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The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via 18F-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (− 8.4%, P = 0.032 vs 15.7%, P P vs 19.1%, P P = 0.024) after adjusting for study design but not BAT volume (β: 0.39, 95% CI [− 0.01–0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.

Head motion is one of the major reasons for artefacts in Magnetic Resonance Imaging (MRI), which is especially challenging for children who are often intimidated by the dimensions of the MR scanner. In order to optimise the MRI acquisition for children in the clinical setting, insights into children's motion patterns are essential. In this work, we analyse motion data from 61 pediatric patients. We compare structural MRI data of children imaged with and without general anaesthesia (GA), all scanned using the same hybrid PET/MR scanner. We analyse several metrics of motion based on the displacement relative to a reference, decompose the transformation matrix into translation and rotation, as well as investigate how different regions in the brain are affected by motion. Head motion for children without GA was significantly higher (mean displacement of $2.19 \pm 0.93$ mm (median $\pm$ standard deviation) during $41.7 \pm 7.5$ min scans); however, even anaesthetised children showed substantial residual head motion (mean displacement of $1.12 \pm 0.35$ mm). For both patient groups translation along the z-axis (along the scanner bore) was significantly larger in absolute terms (GA / no GA: $0.87 \pm 0.29$ mm / $0.92 \pm 0.49$ mm) compared to the other directions. Considering directionality, both patient groups were moving in negative z-direction and thus, out of the scanner. The awake children additionally showed significantly more nodding rotation ($0.33 \pm 0.20~^{\circ}$). Consequently, in future studies as well as in the clinical setting, these predominant types of motion need to be taken into consideration to limit artefacts and reduce re-scans due to poor image quality.

Dorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it is unknown if dorsal striatal dopamine hyperactivity is the cause or consequence of changes elsewhere in the CSTC circuit. Classical pharmacological and neurotoxic manipulations of the CSTC and other brain circuits suffer from various drawbacks related to off-target effects and adaptive changes. Chemogenetics, on the other hand, enables a highly selective targeting of specific neuronal populations within a given circuit. In this study, we developed a chemogenetic method for selective activation of dopamine neurons in the substantia nigra, which innervates the dorsal striatum in the rat. We used this model to investigate effects of targeted dopamine activation on CSTC circuit function, especially in fronto-cortical regions. We found that chemogenetic activation of these neurons increased movement (as expected with increased dopamine release), rearings and time spent in center, while also lower self-grooming. Furthermore, this activation increased prepulse inhibition of the startle response in females. Remarkably, we observed reduced [18F]FDG metabolism in the frontal cortex, following dopamine activation in the dorsal striatum, while total glutamate levels- in this region were increased. This result is in accord with clinical studies of increased [18F]FDG metabolism and lower glutamate levels in similar regions of the brain of people with OCD. Taken together, the present chemogenetic model adds a mechanistic basis with behavioral and translational relevance to prior clinical neuroimaging studies showing deficits in fronto-cortical glucose metabolism across a variety of clinical populations (e.g. addiction, risky decision-making, compulsivity or obesity).

Dorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it is unknown if dorsal striatal dopamine hyperactivity is the cause or consequence of changes elsewhere in the CSTC circuit. Classical pharmacological and neurotoxic manipulations of the CSTC and other brain circuits suffer from various drawbacks related to off-target effects and adaptive changes. Chemogenetics, on the other hand, enables a highly selective targeting of specific neuronal populations within a given circuit. In this study, we developed a chemogenetic method for selective activation of dopamine neurons in the substantia nigra, which innervating the rat dorsal striatum. We used this model to investigate effects of targeted dopamine activation on CSTC circuit function, especially in fronto-cortical regions. We found that chemogenetic activation of these neurons increased movement, as expected from dopamine release, rearings and time spend in center, while it also lowered self-grooming and increased prepulse inhibition in females. Remarkably, we observed reduced [18F]FDG metabolism in frontal cortex, following dopamine activation in the dorsal striatum, yet total glutamate levels-in this region were increased. A finding which may help explain the contradiction in some clinical studies of increased [18F]FDG metabolism and lower glutamate levels in diseases like OCD. Taken together, these results establish the importance of nigro-striatal dopamine transmission for modulating CSTC function, especially with respect to fronto-cortical activity, glutamate levels and behaviors related anxiety and compulsive actions.One Sentence SummaryDorsal striatum dopamine induce fronto-cortical hypoactivity and reduce compulsive behaviors in rats

Patients with Parkinson’s disease (PD) often suffer from non-motor symptoms, which may be caused by serotonergic dysfunction. Apart from alleviating the motor symptoms, Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) may also influence non-motor symptoms. The aim of this study is to investigate how turning DBS off affects the serotonergic system. We here exploit a novel functional PET neuroimaging methodology to evaluate the preservation of serotonergic neurons and capacity to release serotonin. We measured cerebral 5-HT1BR binding in 13 DBS-STN treated PD patients, at baseline and after turning DBS off. Ten age-matched volunteers served as controls. Clinical measures of motor symptoms were assessed under the two conditions and correlated to the PET measures of the static and dynamic integrity of the serotonergic system. PD patients exhibited a significant loss of frontal and parietal 5-HT1BR, and the loss was significantly correlated to motor symptom severity. We saw a corresponding release of serotonin, but only in brain regions with preserved 5-HT1BR, suggesting the presence of a presynaptic serotonergic deficit. Our study demonstrates that DBS-STN dynamically regulates the serotonin system in PD, and that preservation of serotonergic functions may be predictive of DBS-STN effects.

Plasma concentrations of the two pancreatic enzymes, amylase and lipase, are increased within the normal physiological range after initiation of glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment. An association between the use of GLR-1RA and incidence of acute pancreatitis or pancreatic cancer has not been found - neither in rodent studies nor in preclinical studies or in the large cardiovascular outcome trials with GLP-1RAs. The increased concentrations of pancreatic enzymes have been suggested to be explained by increased DNA or protein synthesis found in rodent and acinar cell studies. However, whether this translates into humans is unknown. We therefore investigated the effect of liraglutide, a GLP-1RA, on pancreatic volume, edema and DNA synthesis reflected by 18F-flourothymidine (FLT)-uptake using state-of-the-art positron emission tomography (PET)-magnetic resonance imaging (MRI) before initiation, after four weeks during titration of liraglutide and after six weeks during steady state on maximum dose of liraglutide 3.0 mg in 14 obese men (age 38 ± 3 years, BMI 32 ± 1 kg/m2) without diabetes. Plasma concentrations of amylase and lipase were assessed in parallel. Amylase (+7 U/L [95% confidence intervals, 3 - 11] p In conclusion, six weeks of treatment with liraglutide did not affect pancreatic volume, edema or cellularity in obese individuals. Increased DNA synthesis reflected by FLT-uptake in the pancreas seen after four weeks of liraglutide treatment may be responsible for the increase in pancreatic enzymes. Disclosure M.S. Svane: None. H.H. Johannesen: None. C. Martinussen: None. K.N. Bojsen-Moller: None. M.L. Hansen: None. A.E. Hansen: None. C.F. Deacon: Employee; Spouse/Partner; Merck & Co., Inc. Stock/Shareholder; Spouse/Partner; Merck & Co., Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novartis AG, Novo Nordisk A/S. B. Hartmann: None. S.H. Keller: None. T.L. Klausen: None. A. Loft: None. A. Kjaer: None. S. Madsbad: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. J.O. Löfgren: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp & Dohme Corp.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. The binding of benzodiazepines to the benzodiazepine receptor sites (BZR) located on GABAA receptors (GABAARs) potentiates the inhibitory effect of GABA leading to the anxiolytic, anticonvulsant and sedative effects used for treatment of those disorders. However, the function of GABAARs and the expression of BZR protein is determined by the GABAAR subunit stoichiometry (19 genes coding for individual subunits), and it remains to be established how the pentamer composition varies between brain regions and individuals.Here, we present a quantitative high-resolution in vivo atlas of the human brain BZRs, generated on the basis of [11C]flumazenil Positron Emission Tomography (PET) data. Next, based on autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association with mRNA expression for the 19 subunits in the GABAAR, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein.This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABAAR and the BZR density at each location in the brain.

AIM To investigate the effect of a glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, on pancreatic volume, oedema, cellularity and DNA synthesis in humans. MATERIALS AND METHODS We performed an open-label study in 14 obese men (age 38 ± 11 years, body mass index 32 ± 4 kg/m2 ) without diabetes. Subjects were examined at baseline, during titration (week 4) of liraglutide towards 3.0 mg/day, and 2 weeks after steady-state treatment (week 6) of a final dose of liraglutide. The primary endpoint was pancreatic volume determined by magnetic resonance imaging. Secondary endpoints included pancreatic oedema and cellularity, positron emission tomography-based [18 F]fluorothymidine (FLT) uptake (DNA synthesis) and plasma pancreatic enzymes. RESULTS Plasma amylase (+7 U/L [95% confidence intervals 3-11], P

Background Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy. Aim We evaluated 18F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI. Methods Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response. Results Twelve patients with SCLC completed FLT-PET/MRI 1–9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm2/s in T-sites and 0.88–2.09 × 10−3 mm2/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013). Conclusions FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation. Trial registration Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.

It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data. To facilitate comparison of findings across studies, we first recommend publication standards for tracer characteristics, image acquisition, image preprocessing, and outcome estimation for PET neuroimaging data. The co-authors of this paper, representing more than 25 PET centers worldwide, voted to classify information as mandatory, recommended, or optional. Second, we describe a framework to facilitate data archiving and data sharing within and across centers. Because of the high cost of PET neuroimaging studies, sample sizes tend to be small and relatively few sites worldwide have the required multidisciplinary expertise to properly conduct and analyze PET studies. Data sharing will make it easier to combine datasets from different centers to achieve larger sample sizes and stronger statistical power to test hypotheses. The combining of datasets from different centers may be enhanced by adoption of a common set of best practices in data acquisition and analysis. ispartof: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM vol:40 issue:8 pages:1576-1585 ispartof: location:United States status: published

Endogenous serotonin (5‐HT) release can be measured noninvasively using positron emission tomography (PET) imaging in combination with certain serotonergic radiotracers. This allows us to investigate effects of pharmacological and nonpharmacological interventions on brain 5‐HT levels in living humans. Here, we study the neural responses to a visual stimulus using simultaneous PET/MRI. In a cross‐over design, 11 healthy individuals were PET/MRI scanned with the 5‐HT1B receptor radioligand [11C]AZ10419369, which is sensitive to changes in endogenous 5‐HT. During the last part of the scan, participants either viewed autobiographical images with positive valence (n = 11) or kept their eyes closed (n = 7). The visual stimuli increased cerebral blood flow (CBF) in the occipital cortex, as measured with pseudo‐continuous arterial spin labeling. Simultaneously, we found decreased 5‐HT1B receptor binding in the occipital cortex (−3.6 ± 3.6%), indicating synaptic 5‐HT release. Using a linear regression model, we found that the change in 5‐HT1B receptor binding was significantly negatively associated with change in CBF in the occipital cortex (p = .004). For the first time, we here demonstrate how cerebral 5‐HT levels change in response to nonpharmacological stimuli in humans, as measured with PET. Our findings more directly support a link between 5‐HT signaling and visual processing and/or visual attention., Here, we study the neural responses to a visual stimulus using simultaneous positron emission tomography/magnetic resonance imaging. We find a significant association between anincrease in cerebral blood flow (CBF) in the occipital cortex along and a decrease in [11C]AZ10419369 binding, suggesting synaptic serotonin (5‐HT) release. To the best of our knowledge, this is the first time that simultaneous changes in CBF and 5‐HT levels in response to physiological stimuli have been measured.

Background The increasing use of the pig as a research model in neuroimaging requires standardized processing tools. For example, extraction of regional dynamic time series from brain PET images requires parcellation procedures that benefit from being automated. Comparison with existing methods Manual inter-modality spatial normalization to a MRI atlas is operator-dependent, time-consuming, and can be inaccurate with lack of cortical radiotracer binding or skull uptake. New method A parcellated PET template that allows for automatic spatial normalization to PET images of any radiotracer. Results MRI and [11C]Cimbi-36 PET scans obtained in sixteen pigs made the basis for the atlas. The high resolution MRI scans allowed for creation of an accurately averaged MRI template. By aligning the within-subject PET scans to their MRI counterparts, an averaged PET template was created in the same space. We developed an automatic procedure for spatial normalization of the averaged PET template to new PET images and hereby facilitated transfer of the atlas regional parcellation. Evaluation of the automatic spatial normalization procedure found the median voxel displacement to be 0.22 ± 0.08 mm using the MRI template with individual MRI images and 0.92 ± 0.26 mm using the PET template with individual [11C]Cimbi-36 PET images. We tested the automatic procedure by assessing eleven PET radiotracers with different kinetics and spatial distributions by using perfusion-weighted images of early PET time frames. Conclusion We here present an automatic procedure for accurate and reproducible spatial normalization and parcellation of pig PET images of any radiotracer with reasonable blood-brain barrier penetration.

Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively capture temporal and spatial information about acute changes in brain neurotransmitter systems. We here evaluate the 5-HT1B receptor partial agonist PET radioligand, [11C]AZ10419369, for its sensitivity to detect changes in endogenous cerebral serotonin levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain serotonin levels, we compared the [11C]AZ10419369 PET signal in the pig brain to simultaneous measurements of extracellular serotonin levels with microdialysis after various acute interventions (saline, escitalopram, fenfluramine). The interventions increased the cerebral extracellular serotonin levels to two to six times baseline, with fenfluramine being the most potent pharmacological enhancer of serotonin release. The interventions induced a varying degree of decline in [11C]AZ10419369 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular serotonin level in the pig brain and the 5-HT1B receptor occupancy indicates that [11C]AZ10419369 binding is sensitive to changes in endogenous serotonin levels to a degree equivalent to that reported of [11C]raclopride to dopamine, a much used approach to detect in vivo change in cerebral dopamine.

Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim To examine the cerebral 5-HT1B receptor binding in interictal migraine patients without aura compared to controls. Methods Eighteen migraine patients, who had been migraine free for >48 hours, and 16 controls were scanned after injection of the 5-HT1B receptor specific radioligand [11C]AZ10419369 for quantification of cerebral 5-HT1B receptor binding. Patients who reported migraine Results Our data support a model wherein group status predicts the latent variable ( p = 0.038), with migraine patients having lower 5-HT1B receptor binding across regions compared to controls. Further, in a whole-brain voxel-based analysis, time since last migraine attack correlated positively with 5-HT1B receptor binding in the dorsal raphe and in the midbrain. Conclusion We report here for the first time that migraine patients have low 5-HT1B receptor binding in pain modulating regions, reflecting decreased receptor density. This is either a primary constitutive trait of the migraine brain or secondary to repeated exposure to migraine attacks. We also provide indirect support for the dorsal raphe 5-HT1B receptors being temporarily downregulated during the migraine attack, presumably in response to higher cerebral serotonin levels in the ictal phase.

Background: Cimbi-36 can be 11C-labeled to form an agonist radioligand used for positron emission tomography (PET) imaging of the 5-HT2A receptor in the brain. In its non-labeled form (25B-NBOMe), it is used as a recreational drug that can lead to severe adverse effects, in some cases, with fatal outcome. We investigated human biodistribution and radiation dosimetry of the radioligand with two different radiolabeling positions. Seven healthy volunteers underwent dynamic 120-min whole-body PET scans (injection of 581 ± 16 MBq, n = 5 for 11C-Cimbi-36; 593 ± 14 MBq, n = 2 for 11C-Cimbi-36_5). Time-integrated activity coefficients (TIACs) from time-activity curves (TACs) of selected organs were used as input into the OLINDA/EXM software to obtain dosimetry information for both 11C-labeling positions of Cimbi-36. Results: The effective dose was only slightly higher for 11C-Cimbi-36 (5.5 μSv/MBq) than for 11C-Cimbi-36_5 (5.3 μSv/MBq). Standard uptake value (SUV) curves showed higher uptake of 11C-Cimbi-36 in the pancreas, small intestines, liver, kidney, gallbladder, and urinary bladder compared with 11C-Cimbi-36_5, reflecting differences in radiometabolism for the two radioligands. Variability in uptake in excretory organs for 11C-Cimbi-36 points to inter-individual differences with regard to metabolic rate and route. Surprisingly, moderate uptake was found in brown adipose tissue (BAT) in four subjects, possibly representing specific 5-HT2A/2C receptor binding. Conclusion: The low effective dose of 5.5 μSv/MBq allows for the injection of up to 1.8 GBq for healthy volunteers per study (equivalent to 3 scans if injecting 600 MBq) and still stay below the international guidelines of 10 mSv, making 11C-Cimbi-36 eligible for studies involving a series of PET scans in a single subject. The biodistribution of Cimbi-36 (and its metabolites) may also help to shed light on the toxic effects of 25B-NBOMe when used in pharmacological doses in recreational settings.

Aim: In this work, we evaluate the two $\mu $-map methods, total variation transmission scan processing and reconstruction (TXTV) and maximum a posteriori TX reconstruction (MAPTR), at two different transmission scan acquisition speeds (with different count statistics) against gold standard CT-based $\mu $ -maps on PET pig brain scans. Material and methods: Nine dynamic High Resolution Research Tomograph (HRRT) PET pig brain scans with different tracers reconstructed in 5 versions using different $\mu $maps were registered to a pig brain atlas. The 5 different $\mu $-maps were speed 50 or speed 10 transmission scan (TX), each reconstructed and processed using either TXTV or MAP-TR, and a rigidly co-registered gold standard $\mu $-map from a same day CT scan. From time activity curves (TACs) on relevant volumesof-interest (VOIs) relative differences from the CT-based PET to the 4 HRRT TX-based PET and areas under the curves (AUC) were generated along with $\mu $-map profile plots. Results: AUCs showed 3–16% (TXTV) and 2–10% (MAP-TR) difference from CT-based $\mu $-maps on 11 VOIs with almost no difference between using speed 50 or 10 transmission scan acquisitions. Similar average differences were found in relative difference, but with an unexpected time dependant variability, which we found to correspond with a similar change in scatter fractions over time. This correspondence was likely explained by PET-to-$\mu $-map mismatches. We primarily saw this when using CT-based $\mu $ -maps: The fixation of the pig's head and neck was changed when moving it non-rigidly to the CT scanner, which again caused a considerable mismatch to HRRT PET. Conclusion: Our results suggest that MAP-TR $\mu $-maps made from speed 50 transmission scans is so far the best method for attenuation correction of HRRT PET pig brain images. However, difficulties with relocation between imaging modalities because of different head/neck fixation on the HRRT and (PET/)CT scanners may have hampered the evaluation of HRRT TX methods for pig brain scans. In particular, a non-rigid mapping would have been required to match the CT-based u-map with HRRT data, thus increasing the risk of residual error in the reference (gold standard) data.

Objective— A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used positron emission tomography (PET) and the novel PET ligand [ 64 Cu] [1,4,7,10-tetraazacyclododecane- N , N ′, N ″, N ‴-tetraacetic acid]- d -Phe1,Tyr3-octreotate ( 64 Cu-DOTATATE) to specifically target macrophages via the somatostatin receptor subtype-2 in vivo. Approach and Results— Ten patients underwent simultaneous PET/MRI to measure 64 Cu-DOTATATE uptake in carotid artery plaques before carotid endarterectomy. 64 Cu-DOTATATE uptake was significantly higher in symptomatic plaque versus the contralateral carotid artery ( P 64 Cu-DOTATATE uptake calculated as the mean standardized uptake value. Univariate analysis of real-time quantitative polymerase chain reaction and PET showed that cluster of differentiation 163 (CD163) and CD68 gene expression correlated significantly but weakly with mean standardized uptake value in scans performed 85 minutes post injection ( P P =0.015, respectively). Subsequent multivariate analysis showed that CD163 correlated independently with 64 Cu-DOTATATE uptake ( P =0.031) whereas CD68 did not contribute significantly to the final model. Conclusions— The novel PET tracer 64 Cu-DOTATATE accumulates in atherosclerotic plaques of the carotid artery. CD163 gene expression correlated independently with 64 Cu-DOTATATE uptake measured by real-time quantitative polymerase chain reaction in the final multivariate model, indicating that 64 Cu-DOTATATE PET is detecting alternatively activated macrophages. This association could potentially improve noninvasive identification and characterization of vulnerable plaques.

BACKGROUND: HIV-infected patients are at increased risk of myocardial infarction and arterial inflammation has been suggested as a pathophysiological explanation. We compared the uptake of 18F-fluorodeoxyglucose (FDG) by PET in four arterial regions, and factors associated with FDG uptake in well-treated HIV-infected patients without cardiovascular disease (CVD) and healthy controls. METHODS AND RESULTS: We prospectively scanned 26 HIV-infected patients on stable antiretroviral therapy and 25 healthy volunteers with FDG PET/CT, measuring standardized uptake values (SUV) in the carotid arteries, the ascending, descending, and abdominal aorta. We performed correlation analyses between FDG uptake and intima-media thickness (IMT), and soluble biomarkers of inflammation. We found no difference in arterial FDG uptake between the HIV-infected patients and healthy controls quantified either as mean SUVmax or target-to background ratio in the carotid region, the ascending aorta, the descending aorta, or the abdominal aorta. Correlations between SUV, IMT, and soluble biomarkers were scarce in both groups. CONCLUSION: In a group of optimally treated HIV-infected patients with full viral suppression, low Framingham risk score and no known CVD, we found no evidence of increased arterial inflammation as assessed by FDG PET/CT compared to healthy volunteers. BACKGROUND: HIV-infected patients are at increased risk of myocardial infarction and arterial inflammation has been suggested as a pathophysiological explanation. We compared the uptake of (18)F-fluorodeoxyglucose (FDG) by PET in four arterial regions, and factors associated with FDG uptake in well-treated HIV-infected patients without cardiovascular disease (CVD) and healthy controls.METHODS AND RESULTS: We prospectively scanned 26 HIV-infected patients on stable antiretroviral therapy and 25 healthy volunteers with FDG PET/CT, measuring standardized uptake values (SUV) in the carotid arteries, the ascending, descending, and abdominal aorta. We performed correlation analyses between FDG uptake and intima-media thickness (IMT), and soluble biomarkers of inflammation. We found no difference in arterial FDG uptake between the HIV-infected patients and healthy controls quantified either as mean SUVmax or target-to background ratio in the carotid region, the ascending aorta, the descending aorta, or the abdominal aorta. Correlations between SUV, IMT, and soluble biomarkers were scarce in both groups.CONCLUSION: In a group of optimally treated HIV-infected patients with full viral suppression, low Framingham risk score and no known CVD, we found no evidence of increased arterial inflammation as assessed by FDG PET/CT compared to healthy volunteers.

Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT

Quantitative PET/MRI is dependent on reliable and reproducible MR-based attenuation correction (MR-AC). In this study, we evaluated the quality of current vendor-provided thoracic MR-AC maps and further investigated the reproducibility of their impact on 18F-FDG PET quantification in patients with non-small cell lung cancer. Methods: Eleven patients with inoperable non-small cell lung cancer underwent 2-5 thoracic PET/MRI scan-rescan examinations within 22 d. 18F-FDG PET data were acquired along with 2 Dixon MR-AC maps for each examination. Two PET images (PETA and PETB) were reconstructed using identical PET emission data but with MR-AC from these intrasubject repeated attenuation maps. In total, 90 MR-AC maps were evaluated visually for quality and the occurrence of categorized artifacts by 2 PET/MRI-experienced physicians. Each tumor was outlined by a volume of interest (40% isocontour of maximum) on PETA, which was then projected onto the corresponding PETB SUVmean and SUVmax were assessed from the PET images. Within-examination coefficients of variation and Bland-Altman analyses were conducted for the assessment of SUV variations between PETA and PETBResults: Image artifacts were observed in 86% of the MR-AC maps, and 30% of the MR-AC maps were subjectively expected to affect the tumor SUV. SUVmean and SUVmax resulted in coefficients of variation of 5.6% and 6.6%, respectively, and scan-rescan SUV variations were within ±20% in 95% of the cases. Substantial SUV variations were seen mainly for scan-rescan examinations affected by respiratory motion. Conclusion: Artifacts occur frequently in standard thoracic MR-AC maps, affecting the reproducibility of PET/MRI. These, in combination with other well-known sources of error associated with PET/MRI examinations, lead to inconsistent SUV measurements in serial studies, which may affect the reliability of therapy response assessment. A thorough visual inspection of the thoracic MR-AC map and Dixon images from which it is derived remains crucial for the detection of MR-AC artifacts that may influence the reliability of SUV.

For quantitative tracer distribution in positron emission tomography, attenuation correction is essential. In a hybrid PET/CT system the CT images serve as a basis for generation of the attenuation map, but in PET/MR, the MR images do not have a similarly simple relationship with the attenuation map. Hence attenuation correction in PET/MR systems is more challenging. Typically either of two MR sequences are used: the Dixon or the ultra-short time echo (UTE) techniques. However these sequences have some well-known limitations. In this study, a reconstruction technique based on a modified and optimized non-TOF MLAA is proposed for PET/MR brain imaging. The idea is to tune the parameters of the MLTR applying some information from an attenuation image computed from the UTE sequences and a T1w MR image. In this MLTR algorithm, an [Formula: see text] parameter is introduced and optimized in order to drive the algorithm to a final attenuation map most consistent with the emission data. Because the non-TOF MLAA is used, a technique to reduce the cross-talk effect is proposed. In this study, the proposed algorithm is compared to the common reconstruction methods such as OSEM using a CT attenuation map, considered as the reference, and OSEM using the Dixon and UTE attenuation maps. To show the robustness and the reproducibility of the proposed algorithm, a set of 204 [(18)F]FDG patients, 35 [(11)C]PiB patients and 1 [(18)F]FET patient are used. The results show that by choosing an optimized value of [Formula: see text] in MLTR, the proposed algorithm improves the results compared to the standard MR-based attenuation correction methods (i.e. OSEM using the Dixon or the UTE attenuation maps), and the cross-talk and the scale problem are limited. journal_title: Physics in Medicine and Biology article_type: paper article_title: Optimized MLAA for quantitative non-TOF PET/MR of the brain copyright_information: © 2016 Institute of Physics and Engineering in Medicine license_information: cc-by Original content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. date_received: 2016-05-13 date_accepted: 2016-11-03 date_epub: 2016-12-02 ispartof: Physics in Medicine and Biology vol:61 issue:24 pages:8854-8874 ispartof: location:England status: published

The serotonergic system integrates sex steroid information and plays a central role in mood and stress regulation, cognition, appetite and sleep. This interplay may be critical for likelihood of developing depressive episodes, at least in a subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes central serotonergic tonus, which may be related to endogenous sex-steroid levels in the mentally healthy state even though this remains elusive. Here we evaluate if peripheral levels of estradiol and testosterone are associated with 5-HT4R binding as imaged by [11C]SB207145 positron emission tomography in a group of 41 healthy men. We estimated global 5-HT4R binding using a latent variable model framework, which models shared correlation between 5-HT4R across multiple brain regions (hippocampus, amygdala, posterior and anterior cingulate, thalamus, pallidostriatum and neocortex). We tested whether testosterone and estradiol predict global 5-HT4R, adjusting for age. We found that testosterone, but not estradiol, correlated negatively with global 5-HT4R levels (p=0.02) suggesting that men with high levels of testosterone have higher cerebral serotonergic tonus. Our findings corroborate the link between sex hormone levels and serotonin signalling. Future longitudinal studies in clinical relevant populations are needed to elucidate the potential importance of testosterone in the pathophysiology of e.g. major depression and its treatment.

High Resolution Research Tomograph (HRRT, Siemens) is a dedicated human brain PET scanner with nearly isotropic and shift invariant reconstructed resolution of 2.5 mm (FWHM) as measured using a point source and reconstruction settings of NEMA standard [1]. Spatial resolution can be however significantly degraded if the imaged object is moving during PET scanning resembling impact of partial volume effect (PVE). Head motion is particularly detrimental in brain studies investigating e.g. tracer receptor binding in the small brain nuclei, and their displacement thereof. In fact, decreased tracer uptake as depicted by time-activity curve (TAC) data may often be due to head motion rather than inhibition of tracer binding (c.f. [2]).

Aim: To parallelize scanning and save time and cut costs of preclinical studies we have designed a new hotel holding 4 rats in the HRRT, which has a spatial resolution close to that of preclinical PET scanners. In this work we test the quantitative accuracy on phantoms in the hotel using different attenuation corrections methods on the HRRT. Material and Methods: The rat hotel has 4 compartments made of acrylic plastic with an 8 mm base plate and a 3 mm half-cylinder lid. Four 50 ml syringes filled with [18F]-FDG in water were used as phantoms and scanned in the rat hotel for 20 min. on the HRRT and a high statistics speed 10 transmission scan was acquired. Three μ-map processing/reconstruction methods — MAP-TR with either human head (HH) or water phantom (WP) prior and TXTV — were used and μ-maps and PET images reconstructed with each of the 3 μ-maps evaluated. Results: The μ-maps all underestimated the LAC of the acrylic plastic material as compared to CT, and the base plate thickness was underestimated. Activity concentrations were thus also underestimated: −4.6% using HH −8.7% using TXTV and −13.8% with WP. No noteworthy local variations were found. Conclusion: We found a global underestimation of PET activity, which was within a ±5% acceptance range using MAP-TR with the human head prior and a long transmission scan (speed 10). Fine tuning HH or TXTV parameters might give further improvements.

In the standard software for the Siemens high-resolution research tomograph (HRRT) positron emission tomography (PET) scanner the most commonly used segmentation in the μ-map reconstruction for human brain scans is maximum a posteriori for transmission (MAP-TR). Bias in the lower cerebellum and pons in HRRT brain images have been reported. The two main sources of the problem with MAP-TR are poor bone/soft tissue segmentation below the brain and overestimation of bone mass in the skull. Method: We developed the new transmission processing with total variation (TXTV) method that introduces scatter correction in the μ-map reconstruction and total variation filtering to the transmission processing. Results: Comparing MAP-TR and the new TXTV with gold standard CT-based attenuation correction, we found that TXTV has less bias as compared to MAP-TR. We also compared images acquired at the HRRT scanner using TXTV to the GE Advance scanner images and found high quantitative correspondence. TXTV has been used to reconstruct more than 4000 HRRT scans at seven different sites with no reports of biases. Conclusion: TXTV-based reconstruction is recommended for human brain scans on the HRRT.

Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations.

BACKGROUND: We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens Biograph mMR PET/MR system. We perform regular cross-calibrations (Xcal) of our PET systems, including the PET/MR, using a Siemens mCT water phantom.LONG-TERM STABILITY: The mMR calibration stability was evaluated over a 3-year period where 54 cross-calibrations were acquired, showing that the mMR on average underestimated the concentration by 16 %, consistently due to the use of MR-based μ-maps. The mMR produced the narrowest calibration ratio range with the lowest standard deviation, implying it is the most stable of the six systems in the study over a 3-year period. MMR ACCURACY WITH PREDEFINED μ-MAPS: With the latest mMR software version, VB20P, it is possible to utilize predefined phantom μ-maps. We evaluated both the system-integrated, predefined μ-map of the long mMR water phantom and our own user-defined CT-based μ-map of the mCT water phantom, which is used for cross-calibration. For seven scans, which were reconstructed with correctly segmented μ-maps, the mMR produced cross-calibration ratios of 1.00-1.02, well within the acceptance range [0.95-1.05], showing high accuracy.CONCLUSIONS: The mMR is the most stable PET system in this study, and the mean underestimation is no longer an issue with the easily accessible μ-map, which resulted in correct cross-calibration ratios in all seven tests. We will share the user-defined μ-map of the mCT phantom and the protocol with interested mMR users.

Integrated whole-body PET/MRI tomographs have become available. PET/MR imaging has the potential to supplement, or even replace combined PET/CT imaging in selected clinical indications. However, this is true only if methodological pitfalls and image artifacts arising from novel MR-based attenuation correction (MR-AC) are fully understood.Here we present PET/MR image artifacts following routine MR-AC, as most frequently observed in clinical operations of an integrated whole-body PET/MRI system.A clinical adoption of integrated PET/MRI should entail the joint image display and interpretation of MR data, MR-based attenuation maps and uncorrected plus attenuation-corrected PET images in order to recognize potential pitfalls from MR-AC and to ensure clinically accurate image interpretation.

Many authors have reported the importance of motion correction (MC) for PET. Patient motion during scanning disturbs kinetic analysis and degrades resolution. In addition, using misaligned transmission for attenuation and scatter correction may produce regional quantification bias in the reconstructed emission images. The purpose of this work was the development of quality control (QC) methods for MC procedures based on external motion tracking (EMT) for human scanning using an optical motion tracking system. Methods: Two scans with minor motion and 5 with major motion (as reported by the optical motion tracking system) were selected from 18F-FDG scans acquired on a PET scanner. The motion was measured as the maximum displacement of the markers attached to the subject9s head and was considered to be major if larger than 4 mm and minor if less than 2 mm. After allowing a 40- to 60-min uptake time after tracer injection, we acquired a 6-min transmission scan, followed by a 40-min emission list-mode scan. Each emission list-mode dataset was divided into 8 frames of 5 min. The reconstructed time-framed images were aligned to a selected reference frame using either EMT or the AIR (automated image registration) software. The following 3 QC methods were used to evaluate the EMT and AIR MC: a method using the ratio between 2 regions of interest with gray matter voxels (GM) and white matter voxels (WM), called GM/WM; mutual information; and cross correlation. Results: The results of the 3 QC methods were in agreement with one another and with a visual subjective inspection of the image data. Before MC, the QC method measures varied significantly in scans with major motion and displayed limited variations on scans with minor motion. The variation was significantly reduced and measures improved after MC with AIR, whereas EMT MC performed less well. Conclusion: The 3 presented QC methods produced similar results and are useful for evaluating tracer-independent external-tracking motion-correction methods for human brain scans.

Experimental studies indicate that the 5-HT4 receptor activation influence cognitive function, affective symptoms, and the development of Alzheimer's disease (AD). The prevalence of AD increases with aging, and women have a higher predisposition to both AD and affective disorders than men. This study aimed to investigate sex and age effects on 5-HT4 receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [11C]SB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14 men and 16 women). The output parameter, BPND, was modeled using the simplified reference tissue model, and partial volume correction was performed with the Muller-Gartner method. A decline with age of 1% per decade was found only in striatum. Women had a 13% lower 5-HT4 receptor binding in the limbic system. The lower limbic 5-HT4 receptor binding in women supports a role for 5-HT4 receptors in the sex-specific differences in emotional control and might contribute to the higher prevalence of affective diseases and AD in women. The relatively stable 5-HT4 receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging.

Head movements during brain imaging using high resolution positron emission tomography (PET) impair the image quality which, along with the improvement of the spatial resolution of PET scanners, in general, raises the importance of motion correction. Here, we present a new design for an automatic, movable, mechanical PET phantom to simulate patients' head movements while being scanned. This can be used for evaluating motion correction methods. A low-cost phantom controlled by a rotary stage motor was built and tested for axial rotations of 1°-10° with the multiple acquisition frame method. The phantom is able to perform stepwise and continuous axial rotations with submillimeter accuracy, and the movements are repeatable. The scans were acquired on the high resolution research tomograph dedicated brain scanner. The scans were reconstructed with the new 3-D ordered subset expectation maximization algorithm with modeling of the point spread function (3DOSEM-PSF), and they were corrected for motions based on external tracking information using the Polaris Vicra real-time stereo motion-tracking system. The new automatic, movable phantom has a robust design and is a potential quality assessment tool for the development and evaluation of future motion correction methods.

We present a variational framework for deinterlacing that was originally used for inpainting and subsequently redeveloped for deinterlacing. From the framework, we derive a motion adaptive (MA) deinterlacer and a motion compensated (MC) deinterlacer and test them together with a selection of known deinterlacers. To illustrate the need for MC deinterlacing, the problem of details in motion (DIM) is introduced. It cannot be solved by MA deinterlacers or any simpler deinterlacers but only by MC deinterlacers. The major problem in MC deinterlacing is computing reliable optical flow [motion estimation (ME)] in interlaced video. We discuss a number of strategies for computing optical flows on interlaced video hoping to shed some light on this problem. We produce results on challenging real world video data with our variational MC deinterlacer that in most cases are indistinguishable from the ground truth.

We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens Biograph mMR PET/MR system. We perform regular cross-calibrations (Xcal) of our PET systems, including the PET/MR, using a Siemens mCT water phantom. The mMR calibration stability was evaluated over a 3-year period where 54 cross-calibrations were acquired, showing that the mMR on average underestimated the concentration by 16 %, consistently due to the use of MR-based μ-maps. The mMR produced the narrowest calibration ratio range with the lowest standard deviation, implying it is the most stable of the six systems in the study over a 3-year period. With the latest mMR software version, VB20P, it is possible to utilize predefined phantom μ-maps. We evaluated both the system-integrated, predefined μ-map of the long mMR water phantom and our own user-defined CT-based μ-map of the mCT water phantom, which is used for cross-calibration. For seven scans, which were reconstructed with correctly segmented μ-maps, the mMR produced cross-calibration ratios of 1.00–1.02, well within the acceptance range [0.95–1.05], showing high accuracy. The mMR is the most stable PET system in this study, and the mean underestimation is no longer an issue with the easily accessible μ-map, which resulted in correct cross-calibration ratios in all seven tests. We will share the user-defined μ-map of the mCT phantom and the protocol with interested mMR users.

Background In the absence of CT or traditional transmission sources in combined clinical positron emission tomography/magnetic resonance (PET/MR) systems, MR images are used for MR-based attenuation correction (MR-AC). The susceptibility effects due to metal implants challenge MR-AC in the neck region of patients with dental implants. The purpose of this study was to assess the frequency and magnitude of subsequent PET image distortions following MR-AC. Methods A total of 148 PET/MR patients with clear visual signal voids on the attenuation map in the dental region were included in this study. Patients were injected with [18F]-FDG, [11C]-PiB, [18F]-FET, or [64Cu]-DOTATATE. The PET/MR data were acquired over a single-bed position of 25.8 cm covering the head and neck. MR-AC was based on either standard MR-ACDIXON or MR-ACINPAINTED where the susceptibility-induced signal voids were substituted with soft tissue information. Our inpainting algorithm delineates the outer contour of signal voids breaching the anatomical volume using the non-attenuation-corrected PET image and classifies the inner air regions based on an aligned template of likely dental artifact areas. The reconstructed PET images were evaluated visually and quantitatively using regions of interests in reference regions. The volume of the artifacts and the computed relative differences in mean and max standardized uptake value (SUV) between the two PET images are reported. Results The MR-based volume of the susceptibility-induced signal voids on the MR-AC attenuation maps was between 1.6 and 520.8 mL. The corresponding/resulting bias of the reconstructed tracer distribution was localized mainly in the area of the signal void. The mean and maximum SUVs averaged across all patients increased after inpainting by 52% (± 11%) and 28% (± 11%), respectively, in the corrected region. SUV underestimation decreased with the distance to the signal void and correlated with the volume of the susceptibility artifact on the MR-AC attenuation map. Conclusions Metallic dental work may cause severe MR signal voids. The resulting PET/MR artifacts may exceed the actual volume of the dental fillings. The subsequent bias in PET is severe in regions in and near the signal voids and may affect the conspicuity of lesions in the mandibular region.

A challenge when using current magnetic resonance (MR)-based attenuation correction in positron emission tomography/MR imaging (PET/MRI) is that the MRIs can have a signal void around the dental fillings that is segmented as artificial air-regions in the attenuation map. For artifacts connected to the background, we propose an extension to an existing active contour algorithm to delineate the outer contour using the nonattenuation corrected PET image and the original attenuation map. We propose a combination of two different methods for differentiating the artifacts within the body from the anatomical air-regions by first using a template of artifact regions, and second, representing the artifact regions with a combination of active shape models and k-nearest-neighbors. The accuracy of the combined method has been evaluated using 25 [Formula: see text]-fluorodeoxyglucose PET/MR patients. Results showed that the approach was able to correct an average of [Formula: see text] of the artifact areas.

Introduction: HIV-infected patients are at increased risk of myocardial infarction and arterial inflammation has been suggested as an explanation. Vascular inflammation can be assessed in vivo by 18F-fluorodeoxyglucose (FDG) PET. Hypothesis: Well-treated HIV-infected patients without known cardiovascular disease will have increased uptake of FDG in different arterial regions as compared to healthy controls. Methods: We prospectively included 26 HIV-infected patients on stable antiretroviral therapy and 25 healthy volunteers. All underwent whole-body PET/CT 3 hours after injection of FDG. FDG uptake was assessed (SUV) in the carotid arteries, the ascending, descending, and abdominal aorta. Carotid intima-media thickness was determined by ultrasound. Soluble biomarkers of endothelial dysfunction and inflammation were measured by ELISA. Known cardiovascular risk factors were recorded for all included. Results: The HIV-infected patients were on stable antiretroviral therapy with full viral suppression. The HIV-infected group was older (50 vs 41 yrs; p = 0.01), had higher blood pressure and total cholesterol, and accordingly a higher Framingham risk score. FDG uptake was similar in the two groups quantified as SUVmax (figure) in the carotid region (1.67 ± 0.04 vs. 1.67 ± 0.04, p = 0.98), the ascending aorta (1.84 ± 0.06 vs. 1.97 ± 0.06, p = 0.15), the descending aorta (1.89 ± 0.08 vs. 1.93 ± 0.08, p = 0.70), and the abdominal aorta (1.70 ± 0.06 vs. 1.65 ± 0.06, p = 0.56) even when adjusting for differences in risk profile. No significant correlations between SUV, carotid intima-media thickness, known cardiovascular risk factors and soluble biomarkers were found. Conclusions: We found no evidence of increased arterial inflammation among HIV-infected patients with full viral suppression compared to controls. This may challenge the idea of chronic inflammation as the cause of cardiovascular disease among optimally treated HIV-infected patients.

We describe a novel solution for PET attenuation correction in the head based on the joint reconstruction of simultaneously acquired emission and sparse transmission (sTX) data. We demonstrate that an sTX array can provide better cross-talk reduction than a conventional full-ring transmission source. This initial evaluation is based on synthetic 2D non-time-of-flight data corresponding to 20 fixed line sources placed in a 30 cm diameter ring around the head. A 57.2 cm ring diameter is also considered. The total source activity equals half the total emission activity in the brain. Simultaneous emission/transmission and blank scans are simulated. These data are iteratively reconstructed to estimate both the emission and linear attenuation coefficient (LAC) images of the head. We find that the sTX data effectively constrain cross-talk. Bone, soft tissue and voids are approximately represented in the estimated attenuation image. The results are compared to a continuous ring-source-based joint reconstruction, as well as to a standard MLEM reconstruction of emission-only data assuming a uniform LAC distribution within the head. 10–20% underestimation of activity in the peripheral regions of the brain in the latter two images is reduced to < 5%on average in the sTX case. Initial tests indicate the algorithm is robust to a realistic level of noise. We estimate that such an sTX technique would result in a negligible increase in patient absorbed radiation dose in a typical 18FDG clinical study of the head.

In combined PET/MR, attenuation correction (AC) is performed indirectly based on the available MR image information. Metal implant-induced susceptibility artifacts and subsequent signal voids challenge MR-based AC. Several papers acknowledge the problem in PET attenuation correction when dental artifacts are ignored, but none of them attempts to solve the problem. We propose a clinically feasible correction method which combines Active Shape Models ( ASM ) and k- Nearest-Neighbors ( kNN ) into a simple approach which finds and corrects the dental artifacts within the surface boundaries of the patient anatomy. ASM is used to locate a number of landmarks in the T1-weighted MR-image of a new patient. We calculate a vector of offsets from each voxel within a signal void to each of the landmarks. We then use kNN to classify each voxel as belonging to an artifact or an actual signal void using this offset vector, and fill the artifact voxels with a value representing soft tissue. We tested the method using fourteen patients without artifacts, and eighteen patients with dental artifacts of varying sizes within the anatomical surface of the head/neck region. Though the method wrongly filled a small volume in the bottom part of a maxillary sinus in two patients without any artifacts, due to their abnormal location, it succeeded in filling all dental artifact regions in all patients. In conclusion, we propose a method, which combines ASM and kNN into a simple approach which, as the results show, succeeds to find and correct the dental artifacts within the anatomical surface.

To date, the high resolution research tomograph (HRRT) still offers the highest resolution PET imaging capability of the human brain. Spatial uniformity of the images is of paramount importance, as many radioligand studies require either accurate regional dynamic quantification or, at the very least, accurate measurement of relative activities between regions. Often uniform cylinders, of 68Ge or 18F, are used for quality control and calibration purposes. This work examines the spatial uniformity obtained in reconstructed images of uniform cylinders from seven different HRRT centres, using either 68Ge or 18F, and also considering a head and brain phantom filled with 18F scanned at three of the centres. To account for varying activity levels used in each centre's data acquisition, and possibly different image reconstruction parameters, a progressive smoothing method was used to analyze image uniformity, with metrics designed to assess non-uniformity in image planes as well as in randomly selected region of interest pairs. Unusually high image non-uniformities were found for germanium cylinders at two centres, but of greater concern was the fact that uniformity for the brain phantom was found to be notably inferior at two of the three centres which scanned the phantom. A change of mumap reconstruction parameters, and minor adjustment of a parameter used in the single scatter simulation, was shown to remedy the issue (reducing relative region errors to

We present a complete system for motion correction in high resolution brain positron emission tomography (PET) imaging. The system is based on a compact structured light scanner mounted above the patient tunnel of the Siemens High Resolution Research Tomograph (HRRT) PET brain scanner. The structured light system is equipped with a near infrared diode and uses phase-shift interferometry (PSI) to compute 3D point clouds of the forehead of the patient. These 3D point clouds are progressively aligned to a reference surface, thereby giving the head pose changes. The estimated pose changes are used to reposition a sequence of reconstructed PET frames. To align the structured light system with the PET coordinate system, a novel registration algorithm based on the PET transmission scan and an initial surface has been developed. The performance of the complete setup has been evaluated using a custom-made phantom, based on a plastic mannequin head equipped with two positron-emitting line sources. Two experiments were performed. The first simulates rapid and short head movements, while the second simulates slow and continuous movements. In both cases, the system was able to produce PET scans with focused PET reconstructions. The system is nearly ready for clinical testing.

The scatter estimation method (SC-2D) designed for whole body (WB) scanner is currently used for the HRRT scanner. SC-2D neglects the difference in shape between scattered coincidences in direct and oblique sinograms. However, the difference may be significant for HRRT sinograms with larger oblique angles. We have extended the SC-2D method into a new method (SC-3D), which computes the scatter in oblique sinograms. We have used simulated data of a cylindrical phantom and anthropomorphic phantom to compare the results of the two methods with simulated scatter (SC-SIM). The results showed a negative bias of 5 % in the center of the cylinder image using SC-2D; a bias which was corrected by SC-3D. A similar but smaller bias was found for the anthropomorphic phantom images.

In combined whole-body PET/MR, attenuation correction (AC) is performed indirectly using the available MR image information and subsequent segmentation. Implant-induced susceptibility artifacts and subsequent signal voids may challenge MR-based AC (MR-AC). We evaluated the accuracy of MR-AC in PET/MR in patients with metallic endoprostheses, and propose a clinically feasible correction method. We selected patients with uni- or bilateral endoprostheses from 61 consecutive referrals for whole-body PET/MR imaging (mMR; Siemens Healthcare). Simultaneous whole-body PET/MR imaging was performed at 120 min after injection of about 300 MBq [18F]FDG. MR-AC was performed using (1) original MR images and subsequent Dixon water–fat segmentation, (2) as method 1 with implant-induced signal voids filled with soft tissue, (3) as method 2 with superimposed coregistered endoprostheses from the CT scan, and (4) as method 1 with implant-induced signal voids filled with metal. Following MR-AC (methods 1–4) PET emission images were reconstructed on 344 × 344 matrices using attenuation-weighted OSEM (three iterations, 21 subsets, 4 mm gaussian). Maximum body-weight normalized standardized uptake values (SUVmax) were obtained for both hips. Mean SUV (SUVmean) in homogeneous reference regions in the gluteal muscle and bladder following MR-AC (methods 1–4) are also reported. In total, four patients presented with endoprostheses, unilateral in two and bilateral in two. The fraction of voxels in MR images affected by the implant was at least twice that of the voxels representing the actual implants. MR-AC using methods 2 and 3 recovered the FDG distribution pattern compared to uncorrected PET images and method 1, while method 4 resulted in severe overestimation of FDG uptake (>460 % SUVmax). When compared to method 1, relative changes in SUVmean in the reference regions from method 2 and 3 were generally small albeit not correlated with the fraction of the attenuation image affected by implant-induced artifacts. Endoprostheses cause PET/MR artifacts that exceed the volume occupied by the implants, and bias PET quantification. Artifacts and bias can be corrected by semiautomated inpainting with soft tissue with a single composition prior to MR-AC, thus restoring quantitative activity distribution.