Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease

Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month-old APP(SweLon)/PS1(M146L), a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared with age-matched control mice. We then developed a method of 3-D microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganization of glucose uptake in relation to cerebral amyloidosis.     

Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [C]DASB and [F]altanserin-PET study

In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT_2A) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT_2A receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [¹⁸F]altanserin and [¹¹C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine ([¹¹C]DASB). Overall [¹⁸F]altanserin binding was markedly reduced in AD by 28%-39% (p = 0.02), whereas the reductions in [¹¹C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in [¹¹C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT_2A receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections.     

PET imaging with [18F]AV-45 in an APP/PS1-21 murine model of amyloid plaque deposition

Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the accumulation of β-amyloid peptide. In man, [18F]AV-45 with positron emission tomography (PET) is currently studied and used to track in vivo amyloid accumulation. Here, [18F]-AV45-PET was used to visualize amyloid deposition in a transgenic murine model of amyloidosis (APP/PS1-21). Studies were performed ex vivo by autoradiography and in vivo by microPET. Autoradiograms of the brain sections highlighted an increased uptake of [18F]AV-45 in APP/PS1-21 mice compared with age-matched control mice. From 8 months, an intense labeling was observed in cortex, hippocampus, and striatum. The marked accumulation of radiotracer was found in close association with thioflavin S-positive amyloid plaques. The longitudinal microPET assessment, performed from 3 to 12 months of age, demonstrated an increased [18F]AV-45 uptake in APP/PS1-21 compared with control mice. The elevated tracer uptake was increased in association with age. This study opens the possibility of [18F]AV-45, coupled with microPET, to visualize and quantitatively measure amyloid deposits in the brains of living APP/PS1 mice.     

Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer's disease

In this study 5 patients with mild cognitive impairment (MCI) and 9 Alzheimer’s disease (AD) patients underwent respectively 3- and 5-year follow-up positron emission tomography (PET) studies with N-methyl [¹¹C] 2-(4-methylaminophenyl)-6-hydroxy-benzothiazole (¹¹C-PIB) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) to understand the time courses in AD disease processes. Significant increase in PIB retention as well as decrease in regional cerebral metabolic rate of glucose (rCMRglc) was observed at group level in the MCI patients while no significant change was observed in cognitive function. At group level the AD patients showed unchanged high PIB retention at 5-year follow-up compared with baseline. At the individual level, increased, stable, and decreased PIB retention were observed while disease progression was reflected in significant decrease in rCMRglc and cognition. In conclusion, after a long-term follow-up with PET, we observed an increase in fibrillar amyloid load in MCI patients followed by more stable level in clinical AD patients. The rCMRglc starts to decline in MCI patients and became more pronounced in clinical stage which related to continuous decline in cognition.     

Drug‐induced cardiomyopathy: Characterization of a rat model by [18F]FDG/PET and [99mTc]MIBI/SPECT

BackgroundDrug‐induced cardiomyopathy is a significant medical problem. Clinical diagnosis of myocardial injury is based on initial electrocardiogram, levels of circulating biomarkers, and perfusion imaging with single photon emission computed tomography (SPECT). Positron emission tomography (PET) is an alternative imaging modality that provides better resolution and sensitivity than SPECT, improves diagnostic accuracy, and allows therapeutic monitoring. The objective of this study was to assess the detection of drug‐induced cardiomyopathy by PET using 2‐deoxy‐2‐[¹⁸F]fluoro‐D‐glucose (FDG) and compare it with the conventional SPECT technique with [^99mTc]‐Sestamibi (MIBI).MethodsCardiomyopathy was induced in Sprague Dawley rats using high‐dose isoproterenol. Nuclear [¹⁸F]FDG/PET and [^99mTc]MIBI/SPECT were performed before and after isoproterenol administration. [¹⁸F]FDG (0.1 mCi, 200‐400 µL) and [^99mTc]MIBI (2 mCi, 200‐600 µL) were administered via the tail vein and imaging was performed 1 hour postinjection. Isoproterenol‐induced injury was confirmed by the plasma level of cardiac troponin and triphenyltetrazolium chloride (TTC) staining.ResultsIsoproterenol administration resulted in an increase in circulating cardiac troponin I and showed histologic damage in the myocardium. Visually, preisoproterenol and postisoproterenol images showed alterations in cardiac accumulation of [¹⁸F]FDG, but not of [^99mTc]MIBI. Image analysis revealed that myocardial uptake of [¹⁸F]FDG reduced by 60% after isoproterenol treatment, whereas that of [^99mTc]MIBI decreased by 45%.ConclusionWe conclude that [¹⁸F]FDG is a more sensitive radiotracer than [^99mTc]MIBI for imaging of drug‐induced cardiomyopathy. We theorize that isoproterenol‐induced cardiomyopathy impacts cellular metabolism more than perfusion, which results in more substantial changes in [¹⁸F]FDG uptake than in [^99mTc]MIBI accumulation in cardiac tissue.     

Effects of amyloid-β peptides on the serotoninergic 5-HT1A receptors in the rat hippocampus

A recent [¹⁸F]MPPF-positron emission tomography study has highlighted an overexpression of 5-HT_1A receptors in the hippocampus of patients with mild cognitive impairment compared to a decrease in those with Alzheimer's disease (AD) [Truchot, L., Costes, S.N., Zimmer, L., Laurent, B., Le Bars, D., Thomas-Antérion, C., Croisile, B., Mercier, B., Hermier, M., Vighetto, A., Krolak-Salmon, P., 2007. Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment. Neurology 69 (10), 1012-1017]. We used in vivo and in vitro neuroimaging to evaluate the longitudinal effects of injecting amyloid-β (Aβ) peptides (1-40) into the dorsal hippocampus of rats. In vivo microPET imaging showed no significant change in [¹⁸F]MPPF binding in the dorsal hippocampus over time, perhaps due to spatial resolution. However, in vitro autoradiography with [¹⁸F]MPPF (which is antagonist) displayed a transient increase in 5-HT_1A receptor density 7 days after Aβ injection, whereas [¹⁸F]F15599 (a radiolabelled 5-HT_1A agonist) binding was unchanged suggesting that the overexpressed 5-HT_1A receptors were in a non-functional state. Complementary histology revealed a loss of glutamatergic neurons and an intense astroglial reaction at the injection site. Although a neurogenesis process cannot be excluded, we propose that Aβ injection leads to a transient astroglial overexpression of 5-HT_1A receptors in compensation for the local neuronal loss. Exploration of the functional consequences of these serotoninergic modifications during the neurodegenerative process may have an impact on therapeutics targeting 5-HT_1A receptors in AD.     

Pyruvate‐lactate exchange and glucose uptake in human prostate cancer cell models. A study in xenografts and suspensions by hyperpolarized [1‐13C]pyruvate MRS and [18F]FDG‐PET

Reprogramming of energy metabolism in the development of prostate cancer can be exploited for a better diagnosis and treatment of the disease. The goal of this study was to determine whether differences in glucose and pyruvate metabolism of human prostate cancer cells with dissimilar aggressivenesses can be detected using hyperpolarized [1‐¹³C]pyruvate MRS and [¹⁸F]FDG‐PET imaging, and to evaluate whether these measures correlate. For this purpose, we compared murine xenografts of human prostate cancer LNCaP cells with those of more aggressive PC3 cells. [1‐¹³C]pyruvate was hyperpolarized by dissolution dynamic nuclear polarization (dDNP) and [1‐¹³C]pyruvate to lactate conversion was followed by ¹³C MRS. Subsequently [¹⁸F]FDG uptake was investigated by static and dynamic PET measurements. Standard uptake values (SUVs) for [¹⁸F]FDG were significantly higher for xenografts of PC3 compared with those of LNCaP. However, we did not observe a difference in the average apparent rate constant k_pl of ¹³C label exchange from pyruvate to lactate between the tumor variants. A significant negative correlation was found between SUVs from [¹⁸F]FDG PET measurements and k_pl values for the xenografts of both tumor types. The k_pl rate constant may be influenced by various factors, and studies with a range of prostate cancer cells in suspension suggest that LDH inhibition by pyruvate may be one of these. Our results indicate that glucose and pyruvate metabolism in the prostate cancer cell models differs from that in other tumor models and that [¹⁸F]FDG‐PET can serve as a valuable complementary tool in dDNP studies of aggressive prostate cancer with [1‐¹³C]pyruvate.     

Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study

Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre‐therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high‐grade glioma, where we directly compared the two currently most promising techniques, namely the MR‐based relative oxygen extraction fraction (MR‐rOEF) and the PET hypoxia marker H‐1‐(3‐[¹⁸F]‐fluoro‐2‐hydroxypropyl)‐2‐nitroimidazole ([¹⁸F]‐FMISO). MR‐rOEF was determined from separate measurements of T₂, T₂* and relative cerebral blood volume (rCBV) employing a multi‐parametric approach for quantification of the blood‐oxygenation‐level‐dependent (BOLD) effect. With respect to [¹⁸F]‐FMISO‐PET, besides the commonly used late uptake between 120 and 130 min ([¹⁸F]‐FMISO_{120–130 min}), we also analyzed the hypoxia specific uptake rate [¹⁸F]‐FMISO‐k₃, as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [¹⁸F]‐FMISO data was sensitive to a low signal‐to‐noise‐ratio, analysis was restricted to high‐uptake tumor regions. Individual spatial analyses of deoxygenation and hypoxia‐related parameter maps revealed that high MR‐rOEF values clustered in (edematous) peritumoral tissue, while areas with high [¹⁸F]‐FMISO_{120–130 min} concentrated in and around active tumor with disrupted blood–brain barrier, i.e. contrast enhancement in T₁‐weighted MRI. Volume‐of‐interest‐based correlations between MR‐rOEF and [¹⁸F]‐FMISO_{120–130 min} as well as [¹⁸F]‐FMISO‐k₃, and voxel‐wise analyses in individual patients, yielded limited correlations, supporting the notion that [¹⁸F]‐FMISO uptake, even after 2 h, might still be influenced by perfusion while [¹⁸F]‐FMISO‐k₃ was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR‐rOEF, and severe tissue hypoxia, as measured by [¹⁸F]‐FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high‐grade glioma biology.     

Aluminium hydroxide stabilised MnFe2O4 and Fe3O4 nanoparticles as dual-modality contrasts agent for MRI and PET imaging

Magnetic nanoparticles (NPs) MnFe₂O₄ and Fe₃O₄ were stabilised by depositing an Al(OH)₃ layer via a hydrolysis process. The particles displayed excellent colloidal stability in water and a high affinity to [¹⁸F]-fluoride and bisphosphonate groups. A high radiolabeling efficiency, 97% for ¹⁸F-fluoride and 100% for ⁶⁴Cu-bisphosphonate conjugate, was achieved by simply incubating NPs with radioactivity solution at room temperature for 5 min. The properties of particles were strongly dependant on the thickness and hardness of the Al(OH)₃ layer which could in turn be controlled by the hydrolysis method. The application of these Al(OH)₃ coated magnetic NPs in molecular imaging has been further explored. The results demonstrated that these NPs are potential candidates as dual modal probes for MR and PET. In vivo PET imaging showed a slow release of ¹⁸F from NPs, but no sign of efflux of ⁶⁴Cu.     

Functional neuroimaging of the 6-OHDA lesion rat model of Parkinson's disease

We characterized the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat, a well-known acute model of Parkinson's disease (PD), with [(18)F]-fluoro-2-deoxy-d-glucose (FDG) small-animal positron emission tomography (PET), which we compared with a drug-induced rotation behavioral test. In the 6-OHDA model, significant glucose hypometabolism was present in the primary motor cortex, substantia nigra, and pedunculopontine tegmental nucleus on the ipsilateral side. In contrast, neuronal activations were observed in the primary somatosensory cortex and ventral caudate-putamen area after lesioning. Correlation analysis revealed a significant relationship between the behavioral results and the degree of glucose metabolism impairment in the primary motor cortex, substantia nigra, and pedunculopontine tegmental nucleus. In addition, the pedunculopontine tegmental nucleus correlated significantly with the primary somatosensory cortex, the ventral caudate-putamen, the substantia nigra, and the primary motor cortex. Furthermore, the primary motor cortex also showed significant correlations with the substantia nigra. In conclusion, In vivo cerebral mapping of the 6-OHDA-lesioned rats using [(18)F]-FDG PET showed correspondence at the functional levels to the cortico-subcortical network impairment observed in PD patients.     

Effectiveness of [(124)I]-PET/CT and [(18)F]-FDG-PET/CT for Localizing Recurrence in Patients with Differentiated Thyroid Carcinoma

Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is generally encouraging, a diagnostic dilemma is posed when an increasing level of serum thyroglobulin (Tg) is noted, without detection of a recurrent tumor using conventional imaging tools such as the iodine-131 whole-body scanning (the [(131)I] scan) or neck ultrasonography (US). The objective of the present study was to evaluate the diagnostic value of [(124)I]-PET/CT and [(18)F]-FDG-PET/CT in terms of accurate detection of both iodine- and non-iodine-avid recurrence, compared with that of conventional imaging such as the [(131)I] scan or neck ultrasonography (US). Between July 2009 and June 2010, we prospectively studied 19 DTC patients with elevated thyroglobulin levels but who do not show pathological lesions when conventional imaging modalities are used. All involved patients had undergone total thyroidectomy and radioiodine (RI) treatment, and who had been followed-up for a mean of 13 months (range, 6-21 months) after the last RI session. Combined [(18)F]-FDG-PET/CT and [(124)I]-PET/CT data were evaluated for detecting recurrent DTC lesions in study patients and compared with those of other radiological and/or cytological investigations. Nine of 19 patients (47.4%) showed pathological [(18)F]-FDG (5/19, 26.3%) or [(124)I]-PET (4/19, 21.1%) uptake, and were classed as true-positives. Among such patients, disease management was modified in six (66.7%) and disease was restaged in seven (77.8%). In particular, the use of the described imaging combination optimized planning of surgical resection to deal with locoregional recurrence in 21.1% (4/19) of patients, who were shown to be disease-free during follow-up after surgery. Our results indicate that combination of [(18)F]-FDG-PET/CT and [(124)I]-PET/CT affords a valuable diagnostic method that can be used to make therapeutic decisions in patients with DTC who are tumor-free on conventional imaging studies but who have high Tg levels.     

Improvement of electroacupuncture on APP/PS1 transgenic mice in behavioral probably due to reducing deposition of Aβ in hippocampus

Alzheimer's disease (AD) is a fatal neurodegenerative disease for which currently no cure is available. Electroacupuncture (EA) has been widely used in China as an alternative therapeutic approach for neurological diseases. The cognitive decline in patients with AD has been reported to be closely related to the deposition of amyloid-β (Aβ) in the hippocampus of the brain, and the Morris water maze (MWM) test is a widely used method for assessing the behavior of animal models. In this study, the MWM test was performed to evaluate the effects of EA treatment on cognitive function and memory, and the micro-positron emission tomography scan was used to assess the hippocampal Aβ deposition. The results showed that the cognitive function of APP/PS1 mice was significantly improved and the rate of [18F]AV-45 uptake was reduced in the EA group, compared with the AD group. Our study suggested that EA can exert a therapeutic effect in AD by improving spatial learning and memory and inhibiting the hippocampal Aβ deposition.     

PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease

In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann–Sträussler–Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d -glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between [F-18]FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical [F-18]FDDNP binding, yet progressive [F-18]FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of [F-18]FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with [F-18]FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions.     

Glucose metabolism and PIB binding in carriers of a His163Tyr presenilin 1 mutation

Six young related pre-symptomatic carriers of a His163Tyr mutation in the presenilin 1 gene who will develop early onset familial Alzheimer's disease (eoFAD), and a control group of 23 non-carriers underwent ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET). The mutation carriers were followed-up after 2 years. Multivariate analysis showed clear separation of carriers from non-carriers on both occasions, with the right thalamus being the region contributing most to group differentiation. Statistical parametric mapping (SPM) revealed in the carriers non-significantly lower thalamic cerebral glucose metabolism (CMRglc) at baseline and significantly decreased CMRglc in the right thalamus at follow-up. One mutation carrier was followed-up with FDG PET 10 years after baseline and showed reductions in cognition and CMRglc in the posterior cingulate and the frontal cortex. This subject was diagnosed with AD 1 year later and assessed with an additional FDG as well as an ¹¹C-PIB PET scan 12 years after baseline. Global cortical CMRglc and cognition were distinctly decreased. PIB binding was comparable with sporadic AD patterns but showing slightly higher striatal levels.     

Simultaneous imaging of hyperpolarized [1,4‐13C2]fumarate, [1‐13C]pyruvate and 18F–FDG in a rat model of necrosis in a clinical PET/MR scanner

A co‐polarization scheme for [1,4‐¹³C₂]fumarate and [1‐¹³C]pyruvate is presented to simultaneously assess necrosis and metabolism in rats with hyperpolarized ¹³C magnetic resonance (MR). The co‐polarization was performed in a SPINlab polarizer. In addition, the feasibility of simultaneous positron emission tomography (PET) and MR of small animals with a clinical PET/MR scanner is demonstrated. The hyperpolarized metabolic MR and PET was demonstrated in a rat model of necrosis. The polarization and T₁ of the co‐polarized [1,4‐¹³C₂]fumarate and [1‐¹³C]pyruvate substrates were measured in vitro and compared with those obtained when the substrates were polarized individually. A polarization of 36 ± 4% for fumarate and 37 ± 6% for pyruvate was obtained. We found no significant difference in the polarization and T₁ values between the dual and single substrate polarization. Rats weighing about 400 g were injected intramuscularly in one of the hind legs with 200 μL of turpentine to induce necrosis. Two hours later, ¹³C metabolic maps were obtained with a chemical shift imaging sequence (16 × 16) with a resolution of 3.1 × 5.0 × 25.0 mm³. The ¹³C spectroscopic images were acquired in 12 s, followed by an 8‐min ¹⁸F‐2‐fluoro‐2‐deoxy‐d ‐glucose (¹⁸F–FDG) PET acquisition with a resolution of 3.5 mm. [1,4‐¹³C₂]Malate was observed from the tissue injected with turpentine indicating necrosis. Normal [1‐¹³C]pyruvate metabolism and ¹⁸F–FDG uptake were observed from the same tissue. The proposed co‐polarization scheme provides a means to utilize multiple imaging agents simultaneously, and thus to probe various metabolic pathways in a single examination. Moreover, it demonstrates the feasibility of small animal research on a clinical PET/MR scanner for combined PET and hyperpolarized metabolic MR.     

Para-chloro-2-[18F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging

Introduction: [¹¹C]Metomidate ([¹¹C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [¹¹C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting.Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T_1/2=109.5 min) etomidate analogue, para-chloro-2-[¹⁸F]fluoroethyl etomidate; [¹⁸F]CETO, as an adrenal PET tracer.Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [¹⁸F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [¹¹C]MTO.Results: The binding of [¹⁸F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro K_d of 0.66 nM. Non-specific uptake of [¹⁸F]CETO in NHP liver was found to be low compared to that of [¹¹C]MTO.Conclusions: High specificity of [¹⁸F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [¹¹C]MTO. Non-specific binding to the liver was significantly lower than that of [¹¹C]MTO. [¹⁸F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans.     

Cognition, glucose metabolism and amyloid burden in Alzheimer's disease

The authors investigated relationships between glucose metabolism, amyloid load, and measures of cognitive and functional impairment in Alzheimer's disease (AD). Patients meeting criteria for probable AD underwent ¹¹C-labeled Pittsburgh Compound-B ([¹¹C]PIB) and 18F-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) imaging and were assessed on a set of clinical measures. The Pittsburgh Compound-B (PIB) Distribution volume ratios and fluorodeoxyglucose (FDG) scans were spatially normalized and average PIB counts from regions-of-interest (ROI) were used to compute a measure of global PIB uptake. Separate voxel-wise regressions explored local and global relationships between metabolism, amyloid burden, and clinical measures. Regressions reflected cognitive domains assessed by individual measures, with visuospatial tests associated with more posterior metabolism, and language tests associated with metabolism in the left hemisphere. Correlating regional FDG uptake with these measures confirmed these findings. In contrast, no correlations were found between either voxel-wise or regional PIB uptake and any of the clinical measures. Finally, there were no associations between regional PIB and FDG uptake. We conclude that regional and global amyloid burden does not correlate with clinical status or glucose metabolism in AD.     

Analysis of neuroreceptor PET-data based on cytoarchitectonic maximum probability maps: a feasibility study

Three-dimensional maximum probability maps (MPMs) of cytoarchitectonically defined cortical regions based on postmortem histological studies have recently been made available in the stereotaxic reference space of the Montreal Neurological Institute (MNI) single subject template. This permits the use of cytoarchitectonic maps for the analysis of functional in vivo datasets, including neuroreceptor positron emission tomography (PET) studies. In this feasibility study, we used 5-hydroxytryptamine 2A (5-HT_2A) receptor PET to test the applicability of maximum cytoarchitectonic probability maps for quantitative analysis. As the outcome parameter, we extracted local distribution volume ratios (DVRs) from 19 cytoarchitectonically defined volumes of interest (VOIs) per hemisphere from five healthy subjects. The experimental design included a forward (‘PET to atlas‘ normalization) and a backward (‘atlas to PET’ normalization) procedure to double-check the stability of transformation and overlay. Resulting DVRs were compared with receptor densities (RDs) obtained from postmortem [³H]ketanserin autoradiography of multiple areas. Correlations between the bi-directional normalization procedures (r=0.89; 38 VOIs) as well as between in vivo and vitro data (nine VOIs; r=0.64 and r=0.47 for forward and backward procedure, respectively) suggest that the implementation of cytoarchitectonic maximum probability maps is a promising method for an accurate and observer-independent analysis of neuroreceptor PET data.     

Radiomics based on fluoro-deoxyglucose positron emission tomography predicts liver fibrosis in biopsy-proven MAFLD: a pilot study

Rationale: Since non-invasive tests for prediction of liver fibrosis have a poor diagnostic performance for detecting low levels of fibrosis, it is important to explore the diagnostic capabilities of other non-invasive tests to diagnose low levels of fibrosis. We aimed to evaluate the performance of radiomics based on ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) in predicting any liver fibrosis in individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD).Methods: A total of 22 adults with biopsy-confirmed MAFLD, who underwent ¹⁸F-FDG PET/CT, were enrolled in this study. Sixty radiomics features were extracted from whole liver region of interest in ¹⁸F-FDG PET images. Subsequently, the minimum redundancy maximum relevance (mRMR) method was performed and a subset of two features mostly related to the output classes and low redundancy between them were selected according to an event per variable of 5. Logistic regression, Support Vector Machine, Naive Bayes, 5-Nearest Neighbor and linear discriminant analysis models were built based on selected features. The predictive performances were assessed by the receiver operator characteristic (ROC) curve analysis.Results: The mean (SD) age of the subjects was 38.5 (10.4) years and 17 subjects were men. 12 subjects had histological evidence of any liver fibrosis. The coarseness of neighborhood grey-level difference matrix (NGLDM) and long-run emphasis (LRE) of grey-level run length matrix (GLRLM) were selected to predict fibrosis. The logistic regression model performed best with an AUROC of 0.817 [95% confidence intervals, 0.595-0.947] for prediction of liver fibrosis.Conclusion: These preliminary data suggest that ¹⁸F-FDG PET radiomics may have clinical utility in assessing early liver fibrosis in MAFLD.     

Rapid spread of mannan to the immune system,skin and joints within 6 hours after local exposure

Psoriasis (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are common diseases dependent on environmental factors that activate the immune system in unknown ways. Mannan is a group of polysaccharides common in the environment; they are potentially pathogenic, because at least some of them induce Ps-, PsA- and RA-like inflammation in mice. Here, we used positron emission tomography/computed tomography to examine in-vivo transport and spread of mannan labelled with fluorine-18 [¹⁸F]. The results showed that mannan was transported to joints (knee) and bone marrow (tibia) of mice within 6 h after intraperitoneal injection. The time it took to transport mannan, and its presence in blood, indicated cellular transport of mannan within the circulatory system. In addition, mannan was filtered mainly through the spleen and liver. [¹⁸F]fluoromannan was excreted via kidneys, small intestine and, to some extent, the mouth. In conclusion, mannan reaches joints rapidly after injection, which may explain why mannan-induced inflammatory disease is targeted to these tissues.