096以長TE值之MRI T2影響鑑別診斷肝腫瘤.doc

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1 TE MRI T2

2 ext TE MRI T MR 1. TE (750ms) MR MRI MR T2WI TE T2WI T2 fat sat MRI TE 750ms breath hold T2 fat sat slice thickness 8mm~10mm TE 750ms TE 57 T % 95.7% 96.4% (P<0.001) TE=750ms T2

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4 MR T 2 WI TE T 2 WI T 2 fat sat MRI TE 750ms breath hold T 2 fat sat slice thickness 8mm~10mm TE 750ms TE 57 T % 95.7% 96.4% (P<0.001) TE=750ms T 2 4

5 MR 1,2,3 hemangioma cyst (non-solid) T 2 T 2 relaxation time TE=120msec 4 hemangioma TE 5 MRI ( ) MRI T 2 WI TE TE 4 6 malignant hepatic tumor 85ms(±17ms) hemangima 155ms(±35ms) cystic lesion 583ms(±369ms) TE HCC hemangioma cyst P value 1. MRI ( ) ( hemangioma, cyst) 2. MRI T 2 TE 5

6 hemangioma cyst 3. 1 MRI 4. TE MRI 6

7 1. ( ) MRI AFP 400ng 2. MRI consent form( form ) 3. MRI Dual T 1 TR 210 TE T 2 TSE(TE TR 2000 TSE factor 23) T 2 fat sat Gd-DTPA dynamic phase (T 1 FFE) late phase (T 1 fat sat axial coronal), delay phase(t 1 FFE) 4. T 2 WI T 2 fat sat MRI TE 750ms breath hold T 2 fat sat slice thickness 8mm~10mm T 2 TE T 2 ROI (region of interest) 5~10mm ~ cm~5.7cm( 2.01±1.04cm) 7. MRI MRI TE=750ms T 2 T 2 fat sat T 2 T 2 T MRI 10. Boferrni Correct t test SI(long TE 750ms) SI(T 2 fat sat) SI(T 2 fat sat) SI Receiver of Operating Calculation(ROC) curve 7

8 32 TE=750ms (Fig 1) 57 T 2 (Fig 2) 46 2 (Fig 3) 98.32% 95.7% 96.4% (P<0.001) inter-observer variation kappa value 0.94 p< TE=750ms SI 276.4±19.6 T 2 fat sat 1237±37.8 TE=750ms SI 2172±172.2 T 2 fat sat 1412±49.6 TE=750 Beferroni correct t test P<0.001 SI signal intensity difference ratio ROC curve 0.38 sensitivity 98.4% specificity 97.7% accuracy 98.8% TE=750ms Fig 1 2 S 7 (a) T 2 (b) T 2 fat sat (c)te=750ms a. b. c. 8

9 Fig 2 2 S 7-8 (a) (b)t2 T 2 fat sat (c)te=750 TE a. b. c. Fig 3 (a) (b) )T 2 T 2 fat sat (c) TE=750 TE (d) T 1 FFE a. b. c. d. 9

10 MRI 7 TE (TE=750ms) Fenlon s 8 TE=125ms heavily T2-weighted MR imaging 9,10 Jafari 0.5T MR Rapid Acquisition Relaxation Enhanced sequence with TE=500ms 11 TE=500ms TE TE=750ms TE=750ms ROI signal variation ratio 0.38 sensitivity 98.4% specificity 97.7% accuracy 98.8% 12,13 14 T 2 TE (750ms) TE=750ms TE=750ms T2 10

11 1. TE (750ms) MR MRCP,MRU, MR 2., 3. 11

12 1. Li CS, Chen RC, Chen WT, Lii JM, Tu HY. Temporal peritumoral enhancement of hepatic cavernous hemangioma: findings at multiphase dynamic magnetic resonance imaging. J Comput Assist Tomogr Nov-Dec; 27(6): Itai Y, Furui S, araki T, Yashiro N, Tasaka A. Computed tomography of cavernous hemangioma of the liver. Radiology 1980; 137: Coumbaras M, Wendum D, Monnier-Cholley L, Dahan H, Tubiana JM, Arrive L. CT and MR imaging features of pathologically proven atypical giant hemangiomas of the liver. AJR Am J Roentgenol Dec; 179(6): Ciszanowski A, Szeszkowski W, Golebilwski M, et al. Discrimination of benign from malignant hepatic lesion ased on their T2-relaxation times calculated from moderately T2-weighted turbo SE sequece. Eru Radil.2002 Sep; 12(9): Epub 2002 Apr Ros PR, Lubbers PR, Olmsted WW, Morillo G. Hemangioma of the liver: heterogeneous appearance of T2-weighted images. AJR 1987; 149: Goldberg MA, Hahn PF, Saini S, et al. Value of T1 and T2 relaxation times from echoplanar MR imaging in the characterization of focal hepatic lesion. AJR Am J Roentgenol May; 160 (5) McFarland EG, Mayo-Smith WW, Saini S, et al. Hepatic hemangiomas and malignant tumors:improved differentiation with heavily T2-weighted conventional spin-echo MR imaging. Radiology.1994 Oct; 93 (1): Fenlon HM, Tello R, decarvalho VL, Yucel EK.Signal characteristics of focal liver lesions on double echo T2-weighted conventional spin echo MRI: observer performance versus quantitative measurements of T2 relaxation times. J Comput Assist Tomogr. 2000; 24: Egglin TK, Rummeny E, Stark DD, Wittenberg J, Saini S, Ferrucci JT.Hepatic tumors: quantitative tissue characterization with MR imaging. Radiology. 1990; 176: Bennett GL, Petersein A, Mayo-Smith WW, Hahn PF, Schima W, Saini 12

13 S.Addition of gadolinium chelates to heavily T2-weighted MR imaging: limited role in differentiating hepatic hemangiomas from metastases. AJR Am J Roentgenol. 2000; 174: Jafari F, Nayeri N, Tahsini M, Khodadoust AA. Differentiation of hepatic cavernous hemangioma from metastases by rare sequence MR imaging. Magn Reson Imaging. 1999; 17: Furtado CD, Aguirre DA, Sirlin CB, et al. Whole-Body CT Screening: Spectrum of Findings and Recommendations in 1192 Patients. Radiology. 2005; 237: Goehde SC, Hunold P, Vogt FM, et al. Full-body cardiovascular and tumor MRI for early detection of disease: feasibility and initial experience in 298 subjects. AJR Am J Roentgenol. 2005; 184: Tello R, Fenlon HM, Gagliano T, decarvalho VL, Yucel EK. Prediction rule for characterization of hepatic lesions revealed on MR imaging: estimation of malignancy. AJR Am J Roentgenol. 2001; 176:

14 ( ) Abstract Purpose: Radiologists have generally acknowledged that hepatic hemangioma and hepatic cysts are high signal intensity lesions on conventional T2-weighted images. The T2 signal intensity of HCC is moderate high. The appearance of T2 in long TE might be different. Therefore the purpose of this study is to examine the reliability of very long TE sequence in distinguishing hepatic cysts, hepatic hemangiomas and HCC. Material & Methods: A total of 89 patients, with 32 HCCs, 58 hepatic hemangiomas and 48 hepatic cysts, were recruited for the study. Full approval from the medical ethics committee was obtained. All patients underwent ultrasound and MR imaging (including a heavily T2, TE=750ms), and these were reviewed independently by two radiologists. The signal intensities of the lesions were measured by user-defined region of interest. Each lesion s variation in signal intensities, between heavily T2 with long TE and fat-suppressed T2-weighted images, is calculated using the formula: Signal Variation = (SI in TE 750ms SI in T2 fat-saturated) (SI in T2 fat-saturated) The results were validated using a Receiver of Operating Calculation curve (ROC curve). Results: All of the HCC are not visible in heavily T2 (TE=750ms). The signal intensities of hemangiomas is ± 19.6 on heavily T2 (TE=750ms). 14

15 As for hepatic cysts, their signal intensities on T2W is on heavily T2 (TE=750). These demonstrate a significant difference between the signal intensities of hepatic hemangiomas and cysts, (P<0.001). The Kappa value, representative of the inter-observer variation between the two radiologists in this study, is 0.94 (P<0.0001). Using this, the derived sensitivity is 98.4%, the specificity 97.7%, and the accuracy 98.8%. Conclusion: HCC, Hepatic hemangiomas and cysts have significantly different signal intensities on T2 with very long TE. The long TE T2WI is a non-invasive, reliable, and accurate imaging technique for their differentiation. Introduction From experiences with MRCP and MRU [1,2], we found that although both hepatic cysts and hemangiomas display very high signal intensities on conventional T2 images, they appearances are quite distinct on heavily T2 with very long TE[3]. Whilst hepatic cysts emit very high signal intensity on heavily weighted T2 with long TE, the hepatic hemangiomas display only a slightly high intensity. Their distinct appearances are most likely related to their different MR properties. Previous literatures suggest that for a 1.5T MRI device, the relaxation time of hemangiomas is approximately msec, and for hepatic cysts [4,5]. Despite this piece of well-known information, HCC, hepatic cysts and hemangiomas are still routinely distinguished by contrast-enhanced MR studies. Whether T2WI with very long TE is a feasible technique in the differentiation of HCC, hepatic cysts from hemangiomas has not been examined in detail. Therefore the purpose of this study is to investigate the reliability of the heavily T2 (TE=750ms) as a non-contrast alternative to discriminate these two lesions. 15

16 Material & Methods Patients This was a prospective study which was conducted over, from Jan 2005 to Nov patients, who had hemangioma-like or cystic lesions on sonography, or histologically proved HCC were referred for MRI to have the lesions further characterized. These revealed 32 HCC, 58 hepatic hemangiomas and 48 hepatic cysts, were selected for the study (since only the largest three cysts from each patient was selected). The diagnosis of hepatic cysts relied on its characteristic sonographic and MRI findings, which includes hypoechogeneity with posterior enhancement, and high T2 signal intensity without enhancement in contrast-enhanced MRI. Hemangioma was confirmed by its distinctive variable echogeneity with clear and/or geographic margin, as well as a peripheral white ring. In addition, its MR characteristics are also quite unique. It is lesion of very high T2 signal intensity, which enhances in a peripherally nodular or rapidly homogenous pattern in early arterial phase, and fills-in or remains persistently homogenous in late and delayed phases. All of the HCC were proved by fine needle biopsy and histology findings. Informed consents were obtained from all of them prior to the MR examinations. The MR examinations were composed of conventional pre- and post-iv gadolinium dynamic hepatic series, complemented by multi-slice single shot Heavily T2WI (TE=750ms). The size of the tumors ranged from 0.8cm to 5.7cm in diameter (mean 2.01±1.04 cm). After their MR examinations, all patients with hemangiomas and cysts were followed up by ultrasound for a minimum of six months. Should there be any discrepancies between the findings of the two modalities, then a repeat MR examination similar to the initial set was done for further 16

17 clarification. Imaging The sonographic examinations were performed with a Logiq 700 sonography unit (Logiq 700, GE medical system, Milwaukee, Wisconsin, USA), using a MHZ probe. MR images were acquired through a 1.5T MR scanner (Philips Gyroscan ACS-NT, the Netherlands), and a phased-array body coil. Dual T1-weighted images (TR/TE: 210/2.3 and 4.6; slices thickness 8mm, gap 0.8mm) were performed within one breath hold. Turbo spin-echo (TSE) T2-weighted images (TR/TE: 2500/100; TSE factor, 23) with and without fat saturation, and coronal T2-weighted imaging were obtained with respiratory triggering. Heavily T2WI was axial 2D single shot, multi-slice sequences, with fat-saturation, acquired within one breath hold (TR/TE, 8000/750; TSE factor 128; 12 slices; slice thickness, 8mm; gap, 0.8mm, matrix 256x204, NEX 2). The total acquisition time was only 16 seconds, and all patients were examined using the same techniques described above. The total thickness of tissue scanned for each 2D MR hydrography was 10cm typically, however there are times two separate sequences were required to fully cover the entire livers. Dynamic MR images were obtained by applying T1-weighted fast field echo (FFE) sequence ( / ; flip angle, 80 ) before intravenous contrast administration, and seconds (arterial-dominant phase), seconds (portal venous phase), 5 minutes (5-minute delayed phase) after manual intravenous administration of gadopentetate dimeglumine (Magnevists; Schering, Berlin, Germany; 0.1mmol/kg body weight). Another delayed phase axial images and coronal images were then acquired about 10 minutes after intravenous contrast administration (10-minute delayed phase). These pulse 17

18 sequences were all obtained with single acquisitions during one breath hold. Image Analysis The task of image analysis was subdivided between three separate radiologists. One measured the signal intensity of lesions on T2W images, fat-saturated T2W images, and MR hydrography. This was performed on a PACS system with high-resolution monitor, using an operator-defined region of interest (ROI) which was defined as an ovoid area 5-10mm in diameter. The other two radiologists independently reviewed all MR images in two stages, without prior knowledge of diagnosis. The non-contrast images including heavily T2WI (TE=750ms) were given to the radiologists for review, and they were asked to record lesions signal intensities on T2WI, T2W fat-saturated, and heavily T2WI (TE=750ms), and the variation between them. Preliminary diagnoses were then made based upon these readings. Should a lesion s signal intensity in heavily T2WI (TE=750ms) be comparable with or higher than in T2WI or T2WI with fat-saturation, it is labeled a hepatic cyst. If the reverse occurs and the lesion s heavily T2WI (TE=750ms) signal intensity is lower than that of T2 images, the lesion is regarded as a hemangioma. If the lesions were not defected is heavily T2 (TE=750ms), the lesion is labeled a HCC. After this was completed and the preliminary diagnoses were made, the radiologists then reviewed the dynamic MR images with contrast enhancement. This produced the definitive diagnoses to be used as the gold standard, and these were recorded separately from the preliminary diagnoses. Statistical Analysis For the statistical analysis of the signal intensities of the lesions in different MR 18

19 series, we used the Beferroni Correct T Test. The variation of lesions signal intensities, between heavily T2 (TE=750ms) and T2WI with fat-saturation, is central to this study. This is defined by the formula: SI (in T2WI with TE750ms) SI (in T2 fat sat) / SI (in T2 fat sat). The resulting variations derived from this formula is evaluated and validated by a Receiver of Operating Calculation (ROC) curve, from which an ideal cut-off value was also obtained. Thus lesions with signal intensity variation that falls beneath the cut-off value would be diagnosed as hemangiomas, and lesions with signal intensity variation above the cut-off value considered hepatic cysts. All of the HCC were not detected in T2WI with TE750ms. The formula cannot be calculated. This method s sensitivity and specificity can also be derived from the ROC curve. The sensitivity and specificity of the visual assessment by two radiologist were calculated. Their inter-observer variation was analyzed by the Kappa test. Result The radiologist successfully diagnosed 57 out of 58 hepatic hemangiomas, and 46 out of 48 hepatic cysts, all 32 HCCs based on his visual assessment of their signal intensity variations. The sensitivity is 98.32%, specificity 95.7%, and accuracy 96.4%. The Kappa value was 0.94 in two radiologist. (P<0.0001) The inter-observer variation appeared minimal. We also attempted to quantify the signal intensity variation that distinguish the hepatic hemangioma and hepatic cyst. For hemangiomas, the signal intensity was ± 19.6 on heavily T2WI (TE750ms). (Fig 1) For cysts, the signal intensity was 2172± on heavily T2WI (TE=750ms). (Fig 2) When these 19

20 numbers were analyzed with the Boferroni correct t test, it appears this difference in signal intensity variation is consistent and statistically significant (P<0.001). It also demonstrates that allowing for few exceptions, a ratio of 0.38 appears to be a good cut-off value for discriminating hemangiomas and cysts. Which means that lesions with signal intensity reduction ratio less than 0.38 would be considered as hemangiomas, whereas lesions whose ratio is more than 0.38 should be diagnosed as cysts. The area under the ROC curve was (Fig 4) Quantitative analysis of MR hydrography s performance reveals that MR hydrography has a sensitivity of 98.4%, specificity of 97.7%, and accuracy of 98.8%, when differentiating hepatic hemangiomas from cysts. Discussion Sonography is a common screening tool and diagnostic imaging modality for hepatic lesions. It does however has some difficulty differentiating hepatic hemangiomas and cysts, often because hemangiomas may be hypoechoic. This is especially pronounced in obese patients [7, 8]. Recently, there is an increasing trend to utilize whole body computed tomography or magnetic resonance imaging for routine health examinations. Since these are clinically asymptomatic patients, intravenous contrast medium is seldow use a to avoid unnecessary drag reaction [9,10]. However without the administration of intravenous contrast medium the differentiation of HCC, hepatic hemangiomas and cysts is difficult with conventional MRI. Despite the fact that both diagnoses are benign, patients often prefer to have an exact diagnosis [11]. Heavily T2 WI (TE=750ms) is able to highlight static or very slow-flowing fluid by applying a heavily weighted T2 pulse sequence. In Fenlon s study, extreme T2 weighted imaging with TE of 125ms is useful for distinguishing 20

21 benign hepatic lesions from malignant ones [1]. Other investigators also used heavily T2-weighted MR imaging to differentiate hepatic cysts and hemangiomas from other solid tumors. Jafari et al measured the T1 and T2 signal intensities of liver, spleen, and hemangioma with Rapid Acquisition Relaxation Enhanced (RARE) sequence on a 0.5T MR imager, setting the TE at 500ms. They noted that even with TE set at 500ms the signal intensity of hemangioma remained high. In view of this pre-existing phenomenon we have increased TE to 750ms for our MR hydrography, and noted a significant drop in the signal intensity of the hemangiomas compared to cysts, obvious even to the naked eye. To remove the confounding factor of indigenous signal intensity differences in different lesions, the difference in signal intensity of the lesion between on heavily T2 WI (TE=750ms) and on fat-saturation T2-weighted imaging was expressed in a ratio. It was mentioned earlier that the ideal cut-off value is 0.38, according to the ROC curve and the dot diagram. This gives heavily T2 WI (TE=750ms) a sensitivity of 98.4%, a specificity of 97.7%, and an accuracy of 98.8%. Looking at these figures it is obvious that heavily T2 WI (TE=750ms) is an excellent tool for differentiating hepatic hemangiomas from cysts. A recent paper explored the feasibility of differentiating hepatic cyst from hemangiomas using multisection FLAIR-HASTE. This MR technique appears workable, however there is a particular dilemma. That is the fact that in that study only 85% of the cysts can be nulled effectively by the FLAIR-HASTE. In this study, long TE=750ms accuracy is 96.4%, which is boosted to 98.8% when ROI measurement replaces visual assessment. Therefore, we believed that MR hydro may be a move reliable technique in differentiating these two 21

22 lesions. In our current day to day practice, delayed phase post-contrast MRI sequence is still occasionally required for confirmation of hepatic cysts or hemangiomas, and exclusion of other lesions. This typically adds five to ten minutes to the study duration. In comparison, heavily T2 WI (TE=750ms) does not require contrast enhancement, takes only sixteen seconds for twelve images, and can be done as an add-on as soon as prior MR sequences reveal suspicious hepatic lesions. Most importantly, it is both sensitive and specific, with or without ROI measurement. (p<0.001) Conclusion HCC, Hepatic hemangiomas and cysts may be differentiated by heavily T2 WI (TE=750ms). It is a fast and reliable technique, and does not require the administration of intravenous contrast agent. It can be a useful MRI technique, especially as part of the whole body MRI for routine health examinations. 22

23 References 1. Ferrucci JT. Advances in abdominal MR imaging. Radiographics. 1998; 18: Jara H, Barish MA, Yucel EK, et al. MR hydrography: theory and paractice of static fluid imaging.ajr Am J Roentgenol. 1998;170: Ohgi K, Toyoda M, Yokote H, et al. MR hydrography of the abdomen: technical consideration of data acquisition and future prospects for clinical applications. Nippon Igaku Hoshasen Gakkai Zasshi ;61: McFarland EG, Mayo-Smith WW, Saini S, et al. Hepatic hemangiomas and malignant tumors: improved differentiation with heavily T2-Weighted conventional spin-echo MR imaging. Radiology. 1994;193: Goldberg MA, Hahn PF, Saini S, et al. Value of T1 and T2 relaxation times from echoplanar MR imging in the characterization of focal hepatic lesions. AJR Am J Roentgenol ;160: Mirk P, Rubaltelli L, Bazzocchi M, et al. Ultrasonographic patterns in hepatic hemangiomas. J Clin Ultrasound. 1982;10: Cherqui D. Benign liver tumors. J Chir. 2001;138: Konno K, Ishida H, Sato M, et al. Liver tumors in fatty liver: difficulty in ultrasonographic interpretation. Abdom Imaging. 2001;26: Furtado CD, Aguirre DA, Sirlin CB, et al. Whole-Body CT Screening: Spectrum of Findings and Recommendations in 1192 Patients. Radiology ;237: Goehde SC, Hunold P, Vogt FM, et al. Full-body cardiovascular and tumor MRI for early detection of disease: feasibility and initial experience in 298 subjects. AJR Am J Roentgenol ;184: Ito K, Mitchell DG, Outwater EK, Szklaruk J, Sadek AG. Hepatic lesions: 23

24 discrimination of nonsolid, benign lesions from solid, malignant lesions with heavily T2-weighted fast spin-echo MR imaging. Radiology ;204: Fenlon HM, Tello R, decarvalho VL, Yucel EK.Signal characteristics of focal liver lesions on double echo T2-weighted conventional spin echo MRI: observer performance versus quantitative measurements of T2 relaxation times. J Comput Assist To mogr. 2000; 24: Egglin TK, Rummeny E, Stark DD, Wittenberg J, Saini S, Ferrucci JT.Hepatic tumors: quantitative tissue characterization with MR imaging. Radiology. 1990;176: Bennett GL, Petersein A, Mayo-Smith WW, Hahn PF, Schima W, Saini S.Addition of gadolinium chelates to heavily T2-weighted MR imaging: limited role in differentiating hepatic hemangiomas from metastases. AJR Am J Roentgenol. 2000;174: Jafari F, Nayeri N, Tahsini M, Khodadoust AA. Differentiation of hepatic cavernous hemangioma from metastases by rare sequence MR imaging. Magn Reson Imaging. 1999; 17: Sasaki K, Ito K, Koike S, Fujita T, Okazaki H, Matsunaga N. Differentiation between hepatic cyst and hemangioma: additive value of breath-hold, multisection fluid-attenuated inversion-recovery magnetic resonance imaging using half-fourier acquisition single-shot turbo-spin-echo sequence. J Magn Reson Imaging ;21: Tello R, Fenlon HM, Gagliano T, decarvalho VL, Yucel EK. Prediction rule for characterization of hepatic lesions revealed on MR imaging: estimation of malignancy. AJR Am J Roentgenol. 2001;176: