Further evidence for the dynamic stability of intracranial saccular aneurysms

It has long been thought that intracranial saccular aneurysms enlarge and rupture because of mechanical instabilities. Recent nonlinear analyses suggest, however, that at least certain sub-classes of aneurysms do not exhibit quasi-static limit point instabilities or dynamic instabilities in response to periodic loading, and consequently, that the natural history of these lesions is likely governed by growth and remodeling processes. In this paper, we present additional results that support the finding that one particular sub-class of saccular aneurysms is dynamically stable. Specifically, we extended recent results of Shah and Humphrey, which are based on the assumption that some saccular aneurysms can be modeled as spherical elastic membranes surrounded by a viscous cerebrospinal fluid, to account for a viscohyperelastic behavior of the aneurysm. It is shown that inclusion of a "short-term" viscoelastic contribution to the mechanical behavior of an aneurysm serves to increase its dynamic stability against various disturbances.     

Nonlinear anisotropic stress analysis of anatomically realistic cerebral aneurysms

BACKGROUND: Static deformation analysis and estimation of wall stress distribution of patient-specific cerebral aneurysms can provide useful insights into the disease process and rupture. METHOD OF APPROACH: The three-dimensional geometry of saccular cerebral aneurysms from 27 patients (18 unruptured and nine ruptured) was reconstructed based on computer tomography angiography images. The aneurysm wall tissue was modeled using a nonlinear, anisotropic, hyperelastic material model (Fung-type) which was incorporated in a user subroutine in ABAQUS. Effective material fiber orientations were assumed to align with principal surface curvatures. Static deformation of the aneurysm models were simulated assuming uniform wall thickness and internal pressure load of 100 mm Hg. RESULTS: The numerical analysis technique was validated by quantitative comparisons to results in the literature. For the patient-specific models, in-plane stresses in the aneurysm wall along both the stiff and weak fiber directions showed significant regional variations with the former being higher. The spatial maximum of stress ranged from as low as 0.30 MPa in a small aneurysm to as high as 1.06 MPa in a giant aneurysm. The patterns of distribution of stress, strain, and surface curvature were found to be similar. Sensitivity analyses showed that the computed stress is mesh independent and not very sensitive to reasonable perturbations in model parameters, and the curvature-based criteria for fiber orientations tend to minimize the total elastic strain energy in the aneurysms wall. Within this small study population, there were no statistically significant differences in the spatial means and maximums of stress and strain values between the ruptured and unruptured groups. However, the ratios between the stress components in the stiff and weak fiber directions were significantly higher in the ruptured group than those in the unruptured group. CONCLUSIONS: A methodology for nonlinear, anisotropic static deformation analysis of geometrically realistic aneurysms was developed, which can be used for a more accurate estimation of the stresses and strains than previous methods and to facilitate prospective studies on the role of stress in aneurysm rupture.     

Magnetic Resonance Imaging of Cerebral Aspergillosis: Imaging and Pathological Correlations

Cerebral aspergillosis is associated with a significant morbidity and mortality rate. The imaging data present different patterns and no full consensus exists on typical imaging characteristics of the cerebral lesions. We reviewed MRI findings in 21 patients with cerebral aspergillosis and correlated them to the immune status of the patients and to neuropathological findings when tissue was available. The lesions were characterized by their number, topography, and MRI signal. Dissemination to the brain resulted from direct spread from paranasal sinuses in 8 patients, 6 of them being immunocompetent. Hematogenous dissemination was observed in 13 patients, all were immunosuppressed. In this later group we identified a total of 329 parenchymal abscesses involving the whole brain with a predilection for the corticomedullary junction. More than half the patients had a corpus callosum lesion. Hemorrhagic lesions accounted for 13% and contrast enhancement was observed in 61% of the lesions. Patients with hematogenous dissemination were younger (p = 0.003), had more intracranial lesions (p = 0.0004) and had a higher 12-week mortality rate (p = 0.046) than patients with direct spread from paranasal sinuses. Analysis of 12 aneurysms allowed us to highlight two distinct situations. In case of direct spread from the paranasal sinuses, aneurysms are saccular and located on the proximal artery portions, while the hematogenous dissemination in immunocompromised patients is more frequently associated with distal and fusiform aneurysms. MRI is the exam of choice for cerebral aspergillosis. Number and type of lesions are different according to the mode of dissemination of the infection.     

Finite strain elastodynamics of intracranial saccular aneurysms.

Various investigators suggest that intracranial saccular aneurysms are dynamically unstable, that they resonate in response to pulsatile blood flow. This hypothesis is based on linearized analyses or experiments on rubber "models", however, and there is a need for a more critical examination. Toward this end, we (a) derive a new nonlinear equation of motion for a pulsating spherical aneurysm that is surrounded by cerebral spinal fluid and whose behavior is described by a Fung-type pseudostrain-energy function that fits data on human lesions, and (b) use methods of nonlinear dynamics to examine the stability of such lesions against perturbations to both in vivo and in vitro conditions. The numerical results suggest that this sub-class of lesions is dynamically stable. Moreover, with the exception of transients associated with initial perturbations, inertial effects appear to be insignificant for fundamental forcing frequencies less than 10 Hz and hence for typical physiologic and laboratory conditions. We submit, therefore, that further study of the mechanics of saccular aneurysms should be focused on quasi-static stress analyses that investigate the roles of lesion geometry and material properties, including growth and remodeling.     

Functional and anatomical decomposition of face processing: evidence from prosopagnosia and PET study of normal subjects.

Studies of brain-damaged patients have revealed the existence of a selective impairment of face processing, prosopagnosia, resulting from lesions at different loci in the occipital and temporal lobes. The lesions are often extensive, and it is unclear what functional aspects of face processing are normally served by the damaged areas, and whether they are uniquely devoted to the processing of faces. These issues are further addressed through a combined magnetic resonance imaging (MRI) and positron emission tomography (PET) study of regional cerebral blood flow (rCBF) in normal subjects performing different tasks of face and object processing. The results indicate different patterns of cerebral activation depending on the requirements of the tasks within the processing of faces, as well as a clear dissociation of the neural substrates underlying face and object processing. These results are compared with radiological data from prosopagnosic patients, and are put in relation with the patterns of deficits observed in the patients as a function of the location of their lesions. Together, the findings offer new evidence regarding the functional neuroanatomy of face and object processing.     

Several classes of binding sites for metals and nucleotides on yeast mitochondrial oligomycin sensitive ATPase

The binding properties of Mg²⁺, Mn²⁺ to yeast mitochondrial oligomycin sensitive ATPase complex are studied, as reflected by their catalytic effect (hydrolysis of ATP or pNPP, a pseudo substrate) or by a physical parameter (atomic absorption, electron paramagnetic resonance of Mn²⁺, enhanced fluorescence of chelating chlorotetracyclin). At least two classes of sites with very different affinities respectively around 10⁻⁵ M and 10⁻⁴ M are demonstrated : high affinity sites for cations which participate in pNPP hydrolysis and can bind ADP or ATP, although they have a poor efficiency for ATP hydrolysis, and low affinity sites for cations which participate efficiently in both pNPP and ATP hydrolysis. The possibility that the tight site class has itself two sub-classes is also discussed.     

CLC channels and transporters: Proteins with borderline personalities

Controlled chloride movement across membranes is essential for a variety of physiological processes ranging from salt homeostasis in the kidneys to acidification of cellular compartments. The CLC family is formed by two, not so distinct, sub-classes of membrane transport proteins: Cl^- channels and H⁺/Cl^- exchangers. All CLC's are homodimers with each monomer forming an individual Cl- permeation pathway which appears to be largely unaltered in the two CLC sub-classes. Key residues for ion binding and selectivity are also highly conserved. Most CLC's have large cytosolic carboxy-terminal domains containing two cystathionine β-synthetase (CBS) domains. The C-termini are critical regulators of protein trafficking and directly modulate Cl- by binding intracellular ATP, H+ or oxidizing compounds. This review focuses on the recent mechanistic insights on the how the structural similarities between CLC channels and transporters translate in unexpected mechanistic analogies between these two sub-classes.     

肩袖间隙影像解剖及常见病变的研究进展

肩袖间隙在解剖学上是肩关节的一个复合区域,在维持肩关节稳定性和保护肱二头肌长头肌腱功能起重要作用。对肩袖间隙解剖结构及功能的深入认识有助于肩袖间隙损伤性病变、挛缩性病变等的及时诊断和合理治疗。影像学检查尤其是磁共振逐步成为肩袖间隙疾病最主要的检查方法,包括常规扫描、直接及间接性磁共振肩关节造影、增强扫描等。本文将就肩袖间隙的影像解剖及常见病变的相关研究进行综述。     

Analysing grouping of nucleotides in DNA sequences using lumped processes constructed from Markov chains

The most commonly used models for analysing local dependencies in DNA sequences are (high-order) Markov chains. Incorporating knowledge relative to the possible grouping of the nucleotides enables to define dedicated sub-classes of Markov chains. The problem of formulating lumpability hypotheses for a Markov chain is therefore addressed. In the classical approach to lumpability, this problem can be formulated as the determination of an appropriate state space (smaller than the original state space) such that the lumped chain defined on this state space retains the Markov property. We propose a different perspective on lumpability where the state space is fixed and the partitioning of this state space is represented by a one-to-many probabilistic function within a two-level stochastic process. Three nested classes of lumped processes can be defined in this way as sub-classes of first-order Markov chains. These lumped processes enable parsimonious reparameterizations of Markov chains that help to reveal relevant partitions of the state space. Characterizations of the lumped processes on the original transition probability matrix are derived. Different model selection methods relying either on hypothesis testing or on penalized log-likelihood criteria are presented as well as extensions to lumped processes constructed from high-order Markov chains. The relevance of the proposed approach to lumpability is illustrated by the analysis of DNA sequences. In particular, the use of lumped processes enables to highlight differences between intronic sequences and gene untranslated region sequences.     

On the potentially protective role of contact constraints on saccular aneurysms

Most intracranial saccular aneurysms remain asymptomatic until rupture. Yet, some unruptured lesions present with various symptoms, often related to the compression of a nerve or other intracranial tissue. An obvious question, therefore, is whether or not symptomatic unruptured lesions necessarily have a greater rupture-potential than asymptomatic ones. In this paper, we show numerically that contact constraints can have a protective effect on certain lesions. Specifically, finite element analyses of stress fields in model axisymmetric lesions, with and without the presence of a rigid contacting obstacle at the fundus, reveal that with the exception of near point loads, the constraint decreases the stresses near the fundus. Given that it is well accepted that rupture occurs when wall stress exceeds wall strength, these findings suggest that the rupture-potential will be lower in at least one sub-class of constrained versus comparable unconstrained lesions. Because of the myriad of sizes, shapes, and compositions of saccular aneurysms, however, there is a need to examine this important issue further, hopefully based on an increased awareness for clinical data on lesion-tissue interactions.     

Detection of preclinically latent hyperperfusion due to stroke-like episodes by arterial spin-labeling perfusion MRI in MELAS patients

In stroke-like episodes (SEs) of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), the detection of preclinically latent lesions is a challenge. We report regional cerebral hyperperfusion observed on arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in the preclinical phase more than 3 months before the clinical onset of SEs in 3 MELAS patients. These hyperperfused areas were not detected by conventional MRI in the preclinical phase and developed into acute lesions at the clinical onset of SEs, suggesting that ASL imaging has the potential for predicting the emergence of SEs.     

Birnbaum–Saunders frailty regression models: Diagnostics and application to medical data

In survival models, some covariates affecting the lifetime could not be observed or measured. These covariates may correspond to environmental or genetic factors and be considered as a random effect related to a frailty of the individuals explaining their survival times. We propose a methodology based on a Birnbaum–Saunders frailty regression model, which can be applied to censored or uncensored data. Maximum‐likelihood methods are used to estimate the model parameters and to derive local influence techniques. Diagnostic tools are important in regression to detect anomalies, as departures from error assumptions and presence of outliers and influential cases. Normal curvatures for local influence under different perturbations are computed and two types of residuals are introduced. Two examples with uncensored and censored real‐world data illustrate the proposed methodology. Comparison with classical frailty models is carried out in these examples, which shows the superiority of the proposed model.     

Impact of surgical ventricular restoration on ventricular shape, wall stress, and function in heart failure patients

Surgical ventricular restoration (SVR) was designed to treat patients with aneurysms or large akinetic walls and dilated ventricles. Yet, crucial aspects essential to the efficacy of this procedure like optimal shape and size of the left ventricle (LV) are still debatable. The objective of this study is to quantify the efficacy of SVR based on LV regional shape in terms of curvedness, wall stress, and ventricular systolic function. A total of 40 patients underwent magnetic resonance imaging (MRI) before and after SVR. Both short-axis and long-axis MRI were used to reconstruct end-diastolic and end-systolic three-dimensional LV geometry. The regional shape in terms of surface curvedness, wall thickness, and wall stress indexes were determined for the entire LV. The infarct, border, and remote zones were defined in terms of end-diastolic wall thickness. The LV global systolic function in terms of global ejection fraction, the ratio between stroke work (SW) and end-diastolic volume (SW/EDV), the maximal rate of change of pressure-normalized stress (dσ*/dt(max)), and the regional function in terms of surface area change were examined. The LV end-diastolic and end-systolic volumes were significantly reduced, and global systolic function was improved in ejection fraction, SW/EDV, and dσ*/dt(max). In addition, the end-diastolic and end-systolic stresses in all zones were reduced. Although there was a slight increase in regional curvedness and surface area change in each zone, the change was not significant. Also, while SVR reduced LV wall stress with increased global LV systolic function, regional LV shape and function did not significantly improve.     

Magnetic resonance imaging in the diagnosis of knee joint sarcomas

The purpose of the investigation was to study the potentialities of magnetic resonance imaging (MRI) in the diagnosis of knee joint sarcomas. The paper presents the results of examining 13 patients of different age, shows the potentialities of the technique in the identification of knee joint sarcomas, and describes the MRI semiotics of sarcomas in both the routine study and that using contrast enhancement in lesions of bone and soft tissue elements in the presence of regional metastases.     

The effect of inlet waveforms on computational hemodynamics of patient-specific intracranial aneurysms

Due to the lack of patient-specific inlet flow waveform measurements, most computational fluid dynamics (CFD) simulations of intracranial aneurysms usually employ waveforms that are not patient-specific as inlet boundary conditions for the computational model. The current study examined how this assumption affects the predicted hemodynamics in patient-specific aneurysm geometries. We examined wall shear stress (WSS) and oscillatory shear index (OSI), the two most widely studied hemodynamic quantities that have been shown to predict aneurysm rupture, as well as maximal WSS (MWSS), energy loss (EL) and pressure loss coefficient (PLc). Sixteen pulsatile CFD simulations were carried out on four typical saccular aneurysms using 4 different waveforms and an identical inflow rate as inlet boundary conditions. Our results demonstrated that under the same mean inflow rate, different waveforms produced almost identical WSS distributions and WSS magnitudes, similar OSI distributions but drastically different OSI magnitudes. The OSI magnitude is correlated with the pulsatility index of the waveform. Furthermore, there is a linear relationship between aneurysm-averaged OSI values calculated from one waveform and those calculated from another waveform. In addition, different waveforms produced similar MWSS, EL and PLc in each aneurysm. In conclusion, inlet waveform has minimal effects on WSS, OSI distribution, MWSS, EL and PLc and a strong effect on OSI magnitude, but aneurysm-averaged OSI from different waveforms has a strong linear correlation with each other across different aneurysms, indicating that for the same aneurysm cohort, different waveforms can consistently stratify (rank) OSI of aneurysms.     

Magnetic resonance imaging features for differentiating breast papilloma with high-risk or malignant lesions from benign papilloma: a retrospective study on 158 patients

Background

Benign breast papilloma is currently managed with conservative management with close observation. In contrast, papilloma with high-risk or malignant lesions warrants surgical excision. The purpose of our study was to investigate magnetic resonance imaging (MRI) features of breast papilloma and to identify imaging diagnostic indicators for papilloma with high-risk or malignant lesions.

Methods

MRI features of 175 surgically confirmed papillomas on 158 patients were retrospectively reviewed. The 175 cases included 132 cases of benign papilloma and 43 cases of papilloma with high-risk or malignant lesions. The MRI features of these lesions were classified into three types: mass, non-mass enhancement (NME), and occult lesion. The occult lesion was defined as the presence of only ductal dilation without any enhanced lesions on MRI. For a mass lesion, the mixed mass-NME lesion was considered if linear, segmental or regional enhanced lesion was found adjacent to the mass. Clinical and MRI features were compared by univariate and multivariate analysis between the benign papilloma and the papilloma with high-risk or malignant lesions.

Results

Multivariate logistic regression analysis demonstrated that clinical characteristics including being or older than 50?years (odds ratio [OR]?=?4.506), having bloody nipple discharge (OR?=?4.499), and concurrent breast cancer (OR?=?5.083) were significant indicators for papilloma with high-risk or malignant lesions. On MRI, most papillomas presented as mass (n?=?135, 77.1%), and fewer as NME (n?=?37, 21.1%) and occult lesion (n?=?3, 1.7%). For the mass lesion, the logistic regression analysis demonstrated that a mass size exceeding 10?mm (OR?=?2.956) and mixed mass-NME lesion (OR?=?4.143) were independent risk indicators for a papilloma with high-risk or malignant lesions. For the NME lesion, the segmental or regional distribution was more commonly observed in the papilloma with high-risk or malignant lesions (61.5%) than the benign papilloma (12.5%) (P?=?0.006). All the cases of occult lesions were benign papillomas.

Conclusions

MRI features including a mass size exceeding 10?mm, mixed mass-NME lesion, and NMEs with segmental or regional distribution indicate a papilloma with high-risk or malignant lesions.

     

SUBCUR: Visualization of structural differences between DNA duplexes

A computer program, SUBCUR, is described which permits analysis and rapid identification of geometrical differences and patterns of variance between two DNA duplexes. The program is compatible with the CURVES 3.1 package² and allows graphical visualization of the structural differences. Examples are provided which illustrate the applicability of the program in analyzing the different backbone conformations of two helices and the different curvatures of two helices.     

Blood flow downstream of a two-dimensional bifurcation

Many cardiovascular lesions such as aneurysms, intimal cushions, and atherosclerotic plaques tend to occur near bifurcations. This suggests that hemodynamic factors may be involved. Since measuring devices (such as anemometers) are still too large to allow local measurements of flow disturbances, we have attempted to predict the nature of these factors mathematically. Biological variables include pulsatile flow of a nonNewtonian fluid in distensible branching vessels with different angles and flow rates. Our initial analysis considers the flow in a two-dimensional bifurcation with a symmetrical flow divider perfused with steady flow at variable Reynolds numbers. At all flows, high shear forces develop on either side of the flow divider (i.e. at the apex of the bifurcation). With high flows, regions of sluggish or reverse flow develop near the outer walls of the bifurcation. The analysis confirms that the flow at the apex is quite different from that at the outer angles and that the latter varies more with flow rate than the former.