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author:("5aris, J")
1.  Optimized Preload Leakage-Correction Methods to Improve the Diagnostic Accuracy of Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MR Imaging in Posttreatment Gliomas 
BACKGROUND AND PURPOSE
Relative cerebral blood volume (rCBV) accuracy can vary substantially depending on the dynamic susceptibility-weighted contrast-enhanced (DSC) acquisition and postprocessing methods, due to blood-brain barrier disruption and resulting T1-weighted leakage and T2-and/or T2*-weighted imaging (T2/T2*WI) residual effects. We set out to determine optimal DSC conditions that address these errors and maximize rCBV accuracy in differentiating posttreatment radiation effect (PTRE) and tumor.
MATERIALS AND METHODS
We recruited patients with previously treated high-grade gliomas undergoing image-guided re-resection of recurrent contrast-enhancing MR imaging lesions. Thirty-six surgical tissue samples were collected from 11 subjects. Preoperative 3T DSC used 6 sequential evenly timed acquisitions, each by using a 0.05-mmol/kg gadodiamide bolus. Preload dosing (PLD) and baseline subtraction (BLS) techniques corrected T1-weighted leakage and T2/T2*WI residual effects, respectively. PLD amount and incubation time increased with each sequential acquisition. Corresponding tissue specimen stereotactic locations were coregistered to DSC to measure localized rCBV under varying PLD amounts, incubation times, and the presence of BLS. rCBV thresholds were determined to maximize test accuracy (average of sensitivity and specificity) in distinguishing tumor (n = 21) and PTRE (n = 15) samples under the varying conditions. Receiver operator characteristic (ROC) areas under the curve (AUCs) were statistically compared.
RESULTS
The protocol that combined PLD (0.1-mmol/kg amount, 6-minute incubation time) and BLS correction methods maximized test AUC (0.99) and accuracy (95.2%) compared with uncorrected rCBV AUC (0.85) and accuracy (81.0%) measured without PLD and BLS (P = .01).
CONCLUSIONS
Combining PLD and BLS correction methods for T1-weighted and T2/T2*WI errors, respectively, enables highly accurate differentiation of PTRE and tumor growth.
doi:10.3174/ajnr.A1787
PMCID: PMC4323177  PMID: 19749223
2.  The uncontrollable shaking arm 
The British Journal of Radiology  2011;84(1008):1153-1155.
doi:10.1259/bjr/31650853
PMCID: PMC3473827  PMID: 22101583
3.  Phenotypic Landscape of a Bacterial Cell 
Cell  2010;144(1):143-156.
Summary
The explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action, and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between a broadly used combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set, publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource for both the microbiological and bioinformatic communities, as it provides high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs.
doi:10.1016/j.cell.2010.11.052
PMCID: PMC3060659  PMID: 21185072

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