Development of a computer-assisted forensic radiographic identification method using the lateral cervical and lumbar spine.

Medical examiners and coroners (ME/C) in the United States hold statutory responsibility to identify deceased individuals who fall under their jurisdiction. The computer-assisted decedent identification (CADI) project was designed to modify software used in diagnosis and treatment of spinal injuries into a mathematically validated tool for ME/C identification of fleshed decedents. CADI software analyzes the shapes of targeted vertebral bodies imaged in an array of standard radiographs and quantifies the likelihood that any two of the radiographs contain matching vertebral bodies. Six validation tests measured the repeatability, reliability, and sensitivity of the method, and the effects of age, sex, and number of radiographs in array composition. CADI returned a 92-100% success rate in identifying the true matching pair of vertebrae within arrays of five to 30 radiographs. Further development of CADI is expected to produce a novel identification method for use in ME/C offices that is reliable, timely, and cost-effective.

Assessments of function and biochemistry of the anterior cingulate cortex in schizophrenia.

BACKGROUND: Neuroimaging and electrophysiologic studies have consistently provided evidence of impairment in anterior cingulate cortex/medial frontal cortex function in people with schizophrenia. In this study, we sought to clarify the nature of this abnormality by combining proton magnetic resonance spectroscopy (1H-MRS) with functional magnetic resonance imaging (fMRI) at 3T. METHODS: We used single-voxel MRS acquired in the dorsal anterior cingulate cortex and fMRI during performance of a Stroop color-naming task to investigate the neurochemistry and functional response of the anterior cingulate cortex/medial frontal cortex in 26 stable, medicated subjects with schizophrenia and 23 matched healthy control subjects. RESULTS: In schizophrenia subjects, we found decreased blood oxygen level-dependent signal in the medial frontal wall, with significant clusters restricted to more dorsal regions compared with healthy subjects. In addition, we observed a trend-level decrease in N-acetylaspartate/creatine (NAA/Cr) levels and a significant positive correlation between NAA/Cr level and the blood oxygen level-dependent signal in schizophrenia subjects that did not exist in healthy subjects. Furthermore, in this group of medicated subjects, we did not find evidence of decreased glutamate + glutamine(Glx)/Cr levels, but there was a significant negative correlation between Glx/Cr levels and negative symptoms. CONCLUSIONS: Our results suggest that abnormal NAA levels, which may reflect a neuronal dysfunction related to schizophrenia, affect neuronal physiology, as evidenced by reduced blood oxygen level-dependent response.

Effects of G207, a conditionally replication-competent oncolytic herpes simplex virus, on the developing mammalian brain.

Viral oncolytic therapy for malignant brain tumors involves local intratumoral delivery of a genetically engineered virus with tumor cell-specific lytic activity. Promising preliminary results have been achieved in preclinical models with G207, a replication-competent herpes simplex virus type 1 constructed with multiple directed mutations. Although the safety of G207 has been demonstrated in adults, application of viral oncolytic therapy to children with brain tumors has been delayed because of previous lack of data concerning the impact of a replication-competent oncolytic virus on the developing mammalian brain. In this study there was no significant difference in long-term physical development, cognitive performance, or exploratory behaviors between mice that received intracerebral inoculation of G207 or control saline at 4 days of age. However, histological examination and magnetic resonance imaging revealed frequent unilateral ventriculomegaly ipsilateral to the site of injection in only the G207 group. These results suggest that although it is unlikely that G207 will have significant adverse effects on neurodevelopmental outcomes of pediatric patients with brain tumors, an initial study of G207 in children should exclude those patients with tumors in or near the ventricular system as well as patients less than 2 years of age. Furthermore, patients in such a study will need to be closely monitored for the development of hydrocephalus.

A novel technique to quantify glioma tumor invasion using serial microscopy sections.

Here we present a new technique to quantitatively characterize malignant glioma invasion in a syngeneic mouse model. The GL261 mouse malignant glioma cell line was injected intracerebrally into the C57B1/6 black mouse and allowed to propagate for 10 or 17 days, followed by euthanasia of the animal, harvesting of the brain, fixation, and serial sectioning. Histologic examination was performed and the primary tumor mass and discontinuous sites of tumor invasion were traced on digital images of serial microscopy sections, followed by analysis of the invasion characteristics using a custom-written MATLAB program. We found a significant increase in the number of discontinuous tumor invasion sites and in the distance of these sites from the tumor centroid in mice that were euthanized at 17 days post-tumor cell injection, as compared to mice euthanized at 10 days. Furthermore, a scatter plot analyses indicated that the invasion site data could be grouped based on the characteristics of area and distance from the tumor centroid to reveal significant differences between the two experimental groups of mice. This quantitative method will allow a future in vivo analysis of invasion characteristics in glioma cells expressing altered levels or function of invasion genes, and of new therapy targeting invading glioma cells.

Assessment of brain tumor angiogenesis inhibitors using perfusion magnetic resonance imaging: quality and analysis results of a phase I trial.

PURPOSE: To determine thresholds of quality for a T2*-weighted perfusion magnetic resonance imaging (MRI) study and evaluate the effects of an angiogenesis inhibitor on relative blood flow and volume changes in brain tumor patients in a multi-institution setting. MATERIALS AND METHODS: A total of 36 volunteers from four participating institutions with clinically diagnosed malignant gliomas were studied using perfusion MRI protocols. These included a baseline study and follow-up studies every eight weeks to evaluate the effect of an anti-angiogenic agent on tumor perfusion. Quality tests were performed on the perfusion imaging data by defining statistical thresholds of acceptance. Region of interest (ROI) analysis was performed on tumors and kinetic parameters were normalized with respect to normal tissue. RESULTS: Statistical thresholds for goodness of the gamma variate fit, T2* recovery, and mean signal full-width half-minimum (FWHMin) were computed for our data sets with a 99% one-sided confidence interval; these were 6.91%, 79.48%, and 23.35 seconds, respectively. Decreases in-blood volume and flow measurements were observed in patients with documented clinical response. CONCLUSION: Malignant brain tumors have altered perfusion parameters that may be used to understand and monitor neovascularization. This permits non-invasive assessment of the efficacy of angiogenesis inhibiting drugs.