MRI Evaluation for the Histologic Components of Soft-tissue Tumors: Comparison of MEDIC and Fast SE T2-weighted Imaging

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MRI Evaluation for the Histologic Components of Soft-tissue Tumors: Comparison of MEDIC and Fast SE T2-weighted Imaging Tae Yong Moon, M.D. 1, In Sook Lee, M.D. 1, Jun Woo Lee, M.D. 1, Kyung Un Choi, M.D. 2, Jeung Il Kim, M.D. 3, E. Edmund Kim, M.D. 4 Purpose : To compare Multi Echo Data Image Combination (MEDIC) and fast SE T2- weighted images with fat saturation (T2FS) to suggest more accurate evaluation of the histologic components of soft-tissue tumors. Materials and Methods : The experimental group included 25 histologic tissues (5 vascular, 4 neural, 4 fibrous, 4 hypercellular, 2 hemorrhagic necroses, 2 cystic, 2 lipoid, 1 myxoid stroma, and 1 thrombus) in 10 patients who had pathologically confirmed schwannoma (n = 3), hemangioma (n = 2), lipoma (n = 1), angiokeratoma (n = 1), synovial sarcoma (n = 1), liposarcoma (n = 1), and malignant fibrous histiocytoma (n = 1). The inhomogeneity values were measured using the standard deviation value (SD) divided by the mean value as SD presents an error amount similar to that of imaging heterogeneity. Results : The inhomogeneity values of 25 histologic components were lower on MEDIC than those on T2FS (p <.001). Conclusion : We conclude that MEDIC is more accurate than T2FS for evaluating the tissue components of soft-tissue tumors using digitalized data because MEDIC images have far lower inhomogeneity. Index words : MR, musculoskeletal system MR, soft-tissue tumors MEDIC Introduction Even though high-resolution MR scanners have recently been developed, MR imaging remains limited in its ability to precisely characterize the histologic components of soft tissue tumors as most of these tumors reveal a mosaic or pleomorphic pattern of JKSMRM 12:1-7(2008) 1 Department of Radiology, College of Medicine Pusan National University Hospital, Busan, Koera 2 Department of Pathology, College of Medicine Pusan National University Hospital, Busan, Koera 3 Department of Orthopedics, College of Medicine Pusan National University Hospital, Busan, Koera 4 Department of Radiology, University of Texas Medical School, Houston, TX, USA This study was supported by Medical Research Institute Grant (2005-44), Pusan National University. This study was presented at the 2007 European Society of Musculoskeletal Radiology, Izmir Hilton Hotel, Turkey Received; June 9, 2007, revised; October 15, 2007, accepted; December 2, 2007 Address reprint requests to : Tae-Yong Moon, M.D., Department of Radiology, Pusan National University Hospital 10, Amidong 1Ga, Seo-Gu, Busan 602-739, Korea Tel. 82-51-240-7387 Fax. 82-51-244-7534 E-mail: tymn@pusan.ac.kr - 1 -

Tae Yong Moon et al mesoderm origin on histopathology (1). The gross signal intensities of T2-weighted MR images have been divided as bright signal, high signal, low signal, and signal void according to the relative amount of mobile water in the tissues. However, those visual scales cannot accurately measure the amount of water in the various histologic components of the fibrous, neural, myxoid, hemorrhagic, and necrotic tissues (2, 3). To precisely and non-invasively evaluate the histologic components of soft-tissue tumors, a quantitative digitalized scale of MR signals derived from the monitor screen would be required. The fast SE T2- weighted MR images generally demonstrate too many disturbed artifacts to be able to evaluate their histologic components (4). The newly developed Multi Echo Data Image Combination (MEDIC) pulse sequence is a type of T2-weighted imaging without visible artifacts (5). And yet, there has not been any report of comparison of MEDIC and T2-weighted image. Therefore we have compared both pulse sequences of MR to evaluate the tissue components of soft-tissue tumors. Materials and Methods Patients From January 2005 to March 2006, a total 10 patients with soft-tissue tumors participated in our study. Our Institutional Review Board and the Medical Research Institute approved all of our protocols, and informed consent was obtained from all patients for additional studies of MEDIC imaging and histopathologic specimens by surgical resection. The histopathologic diagnoses of the 10 study patients included schwannoma (n = 3), hemangioma (n = 2), malignant fibrous histiocytoma (n = 1), angiokeratoma (n = 1), lipoma (n = 1), synovial sarcoma (n = 1), and myxoid Table 1. The Inhomogeneity Values as the SD/mean Ratio on MEDIC and T2FS in 25 Histologic Tissue Components Among 10 Softtissue Tumors No. Soft-tissue tumors (ROI) Histologic components MEDIC SD/mean ratio 01 Angiokeratoma (2.08 mm 2 ) hypercellular tissue 0.147 0.218 02 Angiokeratoma (2.08 mm 2 ) vascular tissue 0.135 0.228 03 Hemangioma (3.13 mm 2 ) vascular tissue 0.043 0.038 04 Hemangioma (3.13 mm 2 ) vascular tissue 0.030 0.047 05 Hemangioma (3.13 mm 2 ) thrombus 0.167 0.138 06 Schwannoma (3.66 mm 2 ) fibrous tissue 0.034 0.056 07 Schwannoma (3.66 mm 2 ) neural tissue 0.018 0.022 08 Schwannoma (3.66 mm 2 ) vascular tissue 0.038 0.054 09 Liposarcoma (3.99 mm 2 ) fibrous tissue 0.038 0.039 10 Liposarcoma (3.99 mm 2 ) myxoid stroma 0.037 0.029 11 Liposarcoma (3.99 mm 2 ) hypercellular tissue 0.014 0.038 12 Schwannoma (5.44 mm 2 ) neural tissue 0.028 0.040 13 Schwannoma (5.44 mm 2 ) vascular tissue 0.073 0.152 14 Schwannoma (5.44 mm 2 ) cystic tissue 0.015 0.022 15 Schwannoma (14.94 mm 2 ) fibrous tissue 0.099 0.253 16 Schwannoma (14.94 mm 2 ) neural tissue 0.078 0.130 17 Synovial sarcoma (23.35 mm 2 ) hypercellular tissue 0.009 0.019 18 Synovial sarcoma (23.35 mm 2 ) fibrous tissue 0.014 0.021 19 Synovial sarcoma (23.35 mm 2 ) cystic tissue 0.023 0.023 20 MFH (25.07 mm 2 ) hypercellular tissue 0.038 0.029 21 MFH (25.07 mm 2 ) hemorrhagic necrosis 0.040 0.044 22 MFH (25.07 mm 2 ) hemorrhagic necrosis 0.250 0.716 23 Lipoma (31.78 mm 2 ) lipoid tissue 0.035 0.220 24 Lipoma (31.78 mm 2 )++ lipoid tissue 0.041 0.231 25 Hemangioma (47.46 mm 2 ) vascular tissue 0.025 0.076 Mean 0.059 0.116 Note. -MFH = Malignant fibrous histiocytoma P = 0.0002 T2FS - 2 -

MRI Evaluation for the Histologic Components of Soft-tissue Tumors: Comparison of MEDIC and Fast SE T2-weighted Imaging liposarcoma (n = 1). The mean patient age was 36.5 years (range, 2 to 77 years). The ratio of males to females was nine to one. same plane. For MEDIC, the following scan parameters were used: TR, 442 msec; TE, 26 msec; section thickness, 5 mm with a 1.5 mm gap; field of view, 366 390 mm; number of excitations, 10; acquisition matrix, 256 168; flip angle, 30 degrees; ETL, 7; and echo spacing, 12.5 msec. For T2FS, the following scan parameters were used: TR, 3260 msec; TE, 100 msec; section thickness, 5 mm with a 1.5 mm gap; field of Protocol On the 1.5-T Sonata scanner (Siemens, Erlangen, Germany), both MEDIC and fast SE T2-weighted images with fat saturation (T2FS) were obtained in the a b c d Fig. 1. A 40-year-old female patient with a soft-tissue mass in the axilla, was confirmed with synovial sarcoma by RT-PCR. All inhomogeneity values as well as the SD/mean ratio with 23.35 mm2 of the ROI area on MEDIC image (a), were decreased more than on T2FS image (b) in the hypercellular tissue (arrow), cystic tissue (curved arrow), and fibrous tissue (arrowhead). The Gd-DTPA enhanced T1-weighted MR image with fat saturation (c) shows a non-enhancing area with cystic degeneration (curved arrow), a highly enhanced area with hypercellular tissue as proper sarcoma (arrow), and a moderately-highly enhanced area with somewhat plentiful fibrous tissue (arrowhead), as correlated with a histologic specimen (d). -3-

Tae Yong Moon et al view = 372 390 mm; number of excitations, 2; and acquisition matrix = 256 171. The experimental group included a total 25 histologic tissue components including 5 vascular tissues, 4 neural tissues, 4 fibrous tissues, 4 hypercellular tissues, 2 hemorrhagic necroses, 2 cystic tissues, 2 lipoid tissues, 1 myxoid stroma, and 1 thrombus. The inhomogeneity values of the MEDIC and T2FS images a were obtained from the digitalized data with mean and SD values by drawing ROIs with the areas of 2 to 47 mm2 in the same plane on both MR pulse sequence images coincided with the cut-surface of the pathologic specimens (Table 1, Figs 1, 2). The inhomogeneity values were calculated with the SD/mean ratios presented as the SD values divided by the mean values. b c d Fig. 2. A 51-year-old male patient with a soft-tissue mass in the axilla, was pathologically confirmed with schwannoma. All inhomogeneity values as well as the SD/mean ratios with 3.66 mm2 of the ROI area on MEDIC image (a), were decreased more than on T2FS image (b) in the neural tissue (solid arrow), fibrous tissue (arrow), and vascular tissue (arrowhead). The Gd-DTPA enhanced T1-weighted image with fat saturation (c) shows a highly enhanced area in the fibrous tissue (arrow), a non-enhanced area in the neural tissue (solid arrow), and an irregular, moderately highly enhanced area in the vascular tissue (arrowhead), as correlated with a histologic specimen (d). -4-

MRI Evaluation for the Histologic Components of Soft-tissue Tumors: Comparison of MEDIC and Fast SE T2-weighted Imaging Statistical Analysis The Wilcoxon signed rank test was used to compare the SD/mean ratio of the MEDIC and the T2FS pulse sequences. For this test, the significance was set at p < 0.05, and SPSS software (SPSS Inc. Chicago, US) was used for the statistical analyses. Results The means of the inhomogeneity values on the 25 histologic components were 0.059 and 0.116 on MEDIC and T2FS, respectively (p <.001) (Fig 3). The inhomogeneity values of the 25 histologic components were less on MEDIC than those on T2FS. Discussion Although many investigators have tried to differentiate between malignant and benign musculoskeletal tumors using contrast-enhanced MRI, their results have not been significantly successful (2, 3, 6, 7). The reports have included relatively nonspecific MRI findings, such as fat tissue showing a high-signal intensity on T1-weighted imaging, fluid showing a high-signal intensity pattern on T2-weighted imaging, hypercellularity with enhanced signal intensity on contrasted T1-weighted imaging, etc. (8, 9). As the MR imaging features of most soft-tissue masses are nonspecific, predicting a specific histologic diagnosis remains a challenge. We have tried to evaluate the histologic tissue components of soft-tissue tumors using Fig. 3. Inhomogeneity values (SD/mean ratios ) on MEDIC and T2FS in 25 histologic tissue components (p = 0.0002). digitalized data, but our analyses have been limited as T2-weighted MR sequences produce motion and poor fat saturation artifacts (4). In addition, T2-weighted sequences with fat-suppression techniques, such as double-echo steady-state sequence or spoiled gradient recalled sequence, could not adequately evaluate the amount of water in cartilage because of the many artifacts present (4). MEDIC is a 2D spoiled gradient echo, multi-echo sequence with a magnetization transfer saturation pulse. The MEDIC sequences in combination with the long-term averaging technique, were especially designed for neck and cervical spine imaging in order to completely suppress pulsation artifacts. New, optimized MEDIC sequences have been used with unipolar, high-bandwidth, multi-gradient echo sequence, and gradient motion rephrasing in order to reduce the chemical shift and susceptibility artifacts as well as the flow and motion artifacts (5). However, they have a handicap showing signal void intensity as susceptibility artifacts related to metallic material, hemorrhage, and air accentuated on gradient-echo MR images (10). As the signals of MR imaging represent the mobility of the water molecules into the tissue, histologic components mixed with various tissues cannot be completely evaluated using only T2- relaxation time. Furthermore, the histopathologic diagnosis of malignant tumor make decision with number of mitotic cell existed scantly on microscopic field, that cannot discriminate using with MR image at all. However, MR diagnosis of malignant tumor can make using with indirect signs such as the characterized histologic components of tumor, progressive growing tumor, or central necrotic mass (2). Accurate evaluation of the histologic tissue components of soft-tissue tumors using MR may require a combination of T1-weighted, contrasted T1-weighted, and MEDIC images. The digitalized data obtained from the monitor screen would represent more precise amounts of the mobility of the water molecules than the data obtained by visual signal intensity classified as high to low (11). Statistically, the SD represents the error amounts of the digitalized data as well as the heterogeneity of the imaging. If the SD is great in the value, the error amount in the acquired data from the identical sample is abundant. Similarly, if the SD from the area of the - 5 -

Tae Yong Moon et al ROI on the monitor is great, the imaging confidence is declined, compared with the images lower in the value. We have applied the SD value divided by the mean value as the SD/mean ratio to represent the inhomogeneity values. To our knowledge there has been no report of comparing MEDIC and fast SE T2-weighted image with or without fat saturation for characterizing soft tissue tumors so far. We make sure the MEDIC is better to evaluate histologic components of soft tissue tumors than T2FS. In conclusion, we believe that MEDIC is more accurate than T2FS for evaluating the tissue components of soft tissue tumors with digitalized data because there are lower inhomogeneity on the MEDIC images. Acknowledgments We acknowledge Bonnie Hami, MA (USA) for her editorial assistance and Sharon Davis, CPS, Administrative Assistant to E. Edmund Kim, M.D., UT MD Anderson Cancer Center, for helping with the English version of the manuscript. 1.Kim JL, Choi KU, Lee IS, Moon TY, Lee CG, Kim HW, Kim JY, Park DY, Sol MY. Gene expression in mixed type liposarcoma. Pathology 2006;38:114-119. 2.Crim JR, Seeger LL, Yao L, Chandnani V, Eckardt JJ. Diagnosis of soft-tissue masses with MR imaging: Can benign masses be differentiated from malignant ones? Radiology 1992; 185: 581-586. 3.Nishimura H, Zhang Y, Ohkuma K, Uchida M, Hayabuchi N, Sun S. MR imaging of soft-tissue masses of the extraperitoneal spaces. RadioGraphics 2001;21:1141-1154. 4.Glaser C. New techniques for cartilage imaging: T2 relaxation time and diffusion-weighted MR imaging. Radiol Clin N Am 2005;43:641-653. 5.Held P, Dorenbeck U, Seitz J, Frund R, Albrich H. MRI of the abnormal cervical spinal cord using 2D spoiled gradient echo multiecho sequence (MEDIC) with magnetization transfer saturation pulse. A T2* weighted feasibility study. J Neuroradiol 2003;30:83-90. 6.Benedikt RA, Jelinek JS, Kransdorf MJ, Moser RP, Berrey BH. MR imaging of soft-tissue masses: role of gadopentetate demeglumine. JMRI 1994;4:485-490. 7.Nishimura H. Diagnosis of soft tissue tumors: 10 checkpoints. Nippon Igaku Hoshasen Gakkai Zasshi 2001;61:275-291. 8.Beltran J, Chandnani V, McGhee RA Jr, Kursunoglu-Brahme S. Gadopentetate dimeglumine-enhanced MR imaging of the musculoskeletal system. AJR Am J Roentgenol 1991;156:457-466. 9.Erlemann R, Reiser MF, Peters PE, Vasallo P, Nommensen B, Kusnierz-Glaz CR, Ritter J, Roessner A. Musculoskeletal neoplasms: static and dynamic Gd-DTPA-enhanced MR imaging. Radiology 1989;171:767-773. 10.Imaizumi T, Horita Y, Chiba M, Miyata K, Toyama K, Yoshimoto Y, Niwa J. Dot-like hemosiderin deposition on T2*-weighted MR imaging associated with nonhypertensive intracerebral hemorrhage. J Neuroimaging 2006;16:39-46. 11.Koo KH, Dussault R, Kaplan P, Kim R, Ahn IO, Christopher J, Song HR, Wang GJ. Age-related marrow conversion in the proximal metaphysis of the femur: evaluation with T1- weighted MR imaging. Radiology 1998;206:745-748. - 6 -

MRI Evaluation for the Histologic Components of Soft-tissue Tumors: Comparison of MEDIC and Fast SE T2-weighted Imaging - 7 -