Dataset Information

Quantification of PET infusion studies without true equilibrium: A tissue clearance correction.

ABSTRACT: In some positron emission tomography (PET) studies, a reversibly binding radioligand is administered as a constant infusion to establish true equilibrium for quantification. This approach reduces scanning time and simplifies data analysis, but assumes similar behavior of the radioligand in plasma across the study population to establish true equilibrium in all subjects. Bias in outcome measurements can result if this assumption is not met. This work developed and validated a correction that reduces bias in total distribution volume (V_T) estimates when true equilibrium is not present. This correction, termed tissue clearance correction (TCC), took the form VT=VT(A)/(1+βγVT(A)), where β is the radioligand clearance rate in tissue, γ is a radiotracer-specific constant, and V_T(A) is the apparent V_T. Simulations characterized the robustness of TCC across imperfect values of γ and β and demonstrated reduction to false positive rates. This approach was validated with human infusion data for three radiotracers: [¹⁸F]FPEB, (-)-[¹⁸F]flubatine, and [¹¹C]UCB-J. TCC reduced bias in V_T estimates for all radiotracers and significantly reduced intersubject variance in V_T for [¹⁸F]FPEB data in some brain regions. Thus, TCC improves quantification of data acquired from PET infusion studies.

SUBMITTER: Hillmer AT

PROVIDER: S-EPMC7168787 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Quantification of PET infusion studies without true equilibrium: A tissue clearance correction.

Hillmer Ansel T AT Carson Richard E RE

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20190514 4

In some positron emission tomography (PET) studies, a reversibly binding radioligand is administered as a constant infusion to establish true equilibrium for quantification. This approach reduces scanning time and simplifies data analysis, but assumes similar behavior of the radioligand in plasma across the study population to establish true equilibrium in all subjects. Bias in outcome measurements can result if this assumption is not met. This work developed and validated a correction that redu ...[more]

PMID: 31088233

Similar Datasets

Project description:UNLABELLED:Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVRs) in ligand-receptor dynamic PET studies. The objective of this study was to use a recently developed relative equilibrium-based graphical (RE) plot method to improve and simplify the 2 commonly used methods for quantification of (11)C-Pittsburgh compound B ((11)C-PiB) PET. METHODS:The overestimation of DVR in SUVR was analyzed theoretically using the Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE plot. Seventy-eight (11)C-PiB dynamic PET scans (66 from controls and 12 from participants with mild cognitive impaired [MCI] from the Baltimore Longitudinal Study of Aging) were acquired over 90 min. Regions of interest (ROIs) were defined on coregistered MR images. Both the ROI and the pixelwise time-activity curves were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI time-activity curves were used as a reference for comparison of DVR estimates. RESULTS:Results from the theoretic analysis were confirmed by human studies. ROI estimates from the RE plot and the bcSUVR were nearly identical to those from the Logan plot with ROI time-activity curves. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, and cingulate regions and the striatum were underestimated by the Logan plot (controls, 4%-12%; MCI, 9%-16%) and overestimated by the SUVR (controls, 8%-16%; MCI, 16%-24%). This bias was higher in the MCI group than in controls (P < 0.01) but was not present when data were analyzed using either the RE plot or the bcSUVR. CONCLUSION:The RE plot improves pixelwise quantification of (11)C-PiB dynamic PET, compared with the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates than of SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of (11)C-PiB studies.

Project description:BackgroundSubject motion in positron emission tomography (PET) studies leads to image blurring and artifacts; simultaneously acquired magnetic resonance imaging (MRI) data provides a means for motion correction (MC) in integrated PET/MRI scanners.PurposeTo assess the effect of realistic head motion and MR-based MC on static [18 F]-fluorodeoxyglucose (FDG) PET images in dementia patients.Study typeObservational study.PopulationThirty dementia subjects were recruited.Field strength/sequence3T hybrid PET/MR scanner where EPI-based and T1 -weighted sequences were acquired simultaneously with the PET data.AssessmentHead motion parameters estimated from high temporal resolution MR volumes were used for PET MC. The MR-based MC method was compared to PET frame-based MC methods in which motion parameters were estimated by coregistering 5-minute frames before and after accounting for the attenuation-emission mismatch. The relative changes in standardized uptake value ratios (SUVRs) between the PET volumes processed with the various MC methods, without MC, and the PET volumes with simulated motion were compared in relevant brain regions.Statistical testsThe absolute value of the regional SUVR relative change was assessed with pairwise paired t-tests testing at the P = 0.05 level, comparing the values obtained through different MR-based MC processing methods as well as across different motion groups. The intraregion voxelwise variability of regional SUVRs obtained through different MR-based MC processing methods was also assessed with pairwise paired t-tests testing at the P = 0.05 level.ResultsMC had a greater impact on PET data quantification in subjects with larger amplitude motion (higher than 18% in the medial orbitofrontal cortex) and greater changes were generally observed for the MR-based MC method compared to the frame-based methods. Furthermore, a mean relative change of ∼4% was observed after MC even at the group level, suggesting the importance of routinely applying this correction. The intraregion voxelwise variability of regional SUVRs was also decreased using MR-based MC. All comparisons were significant at the P = 0.05 level.Data conclusionIncorporating temporally correlated MR data to account for intraframe motion has a positive impact on the FDG PET image quality and data quantification in dementia patients.Level of evidence3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1288-1296.

Project description:BACKGROUND:The clinical impact of hypoxia in solid tumours is indisputable and yet questions about the sensitivity of hypoxia-PET imaging have impeded its uptake into routine clinical practice. Notably, the binding rate of hypoxia-sensitive PET tracers is slow, comparable to the rate of diffusive equilibration in some tissue types, including mucinous and necrotic tissue. This means that tracer uptake on the scale of a PET imaging voxel-large enough to include such tissue and hypoxic cells-can be as much determined by tissue transport properties as it is by hypoxia. Dynamic PET imaging of 20 patients with pancreatic ductal adenocarcinoma was used to assess the impact of transport on surrogate metrics of hypoxia: the tumour-to-blood ratio [TBR(t)] at time t post-tracer injection and the trapping rate k 3 inferred from a two-tissue compartment model. Transport quantities obtained from this model included the vascular influx and efflux rate coefficients, k 1 and k 2, and the distribution volume v d ≡k 1/(k 2+k 3). RESULTS:Correlations between voxel- and whole tumour-scale k 3 and TBR values were weak to modest: the population average of the Pearson correlation coefficients (r) between voxel-scale k 3 and TBR (1 h) [TBR(2 h)] values was 0.10 [0.01] in the 20 patients, while the correlation between tumour-scale k 3 and TBR(2 h) values was 0.58. Using Patlak's formula to correct uptake for the distribution volume, correlations became strong (r=0.80[0.52] and r=0.93, respectively). The distribution volume was substantially below unity for a large fraction of tumours studied, with v d ranging from 0.68 to 1 (population average, 0.85). Surprisingly, k 3 values were strongly correlated with v d in all patients. A model was proposed to explain this in which k 3 is a combination of the hypoxia-sensitive tracer binding rate k b and the rate k eq of equilibration in slow-equilibrating regions occupying a volume fraction 1-v d of the imaged tissue. This model was used to calculate the proposed hypoxia surrogate marker k b. CONCLUSIONS:Hypoxia-sensitive PET tracers are slow to reach diffusive equilibrium in a substantial fraction of pancreatic tumours, confounding quantification of hypoxia using both static (TBR) and dynamic (k 3) PET imaging. TBR is reduced by distribution volume effects and k 3 is enhanced by slow equilibration. We proposed a novel model to quantify tissue transport properties and hypoxia-sensitive tracer binding in order to improve the sensitivity of hypoxia-PET imaging.

Dataset Information

Quantification of PET infusion studies without true equilibrium: A tissue clearance correction.

Publications

Quantification of PET infusion studies without true equilibrium: A tissue clearance correction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets