Low-dose CT for the spatial normalization of PET images: A validation procedure for amyloid-PET semi-quantification

Abstract

The reference standard for spatial normalization of brain positron emission tomography (PET) images involves structural Magnetic Resonance Imaging (MRI) data. However, the lack of such structural information is fairly common in clinical settings. This might lead to lack of proper image quantification and to evaluation based only on visual ratings, which does not allow research studies or clinical trials based on quantification.PET/CT systems are widely available and CT normalization procedures need to be explored. Here we describe and validate a procedure for the spatial normalization of PET images based on the low-dose Computed Tomography (CT) images contextually acquired for attenuation correction in PET/CT systems. We included N = 34 subjects, spanning from cognitively normal to mild cognitive impairment and dementia, who underwent amyloid-PET/CT (18F-Florbetaben) and structural MRI scans. The proposed pipeline is based on the SPM12 unified segmentation algorithm applied to low-dose CT images. The validation of the normalization pipeline focused on 1) statistical comparisons between regional and global 18F-Florbetaben-PET/CT standardized uptake value ratios (SUVrs) estimated from both CT-based and MRI-based normalized PET images (SUVrCT, SUVrMRI) and 2) estimation of the degrees of overlap between warped gray matter (GM) segmented maps derived from CT- and MRI-based spatial transformations.We found negligible deviations between regional and global SUVrs in the two CT and MRI-based methods. SUVrCT and SUVrMRI global uptake scores showed negligible differences (mean ± sd 0.01 ± 0.03). Notably, the CT- and MRI-based warped GM maps showed excellent overlap (90% within 1 mm).The proposed analysis pipeline, based on low-dose CT images, allows accurate spatial normalization and subsequent PET image quantification. A CT-based analytical pipeline could benefit both research and clinical practice, allowing the recruitment of larger samples and favoring clinical routine analysis.

Amyloid PETs are commonly negative in suspected Alzheimer’s disease with an increase in CSF phosphorylated-tau protein concentration but an Aβ42 concentration in the very high range: a prospective study

“…Alzheimer's Disease and Related Disorders Association (NINCDS ADRDA) criteria [13,14], 25 exhibited an increase in CSF P-tau concentrations (>60 pg/mL) along with normal Aß42 concentration (>600 pg/mL) and Aß42/Aß40 ratio (>0.07), according to routine cut-off values [3,15]. The patients presenting this CSF biomarker profile were included in this ancillary analysis of the MAF (Maladie d'Alzheimer Florbetaben) study (NCT02556502) [16] with the following main additional inclusion criteria: age ≥18 years old, absence of formal or relative contraindication to 18 F-florbetaben PET, affiliation to a health care system, no guardianship or curatorship, and absence of pregnancy. In addition, patients unable to undergo 18 F-florbetaben PET due to agitation or confusion, as well as those unable to sign the informed consent form, were not included.…”

“…The visual analysis was obtained from 2 experienced nuclear physicians (CM, AV) who were blinded to all other patient data. Amyloid PET results were interpreted in a consensual manner as either "positive" or "negative" by conventional means (6), according to the amount of 18 Fflorbetaben uptake observed on the lateral temporal cortex, frontal cortex, posterior cingulate cortex/precuneus and parietal cortex. Only brain amyloid plaque load (BAPL) scores higher than 1 were considered as reflecting positivity, as currently recommended [6].…”

“…Interestingly, this assessment may now be provided by amyloid positron emission tomography (PET) brain imaging. 18 F-florbetaben is one of the PET tracers of amyloid plaques which may be used in clinical routine [5] following its approval by the United States Food and Drug Administration and of the European Medicines Agency for this purpose [6]. In particular, 18 Fflorbetaben PET is associated with a very high negative predictive value for AD diagnosis (96%), especially when using not only visual but also quantitative analyses (5).…”

“…18 F-florbetaben is one of the PET tracers of amyloid plaques which may be used in clinical routine [5] following its approval by the United States Food and Drug Administration and of the European Medicines Agency for this purpose [6]. In particular, 18 Fflorbetaben PET is associated with a very high negative predictive value for AD diagnosis (96%), especially when using not only visual but also quantitative analyses (5). Such additional quantitative assessments have clearly been shown to improve the interpretation of 18 Fflorbetaben PET in this setting [7][8][9][10][11].…”

“…In particular, 18 Fflorbetaben PET is associated with a very high negative predictive value for AD diagnosis (96%), especially when using not only visual but also quantitative analyses (5). Such additional quantitative assessments have clearly been shown to improve the interpretation of 18 Fflorbetaben PET in this setting [7][8][9][10][11]. Nevertheless, a negative 18 F-florbetaben PET is now established as a reliable indicator of the absence of sufficient plaque pathology in the brain to support a diagnosis of AD [5].…”