Ciftify: A framework for surface-based analysis of legacy MR acquisitions.

The preprocessing pipelines of the Human Connectome Project (HCP) were made publicly available for the neuroimaging community to apply the HCP analytic approach to data from non-HCP sources. The HCP analytic approach is surface-based for the cerebral cortex, uses the CIFTI "grayordinate" file format, provides greater statistical sensitivity than traditional volume-based analysis approaches, and allows for a more neuroanatomically-faithful representation of data. However, the HCP pipelines require the acquisition of specific images (namely T2w and field map) that historically have often not been acquired. Massive amounts of this 'legacy' data could benefit from the adoption of HCP-style methods. However, there is currently no published framework, to our knowledge, for adapting HCP preprocessing to "legacy" data. Here we present the ciftify project, a parsimonious analytic framework for adapting key modules from the HCP pipeline into existing structural workflows using FreeSurfer's recon_all structural and existing functional preprocessing workflows. Within this framework, any functional dataset with an accompanying (i.e. T1w) anatomical data can be analyzed in CIFTI format. To simplify usage for new data, the workflow has been bundled with fMRIPrep following the BIDS-app framework. Finally, we present the package and comment on future neuroinformatics advances that may accelerate the movement to a CIFTI-based grayordinate framework.

Personalized Intrinsic Network Topography Mapping and Functional Connectivity Deficits in Autism Spectrum Disorder.

BACKGROUND: Recent advances in techniques using functional magnetic resonance imaging data demonstrate individually specific variation in brain architecture in healthy individuals. To our knowledge, the effects of individually specific variation in complex brain disorders have not been previously reported. METHODS: We developed a novel approach (Personalized Intrinsic Network Topography, PINT) for localizing individually specific resting-state networks using conventional resting-state functional magnetic resonance imaging scans. Using cross-sectional data from participants with autism spectrum disorder (ASD; n = 393) and typically developing (TD) control participants (n = 496) across 15 sites, we tested: 1) effect of diagnosis and age on the variability of intrinsic network locations and 2) whether prior findings of functional connectivity differences in persons with ASD compared with TD persons remain after PINT application. RESULTS: We found greater variability in the spatial locations of resting-state networks within individuals with ASD compared with those in TD individuals. For TD persons, variability decreased from childhood into adulthood and increased in late life, following a U-shaped pattern that was not present in those with ASD. Comparison of intrinsic connectivity between groups revealed that the application of PINT decreased the number of hypoconnected regions in ASD. CONCLUSIONS: Our results provide a new framework for measuring altered brain functioning in neurodevelopmental disorders that may have implications for tracking developmental course, phenotypic heterogeneity, and ultimately treatment response. We underscore the importance of accounting for individual variation in the study of complex brain disorders.

Vaccine instability in the cold chain: mechanisms, analysis and formulation strategies.

Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines.