Biomedical subjects

J A Detre

Publications and source records attributed to J A Detre.

At least 19 recordsLinked to original sources

PubMed1997

Optical investigations of physiology: a study of intrinsic and extrinsic biomedical contrast.

The utility and performance of optical studies of tissue depends upon the contrast and the changes of contrast in health and disease and in functional activity. The contrast is determined both by the optical properties of extrinsic chromophores and scatterers but especially upon the changes evoked by physiological activity and pathological states. Here, we have focused upon absorption changes of the intrinsic probe, blood absorbance changes due to cortical hypoxia and to haematomas, giving, for particular conditions, absorbance changes of 0.15 and over 0.4 delta OD, respectively. Functional activity may give changes of blood volume of over 0.05 delta OD with some variability due to individual responses that is best expressed as histogram displays of the distribution of response among a significant population. Responses have been observed in prefrontal parietal and occipital functions (242 tests). Extrinsic probes afford signals dependent upon the dose tolerance of the subject and can readily equal or exceed the blood volume and oxygenation signals, and currently afford vascular volume and flow indications. However, contrast agents for the functional activity of cellular function are ultimately to be expected. Finally, light-scattering changes afford osmolyte-related responses and are here shown to indicate a larger signal attributed to cortical depolarization and K+ release in hypoxia/ischaemia. Thus, the optical method affords imaging of manifold contrasts that greatly enhance its specificity and sensitivity for diagnostic procedures.

Animals↗

PubMed1997

Correlation of diffusion MRI and heat shock protein in a rat embolic stroke model.

The expression of 70 kDa heat shock protein (HSP-70) in focal ischemia occurs in regions that sustain sub-lethal ischemic injury, and may therefore be considered as a biological marker of the ischemic penumbra. In a rat embolic stroke model, using fibrin-rich emboli, we correlated the expression of HSP-70 mRNA with diffusion magnetic resonance imaging (MRI) to determine if HSP-70 mRNA expression was associated with alterations in the apparent diffusion coefficient (ADC) of brain tissue water, a putative early marker of cytotoxic injury that is readily measured in vivo. Serial ADC measurements were made for 120 min following embolic infarction in the right carotid artery territory. HSP-70 mRNA expression was observed at the boundaries of the densely ischemic zone, as judged by diffusion imaging. ADC values observed in HSP-70 mRNA-positive regions were intermediate between those observed in the ischemic core or in control regions. In addition, the volume of HSP-70 mRNA-positive tissue correlated positively with the volume of tissue showing intermediate ADC values at 120 min. These findings suggest that intermediate ADC values occur in penumbral regions. Heterogeneity of ischemic cellular injury is suggested as the basis for the intermediate ADC values observed in these regions.

Animals↗

PubMed1997

The effect of pacing of experimental stimuli on observed functional MRI activity.

Neuroimaging activation studies typically observe signals during two or more periods of differing cognitive activity which are then analyzed by a subtraction to test for localized neuroanatomical dissociations between cognitive tasks. Significant activity found between task conditions is frequently assumed to reflect a novel cognitive process present in one task and not the other. We present a conceptual framework that considers the neural mechanisms underlying such observed neuroimaging changes. We propose that neuroimaging experiments which present stimuli at a fixed pace (where each trial takes the same amount of time) will be sensitive to changes in both duration and intensity of neural processing. In contrast, the signal observed during a self-paced design is derived from neural processing averaged over the reaction time and hence could be less sensitive to differences in duration of neural processing. As an empirical demonstration of these ideas, we studied normal subjects using echoplanar functional MRI during two visuospatial tasks (matching of either ROTATED or NONROTATED stimuli) performed using FIXED and SELF-PACED designs. In both pacing designs, reaction times were greater in the ROTATED than NONROTATED task, interpreted as a greater duration of neural processing during the ROTATED compared to the NONROTATED task. In the FIXED-PACED design, significantly greater signal was present within a parieto-occipital cortical region during the ROTATED task compared to the NONROTATED task. This difference was not observed during the SELF-PACED design. This result illustrates the importance of considering trial pacing in the interpretation of functional neuroimaging activation studies.

Adult↗

PubMed1997

A functional MRI study of mental image generation.

The neural substrates of mental image generation were investigated with functional MRI. Subjects listened to words under two different instructional conditions: to generate visual mental images of the words' referents, or to simply listen to each word and wait for the next word. Analyses were performed which directly compared the regional brain activity during each condition, with the goal of discovering whether mental image generation engages modality-specific visual areas, whether it engages primary visual cortex, and whether it recruits the left hemisphere to a greater extent than the right. Results revealed that visual association cortex, and not primary visual cortex, was engaged during the mental image generation condition. Left inferior temporal lobe (Brodmann's area 37) was the most reliably and robustly activated area across subjects, had activity which extended superiorly into occipital association cortex (area 19). The results of this experiment support the hypothesis that visual mental imagery is a function of visual association cortex, and that image generation is asymmetrically localized to the left.

Adolescent↗

PubMed1996

Detection of acute pathologic changes following experimental traumatic brain injury using diffusion-weighted magnetic resonance imaging.

Standard magnetic resonance imaging (MRI) has been shown to be remarkably insensitive to acute changes following traumatic brain injury. Because diffusion-weighted MRI has recently demonstrated excellent sensitivity to acute ischemic injury and other CNS abnormalities, we evaluated the use of diffusion MRI for the detection of pathologic changes in the rat brain during the first hours following parasagittal fluid percussion brain injury. Diffusion MRI was able to demonstrate a significant diffusion decrease in the primary cortical contusion injury and a comparable decrease in the ipsilateral thalamus. Tissue damage in the thalamus region is much weaker than in the cortex, but the thalamus is a primary site of axonal and dendritic injury in this model. T2 imaging in the same subjects showed slight enhancement in the neighborhood of the injured cortex but was unable to demonstrate injury elsewhere. Diffusion imaging was superior to T2 at demonstrating injury and the prominent diffusion decrease in the thalamus suggests that diffusion MRI is preferentially sensitive to axonal or dendritic injury.

Animals↗

PubMed1996

Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow.

Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.

Cerebrovascular Circulation↗

PubMed1996

Functional magnetic resonance imaging of regional brain activity in patients with intracerebral gliomas: findings and implications for clinical management.

Functional magnetic resonance imaging (fMRI) was performed in seven patients harboring intracerebral gliomas proven by histological analysis using a noninvasive blood oxygen level-dependent technique based on the documented discrepancy between regional increases in blood flow and oxygen use in response to regional brain activation. We combined fMRI with conventional magnetic resonance imaging (MRI) during motor or language task activation experiments to investigate the potential usefulness of mapping regional brain activity as part of treatment planning in patients with intracerebral gliomas, in whom preservation of areas of functioning brain tissue is critical. Statistical fMRI maps were generated and directly mapped onto conventional MRI scans obtained at the same session. Of the five patients cooperative enough to remain motionless for the study and perform the task, the location of activation in the primary sensorimotor cortex on the side of the tumor was clearly displaced compared with that in the normal contralateral hemisphere in four patients. Four of the five tumors in these patients showed fMRI activation within the periphery of (or immediately adjacent to) areas of presumed tumor based on spin-echo MRI. In some patients with neurological deficit, the extent of activation was reduced on the side of the tumor as compared with the normal hemisphere. The supplemental motor area and the ipsilateral primary motor cortex were also reproducibly activated during motor tasks. We conclude that blood oxygen level-dependent fMRI can localize areas of cortical function in patients undergoing treatment planning for gliomas so that therapy can be directed away from regions of residual function. Our preliminary data suggest that functioning cortex within or adjacent to tumor margins can be demonstrated, which may correspond to partial preservation of clinical function. Our preliminary data also suggest that there may be a quantifiable difference on fMRI between activation in tumor-bearing cortex and activation in corresponding normal cortex in the contralateral hemisphere. We postulate that the magnitude of this difference may relate to the severity of patient deficit.

Adolescent↗

PubMed1996

Coupling of cortical and thalamic ictal activity in human partial epilepsy: demonstration by functional magnetic resonance imaging.

PURPOSE: To localize metabolic coupling between a cortical seizure focus and other brain regions by using functional magnetic resonance imaging (fMRI) data of ictal events obtained in a patient with frequent partial seizures involving his right face. METHODS: Cross-correlation analysis was used to examine time-dependent alterations in regional signal intensity that correlated with signal-intensity changes from a well-characterized cortical seizure focus in a patient with frequent partial seizures. RESULTS: Signal changes in the left ventrolateral thalamus showed a high degree of temporal correlation with signal changes in the left frontal cortical seizure focus, demonstrating close corticothalamic coupling of metabolism. CONCLUSIONS: A significant role for thalamocortical interactions in the pathophysiology of epilepsy has been suggested by studies in animal models and human patients. This finding provides further support for the integral involvement of the thalamus in human focal epilepsy and underscores the potential for identifying neuronal networks by using cross-correlation analysis of fMRI data.

Adult↗

PubMed1996

Functional magnetic resonance imaging of regional brain activity in patients with intracerebral arteriovenous malformations before surgical or endovascular therapy.

Functional magnetic resonance (MR) imaging was performed in six patients harboring proven intracerebral arteriovenous malformations (AVMs) using a noninvasive blood oxygen level-dependent technique based on the documented discrepancy between regional increases in blood flow and oxygen utilization in response to regional brain activation. Statistical functional MR maps were generated and overlaid directly onto conventional MR images obtained at the same session. In the six patients studied, a total of 23 separate functional MR imaging activation studies were performed. Of these, two runs were discarded because of motion artifacts. All of the remaining 21 studies demonstrated activation in or near expected regions for the paradigm employed. Qualitatively reproducible regional localizations of functional activity in unexpected sites were also seen. The authors' findings indicating aberrant mapping of cortical function may be explained on the basis of the plasticity of brain function, in that the developing brain can take over function that would normally have been performed by regions of brain encompassed by the lesion. Preliminary results in this study's small number of cases also indicate that activity demonstrated within the confines of the apparent AVM nidus may help predict the development of a posttherapy deficit. The authors demonstrate that functional MR imaging can be successfully and reproducibly performed in patients with intracerebral AVMs. Notwithstanding the paucity of normative data using functional MR imaging, the author' findings support cortical reorganization associated with these congenital lesions. Blood oxygen level-dependent MR imaging is a noninvasive method used to localize areas of eloquent cortex in patients harboring AVMs; it may prove to be of value in treatment planning.

Adolescent↗

PubMed1995

The neural basis of the central executive system of working memory.

Working memory refers to a system for temporary storage and manipulation of information in the brain, a function critical for a wide range of cognitive operations. It has been proposed that working memory includes a central executive system (CES) to control attention and information flow to and from verbal and spatial short-term memory buffers. Although the prefrontal cortex is activated during both verbal and spatial passive working memory tasks, the brain regions involved in the CES component of working memory have not been identified. We have used functional magnetic resonance imaging (fMRI) to examine brain activation during the concurrent performance of two tasks, which is expected to engage the CES. Activation of the prefrontal cortex was observed when both tasks are performed together, but not when they are performed separately. These results support the view that the prefrontal cortex is involved in human working memory.

Adult↗

PubMed1995

Localization of subclinical ictal activity by functional magnetic resonance imaging: correlation with invasive monitoring.

Functional magnetic resonance imaging (fMRI) with susceptibility-based contrast was used to detect focal changes in cerebral blood flow and metabolism in a patient with focal epilepsy. The patient presented with frequent partial motor seizures involving his right lower face that spread to produce speech arrest and occasionally right arm jerking. Consciousness was never impaired during these events. A multislice echoplanar technique was used to acquire 16 contiguous axial slices every 4 seconds for 11 minutes. Although no overt seizures were observed or reported by the patient during the scanning, a time series analysis of the functional data revealed focal signal-intensity changes in the posterior left frontal lobe, which correlated well both in duration and spatial localization with ictal activity subsequently recorded by invasive electrophysiological monitoring. The spatial localization of fMRI was more accurate than electroencephalography recorded from a subdural grid in predicting the site of successful surgical therapy. These results illustrate the potential of functional MRI for localizing seizure foci with high spatial and temporal resolution. Such studies can be readily combined with high-resolution anatomical imaging, task-activation studies, and other magnetic resonance techniques.

Adult↗

PubMed1995

Vascular transit times in calcarine cortex: kinetic analysis of R2* changes observed using localized 1H spectroscopy.

A kinetic analysis of water signal intensity changes measured in human visual cortex by PRESS localized 1H spectroscopy at 500 ms resolution with light-emitting diode (LED) goggle stimulation was used to determine vascular transit times for transitions between rest and activation. Monoexponential curve fitting was used to determine both R2* values for each free induction decay and the time constants for R2* changes with activation and deactivation. Measured transit time values were in general agreement with the literature, and were significantly shorter for "Off-->On" than for "On-->Off" transitions, consistent with known alterations in blood flow with activation and deactivation. The differences in transit times between "Off-->On" and "On-->Off" also varied with stimulus frequency in accordance with known physiology. This type of analysis may provide a useful means of analyzing functional activation data and for quantitatively comparing functional activation results from differing subjects and imaging sessions.

Adult↗

PubMed1995

Renal perfusion in humans: MR imaging with spin tagging of arterial water.

The authors tested a noninvasive technique for magnetic resonance imaging of perfusion in human kidneys. Magnetic labeling (spin tagging) of aortic arterial water was performed to generate an endogenous tracer. Breath-hold renal perfusion images obtained in seven volunteers yielded average perfusion rates in cortex and medulla of 278 mL.100 g-1.min-1 +/- 55 (standard error) and 55 mL.100 g-1.min-1 +/- 25, respectively.

Humans↗

PubMed1994

Quantitative magnetic resonance imaging of human brain perfusion at 1.5 T using steady-state inversion of arterial water.

We report our experience using a noninvasive magnetic resonance technique for quantitative imaging of human brain perfusion at 1.5 T. This technique uses magnetically inverted arterial water as a freely diffusible blood flow tracer. A perfusion image is calculated from magnetic resonance images acquired with and without arterial blood inversion and from an image of the apparent spin-lattice relaxation time. Single-slice perfusion maps were obtained from nine volunteers with approximately 1 x 2 x 5-mm resolution in an acquisition time of 15 min. Analysis yielded average perfusion rates of 93 +/- 16 ml.100 g-1.min-1 for gray matter, 38 +/- 10 ml.100 g-1.min-1 for white matter, and 52 +/- 8 ml.100 g-1.min-1 for whole brain. Significant changes in perfusion were observed during hyperventilation and breath holding. This technique may be used for quantitative measurement of perfusion in human brain without the risks and expense of methods which use exogenous tracers.

Brain↗

PubMed1994

Tissue specific perfusion imaging using arterial spin labeling.

Quantitative magnetic resonance measurements of regional tissue perfusion can be obtained using magnetically labeled arterial water as a diffusable tracer. Continuous labeling is achieved in flowing spins using adiabatic inversion. The effects of continuous labeling of proximal arterial spins and T1 relaxation in distal tissue magnetization result in a steady-state change in tissue magnetization which is tissue specific, i.e., it can be quantified in units of blood flow per gram of tissue per unit time. This magnetization is sampled using standard imaging sequences. The theoretical basis for this method, including the effects of macromolecular spin saturation, is reviewed. Recent results demonstrating the successful implementation of this technique in vitro and in vivo in rat brain, heart, and kidney, and in human brain and kidney are presented, as well as the use of a separate RF coil for arterial labeling to produce selective perfusion images in rat brain. This approach allows quantitative perfusion images to be obtained completely non-invasively at the resolution of 1H MRI, and is useful in the clinical and investigational evaluation of organ physiology.

Animals↗

PubMed1993

Response of normal and reperfused livers to glucagon stimulation: NMR detection of blood flow and high-energy phosphates.

The effects of glucagon on blood flow and high-energy phosphates in control and in rat livers damaged by ischemia were studied using in vivo nuclear magnetic resonance (NMR) spectroscopy. Normal livers and livers which had been made ischemic for 20, 40, and 60 min followed by 60 min of reperfusion were studied. Ischemia led to a loss in adenosine triphosphate (ATP) within 30 min. Reperfusion after 20 min of ischemia led to complete recovery of ATP. 60 min of reperfusion after 40 or 60 min of ischemia led to only a 76% and 48% recovery of ATP, respectively. Glucagon, at doses up to 2.5 mg/kg body weight, caused no changes in the inorganic phosphate (P(i)) to ATP ratio in normal livers as measured by 31P-NMR spectroscopy. In livers which had been made ischemic for 20, 40, or 60 min, glucagon caused an increase in the P(i)/ATP ratio of 18%, 40%, and 40%, respectively. 19F-NMR detection of the washout of trifluoromethane from liver was used to measure blood flow. Glucagon-stimulated flow in the normal liver in a dose-dependent manner, with 2.5 mg glucagon/kg body weight leading to a 95% increase in flow. Ischemia for 20, 40, and 60 min followed by 60 min of reperfusion led to hepatic blood flows which were 63%, 68%, and 58% lower than control liver. In reperfused livers, blood flow after glucagon-stimulation was reduced to 56%, 43%, and 48% of control glucagon-stimulated flow after 20, 40, and 60 min of ischemia. These results indicate that ischemia followed by reperfusion leads to decreases in hepatic blood flow prior to alterations in ATP and the response of the liver to glucagon is altered in the reperfused liver.

Adenosine Triphosphate↗

PubMed1993

Continuous inversion angiography.

A subtractive time-of-flight technique for magnetic resonance angiography is described. In this approach, the arterial supply to an organ is inverted in a steady-state fashion by applying off-resonance irradiation in the presence of a linear magnetic field gradient. An angiogram is formed by subtracting an image acquired with arterial inversion from a control image acquired with no arterial inversion. A single coil is used to apply both the inversion and observation pulses. Intracranial angiograms obtained from normal volunteers using a two-dimensional projective implementation of this technique at 1.5 T illustrate excellent small vessel detail and background suppression.

Algorithms↗

PubMed1992

Magnetic resonance imaging of perfusion using spin inversion of arterial water.

A technique has been developed for proton magnetic resonance imaging (MRI) of perfusion, using water as a freely diffusable tracer, and its application to the measurement of cerebral blood flow (CBF) in the rat is demonstrated. The method involves labeling the inflowing water proton spins in the arterial blood by inverting them continuously at the neck region and observing the effects of inversion on the intensity of brain MRI. Solution to the Bloch equations, modified to include the effects of flow, allows regional perfusion rates to be measured from an image with spin inversion, a control image, and a T1 image. Continuous spin inversion labeling the arterial blood water was accomplished, using principles of adiabatic fast passage by applying continuous-wave radiofrequency power in the presence of a magnetic field gradient in the direction of arterial flow. In the detection slice used to measure perfusion, whole brain CBF averaged 1.39 +/- 0.19 ml.g-1.min-1 (mean +/- SEM, n = 5). The technique's sensitivity to changes in CBF was measured by using graded hypercarbia, a condition that is known to increase brain perfusion. CBF vs. pCO2 data yield a best-fit straight line described by CBF (ml.g-1.min-1) = 0.052pCO2 (mm Hg) - 0.173, in excellent agreement with values in the literature. Finally, perfusion images of a freeze-injured rat brain have been obtained, demonstrating the technique's ability to detect regional abnormalities in perfusion.

Animals↗