title: Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging.
abstract: OBJECTIVE
  There is hope that molecular imaging can identify vulnerable atherosclerotic plaques. However, there is a paucity of clinical translational data to guide the future development of this field. Here, we cross-correlate cathepsin-B or matrix metalloproteinase-2/-9 molecular optical imaging data of human atheromata or emboli with conventional imaging data, clinical data, and histopathologic data.
  
  
  RESULTS
  Fifty-two patients undergoing carotid endarterectomy (41 atheromata) or carotid stenting (15 captured emboli) were studied with protease-activatable imaging probes. We show that protease-related fluorescent signal in carotid atheromata or in emboli closely reflects the pathophysiologic alterations of plaque inflammation and statin-mediated therapeutic effects on plaque inflammation. Inflammation-related fluorescent signal was observed in the carotid bifurcation area and around ulcero-hemorrhagic lesions. Pathologically proven unstable plaques had high cathepsin-B-related fluorescent signal. The distribution patterns of the mean cathepsin-B imaging signals showed a difference between the symptomatic vs asymptomatic plaque groups. However, the degree of carotid stenosis or ultrasonographic echodensity was weakly correlated with the inflammatory proteolytic enzyme-related signal, suggesting that molecular imaging yields complimentary new information not available to conventional imaging.
  
  
  CONCLUSIONS
  These results could justify and facilitate clinical trials to evaluate the use of protease-sensing molecular optical imaging in human atherosclerosis patients.
authors.affiliation: Department of Neurology, Dongguk University Ilsan Hospital, 814 Siksa-dong, Goyang, Korea. kdongeog@duih.org
authors.forename: Dong-Eog
authors.initials: DE
authors.lastname: Kim
authors.forename: Jeong-Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Dawid
authors.initials: D
authors.lastname: Schellingerhout
authors.forename: Eo-Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hyang Kyoung
authors.initials: HK
authors.lastname: Kim
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Soo-Min
authors.initials: SM
authors.lastname: Shon
authors.forename: Sang-Wuk
authors.initials: SW
authors.lastname: Jeong
authors.forename: So-Hyang
authors.initials: SH
authors.lastname: Im
authors.forename: Dong Kun
authors.initials: DK
authors.lastname: Lee
authors.forename: Myoung Mook
authors.initials: MM
authors.lastname: Lee
authors.forename: Geun-Eun
authors.initials: GE
authors.lastname: Kim
mesh_terms: D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D016893:Carotid Stenosis / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D002401:Cathepsin B; D016894:Endarterectomy, Carotid; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D057054:Molecular Imaging / Q000379:methods*; D010447:Peptide Hydrolases; D011446:Prospective Studies; D012189:Retrospective Studies; D015607:Stents; D014463:Ultrasonography
chemical_list: D005456:Fluorescent Dyes; D010447:Peptide Hydrolases; D002401:Cathepsin B; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9