Quantitative assessment of background parenchymal enhancement in breast MRI predicts response to risk-reducing salpingo-oophorectomy: preliminary evaluation in a cohort of BRCA1/2 mutation carriers.

INTRODUCTION: We present a fully automated method for deriving quantitative measures of background parenchymal enhancement (BPE) from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perform a preliminary evaluation of these measures to assess the effect of risk-reducing salpingo-oophorectomy (RRSO) in a cohort of breast cancer susceptibility gene 1/2 (BRCA1/2) mutation carriers. METHODS: Breast DCE-MRI data from 50 BRCA1/2 carriers were retrospectively analyzed in compliance with the Health Insurance Portability and Accountability Act and with institutional review board approval. Both the absolute (| |) and relative (%) measures of BPE and fibroglandular tissue (FGT) were computed from the MRI scans acquired before and after RRSO. These pre-RRSO and post-RRSO measures were compared using paired Student's t test. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate the performance of relative changes in the BPE and FGT measures in predicting breast cancer that developed in these women after the RRSO surgery. RESULTS: For the 44 women who did not develop breast cancer after RRSO, the absolute volume of BPE and FGT had a significant decrease (P < 0.05) post-RRSO, whereas for the 6 women who developed breast cancer, there were no significant changes in these measures. Higher values in all BPE and FGT measures were also observed post-RRSO for the women who developed breast cancer, compared with women who did not. Relative changes in BPE percentage were most predictive of women who developed breast cancer after RRSO (P < 0.05), whereas combining BPE percentage and |FGT| yielded an AUC of 0.80, higher than BPE percentage (AUC = 0.78) or |FGT| (AUC = 0.66) alone (both P > 0.02). CONCLUSIONS: Quantitative measures of BPE and FGT are different before and after RRSO, and their relative changes are associated with prediction of developing breast cancer, potentially indicative of women who are more susceptible to develop breast cancer after RRSO in BRCA1/2 mutation carriers.

Breast MRI fibroglandular volume and parenchymal enhancement in BRCA1 and BRCA2 mutation carriers before and immediately after risk-reducing salpingo-oophorectomy.

OBJECTIVE. The purpose of this article is to assess the difference in fibroglandular volume and background parenchymal enhancement in BRCA1 and BRCA2 mutation carriers on contrast-enhanced breast MRI (CE-MRI) performed before and immediately after risk-reducing salpingo-oophorectomy (RRSO). MATERIALS AND METHODS. We retrospectively compared fibroglandular volume and background parenchymal enhancement in 55 female BRCA1 and BRCA2 mutation carriers before and after RRSO using standard BI-RADS categories and a paired Wilcoxon and Mann-Whitney U test. A two-sample Wilcoxon test was performed to compare fibroglandular volume and background parenchymal enhancement in women with and without subsequent breast cancer diagnosis on follow-up. RESULTS. The median time to post-RRSO CE-MRI was 8 months (range, 1-40 months). There was no difference in fibroglandular volume before and after RRSO (p = 0.65). The mean background parenchymal enhancement was 2.5 (range, 1-4) before and 1.5 (range, 1-4) after RRSO (overall range, -2.5 to 1.5; p = 0.0001). Breast cancer was detected in nine women at a median time of 4.8 years (range, 1.8-13.3 years) after RRSO. For women who received a diagnosis of breast cancer after RRSO compared with those who did not, mean background parenchymal enhancement before RRSO was 3 (range, 2-4) versus 2.5 (range, 1-4; p = 0.001), and mean background parenchymal enhancement after RRSO was 2.5 (range, 1.5-4) versus 1.5 (range 2-4; p = 0.0018). There was no difference in fibroglandular volume before and after RRSO. CONCLUSION. In BRCA1 and BRCA2 mutation carriers, we observed a significant reduction in background parenchymal enhancement on the first CE-MRI after RRSO and no significant change in fibroglandular volume. Higher background parenchymal enhancement before and after RRSO was observed in women who subsequently received a diagnosis of breast cancer. This suggests that background parenchymal enhancement, rather than fibro-glandular volume, may be a more sensitive imaging biomarker of breast cancer risk.

Semi-jailing technique for coil embolization of complex, wide-necked intracranial aneurysms.

OBJECTIVE: Stent-assisted coiling of intracranial aneurysms is performed by placing a microcatheter through a stent's interstices or jailing the microcatheter between the stent and the artery. Both approaches impede manipulation of the microcatheter during coiling. We describe a modified jailing technique that improves catheter maneuverability and report the safety and efficacy of the method for the treatment of complex, wide-necked aneurysms. METHODS: The semi-jailing technique involves the partial deployment of a retrievable stent, bridging part of the aneurysm neck while leaving space to maneuver the microcatheter. Twenty-two complex, wide-necked aneurysms, including 3 ruptured and 5 dissecting, were treated using the semi-jailing technique (15 women; mean age, 55.2 years). RESULTS: The semi-jailing technique was successfully applied in all cases. Immediate posttreatment angiograms showed total occlusion of the aneurysm in 17 cases (77%), neck remnant in 3 cases (14%), and aneurysm dome filling in 2 cases (9%). Follow-up angiography available in 10 patients at an average of 8.5 months showed progressive occlusion in 1 aneurysm and 7 remained occluded. In 2 cases of dissecting aneurysms, retreatment was required. No permanent periprocedural morbidity was encountered. One patient died of complications secondary to intracranial hemorrhage 6 days after treatment. In 2 cases (9%), thromboembolic events after final stent placement were successfully treated with intraarterial thrombolysis. No delayed stent migration was seen. CONCLUSION: Semi-jailing is a safe and effective stent-assisted coiling technique that facilitates treatment of complex, wide-necked aneurysms.

Carotid artery brain aneurysm model: in vivo molecular enzyme-specific MR imaging of active inflammation in a pilot study.

PURPOSE: To demonstrate the feasibility of using a myeloperoxidase (MPO)-specific paramagnetic magnetic resonance (MR) contrast agent to identify active inflammation in an animal model of common carotid artery (CCA) aneurysm. MATERIALS AND METHODS: All animal experiments were approved by the institutional animal care and use committee. Elastase-induced saccular aneurysms were created at the root of the right CCA in 16 New Zealand white rabbits. Intramural and perivascular injection of Escherichia coli lipopolysaccharide (LPS) was performed with an endovascular approach to induce aneurysm inflammation. After intraarterial injection of an MPO-specific (di-5-hydroxytryptamide of gadopentetate dimeglumine, 0.1 mmol per kilogram of bodyweight) or a non-MPO-specific (di-tyrosine of gadopentetate dimeglumine, 0.1 mmol/kg) contrast agent, animals underwent 3-T MR imaging. Intramural presence of MPO in aneurysms in which LPS had been injected was confirmed at immunohistologic analysis. Active MPO activity was verified by measuring the spectrophotometric oxidation of guaiacol. RESULTS: Endovascular injection of LPS resulted in inflammatory cell infiltration into the aneurysm wall, and there was a difference in active MPO expression between aneurysms in which LPS had been injected and control aneurysms (20.3 ng of MPO per milligram of tissue vs 0.12 ng of MPO per milligram of tissue, respectively; P < .002). MR imaging with di-5-hydroxytryptamide of gadopentetate dimeglumine revealed a difference in enhancement ratio between inflamed aneurysms in which LPS had been injected and control aneurysms (1.55 +/- 0.05 vs 1.16 +/- 0.10, respectively; P < .02). In inflamed aneurysms, di-5-hydroxytryptamide of gadopentetate dimeglumine exhibited delayed washout kinetics compared with the kinetics of di-tyrosine of gadopentetate dimeglumine. This finding enabled the verification of MPO specificity. CONCLUSION: The findings of this pilot study established the feasibility of an animal model of saccular aneurysm inflammation that can be seen with clinical-field-strength MR imaging and use of the enzyme-sensitive MR contrast agent di-5-hydroxytryptamide of gadopentetate dimeglumine, which is a paramagnetic MPO substrate that specifically enhances MR signal.

Advances in interventional neuroradiology.

In 2008 we witnessed a rapid advancement in stent technology, which is reflected in the high number of case reports, publications of case series, and randomized trials. Stents not only served for a combined intrasaccular and extrasaccular treatment of challenging aneurysms but also assisted the revascularization in acute and chronic ischemic conditions of the neurovascular system. Although a self-expanding nitinol semiopen cell stent is currently used for intracranial occlusive disease, a new retrievable closed-cell designed stent is widely used for aneurysms because of its easy delivery through a microcatheter in frequently tortuous head and neck as well as cerebrovascular circulation (Figure 1). However, despite numerous publications in the field, the widespread acceptance of the use of stents to routinely treat carotid stenosis awaits the results of the multicenter randomized clinical trials that should be available in 2009. The role of interventional neuroradiology in the treatment of acute ischemic stroke continues to expand and excite interest.

The epithelial-mesenchymal transition of colon carcinoma involves expression of IL-8 and CXCR-1-mediated chemotaxis.

The epithelial-mesenchymal transition (EMT) is an essential component of embryonic development, tissue remodeling, and wound repair. In addition, many epithelial tumors, including colorectal carcinomas, appear to undergo this transition that may facilitate their invasion. Using a novel model of EMT in colon carcinoma in which the inflammatory cytokine TNF-alpha accelerates this TGF-beta directed process, we report that TNF-alpha stimulation upregulates expression of the chemokine IL-8, and that this upregulation is dependent on the transcription factor NF-kappaB. Significantly, this effect is not merely an inflammatory response by these colon carcinoma cells because IL-8 expression is induced in cells undergoing a TGF-beta-driven EMT in the absence of exogenous TNF-alpha. During the EMT, a concomitant increase in the chemokine receptor CXCR-1, but not CXCR-2, also occurs. Moreover, both IL-8 and CXCR-1 function in the chemokinetic and chemotactic migration of colon carcinoma cells as assessed by antibody inhibition studies. These studies establish that the regulated expression of a specific chemokine and its receptor are linked to the EMT and they provide a biochemical framework for understanding the mechanisms by which the EMT promotes migration.