体素内无规则运动核磁成像技术在前列腺癌诊断中的应用价值

发布时间：2018-05-26 13:39

本文选题：前列腺癌 + 磁共振成像　；参考：《第二军医大学》2014年硕士论文

【摘要】：一、研究背景在世界范围内，前列腺癌(prostate cancer，PCa)发病率在男性所有恶性肿瘤中高居第二。在美国，前列腺癌的发病率已然超过肺癌，成为危害男性健康的头号肿瘤。在我国等亚洲国家，伴随人口总数的增长、人口老龄化的显现及人们生活习惯的改变，其发病率及死亡率均逐年上升。前列腺癌患者以老年男性人群为主，95%以上明确诊断的患者年龄在45～89岁之间，70%以上前列腺癌患者的年龄大于65岁，平均年龄72岁，高峰年龄段为75～79岁。近年来，，前列腺癌的发病年龄愈发呈现出一种年轻化的趋势。从不同年龄组的发病情况来看，年龄大于65岁人群的发病率持续上升。前列腺癌组织学诊断基于以下两个标准：低倍显微镜下组织结构的改变及高倍显微镜下细胞的异变。前列腺癌中，95%以上为腺泡上皮来源的腺癌，好发部位依次为外周带（75%），移行带（20%）和中央带（5%）。85%的腺癌呈多中心性，这可能是肿瘤前列腺内部转移的结果，以外周带多见。由于其在判断患者预后及疗效上具有更高的准确性，且拥有可重复性强及形态操作简单的优势，Gleason分级法是目前临床上运用最广泛的前列腺癌病理分级法。此法将腺体的分化程度以及肿瘤在间质中的生长方式作为肿瘤分级标准，并以此来评价肿瘤的恶性程度。Gleason分级法主要是在低、中倍显微镜下观察组织结构的改变，并不针对个别肿瘤细胞形态进行判断，并同时兼顾肿瘤不同区域组织结构的变异。临床的实际工作中，前列腺癌起病隐匿，一部分患者甚至是在接受前列腺电切或开放手术时才意外发现。早期前列腺癌缺乏特异性症状，只有当肿瘤侵犯或阻塞尿道或（及）膀胱颈时，才会发生下尿路刺激或（及）梗阻症状，甚至出现急性尿潴留、血尿及尿失禁等急性下尿路症状。晚期患者发生前列腺癌骨转移，易并发骨骼疼痛、病理性骨折、贫血及脊髓压迫导致下肢瘫痪等相关临床症状。总的来说，前列腺癌的早期临床症状与良性前列腺增生症（benign prostatehyperplasia，BPH）相似，以排尿障碍为主；晚期临床表现则以肿瘤组织局部浸润或（及）远处转移所引发的相关症状为主。由于其起病的隐匿性，前列腺癌的诊断，特别是前列腺癌的早期诊断仍为临床上的一大难题。因此，改进前列腺癌诊断方法具有相当重要的意义。现在的临床工作中已经将PSA检测联合直肠指诊(digital rectal examination，DRE)以及经直肠前列腺超声检查（transrectal ultrasonography，TRUS）作为前列腺癌早期筛查指标纳入50岁以上中老年男性常规体检项目。如果发现异常，超声（或核磁）引导下的经直肠前列腺穿刺活检则是下一步。前列腺穿刺活检的组织病理学检查是诊断前列腺癌的金标准，但由于种种原因，此检查仍存15%—34%的假阴性。在高度怀疑癌变，却又缺乏病理学证据支持时，问题更加凸显。这种情况下，磁共振成像术（magnetic resonance imaging MRI）以其在三维空间及软组织对比上的高分辨率和多序列多参数成像体系可提供帮助。 MRI被公认是目前临床前列腺癌的最佳影像学诊断技术。近年来，作为一种确定的基础序列，T2加权成像技术(T2-weighted imaging，T2WI)已经广泛应用于常规前列腺MRI形态学检查。在T2WI图像上，正常前列腺的中央带及移行带均表现出低信号，而外周带则表现为明显的高信号。前列腺癌的典型表现为高信号的外周带中出现低信号缺损区。但是，在外周带诊断肿瘤将受到前列腺活检后出血、良性前列腺增生及前列腺炎等因素的影响，同时更大的挑战来自于对中央带及移行带肿瘤的诊断，因为在此区域肿瘤结节将与良性腺组织的信号强度重叠。与此同时，在MR功能成像方面，动态增强扫描技术(dynamic contrastenhanced MRI，DCE-MRI)、扩散加权成像技术(diffusion weighted imaging，DWI)及MR波谱成像(magnetic resonance spectroscopy, MRS）等一系列技术均取得较大发展，进一步提高了前列腺癌MRI诊断的准确性。而近年来，建立于DWI技术基础上，能更为精确分析组织内水分子扩散情况的体素内无规则运动核磁成像技术（intravoxel incoherent motion MR imaging，IVIM-MRI）在前列腺癌诊断领域也获得了广泛关注。 IVIM成像技术在神经系统检查发展已经超过20年，可以更为全面和精确的分析成像区域体素内水分子的真实扩散情况。目前在临床上有很多的IVIM成像技术分析、计算方法，最常用的是经典双指数模型分析计算。IVIM-MRI技术就是通过将DWI成像技术扫描多个不同b值所获取的水分子扩散数据，导入一系列高斯弥散及非高斯弥散理论公式进行运算，从而计算出相应的扩散系数D(slowD)、灌注因子f以及由于灌注因素导致的伪扩散系数D*(fast D)等参数。最后对这些参数进行定量分析，明确组织内水分子扩散情况，判断组织性质，明确诊断。本研究重点分析以弥散系数D、灌注因子f等IVIM-MRI参数与病理之间的相关性，探讨其在诊断前列腺癌及评估其恶性程度、预后的应用价值。二、目的分析体素内无规则运动核磁成像技术（intravoxel incoherent motion MRimaging，IVIM-MRI）主要参数扩散系数D(slow D)、灌注因子f与前列腺病理诊断的相关性，探讨其在诊断前列腺癌与评估其恶性程度及预后的应用价值。三、方法计算、分析41例前列腺癌患者IVIM-MRI参数扩散系数D及灌注因子f，结合病理结果分别对比良性增生组织及肿瘤组织两组与中高危组及低危组两组之间的区别。所有的测量值均采用平均值±标准差的形式表达。采用SPSS13.0统计软件处理，组间计量资料的比较采用两样本均数t检验，α=0.05。四、结果 1、41例前列腺癌患者的DWI及IVIM-MRI相关参数中，ADC值（1.616±0.391vs0.775±0.309×10-3mm2/s）和D值（1.323±0.312vs0.547±0.341×10-3mm2/s）在良性增生组织与肿瘤组织两组之间均表现出了显著性差异（p0.05）。对于良性增生组织与肿瘤组织中f值的研究则更为有趣。本研究发现，在包含b=800s/mm2所得数据时，良性增生组织与肿瘤组织之间的f值（43.359±37.983vs33.492±23.079%）并不具备显著性差异（p＞0.05）。只有将b=800s/mm2所得数据剔除之后，良性增生组织与肿瘤组织的f值（5.837±3.679vs10.983±7.814%）之间的差异才具有统计学意义（p0.05）。 2、41例前列腺癌患者的DCE-MRI及IVIM-MRI相关参数中，Ktrans值（0.296±0.121vs0.526±0.213min-1）、Ve值（29.631±13.472vs41.569±12.334%）和V值（4.737±2.958vs8.397±6.648%）均与D值、f值（剔除b=800s/mm2P的数据之后）一样在良性增生组织与肿瘤组织两组间表现出了显著性差异（p0.05）。并且，IVIM-MRI技术得到的f值与DCE-MRI技术参数Ktrans及VP存在弱正相关性。 3、在中高危组及低危组的各项相关参数之中，仅扩散系数D值（0.513±0.183vs0.735±0.251×10-3mm2/s）如同同样代表组织内水分子扩散能力的DWI参数ADC值（0.623±0.142vs0.947±0.103×10-3mm2/s）一样在两组间表现出了显著性差异（p0.05）。检测组织灌注情况的DCE-MRI各项参数：Ktrans值（0.562±0.032vs0.507±0.113min-1）、Ve值（39.872±13.637vs37.981±12.739%）和VP值（9.033±7.218vs8.395±6.721%）在两组之间无显著性差异（p＞0.05）。同样值得一提的是，无论包含或剔除b=800s/mm2所测数据，f值（包含b=800s/mm2所测数据：26.946±15.152vs37.425±19.023%；剔除b=800s/mm2所测数据：3.753±3.788vs6.782±6.351%）均没有如期待中的一样表现出具有统计学意义的差异（p＞0.05）。五、结论 1、IVIM-MRI参数中的扩散系数D和灌注因子f (剔除b=800s/mm2数据)在肿瘤组织与良性增生组织之间的差异均具有统计学意义（p 0.05）。对比良性增生组织，在肿瘤组织中，弥散系数D明显降低，灌注分数f则明显升高，这两个参数可能成为一个潜在的前列腺癌鉴别标志。 2、弥散系数D在中高度恶性肿瘤与低度恶性肿瘤具有显著性差异，它的降低与肿瘤的恶性程度具有正相关关系。总之，在选取合适的b值后，IVIM-MRI成像技术可合并到现有的MRI检查体系中来提高诊断前列腺癌的准确率，并可帮助判断预后、减少或消除对比剂的使用及缩短检查时间。
[Abstract]:First, research background
In the world, the incidence of prostate cancer (PCa) is second in all male malignant tumors. In the United States, the incidence of prostate cancer has exceeded lung cancer and has become the number one tumor that endangers male health. In Asian countries such as China, the population growth, the aging of the population and people's living habits in the Asian countries and so on in our country The rate of morbidity and mortality increased year by year.
The majority of the prostate cancer patients are elderly men, more than 95% of the patients have a clear age of 45~89 years of age, more than 70% of the prostate cancer patients are older than 65, the average age is 72 years and the peak age is 75~79 years. In recent years, the age of the prostate cancer is becoming more and more young. From the perspective of disease, the incidence of people over 65 years of age continues to rise.
The histologic diagnosis of prostate cancer is based on the following two criteria: changes in tissue structure under low magnification and microscopically under microscope. In prostate cancer, more than 95% are adenocarcinoma derived from acinar epithelium, and the good location is the peripheral zone (75%). The transitional zone (20%) and the central band (5%).85% are multicentric adenocarcinoma, which may be a tumor The outcome of the internal metastases of the prostate is common in the peripheral zone.
Because of its high accuracy in judging the prognosis and curative effect of the patients, and having the advantages of strong repeatability and simple operation, Gleason classification is the most widely used pathological classification of prostate cancer in clinic. This method uses the degree of differentiation of glands and the growth mode of tumor in the interstitial as the standard of tumor classification. In order to evaluate the malignancy degree of the tumor, the.Gleason classification method is mainly to observe the changes of the tissue structure under the low and medium size microscope, not to judge the morphology of the individual tumor cells, and at the same time take into account the variation of the tissue structure in different regions of the tumor.
In clinical practice, prostate cancer is insidious, and some patients are even undiscovered when they are undergoing prostatic resection or open surgery. Early prostate cancer lacks specific symptoms. Only when the tumor invades or obstruct the urethra or (and) the neck of the bladder, the lower urinary tract irritation or (and) obstruction or even acute urine occurs. Acute lower urinary tract symptoms such as retention, hematuria, and urinary incontinence. Advanced patients have bone metastases of prostate cancer, complicated with bone pain, pathological fractures, anemia, and spinal cord compression leading to lower limb paralysis. In general, the early clinical symptoms of prostate cancer and benign prostatic hyperplasia (benign prostatehyperplasia, BPH) Urinary dysfunction is the main cause. Late clinical manifestations are mainly related to local infiltration or distant metastasis of tumor tissue.
The diagnosis of prostate cancer, especially the early diagnosis of prostate cancer, is still a major clinical problem because of its insidious disease. Therefore, it is of great significance to improve the diagnostic method of prostate cancer.
In the current clinical work, PSA detection (digital rectal examination, DRE) and transrectal prostate ultrasound (transrectal ultrasonography, TRUS) are included in the early screening for prostate cancer as an early screening indicator for normal physical examination in middle-aged and elderly men over 50 years of age. If abnormal, ultrasound (or NMR) is guided Transrectal prostate biopsy is the next step. Histopathological examination of prostate biopsy is the gold standard for the diagnosis of prostate cancer, but for a variety of reasons, the examination remains 15% to 34% false negative. The question is more prominent when highly suspected canceration and lack of pathological evidence. In this case, magnetic resonance imaging (MA Gnetic resonance imaging MRI can provide help for its high resolution and multi sequence multi parameter imaging system in three-dimensional space and soft tissue contrast.
MRI is recognized as the best imaging diagnostic technique for the current clinical prostate cancer. In recent years, as a basic sequence, T2 weighted imaging (T2-weighted imaging, T2WI) has been widely used in conventional prostate MRI morphological examination. On T2WI images, the central and migrating bands of normal anterior glands show low signal, but outside of the normal gland. The typical manifestation of the prostate cancer is the low signal defect area in the peripheral zone of the high signal. However, the diagnosis of the tumor in the peripheral zone will be affected by the factors such as postbiopsy bleeding, benign prostatic hyperplasia and prostatitis, while the greater challenge comes from the tumor in the central and the transitional zone. Diagnosis is made because the nodule in this area will overlap with the signal intensity of benign gland tissue.
At the same time, in MR functional imaging, dynamic contrastenhanced MRI (DCE-MRI), diffusion weighted imaging (diffusion weighted imaging, DWI) and MR spectral imaging (magnetic resonance) have made great progress, which further improved the accuracy of the diagnosis of prostate cancer. In recent years, on the basis of DWI technology, the intravoxel incoherent motion MR imaging (IVIM-MRI), which can more accurately analyze the diffusion of water molecules in tissue, has also received extensive attention in the field of diagnosis of prostate cancer.
IVIM imaging technology has been developed for more than 20 years in nervous system examination. It can be more comprehensive and accurate to analyze the true diffusion of water molecules in the imaging region. At present, there are many clinical IVIM imaging techniques, calculation methods, and the most commonly used double exponential model analysis and calculation.IVIM-MRI technology is through the DWI A series of Gauss dispersion and non Gauss dispersion theory formulas are introduced to calculate the water molecular diffusion data obtained by several different b values. The corresponding diffusion coefficient D (slowD), perfusion factor F, and the pseudo diffusion coefficient D* (fast D) caused by the perfusion factor are calculated. In this study, we analyzed the correlation between IVIM-MRI parameters such as diffusion coefficient D, perfusion factor F and pathology, and discussed the value of the diagnosis of prostate cancer and the evaluation of its malignant degree and prognosis.
Two, the purpose
The correlation between the main parameter diffusion coefficient D (slow D) of intravoxel incoherent motion MRimaging (IVIM-MRI), the perfusion factor F and the pathological diagnosis of the prostate was analyzed, and the value of its application in the diagnosis of prostate cancer and the assessment of its malignancy and precondition was discussed.
Three, method
The diffusion coefficient D and perfusion factor F of IVIM-MRI in 41 patients with prostate cancer were analyzed. The difference between the two groups of benign hyperplastic tissues and tumor tissues and the two groups in the middle risk group and the low risk group were compared with the pathological results.
All the measured values were expressed in the form of mean standard deviation. SPSS13.0 statistical software was used to deal with the data. The comparison of the data between groups was compared with two samples, t test, and alpha =0.05..
Four, the result
In the DWI and IVIM-MRI related parameters of 1,41 patients with prostate cancer, the ADC value (1.616 + 0.391vs0.775 + 0.309 x 10-3mm2/s) and D value (1.323 + 0.312vs0.547 + 0.341 x 10-3mm2/s) showed significant difference between the benign proliferative tissue and the tumor tissue (P0.05). The study on the benign proliferative tissue and the f value in the tumor tissue was more important. It was found that the value of F (43.359 + 37.983vs33.492 + 23.079%) between benign hyperplastic tissue and tumor tissue was not significantly different (P > 0.05) when the data included b=800s/mm2 (P > 0.05). Only after the elimination of the data obtained from b=800s/mm2, the F value of benign hyperplastic tissue and tumor tissue was (5.837 + 3.679vs10.983 + 7.814%). The difference was statistically significant (P0.05).
In the DCE-MRI and IVIM-MRI related parameters of 2,41 cases, the value of Ktrans (0.296 + 0.121vs0.526 + 0.213min-1), Ve value (29.631 + 13.472vs41.569 + 12.334%) and V value (4.737 + 2.958vs8.397 + 6.648%) were all with D. The F values (after eliminating the data) showed significant difference between the benign hyperplasia and the tumor tissue two groups. Sex difference (P0.05). Moreover, the F value obtained by IVIM-MRI technology is weakly positively correlated with DCE-MRI technical parameters Ktrans and VP.
3, among the relevant parameters of middle and high risk group and low risk group, only the D value of diffusion coefficient (0.513 + 0.183vs0.735 + 0.251 x 10-3mm2/s) shows significant difference (P0.05) like the ADC value of DWI parameter (0.623 + 0.142vs0.947 + 0.103 * 10-3mm2/s) that also represents the diffusion capacity of water molecules in the tissue (P0.05). The parameters of DCE-MRI: Ktrans value (0.562 + 0.032vs0.507 + 0.113min-1), Ve value (39.872 + 13.637vs37.981 + 12.739%) and VP value (9.033 + 7.218vs8.395 + 6.721%) have no significant difference between the two groups (P > 0.05). It is also worth mentioning that the F values (26.946) are included or excluded from the b= 800s/mm2 data. 15.152vs37.425 + 19.023%, excluding the data measured by b=800s/mm2: 3.753 + 3.788vs6.782 + 6.351%) did not show a statistically significant difference as expected (P > 0.05).
Five. Conclusion
1, the difference between the diffusion coefficient D and the perfusion factor f (b=800s/mm2 data) in the IVIM-MRI parameters was statistically significant between the tumor tissue and the benign hyperplastic tissue (P 0.05). In the benign hyperplasia tissue, the dispersion coefficient D decreased significantly in the tumor tissue and the perfusion fraction f increased significantly, and these two parameters may become a potential one. Identification of prostate cancer.
2, the diffusion coefficient D has significant difference between the middle and high malignant tumor and the low malignant tumor, and its decrease is positively correlated with the malignancy degree of the tumor.
In summary, after selecting the appropriate b value, the IVIM-MRI imaging technique can be incorporated into the existing MRI examination system to improve the accuracy of the diagnosis of prostate cancer, and can help to judge the prognosis, reduce or eliminate the use of contrast agents and shorten the time of examination.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.25

【参考文献】