PI: Wighton, Paul Title: Unbiased longitudinal neuromorphometry for clinical decision support Received: 09/04/2018 FOA: PAS18-188 Council: 01/2019 Clinical Trial:Optional Competition ID: FORMS-E FOA Title: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's- Disease-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional) 1 R42 AG062026-01A1 Dual: blank Accession Number: 4209265 IPF: 10032164 Organization: CORTICOMETRICS, LLC Former Number: blank Department: blank IRG/SRG: ZRG1 SBIB-T (10)B AIDS: N Expedited: N Subtotal Direct Costs Animals: N New Investigator: blank (excludes consortium F&A) Humans: N Early Stage Investigator: blank Year 1: Clinical Trial: N Year 2: Current HS Code: 10 Year 3: HESC: N Senior/Key Personnel: Organization: Role Category: Paul Wighton CORTICOMETRICS, LLC PD/PI Bruce Fischl Massachusetts General Hospital (The MPI General Hospital Corp) STEVEN ARNOLD MASSACHUSETTS GENERAL Co-Investigator HOSPITAL Otto Rapalino Massachusetts General Hospital (The Co-Investigator General Hospital Corp) Brian Edlow Massachusetts General Hospital (The Co-Investigator General Hospital Corp) Martin Reuter Massachusetts General Hospital (The Co-Investigator General Hospital Corp) STEVEN STUFFLEBEAM Massachusetts General Hospital (The Co-Investigator General Hospital Corp) Nicholas Schmansky CORTICOMETRICS, LLC Other Professional-CEO, Software Engineer OMB Number: 4040-0001 Expiration Date: 10/31/2019 APPLICATION FOR FEDERAL ASSISTANCE 3. DATE RECEIVED BY STATE State Application Identifier SF 424 (R&R) blank blank 1. TYPE OF SUBMISSION* 4.a. Federal Identifier AG062026 ❍ Pre-application ● Application ❍ Changed/Corrected b. Agency Routing Number Application blank 2. DATE SUBMITTED Application Identifier c. Previous Grants.gov Tracking Number 2018-09-04 Longitudinal_FT blank 5. APPLICANT INFORMATION Organizational DUNS*: Legal Name*: CORTICOMETRICS, LLC Department: blank Division: blank Street1*: Street2: blank City*: County: State*: Province: blank Country*: ZIP / Postal Code*: Person to be contacted on matters involving this application blank Prefix: blank First Name*: Nick Middle Name: blank Last Name*: Schmansky Suffix: Position/Title: blank Street1*: Street2: blank City*: County: State*: Province: blank Country*: ZIP / Postal Code*: Phone Number*: Fax Number: blank Email: 6. EMPLOYER IDENTIFICATION NUMBER (EIN) or (TIN)* 7. TYPE OF APPLICANT* R: Small Business Other (Specify): Small Business Organization Type ❍ Women Owned ❍ Socially and Economically Disadvantaged 8. TYPE OF APPLICATION* If Revision, mark appropriate box(es). ❍ New ● Resubmission ❍ A. Increase Award ❍ B. Decrease Award ❍ C. Increase Duration ❍ Renewal ❍ Continuation ❍ Revision ❍ D. Decrease Duration ❍ E. Other (specify) : Is this application being submitted to other agencies?* ❍Yes ●No What other Agencies? blank 9. NAME OF FEDERAL AGENCY* 10. CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER National Institutes of Health TITLE: blank 11. DESCRIPTIVE TITLE OF APPLICANT'S PROJECT* Unbiased longitudinal neuromorphometry for clinical decision support 12. PROPOSED PROJECT 13. CONGRESSIONAL DISTRICTS OF APPLICANT Start Date* Ending Date* 05/01/2019 04/30/2022 Tracking Number: GRANT12703690 Funding Opportunity Number: PAS-18-188 . Received Date: Page 1 2018-09-04T15:35:50.000-04:00 SF 424 (R&R) APPLICATION FOR FEDERAL ASSISTANCE Page 2 14. PROJECT DIRECTOR/PRINCIPAL INVESTIGATOR CONTACT INFORMATION Prefix: blank First Name*: Paul Middle Name: blank Last Name*: Wighton Suffix: blank Position/Title: Staff Scientist Organization Name*: CORTICOMETRICS, LLC Department: blank Division: blank Street1*: Street2: blank City*: County: blank State*: Province: blank Country*: ZIP / Postal Code*: Phone Number*: Fax Number: blank Email*: 15. ESTIMATED PROJECT FUNDING 16. IS APPLICATION SUBJECT TO REVIEW BY STATE EXECUTIVE ORDER 12372 PROCESS?* a. YES ❍ THIS PREAPPLICATION/APPLICATION WAS MADE a. Total Federal Funds Requested* AVAILABLE TO THE STATE EXECUTIVE ORDER 12372 b. Total Non-Federal Funds* PROCESS FOR REVIEW ON: c. Total Federal & Non-Federal Funds* DATE: blank d. Estimated Program Income* b. NO ● PROGRAM IS NOT COVERED BY E.O. 12372; OR ❍ PROGRAM HAS NOT BEEN SELECTED BY STATE FOR REVIEW 17. By signing this application, I certify (1) to the statements contained in the list of certifications* and (2) that the statements herein are true, complete and accurate to the best of my knowledge. I also provide the required assurances * and agree to comply with any resulting terms if I accept an award. I am aware that any false, fictitious, or fraudulent statements or claims may subject me to criminal, civil, or administrative penalties. (U.S. Code, Title 18, Section 1001) ● I agree* * The list of certifications and assurances, or an Internet site where you may obtain this list, is contained in the announcement or agency specific instructions. 18. SFLLL or OTHER EXPLANATORY DOCUMENTATION File Name: blank 19. AUTHORIZED REPRESENTATIVE Prefix: blank First Name*: Nick Middle Name: blank Last Name*: Schmansky Suffix: blank Position/Title*: Co-Founder, CEO Organization Name*: CorticoMetrics LLC Department: blank Division: blank Street1*: Street2: blank City*: County: blank State*: Province: blank Country*: ZIP / Postal Code*: Phone Number*: Fax Number: blank Email*: Signature of Authorized Representative* Date Signed* Nicholas Schmansky 09/04/2018 20. PRE-APPLICATION File Name: blank 21. COVER LETTER ATTACHMENT File Name: blank Tracking Number: GRANT12703690 Funding Opportunity Number: PAS-18-188 . Received Date: Page 2 2018-09-04T15:35:50.000-04:00 Paul null Wighton PHS 398 Cover Page Supplement OMB Number: 0925-0001 Expiration Date: 03/31/2020 1. Vertebrate Animals Section Are vertebrate animals euthanized? ❍ Yes ● No If "Yes" to euthanasia Is the method consistent with American Veterinary Medical Association (AVMA) guidelines? ❍ Yes ❍ No If "No" to AVMA guidelines, describe method and provide scientific justification 2. *Program Income Section *Is program income anticipated during the periods for which the grant support is requested? ❍ Yes ● No If you checked "yes" above (indicating that program income is anticipated), then use the format below to reflect the amount and source(s). Otherwise, leave this section blank. *Budget Period *Anticipated Amount ($) *Source(s) blank blank blank Page 3 Tracking Number: GRANT12703690 Funding Opportunity Number: PAS-18-188 . Received Date: 2018-09-04T15:35:50.000-04:00 Paul null Wighton PHS 398 Cover Page Supplement 3. Human Embryonic Stem Cells Section *Does the proposed project involve human embryonic stem cells? ❍ Yes ● No If the proposed project involves human embryonic stem cells, list below the registration number of the specific cell line(s) from the following list: http://grants.nih.gov/stem_cells/registry/current.htm. Or, if a specific stem cell line cannot be referenced at this time, check the box indicating that one from the registry will be used: ❏ Specific stem cell line cannot be referenced at this time. One from the registry will be used. Cell Line(s) (Example: 0004): blank 4. Inventions and Patents Section (Renewal applications) *Inventions and Patents: ❍ Yes ● No If the answer is "Yes" then please answer the following: *Previously Reported: ❍ Yes ❍ No 5. Change of Investigator/Change of Institution Section ❏ Change of Project Director/Principal Investigator Name of former Project Director/Principal Investigator Prefix: blank *First Name: blank Middle Name: blank *Last Name: blank blank Suffix: ❏ Change of Grantee Institution *Name of former institution: blank Page 4 Tracking Number: GRANT12703690 Funding Opportunity Number: PAS-18-188 . Received Date: 2018-09-04T15:35:50.000-04:00 Project Summary Normal human neuroanatomy is incredibly variable, and increases with age. This impedes the ability of neuroimaging to detect effects in neurological conditions such as Alzheimer's disease (AD), Huntington's disease (HD), multiple sclerosis (MS) and schizophrenia. Most of the recently available state-of-the-art quantitative imaging tools still use cross-sectional methods to analyze repeated scans. These tools lack the sensitivity to monitor subtle progressive changes because such approaches do not account for the large intrinsic variability of normal neuroanatomy. The goal of this project is to commercialize a longitudinal, neuro-morphometric image processing pipeline for use in radiology, neurology and related clinical fields. The successful completion of this project will result in a clinically useful neuro-morphometric longitudinal analysis stream with more statistical power than is currently available commercially. This increase in power will directly translate into an enhanced ability to detect and assess progression at both the individual and group levels. It will also alleviate a major pain point in current longitudinal neuroradiology reading workflows, reducing radiology report turnaround times (RTAT). Project Narrative The proposed project will develop software to help clinicians quantitatively assess and interpret changes in brain MRI data in a way that integrates seamlessly into an existing clinical workflow. It will help radiologists detect changes to brain structures earlier and more accurately, in neurological conditions such as Alzheimer's disease (AD), Huntington's disease (HD), multiple sclerosis (MS) and schizophrenia. The resulting efforts will translate into an enhanced ability to detect and assess disease progression, and reduce radiology report turnaround time. BIOGRAPHICAL SKETCH NAME: Wighton,