| Pancreatic cancer is one of the most lethal human cancers and continues to be a major unsolved health problem at the start of the 21st century. It is well known that the 5-year survival rate of patients with pancreatic adenocarcinoma is dismal. When obtaining initial diagnosis, less than 10-15% of patients still preserve an opportunity to surgical resection, which is the only potential curative treatment. Although much effort has been devoted to improve early detection of pancreatic adeno carcinomas, the sensitivity to detect pancreatic cancer is still insufficient with conventional techniques including tumor-associated antigen testing, ultrasonography, CT and MR imaging. With recent development of the high-field MR systems, high-performance gradient and parallel imaging technique, MR spectroscopy (MRS) and MR diffusion-weighted imaging (DWI) are increasingly used to evaluate diseases involving abdominal organs. In this study, pancreatic DWI, proton MRS and histopathological examination were performed for patients with pancreatic carcinoma, as well for patients with mass-forming chronic pancreatitis and healthy volunteers for control. Our purpose was to evaluate the usefulness of DWI and proton MRS in the diagnosis of pancreatic carcinoma, and to explore the value of apparent diffusion coefficient (ADC) and metabolite quantification in predicting the differentiation degree and proliferation activity for pancreatic carcinoma.Part I: In vivo ~1H MR Spectroscopy of Pancreatic Carcinoma at 3T: with Mass-forming Chronic Pancreatitis and Normal Pancreas in ComparisonObjective: In this part, our purpose was to analyze the !H MR spectroscopic features of in-vivo pancreatic carcinoma, and to explore the value of metabolite quantification in differentiating pancreatic carcinoma from mass-forming chronic pancreatitis.Methods: This study protocol had been approved by our institutional Medical Ethics Committee. With informed consent, single-voxel pancreatic !H MR spectroscopic examination was performed for 27 patients with pancreatic carcinoma (M/F, 15/12; age, 62.2±12.0 years) and 11 patients with mass-forming chronic pancreatitis (M/F, 7/4; age, 52.5±11.4 years), and for 20 healthy volunteers (M/F, 15/5; mean age, 38.6±17.2 years) for control. !H-MR spectroscopic features of pancreatic carcinoma, mass-forming chronic pancreatitis and normal pancreas were pictured; moreover, the relative lipid content (rLip, the ratio of lipid peak area divided by peak areas from 0 to 6 ppm), choline-containing metabolites (CCM) to glutamate and glutamine complex (Glx) ratio (CCM/Glx) were compared between three groups. Furthermore, ROC analysis was made to determine the diagnostic value of metabolite quantification in differenting pancreatic carcinoma from mass-forming chronic pancreatitis.Results: In comparison with normal pancreas, !H spectrum of the pancreatic carcinoma was characterized by large residual water (H2O) resonance peak and small lipid peak; CCM of the pancreatic carcinoma was reduced and varied in size, likely due to the difference in tumor differentiation degree and the heterogeneity in tumor constituents; however, mass-forming chronic pancreatitis presented with an enlarged lipid peak and reduced residual H2O. CCM/Glx ratio of the pancreatic carcinoma (0.367±0.094 [mean±SD]; n=27) was lower than that of mass-forming chronic pancreatitis (0.446±0.039; n=ll) (P=0.011). CCM/Glx ratios of both pancreatic carcinoma and mass-forming pancretitis were significantly lower than that of normal pancreas (0.592±0.233; n=20), with P values of 0.007 and 0.021 respectively. The rLip value of pancreatic carcinoma (0.420±0.164) was lower than those of chronic pancreatitis (P<0.001) and normal pancreas (P<0.001). Significant difference (P=0.020) was also revealed in rLip value between mass-forming pancreatitis (0.725±0.059) and normal pancreas (0.645±0.096). For differentiating pancreatic carcinoma from mass-forming pancreatitis, rLip obtained sensitivity of 90.9% and specificity of 92.6% when using 0.647 as the optimal cut-off value; while CCM/Glx obtained sensitivity of 81.8% and specificity of 70.4% when using cut-off value of 0.423.Conclusion: In !H spectrum, pancreatic carcinoma presented with a decrease of CCM concentration and relative lipid content, as well as an increase of residual water, when compared to normal pancreas and mass-forming chronic pancreatitis. !H MR spectroscopy with metabolite quantification was of potential value in differentiating pancreatic carcinoma from mass-forming chronic pancreatitis.Part II: Usefulness of ADC Quantification in Differentiation between Pancreatic Carcinoma and Mass-forming Chronic Pancreatitis Objective: To explore the imaging features of pancreatic carcinoma in 3-T MR diffusion-weighted imaging (DWI), and to determine the efficacy of ADC quantification for differentiating pancreatic carcinoma from mass-forming chronic pancreatitis.Methods: Our study subjects consisted of 27 patients with pancreatic carcinoma (M/F, 15/12; age, 62.2±12.0 years), 11 patients with mass-forming chronic pancreatitis (M/F, 7/4; age, 52.5±11.4 years) and 20 healthy volunteers (M/F, 15/5; age, 38.6±17.2 years). For all of them, twice pancreatic DWIs with two different sets of b values (0, 500 and 0, 1000 s/mm2) were performed consecutively. ADC values (ADC500, ADC1000) of pancreatic carcinoma, mass-forming pancreatitis and normal pancreas were measured using a circular region of interest (ROI), and rADC was calculated according to the formula: rADC = (ADC500—ADC1000)/ADC500. The diagnostic performance of ADCs and rADC (the rate of variance between ADC500 and ADC1000) were evaluated using ROC analysis.Results: Both pancreatic carcinoma and mass-forming pancreatitis were revealed as high-attenuation mass lesions on DWI with b value of 500 or 1000 s/mm2. The ADCs of pancreatic carcinoma (ADC500, 1.264±0.153; ADC1000, l.lll±0.133) and mass-forming pancreatitis (1.352±0.114; 1.210±0.093) were lower than those of the normalpancreatic tissues (1.983±0.172; 1.658±0.145) (PO.001). Compared to mass-forming pancreatitis, pancreatic carcinoma exhibited an even lower ADC1000 (P=0.045) and ADC500 values (P=0.03). The rADC (%) of pancreatic carcinoma was 9.78±3.50, significantly lower than those of mass-forming pancreatitis (12.76±1.90, P=0.116) and normal pancreas (17.62±4.76, P<0.001). Significant difference was revealed in rADC between the mass-forming pancreatitis and normal pancreas (P=0.003). In ROC analysis, ADC500, ADC1000 and rADC respectively obtained sensitivity of 72.7%, 74.1% and 72.7% and specificity of 74.1%, 81.8% and 66.7% for differentiating pancreatic carcinoma from mass-forming chronic pancreatitis.Conclusion: Pancreatic carcinoma was characterized by more restricted water diffusion (lowered ADC) and lowered microvascular perfiision (lowered rADC) than mass-forming chronic pancreatitis in DWI. DWI combined with ADC quantification might be a potentially useful technique in the diagnosis of pancreatic carcinoma by providing histological information in vivo.Part III: Correlation of Choline-containing Metabolites (CCM), ADC Value and Ki-67 Labeling Index in Pancreatic CarcinomaObjective: To investigate the difference between well-to-moderately and poorly differentiated pancreatic carcinoma in Choline-containing metablites (CCM) content, ADC value and Ki-67 labeling index, and to determine whether there is a correlation of CCM content, ADC value with the Ki-67 protain expression.Materials and methods: Preoperative MRI/MRS and postoperative histopathologic results of 21 patients with pancreatic carcinoma (M/F, 12/9; age, 62.8±12.6 years) were reviewed. CCM content, ADC value and Ki-67 labeling index of tumors with varied differentiating grades were compared using Mann-Whitney U test; and the correlation of CCM, ADC and Ki-67 labeling index were determined using linear regression analysis.Results: In postoperative histopathologic examination, 14 and 7 pancreatic carcinoma were respectively diagnosed as well-to-moderately differentiated and poorly differentiated tumors; the Ki-67 labeling index of well-to-moderately differentiated tumors (40.99±7.56) was lower than that of poorly differentiated (59.91±8.61) (P=0.001). In single-voxel !H-MRS study, the CCM/Glx ratio of well-to-moderately differentiated tumors (54.5±19.7) was significantly lower than that of poorly differentiated (0.441±0.080) (P=0.019). No significant difference was revealed in ADC values between well-to-moderately differentiated (1.08 5±0.161 s/mm2) and poorly differentiated pancreatic carcinoma (1.146±0.062 s/mm2) (P=0.322) in DWI with b value of 1000 mm2/s. There is a significant linear correlation (P=0.017) between CCM/Glx ratio and Ki-67 labeling index, but no significant correlation between ADC value and Ki-67 labeling index (P=0.255).Conclusion: !H MRS may have potential value in predicting the differentiation degree and proliferation activity of pancreatic carcinoma. |
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