Jon Thacker

Evaluation of iron content in human cerebral cavernous malformation using quantitative susceptibility mapping.

ObjectivesThe aims of this study were to investigate and validate quantitative susceptibility mapping (QSM) for lesional iron quantification in cerebral cavernous malformations (CCMs). Materials and MethodsMagnetic resonance imaging studies were performed in phantoms and 16 patients on a 3-T scanner. Susceptibility weighted imaging, QSM, and R2* maps were reconstructed from in vivo data acquired with a 3-dimensional, multi-echo, and T2*-weighted gradient echo sequence. Magnetic susceptibility measurements were correlated to susceptibility weighted imaging and R2* results. In addition, iron concentrations from surgically excised CCM lesion specimens were determined using inductively coupled plasma mass spectrometry and correlated with QSM measurements. ResultsThe QSM images demonstrated excellent image quality for depicting CCM lesions in both sporadic and familial cases. Susceptibility measurements revealed a positive linear correlation with R2* values (R2 = 0.99 for total, R2 = 0.69 for mean; P < 0.01). Quantitative susceptibility mapping values of known iron-rich brain regions matched closely with those of previous studies and in interobserver consistency. A strong correlation was found between QSM and the concentration of iron phantoms (0.925; P < 0.01), as well as between QSM and mass spectroscopy estimation of iron deposition (0.999 for total iron, 0.86 for iron concentration; P < 0.01) in 18 fragments of 4 excised human CCM lesion specimens. ConclusionsThe ability of QSM to evaluate iron deposition in CCM lesions was illustrated via phantom, in vivo, and ex vivo validation studies. Quantitative susceptibility mapping may be a potential biomarker for monitoring CCM disease activity and response to treatments.

Multi-Parametric Evaluation of Chronic Kidney Disease by MRI: A Preliminary Cross-Sectional Study

Background The current clinical classification of chronic kidney disease (CKD) is not perfect and may be overestimating both the prevalence and the risk for progressive disease. Novel markers are being sought to identify those at risk of progression. This preliminary study evaluates the feasibility of magnetic resonance imaging based markers to identify early changes in CKD. Methods Fifty-nine subjects (22 healthy, 7 anemics with no renal disease, 30 subjects with CKD) participated. Data using 3D volume imaging, blood oxygenation level dependent (BOLD) and Diffusion MRI was acquired. BOLD MRI acquisition was repeated after 20 mg of iv furosemide. Results Compared to healthy subjects, those with CKD have lower renal parenchymal volumes (329.6±66.4 vs. 257.1±87.0 ml, p<0.005), higher cortical R2* values (19.7±3.2 vs. 23.2±6.3 s−1, p = 0.013) (suggesting higher levels of hypoxia) and lower response to furosemide on medullary R2* (6.9±3.3 vs. 3.1±7.5 s−1, p = 0.02). All three parameters showed significant correlation with estimated glomerular filtration rate (eGFR). When the groups were matched for age and sex, cortical R2* and kidney volume still showed significant differences between CKD and healthy controls. The most interesting observation is that a small number of subjects (8 of 29) contributed to the increase in mean value observed in CKD. The difference in cortical R2* between these subjects compared to the rest were highly significant and had a large effect size (Cohen’s d = 3.5). While highly suggestive, future studies may be necessary to verify if such higher levels of hypoxia are indicative of progressive disease. Diffusion MRI showed no differences between CKD and healthy controls. Conclusions These data demonstrate that BOLD MRI can be used to identify enhanced hypoxia associated with CKD and the preliminary observations are consistent with the chronic hypoxia model for disease progression in CKD. Longitudinal studies are warranted to further verify these findings and assess their predictive value.

Efficacy of preventive interventions for iodinated contrast-induced acute kidney injury evaluated by intrarenal oxygenation as an early marker.

ObjectiveThe objective of this study was to evaluate the effects of potential renoprotective interventions such as the administration of N-acetylcysteine (NAC; antioxidant) and furosemide (diuretic) on intrarenal oxygenation as evaluated by blood oxygen level–dependent (BOLD) magnetic resonance imaging (MRI) in combination with urinary neutrophil gelatinase–associated lipocalin (NGAL) measurements. Materials and MethodsRats received nitric oxide synthase inhibitor L-NAME (10 mg/kg) and cyclooxygenase inhibitor indomethacin (10 mg/kg) to induce the risk for developing iodinated contrast-induced acute kidney injury before receiving one of the interventions: NAC, furosemide, or placebo. One of the 3 iodinated contrast agents (iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram body weight). Fifty-four Sprague-Dawley rats were allocated in a random order into 9 groups on the basis of the intervention and the contrast agent received.Blood-oxygen-level–dependent MRI–weighted images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after L-NAME, indomethacin, interventions or placebo, and iodinated contrast agents. Data acquisition and analysis were performed in a blind fashion. R2* (=1/T2*) maps were generated inline on the scanner. A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data. Urinary NGAL, a marker of acute kidney injury, was measured at baseline, 2 and 4 hours after the contrast injection. ResultsCompared with the placebo-treated rats, those treated with furosemide showed a significantly lower rate of increase in R2* (P < 0.05) in the renal inner stripe of the outer medulla. The rats treated with NAC showed a lower rate of increase in R2* compared with the controls, but the difference did not reach statistical significance. Urinary NGAL showed little to no increase in R2* after administration of iodixanol in the rats pretreated with furosemide but demonstrated significant increase in the rats pretreated with NAC or placebo (P < 0.05). ConclusionsThis is the first study to evaluate the effects of interventions to mitigate the deleterious effects of contrast media using BOLD MRI. The rate of increase in R2* after administration of iodinated contrast is associated with acute renal injury as evaluated by NGAL. Further studies are warranted to determine the optimum dose of furosemide and NAC for mitigating the ill effects of contrast media. Because NGAL has been shown to be useful in humans to document iodinated contrast-induced acute kidney injury, the method presented in this study using BOLD MRI and NGAL measurements can be translated to humans.

Renal Blood Oxygenation Level-Dependent Magnetic Resonance Imaging: A Sensitive and Objective Analysis.

ObjectivesThe aim of this study was to determine a robust (sensitive and objective) method for analyzing renal blood oxygenation level-dependent magnetic resonance imaging data. Materials and MethodsForty-seven subjects (30 with chronic kidney disease [CKD] and 17 controls) were imaged at baseline and after furosemide with a multiecho gradient recalled echo sequence. Conventional analysis consisted of regional segmentation (small cortex, large cortex, and medulla), followed by computing the mean of each region. In addition, we segmented the entire parenchyma and computed the mean (&mgr;1) plus higher moments (&mgr;2, &mgr;3, and &mgr;4). Two raters performed each of the segmentation steps, and agreement was assessed with intraclass correlation coefficients (ICCs). We used a measure of effect size (Cohen’s d value), in addition to the usual measure of statistical significance, P values, for determining significant results. ResultsThe mean of the renal parenchyma showed the highest agreement between raters (ICC, 0.99), and the higher parenchyma moments were on par with large cortical region of interest (ROI) ICC. The renal parenchymal mean also exhibited significant sensitivity to changes after furosemide administration in healthy subjects (P = 0.002, d = 0.84), in agreement with medullary ROIs (P = 0.002, d = 1.59). When comparing controls and subjects with CKD at baseline, cortical ROI showed a significant difference (P = 0.015, d = −0.69), whereas the parenchyma ROI did not (P = 0.152, d = 0.39). Post-furosemide data in all regions resulted in a significant difference (large cortex: P = 0.026, d = −0.51; medulla: P = 0.019, d = −0.61) with the renal parenchyma ROI resulting in the largest effect size (P = 0.003, d = −0.75). Higher moments of the renal parenchyma showed similar significant differences as well. ConclusionsOverall, our data support the use of the entire parenchyma to evaluate changes in the medulla after administration of furosemide, a widely used pharmacological maneuver. Changes in higher moments indicate that there is more than just a shift in the mean renal R2* and may provide clinically relevant information without the need for subjective regional segmentation. For evaluating differences between controls and subjects with CKD at baseline; large cortical ROI provided the highest sensitivity and objectivity. A combination of renal parenchyma assessment and large cortical ROI may provide the most robust method of evaluating renal blood oxygenation level-dependent magnetic resonance imaging data.

Evaluation of Renal Blood Flow in Chronic Kidney Disease Using Arterial Spin Labeling Perfusion Magnetic Resonance Imaging

Introduction Chronic kidney disease (CKD) is known to be associated with reduced renal blood flow. However, data in humans are limited to date. Methods In this study, noninvasive arterial spin labeling magnetic resonance imaging data were acquired in 33 patients with diabetes and stage 3 CKD as well as in 30 healthy controls. Results A significantly lower renal blood flow in both the cortex (108.4 ± 36.4 vs. 207.3 ± 41.8; P < 0.001, d = 2.52) and medulla (23.2 ± 8.9 vs. 42.6 ± 15.8; P < 0.001, d = 1.5) was observed. Both cortical (ρ = 0.67, P < 0.001) and medullary (ρ = 0.62, P < 0.001) blood flow were correlated with estimated glomerular filtration rate, and cortical blood flow was found to be confounded by age and body mass index. However, in a subset of subjects who were matched for age and body mass index (n = 6), the differences between CKD patients and control subjects remained significant in both the cortex (107.4 ± 42.8 vs. 187.51 ± 20.44; P = 0.002) and medulla (15.43 ± 8.43 vs. 39.18 ± 11.13; P = 0.002). A threshold value to separate healthy controls and CKD patients was estimated to be a cortical blood flow of 142.9 and a medullary blood flow of 24.1. Discussion These results support the use of arterial spin labeling in the evaluation of renal blood flow in patients with a moderate level of CKD. Whether these measurements can identify patients at risk for progressive CKD requires further longitudinal follow-up.

Sensitivity of arterial spin labeling perfusion MRI to pharmacologically induced perfusion changes in rat kidneys

To investigate whether arterial spin labeling (ASL) MRI is sensitive to changes by pharmacologically induced vasodilation and vasoconstriction in rat kidneys.

BOLD quantified renal pO2 is sensitive to pharmacological challenges in rats

Blood oxygen level‐dependent (BOLD) MRI has been effectively used to monitor changes in renal oxygenation. However, R2* (or T2*) is not specific to blood oxygenation and is dependent on other factors. This study investigates the use of a statistical model that takes these factors into account and maps BOLD MRI measurements to blood pO2.

Multicenter Study Evaluating Intrarenal Oxygenation and Fibrosis Using Magnetic Resonance Imaging in Individuals With Advanced CKD

Figure 1. Illustration of typical magnetic resonance imaging data from a representative subject from the control and chronic kidney disease (CKD) groups. Shown are anatomical images, preand postfurosemide R2*, and apparent diffusion coefficient (ADC) maps. The maps are scaled similarly using the same color bar for both control and CKD. Note that changes in medullary regions in control, but not in CKD on the post-furosemide R2* map compared with the prefurosemide R2* map. Also included is an illustration of sample regions of interest (ROIs) defined for the analysis of R2*maps. Cortical ROIs (outlined in green) are defined as thin regions parallel to the outer boundary of the kidney covering the entire length of the kidney. Also shown are whole-kidney ROI and multiple small ROIs in the medulla. To the Editor: The chronic hypoxia theory states that hypoxia and interstitial fibrosis are key contributors to progression of chronic kidney disease (CKD). Presence of fibrosis may further enhance the hypoxia by limiting oxygen transport, resulting in a perpetual cycle of hypoxic injury and progressive loss of kidney function. Blood oxygenation level dependent (BOLD) and diffusion magnetic resonance imaging (MRI) can provide information on renal oxygenation and fibrosis, respectively. The methods rely on endogenous contrast mechanisms that do not require exogenous contrast

Consistency of Multiple Renal Functional MRI Measurements Over 18 Months: Consistency of Longitudinal Renal fMRI

Identification of patients with progressive chronic kidney disease (CKD) and those likely to respond to candidate therapeutics is urgently needed. Functional MRI measurements have shown promise. However, knowledge about the consistency of the measurements is essential to conduct longitudinal studies.

Sensitivity of Arterial Spin Labeling Perfusion Magnetic Resonance Imaging to Evaluate Pharmacologically Induced Changes in Rat Kidneys

To investigate whether arterial spin labeling (ASL) MRI is sensitive to changes by pharmacologically induced vasodilation and vasoconstriction in rat kidneys.