Quantitation of PET signal as an adjunct to visual interpretation of florbetapir imaging

Pontecorvo, Michael J.; Arora, Ankit; Devine, Marybeth; Lu, Ming; Galante, Nick; Siderowf, Andrew; Devadanam, Catherine; Joshi, Abhinay D.; Heun, Stephen L.; Teske, Brian F.; Truocchio, Stephen P; Krautkramer, Michael J.; Devous, Michael D.; Mintun, Mark A.

doi:10.1007/s00259-016-3601-4

Cited by 41 publications

(40 citation statements)

References 25 publications

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“…Because the amyloid tracers share similar uptake patterns, the respective training programs share some similarities: they all focus on teaching the identification of neocortical gray matter-versus-white matter contrast, with the loss of this contrast pointing to amyloid positivity and vice versa. The feasibility, accuracy, and reproducibility of the respective training programs were recently confirmed for all 3 tracers (19)(20)(21). One interesting question recently asked in this context relates to the potential incremental value of semiquantitative image analysis (22).…”

Section: Amyloid Image Analysismentioning

confidence: 91%

“…One interesting question recently asked in this context relates to the potential incremental value of semiquantitative image analysis (22). In this regard, Pontecorvo et al (21) showed that the consideration of SUV ratios during visual readings increases accuracy, especially in "below average" readers. More research on this topic is thus justified to fully understand the potential of combined visual and semiquantitative amyloid image analysis in a routine clinical scenario.…”

Section: Amyloid Image Analysismentioning

confidence: 99%

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Clinical Use and Utility of Amyloid Imaging

Barthel

Sabri

2017

J Nucl Med

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Currently, 3 amyloid PET tracers are approved and commercially available for clinical use. They allow for the accurate in vivo detection of amyloid plaques, one hallmark of Alzheimer disease. Here, we review the current knowledge on the clinical use and utility of amyloid imaging. Appropriate use criteria for the clinical application of amyloid imaging are established, and most currently available data point to their validity. Visual amyloid image analysis is highly standardized. Disclosure of amyloid imaging results is desired by many cognitively impaired subjects and seems to be safe once appropriate education is delivered to the disclosing clinicians. Regarding clinical utility, increasing evidence points to a change in diagnosis via amyloid imaging in about 30% of cases, to an increase in diagnostic confidence in about 60% of cases, to a change in patient management in about 60% of cases, and specifically to a change in medication in about 40% of cases. Also, amyloid imaging results seem to have a relevant impact on caregivers. Further, initial simulation studies point to a potential positive effect on patient outcome and to cost effectiveness of amyloid imaging. These features, however, will require confirmation in prospective clinical trials. More work is also required to determine the clinical utility of amyloid imaging specifically in subjects with mild cognitive impairment and in comparison with or in conjunction with other Alzheimer disease biomarkers. In summary, the clinical use of amyloid imaging is being studied, and the currently available data point to a relevant clinical utility of this imaging technique. Ongoing research will determine whether this accurate and noninvasive approach to amyloid plaque load detection will translate into a benefit to cognitively impaired subjects. Wi th the successful development and subsequent clinical approval of 18 F-florbetapir, 18 F-florbetaben, and 18 F-flutemetamol, the nuclear imaging community has a set of b-amyloid aggregatetargeting PET tracers in hand for clinical use. They allow the in vivo detection or exclusion of neuritic b-amyloid plaques, one histopathologic hallmark in the neocortex of patients with Alzheimer disease (AD), which previously could be diagnosed only histopathologically after death. Of note, brain b-amyloid accumulation is known to be an early event in this disease (1) and is considered by many as the initial trigger of a cascade of other pathobiochemical and pathophysiologic alterations finally leading to neurodegeneration and related cognitive decline in AD (2).The emergence of amyloid imaging technology is hoped to fill a relevant diagnostic gap in the clinic in cognitively impaired subjects and in AD in particular. Most people would like to get a diagnosis when cognitive symptoms are identified (3). Conversely, dementia diagnosis is often missed and delayed (4,5). With regard to the therapeutic implications of an AD diagnosis, it was reported that older people are willing to accept the relevant side effects of AD-modifying therap...

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Section: Amyloid Image Analysismentioning

confidence: 91%

Section: Amyloid Image Analysismentioning

confidence: 99%

Clinical Use and Utility of Amyloid Imaging

Barthel

Sabri

2017

J Nucl Med

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“…In subjects with moderate amyloid load, medial cortical regions are often more visually intense than lateral regions in amyloid PET scans (8,52,53), despite autopsy evaluation indicating that lateral aspects of temporal, frontal, and parietal lobes are involved earlier in the disease than medial regions (14,20,47). To examine this trend, Smith and Buckley (54) performed a post hoc analysis on a substantial subcohort of subjects from the 18 F-flutemetamol autopsy validation cohort (n 5 106) (12) and examined medial and lateral regions with similar levels of pathology.…”

Section: Cortical Generally Precedes Striatal Amyloid Accumulationmentioning

confidence: 99%

The Spatial-Temporal Ordering of Amyloid Pathology and Opportunities for PET Imaging

et al. 2019

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Although clinical routine focuses on dichotomous and visual interpretation of amyloid PET, regional image assessment in research settings may yield additional opportunities. Understanding the regional-temporal evolution of amyloid pathology may enable earlier identification of subjects in the Alzheimer Disease pathologic continuum, as well as a finer-grained assessment of pathology beyond traditional dichotomous measures. This review summarizes current research in the detection of regional amyloid deposition patterns and its potential for staging amyloid pathology. Pathology studies, cross-sectional and longitudinal PET-only studies, and comparative PET and autopsy studies are included. Despite certain differences, cortical deposition generally precedes striatal pathology, and in PETonly studies, medial cortical regions are seen to accumulate amyloid earlier than lateral regions. Based on regional amyloid PET, multiple studies have developed and implemented models for staging amyloid pathology that could improve subject selection into secondary prevention trials and visual assessment in clinical routine.

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“…In total, 215 subjects from a phase 2 study (21) were imaged at baseline, of which 142 returned for a follow-up scan 18 6 2 mo after the screening visit (shown in parentheses in Table 1). Subjects also had screening-visit 18 F-florbetapir scans that were interpreted as Ab-positive (Ab1) or Ab2 based on visual reads augmented by quantitative information, as previously described (26).…”

Section: Cross-sectional and Longitudinal Analysesmentioning

confidence: 99%

Flortaucipir F 18 Quantitation Using Parametric Estimation of Reference Signal Intensity

et al. 2017

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PET imaging of tau pathology in Alzheimer disease may benefit from the use of white matter reference regions. These regions have shown reduced variability compared with conventional cerebellar regions in amyloid imaging. However, they are susceptible to contamination from partial-volume blurring of tracer uptake in the cortex. We present a new technique, PERSI (Parametric Estimation of Reference Signal Intensity), for flortaucipir F 18 count normalization that leverages the advantages of white matter reference regions while mitigating potential partial-volume effects. Subjects with a clinical diagnosis of Alzheimer disease, mild cognitive impairment, or normal cognition underwent T1-weighted MRI and florbetapir imaging (to determine amyloid [Aβ] status) at screening and flortaucipir F 18 imaging at single or multiple time points. Flortaucipir F 18 images, acquired as 4 × 5 min frames 80 min after a 370-MBq injection, were motion-corrected, averaged, and transformed to Montreal Neurological Institute (MNI) space. The PERSI reference region was calculated for each scan by fitting a bimodal gaussian distribution to the voxel-intensity histogram within an atlas-based white matter region and using the center and width of the lower-intensity peak to identify the voxel intensities to be included. Four conventional reference regions were also evaluated: whole cerebellum, cerebellar gray matter, atlas-based white matter, and subject-specific white matter. SUVr (standardized uptake value ratio) was calculated for a statistically defined neocortical volume of interest. Performance was evaluated with respect to test-retest variability in a phase 2 study of 21 subjects (5-34 d between scans). Baseline variability in controls (SD of SUVr and ΔSUVr) and effect sizes for group differences (Cohen d; Aβ-positive impaired vs. Aβ-negative normal) were evaluated in another phase 2 study with cross-sectional data ( = 215) and longitudinal data ( = 142/215; 18 ± 2 mo between scans). PERSI showed superior test-retest reproducibility (1.84%) and group separation ability (cross-sectional Cohen d = 9.45; longitudinal Cohen d = 2.34) compared with other reference regions. Baseline SUVr variability and ΔSUVr were minimal in Aβ control subjects with no specific flortaucipir F 18 uptake (SUVr, 1.0 ± 0.04; ΔSUVr, 0.0 ± 0.02). PERSI reduced variability while enhancing discrimination between diagnostic cohorts. Such improvements could lead to more accurate disease staging and robust measurements of changes in tau burden over time for the evaluation of putative therapies.

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Quantitation of PET signal as an adjunct to visual interpretation of florbetapir imaging

Cited by 41 publications

References 25 publications

Clinical Use and Utility of Amyloid Imaging

Clinical Use and Utility of Amyloid Imaging

The Spatial-Temporal Ordering of Amyloid Pathology and Opportunities for PET Imaging

Flortaucipir F 18 Quantitation Using Parametric Estimation of Reference Signal Intensity

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