title: Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience.
abstract: BACKGROUND
  Inflammation following acute myocardial infarction (MI) has detrimental effects on reperfusion, myocardial remodelling, and ventricular function. Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide can detect cellular inflammation in tissues, and we therefore explored their role in acute MI in humans.
  
  
  RESULTS
  Sixteen patients with acute ST-segment elevation MI were recruited to undergo 3 sequential magnetic resonance scans within 5 days of admission at baseline, 24 and 48 hours following no infusion (controls; n=6) or intravenous infusion of ultrasmall superparamagnetic particles of iron oxide (n=10; 4 mg/kg). T2*-weighted multigradient-echo sequences were acquired and R2* values were calculated for specific regions of interest. In the control group, R2* values remained constant in all tissues across all scans with excellent repeatability (bias of -0.208 s(-1), coefficient of repeatability of 26.96 s(-1); intraclass coefficient 0.989). Consistent with uptake by the reticuloendothelial system, R2* value increased in the liver (84±49.5 to 319±70.0 s(-1); P<0.001) but was unchanged in skeletal muscle (54±8.4 to 67.0±9.5 s(-1); P>0.05) 24 hours after administration of ultrasmall superparamagnetic particles of iron oxide. In the myocardial infarct, R2* value increased from 41.0±12.0 s(-1) (baseline) to 155±45.0 s(-1) (P<0.001) and 124±35.0 s(-1) (P<0.05) at 24 and 48 hours, respectively. A similar but lower magnitude response was seen in the remote myocardium, where it increased from 39±3.2 s(-1) (baseline) to 80±14.9 s(-1) (P<0.001) and 67.0±15.7 s(-1) (P<0.05) at 24 and 48 hours, respectively.
  
  
  CONCLUSIONS
  Following acute MI, uptake of ultrasmall superparamagnetic particles of iron oxide occurs with the infarcted and remote myocardium. This technique holds major promise as a potential method for assessing cellular myocardial inflammation and left ventricular remodelling, which may have a range of applications in patients with MI and other inflammatory cardiac conditions.
authors.affiliation: Centre of Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh, UK. s.r.alam@sms.ed.ac.uk
authors.forename: Shirjel R
authors.initials: SR
authors.lastname: Alam
authors.forename: Anoop S V
authors.initials: AS
authors.lastname: Shah
authors.forename: Jennifer
authors.initials: J
authors.lastname: Richards
authors.forename: Ninian N
authors.initials: NN
authors.lastname: Lang
authors.forename: Gareth
authors.initials: G
authors.lastname: Barnes
authors.forename: Nikhil
authors.initials: N
authors.lastname: Joshi
authors.forename: Tom
authors.initials: T
authors.lastname: MacGillivray
authors.forename: Graham
authors.initials: G
authors.lastname: McKillop
authors.forename: Saeed
authors.initials: S
authors.lastname: Mirsadraee
authors.forename: John
authors.initials: J
authors.lastname: Payne
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Peter
authors.initials: P
authors.lastname: Henriksen
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.forename: Scott I K
authors.initials: SI
authors.lastname: Semple
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009205:Myocarditis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010865:Pilot Projects; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012606:Scotland; D015607:Stents; D015912:Thrombolytic Therapy; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome; D014283:Triiodobenzoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D020257:Ventricular Remodeling
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; D014283:Triiodobenzoic Acids; C097921:ferumoxtran-10; C044834:iodixanol