Eur Radiol (2014) 24:2795–2799 DOI 10.1007/s00330-014-3327-2
UROGENITAL
Dynamic Contrast-Enhanced MR Imaging of Endometrial Cancer: Optimizing the Imaging Delay for Tumour-Myometrium Contrast Sung Bin Park & Min Hoan Moon & Chang Kyu Sung & Sohee Oh & Young Ho Lee
Received: 6 January 2014 / Revised: 1 May 2014 / Accepted: 8 July 2014 / Published online: 24 July 2014 # European Society of Radiology 2014
Abstract Purpose To investigate the optimal imaging delay time of dynamic contrast-enhanced magnetic resonance (MR) imaging in women with endometrial cancer. Materials and Methods This prospective single-institution study was approved by the institutional review board, and informed consent was obtained from the participants. Thirtyfive women (mean age, 54 years; age range, 29–66 years) underwent dynamic contrast-enhanced MR imaging with a temporal resolution of 25–40 seconds. The signal intensity difference ratios between the myometrium and endometrial cancer were analyzed to investigate the optimal imaging delay time using single change-point analysis. Results The optimal imaging delay time for appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The median optimal imaging delay time was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. The median signal intensity difference ratios between the myometrium and endometrial cancer were 0.03, with an interquartile range of -0.01 to 0.06, on the pre-contrast MR S. B. Park Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea M. H. Moon (*) : C. K. Sung Department of Radiology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, 41, Boramae-Gil, Dongjak-Gu, Seoul 156-707, Korea e-mail: [email protected] S. Oh Department of Biostatistics, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, 41, Seoul, Korea Y. H. Lee Department of Radiology, Cheil General Hospital & Women’s Healthcare Center, Kwandong University College of Medicine, Seoul, Korea
imaging and 0.20, with an interquartile range of 0.15 to 0.25, on the post-contrast MR imaging. Conclusion An imaging delay of approximately 90 seconds after initiating contrast material injection may be optimal for obtaining appropriate tumour-myometrium contrast in women with endometrial cancer. Key Points • Recent advances have allowed for MR imaging of high temporal resolution. • Contrast-enhanced MR imaging is helpful for evaluation of endometrial cancer. • An imaging delay of 90 seconds may be optimal. Keywords MR . Gadolinium . K-space . Uterine neoplasms . Staging
Introduction Endometrial cancer is the most common gynaecological malignancy in developed countries, with 47,130 expected new cases and 8,010 deaths in the United States in 2012 [1, 2]. While endometrial cancer is staged on the basis of surgical and pathological finding, preoperative magnetic resonance (MR) staging may be of critical importance in that presumed MR staging can guide the selection of appropriate surgical plans. The incidence of lymph node metastases increases from 3 % in endometrial cancer with superficial myometrial invasion (stage 1A) to 46 % when the endometrial cancer is accompanied by deep myometrial invasion (stage 1B) [3, 4]. Thus, preoperative determination of myometrial invasion allows women the selection of less invasive pelvic or para-aortic lymph node sampling rather than more invasive radical lymph node dissections [5]. MR imaging has proven to be the most accurate imaging modality in the preoperative assessment of endometrial cancer, and the addition of contrast-enhanced MR
2796
imaging has been shown to improve the ability of T2weighted images to assess myometrial invasion [6–12]. Although it is well known that contrast-enhanced MR imaging is the most accurate technique for assessing myometrial invasion, little is known about the optimal imaging delay time after contrast administration for appropriate tumour-myometrium contrast. Therefore, the purpose of our study was to investigate the optimal dynamic contrast-enhanced MR imaging delay for appropriate tumour-myometrium contrast in women with endometrial cancer.
Materials and Methods Study Population This prospective single-institution study was approved by our institutional review board, and informed consent was obtained from the participants. From March 2010 to June 2011, a total of 79 consecutive women who (a) had endometrial cancer histologically documented by microcurettage or hysteroscopic biopsy and who (b) underwent MR imaging as part of the preoperative evaluation for surgical planning were included in this observational study. During data analysis, 44 women were excluded from the study because (a) they had no demonstrable or measurable endometrial masses in the MR images (n=29), (b) they had large endometrial masses without comparable residual myometrium in the MR images (n=5), (c) their source images for the time-signal intensity curve were not available (n=2), (d) their definitive histological diagnoses were not endometrial carcinoma (n=7; carcinosarcoma in four women, cervical cancer in two women, and complex hyperplasia in one woman), or (e) their dynamic contrast-enhanced images were not successfully acquired due to technical error (n=1). The remaining 35 women (mean age, 54 years; age range, 29–66 years) constituted the study population. Twentyfour women (69 %) were postmenopausal and 11 women (31 %) were premenopausal. The mean time interval between MR imaging and surgery was 8.6 days, with a range of 1 to 19 days. Imaging Protocol The MR imaging studies were performed using a 1.5-T MR unit (Achieva and Intera; Philips Medical Systems, Best, Netherlands) and a phased-array torso coil. One-half hour before MR imaging evaluation, patients were given 20 mg of intramuscularly injected scopolamine butylbromide (Buscopan; Boehringer Ingelheim Korea, Seoul, Korea) as an antiperistaltic agent. Turbo spin-echo (TSE) T2-weighted images were obtained in the sagittal and axial planes with the following parameters: repetition time (msec)/echo time (msec), 6000/100; matrix,
Eur Radiol (2014) 24:2795–2799
256×256; number of acquired signals, two; field of view, 25 cm; section thickness, 5 mm; intersection gap, 1 mm; and bandwidth, 250 Hz. TSE T1-weighted images were obtained in the axial plane, with the following parameters: repetition time (msec)/echo time (msec), 620/10; matrix, 256×256; number of acquired signals, two; field of view, 25 cm; section thickness, 5 mm; intersection gap, 1 mm; and bandwidth, 250 Hz. Oblique axial TSE T2-weighted images were obtained with the same parameters as the sagittal and axial TSE T2weighted images, and the oblique axial plane was chosen perpendicular to the endometrial cavity. Dynamic contrastenhanced MR imaging was conducted as a standard part of the MR evaluation. Fat-saturated T1-weighted threedimensional fast field echo, also obtained perpendicular to the endometrial cavity, was used for dynamic contrastenhanced MR imaging, with the following parameters: repetition time (msec)/echo time (msec), 5–6/2–3; flip angle, 10o; matrix, 356×356; number of acquired signals, two; field of view, 25 cm; section thickness, 4 mm, interpolated to 2 mm; and bandwidth, 190 Hz. For a higher temporal resolution, the scan percentage was reduced to 60 %, which allowed for a temporal resolution of 25–40 seconds, depending on the uterine size. The loss of image resolution from reduced scan percentage was compensated with the peripheral part of the k-space of the last dynamic reference scan. Imaging began simultaneously with the administration of 0.1 mmol gadolinium per kilogram of body weight, injected at a rate of 2 ml/sec through an antecubital vein, and approximately 7–12 continuous sets of image series were acquired during 4–6 minutes of examination. Our standardized MR imaging protocol for endometrial cancer is summarized in Table 1. Data Analysis and Statistical Methods For the purposes of this study, time-signal intensity data were obtained from the dynamic contrast-enhanced MR images using operator-defined regions of interest (ROIs) for the myometrium and the endometrial cancer (Fig. 1). The ROIs were drawn to encompass as much of the lesions as possible in order to minimize noise, and care was given to avoid partialvolume artefacts. Because the parallel imaging technique was used, the signal-to-noise and contrast-to-noise ratios could not be calculated. Instead, we used the signal intensity (SI) difference ratio to determine the optimal imaging delay time for appropriate tumour-myometrium contrast. The SI difference ratio was calculated as follows: SI difference ratio=(SIm – SIc) /(SI m + SI c ), where SI m is the signal intensity of the myometrium and SIc is the signal intensity of the endometrial cancer (Fig. 2). This formula provides a unit-less parameter between 0 and 1, with 1 representing the greatest relative contrast. We conducted change-point analysis to determine the optimal dynamic contrast-enhanced MR imaging delay time for
Eur Radiol (2014) 24:2795–2799
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Table 1 MR Imaging Protocol for Endometrial Cancer Sequence
Plane
Reason
T2-weighted TSEa
Sagittal
T2-weighted TSEa
Axial
T1-weighted TSEa
Axial
T2-weighted TSEa
Oblique axialb
Contrast-enhanced T1weighted 3D FFEc with fat saturation T2-weighted SSTSEd
Oblique axialb
General assessment of the pelvic cavity General assessment of the pelvic cavity General assessment of the pelvic cavity Evaluation of myometrial invasion Evaluation of myometrial invasion
a
Axial
Evaluate abdominal lymph nodes
TSE=turbo spin-echo sequence
b
Oblique axial images were obtained perpendicular to the endometrial cavity c
FFE=fast field echo
d
SSTSE=single-shot turbo spin-echo sequence
Results Histopathological confirmation was conducted following hysterectomy in 31 women and dilatation and curettage or endometrial biopsy in four women. The final histological subtypes were as follows: endometrioid adenocarcinoma in 27 women, adenocarcinoma with mucinous differentiation in three women, adenocarcinoma with serous papillary differentiation in two women, adenocarcinoma with mixed pattern in two women, and squamous carcinoma in one woman. The histological grades were grade 1 in 17 women, grade 2 in 11 women, and grade 3 in seven women. Of the 31 women with hysterectomy, the surgical specimens showed less than half myometrial invasion in 22 women and more than half myometrial invasion in nine women. The optimal imaging delay time points for depicting appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The median time point was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. The median signal intensity difference ratios between the myometrium and endometrial cancer were 0.03, with an interquartile range of 0.01 to 0.06, on the pre-contrast MR imaging and 0.20, with an interquartile range of 0.15 to 0.25, on the post-contrast MR imaging (Fig. 3).
appropriate tumour-myometrium contrast. Change-point analysis is a well-established method for analyzing timeordered data to identify the point at which the statistical properties of a sequence of observation changes in the mean, variance, and both the mean and variance under various distributional and distribution-free circumstances [13–15]. In this study, we performed the analysis for single change-points in the mean. The optimal imaging delay times for appropriate tumour-myometrium contrast are summarized as medians and interquartile ranges. All statistical analyses were performed with IBM SPSS version 20 (IBM Software Inc.) and the change-point package in R version 2.15.2 (http://www.r-project.org).
Recent advances in MR imaging hardware and software have allowed for the development of rapid imaging techniques that are particularly suited for dynamic contrast-enhanced MR imaging. The concept of reducing the scan percentage is one such recent advance [16]; reducing the scan percentage has allowed for multiple sequential data acquisition with higher
Fig. 1 Time-signal intensity data from dynamic contrast-enhanced MR images. Regions of interest (ROIs) for endometrial cancer (L1 in a) and the myometrium (L2 in a) were determined on the contrast-enhanced T1weighted oblique axial image and time-signal intensity data (b) were
obtained from the ROIs. Note that the first measurement of the timesignal intensity data was obtained from pre-contrast MR images and the second measurement was obtained from dynamic contrast-enhanced MR images acquired simultaneously with the injection of the contrast material
Discussion
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Eur Radiol (2014) 24:2795–2799
Fig. 2 Signal intensity (SI) difference ratio between the endometrial cancer and the myometrium. The SI of the endometrial cancer (L1) and the myometrium (L2) were 1173.5 and 1289.3 on the pre-contrast MR
imaging (a) and 2065.2 and 3461.5 on the post-contrast MR imaging (b). The calculated SI difference ratios were 0.05 and 0.25 on the pre-contrast and post-contrast MR imaging, respectively
temporal resolution, which allows for perfusion imaging. Reducing the scan percentage means acquiring just the central portion of the k-space, which shortens the scan time in the same proportion. The loss of image resolution from the reduced scan percentage is compensated with the peripheral portion of the k-space of the reference image in which a complete k-space is acquired. Dynamic contrast-enhanced MR imaging has been routinely included in the MR imaging protocols for the evaluation of endometrial cancer, as contrast-enhanced MR imaging can improve the accuracy of T2-weighted images in tumour detection and staging [9–11]. Reduction in the scan percentage for dynamic contrast-enhanced MR imaging has allowed for multiple sequential data acquisition of higher temporal
resolution, which enables perfusion imaging of the uterus. In this era of rapid dynamic contrast-enhanced MR imaging, the selection of an appropriate imaging delay time can be one of the most important imaging parameters, as the selected imaging delay time has a strong influence on the tumourmyometrium contrast of dynamic contrast-enhanced MR imaging. In this study, we sought to investigate the optimal dynamic contrast-enhanced MR imaging delay time for appropriate tumour-myometrium contrast in women with endometrial cancer. The optimal imaging delay time was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. Given that our image data for the centre of k-space, which determines the image contrast, are collected earlier in the acquisition, there might be no need for repeating rapid sequential data acquisition beyond two minutes after initiating the contrast material injection, irrespective of the choices for k-space traversal. In turn, this benefit may save examination time or allow for extra time for performing another MR sequence, such as diffusion-weighted imaging or MR spectroscopy. The determination of the optimal imaging delay time for appropriate tumour-myometrium contrast also has a greater impact on the choice of k-space traversal when considering three-dimensional data acquisition for the reconstruction of three orthogonal planes. Unlike dynamic contrast-enhanced MR imaging for perfusion, imaging for the reconstruction of three orthogonal planes requires a long acquisition time to obtain isotropic voxel data. If the central k-space data are obtained first, the beginning portion of the data acquisition should be centred in the range of 60 to 120 seconds after initiating contrast material injection. In contrast, if the peripheral k-space data are obtained first, the data acquisition should be performed immediately after initiating contrast material injection. This is because the central k-space data would be filled beyond the range of the optimal imaging delay time due to the long acquisition time of approximately five minutes.
Fig. 3 Box and whisker plots showing the SI difference ratio. The median ratios of the SI differences between the myometrium and endometrial cancer were 0.03 (interquartile range: -0.01, 0.06) in the precontrast MR images and 0.20 (interquartile range: 0.15, 0.25) in the post-contrast MR images. Central line=median, top of the box=upper quartile, bottom of the box=lower quartile, whiskers=smallest and largest non-outliers, o=outliers
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A limitation of this study is that we did not consider the effect of the individual patient’s circulation status on the contrast dynamics. In a study of 100 patients with chronic liver damage in whom test bolus imaging was performed to determine the aortic transit time, Kanematsu et al. [17] reported that the aortic transit time ranged widely from 11 to 37 seconds. Thus, the imaging delay should be optimized on the basis of the time between the arrival of contrast material in the abdominal aorta and image acquisition rather than the time between the initiation of contrast material injection and image acquisition. Differences in patient circulation might be partly responsible for the wide range of optimal imaging delay times in this study. The small study population was another limitation of the present study. To overcome these limitations, future studies should be designed with the difference in aortic transit time of individuals in larger patient populations in mind. In conclusion, in the evaluation of dynamic contrastenhanced MR imaging of women with endometrial cancer, an imaging delay of approximately 90 seconds after initiating contrast injection may be optimal for obtaining appropriate tumour-myometrium contrast, with a median signal intensity difference ratio of 0.2. We hope that our results will be helpful in the preoperative MR evaluation of women with endometrial cancer. Acknowledgments This study was supported by the research fund of the Radiological Research Foundation of Korea (2011-03), and we thank Chun Ho Kang, who participated in the acquisition of MR images. The scientific guarantor of this publication is Dr. Min Hoan Moon. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. One of the authors has significant statistical expertise. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective observational study, performed at one institution.
References 1. Freeman SJ, Aly AM, Kataoka MY, Addley HC, Reinhold C, Sala E (2012) The revised FIGO staging system for uterine malignancies: implications for MR imaging. Radiographics 32:1805–1827
2799 2. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA: Cancer J Clin 62:10–29 3. Boronow R, Morrow C, Creasman Wet al (1984) Surgical staging in endometrial cancer: clinical-pathologic findings of a prospective study. Obstet Gynecol 63:825–832 4. PIVER MS, LELE SB, BARLOW JJ, BLUMENSON L (1982) Paraaortic lymph node evaluation in stage I endometrial carcinoma. Obstet Gynecol 59:97–100 5. Sala E, Wakely S, Senior E, Lomas D (2007) MRI of malignant neoplasms of the uterine corpus and cervix. Am J Roentgenol 188: 1577–1587 6. Hori M, Kim T, Onishi H et al (2013) Endometrial cancer: preoperative staging using three-dimensional T2-weighted turbo spin-echo and diffusion-weighted MR imaging at 3.0 T: a prospective comparative study. Eur Radiol 23:2296–2305 7. Sala E, Rockall AG, Freeman SJ, Mitchell DG, Reinhold C (2013) The added role of MR imaging in treatment stratification of patients with gynecologic malignancies: what the radiologist needs to know. Radiology 266:717–740 8. Wakefield JC, Downey K, Kyriazi S, deSouza NM (2013) New MR Techniques in Gynecologic Cancer. Am J Roentgenol 200:249–260 9. Sironi S, Colombo E, Villa G et al (1992) Myometrial invasion by endometrial carcinoma: assessment with plain and gadoliniumenhanced MR imaging. Radiology 185:207–212 10. Seki H, Kimura M, Sakai K (1997) Myometrial invasion of endometrial carcinoma: assessment with dynamic MR and contrast-enhanced T1-weighted images. Clin Radiol 52:18–23 11. Sala E, Crawford R, Senior E et al (2009) Added value of dynamic contrast-enhanced magnetic resonance imaging in predicting advanced stage disease in patients with endometrial carcinoma. Int J Gynecol Cancer 19:141–146 12. Sala E, Rockall A, Rangarajan D, Kubik-Huch RA (2010) The role of dynamic contrast-enhanced and diffusion weighted magnetic resonance imaging in the female pelvis. Eur J Radiol 76:367–385 13. Hinkley DV (1970) Inference about the change-point in a sequence of random variables. Biometrika 57:1–17 14. Killick R, Eckley IA (2011) Changepoint: an R package for changepoint analysis. Lancaster University 15. Killick R, Fearnhead P, Eckley I (2012) Optimal detection of changepoints with a linear computational cost. J Am Stat Assoc 107:1590–1598 16. Moratal D, Vallés-Luch A, Martí-Bonmatí L, Brummer ME (2008) kSpace tutorial: an MRI educational tool for a better understanding of k-space. Biomed Imaging Interv J 4:e15 17. Kanematsu M, Semelka RC, Matsuo M et al (2002) Gadoliniumenhanced MR Imaging of the Liver: Optimizing Imaging Delay for Hepatic Arterial and Portal Venous Phases—A Prospective Randomized Study in Patients with Chronic Liver Damage1. Radiology 225:407–415
UROGENITAL
Dynamic Contrast-Enhanced MR Imaging of Endometrial Cancer: Optimizing the Imaging Delay for Tumour-Myometrium Contrast Sung Bin Park & Min Hoan Moon & Chang Kyu Sung & Sohee Oh & Young Ho Lee
Received: 6 January 2014 / Revised: 1 May 2014 / Accepted: 8 July 2014 / Published online: 24 July 2014 # European Society of Radiology 2014
Abstract Purpose To investigate the optimal imaging delay time of dynamic contrast-enhanced magnetic resonance (MR) imaging in women with endometrial cancer. Materials and Methods This prospective single-institution study was approved by the institutional review board, and informed consent was obtained from the participants. Thirtyfive women (mean age, 54 years; age range, 29–66 years) underwent dynamic contrast-enhanced MR imaging with a temporal resolution of 25–40 seconds. The signal intensity difference ratios between the myometrium and endometrial cancer were analyzed to investigate the optimal imaging delay time using single change-point analysis. Results The optimal imaging delay time for appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The median optimal imaging delay time was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. The median signal intensity difference ratios between the myometrium and endometrial cancer were 0.03, with an interquartile range of -0.01 to 0.06, on the pre-contrast MR S. B. Park Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea M. H. Moon (*) : C. K. Sung Department of Radiology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, 41, Boramae-Gil, Dongjak-Gu, Seoul 156-707, Korea e-mail: [email protected] S. Oh Department of Biostatistics, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, 41, Seoul, Korea Y. H. Lee Department of Radiology, Cheil General Hospital & Women’s Healthcare Center, Kwandong University College of Medicine, Seoul, Korea
imaging and 0.20, with an interquartile range of 0.15 to 0.25, on the post-contrast MR imaging. Conclusion An imaging delay of approximately 90 seconds after initiating contrast material injection may be optimal for obtaining appropriate tumour-myometrium contrast in women with endometrial cancer. Key Points • Recent advances have allowed for MR imaging of high temporal resolution. • Contrast-enhanced MR imaging is helpful for evaluation of endometrial cancer. • An imaging delay of 90 seconds may be optimal. Keywords MR . Gadolinium . K-space . Uterine neoplasms . Staging
Introduction Endometrial cancer is the most common gynaecological malignancy in developed countries, with 47,130 expected new cases and 8,010 deaths in the United States in 2012 [1, 2]. While endometrial cancer is staged on the basis of surgical and pathological finding, preoperative magnetic resonance (MR) staging may be of critical importance in that presumed MR staging can guide the selection of appropriate surgical plans. The incidence of lymph node metastases increases from 3 % in endometrial cancer with superficial myometrial invasion (stage 1A) to 46 % when the endometrial cancer is accompanied by deep myometrial invasion (stage 1B) [3, 4]. Thus, preoperative determination of myometrial invasion allows women the selection of less invasive pelvic or para-aortic lymph node sampling rather than more invasive radical lymph node dissections [5]. MR imaging has proven to be the most accurate imaging modality in the preoperative assessment of endometrial cancer, and the addition of contrast-enhanced MR
2796
imaging has been shown to improve the ability of T2weighted images to assess myometrial invasion [6–12]. Although it is well known that contrast-enhanced MR imaging is the most accurate technique for assessing myometrial invasion, little is known about the optimal imaging delay time after contrast administration for appropriate tumour-myometrium contrast. Therefore, the purpose of our study was to investigate the optimal dynamic contrast-enhanced MR imaging delay for appropriate tumour-myometrium contrast in women with endometrial cancer.
Materials and Methods Study Population This prospective single-institution study was approved by our institutional review board, and informed consent was obtained from the participants. From March 2010 to June 2011, a total of 79 consecutive women who (a) had endometrial cancer histologically documented by microcurettage or hysteroscopic biopsy and who (b) underwent MR imaging as part of the preoperative evaluation for surgical planning were included in this observational study. During data analysis, 44 women were excluded from the study because (a) they had no demonstrable or measurable endometrial masses in the MR images (n=29), (b) they had large endometrial masses without comparable residual myometrium in the MR images (n=5), (c) their source images for the time-signal intensity curve were not available (n=2), (d) their definitive histological diagnoses were not endometrial carcinoma (n=7; carcinosarcoma in four women, cervical cancer in two women, and complex hyperplasia in one woman), or (e) their dynamic contrast-enhanced images were not successfully acquired due to technical error (n=1). The remaining 35 women (mean age, 54 years; age range, 29–66 years) constituted the study population. Twentyfour women (69 %) were postmenopausal and 11 women (31 %) were premenopausal. The mean time interval between MR imaging and surgery was 8.6 days, with a range of 1 to 19 days. Imaging Protocol The MR imaging studies were performed using a 1.5-T MR unit (Achieva and Intera; Philips Medical Systems, Best, Netherlands) and a phased-array torso coil. One-half hour before MR imaging evaluation, patients were given 20 mg of intramuscularly injected scopolamine butylbromide (Buscopan; Boehringer Ingelheim Korea, Seoul, Korea) as an antiperistaltic agent. Turbo spin-echo (TSE) T2-weighted images were obtained in the sagittal and axial planes with the following parameters: repetition time (msec)/echo time (msec), 6000/100; matrix,
Eur Radiol (2014) 24:2795–2799
256×256; number of acquired signals, two; field of view, 25 cm; section thickness, 5 mm; intersection gap, 1 mm; and bandwidth, 250 Hz. TSE T1-weighted images were obtained in the axial plane, with the following parameters: repetition time (msec)/echo time (msec), 620/10; matrix, 256×256; number of acquired signals, two; field of view, 25 cm; section thickness, 5 mm; intersection gap, 1 mm; and bandwidth, 250 Hz. Oblique axial TSE T2-weighted images were obtained with the same parameters as the sagittal and axial TSE T2weighted images, and the oblique axial plane was chosen perpendicular to the endometrial cavity. Dynamic contrastenhanced MR imaging was conducted as a standard part of the MR evaluation. Fat-saturated T1-weighted threedimensional fast field echo, also obtained perpendicular to the endometrial cavity, was used for dynamic contrastenhanced MR imaging, with the following parameters: repetition time (msec)/echo time (msec), 5–6/2–3; flip angle, 10o; matrix, 356×356; number of acquired signals, two; field of view, 25 cm; section thickness, 4 mm, interpolated to 2 mm; and bandwidth, 190 Hz. For a higher temporal resolution, the scan percentage was reduced to 60 %, which allowed for a temporal resolution of 25–40 seconds, depending on the uterine size. The loss of image resolution from reduced scan percentage was compensated with the peripheral part of the k-space of the last dynamic reference scan. Imaging began simultaneously with the administration of 0.1 mmol gadolinium per kilogram of body weight, injected at a rate of 2 ml/sec through an antecubital vein, and approximately 7–12 continuous sets of image series were acquired during 4–6 minutes of examination. Our standardized MR imaging protocol for endometrial cancer is summarized in Table 1. Data Analysis and Statistical Methods For the purposes of this study, time-signal intensity data were obtained from the dynamic contrast-enhanced MR images using operator-defined regions of interest (ROIs) for the myometrium and the endometrial cancer (Fig. 1). The ROIs were drawn to encompass as much of the lesions as possible in order to minimize noise, and care was given to avoid partialvolume artefacts. Because the parallel imaging technique was used, the signal-to-noise and contrast-to-noise ratios could not be calculated. Instead, we used the signal intensity (SI) difference ratio to determine the optimal imaging delay time for appropriate tumour-myometrium contrast. The SI difference ratio was calculated as follows: SI difference ratio=(SIm – SIc) /(SI m + SI c ), where SI m is the signal intensity of the myometrium and SIc is the signal intensity of the endometrial cancer (Fig. 2). This formula provides a unit-less parameter between 0 and 1, with 1 representing the greatest relative contrast. We conducted change-point analysis to determine the optimal dynamic contrast-enhanced MR imaging delay time for
Eur Radiol (2014) 24:2795–2799
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Table 1 MR Imaging Protocol for Endometrial Cancer Sequence
Plane
Reason
T2-weighted TSEa
Sagittal
T2-weighted TSEa
Axial
T1-weighted TSEa
Axial
T2-weighted TSEa
Oblique axialb
Contrast-enhanced T1weighted 3D FFEc with fat saturation T2-weighted SSTSEd
Oblique axialb
General assessment of the pelvic cavity General assessment of the pelvic cavity General assessment of the pelvic cavity Evaluation of myometrial invasion Evaluation of myometrial invasion
a
Axial
Evaluate abdominal lymph nodes
TSE=turbo spin-echo sequence
b
Oblique axial images were obtained perpendicular to the endometrial cavity c
FFE=fast field echo
d
SSTSE=single-shot turbo spin-echo sequence
Results Histopathological confirmation was conducted following hysterectomy in 31 women and dilatation and curettage or endometrial biopsy in four women. The final histological subtypes were as follows: endometrioid adenocarcinoma in 27 women, adenocarcinoma with mucinous differentiation in three women, adenocarcinoma with serous papillary differentiation in two women, adenocarcinoma with mixed pattern in two women, and squamous carcinoma in one woman. The histological grades were grade 1 in 17 women, grade 2 in 11 women, and grade 3 in seven women. Of the 31 women with hysterectomy, the surgical specimens showed less than half myometrial invasion in 22 women and more than half myometrial invasion in nine women. The optimal imaging delay time points for depicting appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The median time point was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. The median signal intensity difference ratios between the myometrium and endometrial cancer were 0.03, with an interquartile range of 0.01 to 0.06, on the pre-contrast MR imaging and 0.20, with an interquartile range of 0.15 to 0.25, on the post-contrast MR imaging (Fig. 3).
appropriate tumour-myometrium contrast. Change-point analysis is a well-established method for analyzing timeordered data to identify the point at which the statistical properties of a sequence of observation changes in the mean, variance, and both the mean and variance under various distributional and distribution-free circumstances [13–15]. In this study, we performed the analysis for single change-points in the mean. The optimal imaging delay times for appropriate tumour-myometrium contrast are summarized as medians and interquartile ranges. All statistical analyses were performed with IBM SPSS version 20 (IBM Software Inc.) and the change-point package in R version 2.15.2 (http://www.r-project.org).
Recent advances in MR imaging hardware and software have allowed for the development of rapid imaging techniques that are particularly suited for dynamic contrast-enhanced MR imaging. The concept of reducing the scan percentage is one such recent advance [16]; reducing the scan percentage has allowed for multiple sequential data acquisition with higher
Fig. 1 Time-signal intensity data from dynamic contrast-enhanced MR images. Regions of interest (ROIs) for endometrial cancer (L1 in a) and the myometrium (L2 in a) were determined on the contrast-enhanced T1weighted oblique axial image and time-signal intensity data (b) were
obtained from the ROIs. Note that the first measurement of the timesignal intensity data was obtained from pre-contrast MR images and the second measurement was obtained from dynamic contrast-enhanced MR images acquired simultaneously with the injection of the contrast material
Discussion
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Fig. 2 Signal intensity (SI) difference ratio between the endometrial cancer and the myometrium. The SI of the endometrial cancer (L1) and the myometrium (L2) were 1173.5 and 1289.3 on the pre-contrast MR
imaging (a) and 2065.2 and 3461.5 on the post-contrast MR imaging (b). The calculated SI difference ratios were 0.05 and 0.25 on the pre-contrast and post-contrast MR imaging, respectively
temporal resolution, which allows for perfusion imaging. Reducing the scan percentage means acquiring just the central portion of the k-space, which shortens the scan time in the same proportion. The loss of image resolution from the reduced scan percentage is compensated with the peripheral portion of the k-space of the reference image in which a complete k-space is acquired. Dynamic contrast-enhanced MR imaging has been routinely included in the MR imaging protocols for the evaluation of endometrial cancer, as contrast-enhanced MR imaging can improve the accuracy of T2-weighted images in tumour detection and staging [9–11]. Reduction in the scan percentage for dynamic contrast-enhanced MR imaging has allowed for multiple sequential data acquisition of higher temporal
resolution, which enables perfusion imaging of the uterus. In this era of rapid dynamic contrast-enhanced MR imaging, the selection of an appropriate imaging delay time can be one of the most important imaging parameters, as the selected imaging delay time has a strong influence on the tumourmyometrium contrast of dynamic contrast-enhanced MR imaging. In this study, we sought to investigate the optimal dynamic contrast-enhanced MR imaging delay time for appropriate tumour-myometrium contrast in women with endometrial cancer. The optimal imaging delay time was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. Given that our image data for the centre of k-space, which determines the image contrast, are collected earlier in the acquisition, there might be no need for repeating rapid sequential data acquisition beyond two minutes after initiating the contrast material injection, irrespective of the choices for k-space traversal. In turn, this benefit may save examination time or allow for extra time for performing another MR sequence, such as diffusion-weighted imaging or MR spectroscopy. The determination of the optimal imaging delay time for appropriate tumour-myometrium contrast also has a greater impact on the choice of k-space traversal when considering three-dimensional data acquisition for the reconstruction of three orthogonal planes. Unlike dynamic contrast-enhanced MR imaging for perfusion, imaging for the reconstruction of three orthogonal planes requires a long acquisition time to obtain isotropic voxel data. If the central k-space data are obtained first, the beginning portion of the data acquisition should be centred in the range of 60 to 120 seconds after initiating contrast material injection. In contrast, if the peripheral k-space data are obtained first, the data acquisition should be performed immediately after initiating contrast material injection. This is because the central k-space data would be filled beyond the range of the optimal imaging delay time due to the long acquisition time of approximately five minutes.
Fig. 3 Box and whisker plots showing the SI difference ratio. The median ratios of the SI differences between the myometrium and endometrial cancer were 0.03 (interquartile range: -0.01, 0.06) in the precontrast MR images and 0.20 (interquartile range: 0.15, 0.25) in the post-contrast MR images. Central line=median, top of the box=upper quartile, bottom of the box=lower quartile, whiskers=smallest and largest non-outliers, o=outliers
Eur Radiol (2014) 24:2795–2799
A limitation of this study is that we did not consider the effect of the individual patient’s circulation status on the contrast dynamics. In a study of 100 patients with chronic liver damage in whom test bolus imaging was performed to determine the aortic transit time, Kanematsu et al. [17] reported that the aortic transit time ranged widely from 11 to 37 seconds. Thus, the imaging delay should be optimized on the basis of the time between the arrival of contrast material in the abdominal aorta and image acquisition rather than the time between the initiation of contrast material injection and image acquisition. Differences in patient circulation might be partly responsible for the wide range of optimal imaging delay times in this study. The small study population was another limitation of the present study. To overcome these limitations, future studies should be designed with the difference in aortic transit time of individuals in larger patient populations in mind. In conclusion, in the evaluation of dynamic contrastenhanced MR imaging of women with endometrial cancer, an imaging delay of approximately 90 seconds after initiating contrast injection may be optimal for obtaining appropriate tumour-myometrium contrast, with a median signal intensity difference ratio of 0.2. We hope that our results will be helpful in the preoperative MR evaluation of women with endometrial cancer. Acknowledgments This study was supported by the research fund of the Radiological Research Foundation of Korea (2011-03), and we thank Chun Ho Kang, who participated in the acquisition of MR images. The scientific guarantor of this publication is Dr. Min Hoan Moon. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. One of the authors has significant statistical expertise. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective observational study, performed at one institution.
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