Biomedical subjects

David G Gadian

Publications and source records attributed to David G Gadian.

16 recordsLinked to original sources

PubMed2005

Gradual changes in the apparent diffusion coefficient of water in selectively vulnerable brain regions following brief ischemia in the gerbil.

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).

Animals↗

PubMed2005

FOXP2 and the neuroanatomy of speech and language.

That speech and language are innate capacities of the human brain has long been widely accepted, but only recently has an entry point into the genetic basis of these remarkable faculties been found. The discovery of a mutation in FOXP2 in a family with a speech and language disorder has enabled neuroscientists to trace the neural expression of this gene during embryological development, track the effects of this gene mutation on brain structure and function, and so begin to decipher that part of our neural inheritance that culminates in articulate speech.

Animals↗

PubMed2004

Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution.

Diffusion-weighted magnetic resonance imaging can provide information related to the arrangement of white matter fibers. The diffusion tensor is the model most commonly used to derive the orientation of the fibers within a voxel. However, this model has been shown to fail in regions containing several fiber populations with distinct orientations. A number of alternative models have been suggested, such as multiple tensor fitting, q-space, and Q-ball imaging. However, each of these has inherent limitations. In this study, we propose a novel method for estimating the fiber orientation distribution directly from high angular resolution diffusion-weighted MR data without the need for prior assumptions regarding the number of fiber populations present. We assume that all white matter fiber bundles in the brain share identical diffusion characteristics, thus implicitly assigning any differences in diffusion anisotropy to partial volume effects. The diffusion-weighted signal attenuation measured over the surface of a sphere can then be expressed as the convolution over the sphere of a response function (the diffusion-weighted attenuation profile for a typical fiber bundle) with the fiber orientation density function (ODF). The fiber ODF (the distribution of fiber orientations within the voxel) can therefore be obtained using spherical deconvolution. The properties of the technique are demonstrated using simulations and on data acquired from a volunteer using a standard 1.5-T clinical scanner. The technique can recover the fiber ODF in regions of multiple fiber crossing and holds promise for applications such as tractography.

Algorithms↗

PubMed2003

Language fMRI abnormalities associated with FOXP2 gene mutation.

Half the members of the KE family suffer from a speech and language disorder caused by a mutation in the FOXP2 gene. We examined functional brain abnormalities associated with this mutation using two fMRI language experiments, one involving covert (silent) verb generation and the other overt (spoken) verb generation and word repetition. The unaffected family members showed a typical left-dominant distribution of activation involving Broca's area in the generation tasks and a more bilateral distribution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported bilateral morphological abnormalities, the affected members showed significant underactivation relative to the unaffected members in Broca's area and its right homolog, as well as in other cortical language-related regions and in the putamen. Our findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language.

Brain Mapping↗

PubMed2003

Hippocampal abnormalities after prolonged febrile convulsion: a longitudinal MRI study.

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 investigated >48 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.

Brain Edema↗

PubMed2003

Abnormalities in hippocampi remote from the seizure focus: a T2 relaxometry study.

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.

Adolescent↗

PubMed2003

Cortical anomalies associated with visuospatial processing deficits.

Children born preterm provide a fruitful population for studying structure-function relationships because they often have specific functional deficits in the context of normal neurological status. We selected a group of preterm adolescents with deficits in judgment of line orientation. Despite their very low birth weight, all were neurologically normal with no consistent abnormalities on conventional magnetic resonance imaging. However, voxel-based morphometric analysis of their magnetic resonance imaging scans showed areas of decreased gray matter and increased white matter most prominently in right ventral extrastriate cortex, close to an area previously implicated in the line orientation task. We suggest that these anomalies of cortical architecture relate to impaired performance on the line orientation task.

Adolescent↗

PubMed2003

Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia.

The KE family is a large three-generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel-based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a bilateral conjunction analysis. This searches specifically for areas of grey matter density that differ bilaterally in the affected members compared with both matched controls and the unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10 affected, 7 unaffected) and matched controls were compared. The most significant findings were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and the left and right inferior frontal gyrus in the affected members. In addition, increased grey matter density was found bilaterally in the planum temporale. These results confirm that a point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in both motor and language related regions. The results also demonstrate the advantages of using a conjunction analysis when bilateral abnormalities are suspected.

Adolescent↗

PubMed2003

Velocity-driven adiabatic fast passage for arterial spin labeling: results from a computer model.

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.

Animals↗

PubMed2003

Quantification of bolus-tracking MRI: Improved characterization of the tissue residue function using Tikhonov regularization.

Quantification of cerebral blood flow (CBF) and the tissue residue function (R) using bolus-tracking MRI requires deconvolution of the arterial input function (AIF). Currently, the most commonly used deconvolution method is singular value decomposition (SVD), which has been shown to produce accurate estimations of CBF. However, this method introduces unwanted oscillations in the time course of R, and there are situations in which the actual shape is of interest (e.g., in calculating flow heterogeneity and assessing bolus dispersion). In such cases, the conventional SVD method may no longer be suitable, and an alternative approach may be required. This work describes the implementation of Tikhonov regularization with the L-curve criterion to quantify CBF and obtain a better characterization of R. The methodology is tested on simulated and patient data, and the results are compared to those found using the conventional SVD approach. Although both methods produce similar CBF values, the deconvolved R shape obtained using SVD is dominated by oscillations and fails to characterize the shape in the presence of dispersion. On the other hand, the use of the proposed regularization method improves the characterization of the tissue residue function.

Carotid Stenosis↗

PubMed2003

Diffusion-weighted magnetic resonance imaging fibre tracking using a front evolution algorithm.

A novel technique is presented for estimating white matter connectivity in vivo using diffusion-weighted magnetic resonance imaging. The concept of a fibre orientation density function (ODF) is described, which characterises the uncertainty in the orientation of the underlying white matter fibres, given the set of diffusion-weighted signal intensities at the point of interest. The proposed algorithm is based on the evolution of a front from a seed region, using the information provided by the fibre ODF. Each point reached by the front is assigned an index of connectivity with the seed region. The algorithm was used to track various major white matter fibre pathways in two data sets acquired on the same healthy adult volunteer over separate occasions. Example tracks are shown to illustrate some of the properties of the algorithm, such as robustness to noise and branching capability. Finally, the dependence of the algorithm on the model used to derive the fibre ODF is discussed.

Adult↗

PubMed2003

Comparative study of the FAIR technique of perfusion quantification with the hydrogen clearance method.

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.

Animals↗

PubMed2003

Temporal relation between the ADC and DC potential responses to transient focal ischemia in the rat: a Markov chain Monte Carlo simulation analysis.

Markov chain Monte Carlo simulation was used in a reanalysis of the longitudinal data obtained by Harris et al. (J Cereb Blood Flow Metab 20:28-36) in a study of the direct current (DC) potential and apparent diffusion coefficient (ADC) responses to focal ischemia. The main purpose was to provide a formal analysis of the temporal relationship between the ADC and DC responses, to explore the possible involvement of a common latent (driving) process. A Bayesian nonlinear hierarchical random coefficients model was adopted. DC and ADC transition parameter posterior probability distributions were generated using three parallel Markov chains created using the Metropolis algorithm. Particular attention was paid to the within-subject differences between the DC and ADC time course characteristics. The results show that the DC response is biphasic, whereas the ADC exhibits monophasic behavior, and that the two DC components are each distinguishable from the ADC response in their time dependencies. The DC and ADC changes are not, therefore, driven by a common latent process. This work demonstrates a general analytical approach to the multivariate, longitudinal data-processing problem that commonly arises in stroke and other biomedical research.

Animals↗

PubMed2002

Is quantification of bolus tracking MRI reliable without deconvolution?

Bolus tracking data obtained with paramagnetic intravascular tracers are commonly analyzed and quantified by the direct measurement of properties of the tissue concentration-time curve (e.g., time to peak (TTP)). The measurement of these "summary parameters" is used as an accessible alternative approach to the complex deconvolution procedure, and provides indirect measures of perfusion. However, summary parameters do not take into account differences in arterial input functions (AIFs) or residue functions (R(t)) between patients or studies. Simulations were performed to assess the variability of summary parameters over a realistic range of AIFs and for differing R(t), to establish whether they can be used as reliable measures of tissue perfusion status. Results showed that the value of each summary parameter investigated is highly dependent upon both the AIF and R(t). The referencing of summary parameters to their corresponding value in the AIF or in normal tissue is a method commonly used to normalize results, but this approach did not lead to any measures that were independent of both the AIF and R(t) in this study. The results presented here show that the use of summary parameters requires considerable caution, since tissue or patient types can easily be incorrectly classified due to the effect of variations in patient AIF and R(t).

Adult↗

PubMed2002

Rapid simultaneous mapping of T2 and T2* by multiple acquisition of spin and gradient echoes using interleaved echo planar imaging (MASAGE-IEPI).

A new MRI sequence for the rapid simultaneous measurement of T2 and T2* is presented. The technique uses the multiple acquisition of spin and gradient echoes with interleaved echo planar imaging (MASAGE-IEPI). IEPI data sets are sampled during and between a pair of short and long echo time spin echoes, allowing the reconstruction of a set of images with different combinations of T2 and T2* weighting and the calculation of T2 and T2* maps. In the context of neuroimaging, these maps can provide information on cerebral hemodynamics and oxygenation status, either via the deoxyhemoglobin-based BOLD signal or by the effect of exogenous paramagnetic contrast agents. MASAGE-IEPI benefits from the inherent advantages of the IEPI approach, i.e., high time resolution and minimal image distortion, and also has good time efficiency due to the acquisition of multiple image data sets following each excitation pulse. The accuracy of the sequence for the measurement of T2 and T2* is verified on phantoms, and the technique is applied to monitor changing hemodynamics in the rat brain during episodes of hypoxia. Data for the generation of maps of T2 and T2* are acquired with a time resolution of 12 s to accurately define the rapidly changing time course. As increasing emphasis is placed on the role of T2 and T2* in the direct measurement of physiological parameters such as cerebral metabolic rate of oxygen consumption and blood vessel sizes, MASAGE-IEPI offers an efficient method for the measurement of these two important MRI parameters.

Animals↗

PubMed2002

Intestinal energy metabolism after ischemia-reperfusion: Effects of moderate hypothermia and perfluorocarbons.

PURPOSE: This study investigated the roles of moderate hypothermia and extraluminal oxygenated perfluorcarbon (PFC) on intestinal metabolism after ischemia-reperfusion. METHODS: A model of 30-minute intestinal ischemia followed by 60 minutes of reperfusion was used. The animals were maintained at either normothermia (36.5 to 37.5 degrees C) or moderate hypothermia (31 to 32 degrees C). Four groups of adult rats were studied (n = 8 per group): (A) sham at normothermia, (B) ischemia-reperfusion at normothermia, (C) ischemia-reperfusion at hypothermia and, (D) ischemia-reperfusion with extraluminal oxygenated PFC perfusion during ischemia at normothermia. Intestinal phosphocreatine, ATP and lactate levels were measured. Histologic changes in the intestine were evaluated. RESULTS: Intestinal ischemia-reperfusion at normothermia caused a marked reduction in phosphocreatine and ATP with an increase in lactate. Moderate hypothermia exerted beneficial effects by attenuating the depletion of high-energy phosphates and the elevation of lactate. Extraluminal PFC perfusion during ischemia failed to produce a protective effect on high-energy phosphates, although it reduced lactate accumulation. Moderate hypothermia significantly decreased the degree of mucosal damage. CONCLUSIONS: Whole-body moderate hypothermia protects the small intestine from reperfusion injury as measured both biochemically and histologically. Extraluminal oxygenated PFC administration during ischemia did not protect the intestine from reperfusion injury in this model.

Adenosine Triphosphate↗