Water Exchange & Binding
Monday 20 April 2009
Room 313BC 16:30-18:30


R. Mark Henkelman and Bruce Pike

16:30  180. Young Investigator Award Finalist: MRI Contrast from Relaxation Along a Fictitious Field (RAFF)
    Timo Liimatainen1, Dennis Sorce1, Michael Garwood1, Shalom Michaeli1
Center for Magnetic Resonance Research, Dept. of Radiology, University of Minnesota, Minneapolis, MN, USA
    A method is described to create MRI contrast using rapid amplitude and frequency modulated RF irradiation in a sub-adiabatic condition, referred to relaxation along a fictitious field (RAFF). Bloch simulation of RAFF shows that magnetization follows a fictitious field when magnetization is oriented initially along the fictitious field. Theoretical calculations show sensitivity of RAFF to slow molecular motions with similar sensitivity as the continuous wave spin-locking experiment. The data obtained from human brain shows images with significant contribution of steady state which can be accounted for in the analysis.
16:50 181.

Balanced SSFP Profile Asymmetries Detect Small Frequency Shifts in White Matter

    Karla L. Miller1, Peter Jezzard1
FMRIB Centre, Oxford University, Oxford, Oxon, UK
    We study a novel contrast mechanism based on the frequency dependence of the balanced SSFP signal. The balanced SSFP profile is theoretically symmetric with respect to frequency if only T1, T2 and diffusion effects are considered. However, the convolution model for the SSFP signal predicts that the profile becomes asymmetric for asymmetric lineshapes. Asymmetries are observed in white matter. The model is fit to data using a simple lineshape parameterization, and data is shown to be consistent with lineshape effects at small frequency offsets. SSFP asymmetries may be a sensitive marker of tissue microstructure, as reflected by small frequency shifts.


17:02 182. Characterizing White Matter Pathology with Quantitative Magnetization Transfer Imaging: Insight from a Four-Pool Model
    Ives R. Levesque1, G. Bruce Pike1
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    Magnetization transfer is usually modeled using two proton pools. A model with four compartments is required to capture all of the commonly observed relaxation and cross-relaxation properties of human white matter; however, it is impractical for in vivo imaging. Simulations of magnetization transfer experiments were performed using variations on a basic four-model model of white matter, to investigate how these changes are reflected in the two-pool model of MT. We show that compartmental water exchange is negligible on an MT time-scale, and that estimation of the semi-solid-to-liquid pool ratio is robust, despite the presence of two liquid and semi-solid pools.


17:14 183. A New, Polynomial-Based (PARA)CEST Analysis Method with B0 Correction and Increased Sensitivity

Lan Lu1, Tejas Shah2, Mark A. Griswold1,2, Chris A. Flask1,2
Radiology, Case Western Reserve University, Cleveland, OH, USA; 2Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

    Chemical Exchange Saturation Transfer (CEST) MRI is rapidly becoming a popular tool for many in vivo imaging applications. However, the analysis of CEST imaging data has been limited for many studies which have utilized simple 2-point subtraction techniques to quantify the CEST effect which is susceptible to significant errors from both B0 and B1 variation. We have developed a new polynomial fitting technique to quantify the chemical exchange from CEST spectra. This new polynomial fitting technique allows for accurate B0 correction and is inherently less sensitive to experimental factors, such as B1 variation, that can broaden the CEST peaks.


17:26 184. 1H-CEST and 19F MRI of Temperature-Responsive Liposomal Contrast Agents for Image Guided Drug Delivery
    Jochen Keupp1, Sander Langereis2, Inge de Roos2, Dirk Burdinski2, Jeroen Pikkemaat2, Holger Gruell2,3
Philips Research Europe, Hamburg, Germany; 2Philips Research Europe, Eindhoven, Netherlands; 3Eindhoven University of Technology, Eindhoven, Netherlands
    Localized delivery of anti-cancer drugs by external stimulation of nanocarriers (temperature, pH) promises a larger therapeutic window with reduced side effects of the treatment. The present imaging study is based on a new type of temperature-responsive liposomes, which are dually labeled for 1H-CEST and 19F MR imaging and release an encapsulated payload near the melting temperature (Tm) of their lipid membrane (38 C). In their lumen, a chemical shift agent for 1H-lipoCEST imaging and NH4PF6 for 19F detection is contained. Inside the liposome, the 19F spectral lines are strongly broadened and not detectable. Upon reaching Tm, the lipoCEST contrast vanishes, due to the release of the chemical shift agent and, simultaneously, the 19F MR signal becomes visible. Hence, the 19F signal could be used to quantify the amount of released drug payload, while the CEST signal could measure the local nanocarrier concentration before the release. The study demonstrates the potential of the new liposomal nanocarriers for MRI-guided drug delivery in cancer therapy.


17:38 185. ZAPI Analysis of Z-Spectral Components in Acute Cerebral Ischemia
    Johanna Närväinen1, Kimmo T. Jokivarsi2, Penny Louise Hubbard3, Olli H. Grohn4, Risto A. Kauppinen5, Gareth A. Morris6
Biomedical Imaging Unit, University of Kuopio, Kuopio, Finland; 2Dept. of Neurobiology, University of Kuopio, Kuopio, Finland; 3School of Medicine, University of Manchester, Manchester, UK; 4Dept. of Neurobiology, University of Kuopio, Kuopio, Finland; 5Dept. of Radiology, Dartmouth College, Hanover, NH, USA; 6School of Chemistry, University of Manchester, Manchester, UK
    T2-selective Z-spectroscopy (ZAPI) was applied to acute cerebral ischemia. It was shown that the magnetization transfer (MT) component can be measured directly at and near water resonance using sinusoidally modulated low-power RF saturation. This information was used to improve the separation of MT from other components in a Z-spectrum. In this study, a small decrease in MT asymmetry in stroke was observed. In the ischemic striatum the amide signals at 3.5 ppm showed decreased amide-water exchange, while aliphatic signals at -3.5 ppm remained unchanged.
17:50 186. PCEST: Positive Contrast Using Chemical Exchange Saturation Transfer
    Elena Vinogradov1, Todd C. Soesbe2, James A. Balschi3, Dean A. Sherry2,4, Robert E. Lenkinski1
Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 2Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3NMR Laboratory for Physiological Chemistry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 4Department of Chemistry, University of Texas at Dallas, Dallas, TX, USA
    Chemical Exchange Saturation Contrast utilizes selective presaturation of a small pool of exchanging protons and is manifested in the decrease of the free water signal. Thus, CEST contrast is negative and requires the detection of small signal changes on top of a strong background signal. Here we introduce a Positive CEST (PCEST) scheme that results in the increased signal intensity in the presence of the agent and RF. Similar to the original CEST, the contrast can be switched “ON” and “OFF”. The sequence leads to better utilization of the dynamic range and results in the substantial background suppression.


18:02 187.  Z-Spectrum Asymmetry : From 3T to 7T

Olivier E. Mougin1, Ron Coxon1, Penny A. Gowland1
Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, UK

    Magnetization Transfer and related effects such as CEST are important sources of contrast in MRI. Studying MT in vivo at 7T is challenging due to the increase in longitudinal relaxation time and SAR limits. We used pulsed saturation with EPI readout a range of offset frequencies and on the approach to steady-state, providing data that can be used to measure MT parameters at 7T in a reasonable imaging time and to compare the z-spectrum at 7 and 3T. We have found considerably increased sensitivity to CEST at 7T.
18:14 188. GlycoCEST Using FISPCEST
    Tejas Jatin Shah1,2, Lan Lu2, Paul R. Ernsberger3, Christopher Allan Flask1,2
Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; 2Department of Radiology, University Hospitals of Cleveland, Cleveland, OH, USA; 3Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA
    In vivo and non-invasive measures of hepatic and muscular glycogen are needed to effectively study diabetes and metabolism in humans and animals. More recently, glycogen’s inherent CEST effect has been proposed as an alternative to C13-MRS1. While this initial “GlycoCEST” work is promising, the in vivo utility of the GlycoCEST technique is limited because of the long acquisition times (1-3 hours) for quantitative CEST-MRI acquisitions. In this study, we have developed and optimized a rapid GlycoCEST acquisition using our recently developed FISP-CEST technique to obtain quantitative glycogen CEST spectra in phantoms and ex vivo livers in 15-45 minutes.