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PURPOSE: Irreversible electroporation (IRE) is a promising new ablation method for hepatocellular carcinoma (HCC) treatment with few side-effects; however, tissue perfusion and differentiation between treatment zones have not been sufficiently studied. In this project, we analyzed HCC tumor perfusion changes immediately after IRE treatment using transcatheter intraarterial perfusion (TRIP)-MRI to monitor treatment zone margins. MATERIALS AND METHODS: All protocols were approved by the institutional animal care and use committee. A total of 34 rabbits were used for this prospective study: tumor liver group (n=17), normal liver group (n=14), and 3 for growing VX2 tumors. All procedures and imaging were performed under anesthesia. VX2 tumors were grown by injection of VX2 cells into rabbit hindlimbs. Liver tumors were induced by percutaneous US-guided injection of VX2 tumor fragments into liver. For digital subtraction angiography (DSA), a 2F catheter was advanced through left hepatic artery via femoral artery access, followed by contrast injection. All rabbits underwent baseline anatomic MRI, then IRE procedure or IRE probe placement only, and lastly post-procedure anatomic and TRIP-MRI. Liver tissues were dissected immediately after imaging for histology. All statistical analyses were performed on GraphPad Prism, with P<0.05 considered significant. RESULTS: IRE generated central IRE zone and peripheral reversible electroporation (RE) zone on anatomic MRI for both normal liver and liver tumor tissues. The semiquantitative analysis showed that IRE zone had the lowest AUC, PE, WIS, Ktrans, ve , and vp as well as the highest TTP, followed by RE zone, then untreated tissues. Receiver operating characteristic analysis showed that WIS and AUC60 had the highest AUCROC. Histologic analysis showed a positive correlation in viable area fraction between MRI and histologic measurements. IRE zone had the highest %apoptosis and lowest CD31+ staining. CONCLUSION: Our results demonstrated that intraprocedural TRIP-MRI can effectively differentiate IRE and RE zones after IRE ablation in normal liver and liver tumor tissues.
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OBJECTIVE: Peripheral protein biomarkers of Alzheimer's disease (AD) may help identify novel treatment avenues by allowing early diagnosis, recruitment to clinical trials, and treatment initiation. The purpose of this review was to determine which proteins have been found to be differentially expressed in the AD brain and whether these proteins are also found within the blood of AD patients. METHODS: A two-stage approach was conducted. The first stage involved conducting a systematic search to identify discovery-based brain proteomic studies of AD. The second stage involved comparing whether proteins found to be differentially expressed in AD brain were also differentially expressed in the blood. RESULTS: Across 11 discovery based brain proteomic studies 371 proteins were at different levels in the AD brain. Nine proteins were frequently found, defined as appearing in at least three separate studies. Of these proteins heat-shock cognate 71 kDa, ubiquitin carboxyl-terminal hydrolase isozyme L1, and 2',3'-cyclic nucleotide 3' phosphodiesterase alone were found to share a consistent direction of change, being consistently upregulated in studies they appeared in. Eighteen proteins seen as being differentially expressed within the AD brain were present in blood proteomic studies of AD. Only complement C4a was seen multiple times within both the blood and brain proteomic studies. INTERPRETATION: We report a number of proteins appearing in both the blood and brain of AD patients. Of these proteins, C4a may be a good candidate for further follow-up in large-scale replication efforts.
