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Biomedical subjects

Alan Connelly

Publications and source records attributed to Alan Connelly.

6 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗