1H magnetic resonance spectroscopy of the prostate

PURPOSE: To provide a brief summary of important technical and biochemical aspects and current clinical applications of magnetic resonance spectroscopy (MRS) of the prostate. MATERIAL AND METHODS: Pertinent radiological and biochemical literature was searched and retrieved via electronic media (Medline, PubMed). Basic concepts of MRS of the prostate and its clinical applications were extracted to provide an overview. RESULTS: The prostate lends itself to MRS due to its unique production, storage, and secretion of citrate. While healthy prostate tissue demonstrates high levels of citrate and low levels of choline that marks cell wall turnover, prostate cancer (PCA) utilizes citrate for energy metabolism and shows high levels of choline. The ratio of (choline + creatine)/citrate differentiates healthy prostate tissue and PCA. The combination of magnetic resonance imaging (MRI) and 3-dimensional MRS (3D-MRSI or 3D-CSI) of the prostate localizes PCA to a sextant of the peripheral zone of the prostate with sensitivity/specificity of up to 80/80%. Combined MRI and 3D-MRSI exceed the sensitivity and specificity of sextant biopsy of the prostate. When MRS and MRI agree on PCA presence, the positive predictive value is about 90%. In principle, combined MRI and 3D-MRSI recognize and localize remnant or recurrent cancer after hormone therapy, radiation therapy and cryo-surgery. CONCLUSIONS: Since it is non-invasive and radiation-free, combined MRI and 3D-MRSI lends itself to the planning of prostate biopsy and therapy as well as to post-therapeutic follow-up. For broad clinical application, it will be necessary to facilitate MRS examinations and their evaluation and make MRS available to a wider range of institutions.     

Magnetic resonance spectroscopy in patients with locally confined prostate cancer: association of prostatic citrate and metabolic atrophy with time on hormone deprivation therapy, PSA level, and biopsy Gleason score

This study was undertaken to determine respective associations between prostatic citrate or metabolic atrophy (no detectable citrate, choline, and creatine) at magnetic resonance spectroscopy (MRS) and time on hormone-deprivation therapy, serum PSA, and biopsy Gleason score. Clinical data, histopathology reports and PSA levels of 36 patients on hormone-deprivation therapy (age, 64±9 years, pre-therapeutic biopsy Gleason sum, median 6, range 3–8, antiandrogens only, n=3, LHRH-analogues only, n=4, combined hormone-deprivation therapy, n=29, duration, 27±19 weeks) for locally confined prostate cancer (PCA) were retrospectively correlated with findings in the peripheral zone of the prostate at 3D-MRS (endorectal coil, PRESS, TR 1,000 ms, TE 130 ms). The results show that citrate was usually detected after 13 weeks or less of hormone-deprivation therapy (10/12 vs. 6/24 patients, chi-square-test, p=0.002). All patients with PSA levels exceeding 0.20 ng/ml had detectable metabolites (citrate, n=12, choline without citrate, n=6), while 9/18 patients with PSA 0.20 ng/ml or less showed metabolic atrophy (Fisher-exact-test, p=0.001). There were no significant associations between citrate, metabolic atrophy, pre-therapeutic PSA, and biopsy Gleason sum, respectively. It has been concluded that hormone-deprivation therapy for locally confined PCA has not reached its full deprivation potential after 13 weeks. MRS detects prostate metabolism in patients with PSA exceeding 0.20 ng/ml after hormone-deprivation therapy.     

Time-dependent effects of hormone-deprivation therapy on prostate metabolism as detected by combined magnetic resonance imaging and 3D magnetic resonance spectroscopic imaging.

Combined MRI and 3D spectroscopic imaging (MRI/3D-MRSI) was used to study the metabolic effects of hormone-deprivation therapy in 65 prostate cancer patients, who underwent either short, intermediate, or long-term therapy, compared to 30 untreated control patients. There was a significant time-dependent loss of the prostatic metabolites choline, creatine, citrate, and polyamines during hormone-deprivation therapy, resulting in the complete loss of all observable metabolites (total metabolic atrophy) in 25% of patients on long-term therapy. The amount and time-course of metabolite loss during therapy significantly differed for healthy and malignant tissues. Citrate levels decreased faster than choline and creatine levels during therapy, resulting in an increase in the mean (choline + creatine)/citrate ratio with duration of therapy. Due to a loss of all MRSI detectable citrate, this ratio could not be used to identify cancer in 69% of patients on long-term therapy. In the absence of citrate, however, residual prostate cancer could still be detected by elevated choline levels (choline/creatine ratio > or =1.5), or the presence of only choline in the proton spectrum. The loss of citrate and the presence of total metabolic atrophy correlated roughly with decreasing serum prostatic specific antigen levels with increasing therapy. In summary, MRI/3D-MRSI provided both a measure of residual cancer and a time-course of metabolic response following hormone-deprivation therapy. Magn Reson Med 46:49-57, 2001.     

前列腺炎的MRI及MRS初步研究

目的研究前列腺炎外周带的MRI表现及MR波谱(MRS)特征。资料与方法 21例前列腺炎患者行MRI平扫加MRS成像,观察前列腺外周带的信号形态及信号强度,同时计算感兴趣区的胆碱(Cho)+肌酸(Cre)/枸橼酸盐(Cit)比值。结果 21例前列腺炎患者平均前列腺特异抗原(PSA)水平是31.80 ng/ml。2例呈非结节局灶低信号,10例显示为双侧外周带弥漫低信号,3例显示为一侧外周带弥漫低信号,1例显示为结节状局灶低信号,其余5例没有信号异常。14例MRS谱线示Cho峰升高,Cit峰下降或消失,另7例MRS谱线正常,21例(Cho+Cre)/Cit均值为6.44。结论前列腺炎外周带低信号(T2WI)对前列腺癌并不具有特异性,前列腺炎的MRS谱线可类似于前列腺癌的波谱特征,可导致前列腺癌的假阳性诊断。     

中国健康成人前列腺3.0T体线圈磁共振波谱表现

目的探讨采用体线圈行前列腺3.0T磁共振波谱（MRS）检查的可行性,总结3D1H-MRS在正常前列腺中的表现。方法收集20名中老年健康志愿者行3.0T MRI常规检查、扩散加权成像及MRS检查。年龄为41～80岁,平均年龄（56±11）岁。MRS以体线圈为信号接收线圈,用Proseme序列进行扫描,体素分为正常外腺区、正常内腺区。然后工作软件自动计算每个体素的胆碱（Cho）相对值、（胆碱＋肌酸）/枸橼酸盐[（Cho＋Cr）/Cit]的比值。正常前列腺内、外腺分为左、右两侧,每侧由上到下分为底部、中部和尖部3部分,这样每个志愿者测量12个感兴趣区,每个感兴趣区包括0～3个可用体素平均计算。结果20名健康志愿者获得体素201个,其中可用体素170个（84.6%）,不可用体素为31个（15.4%）。20名中老年健康志愿者前列腺外腺区的（Cho＋Cr）/Cit平均值是0.39±0.21,内腺区的（Cho＋Cr）/Cit平均值是0.50±0.17,2组间比较差异有统计学意义（t=3.219,P〈0.01）。结论①用3.0T体线圈可以顺利完成对前列腺的MRS检查,并可以获得用于分析的体素,其在临床实践中具有可行性。②中老年正常前列腺内腺和外腺的代谢物含量是不同的,差异有统计学意义（t=3.219,P〈0.01）,内腺区（Cho＋Cr）/Cit平均值高于外腺区,进一步对其病变进行MRS定量研究时应根据解剖进行分区研究。     

Combined quantitative dynamic contrast-enhanced MR imaging and (1)H MR spectroscopic imaging of human prostate cancer

PURPOSE: To differentiate prostate carcinoma from healthy peripheral zone and central gland using quantitative dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and two-dimensional (1)H MR spectroscopic imaging (MRSI) combined into one clinical protocol. MATERIALS AND METHODS: Twenty-three prostate cancer patients were studied with a combined DCE-MRI and MRSI protocol. Cancer regions were localized by histopathology of whole mount sections after radical prostatectomy. Pharmacokinetic modeling parameters, K(trans) and k(ep), as well as the relative levels of the prostate metabolites citrate, choline, and creatine, were determined in cancer, healthy peripheral zone (PZ), and in central gland (CG). RESULTS: K(trans) and k(ep) were higher (P < 0.05) in cancer and in CG than in normal PZ. The (choline + creatine)/citrate ratio was elevated in cancer compared to the PZ and CG (P < 0.05). While a (choline + creatine)/citrate ratio above 0.68 was found to be a reliable indicator of cancer, elevated K(trans) was only a reliable cancer indicator in the diagnosis of individual patients. K(trans) and (choline + creatine)/citrate ratios in cancer were poorly correlated (Pearson r(2) = 0.07), and thus microvascular and metabolic abnormalities may have complementary value in cancer diagnosis. CONCLUSION: The combination of high-resolution spatio-vascular information from dynamic MRI and metabolic information from MRSI has excellent potential for improved localization and characterization of prostate cancer in a clinical setting. J. Magn. Reson. Imaging 2004;20:279-287. Copyright 2004 Wiley-Liss, Inc.     

联合应用MR波谱分析与扩散加权成像定量指标行前列腺癌定量诊断

目的 以前列腺六分区为基础,量化分析并验证MRS与DWI两种功能成像的定量指标在联合诊断前列腺癌时的权重大小.方法 搜集2006年2月至2007年7月间前列腺MR检查数据库中患者资料,并以接受前列腺MR检查的不同时间段,将入选前列腺检查患者分为2组,分别用于定量分析和验证结果,第1组为从2006年2月至12月期间、第2组为从2007年1月至7月期间的患者.每例患者在行常规MRI后,均进行MRS和DWI检查,测量MRS可用体素的(胆碱+肌酸)/枸橼酸盐(CC/C)值和分区内最小ADC值(ADC_(mini)).以CC/C≥0.911作为阳性体素标准,计算前列腺MRS六分区内阳性体素比(PVR).采用聚类分析中的线性判别,计算第1组分区内PVR和ADC_(mini)合用时各自所占的权重.将第2组分区内PVR和ADC_(mini)代入公式,采用ROC分析比较单独及联合诊断的诊断效能.结果 第1组和第2组均有40例患者,非前列腺癌加例,前列腺癌20例.由第1组病例得出的联合诊断线性判别公式为DWI和MRS联合诊断的非标准化线性判别值(D)=3.264×ADC_(mini)-0.205×PVR-4.407,分区内PVR和ADC_(mini)的曲线下面积(Az)分别为0.769和0.910,联合诊断的Az为0.909.第2组病例分区内PVR和ADC_(mini)的Az分别为0.838和0.912,联合诊断的Az为0.915.2组的联合诊断效能与单独使用DWI的诊断效能差异均无统计学意义(X~2值分别为0.32和1.50,P值均＞0.05).结论 DWI对前列腺癌的诊断效能高于MRS,联用2种功能参数不能明显提高总体的诊断效能.     

Proton HR-MAS spectroscopy and quantitative pathologic analysis of MRI/3D-MRSI-targeted postsurgical prostate tissues.

Proton high-resolution magic angle spinning ((1)H HR-MAS) NMR spectroscopy and quantitative histopathology were performed on the same 54 MRI/3D-MRSI-targeted postsurgical prostate tissue samples. Presurgical MRI/3D-MRSI targeted healthy and malignant prostate tissues with an accuracy of 81%. Even in the presence of substantial tissue heterogeneity, distinct (1)H HR-MAS spectral patterns were observed for different benign tissue types and prostate cancer. Specifically, healthy glandular tissue was discriminated from prostate cancer based on significantly higher levels of citrate (P = 0.04) and polyamines (P = 0.01), and lower (P = 0.02) levels of the choline-containing compounds choline, phosphocholine (PC), and glycerophosphocholine (GPC). Predominantly stromal tissue lacked both citrate and polyamines, but demonstrated significantly (P = 0.01) lower levels of choline compounds than cancer. In addition, taurine, myo-inositol, and scyllo-inositol were all higher in prostate cancer vs. healthy glandular and stromal tissues. Among cancer samples, larger increases in choline, and decreases in citrate and polyamines (P = 0.05) were observed with more aggressive cancers, and a MIB-1 labeling index correlated (r = 0.62, P = 0.01) with elevated choline. The elucidation of spectral patterns associated with mixtures of different prostate tissue types and cancer grades, and the inclusion of new metabolic markers for prostate cancer may significantly improve the clinical interpretation of in vivo prostate MRSI data.     

前列腺MRS诊断外周带前列腺癌的价值

目的：分析前列腺外周带的MRS特征,探讨MRS技术及其在外周带前列腺癌诊断中的价值。方法：24例临床及常规MRI检查拟诊局限性前列腺外周带前列腺癌患者均成功行前列腺MRS检查,所有患者均经病理证实为前列腺癌,其中19例行穿刺活检,5例经手术证实。回顾性分析患者的临床资料、病变部位、大小、常规MRI特征、MRS检查结果,计算（胆碱＋肌酸）/枸橼酸盐（CC/C）。采用重复测量方差分析比较正常外周带与前列腺癌组织CC/C值差异。采用操作者工作特征曲线（ROC）分析CC/C值诊断前列腺癌的价值。结果：早期外周带前列腺癌T2WI表现为在外周带高信号内有局灶性低信号区。MRS示前列腺外周带肿瘤组织枸橼酸盐（Cit）峰明显下降,胆碱（Cho）峰升高,CC/C值为1.40±0.33,正常外周带为0.51±0.12,两者差异有统计学意义（F=95.189,P〈0.001）。CC/C值的ROC曲线下面积为0.994,这一指标可用于判断前列腺癌（P=0.002）;以0.85为阈值时,诊断前列腺癌的敏感度为95%,特异度为100%。结论：前列腺MRS检查能反映早期外周带前列腺癌的代谢变化,对常规MRI无法明确诊断的前列腺癌具有重要诊断价值。     

前列腺增生MR波谱分析与病理大切片对照研究

目的 探讨前列腺增生不同组织类型在MR波谱(MRS)检查中的代谢差异、临床应用价值及尿道周围单体MRS代谢特点.方法 对16例前列腺增生患者术前行MRS检查,并测定(胆碱+肌酸)/枸橼酸盐(cc/c)值.行耻骨上经膀胱前列腺摘除术,术后标本行病理大切片检查,采用一一对应的方法,将波谱图像cc/c值与前列腺组织病理类型(包括尿道)分别记录后,采用One-way-ANOVA检验和t检验进行不同组织类型间的比较.结果 前列腺的腺体型组织、间质型组织、混合型组织和尿道周围单体分别为233、130、165和50个,其cc/c值分别为O.59±0.29、1.23±0.38、0.80±0.27和0.68±0.33,差异有统计学意义(F=3.49,P＜0.05).其中腺体型组织与间质型、混合型组织比较,间质型组织与混合型组织、尿道周围组织比较,混合型组织与尿道周围组织比较,差异均有统计学意义(t值分别为19.60、7.09、13.22、9.42和9.42,P值均＜0.05).结论 前列腺增生不同组织类型在MRS分析检查中的cc/c值存在差异,尿道周围单体MRS代谢特点与腺体型组织相近,此方法可能对确定诊断阈值有一定意义.