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Objective: Chronic inflammation in HIV-infected individuals drives disease progression and the development of comorbidities, despite viral suppression with combined antiretroviral therapy. Here, we sought evidence that vagal dysfunction, which occurs commonly as part of HIV-associated autonomic neuropathy, could exacerbate inflammation through gastrointestinal dysmotility, small intestinal bacterial overgrowth (SIBO), and alterations in patterns of soluble immune mediators., Design: This is a cross-sectional observational study., Methods: Forty participants on stable combined antiretroviral therapy with gastrointestinal symptoms, and no causes for vagal or gastrointestinal dysfunction other than HIV, underwent autonomic testing, hydrogen/methane breath testing for SIBO, and gastric emptying scintigraphy. A panel of 41 cytokines, high-mobility group box 1, and markers of bacterial translocation (lipopolysaccharide) and monocyte/macrophage activation (sCD14 and sCD163) were tested in plasma., Results: We found that participants with vagal dysfunction had delayed gastric emptying and higher prevalence of SIBO. SIBO was associated with IL-6, but not sCD14; lipopolysaccharide could not be detected in any participant. We also found alteration of cytokine networks in participants with vagal dysfunction, with stronger and more numerous positive correlations between cytokines. In the vagal dysfunction group, high mobility group box 1 was the only soluble mediator displaying strong negative correlations with other cytokines, especially those cytokines that had numerous other strong positive correlations., Conclusion: The current study provides evidence that the vagal component of HIV-associated autonomic neuropathy is associated with changes in immune and gastrointestinal function in individuals with well treated HIV. Further study will be needed to understand whether therapies targeted at enhancing vagal function could be of benefit in HIV.

Background: Foot ulcer with suspected infection is one of the most common reasons for hospitalization and a major factor contributing to morbidity and high healthcare-related expenses among diabetic patients. Many patients will require amputation; however, major amputation is associated with an alarmingly high 5-year mortality rate. In this study, we assess the diagnosis and management of suspected foot infection in diabetic patients using dual-isotope (DI) single-photon emission computed tomography/computed tomography (SPECT/CT) compared with conventional imaging., Methods: The diagnostic accuracy in and management of 227 patients who had undergone DI SPECT/CT was compared with that of 232 similar patients who had undergone conventional imaging including plain radiography, CT, planar bone scanning, planar indium-111 white blood cell scanning, and MRI. The duration of hospitalization was additionally compared between these two groups of patients after excluding patients with other active comorbidities., Results: Soft-tissue infection, osteomyelitis with or without soft-tissue infection, and other bony pathologies were more accurately and confidently identified with DI SPECT/CT than with conventional imaging. DI SPECT/CT use was associated with significantly fewer major amputations and more selective bony resection as well as with shorter duration of hospitalization when compared with conventional imaging., Conclusion: In this large population of diabetic patients with suspected foot infection DI SPECT/CT was more accurate in diagnosing and localizing infection compared with conventional imaging. In addition, DI SPECT/CT provided clear guidance and promoted many limb salvage procedures. Of equal importance to health economics, DI SPECT/CT use was associated with considerably reduced length of hospitalization compared with conventional imaging.

Objectives: The application of attenuation correction for combined magnetic resonance/positron emission tomography (MR/PET) systems is still a major challenge for accurate quantitative PET. Computed tomographic attenuation correction (CTAC) is the current clinical standard for PET/computed tomographic (CT) scans. Magnetic resonance, unlike CT, has no direct information about photon attenuation but, rather, proton densities. On combined MR/PET scanners, MR-based attenuation correction (MRAC) consists of assigning empirical attenuation coefficients to MR signal intensities. The objective of the current study was to evaluate the MRAC implemented on the combined MR/PET scanner versus the CTAC with the same PET data in an animal model., Materials and Methods: Acquisition was performed using a clinically approved sequential MR/PET scanner (Philips Ingenuity TF). Computed tomographic and MR/PET images of 20 New Zealand White rabbits were retrospectively analyzed. The animals were positioned on a customized animal bed to avoid movement between the CT and MR/PET scanners. Positron emission tomographic images from both methods (MRAC and CTAC) were generated. Voxel-by-voxel and region-of-interest (ROI) analyses were performed to determine differences in standardized uptake values (SUV). Regions of interest were drawn on the coregistered CT images for the aorta, liver, kidney, spine, and soft tissue (muscle) and superimposed on the PET images., Results: The voxel-by-voxel comparison of PET showed excellent correlation between MRAC and CTAC SUV values (R = 0.99; P < 0.0001). The mean of the difference of SUVs between all respective MRAC and CTAC voxels was -0.94% (absolute difference [AD] ± SD, -0.06 ± 0.30), confirming slight underestimation of MRAC. The ROI-based comparison similarly showed that MRAC SUV values were underestimated compared with CTAC SUV values. The mean difference between MRAC and CTAC for all ROIs was 10.8% (AD, -0.08 ± 0.06; R = 0.99; P < 0.0001) and -9.7% (AD, -0.15 ± 0.12; R = 0.99; P < 0.0001) for the SUV mean (SUV mean) and the SUV maximum (SUV max), respectively. The highest differences were found in the spine (SUV mean -26.1% [-0.11]) and areas close to large bones such as the back muscles (SUV mean, -16.8% [-0.04])., Conclusions: In this study, we have compared MRAC and CTAC methods for PET attenuation correction in an animal model. We have confirmed that the MRAC method implemented on a sequential MR/PET scanner underestimates PET values by less than 10% in most regions, except the areas containing or close to large bone structures such as the spine or the back muscles. Bone segmentation is therefore suggested to be included in the MR attenuation map to minimize the quantification error of MRAC methods compared with the clinical standard CTAC. Further clinical studies need to be carried out to validate the clinical use of MRAC.

Background: Fluorodeoxyglucose positron-emission tomography (FDG PET) imaging of atherosclerosis has been used to quantify plaque inflammation and to measure the effect of plaque-stabilizing drugs. We explored how atherosclerotic plaque inflammation varies across arterial territories and how it relates to arterial calcification. We also tested the hypotheses that the degree of local arterial inflammation measured by PET is correlated with the extent of systemic inflammation and presence of risk factors for vascular disease., Methods and Results: Forty-one subjects underwent vascular PET/computed tomography imaging with FDG. All had either vascular disease or multiple risk factors. Forty subjects underwent carotid imaging, 27 subjects underwent aortic, 24 subjects iliac, and 13 subjects femoral imaging. Thirty-three subjects had a panel of biomarkers analyzed. We found strong associations between FDG uptake in neighboring arteries (left versus right carotid, r=0.91, P<0.001; ascending aorta versus aortic arch, r=0.88, P<0.001). Calcification and inflammation rarely overlapped within arteries (carotid artery FDG uptake versus calcium score, r=-0.42, P=0.03). Carotid artery FDG uptake was greater in those with a history of coronary artery disease (target-to-, Background: <0.01) and in males versus females (target-to-, Background: <0.05). Similar findings were also noted in the aorta and iliac arteries. Subjects with the highest levels of FDG uptake also had the greatest concentrations of inflammatory biomarkers (descending aorta target-to-, Background: =0.53, P=0.01; carotid target-to-, Background: =0.50, P=0.01). Nonsignificant positive trends were seen between FDG uptake and levels of interleukin-18, fibrinogen, and C-reactive protein. Finally, we found that the atheroprotective biomarker adiponectin was negatively correlated with the degree of arterial inflammation in the descending aorta (r=-0.49, P=0.03)., Conclusions: This study shows that FDG PET imaging can increase our knowledge of how atherosclerotic plaque inflammation relates to calcification, serum biomarkers, and vascular risk factors. Plaque inflammation and calcification rarely overlap, supporting the theory that calcification represents a late, burnt-out stage of atherosclerosis. Inflammation in one arterial territory is associated with inflammation elsewhere, and the degree of local arterial inflammation is reflected in the blood levels of several circulating biomarkers. We suggest that FDG PET imaging could be used as a surrogate marker of both atherosclerotic disease activity and drug effectiveness. Prospective, event-driven studies are now underway to determine the role of this technique in clinical risk prediction.

Background: Normal or near normal myocardial perfusion stress imaging (MPI) suggests the absence of life-threatening coronary artery disease (CAD). Nevertheless, there are instances where severe left main or three-vessel CAD may be present despite no significant perfusion abnormalities on MPI., Methods: Review of Tl-201 or Tc-99m sestamibi MPI over a period of 5 years to ascertain the features that may prevent misdiagnosis. Out of 9171 tests, 3992 (44%) were interpreted as normal or near normal. For clinical reasons, 98 (2%) of these patients underwent coronary angiography within 6 months., Results: A total of 3992 patients were interpreted as normal or near normal. Seventy (22 men/48 women; 58 +/- 13 years) did not have obstructive CAD. Nine (six men/three women; 64 +/- 8 years) had either left main (n = 3), three-vessel CAD with or without left main (n = 3) or severe proximal left anterior descending (n = 3) disease. Although both normal patients and patients with CAD had similar proportions of imaging artifacts, those with severe CAD had significantly more markers of CAD (increased lung Tl-201 uptake, transient ischemic cavity dilatation, stress-induced ST-segment depression, chest pain, and/or hypotension with exercise; P < 0.01; no CAD vs. severe CAD; two-tail Fisher's Exact Test). Similarly, patients with moderate CAD by coronary angiography (n = 19), and a random sample of 250 patients (82 men/168 women; 62 +/- 14 years) with normal or near normal MPI who did not undergo coronary angiography, had similar proportions of imaging artifacts but significantly fewer markers of CAD., Conclusion: When dealing with individual patients, the referring physician and the interpreter of MPI studies should consider severe CAD when there are markers of CAD despite normal or near normal perfusion images.

Objective: The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis., Methods and Results: Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by DCE-MRI (r=0.89, P=0.016) and (2) 18F-FDG uptake evaluated by PET (r=0.5, P=0.103 after clustered robust, Huber-White, standard errors analysis)., Conclusions: DCE-MRI and 18F-FDG PET may allow for the evaluation of inflammation in atherosclerotic plaques of rabbits. These noninvasive imaging modalities could be proposed as clinical tools in the evaluation of lesion prognosis and monitoring of anti-angiogenic therapies.