffusion anisotropy decreased by up to 20% in pyramidal tracts, primarily driven by increased radial diffusivity consistent with axon preservation. Histopathology showed scattered myelin vacuolation of major white matter tracts as well as many thin myelin sheaths consistent with remyelination in the recovery phase, which was detectable on magnetization transfer imaging. DATA CONCLUSION: Feline irradiated diet-induced demyelination features noninvasively imageable and quantifiable demyelination and remyelination of the CNS. It is therefore a compelling clinical neuroimaging model system. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1304-1311.

Robust Motion Correction Strategy for Structural MRI in Unsedated Children Demonstrated with Three-dimensional Radial MPnRAGE.

Purpose To develop and evaluate a retrospective method to minimize motion artifacts in structural MRI. Materials and Methods The motion-correction strategy was developed for three-dimensional radial data collection and demonstrated with MPnRAGE, a technique that acquires high-resolution volumetric magnetization-prepared rapid gradient-echo, or MPRAGE, images with multiple tissue contrasts. Forty-four pediatric participants (32 with autism spectrum disorder [mean age ± standard deviation, 13 years ± 3] and 12 age-matched control participants [mean age, 12 years ± 3]) were imaged without sedation. Images with and images without retrospective motion correction were scored by using a Likert scale (0-4 for unusable to excellent) by two experienced neuroradiologists. The Tenengrad metric (a reference-free measure of image sharpness) and statistical analyses were performed to determine the effects of performing retrospective motion correction. Results MPnRAGE T1-weighted images with retrospective motion correction were all judged to have good or excellent quality. In some cases, retrospective motion correction improved the image quality from unusable (Likert score of 0) to good (Likert score of 3). Overall, motion correction improved mean Likert scores from 3.0 to 3.8 and reduced standard deviations from 1.1 to 0.4. Image quality was significantly improved with motion correction (Mann-Whitney U test; P < .001). Intraclass correlation coefficients for absolute agreement of Tenengrad scores with reviewers 1 and 2 were 0.92 and 0.88 (P < .0005 for both), respectively. In no cases did the retrospective motion correction induce severe image degradation. Conclusion Retrospective motion correction of MPnRAGE data were shown to be highly effective for consistently improving image quality of T1-weighted MRI in unsedated pediatric participants, while also enabling multiple tissue contrasts to be reconstructed for structural analysis. © RSNA, 2018 Online supplemental material is available for this article.

A General Framework for Monitoring Image Acquisition Workflow in the Radiology Environment: Timeliness for Acute Stroke CT Imaging.

Many facets of an image acquisition workflow leave a digital footprint, making workflow analysis amenable to an informatics-based solution. This paper describes a detailed framework for analyzing workflow and uses acute stroke response timeliness in CT as a practical demonstration. We review methods for accessing the digital footprints resulting from common technologist/device interactions. This overview lays a foundation for obtaining data for workflow analysis. We demonstrate the method by analyzing CT imaging efficiency in the setting of acute stroke. We successfully used digital footprints of CT technologists to analyze their workflow. We presented an overview of other digital footprints including but not limited to contrast administration, patient positioning, billing, reformat creation, and scheduling. A framework for analyzing image acquisition workflow was presented. This framework is transferable to any modality, as the key steps of image acquisition, image reconstruction, image post processing, and image transfer to PACS are common to any imaging modality in diagnostic radiology.

Removal of cerebrospinal fluid partial volume effects in quantitative magnetization transfer imaging using a three-pool model with nonexchanging water component.

PURPOSE: Parameters of the two-pool model describing magnetization transfer (MT) in macromolecule-rich tissues may be significantly biased in partial volume (PV) voxels containing cerebrospinal fluid (CSF). The purpose of this study was to develop a quantitative MT (qMT) method that provides indices insensitive to CSF PV averaging. THEORY AND METHODS: We propose a three-pool MT model, in which PV macro-compartment is modeled as an additional nonexchanging water pool. We demonstrate the feasibility of model parameter estimation from several MT-weighted spoiled gradient echo datasets. We validated the three-pool model in numerical, phantom, and in vivo studies. RESULTS: PV averaging with the free water compartment reduces all qMT parameters, most significantly affecting macromolecular proton fraction (MPF) and cross-relaxation rate. Monte-Carlo simulations confirmed stability of the three-pool model fit. Unlike the standard two-pool model, the three-pool model qMT parameters were not affected by PV averaging in simulations and phantom studies. The three-pool model fit allowed CSF PV correction in brain PV voxels and resulted in good correlation with standard two-pool model parameters in non-PV voxels. CONCLUSION: Quantitative MT imaging based on a three-pool model with a non-exchanging water component yields a set of CSF-insensitive qMT parameters, which may improve MPF-based assessment of myelination in structures strongly affected by CSF PV averaging such as brain gray matter.

MRI and Clinical Variables for Prediction of Outcomes After Pediatric Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is a leading cause of death and disability in children, and predicting functional outcome after TBI is challenging. Magnetic resonance imaging (MRI) is frequently conducted after severe TBI; however, the predictive value of MRI remains uncertain. Objectives: To identify early MRI measures that predict long-term outcome after severe TBI in children and to assess the added predictive value of MRI measures over well-validated clinical predictors. Design, Setting, and Participants: This preplanned prognostic study used data from the Approaches and Decisions in Acute Pediatric TBI (ADAPT) prospective observational comparative effectiveness study. The ADAPT study enrolled 1000 consecutive children (aged <18 years) with severe TBI between February 1, 2014, and September 30, 2017. Participants had a Glasgow Coma Scale (GCS) score of 8 or less and received intracranial pressure monitoring. Magnetic resonance imaging scans performed as part of standard clinical care within 30 days of injury were collected at 24 participating sites in the US, UK, and Australia. Summary imaging measures were correlated with the Glasgow Outcome Scale-Extended for Pediatrics (GOSE-Peds), and the predictive value of MRI measures was compared with the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) core clinical predictors. Data collection, image analysis, and data analyses were completed in July 2023. Exposures: Pediatric severe TBI with an MRI scan performed as part of clinical care. Main Outcomes and Measures: All measures were selected a priori. Magnetic resonance imaging measures included contusion, ischemia, diffuse axonal injury, intracerebral hemorrhage, and brainstem injury. Clinical predictors included the IMPACT core measures (GCS motor score and pupil reactivity). All models adjusted for age and sex. Outcome measures included the GOSE-Peds score obtained at 3, 6, and 12 months after injury. Results: This study included 233 children with severe TBI who were enrolled at participating sites and had an MRI scan and preselected clinical predictors available. Their median age was 6.9 (IQR, 3.0-13.3) years, and more than half of participants (134 [57.5%]) were male. In a multivariable model including MRI measures and IMPACT core clinical variables, contusion volume (odds ratio [OR], 1.13; 95% CI, 1.02-1.26), brain ischemia (OR, 2.11; 95% CI, 1.58-2.81), brainstem lesions (OR, 5.40; 95% CI, 1.90-15.35), and pupil reactivity were each independently associated with GOSE-Peds score. Adding MRI measures to the IMPACT clinical predictors significantly improved model fit and discrimination between favorable and unfavorable outcomes compared with IMPACT predictors alone (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.72-0.85 vs 0.67; 95% CI, 0.61-0.76 for GOSE-Peds score >3 at 6 months after injury). Conclusions and Relevance: In this prognostic study of children with severe TBI, the addition of MRI measures significantly improved outcome prediction over well-established and validated clinical predictors. Magnetic resonance imaging should be considered in children with severe TBI to inform prognosis and may also promote stratification of patients in future clinical trials.

A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using magnetic resonance imaging, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n=24, 13 males, 11 females) and standard (n=17, 8 males, 9 females) diets. Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A Diet X Age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.

Association of functional magnetic resonance imaging indices with postoperative language outcomes in patients with primary brain tumors.

OBJECT: Functional MRI (fMRI) has the potential to be a useful presurgical planning tool to treat patients with primary brain tumor. In this study the authors retrospectively explored relationships between language-related postoperative outcomes in such patients and multiple factors, including measures estimated from task fMRI maps (proximity of lesion to functional activation area, or lesion-to-activation distance [LAD], and activation-based language lateralization, or lateralization index [LI]) used in the clinical setting for presurgical planning, as well as other factors such as patient age, patient sex, tumor grade, and tumor volume. METHODS: Patient information was drawn from a database of patients with brain tumors who had undergone preoperative fMRI-based language mapping of the Broca and Wernicke areas. Patients had performed a battery of tasks, including word-generation tasks and a text-versus-symbols reading task, as part of a clinical fMRI protocol. Individually thresholded task fMRI activation maps had been provided for use in the clinical setting. These clinical imaging maps were used to retrospectively estimate LAD and LI for the Broca and Wernicke areas. RESULTS: There was a relationship between postoperative language deficits and the proximity between tumor and Broca area activation (the LAD estimate), where shorter LADs were related to the presence of postoperative aphasia. Stratification by tumor location further showed that for posterior tumors within the temporal and parietal lobes, more bilaterally oriented Broca area activation (LI estimate close to 0) and a shorter Wernicke area LAD were associated with increased postoperative aphasia. Furthermore, decreasing LAD was related to decreasing LI for both Broca and Wernicke areas. Preoperative deficits were related to increasing patient age and a shorter Wernicke area LAD. CONCLUSIONS: Overall, LAD and LI, as determined using fMRI in the context of these paradigms, may be useful indicators of postsurgical outcomes. Whereas tumor location may influence postoperative deficits, the results indicated that tumor proximity to an activation area might also interact with how the language network is affected as a whole by the lesion. Although the derivation of LI must be further validated in individual patients by using spatially specific statistical methods, the current results indicated that fMRI is a useful tool for predicting postoperative outcomes in patients with a single brain tumor.

Quantitative MR imaging of two-pool magnetization transfer model parameters in myelin mutant shaking pup.

Magnetization transfer (MT) imaging quantitatively assesses cerebral white matter disease through its sensitivity to macromolecule-bound protons including those associated with myelin proteins and lipid bilayers. However, traditional MT contrast measured by the MT ratio (MTR) lacks pathologic specificity as demyelination, axon loss, inflammation and edema all impact MTR, directly and/or indirectly through multiple covariances among imaging parameters (particularly MTR with T(1)) and tissue features (e.g. axon loss with demyelination). In this study, more complex modeling of MT phenomena ("quantitative" MT or qMT) was applied to a less complex disease model (the myelin mutant shaking [sh] pup, featuring hypomyelination but neither inflammation nor axon loss) in order to eliminate the covariances on both sides of the MR-pathology "equation" and characterize these important relationships free from the usual confounds. qMT measurements were acquired longitudinally in 6 sh pups and 4 age-matched controls ranging from 3 to 21 months of age and compared with histology. The qMT parameter, bound pool fraction (f), was the most distinctive between diseased and control animals; both f and longitudinal relaxation rate R(1) tracked myelination with normal aging, whereas MTR did not--presumably owing to counterbalancing MT and R(1) effects. qMT imaging provides a more accurate and potentially more specific non-invasive tissue characterization.

Simultaneous variable flip angle-actual flip angle imaging method for improved accuracy and precision of three-dimensional T1 and B1 measurements.

A new time-efficient and accurate technique for simultaneous mapping of T(1) and B(1) is proposed based on a combination of the actual flip angle (FA) imaging and variable FA methods. Variable FA-actual FA imaging utilizes a single actual FA imaging and one or more spoiled gradient-echo acquisitions with a simultaneous nonlinear fitting procedure to yield accurate T(1)/B(1) maps. The advantage of variable FA-actual FA imaging is high accuracy at either short T(1) times or long repetition times in the actual FA imaging sequence. Simulations show this method is accurate to 0.03% in FA and 0.07% in T(1) for ratios of repetition time to T1 time over the range of 0.01-0.45. We show for the case of brain imaging that it is sufficient to use only one small FA spoiled gradient-echo acquisition, which results in reduced spoiling requirements and a significant scan time reduction compared to the original variable FA method. In vivo validation yielded high-quality 3D T(1) maps and T(1) measurements within 10% of previously published values and within a clinically acceptable scan time. The variable FA-actual FA imaging method will increase the accuracy and clinical feasibility of many quantitative MRI methods requiring T(1)/B(1) mapping such as dynamic contrast enhanced perfusion and quantitative magnetization transfer imaging.

Magnetic Resonance Imaging Findings in Infants with Severe Traumatic Brain Injury and Associations with Abusive Head Trauma.

Young children with severe traumatic brain injury (TBI) have frequently been excluded from studies due to age and/or mechanism of injury. Magnetic resonance imaging (MRI) is now frequently being utilized to detect parenchymal injuries and early cerebral edema. We sought to assess MRI findings in infants with severe TBI, and to determine the association between specific MRI findings and mechanisms of injury, including abusive head trauma (AHT). MRI scans performed within the first 30 days after injury were collected and coded according to NIH/NINDS Common Data Elements (CDEs) for Neuroimaging in subjects age < 2 years old with severe TBI enrolled in the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial. Demographics and injury characteristics were analyzed. A total of 81 children were included from ADAPT sites with MRI scans. Median age was 0.77 years and 57% were male. Most common MRI finding was ischemia, present in 57/81 subjects (70%), in a median of 7 brain regions per subject. Contusion 46/81 (57%) and diffuse axonal injury (DAI) 36/81 (44.4%) subjects followed. Children were dichotomized based on likelihood of AHT with 43/81 subjects classified as AHT. Ischemia was found to be significantly associated with AHT (p = 0.001) and "inflicted" injury mechanism (p = 0.0003). In conclusion, the most common intracerebral injury seen on MRI of infants with severe TBI was ischemia, followed by contusion and DAI. Ischemia was associated with AHT, and ischemia affecting > 4 brain regions was predictive of AHT.

A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24; 13 males, 11 females) and standard diets (n = 17; 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A diet x age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.

Age- and gender-related changes in the normal human brain using hybrid diffusion imaging (HYDI).

Diffusion tensor imaging has been widely used to study brain diseases, disorders, development, and aging. However, few studies have explored the effects of aging on diffusion imaging measures with higher b values. Further, the water diffusion in biological tissues appears biexponential, although this also has not been explored with aging. In this study, hybrid diffusion imaging (HYDI) was used to study 52 healthy subjects with an age range from 18 to 72 years. The HYDI diffusion-encoding scheme consisted of five concentric q-space shells with b values ranging from 0 to 9375 s/mm(2). Quantitative diffusion measures were investigated as a function of age and gender using both region-of-interest (whole-brain white matter, genu and splenium of corpus callosum, posterior limb of the internal capsule) and whole-brain voxel-based analyses. Diffusion measures included measures of the diffusion probability density function (zero displacement probability and mean-squared displacement), biexponential diffusion (i.e., volume fractions of fast/slow diffusion compartments and fast/slow diffusivities), and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). The biexponential volume fraction, the fast diffusivity, and the axial diffusivity measures (f(1), D(1), and D(a)) were found to be more sensitive to normal aging than the restricted, slow and radial diffusion measures (P(0), D(2), and D(r)). The biexponential volume fraction, f(1), showed the most widespread age dependence in the voxel-based analyses, although both FA and mean diffusivity did show changes in frontal white matter regions that may be associated with age-related decline.

High b-value and diffusion tensor imaging in a canine model of dysmyelination and brain maturation.

Recent studies in rodents have demonstrated that diffusion imaging is highly sensitive to differences in myelination. These studies suggest that demyelination/dysmyelination cause increases in the radial diffusivity from diffusion tensor imaging (DTI) measurements and decreases in the restricted diffusion component from high b-value diffusion-weighted imaging experiments. In this study, the shaking pup (sh pup), a canine model of dysmyelination, was studied on a clinical MRI scanner using a combination of conventional diffusion tensor imaging and high b-value diffusion-weighted imaging methods. Diffusion measurements were compared between control dogs and sh pups in the age range 3 months to 16 months, which is similar to the period of early childhood through adolescence in humans. The study revealed significant group differences in nearly all diffusion measures with the largest differences in the zero-displacement probability (Po) from high b-value DWI and the radial diffusivity from DTI, which are consistent with the observations from the published rodent studies. Age-related changes in Po, FA, mean diffusivity, radial diffusivity and axial diffusivity were observed in whole brain white matter for the control dogs, but not the sh pups. Regionally, age-related changes in the sh pup white matter were observed for Po, mean diffusivity and radial diffusivity in the internal capsule, which may be indicative of mild myelination. These studies demonstrate that DWI may be used to study myelin abnormalities and brain development in large animal models on clinical MRI scanners, which are more amenable to translation to human studies.

The Connectomes: Methods of White Matter Tractography and Contributions of Resting State fMRI.

A comprehensive mapping of the structural and functional circuitry of the brain is a major unresolved problem in contemporary neuroimaging research. Diffusion-weighted and functional MRI have provided investigators with the capability to assess structural and functional connectivity in-vivo, driven primarily by methods of white matter tractography and resting-state fMRI, respectively. These techniques have paved the way for the construction of the functional and structural connectomes, which are quantitative representations of brain architecture as neural networks, comprised of nodes and edges. The connectomes, typically depicted as matrices or graphs, possess topological properties that inherently characterize the strength, efficiency, and organization of the connections between distinct brain regions. Graph theory, a general mathematical framework for analyzing networks, can be implemented to derive metrics from the connectomes that are sensitive to changes in brain connectivity associated with age, sex, cognitive function, and disease. These quantities can be assessed at either the global (whole brain) or local levels, allowing for the identification of distinct regional connectivity hubs and associated localized brain networks, which together serve crucial roles in establishing the structural and functional architecture of the brain. As a result, structural and functional connectomes have each been employed to study the brain circuitry underlying early brain development, neuroplasticity, developmental disorders, psychopathology, epilepsy, aging, neurodegenerative disorders, and traumatic brain injury. While these studies have yielded important insights into brain structure, function, and pathology, a precise description of the innate relationship between functional and structural networks across the brain remains unachieved. To date, connectome research has merely scratched the surface of potential clinical applications and related characterizations of brain-wide connectivity. Continued advances in diffusion and functional MRI acquisition, the delineation of functional and structural networks, and the quantification of neural network properties in specific brain regions, will be invaluable to future progress in neuroimaging science.