Diffusion-Weighted MRI in the Genitourinary System.

Diffusion weighted imaging (DWI) constitutes a major functional parameter performed in Magnetic Resonance Imaging (MRI). The DW sequence is performed by acquiring a set of native images described by their b-values, each b-value representing the strength of the diffusion MR gradients specific to that sequence. By fitting the data with models describing the motion of water in tissue, an apparent diffusion coefficient (ADC) map is built and allows the assessment of water mobility inside the tissue. The high cellularity of tumors restricts the water diffusion and decreases the value of ADC within tumors, which makes them appear hypointense on ADC maps. The role of this sequence now largely exceeds its first clinical apparitions in neuroimaging, whereby the method helped diagnose the early phases of cerebral ischemic stroke. The applications extend to whole-body imaging for both neoplastic and non-neoplastic diseases. This review emphasizes the integration of DWI in the genitourinary system imaging by outlining the sequence's usage in female pelvis, prostate, bladder, penis, testis and kidney MRI. In gynecologic imaging, DWI is an essential sequence for the characterization of cervix tumors and endometrial carcinomas, as well as to differentiate between leiomyosarcoma and benign leiomyoma of the uterus. In ovarian epithelial neoplasms, DWI provides key information for the characterization of solid components in heterogeneous complex ovarian masses. In prostate imaging, DWI became an essential part of multi-parametric Magnetic Resonance Imaging (mpMRI) to detect prostate cancer. The Prostate Imaging-Reporting and Data System (PI-RADS) scoring the probability of significant prostate tumors has significantly contributed to this success. Its contribution has established mpMRI as a mandatory examination for the planning of prostate biopsies and radical prostatectomy. Following a similar approach, DWI was included in multiparametric protocols for the bladder and the testis. In renal imaging, DWI is not able to robustly differentiate between malignant and benign renal tumors but may be helpful to characterize tumor subtypes, including clear-cell and non-clear-cell renal carcinomas or low-fat angiomyolipomas. One of the most promising developments of renal DWI is the estimation of renal fibrosis in chronic kidney disease (CKD) patients. In conclusion, DWI constitutes a major advancement in genitourinary imaging with a central role in decision algorithms in the female pelvis and prostate cancer, now allowing promising applications in renal imaging or in the bladder and testicular mpMRI.

[Acute interstitial nephritis: clinical presentation and diagnosis]. / Néphrite interstitielle aiguë : quand la suspecter et quelle prise en charge ?

Acute interstitial nephritis is characterized by renal inflammation and interstitial edema. The clinical presentation is pauci-symptomatic and often non-specific. Acute interstitial nephritis typically presents with acute renal failure, alone or with fever, eosinophilia, hematuria, sterile pyuria and small range proteinuria. An early diagnosis is crucial to prevent the morbidity and mortality associated with renal function decline. The most frequent etiology of this disease is drug-induced. A kidney biopsy is not systematically required to establish the diagnosis. It should be considered in the absence of renal function improvement 5 to 7 days after withdrawal of the causal agent. Although the benefits of glucocorticoid treatment have not been proven to date, its use may be associated with a better kidney function recovery.

La néphrite interstitielle aiguë est caractérisée par une inflammation dans le compartiment interstitiel rénal. La présentation clinique est paucisymptomatique. Elle se présente généralement par une insuffisance rénale aiguë qui peut être accompagnée de fièvre, d'éosinophilie, d'hématurie, de leucocyturie stérile et de protéinurie non néphrotique. Son diagnostic précoce est crucial pour prévenir la morbi-mortalité liée au déclin de la fonction rénale. L'étiologie la plus fréquente est médicamenteuse. Le diagnostic par la ponction-biopsie rénale n'est pas systématique, mais doit être considéré en l'absence d'amélioration de la fonction rénale 5 à 7 jours après l'arrêt de la substance incriminée. Le principal traitement consiste en l'interruption du médicament incriminé et à l'administration de corticostéroïdes.

Diffusion-magnetic resonance imaging predicts decline of kidney function in chronic kidney disease and in patients with a kidney allograft.

Kidney cortical interstitial fibrosis is highly predictive of kidney prognosis and is currently assessed by evaluation of a biopsy. Diffusion-weighted magnetic resonance imaging is a promising non-invasive tool to evaluate kidney fibrosis. We recently adapted diffusion-weighted imaging sequence for discrimination between the kidney cortex and medulla and found that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) correlated with histological interstitial fibrosis. Here, we assessed whether ΔADC as measured with diffusion-weighted magnetic resonance imaging is predictive of kidney function decline and dialysis initiation in chronic kidney disease (CKD) and patients with a kidney allograft in a prospective study encompassing 197 patients. We measured ΔADC in 43 patients with CKD (estimated GFR (eGFR) 55ml/min/1.73m2) and 154 patients with a kidney allograft (eGFR 53ml/min/1.73m2). Patients underwent a kidney biopsy and diffusion-weighted magnetic resonance imaging within one week of biopsy; median follow-up of 2.2 years with measured laboratory parameters. The primary outcome was a rapid decline of kidney function (eGFR decline over 30% or dialysis initiation) during follow up. Significantly, patients with a negative ΔADC had 5.4 times more risk of rapid decline of kidney function or dialysis (95% confidence interval: 2.29-12.58). After correction for kidney function at baseline and proteinuria, low ADC still predicted significant kidney function loss with a hazard ratio of 4.62 (95% confidence interval 1.56-13.67) independent of baseline age, sex, eGFR and proteinuria. Thus, low ΔADC can be a predictor of kidney function decline and dialysis initiation in patients with native kidney disease or kidney allograft, independent of baseline kidney function and proteinuria.

Kinetic GFR Outperforms CKD-EPI for Slow Graft Function Prediction in the Immediate Postoperative Period Following Kidney Transplantation.

BACKGROUND: Rapid identification of patients at high risk for slow graft function (SGF) is of major importance in the immediate period following renal graft transplantation, both for early therapeutic decisions and long-term prognosis. Due to the high variability of serum creatinine levels after surgery, glomerular filtration rate (GFR) estimation is challenging. In this situation, kinetic estimated GFR (KeGFR) equations are interesting tools but have never been assessed for the identification of SGF patients. METHODS: We conducted a single-center retrospective cohort study, including all consecutive kidney allograft recipients in the University Hospitals of Geneva from 2008 to 2016. GFR was estimated using both CKD-EPI and KeGFR formulae. Their accuracies for SGF prediction were compared. Patients were followed up for one year after transplantation. RESULTS: A total of 326 kidney recipients were analyzed. SGF occurred in 76 (23%) patients. KeGFR estimation stabilized from the day following kidney transplantation, more rapidly than CKD-EPI. Discrimination ability for SGF prediction was better for KeGFR than CKD-EPI (AUC 0.82 and 0.66, p < 0.001, respectively). CONCLUSION: KeGFR computed from the first day after renal transplantation was able to predict SGF with good discrimination, outperforming CKD-EPI estimation. SGF patients had lower renal graft function overall at the one-year follow up.

Validation of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for kidney fibrosis detection: a cross-sectional study.

BACKGROUND: Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis. METHODS: This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment. RESULTS: Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity. CONCLUSION: ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF.

Diagnosis and assessment of renal fibrosis: the state of the art.

Chronic kidney disease (CKD) is defined as an alteration of kidney function and/or structure lasting for more than 3 months and is a major public health issue. Histologically, the severity of CKD correlates with the magnitude of kidney cortical interstitial fibrosis. Estimation of kidney fibrosis is crucial to assess prognosis and guide therapy in both native and allograft kidneys. Biopsy is currently the gold standard for assessing fibrosis with histological techniques. Although this procedure has become safer over recent years, complications and limitations remain. Given these restrictions, new, noninvasive techniques are necessary for the evaluation and follow-up of CKD patients. Radiological methods such as ultrasound and magnetic resonance imaging are emerging for assessment kidney fibrosis. These two techniques have advantages but also limitations. In addition to radiological assessment of fibrosis, urinary and plasma biomarkers are being developed and tested as predictive tools for histological lesions in the kidney. This article reviews the current evidence for these novel techniques in the evaluation of kidney interstitial fibrosis.

Comparison of readout-segmented and conventional single-shot for echo-planar diffusion-weighted imaging in the assessment of kidney interstitial fibrosis.

PURPOSE: To compare readout-segmented echo-planar imaging (EPI) (RESOLVE) to single-shot EPI (ss-EPI) diffusion-weighted imaging (DWI) for the assessment of renal interstitial fibrosis. MATERIALS AND METHODS: A phantom, eight healthy volunteers (under 30 years to avoid age-fibrosis related) and 27 chronic kidney disease (CKD) patients (scheduled for kidney biopsy) were scanned (at 3T) with ss-EPI and 5-shot RESOLVE DWI (resolution: 2 × 2 × 5 mm3 , 10 b-values). The cortico-medullary difference for each DW parameter from a monoexponential fit (ΔADC) or, segmented biexponential fit (ΔD, ΔD*, ΔFp ) were compared between both sequences. A fibrosis threshold of 40% was defined to separate all 35 subjects into low and high fibrosis groups. The linear relationship between DW parameters and percentage fibrosis (up to 80%) from Masson trichrome was assessed with the Pearson product-moment correlation coefficient. Fisher Z-transform was used for R2 correlation comparison. RESULTS: A coefficient of variation between ADCs of 3% was measured between both sequences in the phantom. In healthy volunteers, no significant difference was measured for all DW parameters. Both sequences separated low to high level of fibrosis with a significant decrease of ΔADC (RESOLVE P = 3.1 × 10-6 , ss-EPI P = 0.003) and ΔD (RESOLVE P = 8.2 × 10-5 , ss-EPI P = 0.02) in the high level of fibrosis. However, RESOLVE ΔADC had a stronger negative correlation (P = 0.04 for R2 comparison) with fibrosis than ss-EPI ΔADC (RESOLVE R2 = 0.65, P = 5.9 × 10-9 , ss-EPI R2 = 0.29, P = 8.9 × 10-4 ). ΔD (RESOLVE) was correlated (moderately) with fibrosis (R2 = 0.29, P = 9.2 × 10-4 ); however, ΔD* and ΔFp did not show, in our population, a significant correlation with interstitial fibrosis (0.01 < R2 < 0.08). CONCLUSION: ΔADC derived from both sequences correlated with fibrosis. ΔADC from RESOLVE showed better correlation with fibrosis than ΔADC from ss-EPI and therefore has potential to monitor CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1631-1640.

Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients.

Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

Living kidney donation does not adversely affect serum calcification propensity and markers of vascular stiffness.

Living kidney donors (LKDs) experience a decline in glomerular filtration rate (GFR) after donation. Calcification propensity (T50 ) can be determined by a blood test predicting all-cause mortality in patients with chronic kidney disease. We studied the impact of kidney donation on T50 and markers of arterial stiffness. We analyzed T50 prospectively before and 1 year after kidney donation in 21 LKDs along with fetuin-A, mineral metabolism markers, kidney length, pulse wave velocity (PWV), augmentation index (AI), and renal resistive index (RRI) as markers of arterial stiffness. We studied the impact of kidney donation on these parameters. LKDs were 54 ± 10 years old and had a GFR of 101 ± 18 ml/min/1.73 m(2) before donation, decreasing to 67 ± 8 ml/min/1.73 m(2) after donation (P < 0.001). Despite this, T50 improved after donation (290 ± 53 to 312 ± 38 min, P = 0.049). This change was inversely related to plasma phosphate (P = 0.03), which declined after donation (P = 0.002). Fetuin-A levels increased after donation (P = 0.01). Upon donation, the length of the remaining kidney increased (P < 0.001) while PWV, AI, and RRI remained unchanged. Calcification propensity was not adversely affected by kidney donation. This indicates that T50 is independent from GFR in LKDs and that kidney donation does neither worsen calcification propensity nor markers of vascular stiffness at 1 year.