Linking function and structure: the relationship between brain activity and white matter integrity

The National Institutes of Health (NIH), National Institute on Aging (NIA) intends to negotiate, under authority of FAR 6.302-1, on a noncompetitive, sole source basis, with Vanderbilt University, Nashville, Tennessee. This notice of intent is not a request for competitive proposals. A solicitation document will not be issued, and proposals will not be requested. However, responsible sources may express their interest by submitting a capability statement or proposal. All capability statements or proposals received within this notice's response date will be considered by the Government. A determination by the Government not to complete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will normally be considered solely for the purpose of determining whether to conduct a competitive procurement. BACKGROUND The Baltimore Longitudinal Study of Aging (BLSA) Neuroimaging Cohort has a two decade record of structural, white matter, and functional (via positron emission tomography, PET) data. Over the last several years, new high resolution resting state functional magnetic resonance imaging (rs-fMRI) scans have been added to the BLSA MRI imaging protocol to accompany the ongoing collection of modern diffusion tensor imaging (DTI) sequences. Together, these imaging sequences provide new avenues for mapping human brain function, including investigation of the functional connectivity and white matter integrity to better understand how networks of brain activity underlying cognitive processing change with aging and disease. The purpose of this contract is to provide the Government with state-of-the art statistical approaches and analysis of white matter correlates of alterations in functional connectivity as well as functional connectivity correlates of white matter alterations, both of which are integral to mapping of human brain function. Neuroimaging-derived biomarkers based on these imaging data promise to enable earlier and more effective intervention. Notably, multivariate models that include cardiovascular, genetic, and image-based risk factors are showing increasing success at predicting disease onset and progression. Current analytic tools for neuroimaging do not directly assess the temporal causality (even in the weak "Granger" sense) or longitudinal interdependence between complex factors with regional impacts in the brain. New inference models from the statistical community are beginning to be applied in specialized contexts but have not been adapted for use within a general purpose framework. PURPOSE AND OBJECTIVES The contractor shall provide all resources necessary to accomplish the tasks and deliverables described in this Statement of Work (SOW). The 1 year extension should be restricted to the current contractor for continuity of research. Data processing with existing pipelines will be combined with the rs-fMRI and DTI data. The Contractor will use the developed pipelines for imaging processing and new statistical approaches. The Contractor will provide the government with pre-processed imaging data and statistical analyses of the combined rs-fMRI and DTI data. The Contractor will oversee the installation and implementation of software for specialized image analysis of BLSA images. PROJECT REQUIREMENTS The Contractor shall: Retrieve data and co-register all image data into a common coordinate system. The Contractor will coordinate with the NIA to ensure that a consistent common imaging reference space is used across projects. Apply image processing tools developed and validated under a prior contract (HHSN271201300672P). Define gray matter regions of interest. Targeted regions include the Hippocampus, Posterior Cingulate, Precuneus, and Medial Frontal cortex. DTI Pre-processing. The Contractor will perform and provide the Government with pre-processed image data, yielding fractional anisotropy (FA), mean diffusivity (MD), principal eigenvector (v1), and tensor (D) images for each subject. The Contractor shall use the defined gray matter regions of interest for rs-fMRI analysis based on structural data. Define white matter tracts. The FA maps for each subject will be labeled with a white matter atlas (i.e., the Johns Hopkins "Eve" atlas). rs-fMRI Pre-processing. Pre-processing will yield functional connectivity maps for each gray matter and white matter region of interest. Region of Interest Analysis. The Contractor will generate and provide to the LBN, NIA a table of means and standard deviations of rs-fMRI, FA, and MD for all regions of interest. Implement mass-univariate temporal modeling. The Contractor shall work with the LBN/NIA team and their collaborators to select the most promising temporal association inference models (e.g., "causal") and implement this approach in the context of the Biological Parametric Mapping (BPM) toolbox. Characterize temporal inference in simulation. The Contractors shall perform data-driven simulations to verify that the inference method empirically performs according to theoretical predictions and is compatible with standard approaches for multiple comparisons corrections (e.g., false discovery rate [FDR]). Apply multi-modal temporal inference to BLSA 1.5T/3T cohort. The Contractor shall work with LBN investigators to execute structural-functional-covariate analysis in the form of a general linear model (GLM, voxelwise model of the form: Y=? X) where both the regressors and the regressands may be longitudinally sampled imaging variables. The temporal relationships between sequenced regressors and regressands will be assessed. Additional non-imaging data may be provided for each subject in the form of an Excel document. These will be run as additional regressors. Scanner calibration. The Contractor shall develop and evaluate strategies for scanner calibration/correction, including modeling scanner changes as nuisance variables and using image preprocessing corrections. Support method translation to NIA intramural researchers The Contractor shall provide LBN, NIA with documentation of methods, including user manuals, and assist with installation and implementation of software for LBN use. The Contractor shall document methodological contributions in the form of peer-reviewed publications. REPORTS/DELIVERABLES The contractor shall report at least bimonthly by email or phone contact regarding an update of their progress and any image analyses. The Contractor shall deliver at 6 month intervals and at the end of the contract pre-processed images and results of statistical analyses detailed under project description. All data shall be in the form of electronic files. ANTICIPATED PERIOD OF PERFORMANCE The anticipated award is on/about September 2019 with an estimated period of performance of one (1) year. OTHER IMPORTANT CONSIDERATIONS (1) The Government is expected to use procedures in FAR Part 6.302-1 and (2) The North American Industry Classification System (NAICS) Code is 541990 with a size standard of $15 million. DISCLAIMER AND IMPORTANT NOTES This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. All responsible sources may submit a capability statement, proposal, or quotation which shall be considered by the agency. All responses must be received no later than March 13, 2019 at 5:00 p.m., Eastern Standard Time (EST) and must reference solicitation number HHS-NIH-NIDA(AG)-NOI-75N95019R00033. Responses may be submitted electronically (via e-mail) to the Contract Specialist at Heather.Orandi@nih.gov. Facsimile responses are NOT accepted. CONFIDENTIALITY No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s). Contracting Office Address: Contracts Management Branch Blue 6001 Executive Blvd, Rm 3166, MSC 9661 Bethesda, Maryland 20892-9661 Primary Point of Contact: Heather Orandi 6001 Executive Blvd, Rm 3166, MSC 9661 Bethesda, Maryland 20892-9661 Heather.Orandi@nih.gov