[show abstract][hide abstract] ABSTRACT: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults. We combined neuroimaging and DNA microarray analysis to create a multidimensional map of gene-expression patterns in GBM that provided clinically relevant insights into tumor biology. Tumor contrast enhancement and mass effect predicted activation of specific hypoxia and proliferation gene-expression programs, respectively. Overexpression of EGFR, a receptor tyrosine kinase and potential therapeutic target, was also directly inferred by neuroimaging and was validated in an independent set of tumors by immunohistochemistry. Furthermore, imaging provided insights into the intratumoral distribution of gene-expression patterns within GBM. Most notably, an "infiltrative" imaging phenotype was identified that predicted patient outcome. Patients with this imaging phenotype had a greater tendency toward having multiple tumor foci and demonstrated significantly shorter survival than their counterparts. Our findings provide an in vivo portrait of genome-wide gene expression in GBM and offer a potential strategy for noninvasively selecting patients who may be candidates for individualized therapies.
Proceedings of the National Academy of Sciences 05/2008; 105(13):5213-8. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the relative efficacy of three compression adjuncts -- D-Stat Dry (D-Stat), QR Powder (QR), and XS Powder (XS) -- for reducing time to hemostasis in patients who underwent diagnostic and interventional percutaneous procedures.
D-Stat, QR, or XS was applied in 176 percutaneous diagnostic arterial, therapeutic arterial, venous, and arteriovenous dialysis access (AVDA) procedures in 138 patients. The mean time to hemostasis and application-related complications were retrospectively assessed.
Mean time to hemostasis was significantly reduced in all applications of QR (3.1 minutes +/- 1.1) and XS (3.7 minutes +/- 1.1) relative to D-Stat (6.2 minutes +/- 1.1, P < .001 vs both). For therapeutic arterial procedures, mean time to hemostasis for QR and XS was 3.6 minutes +/- 1.1 and 4.8 minutes +/- 1.1, respectively, and this was significantly less than that of D-Stat (10.0 minutes +/- 1.2; P < .001 vs QR, P < .01 vs XS). Mean times to hemostasis for QR and XS were also shorter than that with D-Stat in diagnostic arterial and AVDA procedures (P < .05). For venous procedures, mean time to hemostasis for QR (1.9 minutes +/- 1.2) was significantly shorter than that with both D-Stat (4.0 minutes +/- 1.2, P < .05) and XS (3.7 minutes +/- 1.2, P < .05). Minor immediate complications (hematoma <5 cm) occurred in 2.8% of applications. No access site infections were observed.
All three agents effectively reduced time to hemostasis with minimal associated complications. QR was found to be more effective than D-Stat in all four procedure types.
Journal of Vascular and Interventional Radiology 01/2008; 19(1):72-9. · 2.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: The characterization of human diseases by their underlying molecular and genomic aberrations has been the hallmark of molecular medicine. From this, molecular imaging has emerged as a potentially revolutionary discipline that aims to visually characterize normal and pathologic processes at the cellular and molecular levels within the milieu of living organisms. Molecular imaging holds promise to provide earlier and more precise disease diagnosis, improved disease characterization, and timely assessment of therapeutic response. This primer is intended to provide a broad overview of molecular imaging with specific focus on future clinical applications relevant to interventional radiology.
Journal of Vascular and Interventional Radiology 10/2006; 17(9):1405-23. · 2.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: Endovascular stent grafts are now accepted globally and approved by the US Food and Drug Administration as an alternative to open surgical repair for patients with descending thoracic aortic aneurysm. However, as opposed to the abdominal aorta, application of this technology to manage thoracic aortic disease is not limited to degenerative aneurysms. In fact, international registries and surveys estimate that only 60% of the thoracic cases managed currently with stent-graft placement are aneurysms. The remainder of this experience includes acute dissection, chronic dissection, traumatic aortic injury, penetrating ulcer, intramural hematoma, aortic fistula, anastomotic pseudoaneurysm, and an embolizing lesion. In this regard, it is important to keep in mind that the present devices used in these nonaneurysmal applications are not designed to address the unique anatomical and pathological features that these lesions present. Consequently, in the future, it is possible that we will see stent-graft designs that focus specifically on the challenges of some of the nonaneurysmal thoracic aortic pathologies.
Seminars in Vascular Surgery 04/2006; 19(1):40-7. · 1.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: To test the hypothesis that controlled perivascular release of tissue plasminogen activator (tPA) can generate cleaved extracellular matrix (ECM) chemotactic gradients to guide the migration of vascular smooth muscle cells (SMCs) away from the lumen, thereby limiting neointima formation.
This hypothesis was tested in rabbit models in which the perivascular surface of vein bypass grafts was treated with microspheres releasing tPA (MS-tPA), microspheres containing no drug (MS-blank), or phosphate buffered saline (PBS). Vein graft segments harvested after 7 days were then evaluated for elastin content, proliferating SMCs, intima-to-media (I/M) ratio, and inflammation; late impact on neointima formation was also examined.
The 7-day results demonstrated cleaved elastin gradients and proliferating SMCs that assumed a more peripheral distribution in the MS-tPA group than MS-blank and PBS controls (p<0.05). At 28 days, vein grafts treated with MS-tPA showed a mean I/M ratio (0.35+/-0.04) that was 63.5% lower than PBS controls (0.96+/-0.07, p<0.005) and 43.5% lower than MS-blank specimens (0.62+/-0.08, p<0.05).
Perivascular release of tPA modifies ECM gradients, directionally guides SMC migration away from the lumen, and limits neointima formation.
Journal of Endovascular Therapy 01/2006; 12(6):667-75. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine the effects of oxidative stress on neointimal hyperplasia through local overexpression of human copper-zinc superoxide dismutase (Cu-Zn SOD).
The left common femoral arteries (CFA) of 18 New Zealand white rabbits were subjected to balloon overdilation injury. Each dilated CFA was then incubated with either a nonviral (buffer) or viral (adenovirus overexpressing beta-galactosidase) control or an adenovirus overexpressing Cu-Zn SOD. Animals were then sacrificed at 3, 7, or 28 days (3 arteries per group per time point) and the treated CFA segments were harvested for analysis of esterase-positive inflammatory cells and extracellular matrix elements. The intima-to-media ratio (I/M) was measured to assess the degree of neointimal formation.
At 3 days, local SOD levels in the Cu-Zn SOD-treated group were significantly elevated relative to both controls (p<0.01). Significant reductions in lipid peroxidation byproducts were also seen in the SOD group relative to viral and nonviral controls (p<0.05). Mean I/M at 28 days was 0.582+/-0.088 for the nonviral control group versus 0.565+/-0.133 for the viral control group. The SOD-treated group had a significant reduction relative to both controls: 0.259+/-0.045 (p<0.05). Statistically significant reductions in I/M were also demonstrated in the SOD group relative to control groups at 7 days (p<0.05). The SOD-treated group demonstrated significant preservation of elastin relative to controls, as well as a significant reduction in esterase-positive granulocytes relative to controls (p<0.05).
Direct buffering of oxidative stress in balloon-injured vessels can significantly alter postinjury response and limit neointimal hyperplasia.
Journal of Endovascular Therapy 01/2005; 11(6):585-94. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate effect of controlled stent-based release of an NO donor to limit in-stent restenosis in rabbits.
Bioerodable microspheres containing NO donor or biodegradable polymer (polylactide-co-glycolide-polyethylene glycol) were prepared and loaded in channeled stents. Daily concentrations of NO release from NO-containing microspheres were assayed in vitro. NO- and polymer-containing (control) microsphere-loaded stents were deployed in aortas of New Zealand white rabbits (n = 8). Aortas with stents were harvested at 7 (n = 5) and 28 days (n = 3) and evaluated for cyclic guanosine monophosphate (cGMP) levels (7 days), number of proliferating cell nuclear antigen-positive cells (7 days), and intima-to-media ratio (7 and 28 days), with statistical significance evaluated by using one-way analysis of variance.
NO-containing microspheres released NO with an initial bolus in the 1st week, followed by sustained release for the remaining 3 weeks. Significant increase in cGMP levels and decrease in proliferating cell nuclear antigen-positive cells were found at 7 days for the NO-treated group relative to controls (P <.05). Intima-to-media ratio in the NO-treated group was reduced by 46% and 32% relative to controls at 7 and 28 days, respectively (mean, 0.14 +/- 0.01 [standard error] vs 0.26 +/- 0.02 at 7 days, P <.01; 1.34 +/- 0.05 vs 1.98 +/- 0.08 at 28 days, P <.01).
Stent-based controlled release of NO donor significantly reduces in-stent restenosis and is associated with increase in vascular cGMP and suppression of proliferation.