Measuring anisotropic muscle stiffness properties using elastography

Physiological and pathological changes to the anisotropic mechanical properties of skeletal muscle are still largely unknown, with only a few studies quantifying changes in vivo. This study used the noninvasive MR elastography (MRE) technique, in combination with diffusion tensor imaging (DTI), to measure shear modulus anisotropy in the human skeletal muscle in the lower leg. Shear modulus measurements parallel and perpendicular to the fibre direction were made in 10 healthy subjects in the medial gastrocnemius, soleus and tibialis anterior muscles. The results showed significant differences in the medial gastrocnemius (μ_‖ =0.86 ± 0.15 kPa; μ_⊥ = 0.66 ± 0.19 kPa, P < 0.001), soleus (μ_‖ = 0.83 ± 0.22 kPa; μ_⊥ = 0.65 ± 0.13 kPa, P < 0.001) and the tibialis anterior (μ_‖ = 0.78 ± 0.24 kPa; μ_⊥ = 0.66 ± 0.16 kPa, P = 0.03) muscles, where the shear modulus measured in the direction parallel is greater than that measured in the direction perpendicular to the muscle fibres. No significant differences were measured across muscle groups. This study provides the first direct estimates of the anisotropic shear modulus in the triceps surae muscle group, and shows that the technique may be useful for the probing of mechanical anisotropy changes caused by disease, aging and injury. Copyright © 2013 John Wiley & Sons, Ltd.     

Stiffness mapping of lower leg muscles during passive dorsiflexion

It is challenging to differentiate the mechanical properties of synergist muscles in vivo. Shear wave elastography can be used to quantify the shear modulus (i.e. an index of stiffness) of a specific muscle. This study assessed the passive behavior of lower leg muscles during passive dorsiflexion performed with the knee fully extended (experiment 1, n = 22) or with the knee flexed at 90° (experiment 2, n = 20). The shear modulus measurements were repeated twice during experiment 1 to assess the inter‐day reliability. During both experiments, the shear modulus of the following plantar flexors was randomly measured: gastrocnemii medialis (GM) and lateralis (GL), soleus (SOL), peroneus longus (PL), and the deep muscles flexor digitorum longus (FDL), flexor hallucis longus (FHL), tibialis posterior (TP). Two antagonist muscles tibialis anterior (TA), and extensor digitorum longus (EDL) were also recorded. Measurements were performed in different proximo‐distal regions for GM, GL and SOL. Inter‐day reliability was adequate for all muscles (coefficient of variation < 15%), except for TP. In experiment 1, GM exhibited the highest shear modulus at 80% of the maximal range of motion (128.5 ± 27.3 kPa) and was followed by GL (67.1 ± 24.1 kPa). In experiment 2, SOL exhibited the highest shear modulus (55.1 ± 18.0 kPa). The highest values of shear modulus were found for the distal locations of both the GM (80% of participants in experiment 1) and the SOL (100% of participants in experiment 2). For both experiments, deep muscles and PL exhibited low levels of stiffness during the stretch in young asymptomatic adults, which was unknown until now. These results provide a deeper understanding of passive mechanical properties and the distribution of stiffness between and within the plantar flexor muscles during stretching between them and thus could be relevant to study the effects of aging, disease progression, and rehabilitation on stiffness.     

Magnetic resonance elastography of the lungs: A repeatability and reproducibility study

Lung diseases are one of the leading causes of death worldwide, from which four million people die annually. Lung diseases are associated with changes in the mechanical properties of the lungs. Several studies have shown the feasibility of using magnetic resonance elastography (MRE) to quantify the lungs' shear stiffness. The aim of this study is to investigate the reproducibility and repeatability of lung MRE, and its shear stiffness measurements, obtained using a modified spin echo‐echo planar imaging (SE‐EPI) MRE sequence. In this study, 21 healthy volunteers were scanned twice by repositioning the volunteers to image right lung both at residual volume (RV) and total lung capacity (TLC) to assess the reproducibility of lung shear stiffness measurements. Additionally, 19 out of the 21 volunteers were scanned immediately without moving the volunteers to test the repeatability of the modified SE‐EPI MRE sequence. A paired t‐test was performed to determine the significant difference between stiffness measurements obtained at RV and TLC. Concordance correlation and Bland–Altman's analysis were performed to determine the reproducibility and repeatability of the SE‐EPI MRE‐derived shear stiffness measurements. The SE‐EPI MRE sequence is highly repeatable with a concordance correlation coefficient (CCC) of 0.95 at RV and 0.96 at TLC. Similarly, the stiffness measurements obtained across all volunteers were highly reproducible with a CCC of 0.95 at RV and 0.92 at TLC. The mean shear stiffness of the lung at RV was 0.93 ± 0.22 kPa and at TLC was 1.41 ± 0.41 kPa. TLC showed a significantly higher mean shear stiffness (P = 0.0004) compared with RV. Lung MRE stiffness measurements obtained using the SE‐EPI sequence were reproducible and repeatable, both at RV and TLC. Lung shear stiffness changes across respiratory cycle with significantly higher stiffness at TLC than RV.     

Magnetic resonance elastography of the lumbar back muscles: A preliminary study

Back pain is associated with increased lumbar paraspinal muscle (LPM) stiffness identified by manual palpation and strain elastography. Recently, magnetic resonance elastography (MRE) has allowed the stiffness of muscle to be characterized noninvasively in vivo, providing quantitative 3D stiffness maps (elastograms). The aim of this study was to characterize the stiffness (shear modulus, SM) of the LPM (multifidus and erector spinae) using MRE. MRE of the lumbar region was performed on seven adults in supine position. MRE was acquired in three muscular states: relaxed with outstretched legs, stretched with passive pelvis flexion, and contracted with outstretched legs and tightened trunk muscles. The mean SM was measured within a region of interest manually defined in the multifidus, erector spinae, and the entire paraspinal compartment. The intermuscular difference and the effects of stretching and contraction were assessed by ANOVA and t‐tests. At rest, the mean SM of the paraspinal compartment was 1.6 ± 0.2 kPa. It increased significantly with stretching to 1.65 ± 0.3 kPa, and with contraction to 2.0 ± 0.7 kPa. Irrespective of muscular state, the erector spinae was significantly stiffer than the multifidus. The multifidus underwent proportionally higher stiffness changes from rest to contraction and stretching. MRE can be used to measure the stiffness of the LPM in different muscular states. We hypothesize that, irrespective of posture, the erector spinae behaves as semi‐rigid beam, and ensures permanent stiffness of the spine. The multifidus behaves as an adaptable muscle that provides segmental flexibility to the spine and tunes the spine stiffness. Clin. Anat. 31:514–520, 2018. © 2018 Wiley Periodicals, Inc.     

Measuring changes in muscle stiffness after eccentric exercise using elastography

Muscle stiffness has been reported to increase following eccentric muscle exercise, but to date only indirect methods have been used to measure it. This study aimed to use Magnetic Resonance Elastography (MRE), a noninvasive imaging technique, to assess the time‐course of passive elasticity changes in the medial gastrocnemius and soleus muscles before and after a bout of eccentric exercise. Shear storage modulus (G′) and loss modulus (G′′) measurements were made in eight healthy subjects for both muscles in vivo before, one hour after, 48 hours after and 1 week after eccentric exercise. The results show a 21% increase in medial gastrocnemius storage modulus following eccentric exercise with a peak occurring ~48 hours after exercise (before exercise 1.15 ± 0.23 kPa, 48 hours after 1.38 ± 0.27 kPa). No significant changes in soleus muscle storage modulus were measured for the exercise protocol used in this study, and no significant changes in loss modulus were observed. This study provides the first direct measurements in skeletal muscle before and after eccentric exercise damage and suggests that MRE can be used to detect the time course of changes to muscle properties. Copyright © 2012 John Wiley & Sons, Ltd.     

Decreased water T2 in fatty infiltrated skeletal muscles of patients with neuromuscular diseases

Quantitative imaging techniques are emerging in the field of magnetic resonance imaging of neuromuscular diseases (NMD). T₂ of water (T_2w) is considered an important imaging marker to assess acute and chronic alterations of the muscle fibers, being generally interpreted as an indicator for “disease activity” in the muscle tissue. To validate the accuracy and robustness of quantitative imaging methods, ¹H magnetic resonance spectroscopy (MRS) can be used as a gold standard. The purpose of the present work was to investigate T_2w of remaining muscle tissue in regions of higher proton density fat fraction (PDFF) in 40 patients with defined NMD using multi‐TE single‐voxel ¹H MRS. Patients underwent MR measurements on a 3 T system to perform a multi‐TE single‐voxel stimulated echo acquisition method (STEAM) MRS (TE = 11/15/20/25(/35) ms) in regions of healthy, edematous and fatty thigh muscle tissue. Muscle regions for MRS were selected based on T₂‐weighted water and fat images of a two‐echo 2D Dixon TSE. MRS results were confined to regions with qualitatively defined remaining muscle tissue without edema and high fat content, based on visual grading of the imaging data. The results showed decreased T_2w values with increasing PDFF with R² = 0.45 (p < 10^?3) (linear fit) and with R² = 0.51 (exponential fit). The observed dependence of T_2w on PDFF should be considered when using T_2w as a marker in NMD imaging and when performing single‐voxel MRS for T_2w in regions enclosing edematous, nonedematous and fatty infiltrated muscle tissue.     

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 acquisition of multifrequency,multislice and multidirectional MR elastography data with a fractionally encoded gradient echo sequence

In MR elastography (MRE), periodic tissue motion is phase encoded using motion‐encoding gradients synchronized to an externally applied periodic mechanical excitation. Conventional methods result in extended scan time for quality phase images, thus limiting the broad application of MRE in the clinic. For practical scan times, researchers have been relying on one‐dimensional or two‐dimensional motion‐encoding, low‐phase sampling and a limited number of slices, and artifact‐prone, single‐shot, echo planar imaging (EPI) readout. Here, we introduce a rapid multislice pulse sequence capable of three‐dimensional motion encoding that is also suitable for simultaneously encoding motion with multiple frequency components. This sequence is based on a gradient‐recalled echo (GRE) sequence and exploits the principles of fractional encoding. This GRE MRE pulse sequence was validated as capable of acquiring full three‐dimensional motion encoding of isotropic voxels in a large volume within less than a minute. This sequence is suitable for monofrequency and multifrequency MRE experiments. In homogeneous paraffin phantoms, the eXpresso sequence yielded similar storage modulus values as those obtained with conventional methods, although with markedly reduced variances (7.11 ± 0.26 kPa for GRE MRE versus 7.16 ± 1.33 kPa for the conventional spin‐echo EPI sequence). The GRE MRE sequence obtained better phase‐to‐noise ratios than the equivalent spin‐echo EPI sequence (matched for identical acquisition time) in both paraffin phantoms and in vivo data in the liver (59.62 ± 11.89 versus 27.86 ± 3.81, 61.49 ± 14.16 versus 24.78 ± 2.48 and 58.23 ± 10.39 versus 23.48 ± 2.91 in the X, Y and Z components, respectively, in the case of liver experiments). Phase‐to‐noise ratios were similar between GRE MRE used in monofrequency or multifrequency experiments (75.39 ± 14.93 versus 86.13 ± 18.25 at 28 Hz, 71.52 ± 24.74 versus 86.96 ± 30.53 at 56 Hz and 95.60 ± 36.96 versus 61.35 ± 26.25 at 84Hz, respectively). Copyright © 2013 John Wiley & Sons, Ltd.     

Post‐contractile BOLD contrast in skeletal muscle at 7 T reveals inter‐individual heterogeneity in the physiological responses to muscle contraction

Muscle blood oxygenation‐level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre‐contraction signal intensity were observed in the soleus muscle. We observed considerable inter‐subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (T_R: 1000 and 2500 ms) to determine the potential of T₁‐related inflow effects on the magnitude of the post‐contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two T_R values (3.8 ± 0.9 versus 4.0 ± 0.6% for T_R = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post‐contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction.     

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.     

Magnetic Resonance Elastography of kidneys: SE‐EPI MRE reproducibility and its comparison to GRE MRE

The purpose of this study is 1) to demonstrate reproducibility of spin echo‐echo planar imaging (SE‐EPI) magnetic resonance elastography (MRE) to estimate kidney stiffness; and 2) to compare SE‐EPI MRE and gradient recalled echo (GRE) MRE‐derived stiffness estimations in various anatomical regions of the kidney. Kidney MRE was performed on 33 healthy subjects (8 for SE‐EPI MRE reproducibility and 25 for comparison with GRE MRE; age range: 22–66 years) in a 3 T MRI scanner. To demonstrate SE‐EPI MRE reproducibility, subjects were scanned for the first scan and then asked to leave the scan room and repositioned again for the second (repeat) scan. Similar set‐up was used for GRE MRE as well. The displacement data was then processed to obtain overall stiffness estimates of the kidney. Concordance correlation analyses were performed to determine SE‐EPI MRE reproducibility and agreement between GRE MRE and SE‐EPI MRE derived stiffness. A high concordance correlation (ρ_c = 0.95; p‐value<0.0001) was obtained for SE‐EPI MRE reproducibility. Good concordance correlation was observed (ρ_c = 0.84; p < 0.0001 for both kidneys, ρ_c = 0.91; p < 0.0001 for right kidney and ρ_c = 0.78; p < 0.0001 for left kidney) between GRE MRE and SE‐EPI MRE derived stiffness measurements. Paired t‐test results showed that stiffness value of medulla was significantly (p < 0.0001) greater than cortex using SE‐EPI MRE as well as GRE MRE. SE‐EPI MRE was reproducible and good agreement was observed in MRE‐derived stiffness measurements obtained using SE‐EPI and GRE sequences. Therefore, SE‐EPI can be used for kidney MRE applications.     

Three‐dimensional ultrashort echo time cones T1ρ (3D UTE‐cones‐T1ρ) imaging

We report a novel three‐dimensional (3D) ultrashort echo time (UTE) sequence employing Cones trajectory and T_1ρ preparation (UTE‐Cones‐T_1ρ) for quantitative T_1ρ assessment of short T₂ tissues in the musculoskeletal system. A basic 3D UTE‐Cones sequence was combined with a spin‐locking preparation pulse for T_1ρ contrast. A relatively short TR was used to decrease the scan time, which required T₁ measurement and compensation using 3D UTE‐Cones data acquisitions with variable TRs. Another strategy to reduce the total scan time was to acquire multiple Cones spokes (N_sp) after each T_1ρ preparation and fat saturation. Four spin‐locking times (TSL = 0–20 ms) were acquired over 12 min, plus another 7 min for T₁ measurement. The 3D UTE‐Cones‐T_1ρ sequence was compared with a two‐dimensional (2D) spiral‐T_1ρ sequence for the imaging of a spherical CuSO₄ phantom and ex vivo meniscus and tendon specimens, as well as the knee and ankle joints of healthy volunteers, using a clinical 3‐T scanner. The CuSO₄ phantom showed a T_1ρ value of 76.5 ± 1.6 ms with the 2D spiral‐T_1ρ sequence, as well as 85.7 ± 3.6 and 89.2 ± 1.4 ms for the 3D UTE‐Cones‐T_1ρ sequences with N_sp of 1 and 5, respectively. The 3D UTE‐Cones‐T_1ρ sequence provided shorter T_1ρ values for the bovine meniscus sample relative to the 2D spiral‐T_1ρ sequence (10–12 ms versus 16 ms, respectively). The cadaveric human Achilles tendon sample could only be imaged with the 3D UTE‐Cones‐T_1ρ sequence (T_1ρ = 4.0 ± 0.9 ms), with the 2D spiral‐T_1ρ sequence demonstrating near‐zero signal intensity. Human studies yielded T_1ρ values of 36.1 ± 2.9, 18.3 ± 3.9 and 3.1 ± 0.4 ms for articular cartilage, meniscus and the Achilles tendon, respectively. The 3D UTE‐Cones‐T_1ρ sequence allows volumetric T_1ρ measurement of short T₂ tissues in vivo.     

Bi‐exponential 23Na T2* component analysis in the human brain

The purpose of this study was to measure the sodium transverse relaxation time T₂* in the healthy human brain. Five healthy subjects were scanned with 18 echo times (TEs) as short as 0.17 ms. T₂* values were fitted on a voxel‐by‐voxel basis using a bi‐exponential model. Data were also analysed using a continuous distribution fit with a region of interest‐based inverse Laplace transform. Average T₂* values were 3.4 ± 0.2 ms and 23.5 ± 1.8 ms in white matter (WM) for the short and long components, respectively, and 3.9 ± 0.5 ms and 26.3 ± 2.6 ms in grey matter (GM) for the short and long components, respectively, using the bi‐exponential model. Continuous distribution fits yielded results of 3.1 ± 0.3 ms and 18.8 ± 3.2 ms in WM for the short and long components, respectively, and 2.9 ± 0.4 ms and 17.2 ± 2 ms in GM for the short and long components, respectively. ²³Na T₂* values of the brain for the short and long components for various anatomical locations using ultra‐short TEs are presented for the first time.     

Shortening of apparent transverse relaxation time of inorganic phosphate as a breast cancer biomarker

Phosphorus MRS offers a non‐invasive tool for monitoring cell energy and phospholipid metabolism and can be of additional value in diagnosing cancer and monitoring cancer therapy. In this study, we determined the transverse relaxation times of a number of phosphorous metabolites in a group of breast cancer patients by adiabatic multi‐echo spectroscopic imaging at 7 T. The transverse relaxation times of phosphoethanolamine, phosphocholine, inorganic phosphate (P_i), glycerophosphocholine and glycerophosphatidylcholine were 184 ± 8 ms, 203 ± 17 ms, 87 ± 8 ms, 240 ± 56 ms and 20 ± 10 ms, respectively. The transverse relaxation time of P_i in breast cancer tissue was less than half that of healthy fibroglandular tissue. This effect is most likely caused by an up‐regulation of glycolysis in breast cancer tissue that leads to interaction of P_i with the GAPDH enzyme, which forms part of the reversible pathway of exchange of P_i with gamma‐adenosine tri‐phosphate, thus shortening its apparent transverse relaxation time. As healthy breast tissue shows very little glycolytic activity, the apparent T₂ shortening of P_i due to malignant transformation could possibly be used as a biomarker for cancer.     

Evaluation of normal cadaveric Achilles tendon and enthesis with ultrashort echo time (UTE) magnetic resonance imaging and indentation testing

Entheses are regions where tendons and ligaments attach to bone, and are the primary target in seronegative and other diseases of the musculoskeletal (MSK) system. MRI has been widely used for visualizing features of inflammatory and degenerative MSK disease; however, normal tendons and entheses have short transverse relaxation times (T₂), and show little or no signal with conventional clinical MRI pulse sequences, making it difficult to investigate their MR properties. In this study we examined the normal MR morphology of the cadaveric Achilles tendon and enthesis at 3 T using novel three‐dimensional ultrashort echo time (3D UTE) Cones sequences, and at 11.7 T using conventional MRI sequences. We also studied the MR properties of the Achilles tendon and enthesis including T₂*, T₁, and magnetization transfer ratio (MTR). In addition, MT modeling of macromolecular proton fractions was investigated using 3D UTE Cones sequences at 3 T. Indentation testing was performed to investigate the mechanical properties of the tendons and entheses, and this was followed by histological examination. In total five specimens (<50 years) were investigated. On average, tendons and entheses respectively had T₂* values of 0.93 ± 0.48 ms and 2.77 ± 0.79 ms, T₁ values of 644 ± 22 ms and 780 ± 55 ms, MTRs of 0.373 ± 0.03 and 0.244 ± 0.009 with an MT power of 1000° and frequency offset of 2 kHz, and macromolecular proton fractions of 18.0 ± 2.2% and 13.9 ± 1.9%. Compared with the tendon, the enthesis generally had a longer T₂*, a longer T₁, a lower MTR, and a lower macromolecular proton fraction as well as both a higher Young's modulus and stiffness. Results from this study are likely to provide a useful baseline for identifying deviations from the normal in seronegative arthritis and other disease of the entheses.     

Global brain metabolic quantification with whole‐head proton MRS at 3 T

Total N‐acetyl‐aspartate + N‐acetyl‐aspartate–glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS (¹H–MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%–65% of the brain. Here we wish to demonstrate that non‐localized, whole‐head (WH) ¹H–MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 ± 8.5 years old, were recruited and underwent T₁‐weighted MRI for tissue segmentation, non‐localizing, approximately 3 min WH ¹H–MRS (T_E/T_R/T_I = 5/10 1 /940 ms) and 30 min ¹H–MR spectroscopic imaging (MRSI) (T_E/T_R = 35/2100 ms) in a 360 cm³ volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 ± 0.5, 5.5 ± 0.4 and 1.3 ± 0.2 mM, were all within 10% of the WH: 8.6 ± 1.1, 6.0 ± 1.0 and 1.3 ± 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the “brain‐only” VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 ± 0.03 (brain ≈ 30% of WH volume). Air‐tissue susceptibility‐driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non‐localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH‐¹H‐MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders.     

Single breath‐hold 3D cardiac T1 mapping using through‐time spiral GRAPPA

The quantification of cardiac T₁ relaxation time holds great potential for the detection of various cardiac diseases. However, as a result of both cardiac and respiratory motion, only one two‐dimensional T₁ map can be acquired in one breath‐hold with most current techniques, which limits its application for whole heart evaluation in routine clinical practice. In this study, an electrocardiogram (ECG)‐triggered three‐dimensional Look–Locker method was developed for cardiac T₁ measurement. Fast three‐dimensional data acquisition was achieved with a spoiled gradient‐echo sequence in combination with a stack‐of‐spirals trajectory and through‐time non‐Cartesian generalized autocalibrating partially parallel acquisition (GRAPPA) acceleration. The effects of different magnetic resonance parameters on T₁ quantification with the proposed technique were first examined by simulating data acquisition and T₁ map reconstruction using Bloch equation simulations. Accuracy was evaluated in studies with both phantoms and healthy subjects. These results showed that there was close agreement between the proposed technique and the reference method for a large range of T₁ values in phantom experiments. In vivo studies further demonstrated that rapid cardiac T₁ mapping for 12 three‐dimensional partitions (spatial resolution, 2 × 2 × 8 mm³) could be achieved in a single breath‐hold of ~12 s. The mean T₁ values of myocardial tissue and blood obtained from normal volunteers at 3 T were 1311 ± 66 and 1890 ± 159 ms, respectively. In conclusion, a three‐dimensional T₁ mapping technique was developed using a non‐Cartesian parallel imaging method, which enables fast and accurate T₁ mapping of cardiac tissues in a single short breath‐hold.     

Simultaneous muscle water T2 and fat fraction mapping using transverse relaxometry with stimulated echo compensation

Skeletal muscle inflammation/necrosis and fat infiltration are strong indicators of disease activity and progression in many neuromuscular disorders. They can be assessed by muscle T₂ relaxometry and water‐fat separation techniques, respectively. In the present work, we exploited differences between water and fat T₁ and T₂ relaxivities by applying a bi‐component extended phase graph (EPG) fitting approach to simultaneously quantify the muscle water T₂ and fat fraction from standard multi‐slice multi‐echo (MSME) acquisitions in the presence of stimulated echoes. Experimental decay curves were adjusted to the theoretical model using either an iterative non‐negative least‐squares (NNLS) procedure or a pattern recognition approach. Twenty‐two patients (age, 49 ± 18 years) were selected to cover a large range of muscle fat infiltration. Four cases of chronic or subchronic juvenile dermatomyositis (age, 8 ± 3 years) were investigated before and 3 months following steroid treatment. For control, five healthy volunteers (age, 25 ± 2 years) were recruited. All subjects underwent the MSME sequence and EPG fitting procedure. The EPG fitting algorithm allowed a precise estimation of water T₂ and fat fraction in diseased muscle, even in the presence of large B₁⁺ inhomogeneities. In the whole cohort of patients, there was no overall correlation between water T₂ values obtained with the proposed method and the fat fraction estimated inside muscle tissues (R² = 0.02). In the patients with dermatomyositis, there was a significant decrease in water T₂ (‐4.09 ± 3.7 ms) consequent to steroid treatment. The pattern recognition approach resulted in a 20‐fold decrease in processing time relative to the iterative NNLS procedure. The fat fraction derived from the EPG fitting approach correlated well with the fat fraction derived from a standard three‐point Dixon method (≈1.5% bias). The bi‐component EPG fitting analysis is a precise tool to monitor muscle tissue disease activity and is able to handle bias introduced by fat infiltration and B₁⁺ inhomogeneities. Copyright © 2016 John Wiley & Sons, Ltd.     

Adiabatic multi‐echo 31P spectroscopic imaging (AMESING) at 7 T for the measurement of transverse relaxation times and regaining of sensitivity in tissues with short T2* values

An adiabatic multi‐echo spectroscopic imaging (AMESING) sequence, used for ³¹P MRSI, with spherical k‐space sampling and compensated phase‐encoding gradients, was implemented on a whole‐body 7‐T MR system. One free induction decay (FID) and up to five symmetric echoes can be acquired with this sequence. In tissues with low T₂* and high T₂, this can theoretically lead to a potential maximum signal‐to‐noise ratio (SNR) increase of almost a factor of three, compared with a conventional FID acquisition with Ernst‐angle excitation. However, with T₂ values being, in practice, ≤400 ms, a maximum enhancement of approximately two compared with low flip Ernst‐angle excitation should be feasible. The multi‐echo sequence enables the determination of localized T₂ values, and was validated with ³¹P three‐dimensional MRSI on the calf muscle and breast of a healthy volunteer, and subsequently applied in a patient with breast cancer. The T₂ values of phosphocreatine, phosphodiesters (PDE) and inorganic phosphate in calf muscle were 193 ± 5 ms, 375 ± 44 ms and 96 ± 10 ms, respectively, and the apparent T₂ value of γ‐ATP was 25 ± 6 ms. A T₂ value of 136 ± 15 ms for inorganic phosphate was measured in glandular breast tissue of a healthy volunteer. The T₂ values of phosphomonoesters (PME) and PDE in breast cancer tissue (ductulolobular carcinoma) ranged between 170 and 210 ms, and the PME to PDE ratios were calculated to be phosphoethanolamine/glycerophosphoethanolamine = 2.7, phosphocholine/glycerophosphocholine = 1.8 and PME/PDE = 2.3. Considering the relatively short T₂* values of the metabolites in breast tissue at 7 T, the echo spacing can be short without compromising spectral resolution, whilst maximizing the sensitivity. Copyright © 2013 John Wiley & Sons, Ltd.     

The effect of arterial wall shear stress on the incremental elasticity of a conduit artery

Aims: The purpose of this investigation was to determine the effects of flow mediated dilatation on arterial incremental elasticity (E_inc). Methods: In four female anaesthetized pigs, the iliac artery and vein were connected by a shunt with a variable resistance which allowed blood flow and therefore shear stress to be regulated. E_inc was calculated from simultaneous records of diameter and pressure throughout a minimum of four cardiac cycles. Results: Passive increases in diameter (～1–2%) throughout a cardiac cycle, brought about by pressure, resulted in a two‐ to threefold increase in E_inc. In contrast, increases in shear stress caused active smooth muscle relaxation and a significant increase in diameter from 3.663 ± 0.215 mm to 4.488 ± 0.163 mm (mean ± SEM, P < 0.05) equivalent to a fractional increase in diameter (fD) of 1.5 with no significant change in mean arterial pressure, 108 ± 2 mmHg to 106 ± 1 mmHg (mean ± SEM). The average value of E_inc per cardiac cycle at baseline was 2.17 ± 0.10 × 10³ kPa and remained relatively constant until fD exceeded 1.3 thereafter increasing to a maximum of 9.23 ± 1.0 × 10³ kPa. Conclusion: These results show that in a conduit artery during the dilatory response to shear stress, the interaction between smooth muscle and collagen operates so as to maintain E_inc relatively constant over much of the working range of dilatation. This is consistent with a model of the arterial wall in which collagen is recruited both by passive stretch, in response to an increase in pressure and therefore wall stress, and also by active contraction of smooth muscle.