Image derived input functions for dynamic High Resolution Research Tomograph PET brain studies
TL;DR: The results of this study indicate that the use of IDIFs, extracted from 3D ordinary Poisson ordered subsets expectation maximization and PVC OP-OSEM images, is feasible for dynamic HRRT data, thereby obviating the need for online arterial sampling.
About: This article is published in NeuroImage.The article was published on 2008-12-01. It has received 42 citations till now.
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TL;DR: The aim of the present review was to identify the methodological problems that hinder widespread use of IDIF in PET brain studies and conclude that IDIF can be successfully implemented only with a minority of PET tracers.
Abstract: Quantitative positron emission tomography (PET) brain studies often require that the input function be measured, typically via arterial cannulation. Image-derived input function (IDIF) is an elegant and attractive noninvasive alternative to arterial sampling. However, IDIF is also a very challenging technique associated with several problems that must be overcome before it can be successfully implemented in clinical practice. As a result, IDIF is rarely used as a tool to reduce invasiveness in patients. The aim of the present review was to identify the methodological problems that hinder widespread use of IDIF in PET brain studies. We conclude that IDIF can be successfully implemented only with a minority of PET tracers. Even in those cases, it only rarely translates into a less-invasive procedure for the patient. Finally, we discuss some possible alternative methods for obtaining less-invasive input function.
179 citations
TL;DR: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.
Abstract: After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Julich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. Material, methods: The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. Results: Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. Discussion, conclusion: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.
143 citations
TL;DR: Eight methods for the estimation of the image-derived input function (IDIF) in [18F]-FDG positron emission tomography (PET) dynamic brain studies were compared, and only one of the methods allowed a reliable calculation of the individual rate constants.
Abstract: The aim of this study was to compare eight methods for the estimation of the image-derived input function (IDIF) in [(18)F]-FDG positron emission tomography (PET) dynamic brain studies. The methods were tested on two digital phantoms and on four healthy volunteers. Image-derived input functions obtained with each method were compared with the reference input functions, that is, the activity in the carotid labels of the phantoms and arterial blood samples for the volunteers, in terms of visual inspection, areas under the curve, cerebral metabolic rates of glucose (CMRglc), and individual rate constants. Blood-sample-free methods provided less reliable results as compared with those obtained using the methods that require the use of blood samples. For some of the blood-sample-free methods, CMRglc estimations considerably improved when the IDIF was calibrated with a single blood sample. Only one of the methods tested in this study, and only in phantom studies, allowed a reliable calculation of the individual rate constants. For the estimation of CMRglc values using an IDIF in [(18)F]-FDG PET brain studies, a reliable absolute blood-sample-free procedure is not available yet.
91 citations
TL;DR: Correctly obtained, carotid and femoral artery IDIFs can be used as a substitute for AIFs to perform tracer kinetic modelling in skeletal femoral muscles and brain analyses.
Abstract: Purpose
Despite current advances in PET/CT systems, blood sampling still remains the standard method to obtain the radiotracer input function for tracer kinetic modelling. The purpose of this study was to validate the use of image-derived input functions (IDIF) of the carotid and femoral arteries to measure the arterial input function (AIF) in PET imaging. The data were obtained from two different research studies, one using 18F-FDG for brain imaging and the other using 11C-acetate and 18F-fluoro-6-thioheptadecanoic acid (18F-FTHA) in femoral muscles.
84 citations
Cites background from "Image derived input functions for d..."
...Correction for spill-in was not necessary as the carotid ROIs are located outside of the skull where they are not contaminated by radioactivity from the brain [23]....
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...Now that most human PET/CTscanners can achieve a spatial resolution <5mm, IDIF analysis can be considered for large blood vessels such as the femoral or the carotid arteries [23]....
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TL;DR: Higher values of pharmacokinetic parameter values, obtained from HRRT versus HR+ PET studies, indicate improved HRRT PET quantification primarily due to a reduction in partial-volume effects.
Abstract: The high-resolution research tomograph (HRRT) is a dedicated human brain PET scanner. The purpose of this study was to compare the quantitative accuracy of the HRRT with that of the clinical HR+ PET scanner and to assess effects of differences in spatial resolution between both scanners (∼2.7 mm and ∼7.0 mm for HRRT and HR+, respectively). Methods: Paired 11C-flumazenil scans of 7 healthy volunteers were assessed. For each volunteer, dynamic scans (including arterial sampling) were acquired on both scanners on the same day, thereby minimizing intersubject variability. Volume of distribution was generated using Logan plot analysis with plasma input. In addition, other plasma input, reference tissue (with pons as the reference tissue input), and parametric methods were included in the interscanner comparison. Results: Logan volume-of-distribution analysis of HRRT data showed higher values than that of HR+ data (slope with the intercept fixed at the origin of 1.14 ± 0.10 to 1.19 ± 0.10, depending on the HRRT reconstruction method used). Smoothing HRRT reconstructions with a 6-mm full width at half maximum gaussian kernel reduced this slope toward the line of identity (1.04 ± 0.11 to 1.07 ± 0.11), retaining good correlation between HR+ and HRRT data (r, ∼0.98). Similar trends were observed for other plasma input, reference tissue, and parametric methods. However, after reference matching the reference tissue models showed lower HRRT kinetic parameter values than HR+ values (slope with fixed intercept, 0.90 ± 0.10 to 0.94 ± 0.13). Conclusion: Higher values of pharmacokinetic parameter values, obtained from HRRT versus HR+ PET studies, indicate improved HRRT PET quantification primarily due to a reduction in partial-volume effects.
66 citations
Cites background from "Image derived input functions for d..."
..., because of imperfections in the attenuation correction (15), scatter correction (11,34), or reconstruction (11,20,21,23,24) algorithms)....
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References
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TL;DR: The reference tissue model allows for quantification of receptor kinetics without measuring the arterial input function, thus avoiding arterial cannulation and time-consuming metabolite measurements, and for the ligands tested the three-parameter model is a better choice, combining increased convergence rate with increased stability.
1,962 citations
"Image derived input functions for d..." refers background in this paper
...Tracer kinetic modelling also requires measurements of the time rights reserved. course of the tracer in plasma, unless a reference tissue (Lammertsma and Hume,1996; Lammertsma et al., 1996) can be found inwhich nonspecific tracer uptake is identical to that in the tissue of interest....
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TL;DR: This basis function method (BFM) is compared with conventional nonlinear least squares estimation of parameters (NLM) and is shown to be more stable than NLM at the voxel level and is computationally much faster.
1,056 citations
"Image derived input functions for d..." refers methods in this paper
...Finally, VT and K1 images were generated using a basis function method (BFM) (Gunn et al., 1997; Boellaard et al., 2005) based on the single tissue compartment model....
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Journal Article•
TL;DR: The poor accuracy of the SUV under various conditions may hamper its use for diagnosis, especially in multicenter trials, and it might be more suitable for response-monitoring purposes.
Abstract: Semiquantitative standard uptake values (SUVs) are used for tumor diagnosis and response monitoring. However, the accuracy of the SUV and the accuracy of relative change during treatment are not well documented. Therefore, an experimental and simulation study was performed to determine the effects of noise, image resolution, and region-of-interest (ROI) definition on the accuracy of SUVs. Methods: Experiments and simulations are based on thorax phantoms with tumors of 10-, 15-, 20-, and 30-mm diameter and background ratios (TBRs) of 2, 4, and 8. For the simulation study, sinograms were generated by forward projection of the phantoms. For each phantom, 50 sinograms were generated at 3 noise levels. All sinograms were reconstructed using ordered-subset expectation maximization (OSEM) with 2 iterations and 16 subsets, with or without a 6-mm gaussian filter. For each tumor, the maximum pixel value and the average of a 50%, a 70%, and an adaptive isocontour threshold ROI were derived as well as with an ROI of 15 x 15 mm. The accuracy of SUVs was assessed using the average of 50 ROI values. Treatment response was simulated by varying the tumor size or the TBR. Results: For all situations, a strong correlation was found between maximum and isocontour-based ROI values resulting in similar dependencies on image resolution and noise of all studied SUV measures. A strong variation with tumor size of ≥50% was found for all SUV values. For non-smoothed data with high noise levels this variation was primarily due to noise, whereas for smoothed data with low noise levels partial-volume effects were most important. In general, SUVs showed under- and overestimations of ≥50% and depended on all parameters studied. However, SUV ratios, used for response monitoring, were only slightly dependent of ROI definition but were still affected by noise and resolution. Conclusion: The poor accuracy of the SUV under various conditions may hamper its use for diagnosis, especially in multicenter trials. SUV ratios used to measure response to treatment, however, are less dependent on noise, image resolution, and ROI definition. Therefore, the SUV might be more suitable for response-monitoring purposes.
643 citations
"Image derived input functions for d..." refers background or methods in this paper
...This was previously observed using both simulations and phantom studies (Boellaard et al., 2004)....
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...The observed overestimation of recovery could be expected as a result of noise, especially in large objects, as shownpreviously (Boellaard et al., 2004)....
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Journal Article•
TL;DR: The ECAT EXACT HR+ has an excellent, nearly isotropic spatial resolution, which is advantageous for brain and small animal studies, and offers a sufficient sensitivity and count rate capacity for fully three-dimensional whole-body imaging.
Abstract: This study evaluates the performance of the newly developed high-resolution whole-body PET scanner ECAT EXACT HR+. Methods: The scanner consists of four rings of 72 bismuth germanate block detectors each, covering an axial field of view of 15.5 cm with a patient port of 56.2 cm. A single block detector is divided into an 8 × 8 matrix, giving a total of 32 rings with 576 detectors each. The dimensions of a single detector element are 4.39 × 4.05 × 30 mm3. The scanner is equipped with extendable tungsten septa for two-dimensional two-dimensional measurements, as well as with three 68Ge line sources for transmission scans and daily quality control. The spatial resolution, scatter fraction, count rate, sensitivity, uniformity and accuracy of the implemented correction algorithms were evaluated after the National Electrical Manufacturers Association protocol using the standard acquisition parameters. Results: The transaxial resolution in the two-dimensional mode is 4.3 mm (4.4 mm) in the center and increases to 4.7 mm (4.8 mm) tangential and to 8.3 mm (8.0 mm) radial at a distance of r = 20 cm from the center. The axial slice width measured in the two-dimensional mode varies between 4.2 and 6.6 mm FWHM over the transaxial field of view. In the three-dimensional mode the average axial resolution varies between 4.1 mm FWHM in the center and 7.8 mm at r = 20 cm. The scatter fraction is 17.1% (32.5%) for a lower energy discriminator level of 350 keV. The maximum true event count rate of 263 (345) kcps was measured at an activity concentration of 142 (26.9) kBq/ml. The total system sensitivity for true events is 5.7 (27.7) cps/Bq/ml. From the uniformity measurements, we obtained a volume variance of 3.9% (5.0%) and a system variance of 1.6% (1.7%). The implemented three-dimensional scatter correction algorithm reveals very favorable properties, whereas the three-dimensional attenuation correction yields slightly inaccurate results in low-and high-density regions. Conclusion: The ECAT EXACT HR+ has an excellent, nearly isotropie spatial resolution, which is advantageous for brain and small animal studies. While the relatively low slice sensitivity may hamper the capability for performing fast dynamic two-dimensional studies, the scanner offers a sufficient sensitivity and count rate capacity for fully three-dimensional whole-body imaging.
514 citations
"Image derived input functions for d..." refers background or methods in this paper
...As the scatter gives a larger contribution to the HRRT (∼45%, de Jong et al., 2007) compared to the HR+ (∼33%, 3D mode, Brix et al., 1997), it requires an even more accurate scatter correction....
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...The spatial resolution of the HRRT is between 2.3 and 3.4 mm full width at half maximum (FWHM), which is higher than that of standardwhole-body PET scanners, such as the ECAT EXACT HR+ (CTI/Siemens, Knoxville, TN, USA) scanner (4.1 to 7.8 mm FWHM in 3D mode; Brix et al., 1997)....
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TL;DR: The reference tissue model provided estimates of the binding potential with the same sensitivity for detecting changes as those methods that required a metabolite-corrected plasma input function, indicating that for routine analysis of clinical [11C]raclopride studies, no arterial cannulation is required.
Abstract: Five different methods for the estimation of the binding potential, a measure of Bmax/Kd, of [11C]raclopride in human striatum were compared using data from a dose ranging study of the neuroleptic CP-88,059-01. Binding potential was estimated indirectly, from distribution volumes in striatum and cerebellum, using both single- and two-tissue compartment models with a metabolite-corrected plasma curve as input function. The two-tissue compartment model was also used for a direct estimate of the binding potential. In addition, a direct estimate was obtained from the reference tissue compartment model using the cerebellum as indirect input function. Finally, an estimate of binding potential was calculated from the ratio of striatum over cerebellum counts at late times after injection. The estimates of striatum binding potential from all methods, except the direct determination using a two-tissue compartment model with metabolite-corrected plasma input function, correlated with each other. Use of an average metabolite correction resulted in only a small reduction in accuracy in this series of normal subjects. The reference tissue model provided estimates of the binding potential with the same sensitivity for detecting changes as those methods that required a metabolite-corrected plasma input function. This indicates that for routine analysis of clinical [11C]raclopride studies, no arterial cannulation is required. The range of normal values was significantly less variable with the reference tissue method than when simple striatum-to-cerebellum ratios were used.
477 citations
"Image derived input functions for d..." refers background in this paper
...Tracer kinetic modelling also requires measurements of the time rights reserved. course of the tracer in plasma, unless a reference tissue (Lammertsma and Hume,1996; Lammertsma et al., 1996) can be found inwhich nonspecific tracer uptake is identical to that in the tissue of interest....
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...course of the tracer in plasma, unless a reference tissue (Lammertsma and Hume,1996; Lammertsma et al., 1996) can be found inwhich nonspecific tracer uptake is identical to that in the tissue of interest....
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