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At least 757 records · Page 42Linked to original sources

Diffusion-weighted MR microscopy with fast spin-echo.

A diffusion-weighted fast spin-echo (FSE) imaging sequence for high-field MR microscopy was developed and experimentally validated in a phantom and in a live rat. Pulsed diffusion gradients were executed before and after the initial 180 degrees pulse in the FSE pulse train. This produced diffusion-related reductions in image signal intensity corresponding to gradient ("b") factors between 1.80 and 1352 s/mm2. The degree of diffusion weighting was demonstrated to be independent of echo train length for experiments using trains up to 16 echoes long. Quantitative measurements on a phantom and on a live rat produced diffusion coefficients consistent with literature values. Importantly, the eight- to 16-fold increase in imaging efficiency with FSE was not accompanied by a significant loss of spatial resolution or contrast. This permits acquisition of in vivo three-dimensional data in time periods that are appropriate for evolving biological processes. The combination of accurate diffusion weighting and high spatial resolution provided by FSE makes the technique particularly useful for MR microscopy.

Animals↗

Conditions for achieving artifact-free T2* preparation in MRI.

A theoretical analysis of the stimulated gradient-echo method for achieving T2*-preparation in magnetic resonance imaging is performed. The results show that T2*-weighting without the "shading effect" due to magnetic field variation can only be achieved if the dephasing requirement of the stimulated echo is satisfied. It is also shown that the effective echo-time for T2*-weighting depends on the polarities of the dephasing and the rephasing gradient pulses that generate the stimulated echo. The results from the theoretical analysis are experimentally validated.

Animals↗

The effect of respiration on the contrast and sharpness of liver lesions in MRI.

This work demonstrates the effects of through-plane motion due to respiration on contrast and sharpness of liver lesions in MRI. The effects of slice coverage with and without such respiratory motion is also reported. This work is comprised of two parts: a theoretical prediction of liver-lesion contrast and blur with and without respiration and an experimental validation using gel phantoms of the predicted results. Both theory and experiment show a loss of contrast, increasing with amplitude of the peak-to-peak motion. The loss of contrast for a 5-mm lesion at normal respiration of 15 mm peak-to-peak superior-inferior motion is approximately 10% with a low order sorted respiratory ordered phase encoding acquisition and approximately 50% for an unsorted acquisition. Lesion blur is greatest for the low order sorted acquisition while the unsorted and high sort acquisitions maintain edge definition. Breath-hold imaging is potentially superior to nonbreath-hold imaging in liver lesion contrast and edge definition, but is more sensitive to inadequate slice coverage.

Artifacts↗

Phase-encode reordering to minimize errors caused by motion.

A new method for suppressing the effects of motion in MR images by reordering the acquisition of k space has been developed. Existing reordering methods suffer from image blurring. The method presented here applies specifically to translation along the phase-encoding direction, in which case it reduces both ghosting and blurring. The method is conceptually similar to a linear phase shift of k space, except that it has the advantage of not corrupting stationary structures inadvertently. The method is intended for anatomic sites in which substantial translational motion occurs along the phase-encoding direction, such as the cranial-caudal motion of the liver and kidneys. The reordering method is motivated from an analysis of factors affecting the severity of motion artifacts. The theory behind the reordering method is described and validated experimentally by imaging a moving phantom.

Artifacts↗

The b matrix in diffusion tensor echo-planar imaging.

In diffusion tensor imaging (DTI) an effective diffusion tensor in each voxel is measured by using a set of diffusion-weighted images (DWIs) in which diffusion gradients are applied in a multiplicity of oblique directions. However, to estimate the diffusion tensor accurately, one must account for the effects of all imaging and diffusion gradient pulses on each signal echo, which are embodied in the b matrix. For DTI to be practical clinically, one must also acquire DWIs rapidly and free of motion artifacts, which is now possible with diffusion-weighted echo-planar imaging (DW-EPI). An analytical expression for the b matrix of a general DW-EPI pulse sequence is presented and then validated experimentally by measuring the diffusion tensor in an isotropic phantom whose diffusivity is already known. The b matrix is written in a convenient tabular form as a sum of individual pair-wise contributions arising from gradient pulses applied along parallel and perpendicular directions. While the contributions from readout and phase-encode gradient pulse trains are predicted to have a negligible effect on the echo, the contributions from other imaging and diffusion gradient pulses applied in both parallel and orthogonal directions are shown to be significant in our sequence. In general, one must understand and account for the multiplicity of interactions between gradient pulses and the echo signal to ensure that diffusion tensor imaging is quantitative.

Algorithms↗

A quantitative method for fast diffusion imaging using magnetization-prepared TurboFLASH.

For the in vivo measurement of the apparent diffusion coefficient (ADC), it is desirable for the total imaging time to be as short as possible. One technique is based on a TurboFLASH acquisition in which the diffusion gradients are inserted into a driven equilibrium Fourier transform (DEFT) combination of hard pulses. However, this sequence has the disadvantage that eddy current-induced inhomogeneities lead to incomplete refocusing of the magnetization during the diffusion preparation and to incorrect ADC values. A modification to the sequence is suggested that eliminates this error by phase-cycling the second 90 degrees pulse of the preparation. This study also investigates the effect of a reduced delay time between acquisitions on the accuracy of the measurement. The quality of the TurboFLASH sequence is demonstrated by experimental validation on an agar phantom and in vivo on the rat brain using a high-field (8.5 T) system. Reduction of the interexperiment delay time is shown to be achievable to a certain degree without compromising the measurement accuracy.

Animals↗

Quantification of regional pulmonary blood flow using ASL-FAIRER.

Pulsed arterial spin labeling (ASL) techniques have been theoretically and experimentally validated for cerebral blood flow (CBF) quantification. In this study ASL-FAIRER was used to measure regional pulmonary blood flow (rPBF) in seven healthy subjects. Two general ASL strategies were investigated: 1) a single-subtraction approach using one tag-control pair acquisition at an inversion time (TI) matched to the RR-interval, and 2) a multiple-subtraction approach using tag-control pairs acquired at various TIs. The mean rPBF averaged 1.70 +/- 0.38 ml/min/ml when measured with the multiple-subtraction approach, and was approximately 2% less when measured with the single-subtraction method (1.66 +/- 0.24 ml/min/ml). Assuming an average lung density of 0.33 g/ml, this translates into a regional perfusion of approximately 5.5 ml/g/min, which is comparable to other measures of pulmonary perfusion. As with other ASL applications, a key problem with quantitative interpretation of the results is the physical gap between the tagging region and imaged slice. Because of the high pulsatility of PBF, ASL acquisition and data analysis differ significantly between the lung and the brain. The advantages and drawbacks of the single- vs. multiple-subtraction approaches are considered within a theoretical framework tailored to PBF.

Adult↗

A Simplified Workflow for the Prediction of Putative Viral Reads Using NIPT Data.

OBJECTIVE: Non-invasive prenatal testing (NIPT) identifies fetal chromosomal abnormalities by sequencing cell-free fetal DNA (cffDNA). Recent studies suggest the prediction of viral sequences from NIPT data, but current methods lack cost-effectiveness for routine use. This study develops a straightforward workflow to investigate potential viral signatures in pregnant women using NIPT data from 888 Iranian participants. METHOD: Two bioinformatic workflows were compared for predicting viral reads: the traditional method involved mapping reads to the human genome, followed by mapping unmapped reads to viral references, and a direct mapping approach to viral genomes, as proposed in this research. RESULTS: While maintaining reproducibility comparable to the conventional method, the proposed workflow minimizes computational complexity and time usage for data processing. Ultimately, this analysis suggested viral DNA in 24.2% of samples, encompassing 29 distinct species, implying the diversity of the maternal virome. CONCLUSION: This study presents a computationally efficient workflow for the in silico prediction of viral-like sequences from routine NIPT data. Further experimental validation is essential to verify the presence, viability, or clinical relevance of these sequences.

Humans↗

Predicting peptides bound to I-Ag7 class II histocompatibility molecules using a novel expectation-maximization alignment algorithm.

The useful structural features of class II MHC molecules are rarely integrated into T-cell epitope predictions. We propose an approach that applies a novel expectation-maximization algorithm to align the naturally processed peptides selected by the class II MHC I-A(g7) molecule - focusing on the five MHC-specific anchor positions. Based on the alignment profile, log of odds (LOD) scores supplemented with the Laplace plus-one pseudocounts method are applied to identify the potential T-cell epitopes. In addition, an innovative computational concept of hindering residues using statistical and structural information is developed to refine the prediction. Performance analysis by receiver operating characteristics statistics and the experimental validation of the LOD scores demonstrate the accuracy of our predictive model. Furthermore, our model successfully predicts T-cell epitopes of hen egg-white lysozyme protein antigen. Our study provides a framework for predicting T-cell epitopes in class II MHC molecules.

Algorithms↗

The Multi-Omics Landscape of Enzymatic Alterations in Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease closely associated with enzyme dysfunction, yet its underlying molecular mechanisms remain incompletely understood. This study aims to characterize enzyme-network alterations associated with SLE status and disease activity and to identify candidate molecules with potential clinical relevance. METHODS: We integrated proteomic and phosphoproteomic data from peripheral blood mononuclear cells (PBMCs) of 130 SLE patients and 90 healthy controls (HC), along with transcriptomic data from 1461 SLE patients. Through systematic analysis of key enzyme phosphorylation sites, upstream transcription factors (TFs), and computationally prioritized candidate compounds, we sought to characterize enzyme-centered regulatory associations. RESULTS: Integrated proteomic and phosphoproteomic analyses revealed significant metabolic and signaling pathway disturbances, along with distinct phosphorylation patterns in SLE immune cells. Multiple SLE-associated and disease-activity-associated candidate molecules were identified. Regulatory network analysis uncovered an upstream transcription factor cluster centered around STAT1. Computational drug screening identified computationally prioritized candidate compounds with multi-gene DSigDB associations, which require further clinical safety evaluation and experimental validation. CONCLUSIONS: This study constructs a molecular map of SLE, highlighting associations between enzyme-network alterations, catalytic dysregulation, and SLE-related immune molecular signatures, and identifies candidate molecules for future clinical and functional evaluation.

Humans↗

Membrane protein subunit fractionation by means of inverse pore gradient elution polyacrylamide gel electrophoresis.

We report here the preparative scale isolation of the four subunits of the nicotinic acetylcholine receptor (nAChR) applying short inverse pore gradient SDS gels on an elution-PAGE apparatus. The nAChR subunits are of similar molecular weights (alpha, 50.2 kDa; beta, 53.7 kDa; gamma, 56.3 kDa; delta, 57.6 kDa) and isoelectric point (approx 5.5) and share the typical properties of amphiphatic membrane proteins that are difficult to separate by chromatographic procedures. Preparative PAGE, which has proved to be the method of choice for nAChR-subunit fractionation, however, is time-consuming and achieves only moderate resolutions yielding dilute fractions. We present here the fractionation of a membrane preparation of Torpedo electric organ (2 mg of total protein) on short gels (2 cm) with linear or concave inverse pore gradients. All of the four subunits are isolated in homogeneous fractions of approx 70 micrograms/ml within only 4 h. Compared to the standard method, this means a 50% reduction in separation times with threefold higher concentrated protein fractions. We also give the theoretical explanation and experimental validation of the improved features resulting from short inverse-gradient polyacrylamide gels.

Animals↗

Crossed aphasia in a dextral: a test of the Alexander-Annett theory of anomalous organization of brain function.

A case of crossed aphasia is presented in a strongly right-handed 77-year-old white female without history of familial sinistrality or prior neurological illness. She developed a right middle cerebral artery infarction documented by CT and accompanied by obvious clinical signs of a conduction aphasia with some resolution but continuing obvious language defect after 9 weeks in rehabilitation. Comprehensive neuropsychological and aphasia testing suggested anomalous lateralization of phonologic-output aspects of language, emotional prosody, motor planning and body schema modules with usual lateralization of lexical-semantic aspects of language and visuo-spatial functions. Experimental validation of the uncrossed lexical-semantic aspects of language using tachistoscope methods found support for the Alexander-Annett theory that different aspects of language can be dissociated in their lateralization. The subject had difficulty identifying a semantic associate of a picture presented to the left visual field (7 errors out of 10) relative to right visual field presentation (2 errors out of 10). Bilateral free naming errors (6 and 5 errors in the left and right visual fields, respectively) occurred consistent with the aphasic presentation, suggesting phonologic-output dysfunction from the right cerebral vascular accident. Implications of the results for aphasia classification are discussed.

Aged↗

A comparison between different imaging strategies for diffusion measurements with the centric phase-encoded turboFLASH sequence.

The study compared the results of three centrally reordered phase-encoded turboFLASH sequences for diffusion-weighted imaging (DWI). The sequences were conventional turboFLASH, turboFLASH with subtraction of T1-related effects, and turboFLASH with correction for T1-related effects during the imaging period only. The relative merits were studied with respect to image quality and accuracy by computer simulation and by experimental validation on phantoms and on in vivo rat brain. A T1-related underestimation of the diffusion coefficient ranging from -30% (T1 approximately 200 ms) to -5% (T1 approximately 1 s) was found to exist for the conventional sequence. Image artifacts, caused by longitudinal relaxation during the imaging period, are reflected in calculated diffusion maps. When the correction sequence is used, the artifacts and the systematic errors are reduced but longitudinal relaxation during the delay between preparation and imaging periods remains large enough to induce significant errors (-15% for T1 approximately 200 ms to -3% for T1 approximately 1 s). The subtraction sequence eliminates the influence of T1 effects on the calibrations, but leads to identical artifacts for all diffusion-weighted images.

Animals↗

A novel approach to high resolution fetal brain MR imaging.

This paper describes a novel approach to forming high resolution MR images of the human fetal brain. It addresses the key problem of motion of the fetus by proposing a registration refined compounding of multiple sets of orthogonal fast 2D MRI slices, that are currently acquired for clinical studies, into a single high resolution MRI volume. A robust multi-resolution slice alignment is applied iteratively to the data to correct motion of the fetus that occurs between 2D acquisitions. This is combined with an intensity correction step and a super resolution reconstruction step, to form a single high isotropic resolution volume of the fetal brain. Experimental validation on synthetic image data with known motion types and underlying anatomy, together with retrospective application to sets of clinical acquisitions are included. Results indicate the method promises a unique route to acquiring high resolution MRI of the fetal brain in vivo allowing comparable quality to that of neonatal MRI. Such data is highly valuable in allowing a clinically applicable window into the process of normal and abnormal brain development.

Algorithms↗

Samarium-153 EDTMP therapy of disseminated skeletal metastasis.

153Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow greater than or equal to 270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.

Animals↗

Dietary habits, a non-negligible source of 2-thiothiazolidine-4-carboxylic acid and possible overestimation of carbon disulfide exposure.

2-Thiothiazolidine-4-carboxylic acid (TTCA) is the accepted urinary indicator of occupational exposure to carbon disulfide. This compound was detected in blank urine of individuals unexposed to carbon disulfide during an experimental validation of a new method of determination. Diet was suspected to be the source of TTCA, and particularly the consumption of brassica vegetables. This assumption was confirmed by collection and analysis of urine samples after ingestion of crude cabbage. TTCA was detected at concentrations higher than 2 mg/l in urine, and 3 mg/kg in crude cabbage. The identity of TTCA was confirmed after extraction and separation by capillary electrophoresis, supercritical fluid chromatography, and mass spectrometry. The results show that the diet should be considered as a nonnegligible source of the overestimation of carbon disulfide exposure.

Biomarkers↗

Dopaminergic mechanisms and cognitive deficit in schizophrenia. A neurobiological model.

A hypothesis is briefly discussed proposing that schizophrenic symptoms are due to a breakdown in a mechanism by which conscious attention is limited and directed. It is shown that this mechanism can be modelled in terms of a simple nerve network in which every channel inhibits all the others. Failure of this inhibition would cause the defect hypothesised to occur in schizophrenia. It is shown that if dopamine is given a central role as transmitter in such a network then the various predictions about the biochemistry of schizophrenia that follow are not only consistent with the evidence for the 'dopamine theory' of schizophrenia, but also with much of the evidence held to be contrary to that theory. While not purporting to be an experimentally validated description of schizophrenia, this model goes beyond the single amine theories of schizophrenia and links dysfunctions in amine systems with specific behavioural control mechanisms. Given the current state of knowledge, such models can make only limited predictions about the biochemistry of schizophrenia. However, an attempt to link behavioural and biochemical systems in this way will be crucial for the development of viable animal models of schizophrenia.

Animals↗

Endoscopic retrograde sphincterotomy in swine.

Endoscopic retrograde sphincterotomy was performed on four sedated pigs, ages 3-4 months, using a standard human duodenoscope and papillotome. Sphincterotomies, 1 cm in length, were well-tolerated, and all animals recovered promptly, spontaneously regained gastrointestinal function, and gained weight. The first three animals were sacrificed after one week, and autopsy revealed no complications. The fourth animal was sacrificed immediately following the procedure, and no evidence of perforation was found. These observations demonstrate that the pig is a valid experimental model for endoscopic sphincterotomy. Its use in training is limited by technical and anatomic differences from humans. Potential uses of this technique in research are discussed.

Animals↗