Displacement Imaging of Spinal Cord Using q-Space Diffusion-Weighted MRI Yaniv Assaf, 1 Adi Mayk, 2 and Yoram Cohen 1 * Displacement MR images of water in in vitro rat spinal cord were computed from q-space analysis of high b value diffusion- weighted MRI data. It is demonstrated that q-space analysis of heavily diffusion-weighted MRI (qs-DWI) provides MR images in which physical parameters of the tissues such as the mean displacement and the probability for zero displacement of the water molecules are used as contrasts. It is shown that these MR images provide structural information surpassing the spa- tial resolution of conventional MRI by several orders of magni- tude. This imaging methodology was used to follow spinal cord maturation in the rat. It was found that changes in the diffusion characteristics of white matter upon maturation are responsi- ble for the emergence of gray/white matter contrast. The mean displacement of water molecules in the white and gray matter of the mature rat spinal cord was found to be 2–3, and 8 –10 microns, respectively. The potential and the limitations of this new imaging methodology for early detection of white matter disorders are discussed. Magn Reson Med 44:713–722, 2000. © 2000 Wiley-Liss, Inc. Key words: white matter; spinal cord; maturation; MRI; diffusion MRI; DWI; q-space NMR; q-space DWI Diffusion, as obtained from diffusion-weighted MRI (DWI), is known to be a valuable contrast mechanism in MRI of the CNS (1,2). It was found to be extremely sensitive to early ischemic events (3,4) and useful for the characteriza- tion of several brain pathologies (5– 8). Until recently, in most DWI studies the well-known Stejskal-Tanner equa- tion (9), shown in Eq. [1], was used for analyzing the signal attenuation. ln(E g /E 0 ) =- 2 g 2  2 ( -/3)D=-bD [1] This equation relates the normalized signal decay (E g /E 0 ) with the duration, time separation, and strength of the magnetic field pulse gradients ( and g, respectively),  the magnetogyric ratio, and the self-diffusion coefficient D. However, the Stejskal-Tanner equation, in which signal attenuation is mono-exponential, applies only to a specific situation (namely, to a single population that exhibits un- restricted isotropic diffusion). Indeed, in most DWI studies performed to date mono-exponential decay and the pres- ence of single water population was assumed (2–9). With recent advancements in gradient technology, it became apparent that the decay of the water signal in neuronal tissues in MR diffusion experiments is not mono- exponential, revealing at least two diffusing components (10 –12) differing in their relaxation characteristics and diffusion time dependency (13). However, assignment of the various diffusing components to actual physiological compartments has been difficult and required extensive modeling that called for many assumptions (12,14). We recently demonstrated that q-space diffusion-weighted magnetic resonance spectroscopy (MRS) can assist in mak- ing such assignments (15). As diffusion measurements using the pulse gradient spin echo or stimulated echo MR methods tag the observed spins at two time points, the echo intensity in NMR diffu- sion experiments should depend on the mean displace- ment of the observed spins (16,17). This implies that proper analysis of diffusion in restricted compartments should yield structural information on the compartment in which the diffusion occurs (18). A decade ago, two groups demonstrated that Fourier transformation of the echo in- tensity, E(q), with respect to the so-called “reciprocal spa- tial vector,” q, defined as (2) –1 g, can provide structural information on (pseudo)-periodic samples (19 –21). Ac- cording to this approach the echo attenuation in NMR diffusion measurements relates to the displacement prob- abilities, using the reciprocal spatial vector q, according to Eq. [2], E  ( q) =  P  s ( R, )exp(i2q R)dR [2] where E  (q) represents the echo decay as a function of q, R is the displacement and P  s (R, ) is the displacement probability (19 –21). The key feature here is the Fourier relationship between the echo intensity decay and the displacement probability. This means that in principle, under the narrow pulse approximation and at sufficient long , one can obtain displacement probability profiles even in a complex system by only performing a Fourier transformation of the echo decay with respect to q (19 –22). In the past decade, most q-space NMR diffusion appli- cations were performed in the field of material sciences (20 –24). q-Space studies dealt with pore-size and were used to obtain structural information on porous materials. Most recently, q-space diffusion NMR studies have begun to deal with biological systems (25–29). Gadian’s group (25,26) conducted a q-space spectroscopic study on nor- mal and ischemic brain Kuchel et al. (27) resorted to this approach to study red blood cell size and shape (28,29), and we availed ourselves of this approach to characterize both water and metabolite diffusion in neuronal tissues (15,30). However, all these recent q-space diffusion NMR studies of biological systems dealt with NMR spectroscopy 1 School of Chemistry, Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel. 2 Teva Pharmaceutical Industries and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Grant sponsor: United States-Israel Binational Science Foundation; Grant number: 97-00346; Grant sponsor: Israel Science Foundation. *Correspondence to: Dr. Yoram Cohen, School of Chemistry, Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv 69778, Tel Aviv, Israel. E-mail: ycohen@ccsg.tau.ac.il Received 29 November 1999; revised 2 May 2000; accepted 21 June 2000. Magnetic Resonance in Medicine 44:713–722 (2000) © 2000 Wiley-Liss, Inc. 713