Nallathamby Devasahayam1, Randall H. Pursley2, Thomas J. Pohida2, Shingo Matsumoto3, Keita Saito4, Sankaran Subramanian5, and Murali C. Krishna4
1Radiation Biology Branch, National Cancer Institute, Bethesda, MD, United States, 2Center for Information Technology, Bethesda, MD, United States, 3Graduate School of Information Science and Technology, Sapporo, Japan, 4National Cancer Institute, Bethesda, MD, United States, 5Indian Institute of Technology Madras, Chennai, India
Synopsis
Electron Paramagnetic Resonance (EPR) imaging is suited well for small animal physiological imaging with its unique capability of generating in vivo quantitative oxygen maps. The main bottleneck in scaling up pulsed EPR imaging to human anatomy is that the required RF power of US federal food and drug administration (FDA), specific absorption rate (SAR) limits. In Frank Sequence we are using power levels on the order of 250 microwatts in a crossed coil resonator with ~35 dB isolation. Using a 256 pulse polyphase Frank Sequence, it was possible to obtain images with good SNR.Purpose
Considerable progress is being made in combining
EPR-based quantitative in vivo oximetry in small animal cancer research with
co-registered hyperpolarized MR spectroscopic imaging in our understanding of
tumor physiology and the action cancer drugs (1).
Frank pulse sequence is being developed to reduce the power required to do EPR
animal imaging and as well as the feasibility of scaling up RF EPR imaging of
larger objects.
Methods
The schematic of the low power spectrometer is shown
in Fig. 1. The signal source for the system is a Tektronix 7121B Arbitrary
Waveform Generator (AWG). The maximum
clock rate of 12 GB/s is used to generate the sequences of RF pulses of 300 MHz
with a 50 ns pulse width.
In order to
be able to rapidly pulse the system with low energy pulses and to record
the response in between pulses it is important to have a large isolation (at
least 40 dB) between the transmit coil and the receive coil. A saddle coil of
20 mm diameter and a length of 30 mm is used as the Excitation coil. The
receive coil a surface coil of 10 mm Diameter and is inserted in parallel to
the B1 field of Saddle coil and is shown in Fig. 2a. The surface coil is
inserted through a slit in the Lucite former in the middle of the saddle coil.
Though the surface coil is inserted vertically, it may not be very much
vertical in respect to the point of isolation. To tune the position
of the surface coil to achieve the higher order of isolation a position tuning
mechanism is introduced. The tuning assembly drawing is given in Fig 2b. Since
the surface coil is inside the slit, the position can be changed by tuning the
assembly. By doing tuning, the isolation achieved is 38dB. The total assembly
is shown in Fig. 2C
A Frank sequence, by definition, must contain N2
elements. A length of 256 elements was
chosen for the sequence. The sequences are
generated using a National Instruments LabVIEW software program as an array of
phases. The RF pulses sequences are also generated using LabVIEW. For each phase represented in the Frank sequence (2),
a 300 MHz RF pulse with that phase is generated by LabVIEW and stored. Each RF pulse is 50 ns in width with an
additional 10 ns of zero-padding for a total of 60ns or 720 sampled
points. The LabVIEW program then
constructs
the entire pulse sequence based on the phase designated for each element of the
sequences. The final pulse sequence waveforms
consist of 184,320 total points each.
These are stored in a format that the AWG can import and implement. One of the available AWG digital signals is
used to generate a trigger at the beginning of each pulse sequence.
LabVIEW is also utilized to acquire the EPR signals
from the Signatec PX14400 data acquisition board. The Signatec board is configured to acquire
at a clock rate of 400 MHz and to start acquisition upon receiving a trigger
signal from the AWG. It will then
acquire a complete pulse sequence of 184,320 points. These sequences are
averaged and then passed on to perform band-pass sampling. That extracts the baseband real and imaginary
waveform data resulting in a complex waveform.
This waveform is then broken up into 60 ns segments, each representing a
50 ns RF pulse and the following 10 ns of time until the next pulse. The data is now represented as a 2D array
where each row represents an RF pulse and each column is a coincident time
within each RF pulse. A column of this
data that represents somewhere in the 10 ns zero-padded region is then
correlated with the Frank sequence (3) that the original data was encoded
with. This results in a reconstructed
FID signal and stored as files.
Results
In order to test the feasibility of using low power
Frank pulse sequence for EPR imaging a phantom consisting of a Lucite cylinder
that fits snugly in the receiver coil with four holes of different diameters
filled with TCNQ was imaged. Fig. 3a, Fig. 3b,c
& d, summarizes the results which shows that images with good SNR can be
obtained using a cross coil resonator with >35 dB isolation at power levels
of 0.25 mW. Further progress by way of
designing larger crossed resonators with larger volume will enable extending in
vivo EPR imaging and oximetry to larger subjects
Acknowledgements
We thank Mr. Frank Harrington of Radiation Oncology Branch for making all the mechanical assemblies.References
1. S. Matsumoto et al. Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice, Journal of Clinical Investigation 118, 1965-1973 (2008)
2. B. Blumich B et al. NMR with excitation modulated by Frank sequences, Journal of Magnetic Resonance, 199,18-24 (2009)
3. Mark Tseitlin et al. Use of the Frank sequence in pulsed EPR, Journal of Magnetic Resonance, 209, 306-309 (2011)