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For diffusion-weighted magnetic resonance imaging and under circumstances where patient movement can be modeled as rigid body motion, it is shown both theoretically and experimentally that translations and rotations produce phase errors which are zero- and first-order, respectively, in position. While a navigator echo can be used to correct the imaging data for arbitrary translations, only when the diffusion gradient is applied in the phase encode direction is there sufficient information to correct for rotations around all axes, and therefore for general rigid body motion. Experiments in test objects and human brain imaging confirm theoretical predictions and demonstrate that appropriate corrections dramatically improve image quality in vivo.
Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.
A method that can be used to evaluate the performance of MRI methods for detecting discrete regional activations using functional MRI is presented. Computer derived receiver-operator-characteristic (ROC) curves have been used to evaluate quantitatively a range of conditions encountered in functional MRI studies. ROC analysis allows multiple acquisition strategies and multiple postprocessing strategies to be quantitatively and objectively compared. The authors first present this analysis technique and then illustrate its use for assessing the relative performances of different functional MRI data acquisition strategies using different gradient echo, echoplanar imaging protocols. In addition, the authors have used the ROC analysis to evaluate and compare several methods for analyzing functional MRI data to extract regions of activation. This approach to assessing the performance of different methods is of general use and can be applied to evaluate other data acquisition protocols and postprocessing methods.
In this paper we test the predictions of the differential polarization imaging theory developed in the previous two papers. A characterization of the patterns of polymerization of hemoglobin in red blood cells from patients with sickle cell anemia is presented. This system was chosen because it is relatively easy to handle and because previous studies have been done on it. A differential polarization microscope designed and built in our laboratory was used to carry out this study. This microscope uses an image dissector camera, a photoelastic modulator, and a phase-lock amplifier. This design represents a substantial modification with respect to the instrumentation used in the previous results communicated on this system. Therefore, the results presented here also permit us to confirm the validity of our conclusions. On the basis of the differential polarization images obtained, models of the patterns of polymerization of the hemoglobin S inside the sickle cells are proposed and their M12 and regular images are calculated by the theory. Good agreement between those models and the experimental systems is found, as well as with the results previously reported.
The microcomputer-based image analysis system IB-1000 (developed by Indiana Biotech, Highland, IN) for two-dimensional electrophoresis gels has been described previously (9). It allows the user to compare protein spots between two profiles and identify those spots that are commonly shared in both profiles. This report describes two applications of the system's global comparison routine-profile matching and profile subtraction. This application is able to subtract commonly shared spots from one profile, creating a new profile made up by the unmatched spots in the other profile. These applications can be employed in a large variety of research projects.
The structure of cucumber green mottle mosaic virus has been determined from fiber diffraction data to a resolution of 5 A, using only two derivatives and without making any specific assumptions about the molecular structure of the virus. Because of the cylindrical averaging of fiber diffraction data, large numbers of heavy-atom derivatives have been required in previous structure determinations, but it is shown that simplifying assumptions about the overlapping intensities in fiber diffraction are sufficient for structure determination at this resolution using only two derivatives.
Lysosomes have long been implicated as a factor contributing to the progression and complication of atherosclerosis. The authors' laboratory previously has shown that lysosomal ultrastructure in arterial macrophage foam cells is altered as primary lysosomes give rise to large pleiomorphic organelles on lipid accumulation during lesion progression. To further explore the subcellular alterations in lysosomes and associated organelles during foam cell formation, three-dimensional (3D) intermediate voltage electron microscopy was used to examine monocyte-derived macrophages (monocyte/macrophages) during early in vitro uptake of beta migrating very-low-density lipoproteins (beta VLDL). Lysosomes were identified using acid phosphatase cytochemistry, and in control cells these organelles constituted 3.5% of the total cytoplasmic volume. Both primary and secondary lysosomes were observed. Upon beta VLDL uptake, the total volume of acid-phosphatase-positive organelles increased threefold over 30 minutes, and the reaction product was found in three additional morphologically distinct structures: tubular lysosomes, membrane stacks, and endoplasmic reticulum with widened cisternae. The proportion of the cell occupied by each of the five acid-phosphatase-positive organelles was quantitated at 10 minutes, 30 minutes, 1 hour, and 4 hours of beta VLDL incubation, and their relative abundance was compared with controls that were processed either with no lipoprotein challenge or albumin incubation for 1 hour. Secondary lysosomes compartment volume peaked at 30 minutes; over the ensuing 3.5 hours, however, the reaction progressively shifted to three new membrane-limited locations. Our observations document the complex 3D organization and spacial relationships among the acid-phosphatase-positive structures induced by lipoprotein uptake. The 3D organization patterns for acid-phosphatase-positive lysosomes in lipoprotein-stimulated pigeon monocyte/macrophages were similar in several aspects to the complex lysosomes previously observed in the macrophages of pigeon arterial lesions.
Because of the inherent nature of existing techniques for vascular assessment of the retina, quantitative rigor has been difficult to attain. Computer imaging has now made possible measurement of oxygen-induced alterations in retinal blood vessels that is precise, accurate and repeatable. Newborn rats were exposed to 80% oxygen for 14 days as an animal model for retinopathy of prematurity (ROP). Ink perfusion, followed by retinal dissection, yielded silhouettes of the retinal vascular network. These images were digitized and enhanced by the MegaVision 1024XM imaging system in order to facilitate measuring extent of vasculature and capillary density. Mean grey levels, or 'mu', were 33.1 +/- 3.4 and 20.1 +/- 3.5 for room air- and oxygen-reared rats, respectively. These values are directly proportional to the fraction of the overall image that is vascular material, and, therefore, describe the extent of vaso-obliteration resulting from the oxygen exposure. The values were subsequently converted to square millimeters of vessel area to facilitate comparison to past and future studies. Oxygen rearing does not effect retinal area, but decreases retinal artery and vein diameter and decreases the linear extent of vessels toward the retinal periphery.
The importance to MR image quality of the order of acquisition of different phase-encoded views with sequences that have variable TR and TE has been recently reported. It has been shown that the effective point spread function (PSF) may be manipulated by varying TE or TR, or both, with each phase-encoding step. This paper explores the behavior of the PSF in a variable TE sequence and its dependence on both imaging and tissue parameters. It is shown that the PSF is different for each tissue type and that its effect on tissue contrast is a function of both the shape and size of the structure. The important problem of signal loss from small objects that arises when the effective PSF is broad and the difficulty in detecting this phenomenon in practical MR images is illustrated. It is shown that the PSF can produce significant blurring and loss of object contrast in fast spin-echo images but that this blurring may be not be obvious in practice because the noise is unaffected by the PSF. It is also shown that the signal from small lesions with short T2 can easily be lost through this blurring mechanism. The importance of signal loss from small objects and its implication for the clinical use of such sequences as fast spin-echo or rapid acquisition relaxation-enhanced and echo planar imaging is stressed.
This study was designed to determine whether transforming growth factor alpha (TGF alpha) protects rat gastric mucosa against ethanol- and aspirin-induced injury. Systemic administration of TGF alpha dose-dependently decreased 100% ethanol-induced gastric mucosal injury; a dose of 50 micrograms/kg delivered intraperitoneally 15 min before ethanol decreased macroscopic mucosal injury by > 90%. At the microscopic level, TGF alpha prevented deep gastric necrotic lesions and reduced disruption of surface epithelium. Pretreatment with orogastric TGF alpha (200 micrograms/kg) only partially (40%) decreased macroscopic ethanol damage. Intraperitoneal administration of TGF alpha at a dose of 10 micrograms/kg, which does not significantly inhibit gastric acid secretion, decreased aspirin-induced macroscopic damage by > 80%. TGF alpha protection does not seem to be mediated by prostaglandin, glutathione, or ornithine decarboxylase-related events, as evidenced by lack of influence of the inhibition of their production. Pretreatment with the sulfhydryl blocking agent N-ethylmaleimide partially abolished (40%) the protective effect of TGF alpha. In addition, systemic administration of TGF alpha resulted in a two-fold increase in tyrosine phosphorylation of phospholipase C-gamma 1 and in a time- and dose-dependent increase in levels of immunoreactive insoluble gastric mucin; these events occurred in a time frame consistent with their participation in the protective effect of TGF alpha.