Evaluating Gadolinium Deposition in Rabbit Cortical Bone by Using Ultrashort Echo Time T1 Mapping: Preliminary Results
Kaixuan Zhao1, Shisi Li2, Yingjie Mei1,3, Qinqin Yu2, Keyan Yu2, Cuiling Zhu2, Jian Wang2, Hanwen Deng1, Xiaodong Zhang2, Jiang Du4, and Yanqiu Feng1

1School of Biomedical Engineering, Guangdong Provincial Key Laborary of Medical Image Processing, Southern Medical University, Guang Zhou, China, 2Imaging department of Southern Medical University affiliated the third hospital, Guang Zhou, China, 3Philips Healthcare, Guang Zhou, China, 4Department of Radiology, University of California San Diego, San Diego, California., San Diego, CA, United States


Gadolinium based contrast agents (GBCA) injection for enhanced MRI can induce gadolinium deposition in bones. In this work we investigated the feasibility of evaluating gadolinium deposition in rabbit cortical bone by using ultrashort echo time (UTE) T1 mapping at 7T. Lower T1 values were observed in the GBCA injection group than those in the control group (341±17.6ms vs. 450±10ms). This preliminary result indicates that UTE T1 mapping may be a feasible technique for evaluating bone gadolinium deposition.


Gadolinium based contrast agents (GBCAs) are commonly used in MRI for enhancing tissue contrast. Recently, Nozomu Murata et al1 demonstrated that gadolinium (Gd) deposition in cortical bone was 23 times higher than that in brain after injection of GBCA. The Gd is one of the greatest competitive inhibitor of ionic calcium (Ca2+). The non-invasive technique for assessing Gd deposition is still lacking2. In this work, we aimed to investigate the feasibility of assessing Gd deposition in rabbit cortical bone by using UTE T1 mapping3.


Ethics and Sample preparation:

This study was approved by local Ethics Review Board. Four male adult rabbits (1.9~2.0 Kg) were involved in the present study. Three rabbits were injected through auricular vein with 5ml/kg magnevist (equivalent to 2.5 mmol/kg) per injection, and one rabbit was used for control and injected with saline with 5 ml/kg per injection. The experiment schedule is shown in Fig.1.

For specimens processing, femoral midshafts of freshly slaughtered rabbits were obtained and cleaned of external muscles and soft tissues, and then cut into segments with a thickness of approximately 3 cm. Bone marrow in all specimens was removed. The specimens were soaked in Fomblin during MRI scan.

MR imaging:

All the experiments were performed on a Bruker 7T animal scanner with a volume coil for both signal excitation and detection. T1 mapping was performed by using 3D UTE with variable repetition time (Fig. 2). Rectangular pulse with a duration of 4.3 us and a bandwidth of 300 Khz was used for signal excitation. The protocols of 3D UTE were: TE=8 us, TR = 4,6,8,10,12,16,24,32,64,100,200 ms, FA = 10 degree, number of projections = 51360, FOV = 45Х45Х45 mm3,matrix size = 128Х128Х128, spatial resolution = 0.351Х0.351Х0.351 mm3.

Data analysis:

During bone extraction, one thigh-bone of the rabbit in the control group was found congenitally fractured, and its tibial midshafts (n=2) were used instead. Both the data analysis and ROI delineation were performed on homemade Matlab scripts. For T1 mapping, ROIs were manually drew on images of TR = 200 ms and then copied to other images. Mean signal intensities within ROIs were fitted by using Levenberg-Marquardt optimization4 with the equation:

$$S(TR_{i})=\frac{A(1 - e^{-\frac{TR_{i}}{T1}}))}{1-cos(FA)e^{-\frac{TR_{i}}{T1}}}cos(FA)e^{-\frac{TE}{T2}}$$

Where A is a scaling constant, FA denotes flip angle, TRi denotes the i-th TR, and TE denotes echo time. Fitting quality was indicated by the coefficient of determination R2. Mean T1 value of five slices with slice gap of 8×0.351 mm was considered as the specimen’s T1.


Representative T1 fitting results for GBCA and control groups are shown in Fig.3. Fitting quality was indicated by the coefficient of determination R2, and R2 was 0.9999 in all fittings. Table 1 summarized T1 value of all specimens. The mean T1 value was 341±17.6 ms for the GBCA injection group and 450±10 ms for the control group.


The T1 value of normal cortical bone is approximately 240ms at 3T5, thus, the T1 value of the cortical bone in the control group measured in this study is reasonable ( approximately 450±10 ms). The lower T1 value in the GBCA group than the control group is because gadolinium reduces free-water T1 value. Although the present study is limited in small sample size(n = 6 for GBCA and n = 3 for control), the preliminary results demonstrates that UTE based T1 mapping is a potential method for non-invasively assessing bone gadolinium deposition.




1.Murata N, Gonzalez-Cuyar LF, Murata K, Fligner C, Dills R, Hippe D, Maravilla KR. Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function. Investigative radiology 2016;51(7):447-453.

2.Lord ML, Chettle DR, Grafe JL, Noseworthy MD, McNeill FE. Observed Deposition of Gadolinium in Bone Using a New Noninvasive in Vivo Biomedical Device: Results of a Small Pilot Feasibility Study. Radiology 2018;287(1):96-103.

3.Du J, Carl M, Bydder M, Takahashi A, Chung CB, Bydder GM. Qualitative and quantitative ultrashort echo time (UTE) imaging of cortical bone. Journal of magnetic resonance 2010;207(2):304-311.

4.Marquardt DW. An Algorithm for Least-Squares Estimation of Nonlinear Parameters. Journal of the Society for Industrial and Applied Mathematics 1963;11(2):431-441.

5.Ma YJ, Lu X, Carl M, Zhu Y, Szeverenyi NM, Bydder GM, Chang EY, Du J. Accurate T1 mapping of short T2 tissues using a three-dimensional ultrashort echo time cones actual flip angle imaging-variable repetition time (3D UTE-Cones AFI-VTR) method. Magnetic resonance in medicine 2018;80(2):598-608.


Figure 1. Experiment schedule of the present study. 5 ml/kg magnevist was injected to gadolinium-based contrast agent (GBAC) group once a day, and 6 times a week for 4 weeks. 8 days after the last injection, the rabbits are slaughtered for bone extraction and MR scan. For control group, 5ml/kg saline was used instead

Figure.2, Pulse sequence of 3D UTE. A block pulse with during of 4.3 us and bandwidth of 300 Khz for signal excitation. Signal acquisition was performed on the gradient ramp by non-linear sampling.

Figure.3. Representative slice T1 fitting for GBCA group and control group. ROIs are shown in images with TR = 200ms, red mask for GBCA group and blue mask for control group. The quantified T1 values are 333 ms and 473 ms for GBCA group and control group respectively.

Table 1. Summary of T1 values for GBCA group and control group. Note that right femoral-bone of control group is congenital fractured and was excluded, thus the T1 value of cortical bone at tibial midshaft were measured.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)