USING FLORBETAPIR PET TO INCREASE DIAGNOSTIC CERTAINTY IN ATYPICAL DEMENTIAS

2015 ◽  
Vol 86 (11) ◽  
pp. e4.112-e4
Author(s):  
PSJ Weston ◽  
RW Paterson ◽  
M Lehmann ◽  
M Modat ◽  
JB Bomanji ◽  
...  

Amyloid PET or CSF can be used to determine Alzheimer pathology in vivo. Few studies have assessed the additional value of amyloid imaging where CSF results are equivocal. We recruited 20 cognitive patients (65.5+/–7.6 y) with MRI, neuropsychology, and CSF Aβ1–42 and tau measured during their diagnostic assessment. Individuals were selected to have a range of CSF results; ten had amnestic and ten non-amnestic presentations. Following the investigations, the treating neurologist gave a diagnosis (AD or non-AD). Four controls (63+/–7.0y) also had CSF examination. All subjects had Florbetapir PET imaging, reported as positive/negative. The clinicians were given the PET results and asked to review their diagnoses. Eighteen patients had positive Florbetapir scans; two patients and all controls were Florbetapir negative. Following initial investigations, thirteen patients were diagnosed with AD, and seven with non-AD pathology. Providing the Florbetapir result led to a change in diagnosis in seven patients, five of whom had atypical phenotypes. For all seven the CSF results were close to or in a “grey” area, where results overlapped for positive and negative PET scans. Even in individuals with CSF measures of Aβ1–42, and tau, Florbetapir PET imaging may have diagnostic utility, particularly in atypical cases and/or equivocal CSF results.

2020 ◽  
Vol 20 (6) ◽  
pp. 451-462
Author(s):  
Magdalena A Kolanko ◽  
Zarni Win ◽  
Flavia Loreto ◽  
Neva Patel ◽  
Christopher Carswell ◽  
...  

Amyloid positron emission tomography (PET) imaging enables in vivo detection of brain Aβ deposition, one of the neuropathological hallmarks of Alzheimer’s disease. There is increasing evidence to support its clinical utility, with major studies showing that amyloid PET imaging improves diagnostic accuracy, increases diagnostic certainty and results in therapeutic changes. The Amyloid Imaging Taskforce has developed appropriate use criteria to guide clinicians by predefining certain scenarios where amyloid PET would be justified. This review provides a practical guide on how and when to use amyloid PET, based on the available research and our own experience. We discuss its three main appropriate indications and illustrate these with clinical cases. We stress the importance of a multidisciplinary approach when deciding who might benefit from amyloid PET imaging. Finally, we highlight some practical points and common pitfalls in its interpretation.


2021 ◽  
Author(s):  
Negin Holland ◽  
Maura Malpetti ◽  
Timothy Rittman ◽  
Elijah E Mak ◽  
Luca Passamonti ◽  
...  

AbstractThe relationship betweenin vivosynaptic density and tau burden in primary tauopathies is key to understanding the impact of tauopathy on functional decline and in informing new early therapeutic strategies. In this cross-sectional observational study, we determine thein vivorelationship between synaptic density and molecular pathology, in the primary tauopathies of Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), as a function of disease severity.Twenty three patients with PSP, and twelve patients with Corticobasal Syndrome (CBS) were recruited from a tertiary referral centre. Nineteen education, sex and gender-matched control participants were recruited from the National Institute for Health Research ‘Join Dementia Research’ platform. Cerebral synaptic density and molecular pathology, in all participants, were estimated using PET imaging with the radioligands [11C]UCB-J and [18F]AV-1451, respectively. Patients with CBS also underwent amyloid PET imaging with [11C]PiB to exclude those with likely Alzheimer’s pathology – we refer to the amyloid negative cohort as having CBD although acknowledge other pathologies exist. Disease severity was assessed with the PSP rating scale; regional non-displaceable binding potentials (BPND) of [11C]UCB-J and [18F]AV-1451 were estimated in regions of interest from the Hammersmith Atlas, excluding those with known off-target binding for [18F]AV-1451. As an exploratory analysis, we also investigated the relationship between molecular pathology in cortical brain regions, and synaptic density in connected subcortical areas.Across brain regions, there was apositivecorrelation between [11C]UCB-J and [18F]AV-1451 BPND(β=0.4, t=4.7, p<0.0001). However, the direction of this correlation became less positive as a function of disease severity in patients(β = -0.03, T = -4.0, p = 0.002). Between brain regions, cortical [18F]AV-1451 binding wasnegativelycorrelated with synaptic density in subcortical areas (caudate nucleus, putamen, and substantia nigra).Brain regions with higher synaptic density are associated with a higher [18F]AV-1451 binding in PSP/CBD, but this association diminishes with disease severity. Moreover, higher cortical [18F]AV-1451 binding correlates with lower subcortical synaptic density. Longitudinal imaging is required to confirm the mediation of synaptic loss by molecular pathology. However, the effect of disease severity suggests a biphasic relationship between synaptic density and tauopathy, with synapse rich regions vulnerable to accrual of pathology, followed by a loss of synapses in response to pathology. Given the importance of synaptic function for cognition, our study elucidates the pathophysiology of primary tauopathies and may inform the design of future clinical trials.


2018 ◽  
Vol 24 (11) ◽  
pp. 1399-1412 ◽  
Author(s):  
Heidi Högel ◽  
Eero Rissanen ◽  
Anna Vuorimaa ◽  
Laura Airas

Positron emission tomography (PET) gives an opportunity to quantitate the expression of specific molecular targets in vivo and longitudinally in brain and thus enhances our possibilities to understand and follow up multiple sclerosis (MS)-related pathology. For successful PET imaging, one needs a relevant target molecule within the brain, to which a blood–brain barrier–penetrating specific radioligand will bind. 18-kDa translocator protein (TSPO)-binding radioligands have been used to detect activated microglial cells at different stages of MS, and remyelination has been measured using amyloid PET. Several PET ligands for the detection of other inflammatory targets, besides TSPO, have been developed but not yet been used for imaging MS patients. Finally, synaptic density evaluation has been successfully tested in human subjects and gives opportunities for the evaluation of the development of cortical and deep gray matter pathology in MS. This review will discuss PET imaging modalities relevant for MS today.


2021 ◽  
Vol 8 ◽  
Author(s):  
Maximilian Fischer ◽  
Mathias J. Zacherl ◽  
Ludwig Weckbach ◽  
Lisa Paintmayer ◽  
Tobias Weinberger ◽  
...  

Cardiac monitoring after murine myocardial infarction, using serial non-invasive cardiac 18F-FDG positron emissions tomography (PET) represents a suitable and accurate tool for in vivo studies. Cardiac PET imaging enables tracking metabolic alterations, heart function parameters and provides correlations of the infarct size to histology. ECG-gated 18F-FDG PET scans using a dedicated small-animal PET scanner were performed in mice at baseline, 3, 14, and 30 days after myocardial infarct (MI) by permanent ligation of the left anterior descending (LAD) artery. The percentage of the injected dose per gram (%ID/g) in the heart, left ventricular metabolic volume (LVMV), myocardial defect, and left ventricular function parameters: end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and the ejection fraction (EF%) were estimated. PET assessment of the defect positively correlates with post-infarct histology at 3 and 30 days. Infarcted murine hearts show an immediate decrease in LVMV and an increase in %ID/g early after infarction, diminishing in the remodeling process. This study of serial cardiac PET scans provides insight for murine myocardial infarction models by novel infarct surrogate parameters. It depicts that serial PET imaging is a valid, accurate, and multimodal non-invasive assessment.


2008 ◽  
Vol 1 (2) ◽  
pp. 110-114 ◽  
Author(s):  
A. Gee ◽  
L. Martarello ◽  
J. Passchier ◽  
M. Wishart ◽  
C. Parker ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Cinzia Marceddu ◽  
Adam Hartley ◽  
Mikhail Caga-Anan ◽  
Samata Pandey ◽  
Yasmin Morris ◽  
...  

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naomi S. Sta Maria ◽  
Leslie A. Khawli ◽  
Vyshnavi Pachipulusu ◽  
Sharon W. Lin ◽  
Long Zheng ◽  
...  

AbstractQuantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3–5 h and then migrate to the liver and spleen for up to 2–3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.


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