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Heurling, Kerstin
Publications (10 of 19) Show all publications
Boersma, G. J., Johansson, E., Pereira, M. J., Heurling, K., Skrtic, S., Lau, J., . . . Eriksson, J. (2018). Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study. Hormone and Metabolic Research, 50(8), 627-639
Open this publication in new window or tab >>Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study
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2018 (English)In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 50, no 8, p. 627-639Article in journal (Refereed) Published
Abstract [en]

We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=-0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

Place, publisher, year, edition, pages
Georg Thieme Verlag KG, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-356788 (URN)10.1055/a-0643-4739 (DOI)000440872200007 ()30001566 (PubMedID)
Funder
AstraZenecaEXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes AssociationSwedish Research CouncilErnfors Foundation
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-11-08Bibliographically 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
Miki, T., Shimada, H., Kim, J.-S., Yamamoto, Y., Sugino, M., Kowa, H., . . . Senda, M. (2017). Brain uptake and safety of Flutemetamol F 18 injection in Japanese subjects with probable Alzheimer's disease, subjects with amnestic mild cognitive impairment and healthy volunteers. Annals of Nuclear Medicine, 31(3), 260-272
Open this publication in new window or tab >>Brain uptake and safety of Flutemetamol F 18 injection in Japanese subjects with probable Alzheimer's disease, subjects with amnestic mild cognitive impairment and healthy volunteers
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2017 (English)In: Annals of Nuclear Medicine, ISSN 0914-7187, E-ISSN 1864-6433, Vol. 31, no 3, p. 260-272Article in journal (Refereed) Published
Abstract [en]

Objective This Phase 2 study assessed the performance of positron emission tomography (PET) brain images made with Flutemetamol F 18 Injection in detecting beta-amyloid neuritic plaques in Japanese subjects. Methods Seventy subjects (25 with probable Alzheimer's disease (pAD), 20 with amnestic mild cognitive impairment (aMCI), and 25 cognitively normal healthy volunteers[HVs]) underwent PET brain imaging after intravenous Flutemetamol F 18 Injection (185 MBq). Images were interpreted as normal or abnormal for neuritic plaque density by each of five non-Japanese and five Japanese readers who were blinded to clinical data. The primary efficacy analysis (based on HV and pAD data) was the agreement of the non-Japanese readers' image interpretations with the clinical diagnosis, resulting in estimates of positive percent agreement (PPA; based on AD subjects; similar to sensitivity) and negative percent agreement (NPA; based on HVs; similar to specificity). Secondary analyses included PPA and NPA for the Japanese readers; inter-reader agreement (IRA); intra-reader reproducibility (IRR); quantitative image interpretations (standardized uptake value ratios [SUVRs]) by diagnostic subgroup; test-retest variability in five pAD subjects; and safety. Results PPA was 92% for all non-Japanese readers and ranged from 88 to 92% for the Japanese readers. NPA ranged from 96 to 100% for both the non-Japanese readers and the Japanese readers. The majority image interpretations (the interpretations made independently by ae<yen>3 of 5 readers) resulted in PPA values of 92 and 92% and NPA values of 100 and 96% for the non-Japanese and Japanese readers, respectively. IRA and IRR were strong. Composite SUVR values (mean of multiple regional values) allowed clear differentiation between pAD subjects and HVs. Test-retest variability ranged from 1.14 to 2.27%, and test-retest agreement of the blinded visual interpretations was 100% for all readers. Flutemetamol F 18 Injection was generally well tolerated. Conclusion The detection of brain neuritic plaques in Japanese subjects using [F-18]Flutemetamol PET images gave results highly consistent with clinical diagnosis, with non-Japanese and Japanese readers giving similar results. Inter-reader agreement and intra-reader reproducibility were high for both sets of readers. Visual delineation of abnormal and normal scans was corroborated by quantitative assessment, with low test-retest variability.

Keywords
[F-18] Flutemetamol, Alzheimer's disease, Radiotracer, beta-Amyloid
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-321328 (URN)10.1007/s12149-017-1154-7 (DOI)000398448400008 ()28181118 (PubMedID)
Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2017-05-31Bibliographically approved
Boersma, G. J., Heurling, K., Pereira, M. J., Johansson, E., Lubberink, M., Lau Börjesson, J., . . . Eriksson, J. W. (2017). Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia. Paper presented at 53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL. Diabetologia, 60, S80-S80
Open this publication in new window or tab >>Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia
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2017 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S80-S80Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-346985 (URN)000408315000170 ()
Conference
53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-03-23Bibliographically approved
Heurling, K., Leuzy, A., Jonasson, M., Frick, A., Zimmer, E. R., Nordberg, A. & Lubberink, M. (2017). Quantitative positron emission tomography in brain research. Brain Research, 1670, 220-234, Article ID S0006-8993(17)30270-6.
Open this publication in new window or tab >>Quantitative positron emission tomography in brain research
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2017 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1670, p. 220-234, article id S0006-8993(17)30270-6Article, review/survey (Refereed) Published
Abstract [en]

The application of positron emission tomography (PET) in brain research has increased substantially during the past 20 years, and is still growing. PET provides a unique insight into physiological and pathological processes in vivo. In this article we introduce the fundamentals of PET, and the methods available for acquiring quantitative estimates of the parameters of interest. A short introduction to different areas of application is also given, including basic research of brain function and in neurology, psychiatry, drug receptor occupancy studies, and its application in diagnostics of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Our aim is to inform the unfamiliar reader of the underlying basics and potential applications of PET, hoping to inspire the reader into considering how the technique could be of benefit for his or her own research.

Keywords
Brain, Diagnostics, Imaging biomarkers, Molecular imaging, Positron emission tomography
National Category
Neurosciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-326069 (URN)10.1016/j.brainres.2017.06.022 (DOI)000407666000024 ()28652218 (PubMedID)
Available from: 2017-06-30 Created: 2017-06-30 Last updated: 2018-01-13Bibliographically approved
Heurling, K., Leuzy, A., Zimmer, E. R., Lubberink, M. & Nordberg, A. (2016). Imaging β-amyloid using [(18)F]flutemetamol positron emission tomography: from dosimetry to clinical diagnosis. European Journal of Nuclear Medicine and Molecular Imaging, 43(2), 362-373
Open this publication in new window or tab >>Imaging β-amyloid using [(18)F]flutemetamol positron emission tomography: from dosimetry to clinical diagnosis
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2016 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 2, p. 362-373Article, review/survey (Refereed) Published
Abstract [en]

In Alzheimer's disease (AD), the deposition of β-amyloid (Aβ) is hypothesized to result in a series of secondary neurodegenerative processes, leading ultimately to synaptic dysfunction and neuronal loss. Since the advent of the first Aβ-specific positron emission tomography (PET) ligand, (11)C-Pittsburgh compound B ([(11)C]PIB), several (18)F ligands have been developed that circumvent the limitations of [(11)C]PIB tied to its short half-life. To date, three such compounds have been approved for clinical use by the US and European regulatory bodies, including [(18)F]AV-45 ([(18)F]florbetapir; Amyvid™), [(18)F]-BAY94-9172 ([(18)F]florbetaben; Neuraceq™) and [(18)F]3'-F-PIB ([(18)F]flutemetamol; Vizamyl™). The present review aims to summarize and discuss the currently available knowledge on [(18)F]flutemetamol PET. As the (18)F analogue of [(11)C]PIB, [(18)F]flutemetamol may be of use in the differentiation of AD from related neurodegenerative disorders and may help with subject selection and measurement of target engagement in the context of clinical trials testing anti-amyloid therapeutics. We will also discuss its potential use in non-AD amyloidopathies.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-266304 (URN)10.1007/s00259-015-3208-1 (DOI)000367918200021 ()26440450 (PubMedID)
Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2017-12-01Bibliographically approved
Heurling, K., Moreno, A., Kullberg, J., Rosqvist, F., Antoni, G., Eriksson, J. P., . . . Risérus, U. (2016). Impact of overfeeding with saturated and polyunsaturated fat on hepatic [C-11]palmitate uptake and fat content using PET-MR. Paper presented at Annual Congress of the European-Association-of-Nuclear-Medicine, OCT 15-19, 2016, Barcelona, SPAIN. European Journal of Nuclear Medicine and Molecular Imaging, 43, S448-S448
Open this publication in new window or tab >>Impact of overfeeding with saturated and polyunsaturated fat on hepatic [C-11]palmitate uptake and fat content using PET-MR
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2016 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S448-S448Article in journal, Meeting abstract (Refereed) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-315169 (URN)000391802400579 ()
Conference
Annual Congress of the European-Association-of-Nuclear-Medicine, OCT 15-19, 2016, Barcelona, SPAIN
Available from: 2017-02-09 Created: 2017-02-09 Last updated: 2017-11-29Bibliographically approved
Ikonomovic, M. D., Buckley, C. J., Heurling, K., Sherwin, P., Jones, P. A., Zanette, M., . . . Smith, A. P. (2016). Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection. Acta neuropathologica communications, 4, Article ID 130.
Open this publication in new window or tab >>Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection
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2016 (English)In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 4, article id 130Article in journal (Refereed) Published
Abstract [en]

In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer's disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [(18)F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups. The GE067-026 trial demonstrated 91% sensitivity and 90% specificity of [(18)F]flutemetamol PET by majority read for the presence of moderate or frequent plaques. The probability of an abnormal [(18)F]flutemetamol scan increased with neocortical plaque density and AD diagnosis. All dementia cases with non-AD neurodegenerative diseases and those without histopathological features of β-amyloid deposits were [(18)F]flutemetamol negative. Majority PET assessments accurately reflected the amyloid plaque burden in 90% of cases. However, ten cases demonstrated a mismatch between PET image interpretations and post-mortem findings. Although tracer retention was best associated with amyloid in neuritic plaques, amyloid in diffuse plaques and cerebral amyloid angiopathy best explain three [(18)F]flutemetamol positive cases with mismatched (sparse) neuritic plaque burden. Advanced cortical atrophy was associated with the seven false negative [(18)F]flutemetamol images. The interpretation of images from pathologically equivocal cases was associated with low reader confidence and inter-reader agreement. Our results support that amyloid in neuritic plaque burden is the primary form of β-amyloid pathology detectable with [(18)F]flutemetamol PET imaging.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-312415 (URN)10.1186/s40478-016-0399-z (DOI)000390907100001 ()27955679 (PubMedID)
Available from: 2017-01-09 Created: 2017-01-09 Last updated: 2017-08-08Bibliographically approved
Heurling, K., Buckley, C., Van Laere, K., Vandenberghe, R. & Lubberink, M. (2016). Spectral analysis of [18f]flutemetamol grey and white matter kinetics. Paper presented at 27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, JUN 27-30, 2015, Vancouver, CANADA. Journal of Cerebral Blood Flow and Metabolism, 36(Suppl. 1), 80-81, Article ID 154.
Open this publication in new window or tab >>Spectral analysis of [18f]flutemetamol grey and white matter kinetics
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2016 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, no Suppl. 1, p. 80-81, article id 154Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SAGE PUBLICATIONS INC, 2016
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-321070 (URN)000394956300091 ()
Conference
27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, JUN 27-30, 2015, Vancouver, CANADA
Available from: 2017-05-05 Created: 2017-05-05 Last updated: 2017-05-05Bibliographically approved
Jonasson, M., Wall, A., Chiotis, K., Heurling, K., Saint-Aubert, L., Antoni, G., . . . Lubberink, M. (2016). Supervised Cluster Analysis for Automatic Extraction of Reference Region in Dynamic [F-18]THK5317 PET. Paper presented at Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 15-19, 2016, Barcelona, SPAIN. European Journal of Nuclear Medicine and Molecular Imaging, 43, S25-S25
Open this publication in new window or tab >>Supervised Cluster Analysis for Automatic Extraction of Reference Region in Dynamic [F-18]THK5317 PET
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2016 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S25-S25Article in journal, Meeting abstract (Refereed) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-316219 (URN)000391801600039 ()
Conference
Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 15-19, 2016, Barcelona, SPAIN
Available from: 2017-02-27 Created: 2017-02-27 Last updated: 2017-11-29Bibliographically approved
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