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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

A prospective, longitudinal diffusion tensor imaging study of brain injury in newborns.

OBJECTIVE: To establish the magnitude and time course of the changes in water diffusion coefficient (D(av)) following newborn infant brain injury. METHODS: Ten newborn infants at high risk for perinatal brain injury were recruited from the neonatal intensive care unit. Conventional and diffusion tensor MRI was performed on three occasions during the first week of life. Regions of injury were determined by evaluating conventional MR images (T1, T2, fluid-attenuated inversion recovery) at 1 week after injury. D(av) values were determined for these regions for all three scans. RESULTS: D(av) values were decreased in most infants 1 day after injury, but injury was not evident or underestimated in 4 of 10 infants despite the presence of injury on conventional imaging at 1 week. By the third day, D(av) values were decreased in injured areas in all infants, reaching a nadir of approximately 35% less than normal values. By the seventh day after injury, D(av) values were returning to normal (pseudonormalization). CONCLUSIONS: MR diffusion images (for which contrast is determined by changes in D(av)) obtained on the first day after injury do not necessarily show the full extent of ultimate injury in newborn infants. Images obtained between the second and fourth days of life reliably indicate the extent of injury. By the seventh day, diffusion MR is less sensitive to perinatal brain injury than conventional MR because of transient pseudonormalization of D(av). Overall, diffusion MR may not be suitable as a gold standard for detection of brain injury during the first day after injury in newborn infants.

Brain Injuries↗

Extracellular apparent diffusion in rat brain.

The apparent diffusion coefficients (ADCs) of a series of markers concentrated in the extracellular space of normal rat brain were measured to evaluate, by inference, the ADC of water in the extracellular space. The markers (mannitol, phenylphosphonate, and polyethylene glycols) are defined as "compartment selective" because tissue culture experiments demonstrate some leakage into the intracellular space, making them less "compartment specific" than commonly believed. These primarily extracellular markers have ADCs similar to those of intracellular metabolites of comparable hydrodynamic radius, suggesting that water ADC values in the intra- and extracellular spaces are similar. If this is the case, then it is unlikely that a net shift of water from the extra- to the intracellular space contributes significantly to the reduction in water ADC detected following brain injury. Rather, this reduction is more likely due primarily to a reduction of the ADC of intracellular water associated with injury.

Analysis of Variance↗

Water and lipid MRI of the Xenopus oocyte.

Oocytes of Xenopus laevis are large, single cells that provide a promising model system for the exploration of the MR biophysics fundamental to more complex living systems. Previous studies have generally employed 2D spin-echo sequences with an image slice thickness greater than the thickness of the cellular volumes of interest. Also, the large cytoplasmic lipid signal has typically been ignored. This study describes separate, high-resolution 3D measurements of the water and lipid spin densities, T(1) and T(2) relaxation time constants, and the water apparent diffusion rate constant (ADC) in the Xenopus oocyte without significant partial volume artifacts. The lipid spin-density and values for water MR properties varied monotonically from the vegetal to animal poles, indicating that the border between the poles is not sharply demarcated. Regional water MR property values correlated with lipid signal intensity. Lipid-specific imaging is shown for which water suppression is achieved via high diffusion weighting in the imaging sequence.

Animals↗

Direct, longitudinal comparison of (1)H and (23)Na MRI after transient focal cerebral ischemia.

BACKGROUND AND PURPOSE: (23)Na MRI may offer new insight into the evaluation of tissue injury. We performed a direct, longitudinal, morphological comparison of (1)H T2 relaxation, (1)H apparent diffusion coefficient (ADC), (23)Na content, and histopathology after cerebral ischemia to address the hypotheses that (a) (23)Na MRI is unique in comparison to (1)H MRI, and (b) accumulation of (23)Na is an unambiguous marker for dead tissue. METHODS: Rats underwent 30 minutes of focal ischemia. MRIs of (1)H T2, (1)H ADC, and (23)Na content were acquired from 12 hours up to 1, 2, or 14 days after reperfusion. On excision, brains were stained with triphenyltetrazolium chloride (TTC). RESULTS: In all cases, the region of abnormality increased in size for 2 days. On day 5, both (1)H T2 and ADC temporarily appeared normal despite the presence of TTC-defined infarction. By comparison, the volume of tissue exhibiting abnormally intense (23)Na signal mirrored the TTC-defined infarct at all time points. CONCLUSIONS: Regions of high (23)Na content correlate well with the TTC-defined infarct and may be a quantitative in vivo marker for dead tissue. In contrast, the dynamics of the (1)H T2 and ADC make it difficult to interpret these images without additional information because they may appear normal despite infarction. Neither type of (1)H image delineates dead tissue, and none of these methods predicts the potential infarct size at early time points.

Animals↗

Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging.

OBJECTIVE: MR imaging of central nervous system (CNS) malignancies falls short of a definitive evaluation. Tissue diagnosis remains the gold standard. Diffusion-tensor MR imaging measures the apparent diffusion coefficient and diffusion anisotropy of water in tissue. The purpose of this study was to test the hypothesis that the apparent diffusion coefficient may improve the MR imaging evaluation of newly diagnosed CNS neoplasms. We examined the relationship between the apparent diffusion coefficient, anisotropy, and tumor cellularity in 12 pediatric patients. MATERIALS AND METHODS: On the basis of histopathologic evaluation, tumors in this case series were segregated into three types: low-grade gliomas, embryonal tumors, and nonembryonal high-grade tumors. Mean apparent diffusion coefficient and anisotropy values obtained from the solid components of each tumor were compared with cellularity, total cellular area, and total nuclear area derived from biopsy material. RESULTS: The apparent diffusion coefficient ratio (tumor to normal brain) correlated well with tumor classification (p = 0.001). Anisotropy was decreased similarly in all tumor classifications. The absolute apparent diffusion coefficient correlated well with cellularity (p = 0.014) and total nuclear area (p = 0.005) per high-power field. The correlation between apparent diffusion coefficient and total cellular area per high-power field was not statistically significant. CONCLUSION: The apparent diffusion coefficient may be predictive of tumor classification and may be a useful tool in characterizing tumor cellularity and total nuclear area. These parameters are not available in standard MR imaging. Therefore, diffusion-tensor imaging may enhance the diagnostic process in pediatric CNS malignancies.

Adolescent↗

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↗