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A comparison is made between the relative size of the various thalamic nuclei in man and other primates. Using data for non-human primates predictions are made as to the expected size of the nuclei for the human brain. Of the nuclear groupings five are of the size predicted but three are not. The lateral geniculate is proportionately smaller than predicted, but it is argued that this need not imply a radical change.
A computer model of the cerebrospinal fluid (CSF) compartment and various shunt designs was developed to simulate CSF dynamics, particularly in the upright position in which siphoning is known to occur. This novel mathematical model of the CSF compartment incorporates negative pressure and volume components that permit simulation of siphoning. The model was tested with data from a previously reported animal experiment. The correspondence between the model simulation and the reported intracranial pressure and CSF shunt flow rate was very good. A simulation of a shunted hydrocephalic patient in the recumbent and upright position was then carried out to examine the effects of a standard shunt valve, an externally adjustable valve, a variable resistance valve, and an antisiphon device. The resulting pressure profiles, which conformed to previously reported data, indicate that this model would be useful for the evaluation of current and future shunt designs.
Detailed measurements of vessel lengths and diameters from the coronary network of the human heart are presented. To allow accurate definition of length and diameter, the measurements were made in terms of vessel segments rather than whole vessels. A vessel segment was defined to be the interval between two consecutive branching sites. The results provide the first quantitative description of the coronary network. The new concept of vessel segment and the method of analysis are proposed as a means for an accurate description of the branching characteristics of the coronary network, comparing the network with others in the cardiovascular system and comparing the vasculature in the normal versus that in the diseased heart.
Deep vein thrombosis (DVT) can give rise to chronic debilitating complications, which are expensive to treat. Anticoagulation, the standard therapy for DVT, prevents propagation, but does not remove the existing thrombus, which undergoes slow natural resolution. Alternative forms of treatment that accelerate resolution may arise from a better understanding of the cellular and molecular pathways that regulate the natural resolution of thrombi. This review will outline our current understanding of the mechanisms of thrombus resolution and the role of neovascularisation in this process. Novel experimental treatments that may one day find clinical use are also discussed. The process of thrombus resolution resembles wound healing. The mainly monocytic inflammatory infiltrate, which develops, is associated with the appearance of vascular channels. These cells may drive resolution by encouraging angiogenesis, which contributes to restoration of the vein lumen. Significant numbers of bone marrow-derived progenitor cells have also been found in naturally resolving thrombi, but their precise phenotype and their role in thrombus recanalisation is unclear. Enhanced thrombus neovascularisation and rapid vein recanalisation have been achieved in experimental models with proangiogenic agents. Recent reports of the role of bone marrow-derived progenitor cells in the revascularisation of ischaemic tissues suggest that it may be possible to obtain the same effect by delivering pluripotent or lineage specific stem cells into thrombus. These cells could contribute to thrombus recanalisation by expressing a variety of proangiogenic cytokines or by lining the new vessels that appear within the thrombus.
The wall shear stress pattern was measured in a rigid plastic cast of a canine artery during steady flow by means of an electrochemical technique. The topographic distribution of shear stress is very nonuniform, with regions of high and low shear in close proximity. The steady shear stresses are highest at the leading edge of flow dividers and at the entrance regions to branch vessels. The shapes of the shear stress curves in the celiac branch are primarily a function of the ratio of branch flow to total aortic flow. However, the shapes of the shear stress curves in the adjacent anterior mesenteric branch remain the same for different anterior mesenteric branch flow ratios, although the shear increases with the branch flow ratio. An unstable pattern of flow separation and reattachment is found at the anterior mesenteric flow divider lip and remains localized to that region. A correlation is suggested between sites of high shear stress, extremes in the range of stress, and unstable stress patterns and sites at which atherosclerosis has been shown to develop.
An automated method of modelling the electrical properties of the human thorax from horizontal section data such as computerized tomographic scans has been used to develop both forward and inverse transformations between epicardial and body surface potential distributions. Eleven torso models with varying geometry and organ configurations have been studied. For the forward calculations, a standard dipole-like source is placed along the axis of the heart. Inverse calculations are performed using a measured body surface potential distribution and are based on a division of the surface of the heart into 25 source regions, producing epicardial potentials on these regions. A regularization method is used to stabilize the inverse solutions. Both forward and inverse solutions show substantial differences between models. These findings imply that matching models with patient geometry may be necessary in order to use such solutions in a clinical setting.
During systole a small portion of the mainstream aortic flow is intercepted by the sinus ridge, or downstream corner of the sinus of Valsalva. This fluid curls back toward the ventricle to form a large eddy, or vortex, that spins within the sinus cavity. The fluid motion within similar recirculating flows is known to be unstable with an early transition to turbulence. The stability of the aortic sinus vortex was examined in the current study in an in vitro pulsatile flow rig. The geometry of the experimental test section was the same as the geometry of the natural aortic root. Different model valves, including a natural valve, were placed in the test section, and different flow conditions were studied. Point velocities were measured by hot film probes placed at two locations within the sinus vortex. The velocity waveforms and their power spectra were used to determine the stability of the sinus flow. The experimental results revealed that the aortic sinus vortex becomes turbulent under simulated exercise conditions. Turbulent intensities were highest near the sinus ridge, which is the location of the coronary ostia. Despite the transition to turbulence within the vortex, the mainstream aortic flow upstream from the valve remained laminar. The turbulence within the vortex was also associated with vibration of the valve leaflets under exercise conditions. These vibrations may be related to the systolic ejection murmurs that are heard clinically. Furthermore, the localized turbulence may explain the location of atherosclerotic lesions and dissecting aneurysms, as well as the distribution of the lesions of bacterial endocarditis.
Connexins form a variety of gap junction channels that vary in their developmental and tissue-specific levels of expression, modulation of gating by transjunctional voltage and posttranslational modification, and unitary channel conductance (gamma j). Despite a 10-fold variation in gamma j, whether connexin-specific channels possess distinct ionic and molecular permeabilities is presently unknown. A major assumption of the conventional model for a gap junction channel pore is that gamma j is determined primarily by pore diameter. Hence, molecular size permeability limits should increase and ionic selectivity should decrease with increasing channel gamma j (and pore diameter). Equimolar ion substitution of 120 mmol/L KCl for potassium glutamate was used to determine the unitary conductance ratios for rat connexin40 and connexin43, chicken connexin43 and connexin45, and human connexin37 channels functionally expressed in communication-deficient mouse neuroblastoma (N2A) cells. Comparison of experimental and predicted conductance ratios based on the aqueous mobilities of all ions according to the Goldman-Hodgkin-Katz current equation was used to determine relative anion-to-cation permeability ratios. Direct correlation of junctional conductance with dye transfer of two fluorescein-derivatives (2 mmol/L 6-carboxyfluorescein or 2',7'-dichlorofluorescein) was also performed. Both approaches revealed a range of selectivities and permeabilities for all five different connexins that was independent of channel conductance. These results are not consistent with the conventional simple aqueous pore model of a gap junction channel and suggest a new model for connexin channel conductance and permselectivity based on electrostatic interactions. Divergent conductance and permeability properties are features of other classes of ion channels (eg, Na+ and K+ channels), implying similar mechanisms for selectivity.
BACKGROUND AND PURPOSE: Inertial force of the bloodstream results in the local elevation of intravascular pressure secondary to flow impact. Previous studies suggest that this "impacting force" and the local pressure elevation at the aneurysm may have a large contribution to the development of cerebral aneurysms. The goal of the present study is to evaluate how the bloodstream impacting force and the local pressure elevation at the aneurysm influences the rupture of cerebral aneurysms. METHODS: A total of 29 aneurysms were created in 26 patient-specific vessel models, and computer simulations were used to calculate pressure distributions around the vessel branching points and the aneurysms. RESULTS: Direct impact of the parent artery bloodstream resulted in local elevation in pressure at branch points, and bends in arteries (231.2+/-198.1 Pa; 100 Pa=0.75 mm Hg). The bloodstream entered into the aneurysm with a decreased velocity after it impacted on the branching points or bends. Thus, the flow impact at the aneurysm occurred usually weakly. At the top or the rupture point of the aneurysm, the flow velocity was always delayed. The local pressure elevation at the aneurysm was 119.3+/-91.2 Pa. CONCLUSIONS: The pressure elevation at the area of flow impact and at the aneurysm constituted only 1% to 2% of the peak intravascular pressure. The results suggest that the bloodstream impacting force and the local pressure elevation at the aneurysm may have less contribution to the rupture of cerebral aneurysms than was expected previously.
BACKGROUND AND PURPOSE: The shape and exact size of lacunar infarcts have been investigated only postmortem. Recent imaging techniques based on triangulation and connectivity can now be used for 3D segmentation of cerebral lesions. The shape and size of lacunar infarcts was investigated using these techniques in 10 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients. METHODS: We segmented 102 lacunar infarcts on T1-weighted images. The surface of the corresponding set of voxels was computed as a mesh of triangles. Thereafter, the shape of each lesion in 3D was visually analyzed by 2 investigators. RESULTS: The volume of lesions ranged from 10.5 to 1146 mm, with 93% of them having a volume <500 mm; 83% lacunar infarcts had a spheroid or ovoid shape, but 17% presented as sticks, slabs, or with a complex shape. Lesions with multiple components appeared larger than the others, and a tail extension was noticed in 13 of 102 lesions. CONCLUSIONS: These results suggest the following: (1) most lacunar infarcts in CADASIL have a volume far below one third of that of a sphere of 15 mm in diameter, the upper limit currently used for their identification on 2D imaging; (2) a significant proportion of lacunar infarcts have a shape distinct from the spheroid-ovoid morphology; and (3) lesions with a complex shape may result from the involvement of the largest small arteries, confluence of ischemic lesions, or secondary tissue degeneration. The segmentation of lacunar infarcts appears promising to better understand the pathophysiology of tissue lesions secondary to small vessel diseases.
BACKGROUND AND PURPOSE: Retrospective analysis of clinical data has demonstrated major variations in carotid bifurcation geometry, in support of the notion that an individual's vascular anatomy or local hemodynamics may influence the development of atherosclerosis. On the other hand, anecdotal evidence suggests that vessel geometry is more homogenous in youth, which would tend to undermine this geometric risk hypothesis. The purpose of our study was to test whether the latter is indeed the case. METHODS: Cross-sectional images of the carotid bifurcations of 25 young adults (24+/-4 years) and a control group of 25 older subjects (63+/-10 years) were acquired via MRI. Robust and objective techniques were developed to automatically characterize the 3D geometry of the bifurcation and the relative dimensions of the internal, external, and common carotid arteries (ICA, ECA, and CCA, respectively). RESULTS: Young vessels exhibited significantly less interindividual variation in the following geometric parameters: bifurcation angle (48.5+/-6.3 degrees versus 63.6+/-15.4 degrees); ICA angle (21.6+/-6.7 degrees versus 29.2+/-11.3 degrees); CCA tortuosity (0.010+/-0.003 versus 0.014+/-0.011); ICA tortuosity (0.025+/-0.013 versus 0.086+/-0.105); ECA/CCA diameter ratio (0.81+/-0.06 versus 0.75+/-0.13), ICA/CCA (0.81+/-0.06 versus 0.77+/-0.12) diameter ratio, and bifurcation area ratio (1.32+/-0.15 versus 1.19+/-0.35). CONCLUSIONS: The finding of more modest interindividual variations in young adults suggests that, if there is a geometric risk for atherosclerosis, its early detection may prove challenging. Taken together with the major interindividual variations seen in older vessels, it suggests a more complex interrelationship between vascular geometry, local hemodynamics, vascular aging, and atherosclerosis, the elucidation of which now calls for prospective studies.
Access to limited-capacity neural systems of cognitive control must be restricted to the most relevant information. How the brain identifies and selects items for preferential processing is not fully understood. Anatomical models often place the selection mechanism in the medial frontal cortex (MFC), and one computational model proposes that the mesotelencephalic dopamine (DA) system, via its reward prediction properties, provides a "gate" through which information gains access to limited-capacity systems. There is a medial frontal event-related potential (ERP) index of attention selection, the anterior positivity (P2a), associated with DA reward system input to the MFC for the identification of task-relevant perceptual representations. The P2a has a similar spatio-temporal distribution as the medial frontal negativity (MFN), elicited to error responses or choices resulting in monetary loss. The MFN has also been linked to DA projections to the MFC but for action monitoring rather than attention selection. This study proposes that the P2a and the MFN reflect the same MFC evaluation function and use a passive reward prediction design containing neither instructed attention nor response to demonstrate that the ERP over medial frontal leads at the P2a/MFN latency is consistent with activity of midbrain DA neurons, positive to unpredicted rewards and negative when a predicted reward is withheld. This result suggests that MFC activity is regulated by DA reward system input and may function to identify items or actions that exceed or fail to meet motivational prediction.
This study aimed to examine the performance characteristics of four high-frequency oscillatory-type ventilators, using an in vitro model of the intubated neonatal respiratory system. Each ventilator was examined across its operative range of settings and at varying model lung compliance (C) and resistance. The oscillatory pressure waveform was measured at the airway opening (Pao). Tidal volume (VT) and flow were determined from pressure changes within the model lung (DeltaPA). The spectral content of the Pao waveform differed between ventilators. The maximum ventilator VT ranged from 3.7 to 11.1 ml at 15 Hz and a mean airway pressure (Paw) of 12 cm H(2)O to oscillate a model lung (C = 0.4 ml/cm H(2)O) through a 3.0-mm internal diameter (i.d.) endotracheal tube (ETT). A small drop in C was associated with a decrease in VT and marked increase in DeltaPA from 0.1 to 0.8 ml/cm H(2)O. The influence of C on VT and DeltaPA and the pressure cost of ventilation (DeltaPA/f.VT(2)) was dependent on the oscillatory frequency, ETT inner diameter, and the specific ventilator used. Substantive differences exist between oscillatory ventilators that need to be considered in their clinical application. The rapid establishment of optimal lung volume and oscillatory frequency is important in minimizing barotrauma during high-frequency oscillatory ventilation.
PURPOSE: Zernike polynomials have been successfully used for approximately 70 years in many different fields of optics. Nevertheless, there are some recent discussions regarding the precision and accuracy of these polynomials when applied to surfaces such as the human cornea. The main objective of this work was to investigate the absolute accuracy of Zernike polynomials of different orders when fitting several types of theoretical corneal and wave-front surface data. METHODS: A set of synthetic surfaces resembling several common corneal anomalies was sampled by using cylindrical coordinates to simulate the height output files of commercial videokeratography systems. The same surfaces were used to compute the optical path difference (wave-front [WF] error), by using a simple ray-tracing procedure. Corneal surface and WF error was fit by using a least-squares algorithm and Zernike polynomials of different orders, varying from 1 to 36 OSA-VSIA convention terms. RESULTS: The root mean square error (RMSE) ranged-from the most symmetric corneal surface (spherical shape) through the most complex shape (after radial keratotomy [RK]) for both the optical path difference and the surface elevation for 1 through 36 Zernike terms-from 421.4 to 0.8 microm and 421.4 to 8.2 microm, respectively. The mean RMSE for the maximum Zernike terms for both surfaces was 4.5 microm. CONCLUSIONS: These results suggest that, for surfaces such as that present after RK, in keratoconus, or after keratoplasty, even more than 36 terms may be necessary to obtain minimum accuracy requirements. The author suggests that the number of Zernike polynomials should not be a global fixed conventional or generally accepted value but rather a number based on specific surface properties and desired accuracy.
PURPOSE: A methodology for noninvasively characterizing the three-dimensional (3-D) shape of the complete human eye is not currently available for research into ocular diseases that have a structural substrate, such as myopia. A novel application of a magnetic resonance imaging (MRI) acquisition and analysis technique is presented that, for the first time, allows the 3-D shape of the eye to be investigated fully. METHODS: The technique involves the acquisition of a T2-weighted MRI, which is optimized to reveal the fluid-filled chambers of the eye. Automatic segmentation and meshing algorithms generate a 3-D surface model, which can be shaded with morphologic parameters such as distance from the posterior corneal pole and deviation from sphericity. Full details of the method are illustrated with data from 14 eyes of seven individuals. The spatial accuracy of the calculated models is demonstrated by comparing the MRI-derived axial lengths with values measured in the same eyes using interferometry. RESULTS: The color-coded eye models showed substantial variation in the absolute size of the 14 eyes. Variations in the sphericity of the eyes were also evident, with some appearing approximately spherical whereas others were clearly oblate and one was slightly prolate. Nasal-temporal asymmetries were noted in some subjects. CONCLUSIONS: The MRI acquisition and analysis technique allows a novel way of examining 3-D ocular shape. The ability to stratify and analyze eye shape, ocular volume, and sphericity will further extend the understanding of which specific biometric parameters predispose emmetropic children subsequently to develop myopia.
Vascular spasm is a poorly understood but critical biomedical process because it can acutely reduce blood supply and tissue oxygenation. Cardiomyopathy in mice lacking gamma-sarcoglycan or delta-sarcoglycan is characterized by focal damage. In the heart, sarcoglycan gene mutations produce regional defects in membrane permeability and focal degeneration, and it was hypothesized that vascular spasm was responsible for this focal necrosis. Supporting this notion, vascular spasm was noted in coronary arteries, and disruption of the sarcoglycan complex was observed in vascular smooth muscle providing a molecular mechanism for spasm. Using a transgene rescue strategy in the background of sarcoglycan-null mice, we replaced cardiomyocyte sarcoglycan expression. Cardiomyocyte-specific sarcoglycan expression was sufficient to correct cardiac focal degeneration. Intriguingly, successful restoration of the cardiomyocyte sarcoglycan complex also eliminated coronary artery vascular spasm, while restoration of smooth muscle sarcoglycan in the background of sarcoglycan-null alleles did not. This mechanism, whereby tissue damage leads to vascular spasm, can be partially corrected by NO synthase inhibitors. Therefore, we propose that cytokine release from damaged cardiomyocytes can feed back to produce vascular spasm. Moreover, vascular spasm feeds forward to produce additional cardiac damage.
A set of lung diseases share the tendency for the development of progressive fibrosis ultimately leading to respiratory failure. This review examines the common pathogenetic features of these disorders in light of recent observations in both humans and animal models of disease, which reveal important pathways of lung matrix remodeling.
Skin is at the interface between the complex physiology of the body and the external, often hostile, environment, and the semipermeable epidermal barrier prevents both the escape of moisture and the entry of infectious or toxic substances. Newborns with rare congenital barrier defects underscore the skin's essential role in a terrestrial environment and demonstrate the compensatory responses evoked ex utero to reestablish a barrier. Common inflammatory skin disorders such as atopic dermatitis and psoriasis exhibit decreased barrier function, and recent studies suggest that the complex response of epidermal cells to barrier disruption may aggravate, maintain, or even initiate such conditions. Either aiding barrier reestablishment or dampening the epidermal stress response may improve the treatment of these disorders. This Review discusses the molecular regulation of the epidermal barrier as well as causes and potential treatments for defects of barrier formation and proposes that medical management of barrier disruption may positively affect the course of common skin disorders.