TY - JOUR
T1 - Investigating vulnerable atheroma using combined 18F-FDG PET/CT angiography of carotid plaque with immunohistochemical validation
AU - Menezes, Leon J.
AU - Kotze, Carl W.
AU - Agu, Obi
AU - Richards, Toby
AU - Brookes, Jocelyn
AU - Goh, Vicky J.
AU - Rodriguez-Justo, Manuel
AU - Endozo, Raymondo
AU - Harvey, Richard
AU - Yusuf, Syed W.
AU - Ell, Peter J.
AU - Groves, Ashley M.
PY - 2011/11/1
Y1 - 2011/11/1
N2 - Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. Methods: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid 18F-FDG PET/CT angiography. Plaque 18F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. Results: The mean (±SD) surgically excised carotid plaque 18F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque 18F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ 5 0.47; P 5 0.031). There was an inverse relationship between plaque 18F-FDG metabolism and plaque percentage calcium composition on CT (ρ= -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ 5 20.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. Conclusion: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.
AB - Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. Methods: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid 18F-FDG PET/CT angiography. Plaque 18F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. Results: The mean (±SD) surgically excised carotid plaque 18F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque 18F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ 5 0.47; P 5 0.031). There was an inverse relationship between plaque 18F-FDG metabolism and plaque percentage calcium composition on CT (ρ= -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ 5 20.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. Conclusion: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.
KW - F-FDG positron emission tomography
KW - Carotid atherosclerosis
KW - Computed tomography angiography
UR - http://www.scopus.com/inward/record.url?scp=80455129840&partnerID=8YFLogxK
U2 - 10.2967/jnumed.111.093724
DO - 10.2967/jnumed.111.093724
M3 - Article
C2 - 21990578
AN - SCOPUS:80455129840
SN - 0161-5505
VL - 52
SP - 1698
EP - 1703
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 11
ER -