Faculty Bibliography

OBJECTIVE: To differentiate recurrent tumors from radiation effects and necrosis in patients with irradiated brain tumors using perfusion computed tomographic (PCT) imaging. METHODS: Twenty-two patients with previously treated brain tumors who showed recurrent or progressive enhancing lesions on follow-up magnetic resonance imaging scans and had a histopathological diagnosis underwent first-pass PCT imaging (26 PCT imaging examinations). Another eight patients with treatment-naive, high-grade tumors (control group) also underwent PCT assessment. Perfusion maps of cerebral blood volume, cerebral blood flow, and mean transit time were generated at an Advantage Windows workstation using the CT perfusion 3.0 software (General Electric Medical Systems, Milwaukee, WI). Normalized ratios (normalized to normal white matter) of these perfusion parameters (normalized cerebral blood volume [nCBV], normalized cerebral blood flow [nCBF], and normalized mean transit time [nMTT]) were used for final analysis. RESULTS: Fourteen patients were diagnosed with recurrent tumor, and eight patients had radiation necrosis. There was a statistically significant difference between the two groups, with the recurrent tumor group showing higher mean nCBV (2.65 versus 1.10) and nCBF (2.73 versus 1.08) and shorter nMTT (0.71 versus 1.58) compared with the radiation necrosis group. For nCBV, a cutoff point of 1.65 was found to have a sensitivity of 83.3% and a specificity of 100% to diagnose recurrent tumor and radiation necrosis. Similar sensitivity and specificity were 94.4 and 87.5%, respectively, for nCBF with a cutoff point of 1.28 and 94.4 and 75%, respectively, for nMTT with a cutoff point of 1.44 to diagnose recurrent tumor and radiation necrosis. CONCLUSION: PCT may aid in differentiating recurrent tumors from radiation necrosis on the basis of various perfusion parameters. Recurrent tumors show higher nCBV and nCBF and lower nMTT compared with radiation necrosis.

We present the imaging findings of a case of spinal pilomyxoid astrocytoma in a 29-year-old woman with history of neck and back pain and weakness of bilateral upper extremities. A contrast-enhanced magnetic resonance (MR) imaging study revealed an extensive intradural extramedullary lesion occupying most of the thecal sac extending from mid cervical up to the lumbosacral region with extensive contrast enhancement. Spinal pilomyxoid astrocytoma is rare with only three reported cases in pediatric population in the literature. This report illustrates the MR findings of an unusual case of intradural extramedullary spinal pilomyxoid tumor in an adult patient.

OBJECTIVE:The serine protease thrombin can dramatically alter endothelial gene expression in a manner that confers a proinflammatory phenotype. Recent studies have identified the Kruppel-like factor 2 (KLF2) as a critical regulator of endothelial gene expression. Herein, we provide evidence that KLF2 inhibits thrombin-mediated endothelial activation via alterations in expression of its principal receptor protease-activated receptor-1 (PAR-1). METHODS AND RESULTS/RESULTS:Forced expression of KLF2 in human umbilical vein endothelial cells potently inhibited the ability of thrombin to induce multiple prothrombotic factors (tissue factor, CD40L, plasminogen activator inhibitor-1), cytokines/chemokines (eg, monocyte chemotactic protein-1, interleukin-6 [IL-6], IL-8), and matrix degrading enzymes (eg, matrix metalloproteinases 1, 2, and 9). Mechanistically, KLF2 inhibits PAR-1 expression and, as a consequence, thrombin-mediated nuclear factor kappaB (NF-kappaB) nuclear accumulation and DNA binding. Conversely, small interfering RNA-mediated knockdown of KLF2 increases PAR-1 expression and thrombin-mediated induction of NF-kappaB activation. CONCLUSIONS:These studies identify KLF2 as a novel regulator of PAR-1 expression and thrombin action in endothelial cells.