The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) StudyEvaluation Using Ultrasmall Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging in Carotid Disease
Tjun Y. Tang, MB, BChir*, ,
Simon P.S. Howarth, BMBCh (Oxon)*, ,
Sam R. Miller, MSc||,
Martin J. Graves, MSc*,
Andrew J. Patterson, PhD*,
Jean-Marie U-King-Im, PhD*,
Zhi Y. Li, PhD*,
Stewart R. Walsh, MSc,
Andrew P. Brown, BSc¶,
Peter J. Kirkpatrick, FmedSci,
Elizabeth A. Warburton, DM ,
Paul D. Hayes, MD,
Kevin Varty, MD,
Jonathan R. Boyle, MD,*,
Michael E. Gaunt, MD,
Andrew Zalewski, PhD# and
Jonathan H. Gillard, MD*,*
* University Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
Cambridge Vascular Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
Academic Department of Neurosurgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
Department of Clinical Neurosciences, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
|| Discovery Biometrics, GlaxoSmithKline, Harlow, United Kingdom
¶ GlaxoSmithKline Clinical Imaging Centre, Imperial College, Hammersmith Hospital, London, United Kingdom
# Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
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Figure 1 Example of a Low-Dose Patient
T2*-weighted imaging at the carotid bifurcation, before (1) and after (2) ultrasmall superparamagnetic iron oxide (USPIO) infusion at the 3 time points of (A) 0, (B) 6, and (C) 12 weeks. Plaque demonstrating USPIO uptake can clearly be seen in the right upper quadrant in all cases (yellow arrowheads). Pre-USPIO imaging remains very similar at all 3 time points. No USPIO uptake is seen in the pre-USPIO imaging at 6 or 12 weeks, indicating that the Sinerem has been cycled out of the plaque, an important aspect if repeated infusions are to be used for multiple time point imaging and assessing progression of USPIO-defined inflammation in response to a drug intervention.
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Figure 2 Example of a High-Dose Patient
T2*-weighted imaging of a left common carotid artery before and after ultrasmall superparamagnetic iron oxide (USPIO) infusion at the 3 time points of (A and B) 0, (C and D) 6, and (E and F) 12 weeks. (B) USPIO uptake can clearly be seen in the plaque at baseline (yellow arrowhead). (C and E) Pre-USPIO imaging remains very similar at all 3 time points with Sinerem having been cycled out of the plaque before reimaging (red arrowhead). (D) The plaque begins to enhance at 6 weeks (blue arrowhead). This signifies that there is a predominant T1 effect, indicating minimal USPIO uptake and a lack of activated macrophages (minimal inflammation). (E) No residual USPIO signal is also seen in the pre-USPIO imaging at 12 weeks, and (F) signal enhancement post-USPIO can be seen with no evidence of signal voids (blue arrowheads).
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Figure 3 A High-Dose Patient, Further Example and Quadrant Analysis Approach
T2*-weighted imaging of a right common carotid artery before and after ultrasmall superparamagnetic iron oxide (USPIO) infusion at the 2 time points of (A and B) 0 and (C and D) 12 weeks. (B) USPIO uptake can clearly be seen in the plaque at baseline (yellow arrowheads). (C) Sinerem has been cycled out of the plaque before reinfusion at 12 weeks (red arrowheads). (D) The plaque enhances at 12 weeks (blue arrowheads), indicating that the high-dose statin treatment has damped the USPIO-defined inflammation. Plaque segmentation was performed using a combination of multicontrast sequences. The cross hairs centered through the middle of the lumen divide the vessel into quadrants. Signal from artifact, extravascular structures, and the luminal blood pool (green asterisks) are excluded from the analysis.
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Figure 4 Signal Change
Change from baseline in signal intensity ( SI) is plotted for the 2 treatment groups, low dose (red solid line) and high dose (blue broken line), at 6 and 12 weeks with 95% confidence intervals.
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Figure 5 Transcranial Doppler Data
Relative change from baseline in microemboli count is plotted for the 2 treatment groups, low dose (red solid line) and high dose (blue broken line), at 6 and 12 weeks with 95% confidence intervals.
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