title: Comparison of albumin-(Gd-DTPA)30 and Gd-DTPA-24-cascade-polymer for measurements of normal and abnormal microvascular permeability.
abstract: The purpose of this study was to compare a new MR macromolecular contrast medium (MMCM), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, to a well-studied prototype MMCM, for the potential of distinguishing tissues of varying endothelial permeability. Three tissue models of varying capillary permeability were studied in a total of 46 rats: normal myocardium (normal capillaries), subcutaneously implanted adenocarcinoma (mild capillary leak), and reperfused infarcted myocardium (high capillary leak). TI-weighted MRI was performed before and dynamically after injection of either albumin-(Gd-DTPA)30 or the cascade polymer (each .02 mmol gadolinium [Gd] per kg). Data analysis based on a two-compartment kinetic model yielded estimates of fractional blood volume (BV) (percentage) and fractional leak rate (FLR) (1 per hour). Permeability to the cascade polymer as reflected in FLR was considerable in normal myocardium (8.24 per hour), of similar value in tumors (8.55 per hour), but significantly greater in infarcted myocardium (39.17 per hour, P < .01) versus normal myocardium. The larger albumin-(Gd-DTPA)30 demonstrated minimal extravasation in normal myocardium (FLR .33 per hour); FLR in tumors was 100% higher (.66 per hour, P < .002) and FLR in reperfused capillaries was significantly greater (7.94 per hour, P < .001). Based on capillary permeability measurements, the cascade polymer may have limited utility for detection of mildly increased microvascular permeabilities. For severe tissue injury, the cascade polymer can resolve abnormal microvascular integrity.
authors.affiliation: Department of Radiology, University of California, San Francisco, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Roberts
authors.forename: M
authors.initials: M
authors.lastname: Saeed
authors.forename: T P
authors.initials: TP
authors.lastname: Roberts
authors.forename: A
authors.initials: A
authors.lastname: Mühler
authors.forename: D M
authors.initials: DM
authors.lastname: Shames
authors.forename: J S
authors.initials: JS
authors.lastname: Mann
authors.forename: M
authors.initials: M
authors.lastname: Stiskal
authors.forename: F
authors.initials: F
authors.lastname: Demsar
authors.forename: R C
authors.initials: RC
authors.lastname: Brasch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019559:Capillary Leak Syndrome / Q000175:diagnosis; D002199:Capillary Permeability / Q000502:physiology; D003287:Contrast Media / Q000008:administration & dosage; D046508:Culture Techniques; D004195:Disease Models, Animal; D005260:Female; D019786:Gadolinium DTPA; D006338:Heart Neoplasms / Q000175:diagnosis*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis*; D009942:Organometallic Compounds / Q000008:administration & dosage; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C088920:gadolinium-diethylenetriaminepentaacetic acid-cascade-polymer; D004369:Pentetic Acid; D019786:Gadolinium DTPA