背向散射积分技术在检测慢性肾脏疾病中的应用价值
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摘要
超声背向散射积分（IBS）技术是新近发展较快的一项超声组织定征技术，基于超声背向散射原理，通过分析、处理组织散射的射频信号来判断组织特征。
目的：应用IBS技术检测肾脏，对比肾皮质、肾髓质IBS值，并用不同质指数表示二者IBS值的改变，以期发现二者在慢性肾脏疾病中随肾功能减退而出现的改变及相互关系，旨在探讨该技术对慢性肾病的临床应用价值。
方法：将全部研究对象分为病例组和正常对照组，应用HP5500型超声诊断仪分别检测其肾脏的AII值，并计算IBS%值、HI值，分别对各组间的HI值进行分析比较。
结果：（1）慢性肾病患者皮、髓质IBS%值均较正常对照组明显增高。（p<0.05）（2）随肾功能下降，各组患者的皮、髓质IBS%值较正常组依次递增。（3）病例组（②、③、④）随肾功能损害程度的加重，[IBS%肾皮质-IBS%肾髓质]值逐渐下降，与正常对照（①）组均存在差别，但均无无统计学意义。（4）病例组（②、③、④）随肾功能损害程度的加重，肾实质HI值逐渐下降；病例组（②）肾实质HI值较正常对照组（①）增高，但无统计学意义；病例组（③）肾实质HI值较正常对照（①）组降低，但无统计学意义；病例组（④）肾实质HI值较病例组（②）降低(p<0.05)。
讨论：超声IBS技术通过分析某些声学定量参数来研究组
织特性以达到组织定征的目的，为组织原始回声信号的定量分析提供了新方法。参与构成肾实质的肾小球、肾小管及肾间质成分是产生背向散射良好的散射源，应用IBS技术可定量分析肾皮质、肾髓质IBS值随病变而发生的改变。
年龄因素是肾脏检测中不可忽视的因素，随年龄的增长肾脏自身发生退行性变，引起IBS%值的增加，故在对肾脏进行IBS技术研究时，应尽量减少年龄作为混杂因素造成的选择偏倚，据此，本实验仅对≥30-60岁年龄段人群中的样本进行比较，以增强统计学意义上的可比性。
大量研究表明，在各种原因引起的慢性肾脏疾病中，肾小管间质纤维化都可作为肾功能恶化的一个十分准确的预测指标，肾小管间质纤维化的程度与肾功能的相关性比肾小球硬化与肾功能的相关性更为密切，肾小管间质（主要位于肾髓质）病变程度是反映肾功能下降严重程度和判断预后最重要的指标，其典型的病理改变是肾小管萎缩和消失，间质淋巴细胞、单核细胞浸润和纤维化，二者关系密切，互为因果。
本实验发现，慢性肾病患者皮、髓质IBS%值均较正常对照组明显增高（p<0.05）,慢性肾病各组[IBS%肾皮质-IBS%肾髓质] 值随肾功能损害程度的加重，[IBS%肾皮质-IBS%肾髓质]值逐渐下降，说明病变过程中，肾皮质IBS%值增加幅度较小，而肾髓质相对于肾皮质IBS%值增加幅度大。进一步说明了肾髓质在慢性肾病肾功能变化中的程度较肾皮质的改变更为明显。由此推测，对于肾脏的主要功能结构肾皮质与肾髓质病变的内在联系，可以用某种量化参数反映，进而达到对肾实质病变的全面分析。故引入不同质指数（HI= [（AII肾皮质-AII肾髓质）/AII肾皮
质]╳100%）这一指标，并初次应用于IBS技术对慢性肾病的检测中。
本实验对HI值的分析显示，慢性肾病各组随肾功能损害程度的加重，肾实质HI值逐渐下降；肾功能减退早期肾实质HI值较正常对照组增高，中期肾实质HI值较正常对照组降低，但无统计学意义，晚期（血肌酐浓度≥443μmol/L）肾实质HI值较正常早期（血肌酐浓度<133μmol/L）降低(p<0.05)。HI值改变的根本原因在于肾脏的病理变化，它引起肾脏的超微结构发生改变，致使单位面积内散射源的数目、大小、排列方式等改变，在肾功能减退早期病变以肾小球、皮质肾小管间质炎症为主，中、晚期以广泛的肾髓质内肾小管萎缩和消失、间质纤维化为主，表现为慢性肾病肾功能减退早期以肾皮质AII值增加为主，中、晚期以肾髓质AII值增加为主，从而引起HI值的改变。
实验中初次将HI应用IBS技术检测慢性肾脏疾病中，定量分析肾皮质、肾髓质组织各自的声学密度改变，结果证实HI值可以反映慢性肾脏疾病随肾功能的变化，揭示二者在慢性肾脏疾病中随肾功能减退而出现的改变及相互关系。不同质指数的应用可以相对减少以往由于采用不同方式对背向散射积分值进行标化可能造成的测量误差；为临床医生对病情迅速做出评估提供了又一个新指标，这种差异也可解释尿毒症患者肾脏在常规二维声像图上出现的改变，二者结合可以实现超声对肾脏病变的定性、定量诊断，在临床的超声诊断中可操作性强、简便易行。不同质指数有望应用于除心脏以外，肾脏等人体其它组织结构的定位、定性分析，具有一定的科研与临床应
用价值。
结论：（1）应用IBS技术可以实现超声对肾脏病变的定性、定量诊断。（2）HI可以反映肾脏病变的声学改变。（3）不同质指数有望应用于肾脏等人体其它组织结构的定位、定性分析，具有一定的科研与临床应用价值。
In recent years, integrated backscatter(IBS) imaging technique has been proposed as a new method of ultrasonic tissue characterization. Integrating the radio frequency backscatter signal provides a potentially useful measurement for tissue characterization.
Objective: To compare the IBS of renal cortex and medulla, and explore the clinical application of IBS quantifying chronic nephrosis in heterogeneity index.
Methods: All the people divided into 2 groups: healthy persons and patients, were analyzed with HP 5500 sonograph. Average image intensity(AII) of renal were measured and standardized by IBS of renal sinus and expressed as IBS%. And then, we calculated the heterogeneity index of renal parenchyma.
Results: (1) IBS% of renal cortex and medulla of all the patients were higher significantly than those of the control(p<0.05), but there were no significant difference of renal medulla in group②. (2) With the aggravation of renal function, the value of [cortex – medulla IBS%] had a gradual decrease in patients. However, no significant difference was found among all the people. (3) In patients with aggravation of renal function, only HI of renal parenchyma in group② were
higher than those in control while the others had a gradual decrease. In group④, there was great significant difference (p<0.05).
Discussion: The components of renal parenchyma ,such as glomerulus、renal tubule and renal interstitium are just good scattering sourse. Renal integrated backscatter (IBS) a noninvasive parameter of the acoustic properties of renal parenchyma can reflect pathological changes in nephrosis.
It is necessary that influence of age on renal ultrasonic characters can not be neglected. Because with aging, renal will undergo serial retrogressive changes and eventually lead to the increase of IBS%. According to this, we choice all the people whose ages range from 30y to 60y to reduce selection bias and improve statistical significance.
Many experimental studies have show that tubulointerstitial fibrosis can exactly forecast the aggravation of renal function, and it was more closely related to renal function and prognosis than glomerulus sclerosis. The pathologic change of tubulointerstitial can be directly used to estimate prognosis. The histological changes showed tubular atrophy and disappearance, widening of intertubular spaces with increased lymphocytes and mononuclear cells
infiltration and fibrosis.
In this study, with the aggravation of renal function, the value of [cortex – medulla IBS%] had a gradual decrease in chronic nephrosis. Similarly, the histological change of renal medulla is greater than that of renal cortex. To reflect the relationship between renal cortex and renal medulla, our study introduce heterogeneity index for the first time in examining chronic nephrosis which was calculated as [（renal cortex AII – renal medulla AII）/renal cortexAII] ╳100% .
Examining chronic nephrosis patients, with the aggravation of renal function, only HI of renal parenchyma in early phase were higher than those in control, but in metaphase and advanced phase had a gradual decrease. Especially in advanced phase, there were great significantly decrease in HI. The fundamental cause of the change of HI lies in pathologic change, which result in the changed of microstructure, and consequently, in scattering sourses’ number、size and array ect. In early phase during the impairment of renal function, glomerulus and tubulointerstitial mainly presents inflammatory, thus IBS of renal cortex increases. While in metaphase and advanced phase, tubular atrophy and disappearance, widening of interstitial spaces with increased extracellular matrix
and fibrosis seem to be the key features of this final common pathway, so IBS of renal medulla increases.
This study had been shown for the first time in chronic nephrosis detection that heterogeneity index is reduced in IBS imaging technique. It may produce less metrical error in heterogeneity index than in normalized IBS correspondingly. At the same time
目的：应用IBS技术检测肾脏，对比肾皮质、肾髓质IBS值，并用不同质指数表示二者IBS值的改变，以期发现二者在慢性肾脏疾病中随肾功能减退而出现的改变及相互关系，旨在探讨该技术对慢性肾病的临床应用价值。
方法：将全部研究对象分为病例组和正常对照组，应用HP5500型超声诊断仪分别检测其肾脏的AII值，并计算IBS%值、HI值，分别对各组间的HI值进行分析比较。
结果：（1）慢性肾病患者皮、髓质IBS%值均较正常对照组明显增高。（p<0.05）（2）随肾功能下降，各组患者的皮、髓质IBS%值较正常组依次递增。（3）病例组（②、③、④）随肾功能损害程度的加重，[IBS%肾皮质-IBS%肾髓质]值逐渐下降，与正常对照（①）组均存在差别，但均无无统计学意义。（4）病例组（②、③、④）随肾功能损害程度的加重，肾实质HI值逐渐下降；病例组（②）肾实质HI值较正常对照组（①）增高，但无统计学意义；病例组（③）肾实质HI值较正常对照（①）组降低，但无统计学意义；病例组（④）肾实质HI值较病例组（②）降低(p<0.05)。
讨论：超声IBS技术通过分析某些声学定量参数来研究组
织特性以达到组织定征的目的，为组织原始回声信号的定量分析提供了新方法。参与构成肾实质的肾小球、肾小管及肾间质成分是产生背向散射良好的散射源，应用IBS技术可定量分析肾皮质、肾髓质IBS值随病变而发生的改变。
年龄因素是肾脏检测中不可忽视的因素，随年龄的增长肾脏自身发生退行性变，引起IBS%值的增加，故在对肾脏进行IBS技术研究时，应尽量减少年龄作为混杂因素造成的选择偏倚，据此，本实验仅对≥30-60岁年龄段人群中的样本进行比较，以增强统计学意义上的可比性。
大量研究表明，在各种原因引起的慢性肾脏疾病中，肾小管间质纤维化都可作为肾功能恶化的一个十分准确的预测指标，肾小管间质纤维化的程度与肾功能的相关性比肾小球硬化与肾功能的相关性更为密切，肾小管间质（主要位于肾髓质）病变程度是反映肾功能下降严重程度和判断预后最重要的指标，其典型的病理改变是肾小管萎缩和消失，间质淋巴细胞、单核细胞浸润和纤维化，二者关系密切，互为因果。
本实验发现，慢性肾病患者皮、髓质IBS%值均较正常对照组明显增高（p<0.05）,慢性肾病各组[IBS%肾皮质-IBS%肾髓质] 值随肾功能损害程度的加重，[IBS%肾皮质-IBS%肾髓质]值逐渐下降，说明病变过程中，肾皮质IBS%值增加幅度较小，而肾髓质相对于肾皮质IBS%值增加幅度大。进一步说明了肾髓质在慢性肾病肾功能变化中的程度较肾皮质的改变更为明显。由此推测，对于肾脏的主要功能结构肾皮质与肾髓质病变的内在联系，可以用某种量化参数反映，进而达到对肾实质病变的全面分析。故引入不同质指数（HI= [（AII肾皮质-AII肾髓质）/AII肾皮
质]╳100%）这一指标，并初次应用于IBS技术对慢性肾病的检测中。
本实验对HI值的分析显示，慢性肾病各组随肾功能损害程度的加重，肾实质HI值逐渐下降；肾功能减退早期肾实质HI值较正常对照组增高，中期肾实质HI值较正常对照组降低，但无统计学意义，晚期（血肌酐浓度≥443μmol/L）肾实质HI值较正常早期（血肌酐浓度<133μmol/L）降低(p<0.05)。HI值改变的根本原因在于肾脏的病理变化，它引起肾脏的超微结构发生改变，致使单位面积内散射源的数目、大小、排列方式等改变，在肾功能减退早期病变以肾小球、皮质肾小管间质炎症为主，中、晚期以广泛的肾髓质内肾小管萎缩和消失、间质纤维化为主，表现为慢性肾病肾功能减退早期以肾皮质AII值增加为主，中、晚期以肾髓质AII值增加为主，从而引起HI值的改变。
实验中初次将HI应用IBS技术检测慢性肾脏疾病中，定量分析肾皮质、肾髓质组织各自的声学密度改变，结果证实HI值可以反映慢性肾脏疾病随肾功能的变化，揭示二者在慢性肾脏疾病中随肾功能减退而出现的改变及相互关系。不同质指数的应用可以相对减少以往由于采用不同方式对背向散射积分值进行标化可能造成的测量误差；为临床医生对病情迅速做出评估提供了又一个新指标，这种差异也可解释尿毒症患者肾脏在常规二维声像图上出现的改变，二者结合可以实现超声对肾脏病变的定性、定量诊断，在临床的超声诊断中可操作性强、简便易行。不同质指数有望应用于除心脏以外，肾脏等人体其它组织结构的定位、定性分析，具有一定的科研与临床应
用价值。
结论：（1）应用IBS技术可以实现超声对肾脏病变的定性、定量诊断。（2）HI可以反映肾脏病变的声学改变。（3）不同质指数有望应用于肾脏等人体其它组织结构的定位、定性分析，具有一定的科研与临床应用价值。
In recent years, integrated backscatter(IBS) imaging technique has been proposed as a new method of ultrasonic tissue characterization. Integrating the radio frequency backscatter signal provides a potentially useful measurement for tissue characterization.
Objective: To compare the IBS of renal cortex and medulla, and explore the clinical application of IBS quantifying chronic nephrosis in heterogeneity index.
Methods: All the people divided into 2 groups: healthy persons and patients, were analyzed with HP 5500 sonograph. Average image intensity(AII) of renal were measured and standardized by IBS of renal sinus and expressed as IBS%. And then, we calculated the heterogeneity index of renal parenchyma.
Results: (1) IBS% of renal cortex and medulla of all the patients were higher significantly than those of the control(p<0.05), but there were no significant difference of renal medulla in group②. (2) With the aggravation of renal function, the value of [cortex – medulla IBS%] had a gradual decrease in patients. However, no significant difference was found among all the people. (3) In patients with aggravation of renal function, only HI of renal parenchyma in group② were
higher than those in control while the others had a gradual decrease. In group④, there was great significant difference (p<0.05).
Discussion: The components of renal parenchyma ,such as glomerulus、renal tubule and renal interstitium are just good scattering sourse. Renal integrated backscatter (IBS) a noninvasive parameter of the acoustic properties of renal parenchyma can reflect pathological changes in nephrosis.
It is necessary that influence of age on renal ultrasonic characters can not be neglected. Because with aging, renal will undergo serial retrogressive changes and eventually lead to the increase of IBS%. According to this, we choice all the people whose ages range from 30y to 60y to reduce selection bias and improve statistical significance.
Many experimental studies have show that tubulointerstitial fibrosis can exactly forecast the aggravation of renal function, and it was more closely related to renal function and prognosis than glomerulus sclerosis. The pathologic change of tubulointerstitial can be directly used to estimate prognosis. The histological changes showed tubular atrophy and disappearance, widening of intertubular spaces with increased lymphocytes and mononuclear cells
infiltration and fibrosis.
In this study, with the aggravation of renal function, the value of [cortex – medulla IBS%] had a gradual decrease in chronic nephrosis. Similarly, the histological change of renal medulla is greater than that of renal cortex. To reflect the relationship between renal cortex and renal medulla, our study introduce heterogeneity index for the first time in examining chronic nephrosis which was calculated as [（renal cortex AII – renal medulla AII）/renal cortexAII] ╳100% .
Examining chronic nephrosis patients, with the aggravation of renal function, only HI of renal parenchyma in early phase were higher than those in control, but in metaphase and advanced phase had a gradual decrease. Especially in advanced phase, there were great significantly decrease in HI. The fundamental cause of the change of HI lies in pathologic change, which result in the changed of microstructure, and consequently, in scattering sourses’ number、size and array ect. In early phase during the impairment of renal function, glomerulus and tubulointerstitial mainly presents inflammatory, thus IBS of renal cortex increases. While in metaphase and advanced phase, tubular atrophy and disappearance, widening of interstitial spaces with increased extracellular matrix
and fibrosis seem to be the key features of this final common pathway, so IBS of renal medulla increases.
This study had been shown for the first time in chronic nephrosis detection that heterogeneity index is reduced in IBS imaging technique. It may produce less metrical error in heterogeneity index than in normalized IBS correspondingly. At the same time
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19、Danshi Li, Sanir Fareh, Tack Ki Leung, et al. Promotion of atrial fibrillation by heart failure in dogs: Atrial remodeling of a different sort.Circulation,1999, 6;100(1):87-89.
20、Patrick D, William D, Theodore L, et al. Relation of ultrasonic backscatter and acoustic propagation properties to myofibrillar length and myocardial thickness. Circulation, 1995, 1; 91 (1): 171-175.
21、Paolo Colonma, Roberta Montisci, Leonardo Guliuto, et al. Effects of acute myocardial ischemia on intramyocardial contraction heterogeneity: A study performed with ultrasound integrated backscatter during transesophageal atrial pacing. Circulation, 1999,10; 100(7):1770-1777.
22、Tohji Naito, Yukihiro Koretsume, Noriko Sakamoto, et al. Transmural heterogeneity of myocardial integrated backscatter in diabetic patients with overt cardiac disease. Diabetes Research and Clinical Practice,2001;52:11-20.
23、邹和群，赖德源，张欣洲，主编.实用临床肾脏病学.北京：中国医药科技出版社，2001；第一版，947-948.
24、陈敏章，主编.中华内科学.北京：人民卫生出版社，2000；第一版，2604-2606.
25、郭华，邹万忠.肾小管间质纤维化与单核巨噬细胞的关系.北京大学学报（医学版），2003，10；35（5）：503-507.
26、熊文峰，赵宝珍.超声仪器的设置对背向散射积分测量的影响. 中华超声影像学杂志，2000；9（9）：566-568.
27、朱永胜，钱蕴秋，等.急性中度缺血心肌的组织超声背向散射积分的变化及其与室壁厚度相关性的实验研究. 中国超声医学杂志，1998，14（5）：1-4.
28、Johji Naito, Tohru Masuyama, Toshiaki Mano, et al.Validation of transthoracic myocardical ultrasonic tissue characterization:comparison of transthoracic and open chest measurements of integrated backscatter. Ultrasound in Med & Biol,1995;21(1):33-40.
29、Balen FG, Allen CM, Less UR, et al. Review ultrasound contrast agents. Clinical Radiology, 1994;49:77-82.
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15、田少江，贾汝汉，丁国华.肾小管上皮细胞在肾间质纤维化中的作用. 国外医学泌尿系统分册，2002；22（4）：246-251.
16、郭华，邹万忠.实验性肾小管间质纤维化中肾小管上皮细胞表型转化的研究.中华病理学杂志，2003，8；32（4）：364-367.
17、L.J.Vleming, J.A.Bruijn, L.A.Van ES. The pathogenesis of progressive renal failure. The Netherlands Journal of Medicine,1999;54:114-128.
18、Rodemann HP, Muller GA. Abnormal growth and clonal proliferation of fibroblasts derived from kidneys with interstitial fibrosis. J Exp Biol Med,1990;195:57-63.
19、Danshi Li, Sanir Fareh, Tack Ki Leung, et al. Promotion of atrial fibrillation by heart failure in dogs: Atrial remodeling of a different sort.Circulation,1999, 6;100(1):87-89.
20、Patrick D, William D, Theodore L, et al. Relation of ultrasonic backscatter and acoustic propagation properties to myofibrillar length and myocardial thickness. Circulation, 1995, 1; 91 (1): 171-175.
21、Paolo Colonma, Roberta Montisci, Leonardo Guliuto, et al. Effects of acute myocardial ischemia on intramyocardial contraction heterogeneity: A study performed with ultrasound integrated backscatter during transesophageal atrial pacing. Circulation, 1999,10; 100(7):1770-1777.
22、Tohji Naito, Yukihiro Koretsume, Noriko Sakamoto, et al. Transmural heterogeneity of myocardial integrated backscatter in diabetic patients with overt cardiac disease. Diabetes Research and Clinical Practice,2001;52:11-20.
23、邹和群，赖德源，张欣洲，主编.实用临床肾脏病学.北京：中国医药科技出版社，2001；第一版，947-948.
24、陈敏章，主编.中华内科学.北京：人民卫生出版社，2000；第一版，2604-2606.
25、郭华，邹万忠.肾小管间质纤维化与单核巨噬细胞的关系.北京大学学报（医学版），2003，10；35（5）：503-507.
26、熊文峰，赵宝珍.超声仪器的设置对背向散射积分测量的影响. 中华超声影像学杂志，2000；9（9）：566-568.
27、朱永胜，钱蕴秋，等.急性中度缺血心肌的组织超声背向散射积分的变化及其与室壁厚度相关性的实验研究. 中国超声医学杂志，1998，14（5）：1-4.
28、Johji Naito, Tohru Masuyama, Toshiaki Mano, et al.Validation of transthoracic myocardical ultrasonic tissue characterization:comparison of transthoracic and open chest measurements of integrated backscatter. Ultrasound in Med & Biol,1995;21(1):33-40.
29、Balen FG, Allen CM, Less UR, et al. Review ultrasound contrast agents. Clinical Radiology, 1994;49:77-82.