Diffusion tensor imaging MRI of sickle cell kidney disease: initial results and comparison with iron deposition

Chronic kidney disease (CKD) occurs in over one‐third of patients with sickle cell disease (SCD) and can progress to end‐stage renal disease. Unfortunately, current clinical assessments of kidney function are insensitive to early‐stage CKD. Previous studies have shown that diffusion magnetic resonance imaging (MRI) can sensitively detect regional renal microstructural changes associated with early‐stage CKD. However, previous MRI studies in patients with SCD have been largely limited to the detection of renal iron deposition assessed by T₂* relaxometry. In this pilot imaging study, we compare MRI assessments of renal microstructure (diffusion) and iron deposition (T₂*) in patients with SCD and in non‐SCD control subjects. Diffusion tensor imaging (DTI) and T₂* relaxometry MRI data were obtained for pediatric (n = 5) and adult (n = 4) patients with SCD, as well as for non‐SCD control subjects (n = 10), on a Siemens Espree 1.5‐T MRI scanner. A region‐of‐interest analysis was used to calculate mean medullary and cortical values for each MRI metric. MRI findings were also compared with clinical assessments of renal function and hemolysis. Patients with SCD showed a significant decrease in medullary fractional anisotropy (FA, p = 0.0001) in comparison with non‐SCD subjects, indicative of microstructural alterations in the renal medulla of patients with SCD. Cortical and medullary reductions in T₂* (increased iron deposition, p = ≤0.0001) were also observed. Significant correlations were also observed between kidney T₂* assessments and multiple measures of hemolysis. This is the first DTI MRI study of patients with SCD to demonstrate reductions in medullary FA despite no overt CKD [estimated glomerular filtration rate (eGFR) > 100 mL/min/1.73 m²]. These medullary FA changes are consistent with previous studies in patients with CKD, and suggest that DTI MRI can provide a useful measure of kidney injury to complement MRI assessments of iron deposition.     

Treatment response monitoring in patients with gastrointestinal stromal tumor using diffusion‐weighted imaging: preliminary results in comparison with positron emission tomography/computed tomography

We compared the parameters derived from diffusion‐weighted imaging (DWI) and positron emission tomography/computed tomography (PET/CT) for treatment response evaluation and response prediction in patients with gastrointestinal stromal tumor (GIST). Seven patients with histologically proven metastatic disease were enrolled. DWI and PET/CT data were collected from all patients at diagnosis and from six at follow‐up. All 37 lesions were identifiable in DWI with a sensitivity of 100%. To achieve higher accuracy, we used the apparent diffusion coefficient (ADC) of liver and background noise as thresholds for the measurement of the ADCs of lesions. Significant inverse correlations were found between ADC_{mean_thr} (ADC_mean with thresholds) and SUV_mean (mean standardized uptake value) (R² = 0.523, p < 0.001 at diagnosis, and R² = 0.916, p < 0.001 at follow‐up), between ADC_{mean_thr} and SUV_max (maximum SUV) (R² = 0.529, p < 0.001 at diagnosis, and R² = 0.761, p < 0.001 at follow‐up), between ΔADC_{mean_thr} (percentage change in ADC_{mean_thr}) and ΔSUV_mean (percentage change in SUV_mean) (R² = 0.384, p < 0.001), and between ΔADC_{mean_thr} and ΔSUV_max (percentage change in SUV_max) (R² = 0.500, p < 0.001). In lesion‐based analysis, pre‐treatment ADC_{mean_thr} outperformed SUV_mean and SUV_max in treatment response prediction, with an area under the receiver operating characteristic curve of 0.706. These results show that DWI can provide a quantitative assessment comparable with PET/CT in GIST lesion characterization, treatment response evaluation and response prediction. Copyright © 2012 John Wiley & Sons, Ltd.     

Diffusion tensor imaging of renal ischemia reperfusion injury in an experimental model

Renal ischemia reperfusion injury (IRI) is a major cause of acute renal failure. It occurs in various clinical settings such as renal transplantation, shock and vascular surgery. Serum creatinine level has been used as an index for estimating the degree of renal functional loss in renal IRI. However, it only evaluates the global renal function. In this study, diffusion tensor imaging (DTI) was used to characterize renal IRI in an experimental rat model. Spin‐echo echo‐planar DTI with b‐value of 300 s/mm² and 6 diffusion gradient directions was performed at 7 T in 8 Sprague‐Dawley (SD) with 60‐min unilateral renal IRI and 8 normal SD rats. Apparent diffusion coefficient (ADC), directional diffusivities and fractional anisotropy (FA) were measured at the acute stage of IRI. The IR‐injured animals were also examined by diffusion‐weighted imaging with 7 b‐values up to 1000 s/mm² to estimate true diffusion coefficient (D_true) and perfusion fraction (P_fraction) using a bi‐compartmental model. ADC of injured renal cortex (1.69 ± 0.24 × 10^?3 mm²/s) was significantly lower (p < 0.01) than that of contralateral intact cortex (2.03 ± 0.35 × 10^?3 mm²/s). Meanwhile, both ADC and FA of IR‐injured medulla (1.37 ± 0.27 × 10^?3 mm²/s and 0.28 ± 0.04, respectively) were significantly less (p < 0.01) than those of contralateral intact medulla (2.01 ± 0.38 × 10^?3 mm²/s and 0.36 ± 0.04, respectively). The bi‐compartmental model analysis revealed the decrease in D_true and P_fraction in the IR‐injured kidneys. Kidney histology showed widespread cell swelling and erythrocyte congestion in both cortex and medulla, and cell necrosis/apoptosis and cast formation in medulla. These experimental findings demonstrated that DTI can probe both structural and functional information of kidneys following renal IRI. Copyright © 2010 John Wiley & Sons, Ltd.     

Magnetic resonance elastography‐derived stiffness of the kidneys and its correlation with water perfusion

Stiffness plays an important role in diagnosing renal fibrosis. However, kidney stiffness is altered by perfusion changes in many kidney diseases. Therefore, the aim of the current study is to determine the correlation of kidney stiffness with water intake. We hypothesize that kidney stiffness will increase with 1 L of water intake due to increased water perfusion to the kidneys. Additionally, stiffness of the kidneys will correlate with apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values before and after water intake. A 3 T MRI scanner was used to perform magnetic resonance elastography and diffusion tensor imaging of the kidneys on 24 healthy subjects (age range: 22‐66 years) before and after water intake of 1 L. A 3D T1‐weighted bladder scan was also performed to measure bladder volume before and after water intake. A paired t‐test was performed to evaluate the effect of water intake on the stiffness of kidneys, in addition to bladder volume. A Spearman correlation test was performed to determine the association between stiffness, bladder volume, ADC and FA values of both kidneys before and after water intake. The results show a significant increase in stiffness in different regions of the kidney (ie, percentage increase ranged from 3.6% to 7.5%) and bladder volume after water intake (all P < 0.05). A moderate significant negative correlation was observed between change in kidney stiffness and bladder volume (concordance correlation coefficient = ‐0.468, P < 0.05). No significant correlation was observed between stiffness and ADC or FA values before and after water intake in both kidneys (P > 0.05). Water intake caused a significant increase in the stiffness of the kidneys. The negative correlation between the change in kidney stiffness and bladder volume, before and after water intake, indicates higher perfusion pressure in the kidneys, leading to increased stiffness.     

MRI quantification of non‐Gaussian water diffusion in normal human kidney: a diffusional kurtosis imaging study

Our aim was to prospectively evaluate the feasibility of diffusional kurtosis imaging (DKI) in normal human kidney and to report preliminary DKI measurements. Institutional review board approval and informed consent were obtained. Forty‐two healthy volunteers underwent diffusion‐weighted imaging (DWI) scans with a 3‐T MR scanner. b values of 0, 500 and 1000 s/mm² were adopted. Maps of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (D_⊥), axial diffusivity (D_||), mean kurtosis (MK), radial kurtosis (K_⊥) and axial kurtosis (K_||) were produced. Three representative axial slices in the upper pole, mid‐zone and lower pole were selected in the left and right kidney. On each selected slice, three regions of interest were drawn on the renal cortex and another three on the medulla. Statistical comparison was performed with t‐test and analysis of variance. Thirty‐seven volunteers successfully completed the scans. No statistically significant differences were observed between the left and right kidney for all metrics (p values in the cortex: FA, 0.114; MD, 0.531; D_⊥, 0.576; D_||, 0.691; MK, 0.934; K_⊥, 0.722; K_||, 0.891; p values in the medulla: FA, 0.348; MD, 0.732; D_⊥, 0.470; D_||, 0.289; MK, 0.959; K_⊥, 0.780; K_||, 0.287). Kurtosis metrics (MK, K_||, K_⊥) obtained in the renal medulla were significantly (p <0.001) higher than those in the cortex (0.552 ± 0.04, 0.637 ± 0.07 and 0.530 ± 0.08 in the medulla and 0.373 ± 0.04, 0.492 ± 0.06 and 0.295 ± 0.06 in the cortex, respectively). For the diffusivity measures, FA of the medulla (0.356 ± 0.03) was higher than that of the cortex (0.179 ± 0.03), whereas MD, D_⊥ and D_|| (mm²/ms) were lower in the medulla than in the cortex (3.88 ± 0.09, 3.50 ± 0.23 and 4.65 ± 0.29 in the cortex and 2.88 ± 0.11, 2.32 ± 0.20 and 3.47 ± 0.31 in the medulla, respectively). Our results indicate that DKI is feasible in the human kidney. We have reported the preliminary DKI measurements of normal human kidney that demonstrate well the non‐Gaussian behavior of water diffusion, especially in the renal medulla. Copyright © 2014 John Wiley & Sons, Ltd.     

A multi‐Gaussian model for apparent diffusion coefficient histogram analysis of Wilms’ tumour subtype and response to chemotherapy

Wilms’ tumours (WTs) are large heterogeneous tumours, which typically consist of a mixture of histological cell types, together with regions of chemotherapy‐induced regressive change and necrosis. The predominant cell type in a WT is assessed histologically following nephrectomy, and used to assess the tumour subtype and potential risk. The purpose of this study was to develop a mathematical model to identify subregions within WTs with distinct cellular environments in vivo, determined using apparent diffusion coefficient (ADC) values from diffusion‐weighted imaging (DWI). We recorded the WT subtype from the histopathology of 32 tumours resected in patients who received DWI prior to surgery after pre‐operative chemotherapy had been administered. In 23 of these tumours, DWI data were also available prior to chemotherapy. Histograms of ADC values were analysed using a multi‐Gaussian model fitting procedure, which identified ‘subpopulations’ with distinct cellular environments within the tumour volume. The mean and lower quartile ADC values of the predominant viable tissue subpopulation (ADC_1MEAN, ADC_1LQ), together with the same parameters from the entire tumour volume (ADC_0MEAN, ADC_0LQ), were tested as predictors of WT subtype. ADC_1LQ from the multi‐Gaussian model was the most effective parameter for the stratification of WT subtype, with significantly lower values observed in high‐risk blastemal‐type WTs compared with intermediate‐risk stromal, regressive and mixed‐type WTs (p < 0.05). No significant difference in ADC_1LQ was found between blastemal‐type and intermediate‐risk epithelial‐type WTs. The predominant viable tissue subpopulation in every stromal‐type WT underwent a positive shift in ADC_1MEAN after chemotherapy. Our results suggest that our multi‐Gaussian model is a useful tool for differentiating distinct cellular regions within WTs, which helps to identify the predominant histological cell type in the tumour in vivo. This shows potential for improving the risk‐based stratification of patients at an early stage, and for guiding biopsies to target the most malignant part of the tumour. Copyright © 2015 John Wiley & Sons, Ltd.     

Stroke assessment with intravoxel incoherent motion diffusion‐weighted MRI

Intravoxel incoherent motion (IVIM) diffusion‐weighted MRI can simultaneously measure diffusion and perfusion characteristics in a non‐invasive way. This study aimed to determine the potential utility of IVIM in characterizing brain diffusion and perfusion properties for clinical stroke. The multi‐b‐value diffusion‐weighted images of 101 patients diagnosed with acute/subacute ischemic stroke were retrospectively evaluated. The diffusion coefficient D, representing the water apparent diffusivity, was obtained by fitting the diffusion data with increasing high b‐values to a simple mono‐exponential model. The IVIM‐derived perfusion parameters, pseudodiffusion coefficient D*, vascular volume fraction f and blood flow‐related parameter fD*, were calculated with the bi‐exponential model. Additionally, the apparent diffusion coefficient (ADC) was fitted according to the mono‐exponential model using all b‐values. The diffusion parameters for the ischemic lesion and normal contralateral region were measured in each patient. Statistical analysis was performed using the paired Student t‐test and Pearson correlation test. Diffusion data in both the ischemic lesion and normal contralateral region followed the IVIM bi‐exponential behavior, and the IVIM model showed better goodness of fit than the mono‐exponential model with lower Akaike information criterion values. The paired Student t‐test revealed significant differences for all diffusion parameters (all P < 0.001) except D* (P = 0.218) between ischemic and normal areas. For all patients in both ischemic and normal regions, ADC was significantly positively correlated with D (both r = 1, both P < 0.001) and f (r = 0.541, P < 0.001; r = 0.262, P = 0.008); significant correlation was also found between ADC and fD* in the ischemic region (r = 0.254, P = 0.010). For all pixels within the region of interest from a representative subject in both ischemic and normal regions, ADC was significantly positively correlated with D (both r = 1, both P < 0.001), f (r = 0.823, P < 0.001; r = 0.652, P < 0.001) and fD* (r = 0.294, P < 0.001; r = 0.340, P < 0.001). These findings may have clinical implications for the use of IVIM imaging in the assessment and management of acute/subacute stroke patients. Copyright © 2016 John Wiley & Sons, Ltd.     

Reliable estimation of brain intravoxel incoherent motion parameters using denoised diffusion‐weighted MRI

In this study, we evaluate whether diffusion‐weighted magnetic resonance imaging (DW‐MRI) data after denoising can provide a reliable estimation of brain intravoxel incoherent motion (IVIM) perfusion parameters. Brain DW‐MRI was performed in five healthy volunteers on a 3 T clinical scanner with 12 different b‐values ranging from 0 to 1000 s/mm². DW‐MRI data denoised using the proposed method were fitted with a biexponential model to extract perfusion fraction (PF), diffusion coefficient (D) and pseudo‐diffusion coefficient (D*). To further evaluate the accuracy and precision of parameter estimation, IVIM parametric images obtained from one volunteer were used to resimulate the DW‐MRI data using the biexponential model with the same b‐values. Rician noise was added to generate DW‐MRI data with various signal‐to‐noise ratio (SNR) levels. The experimental results showed that the denoised DW‐MRI data yielded precise estimates for all IVIM parameters. We also found that IVIM parameters were significantly different between gray matter and white matter (P < 0.05), except for D* (P = 0.6). Our simulation results show that the proposed image denoising method displays good performance in estimating IVIM parameters (both bias and coefficient of variation were <12% for PF, D and D*) in the presence of different levels of simulated Rician noise (SNR_b=0 = 20‐40). Simulations and experiments show that brain DW‐MRI data after denoising can provide a reliable estimation of IVIM parameters.     

Comparing diagnostic accuracy of luminal water imaging with diffusion‐weighted and dynamic contrast‐enhanced MRI in prostate cancer: A quantitative MRI study

Luminal water imaging (LWI) is a new MRI T₂ mapping technique that has been developed with the aim of diagnosis of prostate carcinoma (PCa). This technique measures the fractional amount of luminal water in prostate tissue, and has shown promising preliminary results in detection of PCa. To include LWI in clinical settings, further investigation on the accuracy of this technique is required. In this study, we compare the diagnostic accuracy of LWI with those of diffusion‐weighted imaging (DWI) and dynamic contrast‐enhanced (DCE) MRI in detection and grading of PCa. Fifteen patients with biopsy‐proven PCa consented to participate in this ethics‐board‐approved prospective study. Patients were examined with LWI, DWI, and DCE sequences at 3 T prior to radical prostatectomy. Maps of MRI parameters were generated and registered to whole‐mount histology. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of individual and combined MR parameters. Correlation with Gleason score (GS) was evaluated using Spearman's rank correlation test. The results show that area under the ROC curve (AUC) obtained from LWI was equal to or higher than the AUC obtained from DWI, DCE, or their combination, in peripheral zone (0.98 versus 0.90, 0.89, and 0.91 respectively), transition zone (0.99 versus 0.98, n/a, and 0.98), and the entire prostate (0.85 versus 0.81, 0.75, and 0.84). The strongest correlation with GS was achieved from LWI (ρ = ?0.81 ± 0.09, P < 0.001). Results of this pilot study show that LWI performs equally well as, or better than, DWI and DCE in detection of PCa. LWI provides significantly higher correlation with GS than DWI and DCE. This technique can potentially be included in clinical MRI protocols to improve characterization of tumors. However, considering the small size of the patient population in this study, a further study with a larger cohort of patients and broader range of GS is required to confirm the findings and draw a firm conclusion on the applicability of LWI in clinical settings.     

Time‐dependent diffusion MRI as a probe of microstructural changes in a mouse model of Duchenne muscular dystrophy

Dystrophic muscles show a high variability of fibre sizes and altered sarcolemmal integrity, which are typically assessed by histology. Time‐dependent diffusion MRI is sensitive to tissue microstructure and its investigation through age‐related changes in dystrophic and healthy muscles may help the understanding of the onset and progression of Duchenne muscular dystrophy (DMD). We investigated the capability of time‐dependent diffusion MRI to quantify age and disease‐related changes in hind‐limb muscle microstructure between dystrophic (mdx) and wild‐type (WT) mice of three age groups (7.5, 22 and 44 weeks). Diffusion time‐dependent apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined versus age and diffusion‐gradient orientation at six diffusion times (Δ; range: 25–350 ms). Mean muscle ADCs were compared between groups and ages, and correlated with T₂, using Student's t test, one‐way analysis of variance and Pearson correlation, respectively. Muscle fibre sizes and sarcolemmal integrity were evaluated by histology and compared with diffusion measurements. Hind‐limb muscle ADC showed characteristic restricted diffusion behaviour in both mdx and WT animals with decreasing ADC values at longer Δ. Significant differences in ADC were observed at long Δ values (≥ 250 ms; p < 0.05, comparison between groups; p < 0.01, comparison between ages) with ADC increased by 5–15% in dystrophic muscles, indicative of reduced diffusion restriction. No significant correlation was found between T₂ and ADC. Additionally, muscle fibre size distributions showed higher variability and lower mean fibre size in mdx than WT animals (p < 0.001). The extensive Evans Blue Dye uptake shown in dystrophic muscles revealed substantial sarcolemmal damage, suggesting diffusion measurements as more consistent with altered permeability rather than changes in muscle fibre sizes. This study shows the potential of diffusion MRI to non‐invasively discriminate between dystrophic and healthy muscles with enhanced sensitivity when using long Δ.     

High‐resolution diffusion tensor imaging in cervical spondylotic myelopathy: a preliminary follow‐up study

Diffusion imaging is a promising technique as it can provide microstructural tissue information and thus potentially show viable changes in spinal cord. However, the traditional single‐shot imaging method is limited as a result of various image artifacts. In order to improve measurement accuracy, we used a newly developed, multi‐shot, high‐resolution, diffusion tensor imaging (DTI) method to investigate diffusion metric changes and compare them with T₂‐weighted (T2W) images before and after decompressive surgery for cervical spondylotic myelopathy (CSM). T2W imaging, single‐shot DTI and multi‐shot DTI were employed to scan seven patients with CSM before and 3 months after decompressive surgery. High signal intensities were scored using the T2 W images. DTI metrics, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were quantified and compared pre‐ and post‐surgery. In addition, the relationship between imaging metrics and neurological assessments was examined. The reproducibility of multi‐shot DTI was also assessed in 10 healthy volunteers. Post‐surgery, the mean grade of cervical canal stenosis was reduced from grade 3 to normal after 3 months. Compared with single‐shot DTI, multi‐shot DTI provided better images with lower artifact levels, especially following surgery, as a result of reduced artifacts from metal implants. The new method also showed acceptable reproducibility. Both FA and RD values from the new acquisition showed significant differences post‐surgery (FA, p = 0.026; RD, p = 0.048). These changes were consistent with neurological assessments. In contrast, T2W images did not show significant changes before and after surgery. Multi‐shot diffusion imaging showed improved image quality over single‐shot DWI, and presented superior performance in diagnosis and recovery monitoring for patients with CSM compared with T2W imaging. DTI metrics can reflect the pathological conditions of spondylotic spinal cord quantitatively and may serve as a sensitive biomarker for potential CSM management.     

Linking non‐invasive parametric MRI with invasive physiological measurements (MR‐PHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging (MRI) of the kidney. Moreover, the validity of parametric MRI (pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non‐invasive MRI in an integrated hybrid setup (MR‐PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi‐modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation‐dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR‐PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia.     

VERDICT MRI for radiation treatment response assessment in neuroendocrine tumors

Noninvasive methods to study changes in tumor microstructure enable early assessment of treatment response and thus facilitate personalized treatment. The aim of this study was to evaluate the diffusion MRI model, Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT), for early response assessment to external radiation treatment and to compare the results with those of more studied sets of parameters derived from diffusion-weighted MRI data. Mice xenografted with human small intestine tumors were treated with external radiation treatment, and diffusion MRI experiments were performed on the day before and up to 2 weeks after treatment. The diffusion models VERDICT, ADC, IVIM, and DKI were fitted to MRI data, and the treatment response of each tumor was calculated based on pretreatment tumor growth and post-treatment tumor volume regression. Linear regression and correlation analysis were used to evaluate each model and their respective parameters for explaining the treatment response. VERDICT analysis showed significant changes from day −1 to day 3 for the intracellular and extracellular volume fraction, as well as the cell radius index (p < 0.05; Wilcoxon signed-rank test). The strongest correlation between the diffusion model parameters and the tumor treatment response was seen for the ADC, kurtosis-corrected diffusion coefficient, and intracellular volume fraction on day 3 (τ = 0.47, 0.52, and −0.49, respectively, p < 0.05; Kendall rank correlation coefficient). Of all the tested models, VERDICT held the strongest explanatory value for the tumor treatment response on day 3 (R² = 0.75, p < 0.01; linear regression). In conclusion, VERDICT has potential for early assessment of external radiation treatment and may provide further insights into the underlying biological effects of radiation on tumor tissue. In addition, the results suggest that the time window for assessment of treatment response using dMRI may be narrow.     

MRI of neonatal necrotizing enterocolitis in a rodent model

Neonatal necrotizing enterocolitis (NEC) is a poorly understood life‐threatening illness afflicting premature infants. Research is hampered by the absence of a suitable method to monitor disease progression noninvasively. The primary goal of this research was to test in vivo MRI methods for the noninvasive early detection and staging of inflammation in the ileum of an infant rat model of NEC. Neonatal rats were delivered by cesarean section at embryonic stage of day 20 after the beginning of pregnancy and stressed with formula feeding, hypoxia and bacterial colonization to induce NEC. Naturally born and dam‐fed neonatal rats were used as healthy controls. In vivo MRI studies were performed using a Bruker 9.4‐T scanner to obtain high‐resolution anatomical MR images using both gradient echo and spin echo sequences, pixel‐by‐pixel T₂ maps using a multi‐slice–multi‐echo sequence, and maps of the apparent diffusion coefficient (ADC) of water using a spin echo sequence, to assess the degree of ileal damage. Pups were sacrificed at the end of the MRI experiment on day 2 or 4 for histology. T₂ measured by MRI was increased significantly in the ileal regions of pups with NEC by histology (106.3 ± 6.1 ms) compared with experimentally stressed pups without NEC (85.2 ± 6.8 ms) and nonstressed, control rat pups (64.9 ± 2.3 ms). ADC values measured by diffusion‐weighted MRI were also increased in the ileal regions of pups with NEC by histology [(1.98 ± 0.15) × 10^–3 mm²/s] compared with experimentally stressed pups without NEC [(1.43 ± 0.16) × 10^–3 mm²/s] and nonstressed control pups [(1.10 ± 0.06) × 10^–3 mm²/s]. Both T₂ and ADC values between these groups were found to be significantly different (p < 0.03). The correlation of MRI results with histologic images of the excised ileal tissue samples strongly suggests that MRI can noninvasively identify NEC and assess intestinal injury prior to clinical symptoms in a physiologic rat pup model of NEC. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

BOLD background gradient contributions in diffusion‐weighted fMRI—comparison of spin‐echo and twice‐refocused spin‐echo sequences

The interaction (‘cross terms’) between diffusion‐weighting gradients and susceptibility‐induced background gradient fields around vessels has an impact on apparent diffusion coefficient (ADC) measurements and diffusion‐weighted functional magnetic resonance imaging (DFMRI) experiments. Monte‐Carlo (MC) simulations numerically integrating the Bloch equations for a large number of random walks in a vascular model were used to investigate to what extent such interactions would influence the extravascular signal change as well as the ADC change observed in DFMRI experiments. The vascular model consists of a set of independent, randomly oriented, infinite cylinders whose internal magnetic susceptibility varies as the state changes between rest and activation. In such a network, the cross terms result in the observation of a functional increase in ADC accompanied by a descending percent signal change with increasing diffusion weighting. It is shown that the twice‐refocused spin‐echo sequence permits sufficient yet not total suppression of such effects compared to the standard Stejskal‐Tanner spin‐echo diffusion weighting under experimentally relevant conditions. Copyright © 2010 John Wiley & Sons, Ltd.     

DCE‐ and DW‐MRI as early imaging biomarkers of treatment response in a preclinical model of triple negative breast cancer

This work evaluates quantitative dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and diffusion‐weighted MRI (DW‐MRI) parameters as early biomarkers of response in a preclinical model of triple negative breast cancer (TNBC). The standard Tofts' model of DCE‐MRI returns estimates of the volume transfer constant (K^trans) and the extravascular extracellular volume fraction (v_e). DW‐MRI returns estimates of the apparent diffusion coefficient (ADC). Mice (n = 38) were injected subcutaneously with MDA‐MB‐231. Tumors were grown to approximately 275 mm³ and sorted into the following groups: saline controls, low‐dose Abraxane (15 mg/kg) and high‐dose Abraxane (25 mg/kg). Animals were imaged at days zero, one and three. On day three, tumors were extracted for immunohistochemistry. The positive percentage change in ADC on day one was significantly higher in both treatment groups relative to the control group (p < 0.05). In addition, the positive percentage change in K^trans was significantly higher than controls (p < 0.05) on day one for the high‐dose group and on days one and three for the low‐dose group. The percentage change in tumor volume was significantly different between the high‐dose and control groups on day three (p = 0.006). Histology confirmed differences at day three through reduced numbers of proliferating cells (Ki67 staining) in the high‐dose group (p = 0.03) and low‐dose group (p = 0.052) compared with the control group. Co‐immunofluorescent staining of vascular maturity [using von Willebrand Factor (vWF) and α‐smooth muscle actin (α‐SMA)] indicated significantly higher vascular maturation in the low‐dose group compared with the controls on day three (p = 0.03), and trending towards significance in the high‐dose group compared with controls on day three (p = 0.052). These results from quantitative imaging with histological validation indicate that ADC and K^trans have the potential to serve as early biomarkers of treatment response in murine studies of TNBC.     

Probing renal blood volume with magnetic resonance imaging

Damage to the kidney substantially reduces life expectancy. Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. In vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Blood oxygenation level–dependent (BOLD) magnetic resonance imaging (MRI) is sensitive to changes in the effective transversal relaxation time (T₂*) in vivo, and is non‐invasive and indicative of renal tissue oxygenation. However, the renal T₂* to tissue pO₂ relationship is not governed exclusively by renal blood oxygenation, but is affected by physiological confounders with alterations in renal blood volume fraction (BVf) being of particular relevance. To decipher this interference probing renal BVf is essential for the pursuit of renal MR oximetry. Superparamagnetic iron oxide nanoparticle (USPIO) preparations can be used as MRI visible blood pool markers for detailing alterations in BVf. This review promotes the opportunities of MRI‐based assessment of renal BVf. Following an outline on the specifics of renal oxygenation and perfusion, changes in renal BVf upon interventions and their potential impact on renal T₂* are discussed. We also describe the basic principles of renal BVf assessment using ferumoxytol‐enhanced MRI in the equilibrium concentration regimen. We demonstrate that ferumoxytol does not alter control of renal haemodynamics and oxygenation. Preclinical applications of ferumoxytol enhanced renal MRI as well as considerations for its clinical implementation for examining renal BVf changes are provided alongside practical considerations. Finally, we explore the future directions of MRI‐based assessment of renal BVf.     

An intravoxel oriented flow model for diffusion‐weighted imaging of the kidney

By combining intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) we introduce a new diffusion model called intravoxel oriented flow (IVOF) that accounts for anisotropy of diffusion and the flow‐related signal. An IVOF model using a simplified apparent flow fraction tensor (IVOF_f) is applied to diffusion‐weighted imaging of human kidneys. The kidneys of 13 healthy volunteers were examined on a 3 T scanner. Diffusion‐weighted images were acquired with six b values between 0 and 800 s/mm² and 30 diffusion directions. Diffusivity and flow fraction were calculated for different diffusion models. The Akaike information criterion was used to compare the model fit of the proposed IVOF_f model to IVIM and DTI. In the majority of voxels the proposed IVOF_f model with a simplified apparent flow fraction tensor performs better than IVIM and DTI. Mean diffusivity is significantly higher in DTI compared with models that account for the flow‐related signal. The fractional anisotropy of diffusion is significantly reduced when flow fraction is considered to be anisotropic. Anisotropy of the apparent flow fraction tensor is significantly higher in the renal medulla than in the cortex region. The IVOF_f model describes diffusion‐weighted data in the human kidney more accurately than IVIM or DTI. The apparent flow fraction in the kidney proved to be anisotropic.     

Diffusion‐weighted MRI measurements on stroke patients reveal water‐exchange mechanisms in sub‐acute ischaemic lesions

The aim of this study was to investigate the diffusion time dependence of signal‐versus‐b curves obtained from diffusion‐weighted magnetic resonance imaging (DW‐MRI) of sub‐acute ischaemic lesions in stroke patients. In this case series study, 16 patients with sub‐acute ischaemic stroke were examined with DW‐MRI using two different diffusion times (60 and 260 ms). Nine of these patients showed sufficiently large lesions without artefacts to merit further analysis. The signal‐versus‐b curves from the lesions were plotted and analysed using a two‐compartment model including compartmental exchange. To validate the model and to aid the interpretation of the estimated model parameters, Monte Carlo simulations were performed. In eight cases, the plotted signal‐versus‐b curves, obtained from the lesions, showed a signal–curve split‐up when data for the two diffusion times were compared, revealing effects of compartmental water exchange. For one of the patients, parametric maps were generated based on the extracted model parameters. These novel observations suggest that water exchange between different water pools is measurable and thus potentially useful for clinical assessment. The information can improve the understanding of the relationship between the DW‐MRI signal intensity and the microstructural properties of the lesions. Copyright © 2009 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI of the prostate without susceptibility artifacts: Undersampled multi‐shot turbo‐STEAM with rotated radial trajectories

The aim of this study was to develop and evaluate a clinically feasible approach to diffusion‐weighted (DW) MRI of the prostate without susceptibility‐induced artifacts. The proposed method relies on an undersampled multi‐shot DW turbo‐STEAM sequence with rotated radial trajectories and a multi‐step inverse reconstruction with denoised multi‐shot phase maps. The total acquisition time was below 6 min for a resolution of 1.4 × 1.4 × 3.5 mm³ and six directions at b = 600 s mm^?2. Studies of eight healthy subjects and two patients with prostate cancer were performed at 3 T employing an 18‐channel body‐array coil and elements of the spine coil. The method was compared with conventional DW echo‐planar imaging (EPI) of the prostate. The results confirm that DW STEAM MRI avoids geometric distortions and false image intensities, which were present for both single‐shot EPI (ssEPI) and readout‐segmented EPI, particularly near the intestinal wall of the prostate. Quantitative accuracy of the apparent diffusion coefficient (ADC) was validated with use of a numerical phantom providing ground truth. ADC values in the central prostate gland of healthy subjects were consistent with those measured using ssEPI and with literature data. Preliminary results for patients with prostate cancer revealed a correct anatomical localization of lesions with respect to T₂‐weighted MRI in both mean DW STEAM images and ADC maps. In summary, DW STEAM MRI of the prostate offers clinically relevant advantages for the diagnosis of prostate cancer compared with state‐of‐the‐art EPI‐based approaches. The method warrants extended clinical trials.