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Biomedical subjects

J J Neil

Publications and source records attributed to J J Neil.

At least 19 recordsLinked to original sources

Homonuclear J coupling effects in volume localized NMR spectroscopy: pitfalls and solutions.

It has been observed that the signal amplitude of multiplet resonances such as the 1H doublet resonance of lactate varies with pulse sequence timing when echo-driven volume selective methods such as point resolved spectroscopy are used. Herein a standard vectorial description is presented for the mechanism of this artifact, which results from the chemical shift between homonuclear scalar-coupled (i.e., J coupled) nuclei. The chemical shift causes the extent of a signal phase modulation to vary for different spatial regions of the excited voxel. This variation results in spatial interference effects that can lead to marked loss of signal intensity as well as corruption of the size and shape of the voxel from which signal is obtained. The phenomenon is substantial at an imaging field of 1.5 T and becomes especially pronounced at higher field strengths. Several strategies to avoid the artifact are provided.

Humans

Evaluation of extra- and intracellular apparent diffusion in normal and globally ischemic rat brain via 19F NMR.

The biophysical mechanism(s) underlying diffusion-weighted MRI contrast following brain injury remains to be elucidated. Although it is generally accepted that water apparent diffusion coefficient (ADC) decreases after brain injury, it is unknown whether this is associated with a decrease in intracellular or extracellular water displacement, or both. To address this question, 2-[19F]luoro-2-deoxyglucose-6-phosphate (2FDG-6P) was employed as a compartment-specific marker in normal and globally ischemic rat brain. Through judicious choice of routes of administration, 2FDG-6P was confined to the intra- or extracellular space. There was no statistical difference between intra- and extracellular 2FDG-6P ADCs in normal or in globally ischemic brain (P > 0.16), suggesting that water ADCs in both compartments are similar. However, ischemia did result in a 40% ADC decrease in both compartments (P < 0.001). Assuming that 2FDG-6P reflects water motion, this study shows that water ADC decreases in both spaces after ischemia, with the reduction of intracellular water motion being the primary source of diffusion-weighted contrast.

Animals

Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging.

PURPOSE: To establish quantitative standards for the directionally averaged water apparent diffusion coefficient (D) and quantitative diffusion anisotropy (A sigma) of normal brains in newborns by using diffusion tensor magnetic resonance (MR) imaging. MATERIALS AND METHODS: Diffusion tensor MR imaging was performed during the first 36 hours of life in 22 newborns (gestational age range, 31-41 weeks). Values of D and A sigma were measured in regions of interest chosen in the cortical gray matter, centrum semiovale, caudate nuclei, lentiform nuclei, thalami, internal capsules, and cerebellar hemispheres. RESULTS: The D values in the gray and white matter in newborns are considerably higher than those in adults. There is a striking correlation between gestational age and D, with D decreasing as gestational age increases. The A sigma values in the white matter in newborns are lower than those in adults. Values of A sigma show statistically significant correlations with gestational age only in the white matter of the centrum semiovale, in which A sigma values increase sharply near term. CONCLUSION: The D values primarily reflect overall brain water content. The A sigma values are more sensitive to tissue microstructure (e.g., white matter packing and myelination). The D and A sigma images reveal information and not apparent on T1- and T2-weighted images.

Adult

Evaluation of intracellular diffusion in normal and globally-ischemic rat brain via 133Cs NMR.

The question of whether the apparent diffusion coefficient (ADC) of intracellular water changes after brain injury was addressed by using 133Cs as an indicator to report on the state of the intracellular environment. Cesium is an NMR-detectable potassium analog that accumulates in the intracellular space and is detectable in rat brain after being added to the animal's diet. The ADC of cesium was measured before and after the death of the rat. The cesium ADC fell from 0.91 +/- 0.05 x 10(-3) mm2/s (mean +/- SEM, n=5) in the alive rat to 0.71 +/- 0.05 x 10(-3) mm2/s within 20 min (the best time resolution of the experiment) of the death of the animal and stayed at this value for at least 3 h (p < 0.001). Assuming that the ADC of cesium reflects motion in the intracellular environment, these results support the idea that there are changes associated with cell injury that would cause a reduction in the ADC of intracellular water. Hence, one factor contributing to the decrease in water ADC after brain injury is a change in the ADC of intracellular water.

Animals

Masturbation mimicking paroxysmal dystonia or dyskinesia in a young girl.

We present the case of a young girl with periodic posturing during masturbation. The child had been evaluated by several physicians and underwent numerous diagnostic tests before the spells were seen by a physician and determined to be self-stimulatory and not paroxysmal dystonia. Masturbation is a normal and common behavior in young children and should be recognized as such. Failure to recognize this behavior can lead to unnecessary and invasive testing.

Child, Preschool

An evaluation of the sensitivity of the intravoxel incoherent motion (IVIM) method of blood flow measurement to changes in cerebral blood flow.

To evaluate the sensitivity of the intravoxel incoherent motion (IVIM) technique to changes in cerebral blood flow, we made measurements of IVIM parameters in rat brain under conditions of altered arterial pCO2. The arterial pCO2 was varied over a range which would be expected to change cerebral blood flow from roughly 50 to 500 ml/(100 g.min). The IVIM measurements were made with suppression of extravascular water signal. The parameters f' (the apparent fraction of spins which have "fast" pseudodiffusion), D1* (the "fast-pseudodiffusion") coefficient), and D2* (the "slow-pseudodiffusion" coefficient) all showed statistically significant positive linear correlations with arterial pCO2. These results suggest that the IVIM method, when used with suppression of extravascular water signal, is sensitive to changes in blood flow.

Animals

A quantitative interpretation of IVIM measurements of vascular perfusion in the rat brain.

Pulsed gradient spin echo (PGSE) sequences have been used to measure the signal loss of 19F in perfluorinated hydrocarbon blood substitutes moving within the vasculature of the rat brain in the experimental conditions of the study. The signal loss is not characterized by a single apparent pseudodiffusion coefficient. A simple vascular network model based on self-similarity has been used to calculate the shape of the signal loss. Excellent agreement with the experiment has been obtained showing that the IVIM measurements are sensitive to flow over a wide range of vessel diameters and flow rates. This model of vascular structure may serve well for other MR measurements that are sensitive to perfusion.

Animals

On the use of Bayesian probability theory for analysis of exponential decay data: an example taken from intravoxel incoherent motion experiments.

Traditionally, the method of nonlinear least squares (NLLS) analysis has been used to estimate the parameters obtained from exponential decay data. In this study, we evaluated the use of Bayesian probability theory to analyze such data; specifically, that resulting from intravoxel incoherent motion NMR experiments. Analysis was done both on simulated data to which different amounts of Gaussian noise had been added and on actual data derived from rat brain. On simulated data, Bayesian analysis performed substantially better than NLLS under conditions of relatively low signal-to-noise ratio. Bayesian probability theory also offers the advantages of: a) not requiring initial parameter estimates and hence not being susceptible to errors due to incorrect starting values and b) providing a much better representation of the uncertainty in the parameter estimates in the form of the probability density function. Bayesian analysis of rat brain data was used to demonstrate the shape of the probability density function from data sets of different quality.

Animals

Functional imaging of the central nervous system using magnetic resonance imaging and positron emission tomography.

There have been striking advances recently in magnetic resonance imaging and positron emission tomography (PET) imaging of the central nervous system, particularly in the area of "functional" imaging. We discuss these advances with emphasis on the similarities and differences between the PET and magnetic resonance imaging methods. In addition, we examine recent progress and controversies in the use of volume-localized nuclear magnetic resonance spectroscopy. Finally, we review the use of three-dimensional acquisition for PET studies, with an evaluation of the relative advantages and disadvantages of this modification of the PET technique.

Arousal

Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo. II. Validation of the deuterium NMR washout method for measuring organ perfusion.

The deuterium washout technique of measuring tissue blood flow is based upon NMR detection of HOD (administered as D2O saline, but typically detected as HOD because of rapid proton-deuteron exchange) as a freely diffusible tracer. Though this method is coming into more general use, it has not yet been rigorously validated in vivo against an accepted, independent measure of tissue blood flow. To this end, simultaneous radiolabeled microsphere and HOD washout blood flow measurements were made in rat gastrocnemius muscle. D2O saline was administered either intramuscularly or intraarterially (near the aortic bifurcation), and the sciatic nerve was electrically stimulated to increase the muscle blood flow rate. Over a range of flows of 2 to 80 ml/(100 g.min), comparison of microsphere and HOD washout measurements showed good agreement, with r = 0.92 (n = 16) for intramuscular administration and r = 0.91 (n = 12) for intraarterial administration. These data strongly suggest that the HOD washout technique provides accurate blood flow measurements in skeletal muscle.

Animals

The validation of freely diffusible tracer methods with NMR detection for measurement of blood flow.

While the general theory of measuring organ perfusion using exogenously administered freely diffusible tracers was originally formulated over 40 years ago, the application of NMR techniques for tracer detection is a recent development. A brief theoretical review and discussion of the literature validating the use of deuterium and fluorine as NMR-detectable tracers is provided.

Blood Circulation

Sepsis does not impair tricarboxylic acid cycle in the heart.

Sepsis has been reported to cause mitochondrial dysfunction and inhibition of key enzymes that regulate the tricarboxylic acid (TCA) cycle. We investigated the effect of sepsis on high-energy phosphates, glycolytic and TCA cycle intermediates, and specific amino acids that are involved in regulating the size of the TCA cycle pool during changes in metabolic state of the heart. Sepsis was induced in 12 female rats by the cecal ligation and perforation technique under halothane anesthesia; seven control rats underwent cecal manipulation without ligation. At 36-42 h postsurgery, the rats were reanesthetized, the chest was opened, and the hearts were freeze-clamped. Perchloric acid extracts of the hearts were analyzed with fluorometric enzymatic methods and 31P nuclear magnetic resonance spectroscopy. There were no significant differences in the levels of the TCA cycle intermediates or high-energy phosphates between the septic and control rats. The major metabolic changes were the 28% decrease in alanine and the 31% decrease in glutamate in the septic hearts compared with control (P less than 0.05 and P less than 0.005, respectively). Phosphocholine, a component of membrane phospholipids, was increased by 91% in the septic hearts (P less than 0.01). We conclude that sepsis does not impair the TCA cycle or induce significant cellular ischemia in the heart. The increase in phosphocholine may represent significant cellular membrane disruption during sepsis.

Adenosine Triphosphate

Changes in regional blood flow and cardiac output after L-glutamate stimulation of A5 cell group.

Changes in regional blood flow and cardiac output were measured by the reference organ method in pentobarbital-anesthetized rats with radioactive microspheres (15 microns) before and after chemical stimulation of the A5 cell group with the excitatory amino acid L-glutamate an agent that excites cell bodies but not fibers of passage. This stimulation caused a decrease in mean arterial pressure, heart rate, cardiac output, and calculated stroke volume. The limb skeletal muscles showed a large increase in blood flow and decrease in vascular resistance, whereas the trunk musculature showed no change in flow or resistance. The blood flow of the entire gastrointestinal tract decreased. Blood flow in the skin decreased with no change in resistance. The cardiac muscle of the ventricles showed a decrease in flow without a change in resistance. The ipsilateral half of the brain showed a decrease in blood flow, while the contralateral side showed no change. The kidneys exhibited no change in blood flow and a decrease in resistance. A5 stimulation in guanethidine-sympathectomized rats caused no change in regional blood flow. In contrast, an increase in cardiac output was observed, and the possible interpretations for this change are discussed. Rats treated with intraventricular injections of 6-hydroxydopamine showed no changes in regional blood flow or cardiac output, indicating that catecholamine neurons are involved in these responses.

Animals

Actions of N-methyl aspartate and its antagonist aminophosphonovalerate on the A5 catecholamine cell group in rat.

When N-methyl-D,L-aspartic acid was injected into the A5 catecholamine cell group of the rat, a dose-dependent decrease in blood pressure and heart rate was obtained. These cardiovascular changes were subsequently blocked by the (-) and (+) isomers of the aspartate receptor blocker 2-amino-5-phosphonovalerate (2-amino-5-phosphonopentanoic acid). The (-) isomer was 2-4 times more potent than the (+) form.

2-Amino-5-phosphonovalerate

Substance P neurons project from the ventral medulla to the intermediolateral cell column and ventral horn in the rat.

The descending substance P projections from the ventral medulla were studied in the rat. Electrolytic lesions which included the nucleus interfascicularis hypoglossi decreased the substance P-like immunoreactivity (SP-I) in both the intermediolateral cell column and the ventral horn of the spinal cord. Lesions of other ventral medullary areas and midbrain hemisections did not change spinal cord SP-I levels. Intracerebroventricular administration of the serotonin neurotoxin, 5,7-dihydroxytryptamine, reduced the SP-I content of the ventral horn but not of the intermediolateral cell column.

5,7-Dihydroxytryptamine

Effects of kainic acid applied to the ventral surface of the medulla oblongata on vasomotor tone, the baroreceptor reflex and hypothalamic autonomic responses.

Application of an excitotoxic amino acid, kainic acid, to the ventral medullary surface just caudal to the trapezoid bodies (at Feldberg and Guertzenstein's glycine-sensitive area) led to the following observations. (1) Blood pressure began to rise within 25 s and by 10 min rose to high levels (200-240 mm Hg). Blood pressure subsequently fell to levels at or approaching those of a spinal animal. (2) Sympathetic vasomotor activity became insensitive to baroreceptor inhibition shortly after the peak in blood pressure, and the cardioinhibitory action of the reflex was enhanced during this time. (3) The autonomic effects of hypothalamic stimulation were differentially affected--pupillary dilatation and retraction of the nictitating membranes were unaffected, while the increases in blood pressure and renal nerve activity were blocked. (4) Recovery from these effects was observed on two occasions, when the animals were infused with a pressor agent and allowed to survive beyond 6 h after the kainic acid application. These results support the view that vasomotor tone is dependent upon the activity of relatively superficial cells in the ventral medulla. We further suggest that baroreceptor inhibition of sympathetic vasomotor activity acts via these cells and that descending hypothalamic autonomic pathways are organized at this level in terms of separate end organs.

Animals

The role of descending monoaminergic systems in central control of blood pressure.

The descending projections to the intermediolateral cell column arise from several sources. The serotonergic inputs come from the raphe pallidus, raphe obscurus, raphe magnus nuclei, and ventral medulla. The A5 cell group provides a norepinephrine input to the intermediolateral cell column and the A1 cell group appears to be the main source of the epinephrine input. The functional role of monoamines on sympathetic preganglionic neurons is unclear. Iontophoresis studies indicate that serotonin excites and norepinephrine inhibits sympathetic preganglionic neurons. Pharmacological studies indicate that an alpha-2 receptor is located on or near these neurons. In contrast, electrical stimulation of the monoamine cell bodies produces opposite results. Stimulation of the raphe nuclei causes an inhibition of the sympathetic outflow whereas stimulation of some of the noradrenergic cell groups causes pressor responses. The role of monoamines in various cardiovascular reflexes and in experimental hypertension is discussed.

Animals