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DOI:10.2214/AJR.07.2251
AJR 2007; 189:1031-1036
© American Roentgen Ray Society


Original Research

Diffusion-Weighted Imaging in the Differential Diagnosis of Simple and Hydatid Cysts of the Liver

Nagihan Inan1, Arzu Arslan, Gur Akansel, Yonca Anik, H. Tahsin Sarisoy, Ercument Ciftci and Ali Demirci

1 All authors: Department of Radiology, School of Medicine, University of Kocaeli, Kocaeli, Turkey.

Received March 15, 2007; accepted after revision May 25, 2007.

 
Address correspondence to N. Inan (inannagihan{at}ekolay.net).


Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
 
OBJECTIVE. The purpose of our study was to evaluate the value of diffusion-weighted imaging (DWI) in the differential diagnosis of simple and hydatid cysts of the liver, particularly in the completely liquid type of hydatid cyst.

SUBJECTS AND METHODS. Eighty-two cysts (43 simple cysts, 39 hydatid cysts) were included in this prospective study. DWI was performed using a breath-hold single-shot echo-planar spin-echo sequence, and apparent diffusion coefficients (ADCs) were calculated. On DW trace images, the signal intensity of cysts was visually compared with the signal intensity of the liver using a 3-point scale: 0, isointense; 1, moderately hyperintense; and 2, significantly hyperintense. Quantitatively, signal intensity of the cysts, cyst-to-liver signal intensity ratios, ADC of the cysts, and cyst-to-liver ADC ratios were compared between the groups. The statistical significance was determined using the Mann-Whitney U test.

RESULTS. On trace DWI (b = 1,000 s/mm2), most hydatid cysts (37/39, 95%) were hyperintense, whereas most simple cysts (40/43, 93%) were isointense with the liver. Three simple cysts (7%) were moderately hyperintense and two hydatid cysts (5%) were isointense. Quantitatively, both the signal intensity and cyst-to-liver signal intensity ratio of the hydatid cysts were significantly higher than those for simple cysts (p < 0.001). The cutoff value at 1.5 yielded a sensitivity of 77%, a specificity of 86%, and positive predictive value of 83% for the cyst-to-liver signal intensity ratio. The ADC and cyst-to-liver ADC ratio of the hydatid cysts were significantly lower than those of simple cysts (p < 0.005). For the completely liquid type in particular, we observed statistically significant differences in signal intensity, signal intensity ratio, ADC, and ADC ratios from those of simple cysts (p < 0.005). With a cutoff value of 1.5, signal intensity ratio had a sensitivity of 81%, specificity of 86%, and positive predictive value of 74%.

CONCLUSION. DWI may help in the differential diagnosis of hydatid and simple cysts of the liver.

Keywords: apparent diffusion coefficient • diffusion-weighted MRI • hydatid cysts • liver • simple cysts


Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
 
Simple cysts of the liver are relatively common, encountered in about 2.5% of the population. Histopathologically, the simple cyst typically has a wall composed of a thin layer of epithelial cells and containing serous fluid [1]. On sonography, uncomplicated simple cysts present as anechoic, round, well-defined lesions with smooth borders and no septation or mural calcification. The cyst wall is not visible on sonography [2]. On MRI, simple cysts display high signal intensity on T2-weighted and low signal intensity on T1-weighted images and have well-defined margins [13].

Hydatid cysts are usually asymptomatic and discovered incidentally on sonography [1, 3]. The diagnosis of hydatid cyst is usually made by characteristic sonographic features and positive serology. The appearance of hydatid cysts on sonography is variable and depends on the stage of maturity [4]. The diagnostic accuracy of sonography is high for cysts with a visible cyst wall (cystic echinococcosis type 1), cysts with a multivesicular appearance (cystic echinococcosis type 2), cysts with a floating membrane (cystic echinococcosis type 3), and cysts with calcification (cystic echinococcosis types 4 and 5) [5]. However, the remaining hydatid cysts (25–40% of the total) appear as well-defined anechoic cysts with no wall structure (the completely liquid type) and thus are sonographically indistinguishable from simple hepatic cysts [4]. Similarly, on MRI the distinctive morphologic features of cystic echinococcosis types 1, 2, and 3 hydatid cysts are helpful in the differential diagnosis, whereas completely liquid hydatid cysts are indistinguishable from simple cysts [6].

In this study, we evaluated the contribution of diffusion-weighted imaging (DWI) in the differentiation of simple cysts from hydatid cysts, particularly the completely liquid type of hydatid cyst, which poses a challenge in the differential diagnosis on both sonography and conventional MRI.


Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
 
Patients
Eighty-two noncalcified liver cysts with a diameter of at least 1 cm, detected with a variety of radiologic techniques in 57 consecutive patients (34 females, 23 males), were included in this prospective study. Of the cysts, 39 (in 32 patients) were hydatid cysts and 43 (in 25 patients) were simple cysts. All hydatid cysts were examined on sonography and classified according to the World Health Organization classification [5]. Twenty-one hydatid cysts were unilocular cystic lesions with uniform anechoic contents and with no visible wall (the completely liquid type), five cysts were univesicular with a visible cyst wall (cystic echinococcosis type 1), nine had a multivesicular appearance (cystic echinococcosis type 2), and four cysts had a floating membrane (cystic echinococcosis type 3). Cystic echinococcosis types 4 and 5 (completely or partially calcified cysts) were not included in our study.

In addition, because of the limited resolution of the DWI, lesions smaller than 1 cm were not included. The diameter range for hydatid cysts and simple cysts was 16–181 mm (mean diameter, 63.1 mm) and 10–100 mm (mean diameter, 28.4 mm), respectively. Thirteen patients had multiple cysts (two hydatid cysts in three patients, three hydatid cysts in two patients, two simple cysts in two patients, three simple cysts in three patients, four simple cysts in two patients, and five simple cysts in one patient). The mean patient age was 44.5 years (range, 15–67 years) and 57.8 years (range, 2.5–68) in the hydatid cyst group and the simple cyst groups, respectively.

The diagnosis of the hydatid cysts was confirmed by biopsy in 13 patients (the presence of scolices or hooklets in the hydatid liquid) and by positive serology for hydatidosis in 19 patients who were hemagglutinin inhibition–positive for dilutions 1/160. All 43 patients with a tentative radiologic diagnosis of simple cyst had negative hemagglutinin inhibition test results, and these lesions showed no change during follow-up (sonography every 3 months for 6–15 months).

The study was approved by our institutional review board and protocol review committee. Because the tests used were part of the routine clinical workup of these patients, informed consent was not required by the review board. We obtained a blanket consent from all patients for the use of their findings for research and education purposes, with patient privacy secured.

MRI
All patients were examined with a 1.5-T MR scanner (Gyroscan Intera, Philips Medical Systems) using a 4-element phased-array body coil. This system has a maximal gradient strength of 30 mT/m and a slew rate of 150 mT/m/ms. All patients were examined initially with the routine MRI protocol for the upper abdomen that included unenhanced axial T1-weighted breath-hold spoiled gradient-echo (fast-field echo [FFE]) with and without fat suppression (TR/TE, 169/4; flip angle, 80°; number of excitations, 1), coronal and axial T2-weighted single-shot turbo spin-echo (SShTSE) (700/80; number of excitations, 1; TSE factor, 72), and axial T2-weighted SShTSE with fat suppression (700/80; number of excitations, 1; TSE factor, 72). Subsequently, three series of axial single-shot spin-echo echo-planar DW images (1,000/81; echo-planar imaging factor, 77; sensitizing gradients in x, y, and z directions) were acquired using the following b values: 0, 500, and 1,000 s/mm2. ADC maps were reconstructed from these images. Fat suppression was performed using the spectral presaturation with inversion recovery (SPIR) technique.

Subsequently, 0.1 mmol/kg of gadopentetate dimeglumine (Magnevist, Bayer HealthCare) was administered as a hand-injected bolus in 5 seconds followed by a rapid flush with 10–20 mL of saline. Five dynamic series and an additional late phase (fifth minute) image were acquired with a T1-weighted breath-hold FFE (169/4.6; flip angle, 80°) sequence. MRI, including DWI, consisted of a multisection acquisition with a slice thickness of 6 mm, an intersection gap of 1 mm, and an acquisition matrix of 128 x 256. The field of view varied between 455 and 500 mm. All sequences were acquired using a partially parallel imaging acquisition and SENSE (sensitivity encoding) reconstruction with a reduction factor (R) of 2. The scanning time of the acquisition of each DWI series during a single breath-hold was 26 seconds.

Image Analysis
Qualitative analysis—The signal intensity of the cysts relative to the liver in all three diffusion trace images with b factors of 0, 500, and 1,000 s/mm2 was visually assessed using a 3-point scale, as follows: 0, isointense; 1, moderately hyperintense; and 2, significantly hyperintense, compared with the liver.

All images were independently assessed by two radiologists who were blinded to the clinical history and results of prior imaging studies. Results of the interpretations were then compared. In six cases for which the results differed, the final score was reached by consensus after discussion.

Quantitative analysis—Quantitative measurements were made using a dedicated workstation (Dell Workstation Precision 650, View Forum). Signal intensities of the cysts and liver were measured by one of the radiologists for each b factor (0, 500, and 1,000 s/mm2) using a region of interest (ROI) of the same size. The ROI was placed centrally, and the size of the ROI was kept as large as possible, covering at least two thirds of the cyst, yet avoiding interference from the surrounding liver tissue and major blood vessels. In addition, the ADC maps were created automatically, and the mean ADC values of cysts and liver were determined on images with b factors of 0 and 1,000 s/mm2. The average of three measurements was recorded as the final signal intensity or ADC. Signal intensity of the cysts, cyst-to-liver signal intensity ratio, ADC of the cysts, and cyst-to-liver ADC ratio were calculated.

Statistical Analysis
Signal intensity, signal intensity ratio, ADC, and ADC ratio were compared between the groups. The fitness of numeric data set to normal distribution was determined using the Kolmogorov-Smirnov test. The data were not normally distributed, so the differences in signal intensities, signal intensity ratios, ADCs, and ADC ratios were analyzed using the Mann-Whitney U test. A p value of less than 0.05 was considered statistically significant.

To evaluate the diagnostic performance of the quantitative tests (signal intensity ratio and ADC ratio) for differentiating hydatid cysts and simple cysts and to describe the sensitivity and specificity of the tests, receiver operating characteristic (ROC) analysis was performed. The areas and standard errors for each ROC curve were calculated using the method described by Metz [7]. The area under the ROC curve reflects the performance of the tests. The optimum cutoff point was determined as the value that best discriminates between the two groups in terms of maximum sensitivity and minimum number of false-positive results. All statistical analyses were performed using statistical software (SPSS).


Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
 
Qualitative Analysis
Results of the visual evaluation of the signal intensity of the hydatid cysts and simple cysts in diffusion trace images with a b factor of 1,000 s/mm2 are shown in Table 1. On these images, most of the hydatid cysts were hyperintense (Fig. 1A, 1B, 1C, 1D), whereas none of the simple cysts showed significant hyperintensity (Fig. 2A, 2B, 2C, 2D). Except for two hydatid cysts that did not show a high signal (Fig. 3A, 3B, 3C) and three simple cysts that did show high signal, DWI with a b factor of 1,000 s/mm2 successfully differentiated simple cysts from hydatid cysts. DW images with a b factor of 500 s/mm2 did not help in distinguishing simple cysts from hydatid cysts because all hydatid cysts and simple cysts were significantly hyperintense on these images.


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TABLE 1: Signal Intensities of Hydatid and Simple Cysts on Diffusion-Weighted Trace Images (b = 1,000 s/mm2)

 

Figure 1
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Fig. 1A 49-year-old woman with completely liquid type of hydatid cyst in liver. Her hemagglutinin inhibition test was positive. Axial T1-weighted fast-field echo (A) and T2-weighted turbo spin-echo (B) MR images show cyst in right lobe of liver.

 

Figure 2
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Fig. 1B 49-year-old woman with completely liquid type of hydatid cyst in liver. Her hemagglutinin inhibition test was positive. Axial T1-weighted fast-field echo (A) and T2-weighted turbo spin-echo (B) MR images show cyst in right lobe of liver.

 

Figure 3
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Fig. 1C 49-year-old woman with completely liquid type of hydatid cyst in liver. Her hemagglutinin inhibition test was positive. Cyst (arrow) shows higher signal intensity than liver on diffusion-weighted image (b = 1,000 s/mm2).

 

Figure 4
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Fig. 1D 49-year-old woman with completely liquid type of hydatid cyst in liver. Her hemagglutinin inhibition test was positive. Apparent diffusion coefficient (ADC) map shows cyst-to-liver ADC ratio is 1.8.

 

Figure 5
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Fig. 2A 5-year-old boy with simple cyst in liver. Cyst was unchanged during 12 months of follow-up. Completely anechoic cyst is seen on transverse right subcostal sonogram.

 

Figure 6
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Fig. 2B 5-year-old boy with simple cyst in liver. Cyst was unchanged during 12 months of follow-up. Axial T2-weighted turbo spin-echo MR image shows cyst in right lobe of liver.

 

Figure 7
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Fig. 2C 5-year-old boy with simple cyst in liver. Cyst was unchanged during 12 months of follow-up. Cyst is isointense to liver on this diffusion-weighted image (b factor, 1,000 s/mm2).

 

Figure 8
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Fig. 2D 5-year-old boy with simple cyst in liver. Cyst was unchanged during 12 months of follow-up. Apparent diffusion coefficient (ADC) map shows cyst-to-liver apparent diffusion coefficient ratio is 2.4.

 

Figure 9
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Fig. 3A 15-year-old boy with cystic echinococcosis type 3 (cyst with floating membrane) hydatid cyst of liver. Axial T1-weighted fast-field echo (A) and T2-weighted turbo spin-echo (B) MR images show cystic echinococcosis type 3 hydatid cyst in left lobe of liver.

 

Figure 10
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Fig. 3B 15-year-old boy with cystic echinococcosis type 3 (cyst with floating membrane) hydatid cyst of liver. Axial T1-weighted fast-field echo (A) and T2-weighted turbo spin-echo (B) MR images show cystic echinococcosis type 3 hydatid cyst in left lobe of liver.

 

Figure 11
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Fig. 3C 15-year-old boy with cystic echinococcosis type 3 (cyst with floating membrane) hydatid cyst of liver. Cyst is isointense to liver on diffusion-weighted image (b = 1,000 s/mm2).

 

Quantitative Analysis
The results of the quantitative analysis of the DW images are reviewed in Table 2. With b factors of 0 and 500 s/mm2, no difference of statistical significance was achieved (p > 0.05). With a b factor of 1,000 s/mm2, the signal intensities and signal intensity ratios of the hydatid cysts were significantly higher than those of the simple cysts (p < 0.001). The best discriminative parameter was signal intensity ratio. The area under the ROC curve was 0.876 {mp} 0.039. With a cutoff value of 1.5 for the signal intensity ratio, that ratio had a sensitivity of 77%, specificity of 86%, and positive predictive value of 83% (Fig. 4A). The ADCs and ADC ratios of hydatid cysts were significantly lower than those of simple cysts (p < 0.001). The area under the ROC curve was 0.262 {mp} 0.055 for ADC ratio. However, we could not obtain a sufficiently discriminative cutoff value using the ROC analysis. Setting the cutoff value at 1.4, we found a sensitivity of 46%, a specificity of 86%, and positive predictive value of 75% for the ADC ratio. With a cutoff value of 2, we achieved a higher sensitivity (85%) but markedly lower specificity (51%) and positive predictive value (61%).


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TABLE 2: Quantitative Analysis of Diffusion-Weighted Imaging of Hydatid and Simple Cysts (b = 1,000 s/mm2)

 

Figure 12
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Fig. 4A Scattergram distribution of cyst-to-liver signal intensity ratios. Scattergrams of hydatid ({blacksquare}) and simple ({square}) cysts (A) and completely liquid hydatid ({blacksquare}) and simple ({square}) cysts (B) on diffusion-weighted images (b = 1,000 s/mm2) show distribution of signal intensity ratios relative to cutoff values.

 

Considering the completely liquid type hydatid cysts and simple cysts, we observed statistically significant differences in signal intensity, signal intensity ratio, ADC, and ADC ratio (p < 0.005). With a cutoff value of 1.5, signal intensity ratio had a sensitivity of 81%, specificity of 86%, and positive predictive value of 74% (Fig. 4B). Setting the cutoff value at 2, we found a sensitivity of 81%, specificity of 52%, and positive predictive value of 45% for the ADC ratio.


Figure 13
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Fig. 4B Scattergram distribution of cyst-to-liver signal intensity ratios. Scattergrams of hydatid ({blacksquare}) and simple ({square}) cysts (A) and completely liquid hydatid ({blacksquare}) and simple ({square}) cysts (B) on diffusion-weighted images (b = 1,000 s/mm2) show distribution of signal intensity ratios relative to cutoff values.

 

Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
 
DWI is based on the restriction of random translational molecular motion (brownian motion) of water, determined by the diffusion coefficient. It has been used mainly in the brain, especially for the diagnosis of acute cerebral infarction [8]. The use of DWI in the abdomen is hindered by certain limitations such as physiologic motion artifacts caused by respiration and cardiac motion, the short relaxation times of the abdominal organs, and long acquisition times [911]. The adverse effects of respiration and cardiac motion can be reduced by using breath-hold and pulse-triggered sequences. Because the relaxation times are relatively shorter in the liver, short TEs must be used [9]. Because of the rapid acquisition capabilities and high signal-to-noise ratio (SNR), the best image quality is obtained with breath-hold single-shot spin-echo echo-planar imaging sequences [911]. For DWI of the liver, chemical shift selective fat suppression or water-selective excitation techniques are usually used to allow higher SNR and more efficient acquisition than STIR techniques. Parallel imaging is crucial to reduce the distortion of single-shot spin-echo echo-planar DWI [10]. In our study, DW images were obtained using a breath-hold echo-planar sequence that allowed a short TE, SPIR fat-suppression pulse, and SENSE.

Reports have suggested that DWI with single-shot echo-planar imaging may be helpful in the characterization of focal [1217] and diffuse [18, 19] liver lesions, with high specificity and sensitivity. Namimoto et al. [14], Yamada et al. [15], Kim et al. [16], and Taouli et al. [17] reported that the ADC values of benign lesions (such as hemangiomas and cysts) were significantly higher than those of malignant lesions (hepatocellular carcinomas, metastases). This difference was attributed to the difference in cellular density. Because malignant tumors often have higher cellularity than benign lesions, the ADCs of most malignant tumors are lower than those of benign masses [14, 16, 17]. The ADC values of both the normal liver and liver lesions differ significantly at different b values [15]. Namimoto et al. reported a low ADC of the liver (0.69 x 10–3 s/mm2) with low and high b values (30 and 1,200 s/mm2). On the other hand, high ADCs (1.83 x 10–3 s/mm2) were reported by Taouli et al. using low and intermediate b values (0 and 500 s/mm2). In a study of Yamada et al. in which the b values of 30, 300, 900, and 1,100 s/mm2 were used, high ADCs were obtained at low b values.

Only a few reports discuss the use of DWI in cystic lesions of the liver [1417]. Naganawa et al. [10] reported that simple cysts usually show a low to isointense signal on high-b-value DWI. In addition, Chan et al. [20] suggested that ADC values are lower in hepatic abscess cavities than in the necrotic portions of tumors, depending on the viscosity of the lesions. To our knowledge, the role of DWI in the differential diagnosis of hepatic simple cysts and hydatid cysts has not been reported previously.

In our study, significant differences between the signal intensities and signal intensity ratios of hydatid cysts and simple cysts were found only on images with a b factor of 1,000 s/mm2. The differences in signal intensities on b = 0 or b = 500 s/mm2 images were not statistically significant. The signal intensity on a DW image is affected by the diffusion coefficient and the signal without diffusion gradients [21]. The signal of the DW image contains contributions from the spin density and T1 and T2 relaxation times [2123]. Therefore, cysts may display a strong T2 effect (T2 shine-through effect) instead of reduced diffusion, especially with lower b factors. At higher b values, the contribution of the T2 shine-through to the signal intensity decreases, whereas tissue cellularity makes a greater contribution [10]. Hence, the hyperintensity of hydatid cysts on b = 1,000 s/mm2 images cannot be totally attributed to the T2 shine-through effect. However, it is difficult to determine the relative contributions from the reduced diffusion and the T2 value of the tissue to the combined signal in b = 1,000 s/mm2 images [22]. Diffusion can be quantitatively evaluated using ADC, which is free of the T2 shine-through effect [8]. In our series, the mean ADC of the hydatid cysts was significantly lower than that of the simple cysts (p < 0.001). Hence, at least part of the increase in signal on DW images must have been caused by reduced diffusion in hydatid cysts.

Over the past few years, several studies have shown that DWI is helpful in differentiation of epidermoid tumors from arachnoid cysts [2224]. Annet et al. [24] reported that the low ADCs of epidermoid cysts were the result of the dense keratinous content of the cysts, which limits the diffusivity of protons. However, Hakyemez et al. [22] and Chen et al. [23] showed that epidermoid cysts appeared hyperintense on trace DW images compared with the CSF and white matter, and the ADC values of epidermoid tumors were significantly higher than normal white matter. Hence, the hyperintensity of epidermoid tumors on trace DW images was attributed to the T2 shine-through effect rather than a decrease in the ADC.

Nakayama et al. [25] reported that the ADCs were lower in mature cystic teratomas than in endometrial cysts and other benign and malignant ovarian cystic neoplasms. According to this study, the low ADCs of the mature cystic teratomas were attributed to the keratinoid substance in the tumors. Similarly, the difference between the ADCs of the hydatid cysts and those of simple cysts can be attributed to the difference in the cyst contents. Because the hydatid cyst contains viscous hydatid sand that consists of the scolices, hooklets, sodium chloride, proteins, glucose, ions, lipids, and polysaccharides, the ADC of the hydatid cyst is decreased [26, 27]. On the contrary, the simple cyst has lower viscosity, hence the higher ADC [1].

In our study, the ADC measurement yielded a lower accuracy in discrimination between the two types of cysts than DW trace imaging signal intensity measurement. One reason for this may be the use of fixed TRs, due to which the DWI series were acquired in different phases of the cardiac cycle. Therefore, DW images of different patients may have been affected differently by the pulsatile motion. Another reason may be the limited reliability of the measurements of ADC for lesions in the lateral segment and subdiaphragmatic regions of the liver due to distortion artifacts.

Our study has several technical limitations. The main limitation was that the echo-planar sequence used with a higher b value had a lower SNR, resulting in greater image distortion. In addition, the echo-planar sequence causes anatomic distortion due to susceptibility effects [10]. We did not use pulse-triggered DWI. Murtz et al. [9] evaluated 12 patients using a single-shot spin-echo echoplanar sequence with ECG triggering to minimize the influence of cardiac pulsation. They found that DWI without pulse triggering reduces the accuracy of ADC measurements in abdominal organs.

The differential diagnosis of most liver cysts is usually possible with the combined use of specific morphologic features on sonography, CT, and MRI (size, contours, the presence and thickness of a wall, internal structure, enhancement pattern, and calcification) and laboratory and clinical information. However, the differentiation of the completely liquid type of hydatid cyst from simple cysts may still be difficult. Our preliminary data suggest that DWI may be helpful in this setting.


References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
 

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N. Inan, A. Arslan, G. Akansel, Y. Anik, and A. Demirci
Diffusion-Weighted Imaging in the Differential Diagnosis of Cystic Lesions of the Pancreas
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