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PubMed1995

Morphomechanics of the humero-ulnar joint: I. Joint space width and contact areas as a function of load and flexion angle.

BACKGROUND: Previous studies have shown that the trochlear notch is deeper than necessary for an exact fit with the humerus. However, humero-ulnar joint space width and contact areas have so far not been quantified for variations in the load and angle of flexion. METHODS: Six fresh cadaveric specimens were investigated at 30 degrees, 60 degrees, 90 degrees, and 120 degrees of flexion and at loads of 25 and 500 N, simulating resisted elbow extension. The joint space width and contact were determined, using polyether casting material. RESULTS: At 25 N all joints made contact in the ventral and dorsal aspects of the articular surfaces, whereas in the depth of the trochlear notch the joint space was on average between 0.3 and 2.8 mm wide, with some variation between individuals. At 500 N the joint space width was considerably reduced and the contract areas expanded towards the depth of the notch. The size of the dorsal contact areas was significantly smaller at 30 degrees and that of the ventral ones at 120 degrees, their ventro-dorsal ratio decreasing considerably from 30 degrees to 120 degrees (p < 0.01). CONCLUSION: These results indicate that the size of the contact areas depends to a slight extent on the joint position, but that at all loads and flexion angles a bicentric contact and an important central joint space width emerge because of the concave incongruity of the joint. These data may be used for numerical calculations, analysing the effects of incongruity on the joint stress and on the functional adaptation of the subarticular tissues.

Adult↗
PubMed2002

Structural effect of avocado/soybean unsaponifiables on joint space loss in osteoarthritis of the hip.

OBJECTIVE: To evaluate the structural effect of avocado/soybean unsaponifiables (ASU) in the treatment of patients with symptomatic osteoarthritis (OA) of the hip. METHODS: Patients with regular painful primary OA of the hip (European League Against Rheumatism 1980 criteria) and a joint space still > or = 1 mm (Kellgren grade 1 to 3, assessed by an independent observer prior to inclusion) entered a prospective, multicenter, randomized, parallel group, double-blind, placebo-controlled trial of 2 years duration. Patients had at least a 6-month history of regular pain and an algofunctional index (AFI) > or = 4. The primary assessment criterion was a decrease of the joint space width (JSW) on plain anteroposterior radiographs of the pelvis performed in standing position, measured at the narrowest points by 2 independent readers, previously tested and selected and blinded to both the treatment and the time sequence. Secondary criteria were standard clinical outcome measurements (AFI, pain on a visual analog scale, consumption of nonsteroidal antiinflammatory drugs and patient's and investigator's global assessments). RESULTS: One hundred sixty-three patients were included: 102 men and 61 women (mean age 63.2 +/- 8.7 years). A total of 108 patients (72 men and 36 women; mean age 64 +/- 7.9 years) were radiologically evaluable at 23.7 +/- 2.6 months (ASU group; n = 55) and 23.7 +/- 3.2 months (placebo group; n = 53). Overall comparison of the evolution of JSW showed no difference between the ASU and placebo groups, from 2.35 +/- 0.93 to 1.87 +/- 1.10 mm and from 2.5 +/- 0.94 to 1.9 +/- 1.33 mm, respectively (intergroup P value at end point = 0.9). When patients were divided into 2 subgroups according to the median value of the baseline JSW (2.45 mm), the joint space loss in the most severely affected subgroup of patients (baseline JSW < or = median) was significantly greater in the placebo group than in the ASU group: from 1.69 +/- 0.58 to 0.84 +/- 0.77 mm (-0.86 +/- 0.62 mm) and from 1.66 +/- 0.42 to 1.22 +/- 0.7 mm (-0.43 +/- 0.51 mm), respectively (P < 0.01). The JSW decrease was identical, with no difference in ASU and placebo groups, in the less severely affected subgroup of patients (baseline JSW > median). Clinical parameters in the 2 groups did not differ significantly throughout the study. CONCLUSION: This pilot randomized, double-blind, placebo-controlled trial failed to demonstrate a structural effect of ASU in hip OA. However, in a post-hoc analysis, ASU significantly reduced the progression of joint space loss as compared with placebo in the subgroup of patients with advanced joint space narrowing. These results suggest that ASU could have a structural effect but require confirmation in a larger placebo-controlled study in hip OA.

Aged↗
PubMed2001

Variations of dose and electrode spacing for rat breast cancer electrochemical treatment.

Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P </= 0.001). Electrodes spacing was not an important factor within a given range. At 5, 10, and 15 mm spacing, the fraction showing the necrosis were 54.1, 60.4, and 59.2%, respectively (P = 0.552). The overlap rate of necroses was similar in the 5 and 10 mm groups (82.5 and 85%) and lower in the 15 mm group (65%). We conclude that the tumor responses to EChT, local control, survival rates, and necrosis percentages were significantly increased with increasing dose. The changes in electrode spacing (3, 5, and 10 mm) did not significantly affect the tumor responses to EChT within the same dose. For a diameter of 2.0-2.5 cm rat breast cancer, EChT should be applied with 5-10 mm spacing and a minimum dosage of 80 C.

Animals↗
PubMed1999

Consistent infiltration of thymus-derived T cells into the parenchymal space of the liver in normal mice.

We previously reported that extrathymic T cells (intermediate T-cell receptor cells [TCR(int) cells]) are in situ generated in the parenchymal space of the liver in mice. They subsequently migrate to the sinusoidal lumen. In this study, we characterized how such extrathymic T cells, natural killer (NK) cells, and thymus-derived T cells (high T-cell receptor cells [TCR(high) cells]) localized in the parenchymal space or the sinusoidal lumen of mice. To this end, liver irrigation with physiological saline from the portal vein was performed and the distribution of lymphocyte subsets was compared between the liver (i.e., lymphocytes in the parenchymal space) and the irrigation solution (i.e., lymphocytes in the sinusoidal lumen). Extrathymic T cells and NK cells were found to be abundant in both the liver and sinusoidal lumen. As expected, thymus-derived T cells were abundant in the sinusoidal lumen. However, a significant proportion of thymus-derived T cells were always present in the parenchymal space, even after intensive irrigation with or without collagenase. These results suggest that thymus-derived T cells may consistently infiltrate the parenchymal space from the sinusoidal lumen in normal mice. This possibility was confirmed by (1) the injection of B6 splenic cells (TCR(high) cells) or the thymus graft into B6-nu/nu mice (presence of only TCR(int) cells) and by (2) using parabiotic mice of B6.Ly5.1 and B6.Ly5.2 strains (sharing circulation) in conjunction with immunofluorescence tests and immunohistochemical staining. In other words, inverted routes of migration and homing between extrathymic T cells and thymus-derived T cells exist in the liver.

Animals↗
PubMed2003

Temporal spacing of synaptic stimulation critically modulates the dependence of LTP on cyclic AMP-dependent protein kinase.

Genetic and electrophysiological experiments have defined an important role for cAMP-dependent protein kinase (PKA) in certain forms of long-term potentiation (LTP). However, the characteristics of stimulation that are critical for regulating the PKA-dependence of LTP have not been clearly defined. In the present study, we have used PKA mutant mice (R(AB) transgenic mice), which have reduced PKA activity in neurons within the hippocampus, to explore the role of temporal spacing of synaptic stimulation in regulating the PKA-dependence of LTP. The time interval between successive bursts of electrical stimulation was varied while keeping constant the total number of stimulus pulses. LTP induced by temporally spaced tetraburst synaptic stimulation was impaired in the Schaeffer collateral pathway of hippocampal slices from R(AB) mutant mice. In contrast, LTP induced by temporally compressed tetraburst stimulation was normal in slices from R(AB) mutants, and its long-term maintenance was not significantly affected by bath application of KT-5720, an inhibitor of catalytic subunits of PKA. In slices from wildtype mice, LTP induced by spaced tetraburst stimulation was significantly attenuated by KT-5720. These genetic and pharmacological experiments show that LTP induced by these compressed patterns of stimulation does not require PKA activation. Thus, altering the temporal spacing of synaptic stimulation per se critically modulates the PKA-dependence of hippocampal LTP. PKA-dependent LTP is selectively recruited by temporally spaced, multiburst synaptic stimulation.

Animals↗
PubMed1987

Transport of proteins to the mitochondrial intermembrane space: the 'sorting' domain of the cytochrome c1 presequence is a stop-transfer sequence specific for the mitochondrial inner membrane.

The presequence of yeast cytochrome c1 (an inner membrane protein protruding into the intermembrane space) contains a matrix-targeting domain and an intramitochondrial sorting domain. This presequence transports attached subunit IV of cytochrome c oxidase into the intermembrane space (van Loon et al. (1987) EMBO J., 6, 2433-2439). In order to determine how this fusion protein reaches the intermembrane space, we studied the kinetics of its import into isolated mitochondria or mitoplasts and its accumulation in the various submitochondrial compartments. The imported, uncleaved fusion precursor and a cleavage intermediate were bound to the inner membrane and were always exposed to the intermembrane space; they were never found at the matrix side of the inner membrane. In contrast, analogous import experiments with the authentic subunit IV precursor, or the precursor of the iron-sulphur protein of the cytochrome bc1 complex also an inner membrane protein exposed to the intermembrane space), readily showed that these precursors were initially transported across both mitochondrial membranes. We conclude that the intramitochondrial sorting domain within the cytochrome c1 presequence prevents transport of attached proteins across the inner, but not the outer membrane: it is a stop-transfer sequence for the inner membrane. Since the presequence of the iron-sulphur protein lacks such 'stop-transfer' domain, it acts by a different mechanism.

Cytochrome c Group↗
PubMed1993

Functional independence of the protein translocation machineries in mitochondrial outer and inner membranes: passage of preproteins through the intermembrane space.

The protein translocation machineries of the outer and inner mitochondrial membranes usually act in concert during translocation of matrix and inner membrane proteins. We considered whether the two machineries can function independently of each other in a sequential reaction. Fusion proteins (pF-CCHL) were constructed which contained dual targeting information, one for the intermembrane space present in cytochrome c heme lyase (CCHL) and the other for the matrix space contained in the signal sequence of the precursor of F1-ATPase beta-subunit (pF1 beta). In the absence of a membrane potential, delta psi, the fusion proteins moved into the intermembrane space using the CCHL pathway. In contrast, in the presence of delta psi they followed the pF1 beta pathway and eventually were translocated into the matrix. The fusion protein pF51-CCHL containing 51 amino acids of pF1 beta, once transported into the intermembrane space in the absence of a membrane potential, could be further chased into the matrix upon re-establishing delta psi. The sequential and independent movement of the fusion protein across the two membranes demonstrates that the translocation machineries act as distinct entities. Our results support a model in which the two translocation machineries can function independently of each other, but generally interact in a dynamic fashion to achieve simultaneous translocation across both membranes. In addition, the results provide information about the targeting sequences within CCHL. The protein does not contain a signal for retention in the intermembrane space; rather, it lacks matrix targeting information, and therefore is unable to undergo delta psi-dependent interaction with the protein translocation apparatus in the inner membrane.

Biological Transport↗
PubMed2002

New space warping method for the simulation of large-scale macromolecular conformational changes.

A space warping method, facilitating the modeling of large-scale conformational changes in mesoscopic systems, is presented. The method uses a set of "global (or collective) coordinates" that capture overall behavior, in conjunction with the set of atomic coordinates. Application of the space warping method to energy minimization is discussed. Several simulations where the method is used to determine the energy minimizing structures of simple central force systems are analyzed. Comparing the results and behavior of the space warping method to simulations involving atomic coordinates only, it is found that the space warping method scales better with system size and also finds lower minima when the potential energy surface has multiple minima. It is shown that the transformation of [Ala16]+ in vacuo from linear to globular is captured efficiently using the space warping method.

Biopolymers↗
PubMedDate not supplied

Spiral K-space MR imaging of cortical activation.

Brain function can be mapped with magnetic resonance (MR) imaging sensitized to regional changes in blood oxygenation due to cortical activation. Several MR imaging methods, including conventional imaging and echo-planar imaging, have been successfully used for this purpose. The authors investigated spiral k-space MR imaging, implemented with an unmodified 1.5-T clinical imager, for imaging of cortical activation. A gradient-echo, spiral k-space imaging method was used to measure activation in the primary visual cortex (number sequence task), primary motor cortex (fist-clenching task), and prefrontal cortex (verbal fluency task). Comparison of conventional and spiral k-space imaging in the visual and motor cortex, in which signal-to-noise ratio, voxel size, and imaging time were matched, showed that artifacts were reduced with the spiral k-space method, while the area and degree of activation were similar. The number of sections that could be imaged in a fixed time interval was increased by a factor of four with this implementation of spiral k-space imaging compared with conventional imaging.

Brain Mapping↗
PubMedDate not supplied

Planar-motion correction with use of K-space data acquired in Fourier MR imaging.

The authors have developed a method for reducing magnetic resonance (MR) image artifacts caused by planar motion. Segments of k-space acquired with the subject stationary are detected automatically. Each k-space segment is Fourier transformed into an image in which rotational and translational displacements are measured manually. Before correction, k-space is made as Hermitian as allowed by the largest symmetric range of low spatial frequencies acquired with the subject stationary. Segments of k-space acquired with the subject in different positions are corrected separately. Although translation corrections can be applied effectively to both k-space and the spatial domain, rotation corrections are applied in the spatial domain to avoid image artifacts. To complement the correction, data corrupted by rotation are replaced by the complex conjugate of data of the opposite kappa x and kappa y, provided that these data have not been corrupted by rotation. The method reduced ghosts and blurring substantially on sagittal head images acquired with a standard spin-echo pulse sequence while a volunteer subject nodded his head.

Artifacts↗
PubMedDate not supplied

Cardiac imaging: comparison of two-shot echo-planar imaging with fast segmented K-space and conventional gradient-echo cine acquisitions.

We compared the cardiac image quality of multishot echo-planar imaging (EPI), segmented K-space, and conventional cine acquisitions. Three techniques were used to obtain gated multiphase acquisitions of an axial section traversing both ventricles in 10 volunteers: two-shot EPI acquired nonsequentially over two heart beats breath-held; segmented K-space cine with eight K-space lines acquired per cardiac trigger over 16 R-R intervals, also breath-held; and 24 cine phases obtained over 256 R-R intervals. Intraventricular SNRs with two-shot EPI were superior to segmented K-space cine acquisitions (P < .005) and not statistically different from conventional cine acquisitions (P < .1). Intraventricular signal was most homogeneous on conventional cine images (P < .05). Coronary artery visualization and myocardial delineation were better on the EPI image set than on segmented K-space cine images (P < .05). Two-shot EPI provides high-quality gated cardiac images with an acquisition time of only 2 seconds.

Adult↗
PubMedDate not supplied

The effects of time varying intravascular signal intensity and k-space acquisition order on three-dimensional MR angiography image quality.

The optimum infusion timing and k-space ordering for obtaining gadolinium-enhanced three-dimensional MR angiograms was determined through computer modeling using temporal contrast characteristics obtained from patient gadolinium infusion data. The effects of bolus timing were evaluated by varying the relationship between peak intravascular gadolinium concentration and the time at which the center of k space was acquired (tck) for sequential and centric acquisition techniques. Flow phantom experiments were performed to validate the theoretical computations. Gadolinium concentration at the time of central k-space acquisition determines intravascular signal intensity. Artifacts, including vessel broadening and edge ringing, depend on the order in which k space is collected and on how rapidly the gadolinium concentration changes. Artifacts are greatest when the center of k space is acquired before the intravascular gadolinium peak. Application of the optimal infusion timing results in preferential arterial enhancement with a minimum of artifacts in patients undergoing MR angiography.

Algorithms↗
PubMed2006

MR coronary vessel wall imaging: comparison between radial and spiral k-space sampling.

PURPOSE: To compare radial and spiral k-space sampling in navigator-gated ECG-triggered three-dimensional (3D) coronary vessel wall imaging. MATERIALS AND METHODS: The right coronary artery (RCA) vessel walls of eight healthy subjects were imaged using a modified double-inversion prepulse in concert with radial and spiral data acquisition. For data analysis, two investigators blinded to the sequence parameters subjectively assessed image quality in terms of artifacts and vessel wall visualization. Objective measures of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and vessel wall definition were also determined. RESULTS: Radial k-space sampling demonstrated fewer artifacts and led to improved visualization of the coronary vessel wall compared to spiral imaging (P < 0.05). This finding was also reflected in a better vessel wall definition using radial data acquisition (P < 0.05). SNR and CNR were found to be higher when spiral k-space sampling was used (n.s.). CONCLUSION: Radial k-space sampling in concert with free-breathing navigator-gated cardiac-triggered MRI of the coronary vessel wall resulted in fewer motion artifacts and improved vessel wall definition compared to spiral k-space sampling. The proposed approach therefore appears to be preferable.

Adult↗
PubMed2002

High b-value q-space analyzed diffusion-weighted MRI: application to multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) which affects nearly one million people worldwide, leading to a progressive decline of motor and sensory functions, and permanent disability. High b-value diffusion-weighted MR images (b of up to 14000 s/mm(2)) were acquired from the brains of controls and MS patients. These diffusion MR images, in which signal decay is not monoexponential, were analyzed using the q-space approach that emphasizes the diffusion characteristics of the slow-diffusing component. From this analysis, displacement and probability maps were constructed. The computed q-space analyzed MR images that were compared with conventional T(1), T(2) (fluid attenuated inversion recovery (FLAIR)), and diffusion tensor imaging (DTI) images were found to be sensitive to the pathophysiological state of white matter. The indices used to construct this q-space analyzed MR maps, provided a pronounced differentiation between normal tissue and tissues classified as MS plaques by the FLAIR images. More importantly, a pronounced differentiation was also observed between tissues classified by the FLAIR MR images as normal-appearing white matter (NAWM) in the MS brains, which are known to be abnormal, and the respective control tissues. The potential diagnostic capacity of high b-value diffusion q-space analyzed MR images is discussed, and experimental data that explains the consequences of using the q-space approach once the short pulse gradient approximation is violated are presented.

Animals↗
PubMed2002

Relationships between diffusion tensor and q-space MRI.

Fundamental relationships between diffusion tensor (DT) and 3D q-space MRI are derived which establish conditions when these two complementary MR methods are equivalent. It is shown that the displacement distribution measured by q-space MRI in both the large displacement (i.e., large r) and the long-wavelength (i.e., small q) limits is the same 3D Gaussian displacement distribution assumed in DT-MRI. In these limiting cases, q-space MR yields a dispersion tensor that is identical to the effective DT, D, measured in DT-MRI. An experiment is then proposed to measure D using q-space methods. These findings establish that the effective DT, measured in DT-MRI, characterizes molecule motions on a coarse length-scale. Finally, the feasibility of and requirements for performing 3D q-space MRI on a clinical scanner are considered.

Diffusion↗
PubMed2002

Changes in axonal morphology in experimental autoimmune neuritis as studied by high b-value q-space (1)H and (2)H DQF diffusion magnetic resonance spectroscopy.

Experimental autoimmune neuritis (EAN) has been studied in rat sciatic nerves by a combination of high b-value (1)H and (2)H double quantum filtered (DQF) diffusion MRS. The signal decays of water in the (1)H and (2)H DQF diffusion MRS were found to be not monoexponential and were analyzed using the q-space approach. The q-space analysis of the (1)H diffusion data detected two diffusing components, one having broad and the other having narrow displacement profiles. These components were shown to be very sensitive to the progression of EAN disease. The q-space parameters were found to be abnormal at day 9 postimmunization before the appearance of clinical signs. The assignment of the component with the narrow displacement profile to axonal water has been corroborated by the (2)H DQF diffusion MRS results. The displacement and the relative population of this slow and restricted diffusing component followed the processes of demyelination, axonal loss, and remyelination that occur in EAN. The displacements extracted from the slow-diffusing component with the narrow displacement correlated well with the average size of the axons as deduced from electron microscopy (EM). The component with the broad displacement showed significant changes which were attributed to the formation of endoneurial edema. This observation was also corroborated by the (2)H DQF diffusion MRS experiments. It seems, therefore, that q-space analysis of high b-values diffusion MRS is a promising new approach for early detection and better characterization of the different pathologies associated with EAN. This study demonstrates the utility of high-b-value q-space diffusion MRS for studying white matter-associated disorders in general.

Animals↗
PubMed2002

k-space interpretation of the Rose Model: noise limitation on the detectable resolution in MRI.

Noise limitation on the detected spatial resolution, described by the Rose Model, is well known in X-ray imaging and routinely used in designing X-ray imaging protocols. The purpose of this article is to revisit the Rose Model in the context of MRI where image data are acquired in the spatial frequency domain. A k-space signal-to-noise ratio (kSNR) is introduced to measure the relative signal and noise powers in a circular annulus in k-space. It is found that the kSNR diminishes rapidly with k-space radius. The Rose criterion that the voxel SNR approximately 4 is translated to kSNR cutoff values was tested using theoretical derivation and experimental histogram analysis. Experiments demonstrate that data acquisition beyond this cutoff k-space radius adds little or no information to the image. In order to reduce the noise limit on spatial resolution, the signal strength must be improved through means such as increasing the coil sensitivity, contrast enhancement, and signal averaging. This finding implies that the optimal k-space volume to be sampled or the optimal scan time in MRI should be matched to the relative SNR level.

Magnetic Resonance Imaging↗
PubMed2001

Motion artifact reduction and vessel enhancement for free-breathing navigator-gated coronary MRA using 3D k-space reordering.

Breathing-induced bulk motion of the myocardium during data acquisition may cause severe image artifacts in coronary magnetic resonance angiography (MRA). Current motion compensation strategies include breath-holding or free-breathing MR navigator gating and tracking techniques. Navigator-based techniques have been further refined by the applications of sophisticated 2D k-space reordering techniques. A further improvement in image quality and a reduction of relative scanning duration may be expected from a 3D k-space reordering scheme. Therefore, a 3D k-space reordered acquisition scheme including a 3D navigator gated and corrected segmented k-space gradient echo imaging sequence for coronary MRA was implemented. This new zonal motion-adapted acquisition and reordering technique (ZMART) was developed on the basis of a numerical simulation of the Bloch equations. The technique was implemented on a commercial 1.5T MR system, and first phantom and in vivo experiments were performed. Consistent with the results of the theoretical findings, the results obtained in the phantom studies demonstrate a significant reduction of motion artifacts when compared to conventional (non-k-space reordered) gating techniques. Preliminary in vivo findings also compare favorably with the phantom experiments and theoretical considerations. Magn Reson Med 45:645-652, 2001.

Adult↗