Quantitative thoracic aorta calcification assessment by 18F-NaF PET/CT and its correlation with atherosclerotic cardiovascular disorders and increasing age.

OBJECTIVES: We aimed to assess the correlation between age and cardiovascular risk factors with NaF-PET/CT imaging in the thoracic aorta (TA). METHODS: In this prospective study, 80 healthy controls and 44 patients with chest pain underwent NaF-PET/CT imaging, and three segments of the aorta (ascending, arch, and descending) were examined. Average SUVmax, SUVmean, and Alavi-Carlsen Score (ACS) were calculated in each segment and the entire vessel. The degree of NaF uptake in controls and patients and its correlation with age were determined. Multivariate linear regression and logistic regression models were employed to determine the predictabilities of Framingham Risk Score (FRS) and unfavorable cardiovascular disease (CVD) risk profile by these measurements. RESULTS: Average SUVmax, average SUVmean, and ACS were significantly higher in patients than in controls, and all correlated well with age. The correlation of average SUVmean with age was significant in both controls (r = 0.32, p = 0.04) and patients (r = 0.64, p < 0.001). ACS of the entire TA was a stronger predictor of FRS compared with average SUVmax and average SUVmean (adjusted R2 = 0.38, standardized ß = 0.58, p < 0.001). ACS was a significant predictor of unfavorable CVD risk profile as compared with other values (odds ratio = 1.006, 95% CI = 1.000-1.013, p = 0.05). CONCLUSIONS: Active calcification in TA correlates with age, and its correlation is higher among subjects with CVD risk factors. Global assessment (ACS) can predict unfavorable CVD risk profile. These data provide evidence for the potential role of NaF in assessing micro-calcification in arteries and its relations to cardiovascular events. KEY POINTS: • Global micro-calcification in the thoracic aorta as measured by NaF-PET/CT imaging correlates with increasing age. • The extent of the correlation was higher among patients with cardiovascular disease (CVD) risk factors. • These data provide evidence for the potential role of NaF in assessing active calcification in arteries and its relations to cardiovascular events.

The Evolving Role of FDG-PET/CT in the Diagnosis, Staging, and Treatment of Breast Cancer.

The applications of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (PET/CT) in the management of patients with breast cancer have been extensively studied. According to these studies, PET/CT is not routinely performed for the diagnosis of primary breast cancer, although PET/CT in specific subtypes of breast cancer correlates with histopathologic features of the primary tumor. PET/CT can detect metastases to mediastinal, axial, and internal mammary nodes, but it cannot replace the sentinel node biopsy. In detection of distant metastases, this imaging tool may have a better accuracy in detecting lytic bone metastases compared to bone scintigraphy. Thus, PET/CT is recommended when advanced-stage disease is suspected, and conventional modalities are inconclusive. Also, PET/CT has a high sensitivity and specificity to detect loco-regional recurrence and is recommended in asymptomatic patients with rising tumor markers. Numerous studies support the future role of PET/CT in prediction of response to neoadjuvant chemotherapy (NAC). PET/CT has a higher diagnostic value for prognostic risk stratification in comparison with conventional modalities. With the continuing research on the treatment planning and evaluation of patients with breast cancer, the role of PET/CT can be further extended.

Physiologic colonic fluorine-18-fluorodeoxyglucose uptake may predict response to immunotherapy in patients with metastatic melanoma.

The gut microbiota impacts response to immunotherapy in cancer patients. We sought to evaluate the role of physiologic colonic fluorine-18-fluorodeoxyglucose (F-FDG) uptake, a test that was recently shown to reflect colonic bacterial load, as a possible predictor for response to immunotherapy. We carried out a retrospective study in metastatic melanoma patients who received the immune checkpoint inhibitor ipilimumab as first-line therapy. All patients underwent an F-FDG PET scan before treatment initiation. The primary outcome was defined as response to treatment according to the RECIST criteria. Regions of interest were drawn on each transaxial slice around the outer boundaries of the colon. Uptake was measured using maximum and mean standardized uptake value (SUV). A nonparametric test was used to compare SUV between response groups. The study included 14 melanoma patients, of whom two (14.3%) achieved a complete response (CR) following treatment, eight (57.1%) achieved a partial response (PR), and four (28.6%) developed progressive disease (PD). The mean SUVmax was 1.33±0.04, 2.2±0.46, and 3.33±2.67 for individuals with CR, PR, and PD, respectively. The difference between individuals with CR and those without CR (PR or PD) in total colonic SUVmax was statistically significant (P=0.03). Thus, physiologic colonic F-FDG uptake may predict CR to immunotherapy in metastatic melanoma patients.

Functional imaging of the interaction between gut microbiota and the human host: A proof-of-concept clinical study evaluating novel use for 18F-FDG PET-CT.

Recent data comparing germ-free to conventionally-raised mice demonstrated that energy homeostasis of colonocytes is dependent on gut microbiota through regulation of short chain fatty acids (SCFA) production and glucose utilization. We sought to evaluate 18F-FDG PET-CT as a novel technique for functional imaging of alterations in glucose metabolism as a result of the interaction between the gut microbiota and the human host. We conducted a prospective study in healthy humans that underwent 18F-FDG PET-CT and sampling of the gut microbiota before and after orally administered broad-spectrum antibiotics. The primary outcomes were total and regional physiologic colonic 18F-FDG uptake (measured as the mean and max standardized uptake values [SUVmean and SUVmax]). The study demonstrated significant increases in physiologic colonic 18F-FDG uptake in all study participants following antibiotic treatment and a 4-5log reduction of gut bacterial load. The mean increase in SUVmax was 0.63±0.37 SD (p = 0.004) and the median increase was 0.42 with an IQR of 0.40-0.81. The mean increase in SUVmean was 0.31±0.24 SD (p = 0.01) and the median increase was 0.41 with an IQR of 0.06-0.55. A likely explanation for this phenomenon is a shift in colonocyte metabolism to glycolysis due to a shortage of SCFA.

Evolving Role of Molecular Imaging with (18)F-Sodium Fluoride PET as a Biomarker for Calcium Metabolism.

(18)F-sodium fluoride (NaF) as an imaging tracer portrays calcium metabolic activity either in the osseous structures or in soft tissue. Currently, clinical use of NaF-PET is confined to detecting metastasis to the bone, but this approach reveals indirect evidence for disease activity and will have limited use in the future in favor of more direct approaches that visualize cancer cells in the read marrow where they reside. This has proven to be the case with FDG-PET imaging in most cancers. However, a variety of studies support the application of NaF-PET to assess benign osseous diseases. In particular, bone turnover can be measured from NaF uptake to diagnose osteoporosis. Several studies have evaluated the efficacy of bisphosphonates and their lasting effects as treatment for osteoporosis using bone turnover measured by NaF-PET. Additionally, NaF uptake in vessels tracks calcification in the plaques at the molecular level, which is relevant to coronary artery disease. Also, NaF-PET imaging of diseased joints is able to project disease progression in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Further studies suggest potential use of NaF-PET in domains such as back pain, osteosarcoma, stress-related fracture, and bisphosphonate-induced osteonecrosis of the jaw. The critical role of NaF-PET in disease detection and characterization of many musculoskeletal disorders has been clearly demonstrated in the literature, and these methods will become more widespread in the future. The data from PET imaging are quantitative in nature, and as such, it adds a major dimension to assessing disease activity.

Personalized Management Approaches in Lymphoma: Utility of Fluorodeoxyglucose-PET Imaging.

PET/computed tomography (CT) imaging has gained a prominent role in the diagnosis and staging of malignancies. In lymphoma the role of PET/CT imaging continues to evolve as the understanding of its use in prognostication and response assessment improves. Currently, many groups are studying the potential function of PET/CT imaging in helping to direct management decisions for treating clinicians. This article summarizes the most up-to-date literature surrounding the topic of PET/CT-adaptive treatment of different lymphoma subjects. Although more studies are necessary to solidify the role of PET/CT, it is clear that this imaging modality holds much promise for the development of response-adaptive treatment algorithms in the future.

Assessing Cutaneous Psoriasis Activity Using FDG-PET: Nonattenuation Corrected Versus Attenuation Corrected PET Images.

Psoriasis is a chronic inflammatory skin condition characterized by well-circumscribed erythematous plaques with thick silvery scale. Infiltration of inflammatory cells such as lymphocytes, neutrophils, and macrophages and epidermal cell proliferation within psoriatic lesions may result in selective FDG accumulation. We present a 55-year-old patient with a 30-year history of psoriasis. Nonattenuation corrected PET/CT images demonstrated significant cutaneous FDG uptake corresponding to clinically apparent psoriatic lesions. However, in attenuation corrected (AC) FDG-PET images, the signal was substantially diminished and minimally detectable. Nonattenuation corrected FDG-PET images may be useful and preferable to AC images in assessing skin inflammation in psoriasis.

Quantifying [¹8F]fluorodeoxyglucose uptake in the arterial wall: the effects of dual time-point imaging and partial volume effect correction.

PURPOSE: The human arterial wall is smaller than the spatial resolution of current positron emission tomographs. Therefore, partial volume effects should be considered when quantifying arterial wall (18)F-FDG uptake. We evaluated the impact of a novel method for partial volume effect (PVE) correction with contrast-enhanced CT (CECT) assistance on quantification of arterial wall (18)F-FDG uptake at different imaging time-points. METHODS: Ten subjects were assessed by CECT imaging and dual time-point PET/CT imaging at approximately 60 and 180 min after (18)F-FDG administration. For both time-points, uptake of (18)F-FDG was determined in the aortic wall by calculating the blood pool-corrected maximum standardized uptake value (cSUVMAX) and cSUVMEAN. The PVE-corrected SUVMEAN (pvcSUVMEAN) was also calculated using (18)F-FDG PET/CT and CECT images. Finally, corresponding target-to-background ratios (TBR) were calculated. RESULTS: At 60 min, pvcSUVMEAN was on average 3.1 times greater than cSUVMAX (P < .0001) and 8.5 times greater than cSUVMEAN (P < .0001). At 180 min, pvcSUVMEAN was on average 2.6 times greater than cSUVMAX (P < .0001) and 6.6 times greater than cSUVMEAN (P < .0001). CONCLUSION: This study demonstrated that CECT-assisted PVE correction significantly influences quantification of arterial wall (18)F-FDG uptake. Therefore, partial volume effects should be considered when quantifying arterial wall (18)F-FDG uptake with PET.

Assessment of atherosclerosis in large vessel walls: A comprehensive review of FDG-PET/CT image acquisition protocols and methods for uptake quantification.

There is growing evidence showing the importance of fluorodeoxyglucose positron emission tomography (FDG-PET) in the evaluation of vessel wall inflammation and atherosclerosis. Although this imaging modality has been increasingly used, there are various methods for image acquisition and evaluating FDG uptake activity in the vessel walls and atherosclerotic lesions, including qualitative visual scaling, semi-quantitative, and quantitative evaluations. Using each of these image acquisition protocols and measurement methods may result in different findings. In this review, we are going to describe the various image acquisition methods and common measurement strategies reflected in the literature and discuss their advantages and flaws.

Correlation between brain cortex metabolic and perfusion functions in subjective idiopathic tinnitus.

OBJECTIVES: Subjective tinnitus has associated with abnormal brain metabolism and perfusion found in functional imaging studies by fluorodeoxyglucose (FDG) and technetium99m (TC99m). But there is no study evaluating the association of brain metabolism and perfusion abnormalities in a group of these subjects. The aim of this study was to investigate if there is any significant correlation between the brain perfusion and metabolism abnormalities in subjects with tinnitus. MATERIALS AND METHODS: In this cross-sectional study, 52 patients were undergone TC99m-ECD single photon emission computerized tomography (SPECT) scan and F18-FDG positron emission tomography (PET). The results of PET and SPECT scanning were fused with MRI to accurate anatomical localization of abnormalities. The analysis was performed using Kendal's correlation, t-test and chi square. RESULTS: Assessing these 52 tinnitus subjects (containing 42 males [76.4%]) showed that a significant correlation was found between the brain metabolic function and perfusion (p value 0.001).

Pattern of brain blood perfusion in tinnitus patients using technetium-99m SPECT imaging.

BACKGROUND AND PURPOSE: Tinnitus is associated with an increased activity in central auditory system as demonstrated by neuroimaging studies. Brain perfusion scanning using single photon emission computed tomography (SPECT) was done to understand the pattern of brain blood perfusion of tinnitus subjects and find the areas which are mostly abnormal in these patients. MATERIALS AND METHODS: A number of 122 patients with tinnitus were enrolled to this cross-sectional study. They underwent SPECT and magnetic resonance imaging (MRI) of brain, and the images were fused to find the regions with abnormal perfusion. RESULTS: SPECT scan results were abnormal in 101 patients (83%). Most patients had bilateral abnormal perfusion (N = 65, 53.3%), and most subjects had abnormality in middle-temporal gyrus (N = 83, 68%) and temporoparietal cortex (N = 46, 37.7%). Patients with multifocal involvement had the least mean age than other 2 groups (patients with no abnormality and unifocal abnormality) (P value = 0.045). CONCLUSIONS: Brain blood perfusion pattern differs in patient with tinnitus than others. These patients have brain perfusion abnormality, mostly in auditory gyrus (middle temporal) and associative cortex (temporoparietal cortex). Multifocal abnormalities might be due to more cognitive and emotional brain centers involvement due to tinnitus or more stress and anxiety of tinnitus in the young patients.

Doppler echocardiographic indices in aortic coarctation: a comparison of profiles before and after stenting.

BACKGROUND: Diagnosis of aortic coarctation is important as it is a difficult condition to evaluate, especially in adults. A Doppler echocardiographic index could provide a simple tool to evaluate coarctation. This study was performed to compare Doppler echocardiographic profiles before and after stenting and to assess the diagnostic value of a complete list of echocardiographic indices for detecting aortic coarctation. METHODS: This prospective study was conducted on 23 patients with a diagnosis of aortic coarctation based on angiography. Echocardiographic assessment was done twice for all patients before and after stenting. Each time, two-dimensional and Doppler echocardiographic imaging modalities were performed and complete lists of indices were recorded for each case. After comparing the values of indices before and after stenting, diagnostic values of each index were calculated in order to diagnose significant coarctation. RESULTS: Twenty-three patients, including 16 males and seven females with a mean age of 26.14 ± 10.17 years, were enrolled in this study. Except for the mean velocity and mean pressure gradient of the abdominal aorta, the values of the other indices of the abdominal/descending aorta showed enough change after stenting to indicate significant diagnostic accuracy for detecting aortic coarctation. The velocity-time integral and the pressure half-time were among the indices with the highest accuracy rates for this purpose (all p < 0.001). CONCLUSION: Post-stenting echocardiographic profiles could provide a reliable reference value of the normal aortic haemodynamics as a unique identification of each patient and it is presumed that these indices could be used as reliable indicators of response to treatment.

Pulsatility index in aortic coarctation: a possible way to evaluate factors affecting stenting outcome.

BACKGROUND: The pulsatility index (PI) shows continuous blood flow to the end organs and is a significant factor believed to decrease in aortic coarctation. Correction of this factor is of great importance in the treatment of stenotic lesions of the aorta. However, there are minimal data regarding the trend of changes in the PI after stent implantation. Furthermore, the association between the PI and other echocardiographic indices in patients undergoing stent implantation is unclear. This study was designed to evaluate changes in the PI following stenting and its correlation with other echocardiographic indices. METHODS: Twenty-three patients with a diagnosis of aortic coarctation consecutively underwent two-dimensional and Doppler echocardiographic imaging modalities twice (before and after stenting). The patients were divided into two groups based on the percentage of increase in the PI after stenting (< 50% or ≥ 50%). The relation between the post-stenting PI and the baseline echocardiographic indices was assessed. RESULTS: The PI was increased from 0.89 (SD = 0.30) to 1.75 (SD = 0.51) after stenting (p value < 0.001). Baseline diastolic/systolic velocity (D/S velocity) ratio of the abdominal aorta (p value = 0.013), mean velocity (p value = 0.033), and peak gradient of the descending aorta (p value = 0.033) were significantly higher in the patients with ≥ 50% increase in the PI after stenting. CONCLUSION: OUR FINDINGS SHOWED THAT ELEVATION IN THE PI AFTER STENTING WAS A PREDICTABLE CRITERION IN PATIENTS WITH AORTIC COARCTATION: it was predicted by some baseline clinical and echocardiographic indices. Baseline D/S ratio velocity of the abdominal aorta, mean velocity and peak gradient of the descending aorta, and baseline systolic blood pressure were the statistically significant indices to predict ≥ 50% increase in the PI in our patients.

IGF-I concentration and changes in critically ill patients.

BACKGROUND: Insulin-like growth factor 1 (IGF-I) is an anabolic growth factor that affects nitrogen balance and its changing trend is not clearly understood in critically ill patients. This study was carried out to evaluate the association between serum IGF-I levels and its changing trend in critically ill patients. METHODS: In this nested case-control study, all consecutive patients admitted to the medical ICU of Rasoul-e-Akram and Firuzgar hospital (Tehran, Iran) from January through October 2008 were included. IGF1 concentration was measured within the first 24h of ICU admission and the fourth, seventh and tenth day since admission. Patients were followed until discharge from ICU or expiration. RESULTS: The study population consisted of 90 patients (mean age: 58.01 ± 22.56), 31 (34.4%) of who died and 59 (65.6%) were discharged. On admission, 43 patients (47.7%) had low IGF-I levels, whereas 47 (52.3%) had normal or high levels. The concentration of IGF-I was not significantly different in every 4 measurements between expired and discharged patients. Significant decrease was seen between first to fourth day IGF-I concentration (p = 0.005). Changing trend was not statistically different in two groups of patients. CONCLUSIONS: There was no relation between low IGF-I concentration on admission day and increased adverse outcome, but overall these patients had lower IGF1. No clear association was found between changing trend of IGF1 and mortality. Stress on admission time may cause decreasing pattern of IGF-I in the first 4 days of admission.

Coronary flow reserve, strain and strain rate imaging during pharmacological stress before and after percutaneous coronary intervention: comparison and correlation.

INTRODUCTION: Coronary flow reserve (CFR) could apply reliable information about the coronary circulation, and strain (S) and strain rate imaging (SRI) are able to quantify the left ventricular myocardial performance. The aim of this study was to assess myocardial performance in relation to the function of the coronary circulation before and after successful percutaneous coronary intervention (PCI) of the left anterior descending artery. MATERIAL AND METHOD: Fourteen patients (10 men, 4 women, mean age 53.2 ± 11.4 years) with severe left anterior descending stenosis who had a successful selective PCI were recruited into this study. CFR and myocardial deformity indices (S and SR) were recorded before and after percutaneous intervention, both at rest and during stress echo test. RESULTS: CFR, S, and SR increased after intervention significantly. There was significant correlation between CFR ratio and poststress systolic strain (SS) ratio and early diastolic strain rate (ESR) ratio (P < 0.05 and r > 0.6). Also CFR improvement had significant relationship with changes of poststress Systolic SR and poststress Systolic S (P < 0.05 and r > 0.6). Based on regression analysis the amount of change in CFR was independently associated with change in SS during stress and systolic SR. CONCLUSION: PCI improves CFR (a marker of coronary perfusion), strain, and strain rate (markers of regional cardiac wall deformation). The independent association between CFR improvement and poststress systolic strain and strain rate means that SRI parameters can independently predict CFR changes after PCI.

Functional brain abnormalities localized in 55 chronic tinnitus patients: fusion of SPECT coincidence imaging and MRI.

Tinnitus is often defined as the perception of sounds or noise in the absence of any external auditory stimuli. The pathophysiology of subjective idiopathic tinnitus remains unclear. The aim of this study was to investigate the functional brain activities and possible involved cerebral areas in subjective idiopathic tinnitus patients by means of single photon emission computerized tomography (SPECT) coincidence imaging, which was fused with magnetic resonance imaging (MRI). In this cross-sectional study, 56 patients (1 subject excluded) with subjective tinnitus and 8 healthy controls were enrolled. After intravenous injection of 5 mCi F18-FDG (fluorodeoxyglucose), all subjects underwent a brain SPECT coincidence scan, which was then superimposed on their MRIs. In the eight regions of interest (middle temporal, inferotemporal, medial temporal, lateral temporal, temporoparietal, frontal, frontoparietal, and parietal areas), the more pronounced values were represented in medial temporal, inferotemporal, and temporoparietal areas, which showed more important proportion of associative auditory cortices in functional attributions of tinnitus than primary auditory cortex. Brain coincidence SPECT scan, when fused on MRI is a valuable technique in the assessment of patients with tinnitus and could show the significant role of different regions of central nervous system in functional attributions of tinnitus.

Evaluation of mutagenicity of mebudipine, a new calcium channel blocker.

Mebudipine is a new dihydropyridine calcium channel blocker, synthesized in our laboratory, for treatment of hypertension. It has shown a better efficacy than other drugs in this group. For assessing the risks of this drug, certain safety tests in the preclinical stage have been performed. In this study mutagenic effect of mebudipine was evaluated using Ames assay that could assess the mutagenicity of drugs and their metabolites using liver enzymes (S-9 mix). This procedure is approved as a predictive test, with a high predictive value. Salmonella TA102 (Ames assay) was used with and without S-9 in this study. For preparing S-9 mix, rat liver enzymes induced by phenobarbital were separated in KCl 0.154 M (0.154 M), as the solvent. Mebudipine was dissolved in polyethylenglycol 400. Mutagenicity test was performed in 6 doses from 39 µg to 1250 µg per every plate, in the presence and absence of the S-9 mix. The positive control sodium azide was dissolved in a dose of 5 µg/plate dissolved in polyethylenglycol 400 and negative control was polyethylenglycol 400 with no added agent. The colony counts of all doses in plates with S-9 were between 200-400 and in plates without S9 was between100-300. The colony counts in both states (with and without S-9) of all doses were in the range suggested by Ames assay for the safe drugs and were different from the positive control groups and equal to the negative controls. Mebudipine and its metabolites were not found to be mutagen on Salmonella TA102, based on Ames assay.