Computer simulation of glioma growth and morphology

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion

Physiological and histopathological responses following closed rotational head injury depend on direction of head motion

Rotational inertial forces are thought to be the underlying mechanism for most severe brain injuries. However, little is known about the effect of head rotation direction on injury outcomes, particularly in the pediatric population. Neonatal piglets were subjected to a single non-impact head rotation in the horizontal, coronal, or sagittal direction, and physiological and histopathological responses were observed. Sagittal rotation produced the longest duration of unconsciousness, highest incidence of apnea, and largest intracranial pressure increase, while coronal rotation produced little change, and horizontal rotation produced intermediate and variable derangements. Significant cerebral blood flow reductions were observed following sagittal but not coronal or horizontal injury compared to sham. Subarachnoid hemorrhage, ischemia, and brainstem pathology were observed in the sagittal and horizontal groups but not in a single coronal animal. Significant axonal injury occurred following both horizontal and sagittal rotations. For both groups, the distribution of injury was greater in the frontal and parietotemporal lobes than in the occipital lobes, frequently occurred in the absence of ischemia, and did not correlate with regional cerebral blood flow reductions. We postulate that these direction-dependent differences in injury outcomes are due to differences in tissue mechanical loading produced during head rotation

ICAR: endoscopic skull‐base surgery

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A review of cervical fractures and fracture-dislocations without head impacts sustained by restrained occupants

Crash injury reduction via lap-shoulder belt use has been well documented. Like any other interior car component, lap-shoulder belts may be related to injury in certain crashes. Relatively unknown is the fact that cervical fractures or fracture-dislocations to restrained front seat occupants occur where no head contact was evidenced by both medical records and car inspection. A review of the available literature on car crash injuries revealed more than 100 such cases. A review of the National Accident Severity Study (NASS) 80-88 file was also conducted, revealing more examples. Case capsule descriptions from the authors' files are also detailed along with examples of such injuries in infants and children in child restraints. However, cervical fractures or fracture dislocations are rare, as evidenced by the relatively few cases identified in the literature, in the author's files, and by an analysis of NASS 80-90 data that revealed a cervical spine injury frequency of only .4% at the AIS-3 level (Hueike, Morris, and Mackay 1992).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30429/1/0000050.pd

Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition

Objective: To study the relationship between thalamic glucose metabolism and neurological outcome after severe traumatic brain injury (TBI). Methods: Forty-nine patients with severe and closed TBI and 10 healthy control subjects with 18F-FDG PET were studied. Patients were divided into three groups: MCS&VS group (n ¼ 17), patients in a vegetative or a minimally conscious state; In-PTA group (n ¼ 12), patients in a state of post-traumatic amnesia (PTA); and Out-PTA group (n ¼ 20), patients who had emerged from PTA. SPM5 software implemented in MATLAB 7 was used to determine the quantitative differences between patients and controls. FDG-PET images were spatially normalized and an automated thalamic ROI mask was generated. Group differences were analysed with two sample voxel-wise t-tests. Results: Thalamic hypometabolism was the most prominent in patients with low consciousness (MCS&VS group) and the thalamic hypometabolism in the In-PTA group was more prominent than that in the Out-PTA group. Healthy control subjects showed the greatest thalamic metabolism. These differences in metabolism were more pronounced in the internal regions of the thalamus. Conclusions: The results confirm the vulnerability of the thalamus to suffer the effect of the dynamic forces generated during a TBI. Patients with thalamic hypometabolism could represent a sub-set of subjects that are highly vulnerable to neurological disability after TBI.Lull Noguera, N.; Noé, E.; Lull Noguera, JJ.; Garcia Panach, J.; Chirivella, J.; Ferri, J.; López-Aznar, D.... (2010). Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition. Brain Injury. 24(9):1098-1107. doi:10.3109/02699052.2010.494592S10981107249Gallagher, C. 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