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Assessment of attenuation correction methods for quantitative neuro-PET/MR
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2021. , p. 65
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1751
Keywords [en]
PET, MRI, attenuation correction, 68Ge transmission, quantification, 11C-PE2I, MRAC, DAT, CBF
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Medical Radiophysics
Identifiers
URN: urn:nbn:se:uu:diva-440386ISBN: 978-91-513-1215-6 (print)OAI: oai:DiVA.org:uu-440386DiVA, id: diva2:1546389
Public defence
2021-06-11, H:son-Holmdahlsalen, Akademiska sjukhuset, 100/101, 2 tr, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2021-05-19 Created: 2021-04-21 Last updated: 2021-06-21
List of papers
1. Evaluation of zero-echo-time attenuation correction for integrated PET/MR brain imaging-comparison to head atlas and 68Ge-transmission-based attenuation correction
Open this publication in new window or tab >>Evaluation of zero-echo-time attenuation correction for integrated PET/MR brain imaging-comparison to head atlas and 68Ge-transmission-based attenuation correction
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2018 (English)In: EJNMMI Physics, E-ISSN 2197-7364, Vol. 5, no 20Article in journal (Refereed) Published
Abstract [en]

Background: MRI does not offer a direct method to obtain attenuation correction maps as its predecessors (stand-alone PET and PET/CT), and bone visualisation is particularly challenging. Recently, zero-echo-time (ZTE) was suggested for MR-based attenuation correction (AC). The aim of this work was to evaluate ZTE- and atlas-AC by comparison to 68Ge-transmission scan-based AC.

Nine patients underwent brain PET/MR and stand-alone PET scanning using the dopamine transporter ligand 11C-PE2I. For each of them, two AC maps were obtained from the MR images: an atlas-based, obtained from T1-weighted LAVA-FLEX imaging with cortical bone inserted using a CT-based atlas, and an AC map generated from proton-density-weighted ZTE images. Stand-alone PET 68Ge-transmission AC map was used as gold standard. PET images were reconstructed using the three AC methods and standardised uptake value (SUV) values for the striatal, limbic and cortical regions, as well as the cerebellum (VOIs) were compared. SUV ratio (SUVR) values normalised for the cerebellum were also assessed. Bias, precision and agreement were calculated; statistical significance was evaluated using Wilcoxon matched-pairs signed-rank test.

Results: Both ZTE- and atlas-AC showed a similar bias of 6–8% in SUV values across the regions. Correlation coefficients with 68Ge-AC were consistently high for ZTE-AC (r 0.99 for all regions), whereas they were lower for atlas-AC, varying from 0.99 in the striatum to 0.88 in the posterior cortical regions. SUVR showed an overall bias of 2.9 and 0.5% for atlas-AC and ZTE-AC, respectively. Correlations with 68Ge-AC were higher for ZTE-AC, varying from 0.99 in the striatum to 0.96 in the limbic regions, compared to atlas-AC (0.99 striatum to 0.77 posterior cortex).

Conclusions: Absolute SUV values showed less variability for ZTE-AC than for atlas-AC when compared to 68Ge-AC, but bias was similar for both methods. This bias is largely caused by higher linear attenuation coefficients in atlas- and ZTE-AC image compared to 68Ge-images. For SUVR, bias was lower when using ZTE-AC than for atlas-AC. ZTE-AC shows to be a more robust technique than atlas-AC in terms of both intra- and inter-patient variability.

Keywords
Atlas-AC, Attenuation correction, PET/MR, Static imaging, ZTE-AC
National Category
Medical Image Processing Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-364358 (URN)10.1186/s40658-018-0220-0 (DOI)000447946100001 ()30345471 (PubMedID)
Funder
Swedish Research Council
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2022-06-07Bibliographically approved
2. Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging
Open this publication in new window or tab >>Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging
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2020 (English)In: EJNMMI Physics, E-ISSN 2197-7364, Vol. 7, no 1, article id 77Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Atlas, Binding potential, Dopamine transporter, MRAC, MaxProb, ZTE, rCBF
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-430223 (URN)10.1186/s40658-020-00347-2 (DOI)000603296900001 ()33369700 (PubMedID)
Funder
Swedish Research Council, 2011-6269Region Uppsala
Note

De två första författarna delar förstaförfattarskapet

Available from: 2021-01-08 Created: 2021-01-08 Last updated: 2022-06-07Bibliographically approved
3. Composite 68Ge attenuation correction for quantitative brain PET/MR
Open this publication in new window or tab >>Composite 68Ge attenuation correction for quantitative brain PET/MR
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

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.

Keywords
Attenuation correction; 68Ge database; Dopamine transporter; [11C]PE2I, PET/MR, Quantification
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-440382 (URN)
Available from: 2021-04-18 Created: 2021-04-18 Last updated: 2021-04-21
4. Comparison of quantitative [11C]PE2I PET scans acquired on PET/MR and stand-alone PET
Open this publication in new window or tab >>Comparison of quantitative [11C]PE2I PET scans acquired on PET/MR and stand-alone PET
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(English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016Article in journal (Other (popular science, discussion, etc.)) Submitted
Abstract [en]

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.

Keywords
Attenuation correction; Dopamine transporter; Hybrid imaging; Acoustic MR noise; parkinsonism
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-440375 (URN)
Available from: 2021-04-18 Created: 2021-04-18 Last updated: 2021-04-21

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Citation style
  • apa
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Output format
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