Kenneth L. Monson

Axial mechanical properties of fresh human cerebral blood vessels.

Human cerebral blood vessels are frequently damaged in head impact, whether accidental or deliberate, resulting in intracranial bleeding. Additionally, the vasculature constitutes the support structure for the brain and, hence, plays a key role in the cranial load response. Quantification of its mechanical behavior, including limiting loads, is thus required for a proper understanding and modeling of traumatic brain injury--as well as providing substantial assistance in the development and application of preventive measures. It is believed that axial stretching is the dominant loading mode for the blood vessels, regardless of the nature of the insult. Eighteen arteries and fourteen veins were obtained from the cortical surface of the cerebral temporal lobe of patients undergoing surgery. These vessels were stretched to failure in the longitudinal direction, either quasi-statically or dynamically. The significance of specimen and experiment parameters was determined using multivariate analysis of variance (MANOVA) testing. Results demonstrate that the arteries were considerably stiffer than the veins, carrying approximately twice as much stress at failure but withstanding only half as much stretch. No significant rate dependence was measured over a strain rate range of more than four orders of magnitude (0.01 to 500 s -1).

Biaxial Response of Passive Human Cerebral Arteries

The cerebral circulation is fundamental to the health and maintenance of brain tissue, but injury and disease may result in dysfunction of the vessels. Characterization of cerebral vessel mechanical response is an important step toward a more complete understanding of injury mechanisms and disease development in these vessels, paving the way for improved prevention and treatment. We recently reported a large series of uniaxial tests on fresh human cerebral vessels, but the multi-axial behavior of these vessels has not been previously described. Twelve arteries were obtained from the surface of the temporal lobe of patients undergoing surgery and were subjected to various combinations of axial stretch and pressure around typical physiological conditions before being stretched to failure. Axial and circumferential responses were compared, and measured data were fit to a four-parameter, Fung-type hyperelastic constitutive model. Artery behavior was nonlinear and anisotropic, with considerably greater resistance to deformation in the axial direction than around the circumference. Results from axial failure tests of pressurized vessels resulted in a small shift in stress–stretch response compared to previously reported data from unpressurized specimens. These results further define the biaxial response of the cerebral arteries and provide data required for more rigorous study of head injury mechanisms and development of cerebrovascular disease.

Determination and Mechanisms of Motor Vehicle Structural Restitution from Crash Test Data

Using crash test data from the National Highway Traffic Safety Administration (NHTSA), this study investigates the expected magnitude of the coefficient of restitution and mechanisms influencing restitution in automobile collisions. Both vehicle-to-barrier and vehicle-to vehicle tests are considered for all types of collisions. The influence of a variety of collision and vehicle parameters on restitution is also explored. Results show that impact velocity, through its relationship with vehicle crush, is highly influential in determining the magnitude of restitution. Restitution generally decreases as impact velocity increases. In full-frontal barrier collisions involving vehicles with certain engine configuration, however, a contradiction of the trend occurs as the coefficients value shifts upward before continuing to decrease with increasing velocity. Study of other parameters and collision types further clarifies restitution behavior.

Biaxial and failure properties of passive rat middle cerebral arteries

Rodents are commonly used as test subjects in research on traumatic brain injury and stroke. However, study of rat cerebral vessel properties has largely been limited to pressure-diameter response within the physiological loading range. A more complete, multiaxial description is needed to guide experiments on rats and rat vessels and to appropriately translate findings to humans. Accordingly, we dissected twelve rat middle cerebral arteries (MCAs) and subjected them to combined inflation and axial stretch tests around physiological loading conditions while in a passive state. The MCAs were finally stretched axially to failure. Results showed that MCAs under physiological conditions were stiffer in the axial than circumferential direction by a mean (±standard deviation) factor of 1.72 (±0.73), similar to previously reported behavior of human cerebral arteries. However, the stiffness for both directions was lower in rat MCA than in human cerebral arteries (p<0.01). Failure stretch values were higher in rat MCA (1.35±0.08) than in human vessels (1.24±0.09) (p=0.003), but corresponding 1st Piola Kirchhoff stress values for rats (0.42±0.09 MPa) were considerably lower than those for humans (3.29±0.64 MPa) (p<0.001). These differences between human and rat vessel properties should be considered in rat models of human cerebrovascular injury and disease.

Abrupt increase in rat carotid blood flow induces rapid alteration of artery mechanical properties

Vascular remodeling is essential to proper vessel function. Dramatic changes in mechanical environment, however, may initiate pathophysiological vascular remodeling processes that lead to vascular disease. Previous work by some of our group has demonstrated a dramatic rise in matrix metalloproteinase (MMP) expression shortly following an abrupt increase in carotid blood flow. We hypothesized that there would be a corresponding change in carotid mechanical properties. Unilateral carotid ligation surgery was performed to produce an abrupt, sustained increase in blood flow through the contralateral carotid artery of rats. The flow-augmented artery was harvested after sham surgery or 1, 2, or 6 days after flow augmentation. Vessel mechanical response in the circumferential direction was then evaluated through a series of pressure-diameter tests. Results show that the extent of circumferential stretch (normalized change in diameter) at in vivo pressure levels was significantly different (p<0.05) from normo-flow controls at 1 and 2 days following flow augmentation. Measurements at 1, 2, and 6 days were not significantly different from one another, but a trend in the data suggested that circumferential stretch was largest 1 day following surgery and subsequently decreased toward baseline values. Because previous work with this model indicated a similar temporal pattern for MMP-9 expression, an exploratory set of experiments was conducted where vessels were tested 1 day following surgery in animals treated with broad spectrum MMP inhibitors (either doxycycline or GM6001). Results showed a trend for the inhibitors to minimize changes in mechanical properties. Observations demonstrate that vessel mechanical properties change rapidly following flow augmentation and that alterations may be linked to expression of MMPs.

Tensile characteristics and behavior of blood vessels from human brain in uniaxial tensile test

The rupture of blood vessels in the human brain results in serious pathological and medical problems. In particular, brain hemorrhage and hematomas resulting from impact to the head are a major cause of death. As such, investigating the tensile behavior and rupture of blood vessels in the brain is very important from a medical point of view. In the present study, the tensile characteristics of the blood vessels in the human brain were analyzed using a quasi-static uniaxial tensile test, and the properties of the arteries and veins compared. In addition, to compare the tensile behavior and demonstrate the validity of the experimental results, blood vessels from the legs of pigs were also tested and analyzed. The overall results were in accordance with the histological structures and previous medical reports.

Subfailure overstretch induces persistent changes in the passive mechanical response of cerebral arteries.

Cerebral blood vessels are critical in maintaining the health of the brain, but their function can be disrupted by traumatic brain injury (TBI). Even in cases without hemorrhage, vessels are deformed with the surrounding brain tissue. This subfailure deformation could result in altered mechanical behavior. This study investigates the effect of overstretch on the passive behavior of isolated middle cerebral arteries (MCAs), with the hypothesis that axial stretch beyond the in vivo length alters this response. Twenty nine MCA sections from 11 ewes were tested. Vessels were subjected to a baseline test consisting of an axial stretch from a buckled state to 1.05* in vivo stretch (λIV) while pressurized at 13.3 kPa. Specimens were then subjected to a target level of axial overstretch between 1.05*λIV (λz = 1.15) and 1.52*λIV (λz = 1.63). Following overstretch, baseline tests were repeated immediately and then every 10 min, for 60 min, to investigate viscoelastic recovery. Injury was defined as an unrecoverable change in the passive mechanical response following overstretch. Finally, pressurized MCAs were pulled axially to failure. Post-overstretch response exhibited softening such that stress values at a given level of stretch were lower after injury. The observed softening also generally resulted in increased non-linearity of the stress-stretch curve, with toe region slope decreasing and large deformation slope increasing. There was no detectable change in reference configuration or failure values. As hypothesized, the magnitude of these alterations increased with overstretch severity, but only once overstretch exceeded 1.2*λIV (p < 0.001). These changes were persistent over 60 min. These changes may have significant implications in repeated TBI events and in increased susceptibility to stroke post-TBI.

Effect of Ultrasound on the Permeability of Vascular Wall to Nano-emulsion Droplets

The effect of ultrasound on the permeability of blood vessels to nano-emulsion droplets was investigated using excised mouse carotid arteries as model blood vessels. Perfluorocarbon nano-droplets were formed by perfluoro-15-crown-5-ether and stabilized by poly(ethylene oxide)-co-poly(DL-lactide) block co-polymer shells. Nano-droplet fluorescence was imparted by interaction with fluorescein isothiocyanate-dextran (molecular weight = 70,000 Da). The permeability of carotid arteries to nano-droplets was studied in the presence and absence of continuous wave or pulsed therapeutic 1-MHz ultrasound. The data indicated that the application of ultrasound resulted in permeabilization of the vascular wall to nano-droplets. The effect of continuous wave ultrasound was substantially stronger than that of pulsed ultrasound of the same total energy. No effect of blood vessel pre-treatment with ultrasound was observed.

Development of Mechanical and Failure Properties in Sheep Cerebral Arteries

Traumatic brain injury (TBI) is a devastating problem for people of all ages, but the nature of the response to such injury is often different in children than in adults. Cerebral vessel damage and dysfunction are common following TBI, but age-dependent, large-deformation vessel response has not been characterized. Our objective was to investigate the mechanical properties of cerebral arteries as a function of development. Sheep middle cerebral arteries from four age groups (fetal, newborn, juvenile, and adult) were subjected to biaxial loading around physiological conditions and then to failure in the axial direction. Results show little difference among age groups under physiological loading conditions, but response varied significantly with age in response to large axial deformation. Vessels from all age groups reached the same ultimate stretch level, but the amount of stress carried at a given level of stretch increased significantly with age through the developmental period (fetal to juvenile). Our results are the first to identify changes in cerebral vessel response to large deformations with age and may lead to new insights regarding differences in response to TBI with age.

Cerebrovascular dysfunction following subfailure axial stretch.

Cerebral blood vessels are vital to maintaining the health of the brain. Traumatic brain injury (TBI) commonly results in autoregulatory dysfunction and associated failure of cerebral vessels to maintain homeostasis in the brain. While post-injury changes to brain biochemistry are known to contribute to this dysfunction, tissue deformation may also directly alter vascular smooth muscle cell (SMC) function. As a first step toward understanding stretch-induced dysfunction, this study investigates the effect of overstretch on the contractile behavior of SMCs in middle cerebral arteries (MCAs). We hypothesized that vessel function is altered above a threshold of stretch and strain rate. Twenty-four MCAs from Sprague Dawley rats were tested. Following development of basal SMC tone, vessels were subjected to increasing levels of isosmotic extracellular potassium (K+). Samples were then subjected to an axial overstretch of either 1.2*λIV or 1.3*λIV at strain rates of 0.2 or 20s-1. Following overstretch, SMC contractile behavior was measured again, both immediately and 60min after overstretch. Control vessels were subjected to the same protocol but without overstretch. SMC contractile behavior was characterized using both percent contraction (%C) relative to the fully dilated inner diameter and the K+ dose required to evoke the half maximal contractile response (EC50). Control vessels exhibited increased sensitivity to K+ in successive characterization tests, so all effects were quantified relative to the time-matched control response. Samples exhibited the typical biphasic response to extracellular K+, dilating and contracting in response to small and large K+ concentrations, respectively. As hypothesized, axial overstretch altered SMC contractile behavior, as seen in a decrease in %C for sub-maximal contractile K+ doses (p<0.05) and an increase in EC50 (p<0.01), but only for the test group stretched rapidly to 1.3*λIV. While the change in %C was only significantly different immediately after overstretch, the change to EC50 persisted for 60min. These results indicate that deformation can alter SMC contractile behavior and thus potentially play a role in cerebrovascular autoregulatory dysfunction independent of the pathological chemical environment in the brain post-TBI.