Optimisation and usefulness of quantitative analysis of 18F-florbetapir PET.

OBJECTIVES: This study investigates the usefulness of quantitative SUVR thresholds on sub types of typical (type A) and atypical (non-type A) positive (Aß+) and negative (Aß-) 18F-florbetapir scans and aims to optimise the thresholds. METHODS: Clinical 18F-florbetapir scans (n = 100) were categorised by sub type and visual reads were performed independently by three trained readers. Inter-reader agreement and reader-to-reference agreement were measured. Optimal SUVR thresholds were derived by ROC analysis and were compared with thresholds derived from a healthy control group and values from published literature. RESULTS: Sub type division of 18F-florbetapir PET scans improves accuracy and agreement of visual reads for type A: accuracy 90%, 96% and 70% and agreement κ > 0.7, κ ≥ 0.85 and -0.1 < κ < 0.9 for all data, type A and non-type A respectively. Sub type division also improves quantitative classification accuracy of type A: optimum mcSUVR thresholds were found to be 1.32, 1.18 and 1.48 with accuracy 86%, 92% and 76% for all data, type A and non-type A respectively. CONCLUSIONS: Aß+/Aß- mcSUVR threshold of 1.18 is suitable for classification of type A studies (sensitivity = 97%, specificity = 88%). Region-wise SUVR thresholds may improve classification accuracy in non-type A studies. Amyloid PET scans should be divided by sub type before quantification. ADVANCES IN KNOWLEDGE: We have derived and validated mcSUVR thresholds for Aß+/Aß- 18F-florbetapir studies. This work demonstrates that division into sub types improves reader accuracy and agreement and quantification accuracy in scans with typical presentation and highlights the atypical presentations not suited to global SUVR quantification.

Evolution of Diffusion-Weighted Magnetic Resonance Imaging Signal Abnormality in Sporadic Creutzfeldt-Jakob Disease, With Histopathological Correlation.

IMPORTANCE: Prion diseases represent the archetype of brain diseases caused by protein misfolding, with the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. Diffusion-weighted imaging (DWI) has emerged as the most sensitive magnetic resonance imaging (MRI) sequence for the diagnosis of sCJD, but few studies have assessed the evolution of MRI signal as the disease progresses. OBJECTIVES: To assess the natural history of the MRI signal abnormalities on DWI in sCJD to improve our understanding of the pathogenesis and to investigate the potential of DWI as a biomarker of disease progression, with histopathological correlation. DESIGN, SETTING, AND PARTICIPANTS: Gray matter involvement on DWI was assessed among 37 patients with sCJD in 26 cortical and 5 subcortical subdivisions per hemisphere using a semiquantitative scoring system of 0 to 2 at baseline and follow-up. A total brain score was calculated as the summed scores in the individual regions. In 7 patients, serial mean diffusivity measurements were obtained. Age at baseline MRI, disease duration, atrophy, codon 129 methionine valine polymorphism, Medical Research Council Rating Scale score, and histopathological findings were documented. The study setting was the National Prion Clinic, London, England. All participants had a probable or definite diagnosis of sCJD and had at least 2 MRI studies performed during the course of their illness. The study dates were October 1, 2008 to April 1, 2012. The dates of our analysis were January 19 to April 20, 2012. MAIN OUTCOMES AND MEASURES: Correlation of regional and total brain scores with disease duration. RESULTS: Among the 37 patients with sCJD in this study there was a significant increase in the number of regions demonstrating signal abnormality during the study period, with 59 of 62 regions showing increased signal intensity (SI) at follow-up, most substantially in the caudate and putamen (P < .001 for both). The increase in the mean (SD) total brain score from 30.2 (17.3) at baseline to 40.5 (20.6) at follow-up (P = .001) correlated with disease duration (r = 0.47, P = .003 at baseline and r = 0.35, P = .03 at follow-up), and the left frontal SI correlated with the degree of spongiosis (r = 0.64, P = .047). Decreased mean diffusivity in the left caudate at follow-up was seen (P < .001). Eight patients demonstrated decreased SI in cortical regions, including the left inferior temporal gyrus and the right lingual gyrus. CONCLUSIONS AND RELEVANCE: Magnetic resonance images in sCJD show increased extent and degree of SI on DWI that correlates with disease duration and the degree of spongiosis. Although cortical SI may fluctuate, increased basal ganglia SI is a consistent finding and is due to restricted diffusion. Diffusion-weighted imaging in the basal ganglia may provide a noninvasive biomarker in future therapeutic trials.