Major Equipment:
7 T and 3 T Whole body MR scanners: The 3T and 7T research scanners in the UCSF Surbeck Laboratory for Advanced Imaging and the 3T scanner at the CMFI are available to users on a recharge basis with dedicated support staff to assist them in application development. These scanners include the latest technology from GE with 32 receivers and a high speed/high volume data pipeline, multi-nuclear capability and high performance gradients. The body gradient system has peak strength of 50mT/m and slew rate of 150mT/s2. There are multiple exciters for dual-excitation, decoupling and multi-nuclear editing. The frequency converter allows imaging and spectroscopy with H-1, F-19, P-31, Na-23 and C-13 with decoupling and inverse detection capabilities. The system includes software for automated shimming with second order resistive shim coils.
Highfield NMR/Micro-imaging Instruments: A 14 T Varian wide-bore micro-imaging NMR spectrometer and a 11.7 T HRMAS NMR spectrometer are sited in the UCSF Biomedical NMR Lab adjacent to the Surbeck Laboratory for Advanced Imaging.
500 MHz HR-MAS Spectrometer: The facility contains a 11.7 T (500 Mhz 1H) Varian UNITY/INOVA narrow bore spectrometer equipped with a gHX indirect detection nanoprobe and a H-X pulsed field gradient indirect detection 5mm liquids probe for extract studies and a 10 mm probe for cell and tissue culture bioreactor studies, both of which are capable of 1H and hetero-or multi-nuclear detection (31P,13C,15N, etc.). The gHX nanoprobe combines small sample volume (<40 ml) with magic angle spinning for the study of intact tissues and cells. This probe also has a magic angle gradient that can be used for diffusion-based experiments. The spectrometer is equipped with a variable temperature control device, whereby samples may be routinely run over a wide temperature range from below freezing to room temperature and above.
600 MHz Wide Bore HR-MAS/Micro-imaging Spectrometer: The facility also contains a unique 600 MHz WB Varian NMR system with both HR-MAS and micro-imaging capabilities. In close collaboration with Varian Instruments Inc. (Palo Alto, CA), the imaging spectrometer was custom designed to accommodate the technical requirements of performing 1- and 2-D multinuclear spectroscopic studies of tissues, cultured cell and tissue bioreactor studies and micro-imaging and hyperpolarized spectroscopic imaging studies. Specifically the imaging spectrometer will enable: 1) the acquisition of 1H 2D and multinuclear HR-MAS spectra from small samples (6-10 mg), such as image guided biopsies, in a short enough time to avoid pathologic, metabolic and RNA degradation; 2) the ability to perform ex vivo and in vivo 3D anatomic, perfusion, diffusion MRI and spectroscopic imaging studies of cultured tissues and cells, and transgenic mice; and 3) the ability to utilize novel hyperpolarized 13C labeled substrates and 13C spectroscopic imaging techniques to identify exciting new biomarkers.
Preclinical DNP Polarizers: There are three Oxford Instruments HyperSense DNP polarizers for cell and preclinical studies with one positioned between the 3T and 7T scanners in the Surbeck Laboratory and two purchased through NIH grants sited in the adjoining Biomedical NMR Lab next to the 14T NMR imaging spectrometer and 11.7T NMR spectrometer. There is also a prototype GE SpinLab DNP polarizer positioned between the 3T and 7T scanners in the Surbeck Laboratory that is currently used for preclinical studies.
Patient DNP Polarizer: UCSF is currently the only institution in the world with a clinical DNP polarizer capable and approved for HP 13C MR patient studies. This proof-of-concept patient 13C Dynamic Nuclear Polarizer was developed, constructed, refined and validated by this research team through a state UC Discovery matching grant with GE. It is sited in a small clean room adjacent to a clinical 3T MR scanner equipped with a multi-nuclear spectroscopy package, including an 8 kW broadband amplifier, within the UCSF Surbeck Laboratory for Advanced Imaging. It was developed and has passed FDA IND approval to produce sterile hyperpolarized pyruvate meeting Quality Control (QC) specifications (purity, pH, temperature, polarization, etc) for the recent Phase I patient clinical trial of HP [1-13C]pyruvate. Also a new GE SpinLab prototype polarizer purchased through a NIH S10 grant is also sited between the human MR scanners (does not require a clean-room). While not yet approved for human studies, through this project it will be collaboratively developed with GE for the proposed HP [1-13C]pyruvate human studies and ultimately to facilitate widespread usage of this powerful new molecular imaging technology.
Figure: The five dissolution DNP polarizers at UCSF for hyperpolarized carbon-13 MR molecular imaging are shown. From left to right 1) a commercial Oxford Instruments HyperSense preclinical polarizer adjacent to the 3T & 7T human MR scanners for preclinical studies; 2) a HyperSense DNP instrument in the Biomedical NMR Lab for cell/tissue/mouse preclinical imaging; 3) an Oxford Instruments “test-bed” polarizer for technical development; 4) the “Proof-of-concept” sterile polarizer used in the world’s first Phase 1 clinical trial of hyperpolarized 13C-pyruvate in patients; and 5) the new GE SpinLab prototype purchased through an NIH S10 grant being developed for future patient research studies.