- Email: [email protected]
G.P.120
836
Abstracts / Neuromuscular Disorders 24 (2014) 791–924
higher proportion of extracellular space in progressively predominant type I oxidative fibers. It also would make sense to attribute increased T2 heterogeneities to some degree of tissue disorganisation, such as the development of interstitial fibrosis. It would be the case with aging, as indicated by higher heterogeneity indices in the elderly group. These processes were partly slowed down by physical activity. http://dx.doi:10.1016/j.nmd.2014.06.147
G.P.118 Net muscle volumetry by MRI and bioelectrical impedance analysis for healthy volunteers; an observation study T. Nakayama 1, T. Uchiyama 2, S. Kuru 3 1 Yokohama Rosai Hospital, Yokohama, Japan; 2 TANITA Body Scientific Institute, Tokyo, Japan; 3 NHO Suzuka Hosipital, Suzuka, Japan Muscle volume in patients with muscle disease is an index of disease progression and efficacy of the therapy. We had developed the net muscle volumetry using CT (nMV_CT) which is capable of evaluating net muscle volume for over several years. We developed the net muscle volumetry using Dixon MRI (nMV_MRI) whose results were closely correlated to nMV_CT. Here we report a new method of net muscle volume of extremities of healthy volunteers by bioelectrical impedance analysis (BIA), compared with those of Dixon MRI. We evaluated the impedance index at 50 kHz (ZI50), which was generally used for body composition analysis, and the nMV_MRI of six thighs of three healthy volunteers (aged 5–12). An impedance analyzer (BCA-100_CTanita Corp., Japan) and 10 mm wide stainless steel electrodes were used for measuring bioelectrical impedance. A Siemens 1.5T MR scanner was used for Dixon MRI. The impedance and nMV_MRI were measured at the 10 cm section of the middle part of the thigh. The ZI50 of the subjects’ thighs were calculated. The nMV_MRI of thighs were measured as 500–1200 cm3, and ZI50 was calculated as 2.75–4.88 cm2/X. These results were closely correlated with each other with Pearson’s correlation coefficient of 0.866 (p = 0.026). We can estimate ZI50 of thigh which is closely correlated to nMV_MRI. We can evaluate ZI50 easily, noninvasively, and repeatedly, and we consider that this new method is suitable for the biomarker of the disease progression and therapies. http://dx.doi:10.1016/j.nmd.2014.06.148
G.P.119 Skeletal muscle fatty degenerative changes can be evaluated both qualitatively and quantitatively from whole-body Dixon NMR images with an important gain in acquisition time B. Marty 1, P.Y. Baudin 1, B. Robert 2, A. Shukelovich 1, N. Azzabou 1, P.G. Carlier 1 1 Institute of Myology, Paris, France; 2 Siemens Healthcare, Saint-Denis, France Fatty infiltration of muscles is a marker of disease progression in many neuromuscular disorders. Muscle MRI is capable of revealing patterns of muscles involvement that are disease specific and facilitates the diagnostic workup of patients. Although routine T1-weighted (T1w) imaging can give an indication of the presence or absence of muscular fat infiltration, it is difficult to extract quantitative data from these images. On the contrary, Dixon methods provide quantitative measure of fat fraction. Usually, whole-body (WB) exams consist in the acquisition of T1w images, followed by Dixon acquisitions on targeted regions to quantitatively assess fat infiltration. With the aim of improving and accelerating the qualitative assessment of neuromuscular disorders, we propose to avoid the T1w acquisition altogether, by allowing to perform the visual diagnosis workup on a WB Dixon imaging. 20 patients underwent WB
MRI at 3T. WB T1w images were acquired with a 2D TSE sequence (resolution = 1.1 1.1 mm2, slice thickness = 6 mm, Tacq = 5 min 40 s). WB Dixon acquisition consisted in a 3D VIBE sequence with 3 echoes (resolution = 1 1 5 mm3, Tacq = 14 min 5 s). Quantitative fat fraction maps were derived using a standard 3-points Dixon reconstruction method. A customed lookup table was embedded in the DICOM file to provide a colored lecture of fat fraction maps corresponding to the Mercuri’s scale. Our results show that the acquisition of a high resolution WB Dixon imaging is possible in less than 15 min using an optimized VIBE sequence. This provides quantitative data that are more suitable than T1w images for longitudinal natural history studies, or therapeutic clinical trials. Moreover, the color representation renders the visual grading of the muscles more convenient and less operator dependent as it is based on actual fat fraction measurements. WB Dixon might then overcome the use of WB T1w images for diagnostic of neuromuscular disorders. http://dx.doi:10.1016/j.nmd.2014.06.149
G.P.120 The Sodium/Hydrogen Exchanger (NHE-1): A promising novel target for DMD U. Burki 1, E. Greally 1, S. Laval 1, S. Scha¨fer 2, V. Straub 1 1 Newcastle University, Newcastle upon Tyne, UK; 2 Peacock Pharma GmbH, Goch, Germany Abnormal intracellular calcium load is one of the most consistent findings in Duchenne muscular dystrophy (DMD) but previous attempts to improve the dystrophic pathology with calcium antagonists have been unsuccessful. However, there is an intriguing possibility of restoring calcium homeostasis indirectly by exploiting the relationship between the Sodium/Hydrogen Exchanger (NHE-1) and the Sodium/Calcium Exchanger (NCX). NHE-1 has been reported to be abnormally overactive in DMD models, leading to an increased influx of sodium which in turn switches the NCX into reserve mode leading to calcium influx. Using selective NHE-1 inhibitors the influx of sodium can be reduced thereby allowing the NCX to revert back to normal mode, where calcium is extruded, thus reducing the cellular calcium load. In collaboration with our industrial partner Peacock Pharma, we have demonstrated the potential of NHE-1 inhibition in the mdx mouse model for DMD by chronically treating animals with a novel NHE-1 inhibitor. The pilot study showed significantly reduced calcium uptake in treated mice (n = 6) using manganese enhanced MRI (MEMRI). Manganese acts as a contrast agent in T1 weighted MRI and is thought to be taken up by cardiac and skeletal muscle by the same receptors as calcium. There was also an increase in functional grip strength, although not statistically significant the results are nevertheless encouraging and indicate the potential of this novel approach in DMD. This is currently being investigated more thoroughly using a greater number of animals (n = 12) treated chronically via drug in chow over 6-months and assessed using MEMRI and grip test. In addition, in vitro calcium-flux assays (e.g. Fluo-4) are used to determine the potency and investigate the mechanism of action of this drug. The objective of our study is to provide the requisite pre-clinical data that would enable these drugs to progress towards clinical trials. http://dx.doi:10.1016/j.nmd.2014.06.150
G.P.121 Fast, precise, interactive segmentation of skeletal muscle NMR images P.G. Carlier, A. Shukelovich, P.Y. Baudin, J.M. Boisserie, J. Le Louer, N. Azzabou Institute of Myology, Paris, France
Abstracts / Neuromuscular Disorders 24 (2014) 791–924
higher proportion of extracellular space in progressively predominant type I oxidative fibers. It also would make sense to attribute increased T2 heterogeneities to some degree of tissue disorganisation, such as the development of interstitial fibrosis. It would be the case with aging, as indicated by higher heterogeneity indices in the elderly group. These processes were partly slowed down by physical activity. http://dx.doi:10.1016/j.nmd.2014.06.147
G.P.118 Net muscle volumetry by MRI and bioelectrical impedance analysis for healthy volunteers; an observation study T. Nakayama 1, T. Uchiyama 2, S. Kuru 3 1 Yokohama Rosai Hospital, Yokohama, Japan; 2 TANITA Body Scientific Institute, Tokyo, Japan; 3 NHO Suzuka Hosipital, Suzuka, Japan Muscle volume in patients with muscle disease is an index of disease progression and efficacy of the therapy. We had developed the net muscle volumetry using CT (nMV_CT) which is capable of evaluating net muscle volume for over several years. We developed the net muscle volumetry using Dixon MRI (nMV_MRI) whose results were closely correlated to nMV_CT. Here we report a new method of net muscle volume of extremities of healthy volunteers by bioelectrical impedance analysis (BIA), compared with those of Dixon MRI. We evaluated the impedance index at 50 kHz (ZI50), which was generally used for body composition analysis, and the nMV_MRI of six thighs of three healthy volunteers (aged 5–12). An impedance analyzer (BCA-100_CTanita Corp., Japan) and 10 mm wide stainless steel electrodes were used for measuring bioelectrical impedance. A Siemens 1.5T MR scanner was used for Dixon MRI. The impedance and nMV_MRI were measured at the 10 cm section of the middle part of the thigh. The ZI50 of the subjects’ thighs were calculated. The nMV_MRI of thighs were measured as 500–1200 cm3, and ZI50 was calculated as 2.75–4.88 cm2/X. These results were closely correlated with each other with Pearson’s correlation coefficient of 0.866 (p = 0.026). We can estimate ZI50 of thigh which is closely correlated to nMV_MRI. We can evaluate ZI50 easily, noninvasively, and repeatedly, and we consider that this new method is suitable for the biomarker of the disease progression and therapies. http://dx.doi:10.1016/j.nmd.2014.06.148
G.P.119 Skeletal muscle fatty degenerative changes can be evaluated both qualitatively and quantitatively from whole-body Dixon NMR images with an important gain in acquisition time B. Marty 1, P.Y. Baudin 1, B. Robert 2, A. Shukelovich 1, N. Azzabou 1, P.G. Carlier 1 1 Institute of Myology, Paris, France; 2 Siemens Healthcare, Saint-Denis, France Fatty infiltration of muscles is a marker of disease progression in many neuromuscular disorders. Muscle MRI is capable of revealing patterns of muscles involvement that are disease specific and facilitates the diagnostic workup of patients. Although routine T1-weighted (T1w) imaging can give an indication of the presence or absence of muscular fat infiltration, it is difficult to extract quantitative data from these images. On the contrary, Dixon methods provide quantitative measure of fat fraction. Usually, whole-body (WB) exams consist in the acquisition of T1w images, followed by Dixon acquisitions on targeted regions to quantitatively assess fat infiltration. With the aim of improving and accelerating the qualitative assessment of neuromuscular disorders, we propose to avoid the T1w acquisition altogether, by allowing to perform the visual diagnosis workup on a WB Dixon imaging. 20 patients underwent WB
MRI at 3T. WB T1w images were acquired with a 2D TSE sequence (resolution = 1.1 1.1 mm2, slice thickness = 6 mm, Tacq = 5 min 40 s). WB Dixon acquisition consisted in a 3D VIBE sequence with 3 echoes (resolution = 1 1 5 mm3, Tacq = 14 min 5 s). Quantitative fat fraction maps were derived using a standard 3-points Dixon reconstruction method. A customed lookup table was embedded in the DICOM file to provide a colored lecture of fat fraction maps corresponding to the Mercuri’s scale. Our results show that the acquisition of a high resolution WB Dixon imaging is possible in less than 15 min using an optimized VIBE sequence. This provides quantitative data that are more suitable than T1w images for longitudinal natural history studies, or therapeutic clinical trials. Moreover, the color representation renders the visual grading of the muscles more convenient and less operator dependent as it is based on actual fat fraction measurements. WB Dixon might then overcome the use of WB T1w images for diagnostic of neuromuscular disorders. http://dx.doi:10.1016/j.nmd.2014.06.149
G.P.120 The Sodium/Hydrogen Exchanger (NHE-1): A promising novel target for DMD U. Burki 1, E. Greally 1, S. Laval 1, S. Scha¨fer 2, V. Straub 1 1 Newcastle University, Newcastle upon Tyne, UK; 2 Peacock Pharma GmbH, Goch, Germany Abnormal intracellular calcium load is one of the most consistent findings in Duchenne muscular dystrophy (DMD) but previous attempts to improve the dystrophic pathology with calcium antagonists have been unsuccessful. However, there is an intriguing possibility of restoring calcium homeostasis indirectly by exploiting the relationship between the Sodium/Hydrogen Exchanger (NHE-1) and the Sodium/Calcium Exchanger (NCX). NHE-1 has been reported to be abnormally overactive in DMD models, leading to an increased influx of sodium which in turn switches the NCX into reserve mode leading to calcium influx. Using selective NHE-1 inhibitors the influx of sodium can be reduced thereby allowing the NCX to revert back to normal mode, where calcium is extruded, thus reducing the cellular calcium load. In collaboration with our industrial partner Peacock Pharma, we have demonstrated the potential of NHE-1 inhibition in the mdx mouse model for DMD by chronically treating animals with a novel NHE-1 inhibitor. The pilot study showed significantly reduced calcium uptake in treated mice (n = 6) using manganese enhanced MRI (MEMRI). Manganese acts as a contrast agent in T1 weighted MRI and is thought to be taken up by cardiac and skeletal muscle by the same receptors as calcium. There was also an increase in functional grip strength, although not statistically significant the results are nevertheless encouraging and indicate the potential of this novel approach in DMD. This is currently being investigated more thoroughly using a greater number of animals (n = 12) treated chronically via drug in chow over 6-months and assessed using MEMRI and grip test. In addition, in vitro calcium-flux assays (e.g. Fluo-4) are used to determine the potency and investigate the mechanism of action of this drug. The objective of our study is to provide the requisite pre-clinical data that would enable these drugs to progress towards clinical trials. http://dx.doi:10.1016/j.nmd.2014.06.150
G.P.121 Fast, precise, interactive segmentation of skeletal muscle NMR images P.G. Carlier, A. Shukelovich, P.Y. Baudin, J.M. Boisserie, J. Le Louer, N. Azzabou Institute of Myology, Paris, France