The NIH BRAIN Initiative is providing funding to make the Connectome 2.0 scanner at Massachusetts General Hospital (MGH) A. A. Martinos Center for Biomedical Imaging available to the international neuroscience community for advanced diffusion MRI (dMRI) research and related projects. This BRAIN Initiative U24 dissemination funding facilitates Connectome 2.0 3T neuroscience pilot projects by providing scan time, subject recruitment and onsite personnel to conduct these research projects. It also provides remote scanning capabilities to minimize the need for long-distance investigator travel (researchers can travel to MGH if they wish to, but no travel funds are included in this project).
Completed proposals, as well as any questions or concerns, can be sent to connectome2@nmr.mgh.harvard.edu.
Your proposal should clearly and succinctly describe the project’s aims, previous work, background, methods, significance, and an estimated amount of scantime required. Completed submissions should be emailed as a single pdf file to connectome2@nmr.mgh.harvard.edu.
This opportunity is open to PIs from the international academic community. Special attention will be paid to alignment of the proposal to BRAIN 2.0 goals, and ensuring project PIs come from a diverse range of geographic locations and backgrounds.
Your proposal should contain the following sections, clearly indicated. Please respect the indicated page limits. If it’s a resubmission, please indicate so in the beginning of the proposal and highlight the revisions in red font. Font should be Arial, 11 pt and page margins: at least 0.5 inch on all sides.
Abstract (500 words total)
Summarize the significance, innovation, objectives, and approach of the proposed research.
Research Plan (2 pages total)
- Project Title. Put the project title, principal investigator’s name(s) and email address(s) at the top of the first page. Please also list the project’s institution and department, even if it originates from an MGB institution.
- Project Aims. Concisely state the objectives of the project and the goals to be reached during the project.
- Background, significance, and innovation. Provide a description of the relevant literature and the BRAIN 2.0 goals the project aims to address. Indicate how the proposed project leverages the Connectome 2.0 3T hardware and the increased resolution achievable on the Connectome 2.0 3T system.
- Approach. Describe the methodology to achieve the pilot project within 12 months List any specific needs for the proposal including pulse sequences, peripheral equipment or presentation software, and describe how these will be obtained if not already available on the Connectome 2.0. Include an estimated timeline for milestones and the anticipated amount of sequence testing scantime and subject scantime needed. Include a data analysis plan and expected outcomes. Please be sure to include the following:
- Number of subjects and/or ex vivo samples, clearly delineating between healthy volunteers, patient populations, and ex vivo samples
- How subjects will be recruited or how samples will be brought in for scanning, or from what preexisting populations they will be recruited from
- Hours needed per subject and/or ex vivo scan
- Special patient care, imaging, or equipment needs
- Potential pitfalls, and alternatives. Discuss alternative approaches if initial piloting indicates the proposed protocol has insufficient SNR.
- Impact and Sustainability. Discuss the importance of successful outcomes and the plan for extramural funding. If extramural funding has already been secured, please provide details in this section. Please also indicate if this project will be conducted on the MGH Connectome 2.0 IRB, another MGB IRB, or an external IRB protocol.
- References (1 page, not included in the 2-page limit of the Research Plan)
- Study Team Info (1 page, not included in the 2-page limit of the Research Plan)
- Name the principal investigator(s) and co-investigator(s) and briefly outline their respective unique contributions to their fields (including to the diversity of geographic locations and backgrounds). If relevant, state the previous collaborative experience between the study team including evidence of productivity (shared grants and publications). Up to 2 PIs are allowable per submission.
Project Selection Criteria
Project applications will be reviewed by the Martinos MRI Steering Committee, and scored based on the following four (4) criteria. Each criteria are weighted equally and will be given a score between 1 (best) to 5 (worst). The best scoring projects will be selected for data collection on the Connectome 2.0 3T.
Quality and feasibility of the proposed scientific investigations:
- Is the research strategy outlined logically and does it bear an acceptable level of rigor?
- Are the aims achievable within the project period and with the requested number of scan hours?
- If methods/services are proposed which are not currently available through the U24, does the proposal describe a feasible way to obtain them?
- Does the project stand to significantly benefit from the Connectome 2.0 3T; and have the limitations of existing scanners been demonstrated?
Potential to lead to funded research or public engagement:
- Does the proposed project have potential to lead to additional funded research (e.g through NIH R01 funding, or similar funding mechanisms), to perform experiments on the Connectome 2.0 3T?
- Does the project has preexisting funding, as these submissions will be prioritized?
- Is the project likely to lead to engagement within the field, and also within the wider public sphere?
Geographical/background diversity:
- Would the applying lab and institution increase the geographic range represented and offer diverse perspectives and backgrounds for the U24 project, as laid out in the Plan for Enhancing Diverse Perspectives (PEDP)?
Alignment with BRAIN 2.0 goals:
- Does the proposed project address the Priority Areas in BRAIN ACD WG 2.0, including addressing activity at multiple scales (Area 2), elucidating directional flow (Area 5) and leveraging multiple domains as described in (Area 7)?
Eligibility Criteria
- To maximize the number and geographic diversity of project PIs, U24 funded projects will be limited to 1 year in duration and each PI will be eligible for only one U24 funded project per 2 year period. Investigators from institutions local to the Connectome 2.0 3T will only be eligible to submit applications for scanner access but will need to supply their own funding to pay for scan time.
- Ethical and MR safety: The research must be compatible with the local IRB regulations , and with the IRB regulations local to the researchers. In case of experiments that go beyond the scope of the MGH Connectome 2.0 IRB protocol, the researcher is required to work with U24 project staff to obtain ethical and MR safety approval (e.g, pediatric scanning, emotional or physically distressing stimuli, breathing manipulations, metal in the scanner).
Pulse Sequences: The Connectome 2.0 project has developed a suite of pulse sequences tailored to different types of diffusion encoding for inferring the size, orientation distribution, and multi-scale organization of neurons, glial cells, dendrites, and axons in the complex microenvironment of the human brain. Below, we describe one key sequence in this dMRI suite and the explicit benefits that the new gradient system will bring to bear on these measurements, as well as the microstructural metrics that will benefit from ultra-high Gmax/slew:
- MGH Expert Sequence: To maximize diffusion-encoding options, we use the standard ep2d_diff sequence, which allows user control over diffusion gradient pulse duration (δ), diffusion time (∆), and Gmax, making these parameters visible in the MRI interface. The MGH Expert sequence enables multi-gradient strength and multi-diffusion time measurements in a single scan, improving efficiency and keeping TE constant to control for relaxation time differences. It supports parallel imaging, SMS, dual-polarity GRAPPA for ghost correction, and FLEET-ACS for reduced motion sensitivity in accelerated EPI. This sequence is used for axonal diameter mapping, soma and neurite density imaging, and diffusion tractography, and can be integrated with clinical protocols for disease applications.
Proposals requiring methods not currently offered on the Connectome 2.0 should address how these methods can be incorporated on the scanner.
Peripherals: The scanner is equipped with a Panasonic projector for visual stimulus presentation and a 5 button response box for recording behavioral responses. These peripherals are designed to connect to a laptop via the included adapters for stimulus presentation and response recording.
IRB Protocol: Projects undertaken on the Connectome 2.0 3T should be covered by MGH’s IRB protocol. The IRB covers sensory stimuli (visual and auditory), basic behavioral responses (finger tapping) and simple cognitive tasks, and allows for participants over the age of 18. Experiments beyond this remit (e.g., pediatric populations, specific patient populations, emotional or physically distressing stimuli, breathing manipulations, etc.) will need additional IRB approval. Projects should also be compatible with IRB regulations local to the investigators.
Data Sharing: A Data Use Agreement (DUA) may need to be completed prior to the sharing of data collected on the Connectome 2.0 3T with your home institution.
