Role of Diffusion WIs and T 2 * GRE Pulse Sequences in Dubious Vertebral Marrow Pathological Lesions

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1 Journal of the Egyptian Nat. Cancer Inst., Vol. 19, No. 4, December: , 2007 Role of Diffusion WIs and T 2 * GRE Pulse Sequences in Dubious Vertebral Marrow Pathological Lesions OMAR M. OSMAN, M.D.*; YASSER R. FAHMY, M.D.*; ALAA M. EL-ORABY, M.D.**; AYMAN A. EL-BASMY, M.D.* and YASSER E. AMIN, M.D.*** The Department of Radiology, Faculty of Medicine*, National Cancer Institute** and the Department of Rheumatology**, Faculty of Medicine, Cairo University, Egypt. ABSTRACT Pathological lesions of the verteberal bone marrow usually replace, to a variable degree, its normal constituents. This represents a diagnostic dilemma, predominantly in old patients with high possibility of osteoporotic vertebral collapse. In this study we assessed the potentials of diffusion weighted images (DWIs) and T 2 * GRE WIs in differentiation of such pathological changes. The difference between trabecular bone and soft tissue produces distortions in magnetic resonance images according to susceptibility differences of the pathological component. This allows discrimination between benign and malignant lesions. So our purpose was to evaluate the addition of diffusion weighted images (DWIs) and T 2 * GRE WIs for differentiation of benign from malignant vertebral lesions; to endorse the role of MR in such lesions. One hundred cases at different radiological centers were evaluated using the same specified parameters. Our results showed that addition of diffusion and T 2 * GRE WIs to MRI sequences can differentiate, to a certain degree, between bone marrow pathological lesions. Conclusion: Diffusion WIs and T 2 * GRE pulse sequences can be added to previous MRI pulse sequences to support discrimination between vertebral marrow pathological lesions. Key Words: DWIs T 2 *GRE WIs Pathological bone marrow lesion. INTRODUCTION Pathological lesions usually replace normal components of the vertebral bone marrow [1]. Such replacement could be neoplastic cells, inflammatory cells, water, as well as blood degradation products. Therefore, the signal detected Correspondence: Dr Omar M. Osman, Department of Radiology, Faculty of Medicine, Faculty of Medicine, Cairo University, Egypt, Omar5oct@hotmail.com would be changeable to a certain degree depending on the amount and type of cells. Neoplastic and inflammatory cells usually replace all the normal fat in the bone marrow [1-7]. In opposed gradient echo, fat and water resonate at different frequencies. By choosing the appropriate TE we can subtract fat from water during in and out of sequences [8]. This is most profound when the amount of water and fat in each voxel is similar, as in the bone marrow. Susceptibility differences between trabecular bone, soft tissue and blood degradation products also create localized distortions of the magnetic field which induce strong inhomogeneities in the static magnetic field [1]. Diffusion and T 2 * GRE sequences of such magnetic field gradients produce distortion of dephasing. So, both sequences produce shortening of the apparent relaxation time T 2. This can be exploited to the maximum benefit by using diffusion and T 2 * GRE WIs in diagnostic imaging of marrow replacing lesions. Hence, adding such modified MRI sequences can help to solve such problem [1-7]. So our aim was to evaluate the addition of diffusion weighted images (DWIs) and T 2 * GRE WIs in differentiating benign from malignant vertebral lesions, as well as to endorse role of MR in such lesions. MATERIAL AND METHODS We evaluated 100 cases using medium and high field machines, 1, 1.5 and 3 T machines, between June 2005 and June 2007, at EL Iman Radiology Center at Bani swaif and Fayoum 254

2 Role of Diffusion WIs & T 2 * GRE Pulse governorates, Egypt, (15 patients at each center) using Philips 1 T and at the department of Radiology, Faculty of Medicine, Cairo University (15 patients) using Philips 1.5 T. Five patients were investigated at Alpha Scan Center, Cairo, using Philips 3 T. Ten patients were investigated at the National Cancer Institute, Cairo University, using GE 1 T Signa Contour. Forty patients were evaluated at department of Radiology, Erfan Hospital, Jeddah, Saudi Arabia, between June 2005 and December The examinations were performed by 1.0 T Siemens, Magnetom Expert and 1.5 T G.E, Echo speed. All patients had complete MR studies using d array surface coils, sagittal and axial images. Pre and post Gd. T 1 SE with and without fat saturation and T 2 FSE and T 2 STIR. In (TE= 6.4 msec.) and out-of- (TE= 3.2 msec.). Slice thickness 4mm. Matrix 256 X 192. FOV 36 cm, anterior saturation band, NEX 2-4 and TR msec. Diffusion whole body sequence using the following parameters for 1 and 1.5 T (1000/68; flip angle, 90º) and 3 T (850/69; flip angle, 90º) T 2 * GRE. were done in TR shortest msec TE 13. 8msec FA 25 Matrix 256X512. Tumor markers, plain radiographs, bone scintigraphy were done for all patients. Histopathological confirmation and/or follow-up MRI were done for few selected cases whenever possible. Interpretations of cases were blindly carried out by two radiologists. Finally, the two sets of evaluations were compared, with any discrepancy noted to confirm or resolve findings. A final opinion was reached in any case where there was disagreement or consensus. The degree of signal loss was quantified subjectively as marked, intermediate and minimal loss. RESULTS Signal drops specifically characterize all traumatic patients (10 patients-100%) in the opposed technique. In neoplastic and inflammatory lesions (50 cases 100%), there were no signal drops. Table (1) shows the different pathological lesions of our included patients. Osteoporotic fractures were found in ten cases (16 chronic and 4 acute) (Fig. 1). Spondylodiscitis was found in 15 cases (Fig. 2). Giant high risk 255 haemangioma was found in 5 cases (Fig. 3), prostate metastases in 15, breast metastases in 10, bronchogenic metastases in 10, renal metastases in 5, breast metastases with radiotherapy (diagnosis of tumoural activity and response to treatment) in 5, myeloma 5 and lymphoma in 5 cases (Figs. 4-6). In diffusion WIs both types of osteoporotic fracture showed limited diffusion restriction (Fig. 7), while T 2 * GRE showed increase magnetic susceptibility, predominantly in acute fractures, with 100% specificity and sensitivity (Fig. 8). Spondylodiscitis showed intermediate diffusion restriction, with no magnetic susceptibility T 2 * GRE sequences. Malignant lesions, on the other hand, showed marked diffusion restriction with no magnetic susceptibility detected in T 2 * GRE sequences (Fig. 9). Diffusion studies showed high sensitivity and specificity for differentiation of neoplastic and inflammatory processes (Figs ). Table (2) shows the collective different MRI signals in each group. The observation agreements of neoplastic lesions between the two radiologist groups blinded to each others results, regarding opposed and diffusion sequences, combined and separately, were about 80% and 94.5%, respectively. Combination of the two sequences increased the agreement percentage to 96.3% in both groups. Only one inflammatory case (6.6%) was not diagnosed by opposed with one of the groups. This had been corrected by exploiting DWIs data. Both groups showed 100% agreement as regards the osteoporotic lesions and haemagiomas. Table (1): The different pathological lesions of included patients. Pathological lesion Osteoporotic fractures Spondylodiscitis Giant high risk haemangioma Prostate metastases Breast metastases Bronchogenic metastases Renal metastases Breast metastases with radiotherapy Myeloma Lymphoma Number of cases 25 (25%) 15 (15%) 15 (15%) 10 (10%) 10 (10%)

3 256 Omar M. Osman, et al. Table (2): Collective different MRI signals of different pathological lesion in each group. Pathological lesion Osteoporotic fractures Spondylodiscitis Giant high risk haemangioma Prostate metastases Breast metastases Bronch. metastases Renal metastases Breast metastases with radiotherapy Myeloma Lymphoma Opposed Signal drop No signal drop Signal drop No signal drop STIR Diffusion T 2 *GRE Bright Signal Limited restriction Average restriction Average restriction Significant Restriction (Bright signal) Magnetic susceptibility in acute trauma No magnetic susceptibility T 2 STIR In Out Fig. (1): Trauma: signal drop in out. T 1 T 2 STIR In Out Fig. (2): Infection: no signal drop in out.

4 Role of Diffusion WIs & T 2 * GRE Pulse 257 T 1 T 2 In Out Fig. (3): Haemangioma of a known case of breast cancer shows signal drop in out. T 1 T 1 +Cont T 2 In Out Fig. (4): Breast metastasis: no signal drop in out.

5 258 Omar M. Osman, et al. T 1 T2 In Out Fig. (5): Multiple myeloma: no signal drop in out. T 1 T 2 In Out Fig. (6): Lymphoma: no signal drop in out.

6 Role of Diffusion WIs & T2* GRE Pulse T1 T2 259 In Out Fig. (7): Trauma: no diffusion restriction in DWIs. T2* T2 Fig. (8): Acute trauma with blooming of blood degradation products in T2*. T2* T2 Fig. (9): Infection with no blooming in T2*. DWIs

7 260 Omar M. Osman, et al. T 1 T 2 DWIs B=0 DWIs Fig. (10): Breast metastasis with notable diffusion restriction in DWIs. T 1 T 2 STIR Out DWIs Fig. (11): Multiple myeloma with notable diffusion restriction in DWIs.

8 Role of Diffusion WIs & T 2 * GRE Pulse 261 T 1 In T 1 T 2 + Cont Out DWIs Fig. (12): Spondylodiscitis with diffusion restriction in DWIs. DISCUSSION Pathological lesions of vertebral bone marrow usually replace, to a variable degree, its normal constituent. This poses a diagnostic dilemma, predominantly in old patients with a high possibility of osteoporotic vertebral collapse. The feasibility of MRI in depicting trabecular bone structure has been demonstrated in several studies. Conventional MRI sequence signal changes are usually subjective depending on morphology and predominant site of signal changes involvement. However, this sometimes does not solve the problem [9-14]. High or inhomogeneous signal intensities of compressed vertebral body on T 2 weighted images and on contrast-enhanced MR images has been reported to be suggestive of malignancy on conventional spin-echo images [13]. This was contradictory to our study supported by previous results of Jung et al. [14] which revealed that signal intensity on fast spin-echo T 2 - weighted images played little role in distinguishing between acute benign osteoporotic and metastatic compression fractures. Most of the literatures discussed the application of opposed gradient echo in the appendicular skeleton relying mainly on fat suppression. In vertebral bone marrow, with its main constituent s red and yellow marrow, the technique depends mainly on separating fat signal from water signal [8-10]. Our results showed significant signal reduction for benign lesions with limited reduction for malignant lesions. This supports a previous study done by Lingawi and Ragab, revealing that opposed gradient echo sequence is useful in differentiating benign from malignant vertebral lesions [8]. In agreement with Mulligan et al. [12], our study showed that DWIs had about 80% sensitivity for differentiation between neoplastic and inflammatory processes. In our study, we found that both have diffusion restriction showing bright signals as compared to osteoporotic lesions. Additionally, it was easy to discriminate both depending on their signal variability. This can be attributed to the dense cellular components of tumors, as opposed to inflammatory lesions with relatively lower cellular component [12]. This study found that both observers were able to categorize vertebral marrow pathological lesions by opposed and STIR sequences with observers agreement about 80%. Combining them with DWIs sequences further increased the observers agreement to be about 96.3%. This, in our opinion, was due to improved pathological signal resolution due to tissue mixture variability. These findings were similar to those of Rodallec et al. [7] who proved that multiple sequences in different planes were helpful for delineating normal bone marrow architecture,

9 262 fat content within masses and subacute hemorrhage. They stressed that evaluating tissue enhancement, after administration of gadoliniumbased contrast material, results in enhancement proportional to soft-tissue vascularity. This is helpful for differentiating cystic lesions from cyst-like solid masses. They asserted that dynamic contrast-enhanced MR imaging adds information about the rapidity of the enhancement. This could not be compared with our results, as it was not our target. Our study found, in concordance with Rodallec et al. [7], that STIR is a very sensitive sequence for detecting most types of soft-tissue and marrow abnormalities of large field of view, e.g. full-spine. This was very useful in rapid screening assessment and diagnosis of multifocal lesions of the skeleton. Recruitment of the magnetic susceptibility effect of T 2 * GRE showed a significant difference between hemorrhagic and non hemorrhagic pathological processes [10-11]. It was proved to be 100% sensitive for differentiation between acute and chronic osteoporotic vertebral collapse supporting a previous report by Jung et al. [14]. In addition, this was helpful in diagnosis of vertebral hemangiomas, preferentially those of high risk, as increase in size leads to cord compression and structural collapse [7]. In our study we found that T 2 * GRE had poor sensitivity in differentiating haemorrhagic and non haemorrhagic metastases. This could be exploited as an auxiliary sequence in differentiating acute trauma from neoplastic lesions of old osteoporotic patients. Despite the use of different magnet strengths, we evaluated different pulse sequences, our target, regardless of the magnetic field strength. Though, we observed that diagnosis and differentiation was confidently much easier by 3 T machine. Yet, for a better and further conclusion, future comparative study of the same patient is recommended to standardize variables of each patient and machine. In conclusion, addition of diffusion WIs and T 2 * GRE help, opposed, MRI techniques can effectively characterize bone marrow pathological lesion without the need for invasive procedures. REFERENCES Omar M. Osman, et al. 1- Weber M, Sharp J, Latta P, Sramek M, Hassard H, Orr F. Magnetic resonance imaging of trabecular and cortical bone in mice: comparison of high resolution in vivo and ex vivo MR images with corresponding histology Eur J Radiology. 2005, 53 (1): Davis CA, Genant HK, Dunham JS. The effects of bone on proton NMR relaxation times of surrounding liquids. Invest Radiol. 1986, 21: Wehrli F, Ford J, Haddad J. Osteoporosis: Clinical assessment with quantitative MR imaging in diagnosis. Radiology. 1995, 196: Ford J, Wehrli F. In vivo quantitative characterization of trabecular bone by NMR interferometry and localized proton spectroscopy. Magn Reson Med. 1991, 17: Majumdar S, Thomasson D, Shimakawa A, Genant HK. Quantitation of the susceptibility difference between trabecular bone and bone marrow: Experimental studies Magn Reson Med : Majumdar S, Genant HK. In vivo relationship between marrow T 2 * and trabecular bone density determined with a chemical shift-selective asymmetric spin-echo sequence. Magn Reson Imaging. 1992, 2: Rodallec MH, Feydy A, Larousserie F, Anract P, Campagna R, Babinet A, et al. Diagnostic Imaging of Solitary Tumors of the Spine: What to Do and Say. Radiographics. 2008, 28: Lingawi S, Ragab Y. The Role of Opposed Phase Gradient Echo MR in Differentiating Benign from Malignant Vertebral Lesions, Presentation at European Congress of Radiology ECR personal communication Majumdar S, Genant HK. A review of the recent advances in magnetic resonance imaging in the assessment of osteoporosis Osteoporos Int. 1995, 5: Pothuaud L, Laiba A, Levtiz P, Benhamu CL, Majumdar S. Three-Dimensional-Line Skeleton Graph Analysis of High-Resolution Magnetic Resonance Images: A Validation Study From 34-µm-Resolution Microcomputed Tomography. J Bone Miner Res. 2002; 17: Beuf O, Newitt DC, Mosekilde L, Majumdar S. Trabecular Structure Assessment in Lumbar Vertebrae Specimens Using Quantitative Magnetic Resonance Imaging and Relationship with Mechanical Competence. J Bone Miner Res. 2001, 16: Mulligan ME, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone. AJR Am J Roentgenol. 1999, 173 (6): Tan SB, Kozak JA, Mawad ME. The limitations of magnetic resonance imaging in the diagnosis of pathologic vertebral fractures. Spine. 1991, 16: Jung H, Jee W, McCauley T, Ha K, Choi K. Discrimination of Metastatic from Acute Osteoporotic Compression Spinal Fractures with MR Imaging. Radiographics. 2003, 23: