The California Institute for Quantitative Biomedical Research (QB3) Is a Partnership Between

FACILITIES

The California Institute for Quantitative Biomedical Research (QB3) is a partnership between UCSF, UC Berkeley and UC Santa Cruz that was established to bring together the powerful quantitative tools of the physical sciences, engineering and mathematics to tackle complex biological problems. The Institute involves more than 100 scientists housed in a new building on the UCSF Mission Bay campus that is part of a public/private biomedical research park, in a new building at UC Berkeley and in two new facilities at UC Santa Cruz. The QB3 building at Mission Bay has roughly 96,000 sq. ft. of space on five floors designed to house multi-department and multi-disciplinary laboratories, lecture halls, and shared scientific resources.

Surbeck Laboratory for Advanced Imaging: QB3 houses the Surbeck Laboratory for Advanced Imaging which includes a 7T GE whole body scanner and a 3T research scanner, microscopy, computational and other facilities. The only current clinical 13C Dynamic Nuclear Polarizer in the world is installed in a clean room directly adjacent to the 3T scan room to permit human investigations of this new technology. A second, commercial DNP polarizer (Oxford Instrument’s HyperSense) is sited between the 3T and 7T MR scanners to allow development and animal studies on both scanners. A new GE SpinLab prototype polarizer (funded by NIH Shared Equipment grant S10RR029570) is also sited between the human MR scanners and is used currently for preclinical animal studies and is being developed for future human single-agent HP 13C-pyruvate studies. There is also an electronics shop, a machine shop and a server room that is dedicated to meet the heavy computational needs of the research programs in the building. There is also a three-room suite for animal management and housing that will be used for the rodent studies in this project. The Surbeck Laboratory also has facilities for managing human subjects including offices, a changing room, preparation room, and restroom.

UCSF Biomedical NMR Laboratory: The Biomedical NMR Lab on the Mission Bay Campus at UCSF occupies 1660 sq. ft. and currently houses a high field multi-nuclear 500 MHz HR-MAS NMR spectrometer and 600 MHz multinuclear micro-imaging spectrometer that are uniquely integrated with two Oxford Instruments DNP polarizers, one HyperSenseTM commercial instrument funded through NIH equipment grant S10RR024587 and a “test-bed” instrument purchased through NIH P41EB013598. A large number of high- field spectrometers (400 MHz, 2 500 MHz, 2 600 MHz and a 800 MHz) with multi-nuclear capabilities and sensitive cryo-probes are also available within the UCSF NMR lab. Both magnets are dedicated to running biomedical samples with complimentary features, including high-resolution magic angle spinning (HR-MAS) spectroscopy, and micro-imaging capabilities that allow for NMR studies of biopsy and surgical tissues, cell and tissue cultures and murine models of cancer. By placing the HyperSenseTM polarizer between two high field NMR spectrometers we can take advantage of the unique features of each of the magnets.

Tissue Culture and chemistry facilities: This 527 sq. ft laboratory space for tissue culture facility is equipped with two Class II biosafety hoods, two 5% CO2 incubators, a refrigerated 1000 mL centrifuge, a microcentrifuge, two refrigerators, microwave, water bath dry incubator/oven, balance, and a Nikon Eclipse TS100 inspection microscope. The facility also includes cryostats, microtomes, and other tissue sectioning apparatus, as well as all of the equipment necessary to extract and amplify RNA for micro-array studies, and to perform enzyme content and activity studies. The adjacent laboratory spaces permit access to a wide variety of cell and tissue analytical devices while minimizing traffic within the “clean” laboratory space containing the tissue culture hood and incubators. All users of the Tissue Culture and Biomedical NMR laboratories attend mandatory bi-monthly meetings to review issues of safety, sterile lab practices, and equipment usage. There is also 485 sq. ft laboratory space for chemical work equipped with a chemical hood and all of the equipment necessary to develop and test new hyperpolarized MR probes.

NMR compatible bioreactor fabrication facilities: The Biomedical NMR lab houses a 128 sq. ft laboratory space with all of the necessary equipment (computer workstation with solid works software, 3D printer, micro-lathes) to engineer and manufacture NMR compatible cell and tissue culture bioreactors. By combining a bioartificial support system with a noninvasive method for monitoring metabolism, NMR-compatible bioreactors and DNP have become a new and innovative way of studying real time metabolic dynamics.

Office:

Key personnel involved in this project have office space available within QB3. Full office support with dedicated research associates and an academic assistant is also available. Office space includes a combination of private offices (primarily for faculty members); shared offices for senior staff members; and, cubicles for post- graduate fellows, graduate students and other administrative and support staff.

Clinical:

The UCSF Department of Radiology and Biomedical Imaging is a fully equipped teaching, research, and clinical department, including 75 faculty, 40,000 sq. ft of space, performing 120,000 examinations annually. There are 11 MR scanners, including three dedicated to full-time basic and clinical/research studies. All clinical MR systems are kept state-of-the-art with phased-array and spectroscopy capability to meet the department’s goal of rapid translational MR research. Techniques and protocols developed on the dedicated research scanner can rapidly and easily be installed on the clinical scanners and applied to clinical practice. This has occurred in many cases including spectroscopic imaging, echo-planar imaging, high-resolution imaging, image post-processing (reception profile corrections, serial alignments, multimodality registrations), and diffusion and perfusion MRI (both acquisition and analysis). The Ambulatory Care Center houses the Department of Radiology and Biomedical Imaging x-ray facilities as well as a Hologic Bone Densitometry unit. 11,000 square feet of clinical space with examination rooms, clinical scanners are available for patient examinations, clinical assessments and other studies. The Nuclear Medicine Program is part of the UCSF Department of Radiology and Biomedical Imaging at Moffitt-Long Hospital and has 2 ADAC Forte SPECT systems, 1 ADAC Vertex SPECT systems, a GE Discovery VH with x-ray CT and coincidence imaging capabilities, a Siemens Exact HR+ PET System, associated computers for image reconstruction, display, analysis, and interpretation, and an in vitro laboratory with a well-counter and radiopharmacy.

Within the Department of Radiology and Biomedical Imaging, there are eight full-time faculty members of the Interventional Radiology division. All interventional radiologists are board-certified radiologists with advanced training in image-guided procedures and subspecialty certification from the American Board of Radiology in Vascular and Interventional Radiology. UCSF Interventional Radiology has an extensive history of successful collaboration with clinical researchers and members of the Comprehensive Cancer Center in the performance of CT-guided tumor biopsies as part of standard care and for research purposes.

The UCSF Helen Diller Family Comprehensive Cancer Center

The NCI-designated UCSF Comprehensive Cancer Center encompasses an extensive matrix of laboratory, clinical and population research, and clinical care facilities within the San Francisco metropolitan area. UCSF's four medical centers are UCSF Medical Center (Moffitt-Long Hospitals) on Parnassus Heights, UCSF Mount Zion Medical Center (operating under the license of Moffitt-Long Hospital) on Divisadero Street, San Francisco General Hospital (SFGH) on Potrero Avenue, and the San Francisco Veteran Affairs Medical Center (VAMC) on Clement Street. The two latter sites are affiliate institutions; UCSF provides faculty and house staff for the SFGH and the VAMC, which are operated by the City and County of San Francisco and the U.S. Department of Veterans Affairs, respectively. Recently, a major new campus has been developed, at Mission Bay. A major new facility for cancer research, the Helen Diller Family Cancer Research Building is under construction and on schedule to open in fall 2014. Free shuttles run between the major sites at 15-minute intervals.

The UCSF Comprehensive Cancer Center has leading interdisciplinary clinical care programs in all areas of oncology, as well as leading clinical, basic, and translational research programs. The center has a large tissue bank available for studies of archival material by center investigators. The Mt Zion campus has become the major site for cancer-related research and clinical care, and is the Cancer Center’s administrative home. This campus includes the 50,000 sq ft Cancer Research Building and the 65,000 sq ft Cancer Center Clinical Building. The Clinical Building completed in 2000, is home to the Early Phase Clinical Trials Unit, radiation oncology, breast care (including reconstruction and diagnostic mammography), infusion, melanoma, thoracic oncology, gynecological oncology, genitourinary oncology, gastrointestinal oncology, endocrine oncology, and orthopedic oncology. All outpatient solid tumor oncology care, visits, and treatments are administered at this center. Most of the solid tumor oncology therapeutic clinical trials are conducted at this center. The center includes a chemotherapy infusion center and pharmacy, which are actively involved in institutional, industrial, and cooperative group clinical trials. The center also includes a tissue core which collects and stores frozen or fixed tissue specimens for correlative studies being conducted on clinical trials. All clinical trial activities at the Cancer Center are overseen by the Committee on Human Research (the UCSF IRB), the Protocol Review Committee, and the individual program committees. The Cancer Center Data Safety Monitoring Committee oversees all investigator-initiated phase I clinical studies. Animal research studies are overseen by an IACUC.

The UCSF Early Phase Clinical Trials Unit is located on the Mount Zion campus and was created in 2009 in order to create a centralized resource for the treatment of patients on phase I trials. The Early Phase Clinical Trials Unit is an integral component of the Development Therapeutics Program within the UCSF Comprehensive Cancer Center. Patient enrollment has been robust, and the breadth of the study portfolio is expanding. During the three year period from 2009 through December 31st, 2012, 542 patients were enrolled onto phase 1 clinical trials within the Early Phase Clinical Trials unit at UCSF, including 77 and 45 patients of Asian and Hispanic/Latino ethnicity respectively. Many patients enrolled onto clinical trials within the Early Phase Clinical Trials unit undergo paired tumor biopsies and correlative imaging performed for research purposes. The Early Phase Clinical Trials Unit has a history of successful collaboration with the Department of Radiology and Biomedical Imaging and Interventional Radiology in the conduct of correlative imaging and tumor biopsy procedures for patients enrolled onto phase 1 clinical trials.

The Early Phase Clinical Trials Program Site Committee meets every week, and a large group of the investigators join the meeting regularly. Discussions range from basic science topics to clinical trials’ proceedings. Adverse events and safety data for all patients enrolled onto phase 1 trials are reviewed at each weekly site committee meeting. The Site Committee monitors all clinical trials and the group discusses all clinical trial proposals and concepts with the members to optimize opportunities for correlative studies and parallel bench work.

Within the Early Phase Clinical Trials Unit, clinic space consists of eleven patient exam rooms, which also serve as private rooms for administration of chemotherapy infusions for specific use by patients enrolled onto a phase 1 clinical trial. The Unit also contains a patient waiting room, a conference room to review study protocols and other documentation during the conduct of a clinical trial, a medication room for the dispensation of study medication which is closely linked with the Investigational Pharmacy unit, as well as a central administrative space for physician charting and clinic staff. Dedicated nursing, pharmacy, and clinical research coordinators are integral members of the Early Phase unit, assisting in the conduct of clinical research activities and participating in the weekly site committee meetings.

Animal:

UCSF has two facilities one on the main campus at Parnassus and a second one at the Mission Bay campus. These are state-of-the-art facilities overseen by veterinarians and approval is managed by IACUC. The Animal Care Facility has full-time veterinary staff that is on-site to monitor the animals 24 hours a day. There are animal holding facilities and animal preparation rooms at both QB3 and the CMFI, which will be used in this project.

Computer:

The Department of Radiology and Biomedical Imaging has a research computing facility that provides a core infrastructure for networking and systems administration. The staff that supported by this facility manage G4 and Mac laptops for research and investigators running OSX for data storage and generation of reports, and a number of Linux workstations for processing images and spectroscopic data acquired on the MRI scanners. All of the computer workstations and servers have the necessary software tools to perform research data management. The China Basin, QB3 and other research facilities have high speed land/wireless data networks, automatic tape back-up and archival, CD, DVD, RAID, optical disk juke boxes. The MR scanners are linked to the remote workstations, and in addition are connected to GE “Advantage Windows” workstations and an Agfa PACS system. Departmental PACS services include high resolution monitor workstations for film reading, archival facilities, and image retrieval functionality.

Other:

The MR Electronics Laboratory in the UCSF Surbeck Laboratory for Advanced Imaging at QB3 comprises over 400 sq. ft. of floor space with utility sink, counters and storage cabinets along with: a Hewlett Packard 8751A two port network analyzer with s-parameter test set for tuning and troubleshooting new MR detectors; an Agilent E5070B four port (expandable) network analyzer for tuning, troubleshooting and characterizing new single and phased array MR detectors; an Agilent 33250A function/arbitrary waveform generator for MR detector validation; an Agilent E3631A DC power supply for circuitry construction and validation; a Hewlett Packard 6234A power supply for evaluating diode functionality; an Agilent 34401A digital multimeter for testing and troubleshooting circuits; a Pace HW200 soldering stations for precise soldering temperature selection and quicker prototyping; an Olympus 8.0 Mega pixel digital camera for documentation of construction procedures and completed MR detectors; a noise meter for assessment of individual coil and phased array SNR; a high speed bench circuit board prototype milling machine for fabricating new MR circuit designs; and a PC server to expedite information transfer.

The Fabrication/Machine Shop Facility at QB3 comprises 500 sq. ft. of floor space with utility sink, counter and storage cabinets and includes: a Bridgeport 3-axis CNC milling machine for milling necessary detector circuits and housings; a Bridgeport CNC lathe for turning detector housings; a Wilton 20” electronic variable-speed floor-standing drill press for drilling and tapping large housings; a Dayton 17” Bench Drill Press for drilling and tapping smaller housings; a Wilton combination 6” belt/12” disc sander for forming detector housings; a Wilton vertical 20” variable speed bandsaw for material constructions; a Baldor pedestal grinder for tooling construction and maintenance; a TIG welder for machine maintenance; a cross-slide rotary milling table for milling complex bends in housings; Imprex non-magnetic tools for magnet maintenance; and assorted hand- held housing construction tools.