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Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling.

We describe here experimental considerations in the implementation of quantitative perfusion imaging techniques for functional MRI using pulsed arterial spin labeling. Three tagging techniques: EPISTAR, PICORE, and FAIR are found to give very similar perfusion results despite large differences in static tissue contrast. Two major sources of systematic error in the perfusion measurement are identified: the transit delay from the tagging region to the imaging slice; and the inclusion of intravascular tagged signal. A modified technique called QUIPSS II is described that decreases sensitivity to these effects by explicitly controlling the time width of the tag bolus and imaging after the bolus is entirely deposited into the slice. With appropriate saturation pulses the pulse sequence can be arranged so as to allow for simultaneous collection of perfusion and BOLD data that can be cleanly separated. Such perfusion and BOLD signals reveal differences in spatial location and dynamics that may be useful both for functional brain mapping and for study of the BOLD contrast mechanism. The implementation of multislice perfusion imaging introduces additional complications, primarily in the elimination of signal from static tissue. In pulsed ASL, this appears to be related to the slice profile of the inversion tag pulse in the presence of relaxation, rather than magnetization transfer effects as in continuous arterial spin labeling, and can be alleviated with careful adjustment of inversion pulse parameters.

Arteries↗

Sequence-independent segmentation of magnetic resonance images.

We present a set of techniques for embedding the physics of the imaging process that generates a class of magnetic resonance images (MRIs) into a segmentation or registration algorithm. This results in substantial invariance to acquisition parameters, as the effect of these parameters on the contrast properties of various brain structures is explicitly modeled in the segmentation. In addition, the integration of image acquisition with tissue classification allows the derivation of sequences that are optimal for segmentation purposes. Another benefit of these procedures is the generation of probabilistic models of the intrinsic tissue parameters that cause MR contrast (e.g., T1, proton density, T2*), allowing access to these physiologically relevant parameters that may change with disease or demographic, resulting in nonmorphometric alterations in MR images that are otherwise difficult to detect. Finally, we also present a high band width multiecho FLASH pulse sequence that results in high signal-to-noise ratio with minimal image distortion due to B0 effects. This sequence has the added benefit of allowing the explicit estimation of T2* and of reducing test-retest intensity variability.

Algorithms↗

Simultaneous multislice acquisition with arterial-flow tagging (SMART) using echo planar imaging (EPI).

Arterial spin tagging techniques have been used to image tissue perfusion in MR without contrast injection or ionizing radiation. Currently, spin tagging studies are performed primarily using single-slice imaging sequences, which are time consuming. This note reports a multislice echo-planar arterial spin tagging technique (Simultaneous Multislice Acquisition with aRterial-flow Tagging, or "SMART"). Multiband RF encoding (Hadamard) is used to provide simultaneous multislice acquisition capability for spin tagging techniques (such as echo planar imaging signal targeting with alternating radio frequency and flow-sensitive alternative inversion recovery). The method is illustrated with a two-slice pulse sequence that was implemented using the FAIR technique to generate two perfusion weighted images simultaneously. Compared with single-slice sequences, this two-slice sequence provided similar image quality, signal-to-noise ratio, and twice the spatial coverage compared with the single-slice technique within the same scan time.

Blood Flow Velocity↗

Comparison of breath-hold multishot echo-planar and respiratory triggered fast-spin-echo sequences for T2-weighted MRI of liver lesions.

The purpose of this study was to evaluate the usefulness of multishot echo-planar imaging in detecting liver tumors in comparison with respiratory triggered T2-weighted fast-spin-echo (FSE) imaging. Thirty-two patients with 70 focal liver lesions were imaged using a 1.5-T high speed MR imager. Eight-shot echo-planar images covering the whole liver were acquired during a single breath-hold period. FSE images were acquired with respiratory triggering in approximately 4 minutes. Lesion detectability and image quality of the two pulse sequences were analyzed qualitatively. Quantitative analysis was performed by means of signal-to-noise and tumor-liver contrast-to-noise analysis. Lesion detectability was comparable in both solid (86.3% vs 90.2%: .3 < P < .5) and nonsolid lesions (89.5% vs 100%: .3 < P < .5) between echo-planar and FSE images. Echo-planar imaging provided significantly reduced image artifact, better lesion conspicuity, and anatomic detail compared with FSE imaging. The signal-to-noise and contrast-to-noise ratios of echo-planar images were significantly higher than those of FSE images. Breath-hold eight-shot echo-planar imaging can be an alternative to T2-weighted FSE imaging because it can provide comparable image quality in a substantially decreased acquisition time.

Adult↗

Hepatic T2-weighted MRI: a prospective comparison of sequences, including breath-hold, half-Fourier turbo spin echo (HASTE).

The purpose of this study was to quantitatively compare the hepatic contrast characteristics of conventional spin-echo (CSE) and fast spin-echo (FSE) sequences with breath-hold T2-weighted images acquired with half-Fourier turbo spin echo (HASTE). Forty-five patients were examined with a phased-array surface coil. Nineteen patients had focal hepatic lesions, including eight malignant tumors, 10 cavernous hemangiomas, and one hepatic adenoma. Twenty-six patients had no focal hepatic lesions. T2-weighted images with comparable TE were acquired with CSE, FSE, and HASTE pulse sequences. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for liver, spleen, and lesions were measured. FSE demonstrated significantly better quantitative performance than CSE for liver-spleen CNR (P .0084). No statistically significant difference was demonstrated between FSE and CSE for liver or spleen SNR. FSE demonstrated clear scan time and resolution advantages over CSE. HASTE performed significantly poorer than CSE and FSE for liver-spleen CNR (P < .0001), liver SNR (P = .0002 for CSE and P < .0001 for FSE), and spleen SNR (P < .0001). Optimized FSE images with a short echo train length performed comparably to CSE images of equivalent TE. Liver-lesion CNR was suppressed on HASTE images, suggesting that long echo train length FSE sequences could diminish solid lesion detection compared to CSE and short echo train length FSE.

Adenoma, Liver Cell↗

Nickel-doped agarose gel phantoms in MR imaging.

A method for the production of a tissue-mimicking phantom material for MR imaging is described. The material consists of a nickel-doped agarose gel. The T1 and T2 values of the gel can be varied independently by changing the relative amounts of nickel and agarose. Practically any T1 and T2 combination of clinical interest can be obtained. The long-term stability was studied and found to be good. The relaxation times were estimated using an MR analyzer. The accuracy and the reproducibility of these measurements were evaluated and found to be reassuring. Gel phantoms were also scanned in an MR unit. The signal strength of an inversion recovery sequence was evaluated using the gel phantoms in order to verify their usefulness. These measurements were compared to theory with good agreement. Furthermore, tissue-equivalent phantoms were made. Gels resembling gray matter, white matter, and CSF were scanned. Comparisons with clinical in vivo scans, as well as calculated levels were made. It is anticipated that the gel phantoms described here will be useful in quality assurance as well as in pulse sequence optimization.

Gels↗

A general scheme for suppression of ABX strong coupling signals in heteronuclear scalar and dipolar correlation experiments.

Enhanced versions of heteronuclear chemical shift correlation experiments which yield high-quality spectra with efficient suppression of extra peaks arising from strong coupling effects are proposed. The enhanced pulse sequences feature properly designed filtering schemes inserted during preparation, or prior to acquisition, or at both places depending on the particular experiment. These modifications extend the applicability of existing methods, since they exclude misinterpretation of spurious peaks and allow unambiguous assignment of the desired correlations. The general applicability of the filtering method is noteworthy; both scalar- and dipolar-correlated experiments with both X and 1H detection using phase cycling or gradient pulses for coherence selection can be freed of strong coupling artifacts.

Artifacts↗

Vascular interventions guided by ultrafast MR imaging: evaluation of different materials.

The ability of MRI to acquire not only anatomical but also functional information makes MRI guided vascular interventions an interesting goal. Recent developments in ultrafast MR imaging sequences such as fast gradient echo or echo planar (EPI) mean that not only real time MRI but also MRI guided vascular interventions are real possibilities for the not too distant future. However, currently available guide wires and catheters are potentially unusable in MRI because they are either ferromagnetic or MRI invisible. In order to find different materials suitable for real time MRI, various devices were examined with fast gradient echo and interleaved EPI pulse sequences. The measurements were performed using a continuously running, pseudo real time MRI system to investigate the dynamic imaging behavior under guide wire insertion. Suggestions are made as how to construct guide wires and catheters, which can be visualized with ultrafast imaging sequences, while not causing prohibitive artifacts or image distortions.

Alloys↗

Novel methods for characterizing a decoupler channel using "undetectable" quantum coherences.

Exact solutions for the effect of time-independent RF pulses on any initial configuration of an IS J-coupled system demonstrate that on-resonance CW decoupling yields signals whose frequency depends on RF field strength and homogeneity. These signals are enhanced starting with "undetectable" antiphase and multiple quantum coherences, which can also produce centerband intensity to mimic the signal from decoupled Sx. Conversely, these coherences can be generated from Sx using a low-power pulse, B1 = J/2, of length (2J)-1, dubbed a "90J pulse" since it is the selective equivalent of {(2J)-1-90[I]}. Utilizing 90J pulses, new characterization-of-decoupler (COD) pulse sequences can determine the performance of an insensitive I-spin channel by observing large signals from either antiphase or multiple quantum coherences with the S-spin channel, allowing, in minutes rather than hours: (i) frequency calibration to an accuracy of 0.1 Hz; (ii) measurement of RF amplitudes over a 500-fold variation; and (iii) mapping of RF homogeneity along the sample axis with a single 1D B1 spectrum. These 90J coherence transfer pulses are of potential general use for selective spectroscopy.

Magnetic Resonance Spectroscopy↗

Extended flip-back schemes for sensitivity enhancement in multidimensional HSQC-type out-and-back experiments.

In many NMR experiments, only polarisation of a limited sub-set of all protons is converted into observable coherence. As recently shown by the "longitudinal" TROSY implementation (Pervushin et al. (2002) J. Am. Chem. Soc., 124, 12898-12902) and SOFAST-HMQC (Schanda and Brutscher (2005) J. Am. Chem. Soc., 127, 8014-8015), recovery of unused polarisation can be used indirectly and unspecifically to cool the proton lattice and, thus, accelerate re-equilibration for the selected proton subset. Here we illustrate transfer of this principle to HSQC-based multi-dimensional out-and-back experiments that exploit only polarisation of 15N-bound protons. The presented modifications to the pulse sequences can be implemented broadly and easily, extending standard flip-back of water polarisation to a much larger pool of protons that may comprise all non-15N-bound protons. The underlying orthogonal separation of H(N) polarisation (selected by the main transfer path) from unused H(u) polarisation (flipped-back on the recovery path) is thereby achieved through positive or negative selection by J-coupling, or using band-selective pulses. In practice, H(u) polarisation recovery degrades mostly through cumulative pulse imperfections and transverse relaxation; we present, however, strategies to substantially minimise such losses particularly during interim proton decoupling. Depending on the protein's relaxation properties and the extended flip-back scheme employed, we recovered up to 60% H(u) equilibrium polarisation. The concomitant cooling of the proton lattice afforded substantial gains of more than 40%, relative to the water-only flip-back version, in the fast pulsing regime with re-equilibration delays tau much shorter than optimal (tau(opt) = 1.25 x T1(H(N))). These would be typically employed if resolution requirements dominate the total measurement time. Contrarily, if sensitivity is limiting and optimal interscan delays tau(opt) can be set (optimal pulsing regime), the best of the presented flip-back schemes may still afford up to ca. 10% absolute sensitivity enhancement.

Magnetic Resonance Spectroscopy↗

Comparison of various techniques of iron oxide-enhanced breath-hold MR imaging of hepatocellular carcinoma.

The purpose of our study is to compare qualitatively and quantitatively the abilities of various superparamagnetic iron oxide (SPIO)-enhanced breath-hold magnetic resonance imaging (MRI) techniques to detect hepatocellular carcinoma (HCC). Eight patients with HCCs were imaged. The images were obtained with conventional T2-weighted spin-echo imaging (CSE), half-Fourier single-shot turbo spin-echo (HASTE), single-shot gradient-echo type echo planar imaging (GE-EPI), and single-shot spin-echo type echo planar imaging (SE-EPI) before and after SPIO administration. The liver signal-to-noise ratios (SNRs) in CSE and each EPI sequence were significantly decreased after SPIO administration. GE-EPI had the highest decrease ratio (DR) of liver SNR, followed by SE-EPI (TE=98), SE-EPI (TE=28), CSE, and HASTE in this order. The relative contrasts with GE-EPI and SE-EPI (TE=98) were significantly higher than that with CSE after SPIO administration. On receiver operating characteristic (ROC) analysis, diagnostic accuracy did not differ significantly among the pulse sequences after SPIO administration. GE-EPI and SE-EPI (longer TE) were useful for SPIO-enhanced breath-hold MRI performed to detect HCC.

Adult↗

Specification and visualization of anisotropic interaction tensors in polypeptides and numerical simulations in biological solid-state NMR.

Software facilitating numerical simulation of solid-state NMR experiments on polypeptides is presented. The Tcl-controlled SIMMOL program reads in atomic coordinates in the PDB format from which it generates typical or user-defined parameters for the chemical shift, J coupling, quadrupolar coupling, and dipolar coupling tensors. The output is a spin system file for numerical simulations, e.g., using SIMPSON (Bak, Rasmussen, and Nielsen, J. Magn. Reson. 147, 296 (2000)), as well as a 3D visualization of the molecular structure, or selected parts of this, with user-controlled representation of relevant tensors, bonds, atoms, peptide planes, and coordinate systems. The combination of SIMPSON and SIMMOL allows straightforward simulation of the response of advanced solid-state NMR experiments on typical nuclear spin interactions present in polypeptides. Thus, SIMMOL may be considered a "sample changer" to the SIMPSON "computer spectrometer" and proves to be very useful for the design and optimization of pulse sequences for application on uniformly or extensively isotope-labeled peptides where multiple-spin interactions need to be considered. These aspects are demonstrated by optimization and simulation of novel DCP and C7 based 2D N(CO)CA, N(CA)CB, and N(CA)CX MAS correlation experiments for multiple-spin clusters in ubiquitin and by simulation of PISA wheels from PISEMA spectra of uniaxially oriented bacteriorhodopsin and rhodopsin under conditions of finite RF pulses and multiple spin interactions.

Anisotropy↗

Coherence selection and excitation sculpting using RF-gradients in selective 1D experiments and nonselective 2D experiments

The B0 gradient pulses can be replaced with long high-power pulses (RF-gradients) in z-rotation composite sandwiches. By doing this, practically all B0 gradient-based pulse sequences can be performed with instruments lacking a field gradient accessory. We have implemented RF-gradients into selective 1D and nonselective 2D TOCSY and NOESY experiments. The spectral quality obtained with the RF-gradient method was comparable to that of the B0 method for small- to medium-sized molecules. There are also some advantages in using RF-gradients instead of B0 gradients. There is practically no shift or coupling evolution during RF-gradient pulses. This may be significant in some experiments. Copyright 1998 Academic Press.

Journal Article↗

High density barium sulfate suspension for MRI: optimization of concentration for bowel opacification.

In this in vitro study of a potential oral MRI contrast agent, barium sulfate suspension (BSS), the object was to examine the effect of varying barium sulfate concentration on signal intensity while keeping suspension additives the same; and to optimize the concentration of a specific preparation of BSS. A phantom was used to test suspensions with concentrations of barium sulfate ranging from 90% to 220% w/v. T1-weighted, T2-weighted, and gradient echo sequences all showed a decrease in signal as concentration was increased to 170%. Between 170% and 220%, the signal intensity was constant on the T1-weighted and T2-weighted sequences. With the proton density and gradient echo sequences, there was a slower rate of decline in the signal intensity in the 170 to 220% range of BSS concentrations. We conclude that BSS with a concentration in the range of 170% to 220% w/v is optimum for the specific preparation used. We speculate that the behavior of the signal-to-noise ratio with changing concentration is explained by factors including proton density, T1 relaxation enhancement, diffusion effects, and magnetic field inhomogeneity, depending on the particular pulse sequence used.

Administration, Oral↗

Method for image-based measurement of the reversible and irreversible contribution to the transverse-relaxation rate.

A multislice NMR imaging pulse sequence capable of measuring both the reversible and irreversible contribution to the transverse-relaxation rate (R'2 and R2) in a single scan is described. The method, termed GESFIDE (gradient-echo sampling of FID and echo) is based on sampling the descending and ascending portions of a Hahn echo with a train of gradient echoes. R2 and R'2 are computed by exploiting the differential evolution of the transverse magnetization before and after the phase-reversal pulse. Salient features of the method are its insensitivity to RF pulse imperfections and its high precision and efficiency. Applications examined involve the characterization of magnetically inhomogeneous tissues and biomaterials such as trabecular bone marrow in the skeleton and brain iron.

Bone Marrow↗

Improved 3D gd-HCACO and gd-(H)CACO-TOCSY experiments for isotopically enriched proteins dissolved in H2O.

Pulsed field gradients were incorporated into the HCACO experiment for acquiring spectra on isotopically enriched protein samples dissolved in H2O. Excellent water suppression and spectral quality were achieved using the modified pulse sequence (gd-HCACO), as demonstrated for a 13C-/15N-labeled sample of the SH2 domain from the hematopoietic cellular kinase dissolved in 90% H2O/10% D2O. Strong correlations for all residues were observed in the gd-HCACO spectrum, even for residues having alpha-protons resonating exactly at the H2O frequency. The HCACO-TOCSY experiment was modified to correlate intraresidue 13C alpha (rather than 1H alpha), carbonyl (13C'), and aliphatic side-chain protons [(H)CACO-TOCSY]. Pulsed field gradients were also incorporated into the (H)CACO-TOCSY experiment for water suppression.

Magnetic Resonance Spectroscopy↗

Isosignal contours and signal gradients as an aid to choosing MR imaging techniques.

The signal strength of a magnetic resonance (MR) image depends on a variety of factors, including the tissue properties of proton density (p) and relaxation times (T1 and T2) and the scanning sequence. Given this complex interrelation of factors, a graphic method of displaying the image intensity for various tissue properties is needed. In this paper we use isosignal contour curves to display "topographically" the relationships of signal intensity to the tissue properties of p, T1, and T2 for a variety of operator settings in the techniques of saturation recovery, inversion recovery, and spin echo. We further demonstrate the utility of these curves in explaining image appearances and in choosing appropriate pulse sequences for imaging.

Brain Stem↗

[A comparative study between Gd-BOPTA, a biliary excretion contrast medium, and Gd-DTPA in the magnetic resonance imaging of the rat liver].

A new lipophilic compound, Gd-BOPTA, presenting a high rate (38.6%) of biliary excretion was tested as an hepato-specific MR contrast agent. Its adequacy was compared to that of Gd-DTPA in laboratory animals. T1-weighted spin-echo sequences (TR 220 ms, TE 20 ms) both before and after the administration of the 2 contrast agents (doses: 0.25, 0.5, and 1.0 mmol/kg) showed better liver enhancement with Gd-BOPTA than with Gd-DTPA. Gd-BOPTA superiority was more evident at lower doses, while at 1.0 mmol/kg a comparable enhancement was achieved. Inversion recovery sequence at the T-null of liver parenchyma before contrast (TR 800 ms, TE 30 ms, TI 100 ms) was performed after the injection of 0.1 and 0.5 mmol/kg of Gd-DTPA and Gd-BOPTA. This sequence allowed the good and long-lasting liver enhancement achieved with Gd-BOPTA to be even better demonstrated, while Gd-DTPA provided only a slight and early enhancement with 0.1 mmol/kg and returned to baseline values 60' after the injection of the highest dose (0.5 mmol/kg). Gd-BOPTA proved to be a good contrast agent to obtain prolonged liver enhancement, thus providing the radiologist with the long time needed to acquire conventional T1-weighted pulse sequences.

Acetates↗