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,
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Ffluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for
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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 present study hypothesised that whole-body 18FFDG-PET/CT might provide insight into the pathophysiology of long COVID.
Methods
We prospectively enrolled 13 adult long COVID patients who ...complained for at least one persistent symptom for >30 days after infection recovery. A group of 26 melanoma patients with negative PET/CT matched for sex/age was used as controls (2:1 control to case ratio). Qualitative and semi-quantitative analysis of whole-body images was performed. Fisher exact and Mann-Whitney tests were applied to test differences between the two groups. Voxel-based analysis was performed to compare brain metabolism in cases and controls. Cases were further grouped according to prevalent symptoms and analysed accordingly.
Results
In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild 18FFDG uptake. Many healthy organs/parenchyma SUVs and SUV ratios significantly differed between the two groups (
p
≤ 0.05). Long COVID patients exhibited brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected
p
< 0.001 at voxel level). Specific area(s) of hypometabolism characterised patients with persistent anosmia/ageusia, fatigue, and vascular uptake (uncorrected
p
< 0.005 at voxel level).
Conclusion
18FFDG PET/CT acknowledged the multi-organ nature of long COVID, supporting the hypothesis of underlying systemic inflammation. Whole-body images showed increased 18FFDG uptake in several “target” and “non-target” tissues. We found a typical pattern of brain hypometabolism associated with persistent complaints at the PET time, suggesting a different temporal sequence for brain and whole-body inflammatory changes. This evidence underlined the potential value of whole-body 18FFDG PET in disclosing the pathophysiology of long COVID.
The relevant role of pentose phosphate pathway (PPP) in cancer metabolic reprogramming has been usually outlined by studying glucose-6-phosphate dehydrogenase (G6PD). However, recent evidence ...suggests an unexpected role for a less characterized PPP, triggered by hexose-6-phosphate dehydrogenase (H6PD) within the endoplasmic reticulum (ER). Studying H6PD biological role in breast and lung cancer, here we show that gene silencing of this reticular enzyme decreases cell content of PPP intermediates and D-ribose, to a similar extent as G6PD silencing. Decrease in overall NADPH content and increase in cell oxidative status are also comparable. Finally, either gene silencing impairs at a similar degree cell proliferating activity. This unexpected response occurs despite the absence of any cross-interference between the expression of both G6PD and H6PD. Thus, overall cancer PPP reflects the contribution of two different pathways located in the cytosol and ER, respectively. Disregarding the reticular pathway might hamper our comprehension of PPP role in cancer cell biology.
Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and ...National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.
Considering the similarities with other pandemics due to respiratory virus infections and subsequent development of neurological disorders (e.g. encephalitis lethargica after the 1918 influenza), ...there is growing concern about a possible new wave of neurological complications following the worldwide spread of SARS-CoV-2. However, data on COVID-19-related encephalitis and movement disorders are still limited. Herein, we describe the clinical and neuroimaging (FDG-PET/CT, MRI and DaT-SPECT) findings of two patients with COVID-19-related encephalopathy who developed prominent parkinsonism. None of the patients had previous history of parkinsonian signs/symptoms, and none had prodromal features of Parkinson’s disease (hyposmia or RBD). Both developed a rapidly progressive form of atypical parkinsonism along with distinctive features suggestive of encephalitis. A possible immune-mediated etiology was suggested in Patient 2 by the presence of CSF-restricted oligoclonal bands, but none of the patients responded favorably to immunotherapy. Interestingly, FDG-PET/CT findings were similar in both cases and reminiscent of those observed in post-encephalitic parkinsonism, with cortical hypo-metabolism associated with hyper-metabolism in the brainstem, mesial temporal lobes, and basal ganglia. Patient’s FDG-PET/CT findings were validated by performing a Statistical Parametric Mapping analysis and comparing the results with a cohort of healthy controls (
n
= 48). Cerebrum cortical thickness map was obtained in Patient 1 from MRI examinations to evaluate the structural correlates of the metabolic alterations detected with FDG-PET/CT. Hypermetabolic areas correlated with brain regions showing increased cortical thickness, suggesting their involvement during the inflammatory process. Overall, these observations suggest that SARS-CoV-2 infection may trigger an encephalitis with prominent parkinsonism and distinctive brain metabolic alterations.
The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making ...recommendations, performing, interpreting, and reporting results of
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FFDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of
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FFDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain
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FFDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.
Purpose
An appropriate healthy control dataset is mandatory to achieve good performance in voxel-wise analyses. We aimed at evaluating 18FFDG PET brain datasets of healthy controls (HC), based on ...publicly available data, for the extraction of voxel-based brain metabolism maps at the single-subject level.
Methods
Selection of HC images was based on visual rating, after Cook’s distance and jack-knife analyses, to exclude artefacts and/or outliers. The performance of these HC datasets (ADNI-HC and AIMN-HC) to extract hypometabolism patterns in single patients was tested in comparison with the standard reference HC dataset (HSR-HC) by means of Dice score analysis. We evaluated the performance and comparability of the different HC datasets in the assessment of single-subject SPM-based hypometabolism in three independent cohorts of patients, namely, ADD, bvFTD and DLB.
Results
Two-step Cook’s distance analysis and the subsequent jack-knife analysis resulted in the selection of
n
= 125 subjects from the AIMN-HC dataset and
n
= 75 subjects from the ADNI-HC dataset. The average concordance between SPM hypometabolism t-maps in the three patient cohorts, as obtained with the new datasets and compared to the HSR-HC standard reference dataset, was 0.87 for the AIMN-HC dataset and 0.83 for the ADNI-HC dataset. Pattern expression analysis revealed high overall accuracy (> 80%) of the SPM t-map classification according to different statistical thresholds and sample sizes.
Conclusions
The applied procedures ensure validity of these HC datasets for the single-subject estimation of brain metabolism using voxel-wise comparisons. These well-selected HC datasets are ready-to-use in research and clinical settings.
We aimed to evaluate joint and vessel uptake in patients with polymyalgia rheumatica (PMR) by FDG-PET and correlate it with clinical findings.
Consecutive PMR patients, without clinical signs of ...giant cell arteritis, underwent a standardised clinical examination and FDG-PET/CT. Controls were consecutive subjects undergoing FDG-PET for the suspicion of neoplasm not confirmed by the examination. Uptake was evaluated by a qualitative visual score, using the liver uptake as reference and by the semi-quantitative mean standardised uptake value (SUV) and target-to-background ratio (TBR) methods.
Eighty-four patients and 84 controls (55 women, median age 73 years, range 50-92 years in both groups) were studied. Sixteen patients were taking glucocorticoids (GC). PMR patients showed a higher articular uptake than controls. GC-treated patients showed uptake lower than GC-naïve patients, but still higher than controls. PMR patients showed a higher vascular uptake than controls in all districts except in the carotid arteries, when evaluated by the visual score. Conversely, the semi-quantitative approach yielded no significant differences. Forty-two patients (50%) showed PET evidence of large-vessel vasculitis (LVV), defined as uptake ≥ than that of the liver, and 11.9% showed LVV with vascular uptake higher than that of the liver. The correlation between clinical findings and uptake was scarce. Neither clinical nor laboratory findings could predict the presence of LVV.
Patients with PMR show a typical joint pattern at FDG-PET. There are no clinical or laboratory predictors of LVV. Imaging appears to be the only tool to assess LVV in these patients.
The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with ...suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.
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