Publications by authors named "Jacob Horsager"

14 Publications

  • Page 1 of 1

Fasting gallbladder volume is increased in patients with Parkinson's disease.

Parkinsonism Relat Disord 2021 Apr 30;87:56-60. Epub 2021 Apr 30.

Department of Nuclear Medicine and PET, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, J220, 8200, Aarhus N, Denmark.

Introduction: Autonomic denervation in patients with Parkinson's disease (PD) and isolated REM-sleep behavior disorder (iRBD) could impede gallbladder function leading to increased fasting gallbladder volume (fGBV) and higher risk of gallstones. We aimed to determine fGBV in patients with PD, iRBD, and healthy controls (HCs).

Methods: We included 189 subjects; 100 patients with PD, 21 with iRBD, and 68 HCs. fGBV was determined from abdominal CT scans, and radiopaque gallstone frequency was evaluated.

Results: Median fGBV was 35.7 ml in patients with PD, 31.8 ml in iRBD, and 27.8 ml in HCs (Kruskal-Wallis test: P = 0.0055). Post-tests adjusted for multiple comparison revealed a significant group difference between patients with PD and HCs (P = 0.0038). In the PD group, 23% had enlarged fGBV (cut-off at mean + 2 x standard deviation (SD) in the HC group). No difference in fGBV was observed between iRBD and the other two groups. The total prevalence of gallstones was 6.4% with no differences between the three groups.

Conclusion: Almost a quarter of patients with PD in our cohort exhibited increased fGBV. This study illuminates a potentially overlooked topic in PD research and calls for more studies on biliary dysfunction.
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http://dx.doi.org/10.1016/j.parkreldis.2021.04.027DOI Listing
April 2021

Reduced Synaptic Density in Patients with Lewy Body Dementia: An [ C]UCB-J PET Imaging Study.

Mov Disord 2021 Apr 25. Epub 2021 Apr 25.

Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.

Background: Patients with Parkinson's disease (PD) often develop dementia, but the underlying substrate is incompletely understood. Generalized synaptic degeneration may contribute to dysfunction and cognitive decline in Lewy body dementias, but in vivo evidence is lacking.

Objective: The objective of this study was to assess the density of synapses in non-demented PD (nPD) subjects (N = 21), patients with PD-dementia or Dementia with Lewy bodies (DLB) (N = 13), and age-matched healthy controls (N = 15).

Method: Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [11C]UCB-J, SUVR-1 values were obtained for 12 pre-defined regions. Volumes-of-interest were defined on MRI T1 scans. Voxel-level between-group comparisons of [11C]UCB-J SUVR-1 were performed. All subjects underwent neuropsychological assessment. Correlations between [11C]UCB- J PET and domain-specific cognitive functioning were examined.

Results: nPD patients only demonstrated significantly reduced SUVR-1 values in the substantia nigra (SN) compared to HC. DLB/PDD patients demonstrated reduced SUVR-1 values in SN and all cortical VOIs except for the hippocampus and amygdala. The voxel-based analysis supported the VOI results. Significant correlation was seen between middle frontal gyrus [11C]UCB-J SUVR-1 and performance on tests of executive function.

Conclusion: Widespread cortical reduction of synaptic density was documented in a cohort of DLB/PDD subjects using in vivo [11C]UCB-J PET. Our study confirms previously reported synaptic loss in SN of nPD patients. [11C]UCB-J binding in selected cortical VOIs of the DLB/PDD patients correlated with their levels of cognitive function across relevant neuropsychological domains. These findings suggest that the loss of synaptic density contributes to cognitive impairment in nPD and DLB/PDD. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28617DOI Listing
April 2021

Prodromal Parkinson disease subtypes - key to understanding heterogeneity.

Nat Rev Neurol 2021 Jun 20;17(6):349-361. Epub 2021 Apr 20.

Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.

In Parkinson disease (PD), pathological processes and neurodegeneration begin long before the cardinal motor symptoms develop and enable clinical diagnosis. In this prodromal phase, risk and prodromal markers can be used to identify individuals who are likely to develop PD, as in the recently updated International Parkinson and Movement Disorders Society research criteria for prodromal PD. However, increasing evidence suggests that clinical and prodromal PD are heterogeneous, and can be classified into subtypes with different clinical manifestations, pathomechanisms and patterns of spatial and temporal progression in the CNS and PNS. Genetic, pathological and imaging markers, as well as motor and non-motor symptoms, might define prodromal subtypes of PD. Moreover, concomitant pathology or other factors, including amyloid-β and tau pathology, age and environmental factors, can cause variability in prodromal PD. Patients with REM sleep behaviour disorder (RBD) exhibit distinct patterns of α-synuclein pathology propagation and might indicate a body-first subtype rather than a brain-first subtype. Identification of prodromal PD subtypes and a full understanding of variability at this stage of the disease is crucial for early and accurate diagnosis and for targeting of neuroprotective interventions to ensure efficacy.
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http://dx.doi.org/10.1038/s41582-021-00486-9DOI Listing
June 2021

The Logic and Pitfalls of Parkinson's as Brain- Versus Body-First Subtypes.

Mov Disord 2021 03;36(3):785-786

Department of Nuclear Medicine & PET, Aarhus University Hospital, Aarhus, Denmark.

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http://dx.doi.org/10.1002/mds.28526DOI Listing
March 2021

Microsleep disturbances are associated with noradrenergic dysfunction in Parkinson's disease.

Sleep 2021 Feb 20. Epub 2021 Feb 20.

Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Köln, Germany.

Study Objectives: Parkinson's disease (PD) commonly involves degeneration of sleep-wake regulating brainstem nuclei; likewise, sleep-wake disturbances are highly prevalent in PD patients. As polysomnography macroparameters typically show only minor changes in PD, we investigated sleep microstructure, particularly cyclic alternating pattern (CAP), and its relation to alterations of the noradrenergic system in these patients.

Methods: We analysed 27 PD patients and 13 healthy control (HC) subjects who underwent over-night polysomnography and 11C-MeNER positron emission tomography for evaluation of noradrenaline transporter density. Sleep macroparameters as well as CAP metrics were evaluated according to the consensus statement from 2001. Statistical analysis comprised group comparisons and correlation analysis of CAP metrics with clinical characteristics of PD patients as well as noradrenaline transporter density.

Results: PD patients and HC subjects were comparable in demographic characteristics (age, sex, body mass index) and polysomnography macroparameters. CAP rate as well as A index differed significantly between groups, with PD patients having a lower CAP rate (46.7 ± 6.6% versus 38.0 ± 11.6%, p = 0.015) and lower A index (49.0 ± 8.7/hour versus 40.1 ± 15.4/hour, p = 0.042). In PD patients, both CAP metrics correlated significantly with diminished noradrenaline transporter density in arousal prompting brainstem nuclei (locus coeruleus, raphe nuclei) as well as arousal propagating brain structures like thalamus and bitemporal cortex.

Conclusions: Sleep microstructure is more severely altered than sleep macrostructure in PD patients and is associated with widespread dysfunction of the noradrenergic arousal system.
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http://dx.doi.org/10.1093/sleep/zsab040DOI Listing
February 2021

Gastrointestinal Dysfunction in Parkinson's Disease.

J Clin Med 2021 Jan 31;10(3). Epub 2021 Jan 31.

Department of Nuclear Medicine & PET, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, J220, 8200 Aarhus N, Denmark.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Patients show deposits of pathological, aggregated α-synuclein not only in the brain but throughout almost the entire length of the digestive tract. This gives rise to non-motor symptoms particularly within the gastrointestinal tract and patients experience a wide range of frequent and burdensome symptoms such as dysphagia, bloating, and constipation. Recent evidence suggests that progressive accumulation of gastrointestinal pathology is underway several years before a clinical diagnosis of PD. Notably, constipation has been shown to increase the risk of developing PD and in contrast, truncal vagotomy seems to decrease the risk of PD. Animal models have demonstrated gut-to-brain spreading of pathological α-synuclein and it is currently being intensely studied whether PD begins in the gut of some patients. Gastrointestinal symptoms in PD have been investigated by the use of several different questionnaires. However, there is limited correspondence between subjective gastrointestinal symptoms and objective dysfunction along the gastrointestinal tract, and often the magnitude of dysfunction is underestimated by the use of questionnaires. Therefore, objective measures are important tools to clarify the degree of dysfunction in future studies of PD. Here, we summarize the types and prevalence of subjective gastrointestinal symptoms and objective dysfunction in PD. The potential importance of the gastrointestinal tract in the etiopathogenesis of PD is briefly discussed.
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http://dx.doi.org/10.3390/jcm10030493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866791PMC
January 2021

Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study.

Brain 2020 10;143(10):3077-3088

Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.

Parkinson's disease is characterized by the presence of abnormal, intraneuronal α-synuclein aggregates, which may propagate from cell-to-cell in a prion-like manner. However, it remains uncertain where the initial α-synuclein aggregates originate. We have hypothesized that Parkinson's disease comprises two subtypes. A brain-first (top-down) type, where α-synuclein pathology initially arises in the brain with secondary spreading to the peripheral autonomic nervous system; and a body-first (bottom-up) type, where the pathology originates in the enteric or peripheral autonomic nervous system and then spreads to the brain. We also hypothesized that isolated REM sleep behaviour disorder (iRBD) is a prodromal phenotype for the body-first type. Using multimodal imaging, we tested the hypothesis by quantifying neuronal dysfunction in structures corresponding to Braak stages I, II and III involvement in three distinct patient groups. We included 37 consecutive de novo patients with Parkinson's disease into this case-control PET study. Patients with Parkinson's disease were divided into 24 RBD-negative (PDRBD-) and 13 RBD-positive cases (PDRBD+) and a comparator group of 22 iRBD patients. We used 11C-donepezil PET/CT to assess cholinergic (parasympathetic) innervation, 123I-metaiodobenzylguanidine (MIBG) scintigraphy to measure cardiac sympathetic innervation, neuromelanin-sensitive MRI to measure the integrity of locus coeruleus pigmented neurons, and 18F-dihydroxyphenylalanine (FDOPA) PET to assess putaminal dopamine storage capacity. Colon volume and transit times were assessed with CT scans and radiopaque markers. Imaging data from the three groups were interrogated with ANOVA and Kruskal-Wallis tests corrected for multiple comparisons. The PDRBD- and PDRBD+ groups showed similar marked reductions in putaminal FDOPA-specific uptake, whereas two-thirds of iRBD patients had normal scans (P < 10-13, ANOVA). When compared to the PDRBD- patients, the PDRBD+ and iRBD patients showed reduced mean MIBG heart:mediastinum ratios (P < 10-5, ANOVA) and colon 11C-donepezil standard uptake values (P = 0.008, ANOVA). The PDRBD+ group trended towards a reduced mean MRI locus coeruleus: pons ratio compared to PDRBD- (P = 0.07, t-test). In comparison to the other groups, the PDRBD+ group also had enlarged colon volumes (P < 0.001, ANOVA) and delayed colonic transit times (P = 0.01, Kruskal-Wallis). The combined iRBD and PDRBD+ patient data were compatible with a body-first trajectory, characterized by initial loss of cardiac MIBG signal and 11C-colonic donepezil signal followed by loss of putaminal FDOPA uptake. In contrast, the PDRBD- data were compatible with a brain-first trajectory, characterized by primary loss of putaminal FDOPA uptake followed by a secondary loss of cardiac MIBG signal and 11C-donepezil signal. These findings support the existence of brain-first and body-first subtypes of Parkinson's disease.
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http://dx.doi.org/10.1093/brain/awaa238DOI Listing
October 2020

Obeticholic acid improves hepatic bile acid excretion in patients with primary biliary cholangitis.

J Hepatol 2021 Jan 25;74(1):58-65. Epub 2020 Jul 25.

Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark. Electronic address:

Background & Aims: Obeticholic acid (OCA) is an agonist of the nuclear bile acid receptor farnesoid X receptor, which regulates hepatic bile acid metabolism. We tested whether OCA treatment would influence hepatic transport of conjugated bile acids in patients with primary biliary cholangitis (PBC) who responded inadequately to treatment with ursodeoxycholic acid (UDCA).

Methods: Eight UDCA-treated patients with PBC with alkaline phosphatase ≥1.5 times the upper limit of normal range participated in a double-blind, placebo-controlled study. While continuing on UDCA, the patients were randomised to two 3-month crossover treatment periods with placebo and OCA, in random order, separated by a 1-month washout period without study treatment. After each of the two treatment periods, we determined rate constants for transport of conjugated bile acids between blood, hepatocytes, biliary canaliculi, and bile ducts by positron emission tomography of the liver using the conjugated bile acid tracer [N-methyl-C]cholylsarcosine (C-CSar). The hepatic blood perfusion was measured using infusion of indocyanine green and Fick's principle.

Results: Compared with placebo, OCA increased hepatic blood perfusion by a median of 11% (p = 0.045), the unidirectional uptake clearance of C-CSar from blood into hepatocytes by a median of 11% (p = 0.01), and the rate constant for secretion of C-CSar from hepatocytes into biliary canaliculi by a median of 73% (p = 0.03). This resulted in an OCA-induced decrease in the hepatocyte residence time of C-CSar by a median of 30% (p = 0.01), from group median 11 min to 8 min.

Conclusions: This study of UDCA-treated patients with PBC showed that, compared with placebo, OCA increased the hepatic transport of the conjugated bile acid tracer C-CSar, and thus endogenous conjugated bile acids, from hepatocytes into biliary canaliculi. As a result, OCA reduced the time hepatocytes are exposed to potentially cytotoxic bile acids.

Lay Summary: Primary biliary cholangitis is a chronic liver disease in which the small bile ducts are progressively destroyed. We tested whether the treatment with obeticholic acid (OCA) would improve liver excretion of bile acids compared with placebo in 8 patients with primary biliary cholangitis. A special scanning technique (PET scan) showed that OCA increased the transport of bile acids from blood to bile. OCA thereby reduced the time that potentially toxic bile acids reside in the liver by approximately one-third.
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http://dx.doi.org/10.1016/j.jhep.2020.07.028DOI Listing
January 2021

Human biodistribution, dosimetry, radiosynthesis and quality control of the bile acid PET tracer [N-methyl-C]cholylsarcosine.

Nucl Med Biol 2019 May - Jun;72-73:55-61. Epub 2019 Jul 12.

Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark.

Introduction: [N-methyl-C]cholylsarcosine ([C]CSar) is a tracer for imaging and quantitative assessment of intrahepatic cholestatic liver diseases and drug-induced cholestasis by positron emission tomography (PET). The purpose of this study is to determine whole-body biodistribution and dosimetry of [C]CSar in healthy humans. The results are compared with findings in a patient with primary sclerosing cholangitis (PSC) and a patient with primary biliary cholangitis (PBC) as well as with preclinical findings in pigs. Radiosynthesis and quality control for preparation of [C]CSar for clinical use are also presented.

Methods: Radiosynthesis and quality control of [C]CSar were set up in compliance with Danish/European regulations. Both healthy participants (3 females, 3 males) and patients underwent whole-body PET/CT to determine the biodistribution of [C]CSar. The two patients were under treatment with ursodeoxycholic acid at the time of the study. Dosimetry was estimated from the PET data using the Olinda 2.0 software.

Results: The radiosynthesis provided [C]CSar in a solution ready for injection. The biodistribution studies revealed that gallbladder wall, small intestine, and liver were critical organs in both healthy participants and patients with the gallbladder wall receiving the highest dose (up to 0.5 mGy/MBq). The gender-averaged (±SD) effective dose for the healthy participants was 6.2 ± 1.4 μSv/MBq. The effective dose for the PSC and the PBC patient was 5.2 and 7.0 μSv/MBq, respectively.

Conclusion: A radiosynthesis for preparation of [C]CSar for clinical use was developed and approved by the Danish Medicines Agency. The most critical organ was the gallbladder wall although the amount of [C]CSar in the gallbladder was found to vary significantly between individuals. The estimated effective dose for humans was comparable to that estimated in anesthetized pigs although the absorbed dose estimates to some organs, such as the stomach, was different. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: [C]CSar PET/CT enables detailed quantitative assessment of patients with cholestatic liver disease by tracing the separate hepatobiliary transport steps of endogenous bile acids. The present work offers a radiosynthetic method and dosimetry data suitable for clinical implementation of [C]CSar.
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http://dx.doi.org/10.1016/j.nucmedbio.2019.07.006DOI Listing
May 2020

Prognostic modeling for patients with colorectal liver metastases incorporating FDG PET radiomic features.

Eur J Radiol 2019 Apr 8;113:101-109. Epub 2019 Feb 8.

Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark.

Objective: We aimed to improve prediction of outcome for patients with colorectal liver metastases, via prognostic models incorporating PET-derived measures, including radiomic features that move beyond conventional standard uptake value (SUV) measures.

Patients And Methods: A range of parameters including volumetric and heterogeneity measures were derived from FDG PET images of 52 patients with colorectal intrahepatic-only metastases (29 males and 23 females; mean age 62.9 years [SD 9.8; range 32-82]). The patients underwent PET/CT imaging as part of the clinical workup prior to final decision on treatment. Univariate and multivariate models were implemented, which included statistical considerations (to discourage false discovery and overfitting), to predict overall survival (OS), progression-free survival (PFS) and event-free survival (EFS). Kaplan-Meier survival analyses were performed, where the subjects were divided into high-risk and low-risk groups, from which the hazard ratios (HR) were computed via Cox proportional hazards regression.

Results: Commonly-invoked SUV metrics performed relatively poorly for different prediction tasks (SUVmax HR = 1.48, 0.83 and 1.16; SUVpeak HR = 2.05, 1.93, and 1.64, for OS, PFS and EFS, respectively). By contrast, the number of liver metastases and metabolic tumor volume (MTV) each performed well (with respective HR values of 2.71, 2.61 and 2.42, and 2.62, 1.96 and 2.29, for OS, PFS and EFS). Total lesion glycolysis (TLG) also resulted in similar performance as MTV. Multivariate prognostic modeling incorporating different features (including those quantifying intra-tumor heterogeneity) resulted in further enhanced prediction. Specifically, HR values of 4.29, 4.02 and 3.20 (p-values = 0.00004, 0.0019 and 0.0002) were obtained for OS, PFS and EFS, respectively.

Conclusions: PET-derived measures beyond commonly invoked SUV parameters hold significant potential towards improved prediction of clinical outcome in patients with liver metastases, especially when utilizing multivariate models.
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http://dx.doi.org/10.1016/j.ejrad.2019.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507885PMC
April 2019

Cardiac C-Donepezil Binding Increases With Age in Healthy Humans: Potentially Signifying Sigma-1 Receptor Upregulation.

J Cardiovasc Pharmacol Ther 2019 07 26;24(4):365-370. Epub 2019 Mar 26.

1 Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark.

Background: Donepezil may have cardioprotective properties, but the mechanism is unclear. Using positron-emission tomography (PET), we explored C-donepezil uptake in the heart of humans in relation to age. The results are discussed in the context of the cardioprotective property of donepezil.

Methods: We included data from 57 patients with cardiac C-donepezil PET scans. Linear regression analyses were performed to explore the correlation between cardiac C-donepezil standardized uptake value (SUV) and age. Subgroup analyses were performed for healthy controls, patients with prodromal or diagnosed Parkinson disease (PD), males, and females.

Results: In the total group of 57 patients, linear regression analysis revealed a significant positive correlation between cardiac C-donepezil uptake and age ( r = .63, P < .0001). The average increase was ≈1.25 SUV per decade and a 2-fold increase in SUV from age 30 to 65 years. Subgroup analyses also showed significant correlations: healthy control patients alone (n = 28, r = .73, P < .0001), prodromal or diagnosed PD (n = 29, r = .28, P = .03), male patients (n = 34, r = .49, P < .0001), and female patients (n = 23, r = .82, P < .0001). No other organs showed increased C-donepezil binding with age.

Conclusions: C-donepezil SUV increases robustly with age in the normal human heart. We speculate that the increased donepezil binding is caused primarily by sigma-1 receptor upregulation. If our interpretation is correct, it shows that sigma-1 receptors are dynamically regulated and may represent an overlooked target for pharmacological intervention studies.
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http://dx.doi.org/10.1177/1074248419838509DOI Listing
July 2019

Hepatic metabolism of C-methionine and secretion of C-protein measured by PET in pigs.

Am J Nucl Med Mol Imaging 2017 1;7(4):167-173. Epub 2017 Sep 1.

Department of Nuclear Medicine and PET Centre, Aarhus University HospitalAarhus, Denmark.

Hepatic amino acid metabolism and protein secretion are essential liver functions that may be altered during metabolic stress, e.g. after surgery. We wished to develop a dynamic liver PET method using the radiolabeled amino acid C-methionine to examine this question. Eleven 40-kg pigs were allocated to either laparotomy or pneumoperitoneum. 24 hours after surgery a 70-min dynamic PET scanning of the liver with arterial blood sampling was performed immediately after intravenous injection of C-methionine. Time course of arterial plasma C-methionine concentration was used as input function and that of liver tissue C-concentration as output function in an extended Patlak analysis that accounted for irreversible metabolism of C-methionine (hepatic systemic metabolic clearance ) and secretion of C-protein + C-metabolites into blood (rate constant ). Appearance of C-proteins in arterial plasma was measured during the experiment. There were no statistically significant differences between the laparotomy group and the pneumoperitoneum group in any of the calculated parameters. Average mean hepatic systemic metabolic clearance was 0.212 mL plasma/mL liver tissue/min, secretion rate constant from liver to blood 0.0054 min, flux of methionine 3.59 μmol methionine/mL liver tissue/min, and the appearance rate of C-proteins in plasma 0.048 kBq/mL plasma/min. There was significant correlation between and . In conclusion, the hepatic systemic metabolic clearance of C-methionine was significantly correlated to the appearance rate of C-proteins in plasma. It would be interesting to translate the present method to human studies for the development of a clinical quantitative test of hepatic protein secretion.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596319PMC
September 2017

Optimal 2-[(18)F]fluoro-2-deoxy-D-galactose PET/CT protocol for detection of hepatocellular carcinoma.

EJNMMI Res 2016 Dec 24;6(1):56. Epub 2016 Jun 24.

Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, DK8000, Aarhus, Denmark.

Background: Positron emission tomography (PET) with the liver-specific galactose tracer 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) may improve diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to test which of three different (18)F-FDGal PET protocols gives the highest tumour-to-background (T/B) ratio on PET images and thus better detection of HCC tumours.

Methods: Ten patients with a total of 15 hepatic HCC tumours were enrolled prior to treatment. An experienced radiologist defined volumes of interest (VOIs) encircling HCC tumours on contrast-enhanced CT (ce-CT) images. Three PET/CT protocols were conducted following an intravenous (18)F-FDGal injection: (i) a 20-min dynamic PET/CT of the liver (to generate a 3D metabolic image), (ii) a traditional static whole-body PET/CT after 1 h, and (iii) a late static whole-body PET/CT after 2 or 3 h. PET images from each PET/CT protocol were fused with ce-CT images, and the average standardized uptake values (SUV) in tumour and background liver tissue were used to calculate (T/B) ratios. Furthermore, Tpeak/B ratios were calculated using the five hottest voxels in all hot tumours. The ratios for the three different PET protocols were compared.

Results: For the individual tumours, there was no significant difference in the T/B ratio between the three PET protocols. The metabolic image yielded higher Tpeak/B ratios than the two static images, but it was easier to identify tumours on the static images. One extrahepatic metastasis was detected.

Conclusions: Neither metabolic images nor static whole-body images acquired 2 or 3 h after (18)F-FDGal injection offered an advantage to traditional whole-body PET/CT images acquired after 1 h for detection of HCC.
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http://dx.doi.org/10.1186/s13550-016-0206-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920802PMC
December 2016

Metabolic liver function measured in vivo by dynamic (18)F-FDGal PET/CT without arterial blood sampling.

EJNMMI Res 2015 14;5:32. Epub 2015 May 14.

Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, DK-8000 Aarhus, Denmark ; Department of Hepatology & Gastroenterology, Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus C, Denmark.

Background: Metabolic liver function can be measured by dynamic PET/CT with the radio-labelled galactose-analogue 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) in terms of hepatic systemic clearance of (18)F-FDGal (K, ml blood/ml liver tissue/min). The method requires arterial blood sampling from a radial artery (arterial input function), and the aim of this study was to develop a method for extracting an image-derived, non-invasive input function from a volume of interest (VOI).

Methods: Dynamic (18)F-FDGal PET/CT data from 16 subjects without liver disease (healthy subjects) and 16 patients with liver cirrhosis were included in the study. Five different input VOIs were tested: four in the abdominal aorta and one in the left ventricle of the heart. Arterial input function from manual blood sampling was available for all subjects. K*-values were calculated using time-activity curves (TACs) from each VOI as input and compared to the K-value calculated using arterial blood samples as input. Each input VOI was tested on PET data reconstructed with and without resolution modelling.

Results: All five image-derived input VOIs yielded K*-values that correlated significantly with K calculated using arterial blood samples. Furthermore, TACs from two different VOIs yielded K*-values that did not statistically deviate from K calculated using arterial blood samples. A semicircle drawn in the posterior part of the abdominal aorta was the only VOI that was successful for both healthy subjects and patients as well as for PET data reconstructed with and without resolution modelling.

Conclusions: Metabolic liver function using (18)F-FDGal PET/CT can be measured without arterial blood samples by using input data from a semicircle VOI drawn in the posterior part of the abdominal aorta.
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http://dx.doi.org/10.1186/s13550-015-0110-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444932PMC
June 2015