Protein NMR Spectroscopy Cavanagh, John; Skelton, Nicholas J; Fairbrother, Wayne J ...
2006, 2010-07-21
eBook
Protein NMR Spectroscopy combines a comprehensive theoretical treatment of NMR spectroscopy with an extensive exposition of the experimental techniques applicable to proteins and other biological ...macromolecules in solution. Beginning with simple theoretical models and experimental techniques, Protein NMR Spectroscopy develops the complete repertoire of theoretical principles and experimental techniques necessary for understanding and implementing the most sophisticated NMR experiments.Important new techniques and applications of NMR spectroscopy have emerged since the first edition of this extremely successful book was published in 1996. The second edition includes new sections describing measurement and use of residual dipolar coupling constants for structure determination, TROSY and deuterium labeling for application to large macromolecules, and experimental techniques for characterizing conformational dynamics. In addition, the treatments of instrumentation and signal acquisition, field gradients, multidimensional spectroscopy, and structure calculation are updated and enhanced. Protein NMR Spectroscopy is written as a graduate-level textbook and will be of interest to biochemists, chemists, biophysicists, and structural biologists who utilize NMR spectroscopy or who wish to understand the latest developments in this field.
· Provides an understanding of the theoretical principles important for biological NMR spectroscopy· Demonstrates how to implement, optimize and troubleshoot modern multi-dimensional NMR experiments· Allows for the capability of designing effective experimental protocols for investigations of protein structures and dynamics· Includes a comprehensive set of example NMR spectra of ubiquitin provides a reference for validation of experimental methods
Fifty patients with proven multiple myeloma (MM) underwent magnetic resonance (MR) examination of entire spine in sagittal view using T1-weighted image (T1), T2-weighted image (T2), and T2-weighted ...gradient echo (GE). In 18 patients, the myelomatous foci were hyperintensive in GE and T2 and hypointensive in T1. They corresponded with osteolytic lesions in computed tomography (CT) scan. In another 16 patients with MM, the hyperintensive vertebral foci demonstrated by GE, corresponded with unhomogenic pattern of the vertebral bone marrow in T1 and T2, and insignificant computed tomography (CT) scan. Needle biopsy confirmed histologically the diagnosis MM of involved vertebra in all of them. The vertebral bone marrow had lower signal intensity in GE, which ensured a good contrast between the myelomata and the uninvolved bone marrow. Practically GE enabled the radiologic diagnosis of the spine in 16 patients. It also can prevent a diagnostic pitfall when a fatty focus is suspicious for myeloma in T2 and its demonstration in T1 is poor. Fatty foci were demonstrated in a control group, which included 20 elderly patients who had no history of malignancy. The fatty foci had lower signal intensity in GE and different from the hyperintensive myelomata. Gadolinium diethylene triamine pentaocetic acid (Gd-DTPA) which was administered intravenously in three patients with spinal MM offered no advantage and obscured the lesions.
Zadnjih godina mnoge grupe turista različita kova kucaju na samostanska vrata sa željom da se informiraju i razgovaraju o samostanskom životu. Iz kojih razloga? Vodi li ih znatiželja, želja da ...kritiziraju, ili da nešto novo nauče? Događa se to možda zato što ih progoni tjeskoba?
Despite their wide-spread use, only limited information is available on the comparative test-retest reliability of task-based functional and resting state magnetic resonance imaging measures of blood ...oxygen level dependence (tb-fMRI and rs-fMRI) and cerebral blood flow (CBF) using arterial spin labeling. This information is critical to designing properly powered longitudinal studies. Here we comprehensively quantified and compared the test-retest reliability and reproducibility performance of 8 commonly applied fMRI tasks, 6 rs-fMRI metrics and CBF in 30 healthy volunteers. We find large variability in test-retest reliability performance across the different tb-fMRI paradigms and rs-fMRI metrics, ranging from poor to excellent. A larger extent of activation in tb-fMRI is linked to higher between-subject reliability of the respective task suggesting that differences in the amount of activation may be used as a first reliability estimate of novel tb-fMRI paradigms. For rs-fMRI, a good reliability of local activity estimates is paralleled by poor performance of global connectivity metrics. Evaluated CBF measures provide in general a good to excellent test-reliability matching or surpassing the best performing tb-fMRI and rs-fMRI metrics. This comprehensive effort allows for direct comparisons of test-retest reliability between the evaluated MRI domains and measures to aid the design of future tb-fMRI, rs-fMRI and CBF studies.
Compressed sensing magnetic resonance imaging (CS-MRI) enables fast acquisition, which is highly desirable for numerous clinical applications. This can not only reduce the scanning cost and ease ...patient burden, but also potentially reduce motion artefacts and the effect of contrast washout, thus yielding better image quality. Different from parallel imaging-based fast MRI, which utilizes multiple coils to simultaneously receive MR signals, CS-MRI breaks the Nyquist-Shannon sampling barrier to reconstruct MRI images with much less required raw data. This paper provides a deep learning-based strategy for reconstruction of CS-MRI, and bridges a substantial gap between conventional non-learning methods working only on data from a single image, and prior knowledge from large training data sets. In particular, a novel conditional Generative Adversarial Networks-based model (DAGAN)-based model is proposed to reconstruct CS-MRI. In our DAGAN architecture, we have designed a refinement learning method to stabilize our U-Net based generator, which provides an end-to-end network to reduce aliasing artefacts. To better preserve texture and edges in the reconstruction, we have coupled the adversarial loss with an innovative content loss. In addition, we incorporate frequency-domain information to enforce similarity in both the image and frequency domains. We have performed comprehensive comparison studies with both conventional CS-MRI reconstruction methods and newly investigated deep learning approaches. Compared with these methods, our DAGAN method provides superior reconstruction with preserved perceptual image details. Furthermore, each image is reconstructed in about 5 ms, which is suitable for real-time processing.
Resting-state functional magnetic resonance imaging (rfMRI) allows one to study functional connectivity in the brain by acquiring fMRI data while subjects lie inactive in the MRI scanner, and taking ...advantage of the fact that functionally related brain regions spontaneously co-activate. rfMRI is one of the two primary data modalities being acquired for the Human Connectome Project (the other being diffusion MRI). A key objective is to generate a detailed in vivo mapping of functional connectivity in a large cohort of healthy adults (over 1000 subjects), and to make these datasets freely available for use by the neuroimaging community. In each subject we acquire a total of 1h of whole-brain rfMRI data at 3T, with a spatial resolution of 2×2×2mm and a temporal resolution of 0.7s, capitalizing on recent developments in slice-accelerated echo-planar imaging. We will also scan a subset of the cohort at higher field strength and resolution. In this paper we outline the work behind, and rationale for, decisions taken regarding the rfMRI data acquisition protocol and pre-processing pipelines, and present some initial results showing data quality and example functional connectivity analyses.
•The Human Connectome Project is mapping brain connectivity in vivo in detail.•Resting-state fMRI (rfMRI) is a major modality in the Human Connectome Project.•We describe rfMRI acquisition and analysis protocols for the HCP.
Non-invasive assessment of portal hypertension is an area of unmet need. This proof of concept study aimed to evaluate the diagnostic accuracy of a multi-parametric magnetic resonance technique in ...the assessment of portal hypertension. Comparison to other non-invasive technologies was a secondary aim.
T1 and T2* maps through the liver and spleen were acquired prior to trans-jugular liver biopsy and hepatic vein pressure gradient (HVPG) measurement. T1 measurements reflect changes in tissue water content, but this relationship is confounded by the presence of iron, which in turn can be quantified accurately from T2* maps. Data were analysed using LiverMultiScan (Perspectum Diagnostics, Oxford, UK) which applies an algorithm to remove the confounding effect of iron, yielding the "iron corrected T1" (cT1). Sensitivity, specificity, diagnostic values and area under the curve were derived for spleen cT1, liver cT1, transient elastography, and serum fibrosis scores. HVPG was the reference standard.
Nineteen patients (15 men) with median age 57 years were included. Liver disease aetiologies included non-alcoholic fatty liver disease (n = 9; 47%) and viral hepatitis (n = 4; 21%). There was strong correlation between spleen cT1 and HVPG (r = 0.69; p = 0.001). Other non-invasive biomarkers did not correlate with HVPG. Spleen cT1 had excellent diagnostic accuracy for portal hypertension (HVPG >5 mmHg) and clinically significant portal hypertension (HVPG ≥10 mmHg) with an area under the receiver operating characteristic curve of 0.92 for both.
Spleen cT1 is a promising biomarker of portal pressure that outperforms other non-invasive scores and should be explored further.
The extracellular pH of solid tumors is unequivocally acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic metabolism) and poor perfusion. ...This has been documented by us and others in a wide variety of solid tumor models, primarily using magnetic resonance spectroscopic imaging (MRSI). This acidity contributes to tumor progression by inducing genome instability, promoting local invasion and metastases, inhibiting anti-tumor immunity, and conferring resistance to chemo- and radio-therapies. Systemic buffer therapies can neutralize tumor acidity and has been shown to inhibit local invasion and metastasis and improve immune surveillance in a variety of cancer model systems. This review will revisit the causes and consequences of acidosis by summarizing strategies used by cancer cells to adapt to acidosis, and how this acidity associated with carcinogenesis, metastasis, and immune function. Finally, this review will discuss how neutralization of acidity can be used to inhibit carcinogenesis and metastasis and improve anti-cancer immunotherapy.
Measures of overlap of labelled regions of images, such as the Dice and Tanimoto coefficients, have been extensively used to evaluate image registration and segmentation algorithms. Modern studies ...can include multiple labels defined on multiple images yet most evaluation schemes report one overlap per labelled region, simply averaged over multiple images. In this paper, common overlap measures are generalized to measure the total overlap of ensembles of labels defined on multiple test images and account for fractional labels using fuzzy set theory. This framework allows a single "figure-of-merit" to be reported which summarises the results of a complex experiment by image pair, by label or overall. A complementary measure of error, the overlap distance, is defined which captures the spatial extent of the nonoverlapping part and is related to the Hausdorff distance computed on grey level images. The generalized overlap measures are validated on synthetic images for which the overlap can be computed analytically and used as similarity measures in nonrigid registration of three-dimensional magnetic resonance imaging (MRI) brain images. Finally, a pragmatic segmentation ground truth is constructed by registering a magnetic resonance atlas brain to 20 individual scans, and used with the overlap measures to evaluate publicly available brain segmentation algorithms
Simultaneously evaluating resting-state brain glucose metabolism and intrinsic functional activity has potential to impact the clinical neurosciences of Alzheimer Disease (AD). Indeed, integrating ...such combined information obtained in the same physiological setting may clarify how impairments in neuroenergetic and neuronal function interact and contribute to the mechanisms underlying AD. The present study used this multimodality approach to investigate, by means of a hybrid PET/MR scanner, the coupling between glucose consumption and intrinsic functional activity in 23 patients with AD-related cognitive impairment ranging from amnestic mild cognitive impairment (MCI) to mild-moderate AD (aMCI/AD), in comparison with a group of 23 healthy elderly controls. Between-group (Controls > Patients) comparisons were conducted on data from both imaging modalities using voxelwise 2-sample t-tests, corrected for partial-volume effects, head motion, age, gender and multiple tests. FDG-PET/fMRI relationships were assessed within and across subjects using Spearman partial correlations for three different resting-state fMRI (rs-fMRI) metrics sensitive to AD: fractional amplitude of low frequency fluctuations (fALFF), regional homogeneity (ReHo) and group independent component analysis with dual regression (gICA-DR). FDG and rs-fMRI metrics distinguished aMCI/AD from controls according to spatial patterns analogous to those found in stand-alone studies. Within-subject correlations were comparable across the three rs-fMRI metrics. Correlations were overall high in healthy controls (ρ = 0.80 ± 0.04), but showed a significant 17% reduction (p < 0.05) in aMCI/AD patients (ρ = 0.67 ± 0.05). Positive across-subject correlations were overall moderate (ρ = 0.33 ± 0.07) and consistent across rs-fMRI metrics. These were confined around AD-target posterior regions for metrics of functional connectivity (ReHo and gICA-DR). In contrast, FDG/fALFF correlations were distributed in the frontal gyrus, thalami and caudate nuclei. Taken together, these results support the presence of bioenergetic coupling between glucose utilization and rapid transmission of neural information in healthy ageing, which is substantially reduced in aMCI/AD, suggesting that abnormal glucose utilization is in some way linked to communication breakdown among brain regions impacted by the underlying pathological process.
•Simultaneous estimates of glucose metabolism and intrinsic connectivity are both sensitive to aMCI/AD in impacted brain regions.•The relationship between FDG-PET and fMRI metrics is reduced in aMCI/AD patients.•Resting-state fMRI metrics are related to fluorodeoxyglucose metabolism in different regions of the brain.
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