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Discrimination between Metastatic and Nonmetastatic Mesorectal Lymph Nodes in Rectal Cancer Using Intravoxel Incoherent Motion Diffusion-weighted Magnetic Resonance Imaging

Rationale and Objectives

The aim of the study was to investigate the diagnostic value of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM DWI) for discriminating nonmetastatic from metastatic mesorectal lymph nodes in rectal cancer.

Materials and Methods

IVIM DWI was performed preoperatively on 50 patients with rectal carcinoma. The short-axis diameter, short- to long-axis diameter ratio, and IVIM-based parameter (pure diffusion coefficient [D], pseudo-diffusion coefficient [D*] and perfusion fraction [ f ]) values were compared between the metastatic and nonmetastatic lymph node groups.

Results

The short-axis diameter; short- to long-axis diameter ratio; and D, D*, and f values for the nonmetastatic lymph node group ( n = 28) were 6.446 ± 1.201 mm, 0.815 ± 0.099, 1.071 ± 0.234 × 10 −3 mm 2 /s, 15.443 ± 5.946 mm 2 /s and 0.261 ± 0.128, respectively, and were 9.045 ± 3.185 mm, 0.809 ± 0.099, 0.816 ± 0.121 × 10 −3 mm 2 /s, 11.679 ± 7.521 × 10 −3 mm 2 /s, and 0.190 ± 0.064, respectively, for the metastatic lymph node group ( n = 31). The short-axis diameter for the metastatic group was significantly higher than for the nonmetastatic group ( P < 0.001). The metastatic group exhibited significantly lower D and D* values than the nonmetastatic group ( P < 0.01). The short- to long-axis diameter ratio and f values did not differ significantly between the two groups. Optimal cutoff values (area under the curve, sensitivity, and specificity) for distinguishing metastatic from nonmetastatic lymph nodes were as follows: short-axis diameter = 5.563 mm (0.783, 74.2%, 82.1%); D = 0.667 × 10 −3 mm 2 /s (0.885, 77.4%, 89.3%); and D* = 0.485 × 10 −3 mm 2 /s (0.727, 80.6%, 67.9%).

Conclusion

IVIM DWI is useful to differentiate between metastatic and nonmetastatic mesorectal lymph nodes in rectal cancer.

As one of the most common malignant tumors in western countries, colorectal carcinoma is associated with high rates of morbidity and mortality . Lymph node staging in patients with rectal cancer is important for determining the method of surgical excision and whether the patient requires neoadjuvant chemoradiotherapy . Therefore, accurate lymph node staging is essential for optimizing individual treatment regimens. However, preoperative detection of lymph node involvement is always highly challenging for radiologists. Currently, magnetic resonance imaging (MRI) is often used to distinguish metastatic from nonmetastatic lymph nodes in patients with rectal cancer. Differential diagnosis of nodal involvement on conventional MRI is based on the size and shape of the lymph nodes, the presence of capsular involvement and central necrosis, and inhomogeneous enhancement after intravenous administration of a contrast agent . However, the accuracy of discrimination based on morphology-based MRI could be improved. This might be, at least in part, attributed to the fact that morphology-based MRI provides limited useful functional information on tissues, such as perfusion and diffusion information.

Based on an evaluation of the diffusion mobility of water molecules, diffusion-weighted magnetic resonance imaging (DWI) is a well-established functional MRI technique that can reveal the diffusion characteristics of tissues. Several recent studies have reported inconsistent findings on the ability of DWI to determine lymph node status in rectal cancer . For example, Cho et al. found that the apparent diffusion coefficient (ADC) value for metastatic lymph nodes was significantly lower than for nonmetastatic lymph nodes in rectal cancer, and the ADC value could be used to discriminate metastatic and nonmetastatic lymph nodes with a diagnostic accuracy of approximate 70%. By contrast, Heijnen et al. reported that benign and malignant nodes exhibited similar ADC values. These conflicting results might be partly due to the fact that the conventional DWI used in the previously mentioned studies is based on a mono-exponential model using data at b = 0 s/mm 2 and another b value other than zero and ignores the influence of microcirculation perfusion on the signal intensity of diffusion on DWI. Therefore, the conventional DWI parameter (ADC) cannot accurately reflect the diffusion characteristics of tissues. Based on the biexponential model developed by Le Bihan et al. , intravoxel incoherent motion (IVIM) DWI can simultaneously obtain diffusion and perfusion information on tissues. IVIM DWI has been widely used to determine the microenvironmental features of primary tumors and metastatic lymph nodes , discern the primary malignancies from postchemoradiation fibrosis , and differentiate benign from malignant tumors . Nevertheless, the usefulness of IVIM DWI in identifying nodal involvement in patients with rectal cancer is not clear. Therefore, we hypothesized that IVIM-based parameter values would differ between the metastatic and nonmetastatic mesorectal lymph nodes in patients with rectal cancer. In the present study, we aimed to explore the diagnostic efficacy of IVIM DWI for the differentiation between the two types of lymph nodes.

Materials and Methods

Patient Selection

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Conventional MRI Protocol

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IVIM DWI Protocol

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IVIM Analysis

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Sb/S0=(1−f)exp(−bD)+fexp(−b[D*+D]) S

b

/

S

0

=

(

1

f

)

exp

(

bD

)

+

f

exp

(

b

[

D

*

+

D

]

)

where S b is the signal intensity with diffusion gradient b, S 0 is the signal intensity for a b value of 0 s/mm 2 , D is the true diffusion coefficient (in mm 2 /s) indicating the pure diffusion of the water molecules, f is the microvascular volume fraction representing the fraction of diffusion related to microcirculation perfusion, and D* is the pseudo-diffusion coefficient (in mm 2 /s) demonstrating microcirculation perfusion. Because D* is roughly one order of magnitude greater than D , −bD* is less than −3 at a high b value (>200 s/mm 2 ) and f exp(−bD*) is less than 0.05 f . In this case, the contribution of D* to the S b /S 0 signal ratio can be ignored, and Equation (1) can be simplified to Equation (2) to estimate D:

Sb/S0=exp(−bD) S

b

/

S

0

=

exp

(

bD

)

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Histopathology

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Statistical Analysis

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Results

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Table 1

Comparison of the Size, Shape, and IVIM-based Parameter Values (Mean ± Standard Deviation) between the Metastatic and Nonmetastatic Groups

Parameters Nonmetastatic group ( n = 28) Metastatic group ( n = 31)P Value Short-axis diameter (mm) 6.446 ± 1.201 9.045 ± 3.185 # 0.000 Short- to long-axis diameter ratio 0.815 ± 0.099 0.809 ± 0.099 0.838 D (×10 −3 mm 2 /s) 1.071 ± 0.234 0.816 ± 0.121 # 0.000 D* (×10 −3 mm 2 /s) 15.443 ± 5.946 11.679 ± 7.521 # 0.003f 0.261 ± 0.128 0.190 ± 0.064 0.051

IVIM, intravoxel incoherent motion; D, pure diffusion coefficient; D*, pseudo-diffusion coefficient; f , perfusion fraction.

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Figure 1, Representative images of a nonmetastatic mesorectal lymph node in rectal carcinoma. Images ( a–d )s are axial T2-weighted images ADC, D, D*, and f maps, respectively. The ADC, D, D*, and f values for the lymph node were 1.32 × 10 −3 mm 2s, 1.03 × 10 −3 mm 2s, 25.7 × 10 −3 mm 2s, and 0.243, respectively.

Figure 2, Representative images of a metastatic mesorectal lymph node in rectal carcinoma. Images ( a – d ) are axial T2-weighted images ADC, D, D*, and f maps, respectively. The ADC, D, D*, and f values of the lesion were 1.25 × 10 −3 mm 2s, 0.82 × 10 −3 mm 2s, 10.6 × 10 −3 mm 2s, and 0.226, respectively. (Color version of figure is available online).

Figure 3, Receiver-operating characteristic curves for D and D* in the differentiation between the metastatic and nonmetastatic groups.

Figure 4, Receiver-operating characteristic curve for short-axis diameter and the combination of D and short-axis diameter in the differentiation between the metastatic and nonmetastatic groups.

Table 2

Optimal Cutoff Values for Differentiation between the Metastatic and Nonmetastatic Groups Based on Receiver-operating Characteristic Curve Analysis

Parameters Cutoff Value AUC (95% CI) Sensitivity Specificity_P_ Value Short-axis diameter 5.563 mm 0.783 (0.658–0.908) 74.19% 82.14% 0.148 a , 0.474 b D 0.667 × 10 −3 mm 2 /s 0.885 (0.804–0.967) 77.42% 89.29% 0.026 c D* 0.485 × 10 −3 mm 2 /s 0.727 (0.592–0.862) 80.65% 67.86% # 0.007 d Short-axis diameter + D 0.911 (0.842–0.981) 83.87% 82.14% 0.261 e , 0.027 f

AUC, area under the curve; CI, confidence interval; D, pure diffusion coefficient; D*, pseudo-diffusion coefficient. a, short-axis diameter vs D; b, short-axis diameter vs D*; c, D vs D*; d, D* vs short-axis diameter + D; e, short-axis diameter + D vs D; f, short-axis diameter + D vs short-axis diameter.

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Discussion

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Conclusions

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