Signal enhancement in CRAZED experiments

Many of the promising applications of the CRAZED (COSY Revamped with Asymmetric Z-gradient Echo Detection) experiments are in biomedical and clinical technologies. In tissue, however, signal from the typical CRAZED experiment is largely limited by transverse relaxation. When relaxation is included, the maximum achievable signal from a prototypical CRAZED sequence, in the linear regime, is proportional to T(2)/tau(d). This means that for samples with a short T(2), as encountered in vivo, signals from intermolecular multiple-quantum coherences (iMQCs) reach very diminished signal intensities. While relaxation is generally regarded as a fundamental constraint, we show here that when T(2) is short but T(1) is long, as in tissue, there are simple sequence modifications that can increase signal beyond the T(2) limit. To better utilize the available signal intensity from iMQCs we propose a method to substitute part of the transverse magnetization with the longitudinally modulated magnetization. In this paper we show, with both simulations and experimental results, that in the presence of strong transverse relaxation the standard CRAZED scheme is not the optimal method for observing iMQCs, and can be improved upon with simple modifications.     

Intermolecular double-quantum coherence imaging without coherence selection gradients and its application in in vivo MRI

In the COSY Revamped with Asymmetric Z-gradient Echo Detection (CRAZED) experiments, magnetization is modulated by the distant dipolar field (DDF) generated by coherence selection gradient (CSG) commonly in sinusoidal wave-form and results in detectable intermolecular multiple-quantum coherence (iMQC) signal. IMQCs have some attractive features, but their intrinsic weak signal intensity prevents their widespread applications. In this paper, a new phase cycling scheme was applied to obtain intermolecular double-quantum coherence (iDQC) signal. It is found that DDF can arise from nonspherical sample geometry or background inhomogeneous field in the absence of CSGs, which is more efficient than that created from CSGs. The experimental results show that the resulting DDF can refocus the ± iDQC signals simultaneously and thus enhance the signal intensity to about two folds of that from the conventional CRAZED sequence. Theoretical prediction and experiments give coincident results.     

Numerical studies of intermolecular multiple quantum coherences: high-resolution NMR in inhomogeneous fields and contrast enhancement in MRI

A fast, efficient numerical algorithm is used to study intermolecular zero-quantum coherences (iZQCs) and double-quantum coherences (iDQCs) in two applications where the three-dimensional structure of the magnetization is important: high-resolution NMR in inhomogeneous fields and contrast enhancement in MRI. Simulations with up to 2 million coupled volume elements (256 x 256 x 32) show that iZQCs can significantly narrow linewidths in the indirectly detected dimension of systems with inhomogeneous fields and explore the effects of shape and orientation of the inhomogeneities. In addition, this study shows that MR images from iZQC and iDQC CRAZED pulse sequences contain fundamentally new contrast, and a modified CRAZED pulse sequence (modCRAZED) can isolate the contrast from chemically inequivalent spins.     

Diffraction-like phenomena in a periodic magnetization distribution at 1.5 T using the distant dipolar field (DDF)

In the CRAZED experiment (COSY revamped by asymmetric Z-gradient echo detection, Warren et al.), a spatially anisotropic magnetization distribution is created by application of a magnetic field gradient (strength G, duration tau) which in turn generates a response called the distant dipolar field (DDF). The DDF is a source of intermolecular multiple-quantum coherences (iMQC) which contain information on the distance d=pi/(gammaGtau) between pairs of dipolar-coupled spins. Diffraction-like phenomena may result for periodically structured samples. In this study, we report the observation of diffraction owing to the DDF at 1.5 T using a clinical whole-body tomograph. Based on the semi-classical treatment of the problem by Robyr and Bowtell, diffraction conditions were obtained for a CRAZED-type pulse sequence that selects iMQC of order N. The predicted distinct difference in N=2 and N not equal2 coherences, i.e., a dominant continuous course as a function of tau (N=2) and prominent diffraction peaks otherwise, could be verified in CRAZED experiments in a periodically structured sample selecting coherence orders N=2 and N=3. The diffractive signal component contains information on the geometric structure of the sample. Applications of this technique may permit the detection of changes in composition and geometry of periodic structures.     

Theoretical studies of the effect of the dipolar field in multiple spin-echo sequences with refocusing pulses of finite duration

It has been observed recently that the finite duration of refocusing rf pulses in a multiecho acquisition of the signal formed under the influence of the dipolar field leads to significant signal attenuation [S. Kennedy, Z. Chen, C.K. Wong, E.W.-C. Kwok, J. Zhong, Investigation of multiple-echo spin-echo signal acquisition under distant dipole-dipole interactions, Proc. Int. Soc. Magn. Reson. Med. 13 (2005) 2288]. Hereto, we quantify the phenomenon by evaluating analytically the influences of both the distant dipolar field (DDF) and transverse relaxation T2 on the magnetization in a multiecho pulse sequence based on correlation spectroscopy revamped by asymmetric z-gradient echo detection (CRAZED). Analytic expressions for the magnetization were obtained, which demonstrate explicitly the origin of rephased signal in the presence of the finite pi pulses in the multiecho train. The expressions also explain the effects of the DDF and T2 during the refocusing pulses on the signal strength, and show the substantial signal dependence on the phase of the rf pulses. We show that when the DDF effect during the pulse is canceled, the signal rises primarily during the free evolution time in the acquisition period. This elucidates the signal attenuation when the rf pulses cover a significant proportion of time in the sequence. In addition, we performed an optimization on the number of refocusing pulses that maximizes the total acquired signal using parameters for water, brain white matter, and muscle. We found that maximal signal-to-noise ratio is obtained when the pulse duration approximately equals the free evolution time in the samples with a wide range of T2.     

Observation of intermolecular double-quantum coherence signal dips in nuclear magnetic resonance

The correlated spectroscopy revamped by asymmetric Z-gradient echo detection (CRAZED) sequence is modified to investigate intermolecular double-quantum coherence nuclear magnetic resonance signal dips in highly polarized spin systems. It is found that the occurrence of intermolecular double-quantum coherence signal dips is related to sample geometry, field inhomogeneity and dipolar correlation distance. If the field inhomogeneity is refocused, the signal dip occurs at a fixed position whenever the dipolar correlation distance approaches the sample dimension. However, the position is shifted when the field inhomogeneity exists. Experiments and simulations are performed to validate our theoretic analysis. These signal features may offer a unique way to investigate porous structures and may find applications in biomedicine and material science.     

Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.     

Sensitivity to local dipole fields in the CRAZED experiment: an approach to bright spot MRI

Local dipole fields such as those created by small iron-oxide particles are used to produce regions of low intensity (dark contrast) in many molecular magnetic resonance imaging applications. We have investigated, with computer simulations and experiments at 17.6 T, how the COSY revamped with asymmetric z-gradient echo detection (CRAZED) experiment that selects intermolecular double-quantum coherences can also be used to visualize such local dipole fields. Application of the coherence-selection gradient pulses parallel to the main magnetic field produced similar, dark contrast as conventional gradient echo imaging. Application of the gradient along the magic angle leads to total loss of signal intensity in homogeneous samples. In the presence of local dipole fields, the contrast was inverted and bright signals from the dipoles were observed over a very low background. Both simulations and experiments showed that the signal strongly decreased when a phase-cycle suppressing single-quantum coherences was employed. Therefore, we conclude that most of the signal comes from directly refocused magnetization or intermolecular single-quantum coherences. Finally, we demonstrate that bright contrast from local dipole fields can also be obtained, when the pair of coherence-selection gradient pulses is deliberately mismatched. Both methods allowed visualization of local dipole fields in phantoms in experimental times of about 3 min.     

Hepatic alveolar echinococcosis: MRI findings

The purpose of this study was to describe the magnetic resonance imaging (MRI) appearance of hepatic alveolar echinococcosis (HAE) on T(1)-weighted, T(2)-weighted and postgadolinium images. A total of 13 lesions were demonstrated in 13 patients. All patients underwent MR examination at 1 T imager. MR examinations included precontrast T(1)-weighted breathing averaged spin echo (SE), breath-hold spoiled gradient echo, T(2)-weighted TSE sequences with and without fat suppression, and T(1)-weighted breath-hold spoiled gradient echo (SGE) sequence following i.v. after gadolinium administration. All lesions were confirmed with histopathology. HAE hepatic lesions revealed geographic patterns of variable signal intensities on noncontrast T(1)- and T(2)-weighted images. Slightly hyperintense, iso- and hypointense signal on T(1)-weighted images corresponded to calcified regions, which appeared hypo-isointense signal on T(2)-weighted images. Necrotic areas were hypointense signal on T(1)-weighted and hyperintense signal on T(2)-weighted images. On postgadolinium images, lesions did not reveal enhancement. Dilatation of intrahepatic bile ducts distal to HAE abscesses were observed in five patients and portal vein invasion or compression was observed in four patients, lobar atrophy of the liver was coexistent finding in cases with portal vein compression. The MRI appearance of HAE abscesses included large irregularly marginated masses with heterogenous signal on T(1)- and T(2)-weighted images and lack of enhancement with gadolinium.     

Giant hemangioma of the liver: MR imaging characteristics in 24 patients

We retrospectively reviewed the magnetic resonance imaging (MRI) of giant hemangiomas in 24 patients. MRI studies comprised T1-weighted, T2-weighted and serial gadolinium-enhanced spoiled gradient echo (SGE) images. Morphologic features, signal characteristics and enhancement patterns were assessed. Histopathologic evaluation was obtained in nine patients. On T2-weighted images all lesions (size 5.7-24 cm) were hyperintense relative to the spleen and two dominant patterns of heterogeneity were demonstrated: a central heterogeneous area of either bright, dark, or mixed signal intensity, and a network of multiple fibrous septa of low signal intensity. Histopathologic evaluation of two lesions with a central bright area demonstrated the presence of hypocellular myxoid tissue. Central enhancement (9 lesions) and an irregular flame-shaped peripheral pattern of enhancement (12 lesions) were present in lesions with a mean diameter greater than 10 cm. Although giant hemangiomas show greater variability in their MR imaging appearance, an accurate diagnosis can be made through still characteristic features of high signal intensity on T2-weighted images and discontinuous peripheral enhancement.     

Enhanced signal intensities obtained by out-of-phase rapid-passage EPR for samples with long electron spin relaxation times

To understand the signals that are observed under rapid-passage conditions for samples with long electron spin relaxation times, the E' defect in irradiated vitreous SiO(2) was studied. For these samples at room temperature, T(1) is 200 mciro s and T(2) ranged from 35 to 200 micro s, depending on spin concentration. At X band with 100-kHz modulation frequency and 1-G modulation amplitude there was minimal lineshape difference between the low-power, in-phase spectra and high-power spectra detected 90 degrees out-of-phase with respect to the magnetic field modulation. Signal enhancement, defined as the ratio of the intensities of the out-of-phase to the in-phase signals when B(1) for both observation modes is adjusted to give maximum signal, was 3.4 to 9.5 at room temperature. The origin of the out-of-phase signal was modeled by numerical integration of the Bloch equations including magnetic field modulation. The waveforms for the E' signal, prior to phase sensitive detection, were simulated by summing the contributions of many individual spin packets. Good agreement was obtained between experimental and calculated waveforms. At low B(1) the experimental values of T(1) and T(2) were used in the simulations. However, at higher B(1), T(2) was adjusted to match the experimental signal intensity and increased with increasing B(1). At high B(1), T(2)=T(1), consistent with Redfield's and Hyde's models. For the spin concentrations examined, the out-of-phase signals at very high power (B(1) approximately 0.33 G) displayed a linear relationship between peak-to-peak signal amplitude and spin concentration. Under the conditions used for spin quantitation the signal-to-noise for these spectra was up to 5 times higher than for the in-phase signal, which greatly facilitates quantitation for these types of samples. For samples in which T(2) is dominated by electron spin-spin interaction, lower spin concentration results in longer T(2) and the enhancement is increased.     

High-frequency dynamic nuclear polarization in the nuclear rotating frame

A proton dynamic nuclear polarization (DNP) NMR signal enhancement (epsilon) close to thermal equilibrium, epsilon = 0.89, has been obtained at high field (B(0) = 5 T, nu(epr) = 139.5 GHz) using 15 mM trityl radical in a 40:60 water/glycerol frozen solution at 11 K. The electron-nuclear polarization transfer is performed in the nuclear rotating frame with microwave irradiation during a nuclear spin-lock pulse. The growth of the signal enhancement is governed by the rotating frame nuclear spin-lattice relaxation time (T(1rho)), which is four orders of magnitude shorter than the nuclear spin-lattice relaxation time (T(1n)). Due to the rapid polarization transfer in the nuclear rotating frame the experiment can be recycled at a rate of 1/T(1rho) and is not limited by the much slower lab frame nuclear spin-lattice relaxation rate (1/T(1n)). The increased repetition rate allowed in the nuclear rotating frame provides an effective enhancement per unit time(1/2) of epsilon(t) = 197. The nuclear rotating frame-DNP experiment does not require high microwave power; significant signal enhancements were obtained with a low-power (20 mW) Gunn diode microwave source and no microwave resonant structure. The symmetric trityl radical used as the polarization source is water-soluble and has a narrow EPR linewidth of 10 G at 139.5 GHz making it an ideal polarization source for high-field DNP/NMR studies of biological systems.     

MR imaging findings of infectious cholangitis

The purpose of this study was to evaluate the appearance of infectious cholangitis on MRI. The MR images of 13 patients (9 women, 4 men; age range, 14-79 years) with clinically confirmed infectious cholangitis, who represent our complete 9.5 year experience with this entity, were retrospectively evaluated. All MR studies were performed at 1.5 T and included: in-phase and out-of-phase T(1)-weighted spoiled gradient echo (SGE), T(2)-weighted fat-suppressed echo train spin echo, single shot T(2)-weighted sequences, and serial postgadolinium T(1)-weighted SGE sequences without and with fat-suppression. The biliary ductal system was evaluated regarding presence of dilatation, stenosis, wall irregularities, wall thickening, and gadolinium enhancement of duct walls. The liver parenchyma was evaluated regarding focal signal abnormalities on precontrast and serial postgadolinium images. Biliary ductal dilatation was observed in 100% of patients. Mild to moderate thickening of bile duct walls combined with increased enhancement on postgadolinium images was observed in 92% of patients. The liver parenchyma showed periportal or wedge-shaped areas of hyperintense signal on T(2)-weighted images in 69% of patients. On T(1)-weighted images, 54% of patients showed areas of hypointense signal and 15% of patients showed wedge-shaped hyperintense areas. Areas with increased enhancement on immediate postgadolinium SGE were observed in 58% of patients, and in 42% of patients increased enhancement persisted on 2 min postgadolinium fat-suppressed images. Distinctive MRI findings on pre- and postgadolinium images are appreciated for infectious cholangitis.     

Implementation of a rapid inversion-prepared dual-contrast gradient echo sequence for quantitative dynamic contrast-enhanced magnetic resonance imaging of the human prostate

The first step in quantitative pharmacokinetic modeling is to determine the arterial input function (AIF) by deriving the contrast medium (CM) concentration from an appropriate imaging sequence by monitoring changes in either the amplitude or the phase signal of an accommodative artery. The bolus passage is best detected on T2- or T2*-weighted images, while extravasation is best assessed on T1-weighted images. Here, an imaging sequence is used that employs a parallel acquisition technique for the interleaved acquisition of an inversion-prepared T1-weighted image and a T1/T2*-mixed-weighted image for determination of the AIF.

The sequence was applied in six patients with prostate cancer. A method is presented for quantifying the AIF derived from the signal intensity-time courses of both the T1/T2*-mixed-weighted and the T1-weighted image. Furthermore, in some patients the signal intensity-time course of the T1-weighted image exhibits flow-induced signal modulations. To reduce the effect of this flow-related signal enhancement the corresponding phase information was used.

The sequence presented here has the potential to improve the quantification of the AIF at all time points and pharmacokinetic modeling of the CM dynamics of the prostate.     

The effect of Gd-DTPA on T(1)-weighted choline signal in human brain tumours

The influence of Gd-DTPA on T(1)-weighted (T(1)W) proton MR spectra has been investigated in 19 patients with histologically verified low (n = 13) or high-grade (n = 6) gliomas. Repeat measurements were performed on 9 patients (7 low-grade and 2 high-grade), with 28 examinations performed in total. Comparison of spectra obtained before and after 0.2 mmol/kg Gd-DTPA showed contrast agent induced broadening of the choline signal without significant signal area change. Lack of enhancement of the choline signal with the T(1)-weighted acquisitions implies that the contrast agent and the trimethylamine-containing species do not undergo significant direct interaction. Contrast agent induced changes in the choline signal observed in this and previous studies may, therefore, be attributable to T2*/susceptibility-based effects.     

MRI characterization of residual mediastinal masses in Hodgkin's disease: long-term follow-up

Our purpose was to evaluate the role of MRI in distinguishing fibrous from active residual masses in treated Hodgkin's disease. Forty patients with residual mediastinal mass larger than 1.5 cm underwent MRI 1, 3, 6, and 12 months after the end of cycles of prescribed chemotherapy or combined chemoradiotherapy. The MRI examinations were performed on a 0.5 and a 1.5 T systems, using T(1) before and after gadolinium injection and T(2)-weighted sequences. Each time the residual mass was evaluated in size and signal intensity on spin echo (SE) T(2)-weighted images and on SE T(1)-weighted images after contrast medium. Low signal intensity and low contrast enhancement were considered signs of inactive residues; homogeneous high signal intensity and high contrast enhancement were indicative of active residual disease; heterogeneous signal intensity and heterogeneous contrast enhancement were indicative of partial remission or necrotic/inflammatory phenomena. MR showed high diagnostic accuracy in the evaluation of Hodgkin's mediastinal residues after treatment, if performed at least 6 months after the end of therapy, reaching the highest sensitivity and specificity values at 12 month follow-up (considering the three parameters-T(2) signal intensity, contrast-enhancement, and size-all together). If we consider the single parameters individually, we can observe that size variation remains the more valuable parameter to predict or to exclude a relapse. MR diagnostic accuracy at the 6-month follow-up was lower due to the higher incidence of inhomogeneous pattern. The accuracy of MR performed at 1 and at 3 months after the end of therapy was not satisfying. This represents a clinical problem because the most important clinical decisions have to be taken just in this early post-treatment phase.     

Granulomatous hepatitis: MRI findings.

The purpose of this study was to describe the magnetic resonance imaging findings of granulomatous hepatitis on T1-weighted, T2-weighted and postgadolinium images. Eight patients with histopathological diagnosis of granulomatous hepatitis were evaluated in this study. MRI examinations included precontrast T1-weighted breath-hold spoiled gradient echo, breathing independent STIR sequences, and T1-weighted breath-hold spoiled gradient-echo sequence following after i.v. gadolinium administration in arterial, intermediate and late phases. Diffuse nodular liver involvement was visualized in all patients. Nodules were consistent with granulomas and were 0.5-4.5 cm in diameter. Caseating granulomas were intermediate and high signal on T2-weighted, low signal on T1-weighted images. They revealed no enhancement in two patients, and enhanced in one patient. Noncaseating granulomas revealed intermediate signal on T1, and T2-weighted images and increased enhancement on arterial phase images with persisting enhancement in late phase images. Portal lymph nodes were visible in five patients. Splenomegaly was present in five patients. Granulomatous hepatitis has spectrum of MRI features, to be considered in differential diagnosis with other diffuse nodular liver pathologies.     

Small hyperintense hepatic lesions on T1-weighted images in patients with cirrhosis: evaluation with serial MRI and imaging features for clinical benignity

PURPOSE: The aim of this study was to evaluate the frequency and magnetic resonance imaging (MRI) features of clinically benign, small (<2 cm) hyperintense hepatic lesions in the cirrhotic liver on T1-weighted MR images seen at serial MRI. MATERIALS AND METHODS: This study included 189 patients with cirrhosis, who underwent hepatic MRI more than twice with an interval of at least 12 months. The initial MR images were reviewed for the presence of small hyperintense lesions on T1-weighted images. The size, location and signal intensity on T2-weighted images as well as enhancement patterns of the corresponding lesions were recorded. RESULTS: On the initial T1-weighted MR images, 43 small hyperintense hepatic lesions were detected in 23 (12%) of 189 patients. Twelve (28%) of 43 lesions showed early enhancement and were pathologically diagnosed as hepatocellular carcinoma (HCC) during the follow-up period. Thirty-one (72%) of 43 lesions showed no early enhancement with various signal intensity on T2-weighted images (hyperintensity=4, isointensity=20, hypointensity=7). Among these 31 lesions, 12 showed no interval change, while 11 disappeared (n=10) or decreased in size (n=1). In the remaining eight lesions, seven were diagnosed as HCC on the basis of pathologic confirmation or the interval growth. CONCLUSION: Small hyperintense hepatic lesions on T1-weighted magnetic resonance (MR) images without early enhancement on the arterial-phase contrast-enhanced dynamic studies in patients with cirrhosis usually showed no interval growth or disappeared during the serial MRI. These lesions with additional findings of iso- or hypointensity on the T2-weighted MR images without "washout effect" on the contrast-enhanced equilibrium-phase images may more frequently be clinically benign or hyperplastic nodules than HCCs.     

Ultrafast dynamics of electron thermalization in gold

Time-resolved surface second-harmonic generation (SHG) is used to probe electron relaxation processes in gold following intense laser excitation at 1.55 eV. For the first time, an electron temperature ( T(e)) dependent enhancement in the SHG signal is clearly observed at T(e) above 0.7 eV, which is shown to relate to the thermalization of nonequilibrium hot electrons. Therefore, the relaxation dynamics of the transient nonequilibrium electrons in the high T(e) regime is directly resolved by monitoring the time evolution of the SHG signal.     

Initial clinical evaluation of gadolinium DTPA for contrast-enhanced magnetic resonance imaging

Gadolinium DTPA was evaluated as an intravenous contrast agent for magnetic resonance imaging in 15 patients with primary or secondary intracranial neoplastic disease. T1 and T2 weighted images were obtained prior to contrast administration. T1 weighted spin echo 35/800 (TE/TR) images were utilized to detect enhancement. The increase in signal intensity observed, identifying areas of breakdown of the blood-brain barrier (BBB), was similar in magnitude to the contrast enhancement observed on CT. This permitted differentiation of neoplastic tissue from surrounding cerebral edema on MRI. Direct visualization of otherwise "isomagnetic" lesions was also demonstrated. The use of intravenous contrast media should significantly extend the diagnostic potential and specificity of magnetic resonance imaging.