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MRI of Gadolinium (GdDTPA-BMA) uptake in the membranous labyrinth of the cochlea Börje BJELKE1, Zhengguang CHEN2, S. Allen COUNTER3, Tomas KLASON4, Erik BORG5, Maoli DUAN6 1Karolinska Institute, Karolinska MR Research Center, Stockholm, Sweden; 2Karolinska Hospital, MR Research Center, Stockholm, Sweden; 3Harvard University, Neurology Department, Harvard University Biological Laboratories, Cambridge, MA USA; 4Karolinska Institute, Karolinska MR Research Center, Syockholm, Sweden; 5Karolinska Institute, Department of Physiology and Pharmacology, Division of Physiology II, Stockholm, Sweden; 6ENT Research lab., Stockholm, Sweden; presented to ear of unanesthetized guinea pigs. The peak sound pressure level of the impulse noise was ~140 dB linear peak. Results The MRI of fig. 1 (a-i) shows the temporal patterns of Gd-enhanced T1-weighted images of bilateral guinea pig cochleae acquired in vivo before injection and at 10 min intervals up to 80 min post injection. The images reveal a clear pattern of time-related increases in Gd uptake as indicated by image enhancement in the perilymphatic fluids of the scala tympani and scala vestibuli in each of the 4 turns of the cochlea. The time lapsed MRI indicated no Gd penetration of the normal scala media (arrows). The time course curves of figure illustrate the substantial increase in Gd enhancement in the scala tympani and scala vestibuli over the period of 100 minutes, with only slight changes beyond this time. This figure also shows that the uptake of the Gd in the scala tympani was significantly greater and more rapid than the enhancement of the scala vestibuli and the scala media. The difference in initial rise time, speed and quantity of Gd uptake between the scala tympani and the scala vestibuli continued over the time course of the enhancement period, from the initial signal intensity increase at about 10 min post injection to 100 min post injection. Statistical significance in Gd enhancement level was between the scala tympani and scala vestibuli was reached at T-30, T-40, T-50, T-60, and T-70 min. Statistically significant signal intensity levels between the scala tympani and scala media were found at T-20 through T-100. The differences in Gd signal intensity levels between the scala vestibuli and scala media were significant at T-30, T-40, T-50, T-60, T-70, and T100 min. The Gd uptake parameters of the scala vestibuli mirrors the pattern observed in the scala tympani, but remains quantitatively lower in all aspects throughout the course of the measurements. The scala media showed little or no increase in Gd uptake and related enhancement following Gd injection over the 100 minute period of observation. Introduction Impairment of the membranous labyrinth of the cochlea has been implicated in sudden sensorineural hearing loss. Intense impulse noise also may induce ruptures of the intra-cochlear membranes and associated sensorineural hearing loss. Confirmation of structural impairment of the inner ear membranes is inhibited by the difficulty of non-invasive imaging the membranes of the in vivo cochlea. This study investigated the normal and injured membranous labyrinth of the cochlea using gadolinium (Gd) enhanced high field magnetic resonance imaging (MRI). The time course and distribution of the in vivo uptake the gadodiamide chelate bound paramagnetic Gd ion (GdDTPA-BMA) throughout the membranous scalae of the normal and the experimentally damaged guinea pig cochlea was measured at 4.7 T. In vivo perfusions with the Gd induced active signal enhancement of the scalae over a short time course, reaching maximum levels at around 100 minutes post injection. Analysis showed statistically significant differences in the levels and rates of Gd-EDTA enhancement between the scalae, with the scala tympani showing the most rapid and greatest enhancement throughout the test period, while the scala vestibuli showed slower and less enhancement, and the normal scala media indicated insignificant enhancement. The in vivo Gd-EDTA penetration and enhancement of the scala media increased significantly in the impulse noise-damaged cochlea. Methods Seven healthy albino and pigmented guinea pigs (AB Salins, Malmö, Sweden) were used in this study. The animals were then placed in the resonator so that the rostro-caudal position of the cochlea was situated at the isocenter of the magnet. A Bruker Biospec Avance 47/40 experimental MRI system with a magnetic field strength of 4.7 T and a 40 cm bore was used (Bruker Medizintechnik GmbH, Karlsruhe-Ettlingen, Germany. A self shielded gradient system (BG 12) of 200 mT/m (inner diameter 120 mm) were used. The gradient were used in combination with a Bruker cylindrical resonator (inner diameter 72). The Bruker standard implementations of SNAP (snapshot, a fast, low flip angle gradient echo sequence for scout images) and MSME (multi-slice multi-echo) techniques were used. High resolution 2-D images of 0.3 mm to 1.0 mm slice thickness were acquired in vivo using the rapid acquisition with relaxation enhancement (RARE) acquisition strategy with the standard multiecho technique. The scala media of the noise-impaired cochlea showed approximately a 90% increase in Gd enhancement. The scala tympani of the impaired cochlea showed a 40 % increase in signal intensity, while the scala vestibuli showed a 70 % increase Gd enhancement. Discussion The findings of this study also demonstrate the effectiveness of Gd in the enhancement of membranous labyrinth, and the usefulness of the technique in non-invasive in vivo MRI visualization of evidence of ruptures in the cochlear membranes (1). The findings may serve as baseline data for in vivo MRI studies of experimentally-induced labyrinthine pathology and sudden sensorineural hearing loss in animal models. The results also suggest that the guinea pig cochlea is a useful model for experimental studies of conditions that may impair the inner ear and cause sensorineural hearing loss, such as acoustic trauma, endolymphatic hydrops, ototoxic substance exposure, barotrauma and labyrinthitis. References 1. Counter SA, Bjelke B, Klason T, Chen Z, Borg E. Magnetic resonance imaging of the cochlea, spiral ganglia and eighth nerve of the guinea pig. NeuroReport 1999; 10: 1-7. MR images were recorded before and after administration of a T1 contrast agent (Omniscan, Nycomed, 0.5 mmol/ml) which is a gadodiamide (GdDTPA-BMA) chelate bound paramagnetic gadolinium ion given at a dose of 3ml/kg i.v., as a slow bolus injection (femoral artery). Gd enhancement measurements were performed in the 200 mT/m gradient system with the 72 mm resonator using the following parameters for a strong T1 contrast: FOV 3 cm, 3 slices separated by 0.02 mm, slice thickness 0.5 mm, pulse spacing 6.1 ms to give TE 31.5 ms, NEX 100, acquisition matrix 256 reconstructed with 512, recovery time 500 ms, RARE factor 32. Time intervals of 10 minutes were selected after the administration of the contrast agent for visualization and recording of the dynamic distribution of the contrast agent in the cochlear chambers over a period of 100 minutes. The Paravision (Bruker) software was used for post-processing and evaluation in combination with Adobe Photoshop for labeling and presentation of all images. The impulse noise generated by the magnetic coil of a Cadwell model MES 10 magnetic stimulator was used to induce cochlea damage. The 5 cm (diameter), 1.5 cm thick plastic-covered coil was held at the pinna and 50 brief pulses at 100 % stimulation level (or 2 x104 Gauss) with a rise time of about 200 µs and a duration of around 1 ms were Proc. Intl. Soc. Mag. Reson. Med 9 (2001) 88 Proc. Intl. Soc. Mag. Reson. Med 9 (2001) 88