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author:("machat, Josef")
1.  A consecutive case series experience with [18 F] florbetapir PET imaging in an urban dementia center: impact on quality of life, decision making, and disposition 
Background
Identification and quantification of fibrillar amyloid in brain using positron emission tomography (PET) imaging and Amyvid™ ([18 F] Amyvid, [18 F] florbetapir, 18 F-AV-45) was recently approved by the US Food and Drug Administration as a clinical tool to estimate brain amyloid burden in patients being evaluated for cognitive impairment or dementia. Imaging with [18 F] florbetapir offers in vivo confirmation of the presence of cerebral amyloidosis and may increase the accuracy of the diagnosis and likely cause of cognitive impairment (CI) or dementia. Most importantly, amyloid imaging may improve certainty of etiology in situations where the differential diagnosis cannot be resolved on the basis of standard clinical and laboratory criteria.
Results
A consecutive case series of 30 patients (age 50-89; 16 M/14 F) were clinically evaluated at a cognitive evaluation center of urban dementia center and referred for [18 F] florbetapir PET imaging as part of a comprehensive dementia workup. Evaluation included neurological examination and neuropsychological assessment by dementia experts. [18 F] florbetapir PET scans were read by trained nuclear medicine physicians using the qualitative binary approach. Scans were rated as either positive or negative for the presence of cerebral amyloidosis. In addition to a comprehensive dementia evaluation, post [18 F] florbetapir PET imaging results caused diagnoses to be changed in 10 patients and clarified in 9 patients. Four patients presenting with SCI were negative for amyloidosis. These results show that [18 F] florbetapir PET imaging added diagnostic clarification and discrimination in over half of the patients evaluated.
Conclusions
Amyloid imaging provided novel and essential data that: (1) caused diagnosis to be revised; and/or (2) prevented the initiation of incorrect or suboptimal treatment; and/or (3) avoided inappropriate referral to an anti-amyloid clinical trial.
doi:10.1186/1750-1326-9-10
PMCID: PMC3913628  PMID: 24484858
Amyvid™; Florbetapir; PET; Clinical series; Alzheimer’s disease; Neuroimaging
2.  Impact of Non-Insulin Dependent Type-2 Diabetes on Carotid Wall 18F-FDG-PET Uptake 
Objective & Background
Inflammation is a pivotal process in the progression of atherosclerosis, which can be non-invasively imaged by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). In this study, the impact of non-insulin dependent type-2 diabetes on carotid wall FDG uptake in patients with documented or suspected cardiovascular disease was evaluated.
Methods
Carotid artery wall FDG uptake was quantified in 134 patients (age 60.2±9.7 years; diabetic subjects: n=43). The pre-scan glucose (gluc) level corrected mean of the maximum standardized uptake value (SUV) values (meanSUVgluc), mean of the maximum target-to-background ratio (meanTBRgluc), and Single Hottest Segment (SHSgluc) of FDG uptake in the artery wall were calculated. Associations between FDG uptake, the presence of risk factors for atherosclerosis, and diabetes were then assessed by multiple regression analysis with backward elimination.
Results
We demonstrated a significant association between diabetes and FDG uptake in the arterial wall (diabetes: meanSUVgluc; β=0.324, meanTBRgluc; β=0.317, and SHSgluc; β=0.298; for all: p<0.0001, respectively). In addition, in diabetic patients, both body mass index (BMI) ≥30 kg/m2 (BMI ≥30 kg/m2: meanSUVgluc; β=0.4, meanTBRgluc; β=0.357, and SHSgluc; β=0.388; for all: p<0.015) and smoking (smoking: meanTBRgluc; β=0.312, SHSgluc; β=0.324; for all: p<0.04) were significantly associated with FDG uptake.
Conclusions
Type-2 diabetes was significantly associated with carotid wall FDG uptake in patients with known or suspected cardiovascular disease. In diabetic patients, obesity and smoking add to the risk of increased FDG uptake values. Furthermore, the degree of carotid wall FDG uptake increases with increments of fasting glucose levels in diabetic patients.
doi:10.1016/j.jacc.2011.11.069
PMCID: PMC3392202  PMID: 22651864
FDG-PET; Inflammation; Atherosclerosis; Diabetes; Carotid Arteries
3.  Coronary artery and thoracic aorta calcification is inversely related to coronary flow reserve as measured by 82Rb PET/CT in intermediate risk patients 
Journal of Nuclear Cardiology  2013;20:375-384.
Background
The strength and nature of the relationship between myocardial perfusion imaging (MPI), coronary flow reserve (CFR), and coronary artery calcium (CAC) and thoracic aorta calcium (TAC) remain to be clarified.
Methods
Dynamic rest-pharmacological stress 82Rb positron emission tomography/computed tomography MPI with CFR, CAC, and TAC was performed in 75 patients (59 ± 13 years; F/M = 38/37) with intermediate risk of coronary artery disease.
Results
A total of 29 (39%) patients had ischemic and 46 (61%) had normal MPI. CAC was correlated with TAC (ρ = 0.7; P < .001), and CFR was inversely related with CAC and TAC (ρ = −0.6 and −0.5; P < .001, respectively). By gender-specific univariate analysis, age (P = .001), CAC (P = .004), and CFR (P = .008) in males, but CFR (P = .0001), age (P = .002), and TAC (P = .01) in females were significant predictors of ischemic MPI. By multiple regression, the most potent predictor was CFR [odds ratio (OR) = 0.17, P = .01), followed by age (OR = 1.07, P = .02), gender (OR = 4.01, P = .03), and CAC (OR = 1.002, P = .9).
Conclusions
Combination of MPI, CFR, CAC, and TAC has complementary roles in intermediate risk patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s12350-013-9675-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s12350-013-9675-5
PMCID: PMC3653061  PMID: 23468383
PET/CT; coronary flow reserve; coronary artery calcium; thoracic aorta calcium; coronary artery disease
4.  Detection of Neovessels in Atherosclerotic Plaques of Rabbits using Dynamic Contrast Enhanced MRI and 18F-FDG PET 
Introduction
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.
Objective
Our aim was to test two 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 ten rabbits by a combination of two endothelial abrasions and four months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, while four 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).
Conclusion
DCE-MRI and 18F-FDG PET may allow for the evaluation of inflammation in atherosclerotic plaques of rabbits. These non-invasive imaging modalities could be proposed as clinical tools in the evaluation of lesion prognosis and monitoring of anti–angiogenic therapies.
doi:10.1161/ATVBAHA.108.166173
PMCID: PMC3194007  PMID: 18467641
atherosclerosis; inflammation; neovessels; MRI; PET
5.  The Relationships Between Regional Arterial Inflammation, Calcification, Risk Factors and Biomarkers – A Prospective FDG PET/CT Imaging Study 
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. Here we explore how atherosclerotic plaque inflammation varies across arterial territories and how it relates to arterial calcification. We also test 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/CT imaging with FDG. All had either vascular disease or multiple risk factors for it. Forty subjects underwent carotid imaging, twenty-seven underwent aortic, twenty-four iliac and thirteen femoral imaging. Thirty-three subjects had a panel of biomarkers analyzed.
We found strong associations between FDG uptake in neighboring arteries (left vs. right carotid r=0.91, p<0.001, ascending aorta vs. aortic arch r=0.88, p<0.001). Calcification and inflammation rarely overlapped within arteries – carotid artery FDG uptake vs. 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 ratio (TBR) 1.83 vs. 1.61, p<0.01), and in males vs. females (TBR 1.83 vs. 1.63, p<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 TBR vs. matrix metalloproteinase 3 (MMP 3): r=0.53, p=0.01 and carotid TBR vs. MMP 9: r=0.50, p=0.01. Non-significant 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.
doi:10.1161/CIRCIMAGING.108.811752
PMCID: PMC3190196  PMID: 19808576
Atherosclerosis; Imaging; Inflammation; Positron Emission Tomography; Fluorodeoxyglucose; Calcification
6.  Extraperitoneal urine leak after renal transplantation: the role of radionuclide imaging and the value of accompanying SPECT/CT - a case report 
BMC Medical Imaging  2010;10:23.
Background
The differentiation of the nature of a fluid collection as a complication of kidney transplantation is important for management and treatment planning. Early and delayed radionuclide renography can play an important role in the evaluation of a urine leak. However, it is sometimes limited in the evaluation of the exact location and extent of a urine leak.
Case Presentation
A 71-year-old male who had sudden anuria, scrotal swelling and elevated creatinine level after cadaveric renal transplantation performed Tc-99 m MAG3 renography to evaluate the renal function, followed by an ultrasound which was unremarkable. An extensive urine leak was evident on the planar images. However, an exact location of the urine leak was unknown. Accompanying SPECT/CT images confirmed a urine leak extending from the lower aspect of the transplant kidney to the floor of the pelvic cavity, presacral region and the scrotum via right inguinal canal as well as to the right abdominal wall.
Conclusions
Renal scintigraphy is very useful to detect a urine leak after renal transplantation. However, planar imaging is sometimes limited in evaluating the anatomical location and extent of a urine leak accurately. In that case accompanying SPECT/CT images are very helpful and valuable to evaluate the anatomical relationships exactly.
doi:10.1186/1471-2342-10-23
PMCID: PMC2984463  PMID: 20961409
7.  Repeatability of regional myocardial blood flow calculation in 82Rb PET imaging 
Background
We evaluated the repeatability of the calculation of myocardial blood flow (MBF) at rest and pharmacological stress, and calculated the coronary flow reserve (CFR) utilizing 82Rb PET imaging. The aim of the research was to prove high repeatability for global MBF and CFR values and good repeatability for regional MBF and CFR values. The results will have significant impact on cardiac PET imaging in terms of making it more affordable and increasing its use.
Methods
12 normal volunteers were imaged at rest and during pharmacological stress, with 2220 MBq of 82Rb each. A GE Advance PET system was used to acquire dynamic 50-frame studies. MBF was calculated with a 2-compartmental model using a modified PMOD program (PMOD; University Hospital Zurich, Zurich, Switzerland). Two differential equations, describing a 2-compartmental model, were solved by numerical integration and using Levenberg-Marquardt's method for fitting data. The PMOD program defines 16 standard segments and calculates myocardial flow for each segment, as well as average septal, anterior, lateral, inferior and global flow. Repeatability was evaluated according to the method of Bland and Altman.
Results
Global rest and stress MBF, as well as global CFR, showed very good repeatability. No significant differences were found between the paired resting global MBF (0.63 ± 0.13 vs. 0.64 ± 0.13 mL/min/g; mean difference, -1.0% ± 2.6%) and the stress global MBF (1.37 ± 0.23 vs. 1.37 ± 0.24; mean difference, 0.1% ± 2.3%). Global CFR was highly reproducible (2.25 ± 0.56 vs. 2.22 ± 0.54, P = not statistically significant; mean difference, 1.3% ± 14.3%). Repeatability coefficients for global rest MBF were 0.033 (5.2%) and stress MBF 0.062 (4.5%) mL/min/g. Regional rest and stress MBF and CFR have shown good reproducibility. The average per sector repeatability coefficients for rest MBF were 0.056 (8.5%) and stress MBF 0.089 (6.3%) mL/min/g, and average repeatability coefficient for CFR was 0.25 (10.6%).
Conclusion
The results of the study show that software calculation of MBF and CFR with 82Rb myocardial PET imaging is highly repeatable for global values and has good repeatability for regional values.
doi:10.1186/1756-6649-9-2
PMCID: PMC2646684  PMID: 19178700
8.  Comparison of 2D, 3D high dose and 3D low dose gated myocardial 82Rb PET imaging 
Background
We compared 2D, 3D high dose (HD) and 3D low dose (LD) gated myocardial Rb-82 PET imaging in 16 normal human studies. The main goal in the paper is to evaluate whether the images obtained by a 3D LD studies are still of comparable clinical quality to the images obtained with the 2D HD or 3D HD studies.
Methods
All 2D and 3D HD studies were performed with 2220 MBq of Rb-82. The 3D LD were performed with 740 MBq of Rb-82. A GE Advance PET system was used for acquisition. Polar maps were created and used to calculate noise among (NAS) and within (NWS) the segments in the noise analysis. In addition, the contrast between left ventricular (LV) wall and LV cavity was also analysed. For 13 subjects, ejection fraction (EF) on 2D and 3D studies was calculated using QGS program.
Results
For the H20 reconstruction filter, the mean contrast in mid-ventricular short-axis slice was 0.33 ± 0.06 for 2D studies. The same contrast for the 3D HD studies was 0.38 ± 0.07 and for 3D LD, it was 0.34 ± 0.08. For the 6 volunteers where 3D HD was used, NAS was 3.64*10-4 and NWS was 1.79*10-2 for 2D studies, and NAS was 3.70*10-4 and NWS was 1.85*10-2 for 3D HD studies, respectively. For the other 10 volunteers where 3D LD was used, NAS was 3.85*10-4 and NWS was 1.82*10-2 for the 2D studies, and NAS was 5.58*10-4 and NWS was 1.91*10-2 for the 3D LD studies, respectively. For the sharper H13 filter, the data followed the same pattern, with slightly higher values of contrast and noise. EF values in 2D and 3D were close. The Pearson's correlation coefficient was 0.90. The average difference from 13 subjects was 8.3%.
Conclusion
2D and 3D HD gating Rb-82 PET cardiac studies have similar contrast, ejection fractions and noise levels. 3D LD gating imaging, gave comparable results in terms of contrast, EF and noise to either 2D or 3D HD gating PET imaging. 3D LD PET gated imaging can make Rb-82 PET cardiac imaging more affordable with significantly less radiation exposure to the patients.
doi:10.1186/1471-2385-7-4
PMCID: PMC2140263  PMID: 17953754
9.  Comparison of 18F SPECT with PET in myocardial imaging: A realistic thorax-cardiac phantom study 
Background
Positron emission tomography (PET) imaging with fluorine-18 (18F) Fluorodeoxyglucose (FDG) and flow tracer such as Rubidium-82 (82Rb) is an established method for evaluating an ischemic but viable myocardium. However, the high cost of PET imaging restricts its wider clinical use. Therefore, less expensive 18F FDG single photon emission computed tomography (SPECT) imaging has been considered as an alternative to 18F FDG PET imaging. The purpose of the work is to compare SPECT with PET in myocardial perfusion/viability imaging.
Methods
A nonuniform RH-2 thorax-heart phantom was used in the SPECT and PET acquisitions. Three inserts, 3 cm, 2 cm and 1 cm in diameter, were placed in the left ventricular (LV) wall to simulate infarcts. The phantom acquisition was performed sequentially with 7.4 MBq of 18F and 22.2 MBq of Technetium-99m (99mTc) in the SPECT study and with 7.4 MBq of 18F and 370 MBq of 82Rb in the PET study. SPECT and PET data were processed using standard reconstruction software provided by vendors. Circumferential profiles of the short-axis slices, the contrast and viability of the inserts were used to evaluate the SPECT and PET images.
Results
The contrast for 3 cm, 2 cm and 1 cm inserts were for 18F PET data, 1.0 ± 0.01, 0.67 ± 0.02 and 0.25 ± 0.01, respectively. For 82Rb PET data, the corresponding contrast values were 0.61 ± 0.02, 0.37 ± 0.02 and 0.19 ± 0.01, respectively. For 18F SPECT the contrast values were, 0.31 ± 0.03 and 0.20 ± 0.05 for 3 cm and 2 cm inserts, respectively. For 99mTc SPECT the contrast values were, 0.63 ± 0.04 and 0.24 ± 0.05 for 3 cm and 2 cm inserts respectively. In SPECT, the 1 cm insert was not detectable. In the SPECT study, all three inserts were falsely diagnosed as "viable", while in the PET study, only the 1 cm insert was diagnosed falsely "viable".
Conclusion
For smaller defects the 99mTc/18F SPECT imaging cannot entirely replace the more expensive 82Rb/18F PET for myocardial perfusion/viability imaging, due to poorer image spatial resolution and poorer defect contrast.
doi:10.1186/1471-2385-6-5
PMCID: PMC1634842  PMID: 17076890
10.  Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation 
Background
Coronary 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.
Methods
Atherosclerosis 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.
Results
Atherosclerotic 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.
Conclusion
PET 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.
doi:10.1186/1471-2385-6-3
PMCID: PMC1479805  PMID: 16725052
11.  Using the intraoperative hand held probe without lymphoscintigraphy or using only dye correlates with higher sensory morbidity following sentinel lymph node biopsy in breast cancer: A review of the literature 
Background
There are no studies that have directly investigated the incremental reduction in sensory morbidity that lymphoscintigraphy images (LS) and triangulated body marking or other skin marking techniques provide during sentinel lymph node biopsy (SLNB) compared to using only the probe without LS and skin marking or using only dye. However, an indirect assessment of this potential for additional sensory morbidity reduction is possible by extracting morbidity data from studies comparing the morbidity of SLNB to that of axillary lymph node dissection.
Methods
A literature search yielded 13 articles that had data on sensory morbidity at specific time points on pain, numbness or paresthesia from SLNB that used radiotracer and probe or used only dye as a primary method of finding the sentinel node (SN). Of these, 10 utilized LS, while 3 did not utilize LS. By matching the data in studies not employing LS to the studies that did, comparisons regarding the percentage of patients experiencing pain, numbness/paresthesia after SLNB could be reasonably attempted at a cutoff of 9 months.
Results
In the 7 studies reporting on pain after 9 months (> 9 months) that used LS (1347 patients), 13.8% of patients reported these symptoms, while in the one study that did not use LS (143 patients), 28.7% of patients reported these symptoms at > 9 months (P < 0.0001). In the 6 studies reporting on numbness and/or paresthesia at > 9 months that used LS (601 patients), 12.5% of patients reported these symptoms, while in the 3 studies that did not use LS (229 patients), 23.1% of patients reported these symptoms at > 9 months (P = 0.0002). Similar trends were also noted for all these symptoms at ≤ 9 months.
Conclusion
Because of variations in techniques and time of assessing morbidity, direct comparisons between studies are difficult. Nevertheless at a minimum, a clear trend is present: having the LS images and skin markings to assist during SLNB appears to yield more favorable morbidity outcomes for the patients compared to performing SLNB with only the probe or performing SLNB with dye alone. These results are extremely pertinent, as the main reason for performing SLNB itself in the first place is to achieve reduced morbidity.
doi:10.1186/1477-7819-3-64
PMCID: PMC1262786  PMID: 16194276

Results 1-11 (11)