Isky Gordon

How accurate is dynamic contrast-enhanced MRI in the assessment of renal glomerular filtration rate? A critical appraisal

To evaluate the current literature to see if the published results of MRI‐glomerular filtration rate (GFR) stand up to the claim that MRI‐GFR may be used in clinical practice. Claims in the current literature that Gadolinium (Gd) DTPA dynamic contrast enhanced (DCE) MRI clearance provides a reliable estimate of glomerular filtration are an overoptimistic interpretation of the results obtained. Before calculating absolute GFR from Gd‐enhanced MRI, numerous variables must be considered.

Improvement of MRI-Functional measurement with automatic movement correction in native and transplanted kidneys

To improve 2D software for motion correction of renal dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and to evaluate its effect using the Patlak–Rutland model.

Reproducibility of the aortic input function (AIF) derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the kidneys in a volunteer study

PURPOSEnThe aim of this study was to investigate the maximum height, area under the curve (AUC) and full width at half maximum (FWHM) of the aortic input function (AIF) in renal dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) studies. We evaluated the significance of choice of size for regions of interest (ROI) in the aorta, reproducibility and inter-observer agreement of AIF measurements in healthy volunteers for renal DCE-MRI studies.nnnMETHODSnFifteen healthy volunteers (nine males, six females), mean age 28.8 years (range 23-36 years), underwent two DCE-MRI kidney studies under similar conditions. Oblique-coronal DCE-MRI data volumes were acquired on a 1.5 T Siemens Avanto scanner with a 3D-FLASH pulse-sequence (TE/TR=0.53/1.63 ms, flip angle=17 degrees, acquisition matrix=128 x 104 voxels, strong fat saturation, PAT factor=2 (GRAPPA) and 400 mm x 325 mm FOV). Each dynamic dataset consisted of 18 slices of 7.5 mm thickness (no gap) and an in-plane resolution of 3.1 mm x 3.1 mm, acquired every 2.5 s for >5 min. During the MR scan a dose of 0.05 mmol (0.1 mL) kg(-1) body weight of dimeglumine gadopentetate (Magnevist) was injected intravenously (2 mL s(-1) injection rate), followed by a 15 mL saline flush at the same rate, using a MR-compatible automated injector (Spectris). For each DCE-MRI study two observers each drew two ROIs in the abdominal aorta. Both ROIs were 3 voxels in width and had the same inferior limit (just above the emergence of the renal arteries from the aorta) but had different heights (4 voxels for one ROI and 10 voxels for the other). The dimensions, position and time of drawing the ROIs in the dynamic study were standardised between observers prior to data analysis. Mean signal intensities measured in the ROIs were plotted over time, representing the AIF. For each study, AIF 1 was derived from ROI 1 and AIF 2 was derived from ROI 2.nnnRESULTS AND CONCLUSIONnPaired t-tests for inter-observer comparison on the pooled 30 DCE-MRI studies, showed good correlations (correlation coefficients >0.85) with no significant differences (p-values >0.82) when comparing the peak value, AUC and FWHM of the AIFs. Thus the results were operator independent. The size of the aortic ROIs significantly affected all measured parameters of the AIF (p-values <0.039). However, correlation coefficients when comparing AIF 1 and AIF 2 were high for all evaluated AIF parameters (correlation coefficients >0.88), indicating a similar shape and temporal dynamic of the passage of the contrast agent through the aorta. When comparing the intra-individual DCE-MRI studies for each volunteer all AIF parameters had p-values >0.22 and correlation coefficients <0.82, with the exception of the FWHM, which had a correlation coefficient of 0.96 showing a significant variation in AIF parameters in the same volunteer on different days.

The importance of AIF ROI selection in DCE-MRI renography: reproducibility and variability of renal perfusion and filtration.

PURPOSEnThe aim of this study was to investigate (a) the effect the choice of the region of interest (ROI) defining the aortic input function (AIF) has on the estimation of renal perfusion and filtration in dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) renography, and (b) the reproducibility of these parameters. Using renal DCE-MRI and a three-compartment model analysis, this work evaluated the effect two different AIFs, derived from variable sized ROIs in the aorta, has on calculating DCE-MRI renal perfusion and filtration values in a group of healthy adult volunteers who underwent two consecutive renal DCE-MRI studies.nnnMETHODSnFifteen healthy volunteers underwent two DCE-MRI studies under similar physiological conditions. Oblique-coronal DCE-MRI data volumes were acquired on a 1.5 T Siemens Avanto scanner with a 3D-FLASH pulse-sequence (TE/TR=0.53/1.63 ms, flip angle=17 degrees , acquisition matrix=128 x 104 voxels, strong fat saturation, PAT factor=2 (GRAPPA) and 400 mm x 325 mm FOV). Each dynamic dataset consisted of 18 slices of 7.5mm thickness (no gap) and an in-plane resolution of 3.1 mm x 3.1mm, acquired every 2.5s for not less than 5 minutes. During the MR scan a dose of 0.05 m mol (0.1 mL)kg(-1) body weight of dimeglumine gadopentetate (Magnevist) was injected intravenously (2 mLs(-1) injection rate), followed by a 15 mL saline flush at the same rate, using a MR-compatible automated injector (Spectris). Two AIFs were defined for each volunteer by drawing two ROIs in the aorta for each study. Renal perfusion and glomerular filtration rate (GFR) values were then calculated for each of the AIFs using a modified Tofts Renal Model (TRM). Both renal perfusion and GFR were expressed in mL min(-1)100 mL(-1) of tissue.nnnRESULTS AND CONCLUSIONnInter-individual reproducibility tests for renal perfusion and glomerular filtration rate showed that the size of AIF ROIs significantly affects calculated values of perfusion and GFR (p-values <0.02). No significant differences were observed when comparing perfusion and GFR values in the same volunteer between scans performed on different days (p-values >0.22). From our study we conclude that while DCE-MRI derived indices of renal function are reproducible in the same individual when imaged on different days, the size of the aortic ROI and hence the AIF has a significant influence on calculated renal perfusion and GFR values. Currently there is no accepted standard for drawing the aortic ROI and no standardized approach for the AIF definition in renal DCE-MRI studies.

Repeatability of renal arterial spin labelling MRI in healthy subjects

ObjectArterial spin labelling (ASL) can be used to measure renal perfusion non-invasively. The aim of this study was to determine the repeatability of this technique in healthy kidneys to vindicate its use in clinic.Materials and methodsTwo groups of healthy volunteers were imaged two different days to assess intra- and inter-session repeatability. Oblique-coronal data volumes were acquired on a 1.5 T scanner with a dedicated abdominal 32-channel body phased array coil. ASL was performed using a multi-TI FAIR labelling scheme and 3D GRASE imaging module. Background suppression and respiratory triggering were used. T1 maps of the kidney were acquired using the same sequence with background suppression disabled.ResultsFor the group with multiple intra-session ASL measurements, the average cortical perfusion was 197xa0mL min−1100xa0g−1 and average cortical T1 was 1265xa0ms. For both perfusion and T1 the variation shown by the within-subject standard deviation (SDws) (14.6xa0mL min−1100xa0g−1 and 33.4xa0ms) and coefficient of variation (CVws) (7.52 and 2.69%, respectively) was small for all the analyses carried out. Bland–Altman plots were also used to visualise the variation between the same parameters collected from the different scanning sessions in both groups, and demonstrated good reproducibility.ConclusionWe have shown that in healthy volunteers, ASL parameters are repeatable over a short and long period. This supports the overall aim of using ASL in the clinic to assess longitudinal renal perfusion changes in patients.

Comparison of ASL and DCE MRI for the non-invasive measurement of renal blood flow: quantification and reproducibility

AbstractObjectivesTo investigate the reproducibility of arterial spin labelling (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and quantitatively compare these techniques for the measurement of renal blood flow (RBF).MethodsSixteen healthy volunteers were examined on two different occasions. ASL was performed using a multi-TI FAIR labelling scheme with a segmented 3D-GRASE imaging module. DCE MRI was performed using a 3D-FLASH pulse sequence. A Bland-Altman analysis was used to assess repeatability of each technique, and determine the degree of correspondence between the two methods.ResultsThe overall mean cortical renal blood flow (RBF) of the ASL group was 263u2009±u200941xa0mlxa0min−1 [100xa0ml tissue]−1, and using DCE MRI was 287u2009±u200970xa0mlxa0min−1 [100xa0ml tissue]−1. The group coefficient of variation (CVg) was 18xa0% for ASL and 28xa0% for DCE-MRI. Repeatability studies showed that ASL was more reproducible than DCE with CVgs of 16xa0% and 25xa0% for ASL and DCE respectively. Bland-Altman analysis comparing the two techniques showed a good agreement.ConclusionsThe repeated measures analysis shows that the ASL technique has better reproducibility than DCE-MRI. Difference analysis shows no significant difference between the RBF values of the two techniques.Key Points• Reliable non-invasive monitoring of renal blood flow is currently clinically unavailable.n • Renal arterial spin labelling MRI is robust and repeatable.n • Renal dynamic contrast-enhanced MRI is robust and repeatable.n • ASL blood flow values are similar to those obtained using DCE-MRI.

Precise measurement of renal filtration and vascular parameters using a two-compartment model for dynamic contrast-enhanced MRI of the kidney gives realistic normal values

ObjectiveTo model the uptake phase of T1-weighted DCE-MRI data in normal kidneys and to demonstrate that the fitted physiological parameters correlate with published normal values.MethodsThe model incorporates delay and broadening of the arterial vascular peak as it appears in the capillary bed, two distinct compartments for renal intravascular and extravascular Gd tracer, and uses a small-vessel haematocrit value of 24%. Four physiological parameters can be estimated: regional filtration Ktrans (mlxa0min−1 [ml tissue]−1), perfusion F (mlxa0min−1 [100xa0ml tissue]−1), blood volume vb (%) and mean residence time MRT (s). From these are found the filtration fraction (FF; %) and total GFR (mlxa0min−1). Fifteen healthy volunteers were imaged twice using oblique coronal slices every 2.5xa0s to determine the reproducibility.ResultsUsing parenchymal ROIs, group mean values for renal biomarkers all agreed with published values: Ktrans: 0.25; F: 219; vb: 34; MRT: 5.5; FF: 15; GFR: 115. Nominally cortical ROIs consistently underestimated total filtration (by ~50%). Reproducibility was 7–18%. Sensitivity analysis showed that these fitted parameters are most vulnerable to errors in the fixed parameters kidney T1, flip angle, haematocrit and relaxivity.ConclusionsThese renal biomarkers can potentially measure renal physiology in diagnosis and treatment.Key Points• Dynamic contrast-enhanced magnetic resonance imaging can measure renal function.• Filtration and perfusion values in healthy volunteers agree with published normal values.• Precision measured in healthy volunteers is between 7 and 15%.

Pilot study of F18-Fluorodeoxyglucose Positron Emission Tomography/computerised tomography in Wilms’ tumour: Correlation with conventional imaging, pathology and immunohistochemistry

Wilms tumour is the second most common paediatric solid tumour. Prognosis is good although higher stage disease carries significant mortality and treatment related morbidity. In the UK, risk stratification is based on histological response to pre-operative chemotherapy. F(18)-Fluorodeoxyglucose Positron Emission Tomography (F(18)FDG-PET) is an emerging functional imaging technique in paediatric oncology. Little is known about the relationship between F(18)FDG-PET images and the disease process of Wilms tumour. We performed F(18)FDG-PET/CT scans in seven children with Wilms tumour after induction chemotherapy, immediately before surgery. The standard uptake values (SUV) of F(18)FDG-PET/CT images were related to conventional imaging and histopathological findings. In total seven children were studied. F(18)FDG-PET/CT was consistently safely performed. All tumours showed F(18)FDG activity. Four tumours had activity with SUV/bw max >5 g/ml. Histological examination of these active areas revealed viable anaplastic Wilms tumour. Furthermore, in these four tumours GLUT-1 and Ki67 immunostaining was strongly positive. Three further tumours demonstrated lower uptake (SUV/bw max <5 g/ml), which represented areas of microscopic foci of residual viable tumour mixed with post chemotherapy change. Metastatic disease was F(18)FDG avid in two of four children with stage four diseases. In conclusion, following chemotherapy, active Wilms tumour is F(18)FDG avid and higher SUV was seen in histologically high risk disease.

Renal blood flow using arterial spin labelling MRI and calculated filtration fraction in healthy adult kidney donors Pre-nephrectomy and post-nephrectomy

AbstractObjectivesRenal plasma flow (RPF) (derived from renal blood flow, RBF) and glomerular filtration rate (GFR) allow the determination of the filtration fraction (FF), which may have a role as a non-invasive renal biomarker. This is a hypothesis-generating pilot study assessing the effect of nephrectomy on renal function in healthy kidney donors.MethodsEight living kidney donors underwent arterial spin labelling (ASL) magnetic resonance imaging (MRI) and GFR measurement prior to and 1xa0year after nephrectomy. Chromium-51 labelled ethylenediamine tetraacetic acid (51Cr-EDTA) with multi-blood sampling was undertaken and GFR calculated. The RBF and GFR obtained were used to calculate FF.ResultsAll donors showed an increase in single kidney GFR of 24 – 75 %, and all but two showed an increase in FF (−7 to +52 %) after nephrectomy. The increase in RBF, and hence RPF, post-nephrectomy was not as great as the increase in GFR in seven out of eight donors. As with any pilot study, the small number of donors and their relatively narrow age range are potential limiting factors.ConclusionsThe ability to measure RBF, and hence RPF, non-invasively, coupled with GFR measurement, allows calculation of FF, a biomarker that might provide a sensitive indicator of loss of renal reserve in potential donors.Key Points• Non-invasive MRI measured renal blood flow and calculated renal plasma flow.n • Effect of nephrectomy on blood flow and filtration in donors is presented.n • Calculated filtration fraction may be a useful new kidney biomarker.

Partial volume effects in dynamic contrast magnetic resonance renal studies

This is the first study of partial volume effect in quantifying renal function on dynamic contrast enhanced magnetic resonance imaging. Dynamic image data were acquired for a cohort of 10 healthy volunteers. Following respiratory motion correction, each voxel location was assigned a mixing vector representing the overspilling contributions of each tissue due to the convolution action of the imaging systems point spread function. This was used to recover the true intensities associated with each constituent tissue. Thus, non-renal contributions from liver, spleen and other surrounding tissues could be eliminated from the observed time-intensity curves derived from a typical renal cortical region of interest. This analysis produced a change in the early slope of the renal curve, which subsequently resulted in an enhanced glomerular filtration rate estimate. This effect was consistently observed in a Rutland-Patlak analysis of the time-intensity data: the volunteer cohort produced a partial volume effect corrected mean enhancement of 36% in relative glomerular filtration rate with a mean improvement of 7% in r(2) fitting of the Rutland-Patlak model compared to the same analysis undertaken without partial volume effect correction. This analysis strongly supports the notion that dynamic contrast enhanced magnetic resonance imaging of kidneys is substantially affected by the partial volume effect, and that this is a significant obfuscating factor in subsequent glomerular filtration rate estimation.