title: Pharmacokinetic approach for dynamic breast MRI to indicate signal intensity time curves of benign and malignant lesions by using the tumor flow residence time.
abstract: OBJECTIVE
  The objective of this study was to evaluate a novel pharmacokinetic approach integrating a tumor model in a whole-body pharmacokinetic model to simulate contrast media-induced signal intensity time curves of breast tumors on dynamic contrast-enhanced magnetic resonance mammography.
  
  
  METHODS
  A recently developed, whole-body pharmacokinetic model, which describes the distribution and excretion of renally discharged contrast media, has been expanded by integrating a tumor model. The parameters of the general approach including exchange between plasma and interstitium were set as fixed values; only 2 tumor-specific parameters, blood volume fraction Vblood and blood flow kt, were varied. These parameters were adjusted with regard to signal intensity time course data of histologically verified benign and malignant mass-like breast lesions on clinical magnetic resonance imaging examinations (1.5 T) using 2 different contrast media (gadopentetate dimeglumine and gadoterate meglumine) and 2 application doses (0.1 and 0.2 mmol kg body weight). Thus, measured signal intensity time curves were compared with simulated gadolinium (Gd) concentration time curves calculated by the pharmacokinetic model.
  
  
  RESULTS
  Benign lesions showed continuous signal increase; malignant tumors presented fast initial signal increase followed by washout effect. According to the pharmacokinetic approach, the variation of the Vblood/kt ratio, which defined the tumor flow residence time τr, led to Gd concentration time curves congruent with the shapes of the measured signal intensity time curves. Low values of τr were characteristic for malignant tumors, and high values were typical for benign lesions; τr of 200 seconds best separated malignant from benign tumors. Thus, the dynamic magnetic resonance imaging data can be well approximated by the pharmacokinetic model considering 2 contrast media and application doses. The calculated Gd concentration time curves of 0.1 mmol kg body weight gadopentetate dimeglumine and gadoterate meglumine overlapped for benign lesions; the curve of gadoterate meglumine was by a factor of 0.8 below the curve of gadopentetate dimeglumine for malignant tumors. Doubling the application dose of gadopentetate dimeglumine from 0.1 to 0.2 mmol kg led to an increase in the Gd concentration time curves for benign lesions but not for malignant tumors. High Gd concentrations with values greater than 1 mmol L were calculated in the vessels of the malignant tumors, outside the determined range of the linear relationship between Gd concentration and signal intensity due to saturation effects.
  
  
  CONCLUSIONS
  On the basis of this pharmacokinetic model, the contrast media-induced time curves on dynamic contrast-enhanced magnetic resonance mammography can be classified by a single kinetic parameter, the tumor flow residence time τr, into benign (τr >200 seconds) and malignant (τr <200 seconds) curve shapes. Possible clinical application of this model is to create pharmacokinetic maps, displaying tumor flow residence times, for computer-assisted diagnosis, which may be integrated into clinical routine for the diagnosis of breast lesions.
authors.affiliation: Department of Radiology, Charité University Medicine Berlin, Germany. diane.renz@charite.de
authors.forename: Diane Miriam
authors.initials: DM
authors.lastname: Renz
authors.forename: Felix
authors.initials: F
authors.lastname: Diekmann
authors.forename: Florian Frowin
authors.initials: FF
authors.lastname: Schmitzberger
authors.forename: Hubertus
authors.initials: H
authors.lastname: Pietsch
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Fallenberg
authors.forename: Tahir
authors.initials: T
authors.lastname: Durmus
authors.forename: Alexander
authors.initials: A
authors.lastname: Huppertz
authors.forename: Joachim
authors.initials: J
authors.lastname: Böttcher
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bick
authors.forename: Bernd
authors.initials: B
authors.lastname: Hamm
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Lawaczeck
mesh_terms: D001941:Breast Diseases / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008536:Meglumine / Q000493:pharmacokinetics*; D008954:Models, Biological; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D008536:Meglumine; D019786:Gadolinium DTPA; C072417:gadoterate meglumine