Assessment of diffusion parameters by intravoxel incoherent motion MRI in head and neck squamous cell carcinoma

The objectives of this study were to assess the diffusion parameters derived from intravoxel incoherent motion (IVIM) MRI in head and neck squamous cell carcinoma (HNSCC) and to investigate the agreement between different methods of tumor delineation and two numerical methods to extract the perfusion fraction f. Thirty‐seven untreated patients with histopathologically confirmed primary HNSCC were included retrospectively in the study. The entire volume of the primary tumor was outlined on diffusion‐weighted images using co‐registered morphological images as a guide to the tumor location. Apparent diffusion coefficient (ADC) and IVIM diffusion parameters were estimated considering the largest tumor section as well as the entire tumor volume. A bi‐exponential fit was implemented to extract f, D (pure diffusion coefficient) and D* (pseudo‐diffusion coefficient). A second simplified method, based on an asymptotic extrapolation, was used to determine f. The agreement between ADC and IVIM diffusion parameters derived from the delineation of single and multiple slices, and between the two f estimations, was assessed by Bland–Altman plots. The inter‐slice variability of ADC and IVIM diffusion parameters was evaluated. The Kruskal–Wallis test was used to investigate whether the tumor location had a statistically significant influence on the values of the parameters. Comparing the tumor delineation methods, a better accordance was found for ADC and D, with a mean percentage difference of less than 2%. Larger discrepancies were found for f and D*, with mean differences of 4.5% and 5.5%, respectively. When comparing the two f estimation methods, small mean differences were found (<3.5%), suggesting that the two methods may be considered as equivalent for the assessment of f in our patient population. The observed ADC and IVIM diffusion parameters were dependent on the anatomic site of the lesion, carcinoma of the nasopharynx showing more homogeneous and dissimilar estimations than other HNSCCs. Copyright © 2013 John Wiley & Sons, Ltd.     

Intravoxel incoherent motion imaging kinetics during chemoradiotherapy for human papillomavirus‐associated squamous cell carcinoma of the oropharynx: preliminary results from a prospective pilot study

This study aims to identify the temporal kinetics of intravoxel incoherent motion (IVIM) MRI in patients with human papillomavirus‐associated (HPV+) oropharyngeal squamous cell carcinoma. Patients were enrolled under an Institutional Review Board (IRB)‐approved protocol as part of an ongoing prospective clinical trial. All patients underwent two MRI studies: a baseline scan before chemoradiotherapy and a mid‐treatment scan 3–4 weeks after treatment initiation. Parametric maps representing pure diffusion coefficient (D), pseudo‐diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) were generated. The Mann–Whitney U‐test was used to assess the temporal variation of IVIM metrics. Bayesian quadratic discriminant analysis (QDA) was used to evaluate the extent to which mid‐treatment changes in IVIM metrics could be combined to predict sites that would achieve complete response (CR) in multivariate analysis. Thirty‐one patients were included in the final analysis with 59 lesions. Pretreatment ADC and D values of the CR lesions (n = 19) were significantly lower than those of non‐CR lesions (n = 33). Mid‐treatment ADC, D and f values were significantly higher (p < 0.0001) than pretreatment values for all lesions. Each increase in normalized ΔADC of size 0.1 yielded a 1.45‐fold increase in the odds of CR (p < 0.0003), each increase in normalized ΔD of size 0.1 yielded a 1.53‐fold increase in the odds of CR (p < 0.0002), and each unit increase in Δf yielded a 2.29‐fold increase in the odds of CR (p < 0.02). Combined ΔD and ΔADC were integrated into a multivariate prediction model and attained an AUC of 0.87 (95% confidence interval: 0.79, 0.96), as well as a sensitivity of 0.63, specificity of 0.85 and accuracy of 0.78, under leave‐one‐out cross‐validation. In conclusion, IVIM is feasible and potentially useful in the prediction and assessment of the early response of HPV+ oropharyngeal squamous cell carcinoma to chemoradiotherapy. Copyright © 2015 John Wiley & Sons, Ltd.     

Triggered intravoxel incoherent motion MRI for the assessment of calf muscle perfusion during isometric intermittent exercise

The main aim of this paper was to propose triggered intravoxel incoherent motion (IVIM) imaging sequences for the evaluation of perfusion changes in calf muscles before, during and after isometric intermittent exercise. Twelve healthy volunteers were involved in the study. The subjects were asked to perform intermittent isometric plantar flexions inside the MRI bore. MRI of the calf muscles was performed on a 3.0 T scanner and diffusion‐weighted (DW) images were obtained using eight different b values (0 to 500 s/mm²). Acquisitions were performed at rest, during exercise and in the subsequent recovery phase. A motion‐triggered echo‐planar imaging DW sequence was implemented to avoid movement artifacts. Image quality was evaluated using the average edge strength (AES) as a quantitative metric to assess the motion artifact effect. IVIM parameters (diffusion D, perfusion fraction f and pseudo‐diffusion D*) were estimated using a segmented fitting approach and evaluated in gastrocnemius and soleus muscles. No differences were observed in quality of IVIM images between resting state and triggered exercise, whereas the non‐triggered images acquired during exercise had a significantly lower value of AES (reduction of more than 20%). The isometric intermittent plantar‐flexion exercise induced an increase of all IVIM parameters (D by 10%; f by 90%; D* by 124%; fD* by 260%), in agreement with the increased muscle perfusion occurring during exercise. Finally, IVIM parameters reverted to the resting values within 3 min during the recovery phase. In conclusion, the IVIM approach, if properly adapted using motion‐triggered sequences, seems to be a promising method to investigate muscle perfusion during isometric exercise.     

Differentiating the histologic grades of gliomas preoperatively using amide proton transfer‐weighted (APTW) and intravoxel incoherent motion MRI

The purpose of this work was to investigate the diagnostic performance of amide proton transfer‐weighted (APTW) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the preoperative grading of gliomas. Fifty‐one patients with suspected gliomas were recruited and underwent a preoperative MRI examination that included APTW and IVIM sequences. All cases were confirmed by postsurgical histopathology. APTW signal intensity, true diffusion coefficient (D), perfusion fraction (f) and pseudo‐diffusion coefficient (D*) were applied to assess the solid tumor component and contralateral normal‐appearing white matter. The relative APTW signal intensity (rAPTW) was also used. Independent‐sample and paired‐sample t‐tests were used to compare differences in MRI parameters between low‐grade glioma (LGG) and high‐grade glioma (HGG) groups. The diagnostic performance was assessed with the receiver operating characteristic curve. Twenty‐six patients were pathologically diagnosed with LGG and 25 were diagnosed with HGG. APTW, rAPTW and f values were significantly higher (all p < 0.001), whereas D values were significantly lower (p < 0.001) in the HGG group than in the LGG group. There was no significant difference between D* values for the two groups. rAPTW had an area under the curve (AUC) of 0.957, with a sensitivity of 100% and a specificity of 84.6%, followed by APTW, f, D and D*. The combined use of APTW and IVIM showed the best diagnostic performance, with an AUC of 0.986. In conclusion, APTW and IVIM, as two promising supplementary sequences for routine MRI, could be valuable in differentiating LGGs from HGGs.     

Pattern recognition analysis of directional intravoxel incoherent motion MRI in ischemic rodent brains

This study aimed to demonstrate a reliable automatic segmentation method for independently separating reduced diffusion and decreased perfusion areas in ischemic stroke brains using constrained nonnegative matrix factorization (cNMF) pattern recognition in directional intravoxel incoherent motion MRI (IVIM‐MRI). First, the feasibility of cNMF‐based segmentation of IVIM signals was investigated in both simulations and in vivo experiments. The cNMF analysis was independently performed for S₀‐normalized and scaled (by the difference between the maximum and minimum) IVIM signals, respectively. Segmentations of reduced diffusion (from S₀‐normalized IVIM signals) and decreased perfusion (from scaled IVIM signals) areas were performed using the corresponding cNMF pattern weight maps. Second, Monte Carlo simulations were performed for directional IVIM signals to investigate the relationship between the degree of vessel alignment and the direction of the diffusion gradient. Third, directional IVIM‐MRI experiments (x, y and z diffusion‐gradient directions, 20 b values at 7 T) were performed for normal (n = 4), sacrificed (n = 1, no flow) and ischemic stroke models (n = 4, locally reduced flow). The results showed that automatic segmentation of the hypoperfused lesion using cNMF analysis was more accurate than segmentation using the conventional double‐exponential fitting. Consistent with the simulation, the double‐exponential pattern of the IVIM signals was particularly strong in white matter and ventricle regions when the directional flows were aligned with the applied diffusion‐gradient directions. cNMF analysis of directional IVIM signals allowed robust automated segmentation of white matter, ventricle, vascular and hypoperfused regions in the ischemic brain. In conclusion, directional IVIM signals were simultaneously sensitive to diffusion and aligned flow and were particularly useful for automatically segmenting ischemic lesions via cNMF‐based pattern recognition.     

Multi‐centre reproducibility of diffusion MRI parameters for clinical sequences in the brain

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra‐voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice–water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub‐regions. A mixed effect model was used to measure the intra‐ and inter‐scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra‐ and inter‐scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra‐scanner CV of 8.4% and inter‐scanner CV of 24.8%. No major difference in the inter‐scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra‐scanner reproducibility, with the inter‐scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter‐scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi‐centre clinical studies and trials. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.     

Relationship between diffusion parameters derived from intravoxel incoherent motion MRI and perfusion measured by dynamic contrast‐enhanced MRI of soft tissue tumors

Our aim was to evaluate the link between diffusion parameters measured by intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and the perfusion metrics obtained with dynamic contrast‐enhanced (DCE) MRI in soft tissue tumors (STTs). Twenty‐eight patients affected by histopathologically confirmed STT were included in a prospective study. All patients underwent both DCE MRI and IVIM DWI. The perfusion fraction f, diffusion coefficient D and perfusion‐related diffusion coefficient D* were estimated using a bi‐exponential function to fit the DWI data. DCE MRI was acquired with a temporal resolution of 3–5 s. Maps of the initial area under the gadolinium concentration curve (IAUGC), time to peak (TTP) and maximum slope of increase (MSI) were derived using commercial software. The relationships between the DCE MRI and IVIM DWI measurements were assessed by Spearman's test. To exclude false positive results under multiple testing, the false discovery rate (FDR) procedure was applied. The Mann–Whitney test was used to evaluate the differences between all variables in patients with non‐myxoid and myxoid STT. No significant relationship was found between IVIM parameters and any DCE MRI parameters. Higher f and D*f values were found in non‐myxoid tumors compared with myxoid tumors (p = 0.004 and p = 0.003, respectively). MSI was significantly higher in non‐myxoid tumors than in myxoid tumors (p = 0.029). From the visual assessments of single clinical cases, both f and D*f maps were in satisfactory agreement with DCE maps in the extreme cases of an avascular mass and a highly vascularized mass, whereas, for tumors with slight vascularity or with a highly heterogeneous perfusion pattern, this association was not straightforward. Although IVIM DWI was demonstrated to be feasible in STT, our data did not support evident relationships between perfusion‐related IVIM parameters and perfusion measured by DCE MRI. Copyright © 2015 John Wiley & Sons, Ltd.     

Demonstration of asymmetric muscle perfusion of the back after exercise in patients with adolescent idiopathic scoliosis using intravoxel incoherent motion (IVIM) MRI

The purpose of this work was to quantify muscular perfusion patterns of back muscles after exercise in patients with adolescent idiopathic scoliosis (AIS) using intravoxel incoherent motion (IVIM) MR perfusion imaging. The paraspinal muscles of eight patients with AIS (Cobb angle 35 ± 10°, range [25‐47°]) and nine healthy volunteers were scanned with a 1.5 T MRI, at rest and after performing a symmetric back muscle exercise on a Roman chair. An IVIM sequence with 16 b‐values from 0 to 900 s/mm² was acquired, and the IVIM bi‐exponential signal equation model was fitted in two steps. Perfusion asymmetries were evaluated using the blood flow related IVIM fD* parameter in regions of interest placed within the paraspinal muscles. Statistical significance was assessed using a Student t‐test. The observed perfusion pattern after performing a Roman chair muscle exercise differed consistently in patients with AIS compared with healthy normal volunteers, and consisted of an asymmetrical increase in IVIM fD* [10^?3 mm²/s] above the lumbar convexity from 6.5 ± 5.8 to 28.8 ± 26.8 (p < 0.005), with no increase in the concavity (decrease from 6.5 ± 10.0 to 3.2 ± 1.5 (p = 0.19)), compared with a bilateral symmetric increase in the healthy volunteers (right, increase from 3.3 ± 2.1 to 10.1 ± 4.6 (p < 0.05); left, 6.7 ± 10.7 to 13.3 ± 7.0 (p < 0.05)). In conclusion, patients with AIS exhibit significant asymmetric muscle perfusion over the convexity of the scoliotic curvature after Roman chair exercise.     

Interstitial fluid pressure correlates with intravoxel incoherent motion imaging metrics in a mouse mammary carcinoma model

The effective delivery of a therapeutic drug to the core of a tumor is often impeded by physiological barriers, such as the interstitial fluid pressure (IFP). There are a number of therapies that can decrease IFP and induce tumor vascular normalization. However, a lack of a noninvasive means to measure IFP hinders the utilization of such a window of opportunity for the maximization of the treatment response. Thus, the purpose of this study was to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion parameters as noninvasive imaging biomarkers for IFP. Mice bearing the 4T1 mammary carcinoma model were studied using diffusion‐weighted imaging (DWI), immediately followed by wick‐in‐needle IFP measurement. Voxelwise analysis was conducted with a conventional monoexponential diffusion model, as well as a biexponential model taking IVIM into account. There was no significant correlation of IFP with either the median apparent diffusion coefficient from the monoexponential model (r = 0.11, p = 0.78) or the median tissue diffusivity from the biexponential model (r = 0.30, p = 0.44). However, IFP was correlated with the median pseudo‐diffusivity (D_p) of apparent vascular voxels (r = 0.76, p = 0.02) and with the median product of the perfusion fraction and pseudo‐diffusivity (f_pD_p) of apparent vascular voxels (r = 0.77, p = 0.02). Although the effect of IVIM in tumors has been reported previously, to our knowledge, this study represents the first direct comparison of IVIM metrics with IFP, with the results supporting the feasibility of the use of IVIM DWI metrics as noninvasive biomarkers for tumor IFP. Copyright © 2011 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.     

The effect of noise and lipid signals on determination of Gaussian and non‐Gaussian diffusion parameters in skeletal muscle

This work characterizes the effect of lipid and noise signals on muscle diffusion parameter estimation in several conventional and non‐Gaussian models, the ultimate objectives being to characterize popular fat suppression approaches for human muscle diffusion studies, to provide simulations to inform experimental work and to report normative non‐Gaussian parameter values. The models investigated in this work were the Gaussian monoexponential and intravoxel incoherent motion (IVIM) models, and the non‐Gaussian kurtosis and stretched exponential models. These were evaluated via simulations, and in vitro and in vivo experiments. Simulations were performed using literature input values, modeling fat contamination as an additive baseline to data, whereas phantom studies used a phantom containing aliphatic and olefinic fats and muscle‐like gel. Human imaging was performed in the hamstring muscles of 10 volunteers. Diffusion‐weighted imaging was applied with spectral attenuated inversion recovery (SPAIR), slice‐select gradient reversal and water‐specific excitation fat suppression, alone and in combination. Measurement bias (accuracy) and dispersion (precision) were evaluated, together with intra‐ and inter‐scan repeatability. Simulations indicated that noise in magnitude images resulted in <6% bias in diffusion coefficients and non‐Gaussian parameters (α, K), whereas baseline fitting minimized fat bias for all models, except IVIM. In vivo, popular SPAIR fat suppression proved inadequate for accurate parameter estimation, producing non‐physiological parameter estimates without baseline fitting and large biases when it was used. Combining all three fat suppression techniques and fitting data with a baseline offset gave the best results of all the methods studied for both Gaussian diffusion and, overall, for non‐Gaussian diffusion. It produced consistent parameter estimates for all models, except IVIM, and highlighted non‐Gaussian behavior perpendicular to muscle fibers (α ~ 0.95, K ~ 3.1). These results show that effective fat suppression is crucial for accurate measurement of non‐Gaussian diffusion parameters, and will be an essential component of quantitative studies of human muscle quality.     

Quantitative MRI in murine radiation‐induced rectocolitis: comparison with histopathological inflammation score

Murine radiation‐induced rectocolitis is considered to be a relevant animal model of gastrointestinal inflammation. The purpose of our study was to compare quantitative MRI and histopathological features in this gastrointestinal inflammation model. Radiation rectocolitis was induced by localized single‐dose radiation (27 Gy) in Sprague‐Dawley rats. T₂‐weighted, T₁‐weighted and diffusion‐weighted MRI was performed at 7 T in 16 rats between 2 and 4 weeks after irradiation and in 10 control rats. Rats were sacrificed and the histopathological inflammation score of the colorectal samples was assessed. The irradiated rats showed significant increase in colorectal wall thickness (2.1 ± 0.3 mm versus 0.8 ± 0.3 mm in control rats, P < 0.0001), normalized T₂ signal intensity (4 ± 0.8 versus 2 ± 0.4 AU, P < 0.0001), normalized T₁ signal intensity (1.4 ± 0.1 versus 1.1 ± 0.2 AU, P = 0.0009) and apparent and pure diffusion coefficients (ADC and D) (2.06 × 10^?3 ± 0.34 versus 1.51 × 10^?3 ± 0.23 mm²/s, P = 0.0004, and 1.97 × 10^?3 ± 0.43 mm²/s versus 1.48 × 10^?3 ± 0.29 mm²/s, P = 0.008, respectively). Colorectal wall thickness (r = 0.84, P < 0.0001), normalized T₂ signal intensity (r = 0.85, P < 0.0001) and ADC (r = 0.80, P < 0.0001) were strongly correlated with the histopathological inflammation score, whereas normalized T₁ signal intensity and D were moderately correlated (r = 0.64, P = 0.0006, and r = 0.65, P = 0.0003, respectively). High‐field MRI features of single‐dose radiation‐induced rectocolitis in rats differ significantly from those of control rats. Quantitative MRI characteristics, especially wall thickness, normalized T₂ signal intensity, ADC and D, are potential markers of the histopathological inflammation score.     

Dynamic intravoxel incoherent motion imaging of skeletal muscle at rest and after exercise

The purpose of this work was to demonstrate the feasibility of intravoxel incoherent motion imaging (IVIM) for non‐invasive quantification of perfusion and diffusion effects in skeletal muscle at rest and following exercise. After IRB approval, eight healthy volunteers underwent diffusion‐weighted MRI of the forearm at 3 T and eight different b values between 0 and 500 s/mm² with a temporal resolution of 57 s per dataset. Dynamic images were acquired before and after a standardized handgrip exercise. Diffusion (D) and pseudodiffusion (D*) coefficients as well as the perfusion fraction (F_P) were measured in regions of interest in the flexor digitorum superficialis and profundus (FDS/FDP), brachioradialis, and extensor carpi radialis longus and brevis muscles by using a multi‐step bi‐exponential analysis in MATLAB. Parametrical maps were calculated voxel‐wise. Differences in D, D*, and F_P between muscle groups and between time points were calculated using a repeated measures analysis of variance with post hoc Bonferroni tests. Mean values and standard deviations at rest were the following: D*, 28.5 ± 11.4 × 10^?3 mm²/s; F_P, 0.03 ± 0.01; D, 1.45 ± 0.09 × 10^?3 mm²/s. Changes of IVIM parameters were clearly visible on the parametrical maps. In the FDS/FDP, D* increased by 289 ± 236% (p < 0.029), F_P by 138 ± 58% (p < 0.01), and D by 17 ± 9% (p < 0.01). A significant increase of IVIM parameters could also be detected in the brachioradialis muscle, which however was significantly lower than in the FDS/FDP. After 20 min, all parameters were still significantly elevated in the FDS/FDP but not in the brachioradialis muscle compared with the resting state. The IVIM approach allows simultaneous quantification of muscle perfusion and diffusion effects at rest and following exercise. It may thus provide a useful alternative to other non‐invasive methods such as arterial spin labeling. Possible fields of interest for this technique include perfusion‐related muscle diseases, such as peripheral arterial occlusive disease. Copyright © 2014 John Wiley & Sons, Ltd.     

Mapping tissue water T1 in the liver using the MOLLI T1 method in the presence of fat,iron and B0 inhomogeneity

Modified Look‐Locker inversion recovery (MOLLI) T₁ mapping sequences can be useful in cardiac and liver tissue characterization, but determining underlying water T₁ is confounded by iron, fat and frequency offsets. This article proposes an algorithm that provides an independent water MOLLI T₁ (referred to as on‐resonance water T₁) that would have been measured if a subject had no fat and normal iron, and imaging had been done on resonance. Fifteen NiCl₂‐doped agar phantoms with different peanut oil concentrations and 30 adults with various liver diseases, nineteen (63.3%) with liver steatosis, were scanned at 3 T using the shortened MOLLI (shMOLLI) T₁ mapping, multiple‐echo spoiled gradient‐recalled echo and ¹H MR spectroscopy sequences. An algorithm based on Bloch equations was built in MATLAB, and water shMOLLI T₁ values of both phantoms and human participants were determined. The quality of the algorithm's result was assessed by Pearson's correlation coefficient between shMOLLI T₁ values and spectroscopically determined T₁ values of the water, and by linear regression analysis. Correlation between shMOLLI and spectroscopy‐based T₁ values increased, from r = 0.910 (P < 0.001) to r = 0.998 (P < 0.001) in phantoms and from r = 0.493 (for iron‐only correction; P = 0.005) to r = 0.771 (for iron, fat and off‐resonance correction; P < 0.001) in patients. Linear regression analysis revealed that the determined water shMOLLI T₁ values in patients were independent of fat and iron. It can be concluded that determination of on‐resonance water (sh)MOLLI T₁ independent of fat, iron and macroscopic field inhomogeneities was possible in phantoms and human subjects.     

Acute renal impairment characterization using diffusion magnetic resonance imaging: Validation by histology

Diffusion magnetic resonance imaging has been demonstrated to be a simple, noninvasive and accurate method for the detection of renal microstructure and microcirculation, which are closely linked to renal function. Moreover, serum endothelin‐1 (ET‐1) was also reported as a good indicator of early renal injury. The aim of this study was to evaluate the feasibility and capability of diffusion MRI and ET‐1 to detect acute kidney injury by an operation simulating high‐pressure renal pelvic perfusion, which is commonly used during ureteroscopic lithotripsy. Histological findings were used as a reference. Fourteen New Zealand rabbits in an experimental group and 14 in a control group were used in this study. Diffusion tensor imaging and intravoxel incoherent motion diffusion‐weighted imaging were acquired by a 3.0 T MRI scanner. Significant corticomedullary differences were found in the values of the apparent diffusion coefficient (ADC), pure tissue diffusion, volume fraction of pseudo‐diffusion (fp) and fractional anisotropy (FA) (P < 0.05 for all) in both preoperation and postoperation experimental groups. Compared with the control group, the values of cortical fp_mean, medullary ADC_mean and FA_mean decreased significantly (P < 0.05) after the operation in the experimental group. Also, the change rate of medullary ADC_mean in the experimental group was more pronounced than that in the control group (P = 0.018). No significant change was found in serum ET‐1 concentration after surgery in either the experimental (P = 0.80) or control (P = 0.17) groups. In the experimental group, histological changes were observed in the medulla, while no visible change was found in the cortex. This study demonstrated the feasibility of diffusion MRI to detect the changes of renal microstructure and microcirculation in acute kidney injury, with the potential to evaluate renal function. Moreover, the sensitivity of diffusion MRI to acute kidney injury appears to be superior to that of serum ET‐1.     

Tumor apparent diffusion coefficient as an imaging biomarker to predict tumor aggressiveness in patients with estrogen‐receptor‐positive breast cancer

The purpose of this retrospective study was to evaluate whether tumor apparent diffusion coefficient (ADC) was correlated with pathologic biomarkers such as tumor cellularity, Ki67, tumor‐infiltrating lymphocytes (TILs), and peritumoral lymphocytic infiltrate (PLI) in patients with estrogen receptor (ER)‐positive breast cancer. The study was approved by the institutional review board and informed consent was waived. From July 2014 to December 2014, we reviewed 140 ER‐positive tumors in 138 consecutive patients (range, 28–77 years; mean, 52 years) who underwent preoperative breast MRI and definitive surgery. All patients underwent diffusion‐weighted imaging with a 3T scanner. Two radiologists drew the region of interest of the entire tumor and obtained the mean and pixel‐based histogram of ADC. On pathology, two pathologists reviewed tumor cellularity, Ki67, TILs, and PLI. Multiple linear regression analysis was used to determine pathologic variables independently associated with ADC. Tumors with high tumor cellularity and high Ki67 had significantly lower ADCs than those with low tumor cellularity and low Ki67 (P < 0.05 for all). Tumors without PLI had significantly higher standard deviation than those with PLI (0.23 ± 0.08 versus 0.18 ± 0.05; P < 0.001). Median ADC was negatively correlated with tumor cellularity (r = ?0.441), and Ki67 (r = ?0.382). The standard deviation of ADC was also negatively correlated with the degree of PLI (r = ?0.319). On multivariate linear regression analysis, tumor cellularity and Ki67 were independently associated with tumor ADC. Tumor ADC would be an MRI biomarker for the prediction of tumor aggressiveness indicators such as Ki67, tumor cellularity, and PLI in ER‐positive breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.     

Diffusion‐weighted imaging of the abdomen: Impact of b‐values on texture analysis features

The purpose of this work was to systematically assess the impact of the b‐value on texture analysis in MR diffusion‐weighted imaging (DWI) of the abdomen. In eight healthy male volunteers, echo‐planar DWI sequences at 16 b‐values ranging between 0 and 1000 s/mm² were acquired at 3 T. Three different apparent diffusion coefficient (ADC) maps were computed (0, 750/100, 390, 750 s/mm²/all b‐values). Texture analysis of rectangular regions of interest in the liver, kidney, spleen, pancreas, paraspinal muscle and subcutaneous fat was performed on DW images and the ADC maps, applying 19 features computed from the histogram, grey‐level co‐occurrence matrix (GLCM) and grey‐level run‐length matrix (GLRLM). Correlations between b‐values and texture features were tested with a linear and an exponential model; the best fit was determined by the smallest sum of squared residuals. Differences between the ADC maps were assessed with an analysis of variance. A Bonferroni‐corrected p‐value less than 0.008 (=0.05/6) was considered statistically significant. Most GLCM and GLRLM‐derived texture features (12–18 per organ) showed significant correlations with the b‐value. Four texture features correlated significantly with changing b‐values in all organs (p < 0.008). Correlation coefficients varied between 0.7 and 1.0. The best fit varied across different structures, with fat exhibiting mostly exponential (17 features), muscle mostly linear (12 features) and the parenchymatous organs mixed feature alterations. Two GLCM features showed significant variability in the different ADC maps. Several texture features vary systematically in healthy tissues at different b‐values, which needs to be taken into account if DWI data with different b‐values are analyzed. Histogram and GLRLM‐derived texture features are stable on ADC maps computed from different b‐values.     

Diffusion‐weighted MRI with intravoxel incoherent motion modeling for assessment of muscle perfusion in the thigh during post‐exercise hyperemia in younger and older adults

Aging is associated with impaired endothelium‐dependent vasodilation that leads to muscle perfusion impairment and contributes to organ dysfunction. Impaired muscle perfusion may result in inadequate delivery of oxygen and nutrients during and after muscle contraction, leading to muscle damage. The ability to study the relationship between perfusion and muscle damage has been limited using traditional muscle perfusion measures, which are invasive and risky. To overcome this limitation, we optimized a diffusion‐weighted MRI sequence and validated an intravoxel incoherent motion (IVIM) analysis based on Monte Carlo simulation to study muscle perfusion impairment with aging during post‐exercise hyperemia. Simulation results demonstrated that the bias of IVIM‐derived perfusion fraction (f_p ) and diffusion of water molecules in extra‐vascular tissue (D ) ranged from ?3.3% to 14% and from ?16.5% to 0.002%, respectively, in the optimized experimental condition. The dispersion in f_p and D ranged from 3.2% to 9.5% and from 0.9% to 1.1%, respectively. The mid‐thigh of the left leg of four younger (21–30 year old) and four older (60–90 year old) healthy females was studied using the optimized protocol at baseline and at seven time increments occurring every 3.25 min following in‐magnet dynamic knee extension exercise performed using a MR‐compatible ergometer with a workload of 0.4 bar for 2.5 min. After exercise, both f_p and D significantly increased in the rectus femoris (active muscle during exercise) but not in adductor magnus (inactive muscle), reflecting the fact that the local increase in perfusion with both groups showed a maximum value in the second post‐exercise time‐point. A significantly greater increase in perfusion from the baseline (p < 0.05) was observed in the younger group (37 ± 12.05%) compared with the older group (17.57 ± 15.92%) at the first post‐exercise measurement. This work establishes a reliable non‐invasive method that can be used to study the effects of aging on dynamic changes in muscle perfusion as they relate to important measures of physical function.     

Enzyme activities in the tibialis anterior muscle of young moderately active men and women: relationship with body composition,muscle cross‐sectional area and fibre type composition

The aims of this study were (i) to assess the differences between men and women in maximal activities of selected enzymes of aerobic and anaerobic pathways involved in skeletal muscle energy production, and (ii) to assess the relationships between maximal enzyme activities, body composition, muscle cross‐sectional area (CSA) and fibre type composition. Muscle biopsies were obtained from the tibialis anterior (TA) muscle of 15 men and 15 women (age 20–31 years) with comparable physical activity levels. The muscle CSA was determined by magnetic resonance imaging (MRI). Maximal activities of lactate dehydrogenase (LDH), phosphofructokinase (PFK), β‐hydroxyacyl‐coenzyme A dehydrogenase (HAD), succinate dehydrogenase (SDH) and citrate synthase (CS), were assayed spectrophotometrically. The proportion, mean area and relative area (proportion × area) of type 1 and type 2 fibres were determined from muscle biopsies prepared for enzyme histochemistry [myofibrillar adenosine triphosphatase (mATPase)]. The men were significantly taller (+6.6%; P < 0.001) and heavier (+19.1%; P < 0.001), had significantly larger muscle CSA (+19.0%; P < 0.001) and significantly larger areas and relative areas of both type 1 and type 2 fibres (+20.5–31.4%; P = 0.007 to P < 0.001). The men had significantly higher maximal enzyme activities than women for LDH (+27.6%; P = 0.007) and PFK (+25.5%; P = 0.003). There were no significant differences between the men and the women in the activities of HAD (+3.6%; ns), CS (+21.1%; P = 0.084) and SDH (+7.6%; ns). There were significant relationships between height and LDH (r = 0.41; P = 0.023), height and PFK (r = 0.41; P = 0.025), weight and LDH (r = 0.45; P = 0.013), and weight and PFK (r = 0.39; P = 0.032). The relationships were significant between the muscle CSA and the activities of LDH (r = 0.61; P < 0.001) and PFK (r = 0.56; P = 0.001), and between the relative area of type 2 fibres and the activities of LDH (r = 0.49; P = 0.006) and PFK (r = 0.42; P = 0.023). There were no significant relationships between HAD, CS and SDH, and height, weight, muscle CSA and fibre type composition, respectively. These data indicate that the higher maximal activities of LDH and PFK in men are related to the height, weight, muscle CSA and the relative area of type 2 fibres, which are all significantly larger in men than women.     

Simultaneous spin‐echo and gradient‐echo BOLD measurements by dynamic MRS

This study aimed to dissociate the intravascular and extravascular contributions to spin‐echo (SE) and gradient‐echo (GE) blood oxygenation level‐dependent (BOLD) signals at 7 T, using dynamic diffusion‐weighted MRS. We simultaneously acquired SE and GE data using a point‐resolved spectroscopy sequence with diffusion weightings of 0, 600, and 1200 s/mm². The BOLD signals were quantified by fitting the free induction decays starting from the SE center to a mono‐exponential decay function. Without diffusion weighting, BOLD signals measured with SE and GE increased by 1.6 ± 0.5% (TE_SE = 40 ms) and 5.2 ± 1.4% (nominal TE_GE = 40 ms) during stimulation, respectively. With diffusion weighting, the BOLD increase during stimulation measured with SE decreased from 1.6 ± 0.5% to 1.3 ± 0.4% (P < 0.001), whereas that measured by GE was unaffected (P > 0.05); the post‐stimulation undershoots in the BOLD signal time courses were largely preserved in both SE and GE measurements. These results demonstrated the feasiblity of simultaneous SE and GE measurements of BOLD signals with and without interleaved diffusion weighting. The results also indicated a predominant extravascular contribution to the BOLD signal time courses, including post‐stimulation undershoots in both SE and GE measurements at 7 T.