The Clinical Application Study Of 31P MRS Wtih Hepatocellular Carcinoma,Cirrhosis And Normal Liver Tissue

[PURPOSE] 31P MRS (phosphorus -31 magnetic resonance spectroscopy) analysis is one of the clinical study modality using magnetic resonance imaging in recent years. Only a few reports were found in human's application study of liver in vivo, including the analysis and research in 31P MRS of various kinds of hepatitis, cirrhosis and liver cancer separately. The results of those studies were not satisfied, because the different of the 31P MRS parameter selected and the research objects. There hadn't a clinical citation of the spectroscopy of phosphorus chemical compound in the normal human's liver so far. In the clinical work, the differentiation diagnosis the liver cirrhosis and liver cancer is difficult. The biopsy was used to differentiation diagnosis. An effective method of differentiation diagnosis distinguishing liver cirrhosis, hepatocellular carcinoma and normal liver tissue in vivo using 31P MR spectroscopy was study. The author attempt to set up the reference value database of 31P MRS in liver cirrhosis, hepatocellular carcinoma and normal liver tissue also. [MATERIALS AND METHODS]1. Choice of the research objects Thirty three cases with 66 pieces of effective voxel were selected including normal volunteer, cirrhosis and liver cancer patient, median age was 35 years old, 21 male, 12 female. There were 12 normal volunteer (16 effective voxel) in the control group (the first group), 13 liver cirrhosis patients (37 effective voxel) in the second group and 8 hepatocellular carcinoma patients (13 effective voxel) in the third group. Normal volunteers were selected from routine examination of crowd who had not history of liver diseases; all liver cirrhosis cases were confirmed histopathologically by biopsy and operation after 31P MRS study.Primary liver cancer can be divided into hepatocellular carcinoma (HCC), cholangiocarcinoma and mixed type liver cancer. Only HCC confirmed histopath-ologically by biopsy and operation was selected in the study.2. The choices of the parameter and method 31 P MRS was performed by 1.5T superconductive MR scanner using heart / liver spectral surface coil, prostrate location or supine in the location, band of controlling breathe. Scan data was collected using 3IP-liver 2D-csi (chemical shift) large voxel, FOV 300mm, Hamming filter, the number of data collection 48 times equally, TR 440ms, TE 2. 3ms, flip angle 90°, thickness 60 mm. VOI was put on the cross section of the liver with 16*16 or 12*12 matrix, water suppresses 3 5 Hz, bandwidth 4000Hz.The course collecting data of phosphorus spectroscopy and analysis of protocol included the following steps: A, frequency adjusted; B, even field; C, the second frequency adjusted; D, data collection; E, protocol of spectrum and parameter analysis. Because there are mostly different line and chemical compound density and different rate of voxel inside the same VOI of the case examined, so it was useful to selecting different effective voxel in VOI as the target of sampling.3. Analytical method of the parameter(1) Comparison of the parameter After scanning finished, 14 parameters were obtained in each case who were examined. Those parameters were compared with PDA as a control data (its result =1), there were 13 parameters in each examined case was suitable for study: P-ATP,a-ATP,y-ATP,PCr,PDE,Pi, PME, p-ATP /P DE,a-ATP/PDE,y-ATP/PDE,PCr/PDE,Pi/PDE,PME/PDE.These 13 parameters were taken as variable data XI-XI3 representative respectively, and variance analysis were used.(2) Set up function Using the stepwise analytic approach of Sas, the function was set up. Include all of 66 individual voxels data in variable choose range, through variable filtration, there were 6 variables that have significance meanings in 13 variable indexes, those data were XI , X6 , X10 , XI1 , X12 and X13, set up the function of differentiating separately with them. P =0. 0010.05 examined by Wilks1 Lambda of Sas analysis software, the function was observably significance.(3) Protocol of spectrum The spectral protocol of data process were included the metabolize material resonance peak non- including reducing, adjust the collection data (red line peak ) interested in the material and try one's best to match with the real data (white line peak ) (curve fit). There were seven peaks in 31P MRS of liver, including phosphomonoester (PME), inorganic phosphorus (Pi), phosphodiester (PDE), phosphocreatine (PCr) and adenosine triphosphate (p-ATP, a-ATP, y-ATP), adjust the height of every above-mentioned peaks, width and size through a series of the protocol technology, make half a high wide place red-and-white line peaks fit basically. Describe the index of the spectrum curve was mainly as follows: chemical shift, intrgral, peak value, half high width. Chemical shift means the position on the curve abscissa of chemical compound spectrum, express with 1/1000000 (parts per million, ppm) of magnetic resonance frequency; The integral (area under the line) represented the density of this chemical compound, in direct proportion to figure of the resonance atomic nucleus; Peak value mean the height on the curve ordinate, represent the unit of intensity of signal of the chemical compound; Half high width was the distance that reach half height of the curve peak value point between going up curve and down curve. The shape was used for describing the curve, reflecting relaxation time. [RESEARCH RESULTS]1. The author succeeded and carried on some research of compatriot's liver phosphorus spectroscopy, and had set up discrimination function of normal liver tissue and cirrhosis and hepatocellular carcinoma respectively for clinical diagnosis. Certain foundation to diagnose and distinguish of the three groups was established.2. There were significance difference (P value < 0. 05) at three groups compared in the numbers of such 6 parameters as XI , X6 , X10 , XI1 , X12 and X13, which three groups study in the parameter of samples.3. Scanning method, protocol skill and spectrum analytical method of liver phosphorus spectroscopy were obtained and the curve characteristics of three kinds of spectrum were summarized. The characteristic curve and data of 3IP MRS in three groups was showed below.(1) Standard spectroscopy of the normal liver 3IP: Peak value close to zero, PDE value, p-ATP value and a-ATP value were higher relatively with a higher peaks curve. The other chemical compounds form the regular curve and obvious peaks (as figure 4-9 shows).(2) Spectroscopy of the cirrhosis: The characteristic of spectroscopy of the cirrhosis was that there was one obvious higher PCr peak. The y-ATP value was higher than normal liver tissue. The other chemical compounds get lower relatively in peak value (as figure 4-10 shows).(3) Spectroscopy of hepatocellular carcinoma: The characteristic was there was an obvious huge deformity peak. The deformity peak department was due to wider and higher Pi peak merge with part of PDE peak that fall down and take shape to rise. PME and PCr peak increase higher also, but obviously less than cirrhosis. The y- ATP peak fall down obviously than the other groups (as figure 4-11 shows).4. The database of 3 IP MRS parameter as reference value of hepatocellular carcinoma, cirrhosis and normal liver tissue was established primary by this study. This new technology is helpful to the diagnosis and differentiation of some liver diseases.(1) The normal liver tissue: P-ATP[1.27—2.95], a-ATP[2.08~4.94], y-ATP [0.52-1.42], PCr[0.06—0.69], PDE[2.88 —6.78], Pi[0.38—1.08], PME[0.56-2.06], p-ATP/PDE [0.29-0.91], a-ATP / PDE [0.64—1.18], y-ATP/PDE[0.09-0.53], PCr/PDE[0.03-0.15], Pi / PDE[0.11~0.33], PME/PDE[0.11~0.62].(2) Liver cirrhosis: p-ATP[0.81—1.28], a-ATP[ 1.61 — 2.92], y-ATP [0.99-1.43], PCr[1.62—2.80], PDE[2.34— 3.17], Pi[0.56—0.70], PME [0.87 - 1.14], p-ATP/PDE[0.34 - 0.47], a-ATP/PDE [0.61 — 0.84], y-ATP/PDE[0.41 —0.48], PCr/PDE[0.69~0.86], Pi/PDE [0.23 — 0.31], PME/PDE[0.36—0.53].(3) Hepatocellular carcinoma: |3-ATP[0.47— 0.63], a-ATP[0.86— 1.49], y-ATP[0.11~0.41], PCr[0.32—0.72], PDE[0.82— 1.38], Pi[0.43 — 0.60], PME[0.47~0.91], p-ATP/PDE[0.46~0.63], a-ATP/PDE [0.73-1.98],Y-ATP/PDE[0.10~0.42], PCr/PDE[0.25~ 0.76], Pi/PDE[0.43 ~ 0.61], PME/PDE[0.52—0.82].5. The concept of the effective voxel of liver phosphorus spectroscopy was put forward in this study. The so-called effective voxel was that all 7 peak including phosphomonoester (PME), inorganic phosphorus (Pi), phosphodiester (PDE), phosphocreatine (PCr) and adenosine triphosphate (J3-ATP, a-ATP, y-ATP) were showed in the curves of spectroscopy in one VOI, and the each peak were easy to found, especially in the normal volunteer.[THE CONCLUSION AND SIGNIFICANCE] The concentration of phosphorus chemical compound of the liver tissue in vivo can be measured and analyzed using 3IP MRS. By analysis the concentration of different compounds using 3IP MRS, liver normal tissue, liver cirrhosis tissue and hepatocellular carcinoma tissue can be diagnosis and differentiation diagnose. The accuracy rate of diagnosis is 89. 47%. Using 3IP MRS we can exceeding diagnose liver cirrhosis and hepatocellular carcinoma in inferior clinical phase, and can appraise the function state of the liver.