Zhuangyu Zhang

Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation

BackgroundCoronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of 18F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model.MethodsAtherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta.ResultsAtherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity.ConclusionPET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.

Areolar-cutaneous "junction" injections to augment sentinel node count activity.

Purpose The authors report on a modified lymphoscintigraphy protocol for increasing activity in the sentinel node (SN) through a specific technique (LymphoBoost). It consists of an areolar–cutaneous “junction” injection, using a very shallow, high-volume, high-specific-activity injection of 100% filtered Tc-99m sulfur colloid, as an adjunct to their standard protocol. Materials and Methods Results from a previously optimized protocol (group 1, n = 28) were compared with those from their new protocol (group 2, n = 85), which consisted of two sets of consecutively applied (within 12 to 20 minutes) injections: group 2A composed of perilesional and intradermal injections (similar to the previous group 1) followed by group 2B LymphoBoost injections within 12 to 20 minutes in the same patients. Regions of interest were drawn around the SN and the injection sites (IS) at the end of the studies to calculate the end-of-study SN:IS ratio for both group 1 and group 2 studies. The SN:IS ratio is generally independent of dose and is a measurement of the “efficiency” of getting activity from the IS to the SN. Results The mean SN:IS ratio in group 2 was 3.34 times greater than that in group 1 studies (P < 0.0005). The median SN:IS ratio was 3.53 times greater in the group 2 studies. Many cases showed a dramatic increase in SN counts before the LymphoBoost injection was even completed, with more than 5% of injected activity reaching nodes at the end of the study in some patients. Multiple different lymphatic pathways were noted, but all led to the same node(s). No significant disagreement between group 2A and group 2B results was noted. Conclusions Areolar–cutaneous junction injections, performed under these conditions, augment SN activity dramatically in most patients. Hotter nodes provide several benefits, especially when next-day surgery is contemplated, and should also reduce the extent of dissection needed to remove the sentinel node.

Effect of high specific-activity sulfur colloid preparations on sentinel node count rates

&NA; Purpose: Preliminary results by other investigators suggest that increasing the specific activity of Tc‐99m nanocolloid preparations increases the measured counts in sentinel nodes compared with lower specific‐activity (SA) preparations using the same initial injected dose. The authors set out to determine whether a similar result could be perceived with Tc‐99m sulfur colloid (SC) preparations. Methods: Twenty‐three consecutive patients (low SA group) with successful visualization of sentinel nodes by lymphoscintigraphy before our standard protocol was changed to a higher SA preparation were compared with 28 patients (high SA group) just after the switch. Injection techniques were similar in both groups: peritumoral injections at two to four points of a mixture of half‐filtered (0.22 &mgr;m filter) and unfiltered Tc‐99m sulfur colloid in 6 ml followed immediately by intradermal injections of filtered sulfur colloid above the tumor. Activity levels for both types of injections ranged from 3.7 to 11.1 mBq (100 to 300 &mgr;Ci). Preparation of the higher SA mixture of sulfur colloid was achieved by using only one eighth of the sulfur colloid vial contents when the same activity (125 mCi) of Tc‐99 was added. Regions of interest were drawn around the images of sentinel nodes and the initial injection site in the anterior and lateral projections. Ratios of sentinel node to initial injection site count were calculated for both groups. Results: The mean ratio of sentinel node to injection site count in the high SA group was 2.9 times greater than that in the low SA group. The median ratio value was 2.7 times greater in the high SA group. Conclusion: These preliminary results suggest higher counts in the sentinel node are possible with a higher SA preparation.

Differential In Vivo Recovery Of Sinusoidal Endothelial Cells, Hepatocytes, And Kupffer Cells After Cold Preservation And Liver Transplantation In Rats

BACKGROUND The injury resulting from cold preservation/reperfusion primarily affects sinusoidal endothelial cells, while hepatocytes are thought to be less vulnerable; morphological changes and increased cytokine release suggest that Kupffer cells are activated. We evaluated the extent of functional damage to the different cell types in the liver after cold preservation and transplantation. Additionally, we analyzed in vivo the patterns of functional recovery of all three cell types over the first week after transplantation in Lewis rats. METHODS We evaluated the in vivo uptake of hyaluronic acid, indocyanine green, and radio-labeled sulphur colloid to assess the function of sinusoidal endothelial cells, hepatocytes, and Kupffer cells, respectively. Measurements were performed immediately after transplantation using syngeneic grafts preserved in University of Wisconsin solution for different periods. Functional recovery was monitored in animals receiving grafts preserved for 24 hr over the first postoperative week. RESULTS We found that hepatocyte were less affected compared with the profoundly damaged endothelial cells. The phagocytic ability of Kupffer cells was, however, also seriously compromised, which suggests a selective down-regulation. Functional recovery occurs in a differential manner during the first postoperative week starting with hepatocytes followed by sinusoidal endothelial cells. Phagocytic function further deteriorates after transplantation before showing improvement. CONCLUSIONS In viable liver grafts, all cell types recover from preservation/reperfusion injury by the end of the first week after transplantation. The differential time courses of the recovery suggest that successful sinusoidal endothelial cell recovery may depend upon prior hepatocyte regeneration and may involve a paracrine interaction, via cytokines and growth factors.

Characterization of extrahepatic distribution of Tc-99m macroaggregated albumin in hepatic perfusion imaging studies prior to yttrium-90 microsphere therapy.

Tc-99m macroaggregated albumin (MAA) hepatic perfusion study and hepatic angiography are routinely performed prior to yttrium-90 (Y-90) microsphere therapy for patients with hepatocellular carcinoma (HCC) or metastatic cancers to the liver. The purpose of this study was to examine the incidence of altered Tc-99m MAA distribution in these patients and to identify factors that are associated with these changes. A total of 176 Tc-99m MAA hepatic perfusion studies in 159 patients performed in preparation for Y-90 microsphere therapy were retrospectively reviewed. Abnormal findings were identified and correlated with diagnosis, infusion site, tumor volume, and tumor uptake by using bivariate statistical analysis. Abnormal Tc-99m MAA distribution on the hepatic perfusion imaging studies include excessive hepatopulmonary shunting with an elevated shunting fraction (>10%; n=23, 13%) and abnormal intra-abdominal visceral deposition in the GI tract, pancreas, spleen, and umbilical vein (n=19; 11%). Patients with a diagnosis of HCC showed higher incidence of abnormal hepatopulmonary shunting compared with other types of tumors (p<0.05). The incidence of abnormal intra-abdominal visceral deposition is higher with infusion into the left hepatic artery or proper hepatic artery/common hepatic artery compared with infusion into right hepatic artery (p<0.001). In 9 of 12 cases with abnormal deposition in the stomach, duodenum, or pancreas, the cause was identified upon reviewing angiography retrospectively and was subsequently corrected. In conclusion, the hepatic perfusion imaging study is an important imaging modality in preparation and guidance of Y-90 microsphere treatment.