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Lubberink, Mark
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Publications (10 of 156) Show all publications
Nørgaard, M., Ganz, M., Svarer, C., Feng, L., Ichise, M., Lanzenberger, R., . . . Knudsen, G. M. (2018). Cerebral serotonin transporter measurements with [11C]DASB: A review on acquisition and preprocessing across 21 PET centres. Journal of Cerebral Blood Flow and Metabolism, Article ID 271678X18770107.
Open this publication in new window or tab >>Cerebral serotonin transporter measurements with [11C]DASB: A review on acquisition and preprocessing across 21 PET centres
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2018 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, article id 271678X18770107Article in journal (Refereed) Published
Abstract [en]

C]DASB for quantification of cerebral serotonin transporter binding, as an exemplary case. We highlight and quantify the impact of the remarkable variety of ways in which researchers are currently conducting their studies, while implicitly expecting generalizable results across research groups. Our review provides evidence that the foundation for a given choice of a preprocessing pipeline seems to be an overlooked aspect in modern PET neuroscience. Furthermore, we believe that a thorough testing of pipeline performance is necessary to produce reproducible research outcomes, avoiding biased results and allowing for better understanding of human brain function.

Keywords
Positron Emission Tomography, [11C]DASB, data sharing, kinetic modeling, preprocessing
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-349497 (URN)10.1177/0271678X18770107 (DOI)29651896 (PubMedID)
Available from: 2018-04-27 Created: 2018-04-27 Last updated: 2018-05-30Bibliographically approved
Lindström, E., Sundin, A., Trampal, C., Lindsjö, L., Ilan, E., Danfors, T., . . . Lubberink, M. (2018). Evaluation of penalized likelihood estimation reconstruction on a digital time-of-flight PET/CT scanner for 18F-FDG whole-body examinations. Journal of Nuclear Medicine, 59(7), 1152-1158
Open this publication in new window or tab >>Evaluation of penalized likelihood estimation reconstruction on a digital time-of-flight PET/CT scanner for 18F-FDG whole-body examinations
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2018 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 59, no 7, p. 1152-1158Article in journal (Refereed) Published
Abstract [en]

The resolution and quantitative accuracy of PET are highly influenced by the reconstruction method. Penalized-likelihood estimation algorithms allow for fully convergent iterative reconstruction, generating a higher image contrast than ordered-subsets expectation maximization (OSEM) while limiting noise. In this study, a type of penalized reconstruction known as block-sequential regularized expectation maximization (BSREM) was compared with time-of-flight OSEM (TOF OSEM). Various strengths of noise penalization factor β were tested along with various acquisition durations and transaxial fields of view (FOVs) with the aim of evaluating the performance and clinical use of BSREM for 18F-FDG PET/CT, both quantitatively and in a qualitative visual evaluation. Methods: Eleven clinical whole-body 18F-FDG PET/CT examinations acquired on a digital TOF PET/CT scanner were included. The data were reconstructed using BSREM with point-spread function recovery and β-factors of 133, 267, 400, and 533—and using TOF OSEM with point-spread function—for various acquisition times per bed position and various FOVs. Noise level, signal-to-noise ratio (SNR), signal-to-background ratio (SBR), and SUV were analyzed. A masked evaluation of visual image quality, rating several aspects, was performed by 2 nuclear medicine physicians to complement the analysis. Results: The lowest levels of noise were reached with the highest β-factor, resulting in the highest SNR, which in turn resulted in the lowest SBR. A β-factor of 400 gave noise equivalent to TOF OSEM but produced a significant increase in SUVmax (11%), SNR (22%), and SBR (12%). BSREM with a β-factor of 533 at a decreased acquisition duration (2 min/bed position) was comparable to TOF OSEM at a full acquisition duration (3 min/bed position). Reconstructed FOV had an impact on BSREM outcome measures; SNR increased and SBR decreased when FOV was shifted from 70 to 50 cm. The evaluation of visual image quality resulted in similar scores for reconstructions, although a β-factor of 400 obtained the highest mean whereas a β-factor of 267 was ranked best in overall image quality, contrast, sharpness, and tumor detectability. Conclusion: In comparison with TOF OSEM, penalized BSREM reconstruction resulted in an increased tumor SUVmax and an improved SNR and SBR at a matched level of noise. BSREM allowed for a shorter acquisition than TOF OSEM, with equal image quality.

Keywords
FDG, Image Reconstruction, Molecular Imaging, PET/CT, block-sequential regularized expectation maximization, image reconstruction, penalization factor
National Category
Medical and Health Sciences Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-343272 (URN)10.2967/jnumed.117.200790 (DOI)000437237200037 ()29449445 (PubMedID)
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-09-18Bibliographically approved
Leuzy, A., Rodriguez-Vieitez, E., Saint-Aubert, L., Chiotis, K., Almkvist, O., Savitcheva, I., . . . Nordberg, A. (2018). Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease.. Alzheimer's & Dementia, 14(5), 652-663
Open this publication in new window or tab >>Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease.
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2018 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 5, p. 652-663Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Cross-sectional findings using the tau tracer [18F]THK5317 (THK5317) have shown that [18F]fluorodeoxyglucose (FDG) positron emission tomography data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single positron emission tomography study can provide both functional and molecular information.

METHODS: We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change.

RESULTS: Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317.

DISCUSSION: Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.

Keywords
Alzheimer's disease, Alzheimer's disease dementia, FDG, Hypometabolism, Longitudinal study, Mild cognitive impairment, Neurofibrillary tangles, Perfusion SUVR, Perfusion imaging, Positron emission tomography (PET), Prodromal Alzheimer's disease, R(1), THK5317, Tau imaging
National Category
Radiology, Nuclear Medicine and Medical Imaging Medicinal Chemistry Neurosciences
Identifiers
urn:nbn:se:uu:diva-337704 (URN)10.1016/j.jalz.2017.11.008 (DOI)000432438800009 ()29268078 (PubMedID)
Funder
Swedish Research Council, 05817Swedish Foundation for Strategic Research Gun och Bertil Stohnes StiftelseThe Karolinska Institutet's Research FoundationThe Swedish Brain FoundationWenner-Gren Foundations
Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-08-01Bibliographically approved
Hulsart Billström, G., Selvaraju, R., Estrada, S., Lubberink, M., Asplund, V., Bergman, K., . . . Antoni, G. (2018). Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept. Journal of Controlled Release, 285, 178-186
Open this publication in new window or tab >>Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept
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2018 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 285, p. 178-186Article in journal (Refereed) Published
Abstract [en]

Bone morphogenetic proteins (BMP's) are vital for bone and cartilage formation, where bone morphogenetic protein-2 (BMP-2) is acknowledged as a growth factor in osteoblast differentiation. However, uncontrolled delivery may result in adverse clinical effects. In this study we investigated the possibility for longitudinal and non-invasive monitoring of implanted [125I]BMP-2 retention and its relation to ossification at the site of implantation. A unilateral critically sized femoral defect was produced in the left limb of rats while the right femur was retained intact as a paired reference control. The defect was filled with a hyaluronan hydrogel with 25% hydroxyapatite alone (carrier control; n = 2) or combined with a mixture of [125I]BMP-2 (150 μg/ml; n = 4). Bone formation was monitored using micro computed tomography (μCT) scans at 1, 3, 5, 7, 9 and 12 weeks. The retention of [125I]BMP-2 was assessed with single photon emission computed tomography (SPECT), and the bone healing process was followed with sodium fluoride (Na18F) using positron emission tomography (PET) at day 3 and at week 2, 4, and 6. A rapid burst release of [125I]BMP-2 was detected via SPECT. This was followed by a progressive increase in uptake levels of [18F]fluoride depicted by PET imaging that was confirmed as bone formation via μCT. We propose that this functional, non-invasive imaging method allows tri-modal visualisation of the release of BMP-2 and the following in vivo response. We suggest that the potential of this novel technique could be considered for preclinical evaluation of novel smart materials on bone regeneration.

Keywords
Bone morphogenetic protein 2, Bone tissue engineering, Hydrogel, Micro computed tomography, Positron emission tomography, Single-photon emission computed tomography
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-356465 (URN)10.1016/j.jconrel.2018.07.012 (DOI)000441737400015 ()30005906 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 262948
Note

G. Hulsart-Billström and R. K. Selvaraju contributed equally to this work and should be regarded as joint first authors.

Available from: 2018-07-28 Created: 2018-07-28 Last updated: 2018-10-10Bibliographically approved
Kero, T., Sorensen, J., Antoni, G., Wilking, H., Carlson, K., Vedin, O., . . . Lubberink, M. (2018). Quantification of (11)C-PIB kinetics in cardiac amyloidosis. J Nucl Cardiol
Open this publication in new window or tab >>Quantification of (11)C-PIB kinetics in cardiac amyloidosis
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2018 (English)In: J Nucl CardiolArticle in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: The purpose of this work was to determine the optimal tracer kinetic model of (11)C-PIB and to validate the use of the simplified methods retention index (RI) and standardized uptake value (SUV) for quantification of cardiac (11)C-PIB uptake in amyloidosis. METHODS AND RESULTS: Single-tissue, reversible and irreversible two-tissue models were fitted to data from seven cardiac amyloidosis patients who underwent (11)C-PIB PET scans and arterial blood sampling for measurement of blood radioactivity and metabolites. The irreversible two-tissue model (2Tirr) best described cardiac (11)C-PIB uptake. RI and SUV showed high correlation with the rate of irreversible binding (Ki) from the 2Tirr model (r(2 )=0.95 and r(2 )=0.94). Retrospective data from 10 amyloidosis patients and 5 healthy controls were analyzed using RI, SUV, as well as compartment modelling with a population-average metabolite correction. All measures were higher in amyloidosis patients than in healthy controls (p=.001), but with an overlap between groups for Ki. CONCLUSION: An irreversible two-tissue model best describes the (11)C-PIB uptake in cardiac amyloidosis. RI and SUV correlate well with Ki from the 2Tirr model. RI and SUV discriminate better between amyloidosis patients and controls than Ki based on population-average metabolite correction.

Keywords
11c-pib, Cardiac amyloidosis, absolute quantification, retention index, standardized uptake value
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-356695 (URN)10.1007/s12350-018-1349-x (DOI)1532-6551 (Electronic) 1071-3581 (Linking) (ISBN)
Note

Kero, Tanja Sorensen, Jens Antoni, Gunnar Wilking, Helena Carlson, Kristina Vedin, Ola Rosengren, Sara Wikstrom, Gerhard Lubberink, Mark eng J Nucl Cardiol. 2018 Jul 23. pii: 10.1007/s12350-018-1349-x. doi: 10.1007/s12350-018-1349-x.

Available from: 2018-08-03 Created: 2018-08-03 Last updated: 2018-10-10Bibliographically approved
Johansson, E., Lubberink, M., Heurling, K., Eriksson, J. W., Skrtic, S., Ahlström, H. & Kullberg, J. (2018). Whole-Body Imaging of Tissue-specific Insulin Sensitivity and Body Composition by Using an Integrated PET/MR System: A Feasibility Study.. Radiology, 286(1), 271-278
Open this publication in new window or tab >>Whole-Body Imaging of Tissue-specific Insulin Sensitivity and Body Composition by Using an Integrated PET/MR System: A Feasibility Study.
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2018 (English)In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 286, no 1, p. 271-278Article in journal (Refereed) Published
Abstract [en]

Purpose

To develop, evaluate, and demonstrate the feasibility of a whole-body protocol for simultaneous assessment of tissue-specific insulin-mediated fluorine 18 (18F) fluorodeoxyglucose (FDG) influx rates, tissue depots, and whole-body insulin sensitivity (referred to as the M value).

Materials and Methods

An integrated positron emission tomography (PET)/magnetic resonance (MR) imaging system combined with hyperinsulinemic euglycemic clamp (HEC) was used. Dynamic whole-body PET imaging was used to determine the insulin-mediated 18F-FDG tissue influx rate (Ki) in the whole-body region by using the Patlak method. M value was determined with the HEC method at PET imaging. Tissue depots were quantified by using water-fat separated MR imaging and manual segmentations. Feasibility of the imaging protocol was demonstrated by using five healthy control participants and five patients with type 2 diabetes. Associations between M value and Ki were studied in multiple tissues by using the Pearson correlation.

Results

Positive correlations were found between M value and Ki in multiple tissues: the gluteus muscle (r = 0.875; P = .001), thigh muscle (r = 0.903; P , .001), calf muscle (r = 0.825; P = .003), and abdominal visceral adipose tissue (r = 0.820; P = .004). A negative correlation was found in the brain (r = 20.798; P = .006). The MR imaging–based method for quantification of tissue depots was feasible for determining adipose tissue volumes and fat fractions.

Conclusion

This PET/MR imaging protocol may be feasible for simultaneous assessment of tissue-specific insulin-mediated 18F-FDG influx rates, tissue depots, and M value.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-329272 (URN)10.1148/radiol.2017162949 (DOI)000422905200034 ()28846496 (PubMedID)
Funder
AstraZeneca
Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2018-03-16Bibliographically approved
Carlbom, L., Espes, D., Lubberink, M., Martinell, M., Johansson, L., Ahlström, H., . . . Eriksson, O. (2017). [(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes. Diabetes, 66(5), 1286-1292
Open this publication in new window or tab >>[(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes
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2017 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, no 5, p. 1286-1292Article in journal (Refereed) Published
Abstract [en]

[(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-316831 (URN)10.2337/db16-1449 (DOI)000399799800022 ()28246291 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF), K2015-54X-12219-19-4 K2013-64X-08268-26-3 K2013-55X-15043 921-2014-7054Novo NordiskSwedish Child Diabetes Foundation
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2018-01-25Bibliographically approved
Tovedal, T., Lubberink, M., Morell, A., Estrada, S., Golla, S. S., Myrdal, G., . . . Lennmyr, F. (2017). Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion. Annals of Thoracic Surgery, 103(2), 610-616
Open this publication in new window or tab >>Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion
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2017 (English)In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 103, no 2, p. 610-616Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Perfusion strategies during aortic surgery usually comprise hypothermic circulatory arrest (HCA), often combined with selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion. Cerebral blood flow (CBF) is a fundamental parameter for which the optimal level has not been clearly defined. We sought to determine the CBF at a pump flow level of 6 mL/kg/min, previously shown likely to provide adequate SACP at 20°C in pigs.

METHODS: Repeated positron emission tomography (PET) scans were used to quantify the CBF and glucose metabolism throughout HCA and SACP including cooling and rewarming. Eight pigs on cardiopulmonary bypass were assigned to either HCA alone (n = 4) or HCA+SACP (n = 4). The CBF was measured by repeated [(15)O]water PET scans from baseline to rewarming. The cerebral glucose metabolism was examined by [(18)F]fluorodeoxyglucose PET scans after rewarming to 37°C.

RESULTS: Cooling to 20°C decreased the cortical CBF from 0.31 ± 0.06 at baseline to 0.10 ± 0.02 mL/cm(3)/min (p = 0.008). The CBF was maintained stable by SACP of 6 mL/kg/min during 45 minutes. After rewarming to 37°C, the mean CBF increased to 0.24 ± 0.07 mL/cm(3)/min, without significant differences between the groups at any time-point exclusive of the HCA period. The net cortical uptake (Ki) of [(18)F]fluorodeoxyglucose after rewarming showed no significant difference between the groups.

CONCLUSIONS: Cooling autoregulated the CBF to 0.10 mL/cm(3)/min, and 45 minutes of SACP at 6 mL/kg/min maintained the CBF in the present model. Cerebral glucose metabolism after rewarming was similar in the study groups.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-302609 (URN)10.1016/j.athoracsur.2016.06.029 (DOI)000397165400067 ()27592601 (PubMedID)
Available from: 2016-09-07 Created: 2016-09-07 Last updated: 2018-09-03Bibliographically approved
Nordström, J., Kero, T., Harms, H. J., Widström, C., Flachskampf, F., Sörensen, J. & Lubberink, M. (2017). Calculation of left ventricular volumes and ejection fraction from dynamic cardiac-gated 15O-water PET/CT: 5D-PET. EJNMMI Physics, 4(1), Article ID 26.
Open this publication in new window or tab >>Calculation of left ventricular volumes and ejection fraction from dynamic cardiac-gated 15O-water PET/CT: 5D-PET
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2017 (English)In: EJNMMI Physics, ISSN 2197-7364, E-ISSN 2191-219X, Vol. 4, no 1, article id 26Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Quantitative measurement of myocardial blood flow (MBF) is of increasing interest in the clinical assessment of patients with suspected coronary artery disease (CAD). (15)O-water positron emission tomography (PET) is considered the gold standard for non-invasive MBF measurements. However, calculation of left ventricular (LV) volumes and ejection fraction (EF) is not possible from standard (15)O-water uptake images. The purpose of the present work was to investigate the possibility of calculating LV volumes and LVEF from cardiac-gated parametric blood volume (V B) (15)O-water images and from first pass (FP) images. Sixteen patients with mitral or aortic regurgitation underwent an eight-gate dynamic cardiac-gated (15)O-water PET/CT scan and cardiac MRI. V B and FP images were generated for each gate. Calculations of end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV) and LVEF were performed with automatic segmentation of V B and FP images, using commercially available software. LV volumes and LVEF were calculated with surface-, count-, and volume-based methods, and the results were compared with gold standard MRI.

RESULTS: Using V B images, high correlations between PET and MRI ESV (r = 0.89, p < 0.001), EDV (r = 0.85, p < 0.001), SV (r = 0.74, p = 0.006) and LVEF (r = 0.72, p = 0.008) were found for the volume-based method. Correlations for FP images were slightly, but not significantly, lower than those for V B images when compared to MRI. Surface- and count-based methods showed no significant difference compared with the volume-based correlations with MRI. The volume-based method showed the best agreement with MRI with no significant difference on average for EDV and LVEF but with an overestimation of values for ESV (14%, p = 0.005) and SV (18%, p = 0.004) when using V B images. Using FP images, none of the parameters showed a significant difference from MRI. Inter-operator repeatability was excellent for all parameters (ICC > 0.86, p < 0.001).

CONCLUSION: Calculation of LV volumes and LVEF from dynamic (15)O-water PET is feasible and shows good correlation with MRI. However, the analysis method is laborious, and future work is needed for more automation to make the method more easily applicable in a clinical setting.

National Category
Cardiac and Cardiovascular Systems Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-333781 (URN)10.1186/s40658-017-0195-2 (DOI)000415372700001 ()29138942 (PubMedID)
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-02-22Bibliographically approved
Fahlström, M., Lindskog, K., Appel, L., Engström, M., Antoni, G., Kumlien, E., . . . Lubberink, M. (2017). 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. Paper presented at Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), JUN 10-14, 2017, Denver, CO. Journal of Nuclear Medicine, 58(S1), Article ID 362.
Open this publication in new window or tab >>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
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2017 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 362Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

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

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-333332 (URN)000404949901169 ()
Conference
Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), JUN 10-14, 2017, Denver, CO
Note

Title in WoS: Correlation between regional cerebral blood flow based on simultaneously acquired arterial spin labelling MRI and O-15-water-PET using zero-echo-time-based attenuation correction

Available from: 2017-11-15 Created: 2017-11-15 Last updated: 2017-11-15Bibliographically approved
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