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To extend the preservation of donor hearts beyond the current 4-6 h, this paper explores heart cryopreservation by vitrification-cryogenic storage in a glass-like state. While organ vitrification is made possible by using cryoprotective agents (CPA) that inhibit ice during cooling, failure occurs during convective rewarming due to slow and non-uniform rewarming which causes ice crystallization and/or cracking. Here an alternative, "nanowarming", which uses silica-coated iron oxide nanoparticles (sIONPs) perfusion loaded through the vasculature is explored, that allows a radiofrequency coil to rewarm the organ quickly and uniformly to avoid convective failures. Nanowarming has been applied to cells and tissues, and a proof of principle study suggests it is possible in the heart, but proper physical and biological characterization especially in organs is still lacking. Here, using a rat heart model, controlled machine perfusion loading and unloading of CPA and sIONPs, cooling to a vitrified state, and fast and uniform nanowarming without crystallization or cracking is demonstrated. Further, nanowarmed hearts maintain histologic appearance and endothelial integrity superior to convective rewarming and indistinguishable from CPA load/unload control hearts while showing some promising organ-level (electrical) functional activity. This work demonstrates physically successful heart vitrification and nanowarming and that biological outcomes can be expected to improve by reducing or eliminating CPA toxicity during loading and unloading.

Understanding the link between the brain activity and behavior is a key challenge in modern neuroscience. Behavioral neuroscience, however, lacks tools to record whole-brain activity in complex behavioral settings. Here we demonstrate that a novel Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) functional magnetic resonance imaging (fMRI) approach enables whole-brain studies in spontaneously behaving head-fixed rats. First, we show anatomically relevant functional parcellation. Second, we show sensory, motor, exploration, and stress-related brain activity in relevant networks during corresponding spontaneous behavior. Third, we show odor-induced activation of olfactory system with high correlation between the fMRI and behavioral responses. We conclude that the applied methodology enables novel behavioral study designs in rodents focusing on tasks, cognition, emotions, physical exercise, and social interaction. Importantly, novel zero echo time and large bandwidth approaches, such as MB-SWIFT, can be applied for human behavioral studies, allowing more freedom as body movement is dramatically less restricting factor.

Objective: In dental MRI, intraoral coils provide higher signal-to-noise ratio (SNR) than coils placed outside the mouth. This study aims to design an intraoral dipole antenna and demonstrates the feasibility of combining it with an extraoral coil. Methods: Dipole antenna design was chosen over loop design, as it is open toward the distal; therefore, it does not restrain tongue movement. The dipole design offers also an increased depth-of-sensitivity that allows for MRI of dental roots. Different dipole antenna designs were simulated using a finite-difference-time-domain approach. Ribbon, wire, and multi-wire arms were compared. The best design was improved further by covering the ends of the dipole arms with a high-permittivity material. Phantom and in vivo measurements were conducted on a 3T clinical MRI system. Results: The best transmit efficiency and homogeneity was achieved with a multi-wire curved dipole antenna with 7 wires for each arm. With an additional high-permittivity cap the transmit field inhomogeneity was further reduced from 20% to 5% along the dipole arm. When combined with extraoral flexible surface-coil, the coupling between the coils was less than -32dB and SNR was increased. Conclusion: Using intraoral dipole design instead of loop improves patient comfort. We demonstrated feasibility of the intraoral dipole combined with an extraoral flexible coil-array for dental MRI. Dipole antenna enabled decreasing imaging field-of-view, and reduced the prevalent signal from tongue. Significance: This study highlights the advantages and the main challenges of the intraoral RF coils and describes a novel RF coil that addresses those challenges.

Bone is a composite biomaterial of mineral crystals, organic matrix, and water. Each contributes to bone quality and strength and may change independently, or together, with disease progression and treatment. Even so, there is a near ubiquitous reliance on ionizing x-ray-based approaches to measure bone mineral density (BMD) which is unable to fully characterize bone strength and may not adequately predict fracture risk. Characterization of treatment efficacy in bone diseases of altered remodeling is complicated by the lack of imaging modality able to safely monitor material-level and biochemical changes in vivo. To improve upon the current state of bone imaging, we tested the efficacy of Multi Band SWeep Imaging with Fourier Transformation (MB-SWIFT) magnetic resonance imaging (MRI) as a readout of bone derangement in an estrogen deficient ovariectomized (OVX) rat model during growth. MB-SWIFT MRI-derived BMD correlated significantly with BMD measured using micro-computed tomography (μCT). In this rodent model, growth appeared to overcome estrogen deficiency as bone mass continued to increase longitudinally over the duration of the study. Nonetheless, after 10 weeks of intervention, MB-SWIFT detected significant changes consistent with estrogen deficiency in cortical water, cortical matrix organization (T1), and marrow fat. Findings point to MB-SWIFT's ability to quantify BMD in good agreement with μCT while providing additive quantitative outcomes about bone quality in a manner consistent with estrogen deficiency. These results indicate MB-SWIFT as a non-ionizing imaging strategy with value for bone imaging and may be a promising technique to progress to the clinic for monitoring and clinical management of patients with bone diseases such as osteoporosis.

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 T1 , T2 , 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 B0 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 B1 + 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.

Functional magnetic resonance imaging (fMRI) studies in animal models provide invaluable information regarding normal and abnormal brain function, especially when combined with complementary stimulation and recording techniques. The echo planar imaging (EPI) pulse sequence is the most common choice for fMRI investigations, but it has several shortcomings. EPI is one of the loudest sequences and very prone to movement and susceptibility-induced artefacts, making it suboptimal for awake imaging. Additionally, the fast gradient-switching of EPI induces disrupting currents in simultaneous electrophysiological recordings. Therefore, we investigated whether the unique features of Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) overcome these issues at a high 9.4 T magnetic field, making it a potential alternative to EPI. MB-SWIFT had 32-dB and 20-dB lower peak and average sound pressure levels, respectively, than EPI with typical fMRI parameters. Body movements had little to no effect on MB-SWIFT images or functional connectivity analyses, whereas they severely affected EPI data. The minimal gradient steps of MB-SWIFT induced significantly lower currents in simultaneous electrophysiological recordings than EPI, and there were no electrode-induced distortions in MB-SWIFT images. An independent component analysis of the awake rat functional connectivity data obtained with MB-SWIFT resulted in near whole-brain level functional parcellation, and simultaneous electrophysiological and fMRI measurements in isoflurane-anesthetized rats indicated that MB-SWIFT signal is tightly linked to neuronal resting-state activity. Therefore, we conclude that the MB-SWIFT sequence is a robust preclinical brain mapping tool that can overcome many of the drawbacks of conventional EPI fMRI at high magnetic fields. peerReviewed

The dynamics of spin system coupled by chemical exchange between two sites with different chemical shifts during periodic radiofrequency (RF) irradiation was here investigated. When the instantaneous π-flip of effective frequency during the course of frequency sweep was applied, a significant increase of exchange-induced relaxation rate constants was observed for small tip angle of magnetization in the laboratory frame of reference. This increase of the rate constants corresponds to the side bands generated by the periodic irradiation during the RF pulses. The exchange-induced relaxation rate constants depend on the exchange conditions, the RF power and the irradiation period. The described phenomenon promises applications for studying protein dynamics and for generating exchange specific relaxation contrasts in MRI.

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.

Author(s): Magnitsky, Sergey; Zhang, Jinjin; Idiyatullin, Djaudat; Mohan, Geetha; Garwood, Michael; Lane, Nancy E; Majumdar, Sharmila | Abstract: PurposeConventional T2 -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.MethodsMesenchymal 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.ResultsThe 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.ConclusionsThe SWIFT sequence can produce a quantifiable hyperintense MRI signal from iron-labeled cells. The graft of 18 x 106 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.

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, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Purpose To use contrast based on longitudinal relaxation times (T1) or rates (R1) 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 naive 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 T1 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 R1 and the tissue iron concentration despite variations in intra-organ distribution, degradation, and IONP surface charge. Linear correlation between R1 and volumetric SAR in hyperthermia therapy was observed. Conclusion The linear dependence between R1 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

Rotating frame spin–lattice relaxation, with the characteristic time constant T1ρ, provides a means to access motion-restricted (slow) spin dynamics in MRI. As a result of their restricted motion, these spins are sometimes characterized by a short transverse relaxation time constant T2 and thus can be difficult to detect directly with conventional image acquisition techniques. Here, we introduce an approach for three-dimensional adiabatic T1ρ mapping based on a magnetization-prepared sweep imaging with Fourier transformation (MP-SWIFT) sequence, which captures signal from almost all water spin populations, including the extremely fast relaxing pool. A semi-analytical procedure for T1ρ mapping is described. Experiments on phantoms and musculoskeletal tissue specimens (tendon, articular and epiphyseal cartilages) were performed at 9.4 T for both the MP-SWIFT and fast spin echo (FSE) read outs. In the phantom with liquids having fast molecular tumbling and a single-valued T1ρ time constant, the measured T1ρ values obtained with MP-SWIFT and FSE were similar. Conversely, in normal musculoskeletal tissues, T1ρ values measured with MP-SWIFT were much shorter than the values obtained with FSE. Studies of biological tissue specimens demonstrated that T1ρ-weighted SWIFT provides higher contrast between normal and diseased tissues relative to conventional acquisitions. Adiabatic T1ρ mapping with SWIFT readout captures contributions from the otherwise undetected fast relaxing spins, allowing more informative T1ρ measurements of normal and diseased states. Copyright © 2016 John Wiley & Sons, Ltd.

To report the results of sweep imaging with Fourier transformation (SWIFT) magnetic resonance (MR) imaging for diagnostic breast imaging.Informed consent was obtained from all participants under one of two institutional review board-approved, HIPAA-compliant protocols. Twelve female patients (age range, 19-54 years; mean age, 41.2 years) and eight normal control subjects (age range, 22-56 years; mean age, 43.2 years) enrolled and completed the study from January 28, 2011, to March 5, 2013. Patients had previous lesions that were Breast Imaging Reporting and Data System 4 and 5 based on mammography and/or ultrasonographic imaging. Contrast-enhanced SWIFT imaging was completed by using a 4-T research MR imaging system. Noncontrast studies were completed in the normal control subjects. One of two sized single-breast SWIFT-compatible transceiver coils was used for nine patients and five controls. Three patients and five control subjects used a SWIFT-compatible dual breast coil. Temporal resolution was 5.9-7.5 seconds. Spatial resolution was 1.00 mm isotropic, with later examinations at 0.67 mm isotropic, and dual breast at 1.00 mm or 0.75 mm isotropic resolution.Two nonblinded breast radiologists reported SWIFT image findings of normal breast tissue, benign fibroadenomas (six of six lesions), and malignant lesions (10 of 12 lesions) concordant with other imaging modalities and pathologic reports. Two lesions in two patients were not visualized because of coil field of view. The images yielded by SWIFT showed the presence and extent of known breast lesions.The SWIFT technique could become an important addition to breast imaging modalities because it provides high spatial resolution at all points during the dynamic contrast-enhanced examination.

Purpose To evaluate the feasibility of SWIFT with variable flip angle (VFA) for measurement of T1 relaxation time in Gd-agarose-phantoms and osteochondral specimens, including regions of very short T2*, and compare with T1 measured using standard methods Methods T1s of agarose phantoms with variable concentration of Gd-DTPA2− and nine pairs of native and trypsin-treated bovine cartilage-bone specimens were measured. For specimens, VFA-SWIFT, inversion recovery (IR) fast spin echo (FSE) and saturation recovery FSE were used. For phantoms, additionally spectroscopic IR was used. Differences and agreement between the methods were assessed using nonparametric Wilcoxon and Kruskal-Wallis tests and intraclass correlation. Results The different T1 mapping methods agreed well in the phantoms. VFA-SWIFT allowed reliable measurement of T1 in the osteochondral specimens, including regions where FSE-based methods failed. The T1s measured by VFA-SWIFT were shifted toward shorter values in specimens. However, the measurements correlated significantly (highest correlation VFA-SWIFT versus FSE was r = 0.966). SNR efficiency was generally highest for SWIFT, especially in the subchondral bone. Conclusion Feasibility of measuring T1 relaxation time using VFA-SWIFT in osteochondral specimens and phantoms was demonstrated. A shift toward shorter T1s was observed for VFA-SWIFT in specimens, reflecting the higher sensitivity of SWIFT to short T2* spins. Magn Reson Med 74:175–184, 2015. © 2014 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. Magn Reson Med 73:1812–1819, 2015. © 2014 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. Magn Reson Med 71:1982–1988, 2014. © 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 inter-band crosstalk by cycling the pulse and receive gap positions relative to the un-gapped pulse shape. We call this strategy "gap cycling." 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 inter-band crosstalk. 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 inter-band crosstalk in SWIFT data.

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 2nd 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. Magn Reson Med 73:254–262, 2015. © 2014 Wiley Periodicals, Inc.

Introduction Magnetic resonance imaging (MRI) has the potential to aid in determining the presence and extent of cracks/fractures in teeth because of better contrast without ionizing radiation. The objectives were to develop MRI criteria for root crack/fracture identification and to establish reliability and accuracy in their detection. Methods MRI-based criteria for crack/fracture appearance was developed by an MRI physicist and a panel of 6 dentists. Twenty-nine human adult teeth previously extracted after a clinical diagnosis of a root crack/fracture were frequency matched to 29 controls. Samples were scanned using an in vivo MRI protocol and the reference standard (ie, ex vivo limited field of view cone-beam computed tomographic [CBCT] imaging). A blinded, 4-member panel evaluated the images with a proportion randomly retested to establish intrarater reliability. Overall observer agreement, sensitivity, and specificity were computed for each imaging modality. Results Subjectively, MRI has increased crack/fracture contrast and is less prone to artifacts from radiodense materials relative to CBCT imaging. Intrarater reliability for MRI was fair to excellent (κ = 0.38–1.00), and for CBCT imaging, it was moderate to excellent (κ = 0.66–1.00). Sensitivity for MRI was 0.59 (95% confidence interval [CI], 0.39-0.76; P = .46), and for CBCT imaging, it was 0.59 (95% CI, 0.59–0.76; P = .46). Specificity for MRI was 0.83 (95% CI, 0.64–0.94; P Conclusions Despite advantages of increased contrast and the absence of artifacts from radiodense materials in MRI, comparable measures of sensitivity and specificity (to limited field of view CBCT imaging) suggest MRI quality improvements are needed, specifically in image acquisition and postprocessing parameters. Given the early stage of technology development, there may be a use for MRI in detecting cracks/fractures in teeth.

Background Magnetic resonance imaging (MRI) research at the University of Minnesota has resulted in notable advancements, including capture of signal from densely calcified tissues. Application of this technology to address dental questions plus efforts to minimize the cost and size of MRI scanners suggests the potential adoption of MRI in regular clinical dental settings. Objective This abstract reviews advances in the areas that move this technology closer to adoption in dentistry: (1) capture of quickly decaying T2 signal, (2) coil development for dental applications, and (3) redesign of the MRI scanner for cost/size reductions. We present recent data suggesting that existing MRI technology can detect (cracks and blood flow within teeth. Materials and Methods Twenty-nine human teeth extracted after clinical diagnosis of a root crack/fracture were frequency matched to 29 control teeth. Teeth were scanned with MRI and cone beam computed tomography (CBCT). A 4-member panel evaluated the images according to established criteria. Saline was pumped through microtubing inserted into an extracted tooth to resemble pulpal blood flow. Flow rates were controlled within the range of calculated rates of pulpal arterioles. The setup was imaged with a sweep imaging with Fourier transformation (SWIFT)-MRI saturation technique to distinguish the moving fluid from surrounding stationary fluid. Results CBCT and MRI demonstrated similar levels of sensitivity and specificity, despite nonoptimized MRI image processing and limited observer calibration. Images with selective saturation of flowing or still liquids allowed for successful visualization of fluid-flow through the extracted tooth. Discussion Using improved pre- and postprocessing MRI approaches, teeth should be rescanned to enhance sensitivity of detecting cracks. Panelists should be educated and calibrated, and a reliability assessment study should be performed again with a larger sample size. Studies in extracted tooth flow imaging should be conducted to determine the lower limit of flow detection and whole-dentition in vivo images of vascular flow in teeth obtained.

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. Magn Reson Med 72:858–863, 2014. © 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. Magn Reson Med 72:160–165, 2014. © 2013 Wiley Periodicals, Inc.

Purpose T1 quantification of contrast agents, such as super-paramagnetic iron oxide nanoparticles, is a challenging but important task inherent to many in vivo applications in magnetic resonance imaging. In this work, a sweep imaging with Fourier transformation using variable flip angles (VFAs-SWIFT) method was proposed to measure T1 of aqueous super-paramagnetic iron oxide nanoparticle suspensions. Methods T1 values of various iron concentrations (from 1 to 7 mM) were measured using VFA-SWIFT and three-dimensional spoiled gradient-recalled echo with VFAs (VFA-SPGR) sequences on a 7 T MR scanner. For validation, T1 values were also measured using a spectroscopic inversion-recovery sequence on a 7 T spectrometer. Results VFA-SWIFT demonstrated its advantage for quantifying T1 of highly concentrated aqueous super-paramagnetic iron oxide nanoparticle suspensions, but VFA-SPGR failed at the higher end of iron concentrations. Both VFA-SWIFT and VFA-SPGR yielded linear relationships between the relaxation rate and iron concentrations, with relaxivities of 1.006 and 1.051 s−1 mM−1 at 7 T, respectively, in excellent agreement with the spectroscopic measurement of 1.019 s−1 mM−1. Conclusion VFA-SWIFT is able to achieve accurate T1 quantification of aqueous super-paramagnetic iron oxide nanoparticle suspensions up to 7 mM. Magn Reson Med 70:341–347, 2013. © 2013 Wiley Periodicals, Inc.

Three-dimensional phosphorus MR images (31P MRI) of teeth are obtained at a nominal resolution of 0.5 mm in less than 15 minutes using acquisition pulse sequences sensitive to ultra-short transversal relaxation times. The images directly reflect the spatially resolved phosphorus content of mineral tissue in dentin and enamel; they show a lack of signal from pulp tissue and reduced signal from de-mineralized carious lesions. We demonstrate for the first time that the signal in 31P MR images of mineralized tissue is enhanced by a 1H-31P nuclear Overhauser effect (NOE). Using teeth as a model for imaging mineralized human tissue, graded differences in signal enhancement are observed that correlate well with known mineral content. From solid-state NMR experiments we conclude that the NOE is facilitated by spin diffusion and that the NOE difference can be assigned to a higher water content and a different micro-structure of dentin. Thus, a novel method for imaging mineral content without ionizing radiation is proposed. This method has potential use in the assessment of de-mineralization states in humans, such as caries of teeth and osteoporosis of bones.

A recently introduced method called SWIFT (SWeep Imaging with Fourier Transform) is a fundamentally different approach to MRI which is particularly well suited to imaging objects with extremely fast spin–spin relaxation rates. The method exploits a frequency-swept excitation pulse and virtually simultaneous signal acquisition in a time-shared mode. Correlation of the spin system response with the excitation pulse function is used to extract the signals of interest. With SWIFT, image quality is highly dependent on producing uniform and broadband spin excitation. These requirements are satisfied by using frequency-modulated pulses belonging to the hyperbolic secant family (HS n pulses). This article describes the experimental steps needed to properly implement HS n pulses in SWIFT. In addition, properties of HS n pulses in the rapid passage, linear region are investigated, followed by an analysis of the pulses after inserting the “gaps” needed for time-shared excitation and acquisition. Finally, compact expressions are presented to estimate the amplitude and flip angle of the HS n pulses, as well as the relative energy deposited by the SWIFT sequence.

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. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Type I mucopolysaccharidosis (MPS I) is an autosomal recessive lysosomal storage disorder with neurological features. Humans and laboratory animals with MPS I exhibit various white matter abnormalities involving the corpus callosum and other regions. In this study, we first validated a novel MRI technique, entitled Relaxation Along a Fictitious Field in the rotating frame of rank n (RAFFn), as a measure of myelination and dysmyelination in mice. We then examined differences between MPS I mice and heterozygotes using RAFF5 and histology. RAFF5 (i.e., RAFFn with n = 5) relaxation time constants were highly correlated with histological myelin density (R2 = 0.68, P

A novel fast and quiet method of magnetic resonance imaging (MRI) is introduced which creates new opportunities for imaging in medicine and materials science. The method is called SWIFT, sweep imaging with Fourier transformation. In SWIFT, time-domain signals are acquired in a time-shared manner during a swept radiofrequency excitation of the nuclear spins. With negligible time between excitation and signal acquisition, new possibilities exist for imaging objects consisting of spins with extremely fast transverse relaxation rates, such as macromolecules, semi-solids, and quadrupolar nuclei. The field gradient used for spatial-encoding is not pulsed on and off, but rather is stepped in orientation in an incremental manner, which results in low acoustic noise. This unique acquisition method is expected to be relatively insensitive to sample motion, which is important for imaging live objects. Additionally, the frequency-swept excitation distributes the signal energy in time and thus dynamic range requirements for proper signal digitization are reduced compared with conventional MRI. For demonstration, images of a plastic object and cortical bone are shown.

Here we report a modified pulsed gradient spin-echo (PGSTE) pulse sequence to measure diffusion coefficients. This approach incorporates WATERGATE combined with isotopic filtering into a standard PGSTE experiment. Doing this eliminates much of the disadvantages from the combination of diffusion encoding and heteronuclear selection intervals and allows for facile modification of the diffusion pulse sequence with flexibility of the time period between RF pulses. The new diffusion pulse sequence is demonstrated using an 15N-labeled peptide and an 15N-labeled protein in a mixture with a protein of similar size.

A novel approach is described to analyze NMR relaxation data on proteins. This method introduces the frequency-dependent order parameter, S(2)(omega), in order to estimate contributions to the generalized order parameter S(2) from different motional frequencies occurring on the picosecond to nanosecond time scales. S(2)(omega) is defined as the sum of a specified set of weighting coefficients from the Lorentzian expansion of the spectral density function. 15N NMR relaxation data (500, 600, and 800 MHz) on protein GB1 exemplify the method. Using this approach provides information on motional restrictions over specific frequency or time scale ranges and provides a normalized comparison of motional restrictions between proteins having different overall tumbling correlation times.

A new model-free approach that allows visualization of the distribution of motional correlation times is presented and is used to analyze 1 5 N NMR relaxation data [T 1 , T 2 , and { 1 H}- 1 5 N NOE], acquired at 500. 600, and 800 MHz, on the uniformly 1 5 N-enriched, 56 residue B1 domain from immunoglubulin protein G (GB I ). Nanosecond time scale internal motions are found for all NHs of residues in protein GB1, a finding which is consistent with the concept of hierarchical internal motions in proteins first forwarded by Frauenfelder. Order parameters and overall tumbling correlation times derived using this approach are not influenced by the number of internal motional modes. Comparatively, use of the Lipari-Szabo, Clore et al., or Lemaster "model-free" methods yields underestimated order parameters and overestimated overall tumbling correlation times due to the presence of nanosecond time scale internal motions. This new model-free approach provides a straightforward way to derive more accurate order parameters and correlation times for overall tumbling and internal motions.

Protein stability is usually characterized calorimetrically by a melting temperature and related thermodynamic parameters. Despite its importance, the microscopic origin of the melting transition and the relationship between thermodynamic stability and dynamics remains a mystery. Here, NMR relaxation parameters were acquired for backbone 15NH groups of the 56 residue immunoglobulin-binding domain of streptococcal protein G over a pre-denaturation temperature range of 5-50 degrees C. Relaxation data were analyzed using three methods: the standard three-Lorentzian model free approach; the F(omega)=2omegaJ(omega) spectral density approach that yields motional correlation time distributions, and a new approach that determines frequency-dependent order parameters. Regardless of the method of analysis, the temperature dependence of internal motional correlation times and order parameters is essentially the same. Nanosecond time-scale internal motions are found for all NHs in the protein, and their temperature dependence yields activation energies ranging up to about 33kJ/mol residue. NH motional barrier heights are structurally correlated, with the largest energy barriers being found for residues in the most "rigid" segments of the fold: beta-strands 1 and 4 and the alpha-helix. Trends in this landscape also parallel the free energy of folding-unfolding derived from hydrogen-deuterium (H-D) exchange measurements, indicating that the energetics for internal motions occurring on the nanosecond time-scale mirror those occurring on the much slower time-scale of H-D exchange. Residual heat capacities, derived from the temperature dependence of order parameters, range from near zero to near 100J/mol K residue and correlate with this energy landscape. These results provide a unique picture of this protein's energy landscape and a relationship between thermodynamic stability and dynamics that suggests thermosensitive regions in the fold that could initiate the melting process.

A useful extension to SWIFT (SWeep Imaging with Fourier Transformation) utilizing sidebands of the excitation pulse is introduced. This MRI method, called Multi-Band-SWIFT, achieves much higher bandwidth than standard SWIFT by using multiple segmented excitations (bands) of the field of view. A description of the general idea and variants of the pulse sequence are presented. From simulations and semi-phenomenological theory, estimations of power deposition and signal-to-noise ratio are made. MB-SWIFT and ZTE (zero-TE) sequences are compared based on images of a phantom and human mandible. Multi-Band-SWIFT provides a bridge between SWIFT and ZTE sequences and allows greatly increased excitation and acquisition bandwidths relative to standard SWIFT for the same hardware switching parameters and requires less peak amplitude of the radiofrequency field (or greater flip angle at same peak amplitude) as compared to ZTE. Multi-Band-SWIFT appears to be an attractive extension of SWIFT for certain musculoskeletal and other medical imaging applications, as well as for imaging materials.

13C-NMR relaxation experiments (T(1), T(2), T(1)(rho), and NOE) were performed on selectively enriched residues in two peptides, one hydrophobic staple alpha-helix-forming peptide GFSKAELAKARAAKRGGY and one beta-hairpin-forming peptide RGITVNGKTYGR, in water and in water/trifluoroethanol (TFE). Exchange contributions, R(ex), to spin-spin relaxation rates for (13)C(alpha) and (13)C(beta) groups were derived and were ascribed to be mainly due to peptide folding-unfolding. To evaluate the exchange time, tau(ex), from R(ex), the chemical shift difference between folded and unfolded states, Deltadelta, and the populations of these states, p(i), were determined from the temperature dependence of (13)C chemical shifts. For both peptides, values for tau(ex) fell in the 1 micros to 10 micros range. Under conditions where the peptides are most folded (water/TFE, 5 degrees C), tau(ex) values for all residues in each respective peptide were essentially the same, supporting the presence of a global folding-unfolding exchange process. Rounded-up average tau(ex) values were 4 micros for the helix peptide and 9 micros for the hairpin peptide. This 2-3-fold difference in exchange times between helix and hairpin peptides is consistent with that observed for folding-unfolding of other small peptides.

Peptide GFSKAELAKARAAKRGGY folds in an alpha-helical conformation that is stabilized by formation of a hydrophobic staple motif and an N-terminal capping box (Munoz V. Blanco FJ, Serrano L, 1995, Struct Biol 2:380-385). To investigate backbone and side-chain internal motions within the helix and hydrophobic staple, residues F2, A5, L7, A8, and A10 were selectively 13C- and 15N-enriched and NMR relaxation experiments were performed in water and in water/trifluoroethanol (TFE) solution at four Larmor frequencies (62.5, 125, 150, and 200 MHz for 13C). Relaxation data were analyzed using the model free approach and an anisotropic diffusion model. In water, angular variances of motional vectors range from 10 to 20 degrees and backbone phi,psi bond rotations for helix residues A5, L7, A8, and A10 are correlated indicating the presence of Calpha-H, Calpha-Cbeta, and N-H rocking-type motions along the helix dipole axis. L7 side-chain CbetaH2 and CgammaH motions are also correlated and as motionally restricted as backbone CalphaH, suggesting considerable steric hindrance with neighboring groups. In TFE which stabilizes the fold, internal motional amplitudes are attenuated and rotational correlations are increased. For the side chain of hydrophobic staple residue F2, wobbling-in-a-cone type motions dominate in water, whereas in TFE, the Cbeta-Cgamma bond and phenyl ring fluctuate more simply about the Calpha-Cbeta bond. These data support the Daragan-Mayo model of correlated bond rotations (Daragan VA, Mayo KH, 1996, J Phys Chem 100:8378-8388) and contribute to a general understanding of internal motions in peptides and proteins.

To evaluate the limit of tooth crack width visualization by two MRI pulse sequences in comparison with CBCT.Two extracted human teeth with known crack locations and dimensions, as determined by reference standard microCT, were selected for experimental imaging. Crack location/dimension and the presence of common dental restorative materials such as amalgam were typical of that found clinically. Experimental imaging consisted of conventional CBCT scans and MRI scans with two pulse sequences including Sweep Imaging with Fourier Transformation (SWIFT) and gradient echo (GRE). CBCT and MR images of extracted teeth were acquired using acquisition parameters identical to those used for in vivo imaging. Experimental and reference standard images were registered and the limit of tooth crack visualization was determined.Collected images indicate that SWIFT could demonstrate cracks with 20-µm width, which is 10 times narrower than the imaging voxel size. Cracks of this size were not visible in GRE images, even with a short echo time of 2.75 ms. The CBCT images were distorted by artefacts owing to close location of metallic restorations.The successful visualization of cracks with the SWIFT MRI sequence compared with other clinical modalities suggests that SWIFT MRI can effectively detect microcracks in teeth and therefore may have potential to be a non-invasive method for the in vivo detection of cracks in human teeth.

Sweep imaging with Fourier transformation, SWIFT, is a relatively new addition to the class of ultra-short T2-sensitive MRI sequences. It reverses the recent paradigm of pulsed NMR methodology by exploiting features of continuous-wave experiments from the early days of NMR. Images are produced by collecting projections of the object in a radial manner. Each projection is excited by a frequency sweep in the presence of a field gradient. MR signal is acquired in gaps in the frequency-swept pulse, in a time-shared manner. Signals are excited sequentially in time and space, leading to phase variation. Phase variation due to the frequency-swept excitation is removed by correlation of the received data with the pulse waveform. The result is equivalent to FID excitation using a short hard pulse. The phase evolution time of signal prior to acquisition is as low as a few microseconds for high bandwidth SWIFT, so signals from spins with extremely short T2s (tens of microseconds) are preserved. Here we describe the SWIFT sequence and signal processing procedures, along with some applications, including magnetization-prepared imaging of the human brain, in vitro imaging of bone and cartilage, in vitro dental imaging, and high-resolution phase imaging of in vitro rat brain. Keywords: NMR; MRI; frequency modulation; frequency sweep; adiabatic pulses; musculoskeletal imaging; radial MRI

Calcifications represent one component of pathology in many brain diseases. With MRI, they are most often detected by exploiting negative contrast in magnitude images. Calcifications are more diamagnetic than tissue, leading to a magnetic field disturbance that can be seen in phase MR images. Most phase imaging studies use gradient recalled echo based pulse sequences. Here, the phase component of SWIFT, a virtually zero acquisition delay sequence, was used to detect calcifications ex vivo and in vivo in rat models of status epilepticus and traumatic brain injury. Calcifications were detected in phase and imaginary SWIFT images based on their dipole like magnetic field disturbances. In magnitude SWIFT images, calcifications were distinguished as hypointense and hyperintense. Hypointense calcifications showed large crystallized granules with few surrounding inflammatory cells, while hyperintense calcifications contained small granules with the presence of more inflammatory cells. The size of the calcifications in SWIFT magnitude images correlated with that in Alizarin stained histological sections. Our data indicate that SWIFT is likely to better preserve signal in the proximity of a calcification or other field perturber in comparison to gradient echo due to its short acquisition delay and broad excitation bandwidth. Furthermore, a quantitative description for the phase contrast near dipole magnetic field inhomogeneities for the SWIFT pulse sequence is given. In vivo detection of calcifications provides a tool to probe the progression of pathology in neurodegenerative diseases. In particular, it appears to provide a surrogate marker for inflammatory cells around the calcifications after brain injury.

Objective Current imaging techniques are often suboptimal for the detection of mandibular invasion by squamous cell carcinoma. The aim of this study was to determine the feasibility of a magnetic resonance imaging (MRI)-based technique known as sweep imaging with Fourier transform (SWIFT) to visualize the structural changes of intramandibular anatomy during invasion. Design Descriptive case study. Setting Tertiary academic institution. Patients Patients with oral carcinoma who underwent segmental mandibulectomy. Interventions Two specimens from each patient were imaged using a 9.4-T Varian MRI system. The SWIFT images were correlated with histologic sections. Results The SWIFT technique with in vitro specimens produced images with sufficient resolution (156-273 μm) and contrast to allow accurate depiction of tumor invasion of cortical and medullary bone. Both specimens had histopathologic evidence of mandibular invasion with tumor. A high degree of correlation was found between magnetic resonance images and histopathologic findings. Conclusions The SWIFT MRI offers 3-dimensional assessment of cortical and medullary bone in fine detail and excellent qualitative agreement with histopathologic findings. Imaging with the SWIFT MRI technique demonstrates great potential to identify mandibular invasion by oral carcinoma.

We describe a fundamentally different approach to MRI referred to as SWIFT (sweep imaging with Fourier transformation). SWIFT exploits time-shared RF excitation and signal acquisition, allowing capture of signal from spins with extremely short transverse relaxation time, T(2)*. The MR signal is acquired in gaps inserted into a broadband frequency-swept excitation pulse, which results in acquisition delays of only 1 - 2 microseconds. In SWIFT, 3D k-space is sampled in a radial manner, whereby one projection of the object is acquired in the gaps of each frequency-swept pulse, allowing a repetition time (TR) on the order of the pulse length (typically 1 - 3 milliseconds). Since the orientation of consecutive projections varies in a smooth manner (i.e., only small increments in the values of the x, y, z gradients occur from view to view), SWIFT scanning is close to inaudible and is insensitive to gradient timing errors and eddy currents. SWIFT images can be acquired in scan times similar to and sometimes faster than conventional 3D gradient echo techniques. With its ability to capture signals from ultrashort T(2)* spins, SWIFT promises to expand the role of MRI in areas of research where MRI previously played no or negligible role. In this article, we show wood and tooth images obtained with SWIFT as examples of materials with ultrashort T(2)*. Early experience suggests SWIFT can play a role in materials science and porous media research.

Introduction: Clinical dentistry is in need of noninvasive and accurate diagnostic methods to better evaluate dental pathosis. The purpose of this work was to assess the feasibility of a recently developed magnetic resonance imaging (MRI) technique, called SWeep Imaging with Fourier Transform (SWIFT), to visualize dental tissues. Methods: Three in vitro teeth, representing a limited range of clinical conditions of interest, imaged using a 9.4T system with scanning times ranging from 100secondsto25minutes.Invivoimagingofasubject was performed using a 4T system with a 10-minute scanning time. SWIFT images were compared withtraditional two-dimensional radiographs, three-dimensional cone-beam computed tomography (CBCT) scanning, gradient-echo MRI technique, and histological sections. Results: A resolution of 100 mm was obtained from in vitro teeth. SWIFT also identified the presence and extent of dental caries and fine structures of the teeth, including cracks and accessory canals, which are not visible with existing clinical radiography techniques. Intraoral positioning of the radiofrequency coil produced initial images of multiple adjacent teeth at a resolution of 400 mm. Conclusions: SWIFT MRI offers simultaneous three-dimensional hard- and soft-tissue imaging of teeth without the use of ionizing radiation. Furthermore, it has the potential to image minute dental structures within clinically relevant scanning times. This technology has implications for endodontists because it offers a potential method to longitudinally evaluate teeth where pulp and root structures have been regenerated. (J Endod 2011;37:745‐752)

We report initial results from studies using SWeep Imaging with Fourier Transformation (SWIFT) to detect superparamagnetic iron oxide (SPIO) particle-labeled stem cells in the rat heart. In experiments performed on phantoms containing titanium balls or SPIO-labeled cells, frequency-shifted signals surrounding the paramagnetic objects produced a pile-up artifact in SWIFT images, while total signal intensity was retained to a much greater extent on SWIFT images as compared to gradient echo images. SWIFT images of excised and in vivo hearts showed (a) reduced blooming artifact as compared with gradient echo images, which helped reduce ambiguity in the detection of SPIO labeled cells, (b) enhancement of off-resonance signals relative to the background in the imaginary component of images, and (c) detailed myocardial anatomy in magnitude images which provided anatomical reference. These features suggest SWIFT can facilitate the detection of SPIO-labeled cells in the cardiovascular system.

A novel, fast, and quiet method of magnetic resonance imaging (MRI), called SWIFT (sweep imaging with Fourier transformation) has recently been introduced. In addition to SWIFT's potential for in-vivo MRI, it creates new opportunities for MRI of materials. SWIFT currently operates in 3d radial acquisition mode. A series of segmented hyperbolic secant excitation pulses is accompanied by acquisition in the gaps. Each excitation, after correlation with the pulse results in a free induction decay (FID). The spectrum corresponding to the FID is a projection. There is very little “dead time” between excitation and acquisition, making SWIFT useful for imaging of short T2 materials, but in total imaging times comparable to fast gradient echo sequences.

Measurements of chemical-exchange processes by NMR are widely used to obtain valuable information about molecular dynamics and structure. Here, a computational method is introduced to assess the influence of chemical exchange on spin relaxation rates. The method is based on the inclusion of a random exchange process in product operator calculations on a microscopic level. This product operator approach can be applied to estimate exchange contributions when using sophisticated pulse sequences that cannot be easily described analytically. The method applies to the full range of exchange times measurable by NMR and can incorporate interference effects between exchange and other processes such as scalar coupling. To demonstrate its utility, simulated relaxation data were compared with theoretical predictions of spin-locking and Carr-Purcell spin-echo sequences with hard and adiabatic pulses, using different time scales for a two-site chemical-exchange process. Finally, simulations were used to examine a system in which a second random process is superimposed on a simple two-site exchange process. The method was found to provide a simple and robust tool to analyze pulse sequences and equations commonly used to study exchange-induced relaxation.

In the presence of radiofrequency irradiation, relaxation of magnetization aligned with the effective magnetic field is characterized by the time constant T1rho. On the other hand, the time constant T2rho characterizes the relaxation of magnetization that is perpendicular to the effective field. Here, it is shown that T2rho can be measured directly with Carr-Purcell sequences composed of a train of adiabatic full-passage (AFP) pulses. During adiabatic rotation, T2rho characterizes the relaxation of the magnetization, which under adiabatic conditions remains approximately perpendicular to the time-dependent effective field. Theory is derived to describe the influence of chemical exchange on T2rho relaxation in the fast-exchange regime, with time constant defined as T2rho,ex. The derived theory predicts the rate constant R2rho,ex (= 1/T2rho,ex) to be dependent on the choice of amplitude- and frequency-modulation functions used in the AFP pulses. Measurements of R2rho,ex of the water/ethanol exchanging system confirm the predicted dependence on modulation functions. The described theoretical framework and adiabatic methods represent new tools to probe exchanging systems.

Here, we report a method to simultaneously determine CH2 cross-correlation spectral densities and T1 relaxation times in the laboratory and rotating frames. To accomplish this, we have employed an indirect approach that is based on measurement of differences in relaxation rates acquired with and without cross-correlation terms. The new method, which can be employed using multidimensional NMR and standard relaxation pulse sequences, is validated experimentally by investigation of a selectively 13C-enriched hexadecapeptide and the uniformly 13C-enriched immunoglobulin-binding domain of streptococcal protein G (GB1). Use of this approach makes determination of CH2 cross-correlation spectral densities in uniformly 13C-enriched proteins now routine and provides novel information concerning their internal motions.

This study presents a site-resolved experimental view of backbone C(alpha)H and NH internal motions in the 56-residue immunoglobulin-binding domain of streptococcal protein G, GB1. Using (13)C(alpha)H and (15)NH NMR relaxation data [T(1), T(2), and NOE] acquired at three resonance frequencies ((1)H frequencies of 500, 600, and 800 MHz), spectral density functions were calculated as F(omega) = 2omegaJ(omega) to provide a model-independent way to visualize and analyze internal motional correlation time distributions for backbone groups in GB1. Line broadening in F(omega) curves indicates the presence of nanosecond time scale internal motions (0.8 to 5 nsec) for all C(alpha)H and NH groups. Deconvolution of F(omega) curves effectively separates overall tumbling and internal motional correlation time distributions to yield more accurate order parameters than determined by using standard model free approaches. Compared to NH groups, C(alpha)H internal motions are more broadly distributed on the nanosecond time scale, and larger C(alpha)H order parameters are related to correlated bond rotations for C(alpha)H fluctuations. Motional parameters for NH groups are more structurally correlated, with NH order parameters, for example, being larger for residues in more structured regions of beta-sheet and helix and generally smaller for residues in the loop and turns. This is most likely related to the observation that NH order parameters are correlated to hydrogen bonding. This study contributes to the general understanding of protein dynamics and exemplifies an alternative and easier way to analyze NMR relaxation data.

A simple method is presented to accurately determine (15)N-[(1)H] NOEs in biomolecules in the presence of H(N)-water proton chemical exchange. Three measurements are required: one with nonselective proton saturation and two with different water saturation conditions to determine the equilibrium value of the (15)N signal. This approach is exemplified with data on two peptides, one helix-forming 17-mer and one compactly folded 56-mer. Results indicate that (15)N-[(1)H] NOEs determined using the standard approach with short recycle times (3 to 4 s) can be significantly in error when H(N)-water proton chemical exchange is relatively rapid, water proton relaxation is relatively slow, and (15)N-[(1)H] NOEs are away from the value of -1. This new method avoids such inaccuracies resulting from the use of short recycle times.

A new approach to visualizing spectral densities and analyzing NMR relaxation data has been developed. By plotting the spectral density function, J(omega), as F(omega)=2 omega J(omega) on the log-log scale, the distribution of motional correlation times can be easily visualized. F(omega) is calculated from experimental data using a multi-Lorentzian expansion that is insensitive to the number of Lorentzians used and allows contributions from overall tumbling and internal motions to be separated without explicitly determining values for correlation times and their weighting coefficients. To demonstrate the approach, (15)N and (13)C NMR relaxation data have been analyzed for backbone NH and C(alpha)H groups in an alpha-helix-forming peptide 17mer and in a well-folded 138-residue protein, and the functions F(omega) have been calculated and deconvoluted for contributions from overall tumbling and internal motions. Overall tumbling correlation time distribution maxima yield essentially the same overall correlation times obtained using the Lipari-Szabo model and other standard NMR relaxation data analyses. Internal motional correlational times for NH and C(alpha)H bond motions fall in the range from 100 ps to about 1 ns. Slower overall molecular tumbling leads to better separation of internal motional correlation time distributions from those of overall tumbling. The usefulness of the approach rests in its ability to visualize spectral densities and to define and separate frequency distributions for molecular motions.