慢性肾脏病的3.0T功能磁共振研究
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摘要
目的：探讨功能磁共振技术在诊断慢性肾脏病(CKD)、鉴别CKD不同分期,以及评价肾脏功能和小管间质损害程度的应用价值,包括三个部分,第一部分为血氧水平依赖成像(BOLD),第二部分为扩散加权成像(DWI),第三部分为扩散张量成像(DTI)。
对象和方法：搜集2010年3月～2010年12月天津医科大学总医院肾科收治的慢性肾脏病患者59例,测量血清肌酐水平(Scr),根据简化肾脏病膳食改善(MDRD)方程计算肾小球滤过率估算值(eGFR),并根据eGFR确定CKD分期。CKD患者中21例患者接受了肾脏穿刺活组织检查,进行小管间质损伤程度病理评分。同时,搜集27例健康志愿者作为正常对照组。全部受试者均在3.0 TMR扫描仪(3.0T HD-X, GE healthcare)上行如下检查：①第一部分包括常规MRI及BOLD检查,BOLD采用8回波的mGRE序列,单次屏气扫描,扫描时间为18秒；②第二部分为多b值的DWI检查,b值取0、50 s/mm2,0、100 s/mm2, 0、500 s/mm2,0、1000 s/mm2四组,单次屏气扫描,每次扫描时间为21秒；③第三部分为DTI检查,b值取0、300 s/mm2,扩散敏感梯度脉冲施加方向为6,单次屏气扫描,扫描时间为15秒。分别测量并计算：①第一部分评价三个参数,即对照组及CKD患者的皮质、髓质及髓质/皮质R2*值；②第二部分评价6组参数,即4组b值下的皮髓质ADC值,及根据体素内无规律运动(IVIM)模型进行双指数拟合计算得出的皮髓质纯扩散系数ADCd值及皮髓质灌注分数Fp；③第三部分评价6个参数,即皮质、髓质、髓质/皮质FA值及皮质、髓质、髓质/皮质RA值。对上述指标进行如下分析：①比较对照组肾脏皮质与髓质之间的R2*值差异,比较对照组与不同分期CKD患者之间的皮质、髓质及髓质/皮质R2*值差异,并确定髓质/皮质R2*值用于鉴别对照组及不同分期CKD患者之间的最佳诊断阈值;②分析CKD患者皮质、髓质、髓质/皮质R2*值与Scr、eGFR及CKD分期之间的相关性,并分析肾脏穿刺活检患者皮质、髓质、髓质/皮质R2*值与小管间质损伤病理评分之间的相关性；③比较对照组肾脏皮质与髓质之间的ADC值、ADCd值及Fp差异,比较对照组与不同分期CKD患者之间的皮髓质ADC值、皮髓质ADCd值及皮髓质Fp差异,并确定DWI参数用于鉴别对照组及不同分期CKD患者之间的最佳诊断阈值；④分析CKD患者皮髓质ADC值、ADCd值及Fp与Scr、eGFR及CKD分期之间的相关性,并分析肾脏穿刺活检患者皮髓质ADC值、ADCd值及Fp与小管间质损伤病理评分之间的相关性；⑤比较对照组肾脏皮质与髓质之间的FA值、RA值差异,并比较对照组与不同分期CKD患者之间的皮质、髓质、髓质/皮质FA值及皮质、髓质、髓质/皮质RA值差异,绘制ROC曲线,利用曲线下面积比较髓质FA值及髓质RA值鉴别对照组及不同分期CKD患者的诊断效能并确定其最佳阈值；⑥分析CKD患者皮质、髓质、髓质/皮质FA值与Scr、eGFR及CKD分期之间的相关性,并分析肾脏穿刺活检患者皮质、髓质、髓质/皮质FA值与小管间质损伤病理评分之间的相关性。
结果：最终纳入图像分析正常对照组27例,CKD轻度损害组(CKD1期和2期)23例,CKD中重度损害组(CKD3期-5期)29例,CKD患者中肾脏穿刺活检患者21例。①对照组髓质R2*值显著大于皮质(p<0.001)。单因素方差分析显示对照组、CKD轻度损害组、中重度损害组之间的皮质、髓质、髓质/皮质R2*值均存在统计学差异(p<0.01),其中两两比较显示髓质/皮质R2*值在各两组之间的差异最显著(p<0.001)。采用髓质/皮质R2*值鉴别对照组与CKD轻度损害组、CKD轻度损害组与中重度损害组时,所得ROC曲线下面积分别为0.871、0.925,最佳诊断阈值分别为1.858、1.577,其敏感度及特异度均在86%以上；②CKD患者的髓质、髓质/皮质R2*值与Scr、CKD分期均呈负相关(p<0.01),与eGFR呈正相关(p<0.01),以髓质/皮质R2*值的相关强度最高,肾脏穿刺活检患者的髓质、髓质/皮质R2*值与小管间质损伤评分呈负相关(p<0.05),以髓质/皮质R2*值的相关强度最高；③对照组中,皮髓质ADCso值之间无统计学差异(p>0.05),而皮质ADC100、ADC500、ADC1000值均大于髓质(p<0.001),皮质ADCd值大于髓质(p<0.05),而皮质Fp均值大于髓质,但二者之间无统计学差异(p>0.05)。单因素方差分析显示对照组与不同分期CKD患者之间皮髓质ADC值、皮髓质ADCd值、皮髓质Fp均存在统计学差异(p<0.001),其中两两比较显示皮髓质ADC1000值在各两组间的差异最显著(p<0.001)。采用皮髓质ADC1000值鉴别对照组与CKD轻度损害组、CKD轻度损害组与中重度损害组时,所得ROC曲线下面积均大于0.76,敏感度及特异度均在65%以上；④CKD患者的皮髓质ADC1000值均与Scr、CKD分期均呈负相关(p<0.01),与eGFR呈正相关(p<0.01),肾脏穿刺活检患者的皮髓质ADC1000值均与小管间质损伤评分呈负相关(p<0.05)；⑤对照组髓质的FA值、RA值均大于皮质(p<0.001)。单因素方差分析显示对照组与不同分期CKD患者之间的皮质、髓质、髓质/皮质FA值及皮质、髓质、髓质／皮质RA值均存在统计学差异(p<0.05),其中两两比较以髓质FA值及髓质RA值在各两组间的差异最显著(p<0.001)。应用ROC曲线分析显示,鉴别对照组与CKD轻度损害组、CKD轻度损害组与中重度损害组时,髓质FA值的ROC曲线下面积Az值均大于髓质RA值,诊断效能更高,确定髓质FA值的最佳诊断阈值分别为0.367、0.349,其敏感度及特异度均在56%以上；⑥CKD患者的髓质、髓质/皮质FA值与Scr、KD分期均呈负相关(p<0.01),与eGFR均呈正相关(p<0.001),肾脏穿刺活检患者的髓质、髓质/皮质FA值与小管间质损伤病理评分均呈负相关(p<0.05)。
结论：肾脏功能MR成像技术可以从氧合水平、水分子扩散各向同性及各向异性等角度揭示肾脏生理学特征,并能反映CKD的病理生理学改变。①第一部分,肾脏3.0 T BOLD MRI证实正常肾脏皮质的氧合水平高于髓质。髓质/皮质R2*值能够区分正常肾脏与CKD肾脏及不同分期的CKD肾脏,有助于CKD的诊断及分期鉴别,并可作为反映肾脏功能改变程度及小管间质损伤程度的敏感指标；②第二部分,肾脏DWI检查中,应用多b值及IVIM模型能够计算皮髓质的纯扩散系数ADCd值及灌注分数Fp,结果表明正常皮质的水分子扩散程度高于髓质,而皮质的微循环灌注相对丰富,但皮髓质之间无显著差异。ADC值、ADCd值及Fp可反映CKD肾脏水分子扩散程度及微循环灌注不同程度减低,皮髓质ADC1ooo值对CKD的诊断及分期鉴别、反映肾脏功能及小管间质损伤程度有一定价值；③第三部分,肾脏3.0 T DTI MRI切实可行,正常肾脏髓质的水分子扩散各向异性高于皮质。肾髓质FA值可反映CKD患者髓质内水分子扩散的各向异性不同程度减低,对CKD的诊断及不同分期的鉴别均有一定的诊断效能,并能在一定程度上反映肾脏功能变化的程度及肾脏小管间质损伤的程度,为CKD肾脏病变程度的评估提供了一种新的方法。
Objective:To investigate the values of functional magnetic resonance imaging (MRI) techniques in diagnosis and stage of chronic kidney disease (CKD), and the values in evaluation the kidney function and the degree of tubulointerstitial injury. There were three parts included, the first part of blood oxygen level dependent (BOLD), the second part of diffusion-weighted imaging (DWI) and the third part of diffusion tensor imaging (DTI).
Materials and Methods:Fifty-nine patients with chronic kidney disease were enrolled in this study from March 2010 to December 2010, and the serum creatinine level (Scr) were measured, the estimated glomerular filtration rate (eGFR) were calculated with MDRD equation, the stage of CKD were determined. Among the CKD patients, twenty-one received kidney tissue puncturation biopsy examination, and the score of tubulointerstitial injury degree were decided. The control group was composed of 27 healthy volunteers. All of the subjects underwent studies on 3.0T MR scanner(3.0THD-X, GE healthcare) as follows:①The first part were conventional MRI and BOLD examinations, mGRE sequence with 8 echoes were used for BOLD scan with a single breath-hold time of 18s;②The second part was DWI examinations with multiple b values, included 0、50 s/mm2,0、100 s/mm2,0、500 s/mm2 and 0、1000s/mm2 four group of b values, with a single breath-hold time of 21s for each scan;③The third part was DTI examination, with b factor of 0 and 300 s/mm2, with a single breath-hold time of 15s with 6 acquisition directions. Parameters evaluated and calculated consisted of:①Three parameters were evaluated in the first part, include cortical R2* value, medullary R2* value and medullary/cortical R2* ratio of control group and CKD patients;②Six group parameters were evaluated in the second part, include cortical and medullary ADC values with each group of b value, and cortical and medullary ADCd (pure diffusion coefficient) and Fp (perfusion fraction) obtained by biexponential fit calculation with IVIM model;③In the third part, six parameters were assessed, include cortical FA and RA values, medullary FA and RA values, and medullary/cortical FA and RA ratios. The following data were analyzed:①Independent-Samples T Test was used to compare mean R2* value between cortex and medulla in control group. One-Way ANOVA (analysis of variance) were used to compare mean cortical R2* value, medullary R2* value and medullary/ cortical R2* ratio among control group and different stage of CKD patients. Receiver operating characteristics (ROC) analysis was performed in order to evaluate the diagnostic performance of medullary/cortical R2* ratio in differentiating CKD kidney from normal kidney and different stage of CKD kidneys and extracted the optimal cutoff value;②In CKD patient group, Pearson and Spearman rank correlation coefficients were calculated to evaluate the correlations of the kidney R2* parameters with Scr, eGFR and CKD grade. In CKD patients who received kidney tissue biopsy examination, Spearman rank correlation coefficients were calculated to evaluate the correlations of the kidney R2* parameters with pathology score of tubulointerstitial injury of kidney tissue biopsy specimen;③ndependent-Samples T Tests were used to compare mean ADC value, ADCd and Fp between cortex and medulla in control group. One-Way ANOVA were used to compare mean cortical and medullary ADC value, cortical and medullary ADCd, cortical and medullary Fp among control group and different stage of CKD patients. Receiver operating characteristics (ROC) analysis was performed in order to evaluate the diagnostic performance of DWI parameters in differentiating CKD kidney from normal kidney and different stage of CKD kidneys and extracted the optimal cutoff value;④In CKD patient groups, Pearson and Spearman rank correlation coefficients were calculated to evaluate the correlations of the kidney DWI parameters with Scr, eGFR and CKD grade. In CKD patients who received kidney tissue biopsy examination, Spearman rank correlation coefficients were calculated to evaluate the correlations of the kidney DWI parameters with pathology score of tubulointerstitial injury;⑤Mean FA value and RA value between cortex and medulla in control group were compared. Mean kidney FA parameters and RA parameters were compared among control group and different stages of CKD patients by One-Way ANOVA. The diagnostic value of medullary FA and RA value in differentiating CKD kidney from normal kidney and different stages of CKD kidneys were compared by ROC under curve area Az and the optimal cutoff value were determined;⑥Pearson and Spearman rank correlation analyses were used to evaluate the correlations of the kidney DTI parameters with Scr, eGFR and CKD grade of CKD patients. Spearman rank correlation analyses were used to evaluate the correlations of the kidney DTI parameters with the score of tubulointerstitial injury.
Results:The images of 27 healthy volunteers,23 minor CKD patients(CKD 1 and 2 stage),29 moderate/severe CKD patients(CKD 3～5stage) were finally analyzed. Among the CKD patients, twenty one received kidney tissue puncturation biopsy examination. The data analyses revealed:①In control group, the medullary R2* value was higher than cortical (p<0.001). There were statistical differences among the control group, minor CKD and moderate/severe CKD patients in the cortical R2* value, medullary R2* value and medullary/cortical R2* ratio(p<0.01), and the differences of medullary/cortical R2* ratio between every two groups were most significant(p<0.001). The area under the ROC curve for medullary/cortical R2* ratio in differentiating between minor CKD kidneys and normal kidneys and between minor CKD kidneys and moderate/severe CKD kidneys were 0.871,0.925 respectively, and the cutoff value were 1.858、1.577. With the threshold from ROC curve, the sensitivity and specificity were all above 86%;②Negative correlations were found between medullary R2* value with Scr level and CKD grade and also between medullary/cortical R2* ratio with Scr level and CKD grade (p<0.01). Positive correlations were found between medullary R2* value and medullary/ cortical R2* ratio with eGFR(p<0.01). Negative correlations were found between medullary R2* value and medullary/cortical R2* ratio with score of tubulointerstitial injury (p<0.05) The correlation coefficient of medullary/cortical R2* ratio was higher than medullary R2* value;③In control group, no significant difference was found between the cortical and medullary ADC50 value(p>0.05). However, the ADC100, ADC500 and ADC1000 of cortex were all higher than medulla in control group. The ADCd of cortex was higher than medulla in control group (p<0.05), however, the mean value of cortical Fp was higher than medullary but with no statistical significance (p>0.05). There were statistical differences among the control group, minor CKD and moderate/severe CKD patients in the cortical and medullary ADC value, cortical and medullary ADCd and cortical and medullary Fp (p<0.001). The differences of cortical and medullary ADC1000 value between two groups were most significant (p<0.001). Using the cortical and medullary ADC1000 value criteria to differentiate minor CKD kidneys from normal kidneys and discriminate minor CKD kidneys from moderate/severe CKD kidneys, the area under ROC curve were all larger than 0.76, with sensitivity and specificity were all above 65%;④Negative correlations were found between cortical and medullary ADC1000 value with Scr level and CKD grade (p<0.01). Positive correlations were found between cortical and medullary ADC1000 value with eGFR (p<0.01). Negative correlations were found between cortical and medullary ADC1000 value with score of tubulointerstitial injury (p<0.05);⑤The FA and RA value of medullary were higher than that of cortical in control group(p<0.001). There were statistical differences among the control group, minor CKD and moderate/severe CKD patients in the cortical FA value, medullary FA value, medullary/cortical FA ratio and cortical RA value, medullary RA value, medullary/cortical RA ratio (p<0.05). Among the six parameters mentioned above, the differences of medullary FA and medullary R.A value between two groups were most significant (p<0.001). From the ROC curve, the Az of medullary FA value were larger than medullary RA value in differentiating between minor CKD kidneys and normal kidneys and between minor CKD kidneys and moderate/severe CKD kidneys. Medullary FA value of 0.367 and 0.349 were determined as the threshold, with the sensitivity and specificity were all above 56%;⑥Negative correlations were found between medullary FA value and medullary/cortical FA ratio with Scr level and CKD grade (p<0.01). Positive correlations were found between medullary FA value and medullary/cortical FA ratio with eGFR (p<0.001). Negative correlations were found between medullary FA value and medullary/cortical FA ratio with score of tubulointerstitial injury (p<0.05)
Conclusions:Functional magnetic resonance imaging of kidney could reveal the physiological characters and reflect the pathophysiological changes of CKD from different aspects, such as kidney oxygenation, water molecular diffusion isotropy and diffusion anisotropy.①In the first part, renal 3.0 T BOLD MRI demonstrated that the oxygenation level of cortex is higher than medulla in normal kidney. Medullary/ cortical R2* ratio is valuable in diagnosis of CKD and different stages of CKD. Medullary/cortical R2* ratio is a sensitive parameter to reflect the degree of kidney function and tubulointerstitial injury;②In the second part, ADCd value and Fp of cortex and medulla could be calculated with IVIM model and multiple b values. The extent of water molecular diffusion in normal cortex is higher than medulla, and the microperfusion of normal cortex is relatively high but with no significant difference between cortex and medulla. The ADC value, ADCd and Fp can indicate alternation of water diffusion and microcirculation in CKD kidneys. To some extent,the ADC1000 value of cortex and medulla could be used to diagnose and differentiate the stage of CKD and reflect kidney function and tubulointerstitial injury degree;③In the third part, it is feasible to apply DTI to kidney. The anisotropy of water diffusion in medullary is higher than cortical in normal kidney. Lower medullary FA value can reflect the decrease of water diffusion anisotropy in CKD patients. Medullary FA value can represent the kidney function and tubulointerstitial injury degree, and may provide valuable information with diagnosis and stage of CKD. Thus, DTI provides a new method for evaluating the CKD disease.
对象和方法：搜集2010年3月～2010年12月天津医科大学总医院肾科收治的慢性肾脏病患者59例,测量血清肌酐水平(Scr),根据简化肾脏病膳食改善(MDRD)方程计算肾小球滤过率估算值(eGFR),并根据eGFR确定CKD分期。CKD患者中21例患者接受了肾脏穿刺活组织检查,进行小管间质损伤程度病理评分。同时,搜集27例健康志愿者作为正常对照组。全部受试者均在3.0 TMR扫描仪(3.0T HD-X, GE healthcare)上行如下检查：①第一部分包括常规MRI及BOLD检查,BOLD采用8回波的mGRE序列,单次屏气扫描,扫描时间为18秒；②第二部分为多b值的DWI检查,b值取0、50 s/mm2,0、100 s/mm2, 0、500 s/mm2,0、1000 s/mm2四组,单次屏气扫描,每次扫描时间为21秒；③第三部分为DTI检查,b值取0、300 s/mm2,扩散敏感梯度脉冲施加方向为6,单次屏气扫描,扫描时间为15秒。分别测量并计算：①第一部分评价三个参数,即对照组及CKD患者的皮质、髓质及髓质/皮质R2*值；②第二部分评价6组参数,即4组b值下的皮髓质ADC值,及根据体素内无规律运动(IVIM)模型进行双指数拟合计算得出的皮髓质纯扩散系数ADCd值及皮髓质灌注分数Fp；③第三部分评价6个参数,即皮质、髓质、髓质/皮质FA值及皮质、髓质、髓质/皮质RA值。对上述指标进行如下分析：①比较对照组肾脏皮质与髓质之间的R2*值差异,比较对照组与不同分期CKD患者之间的皮质、髓质及髓质/皮质R2*值差异,并确定髓质/皮质R2*值用于鉴别对照组及不同分期CKD患者之间的最佳诊断阈值;②分析CKD患者皮质、髓质、髓质/皮质R2*值与Scr、eGFR及CKD分期之间的相关性,并分析肾脏穿刺活检患者皮质、髓质、髓质/皮质R2*值与小管间质损伤病理评分之间的相关性；③比较对照组肾脏皮质与髓质之间的ADC值、ADCd值及Fp差异,比较对照组与不同分期CKD患者之间的皮髓质ADC值、皮髓质ADCd值及皮髓质Fp差异,并确定DWI参数用于鉴别对照组及不同分期CKD患者之间的最佳诊断阈值；④分析CKD患者皮髓质ADC值、ADCd值及Fp与Scr、eGFR及CKD分期之间的相关性,并分析肾脏穿刺活检患者皮髓质ADC值、ADCd值及Fp与小管间质损伤病理评分之间的相关性；⑤比较对照组肾脏皮质与髓质之间的FA值、RA值差异,并比较对照组与不同分期CKD患者之间的皮质、髓质、髓质/皮质FA值及皮质、髓质、髓质/皮质RA值差异,绘制ROC曲线,利用曲线下面积比较髓质FA值及髓质RA值鉴别对照组及不同分期CKD患者的诊断效能并确定其最佳阈值；⑥分析CKD患者皮质、髓质、髓质/皮质FA值与Scr、eGFR及CKD分期之间的相关性,并分析肾脏穿刺活检患者皮质、髓质、髓质/皮质FA值与小管间质损伤病理评分之间的相关性。
结果：最终纳入图像分析正常对照组27例,CKD轻度损害组(CKD1期和2期)23例,CKD中重度损害组(CKD3期-5期)29例,CKD患者中肾脏穿刺活检患者21例。①对照组髓质R2*值显著大于皮质(p<0.001)。单因素方差分析显示对照组、CKD轻度损害组、中重度损害组之间的皮质、髓质、髓质/皮质R2*值均存在统计学差异(p<0.01),其中两两比较显示髓质/皮质R2*值在各两组之间的差异最显著(p<0.001)。采用髓质/皮质R2*值鉴别对照组与CKD轻度损害组、CKD轻度损害组与中重度损害组时,所得ROC曲线下面积分别为0.871、0.925,最佳诊断阈值分别为1.858、1.577,其敏感度及特异度均在86%以上；②CKD患者的髓质、髓质/皮质R2*值与Scr、CKD分期均呈负相关(p<0.01),与eGFR呈正相关(p<0.01),以髓质/皮质R2*值的相关强度最高,肾脏穿刺活检患者的髓质、髓质/皮质R2*值与小管间质损伤评分呈负相关(p<0.05),以髓质/皮质R2*值的相关强度最高；③对照组中,皮髓质ADCso值之间无统计学差异(p>0.05),而皮质ADC100、ADC500、ADC1000值均大于髓质(p<0.001),皮质ADCd值大于髓质(p<0.05),而皮质Fp均值大于髓质,但二者之间无统计学差异(p>0.05)。单因素方差分析显示对照组与不同分期CKD患者之间皮髓质ADC值、皮髓质ADCd值、皮髓质Fp均存在统计学差异(p<0.001),其中两两比较显示皮髓质ADC1000值在各两组间的差异最显著(p<0.001)。采用皮髓质ADC1000值鉴别对照组与CKD轻度损害组、CKD轻度损害组与中重度损害组时,所得ROC曲线下面积均大于0.76,敏感度及特异度均在65%以上；④CKD患者的皮髓质ADC1000值均与Scr、CKD分期均呈负相关(p<0.01),与eGFR呈正相关(p<0.01),肾脏穿刺活检患者的皮髓质ADC1000值均与小管间质损伤评分呈负相关(p<0.05)；⑤对照组髓质的FA值、RA值均大于皮质(p<0.001)。单因素方差分析显示对照组与不同分期CKD患者之间的皮质、髓质、髓质/皮质FA值及皮质、髓质、髓质／皮质RA值均存在统计学差异(p<0.05),其中两两比较以髓质FA值及髓质RA值在各两组间的差异最显著(p<0.001)。应用ROC曲线分析显示,鉴别对照组与CKD轻度损害组、CKD轻度损害组与中重度损害组时,髓质FA值的ROC曲线下面积Az值均大于髓质RA值,诊断效能更高,确定髓质FA值的最佳诊断阈值分别为0.367、0.349,其敏感度及特异度均在56%以上；⑥CKD患者的髓质、髓质/皮质FA值与Scr、KD分期均呈负相关(p<0.01),与eGFR均呈正相关(p<0.001),肾脏穿刺活检患者的髓质、髓质/皮质FA值与小管间质损伤病理评分均呈负相关(p<0.05)。
结论：肾脏功能MR成像技术可以从氧合水平、水分子扩散各向同性及各向异性等角度揭示肾脏生理学特征,并能反映CKD的病理生理学改变。①第一部分,肾脏3.0 T BOLD MRI证实正常肾脏皮质的氧合水平高于髓质。髓质/皮质R2*值能够区分正常肾脏与CKD肾脏及不同分期的CKD肾脏,有助于CKD的诊断及分期鉴别,并可作为反映肾脏功能改变程度及小管间质损伤程度的敏感指标；②第二部分,肾脏DWI检查中,应用多b值及IVIM模型能够计算皮髓质的纯扩散系数ADCd值及灌注分数Fp,结果表明正常皮质的水分子扩散程度高于髓质,而皮质的微循环灌注相对丰富,但皮髓质之间无显著差异。ADC值、ADCd值及Fp可反映CKD肾脏水分子扩散程度及微循环灌注不同程度减低,皮髓质ADC1ooo值对CKD的诊断及分期鉴别、反映肾脏功能及小管间质损伤程度有一定价值；③第三部分,肾脏3.0 T DTI MRI切实可行,正常肾脏髓质的水分子扩散各向异性高于皮质。肾髓质FA值可反映CKD患者髓质内水分子扩散的各向异性不同程度减低,对CKD的诊断及不同分期的鉴别均有一定的诊断效能,并能在一定程度上反映肾脏功能变化的程度及肾脏小管间质损伤的程度,为CKD肾脏病变程度的评估提供了一种新的方法。
Objective:To investigate the values of functional magnetic resonance imaging (MRI) techniques in diagnosis and stage of chronic kidney disease (CKD), and the values in evaluation the kidney function and the degree of tubulointerstitial injury. There were three parts included, the first part of blood oxygen level dependent (BOLD), the second part of diffusion-weighted imaging (DWI) and the third part of diffusion tensor imaging (DTI).
Materials and Methods:Fifty-nine patients with chronic kidney disease were enrolled in this study from March 2010 to December 2010, and the serum creatinine level (Scr) were measured, the estimated glomerular filtration rate (eGFR) were calculated with MDRD equation, the stage of CKD were determined. Among the CKD patients, twenty-one received kidney tissue puncturation biopsy examination, and the score of tubulointerstitial injury degree were decided. The control group was composed of 27 healthy volunteers. All of the subjects underwent studies on 3.0T MR scanner(3.0THD-X, GE healthcare) as follows:①The first part were conventional MRI and BOLD examinations, mGRE sequence with 8 echoes were used for BOLD scan with a single breath-hold time of 18s;②The second part was DWI examinations with multiple b values, included 0、50 s/mm2,0、100 s/mm2,0、500 s/mm2 and 0、1000s/mm2 four group of b values, with a single breath-hold time of 21s for each scan;③The third part was DTI examination, with b factor of 0 and 300 s/mm2, with a single breath-hold time of 15s with 6 acquisition directions. Parameters evaluated and calculated consisted of:①Three parameters were evaluated in the first part, include cortical R2* value, medullary R2* value and medullary/cortical R2* ratio of control group and CKD patients;②Six group parameters were evaluated in the second part, include cortical and medullary ADC values with each group of b value, and cortical and medullary ADCd (pure diffusion coefficient) and Fp (perfusion fraction) obtained by biexponential fit calculation with IVIM model;③In the third part, six parameters were assessed, include cortical FA and RA values, medullary FA and RA values, and medullary/cortical FA and RA ratios. The following data were analyzed:①Independent-Samples T Test was used to compare mean R2* value between cortex and medulla in control group. One-Way ANOVA (analysis of variance) were used to compare mean cortical R2* value, medullary R2* value and medullary/ cortical R2* ratio among control group and different stage of CKD patients. Receiver operating characteristics (ROC) analysis was performed in order to evaluate the diagnostic performance of medullary/cortical R2* ratio in differentiating CKD kidney from normal kidney and different stage of CKD kidneys and extracted the optimal cutoff value;②In CKD patient group, Pearson and Spearman rank correlation coefficients were calculated to evaluate the correlations of the kidney R2* parameters with Scr, eGFR and CKD grade. In CKD patients who received kidney tissue biopsy examination, Spearman rank correlation coefficients were calculated to evaluate the correlations of the kidney R2* parameters with pathology score of tubulointerstitial injury of kidney tissue biopsy specimen;③ndependent-Samples T Tests were used to compare mean ADC value, ADCd and Fp between cortex and medulla in control group. One-Way ANOVA were used to compare mean cortical and medullary ADC value, cortical and medullary ADCd, cortical and medullary Fp among control group and different stage of CKD patients. Receiver operating characteristics (ROC) analysis was performed in order to evaluate the diagnostic performance of DWI parameters in differentiating CKD kidney from normal kidney and different stage of CKD kidneys and extracted the optimal cutoff value;④In CKD patient groups, Pearson and Spearman rank correlation coefficients were calculated to evaluate the correlations of the kidney DWI parameters with Scr, eGFR and CKD grade. In CKD patients who received kidney tissue biopsy examination, Spearman rank correlation coefficients were calculated to evaluate the correlations of the kidney DWI parameters with pathology score of tubulointerstitial injury;⑤Mean FA value and RA value between cortex and medulla in control group were compared. Mean kidney FA parameters and RA parameters were compared among control group and different stages of CKD patients by One-Way ANOVA. The diagnostic value of medullary FA and RA value in differentiating CKD kidney from normal kidney and different stages of CKD kidneys were compared by ROC under curve area Az and the optimal cutoff value were determined;⑥Pearson and Spearman rank correlation analyses were used to evaluate the correlations of the kidney DTI parameters with Scr, eGFR and CKD grade of CKD patients. Spearman rank correlation analyses were used to evaluate the correlations of the kidney DTI parameters with the score of tubulointerstitial injury.
Results:The images of 27 healthy volunteers,23 minor CKD patients(CKD 1 and 2 stage),29 moderate/severe CKD patients(CKD 3～5stage) were finally analyzed. Among the CKD patients, twenty one received kidney tissue puncturation biopsy examination. The data analyses revealed:①In control group, the medullary R2* value was higher than cortical (p<0.001). There were statistical differences among the control group, minor CKD and moderate/severe CKD patients in the cortical R2* value, medullary R2* value and medullary/cortical R2* ratio(p<0.01), and the differences of medullary/cortical R2* ratio between every two groups were most significant(p<0.001). The area under the ROC curve for medullary/cortical R2* ratio in differentiating between minor CKD kidneys and normal kidneys and between minor CKD kidneys and moderate/severe CKD kidneys were 0.871,0.925 respectively, and the cutoff value were 1.858、1.577. With the threshold from ROC curve, the sensitivity and specificity were all above 86%;②Negative correlations were found between medullary R2* value with Scr level and CKD grade and also between medullary/cortical R2* ratio with Scr level and CKD grade (p<0.01). Positive correlations were found between medullary R2* value and medullary/ cortical R2* ratio with eGFR(p<0.01). Negative correlations were found between medullary R2* value and medullary/cortical R2* ratio with score of tubulointerstitial injury (p<0.05) The correlation coefficient of medullary/cortical R2* ratio was higher than medullary R2* value;③In control group, no significant difference was found between the cortical and medullary ADC50 value(p>0.05). However, the ADC100, ADC500 and ADC1000 of cortex were all higher than medulla in control group. The ADCd of cortex was higher than medulla in control group (p<0.05), however, the mean value of cortical Fp was higher than medullary but with no statistical significance (p>0.05). There were statistical differences among the control group, minor CKD and moderate/severe CKD patients in the cortical and medullary ADC value, cortical and medullary ADCd and cortical and medullary Fp (p<0.001). The differences of cortical and medullary ADC1000 value between two groups were most significant (p<0.001). Using the cortical and medullary ADC1000 value criteria to differentiate minor CKD kidneys from normal kidneys and discriminate minor CKD kidneys from moderate/severe CKD kidneys, the area under ROC curve were all larger than 0.76, with sensitivity and specificity were all above 65%;④Negative correlations were found between cortical and medullary ADC1000 value with Scr level and CKD grade (p<0.01). Positive correlations were found between cortical and medullary ADC1000 value with eGFR (p<0.01). Negative correlations were found between cortical and medullary ADC1000 value with score of tubulointerstitial injury (p<0.05);⑤The FA and RA value of medullary were higher than that of cortical in control group(p<0.001). There were statistical differences among the control group, minor CKD and moderate/severe CKD patients in the cortical FA value, medullary FA value, medullary/cortical FA ratio and cortical RA value, medullary RA value, medullary/cortical RA ratio (p<0.05). Among the six parameters mentioned above, the differences of medullary FA and medullary R.A value between two groups were most significant (p<0.001). From the ROC curve, the Az of medullary FA value were larger than medullary RA value in differentiating between minor CKD kidneys and normal kidneys and between minor CKD kidneys and moderate/severe CKD kidneys. Medullary FA value of 0.367 and 0.349 were determined as the threshold, with the sensitivity and specificity were all above 56%;⑥Negative correlations were found between medullary FA value and medullary/cortical FA ratio with Scr level and CKD grade (p<0.01). Positive correlations were found between medullary FA value and medullary/cortical FA ratio with eGFR (p<0.001). Negative correlations were found between medullary FA value and medullary/cortical FA ratio with score of tubulointerstitial injury (p<0.05)
Conclusions:Functional magnetic resonance imaging of kidney could reveal the physiological characters and reflect the pathophysiological changes of CKD from different aspects, such as kidney oxygenation, water molecular diffusion isotropy and diffusion anisotropy.①In the first part, renal 3.0 T BOLD MRI demonstrated that the oxygenation level of cortex is higher than medulla in normal kidney. Medullary/ cortical R2* ratio is valuable in diagnosis of CKD and different stages of CKD. Medullary/cortical R2* ratio is a sensitive parameter to reflect the degree of kidney function and tubulointerstitial injury;②In the second part, ADCd value and Fp of cortex and medulla could be calculated with IVIM model and multiple b values. The extent of water molecular diffusion in normal cortex is higher than medulla, and the microperfusion of normal cortex is relatively high but with no significant difference between cortex and medulla. The ADC value, ADCd and Fp can indicate alternation of water diffusion and microcirculation in CKD kidneys. To some extent,the ADC1000 value of cortex and medulla could be used to diagnose and differentiate the stage of CKD and reflect kidney function and tubulointerstitial injury degree;③In the third part, it is feasible to apply DTI to kidney. The anisotropy of water diffusion in medullary is higher than cortical in normal kidney. Lower medullary FA value can reflect the decrease of water diffusion anisotropy in CKD patients. Medullary FA value can represent the kidney function and tubulointerstitial injury degree, and may provide valuable information with diagnosis and stage of CKD. Thus, DTI provides a new method for evaluating the CKD disease.
引文
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