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Backbone and methyl dynamics of the regulatory domain of troponin C: anisotropic rotational diffusion and contribution of conformational entropy to calcium affinity.

The N-terminal domain (residues 1 to 90) of chicken skeletal troponin C (NTnC) regulates muscle contraction upon the binding of a calcium ion to each of its two calcium binding loops. In order to characterize the backbone dynamics of NTnC in the apo state (NTnC-apo), we measured and carefully analyzed 15N NMR relaxation parameters T1, T2 and NOE at 1H NMR frequencies of 500 and 600 MHz. The overall rotational correlation time of NTnC-apo at 29.6 degrees C is 4.86 (+/-0.15) ns. The experimental data indicate that the rotational diffusion of NTnC-apo is anisotropic with a diffusion anisotropy, D parallel/D perpendicular, of 1.10. Additionally, the dynamic properties of side-chains having a methyl group were derived from 2H relaxation data of CH2D groups of a partially deuterated sample. Based on the dynamic characteristics of TnC, two different levels of "fine tuning" of the calcium affinity are presented. Significantly lower backbone order parameters (S2), were observed for calcium binding site I relative to site II and the contribution of the bond vector fluctuations to the conformational entropy of sites I and II was calculated. The conformational entropy loss due to calcium binding (DeltaDeltaSp) differs by 1 kcal/mol between sites I and II. This is consistent with the different dissociation constants previously measured for sites I and II of 16 microM and 1. 7 microM, respectively. In addition to the direct role of binding loop dynamics, the side-chain methyl group dynamics play an indirect role through the energetics of the calcium-induced structural change from a closed to an open state. Our results show that the side-chains which will be exposed upon calcium binding have reduced motion in the apo state, suggesting that conformational entropic contributions can be used to offset the free energy cost of exposing hydrophobic groups. It is clear from this work that a complete determination of their dynamic characteristics is necessary in order to fully understand how TnC and other proteins are fine tuned to appropriately carry out their function.

Animals↗

Towards a complete description of the structural and dynamic properties of the denatured state of barnase and the role of residual structure in folding.

The detailed characterization of denatured proteins remains elusive due to their mobility and conformational heterogeneity. NMR studies are beginning to provide clues regarding residual structure in the denatured state but the resulting data are too sparse to be transformed into molecular models using conventional techniques. Molecular dynamics simulations can complement NMR by providing detailed structural information for components of the denatured ensemble. Here, we describe three independent 4 ns high-temperature molecular dynamics simulations of barnase in water. The simulated denatured state was conformationally heterogeneous with respect to the conformations populated both within a single simulation and between simulations. Nonetheless, there were some persistent interactions that occurred to varying degrees in all simulations and primarily involved the formation of fluid hydrophobic clusters with participating residues changing over time. The region of the beta(3-4) hairpin contained a particularly high degree of such side-chain interactions but it lacked beta-structure in two of the three denatured ensembles: beta(3-4) was the only portion of the beta-structure to contain significant residual structure in the denatured state. The two principal alpha-helices (alpha1 and alpha2) adopted dynamic helical structure. In addition, there were persistent contacts that pinched off core 2 from the body of the protein. The rest of the protein was unstructured, aside from transient and mostly local side-chain interactions. Overall, the simulated denatured state contains residual structure in the form of dynamic, fluctuating secondary structure in alpha1 and alpha2, as well as fluctuating tertiary contacts in the beta(3-4) region, and between alpha1 and beta(3-4), in agreement with previous NMR studies. Here, we also show that these regions containing residual structure display impaired mobility by both molecular dynamics and NMR relaxation experiments. The residual structure was important in decreasing the conformational states available to the chain and in repairing disrupted regions. For example, tertiary contacts between beta(3-4) and alpha1 assisted in the refolding of alpha1. This contact-assisted helix formation was confirmed in fragment simulations of beta(3-4) and alpha1 alone and complexed, and, as such, alpha1 and beta(3-4) appear to be folding initiation sites. The role of these sites in folding was investigated by working backwards and considering the simulation in reverse, noting that earlier time-points from the simulations provide models of the major intermediate and transition states in quantitative agreement with data from both unfolding and refolding experiments. Both beta(3-4) and alpha1 are dynamic in the denatured state but when they collide and make enough contacts, they provide a loose structural scaffold onto which further beta-strands pack. The beta-structure condenses about beta(3-4), while alpha1 aids in stabilizing beta(3-4) and maintaining its orientation. The resulting beta-structure is relatively planar and loose in the major intermediate. Further packing ensues, and as a result the beta-sheet twists, leading to the major transition state. The structure is still expanded and loops are not well formed at this point. Fine-tuning of the packing interactions and the final condensation of the structure then occurs to yield the native state.

Amino Acid Sequence↗

Binding free energies and free energy components from molecular dynamics and Poisson-Boltzmann calculations. Application to amino acid recognition by aspartyl-tRNA synthetase.

Specific amino acid binding by aminoacyl-tRNA synthetases (aaRS) is necessary for correct translation of the genetic code. Engineering a modified specificity into aminoacyl-tRNA synthetases has been proposed as a means to incorporate artificial amino acid residues into proteins in vivo. In a previous paper, the binding to aspartyl-tRNA synthetase of the substrate Asp and the analogue Asn were compared by molecular dynamics free energy simulations. Molecular dynamics combined with Poisson-Boltzmann free energy calculations represent a less expensive approach, suitable for examining multiple active site mutations in an engineering effort. Here, Poisson-Boltzmann free energy calculations for aspartyl-tRNA synthetase are first validated by their ability to reproduce selected molecular dynamics binding free energy differences, then used to examine the possibility of Asn binding to native and mutant aspartyl-tRNA synthetase. A component analysis of the Poisson-Boltzmann free energies is employed to identify specific interactions that determine the binding affinities. The combined use of molecular dynamics free energy simulations to study one binding process thoroughly, followed by molecular dynamics and Poisson-Boltzmann free energy calculations to study a series of related ligands or mutations is proposed as a paradigm for protein or ligand design. The binding of Asn in an alternate, "head-to-tail" orientation observed in the homologous asparagine synthetase is analyzed, and found to be more stable than the "Asp-like" orientation studied earlier. The new orientation is probably unsuitable for catalysis. A conserved active site lysine (Lys198 in Escherichia coli) that recognizes the Asp side-chain is changed to a leucine residue, found at the corresponding position in asparaginyl-tRNA synthetase. It is interesting that the binding of Asp is calculated to increase slightly (rather than to decrease), while that of Asn is calculated, as expected, to increase strongly, to the same level as Asp binding. Insight into the origin of these changes is provided by the component analyses. The double mutation (K198L,D233E) has a similar effect, while the triple mutation (K198L,Q199E,D233E) reduces Asp binding strongly. No binding measurements are available, but the three mutants are known to have no ability to adenylate Asn, despite the "Asp-like" binding affinities calculated here. In molecular dynamics simulations of all three mutants, the Asn ligand backbone shifts by 1-2 A compared to the experimental Asp:AspRS complex, and significant side-chain rearrangements occur around the pocket. These could reduce the ATP binding constant and/or the adenylation reaction rate, explaining the lack of catalytic activity in these complexes. Finally, Asn binding to AspRS with neutral K198 or charged H449 is considered, and shown to be less favorable than with the charged K198 and neutral H449 used in the analysis.

Amino Acid Substitution↗

The Role of Weak Interactions in Biological Systems: the Dual Dynamics Model.

The dual dynamics model is a random autonomous network of nodes whose dynamical behavior is determined by both strong and weak interactions. The model combines discrete decision-making features reflective of logical operations with arithmetic features that represent graded influences. Dual dynamics abstracts the ubiquitous fact that biological systems at all levels of organization consist of components that respond both to specific (strong) signals and to the cumulative effect of numerous weak interactions. We have thoroughly studied the dynamical characteristics of three-valued dual dynamics networks in the range from four to 14 nodes and have compared these characteristics to those of non-boolean three-valued networks (without weak interaction) and to Kauffman boolean networks. Properties studied include: attractor length, number of attractors, basin sizes, orbital stability, and evolutionary transformability in response both to individual and cumulative mutations (where mutations are implemented as random changes in the response of a node to the pattern of strong influences impinging on it). The introduction of weak interactions and their manner of coupling to strong interactions has major altering effects on these properties. With suitable coupling it is possible to significantly enhance equifinality and evolutionary transformability. The model demonstrates that self-organizing dynamics are compatible with evolutionary plasticity when weak interactions are taken into account.Copyright 1998 Academic Press

Journal Article↗

Consequences of plant-herbivore coevolution on the dynamics and functioning of ecosystems.

The potential consequences of plant-herbivore coevolution for ecosystem functioning are investigated using a simple nutrient-limited ecosystem model in which plant and herbivore traits are subject to adaptive dynamics. Although the ecological model is very simple and always reaches a stable equilibrium in the absence of evolution, coevolution can generate a great diversity of dynamical behaviors. The evolutionary dynamics can lead to a stable equilibrium. If the evolution of plants is fast enough, certain values of the trade-off parameters lead to complex evolutionary cycles bounded by physiological constraints. The dynamical behavior of the model is very different when the dynamics of inorganic nutrient is ignored and plant competition is modeled by a logistic growth function. This emphasizes the importance of including explicit nutrient dynamics in studies of plant-herbivore coevolution.

Adaptation, Biological↗

Usefulness of turbo-FLASH dynamic MR imaging of dissecting aneurysms of the thoracic aorta.

PURPOSE: We attempted to determine whether Turbo-FLASH dynamic magnetic resonance imaging is clinically useful for the diagnosis of dissecting aneurysm of the thoracic aorta by differentiating slow flow from thrombus in the false lumen. METHODS: Magnetic resonance imaging (MRI) was performed in ten patients using three different pulse sequences (spin echo, cine and turbo-FLASH dynamic MRI). The three imaging techniques were compared for their ability to demonstrate anatomical and hemodynamic abnormalities by visual assessment. RESULTS: In all patients with thrombus in the false lumen, the thrombus was accurately differentiated from slow flow on contrast enhanced turbo-FLASH dynamic MRI, but only with difficulty on spin echo and cine MRI. Dynamic MRI was also useful for the evaluation of flow dynamics in the false lumen. CONCLUSION: Turbo-FLASH dynamic MRI is recommended for patients with dissecting aneurysm of the thoracic aorta, not definitely diagnosed by spin echo and cine MRI.

Aged↗

Simulation study on dynamics transition in neuronal activity during sleep cycle by using asynchronous and symmetry neural network model.

We have found that single neuronal activities in different regions in the brain commonly exhibit the distinct dynamics transition during sleep-waking cycle in cats. Especially, power spectral densities of single neuronal activities change their profiles from the white to the 1/f along with sleep cycle from slow wave sleep (SWS) to paradoxical sleep (PS). Each region has different neural network structure and physiological function. This suggests a globally working mechanism may be underlying the dynamics transition we concern. Pharmacological studies have shown that a change in a wide-spread serotonergic input to these regions possibly causes the neuronal dynamics transition during sleep cycle. In this paper, based on these experimental results, an asynchronous and symmetry neural network model including inhibitory input, which represents the role of the serotonergic system, is utilized to examine the reality of our idea that the inhibitory input level varying during sleep cycle induce that transition. Simulation results show that the globally applied inhibitory input can control the dynamics of single neuronal state evolution in the artificial neural network: 1/f-like power spectral density profiles result under weak inhibition, which possibly corresponds to PS, and white profiles under strong inhibition, which possibly corresponds to SWS. An asynchronous neural network is known to change its state according to its energy function. The geometrical structure of network energy function is thought to vary along with the change in inhibitory level, which is expected to cause the dynamics transition of neuronal state evolution in the network model. These simulation results support the possibility that the serotonergic system is essential for the dynamics transition of single neuronal activities during sleep cycle.

Animals↗

Creative dynamics approach to neural intelligence.

The thrust of this paper is to introduce and discuss a substantially new type of dynamical system for modelling biological behavior. The approach was motivated by an attempt to remove one of the most fundamental limitations of artificial neural networks-their rigid behavior compared with even simplest biological systems. This approach exploits a novel paradigm in nonlinear dynamics based upon the concept of terminal attractors and repellers. It was demonstrated that non-Lipschitzian dynamics based upon the failure of Lipschitz condition exhibits a new qualitative effect--a multi-choice response to periodic external excitations. Based upon this property, a substantially new class of dynamical systems--the unpredictable systems--was introduced and analyzed. These systems are represented in the form of coupled activation and learning dynamical equations whose ability to be spontaneously activated is based upon two pathological characteristics. Firstly, such systems have zero Jacobian. As a result of that, they have an infinite number of equilibrium points which occupy curves, surfaces or hypersurfaces. Secondly, at all these equilibrium points, the Lipschitz conditions fails, so the equilibrium points become terminal attractors or repellers depending upon the sign of the periodic excitation. Both of these pathological characteristics result in multi-choice response of unpredictable dynamical systems. It has been shown that the unpredictable systems can be controlled by sign strings which uniquely define the system behaviors by specifying the direction of the motions in the critical points. By changing the combinations of signs in the code strings the system can reproduce any prescribed behavior to a prescribed accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial Intelligence↗

The fractional-order dynamics of brainstem vestibulo-oculomotor neurons.

The vestibulo-ocular reflex (VOR) and other oculomotor subsystems such as pursuit and saccades are ultimately mediated in the brainstem by premotor neurons in the vestibular and prepositus nuclei that relay eye movement commands to extraocular motoneurons. The premotor neurons receive vestibular signals from canal afferents. Canal afferent frequency responses have a component that can be characterized as a fractional-order differentiation (dkx/dtk where k is a nonnegative real number). This article extends the use of fractional calculus to describe the dynamics of motor and premotor neurons. It suggests that the oculomotor integrator, which converts eye velocity into eye position commands, may be of fractional order. This order is less than one, and the velocity commands have order one or greater, so the resulting net output of motor and premotor neurons can be described as fractional differentiation relative to eye position. The fractional derivative dynamics of motor and premotor neurons may serve to compensate fractional integral dynamics of the eye. Fractional differentiation can be used to account for the constant phase shift across frequencies, and the apparent decrease in time constant as VOR and pursuit frequency increases, that are observed for motor and premotor neurons. Fractional integration can reproduce the time course of motor and premotor neuron saccade-related activity, and the complex dynamics of the eye. Insight into the nature of fractional dynamics can be gained through simulations in which fractional-order differentiators and integrators are approximated by sums of integer-order high-pass and low-pass filters, respectively. Fractional dynamics may be applicable not only to the oculomotor system, but to motor control systems in general.

Brain Stem↗

The characteristics of cerebral meningiomas and surrounding tissues on dynamic CT.

Dynamic CT was utilized to evaluate 11 patients with histologically benign meningiomas. While it was found that all demonstrated macroscopic neovascularity, subtle differences in the dynamic perfusion curves were identified both between different meningiomas and from region to region within the same tumor. Other than basic anatomic differences, these changes may reflect intratumoral ischemia and hypothetically herald cystic/necrotic alteration within the neoplasm. The dynamic calculations over the surrounding brain showed areas of gross hyper- and hypoperfused cerebral cortex, and hypoperfused white matter in regions of peritumoral edema. These latter findings are of uncertain clinical importance. The dynamic examination also confirmed cases of dural venous sinus invasion and calvarial permeation by tumor. In addition, the dynamic series showed macroscopic neovascularity in one case with a completely negative selective cerebral arteriogram. It is felt that certain cases which have previously been evaluated by static CT may benefit from further study utilizing the dynamic method.

Adult↗

Effects of pre-motion electromyographic silent period on dynamic force exertion during a rapid ballistic movement in man.

The effects of pre-motion silent period (PSP) on dynamic force exertion were studied in ten healthy subjects performing ballistic elbow extensions. The experiments were designed to evaluate the significance of mean differences between the averaged dynamic force curves of two groups: PSP-presence groups and PSP-absence groups. The presence of PSP was judged quantitatively and automatically by means of a newly developed method using statistical analysis. The results indicated that there were two effects of PSP on dynamic force exertion: one was a reducing effect, observed prior to the movement; the other was a reinforcing effect, observed in the first part of the ballistic movement. The duration of the reinforcement was significantly correlated with the duration of the reducing effect of PSP. The findings suggested that the reinforcement of dynamic force may be produced by the pre-stretch of agonistic muscles caused by prior force reduction due to PSP occurrence. The fact that PSP plays an important role in dynamic force exertion suggests that PSP may be incorporated in the central motor control system designed to interrupt the background activity, to stretch the agonist and to reinforce the dynamic force.

Adult↗

The acetylcholine-dopamine balance in the basal ganglia of rhesus monkeys and its role in dynamic, dystonic, dyskinetic, and epileptoid motor activities.

Behavioural analyses have been made of effects brought about by both single and combined injections of dopamine, haloperidol, carbachol and atropine into the caput nuclei caudati of rhesus monkeys. High doses of dopamine produced the subsequent development of three types of behavioural changes: an increase in the number of skilled manipulation movements (the dynamic phase); the appearance of a dystonic torticollis (the dystonic phase); and, finally, the appearance of an oro-lingual-facial dyskinesia and a number of dyskinetic activities in the extremities (the dyskinetic phase); low doses of dopamine solely produced the dynamic phase. Haloperidol only inhibited the dopamine-induced dynamic and dystonic phase: it did not suppress the dyskinetic phase. High doses of carbachol produced the subsequent development of four phases: a dynamic, dystonic, dyskinetic and epileptoid phase; the last one was marked by the appearance of secondary generalized epileptic seizures. Low doses of carbachol solely produced the dynamic phase. Atropine inhibited the carbachol-induced dynamic, dystonic and epileptoid phase; it did not suppress the dyskinetic phase. High doses of dopamine strongly modified the carbachol-induced phases: dopamine intensified the dystonic phase on the one hand, but it abolished the generalized epileptic seizures on the other hand. Apart from the fact that the data presented have confirmed that both dopaminergic and cholinergic mechanisms within the basal ganglia of rhesus monkeys are involved in the elicitation and modulation of both normal and abnormal motor activities, they have also revealed that the simple concept of a stristal acetylcholine-dopamine "see-saw" has to be revised. Furthermore, the data have suggested that development of supersensitive dopamine-sensitive sites is not the only mechanism that underlies the elicitation of the oro-lingual-facial dyskinesia. And finally, the present experiments have given clearcut evidence that an intrastriatal acetylcholine-dopamine "see-saw" fulfils and essential role in the process involved in the generalization of epileptic seizures.

Acetylcholine↗

Dynamic magnetic resonance imaging defecography: a diagnostic alternative in the assessment of pelvic floor disorders in proctology.

PURPOSE: Standard diagnostic proctologic procedures in the assessment of pelvic floor disorders include clinical evaluation and endoscopy. Particular aspects of combined pelvic floor disorders, especially those involving more than one pelvic compartment, may remain undetected without additional technical diagnostic procedures such as videoproctoscopy, cinedefecography, or colpocystodefecography. The aim of the study was to review the potentials of dynamic magnetic resonance imaging defecography to elucidate the underlying anatomic and pathophysiologic background of pelvic floor disorders in proctologic patients. PATIENTS AND METHODS: Dynamic magnetic resonance imaging defecography was performed in 20 Patients (13 females) with main diagnoses such as rectal prolapse or intussusception, rectocele, descending perineum, fecal incontinence, outlet obstruction, and dyskinetic puborectalis muscle after clinical evaluation. The investigation was performed on a 1.5 T-magnetic resonance imaging machine in supine position. The rectum was filled with Gd-DTPA enriched ultrasound gel. First a T1/T2 weighted investigation of the pelvis was performed, followed by defecography with evacuation of the rectum. Images were obtained in a sagittal plane in a frequency of 1 image/second (true FISP) at rest and during straining. The obtained magnetic resonance imaging video tapes were analyzed off-line with cinematographic evaluation of bladder base, uterus, and anal canal position in relation to the pubococcygeal line by a blinded radiologist. Investigation time was 20 minutes. RESULTS: In dynamic magnetic resonance imaging defecography of the pelvic floor, 12 patients with descending perineum, 10 rectoceles (10 females), 6 cystoceles (6 females), 4 enteroceles (4 females), 8 intussusceptions (5 females), and a dyskinetic puborectalis muscle in 3 males were detected. In 11 females and 3 males multifocal disorders were found, involving more than one compartment in females, whereas in males complex defects were restricted to the posterior compartment. Magnetic resonance imaging defecography revealed diagnoses consistent with clinical results in 77.3 percent and defects in addition to clinical diagnoses in combined pelvic floor disorders in 34 percent. CONCLUSIONS: In complex pelvic floor disorders, involving more than a single defect, dynamic magnetic resonance imaging represents a convenient diagnostic procedure in females and to a lesser extent in males, in particular in terms of dynamic imaging of pelvic floor organs during defecation. In addition to the clinical assessment, dynamic magnetic resonance imaging had clinical impact in proctologic and interdisciplinary treatment.

Adult↗

Poor correlations between isometric tests and dynamic performance: relationship to muscle activation.

The purpose of this research was to perform isometric tests at two joint angles and examine their relationship to dynamic performance. In addition, electromyograph data were collected from the triceps brachii and pectoralis major muscles to compare underlying neural characteristics between the isometric tests and dynamic movement. A group of 24 healthy male subjects performed two isometric tests in a bench press position, at elbow angles of 90 and 120 degrees. From these data, the maximal force and rate of force development were determined. In addition, each subject performed a seated medicine ball throw as a measure of dynamic upper body performance. Correlations showed that isometric measurements of force (r = 0.47-0.55) and rate of force development (r = 0.08-0.31) were poor predictors of dynamic performance. The angle of isometric assessment had little effect on the relationship between the tests and measurements of performance. The myo-electric data was processed in terms of the integrated electromyogram and the Fourier transformed frequency spectrum. These data demonstrated differences in the neural activation patterns of the musculature, between the isometric 90 degrees test and the medicine ball throw. The poor relationship between isometric tests and medicine ball performance was consequently, at least partially, attributed to differing motor unit activation patterns between isometric and dynamic movement. The results of this research strongly suggest that isometric tests have limited value when assessing dynamic upper body performance.

Adult↗

S(+)-ketamine/propofol maintain dynamic cerebrovascular autoregulation in humans.

PURPOSE: This study investigates the effects of S(+)-ketamine and propofol in comparison to sevoflurane on dynamic cerebrovascular autoregulation in humans. METHODS: Twenty-four patients were randomly assigned to one of the following anesthetic protocols: group I (n=12): 2.5 mg.kg(-1)*hr(-1) S(+)-ketamine, 1.5-2.5 microg*mL(-1) propofol-target plasma concentration; group II (n=12): 2.0 MAC (4.0 %) sevoflurane. Patients were intubated and ventilated with O(2)/air (PaO(2)=0.33). Following 40 min of equilibration dynamic cerebrovascular autoregulation was measured and expressed as the autoregulatory index (ARI), describing the duration of cerebral hemodynamic recovery in relation to changes in mean arterial blood pressure. STATISTICS: Mann-Whitney U test (statistical significance was assumed when P <0.05). RESULTS: Dynamic cerebrovascular autoregulation was intact in all patients with S(+)-ketamine/propofol anesthesia as indicated by an ARI of 5.4 +/- 1.1. In contrast, dynamic cerebrovascular autoregulation was significantly delayed with 2.0 MAC sevoflurane (ARI=2.6 +/- 0.7) CONCLUSION: Dynamic cerebrovascular autoregulation is maintained with S(+)-ketamine/propofol-based total iv anesthesia. In contrast, 2.0 MAC sevoflurane delayed dynamic cerebrovascular autoregulation. This supports the use of S(+)-ketamine in combination with propofol in neurosurgical patients based on its neuroprotective potential along with maintained cerebrovascular physiology.

Adult↗

Dosimetric aspects of physical and dynamic wedge of Clinac 2100C linear accelerator.

AIM: To investigate variation of wedge factors on field size and depth for physical and dynamic wedges of identical wedge angles for Clinac 2100C linear accelerator and its clinical implementation. MATERIAL AND METHODS: A computer controlled water phantom dosimetric system is used to generate profile data for physical wedges, whereas a 0.6 cm3 ion chamber is used for generation of profiles for dynamic wedge and wedge factors for both types of wedges. The method has been discussed to handle the dynamic wedge dosimetry in absence of linear array of detectors or film densitometer. RESULTS: A systematic dependence on wedge factor is observed for physical wedge, with respect to depth and wedge angle but not depending on field size. Whereas dynamic wedge shows strong dependence on field size and is not systematic because the dynamic wedge is controlled by segmented treatment tables depending on field size and energy and no significant variation is observed on depth for various wedge angles. The handling of beam data in a commercially available treatment planning system is discussed and a comparison has been made for iso-doses of both types of wedges. CONCLUSION: The dynamic wedge isodose curves shows rather straight lines than physical wedge but larger hot spots at thin edge which needs careful consideration during planning.

Humans↗

The dynamic infusion test in rats.

Although the hydrocephalic H-Tx rat is a widely used model, data on the cerebrospinal fluid (CSF) dynamics in hydrocephalic rats are rare or - as the pressure volume index (PVI) - not available. We used hydrocephalic and nonhydrocephalic H-Tx rats, a stock with a high percentage of inherited hydrocephalus, for the evaluation of such data. In addition, a new, simple mathematical algorithm ("dynamic infusion test"), which has not formerly been used in animal experiments, was used as a pathophysiological model of CSF dynamics. Compared with classical methods for evaluation of these data, the dynamic infusion test gives a deeper insight into the relation between ICP and CSF dynamics. It was found that the resistance to outflow (ROF) in hydrocephalic rats was at least twice that in nonhydrocephalic rats. The PVI measured was similar in hydrocephalic and nonhydrocephalic animals, but clearly higher than the values reported in the literature. This may be attributable to the fact that the classically used bolus test, in contrast to the "dynamic infusion test", is representative only for the CSF compartment which is directly exposed to the bolus application.

Algorithms↗

[Methodological approaches to quantitative evaluation of microcirculation in tissues with dynamic magnetic resonance tomography].

The development of rapid magnetic resonance imaging (MRI) sequences makes it possible to detect the fast kinetics of tissue response after intravenous administration of paramagnetic contrast media (CM), reflecting the status of tissue microcirculation. In this paper, the basic physical and tracer kinetic principles of dynamic relativity and susceptibility contrast MRI techniques are reviewed. The quantitative analysis of the acquired dynamic image data is broken up into an MR specific part, in which the observed signal variations are related to the CM concentration in the tissue, and an MR independent part, in which the computed concentration-time-courses are analyzed by tracer kinetic modeling. The purpose of the applied models is to describe the underlying physiological processes in mathematical terms and thus to enable the estimation of tissue specific parameters from measured dynamic image series. Whereas the capillary permeability can be estimated from dynamic relativity contrast enhanced MRI studies, the regional blood volume as well as the regional blood flow can be determined from dynamic susceptibility contrast enhanced image series. However, since there are no intravascular but only diffusible CM available at present, the application of the susceptibility technique is currently restricted to brain tissues with intact blood brain barrier. The practical realization of both dynamic MRI techniques is demonstrated by case studies.

Blood Flow Velocity↗