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Jeffrey J Neil

Publications and source records attributed to Jeffrey J Neil.

At least 19 recordsLinked to original sources

Modeling water diffusion anisotropy within fixed newborn primate brain using Bayesian probability theory.

An active area of research involves optimally modeling brain diffusion MRI data for various applications. In this study Bayesian analysis procedures were used to evaluate three models applied to phase-sensitive diffusion MRI data obtained from formalin-fixed perinatal primate brain tissue: conventional diffusion tensor imaging (DTI), a cumulant expansion, and a family of modified DTI expressions. In the latter two cases the optimum expression was selected from the model family for each voxel in the image. The ability of each model to represent the data was evaluated by comparing the magnitude of the residuals to the thermal noise. Consistent with previous findings from other laboratories, the DTI model poorly represented the experimental data. In contrast, the cumulant expansion and modified DTI expressions were both capable of modeling the data to within the noise using six to eight adjustable parameters per voxel. In these cases the model selection results provided a valuable form of image contrast. The successful modeling procedures differ from the conventional DTI model in that they allow the MRI signal to decay to a positive offset. Intuitively, the positive offset can be thought of as spins that are sufficiently restricted to appear immobile over the sampled range of b-values.

Animals↗

Detection of wallerian degeneration in a newborn by diffusion magnetic resonance imaging (MRI).

We present the case of an infant with hypoxic-ischemic encephalopathy in whom wallerian degeneration is demonstrated in white-matter fiber tracts by diffusion magnetic resonance imaging (MRI). MRI was undertaken on days 2 and 9 and then at 9 months of age. On day 2, conventional MRI was normal, but diffusion MRI showed bioccipital abnormalities. On day 9, diffusion MRI showed marked abnormalities in the deep white matter of the occipital regions (left > right), corpus callosum, left posterior limb of the internal capsule, and left cerebral peduncle. Water apparent diffusion coefficient values showed a significant reduction in the left occipital white matter and corpus callosum between days 2 and 9 while demonstrating the expected pseudonormalization in cortical gray matter. Images at 9 months showed left occipital porencephaly and atrophy of the left cerebral peduncle, with the infant displaying right hemiplegia at 18 months of age. In this case, the time course of diffusion changes differed between white and gray matter, with diffusion MRI showing delayed wallerian degeneration of the cerebral white matter. This case characterizes this degeneration with clinical and follow-up MRI at 9 months of age.

Asphyxia Neonatorum↗

Diffusion MR imaging characteristics of the developing primate brain.

Diffusion-based magnetic resonance imaging holds the potential to non-invasively demonstrate cellular-scale structural properties of brain. This method was applied to fixed baboon brains ranging from 90 to 185 days gestational age to characterize the changes in diffusion properties associated with brain development. Within each image voxel, a probability-theory-based approach was employed to choose, from a group of analytic equations, the one that best expressed water displacements. The resulting expressions contain eight or fewer adjustable parameters, indicating that relatively simple expressions are sufficient to obtain a complete description of the diffusion MRI signal in developing brain. The measured diffusion parameters changed systematically with gestational age, reflecting the rich underlying microstructural changes that take place during this developmental period. These changes closely parallel those of live, developing human brain. The information obtained from this primate model of cerebral microstructure is directly applicable to studies of human development.

Algorithms↗

Sodium ion apparent diffusion coefficient in living rat brain.

The apparent diffusion coefficient (ADC) of Na(+) was determined in live rat brain. The brain extracellular-to-intracellular Na(+) content ratio is approximately 8:2, which is the inverse of that for water in these spaces. Consequently, the ADC of Na(+) is primarily affected by motion in the extracellular space, and Na(+) can be viewed as a reporter molecule for motion in that space. Likewise, water ADC is dominated by intracellular motion. The brain Na(+) ADC was 1.15 +/- 0.09 microm(2)/ms, which is 61% of the aqueous Na(+) free diffusion coefficient (D(free)) at 37 degrees C (1.9 microm(2)/ms), while the ADC for brain water is 28% of the water D(free) at 37 degrees C (3 microm(2)/ms). This suggests that the ADC of molecular species within the extracellular space is roughly twofold that within the intracellular space. In postmortem brain, both Na(+) and water decrease to 17% of the respective D(free) values. These results are consistent with Na(+) and water ADC values sharing the same biophysical determinants in postmortem brain. The observed difference between Na(+) and water ADC/D(free) ratios in living brain tissue may be attributable to the extracellular environment hindering molecular displacements twofold less than the intracellular environment.

Animals↗

Formalin fixation alters water diffusion coefficient magnitude but not anisotropy in infarcted brain.

This study was designed to determine whether formalin fixation alters diffusion parameters in the infarcted brain. Diffusion tensor images were obtained from anesthetized mice 1 hr after middle cerebral artery occlusion and repeated after formalin fixation of brains. In live animals, there was a significant decrease in the trace of the diffusion tensor (Tr(D)) in infarcted cortex and external capsule compared with contralateral brain areas, with no change in relative anisotropy (RA). After formalin fixation, Tr(D) was reduced 30-80%. However, the Tr(D) differential present in vivo between injured and healthy tissues was lost, with Tr(D) reduced to similar values in all tissues except for the edge of the cortical infarction, where it was lower than in surrounding tissues. RA values were unchanged after fixation. This study supports the preservation of diffusion anisotropy for both healthy and injured white matter in fixed mouse brain. However, the sensitivity of water diffusion in detecting tissue injury in vivo is not preserved in fixed tissues.

Animals↗

Biomedical applications of 133Cs NMR.

133Cs NMR is a valuable tool for non-invasively probing biological systems. As a congener of potassium, it accumulates in the intracellular space, primarily through the action of the Na+-K+ pump (ATPase). In addition, it is possible to resolve the MR signal of 133Cs in different tissue compartments on the basis of chemical shift or MR relaxation properties. This compartmental resolution applies not only to the intra- and extracellular spaces, but to subcellular compartments as well. In this review, we discuss the studies defining the ion transport, chemical shift and relaxation characteristics of 133Cs in living systems. We also review the application of 133Cs NMR to evaluation of ion transport across membranes and the kinetic/chemical environment of the intracellular space in systems ranging from red blood cells to rat brain.

Animals↗

Effects of physiologic challenge on the ADC of intracellular water in the Xenopus oocyte.

The biophysical determinants of the intracellular water apparent diffusion coefficient (ADC) in mammalian tissues are poorly understood. Model systems that are more amenable to physical measurements may provide insights into the behavior of more complex systems. Toward that end, we used MRI to evaluate the effects of altered microtubule concentration, nuclear breakdown, and ATP depletion on intracellular water ADC in the Xenopus oocyte. Water ADC did not change in response to polymerization of microtubules with taxol or depolymerization with nocodazole. Water ADC did not change following the breakdown of the nucleus in healthy cells. Short-term depletion of ATP (approximately 20% of normal levels following 4 hr of exposure to sodium azide and 2-deoxy-D-glucose) was not associated with a change in intracellular ADC. Long-term depletion of ATP (approximately 20% of normal levels following 2 days of exposure to antimycin A) was associated with a significant decrease in intracellular water ADC. These findings suggest that intracellular water diffusion in oocytes is not dependent on the state of microtubule polymerization or short-term ATP depletion, although long-term ATP depletion is associated with changes that lead to a decrease in intracellular water ADC.

Adenosine Triphosphate↗

Use of magnetic resonance to measure molecular diffusion within the brain extracellular space.

Ion-selective microelectrode measurements of molecular diffusion have provided unique information about the structural characteristics of the extracellular compartment of brain tissue. Magnetic resonance (MR) techniques can also be used to perform diffusion measurements in living tissue in situ. In MR applications, the challenge to study a particular physiological compartment lies in achieving the appropriate specificity in the experimentally-observed MR signal, and many strategies have been used to provide measurements that reflect molecular diffusion within the extracellular space. This review describes how magnetic resonance and microelectrode diffusion measurements are performed, and applications using the MR technique are summarized. Comparisons of experimental results obtained from the two techniques indicate that their use in combination may further augment what is known about extracellular space structure.

Animals↗

Imaging perinatal brain injury in premature infants.

The primary methods currently in use for imaging the infant brain are cranial ultrasound (CUS), computed tomography (CT) and magnetic resonance imaging (MRI). This review outlines the relative strengths and weaknesses of these modalities in relation to the premature infant, with specific focus on the correlations between imaging findings and neurodevelopmental outcome. Since MRI is undergoing rapid development at this time, the newer MRI methods of brain volume measurement and diffusion tensor imaging are reviewed in more detail. Current guidelines regarding the application of these neuroimaging methods to the premature infant are discussed.

Brain Diseases↗

Apparent diffusion coefficient in the posterior limb of the internal capsule predicts outcome after perinatal asphyxia.

OBJECTIVE: Predicting long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) is a difficult task. Magnetic resonance imaging, particularly diffusion imaging, holds promise in this regard as it is more sensitive to brain injury than any other available imaging modality. Previous studies have suggested that abnormal signal intensity in the posterior limb of the internal capsule (PLIC), detectable on inversion-recovery T1-weighted imaging, is a strong predictor of outcome. The aim of this study was to assess the relationship between apparent diffusion coefficient (ADC) values from the PLIC, measured by diffusion imaging, and neuromotor outcome in term infants with HIE. METHODS: Twenty-eight term infants with a clinical diagnosis of HIE underwent magnetic resonance imaging as soon as practicable after birth (mean age: 5.6 days), including diffusion-weighted imaging, from which ADC values in the PLIC were measured. Motor outcome was assessed in 12 of 16 survivors. RESULTS: The ADC value in the PLIC was significantly associated with survival in term infants with HIE. For survivors, the mean ADC value in the PLIC was 0.89 +/- 0.17 microm2/ms, whereas the mean ADC value for nonsurvivors was 0.75 +/- 0.17 microm2/ms (t = 2.25). Among survivors, the ADC value in the PLIC was also associated with neuromotor outcome (F = 5.60). CONCLUSION: The ADC value in the PLIC is an indicator of ischemic injury and may be of use as an objective prognostic marker for infants with HIE.

Asphyxia Neonatorum↗

Equilibrium water exchange between the intra- and extracellular spaces of mammalian brain.

This report describes the measurement of water preexchange lifetimes and intra/extracellular content in intact, functioning mammalian brain. Intra- and extracellular water magnetic resonance (MR) signals from rat brain in vivo were quantitatively resolved in the longitudinal relaxation domain following administration of an MR relaxation agent into the extracellular space. The estimated intracellular water content fraction was 81% +/- 8%, and the intra- to extracellular exchange rate constant was 1.81 +/- 0.89 s(-1) (mean +/- SD, N = 9), corresponding to an intracellular water preexchange lifetime of approximately 550 ms. These results provide a temporal framework for anticipating the water exchange regime (fast, intermediate, or slow) underlying a variety of compartment-sensitive measurements. The method also supplies a means by which to evaluate membrane water permeability and intra/extracellular water content serially in intact tissue. The data are obtained in an imaging mode that permits detection of regional variations in these parameters.

Animals↗

Magnetic resonance measurement of tetramethylammonium diffusion in rat brain: Comparison of magnetic resonance and ionophoresis in vivo diffusion measurements.

Magnetic resonance (MR) and ionophoresis are two experimental methods that provide measurements of molecular diffusion in living tissue. Typical experimental settings yield MR studies that are sensitive to mean molecular displacements of approximately 5 microm, and ionophoresis experiments to displacements of > or =100 microm. An assessment of the correspondence between the methods is hampered by the fact that no common probe molecule has been used. One of the most frequently utilized probe molecules in ionophoresis measurements is the tetramethylammonium (TMA) ion. In the current work the diffusion properties of TMA were studied in rat brain in vivo with localized (1)H MR spectroscopy (MRS). Standard treatment of the MR data yielded a 3.6-fold lower apparent diffusion coefficient (ADC) compared to ionophoresis. To explore the source of this discrepancy, a separate data processing scheme was applied to the MR data to monitor individual elapsed displacement-distance subpopulations of TMA molecules. This analysis revealed a dependence of the ADC estimation on a given subpopulation's elapsed displacement distance. The MR-derived ADC approached the ionophoresis-derived value as the elapsed displacement distance increased to 15 microm. These observations demonstrate that MR and ionophoresis studies provide complementary information, and that ADC estimates obtained from the two techniques are sensitive to different biophysical determinants.

Animals↗

Relative indices of water diffusion anisotropy are equivalent in live and formalin-fixed mouse brains.

Formalin fixation of tissue is a common laboratory practice. A direct comparison of diffusion tensor imaging (DTI) parameters from mouse brains before (in vivo) and after (ex vivo) formalin fixation is reported herein. Five diffusion indices were examined in a cohort of seven mice: relative anisotropy (RA), directional correlation (DC), trace (Tr(D)), trace-normalized axial diffusivity (D(axially)), and radial diffusivity (D(radially)). Seven regions of interest (ROIs), including five in white matter and two in gray matter, were selected for examination. Consistent with previous findings, a significant decrease of Tr(D) was observed for all ROIs after fixation. However, water diffusion anisotropy, as defined by the indices RA, DC, D(axially), and D(radially), remained unchanged after fixation. Thus, fixation does not appear to alter diffusion anisotropy in the mouse brain. This finding supports the utility of diffusion anisotropy analysis of fixed tissue. The combination of DTI measurements and standard histology may shed light on the microstructural determinants of diffusion anisotropy in normal and disease states.

Animals↗

Intracranial hemorrhage progressing to porencephaly as a result of congenitally acquired cytomegalovirus infection--an illustrative report.

OBJECTIVE: To report ultrasound and magnetic resonance imaging (MRI) findings in a fetus with intracranial hemorrhage and porencephaly, presumed secondary to intrauterine cytomegalovirus (CMV) infection. METHODS: A 20-year-old, G2, P1 woman presented at 28.6 weeks' gestation after ultrasound examination demonstrated apparently isolated fetal ascites. Evaluation included maternal serology, amniocentesis, and repeated ultrasound examinations. Fetal MRI evaluation was also performed. The infant was born at 35 weeks' gestational age. RESULTS: Maternal serology was positive for CMV IgG. Intrauterine CMV infection was confirmed using polymerase chain reaction (PCR). At 31.6 weeks' gestation, ultrasound demonstrated borderline lateral cerebral ventriculomegaly. MRI of the fetal brain on the same day demonstrated parenchymal hemorrhage in the right posterior temporal and parietal regions along with mild ventricular enlargement. Sonography one day before delivery revealed brain parenchymal cystic change consistent with porencephaly of the right posterior temporal and parietal region. Postnatal ultrasound, computed tomography (CT), and MRI confirmed the diagnosis of a porencephalic cyst communicating with the posterior body of the right lateral ventricle. Placental pathology was consistent with CMV infection. CONCLUSION: This case report illustrates that fetal MRI is a useful adjunct in the evaluation of intrauterine infection with CMV.

Adult↗

Investigation of mechanisms underlying transient T2 normalization in longitudinal studies of ischemic stroke.

PURPOSE: To determine if the phenomenon of transient normalization of T2 relaxation in the subacute stage of ischemic stroke is associated with either magnetic susceptibility effects secondary to hemorrhage or changes in tissue water content. MATERIALS AND METHODS: We utilized a rat model of transient, focal, cerebral ischemia. The possibility of hemorrhage was evaluated with T2*-weighted (T2*W) imaging and histology. Changes in water content were assessed by brain wet-to-dry weight. RESULTS: Susceptibility effects were not evident in T2*W images, and neither red blood cells nor unchelated Fe(III) was found in hematoxylin and eosin (H-E)- or Prussian Blue-stained sections, respectively. However, between the peak of T2 contrast and the point of transient T2 normalization, water content consistently decreased by an average of 3%. CONCLUSION: Transient T2 normalization is associated with normalization of water content and can occur without evidence of hemorrhage.

Analysis of Variance↗

Apparent diffusion of water, ions, and small molecules in the Xenopus oocyte is consistent with Brownian displacement.

The incoherent displacement of water in living tissues is of considerable interest because of the widespread use of diffusion-weighted MRI, for which image contrast is based on the water apparent diffusion coefficient (ADC). It has been hypothesized that the decrease in water ADC associated with brain injury is primarily due to a reduction in the ADC of water in the intracellular space. Xenopus oocytes permit direct measurement of ADC values for intracellular molecules, thereby providing insight into the nature of intracellular motion. In this study, the measured ADC values of small molecules and ions are shown to be primarily size-dependent, indicating that intracellular water motion in the oocyte is mainly Brownian displacement with little or no role for cytoplasmic streaming. Further, intracellular water ADC values show no dependence on diffusion time over a broad range (3.4-100 ms), suggesting that barriers to displacement are finely spaced (< or = 2-3 microm). The water diffusion shows some small anisotropy, suggesting that the cell has structure, giving water displacement a directional preference. The calculated intracellular apparent viscosity, which reflects the combined effects of barriers to motion, intermolecular binding, and fluid phase viscosity was 2.07 +/- 0.09 cP.

Animals↗

Evidence that both fast and slow water ADC components arise from intracellular space.

Evaluation of water diffusion in the brain has revealed both fast- and slow-diffusing water populations. It has been suggested that these populations represent extra- and intracellular water, respectively. We have identified and characterized both populations in the intracellular space of the Xenopus oocyte. We have also determined their T(1) and T(2) relaxation properties. The fast and slow intracellular populations have diffusion coefficients of 1.06 +/- 0.05 microm(2)/ms and 0.16 +/- 0.02 microm(2)/ms, respectively, with the fast fraction representing 89% +/- 1% of the total water signal. These values are quite similar to those for total water in brain and are observed in the absence of signal from the perfusate (extracellular) water population. Volumetric swelling (16% +/- 4%) of the oocyte in hypoosmotic media increased the diffusion coefficients of both intracellular populations (fast = 1.27 +/- 0.03 microm(2)/ms, slow = 0.22 +/- 0.02 microm(2)/ms), but did not change their relative signal fractions. This phenomenon runs counter to the effects observed in brain injury, following which the apparent diffusion coefficient (ADC) decreases 30-50%. The results presented herein suggest that this ADC decrease in brain occurs despite cell swelling, which by itself would be expected to induce an increase in intracellular diffusion coefficients.

Animals↗