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Understanding the effects of white matter (WM) axon fibre microstructure on T1 relaxation is important for neuroimaging. Here, we have studied the interrelationship between T1 and axon fibre configurations at 3T and 7T. T1 and S0 (=signal intensity at zero TI) were computed from MP2RAGE images acquired with six inversion recovery times. Multishell diffusion MRI images were analysed for fractional anisotropy (FA); MD; V1; the volume fractions for the first (f 1 ), second (f 2 ) and third (f 3 ) fibre configuration; and fibre density cross-section images for the first (fdc 1 ), second (fdc 2 ) and third (fdc 3 ) fibres. T1 values were plotted as a function of FA, f 1 , f 2 , f 3 , fdc 1 , fdc 2 and fdc 3 to examine interrelationships between the longitudinal relaxation and the diffusion MRI microstructural measures. T1 values decreased with increasing FA, f 1 and f 2 in a nonlinear fashion. At low FA values (from 0.2 to 0.4), a steep shortening of T1 was followed by a shallow shortening by 6%-10% at both fields. The steep shortening was associated with decreasing S0 and MD. T1 also decreased with increasing fdc 1 values in a nonlinear fashion. Instead, only a small T1 change as a function of either f 3 or fdc 3 was observed. In WM areas selected by fdc 1 only masks, T1 was shorter than in those with fdc 2 /fdc 3 . In WM areas with high single fibre populations, as delineated by f 1 /fdc 1 masks, T1 was shorter than in tissue with high complex fibre configurations, as segmented by f 2 /fdc 2 or f 3 /fdc 3 masks. T1 differences between these WM areas are attributable to combined effects by T1 anisotropy and lowered FA. The current data show strong interrelationships between T1, axon fibre configuration and orientation in healthy WM. It is concluded that diffusion MRI microstructural measures are essential in the effort to interpret quantitative T1 images in terms of tissue state in health and disease., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: To improve intraoral transverse loop coil design for high-resolution dental MRI., Methods: The transverse intraoral loop coil (tLoop) was modified (mtLoop) by overlapping the feed port conductors, bending the posterior section, introducing a parallel plate capacitor, optimizing the insulation thickness, and using it in receive-only mode. In addition, an MR-silent insulation was introduced. The performances of the mtLoop and tLoop coils were compared in terms of sensitivity, image SNR, and eddy currents using electromagnetic simulations and MRI measurements at 3T., Results: The receive-only mode of the mtLoop increases the sensitivity at the apices of the roots, and the overlapped feed port design eliminated signal voids along the incisors. The bent posterior section with the parallel plate capacitor reduced the unwanted signal of the tongue by a factor of 2.3 in the selected region off interest and lowered the eddy currents by 10%. The proposed new coil provided higher SNR by elevenfold and 2.5-fold at the incisors and apices of the molar roots within the selected regions of interest, respectively, in the experiments, as well as improved comfort. Optimal insulation thickness was determined as 1 mm. With the mtLoop, a (250 μm) 3 isotropic resolution of the dental arch could be realized using a UTE sequence within 2 min total acquisition time. A T 2 -SPACE protocol with (350 μm) 2 in-plane resolution was also demonstrated., Conclusion: The proposed new coil offers higher SNR at the incisors and apices of the molar roots, less unwanted signals from tongue, lower eddy currents, and improved patient comfort., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To design and implement a multi-coil (MC) array for B 0 field generation for image encoding and simultaneous advanced shimming in a novel 1.5T head-only MRI scanner., Methods: A 31-channel MC array was designed following the unique constraints of this scanner design: The vertically oriented magnet is very short, stopping shortly above the shoulders of a sitting subject, and includes a window for the subject to see through. Key characteristics of the MC hardware, the B 0 field generation capabilities, and thermal behavior, were optimized in simulations prior to its construction. The unit was characterized via bench testing. B 0 field generation capabilities were validated on a human 4T MR scanner by analysis of experimental B 0 fields and by comparing images for several MRI sequences acquired with the MC array to those acquired with the system's linear gradients., Results: The MC system was designed to produce a multitude of linear and nonlinear magnetic fields including linear gradients of up to 10 kHz/cm (23.5 mT/m) with MC currents of 5 A per channel. With water cooling it can be driven with a duty cycle of up to 74% and ramp times of 500 μs. MR imaging experiments encoded with the developed multi-coil hardware were largely artifact-free; residual imperfections were predictable, and correctable., Conclusion: The presented compact multi-coil array is capable of generating image encoding fields with amplitudes and quality comparable to clinical systems at very high duty cycles, while additionally enabling high-order B 0 shimming capabilities and the potential for nonlinear encoding fields., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Recent studies indicate that T 1 in white matter (WM) is influenced by fiber orientation in B 0 . The purpose of the study was to investigate the interrelationships between axon fiber orientation in corpus callosum (CC) and T 1 relaxation time in humans in vivo as well as in rat brain ex vivo., Methods: Volunteers were scanned for relaxometric and diffusion MRI at 3 T and 7 T. Angular T 1 plots from WM were computed using fractional anisotropy and fiber-to-field-angle maps. T 1 and fiber-to-field angle were measured in five sections of CC to estimate the effects of inherently varying fiber orientations on T 1 within the same tracts in vivo. Ex vivo rat-brain preparation encompassing posterior CC was rotated in B 0 and T 1 , and diffusion MRI images acquired at 9.4 T. T 1 angular plots were determined at several rotation angles in B 0 ., Results: Angular T 1 plots from global WM provided reference for estimated fiber orientation-linked T 1 changes within CC. In anterior midbody of CC in vivo, where small axons are dominantly present, a shift in axon orientation is accompanied by a change in T 1 , matching that estimated from WM T 1 data. In CC, where large and giant axons are numerous, the measured T 1 change is about 2-fold greater than the estimated one. Ex vivo rotation of the same midsagittal CC region of interest produced angular T 1 plots at 9.4 T, matching those observed at 7 T in vivo., Conclusion: These data causally link axon fiber orientation in B 0 to the T 1 relaxation anisotropy in WM., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

A high degree of structural order by white matter (WM) fibre tracts creates a physicochemical environment where water relaxations are rendered anisotropic. Recently, angularly dependent longitudinal relaxation has been reported in human WM. We have characterised interrelationships between T1 relaxation and diffusion MRI microstructural indices at 3 and 7 T. Eleven volunteers consented to participate in the study. Multishell diffusion MR images were acquired with b-values of 0/1500/3000 and 0/1000/2000 s/mm 2 at 1.5 and 1.05 mm 3 isotropic resolutions at 3 and 7 T, respectively. DTIFIT was used to compute DTI indices; the fibre-to-field angle (θ FB ) maps were obtained using the principal eigenvector images. The orientations and volume fractions of multiple fibre populations were estimated using BedpostX in FSL, and the orientation dispersion index (ODI) was estimated using the NODDI protocol. MP2RAGE was used to acquire images for T1 maps at 1.0 and 0.9 mm 3 isotropic resolutions at 3 and 7 T, respectively. At 3 T, T1 as a function of θ FB in WM with high fractional anisotropy and one-fibre orientation volume fraction or low ODI shows a broad peak centred at 50 o , but a flat baseline at 0 o and 90 o . The broad peak amounted up to 7% of the mean T1. At 7 T, the broad peak appeared at 40 o and T1 in fibres running parallel to B0 was longer by up to 75 ms (8.3% of the mean T1) than in those perpendicular to the field. The peak at 40 o was approximately 5% of mean T1 (i.e., proportionally smaller than that at 54 o at 3 T). The data demonstrate T1 anisotropy in WM with high microstructural order at both fields. The angular patterns are indicative of the B0-dependency of T1 anisotropy. Thus myelinated WM fibres influence T1 contrast both by acting as a T1 contrast agent and rendering T1 dependent on fibre orientation with B0., (© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: Reduce expense and increase accessibility of MRI by eliminating pulsed field (B 0 ) gradient hardware., Methods: A radiofrequency imaging method is described that enables spatial encoding without B 0 gradients. This method, herein referred to as frequency-modulated Rabi-encoded echoes (FREE), utilizes adiabatic full passage pulses and a gradient in the RF field (B 1 ) to produce spatially dependent phase modulation, equivalent to conventional phase encoding. In this work, Cartesian phase encoding was accomplished using FREE in a multi-shot double spin-echo sequence. Theoretical analysis and computer simulations investigated the influence of resonance offset and B 1 -gradient steepness and magnitude on reconstruction quality, which limit other radiofrequency imaging methodologies. Experimentally, FREE was compared to conventional phase-encoded MRI on human visual cortex using a simple surface transceiver coil., Results: Image distortions occurred in FREE when using nonlinear B 1 fields where the phase dependence becomes nonlinear, but with minimal change in signal intensity. Resonance offset effects were minimal for Larmor frequencies within the adiabatic full-passage pulse bandwidth., Conclusion: For the first time, FREE enabled slice-selective 2D imaging of the human brain without a B 0 gradient in the y-direction. FREE achieved high resolution in regions where the B 1 gradient was steepest, whereas images were distorted in regions where nonlinearity in the B 1 gradient was significant. Given that FREE experiences no significant signal loss due to B 1 nonlinearities and resonance offset, image distortions shown in this work might be corrected in the future based on B 1 and B 0 maps., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: The ability to use dual polarity encoded MRI with the missing pulse steady-state free precession (MP-SSFP) sequence is demonstrated to perform robust MRI with low radiofrequency (RF) amplitude, where the field is distorted by embedding metallic screws in an agar phantom. Image-based estimation of the 3D ΔB 0 map and image distortion correction is shown to require ~1 minute to perform., Theory and Methods: Dual polarity encoded MP-SSFP was implemented at 1.5T and used to image agar phantoms with one stainless steel and one titanium screw embedded inside. A multispectral fast spin-echo acquisition was performed for comparison. Self-consistent ΔB 0 estimation is performed iteratively using a 3D B-spline basis, which is compared to the ΔB 0 estimate generated by the multispectral sequence., Results: Dual polarity encoded MP-SSFP yields image quality similar to the multispectral sequence used with substantially less imaging time, provided the MP-SSFP experimental parameters are chosen well. The multispectral sequence appears to visualize modestly closer in proximity to the metallic screws used, despite the spectral bins covering the same bandwidth as the pulses used in MP-SSFP. However, MP-SSFP avoids ripple artifacts characteristic of the multispectral sequence. The ΔB 0 estimate generated by MP-SSFP is qualitatively similar to that generated by the multispectral sequence but larger in magnitude., Conclusion: Despite longer processing time compared to multispectral imaging, MP-SSFP yields similar image quality with significantly lower acquisition times in the absence of parallel imaging. The work herein demonstrates the ability to perform 3D ΔB 0 estimation and image correction within a reasonable amount of time, ~1 minute., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a 3D composite adiabatic spectral-spatial pulse for refocusing in spin-echo spectroscopy acquisitions and to compare its performance against standard acquisition methods., Methods: A 3D composite adiabatic pulse was designed by modulating a train of parallel transmit-optimized 2D subpulses with an adiabatic envelope. The spatial and spectral profiles were simulated and validated by experiments to demonstrate the feasibility of the design in both single and double spin-echo spectroscopy acquisitions. Phantom and in vivo studies were performed to evaluate the pulse performance and compared with semi-LASER with respect to localization performance, sequence timing, signal suppression, and specific absorption rate., Results: Simultaneous 2D spatial localization with water and lipid suppression was achieved with the designed refocusing pulse, allowing high-quality spectra to be acquired with shorter minimum TE/TR, reduced SAR, as well as adaptation to spatially varying B 0 and B 1 + field inhomogeneities in both prostate and brain studies., Conclusion: The proposed composite pulse can serve as a more SAR efficient alternative to conventional localization methods such as semi-LASER at ultrahigh field for spin echo-based spectroscopy studies. Subpulse parallel-transmit optimization provides the flexibility to manage the tradeoff among multiple design criteria to accommodate different field strengths and applications., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: We demonstrate the feasibility of MRI with missing-pulse steady-state free precession (MP-SSFP) in a 4T magnet with artificially degraded homogeneity., Methods: T 1 , T 2 , and diffusion contrast of MP-SSFP was simulated with constant and alternate radiofrequency (RF) phase using an extended phase graph. To validate MP-SSFP performance in human brain imaging, MP-SSFP was tested with two types of artificially introduced inhomogeneous magnetic fields: (1) a pure linear gradient field, and (2) a pseudo-linear gradient field introduced by mounting a head-gradient set at 36 cm from the magnet isocenter. Image distortion induced by the nonlinear inhomogeneous field was corrected using B 0 mapping measured with MP-SSFP., Results: The maximum flip angle in MP-SSFP was limited to ≤10° because of the large range of resonance frequencies in the inhomogeneous magnetic fields tested in this study. Under this flip-angle limitation, MP-SSFP with constant RF phase provided advantages of higher signal-to-noise ratio and insensitivity to B 1 field inhomogeneity as compared with an alternate RF phase. In diffusion simulation, the steady-state magnetization in constant RF phase MP-SSFP increased with an increase of static field gradient up to 8 to 21 mT/m depending on simulation parameters. Experimental results at 4T validated these findings. In human brain imaging, MP-SSFP preserved sufficient signal intensities, but images showed severe image distortion from the pseudo-linear inhomogeneous field. However, following distortion correction, good-quality brain images were achieved.+ field inhomogeneity as compared with an alternate RF phase. In diffusion simulation, the steady-state magnetization in constant RF phase MP-SSFP increased with an increase of static field gradient up to 8 to 21 mT/m depending on simulation parameters. Experimental results at 4T validated these findings. In human brain imaging, MP-SSFP preserved sufficient signal intensities, but images showed severe image distortion from the pseudo-linear inhomogeneous field. However, following distortion correction, good-quality brain images were achieved., Conclusion: MP-SSFP appears to be a feasible MRI technique for brain imaging in an inhomogeneous magnetic field., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: Spatial encoding for MRI is generally based on linear x, y, and z magnetic field gradients generated by a set of dedicated gradient coils. We recently introduced the dynamic multicoil technique (DYNAMITE) for B 0 field control and demonstrated DYNAMITE MRI in a preclinical MR environment. In this study, we report the first realization of DYNAMITE MRI of the in vivo human head., Methods: Gradient fields for DYNAMITE MRI were generated with a 28-channel multicoil hardware arranged in 4 rows of 7 coils on a cylindrical surface (length 359 mm, diameter 344 mm, maximum 5 A per coil). DYNAMITE MRIs of a resolution phantom and in vivo human heads were acquired with multislice gradient-echo, multislice spin-echo, and 3D gradient-echo sequences. The resultant image fidelity was compared to that obtained with conventional gradient coil technology., Results: DYNAMITE field control enabled the realization of all imaging sequences with average gradient errors ≤ 1%. DYNAMITE MRI provided image quality and sensitivity comparable to conventional gradient technology without any obvious artifacts. Some minor geometric deformations were noticed primarily in the image periphery as the result of regional field imperfections. The imperfections can be readily approximated theoretically through numerical integration of the Biot-Savart law and removed through image distortion correction., Conclusion: The first realization of DYNAMITE MRI of the in vivo human head has been presented. The obtained image fidelity is comparable to MRI with conventional gradient coils, paving the way for full-fledged DYNAMITE MRI and B 0 shim systems for human applications., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation., Methods: Magnetic resonance imaging was performed on room-temperature organs and VCAs perfused with IONPs and were assessed at 9.4 T. Quantitative T 1 mapping and T 2 ∗ -weighted images were acquired using sweep imaging with Fourier transformation and gradient-echo sequences, respectively. Verification of IONP localization was performed through histological assessment and microcomputer tomography., Results: Quantitative imaging was achieved for organs and VCAs perfused with up to 642 mM Fe (36 mg Fe /mL), which is above previous demonstrations of upper limit detection in agarose (35.7mM Fe [2 mg Fe /mL]). The stability of IONPs in the perfusate had an effect on the quality of distribution and imaging within organs or VCA. Finally, MRI provided more accurate IONP localization than Prussian blue histological staining in this system, wherein IONPs remain primarily in the vasculature., Conclusion: Using MRI, we were able to assess the distribution of IONPs throughout organs and VCAs varying in complexity. Additional studies are necessary to better understand this system and validate the calibration between T 1 measurements and IONP concentration., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: The sweep imaging with Fourier transformation (SWIFT) imaging technique has been shown to provide positive contrast from diluted cell suspensions labeled with super-paramagnetic iron oxide (SPIO) in a tissue, as an alternative to T2*-weighted imaging. Here we demonstrate a variation of the SWIFT technique that yields a hyperintense signal from a concentrated cell suspension. The proposed technique provides minimal background signal from host tissue and facilitates visualization of injected cells., Methods: The proton resonance frequency and linewidth were determined for SPIO solutions of different concentrations. The original SWIFT sequence was modified and a dual saturation Gaussian shape RF pulse with ~200 Hz bandwidth was incorporated into the acquisition protocol to suppress host tissue and fat signals. This modification of the original acquisition protocol permits the detection of a hyperintense signal from grafted cells with minimal background signal from the host tissue., Results: SPIO particles not only induce broadening of NMR line-width but also an initiate proton resonance frequency shift. This shift is linearly proportional to the concentration of the iron oxide particles and induced by the bulk magnetic susceptibility of SPIOs. The shift of the resonance frequency of iron labeled cells allowed us effectively suppress the host tissues with saturation RF pulse to improve MRI detection of grafted cells., Conclusions: Iron oxide particles increase the resonance frequency of water proton signal. This shift permitted us to add the tissue/fat saturation RF pulse into the original SWIFT acquisition protocol and detect distinct hyperintense signals from grafted cells with minimal background signal from the host tissue., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: Iron-oxide nanoparticles (IONPs) have shown tremendous utility for enhancing image contrast and delivering targeted therapies. Quantification of IONPs has been demonstrated at low concentrations with gradient echo (GRE) and spin echo (SE), and at high concentrations with echoless sequences such as swept imaging with Fourier transform (SWIFT). This work examines the overlap of IONP quantification with GRE, SE, and SWIFT., Methods: The limit of quantification of GRE, SE, inversion-recovery GRE, and SWIFT sequences was assessed using IONPs at a concentration range of 0.02 to 89.29 mM suspended in 1% agarose. Empirically derived limits of quantification were compared with International Union of Pure and Applied Chemistry definitions. Both commercial and experimental IONPs were used., Results: All three IONPs assessed demonstrated an overlap of concentration quantification with GRE, SE, and SWIFT sequences. The largest dynamic range observed was 0.004 to 35.7 mM with Feraheme., Conclusions: The metrics established allow upper and lower quantitative limitations to be estimated given the relaxivity characteristics of the IONP and the concentration range of the material to be assessed. The methods outlined in this paper are applicable to any pulse sequence, IONP formulation, and field strength. Magn Reson Med 79:1420-1428, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To introduce a method of designing single and parallel transmit (pTx) 3D adiabatic π pulses for inverting and refocusing spins that are insensitive to transmit B 1 ( B1+) inhomogeneity., Theory and Methods: A 3D adiabatic pulse is created by replacing each piece-wise constant element (or sub-pulse) of an adiabatic full passage (AFP) by a 2D selective pulse. In this study, the parent AFP is an HS1 and each sub-pulse is a 2D pulse derived from a jinc function designed using a spiral k-trajectory. Spatial selectivity in the third direction is achieved by blipping the slab-selective gradient between sub-pulses, yielding a rectangular slab profile identical to that of the parent AFP. The slew-rate limited sub-pulse can be undersampled utilizing pTx, thus shortening the overall pulse width. Simulations and experiments demonstrate the quality of spatial selectivity and adiabaticity achievable., Results: The 3D adiabatic pulse inverts and refocus spins in a sharply demarcated cylindrical volume. When stepping RF amplitude, an adiabatic threshold is observed above which the flip angle remains π. Experimental results demonstrate that pTx is an effective means to significantly improve pulse performance., Conclusion: A method of designing 3D adiabatic pulses insensitive to B 1 inhomogeneity has been developed. pTx can shorten these pulses while retaining their adiabatic character. Magn Reson Med 79:701-710, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: Conventional T 2 -weighted MRI produces a hypointense signal from iron-labeled cells, which renders quantification unfeasible. We tested a SWeep Imaging with Fourier Transformation (SWIFT) MRI pulse sequence to generate a quantifiable hyperintense signal from iron-labeled cells., Methods: Mesenchymal stem cells (MSCs) were labeled with different concentrations of iron oxide particles and examined for cell viability, proliferation, and differentiation. The SWIFT sequence was optimized to detect and quantify the amount of iron in the muscle tissue after injection of iron oxide solution and iron-labeled MSCs., Results: The incubation of MSCs with iron oxide and low concentration of poly-L-lysine mixture resulted in an internalization of up to 22 pg of iron per cell with no adverse effect on MSCs. Phantom experiments showed a dependence of SWIFT signal intensity on the excitation flip angle. The hyperintense signal from iron-labeled cells or solutions was detected, and an amount of the iron oxide in the tissue was quantified with the variable flip angle method., Conclusions: The SWIFT sequence can produce a quantifiable hyperintense MRI signal from iron-labeled cells. The graft of 18 x 10 6 cells was detectable for 19 days after injection and the amount of iron was quantifiable. The proposed protocol simplifies the detection and provides a means to quantify cell numbers. Magn Reson Med 78:1900-1910, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To use contrast based on longitudinal relaxation times (T 1 ) or rates (R 1 ) to quantify the biodistribution of iron oxide nanoparticles (IONPs), which are of interest for hyperthermia therapy, cell targeting, and drug delivery, within primary clearance organs., Methods: Mesoporous silica-coated IONPs (msIONPs) were intravenously injected into 15 naïve mice. Imaging and mapping of the longitudinal relaxation rate constant at 24 h or 1 week postinjection were performed with an echoless pulse sequence (SWIFT). Alternating magnetic field heating measurements were also performed on ex vivo tissues., Results: Signal enhancement from positive T 1 contrast caused by IONPs was observed and quantified in vivo in liver, spleen, and kidney at concentrations up to 3.2 mg Fe/(g tissue wt.) (61 mM Fe). In most cases, each organ had a linear correlation between the R 1 and the tissue iron concentration despite variations in intra-organ distribution, degradation, and IONP surface charge. Linear correlation between R 1 and volumetric SAR in hyperthermia therapy was observed., Conclusion: The linear dependence between R 1 and tissue iron concentration in major organs allows quantitative monitoring of IONP biodistribution in a dosage range relevant to magnetic hyperthermia applications, which falls into the concentration gap between CT and conventional MRI techniques. Magn Reson Med 78:702-712, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Transplantation of macroencapsulated tissue-engineered grafts (TEGs) is being investigated as a treatment for type 1 diabetes, but there is a critical need to measure TEG viability both in vitro and in vivo. Oxygen deficiency is the most critical issue preventing widespread implementation of TEG transplantation and delivery of supplemental oxygen (DSO) has been shown to enhance TEG survival and function in vivo. In this study, we demonstrate the first use of oxygen-17 magnetic resonance spectroscopy ( 17 O-MRS) to measure the oxygen consumption rate (OCR) of TEGs and show that in addition to providing therapeutic benefits to TEGs, DSO with 17 O 2 can also enable measurements of TEG viability. Macroencapsulated TEGs containing βTC3 murine insulinoma cells were prepared with three fractional viabilities and provided with 17 O 2 . Cellular metabolism of 17 O 2 into nascent mitochondrial water (H 2 17 O) was monitored by 17 O-MRS and, from the measured data, OCR was calculated. For comparison, OCR was simultaneously measured on a separate, but equivalent sample of cells with a well-established stirred microchamber technique. OCR measured by 17 O-MRS can quantify TEG viability noninvasively. Biotechnol. Bioeng. 2017;114: 1118-1121. © 2016 Wiley Periodicals, Inc.17 O-MRS can quantify TEG viability noninvasively. Biotechnol. Bioeng. 2017;114: 1118-1121. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: The frequency-swept pulse known as the hyperbolic-secant (HS) pulse is popular in NMR for achieving adiabatic spin inversion. The HS pulse has also shown utility for achieving excitation and refocusing in gradient-echo and spin-echo sequences, including new ultrashort echo-time imaging (e.g., Sweep Imaging with Fourier Transform, SWIFT) and B 1 mapping techniques. To facilitate the analysis of these techniques, the complete theoretical solution of the Bloch equation, as driven by the HS pulse, was derived for an arbitrary state of initial magnetization., Methods: The solution of the Bloch-Riccati equation for transverse and longitudinal magnetization for an arbitrary initial state was derived analytically in terms of HS pulse parameters. The analytical solution was compared with the solutions using both the Runge-Kutta method and the small-tip approximation., Results: The analytical solution was demonstrated on different initial states at different frequency offsets with/without a combination of HS pulses. Evolution of the transverse magnetization was influenced significantly by the choice of HS pulse parameters. The deviation of the magnitude of the transverse magnetization, as obtained by comparing the small-tip approximation to the analytical solution, was < 5% for flip angles < 30 °, but > 10% for the flip angles > 40 °., Conclusion: The derived analytical solution provides insights into the influence of HS pulse parameters on the magnetization evolution. Magn Reson Med 77:1630-1638, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To use quantitative susceptibility mapping (QSM) to investigate changes in cartilage canals in the distal femur of juvenile goats after their surgical transection., Methods: Chondronecrosis was surgically induced in the right medial femoral condyles of four 4-day-old goats. Both the operated and control knees were harvested at 2, 3, 5, and 10 weeks after the surgeries. Ex vivo MRI scans were conducted at 9.4 Tesla using T RAFF (relaxation time along a fictitious field)-weighted fast spin echo imaging and QSM to detect areas of chondronecrosis and investigate cartilage canal abnormalities. Histological sections from these same areas stained with hematoxylin and eosin and safranin O were evaluated to assess the affected tissues., Results: Both the histological sections and the T RAFF -weighted images of the femoral condyles demonstrated focal areas of chondronecrosis, evidenced by pyknotic chondrocyte nuclei, loss of matrix staining, and altered MR image contrast. At increasing time points after surgery, progressive changes and eventual disappearance of abnormal cartilage canals were observed in areas of chondronecrosis by using QSM., Conclusion: Abnormal cartilage canals were directly visualized in areas of surgically induced chondronecrosis. Quantitative susceptibility mapping enabled investigation of the vascular changes accompanying chondronecrosis in juvenile goats. Magn Reson Med 77:1276-1283, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To present a practical scheme of a simultaneous radiofrequency (RF) transmit (Tx) and receive (Rx) (STAR) system for MRI, discuss the challenges and solutions, and show preliminary in vivo MR images obtained with this new technique., Methods: A remotely controlled STAR system was built and tested with a transverse electromagnetic head coil on a 4T (Oxford, 90 cm-bore) MRI scanner equipped with an Agilent DirectDrive console (Agilent, Santa Clara, CA). In vivo head images have been acquired using continuous sweep excitation and acquisition., Results: The bench test and MR experimental results show our STAR system to have high isolation (60 dB) between Tx and Rx, with insensitivity to load swings created by head motion. To acquire in vivo head images, ultralow RF peak power of 50 mW was used., Conclusion: A novel motion-insensitive STAR MRI technique was developed and experimentally tested. The first in vivo MR images using this method were acquired. Magn Reson Med 76:1932-1938, 2016. © 2016 International Society for Magnetic Resonance in Medicine., Competing Interests: No conflict of interest., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To introduce a method of designing two-dimensional (2D) frequency-modulated pulses that produce phase coherence in a spatiotemporal manner. Uniquely, this class of pulses provides the ability to compensate for field inhomogeneity using a spatiotemporally dependent trajectory of maximum coherence in a single-shot., Theory and Methods: A pulse design method based on a k-space description is developed. Bloch simulations and phantom experiments are used to demonstrate sequential spatiotemporal phase coherence and compensation for B1+ and B 0 inhomogeneity., Results: In the presence of modulated gradients, the 2D frequency-modulated pulses were shown to excite a cylinder in a selective manner. With a surface coil transmitter, compensation of the effect of B1+ inhomogeneity was experimentally verified, in agreement with simulation results. In addition, simulations were used to demonstrate partial compensation for B 0 inhomogeneity., Conclusion: The 2D frequency-modulated pulses are a new class of pulses that generate phase coherence sequentially along a spatial trajectory determined by gradient- and frequency-modulated functions. By exploiting their spatiotemporal nature, 2D frequency-modulated pulses can compensate for spatial variation of the radiofrequency field in a single-shot excitation. Preliminary results shown suggest extensions might also be used to compensate for static field inhomogeneity. Magn Reson Med 76:1364-1374, 2016. © 2015 International Society for Magnetic Resonance in Medicine., (© 2015 International Society for Magnetic Resonance in Medicine.)

Purpose: Methods designed to image fast-relaxing spins, such as sweep imaging with Fourier transformation (SWIFT), often utilize high excitation bandwidth and duty cycle, and in some applications the optimal flip angle cannot be used without exceeding safe specific absorption rate (SAR) levels. The aim is to reduce SAR and increase the flexibility of SWIFT by applying time-varying gradient-modulation (GM). The modified sequence is called GM-SWIFT., Theory and Methods: The method known as gradient-modulated offset independent adiabaticity was used to modulate the radiofrequency (RF) pulse and gradients. An expanded correlation algorithm was developed for GM-SWIFT to correct the phase and scale effects. Simulations and phantom and in vivo human experiments were performed to verify the correlation algorithm and to evaluate imaging performance., Results: GM-SWIFT reduces SAR, RF amplitude, and acquisition time by up to 90%, 70%, and 45%, respectively, while maintaining image quality. The choice of GM parameter influences the lower limit of short T2 (*) sensitivity, which can be exploited to suppress unwanted image haze from unresolvable ultrashort T2 (*) signals originating from plastic materials in the coil housing and fixatives., Conclusions: GM-SWIFT reduces peak and total RF power requirements and provides additional flexibility for optimizing SAR, RF amplitude, scan time, and image quality., (© 2015 Wiley Periodicals, Inc.)

Purpose: Brain myelin plays an important role in normal brain function. Demyelination is involved in many degenerative brain diseases, thus quantitative imaging of myelin has been under active investigation. In previous work, we demonstrated the capability of the method known as Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) to provide image contrast between white and gray matter in human and rat brains. Here, we provide evidence pointing to myelin being the major source of this contrast., Methods: RAFFn relaxation time constant (TRAFFn) was mapped in rat brain ex vivo. TRAFFn was quantified in 12 different brain areas. TRAFFn values were compared with multiple other MRI metrics (T1, T2 , continuous wave T1ρ, adiabatic T1ρ and T2ρ, magnetization transfer ratio), and with histologic measurements of cell density, myelin and iron content., Results: Highest contrast between white and grey matter was obtained with TRAFFn in the rotating frames of ranks n = 4 and 5. TRAFFn values correlated strongly with myelin content, whereas no associations between TRAFFn and iron content or cell density were found., Conclusion: TRAFFn with n = 4 or 5 provides a high sensitivity for selective myelin mapping in the rat brain., (© 2015 Wiley Periodicals, Inc.)

Purpose: To evaluate the capability of longitudinal MR scans using sweep imaging with Fourier transformation (SWIFT) to detect breast cancer metastasis to the lung in mice., Methods: Mice with breast cancer metastatic to the lung were generated by tail vein injection of MDA-MB-231-LM2 cells. Thereafter, MR imaging was performed every week using three different pulse sequences: SWIFT [echo time (TE) ∼3 μs], concurrent dephasing and excitation (CODE; TE ∼300 μs), and three-dimensional (3D) gradient echo (GRE; TE = 2.2 ms). Motion during the long SWIFT MR scans was compensated for by rigid-body motion correction. Maximum intensity projection (MIP) images were generated to visualize changes in lung vascular structures during the development and growth of metastases., Results: SWIFT MRI was more sensitive to signals from the lung parenchyma than CODE or 3D GRE MRI. Metastatic tumor growth in the lungs induced a progressive increase in intensity of parenchymal signals in SWIFT images. MIP images from SWIFT clearly visualized lung vascular structures and their disruption due to progression of breast cancer metastases in the lung., Conclusion: SWIFT MRI's sensitivity to fast-decaying signals and tolerance of magnetic susceptibility enhances its effectiveness at detecting structural changes in lung parenchyma and vasculature due to breast cancer metastases in the lung., (© 2014 Wiley Periodicals, Inc.)

Purpose: SWIFT (SWeep Imaging with Fourier Transformation) is a non-Cartesian MRI method with unique features and capabilities. In SWIFT, radiofrequency (RF) excitation and reception are performed nearly simultaneously, by rapidly switching between transmit and receive during a frequency-swept RF pulse. Because both the transmitted pulse and data acquisition are simultaneously amplitude-modulated in SWIFT (in contrast to continuous RF excitation and uninterrupted data acquisition in more familiar MRI sequences), crosstalk between different frequency bands occurs in the data. This crosstalk leads to a "bulls-eye" artifact in SWIFT images. We present a method to cancel this interband crosstalk by cycling the pulse and receive gap positions relative to the un-gapped pulse shape. We call this strategy "gap cycling.", Theory and Methods: We carry out theoretical analysis, simulation and experiments to characterize the signal chain, resulting artifacts, and their elimination for SWIFT., Results: Theoretical analysis reveals the mechanism for gap-cycling's effectiveness in canceling interband crosstalk in the received data. We show phantom and in vivo results demonstrating bulls-eye artifact free images., Conclusion: Gap cycling is an effective method to remove bulls-eye artifact resulting from interband crosstalk in SWIFT data., (© 2014 Wiley Periodicals, Inc.)

Purpose: To propose a new phase-based B1-mapping method that exploits phase information created by hyperbolic secant (HS) pulses in conventional 2D spin-echo imaging., Methods: In this B1-mapping method, HS pulses are used to accomplish π/2 excitation and π refocusing in standard multislice spin-echo imaging. When setting the ratio of pulse lengths of the π/2 and π HS pulses to 2:1, the spin-echo phase is independent of offset frequency and varies as a function of B1 strength. To eliminate undesired phase accumulations induced by unknown factors other than the B1 strength, two spin-echo images are acquired using HS pulses applied with opposite frequency-sweep directions, and the resulting phase images are subtracted from each other. To demonstrate the performance of the proposed method, phantom and in vivo experiments were performed using a surface coil and a volume coil., Results: The B1 maps obtained by using the proposed method were in accordance with the B1 maps obtained using previous methods in both phantom and in vivo experiments., Conclusion: The proposed method is easy to implement without any sequence modification, is insensitive to B0 inhomogeneity and chemical shift, and is robust in a reasonably wide range of B1 field strength., (© 2014 Wiley Periodicals, Inc.)

Purpose: To introduce a new outer volume suppression (OVS) technique that uses a single pulse and rotating gradients to accomplish frequency-swept excitation. This new technique, which is called gradient rotating outer volume excitation (GROOVE), produces a circular or elliptical suppression band rather than suppressing the entire outer volume., Methods: Theoretical and k-space descriptions of GROOVE are provided. The properties of GROOVE were investigated with simulations, phantom, and human experiments performed using a 4T horizontal bore magnet equipped with a TEM coil., Results: Similar suppression performance was obtained in phantom and human brain using GROOVE with circular and elliptical shapes. Simulations indicate that GROOVE requires less SAR and time than traditional OVS schemes, but traditional schemes provide a sharper transition zone and less residual signal., Conclusion: GROOVE represents a new way of performing OVS in which spins are excited temporally in space on a trajectory that can be tailored to fit the shape of the suppression region. In addition, GROOVE is capable of suppressing tailored regions of space with more flexibility and in a shorter period of time than conventional methods. GROOVE provides a fast, low SAR alternative to conventional OVS methods in some applications (e.g., scalp suppression)., (© 2014 Wiley Periodicals, Inc.)

Purpose: MRI relaxation measurements are performed in the presence of a fictitious magnetic field in the recently described technique known as RAFF (Relaxation Along a Fictitious Field). This method operates in the 2(nd) rotating frame (rank n = 2) by using a nonadiabatic sweep of the radiofrequency effective field to generate the fictitious magnetic field. In the present study, the RAFF method is extended for generating MRI contrasts in rotating frames of ranks 1 ≤ n ≤ 5. The developed method is entitled RAFF in rotating frame of rank n (RAFFn)., Theory and Methods: RAFFn pulses were designed to generate fictitious fields that allow locking of magnetization in rotating frames of rank n. Contrast generated with RAFFn was studied using Bloch-McConnell formalism together with experiments on human and rat brains., Results: Tolerance to B0 and B1 inhomogeneities and reduced specific absorption rate with increasing n in RAFFn were demonstrated. Simulations of exchange-induced relaxations revealed enhanced sensitivity of RAFFn to slow exchange. Consistent with such feature, an increased grey/white matter contrast was observed in human and rat brain as n increased., Conclusion: RAFFn is a robust and safe rotating frame relaxation method to access slow molecular motions in vivo., (© 2014 Wiley Periodicals, Inc.)

Purpose: The limiting factor for MRI of skeletal/mineralized tissue is fast transverse relaxation. A recent advancement in MRI technology, SWIFT (Sweep Imaging with Fourier Transform), is emerging as a new approach to overcome this difficulty. Among other techniques like UTE, ZTE, and WASPI, the application of SWIFT technology has the strong potential to impact preclinical and clinical imaging, particularly in the context of primary or metastatic bone cancers because it has the added advantage of imaging water in mineralized tissues of bone allowing MRI images to be obtained of tissues previously visible only with modalities such as computed tomography (CT). The goal of the current study is to examine the feasibility of SWIFT for the assessment of the prostate cancer induced changes in bone formation (osteogenesis) and destruction (osteolysis) in ex vivo specimens., Methods: A luciferase expressing prostate cancer cell line (PAIII) or saline control was inoculated directly into the tibia of 6-week-old immunocompromised male mice. Tumor growth was assessed weekly for 3 weeks before euthanasia and dissection of the tumor bearing and sham tibias. The ex vivo mouse tibia specimens were imaged with a 9.4 Tesla (T) and 7T MRI systems. SWIFT images are compared with traditional gradient-echo and spin-echo MRI images as well as CT and histological sections., Results: SWIFT images with nominal resolution of 78 μm are obtained with the tumor and different bone structures identified. Prostate cancer induced changes in the bone microstructure are visible in SWIFT images, which is supported by spin-echo, high resolution CT and histological analysis., Conclusion: SWIFT MRI is capable of high-quality high-resolution ex vivo imaging of bone tumor and surrounding bone and soft tissues. Furthermore, SWIFT MRI shows promise for in vivo bone tumor imaging, with the added benefits of nonexposure to ionizing radiation, quietness, and speed., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: This work introduces a technique to excite MR signals locally and to steer this localized region over the object in a spatiotemporal manner. The purpose is to demonstrate the feasibility of MRI with multidimensional spatiotemporal-encoding in a way that provides the ability to compensate extreme field inhomogeneity., Methods: The method is called steering resonance over the object (STEREO). A modulated gradient is applied in concert with a frequency-modulated pulse to steer a resonant region through space and thus produce sequential excitation and echo formation. Images are reconstructed using exclusively an inverse problem solution., Results: Images of phantoms and human brain were produced to demonstrate the feasibility of the STEREO sequence and image reconstruction. Simulations support the postulated capability to compensate for extreme field inhomogeneity., Conclusion: STEREO represents a substantial departure from conventional MRI in which spins contained in the sample, slab, or slice are excited synchronously. By exciting spins sequentially along a curved spatial trajectory, STEREO in principle affords a unique opportunity to adjust for spatial variations in static and radiofrequency fields. By adjusting field amplitudes and frequencies in a temporal manner in STEREO, in future works it should be possible to perform MRI with highly inhomogeneous fields., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: The signal-to-noise ratio and resolution are two competing parameters for dental MRI and are highly dependent on the radiofrequency coil configuration and performance. The purpose of this work is to describe an intraoral approach for imaging teeth with the radiofrequency coil plane oriented orthogonally to the Zeeman field to use the transverse components of the B1 field for transmitting and receiving the NMR signal., Methods: A single loop coil with shape and size fitted to the average adult maxillary arch was built and tested with a phantom and human subjects in vivo on a whole-body 4 T MRI scanner. Supporting Biot-Savart law simulations were performed with Matlab., Results: In the occlusal position (in bite plane between the upper and lower teeth), the sensitive volume of the coil encompasses the most important dental structures, the teeth and their supporting structures, while uninteresting tissues containing much higher proton density (cheeks, lips, and tongue) are outside the sensitive volume. The presented images and simulated data show the advantages of using a coil in the orthogonal orientation for dental applications., Conclusion: The transverse components of the B1 field of a surface coil can effectively be used for imaging of teeth and associated structures., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: Iron-oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2 * mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2 * because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look-Locker method to map T1 of IONPs in high concentrations., Methods: T1 values of agar containing IONPs in different concentrations were measured with the SWIFT Look-Locker method and with inversion recovery spectroscopy. Precisions of Look-Locker and variable flip angle (VFA) methods were compared in simulations., Results: The measured R1 (=1/T1 ) has a linear relationship with IONP concentration up to 53.6 mM of Fe. This concentration exceeds concentrations measured in previous work by almost an order of magnitude. Simulations show SWIFT Look-Locker method is also much less sensitive to B1 inhomogeneity than the VFA method., Conclusion: SWIFT Look-Locker can accurately measure T1 of IONP concentrations ≤53.6 mM. By mapping T1 as a function of IONP concentration, IONP distribution maps might be used in the future to plan effective magnetic nanoparticle hyperthermia therapy., (Copyright © 2014 Wiley Periodicals, Inc.)