Biomedical subjects

T A Carpenter

Publications and source records attributed to T A Carpenter.

At least 37 records · Page 2Linked to original sources

PubMed2001

Mapping of brain activation in response to pharmacological agents using fMRI in the rat.

Functional MRI (fMRI) was used to investigate the effects of psychotropic compound activity in the rat brain in vivo. The effects of dizocilpine (MK-801) an N-methyl-D-aspartate receptor antagonist and m-chlorophenylpiperazine (mCPP), a 5-HT(2b/2c)-receptor agonist on rat brain activity were investigated over a time interval of about 1 h and the results were compared to published glucose utilisation and cerebral blood flow data. Signal magnitude increases were observed predominantly in limbic regions following MK-801 administration (0.5 mg/kg i.v) whereas signal decreases were restricted to neocortical areas; a characteristic, time dependent pattern of regional changes evolved from the thalamic nuclei to cortical regions. In contrast, mCPP (25 mg/kg i.p) produced gradual signal intensity increases in limbic and motor regions with signal decreases restricted to the visual, parietal and motor cortices. The results from both compounds show remarkable similarity with autoradiographic measurements of cerebral blood flow and glucose uptake. These experiments suggest that the spatio-temporal capabilities of fMRI may be applied to the in vivo investigation of psychoactive compound activity with potential for clinical applications.

Animals↗

PubMed2001

MRI analysis of right ventricular function in normal and spontaneously hypertensive rats.

Right ventricular structure and function were characterized in spontaneously hypertensive rats (SHR) using non-invasive magnetic resonance imaging (MRI) techniques. These studies therefore complement previous reports preoccupied with left ventricular changes associated with this condition. Eight SHR and eight control normotensive Wistar-Kyoto (WKY) rats were each subdivided into equal age-matched groups of 8 and 12 weeks. The right ventricle was imaged through a series of twelve contiguous 1.37-1.75 mm transverse sections at twelve equally spaced time-points that covered both systole and most of diastole thereby completely reconstructing right ventricular anatomy. This gave measurements of right ventricular myocardial mass that were consistent through all twelve time-points in all four experimental groups throughout their cardiac cycles. However, spontaneous hypertension increased this right ventricular myocardial mass, as well as the end-diastolic (EDV) and end-systolic volumes (ESV). Although stroke volume (SV) was conserved, decreases in ejection fraction (EF), a positive shift in the relationship between SV and EDV, and reduced indices of systolic ejection rates in SHR rats compared with the age-matched normal WKY controls indicated significant systolic dysfunction. Additionally, reductions in the rates of diastolic relaxation suggested the onset of diastolic dysfunction. Thus, the non-invasive nature of MRI has made it possible for the first time to demonstrate alterations in structure of the right ventricle and in quantitative indicators of its systolic and diastolic function in the SHR model of hypertension.

Animals↗

PubMed2001

Responses of human frontal cortex to surprising events are predicted by formal associative learning theory.

Learning depends on surprise and is not engendered by predictable occurrences. In this functional magnetic resonance imaging (fMRI) study of causal associative learning, we show that dorsolateral prefrontal cortex (DLPFC) is associated specifically with the adjustment of inferential learning on the basis of unpredictability. At the outset, when all associations were unpredictable, DLPFC activation was maximal. This response attenuated with learning but, subsequently, activation here was evoked by surprise violations of the learned association. Furthermore, the magnitude of DLPFC response to a surprise event was sensitive to the relationship that had been learned and was predictive of subsequent behavioral change. In short, the physiological response properties of right DLPFC satisfied specific predictions made by associative learning theory.

Adult↗

PubMed2001

Investigation of feline brain anatomy for the detection of cortical spreading depression with magnetic resonance imaging.

Cortical spreading depression (CSD) and peri-infarct depolarisation (PID) are related phenomena that have been associated with the human clinical syndromes of migraine (CSD), head injury and stroke (PID). Nevertheless the existence of CSD in man remains controversial, despite the detection of this phenomenon in the brains of most, if not all, other animal species investigated. This failure to unambiguously detect CSD clinically may be at least partly due to the anatomically complex, gyrencephalic structure of the human brain. This study was designed to establish conditions for the study of CSD in the brain of a gyrencephalic species using the noninvasive technique of magnetic resonance imaging (MRI). The 3-dimensional (3D) gyrencephalic anatomy of the cat brain was examined to determine the imaging conditions necessary to detect CSD events. Orthogonal transverse, sagittal and horizontal T1-weighted image slices showed that the marginal and suprasylvian gyri were the most appropriate cortical structures to study CSD. This was in view of (1) their simple geometry: (2) their lengthy extent of grey matter orientated rostrocaudally in the cortex: (3) their separation by a sulcus across which CSD spread could be studied and (4) the discontinuity in the grey matter in these regions between the right and left hemispheres dorsal to the corpus callosum. The structure suggested by the T1-weighted images was corroborated by systematic diffusion tensor imaging to map the fractional anisotropy and diffusion trace. Thus a single horizontal image plane could visualise the neighbouring suprasylvian and marginal gyri of both cerebral hemispheres, whereas its complex shape and position ruled out the ectosylvian gyrus for CSD studies. With the horizontal imaging plane, CSD events were reproducibly detected by animating successive diffusion-weighted MR images following local KCl stimulation of the cortical surface. In single image frames, CSD detection and characterisation required image subtraction or statistical mapping methods that, nevertheless, yielded concordant results. In repeat experiments, CSD events were qualitatively similar in appearance whether elicited by sustained or transient KCl applications. Our experimental approach thus successfully describes cat brain anatomy in vivo, and elucidates the necessary conditions for the application of MRI methods to detect CSD propagation.

Animals↗

PubMed2001

MR diffusion tensor imaging of white matter tract disruption in stroke at 3 T.

Recent advances in MR diffusion weighted imaging (DWI) enable the identification of anisotropic white matter tracts with diffusion tensor imaging (DTI). We aimed to use a novel DTI technique to safely study patients with recent stroke in a high field (3 T) MR machine with its intrinsically higher spatial resolution and signal-to-noise ratio. Of ten patients studied, six had disruption of white matter tracts as determined by DTI. A further patient had distortion of white matter tracts around an infarct rather than actual disruption of the tracts themselves. The lack of tract destruction may imply a beneficial prognosis, information that is not available with conventional DWI.

Adult↗

PubMed2000

A quantitative analysis of cortical spreading depression events in the feline brain characterized with diffusion-weighted MRI.

Cortical spreading depression (CSD) in the gyrencephalic cat brain was detected with diffusion-weighted echoplanar (DWEP) magnetic resonance imaging (4-8/min for 1-2 hours) using a horizontal imaging plane through the suprasylvian (SG) and marginal gyri. A t-statistic mapping technique allowed a quantitative characterization of the passage of events through single-image pixels (0.15 mm(2)), thus providing a resolution unavailable to previous studies in which time-dependent changes instead were derived from averaging data over relatively large ROIs. Using the enhanced analysis, CSD events initiated by KCl could be quantified for the first time as primary or secondary according to their spatial and temporal features. Primary events covered 26.2 +/- 9.9 mm(2)of cortical surface (mean +/- SD, n = 7 experiments) and propagated rapidly (3.5 +/- 0.65 mm * min(-1)) with a hemispherical geometry. In contrast, the subsequent secondary events were multiple, spatially restricted (covering 7.6 +/- 4.6 mm(2), P < 0.005), slower in propagation (2.6 +/- 0.41 mm * min(-1), P < 0.012), and often confined to the originating gyrus (26 out of 59 events). However, both event types were associated with significantly reduced apparent diffusion coefficients (ADCs; from 800 to approximately 660 x 10(-6) mm(2)* s(-1), P < 0.05) that were similar for both primary (21 +/- 5.1%) and secondary waves (18 +/- 7. 7%) and that had similar durations (full width at half-maximal height: 86 +/- 17 vs. 79 +/- 20 seconds, respectively). These findings associate CSD for the first time with two categories of ADC disturbance that are similar in amplitude and duration but that differ in spatial extent, velocity, and extensiveness of spread.

Animals↗

PubMed2000

Gradient preemphasis calibration in diffusion-weighted echo-planar imaging.

This article describes a method which enables fast and objective pulse-sequence-specific preemphasis calibration, using standard pulse sequences and system hardware. The method is based on a k-space measurement technique, and has been applied to single-shot, diffusion-weighted, spin-echo, echo-planar imaging (DW-SE-EPI), which is particularly sensitive to eddy-current-induced image distortions. The efficiency of the technique was demonstrated not only by the reduction of eddy-current fields to a negligible level using full preemphasis compensation, but also by the fact that adjustment of the slow time-base alone sufficed for the practical elimination of image distortions in the DW-SE-EPI images and the subsequent diffusion tensor maps (in a phantom and a human brain). By seeking to eliminate directly the effect of eddy-current-induced phase shifts during the EPI data collection, the method is free of the complications and restrictions associated with other eddy-current correction techniques for DW-SE-EPI (such as acquisition of additional calibration scans, intense postprocessing, extensive pulse-sequence modifications), making their use redundant.

Brain↗

PubMed2000

A locally adaptive registration technique for high precision registration of 3-D MRI data.

This study demonstrates how the rigid body registration parameters for good registration of serially acquired 3-D magnetic resonance images vary systematically when the registration routine is presented with a series of cropped data sets that are systematically positioned throughout the entire volume. The results of the registration of these subcubes are compared with the results of a single registration of the complete volume for two consecutive 3-D scans of the brain of a normal volunteer, with one scan having optimized shim coil currents and the other having all second-order shim coil currents set to zero. The technique is sensitive and able to reveal subvoxel misregistrations.

Artifacts↗

PubMed2000

Linear coupling between functional magnetic resonance imaging and evoked potential amplitude in human somatosensory cortex.

The interpretation of task-induced functional imaging of the brain is critically dependent on understanding the relationship between observed blood flow responses and the underlying neuronal changes. However, the exact nature of this neurovascular coupling relationship remains unknown. In particular, it is unclear whether blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) responses principally reflect neuronal synaptic activity. In order to address this issue directly in humans, we measured the increase in somatosensory evoked potential amplitude and fMRI BOLD changes to increases in intensity of median nerve electrical stimulation in five healthy non-anaesthetized subjects. We found that mean N20-P22 amplitudes increased significantly with stimulus intensity in all subjects, as did fMRI BOLD percentage signal intensity change. Moreover, the intensity of the BOLD signal was found to correlate linearly with evoked potential amplitude in four of the five subjects studied. This suggests that the BOLD response correlates with synchronized synaptic activity, which is the major energy consuming process of the cortex.

Adult↗

PubMed2000

Mapping of the cerebral response to hypoxia measured using graded asymmetric spin echo EPI.

Graded asymmetric spin echo-echo planar imaging (ASE-EPI) was used to measure transient alterations in cerebral oxygenation resulting from 60 seconds of anoxia in alpha-chloralose anaesthetised rats. The anoxic period induced a transient fall ( approximately 1 min) in signal intensity followed by a prolonged signal overshoot consistent with an autoregulatory response to oxygen deprivation. The magnitude of signal response, integrated over the entire brain, increased linearly with the echo asymmetry (t(ge)). However, that increase in sensitivity was offset by a reduced signal to noise ratio and quality of the image data. The responses of four regions of interest within the brain to the anoxic stimulus, and the effect of increasing the echo asymmetry, were compared. A comparable magnitude of signal decrease was observed in all brain regions except the superficial cortex that included pial vessels. As t(ge) was incremented differences in signal attenuation between regions became more pronounced. The signal overshoot observed upon restoration of normal breathing gases showed similar trends, producing similar normalised vascular responses for all regions of interest studied. Different regions of interest showed comparable time courses of the signal overshoot suggesting that similar autoregulatory vascular mechanisms operate in all brain regions. These findings additionally show that the use of graded ASE-EPI produced a characteristic profile of maximum signal change measured during and following the anoxic period for each brain region. They suggest that the shape of this profile was determined by the local vasculature within each region of interest; this feature could be exploited in activation studies to eliminate regions with significant signal changes originating from large draining vessels. Finally, the consistent physiological response observed, when the overshoot was compared to the magnitude of the signal drop, demonstrated that modification of the spin echo offset parameter did not mask or detrimentally alter the signal change resulting from the underlying physiological perturbation.

Animals↗

PubMed2000

Potential role of NovoSeven in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage.

Rebleeding following aneurysmal subarachnoid haemorrhage is a major factor contributing to unfavourable outcome. Antifibrinolytic agents reduce the rate of rebleeding but increase the risk of cerebral ischaemia and infarction and hence provide no overall benefit. To address the theoretical concern that recombinant activated factor VII (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) might increase the risk of cerebral ischaemia while stabilizing the clot at the site of aneurysmal rupture, an open-label, dose-escalation safety study has been developed in collaboration with the UK Spontaneous Intracranial Haemorrhage Group. The trial design includes the recruitment of 15 patients (aged 18 years or over) in good grade with subarachnoid haemorrhage verified by computerized tomography scan or lumbar puncture. Safety evaluation includes clinical observation, monitoring of laboratory variables, positron emission tomography (PET) scanning (rCBF, rOEF, rCMRO2) and transcranial Doppler ultrasound. To date, ten patients have been recruited [NovoSeven 80 microg/kg single bolus (n = 2), NovoSeven 80 microg/kg single bolus followed by continuous infusion at 3.5 microg/kg per h (n = 2) or 7 microg/kg per h (n = 1), or control (n = 5)]. Clinical observation, transcranial Doppler ultrasound and PET studies revealed no evidence of cerebral ischaemia in the first nine patients treated with NovoSeven. The last patient developed middle cerebral artery branch thrombosis contralateral to the aneurysm. The study is currently suspended pending further investigation.

Adult↗

PubMed1999

Cortical spreading depression in the gyrencephalic feline brain studied by magnetic resonance imaging.

1.Time-lapse diffusion-weighted magnetic resonance imaging (DWI) was used to detect and characterize complex waves of cortical spreading depression (CSD) evoked with KCL placed upon the suprasylvian gyrus of anaesthetized cats. 2. The time-lapse representations successfully demonstrated primary CSD waves that propagated with elliptical wavefronts selectively over the ipsilateral cerebral hemispheres with a velocity of 3.8 +/- 0.70 mm min(-1) (mean +/- S.E.M. of 5 experiments). 3. In contrast, the succeeding secondary waves often remained within the originating gyrus, were slower (velocity 2.0 +/- 0.18 mm min(-1), more fragmented and varied in number. 4. Computed traces of the apparent diffusion coefficients (ADCs) showed negative deflections followed by monotonic decays (amplitudes: primary wave, -19.9 +/- 2.8%; subsequent waves, -13.6 +/- 1.9% duration at half-maximal decay, 150-200 s) when determined from regions of interest (ROIs) through which both primary and succeeding CSD waves propagated. 5. The passage of both the primary and the succeeding waves often correlated with transient DC potential deflections recorded from the suprasylvian gyrus. 6. The detailed waveforms of the ADC and the T2*-weighted (blood oxygenation level-dependent: BOLD) traces showed a clear reciprocal correlation. These imaging features that reflect disturbances in cellular water balance agree closely with BOLD measurements that followed the propagation velocities of the first and subsequent CSD events. They also provide a close physiological correlate for clinical observations of cortical blood flow disturbances associated with human migraine.

Anesthesia↗

PubMed1999

A comparative study of acquisition schemes for diffusion tensor imaging using MRI.

This study has investigated the effects of the selection of the diffusion-weighted (DW) gradient directions on the precision of a diffusion tensor imaging (DTI) experiment. The theoretical analysis provided a quantitative framework in which the noise performance of DTI schemes could be assessed objectively and for the development of novel DTI schemes, which employ multiple DW gradient directions. This generic framework was first applied to the examination of two commonly used DTI schemes, which employed 6 DW gradient directions and hitherto were used indiscriminately under the sole condition of noncollinearity. It was then used to design and assess a novel 12-DW-gradient-direction DTI protocol, which employed the same total number of DW acquisitions as the two conventional schemes (12). This theoretical investigation was then corroborated using rigorous simulation and DTI experiments on both an isotropic phantom and a healthy human brain. Both the theoretical and the experimental analysis demonstrated that the two conventional schemes showed a significantly different noise performance and that use of the new multiple-DW-gradient-direction scheme clearly improved the precision of the DTI measurements.

Anisotropy↗

PubMed1999

MRI - from basic knowledge to advanced strategies: hardware.

There have been remarkable advances in the hardware used for nuclear magnetic resonance imaging scanners. These advances have enabled an extraordinary range of sophisticated magnetic resonance MR sequences to be performed routinely. This paper focuses on the following particular aspects: (a) Magnet system. Advances in magnet technology have allowed superconducting magnets which are low maintenance and have excellent homogeneity and very small stray field footprints. (b) Gradient system. Optimisation of gradient design has allowed gradient coils which provide excellent field for spatial encoding, have reduced diameter and have technology to minimise the effects of eddy currents. These coils can now routinely provide the strength and switching rate required by modern imaging methods. (c) Radio-frequency (RF) system. The advances in digital electronics can now provide RF electronics which have low noise characteristics, high accuracy and improved stability, which are all essential to the formation of excellent images. The use of surface coils has increased with the availability of phased-array systems, which are ideal for spinal work. (d) Computer system. The largest advance in technology has been in the supporting computer hardware which is now affordable, reliable and with performance to match the processing requirements demanded by present imaging sequences.

Echo-Planar Imaging↗

PubMed1999

Design of biplanar gradient coils for magnetic resonance imaging of the human torso and limbs.

A method is described for design of gradient coils of unconventional geometry for MRI that is based on the superpositions of magnetic fields arising from individual current elements calculated by the Biot-Savart Law. Use of an optimization method based on a genetic algorithm enables a wide diversity in the shapes of coil that can be modeled. To exemplify this a two axis, biplanar gradient set is presented; this geometry offers good access for rectangular objects whilst holding the coils closer to the region of interest than is possible for cylindrical configurations. The inner dimensions of the gradient set were 40.0 x 24.4 x 40.0 cm and the gradient efficiencies were 0.3 and 0.4 mT m(-1) A(-1) in the z- and y- directions respectively over a 15 cm diameter region. Correction of signals arising from regions for which gradient linearity was not optimized was successful for the monotonic region within the set; the largest cuboid from which the MR signal could be processed to produce an undistorted image is of dimensions 36.3 x 17.2 x 24.4 cm.

Algorithms↗

PubMed1999

The reduction of the sorting bias in the eigenvalues of the diffusion tensor.

One of the most intrinsic quantities when measuring the diffusion properties of a system is the set of principal diffusivities, which represents diffusion along the fibre axes. System noise is a well-known cause of systematic sorting bias when closely spaced diffusivities are ordered according to their magnitude and leads to their inaccurate estimation. This paper describes a new method for the ordering of the principal diffusivities in which local fibre directional coherence was used as a basis for sorting. The method was applied and tested in computer simulations and experimental data acquired in an isotropic water phantom and healthy human brain. Our results demonstrate that this method leads to significant reduction in the sorting bias in comparison to other techniques and thus a more accurate estimation of the eigenvalues. The method is advantageous over other proposed alternatives to the conventional magnitude sorting method because it is not reliant on a large region-of-interest averaging scheme.

Anisotropy↗

PubMed1999

A study of rotationally invariant and symmetric indices of diffusion anisotropy.

This study investigated the properties of a class of rotationally invariant and symmetric (relative to the principal diffusivities) indices of the anisotropy of water self-diffusion, namely fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR), with particular emphasis to their measurement in brain tissues. A simplified theoretical analysis predicted significant differences in the sensitivities of the anisotropy indices (AI) over the distribution of the principal diffusivities. Computer simulations were used to investigate the effects on AI image quality of three magnetic resonance (MR) diffusion tensor imaging (DTI) acquisition schemes, one being novel: the schemes were simulated on cerebral model fibres varying in shape and spatial orientation. The theoretical predictions and the results of the simulations were corroborated by experimentally determined spatial maps of the AI in a normal feline brain in vivo. We found that FA mapped diffusion anisotropy with the greatest detail and SNR whereas VR provided the strongest contrast between low- and high-anisotropy areas at the expense of increased noise contamination and decreased resolution in anisotropic regions. RA proved intermediate in quality. By sampling the space of the effective diffusion ellipsoid more densely and uniformly and requiring the same total imaging time as the published schemes, the novel DTI scheme achieved greater rotational invariance than the published schemes, with improved noise characteristics, resulting in improved image quality of the AI examined. Our findings suggest that significant improvements in diffusion anisotropy mapping are possible and provide criteria for the selection of the most appropriate AI for a particular application.

Animals↗

PubMed1999

Testing of adult and paediatric ventilators for use in a magnetic resonance imaging unit.

We have assessed the performance of a series of ventilators (modified versions of the ventiPAC, paraPAC and babyPAC ventilators; SIMS pneuPAC Ltd, Luton, UK) in a magnetic resonance imaging (MRI) scanning environment, with MR safety and compatibility issues being addressed. Following initial modifications to remove ferromagnetic components and replace them with MR-safe materials, all three ventilators performed well in a series of tests in static magnetic fields up to 2 T. Ventilator performance was unaffected by static fields, switching gradients or radio frequency fields within the MR suite. Furthermore, the devices produced no degradation of image quality when used during MR scanning. We discuss management strategies for the care of critically ill ventilated patients during MR procedures.

Adult↗