Dataset Information

Low-dose 18F-FDG TOF-PET/MR for accurate quantification of brown adipose tissue in healthy volunteers.

ABSTRACT: BACKGROUND:Positron emission tomography (PET) is increasingly applied for in vivo brown adipose tissue (BAT) research in healthy volunteers. To limit the radiation exposure, the injected 18F-FDG tracer dose should be as low as possible. With simultaneous PET/MR imaging, the radiation exposure due to computed tomography (CT) can be avoided, but more importantly, the PET acquisition time can often be increased to match the more extensive magnetic resonance (MR) imaging protocol. The potential gain in detected coincidence counts, due to the longer acquisition time, can then be applied to decrease the injected tracer dose. The aim of this study was to investigate the minimal 18F-FDG dose for a 10-min time-of-flight (TOF) PET/MR acquisition that would still allow accurate quantification of supraclavicular BAT volume and activity. METHODS:Twenty datasets from 13 volunteers were retrospectively included from a prospective clinical study. PET emission datasets were modified to simulate step-wise reductions of the original 75?MBq injected dose. The resulting PET images were visually and quantitatively assessed and compared to a 4-min reference scan. For the visual assessment, the image quality and artifacts were scored using a 5-point and a 3-point Likert scale. For the quantitative analysis, image noise and artifacts, BAT metabolic activity, BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were investigated. RESULTS:The visual assessment showed still good image quality for the 35%, 30%, and 25% activity reconstructions with no artifacts. Quantitatively, the background noise was similar to the reference for the 35% and 30% activity reconstructions and the artifacts started to increase significantly in the 25% and lower activity reconstructions. There was no significant difference in supraclavicular BAT metabolic activity, BMV, and TBG between the reference and the 35% to 20% activity reconstructions. CONCLUSIONS:This study indicates that when the PET acquisition time is matched to the 10-min MRI protocol, the injected 18F-FDG tracer dose can be reduced to approximately 19?MBq (25%) while maintaining image quality and accurate supraclavicular BAT quantification. This could decrease the effective dose from 1.4?mSv to 0.36?mSv.

SUBMITTER: Ter Voert EEGW

PROVIDER: S-EPMC6977803 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Low-dose <sup>18</sup>F-FDG TOF-PET/MR for accurate quantification of brown adipose tissue in healthy volunteers.

Ter Voert Edwin E G W EEGW Svirydenka Hanna H Müller Julian J Becker Anton S AS Balaz Miroslav M Efthymiou Vissarion V Maushart Claudia Irene CI Gashi Gani G Wolfrum Christian C Betz Matthias J MJ Burger Irene A IA

EJNMMI research 20200123 1

<h4>Background</h4>Positron emission tomography (PET) is increasingly applied for in vivo brown adipose tissue (BAT) research in healthy volunteers. To limit the radiation exposure, the injected <sup>18</sup>F-FDG tracer dose should be as low as possible. With simultaneous PET/MR imaging, the radiation exposure due to computed tomography (CT) can be avoided, but more importantly, the PET acquisition time can often be increased to match the more extensive magnetic resonance (MR) imaging protocol. ...[more]

PMID: 31974702

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Project description:UnlabelledFor brown adipose tissue (BAT) to be effective at consuming calories, its blood flow must increase enough to provide sufficient fuel to sustain energy expenditure and also transfer the heat created to avoid thermal injury. Here we used a combination of human and rodent models to assess changes in BAT blood flow and glucose utilization.Methods(99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT (n = 7) and SPECT/CT (n = 74) scans done in adult humans for parathyroid imaging were reviewed for uptake in regions consistent with human BAT. Site-directed biopsies of subcutaneous and deep neck fat were obtained for electron microscopy and gene expression profiling. In mice, tissue perfusion was measured with (99m)Tc-MIBI (n = 16) and glucose uptake with (18)F-FDG (n = 16). Animals were kept fasting overnight, anesthetized with pentobarbital, and given intraperitoneally either the β3-adrenergic receptor agonist CL-316,243, 1 mg/kg (n = 8), or saline (n = 8) followed by radiotracer injection 5 min later. After 120 min, the mice were imaged using SPECT/CT or PET/CT. Vital signs were recorded over 30 min during the imaging. BAT, white adipose tissue (WAT), muscle, liver, and heart were resected, and tissue uptake of both (99m)Tc-MIBI and (18)F-FDG was quantified by percentage injected dose per gram of tissue and normalized to total body weight.ResultsIn 5.4% of patients (4/74), (99m)Tc-MIBI SPECT/CT showed increased retention in cervical and supraclavicular fat that displayed multilocular lipid droplets, dense capillary investment, and a high concentration of ovoid mitochondria. Expression levels of the tissue-specific uncoupling protein-1 were 180 times higher in BAT than in subcutaneous WAT (P < 0.001). In mice, BAT tissue perfusion increased by 61% (P < 0.01), with no significant changes in blood flow to WAT, muscle, heart, or liver. CL-316,243 increased glucose uptake in BAT even more, by 440% (P < 0.01).ConclusionPharmacologic activation of BAT requires increased blood flow to deliver glucose and oxygen for thermogenesis. However, the glucose consumption far exceeds the vascular response. These findings demonstrate that activated BAT increases glucose uptake beyond what might occur by increased blood flow alone and suggest that activated BAT likely uses glucose for nonthermogenic purposes.

Project description:BackgroundAssessment of dual time point (DTP) positron emission tomography was carried out with the aim of a quantitative determination of Km, the metabolic uptake rate of [18F]fluorodeoxyglucose as a measure of glucose consumption.MethodsStarting from the Patlak equation, it is shown that Km?mt/ca0+V?r/?a, where mt is the secant slope of the tissue response function between the dual time point measurements centered at t?=?t0. ca0=ca(t0) denotes arterial tracer concentration, V?r is an estimate of the Patlak intercept, and ?a is the time constant of the ca(t) decrease. We compared the theoretical predictions with the observed relation between Ks=mt/ca0 and Km in a group of nine patients with liver metastases of colorectal cancer for which dynamic scans were available, and Km was derived from conventional Patlak analysis. Twenty-two lesion regions of interest (ROIs) were evaluated. ca(t) was determined from a three-dimensional ROI in the aorta. Furthermore, the correlation between Km and late standard uptake value (SUV) as well as retention index was investigated. Additionally, feasibility of the approach was demonstrated in a whole-body investigation.ResultsPatlak analysis yielded a mean Vr of V?r=0.53±0.08 ml/ml. The patient averaged ?a was 99?±?23 min. Linear regression between Patlak-derived Km and DTP-derived Ks according to Ks?=?b?·?Km?+?a yielded b?=?0.98?±?0.05 and a?=?-0.0054?±?0.0013 ml/min/ml (r?=?0.98) in full accordance with the theoretical predictions b?=?1 and a?-V?r/?a. Ks exhibits better correlation with Km than late SUV and retention index, respectively. Ks(c)=Ks+V?r/?a is proposed as a quantitative estimator of Km which is independent of patient weight, scan time, and scanner calibration.ConclusionQuantification of Km from dual time point measurements compatible with clinical routine is feasible. The proposed approach eliminates the issues of static SUV and conventional DTP imaging regarding influence of chosen scanning times and inter-study variability of the input function. Ks and Ks(c) exhibit improved stability and better correlation with the true Km. These properties might prove especially relevant in the context of radiation treatment planning and therapy response control.

Project description:BACKGROUND:Previous studies found that [18F]LSN3316612 was a promising positron emission tomography (PET) radioligand for imaging O-GlcNAcase in nonhuman primates and human volunteers. This study sought to further evaluate the suitability of [18F]LSN3316612 for human clinical research. METHODS:Kinetic evaluation of [18F]LSN3316612 was conducted in a combined set of baseline brain scans from 17 healthy human volunteers and test-retest imaging was conducted in 10 of these volunteers; another 6 volunteers had whole-body scans to measure radiation exposure to body organs. Total distribution volume (VT) estimates were compared for the one- and two-tissue compartment models with the arterial input function. Test-retest variability and reliability were evaluated via mean difference and intraclass correlation coefficient (ICC). The time stability of VT was assessed down to a 30-min scan time. An alternative quantification method for [18F]LSN3316612 binding without blood was also investigated to assess the possibility of eliminating arterial sampling. RESULTS:Brain uptake was generally high and could be quantified as VT with excellent identifiability using the two-tissue compartment model. [18F]LSN3316612 exhibited good absolute test-retest variability (12.5%), but the arithmetic test-retest variability was far from 0 (11.3%), reflecting a near-uniform increase of VT on the retest scan in nine of 10 volunteers. VT values were stable after 110 min in all brain regions, suggesting that no radiometabolites accumulated in the brain. Measurements obtained using only brain activity (i.e., area under the curve (AUC) from 150-180 min) correlated strongly with regional VT values during test-retest conditions (R2 = 0.84), exhibiting similar reliability to VT (ICC = 0.68 vs. 0.64). Estimated radiation exposure for [18F]LSN3316612 PET was 20.5 ± 2.1 ?Sv/MBq, comparable to other 18F-labeled radioligands for brain imaging. CONCLUSIONS:[18F]LSN3316612 is an excellent PET radioligand for imaging O-GlcNAcase in the human brain. Alternative quantification without blood is possible, at least for within-subject repeat studies. However, the unexplained increase of VT under retest conditions requires further investigation.

Project description:PURPOSE:The aim of this study was to evaluate and quantify the effect of improved attenuation correction (AC) including bone segmentation and truncation correction on 18F-Fluordesoxyglucose cardiac positron emission tomography/magnetic resonance (PET/MR) imaging. METHODS:PET data of 32 cardiac PET/MR datasets were reconstructed with three different AC-maps (1. Dixon-VIBE only, 2. HUGE truncation correction and bone segmentation, 3. MLAA). The Dixon-VIBE AC-maps served as reference of reconstructed PET data. 17-segment short-axis polar plots of the left ventricle were analyzed regarding the impact of each of the three AC methods on PET quantification in cardiac PET/MR imaging. Non-AC PET images were segmented to specify the amount of truncation in the Dixon-VIBE AC-map serving as a reference. All AC-maps were evaluated for artifacts. RESULTS:Using HUGE + bone AC results in a homogeneous gain of ca. 6% and for MLAA 8% of PET signal distribution across the myocardium of the left ventricle over all patients compared to Dixon-VIBE AC only. Maximal relative differences up to 18% were observed in segment 17 (apex). The body volume truncation of -12.7 ± 7.1% compared to the segmented non-AC PET images using the Dixon-VIBE AC method was reduced to -1.9 ± 3.9% using HUGE and 7.8 ± 8.3% using MLAA. In each patient, a systematic overestimation in AC-map volume was observed when applying MLAA. Quantitative impact of artifacts showed regional differences up to 6% within single segments of the myocardium. CONCLUSIONS:Improved AC including bone segmentation and truncation correction in cardiac PET/MR imaging is important to ensure best possible diagnostic quality and PET quantification. The results exhibited an overestimation of AC-map volume using MLAA, while HUGE resulted in a more realistic body contouring. Incorporation of bone segmentation into the Dixon-VIBE AC-map resulted in homogeneous gain in PET signal distribution across the myocardium. The majority of observed AC-map artifacts did not significantly affect the quantitative assessment of the myocardium.

Dataset Information

Low-dose 18F-FDG TOF-PET/MR for accurate quantification of brown adipose tissue in healthy volunteers.

Publications

Low-dose <sup>18</sup>F-FDG TOF-PET/MR for accurate quantification of brown adipose tissue in healthy volunteers.

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