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Advantages and drawbacks of breast DTI
European Journal of Radiology 81S1 (2012) S45–S47
Contents lists available at SciVerse ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Advantages and drawbacks of breast DTI Edna Furman-Harana , Erez Eyala , Myra Shapiro-Feinbergb , Noam Nissana , Dov Grobgelda , Noemi Weisenbergb , Hadassa Degania, * a Weizmann
Institute of Science, Rehovot, b Meir Medical Center, Kfar Saba, Israel
In 1965, Stejskal and Tanner developed the pulsed gradient spin echo (PGSE) technique for measuring the diffusion coefficient in solution [1]. The discovery of MRI led to the development of diffusion imaging sequences particularly sequences based on echo planar imaging – EPI that facilitate fast clinical diffusion measurements. As a result of gradient strength limitations in most human scanners, it is necessary to use long finite-width gradient pulses in order to achieve high b values and hence, the short gradient pulse approximation breaks down. Nevertheless, it was shown by Zielinski and Sen [2] that diffusion experiments with long diffusion gradient pulses still measure a physical parameter reflecting self diffusion in systems that have open geometry and large amount of restriction as is the case in most tissues. Water diffusion in tissues presents a highly complex process as the system is composed of several different compartments with partial restriction processes within the compartments. Water diffusion coefficients of tissues are not merely affected by Brownian motion, but also by additional contributions of flow, restriction by cell membrane, extracellular tortuosity and exchange between tissue compartments. Water diffusion in tissues is often anisotropic due to restriction by membranes and walls of various micro-structures. Namely, anisotropic diffusion leads to variable diffusion coefficients for various directions and hence the diffusion coefficients are described by a diffusion tensor. The diffusion of water molecules in the mammary tissue presents a particular example of restricted movement in well defined microstructures composed of the ductal/ glandular trees. The, diffusion in parallel to the walls of the ducts is free; however, it is restricted in the directions perpendicular to the walls. The extent of restriction will depend on the experimental diffusion time versus the size of the ductal and glandular regions. Blockage of the ducts by cancer cells predominantly affects the free diffusion in parallel to the walls, reducing the diffusion coefficient in all directions, and consequently the extent of anisotropy. We have applied an experimental protocol to track this anisotropic motion using diffusion gradients in 30 to 60 directions and two b-values with a relatively high diffusion time [3]. In voxels with anisotropic water diffusion the distribution of the fraction of change in signal intensity in all directions of the field gradients assumed an anisotropic ellipsoid form, whereas in voxels with isotropic * Hadassa Degani, PhD, Department of Biological regulation, Weizmann Institute of Science, Israel. Tel.: +972 8 9342017; fax: +972 8 9346154. E-mail address: [email protected] (H. Degani). 0720-048X/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
water diffusion the change in signal intensity was similar in all directions, close to a sphere form. A non linear regression process to a symmetric tensor fitted the data in each voxel using the StejskalTanner equation The tensor was further diagonalized by principal component analysis, yielding for each voxel the eigenvectors (n) defining the diffusion direction in three orthogonal axes of an ellipsoid and their corresponding eigenvalues (l) that quantify the diffusion coefficient in each direction, arranged from high to low eigenvalues: n1 , l1 ; n2 , l2 ; n3 , l3 . Vector maps of v1 and parametric maps of the prime diffusion coefficient (l1 ) and maximal anisotropy index (l1 -l3 ) enabled separating the ductal/ glandular regions from the connective-fibrous tissue regions and to detect blockage in the ductal/glandular tissue caused by growth of cancer cells. The cancer cells hindered the extracellular diffusion, particularly in the direction parallel to the walls, reducing l1 and also reducing significantly the diffusion maximal anisotropy. We found in our first retrospective study [3] that the DTI detection and diagnostic efficiencies of breast lesions are high and similar to that of DCEMRI, although the spatial resolution of DTI is lower than the spatial resolution achieved by DCE-MRI. Further experiments indicated that DTI is highly useful in dense breasts, where S/N is high and fat suppression is relatively homogeneous. However, in part of the fatty breasts we have encountered technical challenges that need to be resolved in order to achieve routine clinical application for this new method. In general EPI has the advantage of being a very efficient acquisition modality, with excellent signal to noise per unit time. However, it is highly sensitive to eddy currents distortions, and suffers from EPI ghosts artifacts, and from geometrical and intensity distortions along the phase-encoding direction caused by field inhomogeneities. We have used the twice refocused echo planar imaging sequence [4] that reduced the eddy current distortions but we still encountered other sources of artifacts resulting from imperfect fat suppression and geometric image distortions due to field inhomogeneity, particularly in air tissue interfaces. To overcome these distortions it is imperative to focus on improved shimming [5]. In our tests we optimized the shimming through several iterations using automatic and manual shimming tools. In addition, we applied a correction using a field mapping technique described by Jezzard and Balaban [6] that characterizes the field inhomogeneities so that the image can be unwrapped. The application of this method is demonstrated in Figs. 1 and 2. This correction improved image alignment in part of the cases but it failed in fatty breasts and in regions with high field inhomogeneity particularly at the edges and near the nipple.
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E. Furman-Haran et al. / European Journal of Radiology 81S1 (2012) S45–S47
Fig. 1. Correction of geometric EPI distortions in breast DTI using a phase map. (A) A central breast slice acquired at b = 0 using twice-refocused-EPI without distortion correction. (B) The same image as in (A) after distortion correction. (C) A phase map of the same slice as in (A), in the scale of Hz. The phase map was calculated from gradient echo images of the same slice, acquired with different echo times and calculated as described in [6]. (D) A shift map scaled in pixels, calculated from to the phase map in (C).
Fig. 2. The effect of distortions correction on the parametric maps derived from DTI. (A1) T2-weighted image of a slice with infiltrating lobular cancer, in the left breast. (A2) l1 parametric map, overlaid on the image in A1, before distortion correction. Note that the cancer lesion exhibits values of this parameter below 1.7×10−3 mm2 /s. (A3) l1 parametric map that underwent distortion correction, overlaid on the image in A1. (B1) T2-weighted image of a slice with no indications of breast disease. (B2) l1 parametric map, overlaid on the image in B1, before distortion correction. Note that l1 values are above 1.7×10−3 mm2 /s. (B3) l1 parametric map, that underwent distortion correction, overlaid on the image in B1.
Overall, after three years of experience with breast DTI through the scanning of 141 subjects with malignant and benign lesions, as well as with no indications of breast disease (all protocols were approved by the Internal Review Board of Meir Medical Center and a signed informed consent was obtained from all subjects) we find that the main advantages of breast DTI are as follows: 1. Breast DTI is a completely non-invasive method 2. The method requires short scanning times of 5–10 minutes 3. The method yields two independent diffusion parameters associated with the microstructure of the tissue that together improve sensitivity and specificity of breast cancer detection. However, implementing DTI as a routine protocol is currently limited by drawbacks associated with technical issues such as: 1. DTI measures a decrease in signal intensity and hence suffers from low S/N and consequently limited spatial resolution (in our study at 3 tesla 2×2×2 mm3 ) 2. The method is highly sensitive to the presence of fat, requiring an “ideal” and homogeneous fat suppression.
3. Current protocols suffer from EPI related artifacts due to inhomogeneous field and tissue/air susceptibility differences. In conclusion, clinical application of parametric breast DTI is feasible and has the potential to become an important method in breast imaging, particularly for dense breasts. However, improvements are required in hardware, pulse sequence and software, in order to overcome the technical problems causing artifacts and to achieve optimal spatial resolution. Competing interests: All authors have no potential conflicts of interest to disclose with regard to this work. Acknowledgements: We would like to thank Mr. Nahum Stern and Ms. Fanny Attar for their excellent technical assistance. H.D. holds the Fred and Andrea Fallek Chair for Breast Cancer Research. References 1. Stejskal EO, Tanner J. Spin diffusion measurements: spin echos in the presence of a time-dependent field gradient. J Chem Phys 1965;42:288–92.
E. Furman-Haran et al. / European Journal of Radiology 81S1 (2012) S45–S47 2. Zielinski LJ, Sen PN. Effects of finite-width pulses in the pulsed-field gradient measurement of the diffusion coefficient in connected porous media. J Magn Reson 2003;165:153–61. 3. Eyal E, Shapiro-Feinberg M, Furman-Haran E, et al. Parametric diffusion tensor imaging of the breast. Invest Radiol 2012;47:284–91. 4. Reese TG, Heid O, Weisskoff RM, Wedeen VJ. Reduction of eddy-current-induced
S47
distortion in diffusion MRI using a twice-refocused spin echo. Magn Reson Med 2003;49:177–82. 5. Hancu I, Govenkar A, Lenkinski RE, Lee S-K. On shimming approaches in 3T breast MRI. Magn Reson Med, May 2012, [Epub ahead of print]. 6. Jezzard P, Balaban RS. Correction for geometric distortion in echo planar images from B0 field variations. Magn Reson Med 1995;34:65–73.
Contents lists available at SciVerse ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Advantages and drawbacks of breast DTI Edna Furman-Harana , Erez Eyala , Myra Shapiro-Feinbergb , Noam Nissana , Dov Grobgelda , Noemi Weisenbergb , Hadassa Degania, * a Weizmann
Institute of Science, Rehovot, b Meir Medical Center, Kfar Saba, Israel
In 1965, Stejskal and Tanner developed the pulsed gradient spin echo (PGSE) technique for measuring the diffusion coefficient in solution [1]. The discovery of MRI led to the development of diffusion imaging sequences particularly sequences based on echo planar imaging – EPI that facilitate fast clinical diffusion measurements. As a result of gradient strength limitations in most human scanners, it is necessary to use long finite-width gradient pulses in order to achieve high b values and hence, the short gradient pulse approximation breaks down. Nevertheless, it was shown by Zielinski and Sen [2] that diffusion experiments with long diffusion gradient pulses still measure a physical parameter reflecting self diffusion in systems that have open geometry and large amount of restriction as is the case in most tissues. Water diffusion in tissues presents a highly complex process as the system is composed of several different compartments with partial restriction processes within the compartments. Water diffusion coefficients of tissues are not merely affected by Brownian motion, but also by additional contributions of flow, restriction by cell membrane, extracellular tortuosity and exchange between tissue compartments. Water diffusion in tissues is often anisotropic due to restriction by membranes and walls of various micro-structures. Namely, anisotropic diffusion leads to variable diffusion coefficients for various directions and hence the diffusion coefficients are described by a diffusion tensor. The diffusion of water molecules in the mammary tissue presents a particular example of restricted movement in well defined microstructures composed of the ductal/ glandular trees. The, diffusion in parallel to the walls of the ducts is free; however, it is restricted in the directions perpendicular to the walls. The extent of restriction will depend on the experimental diffusion time versus the size of the ductal and glandular regions. Blockage of the ducts by cancer cells predominantly affects the free diffusion in parallel to the walls, reducing the diffusion coefficient in all directions, and consequently the extent of anisotropy. We have applied an experimental protocol to track this anisotropic motion using diffusion gradients in 30 to 60 directions and two b-values with a relatively high diffusion time [3]. In voxels with anisotropic water diffusion the distribution of the fraction of change in signal intensity in all directions of the field gradients assumed an anisotropic ellipsoid form, whereas in voxels with isotropic * Hadassa Degani, PhD, Department of Biological regulation, Weizmann Institute of Science, Israel. Tel.: +972 8 9342017; fax: +972 8 9346154. E-mail address: [email protected] (H. Degani). 0720-048X/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
water diffusion the change in signal intensity was similar in all directions, close to a sphere form. A non linear regression process to a symmetric tensor fitted the data in each voxel using the StejskalTanner equation The tensor was further diagonalized by principal component analysis, yielding for each voxel the eigenvectors (n) defining the diffusion direction in three orthogonal axes of an ellipsoid and their corresponding eigenvalues (l) that quantify the diffusion coefficient in each direction, arranged from high to low eigenvalues: n1 , l1 ; n2 , l2 ; n3 , l3 . Vector maps of v1 and parametric maps of the prime diffusion coefficient (l1 ) and maximal anisotropy index (l1 -l3 ) enabled separating the ductal/ glandular regions from the connective-fibrous tissue regions and to detect blockage in the ductal/glandular tissue caused by growth of cancer cells. The cancer cells hindered the extracellular diffusion, particularly in the direction parallel to the walls, reducing l1 and also reducing significantly the diffusion maximal anisotropy. We found in our first retrospective study [3] that the DTI detection and diagnostic efficiencies of breast lesions are high and similar to that of DCEMRI, although the spatial resolution of DTI is lower than the spatial resolution achieved by DCE-MRI. Further experiments indicated that DTI is highly useful in dense breasts, where S/N is high and fat suppression is relatively homogeneous. However, in part of the fatty breasts we have encountered technical challenges that need to be resolved in order to achieve routine clinical application for this new method. In general EPI has the advantage of being a very efficient acquisition modality, with excellent signal to noise per unit time. However, it is highly sensitive to eddy currents distortions, and suffers from EPI ghosts artifacts, and from geometrical and intensity distortions along the phase-encoding direction caused by field inhomogeneities. We have used the twice refocused echo planar imaging sequence [4] that reduced the eddy current distortions but we still encountered other sources of artifacts resulting from imperfect fat suppression and geometric image distortions due to field inhomogeneity, particularly in air tissue interfaces. To overcome these distortions it is imperative to focus on improved shimming [5]. In our tests we optimized the shimming through several iterations using automatic and manual shimming tools. In addition, we applied a correction using a field mapping technique described by Jezzard and Balaban [6] that characterizes the field inhomogeneities so that the image can be unwrapped. The application of this method is demonstrated in Figs. 1 and 2. This correction improved image alignment in part of the cases but it failed in fatty breasts and in regions with high field inhomogeneity particularly at the edges and near the nipple.
S46
E. Furman-Haran et al. / European Journal of Radiology 81S1 (2012) S45–S47
Fig. 1. Correction of geometric EPI distortions in breast DTI using a phase map. (A) A central breast slice acquired at b = 0 using twice-refocused-EPI without distortion correction. (B) The same image as in (A) after distortion correction. (C) A phase map of the same slice as in (A), in the scale of Hz. The phase map was calculated from gradient echo images of the same slice, acquired with different echo times and calculated as described in [6]. (D) A shift map scaled in pixels, calculated from to the phase map in (C).
Fig. 2. The effect of distortions correction on the parametric maps derived from DTI. (A1) T2-weighted image of a slice with infiltrating lobular cancer, in the left breast. (A2) l1 parametric map, overlaid on the image in A1, before distortion correction. Note that the cancer lesion exhibits values of this parameter below 1.7×10−3 mm2 /s. (A3) l1 parametric map that underwent distortion correction, overlaid on the image in A1. (B1) T2-weighted image of a slice with no indications of breast disease. (B2) l1 parametric map, overlaid on the image in B1, before distortion correction. Note that l1 values are above 1.7×10−3 mm2 /s. (B3) l1 parametric map, that underwent distortion correction, overlaid on the image in B1.
Overall, after three years of experience with breast DTI through the scanning of 141 subjects with malignant and benign lesions, as well as with no indications of breast disease (all protocols were approved by the Internal Review Board of Meir Medical Center and a signed informed consent was obtained from all subjects) we find that the main advantages of breast DTI are as follows: 1. Breast DTI is a completely non-invasive method 2. The method requires short scanning times of 5–10 minutes 3. The method yields two independent diffusion parameters associated with the microstructure of the tissue that together improve sensitivity and specificity of breast cancer detection. However, implementing DTI as a routine protocol is currently limited by drawbacks associated with technical issues such as: 1. DTI measures a decrease in signal intensity and hence suffers from low S/N and consequently limited spatial resolution (in our study at 3 tesla 2×2×2 mm3 ) 2. The method is highly sensitive to the presence of fat, requiring an “ideal” and homogeneous fat suppression.
3. Current protocols suffer from EPI related artifacts due to inhomogeneous field and tissue/air susceptibility differences. In conclusion, clinical application of parametric breast DTI is feasible and has the potential to become an important method in breast imaging, particularly for dense breasts. However, improvements are required in hardware, pulse sequence and software, in order to overcome the technical problems causing artifacts and to achieve optimal spatial resolution. Competing interests: All authors have no potential conflicts of interest to disclose with regard to this work. Acknowledgements: We would like to thank Mr. Nahum Stern and Ms. Fanny Attar for their excellent technical assistance. H.D. holds the Fred and Andrea Fallek Chair for Breast Cancer Research. References 1. Stejskal EO, Tanner J. Spin diffusion measurements: spin echos in the presence of a time-dependent field gradient. J Chem Phys 1965;42:288–92.
E. Furman-Haran et al. / European Journal of Radiology 81S1 (2012) S45–S47 2. Zielinski LJ, Sen PN. Effects of finite-width pulses in the pulsed-field gradient measurement of the diffusion coefficient in connected porous media. J Magn Reson 2003;165:153–61. 3. Eyal E, Shapiro-Feinberg M, Furman-Haran E, et al. Parametric diffusion tensor imaging of the breast. Invest Radiol 2012;47:284–91. 4. Reese TG, Heid O, Weisskoff RM, Wedeen VJ. Reduction of eddy-current-induced
S47
distortion in diffusion MRI using a twice-refocused spin echo. Magn Reson Med 2003;49:177–82. 5. Hancu I, Govenkar A, Lenkinski RE, Lee S-K. On shimming approaches in 3T breast MRI. Magn Reson Med, May 2012, [Epub ahead of print]. 6. Jezzard P, Balaban RS. Correction for geometric distortion in echo planar images from B0 field variations. Magn Reson Med 1995;34:65–73.