3D-OSEM and FP-CIT SPECT quantification: benefit for studies with a high radius of rotation?

Objectives Dopamine transporter imaging with single-photon emission computed tomography (SPECT) is a valuable tool for both clinical routine and research studies. Recently, it was found that the image quality could be improved by introduction of the three-dimensional ordered subset expectation maximization (3D-OSEM) reconstruction algorithm, which provides resolution recovery. The aim of this study was to systematically evaluate the potential benefits of 3D-OSEM in comparison with 2D-OSEM under critical imaging conditions, for example, scans with a high radius of rotation.Materials and methods Monte Carlo simulation scans of a digital brain phantom with various disease states and different radii of rotation ranging from 13 to 30 cm were reconstructed with both 2D-OSEM and 3D-OSEM algorithms. Specific striatal binding and putamen-to-caudate ratios were determined and compared with true values in the phantom.Results The percentage recovery of true striatal binding was similar between both reconstruction algorithms at the minimum rotational radius; however, at the maximum rotational radius, it decreased from 53 to 43% for 3D-OSEM and from 52 to 26% for 2D-OSEM. 3D-OSEM matched the true putamen-to-caudate ratios more closely than did 2D-OSEM in scans with high SPECT rotation radii.Conclusion 3D-OSEM offers a promising image quality gain. It outperforms 2D-OSEM, particularly in studies with limited resolutions (such as scans acquired with a high radius of rotation) but does not improve the accuracy of the putamen-to-caudate ratios. Whether the benefits of better recovery in studies with higher radii of rotation could potentially increase the diagnostic power of dopamine transporter SPECT in patients with borderline striatal radiotracer binding, however, needs to be further examined

Choline PET based dose-painting in prostate cancer - Modelling of dose effects

Background: Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Methods: Based on different assumptions for alpha/beta, gamma 50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Results: Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high gamma 50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Discussion: Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the assumption of high detection rates and low initial TCP values the TCP gain has been shown to be relevant. Conclusions: Based on the employed assumptions, specific dose escalation to choline PET positive areas within the prostate may increase the local control rates. Due to the lack of exact PET sensitivity and prostate alpha/beta parameter, no firm conclusions can be made. Small variations may completely abrogate the clinical benefit of a SIB based on choline PET imaging

Cerebrospinal Fluid Tau Protein Levels and F-18-Fluorodeoxyglucose Positron Emission Tomography in the Differential Diagnosis of Alzheimer's Disease

Aims: In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau(181)) and positron emission tomography with F-18-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer's disease (AD) under clinical conditions. Method: In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitivity and specificity were calculated and compared using ROC analyses. Results: p-tau(181) and FDG-PET were comparable in separating DAT from controls (sensitivity: 67 vs. 79%; specificity: 91% for both) and patients with other dementias (sensitivity: 71 vs. 79%; specificity: 100% for both). The sensitivity of p-tau 181 in differentiating MCI patients from controls was significantly (p < 0.05) superior to that of FDG-PET (75 vs. 44%) at a comparably high specificity (82 vs. 91%); t-tau measures were less accurate in all analyses. Conclusions: FDG-PET and CSF p-tau(181) levels are able to discriminate DAT in heterogeneous and unselected samples with a high accuracy. CSF p-tau(181) might be somewhat superior for a sensitive detection of patients with MCI. Copyright (C) 2010 S. Karger AG, Base

τBu₂SiF-Derivatized D₂-Receptor Ligands: The First SiFA-Containing Small Molecule Radiotracers for Target-Specific PET-Imaging

The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D-2-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D2-receptor affinities for all compounds in the nanomolar range (Ki(SiFA-DMFP) = 13.6 nM, Ki(SiFA-FP) = 33.0 nM, Ki(SiFA-DDMFP) = 62.7 nM and Ki(SiFA-M-FP) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with F-18]fluoride/TBAHCO(3) in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/mu mol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min

The assessment of left ventricular mechanical dyssynchrony from gated 99mTc-tetrofosmin SPECT and gated 18F-FDG PET by QGS: a comparative study

BACKGROUND Due to partly conflicting studies, further research is warranted with the QGS software package, with regard to the performance of gated FDG PET phase analysis as compared to gated MPS as well as the establishment of possible cut-off values for FDG PET to define dyssynchrony. METHODS Gated MPS and gated FDG PET datasets of 93 patients were analyzed with the QGS software. BW, Phase SD, and Entropy were calculated and compared between the methods. The performance of gated PET to identify dyssynchrony was measured against SPECT as reference standard. ROC analysis was performed to identify the best discriminator of dyssynchrony and to define cut-off values. RESULTS BW and Phase SD differed significantly between the SPECT and PET. There was no significant difference in Entropy with a high linear correlation between methods. There was only moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony with a cut-off point at 62%. CONCLUSION Gated MPS and gated FDG PET can assess LVMD. The methods cannot be used interchangeably. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. Further prospective research is necessary

Ventral and dorsal streams processing visual motion perception (FDG-PET study)

Background: Earlier functional imaging studies on visually induced self-motion perception (vection) disclosed a bilateral network of activations within primary and secondary visual cortex areas which was combined with signal decreases, i.e., deactivations, in multisensory vestibular cortex areas. This finding led to the concept of a reciprocal inhibitory interaction between the visual and vestibular systems. In order to define areas involved in special aspects of self-motion perception such as intensity and duration of the perceived circular vection (CV) or the amount of head tilt, correlation analyses of the regional cerebral glucose metabolism, rCGM (measured by fluorodeoxyglucose positron-emission tomography, FDG-PET) and these perceptual covariates were performed in 14 healthy volunteers. For analyses of the visual-vestibular interaction, the CV data were compared to a random dot motion stimulation condition (not inducing vection) and a control group at rest (no stimulation at all). Results: Group subtraction analyses showed that the visual-vestibular interaction was modified during CV, i.e., the activations within the cerebellar vermis and parieto-occipital areas were enhanced. The correlation analysis between the rCGM and the intensity of visually induced vection, experienced as body tilt, showed a relationship for areas of the multisensory vestibular cortical network (inferior parietal lobule bilaterally, anterior cingulate gyrus), the medial parieto-occipital cortex, the frontal eye fields and the cerebellar vermis. The "earlier" multisensory vestibular areas like the parieto-insular vestibular cortex and the superior temporal gyrus did not appear in the latter analysis. The duration of perceived vection after stimulus stop was positively correlated with rCGM in medial temporal lobe areas bilaterally, which included the (para-) hippocampus, known to be involved in various aspects of memory processing. The amount of head tilt was found to be positively correlated with the rCGM of bilateral basal ganglia regions responsible for the control of motor function of the head. Conclusions: Our data gave further insights into subfunctions within the complex cortical network involved in the processing of visual-vestibular interaction during CV. Specific areas of this cortical network could be attributed to the ventral stream ("what" pathway) responsible for the duration after stimulus stop and to the dorsal stream ("where/how" pathway) responsible for intensity aspects

Combined Scintigraphy and Tumor Marker Analysis Predicts Unfavorable Histopathology of Neuroblastic Tumors with High Accuracy

Objectives Our aim was to improve the prediction of unfavorable histopathology (UH) in neuroblastic tumors through combined imaging and biochemical parameters. Methods I-123-MIBG SPECT and MRI was performed before surgical resection or biopsy in 47 consecutive pediatric patients with neuroblastic tumor. Semi-quantitative tumor-to-liver count-rate ratio (TLCRR),MRI tumor size and margins, urine catecholamine and NSE blood levels of neuron specific enolase (NSE) were recorded. Accuracy of single and combined variables for prediction of UH was tested by ROC analysis with Bonferroni correction. Results 34 of 47 patients had UH based on the International Neuroblastoma Pathology Classification (INPC). TLCRR and serum NSE both predicted UH with moderate accuracy. Optimal cut-off for TLCRR was 2.0, resulting in 68% sensitivity and 100% specificity (AUC-ROC 0.86, p < 0.001). Optimal cut-off for NSE was 25.8 ng/ml, resulting in 74% sensitivity and 85% specificity (AUC-ROC 0.81, p = 0.001). Combination of TLCRR/NSE criteria reduced false negative findings from 11/9 to only five, with improved sensitivity and specificity of 85% (AUC-ROC 0.85, p < 0.001). Conclusion Strong I-123-MIBG uptake and high serum level of NSE were each predictive of UH. Combined analysis of both parameters improved the prediction of UH in patients with neuroblastic tumor. MRI parameters and urine catecholamine levels did not predict UH

Reduced FDG-PET brain metabolism and executive function predict clinical progression in elderly healthy subjects

Brain changes reminiscent of Alzheimer disease (AD) have been previously reported in a substantial portion of elderly cognitive healthy (HC) subjects. The major aim was to evaluate the accuracy of MRI assessed regional gray matter (GM) volume, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET),and neuropsychological test scores to identify those HC subjects who subsequently convert to mild cognitive impairment (MCI) or AD dementia. We obtained in 54 healthy control (HC) subjects a priori defined region of interest (ROI) values of medial temporal and parietal FDG-PET and medial temporal GM volume. In logistic regression analyses, these ROI values were tested together with neuropsychological test scores (free recall, trail making test B (TMT-B)) as predictors of HC conversion during a clinical follow-up between 3 and 4 years. In voxelbased analyses, FDG-PET and MRI GM maps were compared between HC converters and HC non-converters. Out of the 54 HC subjects, 11 subjects converted to MCI or AD dementia. Lower FDG-PET ROI values were associated with higher likelihood of conversion (p = 0.004),with the area under the curve (AUC) yielding 82.0% (95% CI = (95.5%,68.5%)). The GM volume ROI was not a significant predictor (p = 0.07). TMT-B but not the free recall tests were a significant predictor (AUC = 71% (95% CI = 50.4%,91.7%)). For the combination of FDG-PET and TMT-B, the AUC was 93.4% (sensitivity = 82%,specificity = 93%). Voxel-based group comparison showed reduced FDG-PET metabolism within the temporo-parietal and prefrontal cortex in HC converters. In conclusion, medial temporal and-parietal FDG-PET and executive function show a clinically acceptable accuracy for predicting clinical progression in elderly HC subjects. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved

Microfluidics: A Groundbreaking Technology for PET Tracer Production?

Application of microfluidics to Positron Emission Tomography ( PET) tracer synthesis has attracted increasing interest within the last decade. The technical advantages of microfluidics, in particular the high surface to volume ratio and resulting fast thermal heating and cooling rates of reagents can lead to reduced reaction times, increased synthesis yields and reduced by-products. In addition automated reaction optimization, reduced consumption of expensive reagents and a path towards a reduced system footprint have been successfully demonstrated. The processing of radioactivity levels required for routine production, use of microfluidic-produced PET tracer doses in preclinical and clinical imaging as well as feasibility studies on autoradiolytic decomposition have all given promising results. However, the number of microfluidic synthesizers utilized for commercial routine production of PET tracers is very limited. This study reviews the state of the art in microfluidic PET tracer synthesis, highlighting critical design aspects, strengths, weaknesses and presenting several characteristics of the diverse PET market space which are thought to have a significant impact on research, development and engineering of microfluidic devices in this field. Furthermore, the topics of batch- and single-dose production, cyclotron to quality control integration as well as centralized versus de-centralized market distribution models are addressed