Researchers and clinicians interested in imaging demyelination and remyelination, to study treatments of disorders such as Multiple Sclerosis (MS). Specifically those interested in the utility of T1 and quantitative magnetization transfer (qMT) in the development of these treatments at clinical and preclinical levels.To determine the relative sensitivity of T1 and qMT parameters to demyelination at different signal to noise ratio’s using the lysolecithin model of MS.Tissue Preparation: 0.5µl of lysolecithin (Sigma-Aldrich) was injected into the thoracic spinal cord of 5 female C57Bl/6 mice causing axons to demyelinate¹. Mice were perfusion fixed 7 days post-injection (peak demyelination). MRI Parameters: MRI was done ex-vivo on a 9.4T Bruker Avance console with a 35mm volume coil (n=5). FLASH-Scout, RARE-Variable TR (VTR) and FLASH qMT images were obtained. (FlASH-Scout: matrix=256x256, FOV=1.5x1.5cm, TE/TR/α=4ms/200ms/30°, and NEX=7; RARE-VTR: matrix=128x128, FOV=1.25x1.25cm, TE/α=11ms/180°, TRs=100/300/700/1400/5000ms, NEX=8, and RARE Factor=2; FLASH qMT: matrix=128x128, FOV=1.25x1.25cm, TE/TR/α=6ms/70ms/10°, and NEX=32, Off-resonance pulses= (RF amplitudes=5/10/20µT, Frequencies=1000/2000/4000/6000/10 000/ 30 000Hz at each power²)). Imaging was repeated using a helium cooled cryo coil (n=3). (FLASH-Scouts: FOV=2.0x2.0cm, TR/α=500ms/45°, and NEX=1. RARE-VTR: TRs=95.5/295.5/695.5/1395.5/4895.5ms, NEX=2, RARE Factor=2. FLASH qMTs: NEX=7. Note: Parameters not listed were unchanged between coils). Analysis: T1 was calculated by fitting RARE-VTR images to the saturation recovery curve². In order to find the bound pool fraction (f), magnetization transfer images were normalized and fit to the two-pool model of magnetization transfer with continuous wave pulse equivalent approximations^2-4. The signal to noise was calculated by taking the signal of a region of interest and dividing by the standard deviation of the background. White matter contralateral to the lesion site was used as a control.The cryo coil has a higher signal to noise for all image types (Table 1). Lesions were visible on FLASH-Scout images (Fig. 1). Visually the T1 appears to higher (whiter) on the T1 map and the bound pool fraction (f) appears to be lower (darker) on the bound pool fraction map at the lesion site for both coils (Fig. 1). Statistically, the mean T1 was found to be significantly higher at the lesion site compared to the control site regardless of coil used (p=0.01 for both coils) (Fig. 2A, Fig. 2C, respectively). The f was not found to be significantly different when using the volume coil (p=0.18) (Fig. 2B) but it was found to be significantly lower at the lesion site when using the cryo coil (p=0.004) (Fig. 2D).It has previously been shown that bound pool fraction (f) has a stronger correlation to the myelin content of tissue than the T1². In this study we confirm that both T1 and f can detect changes to the myelin content of tissue. To the best of our knowledge, this is also the first study to demonstrate that differences in f require a higher signal to noise for detection than differences in T1. This higher signal to noise can be difficult to obtain in both clinical and pre-clinical settings. Imaging was done ex-vivo in this study so that the same time point could be imaged using two different coils. The chemical fixation could have caused a decrease in the T1 and increase in the f found⁵. This works supports the hypothesis that bound pool fraction (f) is not always the ideal parameter to use when developing therapies that reduce demyelination for the treatment of MS. Although f has a strong correlation to tissue myelin content² we show that it is possible for this parameter to miss significant differences due to its high variability at a standard signal to noise for a volume coil. MS treatments should be developed using a multi-modal approach that combines techniques with high sensitivity (T1) and those that have high specificity (f).