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Perfusion imaging by un-inverted flow-sensitive alternating inversion recovery (UNFAIR).

A new pulse sequence for estimating cerebral blood flow called UNFAIR, which uses a combination of sequential hyperbolic secant preparatory pulses, is introduced. This sequence is based on the same generalized conditions as previously introduced inversion recovery techniques except that the spins in the image slice of interest always have +z magnetization and the in-flowing spins are alternately inverted and uninverted. CBF-weighted images of rat brain under conditions of normocpnia and hypercapnia are presented and demonstrate the expected CBF response. A model describing the signal response to this pulse sequence is also presented and compared with in-vivo data acquired from gray and white matter.

Animals↗

T1rho imaging using magnetization-prepared projection encoding (MaPPE).

T1rho contrast weighting using a magnetization-prepared projection encoding (MaPPE) pulse sequence was investigated. Fast radial imaging was implemented by applying magnetization preparation pulses, each followed by multiple RF alpha pulses encoding radial trajectories of k-space. Acquiring multiple views per preparatory pulse imposes view-to-view variation; the resultant distortion of the point-spread function is examined. The issue of maximizing signal while preserving the intended contrast weighting is addressed. Under modification of repetition time and flip angle (alpha), three distinct behavior regimes of the sequence are identified. The utility of the pulse sequence as a quantitative relaxation measurement tool is also examined by comparing imaging and spectroscopy experiments. A mouse was imaged in vitro to demonstrate the viability of application to MR histology. These images exhibit the utility of spinlocking and projection encoding as an aftemative contrast source to both T2-weighted MaPPE images and conventional T2-weighted spin-echo images.

Animals↗

Mitochondrial calcium uptake from physiological-type pulses of calcium. A description of the rapid uptake mode.

A controversy in the field of bioenergetics has been whether mitochondria are capable of sequestering enough Ca2+ from cytosolic Ca2+ pulses to raise their intramitochondrial free Ca2+ level ([Ca2+]m). This is significant because an increase in [Ca2+]m has been linked to an increase in cellular metabolic rate through various mechanisms. To resolve this question, we exposed isolated liver mitochondria to physiological type pulses of Ca2+ produced using a pulse-generating system (Sparagna, G. C., Gunter, K. K., and Gunter, T. E. (1994) Anal. Biochem. 219, 96-103). We then measured the resulting mitochondrial Ca2+ uptake. The uniporter was previously thought to be the only specific Ca2+ uptake mechanism in mitochondria. Our studies have uncovered an additional uptake mechanism, the rapid mode of uptake or RaM, which functions at the beginning of each pulse and allows mitochondria to sequester a considerable amount of Ca2+ from short pulses. We have shown that the RaM is reset by decreasing the [Ca2+] between pulses for a very short time, making this uptake mode ideally suited for Ca2+ sequestration from Ca2+ pulse sequences. With rapid Ca2+ uptake occurring at the beginning of each pulse, liver mitochondria may be able to sequester sufficient Ca2+ from a short sequence of pulses to activate the cellular metabolic rate.

Animals↗

A comparison of local and remote masking on tactile pulse detection using different masking patterns.

Forward and backward masking functions were obtained for the detection of a 2-msec. tactile "test" pulse using two different masking patterns (5- or 10-pulse sequences) under conditions of both local and remote masking. Twelve ISIs (interval between "test" pulse and onset of the masking sequence) ranging from 10 to 76 msec. were used. A two-interval forced-choice (2-IFC) procedure was used in which observers were presented with two successive trains of tactile pulses, one having the "test" pulse at varying intervals prior (backward masking) to or after (forward masking) the masking sequence and one train having only a masking sequence. Observers were asked to report in which train of pulses they detected the "test" pulse. With local masking, i.e., when "test" pulse and masking sequence were presented to the same locus, there was substantially more forward than backward masking, and the 10-pulse sequence resulted in consistently greater amounts of masking than the 5-pulse mask. When the "test" pulse and masking sequence were delivered to different loci, i.e., the remote masking, the results were much less systematic. The data suggest that both peripheral and central factors contribute to the obtained masking functions and that both integration and interruption are producing the masking interference.

Discrimination Learning↗

Carr-Purcell sequences with composite pulses.

We present novel Carr-Purcell-like sequences using composite pulses that exhibit improved performance in strongly inhomogeneous fields. The sequences are designed to retain the intrinsic error correction of the standard Carr-Purcell-Meiboom-Gill (CPMG) sequence. This is achieved by matching the excitation pulse with the refocusing cycle such that the initial transverse magnetization lies along the axis n(Beta) characterizing the overall rotation of the refocusing cycle. Such sequences are suitable for relaxation measurements. It is shown that in sufficiently inhomogeneous fields, the echo amplitudes have an initial transient modulation that is limited to the first few echoes and then decay with the intrinsic relaxation time of the sample. We show different examples of such sequences that are constructed from simple composite pulses. Sequences of the form 90 degrees (0)-(90 degrees (90-theta/2)-theta(180-theta/2)-90 degrees (90-theta/2))(n) with theta approximately 90 degrees and 270 degrees generate signal over a bandwidth larger than that of the conventional CPMG sequence, resulting in an improved signal-to-noise ratio in inhomogeneous fields. The new sequence 127 degrees (x,y)-(127 degrees (x)-127 degrees (-x))(n) only excites signal off-resonance with a spectrum that is bimodal, peaking at Delta omega(0)=+/-omega(1). Depending on the phase and exact timing of the first pulse, symmetric or antisymmetric excitation is obtained. We also demonstrate several new sequences with improved dependence on the RF field strength. The sequence (22.5 degrees (67.5)-90 degrees (-22.5))-(90 degrees (67.5)-45 degrees (157.5)-90 degrees (67.5))(n) has the property that the phase of the signal depends on B(1), allowing coarse B(1) imaging in a one-dimensional experiment.

Magnetic Resonance Spectroscopy↗

Motion-insensitive, steady-state free precession imaging.

Steady-state free precession (SSFP) pulse sequences employing gradient reversal echoes and short repetition time (TR) between successive rf excitation pulses offer high signal-to-noise ratio per unit time. However, SSFP sequences are very sensitive to motion. A new SSFP method is presented which avoids the image artifacts and loss of signal intensity due to motion. The pulse sequence is designed so that the time integral of each of the three gradients is zero over each TR time interval. The signal then consists of numerous echoes which are superimposed. These echoes are isolated by combining the data from N different scans. In each scan a specific phase shift is added during every TR interval. Each of these N isolated echoes produces a motion-insensitive, artifact-free image. Because all the echoes are sampled simultaneously, the signal-to-noise ratio per unit time in this SSFP method is higher than in existing SSFP techniques which sample only one echo at a time. The new method was implemented and used to produce both two- and three-dimensional images of the head and cervical spin of a human patient. In these images the high signal intensity of cerebrospinal fluid is preserved regardless of its motion. Further work is required to evaluate the imaging parameters (TR, TE, rf tip angle) so as to give optimal tissue contrast for the various echoes.

Humans↗

A simple approach for phase-modulated single-scan 2D NMR spectroscopy.

Conventional NMR spectroscopy techniques require long acquisition times due to the recovery time between the repeated excitations necessary for each increment of the evolution times in the indirectly detected dimensions. Here we outline a pulse sequence element for gradient-assisted ultrafast multidimensional NMR spectroscopy using frequency-modulated 'chirp' pulses to generate phase-modulated magnetization in an indirectly detected spectral dimension. The potential of this sequence element is demonstrated by acquiring a correlation spectroscopy (COSY) spectrum in 96 ms. This new pulse sequence element is an extension of ultrafast spectroscopy techniques based on the generation of amplitude modulation of the NMR signal in the indirectly detected spectral dimensions. The use of phase modulation instead of amplitude modulation helps broaden the applicability and may provide an increase of sensitivity in some experiments due to the ability to distinguish between positive and negative frequency offsets relative to the carrier frequency of the sequence element.

Magnetic Resonance Spectroscopy↗

Scalable design of tailored soft pulses for coherent control.

We present a scalable scheme to design optimized soft pulses and pulse sequences for coherent control of interacting quantum many-body systems. The scheme is based on the cluster expansion and the time-dependent perturbation theory implemented numerically. This approach offers a dramatic advantage in numerical efficiency, and it is also more convenient than the commonly used Magnus expansion, especially when dealing with higher-order terms. We illustrate the scheme by designing 2nd-order self-refocusing pi pulses and a 6th-order 8-pulse refocusing sequence for a chain of qubits with nearest-neighbor couplings. We also discuss the performance of soft-pulse refocusing sequences in suppressing decoherence due to low-frequency environment.

Journal Article↗

A one-shot lactate-editing sequence for localized whole-body spectroscopy.

A pulse sequence is presented for performing localized lactate-edited proton spectroscopy in the whole-body environment. The sequence is optimized for relatively low field strength (1.5-T) clinical measurements. Characteristics of this method of lactate editing, which makes it more suitable for clinical applications than previous methods, include the following: The "one shot" nature of the method makes it relatively insensitive to patient motion; water suppression is high as all 90 degrees pulses are binomial pulses; and very narrow band rf pulses, such as used in high-field lactate-editing sequences, but which are necessarily very long at low fields, are not required. Further, this lactate editing scheme can be very easily combined with localized spectroscopic measurements.

Humans↗

Enzyme kinetics and relaxation measurements with surface coils.

A pulse sequence which produces the inversion of magnetization at a selected chemical shift for in vivo surface coil spectroscopy is proposed. The sequence uses a shaped, complex sech inversion pulse and "depth pulse" phase alternation. The sequence can be used for both in vivo inversion transfer and inversion recovery experiments.

Adenosine Triphosphate↗

Quantitative studies of magnetization transfer by selective excitation and T1 recovery.

Water proton longitudinal relaxation has been measured in agar and cross-linked bovine serum albumin (BSA) using modified selective excitation (Goldman-Shen and Edzes-Samulski) pulse sequences. The resulting recovery curves are fit to biexponentials. The fast recovery rate gives magnetization transfer (MT) information, which is complementary to that given by steady-state saturation methods. This rate provides an estimate of the strength of the coupling of the immobile proton pool to the mobile proton pool. Near their optimal pulse power values, the Goldman-Shen and Edzes-Samulski sequences give fast recovery rates that agree with each other. However, these measured fast recovery rates are dependent on the pulse power, an effect not predicted by the coupled two-pool model. For 8% agar and 17% BSA, both methods (at optimal pulse powers) give rates in the neighborhoods of 210 and 64 Hz, respectively. The Goldman-Shen and Edzes-Samulski pulse sequences have several advantages over those techniques based on steady state saturation: no long saturating pulses, shorter measurement time, and reduced necessity for making lineshape or fitting technique assumptions. The principle disadvantages are smaller effects on the NMR signal, less complete characterization of the MT system, and, in the case of the Goldman-Shen sequence, greater pulse power.

Magnetic Resonance Imaging↗

Magnetic resonance image synthesis from an interleaved saturation recovery/inversion recovery sequence.

An interleaved saturation recovery/inversion recovery (SR/IR) pulse sequence allows the sign of the IR signal to be retained even if images are formed from the magnitude of the two-dimensional complex Fourier transforms of the raw data. Synthesis of images by a linear combination of SR and signed IR pixel values has proved a valuable method of relaxation time (T1) contrast manipulation without the need to re-image the slice. Linear combination has also allowed IR images with a wide range of time-to-inversion (TI) values to be synthesized from an SR/IR pair obtained with TI = 200 ms and time-to-recovery (TR) = 1000 ms, thus avoiding the need for computationally intensive calculations based on complicated relaxation equations.

Computer Simulation↗

Real-time position monitoring of invasive devices using magnetic resonance.

Techniques which can be used to follow the position of invasive devices in real-time using magnetic resonance (MR) are described. Tracking of an invasive device is made possible by incorporating one or more small RF coils into the device. These coils detect MR signals from only those spins near the coil. Pulse sequences which employ nonselective RF pulses to excite all nuclear spins within the field-of-view are used. Readout magnetic field gradient pulses, typically applied along one of the primary axes of the imaging system, are then used to frequency encode the position of the receive coil(s). Data are Fourier transformed and one or more peaks located to determine the position of each receiver coil in the direction of the applied field gradient. Subsequent data collected on orthogonal axes permits the localization of the receiver coil in three dimensions. The process can be repeated rapidly and the position of each coil can be displayed in real-time.

Biopsy, Needle↗

Real-time rigid body motion correction and shimming using cloverleaf navigators.

Subject motion during scanning can greatly reduce MRI image quality and is a major reason for discarding data in both clinical and research scanning. The quality of the high-resolution structural data used for morphometric analysis is especially compromised by subject movement because high-resolution scans are of longer duration. A method is presented that measures and corrects rigid body motion and associated first-order shim changes in real time, using a pulse sequence with embedded cloverleaf navigators and a feedback control mechanism. The procedure requires a 12-s preliminary mapping scan. A single-path, 4.2-ms cloverleaf navigator is inserted every repetition time (TR) after the readout of a 3D fast low-angle shot (FLASH) sequence, requiring no additional RF pulses and minimally impacting scan duration. Every TR, a rigid body motion estimate is made and a correction is fed back to adjust the gradients and shim offsets. Images are corrected and reconstructed on the scanner computer for immediate access. Correction for between-scan motion can be accomplished by using the same reference map for each scan repetition. Human and phantom tests demonstrated a consistent improvement in image quality if motion occurred during the acquisition.

Algorithms↗

Detection of Anisotropic Pulsating Flow and Its Velocity-Fluctuation Rate in Fertilized Bird Eggs by NMR Microimaging

Coherent and incoherent flows in fertilized quail and bantam eggs have been studied with the aid of NMR microimaging techniques in the course of incubation until the end of the sixth day. The methods employed were multiplane tagging NMR imaging and a NMR gradient-echo imaging pulse sequence supplemented by bipolar gradient pulses in the coherence-evolution interval. The latter technique is suited for recording of velocity maps as well as for localizing of regions with enhanced echo attenuation by incoherent motions. Slight coherent displacements in the middle of the upper part of the egg white were found after the fourth day of incubation with the aid of both pulse schemes. The maximum velocity was estimated to be 1 mmsoliduss. More pronounced effects revealed themselves in the examination of incoherent motions. After the same time of incubation and in a somewhat more restricted area of the upper part of the egg white, distinct motions could be localized consistently with either technique. It is shown that these motions are directed to and from the yolk. Furthermore, the analysis of the time fluctuations of the local signals with the aid of a Fourier transformation showed that the flow is largely of a pulsating nature. The pulsation frequency was found to be 0.4 Hz.

Journal Article↗

Coherent excitation with phase-incremented pulses.

An outline is given for calculating the evolution of a spin system by a pulse sequence with phase-incremented pulses (PIPs). It is done in a frame with a speed of 2pideltaf=deltaphi/deltatau relative to the rotating frame, where deltaphi and deltatau are the phase- and time-increment of the PIP. This particular frame is defined as the eigenframe, in which the phase of the PIP for the center band is stationary and is subjected to a universal phase shift (UPS=-deltaphi/2), and the strength of the PIP is scaled by a factor of lambda=2[1-cos(deltaphi)]/(deltaphi). The phase differences between different eigenframes can be attributed to the initial phases of the PIPs, making it possible to use the Bloch vector model even in different eigenframes. A new way is provided to construct composite pulses with not only amplitude and phase modulations but also offset modulation. Several examples, including a broadband inversion pulse, a Hahn spin echo, and a selective inversion and null pulse, all composed of PIPs, are discussed in detail.

Magnetic Resonance Spectroscopy↗

Hyperpolarized 3He lung ventilation imaging with B1-inhomogeneity correction in a single breath-hold scan.

The signal-to-noise ratio (SNR) of hyperpolarized noble gas MR images is sensitive to the flip angle used. Variations in flip angle due to B1-inhomogeneity of the RF coil cause intensity variation artifacts in lung ventilation images which may mask or mimic disease. We show these artifacts can be minimized by using the optimal flip angle and corrected if the local flip angle is known. Hyperpolarized 3He lung images were obtained in ten healthy subjects using both a conventional gradient-echo sequence and a new hybrid pulse sequence designed to simultaneously acquire lung ventilation images and corresponding flip-angle maps in comparable imaging time. Flip-angle maps and corrected images were calculated from the hybrid scan and compared with conventional images. The qualitative theoretical dependence of flip angle on SNR was verified. Ventilation images and flip-angle maps were successfully obtained with the hybrid sequence. Corrections to image intensity calculated from the flip-angle maps appeared reasonable for images acquired using an average flip angle near optimal. Use of the optimal flip angle is crucial to the quality of lung ventilation images. Artifactual intensity variations due to RF-coil inhomogeneity may be identified and potentially corrected using our hybrid sequence.

Administration, Inhalation↗

Magnetic resonance imaging of trabecular and cortical bone in mice: comparison of high resolution in vivo and ex vivo MR images with corresponding histology.

Measurements of bone morphometry and remodeling have been shown to reflect bone strength and can be used to diagnose degenerative bone disease. In this study, in vivo and ex vivo magnetic resonance imaging (MRI) techniques to assess trabecular and cortical bone properties have been compared to each other and to histology as a novel means for the quantification of bone. Femurs of C57Bl/6 mice were examined both in vivo and ex vivo on an 11.7 T MRI scanner, followed by histologic processing and morphometry. A thresholding analysis technique was applied to the MRI images to generate contour lines and to delineate the boundaries between bone and marrow. Using MRI, an optimal correlation with histology was obtained with an in vivo longitudinal sectioned short echo time gradient-echo versus an in vivo long echo time spin-echo sequence or an ex vivo pulse sequence. Gradient-echo images were acquired with a maximum in-plane resolution of 35 microm. Our results demonstrated that in both the in vivo and ex vivo data sets, the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases moving from the epiphyseal growth plate to the diaphysis. These changes, observed with MRI, correlate with the histological data. Investigations using in vivo MRI gradient-echo sequences consistently gave the best correlation with histology. Our quantitative evaluation using both ex vivo and in vivo MRI was found to be an effective means to visualize non-invasively the normal variation in trabecular and cortical bone as compared to a histological "gold standard" The experiments validated in vivo MRI as a potential high resolution technique for investigating both soft tissue, such as marrow, and bone without radiation exposure.

Animals↗