Non-small cell lung cancer chemotherapy treatment outcomes and ethnicity: a twenty-year single-centre patterns of care study.

AIM: To investigate the treatment of patients with advanced-stage non-small cell lung cancer (NSCLC) over a 20-year period in a single Aotearoa New Zealand centre with reference to the use of systemic anti-cancer chemotherapy (SACT) and to explore ethnic disparities in treatment and outcomes. METHOD: Using a SACT database maintained by the Oncology Department at Waikato Hospital, Hamilton, Aotearoa New Zealand from 2000 to 2021 we derived summary statistics for patient factors and SACT regimens by ethnicity (Maori and non-Maori). We investigated Kaplan-Meier all-cause survival by ethnicity and SACT. Logistic regression was used to estimate the odds ratios of surviving 12 months and receiving first and second SACT. RESULTS: One thousand and fifty-seven patients with advanced NSCLC were included, with 30% identified as Maori and 53% treated with SACT. The median survival for non-Maori and Maori receiving SACT was 11.9 and 8.5 months respectively (unadjusted odds ratio of surviving 12 months: 1.968; 95% CI: 1.352-2.865; p<0.001). Non-Maori receiving SACT were 86.2% more likely to survive 12 months than Maori. There were no ethnic disparities in the proportion of patients receiving first-line SACT; however, non-Maori were 1.5 times more likely to receive a second SACT than Maori. CONCLUSION: Significant ethnic difference between Maori and non-Maori exists for both survival and receipt of second-line SACT.

Early tau detection in flortaucipir images: validation in autopsy-confirmed data and implications for disease progression.

BACKGROUND: There is an increasing interest in utilizing tau PET to identify patients early in Alzheimer's disease (AD). In this work, a temporal lobe composite (Eτ) volume of interest (VOI) was evaluated in a longitudinal flortaucipir cohort and compared to a previously described global neocortical VOI. In a separate autopsy-confirmed study, the sensitivity of the Eτ VOI for identifying intermediate (B2) neurofibrillary tangle (NFT) pathology was evaluated. METHODS: A total of 427 subjects received flortaucipir, florbetapir, MRI, and cognitive evaluation at baseline and 18 months. In a separate autopsy study, 67 subjects received ante-mortem flortaucipir scans, and neuropathological findings were recorded according to NIA-AA recommendations by two experts. Two VOIs: Eτ comprising FreeSurfer volumes (bilateral entorhinal cortex, fusiform, parahippocampal, and inferior temporal gyri) transformed to MNI space and a previously published global AD signature-weighted neocortical VOI (ADsignature) (Devous et al., J Nucl Med 59:937-43, 2018), were used to calculate SUVr relative to a white matter reference region (PERSI) (Southekal et al., J Nucl Med Off Publ Soc Nucl Med 59:944-51, 2018). SUVr cutoffs for positivity were determined based on a cohort of young, cognitively normal subjects. Subjects were grouped based on positivity on both VOIs (Eτ+/ADsignature+; Eτ+/ADsignature-; Eτ-/ADsignature-). Groupwise comparisons were performed for baseline SUVr, 18-month changes in SUVr, neurodegeneration, and cognition. For the autopsy study, the sensitivity of Eτ in identifying intermediate Braak pathology (B2) subjects was compared to that of AD signature-weighted neocortical VOI. The average surface maps of subjects in the Eτ+/ADsignature- group and B2 NFT scores were created for visual evaluation of uptake. RESULTS: Sixty-four out of 390 analyzable subjects were identified as Eτ+/ADsignature-: 84% were Aß+, 100% were diagnosed as MCI or AD, and 59% were APOE ε4 carriers. Consistent with the hypothesis that Eτ+/ADsignature- status reflects an early stage of AD, Eτ+/ADsignature- subjects deteriorated significantly faster than Eτ-/ADsignature- subjects, but significantly slower than Eτ+/ADsignature+ subjects, on most measures (i.e., change in ADsignature SUVr, Eτ ROI cortical thickness, and MMSE). The ADsignature VOI was selective for subjects who came to autopsy with a B3 NFT score. In the autopsy study, 12/15 B2 subjects (including 10/11 Braak IV) were Eτ+/ADsignature-. Surface maps showed that flortaucipir uptake was largely captured by the Eτ VOI regions in B2 subjects. CONCLUSION: The Eτ VOI identified subjects with elevated temporal but not global tau (Eτ+/ADsignature-) that were primarily Aß+, APOE ε4 carriers, and diagnosed as MCI or AD. Eτ+/ADsignature- subjects had greater accumulation of tau, greater atrophy, and higher decline on MMSE in 18 months compared to Eτ-/ADsignature- subjects. Finally, the Eτ VOI identified the majority of the intermediate NFT score subjects in an autopsy-confirmed study. As far as we know, this is the first study that presents a visualization of ante-mortem FTP retention patterns that at a group level agree with the neurofibrillary tangle staging scheme proposed by Braak. These findings suggest that the Eτ VOI may be sensitive for detecting impaired subjects early in the course of Alzheimer's disease.

Followback Clusters, Satellite Audiences, and Bridge Nodes: Coengagement Networks for the 2020 US Election.

The 2020 United States (US) presidential election was - and has continued to be - the focus of pervasive and persistent mis- and disinformation spreading through our media ecosystems, including social media. This event has driven the collection and analysis of large, directed social network datasets, but such datasets can resist intuitive understanding. In such large datasets, the overwhelming number of nodes and edges present in typical representations create visual artifacts, such as densely overlapping edges and tightly-packed formations of low-degree nodes, which obscure many features of more practical interest. We apply a method, coengagement transformations, to convert such networks of social data into tractable images. Intuitively, this approach allows for parameterized network visualizations that make shared audiences of engaged viewers salient to viewers. Using the interpretative capabilities of this method, we perform an extensive case study of the 2020 United States presidential election on Twitter, contributing an empirical analysis of coengagement. By creating and contrasting different networks at different parameter sets, we define and characterize several structures in this discourse network, including bridging accounts, satellite audiences, and followback communities. We discuss the importance and implications of these empirical network features in this context. In addition, we release open-source code for creating coengagement networks from Twitter and other structured interaction data.

Move-In Fees as a Residential Sorting Mechanism Within Online Rental Markets.

An increasing number of American renters within major metropolitan housing markets rely on online platforms such as Craigslist to find rental units. Landlords that advertise rentals on these websites have been found to tailor the language used in their listings in reference to surrounding neighborhood demographics to influence prospective tenants' rental searches. This work investigates the underexplored subject of move-in fees, referring to upfront costs to secure a lease, such as security deposits, application charges, and advanced rent payments that can affect whether a prospective renter can afford an advertised unit. This study advances a framework for how housing researchers can assess variations in landlord discourse within online housing marketplaces using text analysis methods and web scraping. It then illustrates how the resulting measures about move-in fees have distinct variations in prevalence along sociodemographic, spatial, and policy measures through a series of descriptive analyses, with subsequent conclusions toward policy implications designed to assist low-income renters with overcoming financial barriers in securing rental housing.

Segmented information, segregated outcomes: Housing affordability and neighborhood representation on a voucher-focused online housing platform and three mainstream alternatives.

Online platforms have become an integral component of the housing search process in the United States and other developed contexts, but recent studies have demonstrated that these platforms offer uneven representation of different neighborhoods. In this study, we use listings covering the largest 50 U.S. metropolitan areas to assess how GoSection8, a platform uniquely focused on affordable housing and voucher-assisted households, compares with "mainstream" alternatives of Craigslist, Apartments.com and Zillow. Through descriptive and regression analyses of the housing and neighborhoods represented on these websites and a new way of measuring the distribution of rental housing opportunities, we advance a multisource perspective on the role of online information exchanges in housing search processes. Specifically, we find that GoSection8 and mainstream alternatives capture spatially-segmented information about housing markets, with GoSection8 ads representing units that are more affordable but also more constrained to higher-poverty neighborhoods where assisted households are already concentrated. The findings suggest that disadvantaged households are potentially funneled toward high-poverty, isolated neighborhoods by the operation of stratified information systems available for online housing searches.

Tunneling Spectroscopy of Two-Dimensional Materials Based on Via Contacts.

We introduce a novel planar tunneling architecture for van der Waals heterostructures based on via contacts, namely, metallic contacts embedded into through-holes in hexagonal boron nitride (hBN). We use the via-based tunneling method to study the single-particle density of states of two different two-dimensional (2D) materials, NbSe2 and graphene. In NbSe2 devices, we characterize the barrier strength and interface disorder for barrier thicknesses of 0, 1, and 2 layers of hBN and study the dependence on the tunnel-contact area down to (44 ± 14)2 nm2. For 0-layer hBN devices, we demonstrate a crossover from diffusive to point contacts in the small-contact-area limit. In graphene, we show that reducing the tunnel barrier thickness and area can suppress effects due to phonon-assisted tunneling and defects in the hBN barrier. This via-based architecture overcomes limitations of other planar tunneling designs and produces high-quality, ultraclean tunneling structures from a variety of 2D materials.

Low-temperature exposure has immediate and lasting effects on the stress tolerance, chemotaxis and proteome of entomopathogenic nematodes.

Temperature is one of the most important factors affecting soil organisms, including the infective stages of parasites and entomopathogenic nematodes, which are important biological control agents. We investigated the response of 2 species of entomopathogenic nematodes to different storage regimes: cold (9°C), culture temperature (20°C) and temperature swapped from 9 to 20°C. For Steinernema carpocapsae, cold storage had profound effects on chemotaxis, stress tolerance and protein expression that were retained in temperature-swapped individuals. These effects included reversal of chemotactic response for 3 (prenol, methyl salicylate and hexanol) of the 4 chemicals tested, and enhanced tolerance to freezing (−10°C) and desiccation (75% RH). Label-free quantitative proteomics showed that cold storage induced widespread changes in S. carpocapsae, including an increase in heat-shock proteins and late embryogenesis abundant proteins. For Heterorhabditis megidis, cold storage had a less dramatic effect on chemotaxis (as previously shown for proteomic expression) and changes were not maintained on return to 20°C. Thus, cold temperature exposure has significant effects on entomopathogenic nematodes, but the nature of the change depends on the species. Steinernema carpocapsae, in particular, displays significant plasticity, and its behaviour and stress tolerance may be manipulated by brief exposure to low temperatures, with implications for its use as a biological control agent.

Combining interventions to reduce the spread of viral misinformation.

Misinformation online poses a range of threats, from subverting democratic processes to undermining public health measures. Proposed solutions range from encouraging more selective sharing by individuals to removing false content and accounts that create or promote it. Here we provide a framework to evaluate interventions aimed at reducing viral misinformation online both in isolation and when used in combination. We begin by deriving a generative model of viral misinformation spread, inspired by research on infectious disease. By applying this model to a large corpus (10.5 million tweets) of misinformation events that occurred during the 2020 US election, we reveal that commonly proposed interventions are unlikely to be effective in isolation. However, our framework demonstrates that a combined approach can achieve a substantial reduction in the prevalence of misinformation. Our results highlight a practical path forward as misinformation online continues to threaten vaccination efforts, equity and democratic processes around the globe.

Debtors' Blocks: How Monetary Sanctions Make Between-neighborhood Racial and Economic Inequalities Worse.

Although recent scholarship has enumerated many individual-level consequences of criminal legal citations and sentences involving fines and fees, we know surprisingly little about the structural consequences of monetary sanctions or legal financial obligations (LFOs). We use social disorganization and critical race theories to examine neighborhood-level associations between and among LFO sentence amounts, poverty, and racial and ethnic demographics. Using longitudinal data from the Washington State Administrative Office of the Courts, and the American Community Survey, we find LFOs are more burdensome in high-poverty communities and of color, and that per-capita rates of LFOs sentenced are associated with increased future poverty rates across all neighborhoods.

Racialized Discourse in Seattle Rental Ad Texts.

Racial discrimination has been a central driver of residential segregation for many decades, in the Seattle area as well as in the United States as a whole. In addition to redlining and restrictive housing covenants, housing advertisements included explicit racial language until 1968. Since then, housing patterns have remained racialized, despite overt forms of racial language and discrimination becoming less prevalent. In this paper, we use Structural Topic Models (STM) and qualitative analysis to investigate how contemporary rental listings from the Seattle-Tacoma Craigslist page differ in their description based on neighborhood racial composition. Results show that listings from White neighborhoods emphasize trust and connections to neighborhood history and culture, while listings from non-White neighborhoods offer more incentives and focus on transportation and development features, sundering these units from their surroundings. Without explicitly mentioning race, these listings display racialized neighborhood discourse that might impact neighborhood decision-making in ways that contribute to the perpetuation of housing segregation.

Relationships Between Cognition and Neuropathological Tau in Alzheimer's Disease Assessed by 18F Flortaucipir PET.

BACKGROUND: Tau neurofibrillary tangle burden increases with Alzheimer's disease (AD) stage and correlates with degree of cognitive impairment. Tau PET imaging could facilitate understanding the relationship between tau pathology and cognitive impairment. OBJECTIVE: Evaluate the relationship between 18F flortaucipir uptake patterns and cognition across multiple cognitive domains. METHODS: We acquired flortaucipir PET scans in 84 amyloid-positive control, mild cognitive impairment (MCI), and AD subjects. Flortaucipir standardized uptake value ratio (SUVr) values were obtained from a neocortical volume of interest (VOI), a precuneus VOI, and VOIs defined by the correlation between flortaucipir SUVr images and domain-specific cognitive tests. Cognitive assessments included Mini-Mental State Exam (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), and a neuropsychological test battery (i.e., Wechsler Memory Scale-Revised Logical Memory (WMS-R), Trail Making Test, Boston Naming Test, Digit Symbol Substitution Test, Animal List Generation, WMS-R Digit Span, American National Adult Reading Test, Clock Drawing Test, Judgment of Line Orientation, and WMS-R Logical Memory II (Delayed Recall)) and the Functional Activities Questionnaire (FAQ). Correlation analyses compared regional and voxel-wise VOIs to cognitive scores. RESULTS: Subjects included 5 controls, 47 MCI, and 32 AD subjects. Significant correlations were seen between both flortaucipir and florbetapir SUVrs and MMSE, ADAS-Cog, and FAQ. Cognitive impairment was associated with increased flortaucipir uptake in regionally specific patterns consistent with the neuroanatomy underlying specific cognitive tests. CONCLUSION: Flortaucipir SUVr values demonstrated significant inverse correlations with cognitive scores in domain-specific patterns. Findings support the hypothesis that PET imaging of neuropathologic tau deposits may reflect underlying neurodegeneration in AD.

Toward a Cross-Platform Framework: Assessing the Comprehensiveness of Online Rental Listings.

Research on rental housing markets in the United States has traditionally relied on national or local housing surveys. Those sources lack temporal and spatial specificity, limiting their use for tracking short-term changes in local markets. As rental housing ads have transitioned to digital spaces, a growing body of literature has utilized web scraping to analyze listing practices and variations in rental market dynamics. Those studies have primarily relied on one platform, Craigslist, as a source of data. Despite Craigslist's popularity, the authors contend that rental listings from various websites, rather than from individual ones, provide a more comprehensive picture. Using a mixed-methods approach to study listings across various platforms in five metropolitan areas, this article demonstrates considerable variation in both the types of rental units advertised and the features provided across those platforms. The article begins with an account of the birth and consolidation of online rental platforms and emergent characteristics of several selected websites, including the criteria for posting, search parameters, search results priority, and first-page search results. Visualizations are used to compare features such as the 40th percentile of rent, rent distribution, and bedroom size based on scraped data from six online platforms (Padmapper, Forrent.com, Trulia, Zillow, Craigslist, and GoSection8), 2020 Fair Market Rents, and 2019 American Community Survey data. The analyses indicate that online listing platforms target different audiences and offer distinct information on units within those market segments, resulting in markedly different estimates of local rental costs and unit size distribution depending on the platform.

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study.

BACKGROUND: The objective of this study was to make a quantitative comparison of flortaucipir PET retention with pathological tau and ß-amyloid across a range of brain regions at autopsy. METHODS: Patients with dementia (two with clinical diagnosis of AD, one undetermined), nearing the end of life, underwent 20-min PET, beginning 80 min after an injection of ~370 mBq flortaucipir [18F]. Neocortical, basal ganglia, and limbic tissue samples were obtained bilaterally from 19 regions at autopsy and subject-specific PET regions of interest corresponding to the 19 sampled target tissue regions in each hemisphere were hand drawn on the PET images. SUVr values were calculated for each region using a cerebellar reference region. Abnormally phosphorylated tau (Ptau) and amyloid-ß (Aß) tissue concentrations were measured for each tissue region with an antibody capture assay (Histelide) using AT8 and H31L21 antibodies respectively. RESULTS: The imaging-to-autopsy interval ranged from 4-29 days. All three subjects had intermediate to high levels of AD neuropathologic change at autopsy. Mean cortical SUVr averaged across all three subjects correlated significantly with the Ptau immunoassay (Pearson r = 0.81; p < 0.0001). When Ptau and Aß1-42 were both included in the model, the Ptau correlation with flortaucipir SUVr was preserved but there was no correlation of Aß1-42 with flortaucipir. There was also a modest correlation between limbic (hippocampal/entorhinal and amygdala) flortaucipir SUVr and Ptau (Pearson r = 0.52; p < 0.080). There was no significant correlation between SUVr and Ptau in basal ganglia. CONCLUSIONS: The results of this pilot study support a quantitative relationship between cortical flortaucipir SUVr values and quantitative measures of Ptau at autopsy. Additional research including more cases is needed to confirm the generalizability of these results. Trial registration, NIH Clinicaltrials.gov NCT # 02516046. Registered August 27, 2015. https://clinicaltrials.gov/ct2/show/NCT02516046?term=02516046&draw=2&rank=1.

Positron Emission Tomography Imaging With [18F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes.

Importance: Positron emission tomography (PET) may increase the diagnostic accuracy and confirm the underlying neuropathologic changes of Alzheimer disease (AD). Objective: To determine the accuracy of antemortem [18F]flortaucipir PET images for predicting the presence of AD-type tau pathology at autopsy. Design, Setting, and Participants: This diagnostic study (A16 primary cohort) was conducted from October 2015 to June 2018 at 28 study sites (27 in US sites and 1 in Australia). Individuals with a terminal illness who were older than 50 years and had a projected life expectancy of less than 6 months were enrolled. All participants underwent [18F]flortaucipir PET imaging, and scans were interpreted by 5 independent nuclear medicine physicians or radiologists. Supplemental autopsy [18F]flortaucipir images and pathological samples were also collected from 16 historically collected cases. A second study (FR01 validation study) was conducted from March 26 to April 26, 2019, in which 5 new readers assessed the original PET images for comparison to autopsy. Main Outcomes and Measures: [18F]flortaucipir PET images were visually assessed and compared with immunohistochemical tau pathology. An AD tau pattern of flortaucipir retention was assessed for correspondence with a postmortem B3-level (Braak stage V or VI) pathological pattern of tau accumulation and to the presence of amyloid-ß plaques sufficient to meet the criteria for high levels of AD neuropathological change. Success was defined as having at least 3 of the 5 readers above the lower bounds of the 95% CI for both sensitivity and specificity of 50% or greater. Results: A total of 156 patients were enrolled in the A16 study and underwent [18F]flortaucipir PET imaging. Of these, 73 died during the study, and valid autopsies were performed for 67 of these patients. Three autopsies were evaluated as test cases and removed from the primary cohort (n = 64). Of the 64 primary cohort patients, 34 (53%) were women and 62 (97%) were white; mean (SD) age was 82.5 (9.6) years; and 49 (77%) had dementia, 1 (2%) had mild cognitive impairment, and 14 (22%) had normal cognition. Prespecified success criteria were met for the A16 primary cohort. The flortaucipir PET scans predicted a B3 level of tau pathology, with sensitivity ranging from 92.3% (95% CI, 79.7%-97.3%) to 100.0% (95% CI, 91.0%-100.0%) and specificity ranging from 52.0% (95% CI, 33.5%-70.0%) to 92.0% (95% CI, 75.0%-97.8%). A high level of AD neuropathological change was predicted with sensitivity of 94.7% (95% CI, 82.7%-98.5%) to 100.0% (95% CI, 90.8%-100.0%) and specificity of 50.0% (95% CI, 32.1%-67.9%) to 92.3% (95% CI, 75.9%-97.9%). The FR01 validation study also met prespecified success criteria. Addition of the supplemental autopsy data set and 3 test cases, which comprised a total of 82 patients and autopsies for both the A16 and FR01 studies, resulted in improved specificity and comparable overall accuracy. Among the 156 enrolled participants, 14 (9%) experienced at least 1 treatment-emergent adverse event. Conclusions and Relevance: This study's findings suggest that PET imaging with [18F]flortaucipir could be used to identify the density and distribution of AD-type tau pathology and the presence of high levels of AD neuropathological change, supporting a neuropathological diagnosis of AD.

Case Report: Sustained Complete Response to PI3K Inhibition in a Patient with Metastatic Breast Cancer Harboring PIK3CA, NF1, and CDH1 Mutations.

PIK3CA mutations resulting in disinhibition of the phosphoinositide 3-kinase (PI3K) pathway are present in approximately a third of estrogen receptor (ER)-positive breast cancer. Recent clinical trials of PI3K inhibition in PIK3CA-mutated metastatic breast cancer have shown improvement in progression-free survival of up to 11 months. We report a 68-year-old woman with metastatic ER-positive breast cancer with PIK3CA mutation who despite having disease progression after four lines of endocrine therapy (ET) attained a complete response (CR) after subsequent addition of a PI3K inhibitor. Remarkably, her CR is still maintained at 5 years. We believe this may be due to the co-occurrence of an NF1 mutation, which increases sensitivity to PI3K inhibition. Our case demonstrates restoration of sensitivity to ET by additional inhibition of PI3K, which resulted in exceptional disease response, far exceeding the expected duration. Hence, we believe that PI3K inhibition in addition to ET should be considered in patients with simultaneous PIK3CA and NF1 mutations.

A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia.

The advent of tau-targeted PET tracers such as flortaucipir (18F) (flortaucipir, also known as 18F-AV-1451 or 18F-T807) have made it possible to investigate the sequence of development of tau in relationship to age, amyloid-ß, and to the development of cognitive impairment due to Alzheimer's disease. Here we report a multicentre longitudinal evaluation of the relationships between baseline tau, tau change and cognitive change, using flortaucipir PET imaging. A total of 202 participants 50 years old or older, including 57 cognitively normal subjects, 97 clinically defined mild cognitive impairment and 48 possible or probable Alzheimer's disease dementia patients, received flortaucipir PET scans of 20 min in duration beginning 80 min after intravenous administration of 370 MBq flortaucipir (18F). On separate days, subjects also received florbetapir amyloid PET imaging, and underwent a neuropsychological test battery. Follow-up flortaucipir scans and neuropsychological battery assessments were also performed at 9 and 18 months. Fifty-five amyloid-ß+ and 90 amyloid-ß- subjects completed the baseline and 18-month study visits and had valid quantifiable flortaucipir scans at both time points. There was a statistically significant increase in the global estimate of cortical tau burden as measured by standardized uptake value ratio (SUVr) from baseline to 18 months in amyloid-ß+ but not amyloid-ß- subjects (least squared mean change in flortaucipir SUVr : 0.0524 ± 0.0085, P < 0.0001 and 0.0007 ± 0.0024 P = 0.7850, respectively), and a significant association between magnitude of SUVr increase and baseline tau burden. Voxel-wise evaluations further suggested that the regional pattern of change in flortaucipir PET SUVr over the 18-month study period (i.e. which regions exhibited the greatest change) also varied as a function of baseline global estimate of tau burden. In subjects with lower global SUVr, temporal lobe regions showed the greatest flortaucipir retention, whereas in subjects with higher baseline SUVr, parietal and frontal regions were increasingly affected. Finally, baseline flortaucipir and change in flortaucipir SUVr were both significantly (P < 0.0001) associated with changes in cognitive performance. Taken together, these results provide a preliminary characterization of the longitudinal spread of tau in Alzheimer's disease and suggest that the amount and location of tau may have implications both for the spread of tau and the cognitive deterioration that may occur over an 18-month period.

Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale.

INTRODUCTION: Klunk et al. recently proposed a means of standardizing quantitation of amyloid burden from positron emission tomography scans to a common Centiloid scale, and we have applied that method to florbetapir. METHODS: Florbetapir and Pittsburgh compound B scans were acquired for 46 mixed clinical presentation subjects within 18 ± 20 days. Florbetapir and Pittsburgh compound B cortical standardized uptake value ratio (SUVr) values were well correlated for both standard Centiloid (R2 = 0.894) and Avid (R2 = 0.901) volume of interests (VOIs). The methods of Klunk et al. were applied to establish a conversion first from florbetapir SUVr values obtained using standard Centiloid VOIs to Centiloids and then from Avid VOIs (Joshi et al.) to Centiloids. RESULTS: The equation for conversion of florbetapir SUVr from Avid VOIs to the Centiloid scale was as follows: Florbetapir Centiloids = 183 × SUVrAvid - 177. The threshold that discriminated neuropathologically verified none or sparse versus moderate to frequent plaques in autopsy-confirmed data is 24.1 Centiloids. DISCUSSION: These findings may allow improved tracer-independent amyloid quantitation.

Flortaucipir F 18 Quantitation Using Parametric Estimation of Reference Signal Intensity.

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. Methods: Subjects with a clinical diagnosis of Alzheimer disease, mild cognitive impairment, or normal cognition underwent T1-weighted MRI and florbetapir imaging (to determine amyloid [Aß] 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; Aß-positive impaired vs. Aß-negative normal) were evaluated in another phase 2 study with cross-sectional data (n = 215) and longitudinal data (n = 142/215; 18 ± 2 mo between scans). Results: 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 Aß control subjects with no specific flortaucipir F 18 uptake (SUVr, 1.0 ± 0.04; ΔSUVr, 0.0 ± 0.02). Conclusion: 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.