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Biomedical subjects

G Bruce Pike

Publications and source records attributed to G Bruce Pike.

At least 19 recordsLinked to original sources

3D curve inference for diffusion MRI regularization and fibre tractography.

We develop a differential geometric framework for regularizing diffusion MRI data. The key idea is to model white matter fibres as 3D space curves and to then extend Parent and Zucker's 2D curve inference approach [Parent, P., Zucker, S., 1989. Trace inference, curvature consistency, and curve detection. IEEE Transactions on Pattern Analysis and Machine Intelligence 11, 823-839] by using a notion of co-helicity to indicate compatibility between fibre orientations at each voxel with those in a local neighborhood. We argue that this provides several advantages over earlier regularization methods. We validate the approach quantitatively on a biological phantom and on synthetic data, and qualitatively on data acquired in vivo from a human brain. We also demonstrate the use of the technique to improve the performance of a fibre tracking algorithm.

Algorithms↗

Transcranial magnetic stimulation of frontal oculomotor regions during smooth pursuit.

Both the frontal eye fields (FEFs) and supplementary eye fields (SEFs) are known to be involved in smooth pursuit eye movements. It has been shown recently that stimulation of the smooth-pursuit area of the FEF [frontal pursuit area (FPA)] in monkey increases the pursuit response to unexpected changes in target motion during pursuit. In the current study, we applied transcranial magnetic stimulation (TMS) to the FPA and SEF in humans during sinusoidal pursuit to assess its effects on the pursuit response to predictable, rather than unexpected, changes in target motion. For the FPA, we found that TMS applied immediately before the target reversed direction increased eye velocity in the new direction, whereas TMS applied in mid-cycle, immediately before the target began to slow, decreased eye velocity. For the SEF, TMS applied at target reversal increased eye velocity in the new direction but had no effect on eye velocity when applied at mid-cycle. TMS of the control region (leg region of the somatosensory cortex) did not affect eye velocity at either point. Previous stimulation studies of FPA during pursuit have suggested that this region is involved in controlling the gain of the transformation of visual signals into pursuit motor commands. The current results suggest that the gain of the transformation of predictive signals into motor commands is also controlled by the FPA. The effect of stimulation of the SEF is distinct from that of the FPA and suggests that its role in sinusoidal pursuit is primarily at the target direction reversal.

Adult↗

EEG-fMRI using z-shimming in patients with temporal lobe epilepsy.

PURPOSE: To use z-shimming, a technique that reduces signal loss due to susceptibility artifacts that can result in reduced or absent activation in electroencephalography (EEG) functional MRI (fMRI) sessions in patients with temporal lobe epilepsy (TLE), to determine whether it would result in an increased ability to detect significant regions of blood oxygenation level-dependent (BOLD) signal change. MATERIALS AND METHODS: Eight patients with TL EEG spikes underwent an EEG-fMRI scanning session using z-shimming. The signal intensities in the z-shimmed images were compared with those in the standard images. BOLD activation maps were created from the two sets of images using the timings of the spikes observed on the EEG. RESULTS: The mean signal increase in the TLs as a result of z-shimming was 45.9%+/-4.5%. The percentage of TL voxels above a brain intensity threshold rose from 66.1%+/-7.6% to 77.6%+/-5.7%. This appreciable increase in signal did not lead to any significant differences in the statistical maps created with the two sets of functional images. CONCLUSION: The results suggest that loss of signal is not the limiting factor for the detection of spike-related BOLD signal changes in patients with TLE activity.

Algorithms↗

Reducing contamination while closing the gap: BASSI RF pulses in PASL.

Bandwidth-modulated selective saturation and inversion (BASSI) pulses are a class of frequency- and gradient-modulated radiofrequency (RF) pulses, derived from the hyperbolic secant pulse by temporal variation of the bandwidth parameter. These pulses afford optimal amplitude modulation, achieving uniform and highly selective profiles at any effective flip angle. In this paper, BASSI pulses are parameterized to obtain low RF energy pulsed arterial spin labeling (PASL) label pulses with minimal contamination of static spins outside the label region and highly selective PICORE/QUIPSS II saturation pulses allowing for small label gaps. They are compared to frequency offset corrected inversion (FOCI) label pulses and sinc saturation pulses in simulations and a phantom experiment. Drawing on the outstanding selectivity of bandwidth-modulated saturation pulses, a new noninvasive method to measure in vivo the contamination effects due to direct and indirect saturation of static spins by the label pulse is presented. In an in vivo study on four subjects, contamination effects in a QUIPSS II PASL implementation based on BASSI pulses are compared to those present in a state-of-the-art Q2TIPS sequence employing a FOCI label pulse. Residual contamination in the QUIPSS II/BASSI sequence is shown to be reduced by a factor of 3, compared to the Q2TIPS/FOCI sequence. In vivo human perfusion images obtained with a label gap of only 2 mm are presented.

Adult↗

Twenty new digital brain phantoms for creation of validation image data bases.

Simulations provide a way of generating data where ground truth is known, enabling quantitative testing of image processing methods. In this paper, we present the construction of 20 realistic digital brain phantoms that can be used to simulate medical imaging data. The phantoms are made from 20 normal adults to take into account intersubject anatomical variabilities. Each digital brain phantom was created by registering and averaging four T1, T2, and proton density (PD)-weighted magnetic resonance imaging (MRI) scans from each subject. A fuzzy minimum distance classification was used to classify voxel intensities from T1, T2, and PD average volumes into grey-matter, white matter, cerebro-spinal fluid, and fat. Automatically generated mask volumes were required to separate brain from nonbrain structures and ten fuzzy tissue volumes were created: grey matter, white matter, cerebro-spinal fluid, skull, marrow within the bone, dura, fat, tissue around the fat, muscles, and skin/muscles. A fuzzy vessel class was also obtained from the segmentation of the magnetic resonance angiography scan of the subject. These eleven fuzzy volumes that describe the spatial distribution of anatomical tissues define the digital phantom, where voxel intensity is proportional to the fraction of tissue within the voxel. These fuzzy volumes can be used to drive simulators for different modalities including MRI, PET, or SPECT. These phantoms were used to construct 20 simulated T1-weighted MR scans. To evaluate the realism of these simulations, we propose two approaches to compare them to real data acquired with the same acquisition parameters. The first approach consists of comparing the intensities within the segmented classes in both real and simulated data. In the second approach, a whole brain voxel-wise comparison between simulations and real T1-weighted data is performed. The first comparison underlines that segmented classes appear to properly represent the anatomy on average, and that inside these classes, the simulated and real intensity values are quite similar. The second comparison enables the study of the regional variations with no a priori class. The experiments demonstrate that these variations are small when real data are corrected for intensity nonuniformity.

Adult↗

The effect of global cerebral vasodilation on focal activation hemodynamics.

In view of the potential of global resting blood flow level to confound the interpretation of blood oxygenation level-dependent (BOLD) fMRI studies, we investigated the effect of pronounced elevation in baseline cerebral blood flow (CBF) on BOLD and CBF responses to functional activation. Twelve healthy volunteers performed bilateral finger apposition while attending to a radial yellow/blue checkerboard. Three levels of global CBF increase were achieved by inhaling 5, 7.5 or 10% CO2. CBF and BOLD signals were simultaneously quantified using interleaved multi-slice pulsed arterial spin labeling (PASL) and T2*-weighted gradient echo sequences. Increasing basal CBF produced a significant decrease in the activation-induced BOLD response, with the slope of the optimal linear fit of activation versus basal BOLD signal changes of -0.32 +/- 0.01%/% for motor and visual cortex regions of interest (ROIs). While the modulation in basal flow level also produced a statistically significant effect on the activation-induced CBF change, the degree of relative attenuation of the flow response was slight, with a slope of -0.18 +/- 0.02%/% in the motor and -0.13 +/- 0.01%/% in the visual cortex ROI. The current findings describe a strong attenuation of the BOLD response at significantly elevated basal flow levels and call for independent quantification of resting CBF in BOLD fMRI studies that involve subjects and/or conditions with markedly elevated global perfusion.

Adult↗

Correspondence between EEG-fMRI and EEG dipole localisation of interictal discharges in focal epilepsy.

EEG-fMRI and EEG dipole source localisation are two non-invasive imaging methods that can be applied to the study of the haemodynamic and electrical consequences of epileptic discharges. Using them in combination has the potential to allow imaging with the spatial resolution of fMRI and the temporal resolution of EEG. However, although considerable data are available concerning their concordance in studies involving event-related potentials (ERPs), less is known about how well they agree in epilepsy. To this end, 17 patients were selected from a database of 57 who had undergone an EEG-fMRI scanning session followed by a separate EEG session outside of the scanner. Spatiotemporal dipole modelling was compared with the peak and closest EEG-fMRI activations and deactivations. On average, the dipoles were 58.5 mm from the voxel with the highest positive t value and 32.5 mm from the nearest activated voxel. For deactivations, the corresponding values were 60.8 and 34.0 mm. These values are considerably higher than is generally observed with ERPs, probably as a result of the relatively widespread field, which can lead to artificially deep dipoles, and the occurrence of EEG-fMRI responses remote from the presumed focus of the epileptic activity. The results suggest that EEG and MEG inverse solutions for equivalent current dipole approaches should not be strongly constrained by EEG-fMRI results in epilepsy, and that the use of distributed source modelling will be a more appropriate way of combining EEG-fMRI results with source localisation techniques.

Data Interpretation, Statistical↗

Flow-based fiber tracking with diffusion tensor and q-ball data: validation and comparison to principal diffusion direction techniques.

In this study, we evaluate the performance of a flow-based surface evolution fiber tracking algorithm by means of a physical anisotropic diffusion phantom with known connectivity. We introduce a novel speed function for surface evolution that is derived from either diffusion tensor (DT) data, high angular resolution diffusion (HARD) data, or a combined DT-HARD hybrid approach. We use the model-free q-ball imaging (QBI) approach for HARD reconstruction. The anisotropic diffusion phantom allows us to compare and evaluate the performance of different fiber tracking approaches in the presence of real imaging artifacts, noise, and subvoxel partial volume averaging of fiber directions. The surface evolution approach, using the full diffusion tensor as opposed to the principal diffusion direction (PDD) only, is compared to PDD-based line propagation fiber tracking. Additionally, DT reconstruction is compared to HARD reconstruction for fiber tracking, both using surface evolution. We show the potential for surface evolution using the full diffusion tensor to map connections in regions of subvoxel partial volume averaging of fiber directions, which can be difficult to map with PDD-based methods. We then show that the fiber tracking results can be improved by using high angular resolution reconstruction of the diffusion orientation distribution function in cases where the diffusion tensor model fits the data poorly.

Algorithms↗

Axonal injury in the cerebral normal-appearing white matter of patients with multiple sclerosis is related to concurrent demyelination in lesions but not to concurrent demyelination in normal-appearing white matter.

We assessed axonal injury and demyelination in the cerebral normal-appearing white matter (NAWM) of MS patients in a pilot study using proton magnetic resonance spectroscopic imaging and quantitative magnetization transfer (MT) imaging. Resonance intensities of N-acetylaspartate (NAA) relative to creatine (Cr) were measured in a large central brain volume. NAA/Cr in NAWM was estimated by regression of the NAA/Cr in each voxel against white matter fraction and extrapolation to a white matter fraction of 1. The fractional size of the semi-solid pool (F) was obtained from the binary spin bath model of MT by computing the model parameters from multiple MT-weighted and relaxometry acquisitions. F in NAWM was significantly smaller in the patients [0.109 (0.009)] relative to controls [0.123 (0.007), P = 0.011], but did not differ between RR [0.1085] and SP [0.1087] patients [P > 0.99]. NAA/Cr and F in the NAWM were not correlated (r = 0.16, P > 0.7), mainly due to a lack of variation in F among patients. This may indicate a floor to the extent of myelin pathology that can occur in NAWM before a lesion appears, or that axonal damage is not strictly related to demyelination. The correlation between NAWM NAA/Cr and T2w lesion volume was not significant (P > 0.1). However, dividing the lesion volumes by the mean F in T2w lesions resulted in a quantity that correlated well with NAWM NAA/Cr (r = -0.78, P = 0.038), possibly reflecting the association of Wallerian degeneration in the NAWM with axonal transection associated with demyelination within lesions.

Adult↗

Hemodynamic and metabolic responses to activation, deactivation and epileptic discharges.

To investigate the coupling between the hemodynamic and metabolic changes following functional brain activation as well as interictal epileptiform discharges (IEDs), blood oxygenation level dependent (BOLD), perfusion and oxygen consumption responses to a unilateral distal motor task and interictal epileptiform discharges (IEDs) were examined via continuous EEG-fMRI. Seven epilepsy patients performed a periodic (1 Hz) right-hand pinch grip using approximately 8% of their maximum voluntary contraction, a paradigm previously shown to produce contralateral MI neuronal excitation and ipsilateral MI neuronal inhibition. A multi-slice interleaved pulsed arterial spin labeling and T(2)*-weighted gradient echo sequence was employed to quantify cerebral blood flow (CBF) and BOLD changes. EEG was recorded throughout the imaging session and reviewed to identify the IEDs. During the motor task, BOLD, CBF and cerebral metabolic rate of oxygen consumption (CMR(O(2))) signals increased in the contra- and decreased in the ipsilateral primary motor cortex. The relative changes in CMR(O(2)) and CBF were linearly related, with a slope of 0.46 +/- 0.05. The ratio of contra- to ipsilateral CBF changes was smaller in the present group of epilepsy patients than in the healthy subjects examined previously. IEDs produced both increases and decreases in BOLD and CBF signals. In the two case studies for which the estimation criteria were met, the coupling ratio between IED-induced CMR(O(2)) and CBF changes was estimated at 0.48 +/- 0.17. These findings provide evidence for a preserved coupling between hemodynamic and metabolic changes in response to both functional activation and, for the two case studies available, in response to interictal epileptiform activity.

Adult↗

The role of edema and demyelination in chronic T1 black holes: a quantitative magnetization transfer study.

PURPOSE: To use quantitative magnetization transfer imaging (qMTI) in an investigation of T1-weighted hypointensity observed in clinical magnetic resonance imaging (MRI) scans of multiple sclerosis (MS) patients, which has previously been proposed as a more specific indicator of tissue damage than the more commonly detected T2 hyperintensity. MATERIALS AND METHODS: A cross-sectional study of 10 MS patients was performed using qMTI. A total of 60 MTI measurements were collected in each patient at a resolution of 2 x 2 x 7 mm, over a range of saturation pulses. The observed T1 and T2 were also measured. qMT model parameters were estimated using a voxel-by-voxel fit. RESULTS: A total of 65 T2-hyperintense lesions were identified; 53 were also T1 hypointense. In these black holes, the qMTI-derived semisolid pool fraction F correlated negatively with T(1,obs) (r2 = 0.76; P < 0.0001). The water pool absolute size (PDf) showed a weaker correlation with T(1,obs) (positive, r2 = 0.53; P < 0.0001). The magnetization transfer ratio (MTR) showed a similarly strong correlation with F and a weaker correlation with PDf (r2 = 0.18; P < 0.04). CONCLUSION: T1 increases in chronic black holes strongly correlated with the decline in semisolid pool size, and somewhat less to the confounding effect of edema. MTR was less sensitive than T(1,obs) to liquid pool changes associated with edema.

Adult↗

Venous refocusing for volume estimation: VERVE functional magnetic resonance imaging.

A novel, noninvasive magnetic resonance imaging-based method for measuring changes in venous cerebral blood volume (CBV(v)) is presented. Venous refocusing for volume estimation (VERVE) exploits the dependency of the spin-spin relaxation rate of deoxygenated blood on the refocusing interval. Interleaved CPMG EPI acquisitions following a train of either tightly or sparsely spaced hard refocusing pulses (every 3.7 or 30 msec, respectively) at matched echo time were used to isolate the blood signal while minimizing the intravascular blood oxygenation level dependent (BOLD) signal contribution. The technique was employed to determine the steady-state increase in the CBV(v) in the visual cortex (VC) in seven healthy adult volunteers during flickering checkerboard photic stimulation. A functional activation model and a set of previously collected in vitro human whole blood relaxometry data were used to evaluate the intravascular BOLD effect on the VERVE signal. The average VC venous blood volume change was estimated to be 16 +/- 2%. This method has the potential to provide efficient and continuous monitoring of venous cerebral blood volume, thereby enabling further exploration of the mechanism underlying BOLD signal changes upon physiologic, pathophysiologic, and pharmacologic perturbations.

Algorithms↗

3D curve inference for diffusion MRI regularization.

We develop a differential geometric framework for regularizing diffusion MRI data. The key idea is to model white matter fibers as 3D space curves and to then extend Parent and Zucker's 2D curve inference approach [8] by using a notion of co-helicity to indicate compatibility between fibre orientation estimates at each voxel with those in a local neighborhood. We argue that this provides several advantages over earlier regularization methods. We validate the approach quantitatively on a biological phantom and on synthetic data, and qualitatively on data acquired in vivo from a human brain.

Algorithms↗

Analysis of the EEG-fMRI response to prolonged bursts of interictal epileptiform activity.

The use of combined EEG-fMRI to study interictal epileptiform activity is increasing and has great potential as a clinical tool, but the haemodynamic response to epileptiform activity remains incompletely characterised. To this end, 19 data sets from 14 patients with prolonged bursts of focal or generalised interictal epileptiform activity lasting up to 15 s were analysed. To determine whether the inclusion of the durations of the epileptic events in the general linear model resulted in increased statistical significance of activated regions, statistical maps were generated with and without the event durations. The mean differences when including the durations were a 14.5% increase in peak t value and a 29.5% increase in volume of activation. This suggests that when analysing EEG-fMRI data from patients with prolonged bursts of interictal epileptiform activity, it is better to include the event durations. To determine whether the amplitudes and latencies of the measured responses were consistent with the general linear model, the haemodynamic response functions for bursts of different durations were calculated and compared with the model predictions. The measured amplitude of the response to the shortest duration events was consistently larger than predicted, which is consistent with studies in normal subjects. For the two data sets with the widest range of event durations, the measured amplitudes increased with the durations of the events without evidence of the plateau that was expected from the general linear model. There were no consistent differences between the measured and modelled latencies.

Adolescent↗

EEG-fMRI of focal epileptic spikes: analysis with multiple haemodynamic functions and comparison with gadolinium-enhanced MR angiograms.

Combined EEG-fMRI has recently been used to explore the BOLD responses to interictal epileptiform discharges. This study examines whether misspecification of the form of the haemodynamic response function (HRF) results in significant fMRI responses being missed in the statistical analysis. EEG-fMRI data from 31 patients with focal epilepsy were analysed with four HRFs peaking from 3 to 9 sec after each interictal event, in addition to a standard HRF that peaked after 5.4 sec. In four patients, fMRI responses were correlated with gadolinium-enhanced MR angiograms and with EEG data from intracranial electrodes. In an attempt to understand the absence of BOLD responses in a significant group of patients, the degree of signal loss occurring as a result of magnetic field inhomogeneities was compared with the detected fMRI responses in ten patients with temporal lobe spikes. Using multiple HRFs resulted in an increased percentage of data sets with significant fMRI activations, from 45% when using the standard HRF alone, to 62.5%. The standard HRF was good at detecting positive BOLD responses, but less appropriate for negative BOLD responses, the majority of which were more accurately modelled by an HRF that peaked later than the standard. Co-registration of statistical maps with gadolinium-enhanced MRIs suggested that the detected fMRI responses were not in general related to large veins. Signal loss in the temporal lobes seemed to be an important factor in 7 of 12 patients who did not show fMRI activations with any of the HRFs.

Artifacts↗

Human whole-blood relaxometry at 1.5 T: Assessment of diffusion and exchange models.

Human whole-blood relaxometry experiments were performed to allow the prediction of blood signal changes with blood oxygen saturation (Y) and refocusing interval (tau180). Such predictions are particularly relevant for spin-echo (SE) blood oxygenation level-dependent (BOLD) experiments and a recently proposed noninvasive fMRI method for measuring cerebral blood volume (CBV). Ensemble fitting of the entire set of T2 estimates, obtained over an extensive range of Y and tau180 values, was performed with the use of both a fast chemical exchange model and a model of diffusion in weak magnetic field inhomogeneities. The diffusion modeling resulted in a large reduction in the residual sum-of-squares compared to the fast exchange modeling. The longitudinal relaxation rate decreased linearly with Y, and increased with hematocrit. The results support the application of the recently reported diffusion model to describe deoxyhemoglobin (dHb)-induced blood transverse relaxation rate enhancement at 1.5 T.

Analysis of Variance↗

Bandwidth-modulated adiabatic RF pulses for uniform selective saturation and inversion.

Radiofrequency (RF) inversion and saturation pulses with extremely high spatial selectivity and uniform profiles are a requirement for numerous MR techniques, such as pulsed arterial spin labeling and outer volume suppression. Adiabatic pulses used for inversion of longitudinal magnetization are ubiquitous, but the superior selectivity of adiabatic full passages has not been widely exploited for saturation because a simple way of calibrating the amplitude of these subadiabatic pulses is lacking. An analytically derived calibration equation is presented, applicable to a large class of pulses including the hyperbolic secant (HS) pulse and allowing the determination of the precise amplitude required to achieve any effective flip angle. The properties of this calibration are examined, and a highly selective and homogeneous HS saturation pulse is demonstrated. Based on this calibration a new class of RF pulses is developed. These bandwidth-modulated adiabatic selective saturation and inversion (BASSI) RF pulses afford optimal amplitude modulation, achieving uniform profiles at any effective flip angle. BASSI pulses are compared to existing gradient modulated adiabatic pulses in simulations and phantom experiments and shown to be superior in terms of selectivity and homogeneity, while requiring less RF energy. An application of BASSI pulses to pulsed arterial spin labeling is shown.

Brain↗

Hemodynamic and metabolic responses to neuronal inhibition.

Functional magnetic resonance imaging (fMRI) was used to investigate the changes in blood oxygenation level dependent (BOLD) signal, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMR(O(2))) accompanying neuronal inhibition. Eight healthy volunteers performed a periodic right-hand pinch grip every second using 5% of their maximum voluntary contraction (MVC), a paradigm previously shown to produce robust ipsilateral neuronal inhibition. To simultaneously quantify CBF and BOLD signals, an interleaved multislice pulsed arterial spin labeling (PASL) and T(2)*-weighted gradient echo sequence was employed. The CMR(O(2)) was calculated using the deoxyhemoglobin dilution model, calibrated by data measured during graded hypercapnia. In all subjects, BOLD, CBF and CMR(O(2)) signals increased in the contralateral and decreased in the ipsilateral primary motor (M1) cortex. The relative changes in CMR(O(2)) and CBF were linearly related, with a slope of approximately 0.4. The coupling ratio thus established for both positive and negative CMR(O(2)) and CBF changes is in close agreement with the ones observed by earlier studies investigating M1 perfusion and oxygen consumption increases. These findings characterize the hemodynamic and metabolic downregulation accompanying neuronal inhibition and thereby establish the sustained negative BOLD response as a marker of neuronal deactivation.

Brain↗