MR Imaging Differences in the Circle of Willis between Healthy Children and Adults.

BACKGROUND AND PURPOSE: Asymmetries in the circle of Willis have been associated with several conditions, including migraines and stroke, but they may also be age-dependent. This study examined the impact of age and age-dependent changes in cerebral perfusion on circle of Willis anatomy in healthy children and adults. MATERIALS AND METHODS: We performed an observational, cross-sectional study of bright and black-blood imaging of the proximal cerebral vasculature using TOF-MRA and T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (T2-SPACE) imaging at the level of the circle of Willis in 23 healthy children and 43 healthy adults (4-74 years of age). We compared arterial diameters measured manually and cerebral perfusion via pseudocontinuous arterial spin-labeling between children and adults. RESULTS: We found that the summed cross-sectional area of the circle of Willis is larger in children than in adults, though the effect size was smaller with T2-SPACE-based measurements than with TOF-MRA. The circle of Willis is also more symmetric in children, and nonvisualized segments occur more frequently in adults than in children. Moreover, the size and symmetry of the circle of Willis correlate with cerebral perfusion. CONCLUSIONS: Our results demonstrate that the circle of Willis is different in size and symmetry in healthy children compared with adults, likely associated with developmental changes in cerebral perfusion. Further work is needed to understand why asymmetric vasculature develops in some but not all adults.

A voxel-wise assessment of growth differences in infants developing autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults.

BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings. CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sß0 (HbSß0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSß0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

Functional mapping of the human visual cortex by magnetic resonance imaging.

Knowledge of regional cerebral hemodynamics has widespread application for both physiological research and clinical assessment because of the well-established interrelation between physiological function, energy metabolism, and localized blood supply. A magnetic resonance technique was developed for quantitative imaging of cerebral hemodynamics, allowing for measurement of regional cerebral blood volume during resting and activated cognitive states. This technique was used to generate the first functional magnetic resonance maps of human task activation, by using a visual stimulus paradigm. During photic stimulation, localized increases in blood volume (32 +/- 10 percent, n = 7 subjects) were detected in the primary visual cortex. Center-of-mass coordinates and linear extents of brain activation within the plane of the calcarine fissure are reported.

A prospective, longitudinal diffusion tensor imaging study of brain injury in newborns.

OBJECTIVE: To establish the magnitude and time course of the changes in water diffusion coefficient (D(av)) following newborn infant brain injury. METHODS: Ten newborn infants at high risk for perinatal brain injury were recruited from the neonatal intensive care unit. Conventional and diffusion tensor MRI was performed on three occasions during the first week of life. Regions of injury were determined by evaluating conventional MR images (T1, T2, fluid-attenuated inversion recovery) at 1 week after injury. D(av) values were determined for these regions for all three scans. RESULTS: D(av) values were decreased in most infants 1 day after injury, but injury was not evident or underestimated in 4 of 10 infants despite the presence of injury on conventional imaging at 1 week. By the third day, D(av) values were decreased in injured areas in all infants, reaching a nadir of approximately 35% less than normal values. By the seventh day after injury, D(av) values were returning to normal (pseudonormalization). CONCLUSIONS: MR diffusion images (for which contrast is determined by changes in D(av)) obtained on the first day after injury do not necessarily show the full extent of ultimate injury in newborn infants. Images obtained between the second and fourth days of life reliably indicate the extent of injury. By the seventh day, diffusion MR is less sensitive to perinatal brain injury than conventional MR because of transient pseudonormalization of D(av). Overall, diffusion MR may not be suitable as a gold standard for detection of brain injury during the first day after injury in newborn infants.

The role of ferritin and hemosiderin in the MR appearance of cerebral hemorrhage: a histopathologic biochemical study in rats.

A rat model of cerebral hemorrhage using stereotaxic injection of blood into the right basal ganglia was developed to investigate the influence of iron metabolism on the appearance of cerebral hemorrhage on MR images. Images of in vitro fixed brain sections stained specifically for different iron-storage substances, ferritin and hemosiderin, created by digitization of the pathology sections using an Eikonix CCD camera, were compared with the in vivo MR images of late-phase hematomas. Areas of the pathologic and MR features of the lesions were quantitatively correlated. The single-slice MR images were obtained with the use of T1- and T2-weighted spin-echo pulse sequences, as well as T2-weighted spin-echo pulse sequences in which the 180 degrees refocusing pulse was offset from the center of the echo time; this was termed an asymmetric spin-echo pulse sequence. The symmetric and asymmetric T2-weighted images allowed the calculation of line-width images, which emphasize line broadening from intravoxel magnetic field inhomogeneities that arise from the presence of iron-containing substances. From biochemical and histochemical staining, we conclude that at least two iron-storage substances are present in the late phase of resolving cerebral hematomas. Ferritin has a wider distribution than hemosiderin, showing a similar distribution to the MR signal changes of the calculated line-width images. Line-width mapping is a sensitive means of detecting magnetic field inhomogeneities caused by the magnetic susceptibility differences introduced by the aggregation of these iron-storage substances.

CT for pediatric, acute, minor head trauma: clinician conformity to published guidelines.

BACKGROUND AND PURPOSE: In 2001, pediatric radiologists participating in a panel discussion on CT dose reduction suggested that approximately 30% of head CT examinations were performed unnecessarily. With increasing concern regarding radiation exposure to children and imaging costs, this claim warrants objective study. The purpose of this study was to test the null hypothesis that 30% of head CT studies for clinical evaluation of children with acute, minor head trauma do not follow established clinical guidelines. MATERIALS AND METHODS: Retrospective review of 182 consecutive patients with acute, minor head trauma from February 2009 to January 2010 at a tertiary care children's hospital emergency department was performed, and clinician adherence to published clinical guidelines for children younger than 2 years and children 2-20 years of age was determined. The binomial test was used for a null hypothesis of 30% unnecessary examinations against the actual percentage of head CTs deemed unnecessary on the basis of established guidelines. Statistical testing was performed for children younger than 2 years and 2-20 years of age. RESULTS: For children younger than 2 years of age, 2 of 78 (2.6%; 95% CI, 0.5%-8.3%) and, for children 2-20 years of age, 12 of 104 (11.5%; CI, 6.4%-18.7%) did not conform to established guidelines. These percentages were significantly less than the hypothesized value of 30% (P < .001). CONCLUSIONS: Clinician conformity to published guidelines for use of head CT in acute, minor head trauma is better than suggested by a 2001 informal poll of pediatric radiologists.

White matter microstructural abnormality in children with hydrocephalus detected by probabilistic diffusion tractography.

BACKGROUND AND PURPOSE: Hydrocephalus is a severe pathologic condition in which WM damage is a major factor associated with poor outcomes. The goal of the study was to investigate tract-based WM connectivity and DTI measurements in children with hydrocephalus by using the probabilistic diffusion tractography method. MATERIALS AND METHODS: Twelve children with hydrocephalus and 16 age-matched controls were included in the study. Probabilistic diffusion tractography was conducted to generate tract-based connectivity distribution and DTI measures for the genu of the corpus callosum and the connectivity index. Tract-based summary measurements, including the connectivity index and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity), were calculated and compared between the 2 study groups. RESULTS: Tract-based summary measurement showed a higher percentage of voxels with lower normalized connectivity index values in the WM tracts in children with hydrocephalus. In the genu of the corpus callosum, the left midsegment of the corticospinal tract, and the right midsegment of the corticospinal tract, the normalized connectivity index value in children with hydrocephalus was found to be significantly lower (P < .05, corrected). The tract-based DTI measures showed that the children with hydrocephalus had significantly higher mean diffusivity, axial diffusivity, and radial diffusivity in the genu of the corpus callosum, left midsegment of the corticospinal tract, and right midsegment of corticospinal tract and lower fractional anisotropy in the genu of the corpus callosum (P < .05, corrected). CONCLUSIONS: The analysis of WM connectivity showed that the probabilistic diffusion tractography method is a sensitive tool to detect the decreased continuity in WM tracts that are under the direct influence of mechanical distortion and increased intracranial pressure in hydrocephalus. This voxel-based connectivity method can provide quantitative information complementary to the standard DTI summary measures.

Diffusion tensor imaging properties and neurobehavioral outcomes in children with hydrocephalus.

BACKGROUND AND PURPOSE: White matter structural alterations and the correlation with neuropsychological deficits in children with hydrocephalus have not been well investigated. In this prospective study, the objectives were the following: 1) to apply DTI to detect in vivo white matter alterations based on diffusion properties in children with acute hydrocephalus, 2) to quantify early neuropsychological deficits, and 3) to explore the correlation between potential neuropsychological deficits and abnormalities in functionally related white matter. MATERIALS AND METHODS: A total of 44 children, 24 with hydrocephalus and 20 controls, were enrolled in the study. DTI indices, FA, MD, AD, and RD, were evaluated in the gCC, sCC, PLIC, and ALIC. The ABAS-II was used as a broad screener of development, including conceptual, social, practical, and motor skills. The correlation between the Motor Scale and DTI indices in the PLIC was analyzed. RESULTS: DTI analyses showed that the gCC and sCC in children with hydrocephalus had lower FA and higher MD, driven by the increased RD with statistical significance (P < .05) or trend-level significance (P = .06). The PLIC and ALIC had significantly higher AD in children with hydrocephalus (P < .05). On the ABAS-II, parent ratings of general adaptive skills, conceptual skills, and motor skills were significantly lower in children with hydrocephalus (all at P < .05). The MD and RD values in the PLIC were found to have trend-level or significant correlation with the Motor Scale (P = .057, .041, respectively). CONCLUSIONS: DTI reveals alterations in the white matter structure in children with hydrocephalus with preliminary findings suggesting correlation with clinical motor deficits.

Susceptibility-weighted imaging: a new tool in the diagnosis and evaluation of abnormalities of the vein of Galen in children.

We retrospectively identified 9 consecutive children, 3 males and 6 females (age 5.2 ± 6.3 years, range 1 day to 18 years), with known or suspected AVGs who underwent MR imaging, including SWI, at our institution between January 2007 and March 2011. On the SWI sequence, arterialized blood flow was considered to be present in the vein of Galen or its tributaries when these showed abnormal signal hyperintensity from arteriovenous shunting. SWI findings were correlated with findings from DSA studies or findings from time-of-flight or contrast-enhanced MR angiography sequences. SWI was found to accurately differentiate between high-flow and low-flow AVGs and was also useful in characterizing the arterial supply and venous drainage patterns associated with high-flow AVGs.

The NIH MRI study of normal brain development (Objective-2): newborns, infants, toddlers, and preschoolers.

The Magn. Reson. Imaging (MRI) study of normal brain development currently conducted by the Brain Development Cooperative Group represents the most extensive MRI study of brain and behavioral development from birth through young adulthood ever conducted. This multi-center project, sponsored by four Institutes of the National Institutes of Health, uses a combined longitudinal and cross-sectional design to characterize normal, healthy brain and behavioral development. Children, ages newborn through 18-plus years of age, receive comprehensive behavioral, neurological and multimodal MRI evaluations via Objective-2 (birth through 4-years 5-months of age) and Objective-1 (4-years 6-months through 18 years of age and older). This report presents methods (e.g., neurobehavioral assessment, brain scan) and representative preliminary results (e.g., growth, behavior, brain development) for children from newborn through 4-years 5-months of age. To date, 75 participants from birth through 4-years 5-months have been successfully brain scanned during natural sleep (i.e., without sedation); most with multiple longitudinal scans (i.e., 45 children completing at least three scans, 22 completing four or more scans). Results from this younger age range will increase our knowledge and understanding of healthy brain and neurobehavioral development throughout an important, dynamic, and rapid growth period within the human life span; determine developmental associations among measures of brain, other physical characteristics, and behavior; and facilitate the development of automated, quantitative MR image analyses for neonates, infants and young children. The correlated brain MRI and neurobehavioral database will be released for use by the research and clinical communities at a future date.

A pilot randomized education rehabilitation trial is feasible in sickle cell and strokes.

A randomized trial was completed to assess the feasibility of a 2-year education rehabilitation program for students with sickle cell disease and memory deficits. Eleven students were assigned to tutoring with or without memory training for 2 years. Eighty-two percent completed the program. Evidence of improvement in memory and academic achievement existed. Educational rehabilitation is a feasible strategy, but further investigation is needed to assess the benefit in a multi center trial.

Reversible posterior leukoencephalopathy syndrome: evaluation with diffusion-tensor MR imaging.

PURPOSE: To characterize the changes in brain water diffusion caused by reversible posterior leukoencephalopathy syndrome (RPLS). MATERIALS AND METHODS: Twelve patients with the clinical features and conventional magnetic resonance (MR) imaging findings of RPLS underwent diffusion-tensor echo-planar MR imaging. The isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) were measured in posterior regions of diffusion abnormality and in anterior areas of normal-appearing brain. RESULTS: Across all 12 subjects, the mean D of (1.09 +/- 0.13 [SD]) x 10(-3) mm(2)/sec in affected posterior regions was 26% greater than its value of (0.87 +/- 0.07) x 10(-3) mm(2)/sec in normal-appearing anterior regions. The mean A(sigma) of 0.15 +/- 0.03 in posterior regions was 35% less than its value of 0.23 +/- 0.02 in anterior regions (t(11) = 9.58; P <.001). There was a significant inverse correlation between D and A(sigma) in posterior regions (r = -0.67; P <.018) but not in anterior regions (r = -0.12; P =.719). A follow-up study performed in one patient after resolution of symptoms documented reversal of elevated isotropic diffusion and at least partial recovery of anisotropy loss. CONCLUSION: The increased magnitude of brain water diffusion characteristic of RPLS is accompanied by reduced A(sigma). The magnitudes of these two effects are correlated and may be reversible. These observations support the proposal that vasogenic edema due to cerebrovascular autoregulatory dysfunction is the underlying pathophysiologic mechanism in uncomplicated RPLS.

Diffusion MRI: precision, accuracy and flow effects.

After a decade of evolution and application of diffusion imaging, a large body of literature has been accumulated. It is in this context that the accuracy and precision of diffusion-weighted and quantitative diffusion MRI are reviewed. The emphasis of the review is on practical methods for clinical human imaging, particularly in the brain. The requirements for accuracy and precision are reviewed for various clinical and basic science applications. The methods of measuring and calculating diffusion effects with MRI are reviewed. The pulse gradient spin echo (PGSE) methods are emphasized as these methods are used most commonly in the clinical setting. Processing of PGSE data is reviewed. Various PGSE encoding schemes are also reviewed in terms of the accuracy and precision of isotropic and anisotropic diffusion measurements. The broad range of factors impacting the accuracy of the PGSE methods and other encoding schemes is then considered. Firstly, system inaccuracies such as background imaging gradients, gradient linearity, refocusing RF pulses, eddy currents, image misregistration, noise and dynamic range are considered. A second class of inaccuracies is contributed by the bulk effects of the imaged object, and include sample background gradients, subject motion of cerebrospinal fluid and organs, and aperiodic organ motion. A final category of potential inaccuracies is classified as being contributed by microscopic, biophysical tissue properties and include partial volume effects, anisotropy, restriction, diffusion distance, compartmentation, exchange, multiexponential diffusion decay, T2 weighting and microvascular perfusion. Finally, the application of diffusion methods to studies of blood flow in the microvasculature (i.e. the arterioles, capillaries and venules) are reviewed in detail, particularly in terms of feasibility and the stringent accuracy and precision requirements. Recent provocative studies examining the use of PGSE approaches to suppress microvascular signals in brain functional MRI (fMRI) are also reviewed.

Encoding of anisotropic diffusion with tetrahedral gradients: a general mathematical diffusion formalism and experimental results.

A diffusion imaging method with a tetrahedral sampling pattern has been developed for high-sensitivity diffusion analysis. The tetrahedral gradient pattern consists of four different combinations of x, y, and z gradients applied simultaneously at full strength to uniformly measure diffusion in four different directions. Signal-to-noise can be increased by up to a factor of about three using this approach, compared with diffusion measurements made using separately applied x, y, and z gradients. A mathematical formalism is presented describing six fundamental parameters: the directionally averaged diffusion coefficient D and diffusion element anisotropies eta and epsilon which are rotationally invariant, and diffusion ellipsoid orientation angles theta, phi, and omega which are rotationally variant. These six parameters contain all the information in the symmetric diffusion tensor D. Principal diffusion coefficients, reduced anisotropies, and other rotational invariants are further defined. It is shown that measurement of off-diagonal tensor elements is essential to assess anisotropy and orientation, and that the only parameter which can be measured with the orthogonal method is D. In cases of axial diffusion symmetry (e.g., fibers), the four tetrahedral diffusion measurements efficiently enable determination of D, eta, theta, and phi which contain all the diffusion information. From these four parameters, the diffusion parallel and perpendicular to the symmetry axis (D and D) and the axial anisotropy A can be determined. In more general cases, the six fundamental parameters can be determined with two additional diffusion measurements. Tetrahedral diffusion sequences were implemented on a clinical MR system. A muscle phantom demonstrates orientation independence of D, D, D, and A for large changes in orientation angles. Sample background gradients and diffusion gradient imbalances were directly measured and found to be insignificant in most cases.

Principles and applications of echo-planar imaging: a review for the general radiologist.

Echo-planar imaging is a very fast magnetic resonance (MR) imaging technique capable of acquiring an entire MR image in only a fraction of a second. In single-shot echo-planar imaging, all the spatial-encoding data of an image can be obtained after a single radio-frequency excitation. Multishot echo-planar imaging results in high-quality images comparable to conventional MR images. However, echo-planar imaging offers major advantages over conventional MR imaging, including reduced imaging time, decreased motion artifact, and the ability to image rapid physiologic processes of the human body. The use of echo-planar imaging has already resulted in significant advances in clinical diagnosis and scientific investigation, such as in evaluation of stroke and functional imaging of the human brain, respectively. The clinical indications for echo-planar imaging are expanding rapidly, and it can now be applied to many parts of the body, including the brain, abdomen, and heart. Today, with the availability of echo-planar imaging-capable MR imagers at many sites, the general radiologist can benefit from echo-planar imaging and its clinical applications.

PET and MR studies of experimental focal stroke.

Positron emission tomography (PET) and MR have been compared with histochemical pathology to show affected tissue areas in rat brain after right middle cerebral artery (MCA) occlusion combined with temporary bilateral common carotid artery occlusion in Long Evans rats. The glucose metabolic rate was 65 +/- 8 mumol/100 ml/min in the right cortical gray matter corresponding to the occluded middle cerebral artery territory and 93 +/- 8 mumol/100 ml/min in the corresponding (left) normal side. Infarcted tissue showed decreased PET activity and increased signal in MR T2-weighted scans ipsilateral to the MCA occlusion. These regions correspond to a zone of focal infarction identified in coronal tissue sections stained with 3-4-5 triphenyl tetrazolium chloride. This study demonstrates that PET can be used to study glucose utilization in rat stroke model in vivo and noninvasively.