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Biomedical subjects

P T Fox

Publications and source records attributed to P T Fox.

At least 73 records · Page 4Linked to original sources

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↗

Cerebellum implicated in sensory acquisition and discrimination rather than motor control.

Recent evidence that the cerebellum is involved in perception and cognition challenges the prevailing view that its primary function is fine motor control. A new alternative hypothesis is that the lateral cerebellum is not activated by the control of movement per se, but is strongly engaged during the acquisition and discrimination of sensory information. Magnetic resonance imaging of the lateral cerebellar output (dentate) nucleus during passive and active sensory tasks confirmed this hypothesis. These findings suggest that the lateral cerebellum may be active during motor, perceptual, and cognitive performances specifically because of the requirement to process sensory data.

Adult↗

Improving the temporal resolution of functional MR imaging using keyhole techniques.

Using a keyhole technique, it is shown that the data acquisition rate of gradient-echo imaging for functional MRI (fMRI) studies can be increased substantially. The resulting enhancement of the temporal resolution of fMRIs was accomplished without modifying the hardware of a conventional MRI system. High spatial resolution fMRI images were first collected with conventional full k-space acquisition and image reconstruction. Using the same data set, simulation reconstruction using the keyhole principle and zero-padding were performed for comparison with the full k-space reconstruction. No significant changes were found for fMRI images generated from the keyhole technique with a data sharing profile of 50% of the k-space. As k-space data sharing profiles increased to 75 and 87.5%, the keyhole fMRI images began to show only modest changes in activation intensity and area compared with the standard images. In contrast, zero-padding fMRI images produced a significant disparity both in activation intensity and area relative to the truly high-resolution fMRI images. The keyhole technique's ability to retain the intensity and area of fMRI information, while substantially reducing acquisition time, makes it a promising method for fMRI studies.

Adult↗

Quantitative assessment of blood inflow effects in functional MRI signals.

Functional MRI (fMRI) signal dependence on changes in blood flow velocities were analyzed for both conventional and echo-planar (EPI) gradient-echo pulse sequences. As the flow velocity increases, the fMRI signal increases monotonically in spoiled gradient-echo sequences, while the fMRI signal may increase or decrease in conventional refocused gradient-echo sequences. A larger flip angle generates a larger inflow contribution to the fMRI signal. For conventional gradient-echo sequences, the inflow contribution to the fMRI images is dominated by the cortical draining veins, while its effect on capillaries is generally small and may be negligible in the spoiled sequences. For EPI gradient-echo sequences, the contribution from inflow effects is relatively small, as compared with the blood oxygen level-dependent (BOLD) contribution, to the fMRI signal, not only for capillaries but also for the cortical draining veins.

Blood Flow Velocity↗

Functional-lesion investigation of developmental stuttering with positron emission tomography.

Positron emission tomographic (PET) H2(15)O measurements of resting-state regional cerebral blood flow (CBF) were obtained in 29 right-handed men, 10 of whom stuttered and 19 of whom did not. PET images were analyzed by sampling 74 regions of interest (ROIs), 37 per hemisphere. ROI placement was guided both physiologically and anatomically. Physiological ROI placement was based on speech motor activations. Anatomical ROIs were positioned by reference to a stereotactic, neurosurgical atlas with positions confirmed and finely adjusted by co-registered magnetic-resonance images (MRIs). For all subjects, PET and MR images were normal to visual inspection. Highly significant (p < 0.0001) between-region and between-hemisphere effects were found for both groups, as have been previously reported for normal subjects, but no significant between-group differences were found for any regional CBF values. Analysis by a laterality index found a weakly significant between-groups effect (p = 0.04) that was isolated to five regions, four of which are implicated in speech or hearing. However, these regional laterality effects showed no consistent directionality, nor did these regions have absolute differences in regional blood flow between groups. Present findings do not support recent suggestions that developmental stuttering is associated with abnormalities of brain blood flow at rest. Rather, our findings indicate an essentially normal functional brain terrain with a small number of minor differences in hemispheric symmetry.

Adult↗

Use of implicit motor imagery for visual shape discrimination as revealed by PET.

Positron emission tomography (PET) can be used to map brain regions that are active when a visual object (for example, a hand) is discriminated from its mirror form. Chronometric studies suggest that viewers 'solve' this visual shape task by mentally modelling it as a reaching task, implicitly moving their left hand into the orientation of any left-hand stimulus (and conversely for a right-hand stimulus). Here we describe an experiment in which visual and somatic processing are dissociated by presenting right hands to the left visual field and vice versa. Frontal (motor), parietal (somatosensory) and cerebellar (sensorimotor) regions similar to those activated by actual and imagined movement are strongly activated, whereas primary somatosensory and motor cortices are not. We conclude that mental imagery is realized at intermediate-to-high order, modality-specific cortical systems, but does not require primary cortex and is not constrained to the perceptual systems of the presented stimuli.

Adult↗

Integrating human brain maps.

Perception, action, cognition, and emotion can now be mapped in the brain by a growing family of techniques. Positron emission tomography, functional magnetic resonance imaging, event-related electrical potentials, event-related magnetic fields, and other non-invasive imaging techniques are rapidly evolving and providing an increasingly rich literature on the functional organization of the human brain. Although no two techniques map identical physiological processes or physical parameters, replications of functionally specific maps by different techniques indicate sufficient common ground for multimodality integration. The process of integration is multi-tiered. Recent advances in integration range from simple image fusion, to model-based synthetic analyses, to collective databases for neural-system modeling. Spatially, temporally, physiologically, and cognitively accurate computational models of the neural systems of human behavior are the ultimate objective of functional brain mapping. This objective will be reached only through integrating the diversity of modern brain-mapping methods.

Brain Mapping↗

Evaluation of new algorithms for the interactive measurement of surface area and volume.

The maximum unit normal component (MUNC) method used for surface area measurement and the divergence theorem algorithm (DTA) used for volume measurement were evaluated. The accuracy and precision of these methods were investigated at varying signal-to-noise ratios (SNRs), sampling, spatial averaging, and orientation. The accuracy of the MUNC measured surface area, as indicated by the mean error, was 2.0% for seven spherical samples, with SNRs ranging from 5:1 to 39:1. The precision, as indicated by the percent coefficient of variation (% CV) for these samples, was less than 3.0%. Likewise, the accuracy and precision of the DTA measured volume for these samples were both less than 1.0%. MUNC surface area measurement from 23 samples of a computed tomography (CT) image of a wooden sphere (51.44-mm diameter) with x,y voxel size ranging from 1 to 10 mm and z voxel size ranging from 2 to 14 mm yielded an accuracy of 1.3% and a precision of 2.2%. The DTA volume measurements from 18 samples of the wooden sphere with x,y vowel size ranging from 1 to 8 mm and z size ranging from 2 to 14 mm provided an accuracy of 1.2% and a precision of 1.8%. Measurement of surface area for a cylindrical rod scanned by CT in five different orientations, ranging from along each axis to between all three axes, yielded an accuracy of 3.7% and a precision of 2.0%. The volume of the cylindrical rod measured by the DTA method for these orientations produced an accuracy of 4.0% and a precision of 3.7%. The volume measured by DTA compared well with the volume measured by a modified voxel counting method. The MUNC surface area method was superior to counting surface voxels. The accuracy and precision for five interactive surface area and volume measurements, using paired cut planes to select subsets of a computer-generated sphere with radius 25 pixels, were both less than 1.0%.

Algorithms↗

Functional imaging and language: evidence from positron emission tomography.

Positron emission tomography (PET) provides an unprecedented opportunity to study the organization of cognitive functions in the working brain of normal individuals. A number of PET experiments, based on well-established paradigms derived from cognitive psychology, have investigated several aspects of language processing. These studies show that word processing is carried out by a distributed network of cortical areas with functional specificity. Results of this research sometimes confirm--sometimes clearly contradict--classic axioms of language organization. This article illustrates some of the methodological issues in PET research, then provides an overview of the most relevant studies using PET. Integrated with other functional imaging methodologies and with behavioral data from cognitive psychology and lesion studies, PET will certainly continue to represent a precious tool to enhance our knowledge of the functional organization of language.

Animals↗

Localization of a human system for sustained attention by positron emission tomography.

Positron emission tomographic (PET) studies of human attention have begun to dissect isolable components of this complex higher brain function, including a midline attentional system in a region of the anterior cingulate cortex. The right hemisphere may play a special part in human attention; neglect, an important phenomenon associated with damage to attentional systems, is more severe, extensive and long-lasting after lesions to the right hemisphere. Here we use PET measurements of brain blood flow in healthy subjects to identify changes in regional brain activity during simple visual and somatosensory tasks of sustained attention or vigilance. We find localized increases in blood flow in the prefrontal and superior parietal cortex primarily in the right hemisphere, regardless of the modality or laterality of sensory input. The anterior cingulate was not activated during either task. These data localize the vigilance aspects of normal human attention to sensory stimuli, thereby clarifying the biology underlying asymmetries of attention to such stimuli that have been reported in clinical lesions.

Adult↗

Does inter-subject variability in cortical functional organization increase with neural 'distance' from the periphery?

In mapping the functional anatomy of the human brain, anatomical variability is a recurring concern. The degree to which the functional organization of any one subject or group of subjects is more generally predictive is largely unknown. We have previously reported that the inter-subject variability of primary visual, somatosensory and motor cortices is small (4-8 mm). Many have suggested, however, that higher-order brain areas will be considerably more variable. For this reason we assessed the anatomical variability of several brain areas participating in language perception and production. In 10 anatomically normal subjects undergoing evaluation for partial complex epilepsy we applied a previously described battery of lexical tasks; intra-subject image averaging was used to minimize the effects of variations in response magnitude. We found inter-subject anatomical variability to be uniformly consistent, with no appreciable effect of distance from the neural periphery.

Adolescent↗

Physiological ROI definition by image subtraction.

Quantitative analysis of functional images requires a strategy for reducing to tractable size the overwhelming amount of numeric data contained therein. Region-of-interest (ROI) selection is the most widely used means of image-data reduction, but it has many limitations. Spatial bias, introduced by selection of regions as being "of interest," is probably the greatest limitation of ROI analyses. Change-distribution analysis is a new data-analysis strategy that eliminates this a priori selection bias in a way that can increase the sensitivity, specificity, and localization precision. All image pixels are surveyed for changes from the control condition. Only areas of change are sampled and contribute to statistical analysis. Change-distribution analysis has been validated for within-subject pairs of images, but it is potentially applicable in a wide variety of imaging protocols.

Brain↗