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.     

Immersion of Achilles tendon in phosphate‐buffered saline influences T1 and T2* relaxation times: An ex vivo study

Robust mapping of relaxation parameters in ex vivo tissues is based on hydration and therefore requires control of the tissue treatment to ensure tissue integrity and consistent measurement conditions over long periods of time. One way to maintain the hydration of ex vivo tendon tissue is to immerse the samples in a buffer solution. To this end, various buffer solutions have been proposed; however, many appear to influence the tissue relaxation times, especially with prolonged exposure. In this work, ovine Achilles tendon tissue was used as a model to investigate the effect of immersion in phosphate‐buffered saline (PBS) and the effects on the T₁ and T₂^* relaxation times. Ex vivo samples were measured at 0 (baseline), 30 and 67 hours after immersion in PBS. Ultrashort echo time (UTE) imaging was performed using variable flip angle and echo train‐shifted multi‐echo imaging for T₁ and T₂^* estimation, respectively. Compared with baseline, both T₁ and T₂^* relaxation time constants increased significantly after 30 hours of immersion. T₂^* continued to show a significant increase between 30 and 67 hours. Both T₁ and T₂^* tended to approach saturation at 67 hours. These results exemplify the relevance of stringently controlled tissue preparation and preservation techniques, both before and during MRI experiments.     

Multi‐parametric T2* magnetic resonance fingerprinting using variable echo times

The use of quantitative imaging biomarkers in the imaging of various disease states, including cancer and neurodegenerative disease, has increased in recent years. T₁, T₂, and T₂* relaxation time constants have been shown to be affected by tissue structure or contrast infusion. Acquiring these biomarkers simultaneously in a multi‐parametric acquisition could provide more robust detection of tissue changes in various disease states including neurodegeneration and cancer. Traditional magnetic resonance fingerprinting (MRF) has been shown to provide quick, quantitative mapping of T₁ and T₂ relaxation time constants. In this study, T₂* relaxation is added to the MRF framework using variable echo times (TE). To demonstrate the feasibility of the method and compare incremental and golden angle spiral rotations, simulated phantom data was fit using the proposed method. Additionally, T₁/T₂/T₂*/δf MRF as well as conventional T₁, T₂, and T₂* acquisitions were acquired in agar phantoms and the brains of three healthy volunteers. Golden angle spiral rotation was found to reduce inaccuracy resulting from off resonance effects. Strong correlations were found between conventional and MRF values in the T₁, T₂, and T₂* relaxation time constants of the agar phantoms and healthy volunteers. In this study, T₂* relaxation has been incorporated into the MRF framework by using variable echo times, while still fitting for T₁ and T₂ relaxation time constants. In addition to fitting these relaxation time constants, a novel method for fitting and correcting off resonance effects has been developed.     

Oxygen‐dependent hyperpolarized 129Xe brain MR

Hyperpolarized (HP) ¹²⁹Xe MR offers unique advantages for brain functional imaging (fMRI) because of its extremely high sensitivity to different chemical environments and the total absence of background noise in biological tissues. However, its advancement and applications are currently plagued by issues of signal strength. Generally, xenon atoms found in the brain after inhalation are transferred from the lung via the bloodstream. The longitudinal relaxation time (T₁) of HP ¹²⁹Xe is inversely proportional to the pulmonary oxygen concentration in the lung because oxygen molecules are paramagnetic. However, the T₁ of ¹²⁹Xe is proportional to the pulmonary oxygen concentration in the blood, because the higher pulmonary oxygen concentration will result in a higher concentration of diamagnetic oxyhemoglobin. Accordingly, there should be an optimal pulmonary oxygen concentration for a given quantity of HP ¹²⁹Xe in the brain. In this study, the relationship between pulmonary oxygen concentration and HP ¹²⁹Xe signal in the brain was analyzed using a theoretical model and measured through in vivo experiments. The results from the theoretical model and experiments in rats are found to be in good agreement with each other. The optimal pulmonary oxygen concentration predicted by the theoretical model was 21%, and the in vivo experiments confirmed the presence of such an optimal ratio by reporting measurements between 25% and 35%. These findings are helpful for improving the ¹²⁹Xe signal in the brain and make the most of the limited spin polarization available for brain experiments. Copyright © 2016 John Wiley & Sons, Ltd.     

Modeling of T2* decay in vertebral bone marrow fat quantification

Bone marrow fat fraction mapping using chemical shift encoding‐based water–fat separation is becoming a useful tool in investigating the association between bone marrow adiposity and bone health and in assessing cancer treatment‐induced bone marrow damage. Vertebral bone marrow is characterized by short T₂* relaxation times, which are in general different for the water and fat components and can confound fat quantification. The purpose of the present study is to compare different approaches to T₂* correction in chemical shift encoding‐based water–fat imaging of vertebral bone marrow using single‐voxel MRS as reference. Eight‐echo gradient‐echo imaging and single‐voxel MRS measurements were made on the spine (L3–L5) of 25 healthy volunteers. Different approaches were evaluated for correction of T₂* effects: (a) single‐T₂* correction, (b) dual‐T₂* correction, (c) T₂' correction using the a priori‐known T₂ from the MRS at each vertebral body and (d) T₂' correction using the a priori‐known T₂ equal to previously measured average values. Dual‐T₂* correction resulted in noisier imaging fat fraction maps than single‐T₂* correction or T₂' correction using a priori‐known T₂. Linear regression analysis between imaging and MRS fat fraction showed a slope significantly different from 1 when using single‐T₂* correction (R² = 0.96) or dual‐T₂* correction (R² = 0.87). T₂' correction using the a priori‐known T₂ resulted in a slope not significantly different from 1, an intercept significantly different from 0 (between 2.4% and 3%) and R² = 0.96. Therefore, a T₂' correction using a priori‐known T₂ can remove the fat fraction bias induced by the difference in T₂* between water and fat components without degrading noise performance in fat fraction mapping of vertebral bone marrow. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

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.     

Development of a fast method for quantitative measurement of hyperpolarized 129Xe dynamics in mouse brain

A fast method has been established for the precise measurement and quantification of the dynamics of hyperpolarized (HP) xenon‐129 (¹²⁹Xe) in the mouse brain. The key technique is based on repeatedly applying radio frequency (RF) pulses and measuring the decrease of HP ¹²⁹Xe magnetization after the brain Xe concentration has reached a steady state due to continuous HP ¹²⁹Xe ventilation. The signal decrease of the ¹²⁹Xe nuclear magnetic resonance (NMR) signal was well described by a simple theoretical model. The technique made it possible to rapidly evaluate the rate constant α, which is composed of cerebral blood flow (CBF), the partition coefficient of Xe between the tissue and blood (λ_i), and the longitudinal relaxation time (T_1i) of HP ¹²⁹Xe in the brain tissue, without any effect of depolarization by RF pulses and the dynamics in the lung. The technique enabled the precise determination of α as 0.103 ± 0.018 s^‐1 (± SD, n = 5) on healthy mice. To investigate the potential of this method for detecting physiological changes in the brain of a kainic acid (KA) ‐induced mouse model of epilepsy, an attempt was made to follow the time course of α after KA injection. It was found that the α value changes characteristically with time, reflecting the change in the physiological state of the brain induced by KA injection. By measuring CBF using ¹H MRI and ¹²⁹Xe dynamics simultaneously and comparing these results, it was suggested that the reduction of T_1i, in addition to the increase of CBF due to KA‐induced epilepsy, are possible causes of the change in ¹²⁹Xe dynamics. Thus, the present method would be useful to detect a pathophysiological state in the brain and provide a novel tool for future brain study. Copyright © 2011 John Wiley & Sons, Ltd.     

Visualization of calcium phosphate cement in teeth by zero echo time 1H MRI at high field

¹H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high‐field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo. An ultrashort echo time (UTE) sequence with multiple flip angles and echo times was applied at 11.7 T to measure T₁ and T₂* values of CPC, enamel and dentin. Teeth with CPC were imaged with an optimized ZTE sequence. Goat teeth implanted with CPC in vivo were imaged after 7 weeks ex vivo. T₂* relaxation of implanted CPC, dentin and enamel was better fitted by a model assuming a Gaussian rather than a Lorentzian distribution. For CPC and human enamel and dentin, the average T₂* values were 273 ± 19, 562 ± 221 and 476 ± 147 μs, respectively, the average T₂ values were 1234 ± 27, 963 ± 151 and 577 ± 41 μs, respectively, and the average T₁ values were 1065 ± 45, 972 ± 40 and 903 ± 7 ms, respectively. In ZTE images, CPC had a higher signal‐to‐noise‐ratio than dentin and enamel because of the higher water content. Seven weeks after in vivo implantation, the CPC‐filled lesions showed less homogeneous structures, a lower T₁ value and T₂* separated into two components. MRI by ZTE provides excellent contrast for CPC in teeth and allows its decomposition to be followed.     

Longitudinal assessment of tissue properties and cardiac diffusion metrics of the ex vivo porcine heart at 7 T: Impact of continuous tissue fixation using formalin

In this study we aimed to assess the effects of continuous formalin fixation on diffusion and relaxation metrics of the ex vivo porcine heart at 7 T. Magnetic resonance imaging was performed on eight piglet hearts using a 7 T whole body system. Hearts were measured fresh within 3 hours of cardiac arrest followed by immersion in 10% neutral buffered formalin. T₂^* and T₂ were assessed using a gradient multi‐echo and multi‐echo spin echo sequence, respectively. A spin echo and a custom stimulated echo sequence were employed to assess diffusion time‐dependent changes in metrics of cardiac diffusion tensor imaging. SNR was determined for b = 0 images. Scans were performed for 5 mm thick apical, midcavity and basal slices (in‐plane resolution: 1 mm) and repeated 7, 15, 50, 100 and 200 days postfixation. Eigenvalues of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) decreased significantly (P < 0.05) following fixation. Relative to fresh hearts, FA values 7 and 200 days postfixation were 90% and 80%, while respective relative ADC values at those fixation stages were 78% and 92%. Statistical helix and sheetlet angle distributions as well as respective mean and median values showed no systematic influence of continuous formalin fixation. Similar to changes in the ADC, values for T₂, T₂^* and SNR dropped initially postfixation. Respective relative values compared with fresh hearts at day 7 were 64%, 79% and 68%, whereas continuous fixation restored T₂, T₂^* and SNR leading to relative values of 74%, 100%, and 81% at day 200, respectively. Relaxation parameters and diffusion metrics are significantly altered by continuous formalin fixation. The preservation of microstructure metrics following prolonged fixation is a key finding that may enable future studies of ventricular remodeling in cardiac pathologies.     

Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2O exchange study

Inversion recovery ultrashort echo time (IR‐UTE) imaging holds the potential to directly characterize MR signals from ultrashort T₂ tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR‐UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T₂* signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D₂O exchange model and explored the potential of IR‐UTE imaging for the quantification of ultrashort T₂* signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D₂O. Long T₂ MR signals were measured using a clinical proton density‐weighted fast spin echo (PD‐FSE) sequence. IR‐UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T₂ signals (TI_null). Then, at this TI_null, images with echo times (TEs) of 0.01–4 ms were acquired to measure the T₂* values of STCs. The PD‐FSE signal dropped to near zero after 24 h of immersion in D₂O. A wide range of TI_null values were used at different time points (240–330 ms for white matter and 320–350 ms for gray matter at TR = 1000 ms) because the T₁ values of the long T₂ tissue components changed significantly. The T₂* values of STCs were 200–300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D₂O or H₂O), and showed minimal changes after sequential immersion. The ultrashort T₂* signals seen on IR‐UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D₂O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.     

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.     

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.     

Oxygenation in cervical cancer and normal uterine cervix assessed using blood oxygenation level‐dependent (BOLD) MRI at 3T

Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer. However, a practical noninvasive method is needed for the routine clinical evaluation of tumor hypoxia. This study examined the potential use of blood oxygenation level‐dependent (BOLD) contrast MRI as a noninvasive technique to assess tumor vascular oxygenation at 3T. Following Institutional Review Board‐approved informed consent and in compliance with the Health Insurance Portability and Accountability Act, successful results were achieved in nine patients with locally advanced cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA] and three normal volunteers. In the first four patients, dynamic T₂*‐weighted MRI was performed in the transaxial plane using a multi‐shot echo planar imaging sequence whilst patients breathed room air followed by oxygen (15 dm³/min). Later, a multi‐echo gradient echo examination was added to provide quantitative R₂* measurements. The baseline T₂*‐weighted signal intensity was quite stable, but increased to various extents in tumors on initiation of oxygen breathing. The signal in normal uterus increased significantly, whereas that in the iliacus muscle did not change. R₂* responded significantly in healthy uterus, cervix and eight cervical tumors. This preliminary study demonstrates that BOLD MRI of cervical cancer at 3T is feasible. However, more patients must be evaluated and followed clinically before any prognostic value can be determined. Copyright © 2012 John Wiley & Sons, Ltd.     

39K and 23Na relaxation times and MRI of rat head at 21.1 T

At ultrahigh magnetic field strengths (B₀ ≥ 7.0 T), potassium (³⁹K) MRI might evolve into an interesting tool for biomedical research. However, ³⁹K MRI is still challenging because of the low NMR sensitivity and short relaxation times. In this work, we demonstrated the feasibility of ³⁹K MRI at 21.1 T, determined in vivo relaxation times of the rat head at 21.1 T, and compared ³⁹K and sodium (²³Na) relaxation times of model solutions containing different agarose gel concentrations at 7.0 and 21.1 T. ³⁹K relaxation times were markedly shorter than those of ²³Na. Compared with the lower field strength, ³⁹K relaxation times were up to 1.9‐ (T₁), 1.4‐ (T_2S) and 1.9‐fold (T_2L) longer at 21.1 T. The increase in the ²³Na relaxation times was less pronounced (up to 1.2‐fold). Mono‐exponential fits of the ³⁹K longitudinal relaxation time at 21.1 T revealed T₁ = 14.2 ± 0.1 ms for the healthy rat head. The ³⁹K transverse relaxation times were 1.8 ± 0.2 ms and 14.3 ± 0.3 ms for the short (T_2S) and long (T_2L) components, respectively. ²³Na relaxation times were markedly longer (T₁ = 41.6 ± 0.4 ms; T_2S = 4.9 ± 0.2 ms; T_2L = 33.2 ± 0.2 ms). ³⁹K MRI of the healthy rat head could be performed with a nominal spatial resolution of 1 × 1 × 1 mm³ within an acquisition time of 75 min. The increase in the relaxation times with magnetic field strength is beneficial for ²³Na and ³⁹K MRI at ultrahigh magnetic field strength. Our results demonstrate that ³⁹K MRI at 21.1 T enables acceptable image quality for preclinical research. Copyright © 2016 John Wiley & Sons, Ltd.     

Ultrashort echo time spectroscopic imaging (UTESI): an efficient method for quantifying bound and free water

Biological tissues usually contain distinct water compartments with different transverse relaxation times. In this study, two‐dimensional, multi‐slice, ultrashort echo time spectroscopic imaging (UTESI) was used with bi‐component analysis to detect bound and free water components in musculoskeletal tissues. Feasibility studies were performed using numerical simulation. Imaging was performed on bovine cortical bone, human cadaveric menisci and the Achilles' tendons of volunteers. The simulation study demonstrated that UTESI, together with bi‐component analysis, could reliably quantify both T₂* and fractions of the short and long T₂* components. The in vitro and in vivo studies each took less than 14 min. The bound water components showed a short T₂* of ~0.3 ms for bovine bone, ~1.8 ms for meniscus and ~0.6 ms for the Achilles' tendon. The free water components showed about an order of magnitude longer T₂* values, with ~2 ms for bovine bone, ~14 ms for meniscus and ~8 ms for the Achilles' tendon. Bound water fractions of up to ~76% for bovine bone, 50% for meniscus and ~75% for the Achilles' tendon were measured. The corresponding free water components were up to ~24% for bovine bone, 50% for meniscus and ~25% for the Achilles' tendon by volume. These results demonstrate that UTESI, combined with bi‐component analysis, can quantify the bound and free water components in musculoskeletal tissues in clinically realistic times. Copyright © 2011 John Wiley & Sons, Ltd.     

In vivo GABA T2 determination with J‐refocused echo time extension at 7 T

A method to measure the T₂ relaxation time of GABA with spectral editing techniques is proposed. Spectral editing techniques can be used to unambiguously extract signals of low concentration J‐coupled spins such as γ‐aminobutyric acid (GABA) from overlapping resonances such as creatine and macromolecules. These sequences, however, generally have fixed and relatively long echo times. Therefore, for the absolute quantification of the edited spectrum, the T₂ relaxation time must be taken into account. To measure the T₂ relaxation time, the signal intensity has to be obtained at multiple echo times. However, on a coupled spin system such as GABA this is challenging, since the signal intensity of the target resonances is modulated not only by T₂ decay but also by the J‐coupling, which strongly influences the shapes and amplitudes of the edited signals, depending on the echo time. Here, we propose to refocus the J‐modulation of the edited signal at different echo times by using chemical shift selective refocusing. In this way the echo time can be arbitrarily extended while preserving the shape of the edited signal. The method was applied in combination with the MEGA‐sLASER editing technique to measure the in vivo T₂ relaxation time of GABA (87 ± 11 ms, n = 10) and creatine (109 ± 8 ms, n = 10) at 7 T. The T₁ relaxation time of these metabolites in a single subject was also determined (GABA, 1334 ± 158 ms; Cr, 1753 ± 12 ms). The T₂ decay curve of coupled spin systems can be sampled in an arbitrary fashion without the need for signal shape correction. Furthermore, the method can be applied with any spectral editing technique. The shortest echo time of the method is limited by the echo time of the spectral editing technique. Copyright © 2013 John Wiley & Sons, Ltd.     

Changes in the MR relaxation rate R(2)* induced by respiratory challenges at 3.0 T: a comparison of two quantification methods

The consistent determination of changes in the transverse relaxation rate R₂* (ΔR₂*) is essential for the mapping of the effect of hyperoxic and hypercapnic respiratory challenges, which enables the noninvasive assessment of blood oxygenation changes and vasoreactivity by MRI. The purpose of this study was to compare the performance of two different methods of ΔR₂* quantification from dynamic multigradient‐echo data: (A) subtraction of R₂* values calculated from monoexponential decay functions; and (B) computation of ΔR₂* echo‐wise from signal intensity ratios. A group of healthy volunteers (n = 12) was investigated at 3.0 T, and the brain tissue response to carbogen and CO₂–air inhalation was registered using a dynamic multigradient‐echo sequence with high temporal and spatial resolution. Results of the ΔR₂* quantification obtained by the two methods were compared with respect to the quality of the voxel‐wise ΔR₂* response, the number of responding voxels and the behaviour of the ‘global’ response of all voxels with significant R₂* changes. For the two ΔR₂* quantification methods, we found no differences in the temporal variation of the voxel‐wise ΔR₂* responses or in the detection sensitivity. The maximum change in the ‘global’ response was slightly smaller when ΔR₂* was derived from signal intensity ratios. In conclusion, this first methodological comparison shows that both ΔR₂* quantifications, from monoexponential approximation as well as from signal intensity ratios, are applicable for the monitoring of R₂* changes during respiratory challenges. Copyright © 2010 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.     

An indirect method for in vivo T2 mapping of [1‐13C] pyruvate using hyperpolarized 13C CSI

An indirect method for in vivo T₂ mapping of ¹³C–labeled metabolites using T₂ and T₂* information of water protons obtained a priori is proposed. The T₂ values of ¹³C metabolites are inferred using the relationship to T₂′ of coexisting ¹H and the T₂* of ¹³C metabolites, which is measured using routine hyperpolarized ¹³C CSI data. The concept is verified with phantom studies. Simulations were performed to evaluate the extent of T₂ estimation accuracy due to errors in the other measurements. Also, bias in the ¹³C T₂* estimation from the ¹³C CSI data was studied. In vivo experiments were performed from the brains of normal rats and a rat with C6 glioma. Simulation results indicate that the proposed method provides accurate and unbiased ¹³C T₂ values within typical experimental settings. The in vivo studies found that the estimated T₂ of [1‐¹³C] pyruvate using the indirect method was longer in tumor than in normal tissues and gave values similar to previous reports. This method can estimate localized T₂ relaxation times from multiple voxels using conventional hyperpolarized ¹³C CSI and can potentially be used with time resolved fast CSI.