Issues in quantification of cardiac PET studies.
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Algorithms↗
Biomedical subjects
Mark Lubberink
Publications and source records attributed to Mark Lubberink.
Quantification of dopamine transporter binding using [18F]FP-beta-CIT and positron emission tomography.
The purpose of this study was to compare different kinetic and semi-quantitative methods for analysing human [18F]FP-beta-CIT studies: plasma input models, simplified (SRTM) and full (FRTM) reference tissue models, standard uptake values (SUV) and SUV ratios (SUVr). Both simulations and clinical evaluations were performed to determine the effects of noise, scan duration and blood volume on Akaike model selection, and on precision and accuracy of estimated parameters. For typical noise levels (COV approximately 2.5%) and scan durations (<90 mins), simulations provided poor fits (Akaike criterion) in case of reversible plasma input models showing a relatively high number of outliers compared with the two-tissue irreversible model. Reference tissue models provided more reliable fits, which were nearly independent of noise and scan duration. For clinical data, two tissue irreversible and reversible plasma input models fitted striatum curves equally well (Akaike criterion). BP with plasma input models were less precise and contained more outliers than BP obtained with SRTM or FRTM. Among all methods tested, SRTM showed the highest contrast between patients and controls. When differentiating between patients and controls, SUVr performed almost equally well as SRTM, although contrast between striatum and background was lower. In conclusion, SRTM provided BP estimates with the highest precision and accuracy. Moreover, SRTM provided good contrast between patients and controls, and between striatum and background. SRTM is therefore the method of choice for quantitative [18F]FP-beta-CIT studies. SUVr might be an alternative for larger clinical trials.
Aged↗
Evaluation of tracer kinetic models for quantification of P-glycoprotein function using (R)-[11C]verapamil and PET.
Diminished P-glycoprotein (P-gp)-mediated transport across the blood-brain barrier may play an important role in several neurodegenerative disorders. In previous studies, a racemic mixture of (R)-[(11)C]verapamil and (S)-[(11)C]verapamil has been used as tracer for assessing P-gp function using positron emission tomography (PET). Quantification, however, is compromised by potential differences in kinetics between these two isomers. The aim of the present study was to evaluate the kinetics of pure (R)-[(11)C]verapamil in humans and to develop a tracer kinetic model for the analysis of P-gp-mediated transport of (R)-[(11)C]verapamil, including the putative contribution of its radioactive metabolites. Dynamic (R)-[(11)C]verapamil PET scans of 10 male volunteers were analysed with various single- or two-tissue compartment models, with separate compartments for N-dealkylated and N-demethylated metabolites, assuming that either (R)-[(11)C]verapamil alone or (R)-[(11)C]verapamil and any combination of metabolites cross the BBB. In addition, six of the subjects underwent two (R)-[(11)C]verapamil scans to evaluate test-retest reliability. One hour after injection, 50% of total plasma radioactivity consisted of labelled metabolites. Most models fitted the data well and the analysis did not point to a definite 'best' model, with differences in optimal model between subjects. The lowest mean test-retest variability (2.9%) was found for a single-tissue model without any metabolite correction. Models with separate metabolite compartments lead to high test-retest variability. Assuming that differences in kinetics of (R)-[(11)C]verapamil and N-dealkylated metabolites are small, a one input, one-tissue model with correction for N-demethylated metabolites only leads to a good compromise between fit quality and test-retest variability.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[(11)C]verapamil and positron emission tomography.
INTRODUCTION: P-glycoprotein (P-gp) is an efflux transporter responsible for the transport of various drugs across the blood-brain barrier (BBB). Loss of P-gp function with age may be one factor in the development and progression of neurodegenerative diseases. The aim of this study was to assess the effect of aging on BBB P-gp function. Furthermore, the relationship between BBB P-gp activity and peripheral P-gp activity in CD3-positive leukocytes was investigated. Finally, plasma pharmacokinetics of carbon 11-labeled (R)-verapamil was evaluated. METHODS: (R)-[(11)C]verapamil and positron emission tomography were used to assess gray matter P-gp function. Because (R)-[(11)C]verapamil is a substrate for P-gp, the volume of distribution of (R)-[(11)C]verapamil in the brain inversely reflects P-gp function in the BBB. RESULTS: Mean volume of distribution values for 5 young healthy volunteers (age range, 21-27 years) and 5 elderly healthy volunteers (age range, 59-68 years) were 0.62+/-0.10 and 0.73+/-0.07, respectively (P=.03). The activity index of P-gp activity in CD3-positive leukocytes was 2.88+/-0.77 in young volunteers and 1.76+/-0.58 in elderly volunteers (P=.02). CONCLUSION: This study showed decreased P-gp activity during aging. Consequently, the brain may be exposed to higher drug and toxin levels in elderly subjects.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Acquisition settings for PET of 124I administered simultaneously with therapeutic amounts of 131I.
UNLABELLED: Radiation dosimetry of thyroid cancer therapy with 131I can be performed by coadministration of 124I followed by longitudinal PET scans over several days. The photons emitted by 131I may affect PET image quality. The aim of this study was to assess the influence of large amounts of 131I on PET image quality and accuracy with various acquisition settings. METHODS: Noise equivalent count (NEC) rates of 124I only were measured with a standard clinical PET scanner. Apart from the standard 350- to 650-keV energy window, 425- to 650-keV and 460- to 562-keV windows were used and data were acquired both with (2-dimensional) and without (3-dimensional [3D]) septa. A phantom containing 6 hot spheres, filled with a combination of 131I and 124I and with a sphere-to-background ratio of 18:1, was scanned repeatedly with energy window settings as indicated and emission and transmission scan durations of 7 and 3 min, respectively. NEC rates were calculated and compared with those measured with the phantom filled with only 124I. Sphere-to-background ratios in the reconstructed images were determined. One patient with known metastatic thyroid cancer was scanned using energy window settings and scan times as indicated 3 and 6 d after administration of 5.5 GBq of 131I and 75 MBq of 124I. RESULTS: The highest 124I-only NEC rates were obtained using a 425- to 650-keV energy window in 3D mode. In the presence of (131)I, the settings giving the highest NEC rate and contrast were 425-650 keV and 460-562 keV in 3D mode, with the clinical scans giving the highest quality images with the same settings. CONCLUSION: Acquisition in 3D mode with a 425- to 650-keV or 460- to 562-keV window leads to the highest image quality and contrast when imaging 124I in the presence of large amounts of 131I using a standard clinical PET scanner.
Aged↗
Non-isotropic noise correlation in PET data reconstructed by FBP but not by OSEM demonstrated using auto-correlation function.
BACKGROUND: Positron emission tomography (PET) is a powerful imaging technique with the potential of obtaining functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules in a biological system, both in vitro and in vivo. PET images can be used directly or after kinetic modelling to extract quantitative values of a desired physiological, biochemical or pharmacological entity. Because such images are generally noisy, it is essential to understand how noise affects the derived quantitative values. A pre-requisite for this understanding is that the properties of noise such as variance (magnitude) and texture (correlation) are known. METHODS: In this paper we explored the pattern of noise correlation in experimentally generated PET images, with emphasis on the angular dependence of correlation, using the autocorrelation function (ACF). Experimental PET data were acquired in 2D and 3D acquisition mode and reconstructed by analytical filtered back projection (FBP) and iterative ordered subsets expectation maximisation (OSEM) methods. The 3D data was rebinned to a 2D dataset using FOurier REbinning (FORE) followed by 2D reconstruction using either FBP or OSEM. In synthetic images we compared the ACF results with those from covariance matrix. The results were illustrated as 1D profiles and also visualized as 2D ACF images. RESULTS: We found that the autocorrelation images from PET data obtained after FBP were not fully rotationally symmetric or isotropic if the object deviated from a uniform cylindrical radioactivity distribution. In contrast, similar autocorrelation images obtained after OSEM reconstruction were isotropic even when the phantom was not circular. Simulations indicated that the noise autocorrelation is non-isotropic in images created by FBP when the level of noise in projections is angularly variable. Comparison between 1D cross profiles on autocorrelation images obtained by FBP reconstruction and covariance matrices produced almost identical results in a simulation study. CONCLUSION: With asymmetric radioactivity distribution in PET, reconstruction using FBP, in contrast to OSEM, generates images in which the noise correlation is non-isotropic when the noise magnitude is angular dependent, such as in objects with asymmetric radioactivity distribution. In this respect, iterative reconstruction is superior since it creates isotropic noise correlations in the images.
Journal Article↗
Performance of coincidence imaging with long-lived positron emitters as an alternative to dedicated PET and SPECT.
An important application of quantitative imaging in nuclear medicine is the estimation of absorbed doses in radionuclide therapy. Depending on the radionuclide used for therapy, quantitative imaging of the kinetics of the therapeutic radiopharmaceutical could be done using planar imaging, SPECT or PET. Since many nuclear medicine departments have a gamma camera system that is also suitable for coincidence imaging, the performance of these systems with respect to quantitative imaging of PET isotopes that could be of use in radionuclide dosimetry is of interest. We investigated the performance of a gamma camera with coincidence imaging capabilities with 99mTc, 111In, 18F and 76Br and a dedicated PET system with 18F and 76Br, using a single standard set of phantom measurements. Here, 76Br was taken as a typical example of prompt gamma-emitting PET isotopes that are applicable in radionuclide therapy dosimetry such as 86Y and 124I. Image quality measurements show comparable image contrasts for 76Br coincidence imaging and 111In SPECT. Although the spatial resolution of coincidence imaging is better than single photon imaging, the contrast obtained with 76Br is not better than that with 99mTc or 111In because of the prompt gamma involved. Additional improvements are necessary to allow for quantitative coincidence imaging of long-lived, prompt gamma producing positron emitters.
Algorithms↗
Non-stationary convolution subtraction scatter correction with a dual-exponential scatter kernel for the Hamamatsu SHR-7700 animal PET scanner.
A spatially variant convolution subtraction scatter correction was developed for a Hamamatsu SHR-7700 animal PET scanner. This scanner, with retractable septa and a gantry that can be tilted 90 degrees, was designed for studies of conscious monkeys. The implemented dual-exponential scatter kernel takes into account both radiation scattered inside the object and radiation scattered in gantry and detectors. This is necessary because of the relatively large contribution of gantry and detector scatter in this scanner. The correction is used for scatter correction of emission as well as transmission data. Transmission scatter correction using the dual-exponential kernel leads to a measured attenuation coefficient of 0.096 cm(-1) in water, compared to 0.089 cm(-1) without scatter correction. Scatter correction on both emission and transmission data resulted in a residual correction error of 2.1% in water, as well as improved image contrast and hot spot quantification.
Animals↗
Quantitative comparison of analytic and iterative reconstruction methods in 2- and 3-dimensional dynamic cardiac 18F-FDG PET.
UNLABELLED: The aim of this work was to compare the quantitative accuracy of iteratively reconstructed cardiac (18)F-FDG PET with that of filtered backprojection for both 2-dimensional (2D) and 3-dimensional (3D) acquisitions and to establish an optimal procedure for imaging myocardial viability with (18)F-FDG PET. METHODS: Eight patients underwent dynamic cardiac (18)F-FDG PET using an interleaved 2D/3D scan protocol, enabling comparison of 2D and 3D acquisitions within the same patient and study. A 10-min transmission scan was followed by a 10-min, 25-frame dynamic 3D scan and then by a series of 10 alternating 5-min 3D and 2D scans. Images were reconstructed with filtered backprojection (FBP) or attenuation-weighted ordered-subsets expectation maximization (OSEM), combined with Fourier rebinning (FORE) for 3D acquisitions, applying all usual corrections. Regions of interest (ROIs) were drawn in the myocardium, left ventricle, and ascending aorta, with the last 2 being used to define image-derived input functions (IDIFs). Patlak graphical analysis was used to compare net (18)F-FDG uptake in the myocardium, calculated from either 2D or 3D data, after reconstruction with FBP or OSEM. Either IDIFs or arterial sampling was used as the input function. The same analysis was performed on parametric images. RESULTS: A good correlation (r(2) > 0.99) was found between net (18)F-FDG uptake values for a myocardium ROI determined using each acquisition and reconstruction method and blood-sampling input functions. A similar result was found for parametric images. The ascending aorta was the best choice for IDIF definition. CONCLUSION: Good correlation and no bias of net (18)F-FDG uptake in relation to that based on FBP images, combined with less image noise, make 3D acquisition with FORE plus attenuation-weighted OSEM reconstruction the preferred choice for cardiac (18)F-FDG PET studies.
Aged↗
Pharmacokinetics and red cell utilization of 52Fe/59Fe-labelled iron polymaltose in anaemic patients using positron emission tomography.
Parenteral iron-polysaccharide complexes are increasingly applied. The pharmacokinetics of iron sucrose have been assessed by our group using positron emission tomography (PET). A single intravenous injection of 100 mg iron as iron (III) hydroxide-polymaltose complex, labelled with a tracer in the form of 52Fe/59Fe, was similarly assessed in six patients using PET for about 8 h. Red cell utilization was followed for 4 weeks. Iron polymaltose was similarly distributed to the liver, spleen and bone marrow. However, a larger proportion of this complex was rapidly distributed to the bone marrow. The shorter equilibration phase for the liver, about 25 min, indicates the minimal role of the liver for direct distribution. Splenic uptake also reflected the reticuloendothelial handling of this complex. Red cell utilization ranged from 61% to 99%. Despite the relatively higher uptake by the bone marrow, there was no saturation of marrow transport systems at this dose level. In conclusion, high red cell utilization of iron polymaltose occurred in anaemic patients. The major portion of the injected dose was rapidly distributed to the bone marrow. In addition, the reticuloendothelial uptake of this complex may reflect the safety of polysaccharide complexes. Non-saturation of transport systems to the bone marrow indicated the presence of a large interstitial transport pool, which might possibly be transferrin.
Adult↗
Quantitative imaging and correction for cascade gamma radiation of 76Br with 2D and 3D PET.
Several positron emitting nuclides with applications in PET, such as 76Br, 124I, 110In and 86Y, also emit gamma radiation in their decays. Measured coincidences between annihilation photons and this cascade gamma radiation are essentially true coincidences and the standard PET corrections do not account for them. We investigated the performance of 76Br in 2D and 3D PET, the effect of the gamma radiation emitted by 76Br on quantitative accuracy and the distribution of cascade gamma radiation coincidences in 2D and 3D PET sinograms. A correction method for cascade gamma radiation coincidences was implemented and evaluated. Count rate linearity was affected by the gamma radiation from the 76Br decay. Spatial resolution and sphere recovery were slightly worse for 76Br compared to 18F. Correction for cascade gamma radiation coincidences by subtraction of a linear projection tail fit improved total correction accuracy to similar values as for positron-only emitters such as 18F, and improved image contrast significantly.
Bromine Radioisotopes↗
Production, PET performance and dosimetric considerations of 134Ce/134La, an Auger electron and positron-emitting generator for radionuclide therapy.
We propose the use of the Auger electron and positron-emitting generator 134Ce/134La (half-lives 3.16 d and 6.45 min) for radionuclide therapy. It combines emission of high-energy beta particles with Auger electrons. The high-energy beta particles have similar energies as those emitted by 90Y. Many cancer patients receiving radionuclide therapy have both bulk tumours, which are best treated with high-energy beta particles, and single spread cells or micrometastasis, which are preferably treated with low-energy electrons such as Auger and conversion electrons. Furthermore, the positron-emitting 134La can be used to study kinetics and dosimetry using PET. Production and PET performance were investigated and theoretical dosimetry calculations were made. PET resolution, recovery and quantitative accuracy were slightly degraded for 134La compared to 18F. 134Ce/134La absorbed doses to single cells were higher than absorbed doses from 90Y and 111In. Absorbed doses to spheres representing bulk tumours were almost as high as for 90Y, and a factor 10 higher than for 111In. Whole-body absorbed doses, based on kinetics of the somatostatin analogue octreotide, were higher for 134Ce/134La than for 90Y because of the 134La annihilation photons. This initial study of the therapeutic possibilities of 134Ce/134La is encouraging and justifies further investigations.
Cesium Radioisotopes↗
Comparative biodistribution of the radiohalogenated (Br, I and At) antibody A33. Implications for in vivo dosimetry.
The alpha-emitter astatine-211 (T(1/2) = 7.2 h) has great potential for use in targeted radionuclide therapy. Its potent alpha-radiation makes (211)At unsuitable for dose planning. Its x-rays can be used for gamma-camera monitoring of the radioactivity distribution during therapy but not for accurate estimation of absorbed dose in critical organs. This study was intended to establish whether the absorbed dose delivered by astatinated antibody could be accurately determined by analogue labeling with radiohalogens, better suited for quantitative measurements in vivo. PET facilitates quantitative pharmacokinetics; possible halogen labels are, e.g., (76)Br (T(1/2) = 16.2 h) and (124)I (T(1/2) = 4.18 d). Antibody A33 was labeled with (76)Br, (125)I and (211)At using N-succinimidyl-p-halobenzoates. The conjugates were co-injected into Sprague-Dawley rats. Radioactivity concentrations in different organs and tissues were measured at three time points. Pharmacokinetic data were used to calculate absorbed doses. (125)I and (76)Br reflected the biokinetics of astatine reasonably well. The absorbed doses in bladder, kidney, pancreas, liver, bone and brain were determined with 10% accuracy. The absorbed doses in stomach, spleen and thyroid were underestimated by a factor 2-3. Positron-emitting analogues can be used to predict the astatine-derived dose in critical organs. Correction factors should be used for stomach, spleen and thyroid.
Animals↗
110mIn-DTPA-D-Phe1-octreotide for imaging of neuroendocrine tumors with PET.
UNLABELLED: The somatostatin analog diethylenetriaminepentaacetic acid (DTPA)-D-Phe1-octreotide labeled with 111In has been applied extensively for diagnosis of neuroendocrine tumors using SPECT or planar scintigraphy. However, the spatial resolution of planar scintigraphy and SPECT prohibits imaging of small tumors, and the quantification accuracy of both methods is limited. METHODS: We developed a method to prepare the positron-emitting radiopharmaceutical 110mIn-DTPA-D-Phe1-octreotide based on a commercially available kit. Phantom studies were done to investigate and compare the performance of 110mIn PET and 111In SPECT. A clinical imaging study using 110mIn-DTPA-D-Phe1-octreotide and PET was done to investigate the application of this radiopharmaceutical. RESULTS: An almost 3-fold better resolution and much better quantitative capabilities were found for 110mIn PET than for 111In SPECT. The clinical imaging study demonstrated the potential use of 110mIn-octreotide in PET to image tumors and quantify radioactivity uptake in humans using (110m)In-DTPA-D-Phe1-octreotide. CONCLUSION: PET with 110mIn-DTPA-D-Phe1-octreotide greatly improved detection of small tumors and offers a possibility of more accurate quantification of tumor uptake than can be obtained with 111In-DTPA-D-Phe1-octreotide and SPECT.
Humans↗