Cortical Apparent Diffusion Coefficient Research Articles

Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial.

The apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV). This was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [ΔADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI. Both semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20×10-3 mm2/s [95% CI -0.30, -0.10], p<0.001; empagliflozin: -0.15×10-3 mm2/s [95% CI -0.26, -0.04], p=0.01). No significant change was observed in the combination-therapy group (-0.05×10-3 mm2/s [95%CI -0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed ΔADC significantly from placebo, showing a decrease of -0.13×10-3 mm2/s (95% CI -0.22, -0.04; p=0.01). Compared with placebo, TKV decreased by -3% (95% CI -5%, -0.3%; p=0.04), -3% (95% CI -5%, -0.4%; p=0.02) and -5% (95% CI -8%, -2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA1c. In a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis. European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38.

Assessing renal interstitial fibrosis using compartmental, non-compartmental, and model-free diffusion MRI approaches

ObjectiveTo assess renal interstitial fibrosis (IF) using diffusion MRI approaches, and explore whether corticomedullary difference (CMD) of diffusion parameters, combination among MRI parameters, or combination with estimated glomerular filtration rate (eGFR) benefit IF evaluation.MethodsForty-two patients with chronic kidney disease were included, undergoing MRI examinations. MRI parameters from apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), and diffusion-relaxation correlated spectrum imaging (DR-CSI) were obtained both for renal cortex and medulla. CMD of these parameters was calculated. Pathological IF scores (1–3) were obtained by biopsy. Patients were divided into mild (IF = 1, n = 23) and moderate-severe fibrosis (IF = 2–3, n = 19) groups. Group comparisons for MRI parameters were performed. Diagnostic performances were assessed by the receiver operator’s curve analysis for discriminating mild from moderate-severe IF patients.ResultsSignificant inter-group differences existed for cortical ADC, IVIM-D, IVIM-f, DKI-MD, DR-CSI VB, and DR-CSI VC. Significant inter-group differences existed in ΔADC, ΔMD, ΔVB, ΔVC, ΔQB, and ΔQC. Among the cortical MRI parameters, VB displayed the highest AUC = 0.849, while ADC, f, and MD also showed AUC > 0.8. After combining cortical value and CMD, the diagnostic performances of the MRI parameters were slightly improved except for IVIM-D. Combining VB with f brings the best performance (AUC = 0.903) among MRI bi-variant models. A combination of cortical VB, ΔADC, and eGFR brought obvious improvement in diagnostic performance (AUC 0.963 vs 0.879, specificity 0.826 vs 0.896, and sensitivity 1.000 vs 0.842) than eGFR alone.ConclusionOur study shows promising results for the assessment of renal IF using diffusion MRI approaches.Critical relevance statementOur study explores the non-invasive assessment of renal IF, an independent and effective predictor of renal outcomes, by comparing and combining diffusion MRI approaches including compartmental, non-compartmental, and model-free approaches.Key PointsSignificant difference exists for diffusion parameters between mild and moderate-severe IF.Generally, cortical parameters show better performance than corresponding CMD.Bi-variant model lifts the diagnostic performance for assessing IF.Graphical

Contralateral renal change in a unilateral ureteral obstruction rat model using intravoxel incoherent motion diffusion-weighted imaging

Objectives Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes. Methods Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM. Results On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p < 0.01). The cortical D values showed statistically significant differences between UUO3 group and sham group (p < 0.01) but not among UUO groups at other time point. Additionally, the cortical and medullary f values were statistically significant between the UUO21 group and the sham group (p < 0.01). Especially, the cortical f values exhibited significant differences between the UUO21 group and the UUO groups with shorter obstruction time (at time point of 3, 7, 10, 14 day) (p < 0.01). Conclusions Significant hemodynamic alterations were observed in the contralateral kidney following renal obstruction. IVIM accurately captures changes in the unobstructed kidney. Particularly, the cortical f value exhibits the highest potential for assessing contralateral renal modifications.

Amide Proton Transfer-Weighted Magnetic Resonance Imaging for Application in Renal Fibrosis: A Radiological-Pathological-Based Analysis

Plain Language SummaryAmide proton transfer (APT) MRI, a novel molecular MRI technique, could indirectly measure the peptide or protein concentration within tissues based on frequent exchange between amide proton and the surrounding water protons. This new technology has been used in tumor diagnosis. Given pathological conditions linked to tissue fibrogenesis are similar to carcinogenesis, we proposed the hypothesis that APT MRI can be applied to assess collagen deposition in RF. To test this, we constructed animal models for RF and enrolled CKD patients, respectively. The results suggested APT values were more sensitive to the early stage of fibrosis than ADC values, and the cortical APT was highly positively correlated with the degree of fibrosis. We further identified that the combination of two MRI protocols, cortical apparent diffusion coefficient and cortical APT, was an excellent indicator for the diagnosis of fibrosis, with much higher accuracy than a single method. To the best of our knowledge, this is the first study to explore the value of APT imaging for assessing renal interstitial fibrosis. Our findings identify APT as a novel and precise imaging diagnostic tool for future noninvasive assessment of RF. It complements with the existing imaging biomarkers and adds value to conventional MRI.

FRI619 Kidney Magnetic Resonance Imaging Reveals Altered Tissue Architecture In Young Persons With Type 1 And 2 Diabetes

Abstract Disclosure: S. Poon: None. K. Nash: None. Y. Choi: None. L. Li: None. P. Prasad: None. D. Raalte: Other; Self; consulting relationships with Boehringer Ingelheim, Eli Lilly, Merck and Sanofi, and receives research operating funding from AstraZeneca, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, MSD. A. Karihaloo: Employee; Self; Novo Nordisk. A. Sawyer: None. P. Bjornstad: Advisory Board Member; Self; AstraZeneca, Bayer, Lilly, Boehringer Ingelheim, Novo Nordisk, and XORTX. Other; Self; PB reports serving or having served as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, LG Chemistry, Sanofi, Novo Nordisk, and Horizon Pharma. Background: Apparent diffusion coefficient (ADC) by magnetic resonance imaging (MRI) provides information about the microstructure and cellular organization of the kidney, and has been linked with kidney function decline in adults with chronic kidney disease. However, it is unclear whether alterations in tissue architecture or cellular density are also present in young persons with type 1 and 2 diabetes. Accordingly, the objective of this analysis was to determine early changes in ADC among young persons with and without diabetes. Materials and Method: Kidney MRIs were performed in 37 lean controls (age: 18±6 years, 54% female, eGFR: 106±19 ml/min/1.73m2), 28 participants with youth-onset T1D (age: 20±4 years, 50% female, diabetes duration: 9±6 years, HbA1c: 8.3±1.3%, eGFR: 110±19 ml/min/1.73m2) and 30 participants with youth-onset T2D (age: 17±4 years, 62% female, diabetes duration: 2±2 years, HbA1c: 7.4±2.2%, eGFR: 127±24 ml/min/1.73m2). All scans were performed on 3T whole-body scanners. A single reader at The NorthShore University HealthSystem analyzed all images while blinded to participants’ clinical information. Lower values of cortical ADC on diffusion-weighted MRI may indicate increased cellular density and are often used to estimate fibrosis. Estimated GFR (eGFR) were calculated by Full Age Spectrum serum creatinine equation. We performed multivariable linear regression models adjusted for age and sex. Results: Compared to lean controls (age and sex-adjusted means ± standard errors (SE): (1722±22 × 10−6 mm2/s), young persons with T1D (1636±28 × 10−6 mm2/s, p=0.02) and T2D (1612±27 × 10−6 mm2/s, p=0.002) exhibited lower cortical ADC. Despite younger age and shorter diabetes duration, young persons with T2D had numerically lower cortical ADC compared to those with T1D, although the difference did not reach statistical significance. Higher age and male sex were associated with lower cortical ADC (β±SE: −7.5±2.8 x 10−6 mm2/s per 1 year of age, p=0.009; β±SE: −71.1±28.5 x 10−6 mm2/s per 1 year for male sex, p=0.008) in multivariable models. Lower eGFR was associated with lower cortical ADC (β±SE: 2.3±0.8 x 10−6 mm2/s per 1 ml/min/1.73m2 increment eGFR, p=0.005). HbA1c and urine albumin-to-creatinine ratio did not associate significantly with cortical ADC in multivariable models. Conclusion: Young persons with diabetes exhibit lower cortical ADC compared to healthy lean controls, suggesting alternations in microstructure and cellular density and potentially early signs of fibrosis. Additionally, despite shorter duration of disease and younger age, participants with T2D had the lowest cortical ADC values among the 3 groups. Further research is needed to investigate the role of cortical ADC in predicting kidney function decline in young individuals with diabetes, as well as molecular determinants of the alterations in microstructure and cellular density. Presentation: Friday, June 16, 2023

Early assessment of acute kidney injury in severe acute pancreatitis with multimodal DWI: an animal model.

To evaluate the feasibility of multimodal diffusion-weighted imaging (DWI) for detecting the occurrence and severity of acute kidney injury (AKI) caused by severe acute pancreatitis (SAP) in rats. SAP was induced in thirty rats by the retrograde injection of 5.0% sodium taurocholate through the biliopancreatic duct. Six rats underwent MRI of the kidneys 24h before and 2, 4, 6, and 8h after this AKI model was generated. Conventional and functional MRI sequences were used, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DTI). The main DWI parameters and histological results were analyzed. The fast apparent diffusion coefficient (ADC) of the renal cortex was significantly reduced at 2h, as was the fractional anisotropy (FA) value of the renal cortex on DTI. The mean kurtosis (MK) values for the renal cortex and medulla gradually increased after model generation. The renal histopathological score was negatively correlated with the medullary slow ADC, fast ADC, and perfusion scores for both the renal cortex and medulla, as were the ADC and FA values of the renal medulla in DTI, whereas the MK values of the cortex and medulla were positively correlated (r = 0.733, 0.812). Thus, the cortical fast ADC, medullary MK, FADTI, and slow ADC were optimal parameters for diagnosing AKI. Of these parameters, cortical fast ADC had the highest diagnostic efficacy (AUC = 0.950). The fast ADC of the renal cortex is the core indicator of early AKI, and the medullary MK value might serve as a sensitive biomarker for grading renal injury in SAP rats. The multimodal parameters of renal IVIM, DTI, and DKI are potential beneficial for the early diagnosis and severity grading of renal injury in SAP patients. • The multimodal parameters of renal DWI, including IVIM, DTI, and DKI, may be valuable for the noninvasive detection of early AKI and the severity grading of renal injury in SAP rats. • Cortical fast ADC, medullary MK, FA, and slow ADC are optimal parameters for early diagnosis of AKI, and cortical fast ADC has the highest diagnostic efficacy. • Medullary fast ADC, MK, and FA as well as cortical MK are useful for predicting the severity grade of AKI, and the renal medullary MK value exhibits the strongest correlation with pathological scores.

Value of multiparametric magnetic resonance imaging for evaluating chronic kidney disease and renal fibrosis.

To identify optimized MRI markers for evaluating chronic kidney disease (CKD) and renal interstitial fibrosis (IF). This prospective study included 43 patients with CKD and 20 controls. The CKD group was divided into mild and moderate-to-severe subgroups based on pathological results. Scanned sequences included T1 mapping, R2* mapping, intravoxel incoherent motion imaging, and diffusion-weighted imaging. One-way analyses of variance were used to compare MRI parameters among groups. Correlations of MRI parameters with estimated glomerular filtration rate (eGFR) and renal IF were analyzed using age as covariates. The support vector machine (SVM) model was used to evaluate the diagnostic efficacy of multiparametric MRI. Compared to control values, renal cortical apparent diffusion coefficient (cADC), medullary ADC (mADC), cortical pure diffusion coefficient (cDt), medullary Dt (mDt), cortical shifted apparent diffusion coefficient (csADC), and medullary sADC (msADC) values gradually decreased in the mild and moderate-to-severe groups, while cortical T1 (cT1) and medullary T1 (mT1) values gradually increased. Values of cADC, mADC, cDt, mDt, cT1, mT1, csADC, and msADC were significantly associated with eGFR and IF (p < 0.001). The SVM model indicated that multiparametric MRI combining cT1 and csADC can distinguish patients with CKD from controls with high accuracy (0.84), sensitivity (0.70), and specificity (0.92) (AUC: 0.96). Multiparametric MRI combining cT1 and cADC exhibited high accuracy (0.91), sensitivity (0.95), and specificity (0.81) for evaluating IF severity (AUC: 0.96). Multiparametric MRI combining T1 mapping and diffusion imaging may be of clinical utility in non-invasive assessment of CKD and IF. This study shows that multiparametric MRI combining T1 mapping and diffusion imaging may be clinically useful in the non-invasive assessment of chronic kidney disease (CKD) and interstitial fibrosis; this could provide information for risk stratification, diagnosis, treatment, and prognosis. •Optimized MRI markers for evaluating chronic kidney disease and renal interstitial fibrosis were investigated. •Renal cortex/medullary T1 values increased as interstitial fibrosis increased; cortical shifted apparent diffusion coefficient (csADC) correlated significantly with eGFR and interstitial fibrosis. •Support vector machine (SVM) combining cortical T1 (cT1) and csADC/cADC effectively identifies chronic kidney disease and accurately predicts renal interstitial fibrosis.

Assessment of renal allograft rejection with diffusion tensor imaging.

To investigate the value of DTI in differentiation of renal allograft rejection from well-functioning stable allograft, using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values. In this prospective study, 22 transplant recipients with well-functioning stable allograft (group A) and 20 patients with renal allograft rejection (group B + C) were recruited over a period of 19 months from January 2018 to July 2019. DTI-MRI was performed in all the patients, and FA and ADC values were measured in cortical and medullary regions of the transplanted kidney. On biopsy, graft rejection was classified as acute (group B) (n = 7) and chronic graft rejection (group C) (n = 13) based on the BANNF scoring system. Statistical analysis was performed using STATA v.14.0. Statistically significant difference between group A and group B + C was noted for cortical (p < 0.001), and medullary (p = 0.003) FA values, and cortical (p = 0.020), and medullary (p = 0.046) ADC values. Cortical(p < 0.001) and Medullary(p = 0.020) FA values showed statistically significant difference between group A and group C, and cortical FA value(p = 0.012) also showed statistically significant difference between group B and group C. AUC (to differentiate between renal allograft rejection and well-functioning stable allograft) for cortical, and medullary FA values and cortical and medullary ADC values were 0.853(p < 0.001), 0.757(p = 0.004), 0.709(p = 0.021) and 0.736(p = 0.009), respectively. DTI is a promising functional MRI technique for the non-invasive assessment of renal allograft function. Diffusion parameters, such as FA and ADC values, can be useful in the differentiation of renal allograft rejection from well-functioning stable allograft.

Effectiveness of functional magnetic resonance imaging for early identification of chronic kidney disease: A systematic review and network meta-analysis

PurposeThe commonly used clinical indicators are not sensitive enough on detecting early chronic kidney disease (CKD), whether functional magnetic resonance imaging (fMRI) can be regarded as a new noninvasive method to identify early stages of CKD and even different stages remains unknown. We performed a network meta-analysis to explore the question. MethodsFive databases were searched to identify eligible articles from 2000 to 2022. The outcome indicators were imaging biomarkers of fMRI techniques, including apparent diffusion coefficient (ADC) by diffusion-weighted imaging (DWI), fractional anisotropy (FA) by diffusion tensor imaging (DTI), diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) by intravoxel incoherent motion imaging (IVIM), and apparent relaxation rate (R2*) by blood oxygen level-dependent (BOLD). ResultsA total of 21 articles with 1472 patients were included for analysis. Cortical FA, f, and R2* values in CKD stages 1–2 were found statistically different with healthy controls (mean difference (MD), −0.03, 95% confidence interval (CI) −0.05, −0.01; MD, −0.04, 95% CI −0.06, −0.02; MD, 2.22, 95% CI 0.87, 3.57, respectively), and cortical ADC values were significantly different among different CKD stages (stages 3 and 1–2: MD, −0.15, 95% CI −0.23, −0.06; stages 4–5 and 3: MD −0.27, 95% CI −0.39, −0.14). ConclusionThe results indicated fMRI techniques had great efficacy in assessing early stages and different stages of CKD, among which DTI, IVIM, and BOLD exerted great superiority in differentiating early CKD patients from the general population, while DWI showed the advantage in distinguishing different CKD stages.

Arterial spin labeling and diffusion-weighted MR imaging: quantitative assessment of renal pathological injury in chronic kidney disease.

The aim of the study was to investigate the performance of arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and clinical biomarkers in assessing renal pathological injury in CKD. Forty-five biopsy-proven CKD patients and 17 healthy volunteers underwent DWI and ASL examinations. Renal cortical blood flow (RBF) and apparent diffusion coefficient (ADC) values were acquired. Correlations between RBF, ADC, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), and pathological scores were assessed. The diagnostic efficacy of SCr, eGFR, RBF, and ADC in assessing renal pathological injury was assessed by ROC curve analysis. The cortical RBF, ADC, SCr, and eGFR were significantly correlated with the renal histology score (all p < 0.01). The AUC values of SCr, eGFR, RBF, and ADC were 0.705 (95% confidence interval (CI): 0.536-0.827), 0.718 (0.552-0.839), 0.823 (0.658-0.916), and 0.624 (0.451-0.786), respectively, in discriminating the minimal-mild renal pathological injury group (N = 30) from the control group (N = 17). The diagnostic ability of ASL was significantly higher than that of DWI (p = 0.049) and slightly but not significantly higher than that of eGFR and SCr (p = 0.151 and p = 0.129, respectively). When compared with that of eGFR, the sensitivity of ASL in detecting early renal injury increased from 50 to 70% (p = 0.014). However, in differentiating between the minimal-mild and moderate-severe renal injury groups (N = 15), there was no significant difference in diagnostic ability among the four parameters (all p > 0.05). ASL is practicable for noninvasive evaluation of renal pathology, especially for predicting early renal pathological injury in CKD patients.

Evaluation of interstitial fibrosis in chronic kidney disease by multiparametric functional MRI and histopathologic analysis.

To investigate the diagnostic value of functional MRI to assess renal interstitial fibrosis in patients with chronic kidney disease (CKD). We prospectively recruited 80 CKD patients who underwent renal biopsies and 16 healthy volunteers to undergo multiparametric functional MRI examinations. The Oxford MEST-C classification was used to score the interstitial fibrosis. The diagnostic performance of functional MRI to discriminate interstitial fibrosis was evaluated by calculating the area under the receiver operating characteristic (ROC) curves. IgA nephropathy (60%) accounted for the majority of pathologic type in the CKD patients. Apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) was correlated with interstitial fibrosis (rho = -0.73). Decreased renal blood flow (RBF) derived from arterial spin labeling (rho = -0.78) and decreased perfusion fraction (f) derived from DWI (rho = -0.70) were accompanied by increased interstitial fibrosis. The T1 value from T1 mapping correlated with interstitial fibrosis (rho = 0.67) (all p < 0.01). The areas under the ROC curve for the discrimination of ≤ 25% vs. > 25% and ≤ 50% vs. > 50% interstitial fibrosis were 0.87 (95% confidence interval, 0.78 to 0.94) and 0.93 (0.86 to 0.98) by ADC, 0.84 (0.74 to 0.91) and 0.94 (0.86 to 0.98) by f, 0.93 (0.85 to 0.98) and 0.90 (0.82 to 0.96) by RBF, and 0.91 (0.83 to 0.96) and 0.77 (0.66 to 0.85) by T1, respectively. Functional MRI parameters were strongly correlated with the interstitial fibrosis of CKD. Therefore, it might a powerful tool to assess interstitial fibrosis of CKD noninvasively. • In CKD patients, the renal cortical ADC value decreased and T1 value increased significantly compared with healthy volunteers. • Functional MRI revealed significantly decreased renal perfusion in CKD patients compared with healthy volunteers. • The renal cortical ADC, f, RBF, and T1 values were strongly correlated with the interstitial fibrosis of CKD.

Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models.

Chronic kidney disease (CKD) is common and has huge implications for health and mortality. It is aggravated by intrarenal fibrosis, but the assessment of fibrosis is limited to kidney biopsies, which carry a risk of complications and sampling errors. This calls for a noninvasive modality for diagnosing and staging intrarenal fibrosis. The current, exploratory study evaluates a multiparametric MRI protocol including sodium imaging (23 Na-MRI) to determine the opportunities within this modality to assess kidney injury as a surrogate endpoint of fibrosis. The study includes 43 pigs exposed to ischemia-reperfusion injury (IRI) or unilateral ureteral obstruction (UUO), or serving as healthy controls. Fibrosis was determined using gene expression analysis of collagen. The medulla/cortex ratio of 23 Na-MRI decreased in the injured kidney in the IRI pigs, but not in the UUO pigs (p= 0.0180, p= 0.0754). To assess the combination of MRI parameters in estimating fibrosis, we created a linear regression model consisting of the cortical apparent diffusion coefficient, ΔR2*, ΔT1, the 23 Na medulla/cortex ratio, and plasma creatinine (R2 =0.8009, p= 0.0117). The 23 Na medulla/cortex ratio only slightly improved the fibrosis prediction model, leaving 23 Na-MRI in an ambiguous place for evaluation of intrarenal fibrosis. Use of multiparametric MRI in combination with plasma creatinine shows potential for the estimation of fibrosis in human kidney disease, but more translational and clinical work is warranted before MRI can contribute to earlier diagnosis and evaluation of treatment for acute kidney injury and CKD.

Magnetic Resonance Spectroscopy of Hypoxic-Ischemic Encephalopathy After Cardiac Arrest.

To correlate brain metabolites with clinical outcome using magnetic resonance spectroscopy (MRS) in patients undergoing targeted temperature management (TTM) after cardiac arrest and assess their relationships to MRI and EEG variables. A prospective cohort of 50 patients was studied. The primary outcome was coma recovery to follow commands. Comparison of MRS measures in the posterior cingulate gyrus, parietal white matter, basal ganglia, and brainstem were also made to 25 normative controls. Fourteen of 50 patients achieved coma recovery before hospital discharge. There was a significant decrease in total N-acetylaspartate (NAA/Cr) and an increase in lactate/creatine (Lac/Cr) in patients who did not recover, with changes most prominent in the posterior cingulate gyrus. Patients who recovered had decrease in NAA/Cr as compared to controls. NAA/Cr had a strong monotonic relationship with MRI cortical apparent diffusion coefficient (ADC); Lac level exponentially increased with decreasing ADC. EEG suppression/burst suppression was strongly associated with Lac elevation. NAA and Lac changes are associated with clinical/MRI/EEG changes consistent with hypoxic-ischemic encephalopathy (HIE) and are most prominent in the posterior cingulate gyrus. NAA/Cr decrease observed in patients with good outcomes suggests mild HIE in patients asymptomatic at hospital discharge. The appearance of cortical Lac represents a deterioration of aerobic energy metabolism and is associated with EEG background suppression, synaptic transmission failure, and severe, potentially irreversible HIE. This study provides Class IV evidence that in patients undergoing TTM after cardiac arrest, brain MRS-determined decrease in total NAA/Cr and an increase in Lac/Cr are associated with an increased risk of not recovering.

Study of renal parenchymal changes by diffusion tensor imaging in diabetic nephropathy.

PurposeTo evaluate differences in diffusion imaging parameters, including fractional anisotropy (FA) and the apparent diffusion coefficient (ADC), in control and diabetic subjects, and to assess changes in these parameters to patient’s urine albumin/protein levels, estimated glomerular filtration rate (eGFR), and glycated haemoglobin (HbA1c).Material and methodsThis is a cross-sectional analytical study involving 100 patients who underwent diffusion imaging including diffusion tensor imaging (DTI) of the kidneys in our hospital from 2019 to 2020. Diffusion imaging parameters (ADC and FA) were obtained from the medulla and cortex of both kidneys using dedicated software. Statistical analysis was done.ResultsOut of 100 subjects, 27 were controls and 73 were diabetics (19 normoalbuminuric, 23 microalbuminuric, and 31 proteinuric). The medullary FA (0.419 ± 0.024 vs. 0.346 ± 0.042), cortical FA (0.194 ± 0.035 vs. 0.303 ± 0.067), and cortical ADC (3.307 ± 0.341 vs. 2.309 ± 0.515) values showed significant differences between controls and diabetics. Medullary FA and cortical ADC values showed a decreasing trend with an increasing amount of albumin/protein in the urine, decreasing renal function (reducing eGFR), and increasing HbA1c, whereas the trend was opposite for cortical FA. In addition, on ROC curve analysis a cut-off value for medullary FA of 0.4 had a sensitivity of 64% and specificity of 80.95% to differentiate healthy volunteers and diabetics with normo-albuminuria.ConclusionsDTI has the potential to be a promising non-invasive test for the detection of early renal parenchymal changes in diabetic nephropathy.

Functional MRI in assessment of diabetic kidney disease in people with type 1 diabetes

AimsTo compare levels of renal hypoxia measured by Blood Oxygen Level Dependent (BOLD) magnetic resonance imaging (MRI) with measured transverse relaxation rate (R2*) and renal structural changes including apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in patients with type 1 diabetes and healthy controls. MethodsCohort study comparing MRI metrics in type 1 diabetes (n = 32, GFR 105 (77, 120) ml/min.1.73m2) and controls (n = 10). Renal function and selected inflammatory renal biomarkers were also measured. ResultsFor BOLD, we found reduced cortical [14.7 (13.7,15.8) (1/s) vs 15.7 (15.1,16.6) (1/s), p < 0.001] and medullary [24.8 (21.8,28.2) (1/s) vs. 29.3 (24.3,32.4) (1/s), p < 0.001] R2*, indicating more oxygenated parenchyma, in type 1 diabetes vs. controls, respectively. We observed reduced cortical FA, indicating decreased structural integrity in type 1 diabetes −0.04 (−0.07, −0.01), (p = 0.02). We found reduced cortical ADC, reflecting reduced water diffusion, in non-hyperfiltering [2.40 (2.29,2.53) (103mm2/s)] versus hyperfiltering [2.61 (2.53,2.74) (103mm2/s)] type 1 diabetes patients. MRI parameters correlated with renal function and inflammatory renal biomarkers. ConclusionsMRI derived indices of renal function and structure differed between (i) type 1 diabetes and healthy controls, and (ii) between non-hyperfiltering and hyperfiltering type 1 diabetes patients, providing insight into the role of hypoxia and renal structural, and functional changes in DKD.

Post‐Resuscitation Neuroinflammation in a Porcine Model of Cardiac Arrest: Effect of Systemic Allogeneic Mesenchymal Stem Cell Therapy

Objective Although advances in cardiopulmonary resuscitation (CPR) have increased the likelihood of achieving return of spontaneous circulation (ROSC) after cardiac arrest (CA), >50% of initially resuscitated patients die before hospital discharge. Based on emerging evidence that a systemic inflammatory response exacerbates post-ROSC injury, we recently tested the efficacy of allogeneic mesenchymal stem cell (MSC) administration early after ROSC in a porcine model of CA. Initial results indicate that MSCs attenuate post-ROSC cardiac dysfunction, but it is unclear if these protective effects extend to the brain. Accordingly, the objective of this study was to determine if systemic allogeneic MSCs reduce post-resuscitation neuroinflammation in swine. Methods Swine (n=33) were subjected to 10 min CA followed by mechanical CPR with defibrillation and intravenous epinephrine (EPI; 0.015 mg/kg). Animals that achieved ROSC (n=19) were blindly randomized to intra-arterial saline (n=9) or allogeneic bone marrow-derived MSCs (55±2 x 106; n=10) 30 min post-ROSC. Serial blood sampling was performed for 4 hours post-ROSC to quantify circulating leukocytes and inflammatory cytokines (IL-6, TNF-α, CRP), after which animals underwent diffusion-weighted brain MRI (DWI) to assess cytotoxic edema via apparent diffusion coefficient (ADC) mapping. Five hours post-ROSC, brain tissue samples were collected from the frontal cortex and hippocampus for quantification of inflammatory gene expression via RT-PCR. Gene expression data were normalized to ß-2 microglobulin and compared to results from healthy control swine (n=8). Results Following ROSC, we observed a significant ~3-fold increase in circulating neutrophils and monocytes that was similar between treatment groups (A). Plasma concentrations of inflammatory cytokines also increased post-ROSC and did not differ significantly between groups, although MSCs tended to attenuate the rise in circulating IL-6 (p=0.09; B). A significant ~2-4-fold increase in inflammatory gene expression was observed in the frontal cortex and hippocampus in both CA groups compared with healthy controls, without notable differences between treatment groups (C). DWI showed significantly lower cortical ADC values in saline-treated animals (736±32 x106 mm2/s) vs. normal controls (809±24 x106 mm2/s), consistent with cytotoxic edema. In contrast, cortical ADC values in MSC-treated animals (791±20 x106 mm2/s) did not differ vs. controls (p=0.52). However, between-group differences were not observed in the hippocampus or when ADC thresholds were applied across the entire brain. Conclusions Despite favorable effects on the heart, systemic allogeneic MSC therapy after resuscitation from CA does not significantly affect multiple parameters of neuroinflammation within the first several hours post-ROSC. Although these findings should be confirmed after a longer follow-up duration, the present results suggest that alternative neuroprotective interventions may be necessary to reduce brain inflammation and injury after resuscitation from CA.

Assessment of chronic allograft injury in renal transplantation using diffusional kurtosis imaging

BackgroundChronic allograft injury (CAI) is a significant reason for which many grafts were lost. The study was conducted to assess the usefulness of diffusional kurtosis imaging (DKI) technology in the non-invasive assessment of CAI.MethodsBetween February 2019 and October 2019, 110 renal allograft recipients were included to analyze relevant DKI parameters. According to estimated glomerular filtration rate (eGFR) (mL/min/ 1.73 m2) level, they were divided to 3 groups: group 1, eGFR ≥ 60 (n = 10); group 2, eGFR 30–60 (n = 69); group 3, eGFR < 30 (n = 31). We performed DKI on a clinical 3T magnetic resonance imaging system. We measured the area of interest to determine the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) of the renal cortex and medulla. We performed a Pearson correlation analysis to determine the relationship between eGFR and the DKI parameters. We used the receiver operating characteristic curve to estimate the predicted values of DKI parameters in the CAI evaluation. We randomly selected five patients from group 2 for biopsy to confirm CAI.ResultsWith the increase of creatinine, ADC, and MD of the cortex and medulla decrease, MK of the cortex and medulla gradually increase. Among the three different eGFR groups, significant differences were found in cortical and medullary MK (P = 0.039, P < 0.001, P < 0.001, respectively). Cortical and medullary ADC and MD are negatively correlated with eGFR (r = − 0.49, − 0.44, − 0.57, − 0.57, respectively; P < 0.001), while cortical and medullary MK are positively correlated with eGFR (r = 0.42, 0.38; P < 0.001). When 0.491 was set as the cutoff value, MK's CAI assessment showed 87% sensitivity and 100% specificity. All five patients randomly selected for biopsy from the second group confirmed glomerulosclerosis and tubular atrophy/interstitial fibrosis.ConclusionThe DKI technique is related to eGFR as allograft injury progresses and is expected to become a potential non-invasive method for evaluating CAI.

Detection of renal allograft fibrosis with MRI: arterial spin labeling outperforms reduced field-of-view IVIM.

To compare the value of reduced field-of-view (FOV) intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and arterial spin labeling (ASL) for assessing renal allograft fibrosis and predicting long-term dysfunction. This prospective study included 175 renal transplant recipients undergoing reduced FOV IVIM DWI, ASL, and biopsies. Renal allograft fibrosis was categorized into ci0, ci1, ci2, and ci3 fibrosis according to biopsy results. A total of 83 participants followed for a median of 39 (IQR, 21-42) months were dichotomized into stable and impaired allograft function groups based on follow-up estimated glomerular filtration rate. Total apparent diffusion coefficient (ADCT), pure diffusion ADC, pseudo-perfusion ADC, perfusion fraction f from IVIM DWI, and renal blood flow (RBF) from ASL were calculated and compared. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic and predictive performances. RBF was different in ci0 vs ci1 (147.9 ± 46.3 vs 126.0 ± 49.4 ml/min/100 g, p = .02) and ci2 vs ci3 (92.9 ± 46.9 vs 70.8 ± 37.8 ml/min/100 g, p = .03). RBF in the stable group was higher than that in the impaired group (144.73 ± 49.33 vs 102.19 ± 47.58 ml/min/100 g, p < .001). AUCs in distinguishing renal allograft fibrosis and predicting long-term allograft dysfunction for RBF were higher than cortical ADCT (ci0 vs ci1-3, 0.76 vs 0.59, p < .001; ci0-1 vs ci2-3, 0.79 vs 0.68, p = .01; ci0-2 vs ci3, 0.79 vs 0.68, p = .01; 0.76 vs 0.60, p = .04, respectively). Compared to reduced FOV IVIM DWI, ASL was a more promising technique for noninvasively distinguishing renal allograft fibrosis degree and predicting long-term allograft dysfunction. • Compared to total ADC from rFOV IVIM DWI, RBF from ASL can distinguish no fibrosis (ci0) vs mild fibrosis (ci1) (p = .02) and moderate fibrosis (ci2) vs severe fibrosis (ci3) (p = .04). • RBF had superior performance than diffusion parameters in discriminating fibrosis (no fibrosis [ci0] vs fibrosis [ci1-3], mild fibrosis [ci0-1] vs moderate to severe fibrosis [ci2-3], non-severe [ci0-2] vs severe [ci3] fibrosis; AUC = 0.76 vs 0.59, p < .001; 0.79 vs 0.68, p = .01; 0.79 vs 0.68, p = .01). • Compared to reduced FOV IVIM DWI, ASL was a more promising technique for noninvasively predicting long-term allograft dysfunction (AUC = 0.76 vs 0.60, p = .04).

Pathological assessment of chronic kidney disease with DWI: Is there an added value for diffusion kurtosis imaging?

Chronic kidney disease (CKD) is a worldwide health problem, precise functional and pathological assessment is beneficial to better treatment. Diffusion kurtosis imaging (DKI) can evaluate non-Gaussian diffusion and may help to assess renal pathology and function. To assess pathological and functional alterations in CKD using DKI compared with diffusion-weighted imaging (DWI). Prospective study. 70 CKD patients and 20 healthy volunteers. 1.5 T. All participants underwent DKI, and apparent diffusion coefficient (ADC), mean diffusivity (MD), and mean kurtosis (MK) of renal parenchyma were acquired. Correlation between renal parenchymal ADC, MD, MK, and estimated glomerular filtration rate (eGFR), pathological scores were assessed. The diagnostic efficacy of ADC, MD, and MK for assessing the degree of renal pathological injury were compared. ANOVA, Spearman correlation analysis, and ROC curve analysis. The cortical ADC, MD were significantly higher than medulla for all participants, whereas medullary MK was significantly higher than cortex (P < 0.01). Whether eGFR reduced or not, renal parenchymal MK were significantly higher in patients than controls (P < 0.05). Positive correlation was found between eGFR and ADC (cortex, r=0.562; medulla, r=0.527), and negative correlation between eGFR and MK (cortex, r=-0.786; medulla, r=-0.709) (all P < 0.001). There was positive correlation between MK and glomerular injury (cortex, r=0.681; medulla, r=0.652), tubulointerstitial lesion (cortex, r=0.650; medulla, r=0.599) (all P < 0.001). For discrimination between mild and m-s renal injury group, the AUC values of ADC, MD, MK were cortex: 0.723, 0.655, 0.864 and medulla: 0.718, 0.581, 0.829. The AUC values of ADC, MD, MK were cortex: 0.708, 0.679, 0.770 and medulla: 0.713, 0.830, 0.780 for differentiating control group from mild renal injury group. DKI is practicable for noninvasive assessment of renal pathology and function of CKD, DKI offer better diagnostic performance than DWI. Evidence Level 1 Technical Efficacy 2.

Diffusion Tensor Imaging in early prediction of renal fibrosis in patients with renal disease: Functional and histopathological correlations.

Renal fibrosis (RF) is a well-known marker of chronic kidney disease (CKD) progression. However, renal biopsy is an available tool for evaluation of RF, non-invasive tools are needed not only to detect but also to monitor the progression of fibrosis. The aim of this study is to evaluate the role of diffusion tensor imaging (DTI) in the assessment of renal dysfunction and RF in patients with renal disease. Fifty-six patients with renal disorders and 22 healthy controls were recruited. All participants underwent DTI. Renal biopsy was performed for all patients. Mean renal medullary and cortical fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were compared between patients and healthy controls and correlated to serum creatinine (SCr), estimated glomerular filtration rate (eGFR), 24-h urinary protein (24h-UPRO) and renal histopathological scores. Cortical FA values were significantly higher (P=.001), while cortical ADC values were significantly lower in the patients' group (P=.002). Cortical FA values positively correlated to SCr (P=.006) and negatively correlated to eGFR (P=.03), while cortical ADC negatively correlated to percentage of sclerotic glomeruli, atrophic tubules and interstitial fibrosis (P=.001 for all variables). Medullary ADC negatively correlated to tubular atrophy (P=.02). The diagnostic performance of DTI for detecting RF was supported by ROC curve. Multiple linear regression analysis revealed that the mean cortex ADC was significantly decreased by 0.199mg/dL for patients with >50% glomerulosclerosis in renal biopsy. DTI appears to represent a valuable tool for the non-invasive assessment of renal dysfunction and renal fibrosis.