Constrained modeling for spectroscopic measurement of bi-exponential spin-lattice relaxation of water in vivo Jack Knight-Scott* ,a , Elana Farace b , Virginia I. Simnad c , Helmy M. Siragy d , Carol A. Manning c a Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908-0759, USA b Department of Neurosurgery, University of Virginia, Charlottesville, VA 22908-0759, USA c Department of Neurology, University of Virginia, Charlottesville, VA 22908-0759, USA d Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908-0759, USA Received 20 August 2002; accepted 16 September 2002 The 1 H NMR water signal from spectroscopic voxels localized in gray matter contains contributions from tissue and cerebral spinal fluid (CSF). A typically weak CSF signal at short echo times makes separating the tissue and CSF spin-lattice relaxation times (T 1 ) difficult, often yielding poor precision in a bi-exponential relaxation model. Simulations show that reducing the variables in the T 1 model by using known signal intensity values significantly improves the precision of the T 1 measurement. The method was validated on studies on eight healthy subjects (four males and four females, mean age 21  2 years) through a total of twenty-four spectroscopic relaxation studies. Each study included both T 1 and spin-spin relaxation (T 2 ) experiments. All volumes were localized along the Sylvian fissure using a stimulated echo localization technique with a mixing time of 10 ms. The T 2 experiment consisted of 16 stimulated echo acquisitions ranging from a minimum echo time (TE) of 20 ms to a maximum of 1000 ms, with a repetition time of 12 s. All T 1 experiments consisted of 16 stimulated echo acquisition, using a homospoil saturation recovery technique with a minimum recovery time of 50 ms and a maximum 12 s. The results of the T 2 measurements provided the signal intensity values used in the bi-exponential T 1 model. The mean T 1 values when the signal intensities were constrained by the T 2 results were 1055.4 ms  7.4% for tissue and 5393.5 ms  59% for CSF. When the signal intensities remained free variables in the model, the mean T 1 values were 1085 ms  19.4% and 5038.8 ms  113.0% for tissue and CSF, respectively. The resulting improvement in precision allows the water tissue T 1 value to be included in the spectroscopic characterization of brain tissue. © 2002 Elsevier Science Inc. All rights reserved. Keywords: Magnetic resonance spectroscopy; MRS; Transverse relaxation; Longitudinal relaxation; Brain 1. Introduction The magnetic resonance (MR) spectroscopic model of the brain water signal is a two-compartment model consist- ing of tissue water and cerebral spinal fluid (CSF) [1]. In recent years, bi-exponential analysis of the spin-spin relax- ation curve has become a common MR spectroscopy tech- nique for obtaining the signal contributions for each com- partment [2– 6]. The water signal contributions are employed for volume correction in absolute quantitation of metabolite concentrations, while the spin-spin relaxation times are discarded. However, given that changes in water relaxation rates are the basis for contrast changes in mag- netic resonance imaging (MRI), the inclusion of the water relaxation rates or times in the tissue characterization may improve spectroscopic discrimination between different tis- sue types or diseases [7,8]. Tissue characterization in vivo with 1 H magnetic reso- nance spectroscopy ( 1 H-MRS) is primarily regarded as me- tabolite concentration measurements, but may also include water content, diffusion coefficient, and longitudinal and transverse relaxation times, T 1 and T 2 , respectively. The lengthy acquisition time required to collect all such data makes the measurements prohibitive under normal circum- stances, and so most spectroscopic studies involving hu- mans are reduced to measurements of metabolite concen- trations and water T 2 relaxation curves for volume correction. In theory, T 1 measurements could also be used for volume corrections since the T 1 s of water in brain tissue and CSF in vivo are clearly different, approximately one second for tissue and two to three seconds for CSF at 1.5 T [7,9,10]. Tissue water has an effective T 1 shorter than “pure water” due to chemical and magnetization exchange with * Corresponding author. Tel.: +1-434-243-6321; fax: +1-434-982-3870. E-mail address: Jack.Knight-Scott@Virginia.Edu (J. Knight-Scott). Magnetic Resonance Imaging 20 (2002) 681-689 0730-725X/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0730-725X(02)00597-0