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Biomedical subjects

G B Pike

Publications and source records attributed to G B Pike.

At least 19 recordsLinked to original sources

The cortical deficit in humans with strabismic amblyopia.

To further our understanding of the cortical deficit in strabismic amblyopia, we measured, compared and mapped functional magnetic resonance imaging (fMRI) activation between the fixing and fellow amblyopic eyes of ten strabismic amblyopes. Of specific concern was whether the function of any visual area was spared in strabismic amblyopia, as recently suggested by both positron emission tomography (PET) and fMRI studies, and whether there was a close relationship between the fMRI response and known psychophysical deficits. To answer these questions we measured the psychophysical deficit in each subject and used stimuli whose relationship to the psychophysical deficit was known. We observed that stimuli that were well within the amblyopic passband did produce reduced fMRI activation, even in visual area V1. This suggests that V1 is anomalous in amblyopia. A similar level of reduction was observed in V2. In two subjects, we found that stimuli outside the amblyopic passband produced activation in visual area V3A. We did not find a close relationship between the fMRI response reduction in amblyopia and either of the known psychophysical deficits even though the fMRI response reduction in amblyopia did covary with stimulus spatial frequency.

Adolescent↗

Texture analysis and morphological processing of magnetic resonance imaging assist detection of focal cortical dysplasia in extra-temporal partial epilepsy.

In many patients, focal cortical dysplasia (FCD) is characterized by minor structural changes that may go unrecognized by standard radiological analysis. To increase the sensitivity of magnetic resonance imaging (MRI) for the detection of subtle lesions of FCD, we developed voxel-based image postprocessing methods, including first-order texture analysis and morphological processing modeled on known MRI features of FCD. We selected 16 patients with histologically proven FCD. Image processing features were calculated over a neighborhood for each voxel in the three-dimensional T1-weighted MRI. Three feature maps were generated: (1) gray matter thickness map to model cortical thickening, (2) gradient map to model blurring of the gray matter-white matter junction, and (3) relative intensity map to model the hyperintense signal within the lesion. Two observers detected lesions on conventional MRI in 8/16 and on ratio maps in 14/16 patients. Sensitivity was 87.5% (14/16) for the ratio maps compared to 50% (8/16) for MRI (p < 0.003). Specificity was 95% (19/20) for ratio maps and 100% (20/20) for MRIs. Cohen's kappa was 0.53 for MRIs, indicating moderate agreement, and 0.83 for ratio maps, indicating strong agreement beyond chance between the 2 observers. The image-processing methods developed in this study improve visual detection of FCD, even in cases where no lesion is obvious on MRI. These techniques could increase the number of patients with partial epilepsy who could benefit from surgery.

Cell Movement↗

Relating axonal injury to functional recovery in MS.

A patient was followed after the new onset of hemiparesis from relapse of MS with serial MR spectroscopy and functional MRI. The association of clinical improvement with recovery of N-acetylaspartate, a marker of neuronal integrity, and progressive reduction of abnormally large functional MRI cortical activation with movement demonstrates that dynamic reorganization of the motor cortex accompanies remission of MS.

Adult↗

Correction for B(1) and B(0) variations in quantitative T(2) measurements using MRI.

A new method is described for compensating for the bias introduced by variations in radiofrequency (RF) field strength and main magnetic field strength when making quantitative T(2) measurements using MRI. Field measurements made during the MRI study are used in combination with a signal model for off-resonance and imperfect RF pulses to correct the estimated T(2) value at every voxel. Applicable to both multicomponent and conventional single-component T(2) studies, the method has been validated experimentally using paramagnetic salt solutions in a multicompartment phantom. Studies of the human head are used to demonstrate the method in practice.

Artifacts↗

Quantitative interpretation of magnetization transfer in spoiled gradient echo MRI sequences.

A method for analyzing general pulsed magnetization transfer (MT) experiments in which off-resonance saturation pulses are interleaved with on-resonance excitation pulses is presented. We apply this method to develop a steady-state signal equation for MT-weighted spoiled gradient echo sequences and consider approximations that facilitate its rapid computation. Using this equation, we assess various experimental designs for quantitatively imaging the fractional size of the restricted pool, cross-relaxation rate, and T(1) and T(2) relaxation times of the two pools in a binary spin bath system. From experiments on agar gel, this method is shown to reliably and accurately estimate the exchange and relaxation properties of a material in an imaging context, suggesting the feasibility of using this technique in vivo.

Image Interpretation, Computer-Assisted↗

An inverse problem approach to the correction of distortion in EPI images.

Magnetic resonance imaging using the echo planar imaging (EPI) technique is particularly sensitive to main (B0) field inhomogeneities. The primary effect is geometrical distortion in the phase encoding direction. In this paper, we present a method based on the conjugate gradient algorithm to correct for this geometrical distortion, by solving the EPI imaging equation. Two versions are presented: one that attempts to solve the full four-dimensional (4-D) imaging equation, and one that independently solves for each profile along the blip encoding direction. Results are presented for both phantom and in vivo brain EPI images and compared with other proposed correction methods.

Algorithms↗

Multiple sclerosis: magnetization transfer MR imaging of white matter before lesion appearance on T2-weighted images.

PURPOSE: To determine the evolution of magnetization transfer (MT) in white matter regions before and after plaque development in patients with multiple sclerosis (MS). MATERIALS AND METHODS: In a 5-year longitudinal evaluation, 30 patients with MS underwent conventional magnetic resonance (MR) imaging, MT MR imaging, and clinical assessment. Cross-sectional data in 12 healthy subjects were also collected. Semiautomated lesion classification with use of T2-weighted MR images was used to measure the time course of the MT ratio (calculated with MR data acquired without and with MT saturation) in every voxel and to help analyze the relationship with the status of lesions depicted on T2-weighted images. RESULTS: There was a significant (P <.001) temporal decline in lesion MT ratio after lesion appearance on T2-weighted images. A significant (P <. 001) progressive decline in MT ratio was also present in voxels that later became lesions, prior to initial detection on T2-weighted images. Even 1(1/2) years prior to lesion appearance, the MT ratio (33.3%) in regions destined to become such lesions was significantly (P <.001) lower than that in both white matter in healthy subjects (41.3%) and other normal-appearing white matter in patients with MS (38.1%). CONCLUSION: The MT ratio reveals progressive focal abnormalities in MS that antedate by up to 2 years the appearance of lesions on T2-weighted MR images.

Adult↗

Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex.

The aim of this study was to test the hypothesis that, within a specific cortical unit, fractional changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMR(O(2))) are coupled through an invariant relationship during physiological stimulation. This aim was achieved by simultaneously measuring relative changes in these quantities in human primary visual cortex (V1) during graded stimulation with patterns designed to selectively activate different populations of V1 neurons. Primary visual cortex was delineated individually in each subject by using phase-encoded retinotopic mapping. Flow-sensitive alternating inversion recovery MRI, in conjunction with blood oxygenation-sensitive MRI and hypercapnic calibration, was used to monitor CBF and CMR(O(2)). The stimuli used included (i) diffuse isoluminant chromatic displays; (ii) high spatial-frequency achromatic luminance gratings; and (iii) radial checkerboard patterns containing both color and luminance contrast modulated at different temporal rates. Perfusion responses to each pattern were graded by varying luminance and/or color modulation amplitudes. For all stimulus types, fractional changes in blood flow and oxygen uptake were found to be linearly coupled in a consistent ratio of approximately 2:1. The most potent stimulus produced CBF and CMR(O(2)) increases of 48 +/- 5% and 25 +/- 4%, respectively, with no evidence of a plateau for oxygen consumption. Estimation of aerobic ATP yields from the observed CMR(O(2)) increases and comparison with the maximum possible anaerobic ATP contribution indicate that elevated energy demands during brain activation are met largely through oxidative metabolism.

Brain Mapping↗

Perfusion-based functional magnetic resonance imaging with single-shot RARE and GRASE acquisitions.

For perfusion-based functional magnetic resonance imaging, the previously introduced flow-sensitive alternating inversion recovery (FAIR) technique is combined with single-shot RARE (rapid acquisition with relaxation enhancement) and GRASE (gradient and spin echo) imaging sequences. The advantages of these sequences compared to commonly used echo-planar imaging (EPI) are an increased signal-to-noise ratio and the absence of distortions and artifacts due to magnetic field inhomogeneities. RARE- and GRASE-FAIR are applied to functional brain mapping studies in humans during visual stimulation. Results demonstrate that the presented techniques allow for perfusion maps with higher spatial resolution compared to EPI-FAIR. Relative regional cerebral blood flow change in the occipital cortex during visual stimulation was measured to be 41+/-4% (n = 5). The comparison of FAIR data obtained with RARE and GRASE techniques shows that RARE yields images with the higher signal-to-noise ratio. However, the GRASE technique features a shorter acquisition time and less RF power deposition and is thus better suited for multi-slice acquisitions.

Artifacts↗

Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: the deoxyhemoglobin dilution model.

The relationship between blood oxygenation level-dependent (BOLD) MRI signals, cerebral blood flow (CBF), and oxygen consumption (CMR(O2)) in the physiological steady state was investigated. A quantitative model, based on flow-dependent dilution of metabolically generated deoxyhemoglobin, was validated by measuring BOLD signals and relative CBF simultaneously in the primary visual cortex (V1) of human subjects (N = 12) during graded hypercapnia at different levels of visual stimulation. BOLD and CBF responses to specific conditions were averaged across subjects and plotted as points in the BOLD-CBF plane, tracing out lines of constant CMR(O2). The quantitative deoxyhemoglobin dilution model could be fit to these measured iso-CMR(O2) contours without significant (P </= 0.05) residual error and yielded MRI-based CMR(O2) measurements that were in agreement with PET results for equivalent stimuli. BOLD and CBF data acquired during graded visual stimulation were then substituted into the model with constant parameters varied over plausible ranges. Relative changes in CBF and CMR(O2) appeared to be coupled in an approximate ratio of approximately 2:1 for all realistic parameter settings. Magn Reson Med 42:849-863, 1999.

Brain Mapping↗

Stimulus-dependent BOLD and perfusion dynamics in human V1.

Blood oxygenation level-dependent (BOLD) fMRI signals often exhibit pronounced over- or undershoot upon changes in stimulation state. Current models postulate that this is due to the delayed onset or decay of perfusion-dependent attenuating responses such as increased cerebral blood volume or oxygen consumption, which are presumed to lag behind the rapid adjustment of blood flow rate to a new steady-state level. If this view is correct, then BOLD overshoot amplitudes in a specific tissue volume should be correlated with steady-state increases in perfusion, independent of stimulus type. To test this prediction, we simultaneously recorded BOLD and relative perfusion signals in primary visual cortex while inducing graded perfusion increases with three types of visual stimulus. Two of these, a diffuse chromatic stimulus with no luminance variation and a very high spatial frequency luminance grating, did not produce detectable BOLD overshoot (or undershoot) when an equal mean luminance baseline was used. Radial checkerboard stimuli, however, caused pronounced over/undershoot of both BOLD and perfusion signals even when temporal mean luminance was held constant and stimulus contrast was adjusted to produce the same steady-state blood flow increases evoked by the other stimuli. Transient amplitudes were relatively invariant in spite of large changes in steady-state response, demonstrating nonlinear BOLD and perfusion step responses in human V1. These findings suggest that, rather than a purely tissue-specific biomechanical or metabolic phenomenon, BOLD overshoot and undershoot represent transient features in the perfusion signal whose effects may be amplified by slowly evolving blood volume changes.

Cerebrovascular Circulation↗

MRI simulation-based evaluation of image-processing and classification methods.

With the increased interest in computer-aided image analysis methods, there is a greater need for objective methods of algorithm evaluation. Validation of in vivo MRI studies is complicated by a lack of reference data and the difficulty of constructing anatomically realistic physical phantoms. We present here an extensible MRI simulator that efficiently generates realistic three-dimensional (3-D) brain images using a hybrid Bloch equation and tissue template simulation that accounts for image contrast, partial volume, and noise. This allows image analysis methods to be evaluated with controlled degradations of image data.

Brain↗

Interictal spikes increase cerebral glucose metabolism and blood flow: a PET study.

PURPOSE: In patients with reflex epilepsy, it is sometimes possible to evoke interictal spikes predictably, thus providing an uncommon but important experimental paradigm for examining the physiological changes produced by epileptiform discharges. METHODS: To examine the changes in regional cerebral blood flow (rCBF) and glucose consumption (rCMRglc) produced by interictal spikes, we performed positron emission tomography (PET) scans with the blood-flow tracer [15O]H20 and with [18F]fluorodeoxyglucose in a patient with fixation-off epilepsy. The scans were performed in states of high and low spike frequency produced by eye closure and opening, respectively. RESULTS: The rCBF study revealed a focal increase in blood flow associated with the state of increased interictal spiking. The focus was in the posterior portion of the left superior parietal lobule (Talairach coordinates: x: -36, y: -71, z: 39; t = 4.5; p<0.05) and corresponded to the site of maximal ictal EEG abnormality recorded with implanted electrodes. In a volume of interest of 10-mm diameter centered on the t statistic peak in the rCBF study, the mean rCMRglc was 39.1 micromol/100 g/min with eyes open and 44.1 micromol/100 g/min (13% increase) with eyes closed. An identical activation paradigm was used in six normal subjects studied with functional magnetic resonance imaging. In the normal subjects, no significant activation was observed in the parieto-occipital region, indicating that the changes observed in the patient were due to interictal spiking rather than to task performance alone. CONCLUSIONS: Interictal spiking produces focal increases in cerebral blood flow and glucose metabolism.

Adult↗

Presurgical motor and somatosensory cortex mapping with functional magnetic resonance imaging and positron emission tomography.

OBJECT: Accurate identification of eloquent cortex is important to ensure that resective surgery in the region surrounding the central sulcus is performed with minimum risk of permanent neurological deficit. Functional localization has traditionally been accomplished using intraoperative cortical stimulation (ICS). However, this technique suffers from several disadvantages that make the development and validation of noninvasive methods desirable. Functional localization accomplished by activation studies in which positron emission tomography (PET) scanning and the tracer [15O]H2O have been used has been shown to correlate well with the results of ICS. Another noninvasive method for functional localization is functional magnetic resonance (fMR) imaging. We compared the locations of activation peaks obtained in individual patients using fMR and [15O]H2O PET imaging. METHODS: Twenty-six combined PET activation-fMR imaging studies were performed in 11 patients who were admitted for evaluation before undergoing surgery in the region surrounding the central sulcus. The PET scans were obtained using bolus injections of the cerebral blood flow tracer [15O]H2O (10 mCi). Multislice T2*-weighted gradient-echo echoplanar images were acquired using a 1.5-tesla MR imaging system. Activation maps were aligned with anatomical MR images and transformed into stereotactic space, after which the locations of activation peaks obtained using both modalities were compared. The average distance between activation peaks obtained using fMR imaging and those obtained using PET imaging was 7.9+/-4.8 mm (p>0.05), with 96% of the peaks being located on either the same or adjacent sulci and gyri. Overlapping of voxels activated by each modality occurred in 92% of the studies. Functional MR imaging failed to activate the primary sensorimotor cortex in one study and produced results that were ambiguous in the clinical setting in three cases. CONCLUSIONS: Overall, fMR imaging produced activation that correlated well with that obtained using PET scanning. Discrepancies between the sites of activation identified using these two techniques may reflect differences in their physiological bases.

Brain Diseases↗

Combined magnetization transfer and proton spectroscopic imaging in the assessment of pathologic brain lesions in multiple sclerosis.

BACKGROUND AND PURPOSE: Conventional MR imaging of multiple sclerosis (MS) provides relatively poor pathologic specificity, which has led to the investigation of more sophisticated MR techniques. The purpose of this study was to combine magnetization transfer (MT) imaging and proton MR spectroscopic imaging (MRSI) to evaluate the specific pathologic features of myelination and neuronal integrity in patients with MS and to determine the relationship between these measures within plaques. METHODS: We acquired conventional MR, MT, and proton MRSI data and evaluated clinical disability in 30 patients with MS, whose conditions were categorized as relapsing-remitting, primary progressive, or secondary progressive. The lesions were classified, using a semiautomated edge-following technique, on T2-weighted MR images, and an analysis of MT and proton MRSI data was conducted for lesion regions as well as for tissue that was categorized as normal. RESULTS: The MT ratio (MTR) of normal-appearing white matter in the patients with MS was significantly lower than in the healthy participants, whereas gray matter values were unchanged. MS lesions showed a large reduction in MTR, with old lesions exhibiting a lower MTR than new lesions. The average lesion MTR and the MR spectroscopic imaging-measured relative concentration of N-acetylaspartate, a marker of neuronal integrity, was positively correlated in patients with relapsing-remitting MS. This relationship was strengthened in regions containing new lesions. CONCLUSION: The integrated use of MT and MR spectroscopic imaging provides a more complete description of the pathologic features of MS than does conventional MR imaging alone, and our data suggest that axonal damage occurs in step with new demyelination and is not a late feature of the disease.

Adult↗

Quantitative magnetic resonance imaging in the assessment of degenerative disc disease.

Understanding degenerative intervertebral disc diseases hinges on the ability to objectively and noninvasively assess the disc matrix composition and integrity. The potential of quantitative magnetic resonance imaging to meet these demands was evaluated. Analyzing the T1 and T2 signal patterns in the nucleus pulposus with increasing Thompson morphological grade revealed a significant reduction related to grade. This significant decrease in T1 and T2 in the nucleus pulposus with grade 4 degeneration and the corresponding low correlation coefficients with respect to the content of individual matrix molecules suggest that matrix integrity plays an important and distinct role in determining T1 and T2 signal. Similarly, the significant increase in magnetization transfer in the nucleus pulposus observed in grade 4 degeneration did not correlate with the changes in molecular content in these highly degenerated discs. Again, this lack of correlation clearly indicates that the tissue integrity and matrix composition independently contribute to the magnetization transfer signal. This study presents the first clear evidence that quantitative magnetic resonance analysis reflects not only the disc matrix composition, but also the structural integrity of the matrix of the disc.

Adult↗

Standing-wave and RF penetration artifacts caused by elliptic geometry: an electrodynamic analysis of MRI.

Motivated by the observation that the diagonal pattern of intensity nonuniformity usually associated with linearly polarized radio-frequency (RF) coils is often present in neurological scans using circularly polarized coils, a theoretical analysis has been conducted of the intensity nonuniformity inherent in imaging an elliptically shaped object using 1.5-T magnets and circularly polarized RF coils. This first principle analysis clarifies, for the general case of conducting objects, the relationship between the excitation field and the reception sensitivity of circularly and linearly polarized coils. The results, validated experimentally using a standard spin-echo imaging sequence and an in vivo B1 field mapping technique, are shown to be accurate to within 1%-2% root mean square, suggesting that these electromagnetic interactions with the object account for most of the intensity nonuniformity observed.

Artifacts↗

Density compensation functions for spiral MRI.

In interleaved spiral MRI, an object's Fourier transform is sampled along a set of curved trajectories in the spatial frequency domain (k-space). An image of the object is then reconstructed, usually by interpolating the sampled Fourier data onto a Cartesian grid and applying the fast Fourier transform (FFT) algorithm. To obtain accurate results, it is necessary to account for the nonuniform density with which k-space is sampled. An analytic density compensation function (DCF) for spiral MRI, based on the Jacobian determinant for the transformation between Cartesian coordinates and the spiral sampling parameters of time and interleaf rotation angle, is derived in this paper, and the reconstruction accuracy achieved using this function is compared with that obtained using several previously published expressions. Various nonideal conditions, including intersecting trajectories, are considered. The new DCF eliminated intensity cupping that was encountered in images reconstructed with other functions, and significantly reduced the level of artifact observed when unevenly spaced sampling trajectories, such as those achieved with trapezoidal gradient waveforms, were employed. Modified forms of this function were found to provide similar improvements when intersecting trajectories made the spiral-Cartesian transformation noninvertible, and when the shape of the spiral trajectory varied between interleaves.

Humans↗