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A probe design for the acquisition of homonuclear, heteronuclear, and inverse detected NMR spectra from multiple samples.

A new probe design is presented for obtaining homonuclear, heteronuclear, and inverse detected NMR spectra from more than one sample in the same total data acquisition time as for a single sample, thus increasing data acquisition efficiency. Specifically, a two-coil system, with each solenoidal coil impedance matched to 50 Omega at both proton and nitrogen frequencies, has been designed for operation at 11.7 T with an observe volume of 15 microL for each coil. Isolation between the two frequencies for each individual coil, and at each frequency between coils, was greater than 30 dB. Two-dimensional COSY and HMQC spectra were obtained with negligible NMR cross-talk between the two coils.

Adenosine Triphosphate↗

Practical pulse synthesis via the discrete inverse scattering transform.

This paper provides the practical details required to use the inverse scattering (IST) approach to design selective RF-pulses. As in the Shinnar-Le Roux (SLR) approach, we use a hard pulse approximation to actually design the pulse. Unlike SLR, the pulse is designed using the full inverse scattering data (the reflection coefficient and the bound states) rather than the flip angle profile. We explain how to approximate the reflection coefficient to obtain a pulse with a prescribed rephasing time. In contrast to the SLR approach, we retain direct control on the phase of the magnetization profile throughout the design process. We give explicit recursive algorithms for computing the hard pulse from the inverse scattering data. These algorithms are quite different from the SLR recursion, being essentially discretizations of the Marchenko equations. We call our approach the discrete inverse scattering transform or DIST. Overall, it is as fast as the SLR approach. When bound states are present, we use both the left and right Marchenko equations to improve the numerical stability of the algorithm. We compute a variety of examples and consider the effect of amplitude errors on the magnetization profile.

Algorithms↗

Design of a constant adiabaticity pulse for selective population inversion.

A new adiabatic pulse for population inversion and the principles of its design are presented. The pulse shape is characterized by the combination of two constraints. (i) Adiabatic following of the central isochromat of the spectral region of interest occurs with constant, possibly small adiabaticity parameter; thereby, the center isochromat gets most efficiently inverted. (ii) Frequency and amplitude modulations obey the principle of offset-independent adiabaticity; thus, the inversion dynamics of the center isochromat is extended over the desired bandwidth. Selective population inversion can be achieved rather independently of spatial radio frequency field inhomogeneities and with significantly reduced peak RF amplitude in comparison with the well-known sech/tanh adiabatic pulse.

Journal Article↗

Relative contributions of structural designability and functional diversity in molecular evolution of duplicates.

Analysis of increasingly saturated sequence databases have shown that gene family sizes are highly skewed with many families being small and few containing many, far-diverged homologs. Additionally, recently published results have identified a structural determinant of mutational plasticity: designability that correlates strongly with gene family size. In this paper, we explore the possible links between the two observations, exploring the possible effect of designability on duplication and divergence. We show that designability has an inverse of expected relationship with strength of selection. More designable domains that should have more mutational plasticity evolve slower. However, we also present evidence that recently duplicated genes have variable probability of locus fixation correlated with strength of selection. As expected, paralogs under stronger evolutionary pressure have a lower failure rate. Finally, we show that probability of pseudogene formation from gene duplication can be directly tied to designability and functional flexibility of the family. We present evidence that gene families with higher designability have diverged farther because of lower probability of pseudogenization. Additionally, mutational plasticity may play an integral role by influencing pseudogenization rate. Either way, we show that considering the failure rate of duplications is integral in understanding the determinants and dynamics of molecular evolution.

Chromosome Mapping↗

Tailoring broadband inversion pulses for MAS solid state NMR.

A simple approach is demonstrated for designing optimised broadband inversion pulses for MAS solid state NMR studies of biological systems. The method involves a two step numerical optimisation procedure and takes into account experimental requirements such as the pulse length, resonance offset range and extent of H(1) inhomogeneity compensation needed. A simulated annealing protocol is used initially to find appropriate values for the parameters that define the well known tanh/tan adiabatic pulse such that a satisfactory spin inversion is achieved with minimum RF field strength. This information is then used in the subsequent stage of refinement where the RF pulse characteristics are further tailored via a local optimisation procedure without imposing any restrictions on the amplitude and frequency modulation profiles. We demonstrate that this approach constitutes a generally applicable tool for obtaining pulses with good inversion characteristics. At moderate MAS frequencies the efficacy of the method is experimentally demonstrated for generating double-quantum NMR spectra via the zero-quantum dipolar recoupling scheme RFDR.

Carbon Isotopes↗

In vivo lactate editing with simultaneous detection of choline, creatine, NAA, and lipid singlets at 1.5 T using PRESS excitation with applications to the study of brain and head and neck tumors.

Two T2-independent J-difference lactate editing schemes for the PRESS magnetic resonance spectroscopy localization sequence are introduced. The techniques, which allow for simultaneous acquisition of the lactate doublet (1.3 ppm) and edited singlets upfield of and including choline (3.2 ppm), exploit the dependence of the in-phase intensity of the methyl doublet upon the time interval separating two inversion (BASING) pulses applied to its coupling partner after initial excitation. Editing method 1, which allows for echo times TE = n/J (n = 1, 2, 3, . . . . ), alters the BASING carrier frequency for each of two cycles so that, for one cycle, the quartet is inverted, whereas, for the other cycle, the quartet is unaffected. Method 2, which also provides water suppression, allows for editing for TE > 1/J by alternating, between cycles, the time interval separating the inversion pulses. Experimental results were obtained at 1.5 T using a Shinnar Le-Roux-designed maximum phase inversion pulse with a filter transition bandwidth of 55 Hz. Spectra were acquired from phantoms and in vivo from the human brain and neck. In a neck muscle study, the lipid suppression factor, achieved partly through the use of a novel phase regularization algorithm, was measured to be over 10(3). Spectra acquired from a primary brain and a metastatic neck tumor demonstrated the presence of lactate and choline signals consistent with abnormal spectral patterns. The advantages and limitations of the methods are analyzed theoretically and experimentally, and significance of the results is discussed.

Aspartic Acid↗

A comparison of the Sport Stirrup, Malleoloc, and Swede-O ankle orthoses for the foot-ankle kinematics of a rapid lateral movement.

Little information exists about the efficacy of various brace designs to restrict inversion during lateral movements. The purpose of the study was to determine whether semi-rigid stirrup (AirCast Sport Stirrup), semi-rigid modified stirrup (Malleoloc), or a soft, sleeve design (Swede-O) brace varied in their abilities to restrict inversion without hindering plantar/dorsiflexion when a lateral cutting movement is performed compared to a no-brace condition (No-Br). Nineteen volunteers who had previously sprained their right ankles performed 10 sideward cutting trials/brace condition. Based on kinematic data, captured using high-speed cameras, none of the braces restricted inversion compared to the No-Br condition. Plantar flexion was inhibited for all braces, and less dorsiflexion was exhibited for the Swede-O. For three participants, greater toe-in landings were observed for the Swede-O. Based on chi-square analyses, the participants rank of braces for stability and overall performance in decreasing order: Malleoloc, AirCast, Swede-O. It was concluded that the participants may have exhibited injury avoidance behavior during conditions perceived to be less stable, thereby reducing inversion when wearing no brace or the Swede-O brace. It also is tenable that the motion of the shoe was influenced by the presence of the braces, hence, no inversion restriction was observed.

Adult↗

Conformal radiation treatment of prostate cancer using inversely-planned intensity-modulated photon beams produced with dynamic multileaf collimation.

PURPOSE: To implement radiotherapy with intensity-modulated beams, based on the inverse method of treatment design and using a multileaf collimation system operating in the dynamic mode. METHODS AND MATERIALS: An algorithm, based on the inverse technique, has been integrated into the radiotherapy treatment-planning computer system in our Center. This method of computer-assisted treatment design was used to derive intensity-modulated beams to optimize the boost portion of the treatment plan for a patient with a T1c cancer of the prostate. A dose of 72 Gy (in 40 fractions) was given with a six-field plan, and an additional 9 Gy (in five fractions) with six intensity-modulated beams. The intensity-modulated fields were delivered using dynamic multileaf collimation, that is, individual leaves were in motion during radiation delivery, with the treatment machine operating in the clinical mode. Exhaustive quality assurance measurement and monitoring were carried out to ensure safe and accurate implementation. RESULTS: Dose distribution and dose-volume histogram of the "inverse method" boost plan and of the composite (72 Gy primary + 9 Gy boost) plan were judged clinically acceptable. Compared to a manually designed boost plan, the inverse treatment design gave improved conformality and increased dose homogeneity in the planning target volume. Film and ion chamber dosimetry, performed prior to the first treatment, indicated that each of the six intensity-modulated fields was accurately produced. Thermoluminescent dosimeter (TLD) measurements performed on the patient confirmed that the intended dose was delivered in the treatment. In addition, computer-aided treatment-monitoring programs assured that the multileaf collimator (MLC) position file was executed to the specified precision. In terms of the overall radiation treatment process, there will likely be labor savings in the planning and the treatment phases. CONCLUSIONS: We have placed into clinical use an integrated system of conformal radiation treatment that incorporated the inverse method of treatment design and the use of dynamic multileaf collimation to deliver intensity-modulated beams. The system can provide better treatment design, which can be implemented reliably and safely. We are hopeful that improved treatment efficacy will result.

Humans↗

Relationship between ankle invertor H-reflexes and acute swelling induced by inversion ankle sprain.

STUDY DESIGN: Single group, post-test design using the uninvolved lower extremity as the experimental control. OBJECTIVES: To determine relationships between ankle swelling and flexor digitorum longus and peroneus longus H-reflex amplitude and latency. BACKGROUND: Primary capsuloligamentous injury, neural injury, and joint effusion and swelling may contribute to H-reflex changes following inversion ankle sprain. The relationship between ankle swelling and invertor or evertor H-reflexes has not been reported. METHODS AND MEASURES: Fifteen subjects with acute grade I or II inversion ankle sprains (mean +/- SD) 6.5 +/- 3 days after onset participated in this study. Swelling was estimated using a tape measure and the figure-of-eight girth assessment method. H-reflexes were determined using standard techniques. Paired t-tests were used to compare mean differences in ankle girth (swelling) and ankle invertor or evertor H-reflex amplitude and latency between the involved and uninvolved limbs. Pearson product moment correlations were used to assess relationships between swelling and H-reflex variables. RESULTS: Involved limb ankle girth was increased with respect to the uninvolved limb (1.5 +/- 0.9 cm) and the involved ankle flexor digitorum longus latency was delayed (0.72 +/- 0.7 ms). There was a moderate positive association (r = 0.73) between the latency delay in the involved ankle flexor digitorum longus and swelling. There were no significant differences in H-reflex amplitude and peroneus longus latency between ankles. CONCLUSIONS: Grade I or II inversion sprains and the related swelling appear to delay involved ankle flexor digitorum longus latency to a greater extent than peroneus longus latency. Clinicians need to direct greater attention to the ankle invertors when designing and implementing ankle rehabilitation programs, particularly during the swelling management phase of treatment.

Acute Disease↗

Strategy of exercise prescription using an unloading technique for functional rehabilitation of an athlete with an inversion ankle sprain.

STUDY DESIGN: Case study. OBJECTIVES: To demonstrate how an exercise program can be designed with specific sets, repetitions, and rest periods, and to enhance the healing process in early stages of rehabilitation when injured tissues cannot tolerate full body weight. Our goal was to enhance ankle tissue healing by reducing gravitational force through a prescriptive exercise and unloading program. BACKGROUND: This report describes a treatment method that we used to rehabilitate a collegiate soccer player with a Grade II inversion ankle sprain. This athlete sprained his ankle 6 weeks before the start of rehabilitation and was unable to participate in soccer due to persistent pain and impaired function. METHODS AND MEASURES: A 2-week functional training program was implemented, consisting of exercises chosen for specific task simulation related to soccer. Gravitational force was mechanically altered by suspending the subject or by supporting the subject on a variable incline plane. Weight-bearing was controlled so that the subject could perform exercises without pain. The outcome measures were ankle range of motion (ROM), maximum pain-free isometric strength, vertical force during unilateral squats, and unilateral hop time and distance. RESULTS: Pain-free weight-bearing capacity increased over the 2-week course of rehabilitation and the subject was able to return to playing soccer without pain. The ratios (involved to uninvolved extremity) at time of discharge from physical therapy were 87% to 103% for ankle ROM, 75% to 93% for isometric ankle strength, 91% for unilateral squats, 88% for unilateral hop time, and 86% for unilateral hop distance. CONCLUSIONS: Return to function can be achieved in a short period by exercise that is performed with a gradual increase in pain-free weight-bearing capacity.

Adult↗

An object-oriented designed finite-difference time-domain simulator for electromagnetic analysis and design in MRI--applications to high field analyses.

This paper presents a finite-difference time-domain (FDTD) simulator for electromagnetic analysis and design applications in MRI. It is intended to be a complete FDTD model of an MRI system including all RF and low-frequency field generating units and electrical models of the patient. The program has been constructed in an object-oriented framework. The design procedure is detailed and the numerical solver has been verified against analytical solutions for simple cases and also applied to various field calculation problems. In particular, the simulator is demonstrated for inverse RF coil design, optimized source profile generation, and parallel imaging in high-frequency situations. The examples show new developments enabled by the simulator and demonstrate that the proposed FDTD framework can be used to analyze large-scale computational electromagnetic problems in modern MRI engineering.

Algorithms↗

Elasticity analysis and design for large metabolic responses produced by changes in enzyme activities.

Metabolic control analysis has been extensively used to describe how the sensitivity properties of the component enzymes in a metabolic pathway (represented by the elasticity coefficients) determine the way in which metabolic variables respond (described by the control coefficients). Similarly, metabolic control design addresses the inverse problem of obtaining the sensitivity properties of the component enzymes that are required for the system to show a pre-established pattern of responses. These formalisms, including what is called elasticity analysis and design, were developed for small, strictly speaking infinitesimal, changes. Here we extend them to large metabolic responses. The new approach can be applied to simple two-step pathways or to any arbitrary metabolic system divided into two groups linked by one intermediate. General expressions that relate control and elasticity coefficients for large changes are derived. Concentration and flux connectivity relationships are obtained. The relationships for large changes indicate that the pattern of responses is not necessarily the same as the one obtained with the traditional infinitesimal approach, in some cases the patterns being qualitatively different. The general analysis is used to study the control of ketogenesis in rat liver mitochondria, starting from data available in the literature. The control profile of the pathway subject to large changes shows both quantitative and qualitative differences from the one obtained from an analysis that is performed with infinitesimal coefficients. This exemplifies the type of errors that may be introduced when drawing conclusions about large metabolic responses from results obtained with an infinitesimal treatment.

Animals↗

Technical note: use of a double inversion recovery pulse sequence to image selectively grey or white brain matter.

The design of a double inversion recovery (DIR) sequence, to image selectively grey or white brain matter, is described. Suitable choice of inversion times allows either cerebrospinal fluid (CSF) and white matter to be suppressed, to image the cortex alone, or CSF and grey matter to be suppressed, to image the white matter. The DIR sequence was found to give clear delineation of the cerebral cortex.

Adult↗

Do workplace interventions prevent low-back disorders? If so, why?: a methodologic commentary.

The demand for workplace interventions to prevent low-back disorders has increased in recent years. At the same time, a crisis in the literature has become apparent: there are conflicting reports on whether or not these interventions work. With the aim of understanding the reason for the dissension in the literature, six studies were selected for close examination. These were studies of interventions based on differing principles, i.e. a change in organizational ethos to promote back safety, back belt use, the introduction of ergonomic devices, and back-strengthening exercises. If the studies are taken at face value, any of the interventions, regardless of type, has a tremendous effect. Methodological problems inherent in these studies may provide a clue to why essentially different interventions were found to be consistently successful. Study design quality has long been noted to exert a particular influence on the evaluation of outcomes: the quality of the study design is often inversely related to reported outcomes. Of the six studies selected for examination, four did not include a contemporaneous control group, five did not randomly assign subjects to test and control groups, and none included a placebo group. Given these research designs, variables other than those tested by the studies may have produced the reported results. These variables include 'beliefs of the intervention providers' and 'coalescence of the work group', both of which are discussed. Two approaches, the pragmatic and the explanatory, may be used to study workplace interventions to prevent low-back disorders. Most of the examined studies are pragmatically oriented. Having dealt with study design problems expeditiously, these studies may be characterized as more immediately responsive to the demand to evaluate workplace interventions than explanatory studies. On the other hand, explanatory studies, most notably associated with randomized clinical trials in medicine, are more rigorous. Enough pragmatically oriented studies have been conducted to suggest that workplace interventions may have an effect on low-back disorders. More conclusive explanatory studies may now be conducted.

Accidents, Occupational↗

Inverse planning with constraints to generate smoothed intensity-modulated beams.

Highly conformal dose distributions can be generated by intensity-modulated radiotherapy. Intensity-modulated beams (IMBs) are generally determined by inverse-planning techniques designed to maximize conformality. Usually such techniques apply no constraints on the form of the IMBs which may then develop fine-scale modulation. In this paper we present a technique for generating smoother IMBs, which yields a dose distribution almost identical to that without the constraint on the form of the IMBs. The method applies various filters successively at intervals throughout the iterative inverse planning. It is shown that the IMBs so determined using a simple median window filter have desirable properties in terms of increasing the efficiency of delivery by the dynamic multileaf collimator method and may be 'more like conventional beams' than unconstrained, highly modulated IMBs.

Humans↗

Interventional telemedicine for noninvasive neuroradiosurgery: remote-site high-performance computing, mathematical optimization, and virtual scenario simulation.

Interventional Telemedicine may have potential utility in providing connectivity and access to specialized high performance computing and advanced software resources in support of clinical procedures in the field of Minimally-Invasive Surgery and Stereotactic Linear Accelerator (LINAC) Radiosurgery. Such interventions may benefit from application of nonlinear quadratic inverse solution methods designed to provide the capability to reverse optimize a 'best case' treatment plan. The formidable decision-making challenges posed by increasingly complex optimized data and progressively versatile LINAC delivery systems require volume visualization of projected treatment data and imaging anatomy via photorealistic rendering and virtual scenario simulation techniques. Both these new directions are heavily dependent on access to specialized high performance computing platforms solely accessible via broad-bandwidth network connectivity. This pilot project presents resimulation of retrospective radiosurgical case data using inverse solution optimization models running on workstation clusters and then volume rendered and simulated on the Princeton Graphics Engine Supercomputer. Evidence for effective utilization of such optimization and virtual simulation methods running on remotely accessed, distant high performance computing resources is discussed in view of the potential for long-term clinical investigation and eventual development of Interventional Telemedicine as a clinically practical approach for providing support to remote or non-urban radiosurgery centers in the industrialized and developing world.

Algorithms↗