Application of ultrasonic shear wave elastography in chronic kidney disease

Hou Zuoxian, Ma Yixin, Liu He, Chen Limeng

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Chinese Journal of Nephrology ›› 2022, Vol. 38 ›› Issue (8) : 748-753. DOI: 10.3760/cma.j.cn441217-20220216-00109
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Application of ultrasonic shear wave elastography in chronic kidney disease

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Hou Zuoxian. , Ma Yixin. , Liu He. , Chen Limeng. Application of ultrasonic shear wave elastography in chronic kidney disease[J]. Chinese Journal of Nephrology, 2022, 38(8): 748-753. DOI: 10.3760/cma.j.cn441217-20220216-00109.
慢性肾脏病(chronic kidney disease,CKD)正在成为举世关注的公共卫生问题[1]。根据全球疾病、伤害和风险因素的负担研究(Global Burden of Diseases,Injuries,and Risk Factors Study)基于195个国家患病率数据的报告,截至2017年,CKD患者占全球总人口的9.1%,约为6.98亿,其中19%的患者来自于中国[2]。中国国家CKD调查(China national survey of CKD)的结果则显示人群CKD的患病率高达11.6%[3]。对肾脏结构、功能的动态评估和监测是CKD防治的关键,运用功能影像新技术对肾脏结构和功能进行早期诊断与进展评估具有重要的现实意义,其中最受关注的包括超声剪切波弹性成像(shear wave elastography,SWE)、功能核磁成像、光声成像等。
SWE通过在实体组织外界施加声波激励,使得待探查区域发生微小形变,再通过收集形变导致的剪切波和横波,测量和描述组织的弹性,还原触诊带来的直观感,被广泛用于测量人体脏器的生物力学性能。通过建立组织弹性与CKD病理诊断之间的关系,可以诊断CKD并评估病情进展。本文将简述SWE的技术原理、肾脏病理生理特性、现阶段瓶颈和解决方案,并展望其未来应用前景。

一、 弹性成像技术评估CKD

CKD的进展通常伴随着肾脏结构和功能的变化,其病理生理过程均表现为肾脏结构的同质性改变和肾功能进行性恶化,即肾小球硬化、肾小管萎缩和间质纤维化[4]。纤维化贯穿各种CKD肾脏损伤、修复、组织瘢痕形成的全过程,不仅包括早期的细胞增殖、炎症细胞浸润、间质水肿,随后的功能细胞结构的丧失,还伴随细胞外基质(胶原)的蓄积。这些共同的结构基础为通过功能影像评价CKD结构的组织学(病理)特点提供了辅助诊断和预测预后的可能性。
肾穿刺病理诊断依然是肾脏结构诊断的金标准,但因其侵入性而难以重复、难以评价非均一性肾脏结构改变,影响了其在CKD较晚阶段的临床应用[5]。肾脏纤维化通常伴随着血管闭塞、肾小管萎缩以及细胞外基质的增生沉积,这些病理生理改变会影响肾脏整体的生物物理特性,如肾脏组织内部水分子的运动受限、组织缺氧、肾脏体积缩小等等[6]。如果能使用功能影像技术对这些改变的生物物理特性进行测量,则可能实现对肾脏纤维化进展的无创评价。
SWE技术最早应用于临床肝脏疾病的成像中,通过监测组织弹性这一力学属性,还原触诊带来的直接观感[7],在区分正常肝脏和肝硬化、评估肝脏纤维化进程的严重程度等领域取得良好效果[8],并在乳腺、甲状腺、前列腺、肌肉等脏器更多疾病的诊断和评估中开始新的尝试和探索[9]。应用SWE技术评估CKD也是学者们关注的重点之一[10],肾脏由于炎症和纤维化导致肾小球功能丧失,其肾单位和肾脏组织整体的力学性能改变,而SWE可以捕捉这些变化,结合人工智能辅助诊断技术,有望成为评价肾脏结构和功能,甚至预测预后的重要工具。
超声设备和核磁共振都可以作为搭载SWE成像的平台,但由于核磁共振弹性成像技术相关资料较少,且其技术成本较高,实际临床应用受到限制。超声弹性成像的优点是便捷迅速,临床应用价值高,在CKD中的相应研究和应用前景更加广泛。Leong等[10]在57例接受51Cr-乙二胺四乙酸(EDTA)肾小球滤过率(GFR)测量的患者中使用超声弹性成像,发现患者肾脏剪切模量与GFR相关(右肾剪切模量r=-0.63,P<0.01;左肾剪切模量r=-0.817,P<0.01)。在CKD[11]、糖尿病肾病[12]以及肾脏移植[13]患者的肾脏纤维化程度评价中,超声弹性成像也显现出与GFR的相关性。我们在2013年对部分有明确病理诊断的CKD患者肾脏皮质进行了声辐射力冲击成像(acoustic radiation force impulse,ARFI)评估,尝试建立超声弹性成像结果与IgA肾病病理纤维化程度之间的关联[14]。需要注意的是,肾脏的剪切波成像可能会受到肾脏血流干扰[15],且肾脏本身的组织各向异性也会影响测量结果,故而需要谨慎地解读测量数据,同时也对成像技术本身提出了更高的要求。

二、 SWE的技术特点及分类标准

1. SWE的技术原理: 弹性作为物质的一种固有属性,描述的是其发生形变之后,立刻恢复到原有形状的能力。在SWE中,通过在肾脏等实体组织外界施加激励,使得待探查区域发生微小形变,产生剪切波和横波,如图1所示。而剪切波数值被用以测量和描述组织的弹性,对于不可压缩的各向同性组织而言,剪切波的波速与组织弹性的关系可以近似描述为线弹性关系[16] E=3μ=3ρc2,其中E为组织的弹性模量,μ为组织的剪切模量,c为剪切波在组织中的传播速度。由此,通过组织内波的传播速度计算可以得到组织的弹性模量。肾脏的剪切模量与CKD的进展有着较强的相关性,也是近年来SWE技术关注的重要标志物。
图1 剪切波弹性成像原理示意图
注:从超声探头里发射出来的声辐射压缩波在探查区域内聚焦于软组织内部一点,使组织发生微米级的微小形变,在其恢复形状的过程中产生剪切波,超声探头通过接收剪切波信号,计算得到组织区域的剪切模量

Full size|PPT slide

2. SWE的分类: SWE根据声波的激励方式可以被分为ARFI和瞬时弹性成像(transient elastography,TE)。ARFI使用超声换能器来产生声辐射力(聚焦超声)产生剪切波,其可以表达为数学式[16] F=2αIc,其中 F为声辐射力的幅度, α是超声传播的衰减参数, c是纵向传播超声声速, I为超声声波强度。ARFI有着持续时间较短(<1 ms)、造成的形变微小(微米级)、穿透性强等优点,在肾脏组织研究上更为广泛应用。瞬时弹性成像通过机械振动产生剪切波,目前主要用于测量肝脏组织的弹性,于肾脏领域应用较少。二者的技术特点与应用场景如表1所示。
表1 瞬时弹性成像与声辐射力冲击成像的技术特点与应用场景
特点 瞬时弹性成像 声辐射力冲击成像
激励类型 外部机械力 声辐射力
激励频率 50~400 Hz 2~7 MHz
激励时间 1 s 0.1~0.5 ms
组织形变 毫米级 微米级
应用范围 应用于肝脏 应用于肝脏、肾脏
测量结果 方差较大 方差较小

三、 ARFI应用于肾脏生物力学特性的技术挑战及解决方案

由于肾脏各部分结构具有异质性,肾脏剪切模量测量结果方差较大,因此,SWE技术的应用仍有改进的空间,其可靠性和准确性被诸多因素限制。我们前期对45例有明确病理诊断CKD患者肾脏皮质进行了ARFI评估,尝试建立超声弹性成像结果与IgA肾病病理纤维化程度之间的关联,在测量过程中采取了多种标准化方法,但未能获得阳性结果[14],Takata等[17]的研究也得到了类似的结果。Asano等[18]对319例CKD患者(肾小球肾炎129例、糖尿病肾病108例、肾硬化症83例)及14例健康对照进行了SWE测量,成像位置选在肾皮质下极,肾脏皮质的剪切模量与eGFR呈显著正相关(P<0.01),部分研究得到相同的结论[19-20]。而Leong等[11]对106例CKD患者和203例健康对照进行了SWE测量,成像选在肾脏的中区和下级,则得到了完全相反的结论,即肾脏皮质的剪切模量与eGFR呈显著负相关(P<0.01),同样有部分研究得到类似的结论[21-22]。上述这些研究显示,目前CKD进程中肾脏剪切模量的变化模式依然存在争议(表2)。
表2 超声剪切波弹性成像技术应用于CKD病情评估的研究进展
研究进展及文献 样本量(例) 年龄 症状 感兴趣区位置
剪切模量随肾脏损伤而下降
Bob等[20],2018 20 47.95±13.59 CGN 肾脏中部(包括皮髓质)
57 38.07±17.32 健康
Guo等[19],2013 64 64.72±14.33 CKD 肾脏中部三分之一处
327 43.44±20.24 健康
Asano等[18],2014 129 27.80±29.20 CGN 肾皮质下极(肾实质背侧)
107 65.30±8.80 DN
83 69.90±13.70 肾小球硬化
14 24~41 健康
剪切模量随肾脏损伤而上升
Cui等[22],2014 40 40.37±16.13 轻度纤维化 右肾囊肿皮质
21 中度纤维化
1 重度纤维化
14 无纤维化
Leong等[11],2018 57 65.05±11.12 CKD 2期 肾脏中区和上极
35 66.34±10.40 CKD 3期
10 65.00±12.63 CKD 4期
4 59.50±13.78 CKD 5期
203 50.94±12.71 健康
Yu等[21],2014 50 48.45±12.43 正常蛋白尿 肾皮质中区
34 50.32±16.22 微量蛋白尿
36 52.13±15.8 大量蛋白尿
30 49.24±13.11 健康
剪切模量与肾脏损伤无关联
Takata等[17],2016 39 72 ESRD 垂直于肾实质
31 59 无CKD
59 23 健康
Wang等[14],2014 26 33.0±9.3 CKD 1期 肾脏中部三分之一处
7 45.7±14.5 CKD 2期
6 32.7±8.5 CKD 3期
6 46.0±20.5 CKD 4期
注:CKD:慢性肾脏病;CGN:慢性肾小球肾炎;DN:糖尿病肾病;ESRD:终末期肾病
分析上述研究结果,结合SWE的技术特点,我们认为固然需要关注年龄[17]、感兴趣区(region of interest,ROI)的尺寸[23]等生理因素对SWE测量结果的影响,尝试通过标准化的操作流程来减少干扰,但是,更重要的是必须充分考虑到肾脏复杂的结构和力学性能所带来的混杂因素影响,包括肾脏的黏弹性、肾脏的各向异性和肾脏血流动力学等对SWE测量的影响。这些因素很可能是造成之前数年间多项研究结果不一致的原因,如果能够尝试通过适宜的数理模型对SWE测量数据进行解构,将有可能克服上述困难,取得更为稳定准确的测量结果。
针对肾脏的部分力学特性,可能的改进方案如下:
1. 肾脏组织的黏弹性: 物质的力学特性可以通过弹性和黏性来反映,前者的含义是受到力学刺激后物体瞬间恢复形状的能力,而后者则反映了受到力学刺激后物体抵抗变形的能力[24]。肾脏组织含水量大,在施加外部刺激后,其力学特性的改变过程兼具弹性和黏性的特点,因此肾脏组织的形变可通过复合剪切模量的概念进行近似描述。目前绝大多数的商业SWE系统都默认肾脏仅有弹性而忽略其黏性[25],这样的处理策略有利于诊断模型的简化和推广。但是实际上,使用单纯的线弹性模型来模拟黏弹性组织会导致剪切模量测量值高于实际值,如果肾脏发生复杂病变(如同时存在纤维化与囊肿),肾脏剪切模量的预测值将不够准确[17]。尽管目前还没有成熟的模型来描述CKD进展过程中肾脏黏性的具体变化规律,但是可以借鉴物理学上对复合材料的处理方式,通过如Voigt模型之类的流变模型来测量其复合剪切模量。该模型假设一种材料内的不同成分对于外部力学刺激呈现“同应变”的特点,整体效应相互并联,大量应用领域的研究显示此模型比较接近现实情况因而被广泛采用[26]。如果可以通过类似的模型对肾脏组织的黏性部分尝试进行描述和量化,将很有可能大幅度提升SWE测量结果的准确性。
2. 肾脏组织的各向异性: 各向异性是指物质的力学性能在各方向上存在差异。SWE技术目前在肝脏纤维化程度的测量中应用较多,但是肝脏组织相对均质,在物理学常被近似为不具有各向异性。与之不同的是,肾脏结构更为复杂,髓质含有较多的线性结构(例如集合管、髓袢、毛细血管网等),且各线性结构之间存在组织结构的不同,皮质中多为弯曲结构(如肾小球、鲍曼囊、近远端卷曲小管),整体上呈现出显著的各向异性。剪切波的传播会受到各向异性的显著影响,当传播沿着线性结构方向时,传播速度会更快。故而直接应用现有的商业化SWE测量平台对CKD患者的肾脏进行测量,可能会导致结果欠准确。有不同的研究均提示可以通过将ROI限制在皮质的特定区域以降低测量的误差,但是对操作者的熟练程度提出了较高的要求[27-28]。更为根本的应对策略则是利用非线性模型来评估肾组织的力学性能,以充分反映其各向异性的特点。这样的技术模型笔者已于模式动物的肌肉组织中进行尝试,得到了较好的效果[29]
3. 肾脏的血流动力学: 肾脏和肝脏的血流量都与剪切波的波速互为正相关,但肾脏的常态血压远高于肝脏,导致其剪切波速更高。当肾脏在纤维化进程中,随着肾脏血液微循环的破坏,血流量减少,会降低肾脏的剪切模量[18],一定程度上会抵消纤维化本身导致的肾脏剪切模量的上升。肾脏不同区域的血流量也不相同,由于只有15%的血液被提供给了髓质[30],肾脏髓质相对于皮质,剪切模量变化对血流量变化更不敏感。因此可以将测量的目标控制在近髓质的皮质区域,从而降低血流带来的误差影响,但是这样势必对操作者的技术有很高的要求。已有研究表明人工智能技术可以基于CT影像较为精准地分割肾脏皮髓质[31],在此基础上可开发辅助映射工具,引导SWE对肾脏组织的精准定位测量,从而获得稳定和准确的测量结果。

四、 其他影像评估与SWE技术的优劣比较

除SWE以外,功能核磁技术包括弥散加权核磁成像(diffusion-weighted imaging,DWI)和血氧水平依赖磁共振成像(blood oxygenation level dependent imaging,BOLD-MRI),以及光声成像等技术也被尝试应用于CKD的影像评估,上述技术与SWE之间的技术特点差异见表3
表3 肾脏疾病影像评估方法对比
特点 剪切波弹性成像 功能核磁技术 光声成像
测量指标 剪切模量 水分子/血氧水平 光吸收能力
物理特性描绘 良好 无法反映 无法反映
技术成本
测量效率
影像平台 超声为主 核磁共振 超声
适用对象 人体 人体 小动物
1. 功能核磁技术诊断肾脏病: 弥散加权核磁成像可以反映组织内水分子运动情况。我们前期将弥散加权核磁成像技术用于评价IgA肾病肾脏纤维化程度,证实表观弥散系数(apparent diffusion coefficient,ADC)和eGFR与患者进入终末期肾病的风险独立相关[32-33]。我们将定量核磁成像的纹理分析(texture analysis,TA)技术应用于肾脏评估,相对于健康对照,TA技术分析诊断肾功能不全的敏感度可达83.5%,特异度达79.2%[34]。BOLD-MRI则评估肾脏组织氧合程度,主要测量参数是横向弛豫时间常数(T2*)及横向松弛率(R2*)。目前已有研究团队分别在动物和人体实验中使用BOLD-MRI技术评估肾脏,证实R2*与尿酸、T2*与供氧状态之间的独立相关性[35-36]
2. 光声成像技术诊断肾脏病: 光声成像技术主要基于超声开展,可以测量组织内光吸收能力,间接测量组织局部氧饱和度或探测局部目标分子的浓度变化。因成像深度受到激光在组织中穿透能力的限制,目前在肾脏成像方面多应用于小型动物,可以反映脓毒症诱导急性肾损伤小鼠肾组织的氧合变化,展现出一定的应用潜力[37]

五、 小结与展望

综上所述,肾脏功能影像检测已经成为评价肾脏结构、预测肾脏预后的重要辅助工具,其中SWE具有便捷、直观等优势,有较好的应用前景。由于肾脏组织结构功能的复杂性,需要同时考虑到肾脏的黏弹性、各向异性和血流动力学的影响,故以SWE估计剪切波速度或组织剪切模量时,既可以通过精准的目标定位测量来降低各向异性、肾脏血流对结果的影响,又引入了可描述黏弹性特征的流变模型、可描述各向异性的非线性生物力学模型等交叉学科新技术,以期实现对肾脏结构的精准化解构,真正带来SWE技术在CKD领域应用的突破。

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[2]
GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2020, 395(10225): 709-733. DOI: 10.1016/S0140-6736(20)30045-3.
Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout.The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function.Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, -1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, -1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function.Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI.Bill & Melinda Gates Foundation.Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access Article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
[3]
Wang F, He K, Wang J, et al. Prevalence and risk factors for CKD: a comparison between the adult populations in China and the United States[J]. Kidney Int Rep, 2018, 3(5): 1135-1143. DOI: 10.1016/j.ekir.2018.05.011.
Chronic kidney disease (CKD) is an important noncommunicable disease globally. Overall prevalence of CKD and distribution of its stages differ between countries. We postulate that these differences may not only be due to variation in prevalence of risk factors but also their differential impact in different populations or settings.We used nationally representative data on the adult populations from both the United States (US; National Health and Nutrition Examination Survey [NHANES], 2009 to 2010, N = 5557) and China (China National Survey of CKD, 2009 to 2010, N = 46,949). Age, sex, central obesity, cardiovascular disease, diabetes, hypertension, and hyperuricemia were explored as candidate risk factors for CKD. The prevalence of CKD was calculated using survey weights.The prevalence of decreased estimated glomerular filtration rate (eGFR), defined as eGFR < 60 ml/min per 1.73 m, was 6.5% in the US versus 2.7% in China, whereas the prevalence of albuminuria (defined as urine albumin to creatinine ratio of ≥30 mg/g) was 8.1% in the US versus 9.5% in China. The distribution of eGFR categories differed between the countries ( < 0.001). Stronger associations of diabetes with both indicators were seen in the US participants, whereas stronger associations of male sex with both indicators and of hypertension with albuminuria were observed in the Chinese participants ( < 0.05). After multivariable adjustment, a 65% change in prevalence difference for decreased eGFR was seen between China and the US.People in China and the US share many common risk factors for CKD, but differences in prevalence and the potential impact of these risk factors for CKD were observed.
[4]
Leaf IA, Duffield JS. What can target kidney fibrosis?[J]. Nephrol Dial Transplant, 2017, 32(suppl_1): i89-i97. DOI: 10.1093/ndt/gfw388.
[5]
De Rosa M, Azzato F, Toblli JE, et al. A prospective observational cohort study highlights kidney biopsy findings of lupus nephritis patients in remission who flare following withdrawal of maintenance therapy[J]. Kidney Int, 2018, 94(4): 788-794. DOI: 10.1016/j.kint.2018.05.021.
One of the most difficult management issues in lupus nephritis (LN) is the optimal duration of maintenance immunosuppression after patients are in clinical remission. Most patients receive immunosuppression for years, based mainly on expert opinion. Prospective data are unavailable. Complicating this issue are data that patients in clinical remission can still have histologically active LN; however, the implications of this are unknown. To study this, the Lupus Flares and Histological Renal Activity at the end of Treatment study (ClinicalTrial.gov, NCT02313974) was designed to examine whether residual histologic activity predisposes to LN flares in class III and IV LN. Patients in complete clinical remission for at least 12 months who had received at least 36 months of immunosuppression were eligible. Patients consented to a second kidney biopsy, were tapered off maintenance immunosuppression and were then followed prospectively for LN flares over 24 months. Forty-four patients were enrolled, and 36 completed the study. LN flares occurred in 11 patients, and ten of these had residual histologic activity on the second biopsy. All patients with an NIH activity index over two flared. The activity index and duration of systemic lupus erythematosus at the second biopsy were independent predictors of flare. A predictive equation based on these variables discriminated between flare and no flare with a sensitivity of 100%, specificity of 88%, and a misclassification rate of 8.3%. Thus, a repeat kidney biopsy may be useful in managing maintenance immunosuppression in LN, and patients in histologic remission may be candidates for withdrawal of therapy.Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
[6]
Jiang K, Ferguson CM, Lerman LO. Noninvasive assessment of renal fibrosis by magnetic resonance imaging and ultrasound techniques[J]. Transl Res, 2019, 209: 105-120. DOI: 10.1016/j.trsl.2019.02.009.
Renal fibrosis is a useful biomarker for diagnosis and guidance of therapeutic interventions of chronic kidney disease (CKD), a worldwide disease that affects more than 10% of the population and is one of the major causes of death. Currently, tissue biopsy is the gold standard for assessment of renal fibrosis. However, it is invasive, and prone to sampling error and observer variability, and may also result in complications. Recent advances in diagnostic imaging techniques, including magnetic resonance imaging (MRI) and ultrasonography, have shown promise for noninvasive assessment of renal fibrosis. These imaging techniques measure renal fibrosis by evaluating its impacts on the functional, mechanical, and molecular properties of the kidney, such as water mobility by diffusion MRI, tissue hypoxia by blood oxygenation level dependent MRI, renal stiffness by MR and ultrasound elastography, and macromolecule content by magnetization transfer imaging. Other MR techniques, such as T/T mapping and susceptibility-weighted imaging have also been explored for measuring renal fibrosis. Promising findings have been reported in both preclinical and clinical studies using these techniques. Nevertheless, limited specificity, sensitivity, and practicality in these techniques may hinder their immediate application in clinical routine. In this review, we will introduce methodologies of these techniques, outline their applications in fibrosis imaging, and discuss their limitations and pitfalls.Copyright © 2019 Elsevier Inc. All rights reserved.
[7]
Caroli A, Remuzzi A, Lerman LO. Basic principles and new advances in kidney imaging[J]. Kidney Int, 2021, 100(5): 1001-1011. DOI: 10.1016/j.kint.2021.04.032.
Over the past few years, clinical renal imaging has seen great advances, allowing assessments of kidney structure and morphology, perfusion, function and metabolism, oxygenation, as well as microstructure and interstitium. Medical imaging is becoming increasingly important in the evaluation of kidney physiology and pathophysiology, showing promise in management of patients with renal disease, in particular with regard to diagnosis, classification, and prediction of disease development and progression, monitoring response to therapy, detection of drug toxicity, and patient selection for clinical trials. A variety of imaging modalities, ranging from routine to advanced tools, are currently available to probe the kidney both spatially and temporally, particularly ultrasonography, computed tomography, positron emission tomography, renal scintigraphy, and multiparametric magnetic resonance imaging. Since the range is broad and varied, kidney imaging techniques should be chosen based on the clinical question and specific underlying pathological mechanism, considering contraindications and possible adverse effects. Integration of different modalities providing complementary information will likely bestow the greatest insight into renal pathophysiology. This review aims to highlight major recent advances in key tools currently available or potentially relevant for clinical kidney imaging, with a focus on non-oncological applications. The review also outlines the context of use, limitations, and advantages of different techniques, and finally emphasizes gaps for future development and clinical adoption.Copyright © 2021. Published by Elsevier Inc.
[8]
Zheng J, Guo H, Zeng J, et al. Two-dimensional shear-wave elastography and conventional US: the optimal evaluation of liver fibrosis and cirrhosis[J]. Radiology, 2015, 275(1): 290-300. DOI: 10.1148/radiol.14140828.
To evaluate the individual and combined performances of two-dimensional (2D) shear-wave elastography (SWE) and conventional ultrasonography (US) in assessing liver fibrosis and cirrhosis to determine when 2D SWE should be added to routine US.This prospective study was approved by the institutional ethics committee, and the patients provided written informed consent. Between April 2012 and March 2013, conventional US and 2D SWE examinations were performed in 198 patients (mean age, 37.7 years; age range, 18-67 years) with chronic liver disease. Liver biopsy was used as a reference standard for 167 patients; the other 31 patients had decompensated liver cirrhosis. Receiver operating characteristic (ROC) curves were obtained to assess the diagnostic performance. Differences between the areas under the ROC curves (AUCs) were compared by using a Delong test.Two-dimensional SWE was significantly superior to US in diagnosis of significant fibrosis (score of F2 or greater) (AUC, 0.862 vs 0.725; P =.001) and early cirrhosis (score of F4) (AUC, 0.926 vs 0.789; P =.007). Combining 2D SWE with US did not increase the performance of depicting either significant fibrosis or liver cirrhosis (P =.713 and 0.410, respectively) relative to 2D SWE alone. There was no significant difference between 2D SWE and US in diagnosis of decompensated cirrhosis (AUC, 0.878 vs 0.925; P =.323). In addition, combining 2D SWE with US did not increase the performance relative to that of US alone (P =.372).Conventional US is sufficient to detect decompensated cirrhosis. Two-dimensional SWE is significantly superior to US in detecting liver fibrosis. Combining 2D SWE and US did not improve the diagnostic performance for either fibrosis or cirrhosis.
[9]
Li DD, Xu HX, Guo LH, et al. Combination of two-dimensional shear wave elastography with ultrasound breast imaging reporting and data system in the diagnosis of breast lesions: a new method to increase the diagnostic performance[J]. Eur Radiol, 2016, 26(9): 3290-3300. DOI: 10.1007/s00330-015-4163-8.
[10]
Leong SS, Wong J, Md Shah MN, et al. Comparison of shear wave elastography and conventional ultrasound in assessing kidney function as measured using (51)Cr-ethylenediaminetetraacetic acid and (99)Tc-dimercaptosuccinic acid[J]. Ultrasound Med Biol, 2019, 45(6): 1417-1426. DOI: 10.1016/j.ultrasmedbio.2019.01.024.
The purpose of this study was to assess the potential of shear wave elastography (SWE) as an indicator of abnormal kidney function defined by radiolabeled glomerular filtration rate (GFR). Fifty-seven patients referred for Cr-ethylenediaminetetraacetic acid GFR and Tc-dimercaptosuccinic acid renal scintigraphy were included. Young's modulus (YM) measured with SWE and kidney length, volume, cortical thickness and parenchymal echogenicity measured with conventional ultrasound were correlated with patients' GFR and renal scintigraphy results. Spearman correlation coefficients between SWE and GFR were negative for the right (r = -0.635, p < 0.0001) and left (r = -0.817, p < 0.0001) kidneys. Positive correlations between left renal cortical thickness (r = 0.381, p = 0.04) and left kidney volume (r = 0.356, p = 0.019) with GFR were reported. SWE correctly predicted the dominant functioning kidney in 94.7% of cases. The area under the receiver operating characteristic curve for SWE (0.800) was superior to that for conventional ultrasound (0.252-0.415). The cutoff value of ≥5.52 kPa suggested a kidney function ≤60 mL/min/1.73 m (82.4% sensitivity and 76.2% specificity). SWE has advantages over conventional ultrasound in assessing kidney function and distinguishing the dominant functioning kidney.Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
[11]
Leong SS, Wong J, Md Shah MN, et al. Shear wave elastography in the evaluation of renal parenchymal stiffness in patients with chronic kidney disease[J]. Br J Radiol, 2018, 91(1089): 20180235. DOI: 10.1259/bjr.20180235.
[12]
Bob F, Grosu I, Sporea I, et al. Ultrasound-based shear wave elastography in the assessment of patients with diabetic kidney disease[J]. Ultrasound Med Biol, 2017, 43(10): 2159-2166. DOI: 10.1016/j.ultrasmedbio.2017.04.019.
In previous studies of acoustic radiation force impulse (ARFI) elastography, using Virtual Touch tissue quantification (VTQ) (Siemens Acuson S2000), it was reported that the measurement of renal shear wave speed in patients with chronic kidney disease (CKD) is not influenced exclusively by renal fibrosis. The purpose of the present study was to analyze the role of VTQ in patients with diabetic kidney disease, considered the main cause of CKD. The study group included 164 patients: 80 patients with diabetic kidney disease (DKD) and 84 without renal disease or diabetes mellitus. In each subject in lateral decubitus, five valid VTQ measurements were performed in each kidney and a median value was calculated, the result being expressed in meters/second. The following means of the median values were obtained In DKD patients, the means of the median values were for VTQ right kidney, 2.21 ± 0.71 m/s, and for VTQ left kidney, 2.13 ± 0.72 m/s, whereas in the normal controls statistically significant higher values were obtained: 2.58 ± 0.78 m/s for VTQ right kidney (p = 0.0017) and 2.46 ± 0.81 m/s for VTQ left kidney (p = 0.006). Patients with an estimated glomerular filtration rate (eGFR) >60 mL/min (DKD stages 1 and 2 together with normal controls) had a significantly higher kidney shear wave speed compared with patients with an eGFR <60 mL/min (2.53 m/s vs. 2.09 m/s, p < 0.05). In the DKD group, there was a significant correlation between eGFR and VTQ levels for the right kidney (r = 0.28, p = 0.04). There was no correlation of VTQ values with proteinuria level, stage of diabetic retinopathy or glycated hemoglobin. Our study indicates that shear wave speed values in patients with diabetic kidney disease and eGFRs <60 mL/min are significantly lower compared with those of patients with eGFRs >60 mL/min (either normal controls or diabetic patients with DKD stages 1 and 2), and values decrease with the decrease in eGFR. However, proteinuria, diabetic retinopathy and glycated hemoglobin have no influence on VTQ.Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
[13]
Sommerer C, Scharf M, Seitz C, et al. Assessment of renal allograft fibrosis by transient elastography[J]. Transpl Int, 2013, 26(5): 545-551. DOI: 10.1111/tri.12073.
Transient elastography (TE, Fibroscan) has been established as a noninvasive assessment tool of liver fibrosis. We evaluated potentials and limitations of TE for identifying renal allograft fibrosis. The technical possibility of kidney examination by TE was assessed in two 10-week-old German landrace pigs and kidney stiffness (KS) was evaluated in 164 renal transplant patients. KS could be determined in all animals at the pole and pars media (29 ± 10 kPa vs. 31 ± 17 kPa). In human renal allografts KS was successfully performed in 94.5% of the test series with reliable results in 72% of the measurements. Mean KS at the pole or pars media were comparable (35.0 ± 19.9 kPa vs. 33.2 ± 18.6 kPa). Significantly higher KS was detected in renal allografts with histologically confirmed advanced fibrosis. Body-mass-index, skin-allograft distance, and peri or intrarenal fluid accumulation were important confounders of successful KS measurements (BMI: r = -0.31; P < 0.001; distance: r = -0.50; P < 0.001). Notably, KS did not correlate with renal function. TE represents a noninvasive approach in selected transplant recipients to identify allografts with severe fibrosis. The heterogeneous kidney morphology and several other confounding factors negatively affect measurability of KS by TE. Further technical modifications are required to improve applicability of TE for kidney assessment.© 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.
[14]
Wang L, Xia P, Lv K, et al. Assessment of renal tissue elasticity by acoustic radiation force impulse quantification with histopathological correlation: preliminary experience in chronic kidney disease[J]. Eur Radiol, 2014, 24(7): 1694-1699. DOI: 10.1007/s00330-014-3162-5.
Chronic kidney disease (CKD), a progressive and irreversible pathological syndrome, is the major cause of renal failure. Renal fibrosis is the principal process underlying the progression of CKD. Acoustic radiation force impulse (ARFI) quantification is a promising noninvasive method for assessing tissue stiffness. We evaluated whether the technique could reveal renal tissue fibrosis in CKD patients.ARFI assessments were performed in 45 patients with CKD referred for renal biopsies to measure cortical shear wave velocity (SWV). During measurement, a standardized method was employed, which aimed to minimize the potential impact of variation of transducer force, sampling error of non-cortical tissue and structural anisotropy of the kidney. Then SWV was compared to patients' CKD stage and pathological fibrosis indicators.ARFI could not predict the different stages of CKD. Spearman correlation analysis showed that SWV did not correlate with any pathological indicators of fibrosis.ARFI assesses tissue stiffness of CKD kidneys by measuring cortical SWV. However, SWV did not show significant correlations with CKD stage and fibrosis indicators despite using standardized measurement methods. We therefore suggest that it would be necessary to evaluate the effect of pathological complexity and tissue perfusion of the kidney on stiffness assessment in future studies.• Acoustic radiation force impulse (ARFI) can quantify tissue elasticity of CKD kidney. • Despite standardized measurement, ARFI-estimated elasticity did not correlate with renal fibrosis. • Effects of pathological complexity and tissue perfusion on renal stiffness warrant further study.
[15]
Korsmo MJ, Ebrahimi B, Eirin A, et al. Magnetic resonance elastography noninvasively detects in vivo renal medullary fibrosis secondary to swine renal artery stenosis[J]. Invest Radiol, 2013, 48(2): 61-68. DOI: 10.1097/RLI.0b013e31827a4990.
[16]
Maksuti E, Bini F, Fiorentini S, et al. Influence of wall thickness and diameter on arterial shear wave elastography: a phantom and finite element study[J]. Phys Med Biol, 2017, 62(7): 2694-2718. DOI: 10.1088/1361-6560/aa591d.
Quantitative, non-invasive and local measurements of arterial mechanical properties could be highly beneficial for early diagnosis of cardiovascular disease and follow up of treatment. Arterial shear wave elastography (SWE) and wave velocity dispersion analysis have previously been applied to measure arterial stiffness. Arterial wall thickness (h) and inner diameter (D) vary with age and pathology and may influence the shear wave propagation. Nevertheless, the effect of arterial geometry in SWE has not yet been systematically investigated. In this study the influence of geometry on the estimated mechanical properties of plates (h  =  0.5-3 mm) and hollow cylinders (h  =  1, 2 and 3 mm, D  =  6 mm) was assessed by experiments in phantoms and by finite element method simulations. In addition, simulations in hollow cylinders with wall thickness difficult to achieve in phantoms were performed (h  =  0.5-1.3 mm, D  =  5-8 mm). The phase velocity curves obtained from experiments and simulations were compared in the frequency range 200-1000 Hz and showed good agreement (R   =  0.80  ±  0.07 for plates and R   =  0.82  ±  0.04 for hollow cylinders). Wall thickness had a larger effect than diameter on the dispersion curves, which did not have major effects above 400 Hz. An underestimation of 0.1-0.2 mm in wall thickness introduces an error 4-9 kPa in hollow cylinders with shear modulus of 21-26 kPa. Therefore, wall thickness should correctly be measured in arterial SWE applications for accurate mechanical properties estimation.
[17]
Takata T, Koda M, Sugihara T, et al. Renal shear wave velocity by acoustic radiation force impulse did not reflect advanced renal impairment[J]. Nephrology (Carlton), 2016, 21(12): 1056-1062. DOI: 10.1111/nep.12701.
Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end‐stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors.
[18]
Asano K, Ogata A, Tanaka K, et al. Acoustic radiation force impulse elastography of the kidneys: is shear wave velocity affected by tissue fibrosis or renal blood flow?[J]. J Ultrasound Med, 2014, 33(5): 793-801. DOI: 10.7863/ultra.33.5.793.
The aim of this study was to identify the main influencing factor of the shear wave velocity (SWV) of the kidneys measured by acoustic radiation force impulse elastography.The SWV was measured in the kidneys of 14 healthy volunteers and 319 patients with chronic kidney disease. The estimated glomerular filtration rate was calculated by the serum creatinine concentration and age. As an indicator of arteriosclerosis of large vessels, the brachial-ankle pulse wave velocity was measured in 183 patients.Compared to the degree of interobserver and intraobserver deviation, a large variance of SWV values was observed in the kidneys of the patients with chronic kidney disease. Shear wave velocity values in the right and left kidneys of each patient correlated well, with high correlation coefficients (r = 0.580-0.732). The SWV decreased concurrently with a decline in the estimated glomerular filtration rate. A low SWV was obtained in patients with a high brachial-ankle pulse wave velocity. Despite progression of renal fibrosis in the advanced stages of chronic kidney disease, these results were in contrast to findings for chronic liver disease, in which progression of hepatic fibrosis results in an increase in the SWV. Considering that a high brachial-ankle pulse wave velocity represents the progression of arteriosclerosis in the large vessels, the reduction of elasticity succeeding diminution of blood flow was suspected to be the main influencing factor of the SWV in the kidneys.This study indicates that diminution of blood flow may affect SWV values in the kidneys more than the progression of tissue fibrosis. Future studies for reducing data variance are needed for effective use of acoustic radiation force impulse elastography in patients with chronic kidney disease.
[19]
Guo LH, Xu HX, Fu HJ, et al. Acoustic radiation force impulse imaging for noninvasive evaluation of renal parenchyma elasticity: preliminary findings[J]. PLoS One, 2013, 8(7): e68925. DOI: 10.1371/journal.pone.0068925.
[20]
Bob F, Grosu I, Sporea I, et al. Is there a correlation between kidney shear wave velocity measured with VTQ and histological parameters in patients with chronic glomerulonephritis? A pilot study[J]. Med Ultrason, 2018, 1(1): 27-31. DOI: 10.11152/mu-1117.
To analyze the relationship between shear wave velocity in the kidney measured by point shear wave elastography using Virtual Touch Quantification (VTQ) (Siemens Acuson S2000) and histological parameters obtained from renal biopsies, in patients with chronic glomerulonephritis (CGN).The study group included 20 patients (mean age 47.95±13.59 years) with different types of CGN, that had underwent renal biopsy and 57 normal controls (mean age 38.07±17.32 years). In all patients, five valid stiffness measurements were obtained in each kidney, with the patient in lateral decubitus. Regarding the histological results, we assessed the presence or absence of glomerulosclerosis, interstitial fibrosis, and arteriolo-hyalinosis.In patients with CGN we obtained the following mean values of VTQ values: right kidney: 2.12±0.81 m/s, left kidney 1.65±0.54 m/s, while in the normal controls significantly higher VTQ values were obtained: right kidney 2.69±0.72 m/s (p=0.004), left kidney 2.48±0.73 m/s (p<0.0001). In patients with CGN no statistically significant correlations between VTQ values and eGFR (r=0.37, p=0.12) or proteinuria (r=0.2, p=0.37) were found. We found significantly lower VTQ values in patients with interstitial fibrosis (1.46 vs. 1.99 m/s, p<0.05) and also in patients with arteriolo-hyalinosis (1.55 vs. 2.47 m/s, p<0.05).Our pilot study shows that shear wave velocity values in patients with CGN are significantly lower compared to normal controls, and there is a tendency to decrease with the decrease of eGFR, with the presence of interstitial fibrosis and of arteriolo-hyalinosis.
[21]
Yu N, Zhang Y, Xu Y. Value of virtual touch tissue quantification in stages of diabetic kidney disease[J]. J Ultrasound Med, 2014, 33(5): 787-792. DOI: 10.7863/ultra.33.5.787.
The purpose of this study was to evaluate Virtual Touch tissue quantification (VTQ; Siemens AG, Erlangen, Germany) in stages of diabetic kidney disease.A total of 120 patients with type 2 diabetes mellitus were divided into 3 groups according to their urinary albumin-to-creatinine ratio (ACR): normoalbuminuria (ACR <30 mg/g of creatinine), microalbuminuria (ACR 30-300 mg/g), and macroalbuminuria (ACR ≥ 300 mg/g and estimated glomerular filtration rate ≥30 mL/min/1.73 m(2)). Thirty volunteers served as controls. Virtual Touch tissue quantification was performed in the 4 groups to determine the shear wave velocity (SWV) of the renal cortex, and changes in the SWV were compared between the groups. Correlation analysis was performed between the SWV and ACR in the type 2 diabetes groups.When SWVs were compared, there was no significant difference between the normoalbuminuria and control group (P =.40), but there was a significant difference between the microalbuminuria and macroalbuminuria groups and the control group (P <.05). There was also a significant difference between each pair of type 2 diabetes groups (P <.05). The correlation coefficient for the SWV and log(ACR) in type 2 diabetes was 0.773 (P <.05). Receiver operating characteristic curve analysis showed that the area under the curve for SWV diagnosis of diabetes complicated by renal injury was 0.93; the best cutoff point, sensitivity, and specificity were 2.43 m/s, 85.7%, and 84.5%, respectively.It is feasible to use VTQ to determine the renal cortical SWV for judging renal injury in type 2 diabetes mellitus. The SWV increases as the renal injury progresses and thus plays an important role in diabetic kidney disease stages.
[22]
Cui G, Yang Z, Zhang W, et al. Evaluation of acoustic radiation force impulse imaging for the clinicopathological typing of renal fibrosis[J]. Exp Ther Med, 2014, 7(1): 233-235. DOI: 10.3892/etm.2013.1377.
This study aimed to explore the assessment value of virtual touch quantization (VTQ) for the clinicopathological typing of renal fibrosis. The quantitative detection of 76 patients with nephropathy was performed using acoustic radiation force impulse imaging (ARFI). The extent of the renal fibrosis in each patient was confirmed using ultrasound-guided biopsy pathology. The VTQ values were compared with the degree of renal fibrosis in order to analyze the correlation between them. Patients were divided pathologically into four groups, as follows: non-fibrosis (n=14), mild fibrosis (n=40), moderate fibrosis (n=21) and severe fibrosis (n=1). Compared with the non-fibrosis group, the VTQ values of the mild and moderate fibrosis groups were significantly increased (P<0.01); however, there was no significant difference between the VTQ values of the mild and moderate fibrosis groups (P>0.05). According to the receiver operating characteristic (ROC) curve, a VTQ value of renal parenchyma of >1.67 m/sec was determined to be an indicator of renal fibrosis, with a sensitivity of 86.3% and a specificity of 83.3%. VTQ technology may be significant in the assessment of the extent of renal fibrosis.
[23]
Skerl K, Vinnicombe S, Giannotti E, et al. Influence of region of interest size and ultrasound lesion size on the performance of 2D shear wave elastography (SWE) in solid breast masses[J]. Clin Radiol, 2015, 70(12): 1421-1427. DOI: 10.1016/j.crad.2015.08.010.
To evaluate the influence of the region of interest (ROI) size and lesion diameter on the diagnostic performance of 2D shear wave elastography (SWE) of solid breast lesions.A study group of 206 consecutive patients (age range 21-92 years) with 210 solid breast lesions (70 benign, 140 malignant) who underwent core biopsy or surgical excision was evaluated. Lesions were divided into small (diameter <15 mm, n=112) and large lesions (diameter ≥15 mm, n=98). An ROI with a diameter of 1, 2, and 3 mm was positioned over the stiffest part of the lesion. The maximum elasticity (Emax), mean elasticity (Emean) and standard deviation (SD) for each ROI size were compared to the pathological outcome. Statistical analysis was undertaken using the chi-square test and receiver operating characteristic (ROC) analysis.The ROI size used has a significant impact on the performance of Emean and SD but not on Emax. Youden's indices show a correlation with the ROI size and lesion size: generally, the benign/malignant threshold is lower with increasing ROI size but higher with increasing lesion size.No single SWE parameter has superior performance. Lesion size and ROI size influence diagnostic performance.Copyright © 2015. Published by Elsevier Ltd.
[24]
Meyers M, Chawla K. Mechanical Behavior of Materials[M]. 2nd ed. New York: Cambridge University Press, 2008.
[25]
Sugimoto K, Moriyasu F, Oshiro H, et al. Viscoelasticity measurement in rat livers using shear-wave US elastography[J]. Ultrasound Med Biol, 2018, 44(9): 2018-2024. DOI: 10.1016/j.ultrasmedbio.2018.05.008.
To investigate the usefulness of shear-wave speed and dispersion slope measurements obtained, using an ultrasound elastography system in rat livers with various degrees of necroinflammation and fibrosis. A total of 25 male Sprague Dawley rats were randomly divided into 5 groups of 5 rats each: G0 (control), G1 (CCl injected twice a week for 1 wk), G2 (CCl injected four times a wk for 1 wk), G3 (CCl injected twice a wk for 6 wk) and G4 (CCl injected twice a wk for 10 wk). The shear-wave speed (m/s) and the dispersion slope ([m/s]/kHz) were measured. Histologic features (inflammation, necrosis and fibrosis) were used as reference standards. In multivariable analysis with histologic features as independent variables, the fibrosis grade was significantly related to shear-wave speed (p < 0.05) and the necrosis grade was significantly related to dispersion slope (p < 0.05). Dispersion slope is more useful than shear-wave speed for predicting the degree of necroinflammation.Copyright © 2018 Elsevier Ltd. All rights reserved.
[26]
Zhou B, Zhang X. Comparison of five viscoelastic models for estimating viscoelastic parameters using ultrasound shear wave elastography[J]. J Mech Behav Biomed Mater, 2018, 85: 109-116. DOI: 10.1016/j.jmbbm.2018.05.041.
The purpose of this study is to compare five viscoelastic models (Voigt, Maxwell, standard linear solid, spring-pot, and fractional Voigt models) for estimating viscoelastic properties based on ultrasound shear wave elastography measurements. We performed the forward problem analysis, the inverse problem analysis, and experiments. In the forward problem analysis, the shear wave speeds at different frequencies were calculated using the Voigt model for given shear elasticity and varying shear viscosity. In the inverse problem analysis, the viscoelastic parameters were estimated from the given wave speeds for the five viscoelastic models using the least-square regression. The experiment was performed in a tissue-mimicking phantom. A local harmonic vibration was generated via a mechanical shaker on the phantom at five frequencies (100, 150, 200, 250, and 300 Hz) and an ultrasound transducer was used to capture the tissue motion. Shear wave speed of the phantom was measured using the ultrasound shear wave elastography technique. The parameters for different viscoelastic models for the phantom were identified. For both analytical and experimental studies, ratios of storage to loss modulus as a function of excitation frequency for different viscoelastic models were calculated. We found that the Voigt and fractional Voigt models fit well with the shear wave speed - frequency and ratio of storage to loss modulus - frequency relationships both in analytical and experimental studies.Copyright © 2018 Elsevier Ltd. All rights reserved.
[27]
Borrelli P, Cavaliere C, Basso L, et al. Diffusion tensor imaging of the kidney: design and evaluation of a reliable processing pipeline[J]. Sci Rep, 2019, 9(1): 12789. DOI: 10.1038/s41598-019-49170-5.
Diffusion tensor imaging (DTI) is particularly suitable for kidney studies due to tubules, collector ducts and blood vessels in the medulla that produce spatially restricted diffusion of water molecules, thus reflecting the high grade of anisotropy detectable by DTI. Kidney DTI is still a challenging technique where the off-resonance susceptibility artefacts and subject motion can severely affect the reproducibility of results. The aim of this study is to design a reliable processing pipeline by assessing different image processing approaches in terms of reproducibility and image artefacts correction. The results of four different processing pipelines (eddy: correction of eddy-currents and motion between DTI volume; eddy-s2v: eddy and within DTI volume motion correction; topup: eddy and geometric distortion correction; topup-s2v: topup and within DTI volume motion correction) are compared in terms of reproducibility by test-retest analysis in 14 healthy subjects. Within-subject coefficient of variation (wsCV) and intra-class correlation coefficient (ICC) are measured to assess the reproducibility and Dice similarity index is evaluated for the spatial alignment between DTI and anatomical images. Topup-s2v pipeline provides highest reproducibility (wsCV = 0.053, ICC = 0.814) and best correction of image distortion (Dice = 0.83). This study definitely provides a recipe for data processing, enabling for a clinical suitability of kidney DTI.
[28]
Leong SS, Wong J, Md Shah MN, et al. Stiffness and anisotropy effect on shear wave elastography: a phantom and in vivo renal study[J]. Ultrasound Med Biol, 2020, 46(1): 34-45. DOI: 10.1016/j.ultrasmedbio.2019.08.011.
Tissue elasticity is related to the pathologic state of kidneys and can be measured using shear wave elastography (SWE). However, SWE quantification has not been rigorously validated. The aim of this study was to evaluate the accuracy of SWE-measured stiffness and the effect of tissue anisotropy on SWE measurements. Point SWE (pSWE), 2-D SWE and dynamic mechanical analysis (DMA) were used to measure stiffness and evaluate the effect of tissue anisotropy on the measurements. SWE and DMA were performed on phantoms of different gelatin concentrations. In the tissue anisotropy study, SWE and DMA were performed on the outer cortex of sheep kidneys. In the in vivo study, 15 patients with different levels of interstitial fibrosis were recruited for pSWE measurements. Another 10 healthy volunteers were recruited for tissue anisotropy studies. SWE imaging revealed a non-linear increase with gelatin concentration. There was a significant correlation between pSWE and 2-D SWE, leading to the establishment of a linear regression equation between the two SWE ultrasound measurements. In the anisotropy study, the median difference in stiffness between shear waves oriented at 0° and 90° towards the pyramid axis was significant. In the in vivo study, there was a strong positive linear correlation between pSWE and the percentage of interstitial fibrosis. There was a significant difference in the Young's modulus (YM) between severities of fibrosis. The mean YM values were lower in control patients than in patients with mild, moderate and severe fibrosis. YM values were also significantly higher when shear waves were oriented at 0° toward the pyramid axis. Tissue stiffness and anisotropy affects SWE measurements. These factors should be recognized before applying SWE for the interpretation of measured values.Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
[29]
Hou Z, Guertler CA, Okamoto RJ, et al. Estimation of the mechanical properties of a transversely isotropic material from shear wave fields via artificial neural networks[J]. J Mech Behav Biomed Mater, 2022, 126: 105046. DOI: 10.1016/j.jmbbm.2021.105046.
[30]
Lubas A, Kade G, Saracyn M, et al. Dynamic tissue perfusion assessment reflects associations between antihypertensive treatment and renal cortical perfusion in patients with chronic kidney disease and hypertension[J]. Int Urol Nephrol, 2018, 50(3): 509-516. DOI: 10.1007/s11255-018-1798-9.
Renal cortical perfusion measured in noninvasive, dynamic ultrasonic method is connected with the hemodynamic cardiac properties and renal function. Antihypertensive drugs affect the functioning of the heart and kidneys. The aim of the study was to evaluate the effect of a chronic use of antihypertensive drugs on ultrasound parameters of renal cortical perfusion.The study included 56 consecutive patients (49 M + 7 F, age 54.0 ± 13.3) with stable chronic kidney disease and hypertension. Color Doppler dynamic tissue perfusion measurement was used to assess renal cortical perfusion.Patients were treated with a mean of 2.7 ± 1.4 antihypertensive drugs, of which diuretics accounted for 25%, angiotensin-converting enzyme inhibitors (ACE-I) together with angiotensin receptor blockers (ARB) 24%, beta-blockers (BB) 23%, calcium channel blockers 16%, alpha-1 blockers (α1B) 9% and centrally acting drugs 3%. All investigated groups of drugs correlated significantly with parameters of renal perfusion. In multivariable regression analyses adjusted to age, diuretics were connected with the decrease (r = - 0.473) and ACE-I + ARB (r = 0.390) with the improvement of proximal and whole renal cortex perfusion (R = 0.28; p < 0.001), whereas BB (r = - 0.372) and α1B (r = - 0.280) independently correlated with worsened perfusion of renal distal cortex (R = 0.21, p < 0.01).The type of antihypertensive therapy had a significant influence on the ultrasound parameters of renal cortical perfusion. Noninvasive, ultrasonic dynamic tissue perfusion measurement method appears to be an adequate tool to assess the impact of drugs on renal cortical perfusion.
[31]
Korfiatis P, Denic A, Edwards ME, et al. Automated segmentation of kidney cortex and medulla in CT images: a multisite evaluation study[J]. J Am Soc Nephrol, 2022, 33(2): 420-430. DOI: 10.1681/ASN.2021030404.
Volumetric measurements are needed to characterize kidney structural findings on CT images to evaluate and test their potential utility in clinical decision making. Deep learning can enable this task in a scalable and reliable manner. Although automated kidney segmentation has been previously explored, methods for distinguishing cortex from medulla have never been done before. In addition, automated methods are typically evaluated at a single institution, without testing generalizability and robustness across different institutions. The tool developed in this study performs at the level of human readers and could enable large diverse population studies to evaluate how kidney, cortex, and medulla volumes can be used in various clinical settings, and establish normative values at large scale.
[32]
Liu Y, Zhang GM, Peng X, et al. Diffusion kurtosis imaging as an imaging biomarker for predicting prognosis in chronic kidney disease patients[J]. Nephrol Dial Transplant, 2022, 37(8): 1451-1460. DOI: 10.1093/ndt/gfab229.
Renal fibrosis is the strongest prognostic predictor of end-stage renal disease (ESRD) in chronic kidney disease (CKD). Diffusion kurtosis imaging (DKI) is a promising method of magnetic resonance imaging successfully used to assess renal fibrosis in immunoglobulin A nephropathy. This study aimed to be the first to evaluate the long-term prognostic value of DKI in CKD patients.
[33]
Zhang G, Sun H, Qian T, et al. Diffusion-weighted imaging of the kidney: comparison between simultaneous multi-slice and integrated slice-by-slice shimming echo planar sequence[J]. Clin Radiol, 2019, 74(4): 325. e1-325.e8. DOI: 10.1016/j.crad.2018.12.005.
[34]
Zhang G, Liu Y, Sun H, et al. Texture analysis based on quantitative magnetic resonance imaging to assess kidney function: a preliminary study[J]. Quant Imaging Med Surg, 2021, 11(4): 1256-1270. DOI: 10.21037/qims-20-842.
[35]
Cheng ZY, Lin QT, Chen PK, et al. Combined application of DTI and BOLD-MRI in the assessment of renal injury with hyperuricemia[J]. Abdom Radiol (NY), 2021, 46(4): 1694-1702. DOI: 10.1007/s00261-020-02804-z.
[36]
Zhao K, Pohlmann A, Feng Q, et al. Physiological system analysis of the kidney by high-temporal-resolution T2∗ monitoring of an oxygenation step response[J]. Magn Reson Med, 2021, 85(1): 334-345. DOI: 10.1002/mrm.28399.
Examine the feasibility of characterizing the regulation of renal oxygenation using high‐temporal‐resolution monitoring of the response to a step‐like oxygenation stimulus.
[37]
Sun N, Zheng S, Rosin DL, et al. Development of a photoacoustic microscopy technique to assess peritubular capillary function and oxygen metabolism in the mouse kidney[J]. Kidney Int, 2021, 100(3): 613-620. DOI: 10.1016/j.kint.2021.06.018.
Microcirculatory changes and oxidative stress have long been associated with acute kidney injury. Despite substantial progress made by two-photon microscopy of microvascular responses to acute kidney injury in rodent models, little is known about the underlying changes in blood oxygen delivery and tissue oxygen metabolism. To fill this gap, we developed a label-free kidney imaging technique based on photoacoustic microscopy, which enables simultaneous quantification of hemoglobin concentration, oxygen saturation of hemoglobin, and blood flow in peritubular capillaries in vivo. Based on these microvascular parameters, microregional oxygen metabolism was quantified. We demonstrated the utility of this technique by studying kidney hemodynamic and oxygen-metabolic responses to acute kidney injury in mice subject to lipopolysaccharide-induced sepsis. Dynamic photoacoustic microscopy of the peritubular capillary function and tissue oxygen metabolism revealed that sepsis induced an acute and significant reduction in peritubular capillary oxygen saturation of hemoglobin, concomitant with a marked reduction in kidney ATP levels and contrasted with nominal changes in peritubular capillary flow and plasma creatinine. Thus, our technique opens new opportunities to study microvascular and metabolic dysfunction in acute and chronic kidney diseases.Copyright © 2021. Published by Elsevier Inc.
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