Molecular Ultrasound Imaging of Tissue Inflammation Using an Animal Model of Acute Kidney Injury
Tóm tắt
The objective of this study was to evaluate the use of molecular ultrasound (US) imaging for monitoring the early inflammatory effects following acute kidney injury. A population of rats underwent 30 min of renal ischemia (acute kidney injury, N = 6) or sham injury (N = 4) using established surgical methods. Animals were divided and molecular US imaging was performed during the bolus injection of a targeted microbubble (MB) contrast agent to either P-selectin or vascular cell adhesion molecule 1 (VCAM-1). Imaging was performed before surgery and 4 and 24 h thereafter. After manual segmentation of renal tissue space, the molecular US signal was calculated as the difference between time-intensity curve data before MB injection and after reaching steady-state US image enhancement. All animals were terminated after the 24 h imaging time point and kidneys excised for immunohistochemical (IHC) analysis. Renal inflammation was analyzed using molecular US imaging. While results using the P-selectin and VCAM-1 targeted MBs were comparable, it appears that the former was more sensitive to biomarker expression. All molecular US imaging measures had a positive correlation with IHC findings. Acute kidney injury is a serious disease in need of improved noninvasive methods to help diagnose the extent of injury and monitor the tissue throughout disease progression. Molecular US imaging appears well suited to address this challenge and more research is warranted.
Tài liệu tham khảo
Mehta RL, Kellum JA, Shah SV et al (2007) Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31
Ostermann M, Chang RW (2007) Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med 35:1837–1843, quiz 1852
Kelly KJ, Molitoris BA (2000) Acute renal failure in the new millennium: time to consider combination therapy. Semin Nephrol 20:4–19
Kalantarinia K (2009) Novel imaging techniques in acute kidney injury. Curr Drug Targets 10:1184–1189
Andreucci M, Faga T, Pisani A et al (2014) Acute kidney injury by radiographic contrast media: pathogenesis and prevention. Biomed Res Int 2014:362725
Susantitaphong P, Eiam-Ong S (2014) Nonpharmacological strategies to prevent contrast-induced acute kidney injury. Biomed Res Int 2014:463608
Kogan PJK, Johnson KA, Feingold S et al (2011) Validation of dynamic contrast-enhanced ultrasound in rodent kidneys as an absolute quantitative method for measuring blood perfusion. Ultrasound Med Biol 37:900–9008
Feingold S, Gessner R, Guracar IM, Dayton PA (2010) Quantitative volumetric perfusion mapping of the microvasculature using contrast ultrasound. Invest Radiol 45:669–674
McArthur C, Baxter GM (2012) Current and potential renal applications of contrast-enhanced ultrasound. Clin Radiol 67:909–922
Lassau N, Chapotot L, Benatsou B et al (2012) Standardization of dynamic contrast-enhanced ultrasound for the evaluation of antiangiogenic therapies: the French multicenter Support for Innovative and Expensive Techniques Study. Invest Radiol 47:711–716
Lassau N, Chami L, Benatsou B et al (2007) Dynamic contrast-enhanced ultrasonography (DCE-US) with quantification of tumor perfusion: a new diagnostic tool to evaluate the early effects of antiangiogenic treatment. Eur Radiol 17(Suppl 6):F89–98
Mahoney M, Sorace A, Warram J et al (2014) Volumetric contrast-enhanced ultrasound imaging of renal perfusion. J Ultrasound Med 33:1427–1437
Saini R, Hoyt K (2014) Recent developments in dynamic contrast-enhanced ultrasound imaging of tumor angiogenesis. Imaging Med 6:41–52
Hoyt K, Mahoney M, Sorace A (2014) Four-dimensional molecular ultrasound imaging of tumor angiogenesis in a preclinical animal model of prostate cancer. Proc IEEE Ultrason Sympos 1160–1163
Saini R, Sorace AG, Warram JM et al (2013) An animal model allowing controlled receptor expression for molecular ultrasound imaging. Ultrasound Med Biol 39:172–180
Knowles JA, Heath CH, Saini R et al (2012) Molecular targeting of ultrasonographic contrast agent for detection of head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 138:662–668
Sorace AG, Saini R, Mahoney M, Hoyt K (2012) Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy. J Ultrasound Med 31:1543–1550
Warram JM, Sorace AG, Saini R et al (2011) A triple-targeted ultrasound contrast agent provides improved localization to tumor vasculature. J Ultrasound Med 30:921–931
Lindner JR, Song J, Christiansen J et al (2001) Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin. Circulation 104:2107–2112
Boesen EI, Crislip GR, Sullivan JC (2012) Use of ultrasound to assess renal reperfusion and P-selectin expression following unilateral renal ischemia. Am J Physiol Renal Physiol 303:F1333–1340
Andonian S, Coulthard T, Smith AD et al (2009) Real-time quantitation of renal ischemia using targeted microbubbles: in-vivo measurement of P-selectin expression. J Endourol 23:373–378
Klibanov AL (2009) Preparation of targeted microbubbles: ultrasound contrast agents for molecular imaging. Med Biol Eng Comput 47:875–882
Warram JM, Sorace AG, Mahoney M et al (2014) Biodistribution of P-selectin targeted microbubbles. J Drug Target 22:387–394
Roberts J, Chen B, Curtis LM et al (2007) Detection of early changes in renal function using 99mTc-MAG3 imaging in a murine model of ischemia-reperfusion injury. Am J Physiol Renal Physiol 293:F1408–1412
Frinking PJ, Bouakaz A, Kirkhorn J et al (2000) Ultrasound contrast imaging: current and new potential methods. Ultrasound Med Biol 26:965–975
Sorace A, Hoyt K (2014) Imaging the microvascular response to ultrasound-stimulated therapy in a preclinical animal model of breast cancer. Proc IEEE Ultrasonics Sympos 2145–2148
Yusuf GT, Sellars ME, Huang DY et al (2014) Cortical necrosis secondary to trauma in a child: contrast-enhanced ultrasound comparable to magnetic resonance imaging. Pediatr Radiol 44:484–487
Schneider AG, Goodwin MD, Schelleman A et al (2014) Contrast-enhanced ultrasonography to evaluate changes in renal cortical microcirculation induced by noradrenaline: a pilot study. Crit Care 18:653
Schneider AG, Schelleman A, Goodwin MD et al (2015) Contrast-enhanced ultrasound evaluation of the renal microcirculation response to terlipressin in hepato-renal syndrome: a preliminary report. Ren Fail 37:175–179
Fröhlich E, Muller R, Cui XW et al (2015) Dynamic contrast-enhanced ultrasound for quantification of tissue perfusion. J Ultrasound Med 34:179–196
Göcze I, Wohlgemuth WA, Schlitt HJ, Jung EM (2014) Contrast-enhanced ultrasonography for bedside imaging in subclinical acute kidney injury. Intensive Care Med 40:431
Ferrante EA, Pickard JE, Rychak J et al (2009) Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow. J Control Release 140:100–107
Bettinger T, Bussat P, Tardy I et al (2012) Ultrasound molecular imaging contrast agent binding to both E- and P-selectin in different species. Invest Radiol 47:516–523
Willmann JK, Lutz AM, Paulmurugan R et al (2008) Dual-targeted contrast agent for US assessment of tumor angiogenesis in vivo. Radiology 248:936–944
Hoyt K, Sorace A, Saini R (2012) Quantitative mapping of tumor vascularity using volumetric contrast-enhanced ultrasound. Invest Radiol 47:167–174
Hoyt K, Sorace A, Saini R (2012) Volumetric contrast-enhanced ultrasound imaging to assess early response to apoptosis-inducing anti-death receptor 5 antibody therapy in a breast cancer animal model. J Ultrasound Med 31:1759–1766
Pollard RE, Dayton PA, Watson KD et al (2009) Motion corrected cadence CPS ultrasound for quantifying response to vasoactive drugs in a rat kidney model. Urology 74:675–681
Waikar SS, Betensky RA, Bonventre JV (2009) Creatinine as the gold standard for kidney injury biomarker studies? Nephrol Dial Transplant 24:3263–3265
Waikar SS, Betensky RA, Emerson SC, Bonventre JV (2012) Imperfect gold standards for kidney injury biomarker evaluation. J Am Soc Nephrol 23:13–21