title: The early plasma concentration of 51Cr-EDTA in patients with cirrhosis and ascites: a comparison of three models.
abstract: OBJECTIVE
  The aim of the study was to determine which of three two-parameter fitting functions (exponential, linear-log, and negative-power function of time) most accurately models early chromium-51-EDTA (51Cr-EDTA) plasma concentration data prior to 120 min in patients with cirrhosis and ascites and understand how these fitting functions affect the calculation of the area under the plasma concentration curve (AUC).
  
  
  METHODS
  A bolus, antecubital intravenous injection of 2.6 MBq of 51Cr-EDTA was given to 13 patients with cirrhosis and ascites. Up to 16 blood samples were drawn at time points ranging from 5 to 1440 min following injection. The concentration data prior to 120 min were used as reference data. Early time concentration values, estimated by fitting exponential, linear-log, and negative-power functions of time to the time samples at 120, 180, and 240 min, were then compared with reference data. The AUC was calculated for each patient using the exponential, Bröchner-Mortensen-corrected exponential, and linear-log functions, and these values were compared.
  
  
  RESULTS
  The withheld, observed plasma concentrations were (a) most accurately estimated by linear-log functions (Wilcoxon P=0.4548), (b) significantly underestimated by exponential functions (Wilcoxon P=0.0002), and (c) significantly overestimated by negative-power functions (Wilcoxon P=0.0034). The relative errors when ranked from best to worst were those for the linear-log (12.0%, 9.0%), exponential (22.9%, 14.2%), and negative-power (31.9%, 48.4%) functions of time, respectively (median, interquartile range). For each patient, the values for AUC calculated by the exponential function differed significantly (range=3.4-15.3%, median=8.3%) from those calculated by the corrected Bröchner-Mortensen exponential, as to a lesser extent did those values calculated using linear-log functions (range=0.4-8.0%, median=3.0%).
  
  
  CONCLUSIONS
  In patients with cirrhosis, linear-log functions were significantly more accurate than exponential or power functions in estimating early time plasma concentrations (<120 min). However, the improved linear-log early time plasma concentration model does not provide as much correction to the total AUC as does the corrected Bröchner-Mortensen exponential method. This is likely because of the large contribution of late time data to the AUC, and future work is suggested to explore the late time fit problem.
authors.affiliation: aDepartment of Medical Imaging, Royal University Hospital, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan bDepartment of Radiology, Memorial University of Newfoundland, Nuclear Medicine, The General Hospital, HSC, St. John's, Newfoundland and Labrador, Canada cPixon Imaging Inc., San Diego, California, USA dDepartment of Medical Physics eThe Royal Free Sheila Sherlock Liver Centre and UCL Institute of Liver and Digestive Disease, The Royal Free London NHS Foundation Trust, London, UK.
authors.forename: Surajith N
authors.initials: SN
authors.lastname: Wanasundara
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Wesolowski
authors.forename: Richard C
authors.initials: RC
authors.lastname: Puetter
authors.forename: Maria T
authors.initials: MT
authors.lastname: Burniston
authors.forename: Elias
authors.initials: E
authors.lastname: Xirouchakis
authors.forename: Ioannis G
authors.initials: IG
authors.lastname: Giamalis
authors.forename: Paul S
authors.initials: PS
authors.lastname: Babyn
authors.forename: Carl A
authors.initials: CA
authors.lastname: Wesolowski
mesh_terms: D019540:Area Under Curve; D001201:Ascites / Q000097:blood* / Q000503:physiopathology; D002860:Chromium Radioisotopes; D004492:Edetic Acid / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology; D015233:Models, Statistical; D013997:Time Factors
chemical_list: D002860:Chromium Radioisotopes; D004492:Edetic Acid