Search

To develop a phantom system which can be integrated with an automated injection system, eliminating the experimental variability that arises with manual injection; for the purposes of pulse sequence testing and metric derivation in hyperpolarisedThe custom dynamic phantom was machined from Ultem and filled with a nicotinamide adenine dinucleotide and lactate dehydrogenase mixture dissolved in phosphate buffered saline. Hyperpolarised [1-The phantom showed low coefficient of variation for the lactate to pyruvate peak signal heights (11.6%) and dynamic area-under curve ratios (11.0%). The variance for the lactate dehydrogenase enzyme rate constant (kP) was also seen to be low at 15.6%.The dynamic phantom demonstrates high reproducibility for quantification ofThe dynamic phantom developed during the course of this study will be a useful tool in testing new pulse sequences and standardisation in future hyperpolarised work.

Highlights • We studied manual function in patients exposed to neonatal hypoxia-ischaemia. • Patients had preserved function in motor adaptation learning, and in speed and accuracy of handwriting. • Manual coordination was impaired on a timed pegboard task. • Motor impairment was associated with bilaterally reduced volumes of the caudate nuclei. • Early basal ganglia damage may lead to persistent deficits in fine manual control., Acute sentinel hypoxia-ischaemia in neonates can target the hippocampus, mammillary bodies, thalamus, and the basal ganglia. Our previous work with paediatric patients with a history of hypoxia-ischaemia has revealed hippocampal and diencephalic damage that impacts cognitive memory. However, the structural and functional status of other brain regions vulnerable to hypoxia-ischaemia, such as the basal ganglia, has not been investigated in these patients. Furthermore, it is not known whether there are any behavioural sequelae of such damage, especially in patients with no diagnosis of neurological disorder. Based on the established role of the basal ganglia and the thalamus in movement coordination, we studied manual motor function in 20 participants exposed to neonatal hypoxia-ischaemia, and a group of 17 healthy controls of comparable age. The patients’ handwriting speed and accuracy was within the normal range (Detailed Assessment of Speed of Handwriting), and their movement adaptation learning (Rotary Pursuit task) was comparable to the control group’s performance. However, as a group, patients showed an impairment in the Grooved Pegboard task and a trend for impairment in speed of movement while performing the Rotary Pursuit task, suggesting that some patients have subtle deficits in fine, complex hand movements. Voxel-based morphometry and volumetry showed bilateral reduction in grey matter volume of the thalamus and caudate nucleus. Reduced volumes in the caudate nucleus correlated across patients with performance on the Grooved Pegboard task. In summary, the fine movement coordination deficit affecting the hand and the wrist in patients exposed to early hypoxic-ischaemic brain injury may be related to reduced volumes of the caudate nucleus, and consistent with anecdotal parental reports of clumsiness and coordination difficulties in this cohort.

Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8‐16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2017 Wiley Periodicals, Inc.

Global anterograde amnesia is described in three patients with brain injuries that occurred in one case at birth, in another by age 4, and in the third at age 9. Magnetic resonance techniques revealed bilateral hippocampal pathology in all three cases. Remarkably, despite their pronounced amnesia for the episodes of everyday life, all three patients attended mainstream schools and attained levels of speech and language competence, literacy, and factual knowledge that are within the low average to average range. The findings provide support for the view that the episodic and semantic components of cognitive memory are partly dissociable, with only the episodic component being fully dependent on the hippocampus.

We assessed performance on selected tests of verbal memory in 48 patients who had undergone either anterior temporal lobectomy or selective amygdalo-hippocampectomy for the relief of pharmacologically intractable epilepsy. We related performance both to the side of surgical excision and to the presence or absence of abnormalities in the contralateral, unoperated, temporal lobe, as revealed by proton magnetic resonance spectroscopy (1H MRS) or T2 relaxometry. There were abnormalities on the unoperated side detected by 1H MRS in 50% of the 34 patients who successfully underwent spectroscopy, and by T2 relaxometry in 33% of the complete series of 48 patients. There was no systematic relationship between seizure outcome and the presence or absence of abnormalities on the unoperated side. Verbal memory deficits were present in patients with left-sided excision, regardless of whether there were abnormalities on the unoperated side. The patients with right-sided excision also had verbal memory deficits, but only in the group with magnetic resonance abnormalities on the contralateral (ie, left) side and only on delayed recall. The study extends previous findings on the role of the temporal lobes in memory and highlights the role of these new magnetic resonance techniques in relating cognitive processes to brain structures.

Highlights ► Children with bilateral hippocampal damage are impaired at recalling past events. ► They are intact at imagining fictitious experiences. ► This contrasts with adult amnesic patients who are impaired at both. ► Hippocampal damage affects memory differently depending on when in life it occurs., Compared to adults, relatively little is known about autobiographical memory and the ability to imagine fictitious and future scenarios in school-aged children, despite the importance of these functions for development and subsequent independent living. Even less is understood about the effect of early hippocampal damage on children's memory and imagination abilities. To bridge this gap, we devised a novel naturalistic autobiographical memory task that enabled us to formally assess the memory for recent autobiographical experiences in healthy school-aged children. Contemporaneous with the autobiographical memories being formed, the children also imagined and described fictitious scenarios. Having established the performance of healthy school-aged children on these tasks, we proceeded to make comparisons with children (n = 21) who had experienced neonatal hypoxia/ischaemia, and consequent bilateral hippocampal damage. Our results showed that healthy children could recall autobiographical events, including spatiotemporal information and specific episodic details. By contrast, children who had experienced neonatal hypoxia/ischaemia had impaired recall, with the specific details of episodes being lost. Despite this significant memory deficit they were able to construct fictitious scenarios. This is in clear contrast to adults with hippocampal damage, who typically have impaired autobiographical memory and deficits in the construction of fictitious and future scenarios. We speculate that the paediatric patients’ relatively intact semantic memory and/or some functionality in their residual hippocampi may underpin their scene construction ability.

Continuous arterial spin labeling (CASL) measurements over a range of post-labeling delay (PLD) times can be interpreted to estimate cerebral blood flow (CBF) and arterial transit time (deltaa) with good spatial and temporal resolution. In this work, we present an in vivo demonstration of Hadamard-encoded continuous arterial spin labeling (H-CASL); an efficient method of imaging the inflow of short boli of labeled blood water in the brain at multiple PLD times. We present evidence that H-CASL is viable for in vivo application in the rat brain and can improve the precision of deltaa estimation in 2/3 of the imaging time required for standard multi-PLD CASL. Based on these findings, we propose that H-CASL may have application as an efficient prescan for optimization of ASL imaging parameters to improve the precision of CBF estimation.

Although observational findings linking breast milk to higher scores on cognitive tests may be confounded by factors associated with mothers' choice to breastfeed, it has been suggested that one or more constituents of breast milk facilitate cognitive development, particularly in preterms. Because cognitive scores are related to head size, we hypothesized that breast milk mediates cognitive effects by affecting brain growth. We used detailed data from a randomized feeding trial to calculate percentage of expressed maternal breast milk (%EBM) in the infant diet of 50 adolescents. MRI scans were obtained (mean age=15 y 9 mo), allowing volumes of total brain (TBV) and white and gray matter (WMV, GMV) to be calculated. In the total group, %EBM correlated significantly with verbal intelligence quotient (VIQ); in boys, with all IQ scores, TBV and WMV. VIQ was, in turn, correlated with WMV and, in boys only, additionally with TBV. No significant relationships were seen in girls or with gray matter. These data support the hypothesis that breast milk promotes brain development, particularly white matter growth. The selective effect in males accords with animal and human evidence regarding gender effects of early diet. Our data have important neurobiological and public health implications and identify areas for future mechanistic study.

Convulsive status epilepticus (SE) is a common medical neurological emergency and is associated with hippocampal injury and the subsequent development of epilepsy. However, pathophysiological mechanisms that underlie injury remain unclear, and a clinically useful prognostic biomarker of at-risk patients remains elusive. We hypothesised that non-invasive quantitative multi-parametric MRI characterisation of the early time course in the lithium-pilocarpine rat model would provide insight into pathophysiological processes, and may help to develop a non-invasive prognostic marker of hippocampal injury. T(1), T(2), apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) were measured before and after SE on days 0, 1, 2, 3, 7, 14 and 21. Hippocampal volume measurements were used to assess final structural outcome. MRI changes were found in the parietal cortex, hippocampus, piriform cortex, and thalamus. Each of the regions displayed time-dependent changes, and returned to baseline levels by Day 7. Hippocampal measurements peaked on Day 2, and further analysis revealed that the magnitude of these peak changes was predictive of the hippocampal volumes on Day 21. This time course is consistent with cell death and an inflammatory process. The maximal changes provide a potential clinically useful prognostic marker of final hippocampal volume.

To compare quantitative T2 relaxometry of cerebral white matter (WM) with qualitative assessment of conventional T2-weighted magnetic resonance (MR) images, to assess the relationship between cerebral WM T2 and region-specific apparent diffusion coefficient (ADC), and to examine WM T2 regional variation in preterm infants at term.The local ethical committee granted ethical permission for this study; informed parental consent was obtained for each infant. Sixty-two preterm infants born at less than 32 weeks gestation and nine control infants were examined at 1.5 T; T2-weighted fast spin-echo MR images, T2 relaxometry data, and diffusion-weighted MR images were acquired. Conventional T2-weighted MR images were assessed by a pediatric neuroradiologist for diffuse excessive high signal intensity (DEHSI) in WM. Regions of interest were positioned in frontal WM, central WM, and posterior WM at the level of the centrum semiovale.In preterm infants at term, T2 was longer in all WM regions than in control infants; in infants with DEHSI, T2 was longer than in infants without DEHSI and control infants, with posterior WM T2 being longer than central or frontal WM T2. In control infants, T2 was similar in all WM regions. Frontal and posterior WM ADCs were higher in preterm infants at term than in control infants.Cerebral WM T2 is an objective quantitative measurement that can easily and rapidly be obtained during clinical MR imaging in preterm infants at term.

To determine the clinical value of motor functional magnetic resonance imaging (fMRI) in the presurgical evaluation of a large group of children and adolescents with epilepsy caused by lesions close to the central sulcus., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Neurogenesis occurs at the subependymal zone (SEZ) of the adult brain. Neural progenitor cells give rise to neuroblasts, which migrate to the olfactory bulb (OB) via the rostral migratory stream (RMS). Development of methods capable of labelling and tracking these cells in vivo would be of great benefit to the understanding of neuroblast migration away from the SEZ under normal and pathological conditions. In this study, we demonstrate that endogenous neuroblasts can be labelled in vivo with an MRI contrast agent and that they can be visualised using MRI. We compared two labelling strategies: intraventricular injection of the ferumoxide Endorem, with or without the transfection agent protamine sulphate. Administration of Endorem alone resulted in its distribution outside of the ventricle and into the periventricular space after 48 h. In contrast, we observed that intraventricular injection of Endorem complexed to protamine sulphate forming the FePro complex - is restricted to the ventricular walls after 48 h. The FePro complex successfully labelled Doublecortin(+) neuroblasts in vivo up to 28 days post-injection. FePro-labelled neuroblasts in the RMS could be visualised using MRI in vivo and ex vivo on a 2.35 T MRI system, and FePro-labelled cells were identified in the OB on a 9.4 T MRI system. This study demonstrates the feasibility of in vivo imaging of endogenous neuroblast migration using MRI. (C) 2008 Elsevier Inc. All rights reserved.

Convulsive status epilepticus is associated with subsequent hippocampal damage and development of mesial temporal sclerosis in a subset of individuals. The lithium pilocarpine model of status epilepticus (SE) in the rat provides a model in which to investigate the molecular and pathogenic process leading to hippocampal damage. In this study, a 2-DE-based approach was used to detect proteome changes in the hippocampus, at an early stage (2 days) after SE, when increased T2 values were detectable by magnetic resonance imaging. Gel image analysis was followed by LC-MS/MS identification of protein species that differed in abundance between pilocarpine-treated and control rats. The most significantly up-regulated species in the experimental animals was identified as heat shock 27-kDa protein, in line with findings in humans and in other experimental models of epilepsy. Additional up-regulated species included dihydropyrimidinase-related protein-2, cytoskeletal proteins (alpha-tubulin and ezrin) and dihydropteridine reductase. In summary, the hippocampus of rats subject to pilocarpine-induced SE exhibits specific changes in protein abundance, which likely relate to pathogenic, neuroprotective and neurogenic responses.

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life.

Perfusion maps, which are calculated from dynamic-susceptibility contrast (DSC)-MRI data by deconvolution of the arterial input function (AIF), are commonly used to predict tissue infarction in acute stroke. However, since the AIF is commonly measured in a major artery, there can be perfusion measurement errors associated with bolus delay/dispersion. Although methods to account for delay-related errors have been proposed, the effect of dispersion is more difficult to deal with and is usually left uncorrected. This study presents an assessment of the delay-dispersion relationship in a group of patients. Although a significant correlation was observed with one of the bolus delay definitions used, the estimation of the dispersion from the degree of delay was unreliable. Importantly, the dispersion observed in many patients was sufficient to result in substantial perfusion errors. The results are compared with previous numerical simulations, and their implications for the assessment and management of acute stroke are discussed.

The aim of this study was to identify grey matter density abnormalities in children with temporal lobe epilepsy and mesial temporal sclerosis. Magnetic resonance T1 weighted 3D datasets were obtained in children with temporal lobe epilepsy (20 left and 10 right sided, mean age 11.9 years, range 6.6-17.5) and compared to scans obtained from age-matched controls (n = 22, mean age 12.8 years, range 7.1-17.5) using voxel-based morphometry. This method detected reduced grey matter ipsilateral to the seizure focus not only in the hippocampus, but also in the lateral temporal lobe and in extra-temporal regions including the thalamus, posterior cingulate cortex and cerebellum. Bilateral differences were present in the frontal and parietal opercular cortices and lateral temporal regions. These grey matter density reductions broadly reflect the pattern of hippocampal connections and may be caused by the disruption of cortical development by the recurrent seizures, as well as by loss of functional input from the sclerotic hippocampus. (c) 2005 Elsevier Inc. All rights reserved.

The neural basis of autistic spectrum disorders (ASDs) is poorly understood. Studies of mnemonic function in ASD suggest a profile of impaired episodic memory with relative preservation of semantic memory (at least in high-functioning individuals). Such a pattern is consistent with developmental hippocampal abnormality. However, imaging evidence for abnormality of the hippocampal formation in ASD is inconsistent. These inconsistencies led us to examine the memory profile of children with ASD and the relationship to structural abnormalities. A cohort of high-functioning individuals with ASD and matched controls completed a comprehensive neuropsychological memory battery and underwent magnetic resonance imaging for the purpose of voxel-based morphometric analyses. Correlations between cognitive/behavioural test scores and quantified results of brain scans were also carried out to further examine the role of the medial temporal lobe in ASD. A selective deficit in episodic memory with relative preservation of semantic memory was found. Voxel-based morphometry revealed bilateral abnormalities in several areas implicated in ASD including the hippocampal formation. A significant correlation was found between parental ratings reflecting autistic symptomatology and the measure of grey matter density in the junction area involving the amygdala, hippocampus and entorhinal cortex. The data reveal a pattern of impaired and relatively preserved mnemonic function that is consistent with a hippocampal abnormality of developmental origin. The structural imaging data highlight abnormalities in several brain regions previously implicated in ASD, including the medial temporal lobes.

Although selective vulnerability and delayed neuronal death following global ischemia have been recognized in both the human and animal brain, the underlying mechanisms of cell damage are not fully understood. In this study we investigated the time-dependent changes of the apparent diffusion coefficient (ADC) of water and cerebral blood flow (CBF) in a classic animal model of selective vulnerability and delayed neuronal death, using magnetic resonance (MR) diffusion- and perfusion-weighted imaging. CBF was monitored using the noninvasive MR arterial spin labeling method called flow-sensitive alternating inversion recovery (FAIR). Bilateral common carotid occlusion was induced for 5 min, followed by 10 hr of reperfusion in a gerbil model. The most notable finding was that the lateral portion of the striatum in the basal ganglia exhibited a prolonged and gradual ADC decrease throughout the study following reperfusion. This pattern was not exhibited within the cortex. It is suggested that regions known to exhibit so-called delayed cell death progress to infarction via a gradual process that can be monitored by MR diffusion-weighted imaging (DWI).

Multiple-slice perfusion imaging by continuous arterial spin labeling (CASL) is made possible by amplitude modulation (AM) of the labeling RF pulse, but perfusion sensitivity is reduced relative to the single-slice technique. A computer model of the Bloch equations for velocity driven adiabatic fast passage was developed to elucidate the compromised sensitivity to perfusion of the AM control technique for CASL. Calculations were performed over ranges of RF pulse amplitude, B-1; magnetic field gradient, G; phase, phi, and frequency, f, of the modulation function; velocity, v, and relaxation times, T-1 and T-2, of blood. It was found that unless f > 2 pi B-1, phi determines the performance of the AM control; excessively high B-1 or v reduces the efficiency of the AM control; and T, relaxation dominates if f is too great. In vivo, in rat brain (n = 5) at 2.35 T, the sensitivity of the AM technique to perfusion was 70% of the sensitivity of single-slice CASL.

Mesial temporal sclerosis (MTS) is the most common lesion in patients who require epilepsy surgery, and approximately 50% of patients with MTS have a history of prolonged febrile convulsion (PFC) in childhood. The latter led to the hypothesis that convulsive status epilepticus, including PFC, can cause MTS. Our recently published data on children investigated within 5 days of a PFC showed that children investigated by MRI within 48 h of a PFC had large hippocampal volumes and prolongation of T2 relaxation time. Patients investigated48 h from a PFC had large hippocampal volumes and normal T2 relaxation time. These data are strongly suggestive of hippocampal oedema that is resolving within 5 days of a PFC, but do not exclude the possibility of a pre-existing hippocampal lesion. Fourteen children from the original study had follow-up investigations carried out 4-8 months after the acute investigations. Of the 14 patients, four have had further seizures. Two had short febrile convulsions, one had PFC and one had non-febrile seizures. There was a significant reduction in hippocampal volume and T2 relaxation time between the first and second investigations, and there is now no difference in hippocampal volume or T2 relaxation time in patients compared with a control population. Moreover, there is a significant increase in hippocampal volume asymmetry in patients at follow-up when compared with initial data. Five out of 14 patients had asymmetry outside the 95th percentile for control subjects and, of these, three had one hippocampal volume outside the lower 95% prediction limit for control subjects. A reduction in hippocampal volume or T2 relaxation time, into or below the normal range between the first and second scans, indicates that the earlier findings are temporary and are strongly suggestive of hippocampal oedema as the abnormality in the initial investigations. The change in hippocampal symmetry in the patient group is consistent with injury and neuronal loss associated with a PFC, especially in the three individuals who now have a single small hippocampus. However, as there is no T2 relaxation time abnormality, the hippocampi do not meet the criteria for MTS. There may be a lag period of several years between a PFC and the onset of epilepsy, and therefore some of these patients may be developing MTS. Alternatively, the asymmetry could represent return (post-acute oedema) to a pre-existing hippocampal abnormality similar to that identified in family members of patients with MTS and a history of PFC.

Two groups of adolescents, one born preterm and one with a diagnosis of developmental amnesia, were compared with age-matched normal controls on measures of hippocampal volume and memory function. Relative to control values, the preterm group values showed a mean bilateral reduction in hippocampal volume of 8–9% (ranging to 23%), whereas the developmental amnesic group values showed a reduction of 40% (ranging from 27% to 56%). Despite equivalent IQ and immediate memory scores in the two study groups, there were marked differences between them on a wide variety of verbal and visual delayed memory tasks. Consistent with their diagnosis, the developmental amnesic group was impaired relative to both other groups on nearly all delayed memory measures. The preterm group, by contrast, was significantly impaired relative to the controls on only a few memory measures, i.e., route following and prospective memory. We suggest that early hippocampal pathology leads to the disabling memory impairments associated with developmental amnesia when the volume of this structure is reduced below normal by ≈20–30% on each side. Whether this is a sufficient condition for the disorder or whether abnormality in other brain regions is also necessary remains to be determined.

The aim of this study was to determine whether partial epilepsy is associated with abnormalities in hippocampi that are not the primary seizure focus. As hippocampal T2 relaxometry is useful for identifying abnormalities that are not obvious on visual assessment of MRI, this was the method employed. Of 457 consecutive children and young adults from whom T2 relaxometry data were obtained, 96 had well characterized partial epilepsy and were enrolled, along with 27 control subjects. The patients were divided on the basis of clinical, video-EEG and visual MRI assessment into three groups: (i) those with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS) (MTS-TLE); (ii) lesional TLE (l-TLE); or (iii) extratemporal epilepsy (ETE). There was a significant and similar prolongation of T2 relaxation time identified in hippocampi remote from the seizure focus in all patient groups when compared with control subjects. In the non-sclerotic hippocampus of patients with MTS, T2 relaxation time was prolonged by a mean of 3.3 ms [95% confidence interval (CI), 0.8-5.9 ms; P = 0.01], patients with l-TLE had prolongation of T2 relaxation time by a mean of 4.3 ms (95% CI, 1.8-7.1 ms; P = 0.001) and those with ETE had prolongation of T2 relaxation time by a mean of 3.7 ms (95% CI, 1.6-6.6 ms; P = 0.006) compared with control subjects after adjustment for age. Unsurprisingly, in patients with MTS-TLE, T2 relaxation time in the sclerotic hippocampus was prolonged by a mean of 19 ms (95% CI = 14.6-22.4 ms; P < 0.001). The similarity in the extent of prolongation of T2 relaxation time in hippocampi that are not the primary epileptogenic focus, the wide variety of structural associations and the varied sites of epileptogenic foci, considered together, suggest that the abnormalities are likely to be caused by ongoing seizure activity rather than by underlying aetiology or site of epileptogenic focus.

Arterial spin labeling magnetic resonance methods, including flow-sensitive alternating inversion recovery (FAIR), are becoming increasingly common for the noninvasive quantification of cerebral blood flow (CBF). This report compares the FAIR method with hydrogen clearance. The latter is an established, invasive technique for CBF measurement in animals. Paired readings of CBF were obtained in gerbils to maximize the degree of spatial and temporal correspondence between methods. Flow-sensitive alternating inversion recovery (50 averages, 6.7-minute measurement time) and hydrogen clearance measurements were made concurrently. Cerebral blood flow values measured by both techniques displayed an initial decrease because of the injurious effects of electrode insertion and subsequent recovery. Mixed model regression analysis, structural equations modeling, and a simple concordance correlation coefficient analysis were performed. No evidence of a marked systematic bias in the FAIR measurements was found; mixed model regression analysis yielded relative bias estimates of 0.4 (confidence interval: 3.0, 3.9) mL · 100 g−1 · min−1 and −3.7 (−12.1, 4.7) mL · 100 g−1 · min−1 at 20 and 100 mL · 100 g−1 · min−1, respectively. The principal limitation of the FAIR technique was the magnitude of the random measurement error (imprecision), which had a standard deviation on the order of 10 mL · 100 g−1 · min−1.

Velocity-driven adiabatic fast passage (AFP) is commonly employed for perfusion imaging by continuous arterial spin labeling (CASL). The degree of inversion of protons in blood determines the sensitivity of CASL to perfusion. For this study, a computer model of the modified Bloch equations was developed to establish the optimum conditions for velocity-driven AFP. Natural variations in blood velocity over the course of the cardiac cycle were found to result in significant variations in the degree of inversion. However, the mean degree of inversion was similar to that for blood moving at a constant velocity, equal to the time-averaged mean, at peak velocities and heart rates within normal ranges. A train of RF pulses instead of a continuous RF pulse for labeling was found to result in a highly nonlinear dependence of the degree of inversion on RF duty cycle. This may have serious implications for the quantification of perfusion.

New magnetic resonance techniques now provide increasingly powerful ways of identifying the structural correlates of impaired cerebral function. The aims of this article are to show how we have been using a variety of magnetic resonance techniques to identify focal pathophysiology in children with brain disease, and to describe how these findings have contributed to our understanding of impaired function in these children. An outline is given of the methods that we have chosen to use, and this is followed by their applications in a number of groups of patients. The examples that are given illustrate the importance of detecting brain abnormalities that might previously have gone undetected.

Background — MR techniques have been very powerful in providing indicators of tissue perfusion, particularly in studies of cerebral ischemia. There is considerable interest in performing absolute perfusion measurements, with the aim of improving the characterization of tissue “at risk” of stroke. However, some important caveats relating to absolute measurements need to be taken into account. The purpose of this article is to discuss some of the issues involved and the potential implications for absolute cerebral blood flow measurements in clinical use. Summary of Comment — In bolus tracking MRI, deconvolution of the concentration-time course can in theory provide accurate quantification. However, there are several important assumptions in the tracer kinetic model used, some of which may be invalid in cerebral ischemia. These can introduce significant errors in perfusion quantification. Conclusions — Although we believe that bolus tracking MRI is a powerful technique for the evaluation of perfusion in cerebral ischemia, interpretation of perfusion maps requires caution; this is particularly true when absolute quantification is attempted. Work is currently under way in a number of centers to address these problems, and with appropriate modeling they may be overcome in the future. In the interim, we believe that it is necessary for users of bolus tracking perfusion data to be aware of the current technical limitations if they are to avoid misinterpretation or overinterpretation of their findings.

Objective: To investigate whether quantitative MR techniques can be used to distinguish between mesial temporal sclerosis in patients with a history of prolonged febrile convulsion and in patients without such a history. Methods: Quantitative hippocampal T2 relaxometry, hippocampal volumetry, and single voxel 1 H-MRS data were acquired from 16 children who subsequently underwent temporal lobe resections for intractable temporal lobe epilepsy and histologically were shown to have sclerosis of the horn of Ammon. Eight children had a history of prolonged febrile convulsion in early childhood and eight children had other or no associations. Results: Patients with a history of prolonged febrile convulsion had smaller hippocampi ( p = 0.02) and prolonged T2 relaxation time ( p = 0.03) ipsilateral to the seizure focus when compared with patients without such a history. There was also more side-to-side asymmetry of T2 relaxation time ( p = 0.004) and hippocampal volume ( p = 0.02) in the patients with a history of prolonged febrile convulsion than in those with other or no associations. No differences between the groups were identified using 1 H-MRS. Conclusions: These data support the view that there are at least two types of mesial temporal sclerosis. There may be several pathogenetic pathways from initial insult to later mesial temporal sclerosis, and these pathways are, at least in part, dependent on the initial insult.

Neurological complications are common in sickle cell disease (SCD). However, it is often difficult to relate the clinical presentation to conventional neuroimaging, because subclinical infarction is common and stroke has been described in the absence of large-vessel disease. We studied 48 patients with SCD aged 4-34 (median 13) years with T2-weighted, diffusion and perfusion magnetic resonance imaging (MRI) and with MR angiography. Forty-four underwent transcranial Doppler (TCD). Abnormalities on perfusion imaging were seen in 25 cases, 24 of whom had been symptomatic. The remaining patient had evidence of executive dysfunction and reduced perfusion in the frontal lobes. The perfusion abnormality was larger than the area of infarction in 9 patients and was seen in an arterial distribution with no infarction in a further 9. In 3 patients with transient ischemic attacks, perfusion abnormalities were demonstrated in the absence of any other neuroimaging abnormalities, and perfusion changes were seen in 3 others despite normal MR angiography and TCD. Perfusion abnormalities are associated with neurological symptoms in patients with SCD, whether or not MRI, MR angiography, and TCD are abnormal. It is likely that this technique will guide management in individual patients.

Children who have suffered extensive unilateral brain injury early in life may show a remarkable degree of residual sensorimotor function. It is generally believed that this reflects the high capacity of the immature brain for cerebral reorganization. In this study, we investigated 17 patients who had undergone hemispherectomy for relief from seizures; eight of the patients had congenital brain damage and nine had sustained their initial insult at the age of 1 year or older. Sensorimotor functions of the hand were investigated using functional MRI (fMRI) during a passive movement task, somatosensory evoked potentials (SEPs) arising from electrical and vibration stimulation, and behavioural tests including grip strength, double simultaneous stimulation and joint position sense. On fMRI, two of the eight patients studied with this technique (one with congenital damage and one with damage acquired at the age of 3 years) showed activation in the sensorimotor cortex of the remaining hemisphere with passive movement of the hemiplegic hand. The location of the ipsilateral brain activation was similar to that found on movement of the normal contralateral hand, although the latter was greater in spatial extent. In one of these patients, a greater role was demonstrated for the ipsilateral secondary sensorimotor area (compared with the ipsilateral primary sensorimotor area) for movement of the hemiplegic hand than for movement of the normal hand. Median nerve stimulation of the hemiplegic hand showed reproducible early-latency ipsilateral SEP components in the remaining sensorimotor cortex in 10 of the 17 patients (five with congenital and five with acquired disease). Five of the patients who demonstrated ipsilateral electrical SEPs also showed ipsilateral vibration SEPs (two with congenital and three with acquired disease). The behavioural tests revealed residual sensorimotor function in 14 of the patients; however, not all of the patients who exhibited ipsilateral SEP or fMRI responses had residual sensorimotor function in the hemiplegic hand. Ipsilateral sensorimotor responses were demonstrated both in patients with congenital disease and those with acquired disease, suggesting that factors additional to aetiology and age at injury may influence the degree of residual sensorimotor function and cerebral reorganization.

We recently reported on three young patients with severe impairments of episodic memory resulting from brain injury sustained early in life. These findings have led us to hypothesize that such impairments might be a previously unrecognized consequence of perinatal hypoxic-ischaemic injury. Neuropsychological and quantitative magnetic resonance investigations were carried out on five young patients, all of whom had suffered hypoxic-ischaemic episodes at or shortly after birth. All five patients showed severe impairments of episodic memory (memory for events), with relative preservation of semantic memory (memory for facts). However, none had any of the major neurological deficits that are typically associated with hypoxic-ischaemic injury, and all attended mainstream schools. Quantitative magnetic resonance investigations revealed severe bilateral hippocampal atrophy in all cases. As a group, the patients also showed bilateral reductions in grey matter in the regions of the putamen and the ventral part of the thalamus. On the basis of their clinical histories and the pattern of magnetic resonance findings, we attribute the patients' pathology and associated memory impairments primarily to hypoxic-ischaemic episodes sustained very early in life. We suggest that the degree of hypoxia-ischaemia was sufficient to produce selective damage to particularly vulnerable regions of the brain, notably the hippocampi, but was not sufficient to result in the more severe neurological and cognitive deficits that can follow hypoxic-ischaemic injury. The impairments in episodic memory may be difficult to recognize, particularly in early childhood, but this developmental amnesia can have debilitating consequences, both at home and at school, and may preclude independent life in adulthood.

We are indebted to the KE family for their continued cooperation with our research program. We thank our collaborators at the Wellcome Department of Cognitive Neurology, Institute of Neurology, London, for assistance with the PET study and morphometric analyses, and our colleagues in the Cognitive Neuroscience Unit and Radiology and Physics Unit at the Institute of Child Health, London, for assistance with data collection and analysis. We thank Drs. Mortimer Mishkin, Marcus Pembrey, Tomas Paus, and Gabriel Leonard, for useful discussion and for comments on the manuscript.

Background and Purpose —Existing methods for the quantitative measurement of the changing cerebral blood flow (CBF) during reperfusion suffer from poor spatial or temporal resolution. The aim of this study was to implement a recently developed MRI technique for quantitative perfusion imaging in a gerbil model of reperfusion. Flow-sensitive alternating inversion recovery (FAIR) is a noninvasive procedure that uses blood water as an endogenous tracer. Methods —Bilateral forebrain ischemia of 4 minutes’ duration was induced in gerbils (n=8). A modified version of FAIR with improved time efficiency was used to provide CBF maps with a time resolution of 2.8 minutes after recirculation had been initiated. Quantitative diffusion imaging was also performed at intervals during the reperfusion period. Results —On initiating recirculation after the transient period of ischemia, the FAIR measurements demonstrated either a symmetrical, bilateral pattern of flow impairment (n=4) or an immediate side-to-side difference that became apparent with respect to the cerebral hemispheres in the imaged slice (n=4). The flow in each hemisphere displayed a pattern of recovery close to the preocclusion level or, alternatively, returned to a lower level before displaying a delayed hypoperfusion and a subsequent slow recovery. The diffusion measurements during this latter response suggested the development of cell swelling during the reperfusion phase in the striatum. Conclusions —The CBF during the reperfusion period was monitored with a high time resolution, noninvasive method. This study demonstrates the utility of MRI techniques in following blood flow changes and their pathophysiological consequences.

This study examined the relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow (99mTc-hexamethylpropylene amine oxime) and cerebral hypoxia (125I-iodoazomycin arabinoside) in a rat model of stroke. Middle cerebral artery occlusion in the rat was performed using an intraluminal suture approach. Diffusion, hypoxia, and blood flow maps were acquired 2 hr following occlusion, and were compared with T2 images and histology at 7 hr. Two hours following middle cerebral artery occlusion the lesion distributions from the diffusion maps and hypoxic autoradiographs were similar. The blood flow threshold for increased uptake of the hypoxic marker was approximately 34 +/- 7% of the normal flow. The combination of diffusion or hypoxic images with perfusion maps allowed differentiation between four regions: 1) normal tissue; 2) a region of decreased perfusion but normal diffusion and normal uptake of hypoxic marker; 3) a region of decreased perfusion, decreased diffusion and increased uptake of hypoxic marker; 4) a region of decreased perfusion, decreased diffusion and low uptake of hypoxic marker. The areas for increased uptake of hypoxic marker and decreased diffusion are equivalent, indicating similar blood flow thresholds. Regions of oligaemic misery perfusion, ischaemic misery perfusion and lesion core may be delineated with the combination of diffusion or hypoxic images and perfusion maps.

Flow-sensitive alternating inversion recovery (FAIR) is a pulsed arterial spin labeling magnetic resonance imaging method for perfusion quantification. In its standard implementation for quantification with full longitudinal relaxation between acquisitions, its use in time-course investigations of rapidly changing flow values is limited. The time efficiency can be improved by decreasing the repetition time but quantification becomes problematic. This situation is further complicated if a whole-body radiofrequency transmit coil is not used since fresh blood spins will flow in from outside the coil. To alleviate these problems, the use of global pre-saturation is proposed. The resulting expression for the flow signal depends on the relationship between the imaging parameters and the coil inflow time and can be significantly simplified under certain combinations of these parameters. With this implementation of FAIR, quantitative flow maps of gerbil brains were obtained with a 3 minute time resolution in a study of the effects of reperfusion. The pre-occlusion flow measurements were in good agreement with values obtained by the standard FAIR implementation and by other techniques, but the low values following occlusion were underestimated due to the increased transit times. Magn Reson Med 41:829–840, 1999. © 1999 Wiley-Liss, Inc.

The importance of diffusion-weighted MRI in the assessment of acute stroke is well-recognized, and quantitative maps of the apparent diffusion coefficient (ADC) are now widely used. Echoplanar imaging provides a robust method of acquiring diffusion-weighted images free of motion artifact. However, initial experience with clinical MRI systems indicates that calculation of artifact-free ADC maps from a series of echo-planar diffusion-weighted images is not necessarily straight-forward. One of the problems is that frequency shifts resulting from eddy currents can cause misregistration of base diffusion-weighted images. In this study, an on-line correction method that overcomes this problem is described, and phantom and human images that demonstrate the validity of the technique are presented. The method uses a non-phase-encoded reference scan to correct the phase of each echo in the echo train, and can provide ADC maps that are free of misregistration artifacts, without the need for off-line postprocessing.

For the in vivo measurement of the apparent diffusion coefficient (ADC), it is desirable for the total imaging time to be as short as possible. One technique is based on a TurboFLASH acquisition in which the diffusion gradients are inserted into a driven equilibrium Fourier transform (DEFT) combination of hard pulses. However, this sequence has the disadvantage that eddy current-induced inhomogeneities lead to incomplete refocusing of the magnetization during the diffusion preparation and to incorrect ADC values. A modification to the sequence is suggested that eliminates this error by phase-cycling the second 90 degrees pulse of the preparation. This study also investigates the effect of a reduced delay time between acquisitions on the accuracy of the measurement. The quality of the TurboFLASH sequence is demonstrated by experimental validation on an agar phantom and in vivo on the rat brain using a high-field (8.5 T) system. Reduction of the interexperiment delay time is shown to be achievable to a certain degree without compromising the measurement accuracy.

The effects of white and gray matter diffusion anisotropy on ischemic lesion delineation have been studied in the rat model of middle cerebral artery occlusion. Apparent diffusion coefficient (ADC) maps obtained by conventional pulsed gradient spin echo diffusion-weighted imaging (PGSE-DWI) were compared with maps of the trace of the diffusion tensor in both normal and occluded animals. Diffusion tensor trace maps were derived from the average of the ADC maps from three separate experiments with diffusion weighting along three orthogonal axes, and also from a single-scan method. A marked degree of diffusion anisotropy was observed in both cortical gray matter and white matter from ADC maps of the control animals. In the occluded animals, the systematic effects of anisotropy on ADC and lesion area influenced the delineation of the ischemic territory in the PGSE-DWI ADC maps. However, the two trace methods eliminated these effects and gave consistent ischemic lesion depiction, despite the use of differing diffusion times in the two measurements.

Clinical features, magnetic resonance, and biochemical studies are reported in 7 children with pyruvate dehydrogenase (PDH) deficiency. These findings confirm the diverse clinical presentation of this condition, although neurological abnormalities are consistent features. Imaging results are also varied. Six of the children were investigated with proton magnetic resonance spectroscopy and lactate was demonstrated in brain in all patients. Regional variation in the lactate signal was observed in those patients in whom 2 regions were examined. Advances in molecular genetics have provided some explanations for the clinical variation in pyruvate dehydrogenase deficiency.

A common feature of many magnetic resonance image (MRI) data processing methods is the voxel-by-voxel (a voxel is a volume element) manner in which the processing is performed. In general, however, MRI data are expected to exhibit some level of spatial correlation, rendering an independent-voxels treatment inefficient in its use of the data. Bayesian random effect models are expected to be more efficient owing to their information-borrowing behaviour. To illustrate the Bayesian random effects approach, this paper outlines a Markov chain Monte Carlo (MCMC) analysis of a perfusion MRI dataset, implemented in R using the BRugs package. BRugs provides an interface to WinBUGS and its GeoBUGS add-on. WinBUGS is a widely used programme for performing MCMC analyses, with a focus on Bayesian random effect models. A simultaneous modeling of both voxels (restricted to a region of interest) and multiple subjects is demonstrated. Despite the low signal-to-noise ratio in the magnetic resonance signal intensity data, useful model signal intensity profiles are obtained. The merits of random effects modeling are discussed in comparison with the alternative approaches based on region-of-interest averaging and repeated independent voxels analysis. This paper focuses on perfusion MRI for the purpose of illustration, the main proposition being that random effects modeling is expected to be beneficial in many other MRI applications in which the signal-to-noise ratio is a limiting factor.

The incidence of brain abnormalities determined by magnetic resonance in 30 consecutive children presenting with intractable complex partial seizures is reported. Images were optimised to visualise the hippocampus and cortical grey matter. Abnormalities of the hippocampus or temporal lobe were seen in all 19 children with clinical features of temporal lobe epilepsy and in six of the seven children with clinically unlocalised epilepsy. By contrast, in the four children with a clinical diagnosis of extratemporal epilepsy, no temporal or hippocampal abnormalities were seen. Generalised cortical abnormalities of uncertain significance were found in a total of 14 children from all groups. The identification of focal brain abnormalities using optimised magnetic resonance imaging enables early non-invasive assessment of children with intractable seizure disorders and the identification of patients for whom epilepsy surgery may be appropriate. It may also lead to a better understanding of the structural basis of intractable epilepsy, and thereby contribute to early treatment decisions.

Congenital lactic acidosis form a large group of disorders that are commonly associated with profound neurological dysfunction. Difficulties are frequently encountered in establishing a diagnosis, and the mechanisms underlying brain damage are poorly understood. We have performed proton magnetic resonance spectroscopy (1H-MRS) on 24 patients under investigation for suspected metabolic disorder, and have compared the MRS observations of brain lactate with measurements of cerebrospinal fluid (CSF) lactate. We have shown good concordance between the two types of observation, confirming the value of the CSF measurements. Regional variations in brain lactate are detected in some cases, and these may help to elucidate the mechanisms underlying selective brain damage.

Diffusion-weighted magnetic resonance imaging has been shown to be particularly suited to the study of the acute phase of cerebral ischemia in animal models. The studies reported in this paper were undertaken to determine whether this technique is sensitive to the known ischemic thresholds for cerebral tissue energy failure and disturbance of membrane ion gradients. Diffusion-weighted images of the gerbil brain were acquired under two sets of experimental conditions: as a function of cerebral blood flow after controlled graded occlusion of the common carotid arteries (partial ischemia), as a function of time following complete bilateral carotid artery occlusion (severe global ischemia), and on deocclusion after 60 minutes of ischemia. During partial cerebral ischemia, the diffusion-weighted images remained unchanged until the cerebral blood flow was reduced to 15-20 ml.100 g-1.min-1 and below, when image intensity increased as the cerebral blood flow was lowered further. This is similar to the critical flow threshold for maintenance of tissue high-energy metabolites and ion homeostasis. After the onset of severe global cerebral ischemia, diffusion-weighted image intensity increased gradually after a delay of approximately 2.5 minutes, consistent with complete loss of tissue adenosine triphosphate and with the time course of increase in extracellular potassium. This hyperintensity decreased on deocclusion following 60 minutes of ischemia. The data suggest that diffusion-weighted imaging is sensitive to the disruption of tissue energy metabolism or a consequence of this disruption. This raises the possibility of imaging energy failure noninvasively. In humans, this could have potential in visualizing brain regions where energy metabolism is impaired, particularly during the acute phase following stroke.

We sought to evaluate the application of T2-weighted and diffusion-weighted magnetic resonance imaging techniques in the study of a focal ischemic lesion in the rat brain. Unilateral cortical infarcts were induced using the photosensitive dye rose bengal and 560 nm light irradiation. Magnetic resonance images were recorded from a total of 11 rats at selected intervals from 1.5 hours to several days after induction of the lesion. Parallel experiments were performed in which Evans blue dye was injected into the lesioned animals either immediately after lesion induction (n = 11) or 1 hour before the animals were killed (n = 11). The second procedure was designed to show regions of blood-brain barrier permeability to plasma proteins at the time of sacrifice, whereas the first procedure showed the accumulation and subsequent dispersion of plasma protein following disruption of the blood-brain barrier. Regions of the cortex highlighted by the T2-weighted images corresponded well to the pattern of dye staining seen from the first procedure while the diffusion-weighted images showed visual correspondence with the staining pattern obtained using the second procedure. These results illustrate the complementary use of T2-weighted and diffusion-weighted magnetic resonance imaging in discerning the pathophysiology of developing lesions.

Heat shock protein 27 (HSP27) has a major role in mediating survival responses to a range of central nervous system insults, functioning as a protein chaperone, an antioxidant, and through inhibition of cell death pathways. We have used transgenic mice overexpressing HSP27 (HSP27tg) to examine the role of HSP27 in cerebral ischemia, using model of permanent middle cerebral artery occlusion (MCAO). Infarct size was evaluated using multislice T-2-weighted anatomical magnetic resonance imaging (MRI) after 24 h. A significant reduction of 30% in infarct size was detected in HSP27tg animals compared with wild-type (WT) littermates. To gain some insight into the mechanisms contributing to cell death and its attenuation by HSP27, we monitored the effect of induction of c-jun and ATF3 on tissue survival in MCAO and their effects on the expression of endogenous mouse HSP25 and HSP70. It is important that, the c-jun induction seen at 4 h tended to be localized to regions that were salvageable in HSP27tg mice but became infarcted in WT animals. Our results provide support for the powerful neuroprotective effects of HSP27 in cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 849-856; doi:10.1038/jcbfm.2009.249; published online 9 December 2009

We report here how magnetic resonance imaging can be used to gain definitive information about tissue pathology by the combined use of spin-echo and gradient-echo sequences. We also show how artifacts arising from respiratory motion can be eliminated by using a simple respiratory gating technique. © 1990 Academic Press, Inc.

Autistic spectrum disorder (ASD) refers to a heterogeneous group of social communication problems. Research into the neural basis of ASD has revealed abnormalities in a number of different regions of the brain. However, the literature is highly inconsistent. One possible explanation for these discrepancies is differences in intelligence. Children with ASD and below average intelligence may be hypothesised to show additional or different neural abnormalities. This possibility was explored using structural magnetic resonance imaging (MRI) and event-related potentials (ERP). Two groups of children with ASD were studied, those with average or above average intelligence (high ASD group) and those with below average intelligence (low ASD group). The structural MRI data were analysed using voxel-based morphometry (VBM). Using the family-wise error threshold, results showed bilateral abnormality common to the two ASD groups in the cerebellum, fusiform gyrus and frontal cortex. In addition, a number of regions were found to be significantly different in the two ASD groups: regions of the cerebellum showed increased grey matter density bilaterally in the high ASD group, but decreased grey matter density bilaterally in the low ASD group. Further, compared to the high ASD group, additional bilateral abnormalities were found in the postcentral gyrus and regions of the dorsolateral prefrontal cortex in the low ASD group. Using the less stringent false discovery rate (FDR) threshold, differences were also seen in the medial temporal lobes. ERPs also showed differences between the two ASD groups. Whereas the ERPs of the high ASD group were not significantly different from those of the controls, the low ASD group had delayed novelty P3a responses and reduced amplitude target P3b components. These data provide convergent ERP and MRI evidence for the heterogeneity of neural abnormality in ASD in relation to variations in intelligence.

We examined MRI abnormalities and language function in young patients with infarctions apparently confined to the basal ganglia to establish whether impaired performance was attributable to basal ganglia damage per se or to additional cerebral abnormalities. Seventeen stroke patients (10 with left- and 7 with right-hemispheric damage) and seventeen controls participated. MRI included perfusion imaging and voxel-based morphometry analyses of T1-weighted and diffusion data sets. Language was assessed using the CELF-III test. Analysis of CELF-III scores showed a main effect of presence or absence of stroke, with patients performing more poorly than controls. There was no evidence of differences between the left- and right-hemisphere groups. However individual patients with left-hemisphere lesions showed large variations in performance. In the patients with left-hemisphere damage, voxel-based morphometry showed significant relationships between language function and gray matter density in cortical language areas. The white matter analyses also showed correlations with language function, and in addition there were hemodynamic abnormalities in cortical language areas in the three patients with poorest language function. We suggest that language impairments following basal ganglia damage may be attributable primarily to abnormalities in cortical language areas that are too subtle to detect on conventional structural MRI.

Functional MRI (fMRI) is increasingly being used to evaluate children and adolescents who are candidates for surgical treatment of intractable epilepsy. It has the advantage of being noninvasive and well tolerated by young people. By identifying important functional regions within the brain, including unpredictable patterns of functional reorganization, it can aid in surgical decision-making. Here we illustrate this using a number of case studies from the pediatric epilepsy surgery program at our institution. We describe how fMRI, used in conjunction with conventional investigative methods such as neuropsychological assessment, MRI, and electrophysiology, can 1) help to improve functional outcome by enabling resective surgery that spares functional cortex, 2) guide surgical intervention by revealing when reorganization of function has occurred, and 3) show when abnormal cortex is also functionally active, and hence that surgery may not be the best option. Altogether, these roles have reduced the need for invasive procedures that can be both risky and distressing for young people with epilepsy. In our experience, fMRI has significantly contributed to the decision-making process, and improved the counseling and management of young people with intractable epilepsy. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

A novel method for measuring the longitudinal relaxation time of arterial blood (T1a) is presented. Knowledge of T1a is essential for accurately quantifying cerebral perfusion using arterial spin labeling (ASL) techniques. The method is based on the flow-sensitive alternating inversion recovery (FAIR) pulsed ASL (PASL) approach. We modified the standard FAIR acquisition scheme by incorporating a global saturation pulse at the beginning of the recovery period. With this approach the FAIR tissue signal difference has a simple monoexponential dependence on the recovery time, with T1a as the time constant. Therefore, FAIR measurements performed over a range of recovery times can be fitted to a monoexponential recovery curve and T1a can be calculated directly. This eliminates many of the difficulties associated with the measurement of T1a. Experiments performed in vivo in the mouse at 2.35T produced a mean value of 1.51 s for T1a, consistent with previously published values. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc.

Objective: Sickle cell disease (SCD) is associated with cerebrovascular disease, cerebral infarction, and cognitive dysfunction. This study aimed to detect the presence and extent of white matter abnormalities in individuals with SCD using voxel-based morphometry (VBM). Methods: Thirty-six children and adolescents with SCD (age range, 9-24 years) and 31 controls (8-25 years) underwent magnetic resonance investigations using T1- and T2-weighted protocols. White and gray matter density maps were obtained from three-dimensional magnetic resonance imaging (MRI) data sets. Using VBM, we compared the maps between controls and SCD individuals with silent white matter infarct lesions (SCD+L; n = 16), and those without visible abnormality (SCD-L; n = 20). Results: In comparison with controls, intelligence quotients (IQs) were lower in both SCD groups irrespective of presence of visible lesions. VBM showed widespread bilateral white matter abnormalities in the SCD+L group, extending beyond the regions of focal infarction in the deep anterior and posterior white matter borderzones. Bilateral white matter abnormalities were also observed in the SCD-L group, in locations similar to those in the SCD+L group. Interpretation: VBM is sensitive to detection of widespread white matter injury in SCD patients in borderzones between arterial territories even in the absence of evidence of infarction. Those changes may contribute to cognitive deficits in this population.