Janos Mester

Association of linear 18F-sodium fluoride accumulation in femoral arteries as a measure of diffuse calcification with cardiovascular risk factors: A PET/CT study

BackgroundThe aim of this study was to correlate linear 18F-sodium fluoride accumulation in the femoral arteries as a measure of diffuse mineral deposition in medial elastocalcinosis with cardiovascular risk factors (RFs) and calcified plaque burden (CPB).Methods and ResultsIn this study, 409 patients were examined by 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT). Tracer accumulation was analyzed both qualitatively and semiquantitatively by measuring the target-to-background ratio, and compared with cardiovascular RFs and CPB. Linear 18F-sodium fluoride accumulation was observed in 159 (38.9%) patients and correlated significantly with age (Pxa0<xa0.0001), hypertension (Pxa0<xa0.0001), hypercholesterolemia (Pxa0=xa0.0003), diabetes (Pxa0=xa0.0003), history of smoking (Pxa0=xa0.0007), prior cardiovascular events (Pxa0=xa0.03), and CPB (Pxa0<xa0.0001). The prevalence of linear tracer uptake increased as the number of cardiovascular RFs increased (Pxa0<xa0.0001).ConclusionsLinear 18F-sodium fluoride uptake in the femoral arteries (1) provides a measure of diffuse mineral deposition, (2) demonstrates a highly significant correlation with cardiovascular RFs and CPB, and (3) is found to accumulate more frequently in patients with a high-risk profile for cardiovascular events. 18F-sodium fluoride PET/CT may become a unique tool for in vivo visualization and quantification of ongoing calcification in large arteries.

IBZM tool: a fully automated expert system for the evaluation of IBZM SPECT studies

PurposeVisual reading of [123I]IBZM SPECT scans depends on the experience of the interpreter. Therefore, semi-quantification of striatal IBZM uptake is commonly considered mandatory. However, semi-quantification is time consuming and prone to error, particularly if the volumes of interest (VOIs) are positioned manually. Therefore, the present paper proposes a new software tool (“IBZM tool”) for fully automated and standardised processing, evaluation and documentation of [123I]IBZM SPECT scans.MethodsThe IBZM tool is an easy-to-use SPM toolbox. It includes automated procedures for realignment and summation of multiple frames (motion correction), stereotactic normalisation, scaling, VOI analysis of striatum-to-reference ratio R, classification of R and standardised display. In order to evaluate the tool, which was developed at the University of Hamburg, the tool was transferred to the University of Hannover. There it was applied to 27 well-documented subjects: eight patients with multi-system atrophy (MSA), 12 patients with Parkinson’s disease (PD) and seven controls. The IBZM tool was compared with manual VOI analysis.ResultsThe sensitivity and specificity of the IBZM tool for the differentiation of the MSA subjects from the controls were 100% and 86%, respectively. The IBZM tool provided improved statistical power compared with manual VOI analysis.ConclusionThe IBZM tool is an expert system for the detection of reduced striatal D2 availability on [123I]IBZM SPECT scans. The standardised documentation supports visual and semi-quantitative evaluation, and it is useful for presenting the findings to the referring physician. The IBZM tool has the potential for widespread use, since it appears to be fairly independent of the performance characteristics of the particular SPECT system used. The tool is available free of charge.

Diagnostic value of positron emission tomography combined with computed tomography for evaluating patients with septic shock of unknown origin

PURPOSEn(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography (CT) is a promising new tool for the identification of infectious foci. The aim of our work was to evaluate the diagnostic value of FDG-PET/CT in critically ill patients with septic shock of unknown origin.nnnMETHODSnWe performed a single-center, 6-year retrospective evaluation of the value of FDG-PET/CT in critically ill patients with severe sepsis or septic shock of unknown origin.nnnRESULTSnEighteen patients underwent FDG-PET/CT. Microbiological tests (blood culture, urine, and respiratory secretions), chest x-rays, CT scans, and transesophageal echocardiography were performed on all patients before FDG-PET/CT scanning. Pathologic FDG accumulation could be demonstrated in 14 of 18 FDG-PET/CT scans. On a per-patient basis, 11 were true positive, 3 were false positive, 4 were true negative, and there were no false negatives. In 6 cases, the results of the PET/CT scan had direct therapeutic consequences (surgery, 2; pacemaker removal, 2; initiation of antibiotic therapy, 1; and prolonged antibiotic therapy, 1); 12 (66%) of the 18 patients survived to hospital discharge.nnnCONCLUSIONSnThe FDG-PET/CT is a valuable tool for the localization of infectious foci in critically ill patients with severe sepsis/septic shock in whom conventional diagnostic methods fail to detect these foci. Prospective studies with more patients are warranted to further evaluate the diagnostic accuracy and feasibility of this diagnostic tool in critically ill patients with severe sepsis.

Can 18 F-FDG-PET/CT be generally recommended in patients with differentiated thyroid carcinoma and elevated thyroglobulin levels but negative I-131 whole body scan?

BackgroundExact localization of recurrent iodine-negative thyroid cancer is mandatory, since surgery is the only curative therapy option in patients with iodine-negative tumor tissue. The aim of this study was to evaluate the impact of 18F-FDG-PET/CT as a routine diagnostic tool on clinical management in patients with suspected thyroid cancer recurrence and elevated serum thyroglobulin (Tg) but negative radioiodine whole body scan.Methods and materialsAfter total thyroidectomy followed by radioiodine ablation, 30 consecutive patients with differentiated thyroid cancer, elevated serum thyroglobulin levels and negative whole body radioiodine scan underwent 18F-FDG-PET/CT. Results were verified by histology, ultrasound, or clinical follow-up. Diagnostic accuracy was determined for the whole study population and for subgroups with serum thyroglobulin below and above 10xa0ng/ml, respectively. Impact of PET/CT on clinical management was assessed.ResultsPET/CT identified FDG accumulating lesions in 19 of 30 patients. 17 were true-positive and 2 false-positive. In the true-positive group, 11 of the 17 patients had loco-regional disease, 3 had distant metastases only and 3 patients had both loco-regional and distant metastatic involvement. 18F-FDG-PET/CT was true-negative in 3 patients and false-negative in 8 patients. Overall sensitivity, specificity and accuracy were 68.0, 60.0, and 66.7%, respectively. In the subgroup of patients with serum thyroglobulin above 10xa0ng/ml (nxa0=xa021) the sensitivity, specificity and accuracy were substantially higher with 70.0, 100.0, and 71.4%, respectively. Clinical management was changed for 17 (57%) of 30 patients, guiding to a curative surgical intervention in 9 patients (30%).Conclusions18F-FDG-PET/CT enables detection and precise localization of loco-regional recurrence and distant metastases of differentiated thyroid cancer in patients with elevated serum thyroglobulin but negative radioiodine with significant impact on patient management and can therefore be recommended as a routine diagnostic tool.

Feasibility of 11C-Acetate PET/CT for Imaging of Fatty Acid Synthesis in the Atherosclerotic Vessel Wall

Fatty acids are a common constituent of atherosclerotic plaque and may be synthesized in the plaque itself. Fatty acid synthesis requires acetyl-coenzyme-A (CoA) as a main substrate, which is produced from acetate. Currently, 11C-acetate PET/CT is used for the evaluation of malignancies. There are no data concerning its potential for the characterization of atherosclerotic plaque. Therefore, the purpose of the present study was to examine the prevalence, distribution, and topographic relationship of arterial 11C-acetate uptake and vascular calcification in major arteries. Methods: Thirty-six patients were examined by whole-body 11C-acetate PET/CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool–corrected standardized uptake value (target-to-background ratio). CT images were used to measure calcified plaque burden. Results: 11C-acetate uptake was observed at 220 sites in 32 (88.8%) of the 36 study patients, and mean target-to-background ratio was 2.5 ± 1.0. Calcified atherosclerotic lesions were observed at 483 sites in 30 (83.3%) patients. Sixty-four (29.1%) of the 220 lesions with marked 11C-acetate uptake were colocalized with arterial calcification. However, only 13.3% of all arterial calcification sites demonstrated increased radiotracer accumulation. Conclusion: Our data indicate the feasibility of using 11C-acetate PET/CT for imaging of fatty acid synthesis in the atherosclerotic vessel wall. This study provides a rationale to incorporating 11C-acetate PET into further preclinical and clinical studies to obtain new insights into fatty acid synthesis in atherosclerotic lesions and to evaluate whether it may be used to monitor pharmacologic intervention with fatty acid synthase inhibitors.

Combined correction of recovery effect and motion blur for SUV quantification of solitary pulmonary nodules in FDG PET/CT

ObjectiveWe evaluate a fully data-driven method for the combined recovery and motion blur correction of small solitary pulmonary nodules (SPNs) in F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT).MethodsThe SPN was segmented in the low-dose CT using a variable Hounsfield threshold and morphological constraints. The combined effect of limited spatial resolution and motion blur in the SPN’s PET image was then modelled by an effective Gaussian point-spread function (psf). Both isotropic and non-isotropic psfs were used. To validate the method, PET/CT measurements of the NEMA/IEC spheres phantom were performed. The method was applied to 50 unselected SPNs ≤30xa0mm from routine patient care.ResultsRecovery of standardised uptake value (SUV) in the phantom image was significantly improved by combined recovery and motion blur correction compared with recovery-only correction, particularly with the non-isotropic model (residual average error 10%). In the patient images, automated segmentation and fit of the effective psf worked properly in all cases. Volume-equivalent diameter ranged from 4.9 to 27.8xa0mm. Uncorrected maximum SUV ranged from 0.9 to 13.3. Compared with recovery-only correction, combined correction with the non-isotropic model resulted in a ‘relevant’ (≥30%) SUV increase in 47 SPNs (94%).ConclusionsCorrection of both recovery and motion blur is mandatory for accurate SUV quantification of SPNs.

Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [ 68 Ga]PSMA I&T and comparison with published data of [ 68 Ga]PSMA HBED-CC

PurposeTo determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [68Ga]PSMA I&T and to compare it with published detection rates of [68Ga]PSMA HBED-CC.MethodsWe performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [68Ga]PSMA I&T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [68Ga]PSMA I&T were statistically compared with published detection rates of [68Ga]PSMA HBED-CC using exact Fisher’s test.ResultsMedian PSA was 0.81 (range: 0.01 – 128) ng/mL. In 58/83 patients (70 %) at least one [68Ga]PSMA I&T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [68Ga]PSMA I&T and published detection rates of [68Ga]PSMA HBED-CC (all p>0.05).Conclusions[68Ga]PSMA I&T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [68Ga]PSMA HBED-CC.

Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias.

The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesis.

Quantification of [18F]-FDG uptake in atherosclerotic plaque: impact of renal function

ObjectiveImpaired renal function causes both increased and prolonged tracer availability in the blood-pool which might result in increased tracer accumulation in atherosclerotic lesions. Therefore, the aim of this study was to investigate a possible correlation between the intensity of tracer uptake in atherosclerotic lesions and renal function.MethodsData from 50 [18F]-FDG scans were visually evaluated for tracer uptake in vessel wall alterations. Lesions were analyzed semiquantitatively by determining the blood-pool standardized uptake values (SUVblood-pools), maximum SUVs (SUVmaxs), and the target-to-background ratio (TBR). These parameters were tested for correlation with estimated glomerular filtration rate (eGFR), and cardiovascular risk factors.ResultsBoth SUVblood-pools (rsxa0=xa0−0.32, pxa0=xa00.03) and SUVmaxs for [18F]-FDG (rsxa0=xa0−0.50, pxa0<xa00.0001) showed a significant negative correlation with eGFR. TBRs for [18F]-FDG demonstrated a significant positive correlation with eGFRs (rsxa0=xa00.21, pxa0=xa00.02).ConclusionThis study found that both intravascular tracer availability (SUVblood-pool) and intralesional tracer uptake (SUVmax) are influenced by renal function. Calculation of TBR to account for that effect may result in overcorrection in case of [18F]-FDG. Renal insufficiency or subclinical changes in renal function have to be considered as a confounding factor in PET of atherosclerotic lesions.

Limitations of bi-linear regression analysis for the determination of receptor occupancy with positron emission tomography.

Background and objectivesLinear/multilinear regression methods are widely used in quantitative neuroreceptor positron emission tomography. A reference tissue method based on a bi-linear operational equation, the bi-linear reference tissue method, has been introduced in order to overcome the need for arterial blood sampling. The aim of the present paper was to investigate the sensitivity of the bi-linear reference tissue method to statistical noise, with special regard to the assessment of receptor occupancy. In addition, improvement of the bi-linear reference tissue method by regularization using physiological constraints was evaluated. MethodsApplication of the bi-linear method to dynamic positron emission tomography using the serotonin transporter ligand 11C-(+)McN5652 was considered. Investigations were performed by computer simulations and analysis of 29 patient studies. ResultsThe equilibrium specific-to-non-specific partition coefficient V′′3 was significantly underestimated by the bi-linear reference tissue method. At realistic noise levels the extent of the underestimation ranged from 25% to 75% for partition coefficients ranging from 0.3 to 0.3, respectively. This caused a 15–60% underestimation of changes in receptor occupancy after simulated intervention. The noise dependence of the bias was confirmed in the patient studies. Regularization significantly reduced the underestimation of the occupancy. ConclusionsWhen receptor status or noise level vary substantially, as in receptor occupancy studies, the bias of the bi-linear reference tissue method should be taken into account.