| BackgroundIt is of very vital significance that identifies the nature of bone and soft tissue tumors in early time, whatever benign or malignant, to choose the treatment plan and judge the patient's prognosis. At present pathological inspection is clearly the "golden standard" to identify the pathological change. No doubt the histopathology is the most objective method because of directly examination to the pathological change, but this superiority has also been doomed its inherent shortage, that is it must be invasive inspection. It is always a puzzle in order to understand whether the pathological change need to be identified with the pathological biopsy. Therefore, seeking one kind of noninvasive inspection method, which compares with the pathologic inspection to qualitatively identify the pathological change, has been the clinical urgent need. At present, magnetic resonance spectroscopy (MRS) is one method that can examine noninvasively the alive specimen of the organ, metabolism of the organization and cell, the biochemistry change and can analyze compound quantitative, some people even called it "noninvasive pathology". MRS is one kind of functional imaging inspections; it may provide the pathophysiology information of pathological change from the molecular level that is the basis of making it possible to qualitatively diagnosis disease. MRS provides the biochemistry information that may be used to differentiate the malignant tumor from benign, to identify the tumor type, understand the grade and prognosis of malignant tumor, thus help clinician to choose the reasonable treatment plan, to observe tumor response, to monitor medicine absorption and the metabolism and so on. At present spectrum applied to the medicine domain include 1H, 13C, 31P, 39K, 14N, 19F, et al, but what is commonly used are H, 31P. The MRS research focused on brain, liver, prostate gland, mammary gland and so on in the past, it is extremely few on the musculoskeletal tissue. The research of musculoskeletal system mainly concentrated to 31P-MRS before, in recent years few overseas scholars attempted applied 1H-MRS to the bone research, also to some kinds of blood and the marrow pathological change studies, only limited to surveys of the ration between the fat and water of bone and content of fat, and many took the centrum bone as the research object. Until 2003 domestic Zhou Chun-xiang and in 2004 Wang only then used 1H-MRS to the research of the nature of bone and soft tissue tumors. This article has studied 51 cases of bone and soft tissue tumors, carriyed on preliminary study of the 1H-MRS with the point-resolved spectroscopy (PRESS), observed the height and existence of choline containing compounds(Cho) peak compared with the creatine(Cr) peak, according the results to judge the nature of bone and soft tissue tumors. We have studied 31P-MRS of 41 cases of benign and malignant tumors with 3T magnetic resonance machine which is the most advanced. We have studied pH, phospholipid and energy metabolism and investigated the application of 3T 31P-MRS in diagnosis and differential diagnosis of bone and soft tissue tumors. Study from the earlier MRS research, MRS has been applied in the most common tumor: osteosarcoma, and the Ki-67, proliferating cell nuclear antigen (PCNA) and matrix metalioproteinase (MMP-9) have been studyed at the same time, which have been proved that can judge the histology grade, invasive ability and prognosis. The metabolism measured in the 1H-MRS and the three kind of expression levels of antigens were carryed on comparing research, the relativity was analyzed to clarify whether 1H-MRS could replace the pathologic examination in the judgement of histology grade, invasive ability and prognosis.ObjectiveTo study benign and malignant bone and soft tissue tumors with 1H-MR spectroscopy (1H-MRS) and 31P-MR spectroscopy (31P-MRS) at 3 Tesla MR scanner and to analyze if there is significant correlation between the semi-quantitative data of 1H-MRS and the immunohistochemical tests of the osteosarcoma specimens, then to assess the usefulness of 1H-MRS and 31P-MRS in diagnosing bone and soft tissue tumors and distinguishing benign from malignant tumors, and assess the relationship of the 1H-MRS in the different grade osteosarcoma.Materials and Methods1. 51 patients with bone and soft tissue tumors proved clinically and pathologically were examined with 1H-MRS. 1H-MRS was performed to study malignant musculoskeletal tumors, benign tumors and normal muscule adjacent to lesions to analyze the characteristics, and sigle-volume PRESS sequence was used. PROBE-SV of 1H-MRS directly appeared in the spectrum, observed the peak height of choline compounds(Cho) opposite to the creatine, and whether there was the Cho peak, then according results to judge benign or malignant tumors. Kappa test statistical was used toanalyze MRS result, the histopathology data and the surgery situation. And it was carried on statistics processing using software package of SPSS 11.5 for the windows.2. 41 patients were examined with 31P-MRS which was performed with phosphorus surface coil. The areas under the peaks of various metabolites in spectra were measured. The ratios of the other metabolites toβ-ATP, NTP and Pcr were calculated. Intercellular pH was calculated according to the chemical shift change of Pi relative to Pcr. Sigle-volume PRESS sequence was used. Acoording the area under the peak we calculated the ratios of other metabolite related toβ-ATP, NTP(NTP=ATP+Pi+Pcr) and Pcr, which is PME/β-ATP, PDE/β-ATP,β-ATP/Pi, PME/NTP, PDE/NTP, Pcr/Pi and Pcr/PME. Intracellular pH was calculated according to the chemical shift change of Pi relative to Pcr; formula: pH = 6.75 + log [(X-3.15)/(5.56-X)], the X is difference between Pcr and Pi. The ratios and pH of various metabolite related to the 4 metabolin of 31P-MRS were carried on the statistical process with SPSS11.5 for windows software package through the nonparameter test of several independent samples.3. Before treatment 1H-MRS examination was performed on 25 proved osteosarcoma patients with PRESS sequence, Cho and Cr were the main metabolites that were investigated. And the ratios of Cho/Cr were calculated. The positive expression of Ki-67, PCNA, MMP-9 was shown by immunohistochemical test(SP method). Quantity of positive expression of Ki-67 was expressed by Ki-67 labelling index(Ki-67LI) and calibrated average opacity density(AOD) was used to quantify those of PCNA and MMP. And the relationship between Cho/Cr and Ki-67, PCNA, MMP-9 was analyzed with statistics.Results1. 1H-MRS spectra style of bone and soft tissue tumors was different from that of the normal muscule, and the difference also existed between benign and malignant tumors. Choline level in malignant tumors was markedly higher than that in benign tumors. The true positive ratio of bone and the soft tissue between benign and malignant tumor is 32/34, the true negative rate is 12/15, the false positive is 3/15, the false negative rate is 2/34. Therefore in the group sensitivity of the 1H-MRS is 94% (32/34), the peculiarity is 80%(12/15), really foresees is 91%(32/35), assumes foresight is 86%(12/14), accurate rate is 90%(44/49). The MRS results and the histopathology inspection conclusions has the very good uniformity, theκvalue is 0.76±0.10(P<0.01).2. The ratios of Pcr/PME and PME/NTP in benign and malignant tumors group were significantly different from those of the normal group(P<0.05). Between benign and malignant tumors group, the ratios of PME/β-ATP and PME/NTP were different significantly(P<0.05). PME, PDE, Pi of benign and malignant tumors group were higher than those of normal group, Pcr of benign and malignant lesions group was smaller than that of normal group.3. The choline level in high grade osteosarcoma was higher than in the low grade tumor, Cho/Cr in high grade osteosarcoma was higher than in the low grade tumor. Ki-67LI in the low grade osteosarcoma: 0.1168±0.0473, Ki-67LI in the high grade osteosarcoma: 0.3472±0.1298. Ki-67LI in the low and high grade osteosarcoma showed significant stastistical difference. Cho/Cr, Ki67LI, PCNAAOD and MMP-9AOD of high grade malignant osteosarcoma were all more than those of low grade osteosarcoma significantly. There were strong positive correlation between Cho/Cr and ki-67LI, PCNAAOD, MMP-9A0D respectively.Conclusions 1. The increase of Cho level measured by 1H-MRS is related with the bone and soft tissue malignant tumor, it will play the vital role in the diagnosis and differential diagnosis of bone and soft tissue tumors, as well as the observation of response to the treatment and prognosis of the bone and soft tissue malignant tumors.2. The increase of PME and PDE level measured by 31P-MRS are relevant to the bone and soft tissue tumors. The 31P-MRS will perform a very useful role in the some aspect such as diagnosis and antidiastole of the bone and soft tissue tumors, surveying the reaction and prognosis of the post-treatment bone and soft tissue tumors and so on.3. The 1H-MRS characterizaton could have directing meaning to the malignant grade of the osteosarcoma. Cho/Cr = 2.0 is the standard, which can divid the most osteosarcoma into low grade and high grade malignant group. The antigen expression of the Ki-67, PCNA and MMP-9 have significant difference between the low grade and high grade malignant steosarcoma, which can direct the malignant grade of the osteosarcoma and predict the recurrence and the metastasis tendency of the osteosarcoma. The Cho/Cr of the osteosarcoma 1H-MRS has stong positive correlation with the antigen expression of Ki-67, PCNA and MMP-9, 1H-MRS can have the effect of pathologic examination to some extent.SignificanceOur study shows that functional MR imaging may be used in the diagnosis and differential diagnosis of the bone and soft tissue tumors. 1H-MRS and 31P-MRS could be used to differentiate malignant bone and soft tissue tumors from benign tumors, and diagnose the lesions with the improvement from morphological to microcosmic level, and aquire more information of the lesion, and improve specificity of differential diagnosis of the bone and soft tissue tumors. Our topic want to observe and summarize the characterics of the osteosarcoma 1H-MRS spectrum, and analyze the relationship with the MRI, and compare with the conventional methods(ECT, MRI and biopsy) in the future, and analyze whether 1H-MRS could reflect the curative effect earlier and more sensitively and whether could be an important marker of prognosis. Frankly, our study is really a primitive research in a short time. More experience should be achieved from future work, and more exquisite and well-designed research with large samples on different pathological types of musculoskeletal malignant or benign tumors should be performed to gain more persuasive evidents to verify diagnostic efficacy. With such efforts, the functional MR imaging could become more reliable to diagnose the bone and soft tissue tumors. |
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