Diffusion-tensor imaging implicates prefrontal axonal injury in executive function impairment following very mild traumatic brain injury.

PURPOSE: To determine whether frontal white matter diffusion abnormalities can help predict acute executive function impairment after mild traumatic brain injury (mTBI). MATERIALS AND METHODS: This study had institutional review board approval, included written informed consent, and complied with HIPAA. Diffusion-tensor imaging and standardized neuropsychologic assessments were performed in 20 patients with mTBI within 2 weeks of injury and 20 matched control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) images (imaging parameters: 3.0 T, 25 directions, b = 1000 sec/mm(2)) were compared by using whole-brain voxelwise analysis. Spearman correlation analyses were performed to evaluate associations between diffusion measures and executive function. RESULTS: Multiple clusters of lower frontal white matter FA, including the dorsolateral prefrontal cortex (DLPFC), were present in patients (P < .005), with several clusters also demonstrating higher MD (P < .005). Patients performed worse on tests of executive function. Lower DLPFC FA was significantly correlated with worse executive function performance in patients (P < .05). CONCLUSION: Impaired executive function following mTBI is associated with axonal injury involving the DLPFC.

Diffusion tensor imaging abnormalities in patients with mild traumatic brain injury and neurocognitive impairment.

OBJECTIVE: To determine if diffusion tensor imaging can differentiate patients with chronic cognitive impairment after mild traumatic brain injury (TBI) from normal controls. METHODS: Ten patients with persistent cognitive impairment after mild TBI were evaluated at least 2 years after injury. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured at white matter regions susceptible to axonal injury after TBI. Comparison was made to 10 normal controls. RESULTS: Fractional anisotropy was significantly lower (4.5%; P = 0.01) and ADC higher (7.1%; P = 0.04) in patients at the left side of the genu of the corpus callosum. The mild TBI group also demonstrated a significant increase in FA within the posterior limb of the internal capsule bilaterally (left, 5.1%; P = 0.03; right, 1.9%; P = 0.04). CONCLUSIONS: These results demonstrate low FA and high ADC in the genu of the corpus callosum of mild TBI patients with persistent cognitive impairment, suggesting that permanent white matter ultrastructural damage occurs in mild TBI, and that such damage may be associated with persistent cognitive disability. Further longitudinal studies are warranted to elucidate the full importance of the findings.

Multifocal white matter ultrastructural abnormalities in mild traumatic brain injury with cognitive disability: a voxel-wise analysis of diffusion tensor imaging.

The purpose of the present study is to identify otherwise occult white matter abnormalities in patients suffering persistent cognitive impairment due to mild traumatic brain injury (TBI). The study had Institutional Review Board (IRB) approval, included informed consent and complied with the U.S. Health Insurance Portability and Accountability Act (HIPAA) of 1996. We retrospectively analyzed diffusion tensor MRI (DTI) of 17 patients (nine women, eight men; age range 26-70 years) who had cognitive impairment due to mild TBI that occurred 8 months to 3 years prior to imaging. Comparison was made to 10 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) images derived from DTI (1.5 T; 25 directions; b = 1000) were compared using whole brain histogram and voxel-wise analyses. Histograms of white matter FA show an overall shift toward lower FA in patients. Areas of significantly decreased FA (p < 0.005) were found in the subject group in corpus callosum, subcortical white matter, and internal capsules bilaterally. Co-located elevation of mean diffusivity (MD) was found in the patients within each region. Similar, though less extensive, findings were demonstrated in each individual patient. Multiple foci of low white matter FA and high MD are present in cognitively impaired mild TBI patients, with a distribution that conforms to that of diffuse axonal injury. Evaluation of single subjects also reveals foci of low FA, suggesting that DTI may ultimately be useful for clinical evaluation of individual patients.

CT-guided radiofrequency ablation in the palliative treatment of recurrent advanced head and neck malignancies.

PURPOSE: To evaluate the safety and effectiveness of computed tomography (CT)-guided radiofrequency (RF) ablation in the palliative treatment of recurrent advanced head and neck cancers. MATERIALS AND METHODS: From November 2002 to January 2005, the authors identified 14 patients (median age, 61 years) with 14 recurrent advanced primary head and neck malignancies who underwent 27 CT-guided RF ablation applications during 20 sessions at their institution. RF ablation was performed in all patients with the intent of palliative therapy. Radiologic tumor response was assessed by using Response Evaluation Criteria in Solid Tumors. Patients were assessed clinically by means of University of Washington Head and Neck Quality of Life questionnaires. RESULTS: Technical success in tumor targeting and electrode deployment was 100%. University of Washington quality of life surveys completed by six of 14 patients (43%) showed an index increase by a median of 3.1 percentage points, with four of six patients (67%) demonstrating improvement. Three major complications (in 27 applications, 11%) occurred 7 days to 2 weeks after the procedure. These included stroke, carotid blowout leading to death, and threatened carotid blowout with subsequent stroke. Retrospective analysis of intraprocedural CT scans revealed that the retractable electrodes were within 1 cm of the carotid artery during ablation in these cases. CONCLUSIONS: RF ablation in patients with advanced head and neck malignancies is feasible and effective for palliation. CT-guidance provides accurate probe placement and electrode deployment. The energy level used and proximity of the ablation sphere to the carotid artery may predispose to vascular complications.

Evidence for physical interaction between the immunoglobulin heavy chain variable region and the 3' regulatory region.

B cell-specific expression of immunoglobulin heavy chain (IgH) genes utilizes two cis regulatory regions, the intronic enhancer (Emicro), located in the J(H)-Cmicro intron, and a complex regulatory region that lies 3' to the IgH gene cluster, 3' RR. We hypothesized that the 3' RR is involved in IgH gene transcription in plasma cells via physical interaction between distal 3' RR enhancers and target V(H) sequences, with loop formation by intervening DNA. In support of this hypothesis we report sequence data at DNA recombination breakpoints as evidence for loop formation preceding DNA inversion in a plasma cell line. In addition, using the chromosome conformation capture technique, physical interactions between V(H) and 3' RR were analyzed directly and detected in MPC11 plasma cells and variants and normal splenic B cells but not detected in splenic T cells or in non-B cells. V(H)-3' RR interactions were present in the absence of Emicro, but when the hs1,2 enhancer was replaced by a Neo(R) gene in a variant cell line lacking Emicro, H chain expression was lost, and interactions between V(H) and 3' RR and among the 3' RR regulators themselves were severely disrupted. In addition, the chromosome conformation capture technique detected interactions between the myc promoter and 3' RR elements in MPC11, which like other plasmacytomas contains a reciprocal translocation between the c-myc and the IgH locus. In sum, our data support a hypothesis that cis V(H)-3' RR and myc-3' RR interactions involve physical interactions between these DNA elements.