Med. J. Cairo Univ., Vol. 82, No. 2, March: 153-158, 2014 www.medicaljournalofcairouniversity.net Role of MRI Apparent Diffusion Coefficient Quantification in the Differentiation between Benign and Malignant Mediastinal and Pulmonary Lesions HAITHAM A. DAWOOD, M.D.* and MOATAZ SALAH-ELDIN, M.D.** The Departments of Radiology* and Cardiothoracic Surgery**, Faculty of Medicine, Zagazig University Abstract Objective: The purpose of the study is to evaluate the role of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) value in the differentiation between benign and malignant mediastinal and pulmonary lesions. Patients and Methods: Twenty-nine patients with different chest and mediastinal lesions were included in this study. DW MR imaging was performed in the transverse plane with p- values of 1000 and 0sec/mm 2. Apparent diffusion coefficient (ADC) maps were reconstructed and ADC value was calculated on these maps. A receiver operating curve (ROC) was drawn to detect the cutoff point used to differentiated malignancy from benign lesion with calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: On histo-pathological bases, the 29 cases were subdivided to 12 benign and 17 malignant lesions. The mean ADCs of malignant and benign lesions were 1.03x10-3mm 2 /s and 1.8x10-3mm 2 /s, respectively. The mean ADC for the malignant group was significantly lower than that for the benign group (p=0.002). Using ADC value of 1.18x10-3 mm2/s as the cut-off threshold for the differentiation between benign and malignant lesions the sensitivity, specificity, PPV and NPP were 93.3% and 88.6%, 82.4% and 91.7% respectively. Conclusion: Our data suggest that diffusion weighted MRI with measurement of ADC value is very helpful in the differentiation between malignant and benign lesions of the chest and mediastinum. Key Words: MRI ADC Mediastinum. Introduction DESPITE being the most common modality used for imaging the chest and mediastinum, computed tomography (CT) cannot be used to reliably differentiate benign from malignant lesions [1]. Benign lesions are known to be prevalent in at least 20% of pulmonary nodules more than 2cm Correspondence to: Dr. Haitham A. Dawood, The Department of Radiology, Faculty of Medicine, Zagazig University in diameter, most of which do not require surgical resection. Precise pre-operative diagnosis is essential to reduce un-necessary invasive treatment of benign lesions [2]. Differentiation of malignant mediastinal tumors from benign lesions is essential for treatment planning as well as for prediction of prognosis. [3]. With the advent of the echo-planar magnetic resonance imaging (MRI) technique, diffusion weighted-magnetic resonance imaging (DW-MRI) of the abdomen and thoracic cavity has become possible with fast imaging time that minimize the effect of gross physiological motion from respiration and cardiac movement [4]. There is growing interest in the application of diffusion weighted imaging (DWI) in the evaluation of patients with cancer. The ADC is inversely correlated to tissue cellularity. The motion of water molecules is more restricted in tissues with a high cellular density associated with numerous intact cell membranes. The ADC value is estimated to be lower in viable tumor tissue with densely packed diffusion-hindering obstacles than in tissue with less densely packed obstacles such as tumor necrosis and benign tissue [5,6]. There have been limited reported studies on the role of DWI of mediastinal and pulmonary lesions [3,7,8]. The purpose of our study is to evaluate the role of DWI and ADC value in the differentiation between benign and malignant mediastinal and pulmonary lesions. Patients and Methods From June 2012 till December 2013; 29 patients (19 males and 10 females), aged (12-72 years) with mean age of (49.2). All patients presented with different pulmonary and mediastinal lesions (32 lesions) on the base of contrast enhanced CT and were included in this study after having patients consent and our institutional review board approval. 153
154 Role of MRI Apparent Diffusion Coefficient Quantification Our inclusion criteria were based upon CT, which showed; patient should have chest/mediastinal lesion larger than 1cm, the lesion shows no clue for benignity or malignancy (ex. Fat, calcification or necrosis). CT examinations were carried out by using a 64-slice MDCT scanner (GE Discovery CT750 HD, GE Medical Systems, and Milwaukee, USA). Scans were acquired during a single breathhold after administration of nonionic iodinated contrast material (80-100ml, flow rate 3-4ml/s, scan delay 25-30s from the beginning of the injection). Scan parameters were as follows: Slice thickness 2.5mm (with retro-reconstruction up to 1.25mm); feed 15mm/rotation; rotation speed 0.8s; overall acquisition time 12-15s; 120-140kV; 180-240mA. All MR studies were performed with a 1.5-T imager (Signa Twinspeed HD; GE Healthcare, Waukesha, Wis) by using a phased-array body coil (Eight- Channel Body Array Coil; GE Healthcare). Patients were imaged in the supine position. Prior to DW MR imaging, T 1 - and T2-weighted images were obtained from each patient. Breath-hold T 1 - weighted two-dimensional fast spoiled gradientecho images were obtained in the transverse plane with the following parameters: Repetition time/echo time, 150/4.2msec; flip angle 70º; field of view 30 cm; matrix 288-192; section thickness 4mm, with a 1-mm gap; and number of signals acquired one. T2-weighted, single-shot, fast spin-echo images were obtained in the transverse and coronal planes with the following parameters: 2000/60-90; matrix 320-256; section thickness 4mm, with a 1-mm gap; number of excitations one; and phase field of view, 0.5 (transverse plane) and 1 (coronal plane). If the ratio is 0.5, which means the filling ratio for k- space is 1/2, the field of view is rectangular and suited for axial imaging. DW MR imaging was performed only on pulmonary and mediastinal lesions in the transverse plane on the basis of T 1 - and T2- weighted images. DW MR imaging was obtained during quiet breathing with a motionprobing gradient (MPG) of p-values of 1000 and 0sec/mm2 in all x, y, and z directions, using the following parameters: spin-echo-based echo-planar imaging; 4100-5100/49.8; receiver bandwidth 250kHz; section thickness, 4mm (gapless); field of view 40-48cm; echo space 396-420sec; echo train length 96-128; and real spatial resolution in the phase-encoding direction 2.08-2.50mm. Imaging time was 3-5 minutes for an acquisition of 40-50 sections. Apparent diffusion coefficient (ADC) maps were reconstructed in all cases by using a soft-ware on the basis of the images obtained with a b factor of 1 000s/mm 2 and 0s/mm 2. ADC was calculated on these maps by drawing elliptical regions of interest (ROI) with an average size of 25±5 voxels. ROIs were placed on the most homogeneous portion of the pathological tissue to avoid fallacies due to areas of cytic degeneration. These ADC measurements are repeated for three time and average reading is considered the most accurate. Numerical data are given as mean± standard deviation (SD). After obtaining the histopathological diagnosis, the lesions were subdivided into different groups according to histological type. A receiver operating curve (ROC) was drawn to detect the cutoff point used to differentiated malignancy from benign mediastinal tumors with calculation of sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). The biopsy was done with CT-guided True cut biopsy in 10 patients, bronchoscopic biopsy in 4 patients. Results On histo-pathological bases, the 29 cases are subdivided to 12 benign and 17 malignant chest and mediastinal lesions. Table (1) shows the benign chest and mediastinal lesions that consisted of thymic hyperplasia 1 lesion, non-specific lymphadenitis 2, necrotizing granulomatous lymphadenitis 1, sarcoidosis 2, thymoma 2, tuberculoma 1, pulmonary tuberculosis 1, inflammatory pseudotumor 1 and neurogenic tumor 1 lesion. The malignant mediastinal and chest lesions (Table 2) consisted of bronchogenic carcinoma 4 lesions, which are subdivided to adenocarcinoma 1, large cell pulmonary carcinoma 1, small cell carcinoma 2 and 8 cases with lymphoma, which are subdivided into; Hodgkin lymphoma 3, non- Hodgkin lymphoma 5 and large B-cell lymphoma 1 lesion. Carcinoid was seen in 1 lesion, invasive thymoma 1 and metastasis 2 lesions. Characteristics of benign and malignant lesions on DW images: The signal intensity of both benign and malignant pulmonary lesions on DW images is compared with the adjacent skeletal muscle. Generally the malignant lesions had a tendency to demonstrate hyperintensity, while benign lesions tended to show moderate intensity on DW images. The lesions whose histological type were moderately differentiated (e.g. adenocarcinoma and 2 metastatic lung cancers) showed moderate intensity on DW images. An ADC value is measured for all lesions. The mean ADCs of malignant and benign lesions were 1.03±0.27x10-3mm2/s and 1.8±0.64x10-3mm 2/s, respectively (Table 3). The mean ADC for the malignant group was significantly lower than that
Haitham A. Dawood & Moataz Salah-Eldin 155 for the benign group (p=0.002). The lowest ADC in the malignant group was detected in a patient with small lung carcinoma (0.3±0.23x10-3mm 2 /s), while the highest ADC was adenocarcinoma (1. 5 8± 0.25x10-3mm 2 /s) which would suggest the diagnosis of a benign mass. The lowest ADC among benign tumors was detected in a patient with necrotizing granulomatous lymphadenitis (1.09±0.23x10-3mm 2 /s) which would suggest the diagnosis of malignant lesions, while the highest ADC was massive thymic hyperplasia (3.11±0.23x10-3mm 2 /s). ROC curve analysis: The area under the ROC curve was 0.90 (95% CI, 0.8 1-1.0 1). Using ADC value of 1. 18x10-3mm 2 /s as the cut-off threshold for the differentiation between malignant and benign lesions, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPP) were determined as 93.3% and 88.6%, 82.4% and 91.7% respectively. Fig. (1): Forty three year-old male patient. A- Axial CT of the chest with contrast shows enhanced anterior med-iastinal mass lesion. B- Axial MRI diffusion weighted image shows the mass as hyperintense signal, The mean ADC value is (0.81x10-3mm 2 /s) C- CT guided core biopsy was taken and the histopathology was anaplastic lymphoma. (B) Fig. (2): Forty eight year-old male patient with invasive thymoma. A- Axial CT chest shows anterior mediastinal mass and right pleural thickening. B- Axial MRI diffusion weighted imaging shows hyperintensity of the anterior mediastinal mass. C- ADC map shows hypointensity of the lesion, The ADC value is (0.69x10-3mm 2 /s).
156 Role of MRI Apparent Diffusion Coefficient Quantification Fig. (3): Twelve year-old male patient with thymic hyperplasia. A- coronal T2 WI MRI shows huge hyperintense mass filling most of the left hemithorax. B- Axial DWI shows the same mass as hyperintense lesion. C- ADC map of the same lesion shows hyperintensity of the lesion with high ADC value (3.110.23x10-3 mm2/ s ). (B) (D) Fig. (4): Forty year-old male patient. A- Axial MRI T1 WI shows low signal intensity right upper lobe lesion. B- At axial MRI DWI the lesion shows intermediate hyperintensity. C- ADC map of the same lesion shows slight hypointensity with ADC value measuring (1.51x10-3mm 2 /s). D- CT guided biopsy was taken and histopathology revealed pulmonary tuberculosis.
Haitham A. Dawood & Moataz Salah-Eldin 157 Table (1): Histopathological types of the benign lesions. Lesion Number % Nonspecific lymphadenitis 2 16.66 Necrotizing granulomatous lymphadenitis 1 8.33 Thymic hyperplasia 1 8.33 Thymoma 2 16.66 Sarcoidosis 2 16.66 Pulmonary tuberculosis 1 8.33 Tuberculoma 1 8.33 Inflammatory pseudo-tumor 1 8.33 Neurogenic tumor 1 8.33 Total 12 100 Table (2): Histopathological types of the malignant lesions. Lesion Number % Large cell lung cancer 1 6 Small cell lung cancer 2 12 Adencarcinoma 1 6 Hodgkin lymphoma 3 17 Non-Hodgkin lymphoma 5 29 Large B-cell lymphoma 1 6 Carcinoid 1 6 Invasive thymoma 1 6 Metastasis 2 12 Total 17 100 Table (3): Mean ADC value in both benign and malignant lesions. Lesion X±SD Benign lesions (no=12) 1.8±0.64 Malignant lesions (no=17) 1.03±0.27 t-test 3.92 p-value 0.002 Discussion The introduction of diffusion-weighted MR imaging (DWI) has enabled us to obtain additional information derived from the microscopic motion of water protons, which is not possible using conventional MR imaging [9]. Quantitative tumor assessment is possible by the calculation of ADC, which is related to the proportion of extracellular and intracellular components. ADC values in various malignant lesions generally tend to be decreased, probably because of increased tissue cellularity or cell density, because the latter correlates with malignancy [10]. The results of several clinical studies have demonstrated that ADC values of malignant hepatic, renal, prostatic and uterine cervical tumours were lower than those of benign lesions or normal tissue and diffusionweighted MR images showed these malignant tumors as areas of high signal intensity [8]. In the present study, we found that the mean ADC value of malignant pulmonary and mediastinal lesions was significantly lower than that of benign pulmonary and mediastinal lesions (p=0.002) with an area under the ROC curve of 0.90 (95% CI, 0.81-1.01). This is in agreement with previous reports on the role of DWI and measurement of the ADC value in the differentiation between malignant and benign pulmonary lesions [8,11,12] as well as between the malignant and benign mediastinal masse [3,7]. In our study the cut-off threshold of ADC value for the differentiation between malignant and benign lesion was 1. 18x 1 0-3mm 2 /s. This cut-off threshold is concordant with results of Mori and his colleagues (11) who reported cut-off threshold 1. 1 x 1 0-3mm 2 /s and lower than that of Lui et al (8) with cut-off threshold 1.4x 1 0-3mm 2 /s, Gumustas et al., [7] with cut-off threshold an 1.39x10-3mm 2 /s d Abdel- Razak et al., [3] with cut-off threshold 1.56x10-3mm 2 /s. The ADC cut-off threshold in the present study yields 93% sensitivity that is concordant with 95% sensitivity of Gumustas et al., [7] and 96% sensitivity of Abdel-Razak et al., [3] and higher than 83% sensitivity of Lui et al., [8] and 70% sensitivity of Mori et al., [11]. Also the specificity of our ADC cut-off threshold was 88% that is concordant with 87% of Gumustas et al., [7] and lower than 97% of Mori et al., [11], 94% of Abdel- Razak et al., [3] and higher than 74% sensitivity of Lui et al., [8]. The highest ADC value in the malignant lesions was detected in patient with lung adenocarcinoma (1.58± 0.25x10-3mm 2 /s). This concordant with the results of the study of Matoba et al., [13] who concluded that ADC value of lung carcinomas overlap; but ADC of adenocarcinoma appear to be higher than those of other histologic lung carcinoma types. On the other hand Uto et al., [14] found that there is no significant difference between mean ADC value lung cancer and benign pulmonary lesion and they stated that lesion to spinal cord ratio was more effective. In conclusion: Our data suggest that diffusion weighted MRI with measurement of ADC value is very helpful in the differentiation between malignant and benign lesions of the chest and mediastinum. References 1- WHITTEN C.R., KHAN S., MUNNEKE G.J. and GRUB- NIC S.: A diagnostic approach to mediastinal abnormalities. Radiographics, 27: 657-671, 2007.
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