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P T Fox

Publications and source records attributed to P T Fox.

At least 19 recordsLinked to original sources

Effect of partition coefficient, permeability surface product, and radioisotope on the signal-to-noise ratio in PET functional brain mapping: a computer simulation.

In this work we use a computer simulation to estimate the magnitude of improvement in the signal-to-noise ratio of PET functional brain mapping studies as a function of partition coefficient and permeability surface product for O-14, F-17, and O-15 labeled flow tracers. A model for signal-to-noise ratio is derived from the Kety model for inert diffusible blood flow tracers. The results of the simulation suggest that moderate increases in partition coefficient and permeability surface product compared with water would lead to an increase in signal-to-noise ratio of a factor of about 3.

Artifacts

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

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

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

Use of oxygen-15 to measure oxygen-carrying capacity of blood substitutes in vivo.

A method for determining oxygen-carrying capacity of blood substitutes has been developed using the short-lived cyclotron-produced positron-emitting isotope 15O. This method measures the oxygen-carrying capacity of the blood substitutes in vivo in the presence of red blood cells and allows determination of changes in the oxygen-carrying capacity over time after exchange transfusion. This method is applied to the blood substitutes of liposome-encapsulated hemoglobin (LEH) and cell-free hemoglobin (Hb). We have used 15O (half-life of 2 min) to quantitate the lung uptake and tissue delivery of [15O2]LEH. Lung uptake studies were performed in intubated, catheterized rats after a 40% exchange transfusion of bovine LEH (LEBH; 0.68 g Hb/kg body wt), human hemolysate LEH (LEHH; 1.0 g Hb/kg body wt), or free bovine hemoglobin (SFHS; 0.56 g Hb/kg body wt). A bolus inhalation of 15O2 (3-5 mCi) was given at 15 min, 3 h, and 24 h post-transfusion. Arterial blood samples were collected, spun, and separated into LEH, red blood cell, and plasma fractions. 15O activity and hemoglobin content were determined for each fraction. Oxygen-carrying capacity was calculated as a percentage of the original red blood cell fraction removed. For LEBH, the carrying capacity was 15% at 15 min, 13% at 3 h, and 1% at 24 h. For LEHH, the carrying capacity was 30% at 15 min, 26% at 3 h, and 19% at 24 h. The marked decrease in carrying capacity at 24 h for LEBH compared with LEHH was attributable to the increased formation of methemoglobin in the circulating LEBH rather than increased removal from circulation, because total hemoglobin concentrations measured for both LEH samples decreased at a similar rate during the 24 h. The presence of methemoglobin reductase and other naturally occurring antioxidants in the LEHH may be responsible for maintaining the higher levels of oxyhemoglobin. Oxygen-carrying capacity for SFHS also decreased over time but at a much sharper rate compared with both LEH formulations. The carrying capacity for SFHS of 8% measured at 15 min decreased to 0.3% at 3 h and undetectable levels at 24 h. This sharper decrease in carrying capacity for SFHS is attributable to the rapid removal of the hemoglobin from circulation.

Animals

Characterization of cerebral blood oxygenation and flow changes during prolonged brain activation.

The behavior of cerebral blood flow and oxygenation during prolonged brain activation was studied using magnetic resonance imaging (MRI) sensitized to flow and oxygenation changes, as well as positron emission tomography sensitized to flow. Neuronal habituation effects and hemodynamic changes were evaluated across tasks and cortical regions. Nine types of activation stimuli or tasks, including motor activation, vibrotactile stimulation, and several types of visual stimulation, were used. Both flow and oxygenation were evaluated in separate time course series as well as simultaneously using two different MRI methods. In most cases, the activation-induced increase in flow and oxygenation remained elevated for the entire stimulation duration. These results suggest that both flow rate and oxygenation consumption rate remain constant during the entire time that primary cortical neurons are activated by a task or a stimulus.

Blood Flow Velocity

Basic principles and neurosurgical applications of positron emission tomography.

Positron emission tomography (PET) is a technique for studying functional processes in the human body in vivo. The important clinical applications of PET in neurosurgery include localization of epileptic foci, diagnosis of brain tumors, preoperative brain mapping, and the study of plasticity of the brain following brain damage. The basic physics and neurosurgical applications of PET are presented.

Brain Neoplasms

A PET study of the neural systems of stuttering.

The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking.

Adult