Mark Strudwick

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment

Background: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. Objectives: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. Methods: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. Results: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital–parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson’s correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. Conclusions: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer’s disease.

Correlation of Quantitative EEG in Acute Ischemic Stroke With 30-Day NIHSS Score Comparison With Diffusion and Perfusion MRI

Background and Purpose— Magnetic resonance imaging (MRI) methods such as diffusion- (DWI) and perfusion-weighted (PWI) imaging have been widely studied as surrogate markers to monitor stroke evolution and predict clinical outcome. The utility of quantitative electroencephalography (qEEG) as such a marker in acute stroke has not been intensively studied. The aim of the present study was to correlate ischemic cortical stroke patients’ clinical outcomes with acute qEEG, DWI, and PWI data. Materials and Methods— DWI and PWI data were acquired from 11 patients within 7 and 16 hours after onset of symptoms. Sixty-four channel EEG data were obtained within 2 hours after the initial MRI scan and 1 hour before the second MRI scan. The acute delta change index (aDCI), a measure of the rate of change of average scalp delta power, was compared with the National Institutes of Health Stroke Scale scores (NIHSSS) at 30 days, as were MRI lesion volumes. Results— The aDCI was significantly correlated with the 30-day NIHSSS, as was the initial mean transit time (MTT) abnormality volume (&rgr;=0.80, P <0.01 and &rgr;=0.79, P <0.01, respectively). Modest correlations were obtained between the 15-hour DWI lesion volume and both the aDCI and 30-day NIHSSS (&rgr;=0.62, P <0.05 and &rgr;=0.73, P <0.05, respectively). Conclusions— In this small sample the significant correlation between 30-day NIHSSS and acute qEEG data (aDCI) was equivalent to that between the former and MTT abnormality volume. Both were greater than the modest correlation between acute DWI lesion volume and 30-day NIHSSS. These preliminary results indicate that acute qEEG data might be used to monitor and predict stroke evolution.

Altered white matter diffusion anisotropy in normal and preterm infants at term equivalent age

To investigate white matter (WM) development, voxelwise analyses of diffusion tensor MRI (DTMRI) data, acquired from 12 very preterm and 11 preterm infants with gestational ages (GA) ranging from 25 to 29 and 29 to 32 weeks, respectively, and 10 newborn normal term infants were performed. T2 relaxation measures were also generated to assess brain water content. Compared with newborn term infants, very preterm infants were found to possess reduced fractional anisotropy (FA) within the frontal lobe, and a number of anterior and posterior commissural pathways. Preterm infants possessed reduced FA mainly within the posterior regions of the corpus callosum. Unexpectedly, we observed significantly reduced FA and increased T2 within a number of corticospinal projections in the newborn term infants compared to the preterm groups. This finding may reflect increased water concentration and/or a lowering of FA due to the presence of crossing interhemispheric WM projections. These findings indicate that care should be taken when interpreting FA indices without knowledge of the possible effects of water concentration in the newborn infant brain. Magn Reson Med 60:761–767, 2008.

Neurochemical Enhancement of Conscious Error Awareness

How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited. We conducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors.

Effect of splinting and exercise on intraneural edema of the median nerve in carpal tunnel syndrome—an MRI study to reveal therapeutic mechanisms

Splinting and nerve and tendon gliding exercises are commonly used to treat carpal tunnel syndrome (CTS). It has been postulated that both modalities reduce intraneural edema. To test this hypothesis, 20 patients with mild to moderate CTS were randomly allocated to either night splinting or a home program of nerve and tendon gliding exercises. Magnetic resonance images of the wrist were taken at baseline, immediately after 10 min of splinting or exercise, and following 1 week of intervention. Primary outcome measures were signal intensity of the median nerve at the wrist as a measure of intraneural edema and palmar bowing of the carpal ligament. Secondary outcome measures were changes in symptom severity and function. Following 1 week of intervention, but not immediately after 10 min, signal intensity of the median nerve was reduced by ∼11% at the radioulnar level for both interventions (p = 0.03). This was accompanied by a mild improvement in symptoms and function (p < 0.004). A similar reduction in signal intensity is not observed in patients who only receive advice to remain active. No changes in signal intensity were identified further distally (p > 0.28). Ligament bowing remained unchanged (p > 0.08). Intraneural edema reduction is a likely therapeutic mechanism of splinting and exercise.

Point injection as an alternative acupuncture technique--an exploratory study of responses in healthy subjects.

Introduction Point injection as a therapeutic technique is well documented, but its physiological effects have not been formally compared with traditional acupuncture. One aim of this study was to compare the effects of the two techniques at one acupuncture point, as a step towards understanding the mode of action of point injection and validating its clinical use. A second aim was to explore whether repeated point injection at the same site might provide a way of increasing the dose of stimulation, in the hope of identifying a dose response curve which could be an alternative strategy to placebo control in demonstrating the biological effects of acupuncture. Methods Sixty nine healthy subjects (age range 18–56 years, mean 29.9; 48 females) completed the study, which employed a counterbalanced experimental design with two stimulation sessions of LI4 approximately one week apart. One half of the participants received point injection first, and the other half received traditional acupuncture first. Baseline physiological data were recorded, then measurements were made before, during and after stimulation; each subject also reported needle sensation (de qi). The measures were heart rate, derived pressure rate product and mean arterial pressure. Results Although stronger sensations of de qi were reported with point injection, no significant differences were found for mean heart rate (HR), pressure rate product (PRP) and mean arterial pressure (MAP) before and after stimulation by the two techniques. No subject gender or age bias was encountered and previous exposure to acupuncture had no effect on outcome. Power spectral analysis of heart rate variability (HRV) made on data from a small subset (n=10) of this cohort also showed no significant differences in autonomic response. Conclusion Point injection and traditional acupuncture seem to provoke similar physiological responses, although the greater needle sensation seen with point injection might indicate it could have more powerful clinical effects. Further studies of repeated point injection are necessary to indicate whether this technique may provide a method of increased strength of point stimulation, as an alternative to traditional needling in acupuncture research.

Automatic hip cartilage segmentation from 3D MR images using arc-weighted graph searching

Accurate segmentation of hip joint cartilage from magnetic resonance (MR) images offers opportunities for quantitative investigations of pathoanatomical conditions such as osteoarthritis. In this paper, we present a fully automatic scheme for the segmentation of the individual femoral and acetabular cartilage plates in the human hip joint from high-resolution 3D MR images. The developed scheme uses an improved optimal multi-object multi-surface graph search framework with an arc-weighted graph representation that incorporates prior morphological knowledge as a basis for segmentation of the individual femoral and acetabular cartilage plates despite weak or incomplete boundary interfaces. This automated scheme was validated against manual segmentations from 3D true fast imaging with steady-state precession (TrueFISP) MR examinations of the right hip joints in 52 asymptomatic volunteers. Compared with expert manual segmentations of the combined, femoral and acetabular cartilage volumes, the automatic scheme obtained mean (± standard deviation) Dices similarity coefficients of 0.81 (± 0.03), 0.79 (± 0.03) and 0.72 (± 0.05). The corresponding mean absolute volume difference errors were 8.44% (± 6.36), 9.44% (± 7.19) and 9.05% (± 8.02). The mean absolute differences between manual and automated measures of cartilage thickness for femoral and acetabular cartilage plates were 0.13 mm (± 0.12) and 0.11 mm (± 0.11), respectively.

Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge : A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d‐amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS‐active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. Magn Reson Med, 2006.

Automatic bone segmentation and bone-cartilage interface extraction for the shoulder joint from magnetic resonance images

We present a statistical shape model approach for automated segmentation of the proximal humerus and scapula with subsequent bone-cartilage interface (BCI) extraction from 3D magnetic resonance (MR) images of the shoulder region. Manual and automated bone segmentations from shoulder MR examinations from 25 healthy subjects acquired using steady-state free precession sequences were compared with the Dice similarity coefficient (DSC). The mean DSC scores between the manual and automated segmentations of the humerus and scapula bone volumes surrounding the BCI region were 0.926  ±  0.050 and 0.837  ±  0.059, respectively. The mean DSC values obtained for BCI extraction were 0.806  ±  0.133 for the humerus and 0.795  ±  0.117 for the scapula. The current model-based approach successfully provided automated bone segmentation and BCI extraction from MR images of the shoulder. In future work, this framework appears to provide a promising avenue for automated segmentation and quantitative analysis of cartilage in the glenohumeral joint.

Improving the prediction of final infarct size in acute stroke with bolus delay–corrected perfusion MRI measures

To investigate whether bolus delay‐corrected dynamic susceptibility contrast (DSC) perfusion MRI measures allowed a more accurate estimation of eventual infarct volume in 14 acute stroke patients using a predictive tissue classifier algorithm.