Amide Proton Transfer Imaging: A Novel MR Method for High-grade Brain Tumors.

Transcription

1 Amide Proton Transfer Imaging: A Novel MR Method for High-grade Brain Tumors. Poster No.: C-1732 Congress: ECR 2013 Type: Scientific Exhibit Authors: M. Ida, M. Ishizuka, T. Suzuki, Y. Kubo, K. Hino, S. Ikuta, A. Kitakado; Tokyo/JP Keywords: Tissue characterisation, Molecular imaging, MR, Neuroradiology brain DOI: /ecr2013/C-1732 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 23

2 Purpose INTRDUCTION Chemical exchange-dependent saturation transfer (CEST) imaging is an advanced MR imaging technique in the field of molecular imaging. CEST imaging provides a unique MR contrast originating from magnetization transfer asymmetry. Endogenous or exogenous compounds containing exchangeable protons that resonate at a frequency different from the bulk water are selectively saturated and then, detected indirectly through the water signal suppression due to transfer of magnetization from saturated restricted solute protons into adjacent water protons caused by dipolar cross-relaxation and 2) chemical exchange. Amide proton transfer (APT) imaging is one of CEST imaging in a clinical basis. Amide proton transfer (APT) imaging is one of CEST imaging in which amide protons of solute proteins and peptides are irradiated RF signal at the specific frequency distant from that of the bulk water to accomplish indirect detection using the free water signal. PURPOSE The purpose was to evaluate whether APT imaging can provide additional information in differentiating malignant and anaplastic brain tumors (WHO grade III & IV) from benign tumors (grade II) and chemotherapy-induced pseudoprogression and irradiation necrosis. Page 2 of 23

3 Methods and Materials Principle Mobile protons (i.e. free water and fat) have a relatively long T2 (T2 = ms) and resonate over a narrow range of resonance frequencies. In contrast, restricted protons (i.e. bounded to protein and peptide) have a short T2 (T2 = ms) and wide range of resonance frequencies. Mobile protons can be "visible" on MR images obtained at ordinary TE; however restricted proton bounded to macromolecule cannot be detected at any reasonable TE. Longitudinal proton magnetization can be exchanged continuously between water (mobile protons) and hydrogen bounded to the surface of macromolecules (restricted protons) by direct through-space dipolar coupling and chemical exchange. Principle of chemical exchange saturation transfer (CEST) is similar to that of magnetization transfer (MT); however, some differences are present in measurement approach. MT uses RF irradiation with wide range of resonance frequencies to saturate protons bounded to the surface of macromolecule. In CEST imaging solute protons are selectively saturated using at their specific resonance frequency of the targeted molecule. Fig. 1 on page 5 and Fig. 2 on page 5 Figure 3 shows the difference of and measurement approach between magnetization transfer (MT) and chemical exchange saturation transfer (CEST) Fig. 3 on page 6 In APT imaging, amide protons of endogenous cytosolic protons and peptides in the brain tissue are detected by using RF pulse at 3.5ppm differ from the bulk water. SUBJECTS A total of 13 consecutive patients with intraparenchymal glial tumors of varying grade and chemoradiation-induced necrosis were investigated (table 1). Table 1 on page 9 MR Imaging MR imaging was conducted using a whole-body clinical system operating at 3-tesla (MAGNETOM Trio A Tim system, Siemens, Germany). A body coil was used for RF transmission and a thirty-two channel phased-array head coil for signal reception. APT imaging data of the brain tissue was obtained in a transverse plane with a single-slice gradient-echo sequence with the following parameters (work- Page 3 of 23

4 in-progress): TE/TR, 2.46/ 5.6 msec; matrix, 192 x 256; FOV, 220 mm; slice thickness, 5.0 mm; number of excitation, 2; and a GRAPPA reduction factor, 2. A pulsed wave RF saturation was used of power 1.6uT, duration 100 ms and number of repetition, 5. The APT images were acquired using 13 offsets from ppm to -4.5 ppm Fig. 4 on page 7. The acquisition time was 39 seconds per one slice. To make APT-weighted images, MTR asymmetry (MTRasym) was calculated between +3.5 ppm and ppm Fig. 5 on page 8. The optimized protocol for evaluation of brain tumors in our hospital consisted of high-resolution, fast SE T2-weighted imaging and FLAIR imaging, single-shot EPI diffusion imaging (DWI and ADC, b value =1000), APT imaging (as above), dynamic-enhanced perfusion imaging and contrast-enhanced T1-weighted imaging. Page 4 of 23

5 Images for this section: Fig. 1 Page 5 of 23

6 Fig. 2 Page 6 of 23

7 Fig. 3 Page 7 of 23

8 Fig. 4 Page 8 of 23

9 Fig. 5 Page 9 of 23

10 Table 1 Page 10 of 23

11 Results Findings of APT imaging are summarized in table 2. 1) Increased APT signal was observed in tumor tissues in all patients with grade III and IV. Elevation of APT signal was visible not only the Gd-enhancing core (solid portion) but also cystic portion (degeneration). Figure 6 shows MR images in a patient with glioblastoma multiforme (WHO grade IV) with decreased ADC representing higher cellularity and with increased rcbv representing proliferation of tumor neovascularity. APT signal was increased within the neoplasm. Figure 7 illustrates MR images in a patient with glioblastoma multiforme (WHO grade IV) with increased rcbv representing proliferation of tumor neovascularity. APT signal can be increased not only in the solid portion but also cystic degeneration in GBM Figure 8 represents MR images of anaplastic oligodendroglioma confirmed histopathologically. Reduction of ADC and slightly increased rcbv are observed in a part of the neoplasm, the genu of the corpus callosum, representing anaplastic lesion(over III) ; however, increased ADC and reduction of rcbf are noted in almost part of the intraaxial tumor, suggesting diffuse astrocytoma (II). APT-weighted images show diffuse APT signal in the entire lesion. Total removal of the tumor was carried out and diffuse anaplastic astrocytoma was confirmed histopathologically corresponding to the area with APT signal 2) However, no elevation of APT signal was recognized in patients with grade II or grade I, which was benigh histopathologially. Figure 9 demonstrates MR images in a case with diffuse astrocytoma (II). Ill-defined, hyperintense lesion is recognized in the medio-temporal lobe on T2WI with no Gd-enhancement (not demonstrated). No APT signal is visible with in the lesion (white circle). Figure 10 reveals MR images of clinically-diagnosed dysplastic gangliocytoma (I). T2WI shows intracerebellar neoplasm with folia pattern with no Gd-enhamcement, representing dysplastic gangliocytoma (I). 3) No APT signal was visualized in chemoradiation-induced necrosis with Gdenhancement, i.e. pseudoprogression after temozolomide. Page 11 of 23

12 Figure 11 represents MR images in a case of temozolomide-induced necrosis with Gd-enhancement, so-called "pseudoprogression. There is no increase in APT signal. Page 12 of 23

13 Images for this section: Table 2 Page 13 of 23

14 Fig. 6 Page 14 of 23

15 Fig. 7 Page 15 of 23

16 Fig. 8 Page 16 of 23

17 Fig. 9 Page 17 of 23

18 Fig. 10 Page 18 of 23

19 Fig. 11 Page 19 of 23

20 Conclusion APT images obtained at 3-tesla is able to detect the increase in amide proteins and peptide in the malignant brain neoplasms. APT imaging can provide adjunct information utilized for differentiating malignant brain tumors from benign tumors and from posttherapeutic necrosis. Advantages Increased APT signal observed in GBM (WHO grade IV) and anaplastic glial tumors (III) APT signal was visible not only the Gd-enhancing solid portion but also cystic degeneration of malignant tumors. No elevation of APT signal was recognized in benign (I and II) and chemoradiation-induced necrosis (so-called pseudoprogression with Gdenhancement). Limitations Artifacts due to B0 inhomogeneity. Page 20 of 23

21 Images for this section: Table 3 Page 21 of 23

22 References Zhou J, Lal B, Wilson DA, Laterra J, van Zijl PC. Amide proton transfer (APT) contrast for imaging of brain tumors. MagnReson Med Dec;50(6): Jones CK, Schlosser MJ, van Zijl PC, Pomper MG, Golay X, Zhou J. Amide proton transfer imaging of human brain tumors at 3T. MagnReson Med Sep;56(3): Zhou J, Blakeley JO, Hua J, Kim M, Laterra J, Pomper MG, van Zijl PC. Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging. MagnReson Med Oct;60(4): Law M, Yang S, Wang H, Babb JS, Johnson G, Cha S, Knopp EA, Zagzag D. Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol. 2003;24: Page 22 of 23

23 Personal Information Masahiro Ida M.D. Department of Radiology, Tokyo Metropolitan Ebara Hospital, Tokyo, Japan. Page 23 of 23