[German Society of Nuclear Medicine procedure guideline on beta-amyloid brain PET imaging]. / Beta-Amyloid-PET-Bildgebung des Gehirns. DGN-Handlungsempfehlung.

Recently, a number of positron emission tomography (PET) radiotracers have been approved for clinical use. These tracers target cerebral beta-amyloid (Aß) plaques, a hallmark of Alzheimer's disease. Increasing use of this method implies the need for respective standards. This German Society of Nuclear Medicine guideline describes adequate procedures for Aß plaque PET imaging. It not only discusses the tracers used for that purpose, but also lists measures for correct patient preparation, image data generation, processing, analysis and interpretation. With that, this "S1" category (according to the German Association of the Scientific Medical Societies standard) guideline aims at contributing to quality assurance of nuclear imaging in Germany.

Osteoprotegerin: a new biomarker for impaired bone metabolism in complex regional pain syndrome?

Osteoprotegerin (OPG) is important for bone remodeling and may contribute to complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the value of OPG as a biomarker for CRPS and a possible correlation with radiotracer uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS patients (17 women; mean age 50±9.0 years; disease duration: 12 weeks [IQR 8-24]), 10 controls (6 women; mean age 58±9.6 years) and 21 patients after uncomplicated fractures (12 women; mean age: 43±15 years; time after fracture: 15 weeks [IQR: 6-22]). The CRPS and control patients also underwent TPBS. OPG in CRPS patients was significantly increased by comparison with both control groups (P=0.001; Kruskal-Wallis test; CRPS patients: 74.1 pg/mL [IQR: 47.1-100.7]; controls: 46.7 pg/mL [IQR: 35.5-55.0]; P=0.004; fracture patients: 45.9 pg/mL [IQR: 37.5-56.7]; P=0.001). As a diagnostic test for CRPS, OPG had a sensitivity of 0.74, specificity of 0.80, positive predictive value of 68% and negative predictive value of 84%. Receiver operating characteristic curve analysis showed an area under the curve of 0.80 (CI: 0.68-0.91). For the CRPS-affected hand, a significant correlation between OPG and TPBS region of interest analysis in phase III was detected (carpal bones; r=0.391; P=0.03). The persistent OPG increase in CRPS indicates enhanced osteoblastic activity shown by increased radiotracer uptake in TPBS phase III. A contribution of bone turnover to CRPS pathophysiology is likely. OPG might be useful as a biomarker for CRPS.

Substantia nigra hyperechogenicity in healthy controls: a [¹8Fluoro] Dopa-PET follow-up study.

In order to assess nigrostriatal function over time in healthy subjects with substantia nigra hyperechogenicity (SN+) believed to be at higher risk for Parkinson's disease (PD), ten healthy SN+ subjects underwent [(18)Fluoro] Dopa positron emission tomography (PET) twice-at baseline and after a mean of 7.3 years. Neurological examination took place at study inclusion followed by a structured telephone interview focusing on early Parkinsonian symptoms at the time point of second PET study and 3.5 years later. The [(18)Fluoro] Dopa uptake remained unchanged in eight of ten participants. In the other two subjects marked unilateral reduction of putaminal [(18)Fluoro] Dopa uptake ratios appeared over the time, followed by complaints of a clinically manifest PD in one. We suggest that the progressive pathological PET findings in 20 % and PD conversion in 10 % of our cohort may be in accordance with the presumed proportion of SN+ individuals eventually developing PD based on SN+ prevalence of 10 % within the healthy population, being ten times higher than PD prevalence in the age of over 60 years. Our findings hint towards a significance of SN+ indicating a high risk for PD in some extrapyramidally healthy SN+ individuals.

Ventral and dorsal streams processing visual motion perception (FDG-PET study).

BACKGROUND: Earlier functional imaging studies on visually induced self-motion perception (vection) disclosed a bilateral network of activations within primary and secondary visual cortex areas which was combined with signal decreases, i.e., deactivations, in multisensory vestibular cortex areas. This finding led to the concept of a reciprocal inhibitory interaction between the visual and vestibular systems. In order to define areas involved in special aspects of self-motion perception such as intensity and duration of the perceived circular vection (CV) or the amount of head tilt, correlation analyses of the regional cerebral glucose metabolism, rCGM (measured by fluorodeoxyglucose positron-emission tomography, FDG-PET) and these perceptual covariates were performed in 14 healthy volunteers. For analyses of the visual-vestibular interaction, the CV data were compared to a random dot motion stimulation condition (not inducing vection) and a control group at rest (no stimulation at all). RESULTS: Group subtraction analyses showed that the visual-vestibular interaction was modified during CV, i.e., the activations within the cerebellar vermis and parieto-occipital areas were enhanced. The correlation analysis between the rCGM and the intensity of visually induced vection, experienced as body tilt, showed a relationship for areas of the multisensory vestibular cortical network (inferior parietal lobule bilaterally, anterior cingulate gyrus), the medial parieto-occipital cortex, the frontal eye fields and the cerebellar vermis. The "earlier" multisensory vestibular areas like the parieto-insular vestibular cortex and the superior temporal gyrus did not appear in the latter analysis. The duration of perceived vection after stimulus stop was positively correlated with rCGM in medial temporal lobe areas bilaterally, which included the (para-)hippocampus, known to be involved in various aspects of memory processing. The amount of head tilt was found to be positively correlated with the rCGM of bilateral basal ganglia regions responsible for the control of motor function of the head. CONCLUSIONS: Our data gave further insights into subfunctions within the complex cortical network involved in the processing of visual-vestibular interaction during CV. Specific areas of this cortical network could be attributed to the ventral stream ("what" pathway) responsible for the duration after stimulus stop and to the dorsal stream ("where/how" pathway) responsible for intensity aspects.

Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study.

PURPOSE: Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. METHODS: Twenty patients with early AD (Mini-Mental State Examination 25.7 ± 1.7) were studied with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. RESULTS: Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p < 0.005). The same correlation pattern was found for right hippocampal diffusivity (p < 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. CONCLUSION: These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment.

Relationships between hippocampal microstructure, metabolism, and function in early Alzheimer's disease.

Abnormal microstructural integrity and glucose metabolism of the hippocampus are common in subjects with Alzheimer's disease (AD) that typically manifest as episodic memory impairment. The above-tissue alterations can be captured in vivo using diffusion tensor imaging (DTI) and positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET). Here, we explored relationships between the above neuroimaging and cognitive markers of early AD-specific hippocampal damage. Twenty patients with early AD (MMSE 25.7 ± 1.7) were studied using DTI and FDG-PET. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). In the between-modality correlation analysis, FDG uptake was strongly associated with diffusivity in the left anterior hippocampus only (r = -0.81, p < 0.05 Bonferroni's corrected for multiple tests). Performance on DVR significantly correlated with left anterior (r = -0.80, p < 0.05) and left mean (r = -0.72, p < 0.05) hippocampal diffusivity, while the correlation with left anterior FDG uptake did not reach statistical significance (r = 0.52, n.s.). DTI-derived diffusivity of the anterior hippocampus might be a sensitive early marker of hippocampal dysfunction as reflected at the synaptic and cognitive levels. This neurobiological distinction of the anterior hippocampus might be related to the disruption of the perforant pathway that is known to occur early in the course of AD.

Evidence for modulation of opioidergic activity in central vestibular processing: A [(18)F] diprenorphine PET study.

Animal and functional imaging studies had identified cortical structures such as the parieto-insular vestibular cortex, the retro-insular cortex, or the anterior cingulate cortex belonging to a vestibular cortical network. Basic animal studies revealed that endorphins might be important transmitters involved in cerebral vestibular processing. The aim of the present study was therefore to analyse whether the opioid system is involved in vestibular neurotransmission of humans or not. Changes in opioid receptor availability during caloric air stimulation of the right ear were studied with [(18)F] Fluoroethyl-diprenorphine ([(18)F]FEDPN) PET scans in 10 right-handed healthy volunteers and compared to a control condition. Decrease in receptor availability to [(18)F]FEDPN during vestibular stimulation in comparison to the control condition was significant at the right posterior insular cortex and the postcentral region indicating more endogenous opioidergic binding in these regions during stimulation. These data give evidence that the opioidergic system plays a role in the right hemispheric dominance of the vestibular cortical system in right-handers.

Blood constituents trigger brain swelling, tissue death, and reduction of glucose metabolism early after acute subdural hematoma in rats.

Outcome from acute subdural hematoma is often worse than would be expected from the pure increase of intracranial volume by bleeding. The aim was to test whether volume-independent pathomechanisms aggravate damage by comparing the effects of blood infusion with those of an inert fluid, paraffin oil, on intracranial pressure (ICP), cerebral perfusion pressure (CPP), local cerebral blood flow (CBF), edema formation, glucose metabolism ([18F]-deoxyglucose, MicroPET ), and histological outcome. Rats were injured by subdural infusion of 300 muL venous blood or paraffin. ICP, CPP, and CBF changes, assessed during the first 30 mins after injury, were not different between the injury groups at most time points (n=8 per group). Already at 2 h after injury, blood caused a significantly more pronounced decrease in glucose metabolism in the injured cortex when compared with paraffin (P<0.001, n=5 per group). Ipsilateral brain edema did not differ between groups at 2 h, but was significantly more pronounced in the blood-treated groups at 24 and 48 h after injury (n=8 per group). These changes caused a 56.2% larger lesion after blood when compared with paraffin (48.1+/-23.0 versus 21.1+/-11.8 mm(3); P<0.02). Blood constituent-triggered pathomechanisms aggravate the immediate effects due to ICP, CPP, and CBF during hemorrhage and lead to early reduction of glucose metabolism followed by more severe edema and histological damage.

Clinical improvement in a case of frontotemporal dementia under aripiprazole treatment corresponds to partial recovery of disturbed frontal glucose metabolism.

Frontotemporal dementia (FTD) is increasingly recognized as an important type of degenerative dementia but satisfactory pharmacological treatment has not yet been established. We examined the clinical effects of aripiprazole, a new antipsychotic with partial agonistic properties at serotonin 5-HT(1A) and dopamine D(2) receptors, in parallel with cortical glucose metabolism changes. We conducted a follow-up investigation of clinical status and (18)F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in a 73-year-old male patient with FTD over a 13-month period. Under conventional drug treatment during the first 12 months a marked increase in dementia symptoms was observed. Frontal lobe glucose metabolism clearly decreased during this time period. Under consecutive treatment with aripiprazole a significant and stable improvement of clinical symptoms could be registered, while disturbed frontal glucose metabolism increased significantly. According to this case experience, further investigations should be undertaken to ascertain whether aripiprazole or other atypical antipsychotics with properties to improve impaired dopaminergic transmission in frontal brain regions could qualify for therapy of FTD.