Search PubMed⌕ Search

Biomedical subjects

P T Fox

Publications and source records attributed to P T Fox.

At least 55 records · Page 3Linked to original sources

Quantification of dynamic changes in cerebral venous oxygenation with MR phase imaging at 1.9 T.

A double-echo magnetic resonance (MR) phase imaging method was used to measure the time-dependent changes in regional cerebral venous blood oxygenation during neural stimulation. Our results showed that a finger opposition task induced an absolute increase of blood oxygenation level of deltaY = 0.16+/-0.05 (n = 6), which was measured in the small veins located in the left central sulcus. It was observed that there is a long temporal delay of approximately 27 sec after the onset of the task to reach the steady-state venous oxygenation. This work demonstrated that MRI is a powerful clinical tool for in vivo monitoring of the dynamic nature of organ-specific venous blood oxygenation.

Adult↗

Cerebral blood flow measurement by dynamic contrast MRI using singular value decomposition with an adaptive threshold.

Singular value decomposition (SVD) is a promising deconvolution technique for use in dynamic contrast agent magnetic resonance perfusion imaging. Computer simulations, however, show that the selection of the threshold for SVD affects the accuracy of the cerebral blood flow measurements and may distort the shape of the vascular residue function. In this report, a pixel-by-pixel thresholding method is proposed based on the signal-to-noise ratio of the concentration time curve at maximum concentration (SNRC). Monte Carlo simulations were used to determine the optimal threshold for different SNRC. This technique was used to analyze data from six healthy volunteers, resulting in a mean gray to white matter cerebral blood flow ratio of 2.67 +/- 0.07. This value is in excellent agreement with values published in the literature.

Blood Flow Velocity↗

Accurate high-speed spatial normalization using an octree method.

The goal of regional spatial normalization is to remove anatomical differences between individual three-dimensional (3-D) brain images by warping them to match features of a standard brain atlas. Full-resolution volumetric spatial normalization methods use a high-degree-of-freedom coordinate transform, called a deformation field, for this task. Processing to fit features at the limiting resolution of a 3-D MR image volume is computationally intensive, limiting broad use of full-resolution regional spatial normalization. A highly efficient method, designed using an octree decomposition and analysis scheme, is presented to resolve the speed problem while targeting accuracy comparable to current volumetric methods. Translation and scaling capabilities of octree spatial normalization (OSN) were tested using computer models of solid objects (cubes and spheres). Boundary mismatch between transformed and target objects was zero for cubes and less than 1% for spheres. Regional independence of warping was tested using brain models consisting of a homogenous brain volume with one internal homogenous region (lateral ventricle). Boundary mismatch improved with successively smaller octant-level processing and approached levels of less than 1% for the brain and 5% for the lateral ventricle. Five 3-D MR brain images were transformed to a target 3-D brain image to assess boundary matching. Residual boundary mismatch was approximately 4% for the brain and 8% for the lateral ventricle, not as good as with homogeneous brain models, but similar to other results. Total processing time for OSN with a 256(3) brain image (1-mm voxel spacing) was less than 10 min.

Algorithms↗

The effects of k-space data undersampling and discontinuities in keyhole functional MRI.

The effects of the k-space data undersampling and the discontinuities associated with the keyhole approach in functional magnetic resonance imaging (fMRI) have been addressed. Undersampling of high k-space data increases the high spatial-frequency noise by a factor of square root m, where m is the number of images sharing the high k-space data. However, the effects of the noise can be effectively removed using clustered-pixel statistical analysis. The amplitude and phase discontinuities may result in an increase in the low spatial-frequency noise level, which has no impact on specificity and only a minimal impact on sensitivity. Although dramatically reducing acquisition time and preserving the spatial resolution of functional magnetic resonance imaging, the keyhole technique may have a limited capability in detecting highly focal activations.

Algorithms↗

Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness.

OBJECTIVE: Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state. METHOD: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [15O]water and [18F]fluorodeoxyglucose, respectively. RESULTS: With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen--limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions. CONCLUSIONS: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression.

Affect↗

Altered hypothalamic function in response to glucose ingestion in obese humans.

The hypothalamus plays a central role in the regulation of energy intake and feeding behavior. However, the presence of a functional abnormality in the hypothalamus in humans that may be related to excess energy intake and obesity has yet to be demonstrated in vivo. We, therefore, used functional magnetic resonance imaging (fMRI) to monitor hypothalamic function after oral glucose intake. The 10 obese (34 +/- 2 years of age, BMI 34.2 +/- 1.3 kg/m2) and 10 lean (32 +/- 4 years of age, BMI 22.0 +/- 0.9 kg/m2) subjects with normal glucose tolerance ingested 75 g of glucose while a midsagittal slice through the hypothalamus was continuously imaged for 50 min using a conventional T2*-weighted gradient-echo pulse sequence. After glucose ingestion, lean subjects demonstrated an inhibition of the fMRI signal in the areas corresponding to the paraventricular and ventromedial nuclei. In obese subjects, this inhibitory response was markedly attenuated (4.8 +/- 1.3 vs. 7.0 +/- 0.6% inhibition, P < 0.05) and delayed (9.4 +/- 0.5 vs. 6.4 +/- 0.5 min, P < 0.05) compared with that observed in lean subjects. The time taken to reach the maximum inhibitory response correlated with the fasting plasma glucose (r = 0.75, P < 0.001) and insulin (r = 0.47, P < 0.05) concentrations in both lean and obese subjects. These results demonstrate in vivo, for the first time, the existence of differential hypothalamic function in lean and obese humans that may be secondary to obesity.

Adult↗

Global spatial normalization of human brain using convex hulls.

UNLABELLED: Global spatial normalization transforms a brain image so that its principal global spatial features (position, orientation and dimensions) match those of a standard or atlas brain, supporting consistent analysis and referencing of brain locations. The convex hull (CH), derived from the brain's surface, was selected as the basis for automating and standardizing global spatial normalization. The accuracy and precision of CH global spatial normalization of PET and MR brain images were evaluated in normal human subjects. METHODS: Software was developed to extract CHs of brain surfaces from tomographic brain images. Pelizzari's hat-to-head least-square-error surface-fitting method was modified to fit individual CHs (hats) to a template CH (head) and calculate a nine-parameter coordinate transformation to perform spatial normalization. A template CH was refined using MR images from 12 subjects to optimize global spatial feature conformance to the 1988 Talairach Atlas brain. The template was tested in 12 additional subjects. Three major performance characteristics were evaluated: (a) quality of spatial normalization with anatomical MR images, (b) optimal threshold for PET and (c) quality of spatial normalization for functional PET images. RESULTS: As a surface model of the human brain, the CH was shown to be highly consistent across subjects and imaging modalities. In MR images (n = 24), mean errors for anterior and posterior commissures generally were <1 mm, with SDs < 1.5 mm. Mean brain-dimension errors generally were <1.3 mm, and bounding limits were within 1-2 mm of the Talairach Atlas values. The optimal threshold for defining brain boundaries in both 18F-fluorodeoxyglucose (n = 8) and 15O-water (n = 12) PET images was 40% of the brain maximum value. The accuracy of global spatial normalization of PET images was shown to be similar to that of MR images. CONCLUSION: The global features of CH-spatially normalized brain images (position, orientation and size) were consistently transformed to match the Talairach Atlas in both MR and PET images. The CH method supports intermodality and intersubject global spatial normalization of tomographic brain images.

Adult↗

Evaluation of hemispheric dominance for language using functional MRI: a comparison with positron emission tomography.

The utility of a conventional (i.e., nonecho-planar) functional magnetic resonance imaging (fMRI) technique to determine hemispheric dominance for language was assessed using a semantic generation task in which subjects were presented with a series of nouns and generated aloud a verb for each one. A direct comparison of the fMRI results with positron emission tomography (PET), acquired from the same subjects, was also performed. When analyzed by group averaging, the results of this work were in concordance with those of previous PET studies, showing a left hemispheric dominance for language. Analyzed on a individual basis, 7 out of 9 subjects were left-hemisphere dominant and 2 subjects were right-hemisphere dominant; this applied with both PeT and fMRI methods. The direct comparison between PET and fMRI further demonstrated that fMRI can replicate PET findings. Of the total activation foci detected by PeT, 92% were observed by fMRI. On the other hand, fMRI reported 64% more activations than did PET. This may reflect differences in procedure, spatial resolution, sensitivity, and the underlying physiological mechanism between PET and fMRI. This study suggests that the fMRI technique, even using conventional MRI scanners, could be clinically useful in evaluating hemispheric dominance for language on an individual subject-by-subject basis.

Adult↗

Intersubject variability of functional areas in the human visual cortex.

Intersubject variability of striate and extrastriate areas was mapped by conjoined use of positron emission tomography (PET) and magnetic resonance imaging (MRI). We used two dynamic bowtie-shaped random-dot patterns centered symmetrically around the vertical- and horizontal-meridian, respectively, presented during sequential PET scans in 11 subjects. Control condition was simple fixation on a central dot in absence of a surrounding random dot pattern. V1, V2, VP, V3, V3a, V4, V5, and "wordform" areas were identified. After spatial normalization to Talairach atlas space, mean locations and standard deviations about these mean locations for x-, y-, and z-axes were calculated for each area in both hemispheres and compared for differences. The mean standard deviation for all axes across all areas tested was found to be small (4.9 mm). No significant differences were found in the mean standard deviations for the x-, y-, and z-axes in the left hemisphere vs. their counterparts in the right hemisphere. However, when mean standard deviations in both hemispheres were polled together by axis, the mean standard deviation for the y-axis (5.3 mm) was found to be significantly different from the mean standard deviation for the x-axis (4.3 mm). Furthermore, in the left hemisphere, the mean standard deviation for the z-axis (5.7 mm) was significantly greater than the mean standard deviation for the x-axis (3.9 mm). The values reported in this study for mean location and standard deviation of visual areas can be used to establish confidence intervals for distinguishing normal variations from pathology and consequent brain reorganization.

Adolescent↗

Beyond the single study: function/location metanalysis in cognitive neuroimaging.

Cognitive neuroimaging maps the brain locations of mental operations. This process is iterative, as no single study can fully characterize a mental operation or its brain location. This iterative discovery process, in combination with the location-reporting standard (i.e. spatial coordinates) of the cognitive neuroimaging community, has engendered a new form of metanalysis. Response locations from multiple studies have been analyzed collectively so as to better describe the spatial distribution of brain activations, with promising results. New hypotheses regarding elementary mental operations and their respective brain locations are being generated and refined via metanalysis. These hypotheses are being tested and confirmed by subsequent, prospective experiments. Function/location metanalysis is an important new tool for hypothesis generation in cognitive neuroimaging. This form of metanalysis is fundamentally different from the effect-size metanalyses prevalent in other literatures, with unique advantages and challenges.

Brain Mapping↗

k-tree method for high-speed spatial normalization.

The general approach to spatial normalization using a deformation field is presented. Current high degree-of-freedom deformation methods are extremely time-consuming (10-40 hr), and a k-tree method is proposed to greatly reduce this time. A general k-tree method for analysis of source and target images and synthesis of deformation fields is described. The k-tree method simplifies scale control and feature extraction and matching, making it highly efficient. A two-dimensional (2-D), or quadtree, application program was developed for preliminary testing. The k-tree method was evaluated with 2-D images to test rotating ability, nonhomologous region matching, inner and outer brain-structure independence, and feasibility with human brain images. The results of these tests indicate that a three-dimensional (3-D), or octree, method is feasible. Preliminary work with an octree application program indicates that a processing time of under 10 min for 256(3) image arrays is attainable on a Sun Ultra30 workstation.

Algorithms↗

Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency.

Magnetic resonance imaging (MRI) and MRI relaxometry were used to investigate disturbed brain myelination in 18q- syndrome, a disorder characterized by mental retardation, dysmorphic features, and growth failure. T1-weighted and dual spin-echo T2-weighted MR images were obtained, and T1 and T2 parametric image maps were created for 20 patients and 12 controls. MRI demonstrated abnormal brain white matter in all patients. White matter T1 and T2 relaxation times were significantly prolonged in patients compared to controls at all ages studied, suggesting incomplete myelination. Chromosome analysis using fluorescence in situ hybridization techniques showed that all patients with abnormal MRI scans and prolonged white matter T1 and T2 relaxation times were missing one copy of the myelin basic protein (MBP) gene. The one patient with normal-appearing white matter and normal white matter T1 and T2 relaxation times possessed two copies of the MBP gene. MRI and molecular genetic data suggest that incomplete cerebral myelination in 18q- is associated with haploinsufficiency of the gene for MBP.

Abnormalities, Multiple↗

Cingulate function in depression: a potential predictor of treatment response.

The relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed.

Adult↗

Magnetization and diffusion effects in NMR imaging of hyperpolarized substances.

The special magnetization characteristics of hyperpolarized noble gases have led to an interest in using these agents for new MRI applications. In this note, the magnetization effects and NMR signal dependence of two noble gases, 3He and l29Xe, are modeled across a range of gradient-echo imaging parameters. Pulse-sequence analysis shows a wide variation in optimum flip angles between imaging of gas (e.g., 3He or 129Xe) in air spaces (e.g., trachea and lung) and in blood vessels. To optimize imaging of the air spaces, it is also necessary to reduce the otherwise substantial signal losses from diffusion effects by increasing voxel size. The possibility of using hyperpolarized 129Xe for functional MRI (fMRI) is discussed in view of the results from the blood flow analysis. The short-lived nature of the hyperpolarization opens up new possibilities, as well as new technical challenges, in its potential application as a blood-flow tracer.

Humans↗

Longitudinal relaxation and diffusion measurements using magnetic resonance signals from laser-hyperpolarized 129Xe nuclei.

Methods for T1 relaxation and diffusion measurements based on magnetic resonance signals from laser-hyperpolarized 129Xe nuclei are introduced. The methods involve optimum use of the perishable hyperpolarized magnetization of 129Xe. The necessary theoretical framework for the methods is developed, and then the methods are applied to measure the longitudinal relaxation constant, T1, and the self-diffusion constant, D, of hyperpolarized 129Xe. In a cell containing natural abundance 129Xe at 790 Torr, the T1 value was determined to be 155 +/- 5 min at 20 degrees C and at 2.0 T field. For a second cell at 896 Torr, at the same field and temperature, the T1 value was determined to be 66 +/- 2 min. At a higher field of 7.05 T, the T1 values for the two cells were found to be 185 +/- 10 and 88 +/- 5 min, respectively. The 129Xe self-diffusion constant for the first cell was measured to be 0.057 cm2/ s and for the second cell it was 0.044 cm2/s. The methods were applied to 129Xe in the gas phase, in vitro; however, they are, in principle, applicable for in vivo or ex vivo studies. The potential role of these methods in the development of newly emerging hyper-polarized 129Xe MRI applications is discussed.

Animals↗

Sensory and cognitive functions.

New neuroimaging studies provide striking evidence that the cerebellum is intensely and selectively active during sensory and cognitive tasks, even in the absence of explicit or implicit motor behavior. Focal activity is observed in the lateral cerebellar hemispheres during the processing of auditory, visual, cutaneous, spatial, and tactile information, and in anterior-medial cerebellar regions during somatomotor behavior. Moreover, a double dissociation exists between (a) cerebellar activity and sensory processing and (b) motor behavior and activity in known motor areas in the cerebral cortex. These findings contradict the classical motor coordination theory of cerebellar function but are predicted by, or are at least consistent with, new alternative theories.

Animals↗

Rapid objective measurement of gamma camera resolution using statistical moments.

An easy and rapid method for the measurement of the intrinsic spatial resolution of a gamma camera was developed. The measurement is based on the first and second statistical moments of regions of interest (ROIs) applied to bar phantom images. This leads to an estimate of the modulation transfer function (MTF) and the full-width-at-half-maximum (FWHM) of a line spread function (LSF). Bar phantom images were acquired using four large field-of-view (LFOV) gamma cameras (Scintronix, Picker, Searle, Siemens). The following factors important for routine measurements of gamma camera resolution with this method were tested: ROI placement and shape, phantom orientation, spatial sampling, and procedural consistency. A 0.2% coefficient of variation (CV) between repeat measurements of MTF was observed for a circular ROI. The CVs of less than 2% were observed for measured MTF values for bar orientations ranging from -10 degrees to +10 degrees with respect to the x and y axes of the camera acquisition matrix. A 256 x 256 matrix (1.6 mm pixel spacing) was judged sufficient for routine measurements, giving an estimate of the FWHM to within 0.1 mm of manufacturer-specified values (3% difference). Under simulated clinical conditions, the variation in measurements attributable to procedural effects yielded a CV of less than 2% in newer generation cameras. The moments method for determining MTF correlated well with a peak-valley method, with an average difference of 0.03 across the range of spatial frequencies tested (0.11-0.17 line pairs/mm, corresponding to 4.5-3.0 mm bars). When compared with the NEMA method for measuring intrinsic spatial resolution, the moments method was found to be within 4% of the expected FWHM.

Biophysical Phenomena↗