title: Plaque Neovascularization Is Increased in Human Carotid Atherosclerosis Related to Prior Neck Radiotherapy: A Contrast-Enhanced Ultrasound Study.
abstract: The aim of this study was to determine the effect of radiotherapy (RT) on intraplaque neovascularization (IPN) in human carotid arteries.
  
  
  
  Exposure of the carotid arteries to RT during treatment for head and neck cancer is associated with increased risk for stroke. However, the effect of RT on IPN, a precursor to intraplaque hemorrhage and thus associated with plaque vulnerability, is unknown.
  
  
  
  In this cross-sectional study, patients who had undergone unilateral RT for head and neck cancer ≥2 years previously underwent B-mode and contrast-enhanced ultrasound of both RT-side and non-RT-side carotid arteries. Presence of IPN during contrast-enhanced ultrasound was judged semiquantitatively as grade 0 (absent), grade 1 (present but limited to plaque base), or grade 2 (extensive and noted within plaque body).
  
  
  
  Of 49 patients studied, 38 (78%) had plaques. The number of plaques was significantly greater in the RT than the non-RT arteries. Overall, 48 of 64 RT-side plaques (75%) had IPN compared with 9 of 23 non-RT-side (39%) plaques (p = 0.002). Among patients with plaques, IPN was present in 81% of patients with RT-side plaques and 41% of patients with non-RT-side plaques (p = 0.004). Grade 0 IPN was significantly more common in patients with non-RT-side plaques (25% vs. 61%; p = 0.002), whereas grade 2 plaques were more common on the RT side (31% vs. 9%; p = 0.03). The only clinical variable that predicted the presence or absence of IPN was RT laterality.
  
  
  
  This is the first study in humans to reveal a significant association between RT and the presence and extent of IPN. This may provide insights into the mechanisms underlying the increased stroke risk among survivors of head and neck cancer treated by RT.
authors.affiliation: Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Benoy N
authors.initials: BN
authors.lastname: Shah
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, United Kingdom.
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Gujral
authors.affiliation: Department of Cardiology, Royal Brompton Hospital, London, United Kingdom.
authors.forename: Navtej S
authors.initials: NS
authors.lastname: Chahal
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, United Kingdom.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harrington
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Nutting
authors.affiliation: Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom; Department of Cardiology, Royal Brompton Hospital, London, United Kingdom. Electronic address: roxysenior@cardiac-research.org.
authors.forename: Roxy
authors.initials: R
authors.lastname: Senior
mesh_terms: D000328:Adult; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000528:radiation effects; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000209:etiology; D003287:Contrast Media / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D015588:Observer Variation; D010743:Phospholipids / Q000008:administration & dosage*; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011832:Radiation Injuries / Q000000981:diagnostic imaging* / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects; D015203:Reproducibility of Results; D012307:Risk Factors; D012720:Severity of Illness Index; D013459:Sulfur Hexafluoride / Q000008:administration & dosage*; D013997:Time Factors; D018615:Ultrasonography, Doppler, Color; D018084:Ultrasonography, Interventional
chemical_list: D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride
keywords: contrast; contrast-enhanced ultrasound; plaque neovascularization; radiotherapy; stroke