- Email: [email protected]
New MRI Sequences
Joint Bone Spine 76 (2009) 588–590
Clinical-state-of-the-art
New MRI Sequences Anne Cotten ∗ , Erwan Kermarrec , Antoine Moraux , Jean-Franc¸ois Budzik Service de radiologie et imagerie musculosquelettique, centre de consultation et d’imagerie de l’appareil locomoteur, CHRU, 59037 Lille, France Accepted 1st September 2009
Abstract Every year, manufacturers of MRI machines introduce new sequences. Most of them result in improved spatial resolution and signal contrast, occasionally with a decrease in sequence duration or MRI time (as when a single 3D sequence is substituted for three 2D sequences). Some sequences that are specifically designed to obtain structural or functional information about a specific tissue (ultrashort TE, T2 mapping, spectroMRI) are used only for research purposes. Diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and tractography constitute an original microarchitectural approach based on water molecule diffusion. These methods are nearly ready to be introduced into clinical practice. They are discussed in this article. © 2009 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie. Keywords: Magnetic resonance imaging; Water molecule diffusion
1. Diffusion imaging Diffusion imaging assesses the random (Brownian) micromovements of water molecules within tissues. In the body, these micromovements are limited by various obstacles (e.g., cell membranes, proteins, macromolecules, and fibers) depending on the tissue and disease process. As an approximation, diffusion imaging can be viewed as focusing on extracellular water molecules. Free diffusion is defined as unimpeded molecule displacement in all directions. For instance, water contained in body fluids such as the cerebrospinal fluid can diffuse freely. Diffusion is limited, in contrast, when the molecules bounce against obstacles. Thus, diffusion imaging provides indirect information on the environment in which the water molecules move. The parameter used to assess the magnitude of water molecule movements (or diffusion) is the apparent diffusion coefficient (ADC). Low ADC values indicate limited diffusion and high values near-free diffusion. Diffusion-weighted imaging (DWI) is now widely performed in neuroradiology to detect recent stroke but is still rarely used to assess musculoskeletal diseases. One potential field of application is oncology. The high cell content in primary and secondary malignancies limits the diffusion of water, which is therefore
∗
Corresponding author. E-mail address: [email protected] (A. Cotten).
seen as high signal. This characteristic may also help to differentiate benign from malignant vertebral fractures [1–3]. Although preliminary results with soft-tissue tumors and bone tumors were somewhat disappointing, improvements in spatial resolution (enabling the identification of cystic or necrotic foci) and the optimization of several parameters (such as the b value), together with careful selection of regions of interest in the tumor, may lead to significant increases in specificity [4]. Modifications in the ADC value may correlate closely with the tumor response to chemotherapy or radiation therapy. Necrotic changes related to treatments are associated with increased water-molecule diffusion and, therefore, with higher ADC values [5]. The ADC modifications occur early, often antedating the changes in tumor size or structural appearance (decreased contrast enhancement and development of cystic/necrotic foci), which are the main criteria used to assess treatment efficacy. Thus, DWI may improve the accuracy of the preoperative assessment of viable tumor size and provide a measurement of the extent of tumor necrosis after chemotherapy. Whole-body DWI can be performed within a reasonable examination time to detect metastases (bone, nodes, or parenchymas). Recent technological advances have produced extremely promising results. Sensitivity and the positive predictive value are equal to or higher than those obtained using radionuclide bone scanning. In addition, DWI improves the performance characteristics of the standard MRI sequences (STIR, T2, T1, and T1 after gadolinium injection). Nevertheless, these
1297-319X/$ – see front matter © 2009 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie. doi:10.1016/j.jbspin.2009.09.002
A. Cotten et al. / Joint Bone Spine 76 (2009) 588–590
standard sequences remain indispensable to ensure sufficient specificity. The available data indicate that whole-body DWI compares favorably with positron emission tomography for the detection of metastatic disease. Whole-body DWI may also benefit the staging of multiple myeloma and lymphomas [6]. Emerging indications for whole-body DWI include osteoporosis [7], chondropathies, and chronic inflammatory joint disease. A study of patients with ankylosing spondylitis showed that ADC values within the inflammatory bone lesions diminished during treatment [8]. In some patients, ADC value abnormalities persisted after the regression of the high-signal foci on STIR sequences. 2. Diffusion tensor imaging and tractography Diffusion tensor imaging (DTI) and its direct application tractography are fascinating emerging methods for investigating anisotropic structures. 2.1. Definitions In DTI, the tissue architecture is used to obtain further information on molecular motion. In structures that contain elongated cells (nerve, muscle, or spinal cord, for instance), molecules move preferentially in the direction of the long axis of these cells. In other words, molecular mobility is anisotropic. The degree of diffusion anisotropy can be assessed based on fractional anisotropy (FA). When the water molecules travel along similar distances in all directions (the theoretical case of pure water), FA is close to zero. The maximal theoretical value of FA is one, which indicates that the molecules travel in a single direction. A starting voxel is selected within an anisotropic structure and a computer program then selects only those vectors exhibiting similar directionality. The volume is thus cleared of all voxels containing non-directional structures (fat) or structures with different directionalities. The result is a linear three-dimensional image that represents the selected structure. This procedure can be used to track fibers (tractography). A right-click of the mouse provides the FA and ADC values of the structure of interest. 2.2. DTI for investigating muscles Several studies have established that tractography can be used to investigate the overall structure and internal architecture of the muscles. More specifically, the architectural differences between pennate and non-pennate muscles can be determined, and the pennation angle can be measured [9,10]. FA values may vary with muscle training: thus, a moderate-intensity training program leads to a gradual increase in FA over the first month, whereas intensive training is associated with decreasing FA values. Tractography may provide information on muscle aging. Aging is associated with decreases in the number and diameter of the muscle fibers and with increases in the amount of connective tissue and fat within the muscle, which lead to a decrease in FA. The magnitude of these changes varies across muscle groups (e.g., at the calf they predominate in the flexor muscles).
589
In acute muscle injury, FA was decreased and ADC increased, whereas conventional structural sequences were normal [11]. The high-ADC focus extended beyond the low-FA focus, suggesting a means of differentiating the lesion itself (established architectural disorganization) from the surrounding edema. It has been suggested that the magnitude of the FA decrease may correlate with the severity of the muscle lesions. At foci of chronic muscle injury (microtrauma), collagen deposits limit the diffusion of water molecules, leading to a decrease in FA. Identical abnormalities have been found in patients with inflammatory muscle disease. The ADC changes match the high T2 signal from muscle, whereas the FA decrease reflects muscle atrophy and fat infiltration. Finally, an early ADC increase can be detected within denervated muscles before the development of electromyographic abnormalities [12]. 2.3. DTI for investigating nerves Tractography can be used to investigate peripheral nerves [13,14]. Two studies found decreased FA values of the median nerve in patients with carpal tunnel syndrome [15,16]. The determination of parameters that indicate microstructural nerve lesions holds appeal and may prove useful for monitoring denervation. Three-dimensional nerve reconstruction using tractography may help to plan the surgical treatment of nerve tumors and pseudotumors [17]. 2.4. DTI for investigating the spinal cord In patients with myelopathy due to cervical spondylosis, tractography provides accurate information on the site of spinal cord compression. Several studies found low FA values within the spinal cord subjected to compression [18,19]. Whether these changes have prognostic significance remains to be determined, although these preliminary results are very promising. In conclusion, diffusion imaging holds potential for broadening the realm of MRI beyond the description of structural characteristics to a complementary assessment of function. The development of 3T MRI, which provides considerably higher signal-to-noise ratios compared to 1.5T MRI, can be expected to hasten the dissemination of diffusion imaging as a clinical tool. References [1] Balliu E, Vilanova JC, Peláez I, et al. Diagnostic value of apparent diffusion coefficients to differentiate benign from malignant vertebral bone marrow lesions. Eur J Radiol 2009;69:560–6. [2] Baur A, Stäbler A, Brüning R, et al. Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus pathologic compression fractures. Radiology 1998;207:349–56. [3] Baur A, Dietrich O, Reiser M. Diffusion-weighted imaging of bone marrow: current status. Eur Radiol 2003;13:1699–708. [4] Nagata S, Nishimura H, Uchida M, et al. Diffusion-weighted imaging of soft tissue tumors: usefulness of the apparent diffusion coefficient for differential diagnosis. Radiat Med 2008;6:287–95.
590
A. Cotten et al. / Joint Bone Spine 76 (2009) 588–590
[5] Byun WM, Shin SO, Chang Y, et al. Diffusion-weighted MR imaging of metastatic disease of the spine: assessment of response to therapy. AJNR Am J Neuroradiol 2002;23:906–12. [6] Schmidt GP, Reiser MF, Baur-Melnyk A. Whole-body MRI for the staging and follow-up of patients with metastasis. Eur J Radiol 2009;70:393–400. [7] Hatipoglu HG, Selvi A, Ciliz D, et al. Quantitative and diffusion imaging as a new method to assess osteoporosis. AJNR Am J Neuroradiol 2007;28:1934–7. [8] Gaspersic N, Sersa I, Jevtic V, et al. Monitoring ankylosing spondylitis therapy by dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Skeletal Radiol 2008;37:123–31. [9] Budzik JF, Le Thuc V, Demondion X, et al. In vivo MR tractography of thigh muscles using diffusion imaging: initial results. Eur Radiol 2007;17:3079–85. [10] Kan JH, Heemskerk AM, Ding Z, et al. DTI-based muscle fiber tracking of the quadriceps mechanism in lateral patellar dislocation. J Magn Reson Imaging 2009;29:663–70. [11] Zaraiskaya T, Kumbhare D, Noseworthy MD. Diffusion tensor imaging in evaluation of human skeletal muscle injury. J Magn Reson Imaging 2006;24:402–8. [12] Holl N, Echaniz-Laguna A, Bierry G, et al. Diffusion-weighted MRI of denervated muscle: a clinical and experimental study. Skeletal Radiol 2008;37:1111–7.
[13] Skorpil M, Karlsson M, Nordell A. Peripheral nerve diffusion tensor imaging. Magn Reson Imaging 2004;22:743–5. [14] Hiltunen J, Suortti T, Arvela S, et al. Diffusion tensor imaging and tractography of distal peripheral nerves at 3T. Clin Neurophysiol 2005;116: 2315–23. [15] Khalil C, Hancart C, Le Thuc V, et al. Diffusion tensor imaging and tractography of the median nerve in carpal tunnel syndrome: preliminary results. Eur Radiol 2008;18:2283–91. [16] Stein D, Neufeld A, Pasternak O, et al. Diffusion tensor imaging of the median nerve in healthy and carpal tunnel syndrome subjects. J Magn Reson Imaging 2009;29:657–62. [17] Merlini L, Viallon M, De Coulon G, et al. MRI neurography and diffusion tensor imaging of a sciatic perineuroma in a child. Pediatr Radiol 2008;38:1009–12. [18] Mamata H, Jolesz FA, Maier SE. Apparent diffusion coefficient and fractional anisotropy in spinal cord: age and cervical spondylosis-related changes. J Magn Res Imaging 2005;22: 38–43. [19] Hori M, Okubo T, Aoki S, et al. Line scan diffusion tensor MRI at low magnetic field strength: feasibility study of cervical spondylotic myelopathy in an early clinical stage. J Magn Reson Imaging 2006;23: 183–8.
Clinical-state-of-the-art
New MRI Sequences Anne Cotten ∗ , Erwan Kermarrec , Antoine Moraux , Jean-Franc¸ois Budzik Service de radiologie et imagerie musculosquelettique, centre de consultation et d’imagerie de l’appareil locomoteur, CHRU, 59037 Lille, France Accepted 1st September 2009
Abstract Every year, manufacturers of MRI machines introduce new sequences. Most of them result in improved spatial resolution and signal contrast, occasionally with a decrease in sequence duration or MRI time (as when a single 3D sequence is substituted for three 2D sequences). Some sequences that are specifically designed to obtain structural or functional information about a specific tissue (ultrashort TE, T2 mapping, spectroMRI) are used only for research purposes. Diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and tractography constitute an original microarchitectural approach based on water molecule diffusion. These methods are nearly ready to be introduced into clinical practice. They are discussed in this article. © 2009 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie. Keywords: Magnetic resonance imaging; Water molecule diffusion
1. Diffusion imaging Diffusion imaging assesses the random (Brownian) micromovements of water molecules within tissues. In the body, these micromovements are limited by various obstacles (e.g., cell membranes, proteins, macromolecules, and fibers) depending on the tissue and disease process. As an approximation, diffusion imaging can be viewed as focusing on extracellular water molecules. Free diffusion is defined as unimpeded molecule displacement in all directions. For instance, water contained in body fluids such as the cerebrospinal fluid can diffuse freely. Diffusion is limited, in contrast, when the molecules bounce against obstacles. Thus, diffusion imaging provides indirect information on the environment in which the water molecules move. The parameter used to assess the magnitude of water molecule movements (or diffusion) is the apparent diffusion coefficient (ADC). Low ADC values indicate limited diffusion and high values near-free diffusion. Diffusion-weighted imaging (DWI) is now widely performed in neuroradiology to detect recent stroke but is still rarely used to assess musculoskeletal diseases. One potential field of application is oncology. The high cell content in primary and secondary malignancies limits the diffusion of water, which is therefore
∗
Corresponding author. E-mail address: [email protected] (A. Cotten).
seen as high signal. This characteristic may also help to differentiate benign from malignant vertebral fractures [1–3]. Although preliminary results with soft-tissue tumors and bone tumors were somewhat disappointing, improvements in spatial resolution (enabling the identification of cystic or necrotic foci) and the optimization of several parameters (such as the b value), together with careful selection of regions of interest in the tumor, may lead to significant increases in specificity [4]. Modifications in the ADC value may correlate closely with the tumor response to chemotherapy or radiation therapy. Necrotic changes related to treatments are associated with increased water-molecule diffusion and, therefore, with higher ADC values [5]. The ADC modifications occur early, often antedating the changes in tumor size or structural appearance (decreased contrast enhancement and development of cystic/necrotic foci), which are the main criteria used to assess treatment efficacy. Thus, DWI may improve the accuracy of the preoperative assessment of viable tumor size and provide a measurement of the extent of tumor necrosis after chemotherapy. Whole-body DWI can be performed within a reasonable examination time to detect metastases (bone, nodes, or parenchymas). Recent technological advances have produced extremely promising results. Sensitivity and the positive predictive value are equal to or higher than those obtained using radionuclide bone scanning. In addition, DWI improves the performance characteristics of the standard MRI sequences (STIR, T2, T1, and T1 after gadolinium injection). Nevertheless, these
1297-319X/$ – see front matter © 2009 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie. doi:10.1016/j.jbspin.2009.09.002
A. Cotten et al. / Joint Bone Spine 76 (2009) 588–590
standard sequences remain indispensable to ensure sufficient specificity. The available data indicate that whole-body DWI compares favorably with positron emission tomography for the detection of metastatic disease. Whole-body DWI may also benefit the staging of multiple myeloma and lymphomas [6]. Emerging indications for whole-body DWI include osteoporosis [7], chondropathies, and chronic inflammatory joint disease. A study of patients with ankylosing spondylitis showed that ADC values within the inflammatory bone lesions diminished during treatment [8]. In some patients, ADC value abnormalities persisted after the regression of the high-signal foci on STIR sequences. 2. Diffusion tensor imaging and tractography Diffusion tensor imaging (DTI) and its direct application tractography are fascinating emerging methods for investigating anisotropic structures. 2.1. Definitions In DTI, the tissue architecture is used to obtain further information on molecular motion. In structures that contain elongated cells (nerve, muscle, or spinal cord, for instance), molecules move preferentially in the direction of the long axis of these cells. In other words, molecular mobility is anisotropic. The degree of diffusion anisotropy can be assessed based on fractional anisotropy (FA). When the water molecules travel along similar distances in all directions (the theoretical case of pure water), FA is close to zero. The maximal theoretical value of FA is one, which indicates that the molecules travel in a single direction. A starting voxel is selected within an anisotropic structure and a computer program then selects only those vectors exhibiting similar directionality. The volume is thus cleared of all voxels containing non-directional structures (fat) or structures with different directionalities. The result is a linear three-dimensional image that represents the selected structure. This procedure can be used to track fibers (tractography). A right-click of the mouse provides the FA and ADC values of the structure of interest. 2.2. DTI for investigating muscles Several studies have established that tractography can be used to investigate the overall structure and internal architecture of the muscles. More specifically, the architectural differences between pennate and non-pennate muscles can be determined, and the pennation angle can be measured [9,10]. FA values may vary with muscle training: thus, a moderate-intensity training program leads to a gradual increase in FA over the first month, whereas intensive training is associated with decreasing FA values. Tractography may provide information on muscle aging. Aging is associated with decreases in the number and diameter of the muscle fibers and with increases in the amount of connective tissue and fat within the muscle, which lead to a decrease in FA. The magnitude of these changes varies across muscle groups (e.g., at the calf they predominate in the flexor muscles).
589
In acute muscle injury, FA was decreased and ADC increased, whereas conventional structural sequences were normal [11]. The high-ADC focus extended beyond the low-FA focus, suggesting a means of differentiating the lesion itself (established architectural disorganization) from the surrounding edema. It has been suggested that the magnitude of the FA decrease may correlate with the severity of the muscle lesions. At foci of chronic muscle injury (microtrauma), collagen deposits limit the diffusion of water molecules, leading to a decrease in FA. Identical abnormalities have been found in patients with inflammatory muscle disease. The ADC changes match the high T2 signal from muscle, whereas the FA decrease reflects muscle atrophy and fat infiltration. Finally, an early ADC increase can be detected within denervated muscles before the development of electromyographic abnormalities [12]. 2.3. DTI for investigating nerves Tractography can be used to investigate peripheral nerves [13,14]. Two studies found decreased FA values of the median nerve in patients with carpal tunnel syndrome [15,16]. The determination of parameters that indicate microstructural nerve lesions holds appeal and may prove useful for monitoring denervation. Three-dimensional nerve reconstruction using tractography may help to plan the surgical treatment of nerve tumors and pseudotumors [17]. 2.4. DTI for investigating the spinal cord In patients with myelopathy due to cervical spondylosis, tractography provides accurate information on the site of spinal cord compression. Several studies found low FA values within the spinal cord subjected to compression [18,19]. Whether these changes have prognostic significance remains to be determined, although these preliminary results are very promising. In conclusion, diffusion imaging holds potential for broadening the realm of MRI beyond the description of structural characteristics to a complementary assessment of function. The development of 3T MRI, which provides considerably higher signal-to-noise ratios compared to 1.5T MRI, can be expected to hasten the dissemination of diffusion imaging as a clinical tool. References [1] Balliu E, Vilanova JC, Peláez I, et al. Diagnostic value of apparent diffusion coefficients to differentiate benign from malignant vertebral bone marrow lesions. Eur J Radiol 2009;69:560–6. [2] Baur A, Stäbler A, Brüning R, et al. Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus pathologic compression fractures. Radiology 1998;207:349–56. [3] Baur A, Dietrich O, Reiser M. Diffusion-weighted imaging of bone marrow: current status. Eur Radiol 2003;13:1699–708. [4] Nagata S, Nishimura H, Uchida M, et al. Diffusion-weighted imaging of soft tissue tumors: usefulness of the apparent diffusion coefficient for differential diagnosis. Radiat Med 2008;6:287–95.
590
A. Cotten et al. / Joint Bone Spine 76 (2009) 588–590
[5] Byun WM, Shin SO, Chang Y, et al. Diffusion-weighted MR imaging of metastatic disease of the spine: assessment of response to therapy. AJNR Am J Neuroradiol 2002;23:906–12. [6] Schmidt GP, Reiser MF, Baur-Melnyk A. Whole-body MRI for the staging and follow-up of patients with metastasis. Eur J Radiol 2009;70:393–400. [7] Hatipoglu HG, Selvi A, Ciliz D, et al. Quantitative and diffusion imaging as a new method to assess osteoporosis. AJNR Am J Neuroradiol 2007;28:1934–7. [8] Gaspersic N, Sersa I, Jevtic V, et al. Monitoring ankylosing spondylitis therapy by dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Skeletal Radiol 2008;37:123–31. [9] Budzik JF, Le Thuc V, Demondion X, et al. In vivo MR tractography of thigh muscles using diffusion imaging: initial results. Eur Radiol 2007;17:3079–85. [10] Kan JH, Heemskerk AM, Ding Z, et al. DTI-based muscle fiber tracking of the quadriceps mechanism in lateral patellar dislocation. J Magn Reson Imaging 2009;29:663–70. [11] Zaraiskaya T, Kumbhare D, Noseworthy MD. Diffusion tensor imaging in evaluation of human skeletal muscle injury. J Magn Reson Imaging 2006;24:402–8. [12] Holl N, Echaniz-Laguna A, Bierry G, et al. Diffusion-weighted MRI of denervated muscle: a clinical and experimental study. Skeletal Radiol 2008;37:1111–7.
[13] Skorpil M, Karlsson M, Nordell A. Peripheral nerve diffusion tensor imaging. Magn Reson Imaging 2004;22:743–5. [14] Hiltunen J, Suortti T, Arvela S, et al. Diffusion tensor imaging and tractography of distal peripheral nerves at 3T. Clin Neurophysiol 2005;116: 2315–23. [15] Khalil C, Hancart C, Le Thuc V, et al. Diffusion tensor imaging and tractography of the median nerve in carpal tunnel syndrome: preliminary results. Eur Radiol 2008;18:2283–91. [16] Stein D, Neufeld A, Pasternak O, et al. Diffusion tensor imaging of the median nerve in healthy and carpal tunnel syndrome subjects. J Magn Reson Imaging 2009;29:657–62. [17] Merlini L, Viallon M, De Coulon G, et al. MRI neurography and diffusion tensor imaging of a sciatic perineuroma in a child. Pediatr Radiol 2008;38:1009–12. [18] Mamata H, Jolesz FA, Maier SE. Apparent diffusion coefficient and fractional anisotropy in spinal cord: age and cervical spondylosis-related changes. J Magn Res Imaging 2005;22: 38–43. [19] Hori M, Okubo T, Aoki S, et al. Line scan diffusion tensor MRI at low magnetic field strength: feasibility study of cervical spondylotic myelopathy in an early clinical stage. J Magn Reson Imaging 2006;23: 183–8.