Amblyopia and yellow spectacles.
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Amblyopia↗
Biomedical subjects
M Moseley
Publications and source records attributed to M Moseley.
Diffusion/perfusion MR imaging of acute cerebral ischemia.
In vivo echo-planar MR imaging was used to measure apparent diffusion coefficients (ADC) of cerebral tissues in a comprehensive noninvasive evaluation of early ischemic brain damage induced by occlusion of the middle cerebral artery (MCA) in a cat model of acute regional stroke. Within 10 min after arterial occlusion, ADC was significantly lower in tissues within the vascular territory of the occluded MCA than in normally perfused tissues in the contralateral hemisphere. Sequential echo-planar imaging was then used in conjunction with bolus injections of the magnetic susceptibility contrast agent, dysprosium DTPA-BMA, to characterize the underlying cerebrovascular perfusion deficits. Normally perfused regions of brain were identified by a dose-dependent 35-70% loss of signal intensity within 6-8 s of contrast administration, whereas ischemic regions appeared relatively hyperintense. These data indicate that sequential diffusion/perfusion imaging may be useful in differentiating permanently damaged from reversibly ischemic brain tissue.
Animals↗
Facilitated magnetic resonance imaging diagnosis of pulmonary disease using a macromolecular blood-pool contrast agent, polylysine-(Gd-DTPA)40.
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Animals↗
Magnetic resonance imaging of brain perfusion using the nonionic contrast agents Dy-DTPA-BMA and Gd-DTPA-BMA.
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Animals↗
In vivo diffusion-perfusion magnetic resonance imaging of acute cerebral ischemia.
We compared the anatomic extent and severity of ischemic brain injury shown on diffusion-weighted magnetic resonance (MR) images, with cerebral tissue perfusion deficits demonstrated by a nonionic intravascular T2*-shortening magnetic susceptibility contrast agent used in conjunction with standard T2-weighted spin-echo and gradient-echo echo-planar images. Diffusion-weighted images displayed increased signal intensity in the vascular territory of the middle cerebral artery 25-40 min after permanent occlusion, whereas T2-weighted images without contrast were negative or equivocal for at least 2-3 h after stroke was induced. Contrast-enhanced T2-weighted and echo-planar images revealed perfusion deficits that were spatially closely related to the anatomic regions of ischemic tissue injury. These data indicate that diffusion-weighted MR images are very sensitive to early onset pathophysiologic changes induced by acute cerebral ischemia. Combined sequential diffusion-perfusion imaging enables noninvasive in vivo examination of the relationship between hypoperfusion and evolving ischemic brain injury.
Acute Disease↗
Motor deficits are produced by removing some cortical transplants grafted into injured sensorimotor cortex of neonatal rats.
Fetal frontal cortex was transplanted into cavities formed in the right motor cortex of neonatal rats. As adults, the animals were trained to press two levers in rapid succession with their left forelimb to receive food rewards. Once they had reached an optimal level of performance, the effect of removing their transplants was assessed. Surgical removal of transplants significantly impaired the performance of 2 of 4 subjects. Placing a cross-strain skin graft to induce the immunological rejection of the transplants produced a behavioral deficit in 1 of 2 subjects with complete transplant removal. Skin grafts produced no behavioral effects in four subjects that had surviving transplants. Since the motor deficits produced by transplant removal resembled those observed following the removal of normal motor cortex, we propose that these three transplants functioned within the host brain. Histology showed that the procedures used to remove cortical grafts did not injure any host brains. Therefore, host brain damage is unlikely to account for the behavioral deterioration that followed transplant removals.
Animals↗
Analysis of immunoglobulin and T-cell receptor gene rearrangements in human fetal bone marrow B lineage cells.
Fetal bone marrow B lineage cells representing multiple stages of B cell development were isolated by two-color cell sorting and analyzed for immunoglobulin H and T-cell receptor (TCR) gamma and delta gene rearrangements. Analysis of CD10+/surface mu- cells using a JH probe revealed a high frequency of rearrangements; some of these rearrangements used the 3' D region gene DQ52. Analysis of CD10+/surface mu- cells revealed no detectable TCR-gamma or -delta rearrangements, nor were TCR-delta rearrangements detected in CD10+/surface mu+ cells, despite the limited repertoire of these genes. These observations are surprising given the high frequency of TCR delta/gamma rearrangements in B cell precursor acute lymphoblastic leukemia, and identify a potential difference in patterns of gene rearrangement that distinguish normal and leukemic B cell precursors.
B-Lymphocytes↗
Differentiation of normal human pre-B cells in vitro.
The differentiation of surface Ig- pre-B cells into surface Ig+ B cells is a critical transition in mammalian B cell ontogeny. Elucidation of the growth factor requirements and differentiative potential of human pre-B cells has been hampered by the absence of a reproducible culture system that supports differentiation. Fluorescence-activated cell sorting and magnetic bead depletion were used to purify fetal bone marrow CD10+/surface mu- cells, which contain 60-70% cytoplasmic mu+ pre-B cells. CD10+/surface mu- cells cultured for 2 d were observed to differentiate into surface mu+ cells. Analysis by Southern blotting provided direct evidence that rearrangement of kappa light chain genes occurs in culture, and flow cytometric analysis revealed the appearance of surface Ig+ B cells expressing mu/kappa or mu/lambda. Unexpectedly, the kappa/lambda ratio in differentiated cells was the inverse of what is normally observed in adult peripheral blood. Differentiation occurs in the absence of exogenous growth factors or cytokines, suggesting that a stimulus-independent differentiative inertia might characterize pre-B cells in vivo. Future use of this model will facilitate our understanding of normal and abnormal human pre-B cell differentiation.
Antigens, Differentiation↗
MR evaluation of calcium entry blockers with putative cerebroprotective effects in acute cerebral ischaemia.
MR imaging and spectroscopy were used to investigate whether two calcium channel entry-blockers, nicardipine and RS-87476 (Syntex), would reduce ischaemic brain damage in barbiturate-anaesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery (MCA). The evolution of cerebral injury was assessed in vivo in a total of 38 cats using a combination of diffusion-weighted and T2-weighted spin-echo proton MR imaging and phosphorus 31 (P-31) and proton (H-1) MR spectroscopy for up to 12 h following arterial occlusion. Immediately thereafter, the volume of histochemically ischaemic brain tissue was determined planimetrically. In untreated control animals, diffusion-weighted MR images obtained with strong gradient strengths (5.5 gauss/cm) displayed increased signal intensity (oedema) in the ischaemic MCA territory less than 45 min after stroke. These changes were closely correlated with the appearance of abnormal P-31 and H-1 metabolite levels evaluated with surface coil MR spectroscopy. Cats injected with i.v. nicardipine (10 micrograms/kg bolus, 8 micrograms/kg/h maintenance) or RS-87476 (2-50 micrograms/kg bolus, 0.7-17.5 micrograms/kg/h maintenance) showed a significant reduction in ischaemic injury in the ipsilateral cerebral cortex, internal capsule and basal ganglia. The results of this study suggest that these calcium entry blockers protect against brain damage induced by acute stroke by stabilizing cellular metabolic processes, reducing lactate formation in ischaemic tissues, and attenuating cytotoxic and vasogenic oedema.
Acute Disease↗
Histologic correlation in magnetic resonance imaging of femoral head osteonecrosis.
The present study was undertaken to determine whether a correlation exists between localized magnetic resonance image (MRI) signal behavior and specific histopathologic features of femoral head osteonecrosis. Contiguous, 5-mm coronal MRI sections were compared with corresponding histologic sections from six surgically excised femoral heads. After identifying specific areas of interest on the images, signal intensity was evaluated, both subjectively and objectively, and T1 and T2 relaxation times were calculated. Mean values for these data were compared among the following histologic categories: normal bone, unrepaired dead bone and marrow, unrepaired dead bone with marrow replaced by amorphous debris, and zones of repair. For each type of tissue, MRI signal intensity on T1- and intermediately T2-weighted images behaved in a distinctive fashion. Active repair tissue could be differentiated from both necrotic bone and normal bone by a tendency for the signal to increase in intensity on intermediately T2-weighted images. These findings suggest that MRI may provide a noninvasive means of quantitatively analyzing the volume and spacial distribution of repair tissue in osteonecrotic femoral heads. In clinical practice, such analysis may lead to improvements in disease staging and treatment planning.
Adult↗
Assessment of male infertility: correlation between results of semen analysis and phosphorus-31 magnetic resonance spectroscopy.
To evaluate the usefulness of phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in assessing male infertility, we compared it with conventional semen analysis. Specimens were obtained from otherwise healthy patient groups as follows: group A, 7 fertile control subjects; group B, 12 azoospermic men after vasectomy; and group C, 11 patients presenting for infertility evaluation. Correlations between established semen analysis parameters and the 31P-MRS-derived ratio of glycerylphosphorylcholine to total phosphate (GPC/TP) were investigated. Group A controls had a mean GPC/TC ratio of 0.10 +/- 0.05, which was the same as that of group C. With the exception of significantly lowered motility and normal morphology in group C (p less than 0.001 and 0.05, respectively) semen analysis parameters in these two groups were similar. In contrast, the GPC/TP ratio in group B (0.05 +/- 0.04) was significantly different from the control (p less than 0.05), which appropriately reflected complete vasal occlusion. The results suggest that a significant portion of seminal GPC is derived from epididymal secretion and that 31P-MRS is useful for monitoring the GPC/TP levels when assessing epididymal function and male infertility.
Glycerylphosphorylcholine↗
MRS of ischemic/hypoxic brain disease.
Significant increases in magnetic field strengths and improvements in magnetic field homogeneity have made combined high-resolution magnetic resonance imaging (MRI) and multinuclear spectroscopy (MRS) feasible for investigating the relationship between biochemical and structural changes induced by ischemic brain disease. Magnetic resonance spectroscopy is the only noninvasive technique capable of measuring concentrations of high-energy phosphate metabolites, lactate, and other metabolically relevant compounds. Anticipated advances in localization of the volume of tissue from which spectra are obtained will enhance the clinical potential of MRS in the diagnosis of ischemic disease.
Animals↗
Nicardipine reduces ischemic brain injury. Magnetic resonance imaging/spectroscopy study in cats.
We investigated whether the calcium channel entry blocker nicardipine would reduce ischemic brain damage in barbiturate-anesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery. The evolution of cerebral injury was assessed in vivo in 24 cats by a combination of proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy for 5 hours following occlusion. Immediately thereafter, the volume of histochemically ischemic brain tissue was determined planimetrically in triphenyl tetrazolium chloride-stained serial coronal sections. Nicardipine was initially administered as an intravenous bolus injection of 10 mg/kg/hr 15 minutes before or 15 minutes after occlusion, followed by continuous infusion at 8 mg/kg/hr for the 5 hours of the experiment. Compared with untreated controls, cats that received nicardipine before or after occlusion showed a significant reduction in the extent of edema in the ipsilateral cerebral cortex, internal capsule, and basal ganglia. The results of phosphorus-31 magnetic resonance spectroscopy studies suggest that nicardipine may protect against cerebral ischemic damage by an action on cellular metabolic processes that preserve high-energy phosphates during the ischemic period.
Animals↗
Magnetic resonance imaging and 31P magnetic resonance spectroscopy for evaluating focal cerebral ischemia.
Recent advances in magnetic resonance (MR) imaging and MR spectroscopy (MRS) allow the noninvasive in vivo study of a variety of anatomical, physiological, and biochemical alterations that may occur in different cerebral pathologies. The authors have investigated the use of MR imaging and MRS to monitor the evolution of experimental focal cerebral ischemia in rats. Permanent focal cerebral ischemia was induced in 36 rats, and 12 normal rats were used as a control group. Changes in high-energy phosphate metabolites were followed in vivo using MRS during the 1st hour and at 3 and 6 hours after ischemic insult. Changes in vivo MR images were evaluated at 1, 3, 6, 12, and 24 hours after ischemic insult. Significant decreases (p less than 0.05) in phosphocreatine/inorganic phosphate ratios and intracellular pH values occurred immediately after the induction of ischemia. The presence of an infarcted area seen on MR images was a constant finding at 3 hours after ischemic insult, and was well defined and localized at 12 and 24 hours. The location of areas of infarction seen on MR images correlated well with areas identified histopathologically. The T1 and T2 MR relaxation times were significantly increased 3 hours after ischemic insult and remained prolonged for at least 24 hours. The results show that MR imaging is a sensitive method to measure cerebral infarction, and that MRS is a sensitive measure of changes that occur in the early phases of ischemia, perhaps when cellular changes may still be reversible. At 3 and 6 hours after the ischemic insult, however, 31P-MRS spectra may appear to be "normal" despite the presence of well-documented areas of infarction.
Animals↗
Ferrous intraocular foreign bodies and magnetic resonance imaging.
We placed various sized ferrous foreign bodies in and around the eye, sclera, and orbit in a rabbit model before performing magnetic resonance imaging studies. All foreign bodies were detected on plain x-rays. Only one of the largest fragments (3 x 1 x 1 mm) demonstrated movement on exposure to the magnetic field.
Animals↗
Localized imaging using stimulated echoes.
Stimulated-echo localized spectroscopy was combined with phase- and frequency-encoding gradients to obtain "zoom" or magnified images of specific organs in situ. The technique requires neither surface coils nor an imaging coil arrangement that exclusively isolates the target organ. This technique can be readily applied to conventional spectrometer imagers that have limited computational capabilities.
Animals↗
An in vivo study of halothane uptake and elimination in the rat brain with fluorine nuclear magnetic resonance spectroscopy.
A recent NMR study reported the elimination of halothane from the brain of rabbits to be ten times slower than expected, based on known anesthetic solubility and cerebral blood flow. The authors conducted a study in five rats using fluorine nuclear magnetic resonance (NMR) spectroscopy to see if major pharmacokinetic discrepancies are associated with the uptake, maintenance, and elimination of halothane from the brain. The rats underwent a 60-min period of halothane anesthesia. They employed a spatially selective NMR spectroscopy technique known as surface coil "depth-pulsing" to assure that the fluorine NMR signals originated in brain tissue, and not in the scalp, muscle, adipose tissue, and bone marrow that surround the brain. After the inspired anesthetic concentration was decreased to zero, the amplitude of the fluorine NMR signal decreased to 40% of its maximum value within 34 +/- 8.0 minutes (n = 5), rather than after 7 h as in the recent study, where the fluorine signal may have contained substantial contributions from metabolites or tissues outside the brain. Fluorine was barely detectable in all of the animals 90 min after stopping the administration of halothane. The authors' results are in agreement with model calculations and several other investigations.
Anesthesia↗
An in vivo 19F nuclear magnetic resonance study of isoflurane elimination from the rabbit brain.
19F nuclear magnetic resonance spectroscopy was performed at 2.0 Tesla to evaluate the washout of isoflurane from the adult rabbit brain after 90 min of anesthesia. This investigation reconciles previous in vivo NMR studies of others, which observed a slow anesthetic washout, with invasive non-NMR studies that found a rapid washout, as predicted by perfusion-limited models of anesthetic uptake and elimination. Two NMR surface coil experiments were performed: in the first, a 1-cm surface coil was placed directly over the exposed dura to be certain that the washout was observed only from the brain; in the second, a 3-cm coil was placed noninvasively over the intact scalp to emulate previous NMR experiments. As in previous NMR experiments, a slow washout of isoflurane was observed with the large coil. The NMR signal that is observed with the large coil cannot be attributed solely to brain tissue. Fat surrounding the brain contributes significantly to the fluorine NMR spectra that are observed with the 3-cm coil, and its contributions lengthen the apparent washout time. A rapid washout of isoflurane from the rabbit brain was observed with the small coil, whose signal unambiguously arises only from brain tissue. The observed rapid washout is consistent with previous invasive biochemical measurements of anesthetic washout from the brain.
Anesthesia↗