NCC Outreach

Intro

The CMRR in partnership with Mayo Clinical College of Medicine has been awarded a five year $7.9M Neuroscience Blueprint Interdisciplinary Center Core Grant by NIH to establish a Neuroscience Core Center (NCC). See the "umn news" article: . The mind's eye: New grant opens neuroscience imaging opportunities

The NCC will provide infrastructure support in order to advance the Blueprint institutes' missions to further the understanding of the functions and disorders of the nervous system. The goal of providing this support is to assure a greater productivity than would be possible from the separate projects alone. NCC support provided to a project can not be a duplication of any already NIH funded resources, but rather is to be used to expand and enhance the project's neuroscience research.

The NCC (Neuroscience Core Center) consists of the following 5 cores areas of support

Magnets

Currently the CMRR houses six MR systems and although the NCC does not provide funding for magnet time, the CMRR will provide some projects with a limited amount of unfunded time as availability allows.

Application Process

New project requests will be reviewed and access to NCC resources approved based on the Steering Committee guidelines. All allocated resources will be for a specified quantity and duration to allow the annual review of productivity. In addition, there will be a systematic review of all active projects to examine the amount of NCC resources being used. The NCC Resources will be allocated using a application and review process (Note support is subject to annual review). Investigators interested in using NCC resources will provide a brief application describing the scientific question being pursued, the techniques to be used and the NCC resources being requested. An on-line applications is available on the CMRR website. It is highly encouraged for investigators to contact the appropriate Core Directors and consultants to discuss their project prior to submitting an application. For protocols requesting support from the Core, the following assessments will be made by the Operations Committee, based on guidelines by the Steering Committee: Following this review, the Operations Committee will make a decision on whether the project will be supported. If the project will be supported, it will then determine the quantity and duration of resources that will be provided by the Cores. This general outline will be followed for all cores. However, core specific modifications if present are addressed in the specific CORE descriptions. An explicit expectation of this RFA is to provide access to PIs who do not hold qualifying grants . We see this as an opportunity to expand the user group by including investigators who may not currently hold NIH funding or investigators who have NIH funding from Institutes not part of the Blueprint. These projects will be considered for support using the above review project, with the general goal that ultimately they will impact neuroscientific discovery. If the demand on the Neuroscience COREs Center exceed its capabilities, however, priority will be given to qualifying Blueprint institute funded projects.

Controlled Substances

Please note that the US DEA (Drug Enforcement Agency) requires that all controlled substances used at our location be purchased by us under our DEA license. Please consult with our staff when planning a project using controlled substances. If your project require the use of a controlled substances see the controlled substance coordination web page for details.

Database Access

A University of Minnesota Internet id (aka X.500) is required to access the NCC on-line database for resource scheduling. Team members can register for a guest X.500 id at: guestportal

Protocol

When using a protocol approved by an outside institution, please refer to the crossinstitutional protocol approval instructions: protocols

Training

See Safety Training Guidelines for training mandates and descriptions.

CORE I: RESEARCH SUBJECTS CORE

(PI: Kelvin Lim) The Research Subject Core is an infrastructural support service whose overall objective is to provide Regulatory and Experiment support to Investigators using the Neuroscience Core Center (NCC) resources. Recognizing the translational nature of research, we have combined support for both human and animal research subjects into this Research Subject Core. Regulatory Support is conceptualized as providing direct support to the Investigator in successfully navigating the increasingly complex web of national, local and institutional requirements for carrying out research. Experiment Support is conceptualized as providing direct subject-related services necessary for carrying out experiments. Our Aims are the following:
  1. Regulatory Support - To provide to NCC investigators, the administrative support necessary to obtain and maintain regulatory approval for their research. (e.g., assistance with IRB, IACUC, DEA)
  2. Experiment Support To provide to NCC investigators, the subject support services needed to carry out their NCC related work. (e.g. installation of IV lines in animals and humans, animal surgery, installation of subject into magnet, training of subjects in mock scanner, monitoring of animal anesthesia). The proposed Experiment Support services do not overlap with those services provided by the Data Acquisition Core, as the latter provides direct support for operation of the scanner and preprocessing of collected data.

CORE II: DATA_ACQUISITION_CORE

(PI: Pierre-Francois Van De Moortele) Today is a time of great excitement for neuroscientists and MR physicists as spectacular advances have been made in their fields over the recent years. Specifically, very high magnetic fields along with sophisticated MR data acquisition techniques have opened new doors to non-invasive studies of brain structure and function at very high spatial resolution, as well as to detailed investigations of brain metabolism through measurements of numerous neurochemicals from small brain regions. At the same time, significant advances in our knowledge on brain metabolism and function have yielded new models and hypotheses that precisely require access to more detailed neurochemistry measurements and to highly localized structural and functional investigations of brain tissue. However, acquiring data at very high magnetic fields requires very specific and innovative tools, hardware developments, processing techniques and highly specialized expertise. Thus, without a support structure providing access to the most advanced data acquisition techniques, it is difficult for many neuroscientists to reach excellence in both cutting edge neuroscience and state-of-the-art MR technology at high magnetic fields. The lack of access to cutting-edge technology can slow down and/or limit the scope of neuroscience research in areas where high magnetic field MR scanners are strongly beneficial. Therefore, significantneed to make the use of such powerful technology seamless to neuroscientists and facilitate highly ambitious brain research. Our long term goal and motivation is to make basic and clinical neuroscience research benefit from most advanced MR data acquisition techniques in order to enable investigations which are out of reach with more conventional modalities, and to improve research efficiency in ongoing studies. The objective of the Data Acquisition CORE is to organize and promote shared infrastructure in the CMRR which will significantly improve and facilitate access for a larger community of neuroscientists to state-ofthe- art, high magnetic field MR data acquisition. The CMRR is remarkably well prepared to achieve this objective. Indeed, the center is well renowned for its pioneering role in demonstrating the benefits of higher magnetic field in animals and humans. Energized with the very strong expertise of its faculty and research members, the center develops a constant stream of MR sequences, preprocessing techniques and RF coils that specifically address obstacles and artifacts brought about by higher magnetic fields. With four human (3T, 4T, 7T, 9.4T) and two animal (4.7T, 9.4T) MR scanners, the CMRR has the capability to support a large array of neuroscience research. The specific aims of the data acquisition core are:
  1. To provide neuroscience researchers assistance, service and training for advanced data acquisition and pre-processing techniques in human and animal, MRI and MRS brain studies at high magnetic field.
  2. To implement MR sequences, transfer acquisition methods between different MR scanners, and perform quality control in order to uphold state-of-the-art high magnetic field data acquisition performance.
  3. To build and maintain high performance RF coils in order to enable routine MR acquisitions at 4T, 4.7T, 7T and 9.4T.

CORE III: DATA_ANALYSIS_and_VISUALIZATION_CORE

(PI: Cliff Jack) This Core is organized across two physical sites and two institutions the CMRR in Minneapolis, MN, and the Mayo Clinic in Rochester MN. The two institutions are roughly 90 miles apart, easily accessible to each other by car. This organizational structure for this Core was conceived on the basis of an ongoing successful collaboration between investigators at CMRR and Mayo, which has been in place for several years in the area of high resolution MRI and MRS of transgenic Alzheimer s mice. The proven track record of successful inter-institutional research collaboration as well as the synergistic skills brought together by the groups at CMRR and Mayo justifies the formation of a dual site Core. Functionality of this Core is conceptually divided into three categories: Magnetic Resonance Imagining (MRI) which includes the modalities structural MRI, diffusion tensor imaging (DTI), and arterial spin labeling (ASL); functional MRI (fMRI); and MR spectroscopy (MRS). The sometimes unique needs of each of these three modalities will be served through shared equipment and personnel in the Core. Additionally, when in place the Core could be leveraged to help support multi-modality image analysis. The description of Core functionality is organized in the temporal sequence MR data would naturally flow. The Core functionality will be brought to bear beginning at the point at which the MRI data leaves the scanner on which it has been acquired, and ending with production of data visualization appropriate for scientific publication and/or image data quantitation appropriate for conventional biostatistical analyses. 1. The Core Aims are
  1. To Facilitate Secure Data Transmission
  2. To provide secure Data Archival and backup functionality
  3. To provide Data Preprocessing functionality in order to correct data artifacts
  4. To provide Image Analysis and visualization functionality
  5. To provide Spectra Processing and Metabolite Quantification using LCModel analysis

CORE IV: MULTIMODALITY CORE

(PI: Geoff Ghose) Because of our expertise in high field MR, the CMRR offers experimental resources that are uniquely suited to pursue high-resolution in-vivo studies on spatial scales that have been demonstrated by classic neuroscience methods to be relevant for the understanding of brain function and disease. The aim of this core is to serve and further develop research efforts by the broad neuroscience community here at the University of Minnesota and elsewhere by offering multimodal capabilities and associated support in which traditional neuroscience methodologies can be readily combined with the MR research capabilities of the CMRR. This Core aims to support both human and animal model studies. The specific aims of this core are
  1. Provide experimental resources capable of generating data that are complementary to, but not currently available, with current MR techniques. Although MR techniques offer enormous potential for non-invasive in-vivo measurements, the interpretation of the measurements can be greatly enhanced when combined with classical neuroscience techniques. For example, although MR is particularly well suited for population level studies of neuronal chemistry or activity, its temporal resolution is often limited by sampling rate or hemodynamic factors. By combining high temporal resolution, but localized measurements, such as provided by oxygen or extracellular electrodes, with more global MR measurements, a more complete picture of brain metabolism and function is possible.
  2. Provide methods for the validation of novel high-field MR applications. Projects in the CMRR have pioneered the use of high field and contrast agents to study brain activation and anatomy at the sub-millimeter scale. Validation of these methods requires the application of well established invasive methods such as anatomical reconstruction or electrophysiological recordings.
  3. Develop longitudinal same-subject protocols suitable for studying the correlations between MR techniques and classical methodologies, and the circumstances under which those correlations change. Such studies are imperative for both understanding the underlying physiological bases of MR signals, as well as the development of diagnostic MR techniques for clinical applications.

CORE V: CHEMISTRY_CORE

(PI: Joe Poduslo) The Chemistry Core laboratory will be located on the 15th floor of the Guggenheim Building at the Mayo Clinic College of Medicine. Although this facility is located in Rochester, Minnesota, it is closely coupled to the CMRR by a successful ongoing collaboration in the area of high resolution MRI and MRS of transgenic Alzheimer s mice (3,179,180). The laboratory director and principle collaborator from Mayo, Dr. Poduslo, currently spends at least one day per week at the CMRR interacting with researchers and conducting experiments. He will be responsible for directing this Peptide synthesis and mass spectrometry will be performed utilizing the Proteomics Core facilities at Mayo. Diamine inserts will be synthesized in this Chemistry Core and incorporated into synthesized protein as a means to increase BBB permeability. These novel agents will be utilized by funded and future projects that will require contrast-enhanced MRI to visualize, characterize, and monitor disease progression in various neurodegenerative disease models. Monoclonal antibodies against human A AB42 already been prepared and isolated. Monoclonal antibodies to other nervous system antigens will also be developed to support and enhance expanding MRI research using animal models of neurodegenerative diseases. The IgG fragmentation and subsequent modification with polyamines and chelating agents will be done in the Poduslo laboratory with the appropriate purification steps. All other techniques and procedures will be performed in the Poduslo laboratory. Dr. Poduslo will oversee the work of two core employees: Ramakrishnan Muthu, Ph.D., Chemist, and Geoffry Curran, B.S., Senior Technician. Dr. Muthu has developed the technology in the Poduslo laboratory to fragment IgG into Fab and F(ab2)2 derivatives. He has developed appropriate purification steps that result in high-yield production of F(ab2)2 of high purity. He has developed the technology to chelate DOTA to the F(ab2)2 and has assayed the chelation of radioactive 153Gd to this antibody derivative. He has also established an ELISA to verify the antigen binding capacity of this derivatized F(ab2)2. Using the ELISA he has determined the optimum pH for modification with polyamines by the carbodiimide reaction. Mr. Curran will be responsible for the peptide synthesis and assessment of BBB permeability and SDS-PAGE and IEF gel analysis. He will perform all radiolabeling procedures that are used to evaluate the BBB permeability, in vitro binding, and in vivo targeting of the contrast agents.
  1. To develop peptide-based contrast agents with high blood-brain barrier (BBB) permeability and selective targeting to molecules/structures in the brain after i.v. administration
  2. To develop antibody-based contrast agents with high BBB permeability and selective targeting to antigens/structures in the brain after i.v. administration
  3. To provide a source of MRI contrast agents which includes: Gd-DTPA-, Gd-DOTA-, PARACEST using other lanthanide elements-; and 19F-Tyrosine-peptide-based and antibody-based agents