Diverse neurodegenerative disorders are characterized by deposition of tau fibrils composed of conformers (i.e. strains) unique to each illness. The development of tau imaging agents has enabled ...visualization of tau lesions in tauopathy patients, but the modes of their binding to different tau strains remain elusive. Here we compared binding of tau positron emission tomography ligands, PBB3 and AV-1451, by fluorescence, autoradiography and homogenate binding assays with homologous and heterologous blockades using tauopathy brain samples. Fluorescence microscopy demonstrated intense labelling of non-ghost and ghost tangles with PBB3 and AV-1451, while dystrophic neurites were more clearly detected by PBB3 in brains of Alzheimer's disease and diffuse neurofibrillary tangles with calcification, characterized by accumulation of all six tau isoforms. Correspondingly, partially distinct distributions of autoradiographic labelling of Alzheimer's disease slices with 11C-PBB3 and 18F-AV-1451 were noted. Neuronal and glial tau lesions comprised of 4-repeat isoforms in brains of progressive supranuclear palsy, corticobasal degeneration and familial tauopathy due to N279K tau mutation and 3-repeat isoforms in brains of Pick's disease and familial tauopathy due to G272V tau mutation were sensitively detected by PBB3 fluorescence in contrast to very weak AV-1451 signals. This was in line with moderate 11C-PBB3 versus faint 18F-AV-1451 autoradiographic labelling of these tissues. Radioligand binding to brain homogenates revealed multiple binding components with differential affinities for 11C-PBB3 and 18F-AV-1451, and higher availability of binding sites on progressive supranuclear palsy tau deposits for 11C-PBB3 than 18F-AV-1451. Our data indicate distinct selectivity of PBB3 compared to AV-1451 for diverse tau fibril strains. This highlights the more robust ability of PBB3 to capture wide-range tau pathologies.
OBJECTIVESNuclear Medicine is a quantitative imaging modality. However, until recently, quantitative single photon emission computed tomography (SPECT) has been limited to ratios or comparisons to ...databases, or indeed volume measurements, and therefore has not truly quantified uptake in areas of interest. Following the growth of dosimetry associated with nuclear medicine therapies, tools to perform quantitative SPECT in terms of kBq/cc or standardised uptake value (SUV) have become more readily available, although its use does not appear to be widespread. The aim of this study was to get a snapshot of quantitative SPECT use, and to determine where the future of this technology may lie.
METHODSThe data for this survey were collected through a web-based form made available at a national quantitative SPECT meeting, and later distributed to the UK nuclear medicine community. A series of questions looking at current practice, technique and future thoughts were presented to respondents in the form of multiple-choice questions where single and multiple selections could be made.
RESULTSThe responses showed significant use of quantitative SPECT for established techniques, in alignment with the prevalence of the relevant imaging studies. There was a significant minority of respondents performing kBq/cc and SUV SPECT, and SPECT for radionuclide therapy dosimetry. Technique for quantitative SPECT varied significantly typically but nevertheless the predicted future for quantitative SPECT was positiveparticularly for kBq/cc and SUV SPECT. Impediments to the success of the technology were mostly around software availability and uncertainties around usefulness.
CONCLUSIONThe results of this survey suggest that the future of truly quantitative SPECT looks promising.
Purpose
To assess the quantitative accuracy of current MR attenuation correction (AC) methods in neurological PET, in comparison to data derived using CT AC.
Methods
This retrospective study included ...25 patients who were referred for a neurological FDG PET examination and were imaged sequentially by PET/CT and simultaneous PET/MR. Differences between activity concentrations derived using Dixon and ultrashort echo time (UTE) MR-based AC and those derived from CT AC were compared using volume of interest and voxel-based approaches. The same comparisons were also made using PET data represented as SUV ratios (SUVr) using grey matter cerebellum as the reference region.
Results
Extensive and statistically significant regional underestimations of activity concentrations were found with both Dixon AC (
P
< 0.001) and UTE AC (
P
< 0.001) in all brain regions when compared to CT AC. The greatest differences were found in the cortical grey matter (Dixon AC 21.3 %, UTE AC 15.7 %) and cerebellum (Dixon AC 19.8 %, UTE AC 17.3 %). The underestimation using UTE AC was significantly less than with Dixon AC (
P
< 0.001) in most regions. Voxel-based comparisons showed that all cortical grey matter and cerebellum uptake was underestimated with Dixon AC compared to CT AC. Using UTE AC the extent and significance of these differences were reduced. Inaccuracies in cerebellar activity concentrations led to a mixture of predominantly cortical underestimation and subcortical overestimation in SUVr PET data for both MR AC methodologies.
Conclusion
MR-based AC results in significant underestimation of activity concentrations throughout the brain, which makes the use of SUVr data difficult. These effects limit the quantitative accuracy of neurological PET/MR.
Highlights • 194 consecutive patients with drug resistant epilepsy. • 158 had normal MRI. • Underwent FDG PET as initial data were non-localizing. • Utility of FDG PET was evaluated in a pragmatic, ...clinical setting. • FDG PET helped in decision making in 53% patients.
Purpose
Dopamine transporter (DAT) imaging with
123
IFP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT ...quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of
123
IFP-CIT SPECT scans in healthy controls.
Methods
SPECT data from 139 healthy controls (74 men, 65 women; age range 20 – 83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (
SBR
).
Results
A significant effect of age on
SBR
was found for all data. Gender had a significant effect on
SBR
in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal
SBR
were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in
SBR
of between 4 % and 6.7 % per decade.
Conclusion
This study provides a large database of
123
IFP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference database for nuclear medicine centres and for clinical trials using
123
IFP-CIT SPECT as the imaging marker.
EANM practice guideline for quantitative SPECT-CT Dickson, John C.; Armstrong, Ian S.; Gabiña, Pablo Minguez ...
European journal of nuclear medicine and molecular imaging,
03/2023, Letnik:
50, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Purpose
Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging ...together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases.
Methods
These practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT. The guidelines have also been reviewed and approved by all EANM committees and have been endorsed by the European Association of Nuclear Medicine.
Conclusion
The present practice guidelines will help practitioners, scientists and researchers perform high-quality quantitative SPECT-CT and will provide a framework for the continuing development of quantitative SPECT-CT as an established modality.
There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA).
To determine the profile of biomarkers relevant to neurodegenerative ...disease in the CSF of patients with CAA.
We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer's disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service.
We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ38, Aβ40, Aβ42, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF Aβ42, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an "AD-like" profile.
CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed.
Alzheimer's disease has a preclinical stage when cerebral amyloid-β deposition occurs before symptoms emerge, and when amyloid-β-targeted therapies may have maximum benefits. Existing amyloid-β ...status measurement techniques, including amyloid PET and CSF testing, are difficult to deploy at scale, so blood biomarkers are increasingly considered for screening. We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-β, and single molecule array (Simoa) measures of plasma amyloid-β and phospho-tau181-to detect cortical 18F-florbetapir amyloid PET positivity (defined as a standardized uptake value ratio of >0.61 between a predefined cortical region of interest and eroded subcortical white matter) in dementia-free members of Insight 46, a substudy of the population-based British 1946 birth cohort. We used logistic regression models with blood biomarkers as predictors of amyloid PET status, with or without age, sex and APOE ε4 carrier status as covariates. We generated receiver operating characteristics curves and quantified areas under the curves to compare the concordance of the different blood tests with amyloid PET. We determined blood test cut-off points using Youden's index, then estimated numbers needed to screen to obtain 100 amyloid PET-positive individuals. Of the 502 individuals assessed, 441 dementia-free individuals with complete data were included; 82 (18.6%) were amyloid PET-positive. The area under the curve for amyloid PET status using a base model comprising age, sex and APOE ε4 carrier status was 0.695 (95% confidence interval: 0.628-0.762). The two best-performing Simoa plasma biomarkers were amyloid-β42/40 (0.620; 0.548-0.691) and phospho-tau181 (0.707; 0.646-0.768), but neither outperformed the base model. Mass spectrometry plasma measures performed significantly better than any other measure (amyloid-β1-42/1-40: 0.817; 0.770-0.864 and amyloid-β composite: 0.820; 0.775-0.866). At a cut-off point of 0.095, mass spectrometry measures of amyloid-β1-42/1-40 detected amyloid PET positivity with 86.6% sensitivity and 71.9% specificity. Without screening, to obtain 100 PET-positive individuals from a population with similar amyloid PET positivity prevalence to Insight 46, 543 PET scans would need to be performed. Screening using age, sex and APOE ε4 status would require 940 individuals, of whom 266 would proceed to scan. Using mass spectrometry amyloid-β1-42/1-40 alone would reduce these numbers to 623 individuals and 243 individuals, respectively. Across a theoretical range of amyloid PET positivity prevalence of 10-50%, mass spectrometry measures of amyloid-β1-42/1-40 would consistently reduce the numbers proceeding to scans, with greater cost savings demonstrated at lower prevalence.
Purpose
This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular ...Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes.
Methods
Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally,
18
Ffluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for
18
Ffluorodopa imaging in this setting are still lacking.
Conclusion
All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.
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