High Tyrosol and Hydroxytyrosol Intake Reduces Arterial Inflammation and Atherosclerotic Lesion Microcalcification in Healthy Older Populations.

Aging is an important risk factor for cardiovascular diseases and convincing data have shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. The present study aimed to use 18F-FDG/18F-NaF-PET/CT imaging to, respectively, gauge arterial inflammation and microcalcification in a healthy elderly population and to assess the potential benefits of a tyrosol- and hydroxytyrosol-rich diet on these two markers of atherosclerotic plaque fragility. Eleven healthy participants (mean age 75 ± 5.67 years) were supplemented for 6 months with high polyphenol-rich extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO). The participants underwent PET/CT imaging with 18F-FDG and 18F-NaF radiotracers at baseline and after 6 months. 18F-FDG and 18F-NaF uptakes were quantified using standardized uptake values (SUV) and were categorized based on artery calcification and olive oil type. A total of 324 slices of the aortas of the imaged participants were analyzed for arterial inflammation and 327 slices were analyzed for microcalcification. 18F-FDG uptake was significantly higher in the non-calcified segments than in the calcified segments (SUVmax = 2.70 ± 0.62 and SUVmax = 2.54 ± 0.44, respectively, p < 0.042). Conversely, the non-calcified segments displayed significantly lower 18F-NaF uptake than the calcified segments (SUVmax = 1.90 ± 0.37 and 2.09 ± 0.24, respectively, p < 0.0001). The 6-month supplementation with HP-EVOO induced a significant reduction in 18F-FDG uptake in both the non-calcified (2.93 ± 0.23 to 2.75 ± 0.38, p < 0.004) and calcified segments of the aortas (2.25 ± 0.29 to 2.15 ± 0.19, p < 0.02). 18F-NaF uptake was also significantly lower in patients supplemented with HP-EVOO (SUVmax = 1.98 ± 0.33 at baseline compared to 1.85 ± 0.28, after the 6-month supplementation, p < 0.004), whereas no significant effect was observed with EVOO. Conversely, participants supplemented with ROO displayed a significant increase in 18F-NaF uptake (SUVmax = 1.78 ± 0.34 to 1.95 ± 0.34, p < 0.0001). The present study confirmed that a phenolic-compound-rich diet reduces both arterial inflammation and atherosclerotic lesion microcalcification and demonstrated that 18F-FDG/18F-NaF-PET/CT imaging is a valuable approach for assessing age-related arterial damage.

Quantification of Hypoxia in Human Glioblastoma using PET with 18F-FMISO.

PURPOSE: This study aimed to investigate the results of compartmental modeling (CM) and spectral analysis (SA) generated with dynamic 18F-FMISO tumor images. Besides, the regular tissue-to-blood ratio (TBR) images were derived and compared with the dynamic models. METHODS: Nine subjects with glioblastoma underwent PET/CT imaging with the 18F-FMISO tracer. The protocol for PET imaging began with 15 min in dynamic mode and two 10-min duration static images at 120 min and 180 min post-injection. We used the two-tissue compartmental model for CM at the voxel basis, and we conducted SA to estimate the 18F-FMISO accumulation within each voxel. We also investigated the usual tumor-to-blood ratio (TBR) for comparison. RESULTS: The images of the tumor showed different patterns of hypoxia and necrosis as a function of PET scanning times, while CM and SA methods based on dynamic PET imaging equally located tumor hypoxia. The mean correlation of Ki images of all subjects between CM and SA was 0.63 ± 0.19 (0.24-0.86). CM produced less noisy K i images than SA, and, in the contrary, SA produced accumulation component images more clear than with CM. CM-K i and SA-K i images were correlated with TBR images (r = 0.72 ± 0.20 and 0.56 ± 0.26, respectively). In the only subject having a continuously increasing tumor time-activity curve, the k 3 image showed a high uptake in the necrosis region which was not apparent in TBR or K i images. CONCLUSION: Based on these results, the combination of CM and SA approaches was found more appropriate in generating voxel-based hypoxia images.

Analysis of hypoxia in human glioblastoma tumors with dynamic 18F-FMISO PET imaging.

Gliomas are the most common type of primary brain tumors and are classified as grade IV. Necrosis and hypoxia are essential diagnostic features which result in poor prognosis of gliomas. The aim of this study was to report quantitative temporal analyses aiming at determining the hypoxic regions in glioblastoma multiforme and to suggest an optimal time for the clinical single scan of hypoxia. Nine subjects were imaged with PET and 18F-FMISO in dynamic mode for 15 min followed with static scans at 2, 3 and 4 h post-injection. Spectral analysis, tumor-to-blood ratio (TBR) and tumor-to-normal tissue ratio (TNR) were used to delimit perfused and hypoxic tumor regions. TBR and TNR images were further scaled by thresholding at 1.2, 1.4, 2 and 2.5 levels. The images showed a varying tumor volume with time. TBR produced broader images of the tumor than TNR considering the same thresholds on intensity. Spectral analysis reliably determined hypoxia with different degrees of perfusion. By comparing TBR and TNR with spectral analysis images, weak to moderate correlation coefficients were found for most thresholding values and imaging times (range: 0 to 0.69). Hypoxic volume (HV) estimated from the net uptake rate (Ki) were changing among imaging times. The minimum HV changes were found between 3 h and 4 h, confirming that after 3 h, there was a very low exchange of 81F-FMISO between blood and tumor. On the other hand, hypoxia started to dominate the perfused tissue at 90 min, suggesting this time is suitable for a single scan acquisition irrespective of tumor status being highly hypoxic or perfused. At this time, TBR and TNR were respectively found in the nine subjects as 1.72 ± 0.22 and 1.74 ± 0.19.

Assessment of artery calcification in atherosclerosis with dynamic 18F-FDG-PET/CT imaging in elderly subjects.

Glucose metabolism in atherosclerotic arteries has been shown to be an indicator of inflammation, which might be a precursor of plaque rupture. In this prospective study, we assessed the correlation between artery calcification and glucose metabolism by means of 18F-FDG PET/CT imaging in elderly subjects. Nineteen elderly subjects, with age ranging from 65 to 85 years, underwent CT and dynamic 18F-FDG-PET imaging. The artery calcification was determined with a threshold of 130 Hounsfield units. Intensity of calcification and ratio of calcification area to total artery area were classified in four sequential classes from CT images. The CT artery images were also classified as having single or multi-spot calcifications. Their respective glucose metabolism was assessed with fractional uptake rate (FUR). Factor analysis was used in this study to separate blood images from tissue to extract the blood time activity curves for FUR calculations. The artery images in PET data were corrected for partial volume effect. The total arterial segments analyzed were 1332, with 1085 without calcification (81%), 247 (19%) with calcification, and 94 segments were having multi-spot of calcifications. There was a statistically significant difference in FUR values between non-calcified to calcified segments and between subjects under medication to non-medication when comparing the subjects based on calcification area. No statistically significant differences of FUR were found between single spot as a function of intensity, while in the multi-spots, there was a statistically significant difference for all artery segments. Metabolism activity varies for non-calcified to calcified segments. Based on the metabolic activity represented by FUR, calcifications in multi-spots have different effects than in single spots.

Imaging of hypoxia in human glioblastoma with dynamic 18F-fluoromisonidazole PET.

Aim: The purpose of this study was to locate the levels of hypoxia in glioblastoma PET images measured with 18F-fluoromisonidazole in human subjects. It is recognized that tumors with hypoxia are resistant to treatment by radiotherapy and chemotherapy. Methods: The images were acquired in dynamic mode for 15 min or 30 min and in static mode for two single scans at 2 h and 3 h to allow the accumulation of the radiotracer in the tumor. The images were analyzed at the voxel basis with compartmental analysis (CA) and with the usual tumor-to-blood uptake ratio (TBR). Kmeans algorithm was applied to cluster the levels of hypoxia in the images. Results: TBR at a threshold of 1.2 at imaging times of 15 min, 2 h and 3 h produced images with different clusters. Also, the comparison of TBR with the distribution volume obtained with CA had a similarity index of 0.61 ± 0.05. Conclusion: We found some differences in defining the hypoxic volume within a tumor using TBR. The compartmental analysis allowed discrimination of the tumor hypoxic sub-volumes which can be useful for a better treatment with radiotherapy.