An empirical equation for the magnetization transfer (MT)FLASH signal is derived by analogy to dual-excitation FLASH, introducing a novel semiquantitative parameter for MT, the percentage saturation imposed by one MT pulse during TR. This parameter is obtained by a linear transformation of the inverse signal, using two reference experiments of proton density and T 1 weighting. The influence of sequence parameters on the MT saturation was studied. An 8.5-min protocol for brain imaging at 3 T was based on nonselective sagittal 3D-FLASH at 1.25 mm isotropic resolution using partial acquisition techniques (TR/TE/ ␣ ‫؍‬ 25ms/4.9ms/5°or 11ms/4.9ms/15°for the T 1 reference). A 12.8 ms Gaussian MT pulse was applied 2.2 kHz off-resonance with 540°flip angle. The MT saturation maps showed an excellent contrast in the brain due to clearly separated distributions for white and gray matter and cerebrospinal fluid. Magnetization transfer (MT) is a contrast mechanism in tissue that is based on cross-relaxation or chemical exchange between protons in bulk water and rotationally immobilized macromolecules (1,2). In clinical MRI, MT contrast is invoked by application of a T 2 -selective RF pulse applied prior to slice excitation. The "MT pulse" saturates specifically the macromolecular magnetization, and MT is then observed as a reduction in image intensity. Its normalized value, the MT ratio (MTR), is commonly taken as a measure for the strength of the MT effect, and hence interpreted as a surrogate parameter for macromolecular content or myelination. However, the MTR is not an absolute measure, but depends on the sequence parameters and is influenced by T 1 relaxation and flip angle inhomogeneities.This limitation can be overcome by quantitative Z-spectroscopy measurements to obtain parameter estimates for the binary spin-bath (BSB) model and suitable absorption line shapes (3,4). On clinical MR systems, pulsed MT is combined with spoiled gradient echo sequences (FLASH, fast low angle shot) and suitable adaptations of Henkelman's continuous wave model (5-7). Alternatively, pulsed MT experiments can be approximated by instantaneous events of saturation separating intervals free of irradiation (8). Since brain tissue is characterized by conditions of fast-exchange, this "free" evolution can be described by two exponential time courses, the common T 1 relaxation and the MT. The latter is observed as a reduction of the longitudinal magnetization of free water subsequent to the MT pulse (9). This MT-related saturation increases in time until the exchange equilibrium in the BSB model is restored.The concept of separating T 1 relaxation and MT has been previously applied to progressive partial saturation by repetitive MT pulses (10). Here, it is transferred to the MT-w(eighted) FLASH sequence. A phenomenological signal equation is derived by analogy from a FLASH experiment with two interleaved excitations and recovery times. This equation represents the effects of excitation and relaxation during TR, while any additional saturation du...

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Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency. We identified an inherited brain-specific folate transport defect that is caused by mutations in the folate receptor 1 (FOLR1) gene coding for folate receptor alpha (FRalpha). Three patients carrying FOLR1 mutations developed progressive movement disturbance, psychomotor decline, and epilepsy and showed severely reduced folate concentrations in the cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) demonstrated profound hypomyelination, and MR-based in vivo metabolite analysis indicated a combined depletion of white-matter choline and inositol. Retroviral transfection of patient cells with either FRalpha or FRbeta could rescue folate binding. Furthermore, CSF folate concentrations, as well as glial choline and inositol depletion, were restored by folinic acid therapy and preceded clinical improvements. Our studies not only characterize a previously unknown and treatable disorder of early childhood, but also provide new insights into the folate metabolic pathways involved in postnatal myelination and brain development.

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