ECAT EXACT HR Research Articles

Decreased 5-HT1A binding in mild Alzheimer's disease-A positron emission tomography study.

Decreased 5‐HT1A receptor binding has been associated with Alzheimer's disease (AD) and interpreted as a consequence of neuron loss. The purpose of the present study was to compare [11C]WAY100635 binding to the 5‐HT1A receptor in the hippocampus, entorhinal cortex, amygdala and pericalcarine cortex in mild AD patients and elderly controls. AD patients (n = 7) and elderly control subjects (n = 8) were examined with positron emission tomography (PET) and [11C]WAY100635. PET data acquisition was performed with an ECAT EXACT HR system. Wavelet‐aided parametric images of nondisplaceable binding potential (BP ND) were generated using Logan's graphical analysis with cerebellum as the reference region. Correction for partial volume effects was performed with the Müller–Gärtner method. Regions of interest (ROIs) were applied to the individual parametric images, and the regional BP ND was calculated as the average parametric voxel value within each ROI. In addition to comparisons between subject groups, correlations between BP ND values and scores on the Mini‐Mental State Examination, Disability Assessment for Dementia (DAD), and Neuropsychiatric Inventory were expressed by Pearson correlation coefficients. Mean regional BP ND was lower in AD patients than in control subjects, and the difference was statistically significant for the hippocampus, entorhinal cortex, and amygdala. A statistically significant correlation was obtained between hippocampal BP ND values and DAD scores. The results of the present study corroborate and extend previous findings of decreased 5‐HT1A binding in AD and strengthen the support for 5‐HT1A receptor PET as a tool for the assessment of neurodegenerative changes in mild AD.

Technical note: A PET/MR coil with an integrated, orbiting 511keV transmission source for PET/MR imaging validated in an animal study.

BackgroundMR‐based methods for attenuation correction (AC) in PET/MRI either neglect attenuation of bone, or use MR‐signal derived information about bone, which leads to a bias in quantification of tracer uptake in PET. In a previous study, we presented a PET/MRI specific MR coil with an integrated transmission source (TX) system allowing for direct measurement of attenuation. In phantom measurements, this system successfully reproduced the linear attenuation coefficient of water.PurposeThe purpose of this study is to validate the TX system in a clinical setting using animals and to show its applicability compared to standard clinical methods.MethodsAs test subject, a 15‐kg piglet was injected with 53 MBq of 18F‐NaF. The μ‐map obtained with the TX system and the reconstructed activity distribution were compared to four established AC methods: a Dixon sequence, an ultra‐short echo time (UTE) sequence, a CT scan, and a 511 keV transmission scan using a Siemens ECAT EXACT HR+ as the reference. The PET/MRI measurements were performed on a Siemens Biograph mMR to obtain the μ‐map using the TX system as well as the Dixon and UTE sequence directly followed by the CT and ECAT measurements.ResultsThe reconstructed activity distribution using the TX system for AC showed similar results compared to the reference (<5% difference in hot regions) and outperformed the MR‐based methods as implemented in the PET/MRI system (<10% difference in hot regions). However, the additional hardware of the TX system adds complexity to the acquisition process.ConclusionOur porcine study demonstrates the feasibility of post‐injection transmission scans using the developed TX system in a clinical setting. This makes it a useful tool for PET/MRI in cases where transmission information is needed for AC. Potential applications are studies using larger animals where state‐of‐the‐art atlas‐based or artificial intelligence AC methods are not available.

Test‐retest variability of relative tracer delivery rate as measured by [11C]PiB

AbstractBackgroundIn Alzheimer’s disease (AD), reductions in cerebral blood flow (CBF) have been reported and these may be used as proxy for measuring treatment efficacy or disease progression. The gold standard technique for measuring CBF is [15O]H2O positron emission tomography (PET). Recent studies, however, have reported high correlations between [11C]PiB PET derived relative tracer delivery rate R 1 and [15O]H2O derived relative CBF, suggesting that [11C]PiB R 1 may be a good proxy of relative CBF. As longitudinal PET studies become more common for measuring disease progression, it is important to know the intrinsic variability of R 1. The purpose of the present study was to determine R 1 test‐retest (TRT) variability.MethodPreviously, TRT variability of [11C]PiB binding potential has been reported for a group of twelve participants (five cognitively unimpaired (CU), one with mild cognitive impairment and six with AD dementia), in which all participants underwent two 90 min [11C]PiB PET scans using a Siemens ECAT EXACT HR+ scanner1. This dataset was reanalysed to also determine TRT variability of [11C]PiB R1. The voxel‐based implementation of the two‐step simplified reference tissue model with cerebellar grey matter as reference tissue was used to generate R1 images. Next, TRT variability was calculated both globally and regionally, and global R1 measures were compared between diagnostic groups using a non‐parametric Mann‐Whitney U test. Next, correlation analysis was used to assess the relationship between TRT variability and regional volume. Finally, regional test and retest R1 measures were compared using Linear Mixed Effect Models and Bland‐Altman analysis.ResultGlobal relative tracer delivery (R1) was significantly lower in AD patients (test R1:0.82±0.04, retest R1:0.82±0.03) compared with CU participants (test R1:0.93±0.04 retest R1:0.91±0.03, p&lt;0.01). TRT variability was low across regions (range:1.5‐5.8%), with a trend effect towards smaller TRT for larger regions (R2=0.14, p=0.09). Furthermore, test and retest measures showed high, significant correlations (R2=0.92, slope=0.98) and negligible bias (0.69±3.07%).ConclusionThe high precision of [11C]PiB R1 suggests suitable applicability for cross‐sectional and longitudinal studies. This finding further demonstrates the utility of dynamic [11C]PiB PET scans for dual‐biomarker imaging in AD research. Reference: Tolboom et al.(2009) Eur J Nucl Med Mol Imaging 36:1629‐38.

In vivo PET Imaging of [11C]CIMBI-5, a 5-HT2AR Agonist Radiotracer in Nonhuman Primates.

5-HT2AR exists in high and low affinity states. Agonist PET tracers measure binding to the active high affinity site and thus provide a functionally relevant measure of the receptor. Limited in vivo data have been reported so far for a comparison of agonist versus antagonist tracers for 5-HT2AR used as a proof of principle for measurement of high and low affinity states of this receptor. We compared the in vivo binding of [11C]CIMBI-5, a 5-HT2AR agonist, and of the antagonist [11C]M100907, in monkeys and baboons. [11C]CIMBI-5 and [11C]M100907 baseline PET scans were performed in anesthetized male baboons (n=2) and male vervet monkeys (n=2) with an ECAT EXACT HR+ and GE 64-slice PET/CT Discovery VCT scanners. Blocking studies were performed in vervet monkeys by pretreatment with MDL100907 (0.5 mg/kg, i.v.) 60 minutes prior to the scan. Regional distribution volumes and binding potentials were calculated for each ROI using the likelihood estimation in graphical analysis and Logan plot, with either plasma input function or reference region as input, and simplified reference tissue model approaches. PET imaging of [11C]CIMBI-5 in baboons and monkeys showed the highest binding in 5-HT2AR-rich cortical regions, while the lowest binding was observed in cerebellum, consistent with the expected distribution of 5-HT2AR. Very low free fractions and rapid metabolism were observed for [11C]CIMBI-5 in baboon plasma. Binding potential values for [11C]CIMBI-5 were 25-33% lower than those for [11C]MDL100907 in the considered brain regions. The lower binding potential of [11C]CIMBI-5 in comparison to [11C]MDL100907 is likely due to the preferential binding of the former to the high affinity site in vivo in contrast to the antagonist, [11C]MDL100907, which binds to both high and low affinity sites.

The Jülich Experience With Simultaneous 3T MR-BrainPET: Methods and Technology

Building on the success of positron emission tomography (PET)/CT scanners, a hybrid imaging technology, combining PET with the versatile attributes of magnetic resonance imaging (MRI), has been in use for over ten years. At the Forschungszentrum Julich, one of the four prototypes available worldwide, combining a commercial 3T MRI with a newly developed BrainPET insert, was installed in 2008, allowing simultaneous data acquisition with PET and MRI. Here, we report on our ten-year-long experience of the methods and technology developed through this paper with numerous patients and volunteers. In the course of our research, a number of different radiotracers, such as [18F]Fluoroethyltyrosine, [11C]Flumazenil, [11C]Raclopride, and [15O]H2O, have been applied while simultaneously measuring several different MR sequences. The PET data obtained with the BrainPET has demonstrated higher image quality and superior resolution capability compared to the stand-alone PET scanner, ECAT Exact HR+. Furthermore, the simultaneous acquisition of MR images alongside BrainPET scans, using different sequences, showed an excellent quality without any relevant artifacts and provided useful complementary information. Our experiences with the hybrid 3T MR-BrainPET indicate a promising basis for further developments of this unique technique, allowing simultaneous brain imaging in a clinical setting.

High resolution reconstruction of PET images using the iterative OSEM algorithm

Improvement of the spatial resolution in positron emission tomography (PET) by incorporation of the image-forming characteristics of the scanner into the process of iterative image reconstruction. All measurements were performed at the whole-body PET system ECAT EXACT HR(+) in 3D mode. The acquired 3D sinograms were sorted into 2D sinograms by means of the Fourier rebinning (FORE) algorithm, which allows the usage of 2D algorithms for image reconstruction. The scanner characteristics were described by a spatially variant line-spread function (LSF), which was determined from activated copper-64 line sources. This information was used to model the physical degradation processes in PET measurements during the course of 2D image reconstruction with the iterative OSEM algorithm. To assess the performance of the high-resolution OSEM algorithm, phantom measurements performed at a cylinder phantom, the hotspot Jaszczack phantom, and the 3D Hoffmann brain phantom as well as different patient examinations were analyzed. Scanner characteristics could be described by a Gaussian-shaped LSF with a full-width at half-maximum increasing from 4.8 mm at the center to 5.5 mm at a radial distance of 10.5 cm. Incorporation of the LSF into the iteration formula resulted in a markedly improved resolution of 3.0 and 3.5 mm, respectively. The evaluation of phantom and patient studies showed that the high-resolution OSEM algorithm not only lead to a better contrast resolution in the reconstructed activity distributions but also to an improved accuracy in the quantification of activity concentrations in small structures without leading to an amplification of image noise or even the occurrence of image artifacts. The spatial and contrast resolution of PET scans can markedly be improved by the presented image restauration algorithm, which is of special interest for the examination of both patients with brain disorders and small animals.

Comparison of Template-Based Versus CT-Based Attenuation Correction for Hybrid MR/PET Scanners

Attenuation correction (AC) of cerebral PET data acquired in hybrid MR/PET scanners is still a challenge. To overcome this problem we previously proposed a correction method by obtaining template-based attenuation maps (AM) using MR and ECAT EXACT HR+ transmission scans. In the present study we investigated (a) the basic difference between template-based and CT-based AC methods and (b) their influence on reconstructed PET images. The data of 11 subjects undergoing $^{18}{\rm FDG}$ imaging in the Siemens 3T MR-BrainPET scanner were used. Additionally, from all participants a CT scan of the whole head was acquired at the same day. These CT images were transformed to CT-based AMs. They were filtered by a 3D Gaussian kernel with 3 mm (BrainPET resolution) filter width, which was considered as reference. Comparisons between both AMs (CT-based and template-based) were performed by estimating the Dice coefficients D and calculating the numbers of true positive, true negative and false negative voxels. The BrainPET emission data were reconstructed with both AMs ( ${\rm AM}_{{\rm CT}3{\rm mm}}$ and ${\rm AM}_{\rm Template}$ ). All reconstructed PET images were scaled to standardized uptake values (SUVs) and normalized to the MNI brain for using the AAL-VOI Atlas analysis. Correlation plots with regression equation, coefficients of determination ${{\rm R}^2}$ and relative differences (RD) between ${\rm AM}_{{\rm CT}3{\rm mm}}$ and the ${\rm AM}_{\rm Template}$ were derived. The fraction of the overall true positive voxels averaged over the 11 subjects was $80.4 \pm 7.5\% $ for ${\rm AM}_{\rm Template}$ compared to ${\rm AM}_{{\rm CT}3{\rm mm}}$ ( ${{\rm D}_{\rm bone}} = 0.63 \pm 0.08$ ; ${{\rm D}_{\rm soft - tissue}} = 0.85 \pm 0.08$ ; ${{\rm D}_{\rm air}} = 0.79 \pm 0.04$ ). A misclassification of bone as soft tissue and vice versa was evident in the comparison. The correlation plot of all VOIs considered (1,276 values) showed a mean ${{\rm R}^2}$ of 0.964 and a slope of 1.02. A mean RD of $1.33 \pm 0.95\%$ ( ${\min} = - 0.12\% $ , ${\max} = 2.85\% $ ) was found. The template-based AC method proposed by our group shows considerable differences in comparison to the higher resolution CT-based AM with respect to the Dice coefficients, in particular in the classification of bone and soft tissue. However, this has no major influence on the reconstructed $^{18}{\rm FDG}$ PET data.

First-in-human PET quantification study of cerebral α4β2* nicotinic acetylcholine receptors using the novel specific radioligand (−)-[18F]Flubatine

α4β2* nicotinic receptors (α4β2* nAChRs) could provide a biomarker in neuropsychiatric disorders (e.g., Alzheimer's and Parkinson's diseases, depressive disorders, and nicotine addiction). However, there is a lack of α4β2* nAChR specific PET radioligands with kinetics fast enough to enable quantification of nAChR within a reasonable time frame. Following on from promising preclinical results, the aim of the present study was to evaluate for the first time in humans the novel PET radioligand (−)-[18F]Flubatine, formerly known as (−)-[18F]NCFHEB, as a tool for α4β2* nAChR imaging and in vivo quantification.Dynamic PET emission recordings lasting 270min were acquired on an ECAT EXACT HR+ scanner in 12 healthy male non-smoking subjects (71.0±5.0years) following the intravenous injection of 353.7±9.4MBq of (−)-[18F]Flubatine. Individual magnetic resonance imaging (MRI) was performed for co-registration. PET frames were motion-corrected, before the kinetics in 29 brain regions were characterized using 1- and 2-tissue compartment models (1TCM, 2TCM). Given the low amounts of metabolite present in plasma, we tested arterial input functions with and without metabolite corrections. In addition, pixel-based graphical analysis (Logan plot) was used. The model's goodness of fit, with and without metabolite correction was assessed by Akaike's information criterion. Model parameters of interest were the total distribution volume VT (mL/cm3), and the binding potential BPND relative to the corpus callosum, which served as a reference region.The tracer proved to have high stability in vivo, with 90% of the plasma radioactivity remaining as untransformed parent compound at 90min, fast brain kinetics with rapid uptake and equilibration between free and receptor-bound tracer. Adequate fits of brain TACs were obtained with the 1TCM. VT could be reliably estimated within 90min for all regions investigated, and within 30min for low-binding regions such as the cerebral cortex.The rank order of VT by region corresponded well with the known distribution of α4β2* receptors (VT [thalamus] 27.4±3.8, VT [putamen] 12.7±0.9, VT [frontal cortex] 10.0±0.8, and VT [corpus callosum] 6.3±0.8). The BPND, which is a parameter of α4β2* nAChR availability, was 3.41±0.79 for the thalamus, 1.04±0.25 for the putamen and 0.61±0.23 for the frontal cortex, indicating high specific tracer binding. Use of the arterial input function without metabolite correction resulted in a 10% underestimation in VT, and was without important biasing effects on BPND.Altogether, kinetics and imaging properties of (−)-[18F]Flubatine appear favorable and suggest that (−)-[18F]Flubatine is a very suitable and clinically applicable PET tracer for in vivo imaging of α4β2* nAChRs in neuropsychiatric disorders.

Evaluation of PET quantification accuracy in vivo

SummaryQuantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans. Aim: We, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions. Patients, methods: We determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21; Siemens Biograph 16 PET/CT: n = 16; Philips Gemini-TF PET/CT: n = 19). Urine samples were collected immediately after scan. Activity concentration in the samples was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine sample) activity concentration ratio was determined. Results: Activity concentration in the bladder (PET) was systematically lower than in the urine samples (well The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively. Conclusions: The investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine samples with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.

Application of positron emission tomography with 18ffdg in combined diagnosis of anxiety and depressive disorders in elderly patients with chronic heart failure

35 patients with chronic cardiac failure of the third functional class and anxiety depressive disorders were examined. The screening group consisted of 35 patients with chronic cardiac insufficiency without affective disorders. Evaluation of the clinical state was carried out by echocardiography, 6 minute walk and estimation of therapy compliance. Severity of the symptoms of anxiety and depressive disorders were studied by MMPI test, Beck`s test, Hamilton`s scale, Spielberg scale. PET with 18FFDG was carried out on PET tomographs «EcatExact 47» and «Ecat Exact HR+» (Siemens, Germany). It was found that anxiety depressive disorders have negative effect on the clinical state and the therapy compliance in the patients with chronic cardiac failure. Significant correlation between the clinical data and the brain 18FFDG PET results was seen in most cases.

In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer’s disease patients

Imaging the 18-kDa translocator protein (TSPO) is considered a potential tool for in vivo evaluation of microglial activation and neuroinflammation in the early stages of Alzheimer's disease (AD). ((R)-1-(2-chlorophenyl)-N-[(11)C]-methyl-N-(1-methylpropyl)-3-isoquinoline caboxamide ([(11)C]-(R)-PK11195) has been widely used for PET imaging of TSPO and, despite its low specific-to-nondisplaceable binding ratio, increased TSPO binding has been shown in AD patients. The high-affinity radioligand N-(5-fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoroethyl-5-methoxybenzyl)acetamide ([(18)F]FEDAA1106) has been developed as a potential in vivo imaging tool for better quantification of TSPO binding. The aim of this study was to quantify in vivo binding of [(18)F]FEDAA1106 to TSPO in control subjects and AD patients. Seven controls (five men, two women, age 68±3 years, MMSE score 29±1) and nine AD patients (six men, three women, age 69±4 years, MMSE score 25±3) were studied with [(18)F]FEDAA1106. PET measurements were performed on an ECAT EXACT HR system (Siemens Medical Solutions) in two 60-min dynamic PET sessions with a 30-min interval between sessions. Arterial blood radioactivity was measured using an automated blood sampling system for the first 5 min and using manually drawn samples thereafter. Quantification was performed using both kinetic analysis based on a two-tissue compartment model and Logan graphical analysis. Outcome measures were total distribution volume (V T) and binding potential (BP(ND)=k3/k4). An estimate of nondisplaceable distribution volume was obtained with the Logan graphical analysis using the first 15 min of PET measurements (V(ND 1-15 min)). Binding potential (BP(ND)) was also calculated as: V(T)/V(ND 1-15 min) - 1. No statistically significant differences in V(T), k3/k4 or BP(ND) were observed between controls and AD patients. This study suggests that TSPO imaging with [(18)F]FEDAA1106 does not enable the detection of microglial activation in AD.

In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18F]FEDAA1106

BackgroundThe activation of microglia, in general, and the upregulation of the translocator protein (18 kDa) (TSPO) system, in particular, are key features of neuroinflammation, of which the in vivo visualization and quantitative assessment are still challenging due to the lack of appropriate molecular imaging biomarkers. Recent positron emission tomography (PET) studies using TSPO radioligands such as [11C]PK11195 and [11C]PBR28 have indicated the usefulness of these PET biomarkers in patients with neuroinflammatory diseases, including multiple sclerosis (MS). [18F]FEDAA1106 is a recently developed PET radioligand for the in vivo quantification of TSPO. In the present study, we aimed at investigating the diagnostic usefulness of [18F]FEDAA1106 in patients with MS.MethodsNine patients (three on the interferon beta therapy and six without immunomodulatory therapy; seven females/two males; age 34.2 ± 9.1 years old) with relapsing-remitting MS in acute relapse and with gadolinium (Gd)-enhancing lesion(s) in the magnetic resonance imaging (MRI) scans and five healthy controls (four females/one male, age 38.0 ± 9.7 years old) were investigated in this study. Genetic information about the TSPO binding could not be obtained because knowledge about the importance of genetic background for TSPO binding was not available at the time the study was performed. Dynamic PET measurements were performed using an ECAT EXACT HR system (CTI/Siemens, Knoxville, TN, USA) for a total of 150 min, with a 30-min break after the injection of 153.4 ± 10.2 MBq of [18F]FEDAA1106. Metabolite-corrected arterial plasma samples were used to calculate the input function. PET data were analyzed in the following ways: (1) region-of-interest analysis for cortical and subcortical regions was performed using a two-tissue compartment kinetic model in order to estimate binding potentials (BPND) and distribution volume (VT), (2) the feasibility of the estimation of BPND and VT was investigated for MS lesions, and (3) VT parametric images by a Logan plot and standard uptake value (SUV) images were visually compared with the corresponding MRI, focusing on MRI-identified MS lesions.ResultsThere were no significant differences in the BPND or VT values between patients with MS and healthy controls. Robust BPND and VT values could not be obtained for most MS lesions due to noisy time-activity curves. Visual inspection of VT and SUV images in all nine patients did not reveal high uptake of the radioligand inside and beyond MRI-identified active MS lesions with the exception of one Gd-enhanced MS lesion in the whole patient population.ConclusionsIn our study, [18F]FEDAA1106 as a PET radioligand could neither differentiate patients with MS from healthy controls nor detect active plaques in the brain of MS patients. Stratification with respect to genetics and binder status might help to uncover the differences between the groups, which could not be detected here.Trial registrationClinicalTrials.gov, NCT01031199

Improved mapping and quantification of serotonin transporter availability in the human brainstem with the HRRT

The serotonin system is involved in many physiological functions and clinical conditions. Serotonergic neurons originate from the raphe nuclei in the brainstem, and reliable estimates of receptor/transporter availability in the raphe in vivo are thus of interest. Though positron emission tomography (PET) can be used to quantify receptor distribution in the brain, high noise levels prevent reliable estimation of radioligand binding in small regions such as the raphe. For this purpose, parametric imaging in combination with high-resolution PET systems may provide images with reduced noise levels and sufficient contrast for reliable quantification. This study examined the potential to evaluate radioligand binding in brainstem nuclei, and assessed the effect of improved resolution on the outcome measures. For comparative purposes, radioligand binding was measured with an ECAT EXACT HR PET system (resolution about 4.5 mm FWHM) and a high-resolution research tomograph (HRRT) system (resolution about 1.5 mm FWHM). Six subjects were examined with both systems on the same day using the serotonin transporter radioligand [(11)C]MADAM. Parametric images of binding potential (BP (ND)) were obtained using a wavelet-aided approach. Regions of interest (ROIs) were delineated using a threshold-based semiautomatic delineation procedure for five brainstem structures. Regional BP (ND) values were estimated by applying the ROIs to the parametric images, and the percentage difference in BP (ND) between the systems was calculated. Signals for [(11)C]MADAM binding were obtained for all five brainstem structures. Overall, the HRRT provided 30-40 % higher BP (ND) values than the HR (p = 0.0017), independent of thresholds used in the ROI delineation procedure. The methodology used enabled the estimation of [(11)C]MADAM binding in the small nuclei of the brainstem. Differences in the BP (ND) values calculated using data from the two systems were mainly attributable to their differing resolutions. The estimated BP (ND) values provided lower across-subject variability than those previously obtained using compartment analysis. This procedure may therefore facilitate quantitative studies of receptor/transporter availability in the brainstem.

Quantitative accuracy of attenuation correction in the Philips Ingenuity TF whole-body PET/MR system: a direct comparison with transmission-based attenuation correction

ObjectiveEvaluation of the quantitative accuracy of MR-based attenuation correction (MRAC) in the Philips Ingenuity TF whole-body PET/MR.Materials and methodsIn 13 patients, PET emission data from the PET/MR were reconstructed using two different methods for attenuation correction. In the first reconstruction, the vendor-provided standard MRAC was used. In the second reconstruction, a coregistered transmission-based attenuation map from a second immediately preceding investigation with a stand-alone Siemens ECAT EXACT HR+ PET scanner was used (TRAC). The two attenuation maps were compared regarding occurrence of segmentation artifacts in the MRAC procedure. Standard uptake values (SUVs) of multiple VOIs (liver, cerebellum, hot focal structures at various locations in the trunk) were compared between both reconstructed data sets. Furthermore, a voxel-wise intensity correlation analysis of both data sets in the lung and trunk was performed.ResultsVOI averaged SUV differences between MRAC and TRAC were as follows (relative differences, mean ± standard deviation): (+12 ± 6) % cerebellum, (−4 ± 9) % liver, (−2 ± 11) % hot focal structures. The fitted slopes of the voxel-wise correlations in the lung and trunk were 0.87 ± 0.17 and 0.95 ± 0.10 with averaged adjusted R 2 values of 0.96 and 0.98, respectively. These figures include two instances with partially erroneous lung segmentation due to artifacts in the underlying MR images.ConclusionThe MR-based attenuation correction implemented on the Philips Ingenuity PET/MR provides reasonable quantitative accuracy. On average, deviations from TRAC-based results are small (on the order of 10 % or below) across the trunk, but due to interindividual variability of the segmentation quality, deviations of more than 20 % can occur. Future improvement of the segmentation quality would help to increase the quantitation accuracy further and to reduce the inter-subject variability.

Effect of MR contrast agents on quantitative accuracy of PET in combined whole-body PET/MR imaging

Clinical PET/MR acquisition protocols entail the use of MR contrast agents (MRCA) that could potentially affect PET quantification following MR-based attenuation correction (AC). We assessed the effect of oral and intravenous (IV) MRCA on PET quantification in PET/MR imaging. We employed two MRCA: Lumirem (oral) and Gadovist (IV). First, we determined their reference PET attenuation values using a PET transmission scan (ECAT-EXACT HR+, Siemens) and a CT scan (PET/CT Biograph 16 HI-REZ, Siemens). Second, we evaluated the attenuation of PET signals in the presence of MRCA. Phantoms were filled with clinically relevant concentrations of MRCA in a background of water and (18)F-fluoride, and imaged using a PET/CT scanner (Biograph 16 HI-REZ, Siemens) and a PET/MR scanner (Biograph mMR, Siemens). Third, we investigated the effect of clinically relevant volumes of MRCA on MR-based AC using human pilot data: a patient study employing Gadovist (IV) and a volunteer study employing two different oral MRCA (Lumirem and pineapple juice). MR-based attenuation maps were calculated following Dixon-based fat-water segmentation and an external atlas-based and pattern recognition (AT&PR) algorithm. IV and oral MRCA in clinically relevant concentrations were found to have PET attenuation values similar to those of water. The phantom experiments showed that under clinical conditions IV and oral MRCA did not yield additional attenuation of PET emission signals. Patient scans showed that PET attenuation maps are not biased after the administration of IV MRCA but may be biased, however, after ingestion of iron oxide-based oral MRCA when segmentation-based AC algorithms are used. Alternative AC algorithms, such as AT&PR, or alternative oral contrast agents, such as pineapple juice, can yield unbiased attenuation maps. In clinical PET/MR scenarios MRCA are not expected to lead to markedly increased attenuation of the PET emission signals. MR-based attenuation maps may be biased by oral iron oxide-based MRCA unless advanced AC algorithms are used.

Development of a High-Sensitivity Radiation Detector for Chromatography

We describe a radiotracer imaging system for measuring the biochemical production rates of organic compounds from animals or plants. It uses a high performance liquid chromatography (HPLC) column to separate the compounds and a parallel-plane radiation detector to measure the disintegrations from each compound over a period of time. Because the measurement time is much longer than conventional techniques, the sensitivity is greatly improved. This high-sensitivity radiation detector can be used to image radioactivity in the HPLC flow cell or column and can be used for a variety of analytical HPLC applications. The detector is comprised of 8 Siemens ECAT EXACT HR+ PET detector modules arranged into a parallel plane and read out with modified Siemens ECAT HRRT electronics. This high-sensitivity radiation detector was placed in line after a conventional HPLC radiation detector (a small CsI:Tl scintillator crystal coupled to a PIN photodiode) to allow a direct comparison. If we inject 9.3 μCi of [ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F]FDG into the system, we see consistently shaped peaks with an excellent signal-to-noise ratio from both radiation detectors. If we inject only 5.4 nCi of [ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F]FDG, we measure a signal-to-noise ratio of 28:1 with the high-sensitivity radiation detector and 5:1 with the conventional radiation detector. We have therefore achieved a sensitivity gain of 32 at low radioactivity concentrations using our high-sensitivity radiation detector compared to a conventional radiation detector. We believe that a high-sensitivity radiation detector, using parallel-plane PET detector modules, could become an important tool for analytical HPLC research.

Suitability of bilateral filtering for edge-preserving noise reduction in PET

BackgroundTo achieve an acceptable signal-to-noise ratio (SNR) in PET images, smoothing filters (SF) are usually employed during or after image reconstruction preventing utilisation of the full intrinsic resolution of the respective scanner. Quite generally Gaussian-shaped moving average filters (MAF) are used for this purpose. A potential alternative to MAF is the group of so-called bilateral filters (BF) which provide a combination of noise reduction and edge preservation thus minimising resolution deterioration of the images. We have investigated the performance of this filter type with respect to improvement of SNR, influence on spatial resolution and for derivation of SUVmax values in target structures of varying size.MethodsData of ten patients with head and neck cancer were evaluated. The patients had been investigated by routine whole body scans (ECAT EXACT HR+, Siemens, Erlangen). Tomographic images were reconstructed (OSEM 6i/16s) using a Gaussian filter (full width half maximum (FWHM): Γ0 = 4 mm). Image data were then post-processed with a Gaussian MAF (FWHM: ΓM = 7 mm) and a Gaussian BF (spatial domain: ΓS = 9 mm, intensity domain: ΓI = 2.5 SUV), respectively. Images were assessed regarding SNR as well as spatial resolution. Thirty-four lesions (volumes of about 1-100 mL) were analysed with respect to their SUVmax values in the original as well as in the MAF and BF filtered images.ResultsWith the chosen filter parameters both filters improved SNR approximately by a factor of two in comparison to the original data. Spatial resolution was significantly better in the BF-filtered images in comparison to MAF (MAF: 9.5 mm, BF: 6.8 mm). In MAF-filtered data, the SUVmax was lower by 24.1 ± 9.9% compared to the original data and showed a strong size dependency. In the BF-filtered data, the SUVmax was lower by 4.6 ± 3.7% and no size effects were observed.ConclusionBilateral filtering allows to increase the SNR of PET image data while preserving spatial resolution and preventing smoothing-induced underestimation of SUVmax values in small lesions. Bilateral filtering seems a promising and superior alternative to standard smoothing filters.

Positron emission tomography inter-scanner differences in dopamine D2 receptor binding measured with [11C]FLB457

It is well known that the positron emission tomography (PET) system is subject to inter-scanner differences of regional radioactivity distribution. In the present study, the effect of inter-scanner difference of regional radioactivity on estimated binding potential (BP(ND)) of [¹¹C]FLB457 using the simplified reference tissue model (SRTM) was investigated. Each of the 11 subjects was given two PET scans using [¹¹C]FLB457, one each with both SET-3000 GCT/X (Shimadzu) and with ECAT EXACT HR+ (Siemens/CTI). In order to assess regional differences between the two scanners, estimated BP(ND) values in six volumes of interest (VOIs) by SRTM method were compared in both individual PET space and anatomical template space after anatomical normalization. Statistical voxel-by-voxel paired t test of BP(ND) images between SET-3000 GCT/X and ECAT EXACT HR+ was also performed. Shapes of time-activity curves of the two PET scanners were slightly different in each VOI, with estimated BP(ND) values from ECAT EXACT HR+ appearing greater in the cerebral cortical regions and thalamus than that of SET-3000 GCT/X in both individual PET space and anatomical template space after anatomical normalization. Statistical voxel-by-voxel analysis showed similar tendency to BP(ND) value estimation, with greater BP(ND) values from ECAT EXACT HR+ than from SET-3000 GCT/X. We demonstrated the inter-scanner differences in dopamine D(2) receptor binding measured with [¹¹C]FLB457. In particular, statistically significant differences of BP(ND) in certain regions were observed between two PET scanners, despite the subject groups being the same. Our results suggest that we reconsider the effect of the scanner model on the measurement of receptor binding.

Striatal and Extrastriatal Dopamine D 2/D 3 Receptors in Schizophrenia Evaluated With [ 18F]fallypride Positron Emission Tomography

Alterations in dopamine D(2)/D(3) receptor binding have been reported in schizophrenia, and a meta-analysis of imaging studies has shown a modest elevation in striatum. Newer radioligands now allow the assessment of these receptors in extrastriatal regions. We used positron emission tomography with [(18)F]fallypride to evaluate D(2)/D(3) receptors in both striatal and extrastriatal regions in schizophrenia. Twenty-one patients with schizophrenia and 22 matched healthy control subjects were scanned with an ECAT EXACT HR+ camera. Two-tissue compartment modeling and the reference tissue method gave binding potentials relative to nondisplaceable uptake, total plasma concentration, and free plasma concentration. These were compared between groups in five striatal and eight extrastriatal regions. Several regional volumes were lower in the patient group, and positron emission tomography data were corrected for partial volume effects. Binding potential values differed in three regions between groups. Values for binding potential relative to nondisplaceable uptake from two-tissue compartment modeling in patients and control subjects, respectively, were 28.7 ± 6.8 and 25.3 ± 4.3 in postcommissural caudate, 2.9 ± .7 and 2.6 ± .4 in thalamus, and 1.8 ± .5 and 2.1 ± .7 in uncus. Loss of D(2)/D(3) receptors with age was found in striatal and extrastriatal regions and was greater in neocortex. Our study found selective alterations in D(2)/D(3) receptors in striatal and extrastriatal regions, consistent with some but not all previously published reports. As previously shown for the striatum, a more sensitive imaging approach for studying the role of dopamine in the pathophysiology of schizophrenia might be assessment of neurotransmitter levels rather than D(2)/D(3) receptor levels in extrastriatal regions.

OncoPET_DB: A Freely Distributed Database of Realistic Simulated Whole Body 18F-FDG PET Images for Oncology

The purpose of this paper is to generate and distribute a database of simulated whole body 18F-FDG positron emission tomography (PET) oncology images. As far as we know, this database is the first addressing the need for simulated 18F-FDG PET oncology images by providing a series of realistic whole-body patient images with well-controlled inserted lesions of calibrated uptakes. It also fulfills the requirements of detection performance studies by including normal and pathological cases. The originality of the database is based on three points. First, we built a complex model of 18F-FDG patient based on the Zubal phantom in combination with activity distributions in the main organs of interest derived from a series of 70 clinical cases. Secondly, we proposed a model of lesions extent corresponding to real lymphoma patients. The lesion contrast levels were derived from a human observer detection study so as to cover the entire range of detectability. Lastly, the simulated database was generated with the PET-SORTEO Monte Carlo simulation tool that was fully validated against the geometry of the ECAT EXACT HR+ (CTI/Siemens Knoxville). The oncoPET_DB database is composed of 100 whole-body PET simulated images, including 50 normal cases coming from different realizations of noise of the healthy model and 50 pathological cases including lesions of calibrated uptakes and various diameters. Such a database will be useful to evaluate algorithms that may impact quantification or contrast recovery, to perform observer studies or to assess computer-aided diagnosis methods. Perspectives include enriching the present database with new pathological and normal cases accounting for interindividual variability of anatomy and FDG uptake.