Contrast agents for functional and cellular MRI of the kidney

Low-molecular-weight gadolinium (Gd) chelates are glomerular tracers but their role in evaluation of renal function with magnetic resonance (MR) imaging is still marginal. Because of their small size, they diffuse freely into the interstitium and the relationship between measured signal intensity and concentration is complex. New categories of contrast agents, such as large Gd-chelates or iron oxide particules, with different pharmacokinetic and magnetic properties have been developed. These large molecules could be useful for both functional (quantification of perfusion, quantification of glomerular filtration rate, estimation of tubular function) and cellular imaging (intrarenal phagocytosis in inflammatory renal diseases).Continuous development of new contrast agents remains worthwhile to get the best adequacy between the physiological phenomenon of interest and the pharmacokinetic of the agent.     

Functional assessment of transplanted kidneys with magnetic resonance imaging

Kidney transplantation has emerged as the treatment of choice for many patients with end-stage renal disease, which is a significant cause of morbidity and mortality. Given the shortage of clinically available donor kidneys and the significant incidence of allograft dysfunction, a noninvasive and accurate assessment of the allograft renal function is critical for postoperative management. Prompt diagnosis of graft dysfunction facilitates clinical intervention of kidneys with salvageable function. New advances in magnetic resonance imaging (MRI) technology have enabled the calculation of various renal parameters that were previously not feasible to measure noninvasively. Diffusion-weighted imaging provides information on renal diffusion and perfusion simultaneously, with quantification by the apparent diffusion coefficient, the decrease of which reflects renal function impairment. Diffusion-tensor imaging accounts for the directionality of molecular motion and measures fractional anisotropy of the kidneys. Blood oxygen level-dependent MR evaluates intrarenal oxygen bioavailability, generating the parameter of R2* (reflecting the concentration of deoxyhemoglobin). A decrease in R2* could happen during acute rejection. MR nephro-urography/renography demonstrates structural data depicting urinary tract obstructions and functional data regarding the glomerular filtration and blood flow. MR angiography details the transplant vasculature and is particularly suitable for detecting vascular complications, with good correlation with digital subtraction angiography. Other functional MRI technologies, such as arterial spin labeling and MR spectroscopy, are showing additional promise. This review highlights MRI as a comprehensive modality to diagnose a variety of etiologies of graft dysfunction, including prerenal (e.g., renal vasculature), renal (intrinsic causes) and postrenal (e.g., obstruction of the collecting system) etiologies.     

^99mTc—EC与^99mTc—DTPA肾动态显像的对比研究

应用９９ｍＴｃ－ＥＣ肾小管分泌型显像剂和９９ｍＴｃ－ＤＴＰＡ肾小球滤过型显像剂，分别对８０例肾功能正常者以及２１０例患有泌尿系疾患患者进行了肾动态显像的对比研究。其中对照组９９ｍＴｃ－ＤＴＰＡ肾动态显像的１０ｍｉｎ和２０ｍｉｎ滞留率明显高于９９ｍＴｃ－ＥＣ，而两者的峰时无差别。本文还总结了以肾小球和肾小管功能受损为主的肾脏疾患，应用两类显像剂肾动态显像的峰时、滞留率及ＧＦＲ与对照组相比较的结果，认为在肾功能严重受损时，应首选９９ｍＴｃ－ＥＣ，但在肾脏疾病诊断不明确时，应同时应用这两种显像剂进行检查，以明确肾小球功能或肾小管功能的受损程度。     

Partial volume effects in dynamic contrast magnetic resonance renal studies

This is the first study of partial volume effect in quantifying renal function on dynamic contrast enhanced magnetic resonance imaging. Dynamic image data were acquired for a cohort of 10 healthy volunteers. Following respiratory motion correction, each voxel location was assigned a mixing vector representing the ‘overspilling’ contributions of each tissue due to the convolution action of the imaging system's point spread function. This was used to recover the true intensities associated with each constituent tissue. Thus, non-renal contributions from liver, spleen and other surrounding tissues could be eliminated from the observed time-intensity curves derived from a typical renal cortical region of interest. This analysis produced a change in the early slope of the renal curve, which subsequently resulted in an enhanced glomerular filtration rate estimate. This effect was consistently observed in a Rutland-Patlak analysis of the time-intensity data: the volunteer cohort produced a partial volume effect corrected mean enhancement of 36% in relative glomerular filtration rate with a mean improvement of 7% in r² fitting of the Rutland-Patlak model compared to the same analysis undertaken without partial volume effect correction. This analysis strongly supports the notion that dynamic contrast enhanced magnetic resonance imaging of kidneys is substantially affected by the partial volume effect, and that this is a significant obfuscating factor in subsequent glomerular filtration rate estimation.     

Pharmacokinetics of Gd-DTPA in patients with chronic renal failure.

We investigated the pharmacokinetics of dimeglumine gadopentetate (Gd-DTPA), a contrast agent for magnetic resonance imaging (MRI), in 24 patients with chronic renal failure whose creatinine clearance ranged from 7.2 to 70.0 mL/minute (median 25.4 mL/minute). After single intravenous administration of 0.1 mmol/kg, the serum levels of Gd-DTPA were monitored up to five days and urine and feces were collected quantitatively up to two days. The pharmacokinetic parameters were calculated from the concentration-time profile in the serum and urine using an open two-compartment model. No changes in the volume of distribution (Vc and Varea) or in the half-life of distribution were found for patients with chronic renal failure as compared to patients with normal renal function. However, in correlation with the reduced glomerular filtration rate in patients with chronic renal failure, the half-life of elimination was prolonged and serum and renal clearance were decreased. The recovery of Gd-DTPA in urine was 92.1% +/- 12.1% of the dose administered, and extrarenal elimination was less than 0.4%, indicating that glomerular filtration remains the predominant route of elimination. Only for patients with highly impaired renal function (creatinine clearance less than 20 mL/minute) was the recovery in the urine less than complete.     

Hepatobiliary MR imaging with gadolinium-based contrast agents

The advent of gadolinium-based "hepatobiliary" contrast agents offers new opportunities for diagnostic magnetic resonance imaging (MRI) and has triggered great interest for innovative imaging approaches to the liver and bile ducts. In this review article we discuss the imaging properties of the two gadolinium-based hepatobiliary contrast agents currently available in the U.S., gadobenate dimeglumine and gadoxetic acid, as well as important pharmacokinetic differences that affect their diagnostic performance. We review potential applications, protocol optimization strategies, as well as diagnostic pitfalls. A variety of illustrative case examples will be used to demonstrate the role of these agents in detection and characterization of liver lesions as well as for imaging the biliary system. Changes in MR protocols geared toward optimizing workflow and imaging quality are also discussed. It is our aim that the information provided in this article will facilitate the optimal utilization of these agents and will stimulate the reader's pursuit of new applications for future benefit.     

Nephrogenic systemic fibrosis: A survey of the use of gadolinium-based contrast agents in Ghana

IntroductionThe aim of this study is to identify current practice of administration of gadolinium-based contrast agents (GBCAs) in Ghana.MethodA total of 13 MRI (magnetic resonance imaging) facilities were sent a survey questionnaire to request information on their current practice with the use of GBCAs.ResultsGadodiamide, a high risk GBCA accounted for 67% of first line agents. 5 (42%) had a departmental protocol on the administration of GBCAs with regards to its association with nephrogenic systemic fibrosis (NSF). Of the 8 that use gadodiamide, 3 check kidney function in all patients, 2 check in selected patients, and 3 do not check at all. All 3 that screen all patients do not use contrast if the patient has an eGFR (estimated glomerular filtration rate) of 30–59 ml/min, 1 considers other modality; and if the patient has an eGFR of <30 ml/min, 2 do not use contrast but consider other modality, however 1 continues with the high risk agent.ConclusionGadodiamide is widely used, with varied practice in screening for renal function, and risk factors associated with NSF. Current evidence shows that it is advisable to administer macrocyclic agents in patients with compromised renal function. It is also imperative to establish local guidelines in line with international guidelines in order to minimize the incidence of NSF.     

Quantitative Erfassung der renalen Funktion mit der Magnetresonanztomographie

Aim. To show the potential of various methods in magnetic resonance imaging for the evaluation of renal function. Material and Methods. A combined assessment of renal morphology, renal hemodynamics and function is proposed. Various techniques are explained, including multiphasic 3D gadolinium MR angiography, MR phase-contrast flow measurements, quantitative perfusion measurements with intravascular contrast agents, and MR renography and MR urography. The use of these techniques is demonstrated for renovascular diseases. Results. The combined use of these techniques allows renal artery stenosis to be accurately detected and evaluation of renal blood flow, perfusion, glomerular filtration rate, and renal excretion. Based on true quantitative parameters, the hemodynamic and functional significance of the stenosis can be assessed. Renovascular diseases can be differentiated from renoparenchymal disease. Conclusion. For the assessment of renal function, functional magnetic resonance imaging techniques are an important alternative to nuclear medicine. The predictive value regarding the effect of revascularization is currently under investigation.     

Intravascular contrast agents suitable for magnetic resonance imaging

Two paramagnetic chelates, chromium EDTA and gadolinium DTPA, were evaluated as potential intravenous contrast agents for magnetic resonance imaging (MR) using a 0.5-T superconducting scanner. After evaluating both agents in vitro, in vivo studies were conducted in dogs to document changes in renal appearance produced by contrast injection. Acute splenic and renal infarction were diagnosed with contrast-enhanced MR and confirmed by gamma camera imaging following administration of Tc-99m-labeled DMSA and sulfur colloid. The authors conclude that intravenous paramagnetic contrast agents presently offer the best mechanism for assessment of tissue function and changes in perfusion with MR.     

用肾皮质区ROI计算GFR评价尿路梗阻患者肾功能

目的探讨设定不同肾感兴趣区（ROI）计算肾小球滤过率（GFR）评价尿路梗阻患者肾功能改变的临床价值。方法采用^99Tc^m-DTPA肾动态显像，应用Gates法计算30例不同程度单侧上尿路梗阻患者在设定全肾ROI及肾皮质ROI时各自的GFR值，并与同期检测的患肾尿微量白蛋白（MAlb）进行相关性分析。结果随积水程度加深，由2种ROI计算的GFR均下降；设定全肾ROI时，重度与轻及中度积水组相比GFR显著降低（P〈0．01）；设定肾皮质ROI时，各组GFR组间差异均显著（P〈0．01）；随积水程度加重，各组尿MAlb显著升高（P〈0．01）；设定肾皮质ROI时，各组GFR与MAlb均显著相关。结论由肾皮质ROI计算GFR值可更灵敏、更准确地发现尿路梗阻肾功能改变。     

Noninvasive measurement of extraction fraction and single-kidney glomerular filtration rate with MR imaging in swine with surgically created renal arterial stenoses

PURPOSE: To test whether magnetic resonance (MR) imaging enables accurate measurement of extraction fraction (EF) in swine with unilateral renal ischemia and to evaluate effects of renal arterial stenosis on EF and single-kidney glomerular filtration rate. MATERIALS AND METHODS: High-grade unilateral renal arterial stenoses were surgically created in eight pigs. Direct measurements of renal venous and arterial inulin concentration provided reference standard estimates of single-kidney EF. Pigs were imaged with a 1.5-T imager to estimate EF, renal blood flow, and glomerular filtration rate. A breath-hold inversion-recovery spiral sequence was used to measure T1 of blood in the infrarenal inferior vena cava and renal veins after intravenous administration of gadopentetate dimeglumine, and these data were used to calculate EF. Cine-phase contrast material-enhanced imaging of the renal arteries provided quantitative renal blood flow measurements. Bilateral single-kidney glomerular filtration rate was then determined: glomerular filtration rate = renal blood flow x (1 - hematocrit level) x EF. RESULTS: A statistically significant linear correlation was found between EF, as determined with MR imaging, and inulin (r = 0.77). As compared with kidneys without renal arterial stenosis, kidneys with renal arterial stenosis showed 50% (0.14/0.28) EF reduction (P <.01) and 59% glomerular filtration rate reduction (P <.01). CONCLUSION: MR imaging shows promise for in vivo measurement of EF and glomerular filtration rate, which may be useful in assessing the clinical importance of renal arterial stenosis.     

Diffusion‐weighted MRI in Crohn's disease: Current status and recommendations

Over the past years, technological improvements and refinements in magnetic resonance imaging (MRI) hardware have made high‐quality diffusion‐weighted imaging (DWI) routinely possible for the bowel. DWI is promising for the detection and characterization of lesions in Crohn's disease (CD) and has been advocated as an alternative to intravenous gadolinium‐based contrast agents. Furthermore, quantification using the apparent diffusion coefficient may have value as a biomarker of CD activity and has shown promise. In this article we critically review the literature pertaining to the value of DWI in CD for detection, characterization, and quantification of disease activity and complications. Although the body of supportive evidence is growing, it is clear that well‐designed, multicenter studies are required before the role of DWI in clinical practice can be fully established. J. Magn. Reson. Imaging 2016;44:1381–1396.     

不同病理类型IgA肾病肾动态显像分析

目的：探讨肾动态显像在判断各类IgA肾病的组织病变程度及预后中的价值。方法：70例经知组织检查证实的IgA肾病患者根据病理分级进行分组，比较各组肾功能变化。结果：肾动态显像测得的肾小球滤过率（GFR）与实验室检查测得的血肌酐（SCr)和尿素氮（BUN）水平基本一致；肾功能受损患者的GFR下降早于SCr的升高，GFR是反映肾功能变化敏感而可靠的指标；早期现核素20min清除率（C20）的下降则提示较重的病理改变。结论：肾动态显像对判断IgA肾病的组织病变程度及预后具有重要价值。     

Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging

Superparamagnetic iron oxide MR imaging contrast agents have been the subjects of extensive research over the past decade. The iron oxide particle size of these contrast agents varies widely, and influences their physicochemical and pharmacokinetic properties, and thus clinical application. Superparamagnetic agents enhance both T1 and T2/T2* relaxation. In most situations it is their significant capacity to reduce the T2/T2* relaxation time to be utilized. The T1 relaxivity can be improved (and the T2/T2* effect can be reduced) using small particles and T1-weighted imaging sequences. Large iron oxide particles are used for bowel contrast [AMI-121 (i.e. Lumirem and Gastromark) and OMP (i.e. Abdoscan), mean diameter no less than 300 nm] and liver/spleen imaging [AMI-25 (i.e. Endorem and Feridex IV, diameter 80-150 nm); SHU 555A (i.e. Resovist, mean diameter 60 nm)]. Smaller iron oxide particles are selected for lymph node imaging [AMI-227 (i.e. Sinerem and Combidex, diameter 20-40 nm)], bone marrow imaging (AMI-227), perfusion imaging [NC100150 (i.e. Clariscan, mean diameter 20 nm)] and MR angiography (NC100150). Even smaller monocrystalline iron oxide nanoparticles are under research for receptor-directed MR imaging and magnetically labeled cell probe MR imaging. Iron oxide particles for bowel contrast are coated with insoluble material, and all iron oxide particles for intravenous injection are biodegradable. Superparamagnetic agents open up an important field for research in MR imaging.     

In vivo NMR imaging and spectroscopic investigation of renal pathology in lean and obese rat kidneys

Diabetic nephropathy is a major cause of end-stage renal failure. While our understanding of the pathogenesis of nephropathy is incomplete, progressive glomerular injury appears to play a significant role in the decline of renal function. Proton NMR spectroscopy and imaging techniques were used to address changes in renal pathology associated with glomerular mesangial expansion in vivo in kidneys from spontaneously obese and lean (control) littermate Zucker rats. Fully functioning rat kidneys were surgically exposed and externalized for direct NMR signal detection via a coil placed around the organ. High-resolution (78 μm in plane) proton images were obtained at 4.7 T magnetic field strength revealing fine structure within the well-defined cortical and medullary regions. The obese rat kidney images were distinct in appearance from the lean kidney images and exhibited marked cortical expansion as well as increased overall kidney size. Enlargement of mean glomerular diameter was verified histologically in the obese kidneys as compared with the lean kidneys. Proton T₁ and T₂ relaxation times were determined from the entire kidney using standard spectroscopic techniques, and from specific regions within the kidney from multiple T₁ and T₂-weighted images. Additionally, image contrast enhancement resulting from saturation transfer between protons in restricted-mobility environments and mobile water protons within the kidney was investigated in the lean and obese rat kidneys using magnetization-transfer imaging techniques. At the early stage of renal injury examined in this study, diseased and healthy kidneys could not be differentiated on the basis of relaxation times alone. The magnitude of saturation transfer obtained in cortical tissue in the lean and obese kidneys was also not statistically significantly different. However, the magnitude of saturation transfer achieved in the medullary tissue of obese kidneys was statistically significantly less than that achieved in lean kidneys.     

Functional dynamic MRI,pharmacokinetics and safety of Gd-DTPA in patients with impaired renal function

Renal elimination of the paramagnetic contrast agent Gadolinium-DTPA (Gd-DTPA) was analyzed in 24 patients with impaired renal function and 3 normal controls. Dynamic magnetic resonance studies were performed using fast gradient-echo sequences with single images during suspended respiration and a temporal resolution of 10s per image. The time between appearance of the contrast agent in the renal cortex and signal intensity drop mL/min the medulla, due to a high concentration of Gd-DTPA and predominant T2-shortening, was an indicator of glomerular filtration rate and correlated well with creatinine clearance values (r=0.81). Fractionate urine collections and serum analysis up to 120h following administration showed a prolonged but complete elimination of Gd-DTPA mL/min patients with creatinine clearance above 20 mL/min. Renal functional parameters did not change after administration of Gd-DTPA and no nephrotoxic effects were observed.     

Dynamic three-dimensional MR renography for the measurement of single kidney function: initial experience

A three-dimensional magnetic resonance (MR) renographic method to measure single kidney glomerular filtration rate (GFR) and split renal function was developed that is based on renal signal intensity measurements during 2-3 minutes after intravenous injection of a low dose (2 mL or 0.01 mmol/kg) of gadopentetate dimeglumine. In nine subjects, single kidney MR GFR indices correlated well with technetium 99m (99mTc) diethylenetriaminepentaacetic acid (DTPA) clearance (r = 0.7-0.8) for GFR values of 7-48 mL/min. MR right kidney split renal function values (range, 32%-59%) also correlated well with 99mTc-DTPA radionuclide measurements (r = 0.76); differences between the two methods averaged 0.8% +/- 8. MR renography was performed along with contrast material-enhanced MR imaging of the kidneys and renal arteries and added 8 minutes or less to the total examination time.     

346例上尿路结石患者99Tcm-DTPA肾动态显像结果分析

目的 探讨99Tcm-二亚乙基三胺五乙酸(99Tcm-DTPA)肾动态显像在上尿路结石患者肾功能评价中的临床价值.方法 回顾性分析了346例上尿路结石患者的核素肾动态显像、静脉肾盂造影(IVP)和血尿素氮(BUN)、血清肌酐(SCr)值,并依据总肾肾小球滤过率(GFR)将BUN和SCr结果分成4组进行分析.结果 ①346例肾动态显像患者,总肾GFR与BUN、SCr水平呈明显负相关(r=-0.458,P=0.000;r=-0.542,P=0.000).②4组之间比较,BUN和SCr均存在统计学差异(F=49.23,P=0.000;F=80.66,P=0.000);经最小显著差别法分析,组1与组2之间比较,BUN和SCr均无统计学差异(P=0.119和P=0.088);而其余各组之间比较,BUN和SCr均存在统计学差异(P均＜0.05).③IVP不显影的43只患肾中,经99Tcm-DTPA肾动态显像提示有18只(41.9%)有残余肾功能(GFR≥10 ml/min),平均GFR为(21.89±12.81)ml/min.结论 99Tcm-DTPA肾动态显像能早期评价肾功能,特别是对IVP不显影的患肾功能的评价具有重要临床价值.     

Yb-DTPA, a novel contrast agent in magnetic resonance imaging: application to rat kidney

We have developed a novel contrast agent, ytterbium-diethylenetriamine pentaacetic acid (Yb-DTPA), for magnetic resonance imaging (MRI) and its mechanism of action is predominantly by the susceptibility mechanism. We have applied this contrast agent for renal MRI studies. We also demonstrate that Yb-DTPA has a renal clearance similar to that of inulin in rats and may therefore be useful for the estimation of glomerular filtration rate.     

Contrastes basados en gadolinio utilizados en resonancia magnética

Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity.We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article.Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients.