DOI: 10.1148/radiol.2433051978
(Radiology 2007;243:760-765.)
© RSNA, 2007
Comparison of Delayed Enhanced CT and Chemical Shift MR for Evaluating Hyperattenuating Incidental Adrenal Masses1
Byung Kwan Park, MD,
Chan Kyo Kim, MD,
Bohyun Kim, MD, and
Jung Hee Lee, PhD
1 From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea (B.K.P., C.K.K., J.H.L.); and Department of Radiology, Mayo Clinic, Rochester, Minn (B.K.). Received January 26, 2006; revision requested March 27; revision received June 27; accepted August 2; final version accepted October 4.
Address correspondence to B.K.P. (e-mail: rapark{at}skku.edu).
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ABSTRACT
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Purpose: To retrospectively compare the accuracy of delayed enhanced computed tomography (CT) and chemical shift magnetic resonance (MR) imaging for characterizing hyperattenuating adrenal masses at CT, with either follow-up imaging or pathologic review as the reference standard.
Materials and Methods: The institutional review board approved this retrospective study with a waiver of patient informed consent. Forty-three hyperattenuating adrenal masses (>10 HU) on unenhanced CT images were found in 34 patients (23 men and 11 women; mean age, 52.7 years) by reviewing radiologic reports. These lesions were retrospectively analyzed with delayed enhanced CT and chemical shift MR. The diagnostic accuracy of CT by using absolute percentage loss of enhancement (PLE) and relative PLE and of chemical shift MR by using adrenal-to-spleen ratio (ASR) or signal intensity index (SII) were obtained to determine which modality was more accurate for lipid-poor adenoma. For CT, an adenoma was diagnosed if a mass had an absolute PLE greater than 60% and a relative PLE greater than 40%. For MR, an adenoma was diagnosed if a mass had an ASR of 0.71 or an SII greater than 16.5%. McNemar test was used to compare diagnostic performance of CT and MR.
Results: Hyperattenuating adrenal masses included 37 adenomas and six nonadenomas. The sensitivity, specificity, and accuracy for adenoma at CT were 97% (36 of 37), 100% (six of six), and 98% (42 of 43), respectively, and at MR were 86% (32 of 37), 50% (three of six), and 49% (21 of 43), respectively. CT helped confirm five more adenomas and three more metastatic tumors than did MR. However, there was no significant difference for diagnostic accuracy between these two imaging modalities (P > .05)
Conclusion: Delayed enhanced CT can characterize additional hyperattenuating adrenal masses that cannot be characterized with chemical shift MR.
© RSNA, 2007
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INTRODUCTION
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Incidental adrenal masses are reported to occur in up to 5% of patients undergoing abdominal computed tomography (CT) (1). Although unenhanced CT has become the mainstay for characterizing lipid-rich adrenal adenomas, this imaging modality cannot help differentiate lipid-poor adenomas from nonadenomas (2,3). Several reports have demonstrated that delayed contrast material–enhanced CT or chemical shift magnetic resonance (MR) imaging are useful for the differentiation of lipid-poor adenomas (>10 HU) and nonadenomas (4–8). However, a direct comparison of delayed enhanced CT and chemical shift MR both performed in the same patient with hyperattenuating incidental adrenal masses has, to our knowledge, not yet been reported for the diagnosis of the lipid-poor adenoma.
The purpose of our study was to retrospectively compare the accuracy of delayed enhanced CT and chemical shift MR for characterizing hyperattenuating adrenal masses at CT, with either follow-up imaging or pathologic review as the reference standard.
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MATERIALS AND METHODS
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Patients
Our institutional review board approved this retrospective study with a waiver of patient informed consent. The CT reports were initially searched, and these were cross-referenced with the database to identify which patients had also undergone MR. We searched radiologic database records at our hospital from January 2002 to April 2005 and reviewed CT reports in which the words adrenal mass were present and obtained a total of 255 adrenal lesions in 240 patients. Among these lesions, 44 adrenal masses were identified as hyperattenuating (>10 HU on unenhanced CT images) in 35 patients. One patient with a single hyperattenuating adrenal mass was excluded because the lesion was considered a nonadenoma on both delayed enhanced CT and chemical shift MR images but was not pathologically confirmed. Our study finally included 43 adrenal masses in 34 patients (23 men and 11 women; average age, 52.7 years; range, 30–76 years) who had undergone both CT and MR. These adrenal masses ranged from 0.9 to 7 cm in maximum transverse diameter (average, 2.1 cm; median, 1.6 cm; standard deviation, 1.3). Five patients had bilateral masses (n = 14). The mean interval between the CT and MR examinations was 4.2 months (range, 1–10 months). All MR examinations had been performed prior to the dedicated CT scan for the adrenal mass when a hyperattenuating adrenal mass had been incidentally detected at abdominal CT performed for preoperative tumor staging (n = 10), postoperative follow-up imaging (n = 1), and evaluation of other diseases (n = 23).
Imaging Protocols
All CT examinations were performed with either a single-detector unit (HiSpeed advantage, GE Healthcare, Milwaukee, Wis) or one of three multidetector units (LightSpeed QX/i, LightSpeed Ultra 8, LightSpeed Ultra 16, GE Healthcare). Imaging parameters for unenhanced and contrast-enhanced CT examinations included 2.5–5.0 mm collimation, 1:1 pitch for single detector, 0.75:1 or 0.875:1 pitch for multidetector, 120 kVp, and 180–240 mA. Enhanced scans were obtained after the intravenous administration of 120 mL of iopromide (Ultravist 370, Schering, Germany) at a rate of 3.0 mL/sec by using a power injector. All patients underwent unenhanced CT and two-phase contrast-enhanced CT, which were performed at 60 seconds (early contrast-enhanced) and 15 minutes (delayed contrast-enhanced) from the beginning of the contrast agent bolus injection, the same method used in the study of Caoili et al (8). The same section collimation was used for all three CT acquisitions in the same patient. A section collimation of 5 mm was used in the evaluation of three patients with three large adrenal masses of more than 5 cm in maximum diameter.
All MR examinations were performed with either a 1.5-T system (Signa Horizon, GE Healthcare) and a torso phased-array coil in 12 patients or a 3-T system (Intera Achieva 3T, Philips Medical System, Best, the Netherlands) and a phased-array coil (Cardiac SENSE; Philips Medical System, Best, The Netherlands) in 22 patients. All patients underwent transverse breath-hold gradient-echo T1-weighted in- and opposed-phase imaging. For the 1.5-T system, the repetition time was 160–210 msec and the echo time was 2.1–2.4 msec for opposed-phase imaging and 4.2–4.8 msec for in-phase imaging. For the 3-T system, the repetition time was 130–160 msec and the echo time was 2.1–2.3 msec for opposed-phase imaging and 3.1–3.6 msec for in-phase imaging. Other imaging parameters of the 1.5-T and 3-T systems, respectively, were as follows: matrix, 256 x 156 and 320 x 256; number of signals acquired, one and one; section thickness, 4 and 3 mm; intersection gap, 1.0 and 0.5 mm; rectangular field of view, 38 and 38 cm; and flip angle, 90° and 55°. A single-echo sequence was used for in- and opposed-phase MR imaging at both 1.5 and 3.0 T.
Image Analysis
The CT and MR images were reloaded onto a picture archiving and communication system and were independently reviewed by two radiologists (for CT images, B.K.P. with 6 years experience; for MR images, B.K. with 16 years experience) without knowledge of clinical or histologic information.
For all masses on CT scans, absolute and relative percentage losses of enhancement (PLE) were calculated as follows: Absolute PLE = (CTEE – CTDE)·100/(CTEE – CTUE), and relative PLE = (CTEE – CTDE)·100/CTEE, where CTUE, CTEE, and CTDE are attenuation values of the adrenal mass at unenhanced, early enhanced, and delayed enhanced CT, respectively.
For all masses on MR images, the adrenal-to-spleen chemical shift ratio (ASR) was calculated as ASR = (SIAO/SISO)/(SIAI/SISI), where SIAO is the signal intensity of adrenal mass on opposed-phase images, SISO is the signal intensity of spleen on opposed-phase images, SIAI is the signal intensity of adrenal mass on in-phase images, and SISI is the signal intensity of spleen on in-phase images. The signal intensity index (SII) was calculated as SII = (SIAI – SOAO)·100/SOAI.
For CT and MR images, a round or ovoid manually controllable region of interest was placed in the center of the adrenal mass and/or spleen to obtain Hounsfield unit or signal intensity measurements. We tried to use a large enough region to cover more than half of the adrenal mass but avoided peripheral areas of the adrenal mass to avoid causing partial volume effect from the adjacent fat or from the dark line seen at the interface between fatty tissue and water on opposed-phase MR images. In addition, calcification, blood vessels, and necrotic and cystic areas were not included for region-of-interest measurements. All CT or MR image equations were calculated with mean values by averaging CT numbers or MR signal intensities, which were measured three times during each phase of imaging.
For CT, a lipid-poor adenoma was diagnosed if the mass had an absolute PLE greater than 60% and a relative PLE greater than 40% (7). For MR, the diagnosis of a lipid-poor adenoma was made if the mass had an ASR less than 0.71 (9) or an SII greater than 16.5% (10).
Reference Standard
The final diagnosis of lipid-poor adenoma was made if a mass had a CT number greater than 10 HU and was unchanged in size for at least 6 months at follow-up CT performed 6–12 months (mean, 8.7 months) after the delayed enhanced CT scan. The final diagnosis of nonadenoma was made if a mass was pathologically proved or if a mass grew to double volume or more within 6 months in a patient with a history of previous or present extraadrenal malignancy.
Statistical Analysis
For the diagnosis of lipid-poor adenoma, the sensitivities, specificities, and overall accuracies of CT and MR were obtained. The accuracies of each quantitative equation obtained from CT and MR findings were compared to determine which one was the most accurate for adenoma characterization. The sensitivity of MR and CT for lipid-poor adenoma was stratified in terms of lesions 1 cm or smaller (n = 3), 1.0–1.5-cm lesions (n = 17), and lesions larger than 1.5 cm (n = 23) to determine whether or not MR showed improved diagnostic performance according to the lesion size. The McNemar test was used to compare paired measurements from CT and MR of the same adrenal mass and to determinate which modality is more accurate for the characterization of hyperattenuating adenoma. Multiple masses in the same patient may behave differently from multiple masses from different patients, but we compared lesion-based accuracy of two imaging modalities rather than patient-based accuracy. A P value of less than .05 was considered to indicate a statistically significant difference. Statistical analysis was performed by using SAS for Windows (version 9, 2005; SAS Institute, Cary, NC).
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RESULTS
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The flow diagram in Figure 1 provides information about the method of patient inclusion, the tests performed, the patient number, and the reference test.
Final Diagnosis
The final diagnoses in the 43 adrenal masses were as follows: adenoma (n = 37), metastasis (n = 4), ganglioneuroma (n = 1), and angiomyolipoma (n = 1). Four adrenal masses had metastasized from cervical cancer (n = 3) and stomach cancer (n = 1). A definitive diagnosis of nonadenoma was made by obtaining histologic proof at surgery of one metastastic lesion from the stomach cancer, ganglioneuroma, or angiomyolipoma. Three metastatic lesions from cervical cancer rapidly increased in size at follow-up CT examination performed 3 months later. The adrenal angiomyolipoma measuring 5.4 cm in maximum transverse diameter showed that over 90% of this lesion had an extensive infarction and was not identified as a fat-containing adrenal tumor on preoperative CT and MR images.
Accuracy
For CT, the sensitivity and specificity of absolute PLE were 100% (37 of 37) and 83% (five of six), respectively, and those of relative PLE were 97% (36 of 37) and 100% (six of six), respectively. There was no difference in overall accuracy of 98% (42 of 43) for lipid-poor adenoma between absolute PLE and relative PLE, although both of these CT equations yielded different sensitivity and specificity (Table 1). One metastatic lesion from stomach cancer had an absolute PLE of 63% but a relative PLE of 36%, leading to reduced specificity of absolute PLE for lipid-poor adenoma. One lipid-poor adenoma had an absolute PLE of 79% but a relative PLE of 38%, leading to lowered sensitivity of relative PLE for lipid-poor adenoma. The combinations of absolute PLE and/or relative PLE for the diagnosis of adenoma had an accuracy of 98% (42 of 43) and did not improve diagnostic performance when compared with a single CT equation, because there was no difference in overall accuracy between absolute PLE, relative PLE, and their combinations.
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Table 1. Comparison of Diagnostic Accuracies of Delayed Enhanced CT and Chemical Shift MR for the Characterization of Lipid-poor Adenoma
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For MR, the sensitivity, specificity, and accuracy of ASR were 41% (15 of 37), 100% (six of six), and 49% (21 of 43), respectively; those of SII were 86% (32 of 37), 50% (three of six), and 81% (35 of 43), respectively. MR with ASR did not help characterize 22 lipid-poor adenomas, resulting in poor sensitivity and accuracy for lipid-poor adenoma, although it helped identify all nonadenomas (n = 6). MR with SII failed to characterize five lipid-poor adenomas, leading to higher sensitivity and accuracy than did ASR. However, three metastatic lesions from cervical cancer were not characterized by using SII, which showed a poor specificity for lipid-poor adenoma, unlike ASR. The combination of ASR or SII (81%) had a higher accuracy than that of ASR and SII (49%).
Delayed enhanced CT with absolute and relative PLEs helped identify five more lipid-poor adenomas and three more metastatic tumors, all of which were misdiagnosed as nonadenoma and adenoma, respectively, at chemical shift MR with ASR or SII (Fig 2). However, there was no significant difference between these two imaging modalities (P > .05, McNemar test).
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Figure 2a: Comparison of delayed enhanced CT and chemical shift MR imaging in 74-year-old man who underwent right partial nephrectomy for renal cell carcinoma. (a) Transverse unenhanced CT image shows hyperattenuating (32-HU) mass (arrow). (b) Transverse CT scan obtained 1 minute after intravenous injection of contrast material shows early wash-in into adrenal mass (arrow) measuring 116 HU. Abdominal aortic dissection is incidentally detected. (c) Transverse CT scan obtained 15 minutes after intravenous injection of contrast material shows early washout from adrenal mass (arrow) measuring 41 HU. Absolute (89%) and relative (65%) PLEs are consistent with lipid-poor adenoma. The lesion was unchanged for 1 year. (d, e) Adrenal mass (arrow) shows no visual signal intensity loss between in-phase (repetition time msec/echo time msec, 200/4.2) and opposed-phase (175/2.2) spoiled-gradient-echo coronal MR images. ASR was 1.1; SII was 3.1%.
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Figure 2b: Comparison of delayed enhanced CT and chemical shift MR imaging in 74-year-old man who underwent right partial nephrectomy for renal cell carcinoma. (a) Transverse unenhanced CT image shows hyperattenuating (32-HU) mass (arrow). (b) Transverse CT scan obtained 1 minute after intravenous injection of contrast material shows early wash-in into adrenal mass (arrow) measuring 116 HU. Abdominal aortic dissection is incidentally detected. (c) Transverse CT scan obtained 15 minutes after intravenous injection of contrast material shows early washout from adrenal mass (arrow) measuring 41 HU. Absolute (89%) and relative (65%) PLEs are consistent with lipid-poor adenoma. The lesion was unchanged for 1 year. (d, e) Adrenal mass (arrow) shows no visual signal intensity loss between in-phase (repetition time msec/echo time msec, 200/4.2) and opposed-phase (175/2.2) spoiled-gradient-echo coronal MR images. ASR was 1.1; SII was 3.1%.
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Figure 2c: Comparison of delayed enhanced CT and chemical shift MR imaging in 74-year-old man who underwent right partial nephrectomy for renal cell carcinoma. (a) Transverse unenhanced CT image shows hyperattenuating (32-HU) mass (arrow). (b) Transverse CT scan obtained 1 minute after intravenous injection of contrast material shows early wash-in into adrenal mass (arrow) measuring 116 HU. Abdominal aortic dissection is incidentally detected. (c) Transverse CT scan obtained 15 minutes after intravenous injection of contrast material shows early washout from adrenal mass (arrow) measuring 41 HU. Absolute (89%) and relative (65%) PLEs are consistent with lipid-poor adenoma. The lesion was unchanged for 1 year. (d, e) Adrenal mass (arrow) shows no visual signal intensity loss between in-phase (repetition time msec/echo time msec, 200/4.2) and opposed-phase (175/2.2) spoiled-gradient-echo coronal MR images. ASR was 1.1; SII was 3.1%.
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Figure 2d: Comparison of delayed enhanced CT and chemical shift MR imaging in 74-year-old man who underwent right partial nephrectomy for renal cell carcinoma. (a) Transverse unenhanced CT image shows hyperattenuating (32-HU) mass (arrow). (b) Transverse CT scan obtained 1 minute after intravenous injection of contrast material shows early wash-in into adrenal mass (arrow) measuring 116 HU. Abdominal aortic dissection is incidentally detected. (c) Transverse CT scan obtained 15 minutes after intravenous injection of contrast material shows early washout from adrenal mass (arrow) measuring 41 HU. Absolute (89%) and relative (65%) PLEs are consistent with lipid-poor adenoma. The lesion was unchanged for 1 year. (d, e) Adrenal mass (arrow) shows no visual signal intensity loss between in-phase (repetition time msec/echo time msec, 200/4.2) and opposed-phase (175/2.2) spoiled-gradient-echo coronal MR images. ASR was 1.1; SII was 3.1%.
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Figure 2e: Comparison of delayed enhanced CT and chemical shift MR imaging in 74-year-old man who underwent right partial nephrectomy for renal cell carcinoma. (a) Transverse unenhanced CT image shows hyperattenuating (32-HU) mass (arrow). (b) Transverse CT scan obtained 1 minute after intravenous injection of contrast material shows early wash-in into adrenal mass (arrow) measuring 116 HU. Abdominal aortic dissection is incidentally detected. (c) Transverse CT scan obtained 15 minutes after intravenous injection of contrast material shows early washout from adrenal mass (arrow) measuring 41 HU. Absolute (89%) and relative (65%) PLEs are consistent with lipid-poor adenoma. The lesion was unchanged for 1 year. (d, e) Adrenal mass (arrow) shows no visual signal intensity loss between in-phase (repetition time msec/echo time msec, 200/4.2) and opposed-phase (175/2.2) spoiled-gradient-echo coronal MR images. ASR was 1.1; SII was 3.1%.
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For adrenal masses measuring 10–30 HU, the MR sensitivity for adenoma was 100% (17 of 17); for adrenal masses with attenuation greater than 30 HU, however, the MR sensitivity was 75% (15 of 20) (Fig 3). In terms of lesions (n = 3) 1 cm or smaller, lesions (n = 17) 1.0–1.5 cm, and lesions (n = 23) greater than 1.5 cm, MR sensitivity for adenoma was 100%, 94%, and 76%, respectively, whereas CT sensitivity for adenoma was 100%, 100%, and 94%, respectively (Table 2).
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Table 2. Sensitivities of Chemical Shift MR and Delayed Enhanced CT for Lipid-poor Adenomas (n = 37) at Different Lesion Sizes
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DISCUSSION
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Unenhanced CT is commonly used to help diagnose lipid-rich adenoma measuring 10 HU or less. However, attenuation values greater than 10 HU are seen in approximately 29% of adenomas (lipid-poor adenomas); therefore, these remain indeterminate on unenhanced CT images (11). Delayed enhanced CT performed 10–15 minutes following the intravenous administration of contrast material has been demonstrated to be highly accurate in characterizing lipid-poor adenoma when combined with portal venous phase CT (4,7). However, in daily practice, radiologists find it difficult to check every unenhanced CT image to determine whether the adrenal mass measures less than 10 HU, which often can result in delays. Dedicated CT for hyperattenuating adrenal masses usually requires three scans that fully cover the adrenal glands: one unenhanced CT scan and two additional CT scans after contrast material injection. Therefore, multiphase CT examinations result in additional radiation and potential side effects from the contrast material. Unlike CT, chemical shift MR does not use ionizing radiation and can be performed without a radiologist and contrast material injection.
Authors of previous studies (6,9) have reported that the role of MR for characterizing hyperattenuating adrenal masses is limited because of a strong correlation between decrease in signal intensity on opposed-phase images and CT attenuation. Haider et al (6) mentioned that chemical shift MR had a high sensitivity (89%) for adenomas measuring 10–30 HU. However, we found a higher sensitivity (100%) for hyperattenuating adenomas with the same range of attenuation. MR and the use of an SII threshold of 16.5% slightly increased sensitivity and accuracy for lipid-poor adenoma, as compared with the previous study results (6). Fujiyoshi et al (10) reported that SII with a threshold of 11.2%–16.5% had an MR accuracy of 100% and was the best equation for distinguishing adenomas from metastatic tumors; other quantitative methods, including ASR, adrenal-to-muscle ratio, and adrenal-to-liver ratio, had a considerable overlap between adenomas and metastatic tumors. Our study also showed that SII had a higher diagnostic performance than did ASR. Qualitative visual assessment is commonly used to characterize adrenal adenoma without measuring lesion signal intensity on chemical shift MR images. However, in our study, we did not include a qualitative method to identify signal loss of adrenal adenoma on opposed-phase MR images. Israel et al (5) reported an MR imaging discrepancy in 15 of 42 (36%) adrenal masses between qualitative and quantitative analyses and found that qualitative analysis may be less sensitive than quantitative analysis for the characterization of adenoma.
Undoubtedly, delayed enhanced CT has demonstrated excellent diagnostic performance for hyperattenuating adrenal adenoma, with sensitivities of 98% and specificities of 92%–100% regardless of their attenuation values on unenhanced CT images (4,8). Similarly, our study demonstrated that CT with absolute and relative PLEs had higher sensitivity and specificity for lipid-poor adenoma than did chemical shift MR with ASR or SII. Although there was no significant difference between the two imaging modalities, CT characterized five more adenomas and three more metastatic tumors than did MR and helped prevent unnecessary adrenal biopsy in these cases. The accuracies of absolute and relative PLEs for the characterization of lipid-poor adenoma were not different from each other and their combinations.
Our study had several limitations. First, pathologically unconfirmed lipid-poor adenoma was included under criteria that the lesion measured greater than 10 HU on unenhanced CT images with no interval change in size for at least 6 months. However, rare benign adrenal tumors may also satisfy these criteria. One of these lesions is pheochromocytoma. If this tumor is incidentally detected at CT, it is problematic because its washout characteristics are similar to those of metastasis or adrenal carcinoma (12). Authors of previous studies reported that lipid-poor adenoma has similar enhancement characteristics to lipid-rich adenoma and can be differentiated from nonadenoma by using delayed enhanced CT with absolute or relative PLE (4,7,8).
We did not choose the inclusion criteria based on the CT enhancement characteristics described above, since absolute or relative PLE is one of the variables involved in the test of accuracy for lipid-poor adenoma and thus might introduce bias to the study. Ganglioneuroma and infarcted angiomyolipoma, seen in our study, are rare benign adrenal tumors and usually manifest as large tumors, unlike nonfunctioning cortical adenoma, which usually measures less than 3 cm in diameter. In addition, these tumors do not have high absolute or relative PLE equivalent to adenoma. Therefore, these lesions are not so clinically problematic in the differentiation of adenoma.
Second, our study was retrospective in nature and thus had a potential for sampling bias. A prospective study with a larger population is required to confirm our results.
Third, our MR unit cannot provide dual-echo acquisition, which is not affected by misregistration and would allow radiologists to perform more reliable measurements (6). However, experienced radiologists took part in our study and objectively measured the SII and CT number of the adrenal masses in the same imaging plane.
Fourth, our study had an additional limitation: the low prevalence and small number of nonadenomas (n = 6), which limited the specificity data.
In conclusion, delayed enhanced CT can help characterize additional hyperattenuating adrenal masses that cannot be characterized with chemical shift MR imaging, although no statistically significant difference was noted between these imaging modalities regarding diagnostic accuracy.
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ADVANCE IN KNOWLEDGE
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- Delayed enhanced CT can better characterize additional hyperattenuating adrenal masses when compared with chemical shift MR imaging, although there was no statistically significant difference of diagnostic accuracy between these imaging modalities.
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FOOTNOTES
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Abbreviations: ASR = adrenal-to-spleen chemical shift ratio • PLE = percentage loss of enhancement • SII = signal intensity index
Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, B.K.P.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, B.K.P., B.K., J.H.L.; clinical studies, B.K.P., C.K.K.; statistical analysis, B.K.P., C.K.K., J.H.L.; and manuscript editing, B.K.P., B.K.
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ABSTRACT
INTRODUCTION
