Magnetic resonance elastography studies of the musculoskeletal system

Manual palpation is a clinical methodology to determine tissue mechanical properties, such as viscoelasticity (i.e. stiffness and viscosity), which is a primary indicator of the development of tissue pathology. Advancing medical imaging technology means it is now possible to reliably non-invasively measure tissue stiffness in-vivo through the use of Magnetic Resonance Elastography (MRE). Muscle pathology is traditionally assessed in the clinic through measurement of muscle morphology and function (e.g. Maximum Voluntary Contraction [MVC]). However, MRE has been shown to be an effective method to study muscle pathology and may offer novel biomechanical insight into, for example, muscle engagement, injury and recovery, which cannot be obtained through conventional testing. The aim of this thesis is to perform a series of exploratory investigations to determine the precision, sensitivity and reliability of the muscle MRE technique for studying the relationships between muscle mechanical properties and morphology. This is especially relevant to the clinical application of the technique which is investigated in two pilot studies. Specific interests are to investigate whether muscle MRE offers reliable insight regarding muscle ageing, injury and loading and has potential clinical application such as in monitoring recovery after time in Critical Care and the effects of Total Knee Replacement (TKR) in patients with osteoarthritis of the knee. This thesis begins with a review of musculoskeletal biomechanics, Magnetic Resonance Imaging (MRI) and MRE research to date. A limited number of clinical musculoskeletal elastography research studies were identified and which motivated several investigations conducted in this thesis. A musculoskeletal MRE analysis pipeline was developed to accurately acquire and analyse MRE data and consists of image co-registration, quantification of muscle mechanical (i.e. stiffness) and morphological properties (i.e. muscle cross-sectional area and a shape measure referred to as circularity), which may be related to clinical measures and relevant functional indices such as MVC. The pipeline includes quality control procedures to detect image artefacts and provides results which can be potentially reliably compared with those of other research groups. The first two investigations to be reported concern the study of changes in the mechanical properties of muscles that have occurred passively. In particular, the effects of ageing are studied together with the effect of time spent in Critical Care and subsequent rehabilitation. The effect of ageing was primarily evident in the quadriceps muscle group which decreased significantly in cross-sectional area and significantly increased in stiffness. The effects produced by immobilisation were also predominantly in the quadriceps but here a significant decrease in muscle cross-sectional area was associated with a decrease in muscle stiffness. The next three exploratory studies all involve an intervention or manipulation in terms of an eccentric exercise protocol which produces muscle injury as well as muscle loading. The former was based on a re-analysis of previously published work with the aim of determining whether there was a significant difference in muscle stiffness in subjects in whom injury was shown to be associated with muscle oedema on T2-weighted MR images. Here the new pixel-wise analysis of the data showed that although the two groups of subjects performed a similar workload, subjects who developed oedema may have used a different combination of muscles to perform the task, and especially may have additionally recruited medial muscles rather than efficiently co-contracting the quadriceps and hamstrings. A loading study revealed a significant relationship between the stiffness and shape (i.e. circularity) of especially rectus femoris and first steps were taken to investigate whether this relationship may show insight into the recovery of patients following TKR surgery. Taken together these exploratory investigations demonstrate the precision, sensitivity and viability of the muscle MRE technique and its promise for potential clinical application

A new performance bound for PAM-based CPM detectors

©2005 IEEE. Personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution to servers or lists, or to reuse any copyrighted component of this work in other works must be obtained from the IEEE.It is well understood that the pulse amplitude modulation (PAM) representation of continuous phase modulation (CPM) can lead to reduced-complexity detectors with near optimum performance. It has recently been shown that the PAM representation also extends to CPM schemes with multiple modulation indexes (multi-h CPM). In this paper, we present a detector for multi-h CPM which is based on the PAM representation. We also give an exact expression for the pairwise error probability for the entire class of PAM-based CPM detectors (single- and multi-h, optimal, and reduced-complexity) over the additive white Gaussian noise (AWGN) channel and show that this bound is tighter than the previously published bound for approximate PAM-based detectors. In arriving at this expression, we show that PAM-based detectors for CPM are a special case of the broad class of mismatched CPM detectors. We also show that the metrics for PAM-based detectors accumulate distance in a different manner than metrics for other CPM detectors. These distance properties are especially useful in applications with greatly reduced trellis sizes. We give thorough examples of the analysis for different single- and multi-h signaling schemes. We also apply the new bound in comparing the performance of PAM-based detectors with other reduced-complexity detectors for CPM

Ventrolateral Origin of Each Cycle of Rhythmic Activity Generated by the Spinal Cord of the Chick Embryo

BACKGROUND: The mechanisms responsible for generating rhythmic motor activity in the developing spinal cord of the chick embryo are poorly understood. Here we investigate whether the activity of motoneurons occurs before other neuronal populations at the beginning of each cycle of rhythmic discharge. METHODOLOGY/PRINCIPAL FINDINGS: The spatiotemporal organization of neural activity in transverse slices of the lumbosacral cord of the chick embryo (E8-E11) was investigated using intrinsic and voltage-sensitive dye (VSD) imaging. VSD signals accompanying episodes of activity comprised a rhythmic decrease in light transmission that corresponded to each cycle of electrical activity recorded from the ipsilateral ventral root. The rhythmic signals were widely synchronized across the cord face, and the largest signal amplitude was in the ventrolateral region where motoneurons are located. In unstained slices we recorded two classes of intrinsic signal. In the first, an episode of rhythmic activity was accompanied by a slow decrease in light transmission that peaked in the dorsal horn and decayed dorsoventrally. Superimposed on this signal was a much smaller rhythmic increase in transmission that was coincident with each cycle of discharge and whose amplitude and spatial distribution was similar to that of the VSD signals. At the onset of a spontaneously occurring episode and each subsequent cycle, both the intrinsic and VSD signals originated within the lateral motor column and spread medially and then dorsally. By contrast, following a dorsal root stimulus, the optical signals originated within the dorsal horn and traveled ventrally to reach the lateral motor column. CONCLUSIONS/SIGNIFICANCE: These findings suggest that motoneuron activity contributes to the initiation of each cycle of rhythmic activity, and that motoneuron and/or R-interneuron synapses are a plausible site for the activity-dependent synaptic depression that modeling studies have identified as a critical mechanism for cycling within an episode

Functional Characterization of a First Avian Cytochrome P450 of the CYP2D Subfamily (CYP2D49)

The CYP2D family members are instrumental in the metabolism of 20–25% of commonly prescribed drugs. Although many CYP2D isoforms have been well characterized in other animal models, research concerning the chicken CYP2Ds is limited. In this study, a cDNA encoding a novel CYP2D enzyme (CYP2D49) was cloned from the chicken liver for the first time. The CYP2D49 cDNA contained an open reading frame of 502 amino acids that shared 52%–57% identities with other CYP2Ds. The gene structure and neighboring genes of CYP2D49 are conserved and similar to those of human CYP2D6. Additionally, similar to human CYP2D6, CYP2D49 is un-inducible in the liver and expressed predominantly in the liver, kidney and small intestine, with detectable levels in several other tissues. Metabolic assays of the CYP2D49 protein heterologously expressed in E. coli and Hela cells indicated that CYP2D49 metabolized the human CYP2D6 substrate, bufuralol, but not debrisoquine. Moreover, quinidine, a potent inhibitor of human CYP2D6, only inhibited the bufuralol 1′-hydroxylation activity of CYP2D49 to a negligible degree. All these results indicated that CYP2D49 had functional characteristics similar to those of human CYP2D6 but measurably differed in the debrisoquine 4′-hydroxylation and quinidine inhibitory profile. Further structure-function investigations that employed site-directed mutagenesis and circular dichroism spectroscopy identified the importance of Val-126, Glu-222, Asp-306, Phe-486 and Phe-488 in keeping the enzymatic activity of CYP2D49 toward bufuralol as well as the importance of Asp-306, Phe-486 and Phe-488 in maintaining the conformation of CYP2D49 protein. The current study is only the first step in characterizing the metabolic mechanism of CYP2D49; further studies are still required

Modelling Feedback Excitation, Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity

What cellular and network properties allow reliable neuronal rhythm generation or firing that can be started and stopped by brief synaptic inputs? We investigate rhythmic activity in an electrically-coupled population of brainstem neurons driving swimming locomotion in young frog tadpoles, and how activity is switched on and off by brief sensory stimulation. We build a computational model of 30 electrically-coupled conditional pacemaker neurons on one side of the tadpole hindbrain and spinal cord. Based on experimental estimates for neuron properties, population sizes, synapse strengths and connections, we show that: long-lasting, mutual, glutamatergic excitation between the neurons allows the network to sustain rhythmic pacemaker firing at swimming frequencies following brief synaptic excitation; activity persists but rhythm breaks down without electrical coupling; NMDA voltage-dependency doubles the range of synaptic feedback strengths generating sustained rhythm. The network can be switched on and off at short latency by brief synaptic excitation and inhibition. We demonstrate that a population of generic Hodgkin-Huxley type neurons coupled by glutamatergic excitatory feedback can generate sustained asynchronous firing switched on and off synaptically. We conclude that networks of neurons with NMDAR mediated feedback excitation can generate self-sustained activity following brief synaptic excitation. The frequency of activity is limited by the kinetics of the neuron membrane channels and can be stopped by brief inhibitory input. Network activity can be rhythmic at lower frequencies if the neurons are electrically coupled. Our key finding is that excitatory synaptic feedback within a population of neurons can produce switchable, stable, sustained firing without synaptic inhibition

UNIFICATION OF SIGNAL MODELS FOR SOQPSK

This paper begins by summarizing a recent advancement in the way that shaped offset quadrature phase shift keying (SOQPSK) waveforms can be viewed. This new viewpoint succeeds in eliminating the need for SOQPSK to be thought of as a “special” kind of correlated, ternary continuous phase modulation (CPM). Instead, SOQPSK can be viewed as an ordinary, binary CPM. We provide all of the details necessary to achieve a complete unification of SOQPSK models at the waveform level, at the bit sequence level, and in terms of waveform initialization. With this information, SOQPSK users can easily mix and match SOQPSK models at the transmitter and receiver in order to make use of the advantages of each model.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

SURVEY OF DETECTION METHODS FOR ARTM CPM

International Telemetering Conference Proceedings / October 18-21, 2004 / Town & Country Resort, San Diego, CaliforniaThe ARTM Tier-2 waveform, called “ARTM CPM” in IRIG 106-04, has almost three times the spectral efficiency of PCM/FM and approximately the same detection efficiency. The improved spectral efficiency comes at the price of computational complexity in the receiver. The optimum receiver requires 128 real-valued matched filters and keeps track of the waveform state with a trellis of 512 states and 2048 branches. Various complexity reducing techniques are applied and the resulting loss in detection efficiency is quantified. It is shown that the full 512-state trellis is not required to achieve the desired detection efficiency: two different 32-state configurations were found to perform within one tenth of a dB of optimal. Noncoherent techniques are also evaluated. It is shown that the required complexity can be quite large to achieve a respectable detection efficiency. One noncoherent technique performed within 1.9 dB of the optimal with only 64 states, which is significant when considering the additional complexity savings of not having to track the carrier phase.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection