The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m, or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries.Copyright © 2017 Elsevier Ltd. All rights reserved.

To provide the first comparison of absolute renal perfusion obtained by arterial spin labeling (ASL) and separable compartment modeling of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Moreover, we provide the first application of the dual bolus approach to quantitative DCE-MRI perfusion measurements in the kidney.Consecutive ASL and DCE-MRI acquisitions were performed on six rabbits on a 1.5 T MRI system. Gadolinium (Gd)-DTPA was administered in two separate injections to decouple measurement of the arterial input function and tissue uptake curves. For DCE perfusion, pixel-wise and mean cortex region-of-interest tissue curves were fit to a separable compartment model.Absolute renal cortex perfusion estimates obtained by DCE and ASL were in close agreement: 3.28 ± 0.59 mL/g/min (ASL), 2.98 ± 0.60 mL/g/min (DCE), and 3.57 ± 0.96 mL/g/min (pixel-wise DCE). Renal medulla perfusion was 1.53 ± 0.35 mL/g/min (ASL) but was not adequately described by the separable compartment model.ASL and DCE-MRI provided similar measures of absolute perfusion in the renal cortex, offering both noncontrast and contrast-based alternatives to improve current renal MRI assessment of kidney function.Copyright © 2011 Wiley-Liss, Inc.

Background: Measurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers. Methods: ASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning. Results: 12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 +/- 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 +/- 15.1 ml/min/1.73 m(2). Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 +/- 25.5 cm(3), and 156.7 +/- 28.9 cm(3) respectively. Mean kidney perfusion was 229 +/- 41 ml/min/100 g and mean cortical perfusion was 327 +/- 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 +/- 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%. Conclusions: ASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers.

To evaluate the diagnostic value of 3D arterial spin labeling (ASL) for noninvasive quantification of renal blood flow (RBF) in patients with chronic kidney disease (CKD).

<b><i>Aims:</i></b> Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. <b><i>Methods:</i></b> We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and flow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. <b><i>Results:</i></b> T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p < 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = -0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion. <b><i>Conclusions:</i></b> Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD.

To investigate whether arterial spin labeling (ASL) MRI could detect renal hemodynamic impairment in diabetes mellitus (DM) along different stages of chronic kidney disease (CKD).Three Tesla (3T) ASL-MRI was performed to evaluate renal blood flow (RBF) in 91 subjects (46 healthy volunteers and 45 type 2 diabetic patients). Patients were classified according to their estimated glomerular filtration rate (eGFR) as group I (eGFR > 60 mL/min/1.73 m ), group II (60 ≥ eGFR>30 mL/min/1.73 m ), or group III (eGFR ≤ 30 mL/min/1.73 m ), to determine differences depending on renal function. Studies were performed at 3T using a 12-channel flexible body array combined with the spine array coil as receiver.A 28% reduction in cortical RBF was seen in diabetics in comparison with healthy controls (185.79 [54.60] versus 258.83 [37.96] mL/min/100 g, P < 3 × 10 ). Differences were also seen between controls and diabetic patients despite normal eGFR and absence of overt albuminuria (RBF [mL/min/100 g]: controls=258.83 [37.96], group I=208.89 [58.83], P = 0.0018; eGFR [mL/min/1.73 m ]: controls = 95.50 [12.60], group I = 82.00 [20.76], P > 0.05; albumin-creatinine ratio [mg/g]: controls = 3.50 [4.45], group I = 17.50 [21.20], P > 0.05). A marked decrease in RBF was noted a long with progression of diabetic nephropathy (DN) through the five stages of CKD (χ  = 43.58; P = 1.85 × 10 ). Strong correlation (r = 0.62; P = 4 × 10 ) was obtained between RBF and GFR estimated by cystatin C.ASL-MRI is able to quantify early renal perfusion impairment in DM, as well as changes according to different CKD stages of DN. In addition, we demonstrated a correlation of RBF quantified by ASL and GFR estimated by cystatin C.3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1810-1817.© 2017 International Society for Magnetic Resonance in Medicine.

Measurement of single-kidney filtration fraction and glomerular filtration rate (GFR) without exogenous contrast is clinically important to assess renal function and pathophysiology, especially for patients with comprised renal function. The objective of this study is to develop a novel MR-based tool for noninvasive quantification of renal function using conventional MR arterial spin labeling water as endogenous tracer.The regional differentiation of the arterial spin labeling water between the glomerular capsular space and the renal parenchyma was characterized and measured according to their MR relaxation properties (T1ρ or T2 ), and applied to the estimation of filtration fraction and single-kidney GFR. The proposed approach was tested to quantify GFR in healthy volunteers at baseline and after a protein-loading challenge.Biexponential decay of the cortical arterial spin labeling water MR signal was observed. The major component decays the same as parenchyma water; the minor component decays much slower as expected from glomerular ultra-filtrates. The mean single-kidney GFR was estimated to be 49 ± 9 mL/min at baseline and increased by 28% after a protein-loading challenge.We developed an arterial spin labeling-based MR imaging method that allows us to estimate renal filtration fraction and singe-kidney GFR without use of exogenous contrast.Copyright © 2013 Wiley Periodicals, Inc.

The purpose of this study was to evaluate contrast‐media–free arterial spin labeling, a technique of functional magnetic resonance imaging (MRI), for assessment of kidney perfusion in a clinical study. We examined renal perfusion by arterial spin labeling in 15 healthy adults using a clinical 1.5‐T MRI system, twice under baseline conditions and 60 minutes after a single oral dose of 50 mg captopril. Data evaluation included assessment of interstudy and interrater reproducibility in addition to the pharmacological effect of captopril on kidney perfusion and a sample size calculation for potential application of the technique in pharmacological intervention studies. Interstudy reproducibility of cortical and medullary kidney perfusion was excellent (intraclass correlation coefficients 0.77 and 0.83, respectively). Interrater reproducibility was excellent in the cortex and good in the medulla (intraclass correlation coefficients 0.97 and 0.66, respectively). Ingestion of 50 mg captopril was associated with an 11% drop of systolic blood pressure and a rise in kidney perfusion by 22% in the cortex (369 ± 48 vs 452 ± 56 mL/[min·100 g], P <.001) and 26% in the medulla (157 ± 39 to 198 ± 45 ml/[min·100 g]; P <.01). Statistical power analysis revealed that a small sample size of only 6 participants is needed in a clinical trial to capture an equal change in kidney perfusion to the one induced by 50 mg captopril with a statistical power of 82% and an α error of 0.05. In conclusion, funtional MRI with arterial spin labeling is a reliable method for quantification of kidney perfusion and for fast assessment of pharmacologically induced renal perfusion changes, allowing low case numbers.

We investigated the feasibility and reproducibility of free-breathing motion-corrected multiple inversion time (multi-TI) pulsed renal arterial spin labelling (PASL), with general kinetic model parametric mapping, to simultaneously quantify renal perfusion (RBF), bolus arrival time (BAT) and tissue T.In a study approved by the Health Research Authority, 12 healthy volunteers (mean age, 27.6 ± 18.5 years; 5 male) gave informed consent for renal imaging at 3 T using multi-TI ASL and conventional single-TI ASL. Glyceryl trinitrate (GTN) was used as a vasodilator challenge in six subjects. Flow-sensitive alternating inversion recovery (FAIR) preparation was used with background suppression and 3D-GRASE (gradient and spin echo) read-out, and images were motion-corrected. Parametric maps of RBF, BAT and T were derived for both kidneys. Agreement was assessed using Pearson correlation and Bland-Altman plots.Inter-study correlation of whole-kidney RBF was good for both single-TI (r = 0.90), and multi-TI ASL (r = 0.92). Single-TI ASL gave a higher estimate of whole-kidney RBF compared to multi-TI ASL (mean bias, 29.3 ml/min/100 g; p <0.001). Using multi-TI ASL, the median T of renal cortex was shorter than that of medulla (799.6 ms vs 807.1 ms, p = 0.01), and mean whole-kidney BAT was 269.7 ± 56.5 ms. GTN had an effect on systolic blood pressure (p < 0.05) but the change in RBF was not significant.Free-breathing multi-TI renal ASL is feasible and reproducible at 3 T, providing simultaneous measurement of renal perfusion, haemodynamic parameters and tissue characteristics at baseline and during pharmacological challenge.• Multiple inversion time arterial spin labelling (ASL) of the kidneys is feasible and reproducible at 3 T. • This approach allows simultaneous mapping of renal perfusion, bolus arrival time and tissue T during free breathing. • This technique enables repeated measures of renal haemodynamic characteristics during pharmacological challenge.

To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers.PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland-Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined.Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m. Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland-Altman plot for cortical RBF showed good agreement between the two measurements.PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation.2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813-819.© 2017 International Society for Magnetic Resonance in Medicine.

To demonstrate the feasibility of diffusion tensor imaging (DTI) of kidneys with respiratory triggering, and determine the optimal imaging parameters for fraction anisotropy (FA) maps.DTI of kidneys from 16 healthy volunteers was performed using a 1.5T scanner. Five different sequences with different parameters including respiration-triggered acquisition or multiple breath-holding, slice thicknesses of 3 or 5 mm, and different numbers of signal averaging and b values were compared. FA and apparent diffusion coefficients (ADCs) of the cortex and medulla were measured. Measurement error within the same and repeated examination was examined using within-individual standard deviation (Sw).FAs of the renal cortex were lower than the medulla (mean value of a sequence ranging 0.148-0.224, 0.433-0.476) and the ADCs of the cortex were higher than the medulla (2.26-2.69x10(-3) mm2/s, 1.77-2.19x10(-3) mm2/s) in all sequences (P<0.001). The renal cortex-medulla difference was the largest, with respiratory trigger- ing including a 3-mm slice thickness, three signal averages,and a b-value=0, 200, or 400 s/mm2 (P<0.001). Sw tended to be smaller in the sequence with a b-value of 400 s/mm2.DTI of kidneys with respiratory triggering is feasible with excellent cortex-medulla differentiation.Copyright (c) 2009 Wiley-Liss, Inc.

\n Context: Diffusion Tensor Imaging (DTI) is a reliable noninvasive tool to assess renal function with medullary Fractional Anisotropy (FA) values showing the most consistent results. Aims: Evaluation of FA, Apparent Diffusion Coefficient (ADC) for detecting diabetic nephropathy (DN) using 1.5-Tesla magnetic resonance imaging (MRI). To determine FA and ADC values in chronic kidney disease (CKD) patients and controls, and comparing these with estimated glomerular filtiration rate (eGFR) and categorizing the stage of CKD. Patients and Methods: Thirty nondiabetic volunteers underwent DTI.The study included 83 diabetics, 30 frank urine proteinuric, 30 micro-albuminuric, 23 normo-albuminuric with only raised blood sugar patients.Patients were stratified by eGFR into groups: eGFR <60 and eGFR>60ml/min. ADC and FA values in cortex and medulla were compared between controls and study groups. Statistical Analysis Used: Analysis of variance and Pearson correlation using SPSS 16 were performed. Results: There was significant difference of FA medulla in controls versus albuminuric and micro-albuminuric versus frank proteinuric patients (P < 0.001).Also, there was significant difference between cortical ADC values between normal, microalbuminuric/proteinuric groups (P = 0.010, P =0.000, respectively). Significant difference between medullary FA values of patients with eGFR >60 and eGFR < 60 versus normal controls (P < 0.001) was noted.With declining renal function from normal to CKD category 5, a negative correlation between medullary FA (r= −0.785, P = 0.001) and ADC cortex values (r= −0.436, P = 0.001) was noted. A strong positive correlation between medullary FA and cortex ADC with eGFR (r = 0.598 and 0.344, respectively) was noted. Conclusion: Medullary FA of diabetics with relatively intact kidney function were significantly lower than those of controls. Hence, drop in medullary FA values can be an indicator of early nephropathy/patients at risk where eGFR is in near normal range. Cortical ADC and medullary FA demonstrated a significant correlation with eGFR with the latter showing a stronger positive correlation.

To assess renal dysfunction in chronic kidney diseases using diffusion tensor imaging (DTI).Forty-seven patients with impaired renal function (study group) and 17 patients without renal diseases (control group) were examined using DTI sequences. Cortical and medullary regions of interest (ROIs) were located to obtain the corresponding values of the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA). The mean values of the ADC and FA, for each ROI site, were obtained in each group and were compared. Furthermore, the correlations between the diffusion parameters and the estimated glomerular filtration rate (eGFR) were determined.In both the normal and affected kidneys, we obtained the cortico-medullary difference of the ADC and the FA values. The FA value in the medulla was significantly lower (P = 0.0149) in patients with renal function impairment as compared to patients with normal renal function. A direct correlation between DTI parameters and the eGFR was not found. Tractography visualised disruption of the regular arrangement of the tracts in patient with renal function alteration.DTI could be a useful tool in the evaluation of chronic kidney disease and, in particular, the medullary FA value seems to be the main parameter for assessing renal damage.• Magnetic resonance diffusion tensor imaging (MRDTI) provides new information about renal problems. • DTI allows non-invasive repeatable evaluation of the renal parenchyma, without contrast media. • DTI could become useful in the management of chronic parenchymal disease. • DTI seems more appropriate for renal evaluation than diffusion-weighted imaging.

To investigate the clinical value of diffusion tensor imaging (DTI) in assessing renal function changes in diabetic patients with early-stage chronic kidney disease (CKD), and the relationship of DTI parameters with estimated glomerular filtration rate (eGFR) and urinary biomarkers.Thirty-six patients with diabetes mellitus (DM; 30 CKD stage 1 and 6 CKD stage 2) and 26 healthy control subjects were enrolled. DTI was performed using a clinical 3 T MRI system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were calculated from the renal cortex and medulla. The correlation of the DTI parameters with eGFR and urinary biomarkers was evaluated.FA values were significantly reduced in the renal cortex and medulla of DM group compared with the control group (cortical FA, Z=-2.834, p=0.005; medullary FA, t=2.768, p=0.007). In the DM group, FA values in the renal cortex and medulla were positively correlated with eGFR, while FA values in the medulla were negatively correlated with the urinary albumin/creatinine ratio, urinary alpha-1 microglobulin/creatinine ratio, and urinary transferring/creatinine ratio. ADC values in the renal cortex and medulla showed a trend towards an increase in the DM group compared with the control group.Renal DTI is a promising method for assessing early renal function changes in DM patients.Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Our objective was to evaluate pathological and functional changes in chronic kidney disease (CKD) using diffusion tensor imaging (DTI) at 3 T.There were fifty-one patients with CKD who required biopsy and 19 healthy volunteers who were examined using DTI at 3 T. The mean values of fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were obtained from the renal parenchyma (cortex and medulla). Correlations between imaging results and the estimated glomerular filtration rate (eGFR), as well as pathological damage (glomerular lesion and tubulointerstitial injury), were evaluated.The renal cortical FA was significantly lower than the medullary in both normal and affected kidneys (p < 0.001). The parenchymal FA was significantly lower in patients than healthy controls, regardless of whether eGFR was reduced. There were positive correlations between eGFR and FA (cortex, r = 0.689, p = 0.000; and medulla, r = 0.696, p = 0.000), and between eGFR and ADC (cortex, r = 0.310, p = 0.017; and medulla, r = 0.356, p = 0.010). Negative correlations were found between FA and the glomerular lesion (cortex, r = -0.499, p = 0.000; and medulla, r = -0.530, p = 0.000), and between FA and tubulointerstitial injury (cortex, r = -0.631, p = 0.000; and medulla, r = -0.724, p = 0.000).DTI is valuable for noninvasive assessment of renal function and pathology in patients with CKD. A decrease in FA could identify the glomerular lesions, tubulointerstitial injuries, and eGFR.

To demonstrate role of diffusion tensor imaging of the kidney in diabetic patients and to correlate renal fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the renal cortex with urinary and serum biomarkers of diabetes.Prospective study was conducted upon 42 diabetic patients (28 males, 14 females; mean age = 33 years) and 17 age- and sex-matched volunteers. Diabetic patients were micro-normoalbuminuric (n = 27) and macroalbuminuric (n = 15). Patients and volunteers underwent diffusion tensor imaging of the kidney. The FA and ADC of the renal cortex were calculated from 3 regions of interests of both kidneys.The mean FA and ADC of the renal cortex in diabetic patients (0.36 ± 0.10 and 1.74 ± 0.16 × 10 mm/s) was significantly different (p = 0.001) from that of volunteers (0.26 ± 0.02 and 1.88 ± 0.03 × 10 mm/s). The cut-off renal FA and ADC used to differentiate diabetic patients from volunteers were 0.28 and 1.89 × 10 mm/s with AUC of 0.791 and 0.773 and accuracy of 71% and 76%. The FA and ADC calculated in the renal cortex in patients with macroalbuminuria (0.43 ± 0.10 and 1.63 ± 0.19 × 10 mm/s) was significantly different (p = 0.001) from that of patients with micro-normoalbuminuria (0.35 ± 0.12 and 1.80 ± 0.18 × 10 mm/s). The FA and ADC of the renal cortex in diabetic patients correlated with urinary albumin (r = 0.530; p = 0.001, r = -0.421; p = 0.006), urinary NAG (r = 0.376; p = 0.014, r = -0.245; p = 0.01), urinary TGF-β1 (r = 0.287; p = 0.065, r = -0.214; p = 0.175), and serum creatinine (r = 0.381; p = 0.013, r = -0.349; p = 0.023).The FA and ADC of the renal cortex may help in differentiation of diabetic kidney from volunteers and prediction of the presence of macroalbuminuria in diabetic patients and correlated with some of the urinary and serum biomarkers of diabetes.

Intravoxel incoherent motion (IVIM) imaging is a method the authors developed to visualize microscopic motions of water. In biologic tissues, these motions include molecular diffusion and microcirculation of blood in the capillary network. IVIM images are quantified by an apparent diffusion coefficient (ADC), which integrates the effects of both diffusion and perfusion. The aim of this work was to demonstrate how much perfusion contributes to the ADC and to present a method for obtaining separate images of diffusion and perfusion. Images were obtained at 0.5 T with high-resolution multisection sequences and without the use of contrast material. Results in a phantom made of resin microspheres demonstrated the ability of the method to separately evaluate diffusion and perfusion. The method was then applied in patients with brain and bone tumors and brain ischemia. Clinical results showed significant promise of the method for tissue characterization by perfusion patterns and for functional studies in the evaluation of the microcirculation in physiologic and pathologic conditions, as, for instance, in brain ischemia.

To investigate the potential of Intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI) for the assessment of renal fibrosis in chronic kidney disease (CKD), using histopathology as a reference standard.Eighty-five CKD patients and twenty healthy volunteers were recruited in this study. IVIM-DWI was performed in all of the participants, and all of the CKD patients underwent renal biopsy. The mean values of the true diffusion coefficient (D), pseudo diffusion coefficient (D*) and perfusion fraction (f) in the renal cortex and medulla were compared between the CKD patients and healthy volunteers. The Spearman correlation coefficient was calculated to assess the relationship between the D, D*,f values and the estimated glomerular filtration rate (eGFR), serum creatinine level (SCr), 24h urinary protein level (24h-UPRO), histopathological fibrosis scores.The D, D* and f values were significantly lower in medulla than in the cortex for all of the participants. All of the IVIM parameters were significantly lower in the CKD patients than in the healthy controls. In the CKD patients, a significant negative correlation was found between the renal parenchymal D, D*,f values and the 24h-UPRO, as well as between the renal parenchymal D, f values and the SCr. There was a significant positive correlation between all of the IVIM parameters and the eGFR. All of the IVIM parameters exhibited a significant negative correlation with the histopathological fibrosis score.IVIM-DWI shows great potential in the noninvasive assessment of renal fibrosis in CKD.Copyright © 2017 Elsevier Inc. All rights reserved.

A magnetic resonance imaging method is presented for quantifying the degree to which water diffusion in biologic tissues is non-Gaussian. Since tissue structure is responsible for the deviation of water diffusion from the Gaussian behavior typically observed in homogeneous solutions, this method provides a specific measure of tissue structure, such as cellular compartments and membranes. The method is an extension of conventional diffusion-weighted imaging that requires the use of somewhat higher b values and a modified image postprocessing procedure. In addition to the diffusion coefficient, the method provides an estimate for the excess kurtosis of the diffusion displacement probability distribution, which is a dimensionless metric of the departure from a Gaussian form. From the study of six healthy adult subjects, the excess diffusional kurtosis is found to be significantly higher in white matter than in gray matter, reflecting the structural differences between these two types of cerebral tissues. Diffusional kurtosis imaging is related to q-space imaging methods, but is less demanding in terms of imaging time, hardware requirements, and postprocessing effort. It may be useful for assessing tissue structure abnormalities associated with a variety of neuropathologies.

Quantification of non-Gaussianity for water diffusion in brain by means of diffusional kurtosis imaging (DKI) is reviewed. Diffusional non-Gaussianity is a consequence of tissue structure that creates diffusion barriers and compartments. The degree of non-Gaussianity is conveniently quantified by the diffusional kurtosis and derivative metrics, such as the mean, axial, and radial kurtoses. DKI is a diffusion-weighted MRI technique that allows the diffusional kurtosis to be estimated with clinical scanners using standard diffusion-weighted pulse sequences and relatively modest acquisition times. DKI is an extension of the widely used diffusion tensor imaging method, but requires the use of at least 3 b-values and 15 diffusion directions. This review discusses the underlying theory of DKI as well as practical considerations related to data acquisition and post-processing. It is argued that the diffusional kurtosis is sensitive to diffusional heterogeneity and suggested that DKI may be useful for investigating ischemic stroke and neuropathologies, such as Alzheimer's disease and schizophrenia.Copyright © 2010 John Wiley & Sons, Ltd.

Our aim was to prospectively evaluate the feasibility of diffusional kurtosis imaging (DKI) in normal human kidney and to report preliminary DKI measurements. Institutional review board approval and informed consent were obtained. Forty-two healthy volunteers underwent diffusion-weighted imaging (DWI) scans with a 3-T MR scanner. b values of 0, 500 and 1000 s/mm(2) were adopted. Maps of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (D⊥), axial diffusivity (D||), mean kurtosis (MK), radial kurtosis (K⊥) and axial kurtosis (K||) were produced. Three representative axial slices in the upper pole, mid-zone and lower pole were selected in the left and right kidney. On each selected slice, three regions of interest were drawn on the renal cortex and another three on the medulla. Statistical comparison was performed with t-test and analysis of variance. Thirty-seven volunteers successfully completed the scans. No statistically significant differences were observed between the left and right kidney for all metrics (p values in the cortex: FA, 0.114; MD, 0.531; D⊥, 0.576; D||, 0.691; MK, 0.934; K⊥, 0.722; K||, 0.891; p values in the medulla: FA, 0.348; MD, 0.732; D⊥, 0.470; D||, 0.289; MK, 0.959; K⊥, 0.780; K||, 0.287). Kurtosis metrics (MK, K||, K⊥) obtained in the renal medulla were significantly (p <0.001) higher than those in the cortex (0.552 ± 0.04, 0.637 ± 0.07 and 0.530 ± 0.08 in the medulla and 0.373 ± 0.04, 0.492 ± 0.06 and 0.295 ± 0.06 in the cortex, respectively). For the diffusivity measures, FA of the medulla (0.356 ± 0.03) was higher than that of the cortex (0.179 ± 0.03), whereas MD, D⊥ and D|| (mm(2) /ms) were lower in the medulla than in the cortex (3.88 ± 0.09, 3.50 ± 0.23 and 4.65 ± 0.29 in the cortex and 2.88 ± 0.11, 2.32 ± 0.20 and 3.47 ± 0.31 in the medulla, respectively). Our results indicate that DKI is feasible in the human kidney. We have reported the preliminary DKI measurements of normal human kidney that demonstrate well the non-Gaussian behavior of water diffusion, especially in the renal medulla.Copyright © 2014 John Wiley & Sons, Ltd.

To evaluate renal fibrosis in immunoglobulin A nephropathy (IgAN) using diffusion kurtosis imaging (DKI).Twenty patients with biopsy-proven IgAN were enrolled. DKI was performed on a clinical 3 T magnetic resonance imaging (MRI) system, and region-of-interest measurements were conducted to determine mean kurtosis (K), mean diffusivity (D), and apparent diffusion coefficient (ADC) of the kidney cortex. Renal biopsy specimens were scored based on the severity of renal fibrosis. The associations between the DKI data and clinicopathological parameters were investigated.Both the K and ADC were not only well correlated with the estimated glomerular filtration rate, but also significantly associated with the pathological scores of fibrosis, including the glomerular sclerosis index (K: r=0.759, p<0.001; ADC: r=-0.636, p=0.003) and the percentage of tubular atrophy and interstitial fibrosis (K: r=0.767, p<0.001; ADC: r=-0.702, p=0.001). Further receiver operating characteristic analysis showed that K demonstrated better diagnostic performance in discriminating severe glomerulosclerosis (area under curve [AUC] 0.970, sensitivity 81.8%, specificity 100%), and ADC displayed better capabilities in identifying severe tubular atrophy/interstitial fibrosis (AUC 0.976, sensitivity 100%, specificity 92.9%).This DKI method can be used to detect renal fibrosis in IgAN in a non-invasive manner and may provide additional information for characterisation and surveillance.Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

To examine the benefit of using higher field strengths for BOLD MRI to detect changes in renal medullary oxygenation following pharmacological maneuvers.

目的 通过狼疮肾炎（LN）小鼠模型，探讨功能性磁共振成像（MRI）在评估肾功能损害、肾脏病理改变及肾内缺氧状态中的作用。 方法 自发性LN模型MRL/lpr小鼠13只，对照组C57BL/6小鼠10只，检测尿白蛋白/肌酐比值（ACR）、血肌酐（Scr）、抗ds-DNA抗体和补体C3水平；14~16周龄小鼠处死前进行肾脏横断面T1加权像（T1WI）、T2加权像（T2WI）、扩散加权成像（DWI）及血氧水平依赖法（BOLD）成像。处死前1 h腹腔注射缺氧探针，采用免疫组化、Western印迹法检测小鼠肾组织中缺氧探针（HypoxyprobeTM-1）、缺氧诱导因子1α（HIF-1α）和血红素加氧酶1（HO-1）的分布。 结果 MRL/lpr小鼠的尿ACR、Scr和抗ds-DNA抗体水平均显著高于对照组，LN模型小鼠肾组织中HypoxyprobeTM-1、HIF-1α和HO-1广泛分布，且在肾髓质的小管间质呈弥漫分布，并与肾小管间质病变密切相关。肾脏功能MRI示LN组平均表观扩散系数（ADC）为（1.52±0.27）×10-3 mm2/s，皮质和髓质R2*值分别为（30.95±4.59）/s和（23.43±3.06）/s，均低于对照组（P分别为0.037、0.030、0.043）。当b=500 s/mm2和800 s/mm2时，髓质ADC值与尿ACR呈负相关（r=-0.364，P=0.032；r=-0.329，P=0.050），皮质ADC值与血肌酐亦呈负相关（r=-0.814，P=0.014；r=-0.755，P=0.031），平均R2*值与尿ACR、肾小管间质病变程度及肾组织缺氧指标表达均呈负相关（均P＜0.05）。 结论 肾内缺氧可能在LN肾小管间质病变发生中具有重要作用。无创性的功能性MRI可监测LN小鼠的肾功能变化、肾脏病理改变及肾内缺氧情况。

Vesicoureteral reflux (VUR) is a frequent cause of chronic kidney disease (CKD) in children. Using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), we measured cortical and medullary oxygenation in children with CKD due to VUR and compared the results to those obtained on healthy controls.The study population comprised 37 children (19 with CKD due to VUR and 18 healthy age-matched controls). BOLD-MRI was performed before and after furosemide treatment. MR images were analyzed with the region-of-interest (ROI) technique to assess the mean R2* values (=1/T2*) of the cortex and medulla of each kidney and with the concentric object (CO) technique that divides renal parenchyma in 12 equal layers.R2* values were significantly lower (corresponding to higher oxygenation) in the cortex and medulla of kidneys of children with CKD due to VUR than in those of the healthy controls (cortex 16.4 ± 1.4 vs. 17.2 ± 1.6 s(-1), respectively; medulla 28.4 ± 3.2 vs. 30.3 ± 1.9 s(-1), respectively; P < 0.05), and furosemide-induced changes in medullary R2* were smaller in the former than in the latter (-5.7 ± 3.0 vs. -6.9 ± 3.4 s(-1), respectively; P < 0.05). Similar results were found with the CO technique. In children with a history of unilateral reflux (n = 9), the non-affected contralateral kidneys presented similar R2* values as the diseased kidneys, but their response to furosemide was significantly larger (-7.4 ± 3.2 vs. -5.7 ± 3.0, respectively; P = 0.05).Chronic kidney disease due to VUR is not associated with kidney tissue hypoxia in children. The significantly larger furosemide-induced decrease in medullary R2* levels in the healthy group and unaffected contralateral kidneys of the VUR group points towards more intense renal sodium transport in these kidneys.

Animal studies suggest that progression of chronic kidney disease (CKD) is related to renal hypoxia. With renal blood supply determining oxygen delivery and sodium absorption being the main contributor to oxygen consumption, we describe the relationship between renal oxygenation, renal artery blood flow, and sodium absorption in patients with CKD and healthy controls.Cross-sectional study.62 stable patients with CKD stages 3 to 4 (mean age, 61±13 [SD] years) and 24 age- and sex-matched controls.CKD versus control status.Renal artery blood flow, tissue oxygenation (relative changes in deoxyhemoglobin concentration of the renal medulla [MR2*] and cortex [CR2*]), and sodium absorption.Renal artery blood flow was determined by phase-contrast magnetic resonance imaging (MRI); MR2* and CR2* were determined by blood oxygen level-dependent MRI. Ultrafiltered and reabsorbed sodium were determined from measured glomerular filtration rate (mGFR) and 24-hour urine collections.mGFR in patients was 37% that of controls (36±15 vs 97±23 mL/min/1.73 m(2); P < 0.001), and reabsorbed sodium was 37% that of controls (6.9 vs 19.1 mol/24 h; P < 0.001). Single-kidney patient renal artery blood flow was 72% that of controls (319 vs 443 mL/min; P < 0.001). Glomerular filtration fraction was 9% in patients and 18% in controls (P < 0.001). Patients and controls had similar CR2* (13.4 vs 13.3 s(-1)) and medullary MR2* (26.4 vs 26.5 s(-1)) values. Linear regression analysis demonstrated no associations between R2* and renal artery blood flow or sodium absorption. Increasing arterial blood oxygen tension by breathing 100% oxygen had very small effects on CR2*, but reduced MR2* in both groups.Only renal artery blood flow was determined and thus regional perfusion could not be related to CR2* or MR2*.In CKD, reductions of mGFR and reabsorbed sodium are more than double that of renal artery blood flow, whereas cortical and medullary oxygenation are within the range of healthy persons. Reduction in glomerular filtration fraction may prevent renal hypoxia in CKD.Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Renal tissue hypoxia is a final pathway in the development and progression of chronic kidney disease (CKD), but whether renal oxygenation predicts renal function decline in humans has not been proven. Therefore, we performed a prospective study and measured renal tissue oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in 112 patients with CKD, 47 with hypertension without CKD, and 24 healthy control individuals. Images were analyzed with the twelve-layer concentric objects method that divided the renal parenchyma in 12 layers of equal thickness and reports the mean R2* value of each layer (a high R2* corresponds to low oxygenation), along with the change in R2* between layers called the R2* slope. Serum creatinine values were collected to calculate the yearly change in estimated glomerular function rate (MDRD eGFR). Follow up was three years. The change in eGFR in CKD, hypertensive and control individuals was -2.0, 0.5 and -0.2 ml/min/1.73m/year, respectively. In multivariable regression analysis adjusted for age, sex, diabetes, RAS-blockers, eGFR, and proteinuria the yearly eGFR change correlated negatively with baseline 24 hour proteinuria and the mean R2* value of the cortical layers, and positively with the R2* slope, but not with the other covariates. Patients with CKD and high outer R2* or a flat R2* slope were three times more likely to develop an adverse renal outcome (renal replacement therapy or over a 30% increase in serum creatinine). Thus, low cortical oxygenation is an independent predictor of renal function decline. This finding should stimulate studies exploring the therapeutic impact of improving renal oxygenation on renal disease progression.Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

To assess inter-observer variability of renal blood oxygenation level-dependent MRI (BOLD-MRI) using a new method of analysis, called the concentric objects (CO) technique, in comparison with the classical ROI (region of interest)-based technique.MR imaging (3T) was performed before and after furosemide in 10 chronic kidney disease (CKD) patients (mean eGFR 43±24ml/min/1.73m(2)) and 10 healthy volunteers (eGFR 101±28ml/min1.73m(2)), and R2* maps were determined on four coronal slices. In the CO-technique, R2* values were based on a semi-automatic procedure that divided each kidney in six equal layers, whereas in the ROI-technique, all circles (ROIs) were placed manually in the cortex and medulla. The mean R2*values as assessed by two independent investigators were compared.With the CO-technique, inter-observer variability was 0.7%-1.9% across all layers in non-CKD, versus 1.6%-3.8% in CKD. With the ROI-technique, median variability for cortical and medullary R2* values was 3.6 and 6.8% in non-CKD, versus 4.7 and 12.5% in CKD; similar results were observed after furosemide.The CO-technique offers a new, investigator-independent, highly reproducible alternative to the ROI-based technique to estimate renal tissue oxygenation in CKD.Copyright © 2015 Elsevier Inc. All rights reserved.

Blood oxygen level-dependent (BOLD)-MRI is a novel and noninvasive tool that can assess renal oxygenation. The R2* value is a parameter of tissue deoxyhemoglobin concentration detected by BOLD-MRI. The purpose of the current study was to determine the relationships between renal R2* values and clinical parameters and to determine whether renal R2* values were associated with the risk for progression of chronic kidney disease (CKD).Sixty patients with CKD were enrolled in this prospective observational study in China from March 2013 to August 2014. A region of interest-based BOLD-MRI was performed to obtain cortical and medullary R2* (CR2* and MR2*) values. Data on demographics and clinical characteristics were collected. The primary end point (CKD progression) was defined as an absolute 30% decline in the estimated glomerular filtration rates (eGFR; CKD-Epidemiology Collaboration equations) or initiation of dialysis during follow-up.The CR2* and MR2* values in patients with CKD were significantly higher compared with those of healthy controls. The CR2* levels were positively associated with 24-h urinary protein excretion, blood urea nitrogen, creatinine, and uric acid but negatively associated with baseline eGFR, 24-h creatinine clearance, eGFR slope, serum albumin, and the use of angiotensin II type 1 receptor blockade. The CR2* levels had the highest areas under the curve during follow-up compared with the MR2* levels and medullary cortical ratios. The Kaplan-Meier survival analysis showed that patients with CKD in the lowest tertile of the CR2* levels had the best prognosis compared with the other 2 tertiles. Moreover, baseline eGFR and CR2* tertiles were associated with the progression of CKD in Cox proportional hazard regression models. Only CR2* tertiles correlated negatively with the eGFR slope.We have demonstrated that the clinical feasibility of BOLD-MRI to evaluate renal oxygenation and cortex hypoxia aggravates with the decline of renal function, and cortex hypoxia was a prognostic marker in the progression of CKD.© 2018 S. Karger AG, Basel.

Diabetic nephropathy (DN) is the leading cause of renal failure; however, current clinical tests are insufficient for assessing this disease. DN is associated with changes in renal metabolites, so we evaluated the utility of chemical exchange saturation transfer (CEST) imaging to detect changes characteristic of this disease.Sensitivity of CEST imaging at 7 Tesla to DN was evaluated by imaging diabetic mice [db/db, db/db endothelial nitric oxide synthase (eNOS)-/-] that show different levels of nephropathy as well as by longitudinal imaging (8 to 24 weeks). Nondiabetic (db/m) mice were used as controls.Compared with nondiabetic mice, the CEST contrasts of hydroxyl metabolites that correspond to glucose and glycogen were significantly increased in papilla (P), inner medulla (IM), and outer medulla (OM) in db/db and db/db eNOS-/- kidneys at 16 weeks. The db/db eNOS-/- mice that showed advanced nephropathy exhibited greater CEST effects in OM and significant CEST contrasts were also observed in cortex. Longitudinally, db/db mice exhibited progressive increases in hydroxyl signals in IM+P and OM from 12 to 24 weeks and an increase was also observed in cortex at 24 weeks.CEST MRI can be used to measure changes of hydroxyl metabolites in kidney during progression of DN. Magn Reson Med 76:1531-1541, 2016. © 2015 International Society for Magnetic Resonance in Medicine.© 2015 International Society for Magnetic Resonance in Medicine.

Identification of chronic kidney disease patients at risk of progressing to end-stage renal disease (ESRD) is essential for treatment decision-making and clinical trial design. Here, we explored whether proton nuclear magnetic resonance (NMR) spectroscopy of blood plasma improves the currently best performing kidney failure risk equation, the so-called Tangri score. Our study cohort comprised 4640 participants from the German Chronic Kidney Disease (GCKD) study, of whom 185 (3.99%) progressed over a mean observation time of 3.70 ± 0.88 years to ESRD requiring either dialysis or transplantation. The original four-variable Tangri risk equation yielded a C statistic of 0.863 (95% CI, 0.831-0.900). Upon inclusion of NMR features by state-of-the-art machine learning methods, the C statistic improved to 0.875 (95% CI, 0.850-0.911), thereby outperforming the Tangri score in 94 out of 100 subsampling rounds. Of the 24 NMR features included in the model, creatinine, high-density lipoprotein, valine, acetyl groups of glycoproteins, and Ca-EDTA carried the highest weights. In conclusion, proton NMR-based plasma fingerprinting improved markedly the detection of patients at risk of developing ESRD, thus enabling enhanced patient treatment.

<b><i>Background/Aims:</i></b> Psychological complications are prevalent in patients with chronic kidney disease (CKD). This study aimed to investigate mental disorders in stage 4-5 CKD patients, to detect metabolite concentrations in the brain by proton magnetic resonance spectroscopy (¹H-MRS) and to compare the effects of different dialysis therapies on mental disorders in end-stage renal disease (ESRD). <b><i>Methods:</i></b> The sample population was made up of predialysis (13), hemodialysis (HD) (13), and peritoneal dialysis (PD) patients (12). We collected the baseline data of patients’ age, sex, hemoglobin (Hb) and parathyroid hormone（PTH） levels. The predialysis patients served as the control group. The psychological status of the three groups was assessed using three psychological scales. ¹H-MRS was used to evaluate the relative metabolite concentrations in the bilateral amygdala, hippocampus and unilateral anterior cingulated cortex (ACC). <b><i>Results:</i></b> The psychological status was better in HD patients than in predialysis and PD patients. ¹H-MRS alterations were predominantly found in the ACC. Choline-containing compounds relative to creatine (Cho/Cr), myo-inositol relative to creatine (MI/Cr) and glutamate and glutamine relative to creatine (Glx/Cr) in the ACC were higher in HD patients. ¹H-MRS results were correlated with the baseline data and the scores of psychological scales. <b><i>Conclusions:</i></b> CKD patients showed different types of mental disorders as well as metabolite disturbances in the brain. The metabolite concentrations correlated with the psychological status which was better in HD than in predialytic and PD patients.

Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well‐established murine model with progressive renal disease. MR images were acquired from 16‐week‐old fibrotic hHB‐EGFTg/Tg mice and normal wild‐type (WT) mice (N = 12) at 7 T. QMT parameters were derived using a two‐pool five‐parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value (tPSR) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB‐EGFTg/Tg mouse kidneys. Moderate increases in mean PSR (mPSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the tPSR were significantly increased in hHB‐EGFTg/Tg mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.