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PubMedDate not supplied

The effect of vascular curvature on three-dimensional reconstruction of intravascular ultrasound images.

OBJECTIVE: To characterize the effect of vessel curvature on the geometric accuracy of conventional three-dimensional reconstruction (3DR) algorithms for intravascular ultrasound image data. BACKGROUND: A common method of 3DR for intravascular ultrasound image data involves geometric reassembly and volumetric interpolation of a spatially related sequence of tomographic cross sections generated by an ultrasound catheter withdrawn at a constant rate through a vascular segment of interest. The resulting 3DR is displayed as a straight segment, with inherent vascular curvature neglected. Most vascular structures, however, are not straight but curved to some degree. For this reason, vascular curvature may influence the accuracy of computer-generated 3DR. METHODS: We collected image data using three different intravascular ultrasound catheters (2.9 Fr, 4.3 Fr, 8.0 Fr) during a constant-rate pullback of 1 mm/sec through tubing of known diameter with imposed radii of curvature ranging from 2 to 10 cm. Image data were also collected from straight tubing. Image data were digitized at 1.0-mm intervals through a length of 25 mm. Two passes through each radius of curvature were performed with each intravascular ultrasound catheter. 3DR lumen volume for each radius of curvature was compared to that theoretically expected from a straight cylindrical segment. Differences between 3DR lumen volume of theoretical versus curved (actual) tubes were quantified as absolute percentage error and categorized as a function of curvature. Tubing deformation error was quantified by quantitative coronary angiography (QCA). RESULTS: Volumetric errors ranged from 1% to 35%, with an inverse relationship demonstrated between 3DR lumen volume and segmental radius of curvature. Higher curvatures (r < 6.0 cm) induced greater lumen volume error when compared to lower curvatures (r > 6.0 cm). This trend was exhibited for all three catheters and was shown to be independent of tubing deformation artifacts. QCA-determined percentage diameter stenosis indicated no deformation error as a function of curvature. Total volumetric error contributed by tubing deformation was estimated to be 0.05%. CONCLUSIONS: Catheter-dependent geometrical error arises in three-dimensionally reconstructed timed linear pullbacks of intravascular ultrasound images due in part to uniplanar vascular curvature. Three-dimensional reconstruction of timed linear pullbacks is robust for vessels with low radii of curvature; however, careful interpretation of three-dimensional reconstructions from timed linear pullbacks for higher radii of curvature is warranted. These data suggest that methods of spatially correct three-dimensional reconstruction of intravascular ultrasound images should be considered when more pronounced vascular curvature is present.

Algorithms↗
PubMed1999

Humanization of a murine monoclonal antibody by simultaneous optimization of framework and CDR residues.

Optimal protein function often depends on co-operative interactions between amino acid residues distant in the protein primary sequence yet spatially near one another following protein folding. For example, antibody affinity is influenced by interactions of framework residues with complementarity-determining region (CDR) residues. However, despite the abundance of antibody structural information and computational tools the humanization of rodent antibodies for clinical use often results in a significant loss of affinity. To date, antibody engineering efforts have focused either on optimizing CDR residues involved in antigen binding or on optimizing antibody framework residues that serve critical roles in preserving the conformation of CDRs. In the present study a new approach which permits the rapid identification of co-operatively interacting framework and CDR residues was used to simultaneously humanize and optimize a murine antibody directed against CD40. Specifically, a combinatorial library that examined eight potentially important framework positions concomitantly with focused CDR libraries consisting of variants containing random single amino acid mutations in the third CDR of the heavy and light chains was expressed. Multiple anti-CD40 Fab variants containing as few as one murine framework residue and displaying up to approximately 500-fold higher affinity than the initial chimeric Fab were identified. The higher affinity humanized variants demonstrated a co-operative interaction between light chain framework residue Y49 and heavy chain CDR3 residue R/K101 (coupling energy, DeltaGI=0.9 kcal/mol). Screening of combinatorial framework-CDR libraries permits identification of monoclonal antibodies (mAb) with structures optimized for function, including instances in which the antigen induces conformational changes in the mAb. Moreover, the enhanced humanized variants contain fewer murine framework residues and could not be identified by sequential in vitro humanization and affinity muturation strategies. This approach to identifying co-operatively interacting residues is not restricted to antibody-antigen interactions and consequently, may be used broadly to gain insight into protein structure-function relationships, including proteins that serve as catalysts.

Amino Acid Sequence↗
PubMed2000

A weighted least-squares algorithm for estimation and visualization of relative latencies in event-related functional MRI.

The properties of the hemodynamic latencies in functional maps have been relatively unexplored. Accurate methods of estimating hemodynamic latencies are needed to take advantage of this feature of fMRI. A fully automated, weighted least-squares (WLS) method for estimating temporal latencies is reported. Using a weighted linear model, the optimal latency and amplitude of the fMRI response can be determined for those voxels that pass a detection threshold. There is evidence from previous studies that the hemodynamic response may be time-locked to the stimulus within certain limits, less variable earlier in its evolution, and able to resolve information about relative hemodynamic timing. This information can be used to test hypotheses about the sequence and spatial distribution of neural activity. The method can be used to weight the earliest evolution of the hemodynamic response more heavily and decrease bias resulting from the hemodynamic response function. Additionally, the WLS method can control for varying response shapes across the brain and improve latency comparisons between brain regions. The WLS method was developed to study the properties of hemodynamic latencies, which may be increasingly important as event-related fMRI continues to be advanced.

Algorithms↗
PubMed1991

Ultrastructural and morphometric analysis of the separation of two thigh muscles in the chick.

Limb muscles separate from one another in a complex but highly stereotyped sequence and spatial pattern. The process of separation is characterized by the progression of a region of increased extracellular space, the cleavage zone, along the proximodistal axis between the individual muscle anlagen. We analyzed ultrastructurally the muscles and cleavage zone during the separation of two representative muscles, the developing sartorius and iliotibialis in the chick thigh, to establish an accurate baseline for an analysis of the mechanisms of separation. Comparisons of the morphology and distribution of cells before and after separation show no evidence that muscles became separated by the massive influx of an exterior cell population; if populations invade the cleavage zone, they are small. We do find characteristic transitions within the cell population of the cleavage zone in situ that could accomplish cleavage without invoking massive cell movements. These progressive transitions within the cleavage zone include a loss of close cell-cell interactions, an increase in extracellular space, the assumption of a more stellate morphology by mesenchyme cells, and a gradual alteration in the composition of the extracellular matrix from one typical of early muscle to one typical of loose connective tissue. Myotubes do differentiate between the incipient muscles, ruling out the possibility that the location where muscles will separate is defined by sites where myotubes fail to differentiate. Instead, the myotubes in the cleavage zone gradually diminish in number and appear to be specifically recognized and removed from the cleavage zone by phagocytes. We suggest that the transitions within the cleavage zone, including the loss of muscle cells, are a result of the progressive differentiation of loose connective tissue. If so, then the spatial pattern and process of cleavage is a consequence of spatially programmed cell differentiation.

Animals↗
PubMed1996

Observing N-acetyl aspartate via both its N-acetyl and its strongly coupled aspartate groups in in vivo proton magnetic resonance spectroscopy.

The approximately 2.6 ppm aspartate multiplet of N-acetyl aspartate (NAA) is considered a potential source of additional information on N-acetyl aspartate in vivo. Because the aspartate multiplet is the AB part of a strongly coupled ABX system it gives rise, as is shown in the analysis presented, to a significant field-strength dependence in the echo-time-dependent modulations of the response to typical spatial-localization sequences. The echo-time dependence of this response is developed analytically, not only for the STEAM and the PRESS localization sequences, but also for a spin-echo sequence. It is then verified experimentally at 2.35 T. The field-strength dependence of the response is demonstrated by evaluating the changes in the echo-time-dependent responses to each of the three sequences at field strengths of 1.5, 2.35, and 4.0 T. By means of these results, the preferred sequence (PRESS) can be optimized for the NAA aspartate multiplet at each field strength, as is illustrated with the human brain spectra obtained in vivo at 1.5 T. These in vivo spectra compare the optimal, long TE timing (163 ms) with a suboptimal TE (70 ms), for the observation of the approximately 2.6 ppm aspartate resonances of NAA.

Aspartic Acid↗
PubMed1995

A mechanochemical model for adult dermal wound contraction and the permanence of the contracted tissue displacement profile.

The healing of adult mammalian skin wounds involves a complex sequence of spatially and temporally coordinated processes. Wound contraction, by reducing the size of the injury, is an intrinsic component of full-thickness excisional dermal wound healing. The underlying biomechanics of wound contraction, however, are not fully understood, and little is known about the pathogenesis of severe medical conditions known as fibrocontractive diseases. The aim of this work is to investigate a deterministic mathematical model in order to obtain insight into the mechanistic relationships between wound contraction and associated normal and pathological healing processes. The model describes the essential roles of fibroblast and myofibroblast cells, a chemical growth factor and the extracellular matrix which includes type I collagen. The model results are qualitatively consistent with the biology of fibroplasia and wound contraction. It is shown that a contracted state evolves during a (long) transient phase of healing known as "proliferation", while collagen kinetics are fundamental to the considerably longer "remodelling" phase. Some quantitative results, notably on the evolution of wound contraction, compare favourably with experimental data. Application of the model to adult human dermal wound healing in vivo, with a greater understanding of the underlying biological mechanisms involved, may suggest strategies for controlling contraction and fibrocontractive diseases.

Adult↗
PubMed1985

Control of DNA replication and spatial distribution of defined DNA sequences in salivary gland cells of Drosophila melanogaster.

In dividing cells, each sequence replicates exactly once in each S-phase, but in cells with polytene chromosomes, some sequences may replicate more than once or fail to replicate during S-phase. Because of this differential replication, the control of replication in polytene cells must have some unusual features. Dennhöfer (1982a) has recently concluded that the total DNA content of the polytene cells of Drosophila salivary glands exactly doubles in each S-phase. This observation, along with previous studies demonstrating satellite underreplication in salivary gland cells, led us to consider the hypothesis that there is a "doubling of DNA" mechanism for the control of DNA replication in polytene cells. With this mechanism, a doubling of DNA content, rather than the replication of each sequence, would signal the end of a cycle of DNA replication. To test this hypothesis, we have reinvestigated the replication of several sequences (satellite, ribosomal, histone and telomere) in salivary gland cells using quantitative in situ hybridization. We find that underreplication of some sequences does occur. In addition we have repeated Dennhöfer's cytophotometric and labeling studies. In contrast to Dennhöfer, we find that the total DNA contents of nonreplicating nuclei do reflect this partial replication, in accord with Rudkin's (1969) result. We conclude that DNA replication in polytene cells is controlled by modifications of the mechanism operating in dividing cells, where control is sequence autonomous, and not by a "doubling of DNA" mechanism. In situ hybridization to unbroken salivary gland nuclei reveals the distribution of specific sequences. As expected, satellite, histone and 5S sequences are usually in a single cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Dual role of calmodulin in excitable cells.

Consideration of the enzymatic reactions governing calcium channel phosphorylation and dephosphorylation leads one to deduce that there exist separate groups of enzymes, membrane-bound and cytoplasmic that are activated by a common mediator, calmodulin (CaM), whose time-dependent appearance (via diffusion) at both locales is controlled by both intracellular calcium levels and electrostatic interaction with the membrane. In brief, the change in the sign and extent of the electrical charge borne by the modulator in the presence of calcium (Ca) brings about the electrostatic attraction that enables the transport of [Ca-CaM] to the membrane. This translocation of Ca-CaM makes possible a sequential activation of cellular enzymes whose locations differ. The sequence, both spatial and temporal, of the activation of various cellular enzymes by Ca-CaM appears to be a control network shared in common by excitable cells containing a stimulus-response pathway mediated by second messengers.

Adenylyl Cyclases↗
PubMed2000

A neural mechanism of hierarchical discrimination of odors in the olfactory cortex based on spatiotemporal encoding of odor information.

We propose a neural mechanism for discrimination of different complex odors in the olfactory cortex based on the dynamical encoding scheme. Both constituent molecules of the odor and their mixing ratios are encoded simultaneously into a spatiotemporal activity pattern (limit cycle attractor) in the olfactory bulb [Hoshino O, Kashimori Y, Kambara T (1998) Biol Cybern 79:109-120]. We present a functional model of the olfactory cortex consisting of some dynamical mapping modules. Each dynamical map is represented by itinerancy among the limit cycle attractors. When a temporal sequence of spatial activity patterns corresponding to a complex odor is injected from the bulb to the network of the olfactory cortex, the neural activity state of each mapping module is fixed to a relevant spatial pattern injected. Recognition of an odor is accomplished by a combination of firing patterns fixed in all the mapping modules. The stronger the response strength of the component, the earlier the component is recognized. The hierarchical discrimination of an odor is made by recognizing the components in order of decreasing response strengths.

Discrimination Learning↗
PubMed1990

Topographic segmentation of waking EEG in medication-free schizophrenic patients.

Lehmann has demonstrated that EEG topography can be used to segment EEG map series into a sequence of spatially stationary segments characterized by location of potential maxima and minima. We employed topographic segmentation techniques to study 9 channel EEGs recorded from 11 medication-free schizophrenic patients and 10 normal controls during resting and active task conditions, retesting 8 patients after neuroleptic treatment. To define EEG segments, average reference potential maps corresponding to global field power peaks in theta, alpha, and low beta activity were classified according to locations of extreme minimum and maximum values. Normals and schizophrenics did not differ in the number or types of switches between segments, or the frequency of hemisphere crossing of potential extrema. However, EEGs of normal subjects were characterized by significantly more (P less than 0.003) unused theta segment types (of a theoretically possible 36). Moreover, medication significantly (P less than 0.02) increased the number of unused theta segment types in EEGs of schizophrenics. We interpret these findings as evidence of increased spatial variability of brain electrical activity in schizophrenics and discuss their functional implications.

Adult↗
PubMed1993

MR imaging of fat-containing tissues: valuation of two quantitative imaging techniques in comparison with localized proton spectroscopy.

Since lipid protons, consisting mainly of triacylglycerols (TAG), are rather mobile, magnetic resonance imaging (MRI) is ideally suited for the examination of fat-containing tissues such as bone marrow. In contrast to water protons, however, lipid protons are chemically distinct and give rise to at least eight resonance peaks with different T1 and T2 relaxation times in the 1H spectrum. This is why the characterization of fat-containing tissues by quantitative MRI is much more difficult than that of most other tissues. In our study we wanted to examine the accuracy and the potential of a 1H chemical shift imaging (CSI) technique and a multiple spin-echo imaging (MSEI) technique. A stimulated-echo (STEAM) sequence for spatially localized proton spectroscopy was used as the reference method. In the first part of this paper, we describe quantitative imaging experiments which were performed to assess the accuracy of the fat-water separation according to the Dixon method and the bi-exponential decomposition of the MSEI data. For that purpose, we used a two-compartment phantom filled with either an aqueous Gd-DTPA solution and vegetable oil or with two different aqueous Gd-DTPA solutions, respectively. The analysis of the 1H CSI data revealed that the presence of non-methylen protons in neutral fats leads to a slight under-estimation (of about 15%) of the relative fat fraction. The error is described theoretically and verified quantitatively by STEAM measurements. The bi-exponential analysis of the transverse relaxation data, on the other hand, yields reliable T2 values if the relative proton density of both components is higher than 15%. IN the second part of our investigation, the same techniques were applied to acquire data from the subcutaneous fatty tissue, the femoral head, and the lumbar vertebrae of three healthy volunteers. In the bone marrow spectra, only two broad resonances could be resolved; they were superpositions of diverse molecular groups with different T1 and T2 relaxation times. In these cases, localized proton spectroscopy does not provide additional information with respect to 1H CSI. The MSEI data of the three examined fat containing tissue regions were adequately fitted by a bi-exponential function despite the fact that there were much more chemically distinct protons present in fatty tissues.

Adipose Tissue↗
PubMed1996

Visualizing the spatial relationships between defined DNA sequences and the axial region of extracted metaphase chromosomes.

Using fluorescence in situ hybridization to extracted metaphase chromosomes, we present visual evidence that specific human DNA sequences occupy distinctive positions with respect to the axial region of chromosomes and that the DNA is organized into loops emanating from this region. In a stretch of unique DNA on chromosome 11, large loops of DNA can be traced and one specific region associated with the axial region of the chromosome. Within rDNA, nontranscribed spacer sequences are more closely apposed to the chromosome axis than are rRNA genes. Heterochromatic and euchromatic DNAs appear to be organized into loops of similar size. We could not detect loops at centromeres; most alphoid DNA appears to remain close to the axial region.

Centromere↗
PubMedDate not supplied

Phosphorylation of tau, Abeta-formation, and apoptosis after in vivo inhibition of PP-1 and PP-2A.

Chronic inhibition of protein phosphatases 1 and 2A in vivo was induced by infusion of okadaic acid into lateral ventricles of rat brain for up to 4 months. Cytoskeletal pathology, alterations of the amyloid precursor protein, and apoptotic cell death induced by this treatment followed a certain sequence and spatial distribution. Changes in the expression, phosphorylation, and subcellular distribution of neurofilament proteins and tau, as well as first signs of apoptotic cell death, occurred already after about 2 weeks. The distribution of apoptotic cells, however, was different from those revealing a high accumulation of hyperphosphorylated tau, indicating that those cytoskeletal pathology had no obvious sequelae for the viability of these neurones. A continuation of treatment for longer than 2 weeks induced diffuse deposits of both hyperphosphorylated tau and A beta-amyloid-immunoreactive material in white matter areas that increased in size and number over time. Because tau-phosphorylation is a regulator of the dynamic stability of microtubules, the pathology observed in the present experimental paradigm in the white matter might be viewed as an indication of a disturbed axonal transport. It is hypothesized that perturbations of the axonal transport might also be critically involved in the formation of paired helical filaments and amyloid deposits in Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed1998

The latest in ultrasound: three-dimensional imaging. Part II.

INTRODUCTION: The three-dimensional (3D) reconstruction of ultrasound images has become a widespread option in ultrasound equipment. Specific softwares have become available and 3D reconstruction feasible since the early 1990s, particularly since 1994. POSSIBLE CLINICAL APPLICATIONS: Several clinical applications are feasible in all parenchymatous organs (mainly the liver and prostate), hollow viscera (e.g. the bladder and gallbladder), peripheral vessels (supra-aortic trunks and limb vessels) and central (the aorta and iliac arteries) or cerebral vessels. Moreover, tumoral vessels in parenchymatous organs can be reconstructed, and even the fetus in the uterine cavity, with excellent detailing. The recent introduction of echocontrast agents and second harmonic imaging has permitted to study normal and abnormal peripheral, central and parenchymatous vessels, with similar patterns to those obtained with digital angiography. The spatial relationships between the vascular structures of the liver, kidney and placenta were studied with 3D ultrasound angiograms. The applications of this new technique include the analysis of vascular anatomy and the potential assessment of organ perfusion. THE LATEST APPLICATIONS--INTRAVASCULAR STUDIES: Some catheters with an ultrasound transducer in the tip have been tested for intravascular studies. Just like conventional transducers, they provide two-dimensional (2D) images which are then postprocessed into longitudinal 3D or volume reconstructions. The former resemble angiographic images and can be viewed 3D rotating the image along its longitudinal axis. Volume images, which are more complex and slower to obtain, can be rotated on any spatial plane and provide rich detailing of the internal vascular lumen. The clinical importance of intravascular ultrasound with 3D volume reconstructions lies in the diagnosis of vascular conditions and the assessment and monitoring of intravascular interventional procedures--e.g. to detect inaccurate deployment of intravascular stents and endoluminal grafts during the maneuver. Three-dimensional reconstructions involve geometric data assembly and volumetric interpolation of a spatially related sequence of tomographic cross sections generated by an ultrasound catheter withdrawn at a constant rate through a vascular segment of interest, resulting in the display of a straight segment. Therefore particular care is needed and there are some useful hints to avoid mistakes. CONCLUSIONS: Three dimensional reconstructions of B-mode and color Doppler images are no longer a work in progress and their clinical importance and possible applications are both established and ever-increasing. On the other hand, independent of the different types of energy used, also computed tomography and magnetic resonance 3D reconstructions are very useful from a clinical viewpoint and they have become an established routine technique for both these methods. It is very likely that 3D volume reconstructions in ultrasound will find numerous applications in the near future. They may help to increase the diagnostic confidence and to facilitate diagnosis, intraprocedure monitoring in interventional radiology and follow-up and also to reduce the number of invasive examinations with iodinated contrast agents. This could result in cutting the cost and duration of the most expensive examinations. New, although invasive, applications can be hypothesized for intravascular or intraluminal catheters with an ultrasound transducer inside.

Blood Vessels↗
PubMed2000

Dynamic brain topography of somatosensory evoked potentials and equivalent dipoles in response to graded painful skin and muscle stimulation.

The differential effects of painful stimulation of skin vs. muscle on the cerebral electrophysiology have been poorly described. This study examined the somatosensory evoked potentials (SEPs) and the associated dipole models of non-painful and graded painful electrical stimulation applied to the skin and muscle in 20 healthy subjects. With the psychophysical stimulus-response functions determined, the skin stimulation showed a steeper slope than muscle stimulation. For both types of stimulation, the SEPs indicated a similar temporo-spatial activation sequence: F4/N90-P4/P95, Fc2/N135, Cz/P250, Cz/P300, and Cz/N460. The SEP amplitudes increased significantly with the stimulus intensities in these components. The peak SEP latencies of skin stimulation were in general shorter than that of muscle stimulation. The SEP amplitudes to skin stimulation were significantly larger than those caused by muscle stimulation at every stimulus intensity level, except the early mid-latency component. In this case, muscle stimulation caused higher amplitudes over the contralateral parietal-frontal sites. For both types of stimulation, the topographic maps were quite similar. Equivalent dipole modeling revealed identical site parameters (<1.0 cm) between skin and muscle stimulation. However, the electrical skin stimulation did not correlate with the pain intensity. Pain intensity, in contrast, was uniquely associated with the Cz/P250 amplitudes for the muscle stimulation. It is concluded that non-nociceptive and nociceptive electrical stimuli applied to skin and muscle are processed in the common cerebral areas, but exhibit differential SEP effects.

Adult↗
PubMed1996

Correct Hox gene expression established independently of position in Caenorhabditis elegans.

The Hox genes are expressed in a conserved sequence of spatial domains along the anteroposterior (A/P) body axes of many organisms. In Drosophila, position-specific signals located along the A/P axis establish the pattern of Hox gene expression. In the nematode Caenorhabditis elegans, it is not known how the pattern of Hox gene expression is established. C. elegans uses lineal control mechanisms and local cell interactions to specify early blastomere identities. However, many cells expressing the same Hox gene are unrelated by lineage, suggesting that, as in Drosophila, domains of Hox gene expression may be defined by cell-extrinsic A/P positional signals. To test this, we have investigated whether posterior mesodermal and ectodermal cells will express their normal posterior Hox gene when they are mispositioned in the anterior. Surprisingly, we find that correct Hox gene expression does not depend on cell position, but is highly correlated with cell lineage. Thus, although the most striking feature of Hox gene expression is its positional specificity, in C. elegans the pattern is achieved, at least in part, by a lineage-specific control system that operates without regard to A/P position.

Animals↗