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Purpose: The diffusion-weighted SPLICE (split acquisition of fast spin-echo signals) sequence employs split-echo rapid acquisition with relaxation enhancement (RARE) readout to provide images almost free of geometric distortions. However, due to the varying T (Formula presented.) -weighting during k-space traversal, SPLICE suffers from blurring. This work extends a method for controlling the spatial point spread function (PSF) while optimizing the signal-to-noise ratio (SNR) achieved by adjusting the flip angles in the refocusing pulse train of SPLICE. Methods: An algorithm based on extended phase graph (EPG) simulations optimizes the flip angles by maximizing SNR for a flexibly chosen predefined target PSF that describes the desired k-space density weighting and spatial resolution. An optimized flip angle scheme and a corresponding post-processing correction filter which together achieve the target PSF was tested by healthy subject brain imaging using a clinical 1.5 T scanner. Results: Brain images showed a clear and consistent improvement over those obtained with a standard constant flip angle scheme. SNR was increased and apparent diffusion coefficient estimates were more accurate. For a modified Hann k-space weighting example, considerable benefits resulted from acquisition weighting by flip angle control. Conclusion: The presented flexible method for optimizing SPLICE flip angle schemes offers improved MR image quality of geometrically accurate diffusion-weighted images that makes the sequence a strong candidate for radiotherapy planning or stereotactic surgery.

Protein design is the field of synthetic biology that aims at developing de-novo custom made proteins and peptides for specific applications. Despite exploring an ambitious goal, recent computational advances in both hardware and software technologies have paved the way to high-throughput screening and detailed design of novel folds and improved functionalities. Modern advances in the field of protein design for small molecule targeting are described in this review, organized in a step-by-step fashion: from the conception of a new or upgraded active binding site, to scaffold design, sequence optimization and experimental expression of the custom protein. In each step, contemporary examples are described, and state-of-the art software is briefly explored. published

Purpose Knowledge of blood T1 and T2 is of major importance in many applications of MRI in neonates. However, to date, there has not been a systematic study to examine neonatal blood T1/T2 relaxometry. This present study aims to investigate this topic. Methods Using freshly collected blood samples from human umbilical cord, we performed in vitro experiments under controlled physiological conditions to measure blood T1 and T2 at 3 Tesla (T) and their dependence on several factors, including hematocrit (Hct), oxygenation (Y) and temperature. Results The arterial T1 in neonates was 1825 ± 184 ms (Hct = 0.42 ± 0.08), longer than that of adult blood. Neonatal blood T1 was strongly dependent on Hct (P

Purpose The transient and nonrenewable signal from hyperpolarized metabolites necessitates extensive sequence optimization for encoding spatial, spectral, and dynamic information. In this work, we evaluate the utility of radial single-timepoint and cumulative spectroscopic MRI of hyperpolarized [1-13C] pyruvate and its metabolic products at 7 Tesla (T). Methods Simulations of radial echo planar spectroscopic imaging (EPSI) and multiband frequency encoding (MBFE) acquisitions were performed to confirm feasibility and evaluate performance for HP 13C imaging. Corresponding sequences were implemented on a 7T small-animal MRI system, tested in phantom, and demonstrated in a murine model of anaplastic thyroid cancer. Results MBFE provides excellent spectral separation but is susceptible to blurring and T2* signal loss inherent to using low readout gradients. The higher readout gradients and more flexible spectral encoding for EPSI result in good spatial resolution and spectral separation. Radial acquisition throughout HP signal evolution offers the flexibility for reconstructing spatial maps of mean metabolite distribution and global dynamic time courses of multiple metabolites. Conclusion Radial EPSI and MBFE acquisitions are well-suited for hyperpolarized 13C MRI over short and long durations. Advantages to this approach include robustness to nonstationary magnetization, insensitivity to precise acquisition timing, and versatility for reconstructing dynamically acquired spectroscopic data. Magn Reson Med 72:986–995, 2014. © 2013 Wiley Periodicals, Inc.

Purpose To optimize acquisition parameters for three-dimensional fast spin-echo (3D FSE) imaging of the knee.

The purpose of this article is to introduce the underlying challenges associated with the incorporation of magnetic resonance imaging (MRI) into the new hybrid imaging modality simultaneous positron emission tomography (PET)/MR and their impact on attenuation correction, sequence optimization, and protocol development. Many adjustments to MR sequences are necessary for optimal whole-body and fused image results. J. Magn. Reson. Imaging 2014;39:259–268. © 2013 Wiley Periodicals, Inc.

Membrane proteins are extremely challenging to produce in sufficient quantities for biochemical and structural analysis and there is a growing demand for solutions to this problem. In this study we attempted to improve expression of two difficult-to-express coding sequences (araH and narK) for membrane transporters. For both coding sequences, synonymous codon substitutions in the region adjacent to the AUG start led to significant improvements in expression, whereas multi-parameter sequence optimization of codons throughout the coding sequence failed. We conclude that coding sequences can be re-wired for high-level protein expression by selective engineering of the 5′ coding sequence with synonymous codons, thus circumventing the need to consider whole sequence optimization.

Purpose: To implement a method using an extended phase graph (EPG)-based simulation to optimize inversion-prepared gradient echo sequences with respect to signal and contrast within the shortest acquisition time. Materials and Methods: A critical issue in rapid gradient-echo imaging is the effect of residual transverse magnetization between consecutive data acquisition windows. Various spoiling schemes have been proposed to mitigate this problem, and while spoiling is often considered to be perfect, imaging can be more truthfully described using the EPG. An EPG-based simulation is used to analyze and predict the image signal and contrast to serve as a basis for sequence optimization. Results: Fourteen biological phantom experiments and five brain imaging experiments on each of five healthy volunteers was performed to validate and verify the accuracy of the EPG-based simulation. In addition, two experiments on an in-cranial cadaver brain were performed to show the ability of the proposed method for improving overall image quality. Conclusion: From the experiment results, it is demonstrated that optimization of 3D magnetization-prepared rapid gradient-echo imaging sequences can be performed with an EPG-based simulation to manipulate the sequence parameters for generating images with highly specific signal and contrast characteristics for quantitative T1-weighted human brain imaging. J. Magn. Reson. Imaging 2012;36:748–755. © 2012 Wiley Periodicals, Inc.

A fast and robust methodology for in vivo T2 mapping is presented. The approach is based on the partially spoiled steady state free precession technique recently proposed by Bieri et al. (Magn Reson Med 2011). The accuracy of this method was demonstrated in simulations and phantom experiments. Variations in skeletal muscle T2 relaxation time have been correlated with cell damage and inflammatory response. Nonetheless, the lack of easily implementable, fast, accurate and reproducible methods has hampered the adoption of T2 measurement as a noninvasive tool for skeletal muscle characterization. The applicability of the partially spoiled steady state free precession method for tissue characterization in muscle disease is illustrated in this work by several examples. Quantitative MRI, in particular T2 mapping based on partially spoiled steady state free precession acquisitions, might provide objective markers of muscle damage and degenerative changes, and an alternative to serial muscle biopsies. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.

Systematic Monte Carlo simulations of simple lattice models show that the final stage of protein folding is an ordered process where native contacts get locked (i.e., the residues come into contact and remain in contact for the duration of the folding process) in a well-defined order. The detailed study of the folding dynamics of protein-like sequences designed as to exhibit different contact energy distributions, as well as different degrees of sequence optimization (i.e., participation of non-native interactions in the folding process), reveals significant differences in the corresponding locking scenarios—the collection of native contacts and their average locking times, which are largely ascribable to the dynamics of non-native contacts. Furthermore, strong evidence for a positive role played by non-native contacts at an early folding stage was also found. Interestingly, for topologically simple target structures, a positive interplay between native and non-native contacts is observed also toward the end of the folding process, suggesting that non-native contacts may indeed affect the overall folding process. For target models exhibiting clear two-state kinetics, the relation between the nucleation mechanism of folding and the locking scenario is investigated. Our results suggest that the stabilization of the folding transition state can be achieved through the establishment of a very small network of native contacts that are the first to lock during the folding process.

We demonstrate the feasibility of a new versatile hybrid imaging concept, the combined acquisition technique (CAT), for cardiac imaging. The cardiac CAT approach, which combines new methodology with existing technology, essentially integrates fast low-angle shot (FLASH) and echoplanar imaging (EPI) modules in a sequential fashion, whereby each acquisition module is employed with independently optimized imaging parameters. One important CAT sequence optimization feature is the ability to use different bandwidths for different acquisition modules. Twelve healthy subjects were imaged using three cardiac CAT acquisition strategies: a) CAT was used to reduce breath-hold duration times while maintaining constant spatial resolution; b) CAT was used to increase spatial resolution in a given breath-hold time; and c) single-heart beat CAT imaging was performed. The results obtained demonstrate the feasibility of cardiac imaging using the CAT approach and the potential of this technique to accelerate the imaging process with almost conserved image quality.

A sequence optimization strategy combining an artificial neural network (ANN) and a chromatographic response function (CRF) for chromatographic separation in reversed-phase high-performance liquid chromatography has been proposed. Experiments were appropriately designed to obtain unbiased data concerning the effects of varying the mobile phase composition, flow-rate, and temperature. The ANN was then used to simultaneously predict the resolution and analysis time, which are the two most important features of chromatographic separation. Subsequently, a CRF consisting of resolution and analysis time was used to predict the optimum operating conditions for different specialized purposes. The experimental chromatograms were consistent with those predicted for given conditions, which verified the applicability of the method. Furthermore, the proposed optimization strategy was applied to literature data and very good agreement was obtained. The results show that a strategy of sequential combination of ANN and CRF can provide a more flexible and efficient optimization method for chromatographic separation. © 2009 American Institute of Chemical Engineers AIChE J, 2010