| 1. |
- Andersson, Jonathan, et al.
(author)
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Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.
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| 2. |
- Fahlström, Markus, et al.
(author)
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Correlation between regional cerebral blood flow based on simultaneously acquired arterial spin labelling MRI and 15O-water-PET using zero-echo-time-based attenuation correction
- 2017
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In: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:S1
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Journal article (other academic/artistic)abstract
- Objectives: Arterial spin labelling (ASL) MRI promises clinical value in several common neurological disorders. Its quantitative accuracy and reproducibility, however, need to be further validated, ideally using simultaneously acquired measurements with 15O-water-PET on an integrated PET-MR scanner. However, so far, few studies have attempted this and the inclusion of bone in MR-based attenuation correction for PET has thus far been a challenge, compromising the quantitative accuracy of PET-MR based 15O-water PET data. The aim of the present work was to assess the correlation of ASL- and 15O-water-PET based regional cerebral blood flow (rCBF) values based on simultaneously acquired data, using zero-echo-time (ZTE)-based attenuation correction, as well as to assess the reproducibility of ASL-based rCBF.Methods: Six subjects underwent 10 min PET scans after automated bolus injection of 400 MBq 15O-water (1 mL/s during 5 s followed by 35 mL saline at 2 mL/s) on a time-of-flight integrated PET-MR scanner (Signa PET-MR, GE Healthcare). Arterial blood radioactivity concentrations were monitored using continuous sampling from the radial artery (Swisstrace Twilite Two). Simultaneously, a 3D FSE pseudo-continuous ASL (3D pCASL) with a spiral read-out as supplied by the scanner manufacturer in the commercial software were acquired using an 8 channel head coil (Invivo Hi-Res Head Coil). In addition, 3D T1-w, ZTE and Dixon fat-water MRI were acquired. The ASL procedure was repeated after 2 h (patients remained in the scanner). Quantifiable ASL-based CBF maps were generated. PET images were reconstructed into 26 frames of increasing durations using time-of-flight OSEM (2 iterations, 28 subsets) and a 5 mm post-filter, with ZTE-based attenuation correction. Blood sampler data were corrected for delay and dispersion and 15O-water-based CBF maps were calculated using a basis function implementation of the single tissue compartment model including a fitted blood volume parameter. CBF maps were co-registered to each patient's T1-w image. 3D T1-w images were segmented and normalised to MNI space using SPM12, and anterior, middle and posterior flow territory volumes of interest (VOIs) were created from a standard template in MNI space and inversely transformed for each patient. In addition, a 45-VOI probabilistic template was applied using PVElab software. Correlations between PET- and ASL-based rCBF values were assessed using regression analysis, and reproducibility of ASL using a paired t-test.Results: Mean (CI) total brain grey matter CBF values were 67.2 (48.0-86.5) mL/min/100 g for 15O-water-PET and 65.5 (55.7-75.5) mL/min/100 g for ASL. Although correlation and agreement between 15O-water and ASL-based rCBF for individual VOIs in the 45-VOI template were generally poor, significant correlations were found on a grey matter flow territory basis, with R2 ranging from 0.70 in the anterior flow territory to 0.86 in the middle flow territory. rCBF values were significantly reduced between second and first ASL for all flow territories (p<0.01), with a mean decrease of 10%.Conclusion: A good correlation between regional flow territory CBF values based on ASL and 15O-water-PET was found, using ZTE-based attenuation correction for PET data which takes bone tissue into account. ASL values for regional flow territories may have potential applications in patients with dementia or cerebrovascular diseases affecting blood flow such as moya moya. The decrease of ASL-based rCBF values in the reproducibility study needs to be investigated further to assess whether this is a methodological issue or reflects a true decrease in rCBF. Research Support: Uppsala County Council
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| 3. |
- Fahlström, Markus, et al.
(author)
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Evaluation of Arterial Spin Labeling MRI : Comparison with 15O-Water PET on an Integrated PET/MR Scanner
- 2021
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In: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 11:5
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Journal article (peer-reviewed)abstract
- Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.
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| 4. |
- Kero, Tanja, et al.
(author)
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Evaluation of quantitative CMR perfusion imaging by comparison with simultaneous 15O-water-PET
- 2021
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In: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 28, s. 1252-1266
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Journal article (peer-reviewed)abstract
- BackgroundWe assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference with a fully integrated PET-MR scanner.Methods15 patients underwent simultaneous DCE MRI and 15O-water PET scans at rest and adenosine-stress on an integrated PET-MR scanner. Correlation and agreement between MRI- and PET-based global and regional MBF values were assessed using correlation and Bland–Altman analysis.ResultsThree subjects were excluded due to technical problems. Global mean (± SD) MBF values at rest and stress were 0.97 ± 0.27 and 3.19 ± 0.70 mL/g/min for MRI and 1.02 ± 0.28 and 3.13 ± 1.16 mL/g/min for PET (P = 0.66 and P = 0.81). The correlations between global and regional MRI- and PET-based MBF values were strong (r = 0.86 and r = 0.75). The biases were negligible for both global and regional MBF comparisons (0.01 and 0.00 mL/min/g for both), but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values.ConclusionThe correlation between simultaneous MBF measurements with DCE MRI and 15O-water PET measured in an integrated PET-MRI was strong but the agreement was only moderate indicating that MRI-based quantitative MBF measurements is not ready for clinical introduction.
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| 5. |
- Khalighi, Mohammad Mehdi, et al.
(author)
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Validation of an image derived input function estimation method on PET/MR
- 2017
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In: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:S1
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Journal article (other academic/artistic)abstract
- Objectives: The study objective was to validate a recently introduced non-invasive image derived input function (IDIF) estimation method with the gold standard arterial blood sampling.Methods: Six subjects (31-50 years old) were injected with 408±62 MBq of 15O-water simultaneously with the start of a 10 min PET scan on the SIGNA PET-MR (GE Healthcare, WI, Waukesha). During PET scanning, a sagittal vascular (inhance 3D velocity) MR series was used with the following parameters: TR=8.7 ms, TE=4.1 ms, FOV=24×21.6 cm, slice thickness=3 mm, 32 slices, velocity encoding=40, phase acceleration=2.0, and scan time=1:21 min. The PET list file was unlisted for every second and total true and scatter coincident events were plotted to identify tracer arrival into the brain arteries. Then, a short time frame over the arrival of the tracer to the cervical region was reconstructed to obtain a PET angiogram. The cervical arteries were then segmented using the MR vascular images and PETA images. Spill-over and spill- in artifacts were estimated using PETA images and the actual arterial volume was measured from the MR vascular images. The PET list file was unlisted and images were reconstructed for every 1 s for the first 30 s, every 3 s for the next 30 s, every 5 s for the 2nd minute, every 10 s for the 3rd and 4th minute and every 30 s for 5th to 10th minutes. The AIF was estimated by dividing total counts from the cervical arteries of each frame by the MR-based arterial volume. For each patient, blood samples were continuously drawn from the radial artery at the wrist using a peristaltic pump, and the tracer concentration in the arterial blood was measured using a Twilite two detector (Swisstrace) to estimate the AIF. In order to calculate the AIF at the brain arteries from these blood samples, the delay and dispersion of the arterial input function was corrected using standard PET-based methods. The CBF and distribution volume were calculated using both the IDIF method and the blood samples by minimizing the mean square of the error between the PET observations and model fit using the Nelder-Mead simplex algorithm in MATLAB (Mathworks, Wilmington, MA).Results: Figure 1 shows the (a) PETA and (b) MR vascular images for one of the patients. The PETA images clearly show the arteries and the extent of the spill-over. Figure 2 compares the AIF curve estimated by the proposed IDIF method and the AIF curve measured by the blood samples. The comparison shows excellent correspondence between the IDIF method and the gold standard blood sampling method with 9% and 11% difference for the 1st pass and the entire AIF, respectively. The IDIF captures the AIF peak correctly and has increased signal-to-noise ratio compared to the blood sampling method. The delay and the dispersion of the AIF curve is nearly identical between the two methods. The CBF over the whole brain was measured 29.5±8.7 and 27.0±14 ml/s/100g with the AIF measured by IDIF method and blood samples, respectively with a mean difference of 14% between the two methods. The volume distribution over the whole brain was measured 0.5±0.1 for both methods with a mean difference of 15% between them.Conclusion: As the results show, the proposed method is capable of determining a high fidelity IDIF from simultaneous PET/MRI data. Having a “blood-free” method that obviates the need for direct arterial sampling is of benefit to both investigators and their subjects, because of the high costs, inconvenience, and potential risks associated with arterial cannulation. It has applications beyond 15O-water PET, enabling pharmacokinetic modeling to be performed that is required for quantitative PET tracer studies. Research Support: GE Healthcare, Stanford University Lucas Center, Uppsala University.
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| 6. |
- Lundström, Elin, et al.
(author)
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PET/MRI of glucose metabolic rate, lipid content and perfusion in human brown adipose tissue
- 2021
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Journal article (peer-reviewed)abstract
- This study evaluated the MRI-derived fat fraction (FF), from a Cooling-reheating protocol, for estimating the cold-induced brown adipose tissue (BAT) metabolic rate of glucose (MRglu) and changes in lipid content, perfusion and arterial blood volume (V-A) within cervical-supraclavicular fat (sBAT). Twelve volunteers underwent PET/MRI at baseline, during cold exposure and reheating. For each temperature condition, perfusion and V-A were quantified with dynamic [O-15]water-PET, and FF, with water-fat MRI. MRglu was assessed with dynamic [F-18]fluorodeoxyglucose-PET during cold exposure. sBAT was defined using anatomical criteria, and its subregion sBAT(HI), by MRglu>11 mu mol/100 cm(3)/min. For all temperature conditions, sBAT-FF correlated negatively with sBAT-MRglu (rho <=- 0.87). After 3 h of cold, sBAT-FF decreased (- 2.13 percentage points) but tended to normalize during reheating although sBAT(HI)-FF remained low. sBAT-perfusion and sBAT-V-A increased during cold exposure (perfusion:+5.2 ml/100 cm(3)/min, V-A:+4.0 ml/100 cm(3)). sBAT-perfusion remained elevated and sBAT-V-A normalized during reheating. Regardless of temperature condition during the Cooling-reheating protocol, sBAT-FF could predict the cold-induced sBAT-MRglu. The FF decreases observed after reheating were mainly due to lipid consumption, but could potentially be underestimated due to intracellular lipid replenishment. The influence of perfusion and V-A, on the changes in FF observed during cold exposure, could not be ruled out.
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| 7. |
- Sousa, João M., et al.
(author)
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Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging
- 2020
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In: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain.METHODS: Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [11C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The 68Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R1) images and binding potential (BPND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [11C]PE2I BPND and R1 estimates, and [11C]PE2I time-activity curves. BPND was examined for striatal regions and R1 in clusters of regions across the brain.RESULTS: For BPND, ZTE-MRAC showed the highest accuracy (bias < 2%) in striatal regions. Atlas-MRAC exhibited a significant bias in caudate nucleus (- 12%) while MaxProb-MRAC revealed a substantial, non-significant bias in the putamen (9%). R1 estimates had a marginal bias for all MRAC methods (- 1.0-3.2%). MaxProb-MRAC showed the largest intersubject variability for both R1 and BPND. Standardized uptake values (SUV) of striatal regions displayed the strongest average bias for ZTE-MRAC (~ 10%), although constant over time and with the smallest intersubject variability. Atlas-MRAC had highest variation in bias over time (+10 to - 10%), followed by MaxProb-MRAC (+5 to - 5%), but MaxProb showed the lowest mean bias. For the cerebellum, MaxProb-MRAC showed the highest variability while bias was constant over time for Atlas- and ZTE-MRAC.CONCLUSIONS: Both Maxprob- and ZTE-MRAC performed better than Atlas-MRAC when using a 68Ge transmission scan as reference method. Overall, ZTE-MRAC showed the highest precision and accuracy in outcome parameters of dynamic [11C]PE2I PET analysis with use of kinetic modelling.
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| 8. |
- Sousa, Joao M., 1989-
(author)
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Assessment of attenuation correction methods for quantitative neuro-PET/MR
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Hybrid PET/magnetic resonance (MR) can provide physiological, functional, and structural information simultaneously, facilitating research in neurological disorders. For quantitative PET, correction for photon attenuation (AC) is necessary. However, in contrast to dedicated PET and PET/computed tomography (CT) systems, PET/MR has no direct possibility to measure photon attenuation. As such, MR-based methods are required for AC (MRAC), and these need to be thoroughly validated before clinical implementation.The primary aim of this thesis was to evaluate two vendor-provided MRAC methods (single-atlas and zero echo time, ZTE), a previously published maximum probability (MaxProb) method, and a composite transmission scan atlas (CTR) method for a SIGNA PET/MR. This evaluation was done both in terms of absolute quantification in static scans and of outcome measures of tracer kinetic modelling based on dynamic scans. The secondary aim was to compare quantitative brain PET measurements acquired on the SIGNA PET/MR with those acquired on a dedicated PET scanner. Ten patients with parkinsonism who underwent dynamic dopamine transporter scans using 11C-PE2I in a PET/MR and dedicated PET were included. Standardized uptake values (SUV), binding potential (BPND), and relative delivery (R1) were assessed at volume of interest (VOI) and voxel level to compare the various MRAC methods with the gold-standard, a 68Ge transmission scan, and to compare quantitative outcomes between scanners.In general, ZTE provided the highest precision in SUV, R1 and BPND, showing the least inter-subject variability in bias compared to 68Ge-transmission AC, whereas MaxProb and CTR showed the lowest precision. Contrary to this, accuracy of absolute SUV values was best for CTR followed by MaxProb, with ZTE showing a homogeneous positive bias of about 10%. ZTE provided the highest accuracy in outcome measures of tracer kinetic analysis. Differences in quantitative results between stand-alone PET and PET/MR exceeded what can be explained by difference in AC alone, although they were still comparable to previously published test-retest variability of 11C-PE2I. Additionally, an activation in the auditory cortex was seen in PET data from the PET/MR because of the noise produced by the MR gradients.ZTE-MRAC appears to be the best method for dynamic scanning and tracer kinetic analysis using reference methods, while CTR- and MaxProb-MRAC appear the most appropriate for absolute quantification. Also, attention should be taken to the auditory cortex activation in R1 images when comparing data from PET/MR and other PET- systems.
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| 9. |
- Sousa, Joao M., 1989-, et al.
(author)
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Comparison of quantitative [11C]PE2I PET scans acquired on PET/MR and stand-alone PET
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In: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X .- 1559-7016.
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Journal article (pop. science, debate, etc.)abstract
- Dedicated PET systems using transmission-based attenuation correction (AC) are regarded as the gold standard for quantitative brain PET. PET/MR systems demanded great efforts for accurate AC but differences in technology, geometry and hardware attenuation may also affect quantitative results. This study compares PET quantitative outcomes between a stand-alone PET and PET/MR scanner. Ten patients with parkinsonism underwent two 80-min dynamic PET scans with the dopamine transporter ligand [11C]PE2I. Images were reconstructed using resolution-matched settings and transmission scans (stand-alone PET) and zero-echo-time (PET/MR) for AC. SUV, relative delivery (R1), and dopamine transporter availability (BPND) were compared on a VOI- and voxel-basis. Correlations between systems were high (≥ 0.85) for all quantitative parameters. On VOI-basis, striatal BPND was significantly lower on PET/MR than on stand-alone PET (-7%). R1 was significantly overestimated in posterior cortical regions (9%) and underestimated in striatal (-9%) and limbic areas (-6%). SUV showed a similar pattern as R1. Voxel-by-voxel analysis showed significant positive bias of R1 in the auditory cortex. PET/MR significantly underestimated striatal BPND, similar to previously reported [11C]PE2I BPND test-retest variability. The acoustic noise in the PET/MR environment may attribute to an overestimation of R1 in the auditory cortex, which needs consideration when using PET/MR data.
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| 10. |
- Sousa, Joao M., 1989-, et al.
(author)
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Composite 68Ge attenuation correction for quantitative brain PET/MR
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Other publication (other academic/artistic)abstract
- Accurate attenuation correction (AC) in positron emission tomography (PET) imaging is a prerequisite for obtaining quantitatively correct images and 68Ge-AC is considered the gold standard for PET AC. In this study we developed an alternative AC method for PET/MR, based on the registration of a database of 68Ge-AC maps and T1-weighted MR image pairs. The present work aimed to evaluate this composite 68Ge transmission AC (CTR-AC) method’s reliability compared to 68Ge-AC. The CTR database comprised 125 pairs of previously acquired 68Ge-AC maps and T1-MRI scans. Ten patients underwent 80-min dynamic PET scans with the dopamine transporter ligand [11C]PE2I on a SIGNA PET/MR. Images were reconstructed using a CTR-AC map and a previously acquired patient-specific 68Ge-AC map on a stand-alone PET scanner. SUV as well as outcome parameters of [11C]PE2I kinetic analysis, i.e., relative delivery (R1) and dopamine transporter availability (BPND), were compared on a VOI and voxel-by-voxel basis.CTR-AC showed high accuracy, with a mean bias of 0 ± 3% for whole-brain SUV, -0.1 ± 3.2% for whole-brain R1, and 3.7 ± 8.1% for striatal BPND. The precision of SUV and R1 was modest and lowest in the anterior cortex, with an R1 bias of -1.1 ± 6.4%.CTR-AC is straightforward and provides MRAC maps with continuous linear attenuation coefficient values. The method’s accuracy is comparable to the best MRAC methods published so far, with a near-zero bias in SUV and a bias similar to that previously found for ZTE-AC in outcome parameters of kinetic modelling.
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