High‐resolution diffusion tensor imaging of the human kidneys using a free‐breathing,multi‐slice,targeted field of view approach

Fractional anisotropy (FA) obtained by diffusion tensor imaging (DTI) can be used to image the kidneys without any contrast media. FA of the medulla has been shown to correlate with kidney function. It is expected that higher spatial resolution would improve the depiction of small structures within the kidney. However, the achievement of high spatial resolution in renal DTI remains challenging as a result of respiratory motion and susceptibility to diffusion imaging artefacts. In this study, a targeted field of view (TFOV) method was used to obtain high‐resolution FA maps and colour‐coded diffusion tensor orientations, together with measures of the medullary and cortical FA, in 12 healthy subjects. Subjects were scanned with two implementations (dual and single kidney) of a TFOV DTI method. DTI scans were performed during free breathing with a navigator‐triggered sequence. Results showed high consistency in the greyscale FA, colour‐coded FA and diffusion tensors across subjects and between dual‐ and single‐kidney scans, which have in‐plane voxel sizes of 2 × 2 mm² and 1.2 × 1.2 mm², respectively. The ability to acquire multiple contiguous slices allowed the medulla and cortical FA to be quantified over the entire kidney volume. The mean medulla and cortical FA values were 0.38 ± 0.017 and 0.21 ± 0.019, respectively, for the dual‐kidney scan, and 0.35 ± 0.032 and 0.20 ± 0.014, respectively, for the single‐kidney scan. The mean FA between the medulla and cortex was significantly different (p < 0.001) for both dual‐ and single‐kidney implementations. High‐spatial‐resolution DTI shows promise for improving the characterization and non‐invasive assessment of kidney function. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Quantification of MRI signal of transgenic grafts overexpressing ferritin in murine myocardial infarcts

The noninvasive detection of transplanted cells in damaged organs and the longitudinal follow‐up of cell fate and graft size are important for the evaluation of cell therapy. We have shown previously that the overexpression of the natural iron storage protein, ferritin, permits the detection of engrafted cells in mouse heart by MRI, but further imaging optimization is required. Here, we report a systematic evaluation of ferritin‐based stem cell imaging in infarcted mouse hearts in vivo using three cardiac‐gated pulse sequences in a 3‐T scanner: black‐blood proton‐density‐weighted turbo spin echo (PD TSE BB), bright‐blood T₂*‐weighted gradient echo (GRE) and black‐blood T₂*‐weighted GRE with improved motion‐sensitized‐driven equilibrium (iMSDE) preparation. Transgenic C2C12 myoblast grafts overexpressing ferritin did not change MRI contrast in the PD TSE BB images, but showed a 20% reduction in signal intensity ratio in black‐blood T₂*‐weighted iMSDE (p < 0.05) and a 30% reduction in bright‐blood T₂*‐weighted GRE (p < 0.0001). Graft size measurements by T₂* iMSDE and T₂* GRE were highly correlated with histological assessments (r = 0.79 and r = 0.89, respectively). Unlabeled wild‐type C2C12 cells transplanted to mouse heart did not change the MRI signal intensity, although endogenous hemosiderin was seen in some infarcts. These data support the use of ferritin to track the survival, growth and migration of stem cells transplanted into the injured heart. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

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.     

Quantitative BOLD response of the renal medulla to hyperoxic challenge at 1.5 T and 3.0 T

The aim of this study was to gage the magnitude of changes of the apparent renal medullary transverse relaxation time (ΔT₂*) induced by inhalation of pure oxygen (O₂) or carbogen (95% O₂, 5% CO₂) versus baseline breathing of room air. Eight healthy volunteers underwent 2D multi‐gradient echo MR imaging at 1.5 T and 3.0 T. Parametrical T₂* relaxation time maps were computed and average T₂* was measured in regions of interest placed in the renal medulla and cortex. The largest T₂* changes were measured in the renal medulla, with a relative ?T₂* of 33.8 ± 22.0% (right medulla) and 34.7 ± 17.6% (left medulla) as compared to room air for oxygen breathing (p > 0.01), and 53.8 ± 23.9% and 53.5 ± 33.9% (p < 0.01) for carbogen breathing, respectively at 3 T. At 1.5 T, the corresponding values were 13.7 ± 18.5% and 24.1 ± 17.1% (p < 0.01) for oxygen breathing and 23.9 ± 17.2% and 38.9 ± 37.6% (p < 0.01) for carbogen breathing. As a result, we showed that renal medullary T₂* times responded strongly to inhalation of hyperoxic gases, which may be attributed to the hypoxic condition of the medulla and subsequent reduction in deoxyhemoglobin. Copyright © 2012 John Wiley & Sons, Ltd.     

Relaxometry and quantification in sodium MRI of cerebral gliomas: A FET‐PET and MRI small‐scale study

Sodium MRI is a promising method for assessing the metabolic properties of brain tumours. In a recent study, a strong relationship between semi‐quantitative abnormalities in sodium MRI and the mutational status of the isocitrate dehydrogenase enzyme (IDH) with untreated cerebral gliomas was observed. Here, sodium relaxometry in brain tumour tissue was investigated in relation to molecular markers in order to reveal quantitative sodium tissue parameters and the differences between healthy tissue and brain tumour. The previous semi‐quantitative approach is extended by use of suitable relaxometry methods accompanied by numerical simulation to achieve detailed quantitative analysis of intra‐ and extracellular sodium concentration using an enhanced SISTINA sequence at 4 T. Using optimised techniques, biexponential sodium relaxation times in tumour (T*_2f, T*_2s) and in healthy contralateral brain tissue (T*_2f,CL, T*_2s,CL) were estimated in 10 patients, along with intracellular sodium molar fractions (χ, χ_CL), volume fractions (η, η_CL) and concentrations (ρ_in, ρ_in,CL). The total sodium tissue concentrations (ρ_T, ρ_T,CL) were also estimated. The ratios T*_2f/T*_2f,CL (P = .05), η/η_CL (P = .02) and χ/χ_CL (P = .02) were significantly lower in IDH mutated than in IDH wildtype gliomas (n = 4 and n = 5 patients, respectively). The Wilcoxon rank‐sum test was used to compare sodium MRI parameters in patients with and without IDH mutation. Thus, quantitative analysis of relaxation rates, intra‐ and extracellular sodium concentrations, intracellular molar and volume fractions based on enhanced SISTINA confirmed a relationship between abnormalities in sodium parameters and the IDH mutational status in cerebral gliomas, hence catering for the potential to provide further insights into the status of the disease.     

Evaluation of skeletal muscle DTI in patients with duchenne muscular dystrophy

Diffusion tensor imaging (DTI) is a popular method to assess differences in fiber organization in diseased and healthy muscle tissue. Previous work has shown that muscle DTI measurements depend on signal‐to‐noise ratio (SNR), %fat, and tissue T₂. The goal of this study was to evaluate the potential biasing effects of these factors on skeletal muscle DTI data in patients with Duchenne Muscular Dystrophy (DMD). MR images were obtained of the right lower leg of 21 DMD patients and 12 healthy controls on a Philips 3T system. DTI measurements were combined with quantitative in‐vivo measures of mean water T₂, %fat and SNR to evaluate their effect on DTI parameter estimation. All outcome measures were determined within ROIs drawn for six lower leg muscles. Between group analysis, using all ROIs, revealed a significantly elevated FA in the GCL, SOL and PER muscles (p<0.05) and an increased mean diffusivity (p<0.05) and λ₃ (p<0.05) in the TA muscle of DMD patients. In‐vivo evaluation of the individual confounders showed behaviour in line with predictions from previous simulation work. To account for these confounders, subsequent analysis used only ROIs with SNR greater than 20. With this criterion we found significantly greater MD in the TA muscle of DMD patient (p<0.009) and λ₃ in the TA and GCL muscles (p<0.001) of DMD patients, but no differences in FA. As both increased %fat and lower SNR are expected to reduce the apparent MD and λ₃, these between‐group differences are likely due to pathophysiology. However, the increased FA, observed when using all ROIs, likely reflects the effect of low SNR and %fat on the DTI parameter estimation. These findings suggest that measuring mean water T₂, %fat and SNR is essential to ascribe changes in DTI measures to intrinsic diffusion changes or to confounding influences. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

Quantitative T2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T

This study uses quantitative T₂* imaging to track ferumoxides–protamine sulfate (FEPro)‐labeled MDA‐MB‐231BR‐Luc (231BRL) human breast cancer cells that metastasize to the nude rat brain. Four cohorts of nude rats were injected intracardially with FEPro‐labeled, unlabeled or tumor necrosis factor‐related apoptosis‐inducing ligand(TRAIL)‐treated (to induce apoptosis) 231BRL cells, or saline, in order to develop metastatic breast cancer in the brain. The heads of the rats were imaged serially over 3–4 weeks using gradient multi‐echo and turbo spin‐echo pulse sequences at 3 T with a solenoid receive‐only 4‐cm‐diameter coil. Quantitative T₂* maps of the whole brain were obtained by the application of single‐exponential fitting to the signal intensity of T₂* images, and the distribution of T₂* values in brain voxels was calculated. MRI findings were correlated with Prussian blue staining and immunohistochemical staining for iron in breast cancer and macrophages. Quantitative analysis of T₂* from brain voxels demonstrated a significant shift to lower values following the intracardiac injection of FEPro‐labeled 231BRL cells, relative to animals receiving unlabeled cells, apoptotic cells or saline. Quartile analysis based on the T₂* distribution obtained from brain voxels demonstrated significant differences (p < 0.0083) in the number of voxels with T₂* values in the ranges 10–35 ms (Q1), 36–60 ms (Q2) and 61–86 ms (Q3) from 1 day to 3 weeks post‐infusion of labeled 231BRL cells, compared with baseline scans. There were no significant differences in the distribution of T₂* obtained from serial MRI in rats receiving unlabeled or TRAIL‐treated cells or saline. Histologic analysis demonstrated isolated Prussian blue‐positive breast cancer cells scattered in the brains of rats receiving labeled cells, relative to animals receiving unlabeled or apoptotic cells. Quantitative T₂* analysis of FEPro‐labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T₂*‐weighted images. Published in 2010 by John Wiley & Sons, Ltd.     

In vivo carotid plaque MRI using quantitative T2* measurements with ultrasmall superparamagnetic iron oxide particles: a dose-response study to statin therapy

This study investigates T₂* quantification in carotid plaques before and after the administration of ultrasmall superparamagnetic iron oxide particles (USPIOs) in a cohort of patients receiving statin therapy. Phantom studies were performed using gels with varying concentrations of USPIOs. In the phantom study, 12 gels were prepared with a range of freely distributed concentrations of USPIO nanoparticles (0–0.05 mg/mL). Relative signal intensity measurements were obtained from a T₂*‐weighted sequence as well as quantitative T₂* (qT₂*) measurements. In the patient study, 40 patients with >40% carotid stenosis were randomised to low‐ and high‐dose statin therapy (10 and 80 mg of atorvastatin). Pre‐ and post‐ (36 h) USPIO‐enhanced MRI were performed at baseline, and at 6 and 12 weeks. A linear mixed‐effects model was applied to account for the inherent correlation of multiple‐plaque measurements from the same patient and to assess dose–response differences to statin therapy. In the phantom study, the T₂*‐weighted sequence demonstrated an initial increase (T₁ effect), followed by a decrease (T₂* effect), in relative signal intensity with increasing concentrations of USPIO. The qT₂* values decreased exponentially with increasing concentrations of USPIO. In the patient study, there was a highly significant difference in post‐USPIO T₂* measurements in plaques between the low‐ and high‐dose statin groups. This was observed for both the difference in qT₂* measurements (post‐USPIO minus pre‐USPIO) (p < 0.001) and for qT₂* post‐USPIO only (p < 0.001). The post‐USPIO qT₂* values were as follows: baseline: low dose, 13.6 ± 5.5 ms; high dose, 12.9 ± 6.2 ms; 6 weeks: low dose, 13.3 ± 6.7 ms; high dose, 14.3 ± 7.7 ms; 12 weeks: low dose, 14.0 ± 7.6 ms; high dose, 18.3 ± 11.2 ms. It can be concluded that qT₂* measurements provide an alternative method of quantifying USPIO uptake. These results also demonstrate that changes in USPIO uptake can be measured using post‐USPIO imaging only. Copyright © 2010 John Wiley & Sons, Ltd.     

Is renal medullary carcinoma the seventh nephropathy in sickle cell disease? A multi-center Nigerian survey

IntroductionPrevious studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption.ObjectiveTo estimate the prevalence of RMC and describe other renal complications in SCD.ResultsOf the 3,596 registered sickle patients, 2 (0.056%) had been diagnosed with RMC over a ten year period, thereby giving an estimated prevalence rate of 5.6 per 100,000. The most common renal complication reported by the attending physicians was chronic kidney disease (CKD). The frequency of routine renal screening for SCD patients varied widely between centres — most were done at diagnosis, annually or bi-annually.ConclusionThe ten year prevalence of RMC in Nigerian SCD patients was determined to be 5.6 (estimated incidence of 0.56). RMC is not more common in SCD patients and therefore cannot be regarded as a “Seventh Sickle nephropathy”. Most of the managing physicians reported that the commonest nephropathy observed in their SCD patients was chronic kidney disease.     

In vitro mapping of 1H ultrashort T2* and T2 of porcine menisci

In this study, mapping of ultrashort T₂ and T₂* of acutely isolated porcine menisci at B₀ = 9.4 T was investigated. Maps of T₂ were measured from a slice through the pars intermedia with a spin echo‐prepared two‐dimensional ultrashort‐TE T₂ mapping technique published previously. T₂* mapping was performed by two‐dimensional ultrashort‐TE MRI with variable acquisition delay. The measured signal decays were fitted by monoexponential, biexponential and Gaussian‐exponential fitting functions. The occurrence of Gaussian‐like signal decays is outlined theoretically. The quality of the curve fits was visualized by mapping the value δ = abs(1 – χ²_red). For T₂* mapping, the Gaussian‐exponential fit showed the best performance, whereas the monoexponential and biexponential fits showed regionally high values of δ (δ > 20). Interpretation of the Gaussian‐exponential parameter maps was found to be difficult, because a Gaussian signal component can be related to mesoscopic (collagen texture) or macroscopic (slice profile, shim, sample geometry) magnetic field inhomogeneities and/or residual ¹H dipole–dipole couplings. It seems likely that an interplay of these effects yielded the observed signal decays. Modulation of the T₂* signal decay caused by chemical shift was observed and addressed to fat protons by means of histology. In the T₂ measurements, no modulation of the signal decay was observed and the biexponential and Gaussian‐exponential fits showed the best performance with comparable values of δ. Our results suggest that T₂ mapping provides the more robust method for the characterization of meniscal tissue by means of MRI relaxometry. However, mapping of ultrashort T₂, as performed in this study, is time consuming and provides less signal‐to‐noise ratio per time than the mapping of T₂*. If T₂* mapping is used, pixel‐wise monitoring of the fitting quality based on reduced χ² should be employed and great care should be taken when interpreting the parameter maps of the fits. Copyright © 2013 John Wiley & Sons, Ltd.     

Rapid MR relaxometry using deep learning: An overview of current techniques and emerging trends

Quantitative mapping of MR tissue parameters such as the spin-lattice relaxation time (T₁), the spin-spin relaxation time (T₂), and the spin-lattice relaxation in the rotating frame (T_1ρ), referred to as MR relaxometry in general, has demonstrated improved assessment in a wide range of clinical applications. Compared with conventional contrast-weighted (eg T₁-, T₂-, or T_1ρ-weighted) MRI, MR relaxometry provides increased sensitivity to pathologies and delivers important information that can be more specific to tissue composition and microenvironment. The rise of deep learning in the past several years has been revolutionizing many aspects of MRI research, including image reconstruction, image analysis, and disease diagnosis and prognosis. Although deep learning has also shown great potential for MR relaxometry and quantitative MRI in general, this research direction has been much less explored to date. The goal of this paper is to discuss the applications of deep learning for rapid MR relaxometry and to review emerging deep-learning-based techniques that can be applied to improve MR relaxometry in terms of imaging speed, image quality, and quantification robustness. The paper is comprised of an introduction and four more sections. Section 2 describes a summary of the imaging models of quantitative MR relaxometry. In Section 3, we review existing “classical” methods for accelerating MR relaxometry, including state-of-the-art spatiotemporal acceleration techniques, model-based reconstruction methods, and efficient parameter generation approaches. Section 4 then presents how deep learning can be used to improve MR relaxometry and how it is linked to conventional techniques. The final section concludes the review by discussing the promise and existing challenges of deep learning for rapid MR relaxometry and potential solutions to address these challenges.     

Characterization of trabecular bone density with ultra‐short echo‐time MRI at 1.5, 3.0 and 7.0 T – comparison with micro‐computed tomography

The goal of this study was to test the potential of ultra‐short echo‐time (UTE) MRI at 1.5, 3.0 and 7.0 T for depiction of trabecular bone structure (of the wrist bones), to evaluate whether T₂* relaxation times of bone water and parametric maps of T₂* of trabecular bone could be obtained at all three field strengths, and to compare the T₂* relaxation times with structural parameters obtained from micro‐computed tomography (micro‐CT) as a reference standard. Ex vivo carpal bones of six wrists were excised en bloc and underwent MRI at 1.5, 3.0 and 7.0 T in a whole‐body MR imager using the head coil. A three‐dimensional radial fat‐suppressed UTE sequence was applied with subsequent acquisitions, with six different echo times T_E of 150, 300, 600, 1200, 3500 and 7000 µs. The T₂* relaxation time and pixel‐wise computed T₂* parametric maps were compared with a micro‐computed‐tomography reference standard providing trabecular bone structural parameters including porosity (defined as the bone‐free fraction within a region of interest), trabecular thickness, trabecular separation, trabecular number and fractal dimension (D_k). T₂* relaxation curves and parametric maps could be computed from datasets acquired at all field strengths. Mean T₂* relaxation times of trabecular bone were 4580 ± 1040 µs at 1.5 T, 2420 ± 560 µs at 3.0 T and 1220 ± 300 µs at 7.0 T, when averaged over all carpal bones. A positive correlation of T₂* with trabecular bone porosity and trabecular separation, and a negative correlation of T₂* relaxation time with trabecular thickness, trabecular number and fractal dimension, was detected (p < 0.01 for all field strengths and micro‐CT parameters). We conclude that UTE MRI may be useful to characterize the structure of trabecular bone, comparable to micro‐CT. Copyright © 2014 John Wiley & Sons, Ltd.     

Feasibility of quantitative ultrashort echo time (UTE)‐based methods for MRI of peripheral nerve

Peripheral nerves are a composite tissue consisting of neurovascular elements packaged within a well‐organized extracellular matrix. Their composition, size, and anatomy render nerves a challenging medical imaging target. In contrast to morphological MRI, which represents the predominant approach to nerve imaging, quantitative MRI sequences can provide information regarding tissue composition. Here, we applied standard clinical Carr‐Purcell‐Meiboom‐Gill (CPMG) and experimental three‐dimensional (3D) ultrashort echo time (UTE) Cones sequences for quantitative nerve imaging including T₂ measurement with single‐component analysis, T₂* measurement with single‐component and bi‐component analyses, and magnetization transfer ratio (MTR) analysis. We demonstrated the feasibility and the high quality of single‐component T₂*, bi‐component T₂*, and MTR approaches to analyze nerves imaged with clinically deployed 3D UTE Cones pulse sequences. For 24 single fascicles from eight nerves, we measured a mean single‐component T₂* of 22.6 ±8.9 ms, and a short T₂* component (STC) with a mean T₂* of 1.7 ±1.0 ms and a mean fraction of (6.74 ±4.31)% in bi‐component analysis. For eight whole nerves, we measured a mean single‐component T₂* of 16.7 ±2.2 ms, and an STC with a mean T₂* of 3.0 ±1.0 ms and a mean fraction of (15.56 ±7.07)% in bi‐component analysis. For nine fascicles from three healthy nerves, we measured a mean MTR of (25.2 ±1.9)% for single fascicles and a mean MTR of (23.6 ±0.9)% for whole nerves. No statistically significant correlation was observed between any MRI parameter and routine histological outcomes, perhaps due to the small sample size and lack of apparent sample pathology. Overall, we have successfully demonstrated the feasibility of measuring quantitative MR outcomes ex vivo, which might reflect features of nerve structure and macromolecular content. These methods should be validated comprehensively on a larger and more diverse set of nerve samples, towards the interpretation of in vivo outcomes. These approaches have new and broad implications for the management of nerve disease, injury, and repair.     

Rapid assessment of quantitative T1, T2 and T2* in lower extremity muscles in response to maximal treadmill exercise

MRI provides a non‐invasive diagnostic platform to quantify the physical and physiological attributes of skeletal muscle at rest and in response to exercise. MR relaxation parameters (T₁, T₂ and T₂*) are characteristic of tissue composition and metabolic properties. With the recent advent of quantitative techniques that allow rapid acquisition of T₁, T₂ and T₂* maps, we posited that an integrated treadmill exercise–quantitative relaxometry paradigm can rapidly characterize exercise‐induced changes in skeletal muscle relaxation parameters. Accordingly, we investigated the rest/recovery kinetics of T₁, T₂ and T₂* in response to treadmill exercise in the anterior tibialis, soleus and gastrocnemius muscles of healthy volunteers, and the relationship of these parameters to age and gender. Thirty healthy volunteers (50.3 ± 16.6 years) performed the Bruce treadmill exercise protocol to maximal exhaustion. Relaxometric maps were sequentially acquired at baseline and for approximately 44 minutes post‐exercise. Our results show that T₁, T₂ and T₂* are significantly and differentially increased immediately post‐exercise among the leg muscle groups, and these values recover to near baseline within 30–44 minutes. Our results demonstrate the potential to characterize the kinetics of relaxation parameters with quantitative mapping and upright exercise, providing normative values and some clarity on the impact of age and gender. Copyright © 2015 John Wiley & Sons, Ltd.     

Technical considerations on the validity of blood oxygenation level‐dependent‐based MR assessment of vascular deoxygenation

A blood oxygenation level‐dependent (BOLD)‐based apparent relative oxygen extraction fraction (rOEF) as a semi‐quantitative marker of vascular deoxygenation has recently been introduced in clinical studies of patients with glioma and stroke, yielding promising results. These rOEF measurements are based on independent quantification of the transverse relaxation times T₂ and T₂* and relative cerebral blood volume (rCBV). Simulations demonstrate that small errors in any of the underlying measures may result in a large deviation of the calculated rOEF. Therefore, we investigated the validity of such measurements. For this, we evaluated the quantitative measurements of T₂ and T₂* at 3 T in a gel phantom, in healthy subjects and in healthy tissue of patients with brain tumors. We calculated rOEF maps covering large portions of the brain from T₂, T₂* and rCBV [routinely measured in patients using dynamic susceptibility contrast (DSC)], and obtained rOEF values of 0.63 ± 0.16 and 0.90 ± 0.21 in healthy‐appearing gray matter (GM) and white matter (WM), respectively; values of about 0.4 are usually reported. Quantitative T₂ mapping using the fast, clinically feasible, multi‐echo gradient spin echo (GRASE) approach yields significantly higher values than much slower multiple single spin echo (SE) experiments. Although T₂* mapping is reliable in magnetically homogeneous tissues, uncorrectable macroscopic background gradients and other effects (e.g. iron deposition) shorten T₂*. Cerebral blood volume (CBV) measurement using DSC and normalization to WM yields robust estimates of rCBV in healthy‐appearing brain tissue; absolute quantification of the venous fraction of CBV, however, is difficult to achieve. Our study demonstrates that quantitative measurements of rOEF are currently biased by inherent difficulties in T₂ and CBV quantification, but also by inadequacies of the underlying model. We argue, however, that standardized, reproducible measurements of apparent T₂, T₂* and rCBV may still allow the estimation of a meaningful apparent rOEF, which requires further validation in clinical studies. Copyright © 2014 John Wiley & Sons, Ltd.     

Molecular Dynamics of Amphiphilic Random Copolymers in the Bulk: A 1H and 19F NMR Relaxometry Study

A set of amphiphilic random copolymers of poly(ethylene glycol) methacrylate (PEGMA) and perfluorohexylethyl acrylate (FA) with different compositions synthesized by atom transfer radical polymerization (ATRP) is investigated by ¹H and ¹⁹F NMR relaxometry. In particular, a thorough investigation of T₁ and T₂ relaxation times at variable temperature and copolymer composition provides the first complete and detailed characterization of the dynamics of both the main chain backbone and the side chains of the PEGMA‐co‐FA copolymers. The results highlight an intramolecular segregation of rigid main chain and mobile side chains, and an additional self‐assembling of the PEGMA and FA side chains into distinct nanodomains, driven by the hydrophobic interactions between FA side chains. The obtainment and observation of nanoscale phase separation in random copolymers is a promising achievement to the aim of controlling self‐assembly in the bulk by suitably modulating copolymers composition, which can open novel avenues to easier fabrications and applications in nanotechnologies.     

Multi‐parametric MRI characterization of healthy human thigh muscles at 3.0 T – relaxation,magnetization transfer,fat/water,and diffusion tensor imaging

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo‐pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin‐echo T₂ imaging (with and without fat signal suppression, FS), selective inversion recovery for T₁ and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re‐imaged an average of 35 days later. Pre‐testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between‐day intra‐class correlations were observed in all quantitative indices except for the macromolecular‐to‐free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two‐way analysis of variance revealed no significant between‐day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland–Altman plots, and low repeatability coefficients were obtained for all parameters. Among‐muscle differences in the quantitative MRI indices and inter‐class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T₁, T₂, fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters. Copyright © 2014 John Wiley & Sons, Ltd.     

Overhauser‐enhanced magnetic resonance elastography

Magnetic resonance elastography (MRE) is a powerful technique to assess the mechanical properties of living tissue. However, it suffers from reduced sensitivity in regions with short T₂ and T₂* such as in tissue with high concentrations of paramagnetic iron, or in regions surrounding implanted devices. In this work, we exploit the longer T₂* attainable at ultra‐low magnetic fields in combination with Overhauser dynamic nuclear polarization (DNP) to enable rapid MRE at 0.0065 T. A 3D balanced steady‐state free precession based MRE sequence with undersampling and fractional encoding was implemented on a 0.0065 T MRI scanner. A custom‐built RF coil for DNP and a programmable vibration system for elastography were developed. Displacement fields and stiffness maps were reconstructed from data recorded in a polyvinyl alcohol gel phantom loaded with stable nitroxide radicals. A DNP enhancement of 25 was achieved during the MRE sequence, allowing the acquisition of 3D Overhauser‐enhanced MRE (OMRE) images with (1.5 × 2.7 × 9) mm³ resolution over eight temporal steps and 11 slices in 6 minutes. In conclusion, OMRE at ultra‐low magnetic field can be used to detect mechanical waves over short acquisition times. This new modality shows promise to broaden the scope of conventional MRE applications, and may extend the utility of low‐cost, portable MRI systems to detect elasticity changes in patients with implanted devices or iron overload. Copyright © 2016 John Wiley & Sons, Ltd.