NMR IN BIOMEDICINE NMR Biomed. 2005;18:186–194 Published online 1 December 2004 in Wiley InterScience (www.interscience.wiley.com). DOI:10.1002/nbm.939 Magnetization transfer studies of the fast and slow tissue water diffusion components in the human brain Robert V. Mulkern, 1,2 * Sridhar Vajapeyam, 1 Steven J. Haker 2 and Stephan E. Maier 2 1 Department of Radiology, Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA 2 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA Received 4 February 2004; Revised 8 July 2004; Accepted 16 September 2004 ABSTRACT: Magnetization transfer (MT) properties of the fast and slow diffusion components recently observed in the human brain were assessed experimentally. One set of experiments, performed at 1.5 T in healthy volunteers, was designed to determine whether the amplitudes of fast and slow diffusion components, differentiated on the basis of biexponential fits to signal decays over a wide range of b-factors, demonstrated a different or similar magnetization transfer ratio (MTR). Another set of experiments, performed at 3 T in healthy volunteers, was designed to determine whether MTRs differed when measured from high signal-to-noise images acquired with b-factor weightings of 350 vs 3500 s/mm 2 . The 3 T studies included measurements of MTR as a function of off-resonance frequency for the MT pulse at both low and high b-factors. The primary conclusion drawn from all the studies is that there appears to be no significant difference between the magnetization transfer properties of the fast and slow tissue water diffusion components. The conclusions do not lend support to a direct interpretation of the ‘components’ of the biexponential diffusion decay in terms of the ‘compartments’ associated with intra- and extracellular water. Copyright # 2004 John Wiley & Sons, Ltd. KEYWORDS: magnetization transfer; tissue diffusion; brain INTRODUCTION Several studies have now shown that human brain water signal decays over an extended b-factor range up to 5000 s/mm 2 are well-characterized with biexponential decay functions. 1–6 The assignment of the fast and slow tissue water diffusion components to extra- and intracel- lular water, respectively, has been discussed, if not uni- versally espoused, as a possibility in these 1–6 and several other related works. 7–15 This assignment remains intri- guing but controversial since restricted diffusion effects alone can lead to decay curves which appear to be biexponential in form but do not require an underlying assumption of two or more distinct water compart- ments. 15–22 We hypothesize that if the physical basis of empirically useful biexponential decay analyses is two distinct water compartments with widely disparate diffu- sion coefficients, then it would reasonably follow that the two compartments might have substantially different magnetization transfer ratios. 23–26 For example, within the context of an intra- vs extracellular water compart- mentation model, the intracellular water molecules re- sponsible for the ‘slow’ diffusion component might reasonably be expected to experience more interactions with macromolecules, intracellular organelles, etc, than those responsible for the ‘fast’ diffusion component within the extracellular matrix. This in turn would lead to a larger ‘bound’ water fraction and so an enhanced MTR for the slow vs the fast tissue water diffusion component. This is the primary hypothesis tested in this work. METHODS Data acquisition All studies were performed with the written consent of the volunteers as specified and approved by the local Institutional Review Board (IRB). Five healthy male volunteers, mean age 39  9 years, were scanned using a 1.5 T scanner (General Electric LX 8.2.5, Milwaukee, WI, USA). A line scan diffusion imaging (LSDI) se- quence 4,5,27,28 using 48 columns, a  2.2 kHz receiver bandwidth, 64 frequency encodes, and a TR/TE combina- tion of 3000/91 (ms/ms) was used to scan a 6 mm-thick axial slice at the level of the third ventricle. An asym- metric field of view of 220  165 mm 2 was employed with an in-plane resolution of 3.4  3.4 mm 2 and resultant Copyright # 2004 John Wiley & Sons, Ltd. NMR Biomed. 2005;18:186–194 *Correspondence to: R. V. Mulkern, Department of Radiology, Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. E-mail: rmulkern@yahoo.com Contract/grant sponsor: NIH; contract/grant number: 1RO1 NS39335. Abbreviations used: LSDI, line scan diffusion imaging; MT, magne- tization transfer; MTR, magnetization transfer ratios.