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Zarei, M., Wallstén, E., Grefve, J., Söderkvist, K., Gunnlaugsson, A., Sandgren, K., . . . Nyholm, T. (2024). Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer. Acta Oncologica, 63, 503-510
Open this publication in new window or tab >>Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer
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2024 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 63, p. 503-510Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.

MATERIALS AND METHODS: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.

RESULTS: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.

INTERPRETATION: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.

Place, publisher, year, edition, pages
MJS Publishing, Medical Journals Sweden, 2024
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-227761 (URN)10.2340/1651-226X.2024.39041 (DOI)001258458500005 ()38912830 (PubMedID)2-s2.0-85197008510 (Scopus ID)
Funder
Cancerforskningsfonden i NorrlandSwedish Cancer SocietyRegion Västerbotten
Available from: 2024-07-09 Created: 2024-07-09 Last updated: 2024-07-09Bibliographically approved
Johansson, J., Ericsson, M., Axelsson, J., af Bjerkén, S., Virel, A. & Karalija, N. (2024). Amphetamine-induced dopamine release in rat: Whole-brain spatiotemporal analysis with [11C]raclopride and positron emission tomography. Journal of Cerebral Blood Flow and Metabolism, 44(3), 434-445
Open this publication in new window or tab >>Amphetamine-induced dopamine release in rat: Whole-brain spatiotemporal analysis with [11C]raclopride and positron emission tomography
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2024 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 44, no 3, p. 434-445Article in journal (Refereed) Published
Abstract [en]

Whole-brain mapping of drug effects are needed to understand the neural underpinnings of drug-related behaviors. Amphetamine administration is associated with robust increases in striatal dopamine (DA) release. Dopaminergic terminals are, however, present across several associative brain regions, which may contribute to behavioral effects of amphetamine. Yet the assessment of DA release has been restricted to a few brain regions of interest. The present work employed positron emission tomography (PET) with [11C]raclopride to investigate regional and temporal characteristics of amphetamine-induced DA release across twenty sessions in adult female Sprague Dawley rats. Amphetamine was injected intravenously (2 mg/kg) to cause displacement of [11C]raclopride binding from DA D2-like receptors, assessed using temporally sensitive pharmacokinetic PET model (lp-ntPET). We show amphetamine-induced [11C]raclopride displacement in the basal ganglia, and no changes following saline injections. Peak occupancy was highest in nucleus accumbens, followed by caudate-putamen and globus pallidus. Importantly, significant amphetamine-induced displacement was also observed in several extrastriatal regions, and specifically in thalamus, insula, orbitofrontal cortex, and secondary somatosensory area. For these, peak occupancy occurred later and was lower as compared to the striatum. Collectively, these findings demonstrate distinct amphetamine-induced DA responses across the brain, and that [11C]raclopride-PET can be employed to detect such spatiotemporal differences.

Place, publisher, year, edition, pages
Sage Publications, 2024
Keywords
Amphetamine, displacement, dopamine, imaging, receptor
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-216126 (URN)10.1177/0271678X231210128 (DOI)001089209600001 ()37882727 (PubMedID)2-s2.0-85174906502 (Scopus ID)
Funder
Swedish Research Council
Available from: 2023-11-06 Created: 2023-11-06 Last updated: 2024-06-19Bibliographically approved
Grill, F., Guitart-Masip, M., Johansson, J., Stiernman, L., Axelsson, J., Nyberg, L. & Rieckmann, A. (2024). Dopamine release in human associative striatum during reversal learning. Nature Communications, 15(1), Article ID 59.
Open this publication in new window or tab >>Dopamine release in human associative striatum during reversal learning
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 59Article in journal (Refereed) Published
Abstract [en]

The dopaminergic system is firmly implicated in reversal learning but human measurements of dopamine release as a correlate of reversal learning success are lacking. Dopamine release and hemodynamic brain activity in response to unexpected changes in action-outcome probabilities are here explored using simultaneous dynamic [11C]Raclopride PET-fMRI and computational modelling of behavior. When participants encounter reversed reward probabilities during a card guessing game, dopamine release is observed in associative striatum. Individual differences in absolute reward prediction error and sensitivity to errors are associated with peak dopamine receptor occupancy. The fMRI response to perseverance errors at the onset of a reversal spatially overlap with the site of dopamine release. Trial-by-trial fMRI correlates of absolute prediction errors show a response in striatum and association cortices, closely overlapping with the location of dopamine release, and separable from a valence signal in ventral striatum. The results converge to implicate striatal dopamine release in associative striatum as a central component of reversal learning, possibly signifying the need for increased cognitive control when new stimuli-responses should be learned.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-219310 (URN)10.1038/s41467-023-44358-w (DOI)38167691 (PubMedID)2-s2.0-85181231291 (Scopus ID)
Available from: 2024-01-12 Created: 2024-01-12 Last updated: 2024-01-12Bibliographically approved
Senem, I., Foss, M. P., Lavigne-Moreira, C., dos Santos, A. C., Nunes, R. F., Franca Jr, M. C., . . . Marques Jr, W. (2024). Exploring cognitive functions and brain structure in hereditary transthyretin amyloidosis using brain MRI and neuropsychological assessment. Neurological Sciences
Open this publication in new window or tab >>Exploring cognitive functions and brain structure in hereditary transthyretin amyloidosis using brain MRI and neuropsychological assessment
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2024 (English)In: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Central nervous system symptoms, such as cognitive dysfunction, have been reported in Hereditary Transthyretin Amyloidosis (ATTRv). However, there is a lack of neuroimaging studies investigating structural alterations in the brain related to cognition in ATTRv amyloidosis. This study aimed to investigate cognition and cortical morphology in a cohort of ATTRv patients.

Methods: 29 ATTRv patients and 26 healthy controls completed neuropsychological assessment. 21 of these patients underwent 3T brain MRI, and 23 healthy subjects constituted the control group for MRI. Cortical measures of volume, thickness, fractional anisotropy (FA), and mean diffusivity (MD) were obtained for both groups. Correlation analyses between brain and cognitive measurements were performed.

Results: Patients displayed worse performance than controls in executive functions, verbal and visual memory, visuospatial domains, and language tests. Our study indicated cortical thinning in ATTRv patients in the temporal, occipital, frontal, and parietal areas. The inferior temporal gyrus correlated with verbal memory. Insula and, pars opercularis correlated with both verbal memory and executive function.

Conclusions: Cortical thickness in the inferior temporal gyrus, pars opercularis, and insula were linked to memory and executive function. We observed no correlations between cortical volume measures and cognition. Further investigations are imperative to confirm these findings across different populations.

Place, publisher, year, edition, pages
Springer Nature, 2024
Keywords
ATTRv amyloidosis, Brain, Central nervous system, Cognition, Transthyretin
National Category
Neurosciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-232525 (URN)10.1007/s10072-024-07846-5 (DOI)001350648800002 ()39499456 (PubMedID)2-s2.0-85208191427 (Scopus ID)
Funder
Region Västerbotten
Available from: 2024-12-03 Created: 2024-12-03 Last updated: 2024-12-03
Grefve, J., Söderkvist, K., Gunnlaugsson, A., Sandgren, K., Jonsson, J., Keeratijarut Lindberg, A., . . . Nyholm, T. (2024). Histopathology-validated gross tumor volume delineations of intraprostatic lesions using PSMA-positron emission tomography/multiparametric magnetic resonance imaging. Physics and Imaging in Radiation Oncology, 31, Article ID 100633.
Open this publication in new window or tab >>Histopathology-validated gross tumor volume delineations of intraprostatic lesions using PSMA-positron emission tomography/multiparametric magnetic resonance imaging
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2024 (English)In: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 31, article id 100633Article in journal (Refereed) Published
Abstract [en]

Background and purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions.

Material and methods: The study participants were examined with [68Ga]PSMA-PET/mpMRI prior to radical prostatectomy. Four radiation oncologists delineated GTVs in 15 study participants, on four different image types; T2-weighted (T2w), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and PSMA-PET scans separately. The simultaneous truth and performance level estimation (STAPLE) algorithm was used to generate combined GTVs. GTVs were subsequently compared to histopathology. We analysed how Dice similarity coefficient (DSC) and lesion coverage are affected by using single versus multiple image types as well as by adding a clinical target volume (CTV) margin.

Results: Median DSC (STAPLE) for different GTVs varied between 0.33 and 0.52. GTVPSMA-PET/mpMRI generated the highest median lesion coverage at 0.66. Combining different image types achieved similar lesion coverage as adding a CTV margin to contours from a single image type, while reducing non-malignant tissue inclusion within the target volume.

Conclusion: The combined use of mpMRI or PSMA-PET/mpMRI shows promise, achieving higher DSC and lesion coverage while minimizing non-malignant tissue inclusion, in comparison to the use of a single image type with an added CTV margin.

Place, publisher, year, edition, pages
Elsevier, 2024
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-229329 (URN)10.1016/j.phro.2024.100633 (DOI)2-s2.0-85202586079 (Scopus ID)
Funder
Swedish Cancer SocietyCancerforskningsfonden i NorrlandProstatacancerförbundetRegion Västerbotten
Available from: 2024-09-13 Created: 2024-09-13 Last updated: 2024-09-13Bibliographically approved
Young, P., Heeman, F., Axelsson, J., Collij, L. E., Hitzel, A., Sanaat, A., . . . Schöll, M. (2024). Impact of simulated reduced injected dose on the assessment of amyloid PET scans. European Journal of Nuclear Medicine and Molecular Imaging, 51(3), 734-748
Open this publication in new window or tab >>Impact of simulated reduced injected dose on the assessment of amyloid PET scans
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2024 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 51, no 3, p. 734-748Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben.

Methods: Cognitively impaired and unimpaired individuals (N = 250, 36% Aβ-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90–110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aβ-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aβ- and Aβ + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated.

Results: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were < 1.5%. AUCs for discriminating Aβ- from Aβ + scans were high (AUC ≥ 0.94) across dose levels, and visual assessment showed intra-reader agreement of > 80% for both tracers.

Conclusion: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.

Keywords
Alzheimer’s disease, Amyloid, Dose reduction, Neuroimaging, PET
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-216200 (URN)10.1007/s00259-023-06481-0 (DOI)37897616 (PubMedID)2-s2.0-85175066219 (Scopus ID)
Funder
University of Gothenburg
Available from: 2023-11-07 Created: 2023-11-07 Last updated: 2024-05-02Bibliographically approved
Karalija, N., Papenberg, G., Johansson, J., Wåhlin, A., Salami, A., Andersson, M., . . . Nyberg, L. (2024). Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline. Neurobiology of Aging, 136, 125-132
Open this publication in new window or tab >>Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
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2024 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 136, p. 125-132Article in journal (Refereed) Published
Abstract [en]

Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64–68 years; 5-year follow-up: n = 129) who underwent positron emission tomography with 11C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.

Keywords
11C-raclopride, Aging, Dopamine D2-like receptor, Longitudinal, Magnetic resonance imaging, Positron emission tomography, Working memory
National Category
Geriatrics
Identifiers
urn:nbn:se:umu:diva-221540 (URN)10.1016/j.neurobiolaging.2024.02.001 (DOI)38359585 (PubMedID)2-s2.0-85185304249 (Scopus ID)
Funder
Swedish Research Council, 421-2012-648Swedish Research Council, 2017-02217Swedish Research Council, 2022-01804Umeå UniversityKnut and Alice Wallenberg Foundation, 2015.0277Jonas and Christina af Jochnick FoundationAlzheimerfonden, AF-967710Riksbankens Jubileumsfond, P20-0779Region Västerbotten
Available from: 2024-03-15 Created: 2024-03-15 Last updated: 2024-03-15Bibliographically approved
Papenberg, G., Karalija, N., Johansson, J., Andersson, M., Axelsson, J., Riklund, K., . . . Bäckman, L. (2024). The influence of hippocampal dopamine D2 receptor losses on episodic-memory decline across 5 years is moderated by BDNF and KIBRA polymorphisms. Cortex, 176, 53-61
Open this publication in new window or tab >>The influence of hippocampal dopamine D2 receptor losses on episodic-memory decline across 5 years is moderated by BDNF and KIBRA polymorphisms
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2024 (English)In: Cortex, ISSN 0010-9452, E-ISSN 1973-8102, Vol. 176, p. 53-61Article in journal (Refereed) Published
Abstract [en]

Losses in dopamine (DA) functioning may contribute to aging-related decline in cognition. Hippocampal DA is necessary for successful episodic memory formation. Previously, we reported that higher DA D2 receptor (D2DR) availability in hippocampus is beneficial for episodic memory only in older carriers of more advantageous genotypes of well-established plasticity-related genetic variations, the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. Extending our observations to the longitudinal level, the current data show that individuals with one or no beneficial BDNF and KIBRA genotype (n = 80) decline more in episodic memory across five years, without any contribution of losses in hippocampal D2DR availability to memory decline. Although carriers of two beneficial genotypes (n = 39) did not decline overall in episodic memory, losses of hippocampal D2DR availability were predictive of episodic-memory decline among these individuals. Our findings have implications for interventions targeting DA modulation to enhance episodic memory in aging, which may not benefit all older individuals.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
BNDF, Dopamine D2 receptors, Episodic memory, Inter-individual differences, KIBRA, Longitudinal, [11C]raclopride
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-224932 (URN)10.1016/j.cortex.2024.01.014 (DOI)38749085 (PubMedID)2-s2.0-85192831317 (Scopus ID)
Funder
Swedish Research CouncilRegion VästerbottenKnut and Alice Wallenberg FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseJonas and Christina af Jochnick FoundationThe Swedish Brain FoundationRegion VästerbottenMax Planck SocietyGerman Research Foundation (DFG)
Available from: 2024-05-30 Created: 2024-05-30 Last updated: 2024-05-30Bibliographically approved
Renman, D., van Guelpen, B., Anderson, F., Axelsson, J., Riklund, K., Strigård, K., . . . Gylling, B. (2023). Association of pre-diagnostic physical exercise and peri-diagnostic body composition with mortality in non-metastatic colorectal cancer. International Journal of Colorectal Disease, 38(1), Article ID 239.
Open this publication in new window or tab >>Association of pre-diagnostic physical exercise and peri-diagnostic body composition with mortality in non-metastatic colorectal cancer
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2023 (English)In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 38, no 1, article id 239Article in journal (Refereed) Published
Abstract [en]

Purpose: Sarcopenia and myosteatosis, quantified via computed tomography (CT), are associated with poor colorectal cancer outcomes. These body composition estimates can be influenced by physical exercise. We explored the correlation between pre-diagnostic physical exercise, body composition close to diagnosis, and the combined prognosis impact of these factors.

Methods: We studied 519 stage I–III colorectal cancer (CRC) cases diagnosed 2000–2016 with pre-diagnostic self-reported recreational physical exercise data collected in the prospective, population-based Northern Sweden Health and Disease Study, and CT-estimated skeletal muscle index (SMI) or skeletal muscle density (SMD). Risk estimates were calculated by multivariable logistic regression and Cox proportional hazards models.

Results: No association was seen between low pre-diagnostic physical exercise and sarcopenia/myosteatosis in the multivariable model adjusted for age, sex, educational level, tumor stage, and tumor location. In multivariable Cox regression models, the combination of low pre-diagnostic physical exercise and either sarcopenia or myosteatosis at the time of diagnosis was associated with cancer-specific mortality compared to the reference group of high physical exercise combined with no sarcopenia/myosteatosis (adjusted HR 1.94 95% CI 1.00–3.76 for sarcopenia and adjusted HR 2.39 95% CI 1.16–4.94 for myosteatosis).

Conclusions: The combined presence of low pre-diagnostic physical exercise and sarcopenia or myosteatosis was associated with increased CRC-specific mortality. Despite the positive effect on prognosis, physical exercise did not alter body composition estimates at diagnosis, which could indicate attenuation from other factors.

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Colorectal cancer, Exercise, Myosteatosis, Physical activity, Sarcopenia
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-215081 (URN)10.1007/s00384-023-04536-0 (DOI)37755537 (PubMedID)2-s2.0-85172659066 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, AMP 20-999Visare Norr, 967732Region Västerbotten, ALF RV-968855Region Västerbotten, ALF RV-982739
Available from: 2023-10-13 Created: 2023-10-13 Last updated: 2024-02-08Bibliographically approved
Leffler, K., Tommaso Luppino, L., Kuttner, S. & Axelsson, J. (2023). Deep learning-based filling of incomplete sinograms from low-cost, long axial field-of-view PET scanners with inter-detector gaps. In: The international networking symposiumon artificial intelligence and informatics in nuclear medicine: Program book. Paper presented at International Symposium on Artificial Intelligence and Informatics in Nuclear Medicine, Groningen, Netherlands, October 9-11, 2023. (pp. 59-59). University Medical Center Groningen
Open this publication in new window or tab >>Deep learning-based filling of incomplete sinograms from low-cost, long axial field-of-view PET scanners with inter-detector gaps
2023 (English)In: The international networking symposiumon artificial intelligence and informatics in nuclear medicine: Program book, University Medical Center Groningen , 2023, p. 59-59Conference paper, Oral presentation with published abstract (Refereed)
Place, publisher, year, edition, pages
University Medical Center Groningen, 2023
Keywords
positron emission tomography (PET), sparse PET, deep learning - artificial intelligence, residual U-net, gap filling, long axial field of view PET, total body PET
National Category
Medical Imaging Computational Mathematics Computer graphics and computer vision
Research subject
Mathematical Statistics
Identifiers
urn:nbn:se:umu:diva-224909 (URN)
Conference
International Symposium on Artificial Intelligence and Informatics in Nuclear Medicine, Groningen, Netherlands, October 9-11, 2023.
Funder
Swedish Research Council, 340-2013-5342
Available from: 2024-05-24 Created: 2024-05-24 Last updated: 2025-02-09Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3731-3612

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