分享:
分享到微信朋友圈
X
综述
磁共振波谱成像在前列腺癌中的应用
陈慧铀 王利伟 殷信道

Janesya Sutedjo and Chen Hui-you to make the same contribution to this workSutedjo J,陈慧铀,王利伟,等.磁共振波谱成像在前列腺癌中的应用.磁共振成像, 2015, 6(1): 71-75. DOI:10.3969/j.issn.1674-8034.2015.01.015.


[摘要] 前列腺癌在男性已成为第二个最常见的被诊断的癌症。前列腺癌的早期检测对该病的治疗尤为重要。有许多方法来检测前列腺癌。MR波谱成像(MRS )可较好地早期检测前列腺癌。作者将讨论MRS的原理,前列腺癌的不同诊断前方法,以及目前已应用于临床的不同的机器和设备。
[Abstract] Prostate cancer had become the second most commonly diagnosed cancer in men. Early detection of the prostate cancer is important for the management of this disease. There are many methods to detect the prostate cancer. Magnetic resonance spectroscopy (MRS) is one of the methods that promising for early detection of prostate cancer. This article will talk about how MRS works, different method of diagnosing the prostate cancer, and different kind of machine and equipment that had been used in the clinical nowadays.
[关键词] 前列腺癌;磁共振波谱;综述
[Keywords] Prostate cancer;Magnetic resonance spectroscopy;Review

南京医科大学附属南京医院(南京市第一医院)医学影像科,南京 210006

陈慧铀 南京医科大学附属南京医院(南京市第一医院)医学影像科,南京 210006

王利伟 南京医科大学附属南京医院(南京市第一医院)医学影像科,南京 210006

殷信道* 南京医科大学附属南京医院(南京市第一医院)医学影像科,南京 210006

通讯作者:殷信道,E-mail:y.163yy@163.com


收稿日期:2014-09-10
接受日期:2014-12-15
中图分类号:R445.2; R697+.3 
文献标识码:A
DOI: 10.3969/j.issn.1674-8034.2015.01.015
Sutedjo J,陈慧铀,王利伟,等.磁共振波谱成像在前列腺癌中的应用.磁共振成像, 2015, 6(1): 71-75. DOI:10.3969/j.issn.1674-8034.2015.01.015.

1 Introduction

       Based on the GLOBOCAN 2008 estimates, prostate cancer is the second most commonly diagnosed cancer and also the sixth leading cause of mortality in cancer in males worldwide[1]. An early detection of the prostate cancer is an important part to have an effective treatment of prostate cancer[2,3]. For this reason, detection of the prostate cancer is a major topic of diagnostic imaging, while screening for prostate cancer is still problematic and remains controversial[3,4].

       Presently, the common methods used for detecting the prostate cancer are digital rectal examination (DRE), serum prostate-specific antigen (PSA) level, transrectal ultrasound (TRUS), and sextant biopsy[2,3, 5,6,7,8]. The gold standard of prostate cancer diagnosis includes a histological examination of biopsy specimens obtained via a blinded sextant TRUS directed biopsy for patients with elevated PSA levels or abnormal DRE[3, 9]. However, this method is still insufficient and limited in the detection and local staging of prostate cancer because of the low sensitivity and specificity to indicate the malignancy, as the result from the location of the sextant biopsy that chosen randomly and the heterogeneous distribution of the tumor within the prostate[2,3,4, 8,9,10].

       Magnetic resonance imaging (MRI) of the prostate is better in giving a clear and detailed image of soft-tissue structure than other imaging methods, it provides a high-resolution anatomical images based on numerous basic tissue characteristics that could show the best description of prostate contour and anatomy of the internal zone. The degree of details and high resolution of images given by MRI, makes it an excellent tool for early diagnosis and staging of prostate cancer[2, 6, 11,12,13]. The role of MRI has advanced in the past decade with development of newer techniques to localize, stage, and obtain functional information about the tumor. Such as diffusion-weighted imaging (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and MR spectroscopy (MRS), which are highly sensitive and specific for detection, staging, and localization of prostate cancer, also could describe the extracapsular spread due to high soft tissue resolution[2, 5, 14,15]. MRS is the most commonly used functional MRI technique for prostate cancer detection[3].

       In this article we will talk about how the MRS work and the different strength of magnetic field, and coils that commonly used nowadays.

2 Prostate Metabolism

2.1 Normal Prostate

       Normal prostate gland epithelial cells contain a high concentration of zinc. These high concentrations of zinc are primarily due to increased expression of ZIP-type plasma membrane Zn uptake transporters (primarily Human ZIP-1). Zinc suppresses aconitase activity that caused suppression of the first step of Krebs’ cycle that converts citrate to isocitrate. Thus, preventing the consumptions of citric acid and causing the prostate to synthesize and secrete large amounts of citrate into the glandular cavity, which resulting in high levels of citrate. Normal prostate epithelial cells also contain very high concentrations of polyamines, particularly spermine[6, 10,11, 16]. So MRS of a healthy prostate will have a high peak of citrate and polyamine, and a low peak of choline[11, 16].

2.2 Prostate Cancer

       Prostate cancers frequently occur in the peripheral zone of the prostate gland. Human ZIP-1 is reduced and zinc levels are dramatically reduced in prostate cancer and the malignant epithelial cells, and there exists evidence that the loss of the capability to retain high levels of zinc is an important factor in the development and progression of prostate cancer[17,18]. It is also believed that the transformation of prostate epithelial cells to citrateoxidizing cells, which increases energy production capability, is essential to the process of malignancy and metastasis[19].

       In addition, in cancer cells, there is an elevation of choline-containing metabolites [phosphocholine (PC), glycerophosphocholine (GPC), free choline (Cho)] and the over and under-expression of key enzymes in phospholiopid membrane sysnthesis and degradation, specifically choline kinase and a number of the phospholipases, have been associated with the presence, progression and therapeutic response of a variety of human cancers including prostate[16, 20].

       Similar to citrate, polyamines are dramatically reduced in prostate cancer and this reduction is associated with significant changes of the degree of polyamine metabolism regulatory genes expression. The first step of spermine synthesis, ornithine decarboxylase catalyzes has been found to be over-expressed in prostate cancer. The polyamines also exert diverse effects on protein synthesis and act as inhibitors of numerous enzymes including several kinases. However, similar to citrate high levels of spermine found in the prostatic ducts and the observed changes in spermine may also be due to the loss of ductal morphology or a reduction in the secretion of polyamines in cancer[11].

       So MRS of a prostate cancer mostly in its peripheral zone will have an increased level of choline and a decreased level of citrate and polyamine compared to the healthy prostate tissue. These metabolic changes in prostate tissue might occur before morphological changes in tissues and theoretically might be valuable to detect hidden, unsuspected prostate cancer where routine histological sections have failed to detect malignancy[6].

3 Magnetic Resonance Spectroscopy

3.1 How it works

       MRS is one of functional methods of MRI that indirectly measures the relative metabolite concentration of specific biochemical compound of tissue in a single or multiple voxels by detecting the chemical shift differences of metabolites. Thus, MRS can assess the normal and abnormal prostate tissue metabolism[4, 8, 21]. On prostate MRS, the resonances for the prostate metabolic fingerprint which are choline, creatine, polyamines, and citrate, that occur at distinct frequencies (≈ 3.2, 3.0, 3.1, and 2.6 ppm, respectively) or positions in the spectrum[5, 9, 22].

       Areas of prostate cancer were metabolically recognized based on the ratio of choline plus creatine to citrate (CC/C) and choline to creatine (C/C) peak area ratios[13, 22,23]. The first ratio is used because the creatine peak is very close to the choline peak in the spectral trace, the two may be inseparable; so, the CC/C is used for the spectral analysis in the clinical setting[3, 24]. MR spectra from areas of prostate cancer specifically shows a significant decrease or absence of citrate and polyamines, while the choline level is increased relative to the creatine level, thus resulting in significant changes in the CC/C in areas of cancer[23, 25]. Since the polyamine peak is not always resolvable from creatine and choline in healthy tissues, it was incorporated in the choline plus creatine peak area. For the same reason, the choline to creatine peak area ratio was only reliable in regions containing cancer, partially or completely, where polyamines are markedly decreased or absent subsequently[23, 26].

3.2 Diagnosis Method

       There are varieties methods to diagnose prostate cancer based on the CC/C or C/C ratio value. Some of them vary in the cut-off value that they use to diagnose the prostate cancer. Some are also different in the classification of the malignancy of the lesion based on the value given by the ratio. Some of the methods use the CC/C ratios for different tissue in the prostate on a 5-point scale to diagnose the lesion as definitely benign tissue; probably benign tissue; possible malignant tissue; probably benign tissue; or definitely malignant tissue[27,28].

       Some other method is using a qualitative approach to diagnosed prostate cancer. All spectroscopic data were scored through a 4-point scale 1 = normal (citrate peak at least two times higher than choline/creatine peak); 2 = probably benign (citrate peak smaller than two times or equal to choline/creatine peak); 3 = probably malignant (choline/creatine peak smaller than two times but higher than citrate peak); 4 = definitely malignant (choline/creatine peak at least two times higher than citrate peak)[29,30,31].

       The benefit of MRS for detecting, localizing, and characterizing prostate cancer is highly dependent on the quality of the spectral examinations obtained[9]. The quality of the spectral depends on the magnetic field strength and the coil chosen during the MRS examination.

3.3 Equipments Choice

       There are several methods of choice that we could use for the MRS scanning based on the combination of the magnetic field strength and the coils. But the minimum standard is the MRI with magnetic field strength of 1.5 T[5, 21, 24,25,26,27,28,29,30,31,32]. Below are the methods of choice that are commonly used in the clinical.

3.3.1 1.5 T with body-surface coils

       The use of body-surface coils, especially in 1.5 T MRI, has been considered technically difficult because of the small size and deep location of the prostate gland with low signal-to-noise ratio[33]. But Kumar et.al[34]. study demonstrates good spectral acquisition and has obtained clear spectra in all subjects with high signal-to-noise ratio, they got (0.31±0.25) of the CC/C ratio.

3.3.2 1.5 T with endorectal coils

       Nowadays the most popular clinical studies of prostate MRS that published are studies using 1.5 T magnet MRI with endorectal coil. The body coil was used for homogenous excitation, and an endorectal coil for signal reception, granting maximum signal-to noise ratio (SNR)[7]. Casciani et al[35] study has a CC/C cut-off value of 0.75 that obtained 89% sensitivity and 79% specificity. Wetter et al[7] got a sensitivity of 100% and a specificity of 69% with a CC/C cut-off value of 0.6. Amsellem-Ouazana et al[36] with CC/C cut-off value of 0.86 got a 76% sensitivity and 68% specificity.

3.3.3 3.0 T with body-surface coils

       Theoretically, doubling in SNR is expected when moving from 1.5 to 3.0 T. Although a full doubling of SNR is not reached in clinical applications due to Specific Absorption Rate (SAR) (measure of the rate of absorption of RF energy in the body) related sequence modifications, the SNR gain at 3.0 T maybe utilized to reduce the voxel size for high resolution imaging or to reduce the acquisition time in MRI of the pelvis[37]. Alternatively, the improvement in SNR may be invested in turn into less patient's discomfort and the use of more comfortable receiver coils set-ups by the use of "non-invasive" external body-surface coils at 3.0 T instead of "invasive" internal endorectal coils at 1.5 T[12, 37]. In Caivano et al[38] study they use a CC/C cut-off value of 1 got a 93% sensitivity and a 78% specificity.

3.3.4 3.0 T with endorectal coils

       The use of an endorectal coils in MRS for localizing prostate cancer at 3T slightly but significantly increased the localization performance compared with the use of body-surface coils[28]. A 3.0 T MRI of the prostate with an endorectal coil may be considered as state-of-the-art as it yields very good results in terms of high diagnostic accuracy[37]. Yakar et al[28] study showed that diagnosis using MRS for the more experienced readers with an endorectal coils had a high specificity (82%—92%), but a low sensitivity (20%—57%) and for the novice reader, MRSI with the use of an endorectal coils had a high sensitivity (80%) and a low specificity (34%).

4 Conclusion

       Nowadays there are a lot of methods to diagnose prostate cancer and it still becomes the controversy which one is the best method for early detection of the prostate cancer. MRS is one of the methods that is promising. But there are a lot of varieties of choice in MRS like the magnetic field strength and the choice of coils. In clinical usage the most used method is scanning with 1.5 T MRI with endorectal coils, but the best way to get a good SNR and images for a rateable MRS voxel is 3.0 T MRI with endorectal coils. Although for the sake of the comfort of the patients we could use the 3.0 T MRI with body-surface coils which still could give us the result that is comparable to 1.5 T MRI with endorectal coils.

       Outside the clinical usage there are some studies using MRI magnetic field strength more than 3.0 T. Further improvement of SNR could be expected from the use of even higher field strengths, such as 4.0 T and 7.0 T, so we could get higher sensitivity and specificity in the future[39,40,41].

[1]
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 69-90.
[2]
Aydin H, Kizilgoz V, Tatar IG, et al. Detection of prostate cancer with magnetic resonance imaging: optimization of T1-weighted, T2-weighted, dynamic-enhanced T1-weighted, diffusion-weighted imaging apparent diffusion coefficient mapping sequences and MR spectroscopy, correlated with biopsy and histopathological findings. J Comput Assist Tomogr, 2012, 36(1): 30-45.
[3]
Aigner F, Pallwein L, Pelzer A, et al. Value of magnetic resonance imaging in prostate cancer diagnosis. World J Urol, 2007, 25(4): 351-359.
[4]
Thompson J, Lawrentschuk N, Frydenberg M, et al. The role of magnetic resonance imaging in the diagnosis and management of prostate cancer. BJU international, 2013, 112(Suppl 2): 6-20.
[5]
Verma S, Rajesh A. A clinically relevant approach to imaging prostate cancer: review. AJR Am J Roentgenol, 2011, 196(3Suppl): S1-14.
[6]
Nayyar R, Kumar R, Kumar V, et al. Magnetic resonance spectroscopic imaging: current status in the management of prostate cancer. BJU International, 2009, 103(12): 1614-1620.
[7]
Wetter A, Hubner F, Lehnert T, et al. Three-dimensional 1H-magnetic resonance spectroscopy of the prostate in clinical practice: technique and results in patients with elevated prostate-specific antigen and negative or no previous prostate biopsies. Eur Radiol, 2005, 15(4): 645-652.
[8]
Rajesh A, Coakley FV, Kurhanewicz J. 3D MR spectroscopic imaging in the evaluation of prostate cancer. Clin Radiol, 2007, 62(10): 921-929.
[9]
Tiwari P, Rosen M, Madabhushi A. A hierarchical spectral clustering and nonlinear dimensionality reduction scheme for detection of prostate cancer from magnetic resonance spectroscopy (MRS). Med Phys, 2009, 36(9): 3927.
[10]
Wang P, Guo YM, Liu M, et al. A meta-analysis of the accuracy of prostate cancer studies which use magnetic resonance spectroscopy as a diagnostic tool. Korean J Radiol, 2008, 9(5): 432-438.
[11]
Kurhanewicz J, Vigneron DB. Advances in MR spectroscopy of the prostate. Magn Reson Imaging Clin N Am, 2008, 16(4): 697-710.
[12]
Kaji Y, Kuroda K, Maeda T, et al. Anatomical and metabolic assessment of prostate using a 3-Tesla MR scanner with a custom-made external transceive coil: healthy volunteer study. J Magn Reson Imaging, 2007, 25(3): 517-526.
[13]
Ghafoori M, Alavi M, Aliyari Ghasabeh M. MRI in prostate cancer. Iran Red Crescent Med J, 2013, 15(12): e16620.
[14]
Soylu FN, Eggener S, Oto A. Local staging of prostate cancer with MRI. Diagn Interv Radiol, 2012, 18(4): 365-373.
[15]
Kim CK, Park BK. Update of prostate magnetic resonance imaging at 3 T. J Comput Assist Tomogr, 2008, 32(2): 163-172.
[16]
Saito K, Kaminaga T, Muto S, et al. Clinical efficacy of proton magnetic resonance spectroscopy (H-1-MRS) in the diagnosis of localized prostate cancer. Anticancer Res, 2008, 28(3B): 1899-1904.
[17]
Costello LC, Franklin RB. Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer. Prostate, 1998, 35(4): 285-296.
[18]
Liang JY, Liu YY, Zou J, et al. Inhibitory effect of zinc on human prostatic carcinoma cell growth. Prostate, 1999, 40(3): 200-207.
[19]
Costello LC, Franklin RB. Bioenergetic theory of prostate malignancy. Prostate, 1994, 25(3): 162-166.
[20]
Cohen JS. Phospholipid and energy metabolism of cancer cells monitored by 31P magnetic resonance spectroscopy: possible clinical significance. Mayo Clin Proc, 1988, 63(12): 1199-1207.
[21]
Pinto F, Totaro A, Calarco A, et al. Imaging in prostate cancer diagnosis: present role and future perspectives. Urol Int, 2011, 86(4): 373-382.
[22]
Scheenen TW, Futterer J, Weiland E, et al. Discriminating cancer from noncancer tissue in the prostate by 3-dimensional proton magnetic resonance spectroscopic imaging: a prospective multicenter validation study. Invest Radiol, 2011, 46(1): 25-33.
[23]
Testa C, Schiavina R, Lodi R, et al. Accuracy of MRI/MRSI-based transrectal ultrasound biopsy in peripheral and transition zones of the prostate gland in patients with prior negative biopsy. NMR Biomed, 2010, 23(9): 1017-1026.
[24]
Claus FG, Hricak H, Hattery RR. Pretreatment evaluation of prostate cancer: role of MR imaging and 1H MR spectroscopy. Radiographics, 2004, 24(Suppl 1): S167-180.
[25]
Kurhanewicz J, Swanson MG, Nelson SJ, et al. Combined magnetic resonance imaging and spectroscopic imaging approach to molecular imaging of prostate cancer. J Magn Reson Imaging, 2002, 16(4): 451-463.
[26]
Jung JA, Coakley FV, Vigneron DB, et al. Prostate depiction at endorectal MR spectroscopic imaging: Investigation of a standardized evaluation system. Radiology, 2004, 233(3): 701-708.
[27]
Futterer JJ, Scheenen TW, Heijmink SW, et al. Standardized threshold approach using three-dimensional proton magnetic resonance spectroscopic imaging in prostate cancer localization of the entire prostate. Invest Radiol, 2007, 42(2): 116-122.
[28]
Yakar D, Heijmink SW, Hulsbergen-van de Kaa CA, et al. Initial results of 3-dimensional 1H-magnetic resonance spectroscopic imaging in the localization of prostate cancer at 3 Tesla: should we use an endorectal coil? Invest Radiol, 2011, 46(5): 301-306.
[29]
Villeirs GM, De Meerleer GO, De Visschere PJ, et al. Combined magnetic resonance imaging and spectroscopy in the assessment of high grade prostate carcinoma in patients with elevated PSA: a single-institution experience of 356 patients. Eur J Radiol. 2011, 77(2): 340-345.
[30]
Villeirs GM, Oosterlinck W, Vanherreweghe E, et al. A qualitative approach to combined magnetic resonance imaging and spectroscopy in the diagnosis of prostate cancer. Eur J Radiol, 2010, 73(2): 352-356.
[31]
Klijn S, De Visschere PJ, De Meerleer GO, et al. Comparison of qualitative and quantitative approach to prostate MR spectroscopy in peripheral zone cancer detection. Eur J Radiol, 2012, 81(3): 411-416.
[32]
Heijmink SW, Futterer JJ, Hambrock T, et al. Prostate cancer: body-array versus endorectal coil MR imaging at 3 T: comparison of image quality, localization, and staging performance. Radiology, 2007, 244(1): 184-195.
[33]
Lowry M, Liney GP, Turnbull LW, et al. Quantification of citrate concentration in the prostate by proton magnetic resonance spectroscopy: zonal and age-related differences. Magn Reson Med, 1996, 36(3): 352-358.
[34]
Kumar R, Kumar M, Jagannathan NR, et al. Proton magnetic resonance spectroscopy with a body coil in the diagnosis of carcinoma prostate. Urol Res, 2004, 32(1): 36-40.
[35]
Casciani E, Polettini E, Bertini L, et al. Contribution of the MR spectroscopic imaging in the diagnosis of prostate cancer in the peripheral zone. Abdom Imaging, 2007, 32(6): 796-802.
[36]
Amsellem-Ouazana D, Younes P, Conquy S, et al. Negative prostatic biopsies in patients with a high risk of prostate cancer. Is the combination of endorectal MRI and magnetic resonance spectroscopy imaging (MRSI) a useful tool? A preliminary study. Eur Urol, 2005, 47(5): 582-586.
[37]
Willinek WA, Schild HH. Clinical advantages of 3.0 T MRI over 1.5 T. Eur J radiol, 2008, 65(1): 2-14.
[38]
Caivano R, Cirillo P, Balestra A, et al. Prostate cancer in magnetic resonance imaging: diagnostic utilities of spectroscopic sequences. J Med Imaging Radiat Ooncol, 2012, 56(6): 606-616.
[39]
Near J, Romagnoli C, Bartha R. Reduced power magnetic resonance spectroscopic imaging of the prostate at 4.0 Tesla. Magn Reson Med, 2009, 61(2): 273-281.
[40]
Klomp DW, Bitz AK, Heerschap A, et al. Proton spectroscopic imaging of the human prostate at 7 T. NMR Biomed, 2009, 22(5): 495-501.
[41]
van den Bergen B, Klomp DW, Raaijmakers AJ, et al. Uniform prostate imaging and spectroscopy at 7 T: comparison between a microstrip array and an endorectal coil. NMR Biomed, 2011, 24(4): 358-365.

上一篇 三阴乳腺癌磁共振成像研究
下一篇 磁共振扩散张量成像诊断前列腺癌的理论基础
  
诚聘英才 | 广告合作 | 免责声明 | 版权声明
联系电话:010-67113815
京ICP备19028836号-2