Differentiating radiation necrosis from tumor recurrence in high-grade gliomas: Assessing the efficacy of F-FDG PET,C-methionine PET and perfusion MRI

Purpose

The authors analyzed the characteristics of perfusion magnetic resonance imaging (MRI), ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and ¹¹C-methionine (MET) PET to compare the efficacies of these modalities in making the distinction between radiation necrosis and tumor recurrence of high-grade glioma.

Patients and methods

Ten patients were evaluated with dynamic susceptibility contrast perfusion MRI, ¹¹C-MET PET and ¹⁸F-FDG PET to visualize gadolinium-enhanced lesions during the post-radiation follow-up period. In the perfusion MRI, four regions of interest (ROIs) were identified and average values were calculated. A reference ROI of the same size was defined in the contralateral white matter to obtain the relative cerebral blood volume (rCBV). After coregistering the PET images with the MRI, we measured the maximum uptake values of the lesion and of the contralateral cerebral white matter as reference area to calculate the L_max/R_max ratio.

Results

The rCBV was higher in the recurrence group than in the necrosis group (p = 0.010). There was no difference between groups in terms of the L_max/R_max ratio as derived from the ¹⁸F-FDG and ¹¹C-MET PET.

Conclusion

A quantitative rCBV as calculated from a perfusion MRI scan might be superior to the L_max/R_max ratio as derived from ¹⁸F-FDG and ¹¹C-MET PET in order to distinguish a recurrence of high-grade glioma from radiation necrosis.     

Inflammation Coupling Between Unstable Carotid Plaque and Spleen—A 18F-Fluorodeoxyglucos Positron Emission Tomography Study

Background and purpose

This study was aimed to assess the hypothesis that unstable plaque formation in the carotid artery is one of phenotypes of chronic and systemic inflammation.

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II

Objective

Favorable seizure outcome is reported following resection of bottom-of-sulcus dysplasia (BOSD). We assessed the distribution of epileptogenicity and dysplasia in and around BOSD to better understand this clinical outcome and the optimal surgical approach.

Methods

We studied 27 children and adolescents with magnetic resonance imaging (MRI)-positive BOSD who underwent epilepsy surgery; 85% became seizure-free postresection (median = 5.0 years follow-up). All patients had resection of the dysplastic sulcus, and 11 had additional resection of the gyral crown (GC) or adjacent gyri (AG). Markers of epileptogenicity were relative cortical hypometabolism on preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and spiking, ripples, fast ripples, spike–high-frequency oscillation cross-rate, and phase amplitude coupling (PAC) on preresection and postresection electrocorticography (ECoG), all analyzed at the bottom-of-sulcus (BOS), top-of-sulcus (TOS), GC, and AG. Markers of dysplasia were increased cortical thickness on preoperative MRI, and dysmorphic neuron density and variant allele frequency of somatic MTOR mutations in resected tissue, analyzed at similar locations.

Results

Relative cortical metabolism was significantly reduced and ECoG markers were significantly increased at the BOS compared to other regions. Apart from spiking and PAC, which were greater at the TOS compared to the GC, there were no significant differences in PET and other ECoG markers between the TOS, GC, and AG, suggesting a cutoff of epileptogenicity at the TOS rather than a tapering gradient on the cortical surface. MRI and tissue markers of dysplasia were all maximal in the BOS, reduced in the TOS, and mostly absent in the GC. Spiking and PAC reduced significantly over the GC after resection of the dysplastic sulcus.

Significance

These findings support the concept that dysplasia and intrinsic epileptogenicity are mostly limited to the dysplastic sulcus in BOSD and support resection or ablation confined to the MRI-visible lesion as a first-line surgical approach. ¹⁸F-FDG PET and ECoG abnormalities in surrounding cortex seem to be secondary phenomena.     

Diagnostic value of brain MRI and 18F‐FDG PET in the differentiation of parkinsonian type multiple system atrophy from Parkinson’s disease

Background and purpose: Differentiation between parkinsonian type multiple system atrophy (MSA‐P) and Parkinson’s disease (PD) is important but often difficult. We investigated the diagnostic value of brain magnetic resonance imaging (MRI) and ¹⁸F‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) in differentiating MSA‐P from PD. Methods: Twenty‐four patients with MSA‐P (16 probable and 8 possible) and eight patients with PD were included in this study. Results: For analysis using the putaminal findings, the sensitivities were 58.3% by visual analysis of brain MRI, 95.8% by visual analysis of ¹⁸F‐FDG PET, and 79.2% by statistical parametric mapping (SPM) analysis of ¹⁸F‐FDG PET in differentiating MSA‐P from PD; the specificity was 100% for each analysis. Using the putaminal findings, visual analysis of ¹⁸F‐FDG PET had a higher sensitivity compared with brain MRI (P = 0.004) and SPM analysis of ¹⁸F‐FDG PET revealed a tendency towards higher sensitivity compared with brain MRI (P = 0.063). For analysis using both putaminal and infratentorial findings, the sensitivities were 79.2% by visual analysis of brain MRI, 95.8% by visual analysis of ¹⁸F‐FDG PET, 95.8% by SPM analysis of ¹⁸F‐FDG PET in differentiating MSA‐P from PD; the specificity was 100% for each analysis. Conclusion: Both brain MRI and ¹⁸F‐FDG PET showed diagnostic usefulness in differentiating MSA‐P from PD, with ¹⁸F‐FDG PET being more sensitive than brain MRI.     

Longitudinal Synaptic Loss in Primary Tauopathies: An In Vivo [11C]UCB-J Positron Emission Tomography Study

Background

Synaptic loss is characteristic of many neurodegenerative diseases; it occurs early and is strongly related to functional deficits.

Objective

In this longitudinal observational study, we determine the rate at which synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and we test the relationship with disease progression.

Methods

Our cross-sectional cohort included 32 participants with probable PSP and 16 with probable CBD (all amyloid-negative corticobasal syndrome), recruited from tertiary care centers in the United Kingdom, and 33 sex- and age-matched healthy control subjects. Synaptic density was estimated by positron emission tomography imaging with the radioligand [¹¹C]UCB-J that binds synaptic vesicle 2A. Clinical severity and cognition were assessed by the PSP Rating Scale and the Addenbrooke's cognitive examination. Regional [¹¹C]UCB-J nondisplaceable binding potential was estimated in Hammersmith Atlas regions of interest. Twenty-two participants with PSP/CBD had a follow-up [¹¹C]UCB-J positron emission tomography scan after 1 year. We calculated the annualized change in [¹¹C]UCB-J nondisplaceable binding potential and correlated this with the change in clinical severity.

Results

We found significant annual synaptic loss within the frontal lobe (−3.5%, P = 0.03) and the right caudate (−3.9%, P = 0.046). The degree of longitudinal synaptic loss within the frontal lobe correlated with the rate of change in the PSP Rating Scale (R = 0.47, P = 0.03) and cognition (Addenbrooke's Cognitive Examination–Revised, R = −0.62, P = 0.003).

Conclusions

We provide in vivo evidence for rapid progressive synaptic loss, correlating with clinical progression in primary tauopathies. Synaptic loss may be an important therapeutic target and outcome variable for early-phase clinical trials of disease-modifying treatments. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Predicting diagnosis and cognition with 18F-AV-1451 tau PET and structural MRI in Alzheimer's disease

Introduction

The relative importance of structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) to predict diagnosis and cognition in Alzheimer's disease (AD) is unclear.

Effects of constraint-induced movement therapy on brain glucose metabolism in a rat model of cerebral ischemia: a micro PET/CT study

Purpose: Constraint-induced movement therapy (CIMT) can improve motor functions in stroke patients and ischemic rats. This study examined the effect of CIMT in ischemic rats using positron emission tomography (PET).

Methods: We used middle cerebral artery occlusion (MCAO) procedure to induce cerebral ischemia in rats. Male rats were divided into a negative control group (Normal, n = 4), a sham-operated group (Sham, n = 6), an ischemic group (Control, n = 6) and an ischemic CIMT-treated group (CIMT, n = 6). CIMT started at postoperative day 8 (d8) and lasted for 2 weeks. We utilized 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) micro PET/CT imaging to evaluate glucose metabolism in different brain regions at baseline, before, and after treatment, respectively.

Results: CIMT improved behavioral performance in the ischemic CIMT group. At the end of treatment, the CIMT group showed lower standardized uptake values (SUVs) in the ipsilateral cingulate, motor and somatosensory cortex, respectively; as well as the anterodorsal hippocampus compared to the Control group (1.80% ± 0.10% vs. 1.92% ± 0.08%, 1.32% ± 0.14% vs. 1.48% ± 0.09%, 1.18% ± 0.14% vs. 1.42% ± 0.15%, 1.68% ± 0.09% vs. 1.79% ± 0.06%, P < 0.05). We also observed higher SUVs in the acbcore shell and cortex insular of the contralateral hemisphere compared to the Control group (2.07% group in the acbcore shell and cortex insular of contralateral P < 0.05).

Conclusion: CIMT improved behavioral outcomes in cerebral ischemic rats and this effect can be attributed to increased glucose utilization in the contralateral hemisphere.     

Contemporary Encephalitis Lethargica: Phenotype,laboratory findings and treatment outcomes

Abstract Background   Encephalitis lethargica (EL) is a CNS disorder that manifests with lethargy sleep cycle disturbances, extrapyramidal symptomatology, neuropsychiatric manifestations, ocular features and cardio-respiratory abnormalities. Although there have been no reported outbreaks of EL recently, a number of reports show that cases of EL are still encountered regularly. Against this background we conducted a study aiming to elucidate the clinical characteristics, describe laboratory/ neuroimaging findings (MRI, PET) and present treatment options and outcomes in sporadic EL. Methods   Patients were diagnosed over a period of 3 years using proposed diagnostic criteria. Extensive laboratory and imaging tests were performed for exclusion of other causes. Anti-neuronal antibodies against human basal ganglia were detected with western immunoblotting and ¹⁸F-FDG PET imaging was performed. Selected cases were videotaped. Results   Our patients (M/F: 5/3) ranged from 2–28 years (mean 9.3 ± 9.5). Encephalopathy, sleep disturbances and extrapyramidal symptoms were present in all cases. Laboratory investigations revealed CSF leukocytosis in 5/8 patients and anti-BG Ab in 4/7 patients. MRIs revealed structural abnormalities in 7/8 cases. ¹⁸F-FDG PET showed basal ganglionic hypermetabolism in 4/7 patients. Treatment approaches included immunomodulating and symptomatic therapies. We report no mortality from EL in our series. Conclusions   There seems to be little doubt that cases of EL still occur. Diagnosis may be based on clinical suspicion and laboratory/imaging tests may lead to early initiation of immunomodulating and supporting therapies. We suggest that in addition to anti-BG Abs FDG PET should be considered as a diagnostic tool for EL. Electronic Supplementary Material  Theonline version of this article (DOI) contains supplementarymaterial, which is available to authorized users.     

Comparison of brain MRI and 18F-FDG PET in the differential diagnosis of multiple system atrophy from Parkinson's disease.

To investigate the diagnostic value of brain magnetic resonance image (MRI) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD). Thirty-five patients with MSA (23 MSA-P and 12 MSA-C) and 17 patients with PD were included in this study. Overall correct diagnosis rates between clinical and imaging diagnosis among MSA-P, MSA-C, and PD patients were 80% for visual MRI analysis, 88.5% for visual (18)F-FDG PET analysis, and 84.3% for SPM-supported analysis of (18)F-FDG PET. The sensitivity of brain MRI, and visual and SPM analysis of (18)F-FDG PET in differentiating MSA from PD was 72.7%, 90.9%, and 95.5%, respectively, the specificity was 100% for each imaging analysis, the positive predictive value was 100% for each imaging analysis, and the negative predictive value was 60%, 81.8%, and 90%, respectively. Our results suggest that brain MRI and (18)F-FDG PET are diagnostically useful in differentiating MSA (MSA-P and MSA-C) from PD, and indicate that (18)F-FDG PET has a tendency toward higher sensitivity compared to brain MRI, but a larger longitudinal study including pathological data will be required to confirm our findings.     

Effect of APOE ε4 genotype on amyloid-β, glucose metabolism,and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment

Background and purpose

The presence of apolipoprotein E ε4 (APOE ε4) is associated with an increased risk of developing Alzheimer disease (AD). The aim of this study was to assess the effects of APOE ε4 on amyloid-β (Aβ) pathology, glucose metabolism, and gray matter (GM) volume and their longitudinal changes in healthy control (HC) and amnestic mild cognitive impairment (aMCI).

Methods

We included 50 HCs and 109 aMCI patients from the Alzheimer's Disease Neuroimaging Initiative phase 2/GO based on availability of baseline T1-weighted magnetic resonance imaging, ¹⁸F-florbetapir positron emission tomography (PET), and ¹⁸F-fluorodeoxyglucose (FDG) PET. Of these, 35 HCs and 67 aMCI patients who underwent 24-month scans were included for follow-up study.

Results

Voxelwise analysis revealed that APOE ε4 carriers exhibited greater baseline Aβ deposition than APOE ε4 noncarriers in both diagnostic groups. However, there was no significant difference between APOE ε4 noncarriers and APOE ε4 carriers in terms of ¹⁸F-FDG PET standardized uptake value ratio and GM volume. Region of interest-based analysis showed statistically significant greater Aβ deposition in APOE ε4 carriers than APOE ε4 noncarriers only in aMCI patients. Furthermore, APOE ε4 carriers generally exhibited a greater magnitude and spatial extent of longitudinal changes in Aβ deposition than APOE ε4 noncarriers in both diagnostic groups.

Conclusions

Our findings suggest a differential effect of APOE ε4 on Aβ pathology, glucose metabolism, and GM volume. Studying APOE ε4-related brain changes with neuroimaging biomarkers in preclinical AD offers an opportunity to further our understanding of the pathophysiology of AD at an early stage.     

Evaluation of FDG-PET and ECD-SPECT in patients with subcortical band heterotopia

Objective: The purpose of this retrospective study was to clarify the cellular activities of ectopic neurons in subcortical bands and to evaluate the imaging features of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and ^99mTc ethyl cysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in a series of patients with subcortical band heterotopia (SBH). Materials and methods: The cases of 12 patients with SBH (3 men and 9 women; age range, 2–51 years) were evaluated on the basis of their MRI findings. Eight ¹⁸F-FDG PET and 12 ^99mTc-ECD SPECT images were obtained. The uptakes of these images were compared with electroencephalography (EEG) or MRI findings such as band thickness. In all patients, easy Z-score Imaging System (eZIS) software was used to statistically analyze the SPECT images. Results: Of the eight ¹⁸F-FDG PET images, five showed higher uptake in the thick subcortical bands than in the overlying cortex. Of the 12 ^99mTc-ECD SPECT examinations with eZIS images, nine indicated increased regional cerebral blood flow (rCBF) areas corresponding to the band locations. Of the eight ¹⁸F-FDG PET examination findings, six were congruent with the rCBF distributions on the eZIS images. Eight of the 12 patients showed correspondence to the increased rCBF on the eZIS images, the band locations on MRI, and abnormal discharge sites on EEG. Conclusions: Ectopic neurons in subcortical bands may have higher glucose metabolism and/or increased rCBF compared to the overlying cortex. ¹⁸F-FDG PET and ^99mTc-ECD SPECT using eZIS can be helpful to clearly detect the cellular activities of ectopic neurons in patients with SBH.     

Magnetic resonance imaging as a non-invasive tool to assess gastric emptying in mice

Background

Methods to study gastric emptying in rodents are time consuming or terminal, preventing repetitive assessment in the same animal. Magnetic resonance imaging (MRI) is a non-invasive technique increasingly used to investigate gastrointestinal function devoid of these shortcomings. Here, we evaluated MRI to measure gastric emptying in control animals and in two different models of gastroparesis.

Methods

Mice were scanned using a 9.4 Tesla MR scanner. Gastric volume was measured by delineating the stomach lumen area. Control mice were scanned every 30 min after ingestion of a 0.2 g meal and stomach volume was quantified. The ability of MRI to detect delayed gastric emptying was evaluated in models of morphine-induced gastroparesis and streptozotocin-induced diabetes.

Key Results

Magnetic resonance imaging reproducibly detected increased gastric volume following ingestion of a standard meal and progressively decreased with a half emptying time of 59 ± 5 min. Morphine significantly increased gastric volume measured at t = 120 min (saline: 20 ± 2 vs morphine: 34 ± 5 mm³; n = 8–10; p < 0.001) and increased half emptying time using the breath test (saline: 85 ± 22 vs morphine: 161 ± 46 min; n = 10; p < 0.001). In diabetic mice, gastric volume assessed by MRI at t = 60 min (control: 23 ± 2 mm³; n = 14 vs diabetic: 26 ± 5 mm³; n = 18; p = 0.014) but not at t = 120 min (control: 21 ± 3 mm³; n = 13 vs diabetic: 18 ± 5 mm³; n = 18; p = 0.115) was significantly increased compared to nondiabetic mice.

Conclusions and Inferences

Our data indicate that MRI is a reliable and reproducible tool to assess gastric emptying in mice and represents a useful technique to study gastroparesis in disease models or for evaluation of pharmacological compounds.     

The value of putaminal diffusion imaging versus 18‐fluorodeoxyglucose positron emission tomography for the differential diagnosis of the Parkinson variant of multiple system atrophy

Differentiating the Parkinson variant of multiple system atrophy (MSA‐P) from idiopathic Parkinson's disease (PD) and other forms of atypical parkinsonism can be difficult because symptoms overlap considerably. 18‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is a powerful imaging technique that can assist in the diagnosis of MSA‐P via detection of putaminal and cerebellar hypometabolism. Recent studies suggest that diffusion‐weighted imaging (DWI) might be of similar diagnostic value, as it can detect microstructural damage in the putamen by means of an increased mean diffusivity (MD). The aim of this study was a direct comparison of DWI and FDG‐PET by using both methods on the same subject cohort. To this end, combined DWI and FDG‐PET were employed in patients with MSA‐P (n = 11), PD (n = 13), progressive supranuclear palsy (n = 8), and in 6 control subjects. MD values and FDG uptake ratios were derived from volumetric parcellations of the putamen and subjected to further analysis of covariance (ANCOVA) and receiver operating characteristics analyses. MSA‐P was found to be associated with an increased posterior putaminal MD (P < 0.001 in all subgroup comparisons) that correlated strongly with local reductions in FDG uptake (r = ?0.85, P = 0.002). DWI discriminated patients with MSA‐P from other subgroups nearly as accurately as FDG‐PET (area under the curve = 0.89 vs 0.95, P = 0.27 [pooled data]). Our data suggest a close association between the amount of putaminal microstructural damage and a reduced energy metabolism in patients with MSA‐P. The clinical use of DWI for the differential diagnosis of MSA‐P is encouraged. © 2013 International Parkinson and Movement Disorder Society     

Construction of a novel Chinese normal brain database using 18F-FDG PET images and MIMneuro software,the initial application in epilepsy

Purpose: To create a standard Western Chinese normal functional brain database for quantitative analysis using 2-deoxy-2-[18F] fluoro-d-glucose (¹⁸F-FDG) positron emission tomography (PET) images and MIMneuro software.

Methods: 78 healthy right-handed Chinese volunteers from Tangdu Hospital were scanned using ¹⁸F-FDG PET to evaluate brain metabolism between March and October 2016. All PET images were processed using MIMneuro software to create a normal database platform. The platform included anatomical optimization to facilitate spatial localization of abnormalities and a statistical comparison with normal cases utilizing the Z-scores, which represent the number of standard deviations from the mean of the normal controls in the database.

Results: The novel Chinese brain metabolism database platform including 78 healthy volunteers (male: female 40:38; age 3–78 years, mean age, 45 years) was constructed based on the MIMneuro software, which increased the diagnostic confidence in the test patient by quantifying and emphasizing the abnormality. The BrainAlign^TM deformation algorithm of MIMneuro matched the size, shape, and orientation of the patient's brain scan to a template brain for comparison against a database of normal controls. The quantitative analysis performed on a voxel and regional level was useful in assessing the areas of abnormalities.

Conclusions: A novel Chinese ¹⁸F-FDG PET-based normal brain function database was created to highlight the local regions of abnormal metabolic activity through quantitative comparisons against the normal database. The Z-scores obtained by MIMneuro potentially aid in visualizing and quantifying the subtle lesions on ¹⁸FDG-PET scan images as observed in a patient diagnosed with epilepsy.     

Synaptic Density and Glucose Consumption in Patients with Lewy Body Diseases: An [11C]UCB-J and [18F]FDG PET Study

Background

Patients with Lewy body diseases exhibit variable degrees of cortical and subcortical hypometabolism. However, the underlying causes behind this progressive hypometabolism remain unresolved. Generalized synaptic degeneration may be one key contributor.

Objective

The objective of this study was to investigate whether local cortical synaptic loss is proportionally linked to the magnitude of hypometabolism in Lewy body disease.

Method

Using in vivo positron emission tomography (PET) we investigated cerebral glucose metabolism and quantified the density of cerebral synapses, as measured with [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) PET and [¹¹C]UCB-J, respectively. Volumes-of-interest were defined on magnetic resonance T1 scans and regional standard uptake value ratios-1 values were obtained for 14 pre-selected brain regions. Between-group comparisons were conducted at voxel-level.

Results

We observed regional differences in both synaptic density and cerebral glucose consumption in our cohorts of non-demented and demented patients with Parkinson's disease or dementia with Lewy bodies compared to healthy subjects. Additionally, voxel-wise comparisons showed a clear difference in cortical regions between demented patients and controls for both tracers. Importantly, our findings strongly suggested that the magnitude of reduced glucose uptake exceeded the magnitude of reduced cortical synaptic density.

Conclusion

Here, we investigated the relationship between in vivo glucose uptake and the magnitude of synaptic density as measured using [¹⁸F]FDG PET and [¹¹C]UCB-J PET in Lewy body patients. The magnitude of reduced [¹⁸F]FDG uptake was greater than the corresponding decline in [¹¹C]UCB-J binding. Therefore, the progressive hypometabolism seen in Lewy body disorders cannot be fully explained by generalized synaptic degeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Crossed cerebellar diaschisis on 18F-FDG PET: Frequency across neurodegenerative syndromes and association with 11C-PIB and 18F-Flortaucipir

We used ¹⁸F-FDG-PET to investigate the frequency of crossed cerebellar diaschisis (CCD) in 197 patients with various syndromes associated with neurodegenerative diseases. In a subset of 117 patients, we studied relationships between CCD and cortical asymmetry of Alzheimer’s pathology (β-amyloid (¹¹C-PIB) and tau (¹⁸F-Flortaucipir)). PET images were processed using MRIs to derive parametric SUVR images and define regions of interest. Indices of asymmetry were calculated in the cerebral cortex, basal ganglia and cerebellar cortex. Across all patients, cerebellar ¹⁸F-FDG asymmetry was associated with reverse asymmetry of ¹⁸F-FDG in the cerebral cortex (especially frontal and parietal areas) and basal ganglia. Based on our operational definition (cerebellar asymmetry >3% with contralateral supratentorial hypometabolism), significant CCD was present in 47/197 (24%) patients and was most frequent in corticobasal syndrome and semantic and logopenic variants of primary progressive aphasia. In β-amyloid-positive patients, mediation analyses showed that ¹⁸F-Flortaucipir cortical asymmetry was associated with cerebellar ¹⁸F-FDG asymmetry, but that cortical ¹⁸F-FDG asymmetry mediated this relationship. Analysis of ¹⁸F-FDG-SUVR values suggested that CCD might also occur in the absence of frank cerebellar ¹⁸F-FDG asymmetry due to symmetrical supratentorial degeneration resulting in a bilateral diaschisis process.     

A follow‐up study on 6‐[18F]fluoro‐L‐dopa uptake in early Parkinson's disease shows nonlinear progression in the putamen

Sixteen subjects with de novo Parkinson's disease (PD) underwent three 6‐[18F]fluoro‐L‐dopa (Fdopa) positron emission tomography (PET) scans during a follow‐up time of 5 years (mean ± SD 5.5 ± 0.4 years) to study the progression of striatal dopaminergic hypofunction. Throughout the study, the smallest Fdopa uptake values were found in the dorso‐caudal part of the putamen contralateral to the side with dominant motor symptoms. The rate of decline in Fdopa uptake in the contralateral putamen was faster in the beginning of the disease and slowed down as the disease progressed. The annual decline in Fdopa influx constant (Ki, unit × 10^?3 min^?1) was on average 0.5 during the first 2 years and 0.2 during the subsequent 3 years (P = 0.002) in the contralateral putamen. In caudate, the rate of decline in Fdopa values was slower than in the putamen and did not change significantly during the follow‐up time, annual decline in the contralateral caudate being 0.1 between baseline and 2 years and 0.3 between 2 and 5 years (P = 0.4). These results suggest that progression of putaminal dopaminergic hypofuncion in PD follows a nonlinear pattern at least in the contralateral side being faster in the beginning of the disease. © 2009 Movement Disorder Society     

Imaging of dopamine D2/3 agonist binding in cocaine dependence: a [11C]NPA positron emission tomography study

Objective: Positron emission tomography (PET) studies performed with [¹¹C]raclopride have consistently reported lower binding to D_2/3 receptors and lower amphetamine‐induced dopamine (DA) release in cocaine abusers relative to healthy controls. A limitation of these studies that were performed with D_2/3 antagonist radiotracers such as [¹¹C]raclopride is the failure to provide information that is specific to D_2/3 receptors configured in a state of high affinity for the agonists (i.e., D_2/3 receptors coupled to G‐proteins, D_{2/3 HIGH}). As the endogenous agonist DA binds with preference to D_{2/3 HIGH} relative to D_{2/3 LOW} receptors (i.e., D_2/3 receptors uncoupled to G‐proteins) it is critical to understand the in vivo status of D_{2/3 HIGH} receptors in cocaine dependence. Thus, we measured the available fraction of D_{2/3 HIGH} receptors in 10 recently abstinent cocaine abusers (CD) and matched healthy controls (HC) with the D_2/3 antagonist and agonist PET radiotracers [¹¹C]raclopride and [¹¹C]NPA. Methods: [¹¹C]raclopride and [¹¹C]NPA binding potential (BP) (BP_ND) in the striatum were measured with kinetic analysis using the arterial input function. The available fraction of D_{2/3 HIGH} receptors, i.e., % R_HIGH available = D_{2/3 HIGH}/(D_{2/3 HIGH} + D_{2/3 LOW}) was then computed as the ratio of [¹¹C]NPA BP_ND/[¹¹C]raclopride BP_ND. Results: No differences in striatal [¹¹C]NPA BP_ND (HC = 1.00 ± 0.17; CD = 0.97 ± 0.17, P = 0.67) or available % R_HIGH (HC = 39% ± 5%; CD = 41% ± 5%, P = 0.50) was observed between cocaine abusers and matched controls. Conclusions: The results of this [¹¹C]NPA PET study do not support alterations in D_{2/3 HIGH} binding in the striatum in cocaine dependence. Synapse, 2011. © 2011 Wiley‐Liss, Inc.     

P11 expression and PET in bipolar disorders

Background

Bipolar disorder (BD) is a common mental disorder, subdivided into BD-I and BD-II. Currently, few biomarkers differentiate BD-I from BD-II. However, it is suggested that peripheral blood mononuclear cell (PBMC) mRNA levels of p11 and positron emission tomography (PET) might be potential biomarkers for BD.

Methods

Healthy controls (HCs), BD-I, and BD-II patients in remission (n = 20 in each group) underwent a resting PET study with the radiotracer [¹⁸F]-2-deoxy-2-fluoro-d-glucose (¹⁸F-FDG). PBMC p11 mRNA levels were determined by quantitative real-time PCR.

Results

Comparing BD patients to HCs, normalized glucose metabolism (NGM) was higher in the hippocampus, parahippocampus, and amygdala, but lower in the anterior cingulate cortex (aCC), medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), insula and thalamus. Compared to BD-II, BD-I had hypometabolism of glucose in the aCC, bilateral middle and inferior gyrus, insula and striatum, and hypermetabolism of glucose in the left parahippocampus. PBMC p11 mRNA was over-expressed in both BD-I and BD-II, although there was no significant difference in its expression levels between BD-I and B-II patients. Further, there were significant positive correlations between PBMC p11 mRNA and NGM in the mPFC, aCC, left insula, bilateral orbitofrontal cortex (OFC), and left middle, inferior and superior temporal gyri. Also, PBMC p11 mRNA was positively correlated to the number of depressive episodes in BD patients, especially in BD-I patients.

Discussion

This study demonstrates that PBMC p11 mRNA expression is associated with neural activation in the brain of BD patients and warrants a larger translational study to determine its clinical utility.     

Role of FDG‐PET/MRI,FDG‐PET/CT,and Dynamic Susceptibility Contrast Perfusion MRI in Differentiating Radiation Necrosis from Tumor Recurrence in Glioblastomas

BACKGROUND AND PURPOSE

To compare the utility of quantitative PET/MRI, dynamic susceptibility contrast (DSC) perfusion MRI (pMRI), and PET/CT in differentiating radiation necrosis (RN) from tumor recurrence (TR) in patients with treated glioblastoma multiforme (GBM).

METHODS

The study included 24 patients with GBM treated with surgery, radiotherapy, and temozolomide who presented with progression on imaging follow‐up. All patients underwent PET/MRI and pMRI during a single examination. Additionally, 19 of 24 patients underwent PET/CT on the same day. Diagnosis was established by pathology in 17 of 24 and by clinical/radiologic consensus in 7 of 24. For the quantitative PET/MRI and PET/CT analysis, a region of interest (ROI) was drawn around each lesion and within the contralateral white matter. Lesion to contralateral white matter ratios for relative maximum, mean, and median were calculated. For pMRI, lesion ROI was drawn on the cerebral blood volume (CBV) maps and histogram metrics were calculated. Diagnostic performance for each metric was assessed using receiver operating characteristic curve analysis and area under curve (AUC) was calculated.

RESULTS

In 24 patients, 28 lesions were identified. For PET/MRI, relative mean ≥ 1.31 resulted in AUC of .94 with both sensitivity and negative predictive values (NPVs) of 100%. For pMRI, CBV max ≥3.32 yielded an AUC of .94 with both sensitivity and NPV measuring 100%. The joint model utilizing r‐mean (PET/MRI) and CBV mode (pMRI) resulted in AUC of 1.0.

CONCLUSION

Our study demonstrates that quantitative PET/MRI parameters in combination with DSC pMRI provide the best diagnostic utility in distinguishing RN from TR in treated GBMs.