Preclinical MR Imaging and Spectroscopy Lab

Applications: high-field MR imaging and spectroscopy in mice, hyperpolarized ¹³C in vivo studies

The 14.1 Tesla Agilent wide-bore micro-imaging NMR spectrometer is equipped with 100mT/m gradients. It has excellent cardiac and respiratory gating performance and has demonstrated the ability to obtain high-resolution ¹H and hyperpolarized ¹³C MRSI data in mice, in multiple organs (brain, prostate, liver, etc...).  In close collaboration with Agilent 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 cells and tissue bioreactor studies, and micro-imaging and hyperpolarized spectroscopic imaging studies. Specifically, the imaging spectrometer enables: 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 mouse models; and 3) the ability to utilize novel hyperpolarized ¹³C labeled substrates and ¹³C spectroscopic imaging techniques to identify exciting new biomarkers. Furthermore, an isoflurane-based inhalant anesthesia system is located next to the system for preclinical studies. Thermal support for animals during preparation and imaging is provided by a combination of heat lamps and heated thermal water pads (with deuterated or Mn-doped water during imaging), and temperature-regulated hot air fans according to individual project needs. A kit (SA Instruments, Inc.) allowing rectal thermometry, ECG probes/amplifier with TTL trigger for external gating, and respiratory pick-up is also available for continuous monitoring of the animal's physiological parameters.

Applications: MR imaging and spectroscopy in mice and rats, hyperpolarized ¹³C in vivo studies in mice and rats

Especially designed for study of mice and rats with a magnet bore of 180mm, the BioSpec 3T comprises the latest Bruker MRI technology, Paravision software application packages and multimodal options at the translational field of 3 Tesla. The magnet hardware is the best in its class, with two channels (¹H and broadband) and a gradient strength of 960 mT/m, guaranteeing optimal performance for MR spectroscopy and MRI. A wide range of ¹H and ¹³C RF coils for mice and rats are available, including coils for head, brain, cardiac and body, enabling to easily perform hyperpolarized studies. Thanks to its lower field strength, the 3T BioSpec system is an ideal platform to 1) develop novel hyperpolarized ¹³C labeled substrates whose lifetime (T1) would benefit from lower field, and 2) optimize ¹³C spectroscopic imaging techniques for specific detection of new biomarkers. Both probes and sequences can then be readily translated to the clinical setting on 3T human scanners. An isoflurane anesthesia system is located next to the system for all preclinical studies. Animal body temperature is maintained during all MR acquisitions. A dedicated monitoring system (SA Instruments, Inc.) is also used during all experiments to monitor animal well-being and ensure experimental reproducibility.

Applications: HR-MAS of tissue samples/biopsies, high-resolution MRS, MRS and hyperpolarized ¹³C bioreactors studies

The Preclinical MR Imaging and Spectroscopy Lab also has an 11.7 Tesla Agilent narrow bore NMR spectrometer. Over the last decade this system has been optimized for 1) hyperpolarized ¹³C spectroscopic imaging studies of cultured tissues and cells as well as 2) 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.

Applications: MRS and hyperpolarized ¹³C bioreactor studies

The 1.5T Pulsar spectrometer is a low footprint benchtop spectrometer which can be easily moved on a cart. The spectrometer is equipped to detect protons as well as carbon and is used primarily for hyperpolarized studies using ¹³C labelled tracers in bioreactors. The low field is beneficial for hyperpolarized studies because of the substantial increase of the T1’s of the ¹³C labelled probes at low field.

• Hypersense^TM polarizer (Oxford Instruments) (Applications: hyperpolarized ¹³C in vivo and bioreactor studies)
• Test bed polarizer (Oxford Instruments) (Applications: hyperpolarized ¹³C in vivo and bioreactor studies)

There are two Oxford Instruments HyperSense DNP polarizers for cells and preclinical studies situated in the Preclinical MR Imaging and Spectroscopy Lab. The Test bed polarizer is located next to the 14.1T NMR imaging spectrometer and the 1.5T Pulsar system. The Hypersense polarizer is located next to the 3T Bruker imaging sytem and the 11.7T narrow bore spectrometer. This layout was optimized to enable hyperpolarized ¹³C studies on all MR systems with high sensitivity and minimal polarization loss.