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Magnetic resonance imaging biomarkers for pulsed focused ultrasound treatment of pancreatic ductal adenocarcinoma

World Journal of Gastroenterology 2020年第9期26卷 904-917页

作者： Ezekiel Maloney Yak-Nam Wang Ravneet Vohra Helena Son Stella Whang Tatiana Khokhlova Joshua Park Kayla Gravelle stephanie totten Joo Ha Hwang Donghoon Lee Department of Radiology University of WashingtonSeattleWA 98195United States Applied Physics Laboratory University of WashingtonSeattleWA 98195United States Division of Gastroenterology University of WashingtonSeattle 98195WAUnited States Division of Gastroenterology&Hepatology Stanford University School of MedicineRedwood CityCA 94063United States

BACKGROUND The robust fibroinflammatory stroma characteristic of pancreatic ductal adenocarcinoma(PDA)impedes effective drug *** focused ultrasound(pFUS)can disrupt this stroma and has improved survival in an early clinical ***-invasive methods to characterize pFUS treatment effects are desirable for advancement of this promising treatment modality in larger clinical *** To identify promising,non-invasive pre-clinical imaging methods to characterize acute pFUS treatment effects for in vivo models of *** We utilized quantitative magnetic resonance imaging methods at 14 tesla in three mouse models of PDA(subcutaneous,orthotopic and transgenic-KrasLSLG12D/+,Trp53LSL-R172H/+,Cre or“KPC”)to assess immediate tumor response to pFUS treatment(VIFU 2000 Alpinion Medical Systems;475 W peak electric power,1 ms pulse duration,1 Hz,duty cycle 0.1%)vs sham therapy,and correlated our results with histochemical *** pFUS treatment parameters were previously shown to enhance tumor permeability to chemotherapeutics.T1 and T2 relaxation maps,high(126,180,234,340,549)vs low(7,47,81)b-value apparent diffusion coefficient(ADC)maps,magnetization transfer ratio(MTR)maps,and chemical exchange saturation transfer(CEST)maps for the amide proton spectrum(3.5 parts per million or“ppm”)and the glycosaminoglycan spectrum(0.5-1.5 ppm)were generated and analyzed pre-treatment,and immediately post-treatment,using *** were sacrificed immediately following post-treatment *** whole-tumor was selected as the region of interest for data analysis and subsequent statistical analysis.T-tests and Pearson correlation were used for statistical *** Mean high-b value ADC measurements increased significantly with pFUS treatment for all *** glycosaminoglycan CEST and T2 measurements decreased significantly post-treatment for the KPC *** MTR and amide CEST values increased significantly for the KPC *** acid focal int

关键词： Pancreatic adenocarcinoma Multiparametric magnetic resonance imaging Focused ultrasound

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