Department: Physics and Astronomy
We develop new approaches and methodologies for Magnetic Resonance Imaging (MRI) and Nuclear Magnetic Resonance (NMR) spectroscopy to study biological systems, with an emphasis on non-linear magnetic resonance and hyperpolarized gas imaging.
Investigation of non-linear spin dynamics from dipolar-dipolar field interactions
At high magnetic fields, non-linear NMR effects contribute significantly to the detected signal from highly polarized samples (such as humans at normal clinical field strength, which consist of more than 70% water). These effects are observed as high-order spin echoes, seen as additional peaks in NMR spectra. Theoretically, these effects can be explained classically by the action of the Distant Dipolar Field (DDF) or, quantum mechanically, by intermolecular multiple-quantum coherences (iMQC). These coherences have special properties, such as insensitivity to local magnetic field inhomogeneities and high sensitivity to tissue structure that enable new applications in NMR spectroscopy and imaging.
We exploit this sensitivity to structure to detect the structure and activity of Brown Adipose Tissue (BAT), a tissue whose malfunction has recently been linked to the development of obesity in humans. The sensitivity of iMQC to cellular structure allows us to specifically detect this tissue with unprecedented sensitivity and specificity.
Figure 1: In vivo BAT and WAT (White Adipose Tissue) detection on a mouse showing different BAT (yellow) and WAT (red) distribution patterns. These data were recently presented at the 52st ENC conference as well as at the recent water-fat ISMRM workshop.
We also use the sensitivity of this signal to map microscopic susceptibility and to explore its insensitivity to macroscopic inhomogeneities to detect tissue activity with better sensitivity and specificity than conventional BOLD (blood oxygen level dependent) based methods. Local susceptibility changes, used to detect increased tissue metabolism, are often offset by macroscopic susceptibility changes related to motion. The iZQC signal removes these global magnetic field inhomogeneities while retaining those that are present at a smaller length scale, which contain information specific to tissue metabolism.
Hyperpolarized gas MRI
In the field of hyperpolarized gas we have recently developed a new approach that enables molecular MR lung imaging. By using magnetic nanoprobes in combination with hyperpolarized gas MRI, we can easily target and detect cancer cells in the lungs with unprecedented sensitivity and specificity. Smart magnetic nanoprobes are used to specifically target cancer cells in the lungs, while the magnetic field perturbation caused by these nanoprobes is used to enhance sensitivity (Figure 2)
Figure 2: 3D and 2D hyperpolarized helium gas images of a mouse lung. The highlighted area represents signal loss caused by the accumulation of magnetic nanoprobes in a nearby lymph node. The signal loss, with ~ 3mm diameter, extends well behyond the actual size of the lymph node, which is about 300 microns in diameter. Figures from Branca et al, PNAS 2010.
We use 3D Monte Carlo simulations of gas diffusion across the complex magnetic field gradients of the lung airspaces to estimate the ultimate sensitivity of this modality for the detection of cancer cells. Figure 3 shows the strong magnetic field gradient generated in the lung tissue by susceptibility mismatch between tissue and air that causes signal decay, computed using a Fourier based method commonly used to compute spin dynamics in presence of dipolar field interactions. This work, currently funded by NCI, is done in collaboration with Duke University .
Figure 3: H&E staining of a mouse lung tissue. b) Magnetic field map generated by tissue-air susceptibility mismatches.
Our research with hyperpolarized gas has recently moved beyond lung imaging. We exploit the high solubility of 129Xe gas in biological tissue and its sensitivity to the local chemical environment to obtain structural and functional information of fatty tissues that can not be obtained with conventional proton-based MRI methods.
A. Khanna, R.T. Branca, “Detecting brown adipose tissue activity with BOLD MRI in mice”, Magn. Reson. in Medicine, published online (2012). PMID: 22231619 R.T. Branca, “MRI using intermolecular multiple-quantum coherences”, Methods Mol Biol. 771:241-52 (2011). PMID: 21874482
R.T. Branca, W.S. Warren, "In vivo brown adipose tissue detection and characterization using water-lipid intermolecular zero-quantum coherences", Magn Reson Med, 65 (2), 313-9 (2011). PMID: 20939093
R.T. Branca, W.S. Warren, "In vivo NMR detection of diet induced changes in adipose tissue composition", J Lipid Res, 52 (4), 833-9 (2011). PMID: 21270099 R.T. Branca, E.R. Jenista, W.S. Warren, "Inhomogeneity-free heteronuclear iMQC", J Magn Reson, 209 (2), 347-51 (2011). PMID: 21316278
E.R. Jenista, R.T. Branca, W.S. Warren, "Absolute temperature imaging using intermolecular multiple quantum MRI", Int J Hyperthermia, 26 (7), 725-34 (2010) PMID: 20849265
E.R. Jenista, G. Galiana, R.T. Branca, P.S. Yarmolenko, A.M. Stokes, M. W. Dewhirst, W.S. Warren, “Application of mixed spin iMQCs for temperature and chemical-selective imaging”, J. Magn. Reson. 204 (2), 208-18 (2010). PMID: 20303808
E.R. Jenista, A.M. Stokes, R.T. Branca, W.S. Warren, “Optimized, unequal pulse spacing in multiple echo sequences improves refocusing in magnetic resonance”, J. Chem. Phys.131(20):204510 (2009). PMID: 19947697
R.T. Branca, Z.I. Cleveland, B. Fubara, C. Kumar, C. Leuschner, R.R. Maronpot, W.S. Warren, B. Driehuys, “Molecular MRI for sensitive and specific detection of lung metastases”, PNAS 107(8):3693-7. PMID: 20142483
W.S. Warren, E.R. Jenista, R.T. Branca, “Increasing hyperpolarized spin lifetimes through true singlet eigenstates”, Science 323(5922), 1711-1714 (2009). PMID: 19325112
R.T. Branca, W. S. Warren, “Solvent suppression without crosspeak attenuation in iZQC experiments”, Chem. Phys. Lett., 470(4-6), 325-331 (2009).
R.T. Branca, Y. M. Chen, V. Mouraviev, G. Galiana, E. Jenista, C. Kumar, C. Leuschner, W. S. Warren, “iDQC anisotropy map imaging for tumor tissue characterization in vivo”, Magn. Reson. in Med. 61(4), 937 - 943 (2009). PMID: 19215050