Multi-component Apparent Diffusion Coefficients in Human Brain: Relationship to Spin-Lattice Relaxation Robert V. Mulkern, 1,2 * Hale Pinar Zengingonul, 2 Richard L. Robertson, 1 Peter Bogner, 3 Kelly H. Zou, 2 Hakon Gudbjartsson, 4 Charles R.G. Guttmann, 2 David Holtzman, 2 Walid Kyriakos, 1 Ferenc A. Jolesz, 2 and Stephan E. Maier 2 In vivo measurements of the human brain tissue water signal decay with b-factor over an extended b-factor range up to 6,000 s/mm 2 reveal a nonmonoexponential decay behavior for both gray and white matter. Biexponential parametriza- tion of the decay curves from cortical gray (CG) and white matter voxels from the internal capsule (IC) of healthy adult volunteers describes the decay process and serves to differ- entiate between these two tissues. Inversion recovery exper- iments performed in conjunction with the extended b-factor signal decay measurements are used to make separate mea- surements of the spin-lattice relaxation times of the fast and slow apparent diffusion coefficient (ADC) components. Dif- ferences between the spin-lattice relaxation times of the fast and slow ADC components were not statistically significant in either the CG or IC voxels. It is possible that the two ADC components observed from the extended b-factor measure- ments arise from two distinct water compartments with dif- ferent intrinsic diffusion coefficients. If so, then the relax- ation results are consistent with two possibilities. Either the spin-lattice relaxation times within the compartments are similar or the rate of water exchange between compartments is “fast” enough to ensure volume averaged T 1 relaxation yet “slow” enough to allow for the observation of biexponential ADC decay curves over an extended b-factor range. Magn Reson Med 44:292–300, 2000. © 2000 Wiley-Liss, Inc. Key words: apparent diffusion coefficient; brain; biexponential decay; spin-lattice relaxation Diffusion imaging is playing an increasingly important diagnostic role due to its extreme sensitivity to acute stroke in comparison with conventional T 1 - and T 2 - weighted imaging (1–3). Due to the effects of anisotropic diffusion (4,5), it is now generally realized that at least three directions of the diffusion sensitization gradient should be sampled to generate trace images free from the effects of preferred directional diffusion. Indeed a mini- mum of 6 directions must be sampled if a full diffusion tensor for each voxel is to be evaluated (6 – 8) for studies of myelin development and brain microarchitecture (9,10). Thus, the current trend towards clinical implementation of diffusion imaging is to sample multiple slices of the brain each at a low and a high b-factor, the latter being typically on the order of 1,000 s/mm 2 , and to repeat the high b-factor sampling for at least three and up to six directions of the diffusion sensitization gradient. To this inherent complexity of brain tissue water diffu- sion measurement and interpretation, yet another compli- cating factor has recently emerged. Namely, when sampled over an extended b-factor range much larger than typically used clinically, the brain water signal decay in vivo from both rats and humans does not display the monoexponen- tial signal decay so commonly assumed (11,12). Indeed a bi- as opposed to monoexponential model of decay is required to fit the ADC decay data. This finding is not explainable within the confines of the diffusion tensor formalism alone. Furthermore, the extended b-factor range required for observing and measuring the biexponential decay is readily accessible with conventional scanners using long echo times and standard gradient strengths of 1 Gauss/cm. This endows the finding with significant clini- cal ramifications and motivates further studies designed to explore the nature of the nonmonoexponential brain water signal decay. In this work, the spin-lattice relaxation behavior of hu- man brain water signal decay over an extended b-factor range was examined by combining multi-b-factor sampling techniques with inversion recovery methods. Voxels from internal capsule (IC) white matter and cortical gray (CG) matter were sampled to determine relaxation in tissues with and without anisotropic diffusion effects. The spin- lattice relaxation times of the fast and slow ADC compo- nents, evaluated on the basis of biexponential ADC decom- position as a function of inversion time, were found to be quite similar in either voxel type. Similarly, T 1 values evaluated directly from the data without the use of biex- ponential decompositions showed no systematic depen- dence on b-factor over the range sampled. Implications of these results are discussed within the context of a two- compartment model for explaining the observed biexpo- nential ADC behavior of brain water signal decay over extended b-factor ranges in both gray and white matter. MATERIALS AND METHODS Data Acquisition All studies were performed with a 1.5 T Signa scanner (General Electric Medical Systems, Milwaukee, WI) oper- ating at the 5.4 hardware/software configuration using a quadrature head coil. Eight healthy adult volunteers rang- ing from 24 to 38 years of age participated in the study, providing informed consent according to the rules of the institutional review board. A set of 10-mm thick axial 1 Department of Radiology, Children’s Hospital, Harvard Medical School, Bos- ton, Massachusetts. 2 Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. 3 Diagnostic Center, Pannon University of Agriculture, Kaposvar, Hungary. 4 deCODE Genetics, Inc., Reykjavik, Iceland. *Correspondence to: Robert V. Mulkern, Department of Radiology, Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. E-mail: mulkern@bwh.harvard.edu Received 4 March 1999; revised 21 March 2000; accepted 30 March 2000. Magnetic Resonance in Medicine 44:292–300 (2000) © 2000 Wiley-Liss, Inc. 292