title: MRI assessment of drug-induced fluid accumulation in humans: validation of the technology.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the feasibility of using proton and sodium magnetic resonance imaging (MRI) to detect fluid accumulation produced by fludrocortisone and nifedipine - two drugs known to cause salt/water retention by different mechanisms.
  
  
  METHODS
  Twelve young healthy male subjects were randomly assigned to one of two groups and treated with either fludrocortisone or nifedipine for 14 or 25 days, respectively. The change in sodium MRI, as well as in proton T(2) value and T(1)-weighted signal intensity in the calf following postural change [referred to here as 'postural delta signal'(PDS)], was evaluated before, during and after drug administration. The changes in MRI PDS were compared to conventional physiological parameters, including body weight, calf volume and pitting edema.
  
  
  RESULTS
  When compared to the baseline pretreatment values, the subjects treated with fludrocortisone showed a 5.5% increase in sodium MRI PDS (P=.01), a 2-ms increase in proton T(2) PDS of the gastrocnemius muscle (P=.06) and a body weight gain of 2.3% (P=.001) within 1 week. In the nifedipine-treated subjects, the sodium MRI PDS increased by 6% versus baseline (P=.03), while the proton T(2) PDS of the gastrocnemius muscle increased by 3.7 ms (P=.01), associated with a 0.5% weight gain (P=.55), within 3 weeks. No significant changes were noted in the T(1)-weighed images following postural change. Measurements of calf circumference, volume and pitting edema did not show consistent changes associated with the drug administration.
  
  
  CONCLUSIONS
  The postural change in sodium MRI and proton T(2) signals provides a sensitive method for detecting the fluid accumulation produced by fludrocortisone and nifedipine. The MRI results are consistent with treatment-induced increases in extracellular fluid volume and correlate well with the observed weight gain. These findings support the potential utility of MRI for the evaluation of medication-induced fluid retention.
authors.affiliation: Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. chun@mclean.harvard.edu
authors.forename: Chun S
authors.initials: CS
authors.lastname: Zuo
authors.forename: Rosemond A
authors.initials: RA
authors.lastname: Villafuerte
authors.forename: Michael E
authors.initials: ME
authors.lastname: Henry
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dobbins
authors.forename: Chunnin
authors.initials: C
authors.lastname: Lee
authors.forename: Younghoon
authors.initials: Y
authors.lastname: Sung
authors.forename: Charlotte
authors.initials: C
authors.lastname: Haws
authors.forename: Michelle
authors.initials: M
authors.lastname: Butman
authors.forename: Sam
authors.initials: S
authors.lastname: Miller
authors.forename: Alan
authors.initials: A
authors.lastname: Manos
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Orban
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Brown
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hodge
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Nunez
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000328:Adult; D001826:Body Fluids / Q000187:drug effects*; D005438:Fludrocortisone / Q000494:pharmacology*; D006801:Humans; D007866:Leg; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D015203:Reproducibility of Results; D012964:Sodium / Q000494:pharmacology
chemical_list: D012964:Sodium; D009543:Nifedipine; D005438:Fludrocortisone