Purpose
This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular ...Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes.
Methods
Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally,
18
Ffluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for
18
Ffluorodopa imaging in this setting are still lacking.
Conclusion
All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.
Purpose
The cannabinoid type 2 receptor (CB
2
R) is expressed by immune cells such as monocytes and macrophages. In the brain, CB
2
R is primarily found on microglia. CB
2
R upregulation has been ...reported in animal models of Alzheimer’s disease, with a preferential localization near amyloid beta (Aβ) plaques, and in patients post mortem. We performed in vivo brain imaging and kinetic modelling of the CB
2
R tracer
11
CNE40 in healthy controls (HC) and in patients with Alzheimer’s disease (AD) to investigate whether higher CB
2
R availability regionally colocalized to Aβ deposits is present in vivo.
Methods
Dynamic 90-min
11
CNE40 PET scans were performed in eight HC and nine AD patients with full kinetic modelling using arterial sampling and metabolite correction and partial volume correction. All AD patients received a static
11
CPIB scan 40 min after injection. In four HC, a retest scan with
11
CNE40 PET was performed within 9 weeks to investigate test–retest characteristics.
Results
11
CNE40 was metabolized quickly leading to 50 % of intact tracer 20 min after injection and 20 % at 90 min. A two-tissue kinetic model fitted most of the time–activity curves best; both binding potential (BP
ND
) and distribution volume (
V
T
) parameters could be used. Brain uptake was generally low with an average
K
1
value of 0.07 ml/min/ml tissue.
V
T
and BP
ND
were in the range of 0.7 – 1.8 and 0.6 – 1.6, respectively. Test values in HC were about 30 % for
V
T
and BP
ND
. AD patients showed overall significantly lower CB
2
R binding. No relationship was found between regional or global amyloid load and CB
2
R availability.
Conclusion
Kinetic modelling of
11
CNE40 is possible with a two-tissue reversible model. In contrast to preclinical and post-mortem data,
11
CNE40 PET shows lower CB
2
R availability in vivo in AD patients, with no relationship to Aβ plaques. A possible explanation for these findings is that
11
CNE40 binds to CB
2
R with lower affinity and/or selectivity than to CB
1
R.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting the motor system, with extramotor involvement to a variable extent. Biomarkers for early differential diagnosis ...and prognosis are needed. An autosomal dominant hexanucleotide (GGGGCC) expansion in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent genetic cause of ALS, but its metabolic pattern has not been studied systematically.
To evaluate the use of 18fluorodeoxyglucose-positron-emission tomography as a marker of ALS pathology and investigate whether a specific metabolic signature is present in patients with C9orf72 mutations.
In total, 81 patients with a suspected diagnosis of ALS at University Hospital Leuven were prospectively investigated. All underwent detailed neurological examination and electrodiagnostic and genetic testing for the major known genetic causes of ALS (C9orf72, SOD1, TARDBP, and FUS). A diagnosis of ALS was made in 70 of 81 patients. Of these, 11 were C9orf72 positive and 59 were C9orf72 negative. In 7 patients, the diagnosis of primary lateral sclerosis was made; 4 patients had progressive muscular atrophy. A screened healthy control population was used for comparison.
Positron-emission tomographic data were spatially normalized and analyzed using a predefined volume of interest and a voxel-based analysis (SPM8). Discriminant analysis was done both volume of interest based and voxel based using a support vector machine approach.
Compared with control participants, 18fluorodeoxyglucose-positron-emission tomography showed perirolandic and variable prefrontal hypometabolism in most patients. Patients with primary lateral sclerosis showed a similar pattern. Patients with C9orf72-positive ALS had discrete relative hypometabolism in the thalamus and posterior cingulate compared with those with C9orf72-negative ALS. A posteriori-corrected discriminant analysis was able to correctly classify 95% of ALS cases and 71% of primary lateral sclerosis cases. Prefrontal hypometabolism was associated with reduced clinical functioning (ALS Functional Rating Scale). Extensive hypometabolism in the prefrontal or anterior temporal areas was present in 10% of patients and associated with significantly shorter survival as an independent factor (n = 63, P < .001). Patients who were C9orf72 positive did not differ in survival compared with those who were C9orf72 negative.
18Fluorodeoxyglucose-positron-emission tomography is a useful early diagnostic and prognostic marker for ALS. Amyotrophic lateral sclerosis that is positive for C9orf72 is characterized by only mild cerebral metabolic differences that show no prognostic difference.
Metabotropic glutamate receptors (mGluRs) have been proposed as promising therapeutic targets to correct the dysregulated glutamate signaling, associated with neurodegenerative pathologies. Of all ...mGluR subtypes, especially mGluR5 acts as a modulator of glutamate-induced excitotoxicity. To study the behavior of mGluR5 following localized excitotoxicity, we utilised a pharmacological model that portrays exacerbated neuronal glutamate release, mediated by the endogenous excitotoxin quinolinic acid (QA). Using longitudinal positron emission tomography (PET) with
FFPEB, we investigated cerebral changes in mGluR5 following striatal QA-lesioning. Behavioral tests were executed to monitor motor and cognitive performance. Decreased mGluR5 binding potential (BP
) was found in the affected striatum and globus pallidus of QA-lesioned rats at week 3, and further decreased at week 7, as compared to sham-injected controls. mGluR5 availability in the ipsilateral nucleus accumbens was significantly decreased at 7 weeks post-injection. QA rats performed significantly worse on motor coordination and balance compared to control rats. Correlation analysis indicated a positive correlation between striatal mGluR5 BP
and rotarod performance whereas print width of the unaffected forepaws showed a positive relation with mGluR5 BP
in the contralateral motor cortex. Together, our results suggest decreased mGluR5 availability to be related to excitotoxin-induced neurodegeneration and symptomatology although late stage effects do indicate possible cortical mGluR5-mediated effects on motor behavior.
Background The endocannabinoid system is a possible target in the treatment of eating disorders. We used positron emission tomography to investigate the type 1 cannabinoid receptor (CB1R) in bulimic ...and anorectic patients. Methods We investigated 16 female bulimia nervosa patients (BN) (age = 23.8 ± 7.1 years) and 14 female anorexia nervosa patients (AN) (age = 20.5 ± 3.6 years) using the selective CB1R ligand 18 FMK-9470. The control group consisted of 19 age-matched women (age = 25.2 ± 8.5 years). Statistical parametric mapping ( pfamily-wise error < .05) and volume-of-interest analyses of CB1R availability were performed. Results Global CB1R availability was significantly increased in cortical and subcortical brain areas in AN patients compared with healthy control subjects (+24.5%, p = .0003). Regionally, CB1R availability was increased in the insula in both AN and BN patients ( p = .01 and p = .0004) and the inferior frontal and temporal cortex in AN patients only ( p = .02). Conclusions Global CB1R upregulation in AN patients is a possible long-term compensatory mechanism to an underactive endocannabinoid system in anorectic conditions. There is a similarity in CB1R dysregulation both in AN and BN in the insular cortex, which is involved in the integration of interoceptive information, gustatory information, reward, and emotion processing.
Purpose
The aim of this study was to evaluate different non-invasive methods for generating (R)-1-((3-(
11
Cmethyl)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) (
11
CUCB-J) ...parametric maps using white matter (centrum semi-ovale–SO) as reference tissue.
Procedures
Ten healthy volunteers (8 M/2F; age 27.6 ± 10.0 years) underwent a 90-min dynamic
11
CUCB-J positron emission tomography (PET) scan with full arterial blood sampling and metabolite analysis before and after administration of a novel chemical entity with high affinity for presynaptic synaptic vesicle glycoprotein 2A (SV2A). A simplified reference tissue model (SRTM2), multilinear reference tissue model (MRTM2), and reference Logan graphical analysis (rLGA) were used to generate binding potential maps using SO as reference tissue (BP
SO
). Shorter dynamic acquisitions down to 50 min were also considered. In addition, standard uptake value ratios (SUVR) relative to SO were evaluated for three post-injection intervals (SUVR
SO,40-70min
, SUVR
SO,50-80min
, and SUVR
SO,60-90min
respectively). Regional parametric BP
SO
+ 1 and SUVR
SO
were compared with regional distribution volume ratios of a 1-tissue compartment model (1TCM DVR
SO
) using Spearman correlation and Bland-Altman analysis.
Results
For all methods, highly significant correlations were found between regional, parametric BP
SO
+ 1 (
r
= 0.63;0.96) or SUVR
SO
(
r
= 0.90;0.91) estimates and regional 1TCM DVR
SO
. For a 90-min dynamic scan, parametric SRTM2 and MRTM2 values presented similar small bias and variability (− 3.0 ± 2.9 % for baseline SRTM2) and outperformed rLGA (− 10.0 ± 5.3 % for baseline rLGA). Reducing the dynamic acquisition to 60 min had limited impact on the bias and variability of parametric SRTM2 BP
SO
estimates (− 1.0 ± 9.9 % for baseline SRTM2) while a higher variability (− 1.83 ± 10.8 %) for baseline MRTM2 was observed for shorter acquisition times. Both SUVR
SO,60-90min
and SUVR
SO,50-80min
showed similar small bias and variability (− 2.8 ± 4.6 % bias for baseline SUVR
SO,60-90min
).
Conclusion
SRTM2 is the preferred method for a voxelwise analysis of dynamic
11
CUCB-J PET using SO as reference tissue, while reducing the dynamic acquisition to 60 min has limited impact on
11
CUCB-J BP
SO
parametric maps. For a static PET protocol, both SUVR
SO,60-90min
and SUVR
SO,50-80min
images are an excellent proxy for
11
CUCB-J BP
SO
parametric maps.
These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners in ...making recommendations, performing, interpreting, and reporting the results of fluorine-18 fluoro-2-deoxyglucose (
18
FFDG) PET imaging of the brain. The aim is to help achieve a high standard of FDG imaging, which will increase the diagnostic impact of this technique in neurological and psychiatric practice. The present document replaces a former version of the guidelines that were published in 2002
1
and includes an update in the light of advances in PET technology, the introduction of hybrid PET/CT systems and the broadening clinical indications for FDG brain imaging. These guidelines are intended to present information specifically adapted for European practice. The information provided should be taken in the context of local conditions and regulations.
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