Simultaneous acquisition of multiple orders of intermolecular multiple-quantum coherence images

Recent studies have demonstrated the ability to detect images based on intermolecular multiple-quantum coherences (iMQCs) that correspond to flipping of two or more separated spins simultaneously, as opposed to conventional magnetic resonance where only one spin is flipped at a time. Until now, iMQC imaging has only acquired one coherence signal per pulse sequence. Here we report a new sequence that successfully detects five orders of coherence (2, 1, 0, −1, and −2-quantum coherence images) in one pulse sequence, with each signal having its full intensity. The simultaneous acquisition highlights substantial contrast differences between conventional and iMQC images, and between the different types of iMQC images.     

Isolating quantum coherences in structural imaging using intermolecular double-quantum coherence MRI

Intermolecular multiple-quantum coherence (iMQC) MR imaging provides a fundamentally different contrast mechanism. It allows probing tissue microstructure by tuning the direction and strength of the correlation gradient. However, iMQC images of a specific quantum-coherence can easily be contaminated by leakage signals from undesired quantum coherences (zero, single, and triple quantum coherence in this work). Using a modified double-quantum CRAZED imaging sequence, we show that signals originating from various coherence orders (M=0, 1, 2, 3) can be predicted in k-space and effectively isolated by means of a four-step phase cycling scheme and judicious choice of flip angles. Finally, preliminary data suggest the method to be able to provide information on trabecular bone architecture such as regional mean trabecular plate separation.     

基于分子间多量子相干的矢量场磁共振成像模拟

对基于分子间多量子相干的矢量场成像进行了系统的模拟研究. 模拟结果表明：这类成像能够对几十微米量级的异质结构进行成像,并较好地抑制来自均匀介质的信号. 即使不存在梯度磁场情况下,通过相位循环该方法亦可实现对异质结构的成像. 这将有助于开拓基于分子间多量子相干成像的应用领域,深化对其成像机制的理解.     

Magnetic resonance microscopic imaging based on high-order intermolecular multiple-quantum coherences

Most imaging studies using intermolecular multiple-quantum coherences (iMQCs) have focused on the two-spin dipolar interactions--zero and double quantum coherences. Here, we report the results of various experimental studies to assess the feasibility of magnetic resonance microscopy with high-order iMQCs in model systems at 7 and 14 T. Experimental results demonstrated that the iMQC microscopic images with high coherence orders are readily observable at high field and have unique contrast depending on the sample microstructure and coherence order.     

MR IMAGING WITH INTERMOLECULAR MULTIPLE-QUANTUM COHERENCES (iMQCs):Fundamental Questions and Potentials

Pursuit of new contrast in imaging has been the driving force behind many innovative applications of physics in medical MRI. Even though the use of intramolecular multiple quantum coherence in NMR spectroscopy has a long history, intermolecular multiple quantum coherence (iMQC) among spins on different molecules, such as proton proton iMQC in water, was considered impossible for many years.     

Enhancement of magnetization transfer effects by inter-molecular multiple quantum filtered NMR

There are a number of methods that give MRI contrasts based on changes of the water M(z) magnetization as a result of magnetization transfer to macromolecules. In the present work we report that a combination of these methods with inter-molecular multiple quantum coherences (iMQC) gives enhanced effects. For the magnetization transfer contrast (MTC) method an effect of (M(z)/M(0)) becomes (M(z)/M(0))(l) where l is the rank of the tensors constituting the iMQC. A similar trend was found upon combining iMQC with the Goldman-Shen experiment. It is pointed out that the method is general for all magnetization transfer methods, including the nuclear Overhauser effect.     

Fast high-resolution 2D correlation spectroscopy in inhomogeneous fields via Hadamard intermolecular multiple quantum coherences technique

Recently, a method based on intermolecular multiple quantum coherences (iMQCs) has been proposed to obtain high-resolution 2D COSY spectra in inhomogeneous fields via 3D acquisitions. However, the very long acquisition time prevents its practical application. To overcome this shortage, the Hadamard technique was applied for the iMQC method in this paper. For the new pulse sequence, the direct frequency-domain excitation is used in the first indirect detection dimension, so the 3D acquisition was replaced by an array of 2D acquisitions. The acquisition time can be reduced to 10 min. The resulting spectra retain useful structural information including chemical shifts and multiplet patterns of J coupling even when the inhomogeneous line broadening leads to overlap of neighboring diagonal resonances in the conventional COSY spectrum. The experimental results are consistent with the theoretical predictions and computer simulations. The new sequence may provide a time-efficient way for the studies of chemical solution in inhomogeneous fields.     

High-resolution absorptive intermolecular multiple-quantum coherence NMR spectroscopy under inhomogeneous fields

Intermolecular multiple-quantum coherence (iMQC) is capable of improving NMR spectral resolution using a 2D shearing manipulation method. A pulse sequence termed CT-iDH, which combines intermolecular double-quantum filter (iDQF) with a modified constant-time (CT) scheme, is designed to achieve fast acquisition of high-resolution intermolecular zero-quantum coherences (iZQCs) and intermolecular double-quantum coherences (iDQCs) spectra without strong coupling artifacts. Furthermore, double-absorption lineshapes are first realized in 2D intermolecular multi-quantum coherences (iMQCs) spectra under inhomogeneous fields through a combination of iZQC and iDQC signals to double the resolution without loss of sensitivity. Theoretically the spectral linewidth can be further reduced by half compared to original iMQC high-resolution spectra. Several experiments were performed to test the feasibility of the new method and the improvements are evaluated quantitatively. The study suggests potential applications for in vivo spectroscopy.     

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.     

3D imaging with a single-sided sensor: an open tomograph

An open tomograph to image volume regions near the surface of large objects is described. The central achievement in getting such a tomograph to work is the design of a fast two-dimensional pure phase encoding imaging method to produce a cross-sectional image in the presence of highly inhomogeneous fields. The method takes advantage of the multi-echo acquisition in a Carr-Purcell-Meiboom-Gill (CPMG)-like sequence to significantly reduce the experimental time to obtain a 2D image or to spatially resolve relaxation times across the sensitive volume in a single imaging experiment. Depending on T(2) the imaging time can be reduced by a factor of up to two orders of magnitude compared to the one needed by the single-echo imaging technique. The complete echo train decay has been also used to produce T(2) contrast in the images and to spatially resolve the T(2) distribution of an inhomogeneous object, showing that variations of structural properties like the cross-link density of rubber samples can be distinguished by this method. The sequence has been implemented on a single-sided sensor equipped with an optimized magnet geometry and a suitable gradient coil system that provides two perpendicular pulsed gradient fields. The static magnetic field defines flat planes of constant frequency parallel to the surface of the scanner that can be selected by retuning the probe frequency to achieve slice selection into the object. Combining the slice selection obtained under the presence of the static gradient of the open magnet with the two perpendicular pulsed gradient fields, 3D spatial resolution is obtained.     

Functional magnetic resonance imaging with intermolecular multiple-quantum coherences

For the first time, we demonstrate here functional magnetic resonance imaging (fMRI) using intermolecular multiple-quantum coherences (iMQCs). iMQCs are normally not observed in liquid-state NMR because dipolar interactions between spins average to zero. If the magnetic isotropy of the sample is broken through the use of magnetic field gradients, dipolar couplings can reappear, and hence iMQCs can be observed. Conventional (BOLD) fMRI measures susceptibility variations averaged over each voxel. In the experiment performed here, the sensitivity of iMQCs to frequency variations over mesoscopic and well-defined distances is exploited. We show that iMQC contrast is qualitatively and quantitatively different from BOLD contrast in a visual stimulation task. While the number of activated pixels is smaller in iMQC contrast, the intensity change in some pixels exceeds that of BOLD contrast severalfold.     

微型快照式窄带多光谱成像宫颈癌筛查方法

白光阴道镜图像对比度较低,不利于医生鉴别不同病变程度组织,也不利于自动化宫颈癌筛查。利用癌变组织富含血红蛋白成分及血红蛋白具有特征波段这一特性,与传统高光谱空间扫描成像及分时获取不同波段多光谱成像方法相反,利用快照式多光谱窄带成像来加速光谱图像获取过程,提升不同病变程度组织之间灰度对比度同时,降低后续图像分析处理算法难度,实现对宫颈组织病变类型高帧率自动化分类。首先,使用微型快照式窄带多光谱摄像方法,在血红蛋白的两个强吸收峰(415±10)和(525±10) nm、一个反射带(620±10) nm和一个背景波段(450±10) nm共四个波段对宫颈组织进行快照式零时差获取四幅窄带光谱图像。而后,对所获取的光谱图像进行简单代数加减,以生成突显病变组织的融合图像,提高不同病变程度组织之间的对比度。最后,使用欧式距离分类算法,对光谱融合图像中不同病变级别进行分类,建立计算机辅助宫颈癌筛查方法。创新点在于实现了高帧率计算机辅助光学病理诊断方法。分别采用临床常规白光阴道镜及微型快照式窄带多光谱摄像对宫颈癌手术切下的新鲜组织进行彩色图像及光谱融合图像的高帧率采集,并使用同一个欧式距离分类算法对两种图像进行自动分类,分类结果都以组织病理诊断作为标准来计算正确率。通过对比两种分类结果正确率来检验光谱融合图像相对于彩色图像是否提升对比度,及其是否可以实现与组织病理诊断(金标准)结果一致的诊断。欧式距离分类算法对光谱融合图像分类准确率接近100%,远高于对白光阴道镜图像约50%的准确率。多位临床医生对基于微型快照式多光谱摄像头光谱融合图像的计算机自动分类结果表示接受。微型快照式窄带多光谱成像方法能有效提升光谱融合图像获取帧率及不同病变程度组织之间灰度对比度,能有效快速地将宫颈组织划分为与组织病理诊断结果一致的病变类型。由于诊断客观、无创伤、结果立等可得,该方法将有助于实现落后地区宫颈癌筛查的普及以及图像导航下的宫颈癌精准治疗手术。     

三维多回波流动补偿定量磁化率成像(QSM)方法研究

定量磁化率成像(QSM)利用一般成像技术舍弃的相位信息得到局部磁场变化特性,通过复杂的场到源反演计算,可直接得到定量的磁化率图,它广泛应用于测量血氧饱和度、脑部微出血、铁沉积、组织钙化等方面．然而,梯度磁场中流动会引起相位错误,并且产生显著的流动伪影,最终得到错误的QSM图像．为了矫正流动的影响,该文在3 T磁共振系统上实现了三维多回波流动补偿梯度回波序列,并用该序列采集流动水模和志愿者颅脑数据．流动水模和颅脑数据均显示,流动补偿能够明显矫正相位错误,消除流动伪影．颅脑横断位QSM结果证明,流动补偿序列可以消除血液流动引起的QSM的错误,提高QSM的准确性．     

An investigation of the origins of contrast in NMR spin echo images of plant tissue.

The effects that the spatial distribution of water protons and their transverse relaxation times have on the image contrast of spin echo images of courgette was investigated. The T2-weighted image of courgette contains the most anatomical information. The image contrast was explained using a phenomenological theory based on the Bloch equations, which gave an insight into the morphology and microdynamics of water in the plant tissue. The perceived contrast in the spin echo images of courgette, glucose and Sephadex bead solutions can be dramatically altered by keeping all the imaging acquisition parameters constant, such as the recycle and echo time, but reducing the interpulse spacing by introducing a CPMG train of 180 degrees pulses into the middle of the sequence. These changes were interpreted by considering the microenvironment of the water. This work demonstrates that the origin of image contrast in T2-weighted images of plant tissue can be understood using the water proton transverse relaxation theory developed by Hills et al.     

A brain phantom for motion-corrected PROPELLER showing image contrast and construction similar to those of in vivo MRI

PurposeA fast spin-echo sequence based on the Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction (PROPELLER) technique is a magnetic resonance (MR) imaging data acquisition and reconstruction method for correcting motion during scans. Previous studies attempted to verify the in vivo capabilities of motion-corrected PROPELLER in real clinical situations. However, such experiments are limited by repeated, stray head motion by research participants during the prescribed and precise head motion protocol of a PROPELLER acquisition. Therefore, our purpose was to develop a brain phantom set for motion-corrected PROPELLER.Materials and methodsThe profile curves of the signal intensities on the in vivo T₂-weighted image (T₂WI) and 3-D rapid prototyping technology were used to produce the phantom. In addition, we used a homemade driver system to achieve in-plane motion at the intended timing. We calculated the Pearson's correlation coefficient (R²) between the signal intensities of the in vivo T₂WI and the phantom T₂WI and clarified the rotation precision of the driver system. In addition, we used the phantom set to perform initial experiments to show the rotational angle and frequency dependences of PROPELLER.ResultsThe in vivo and phantom T₂WIs were visually congruent, with a significant correlation (R²) of 0.955 (p < .001). The rotational precision of the driver system was within 1 degree of tolerance. The experiment on the rotational angle dependency showed image discrepancies between the rotational angles. The experiment on the rotational frequency dependency showed that the reconstructed images became increasingly blurred by the corruption of the blades as the number of motions increased.ConclusionsIn this study, we developed a phantom that showed image contrasts and construction similar to the in vivo T₂WI. In addition, our homemade driver system achieved precise in-plane motion at the intended timing. Our proposed phantom set could perform systematic experiments with a real clinical MR image, which to date has not been possible in in vivo studies. Further investigation should focus on the improvement of the motion-correction algorithm in PROPELLER using our phantom set for what would traditionally be considered problematic patients (children, emergency patients, elderly, those with dementia, and so on).     

Isointense model for the evaluation of tumor-specific MRI contrast agents

An isointense model has been developed to evaluate the applicability of putative tumor-specific MRI contrast agents. Data for tissue relaxation measurements in the presence of Mn(III)TPPS4 are used to illustrate the model. The concentration of contrast agent in tumor tissue required for a tumor/normal tissue signal difference-to-noise ratio of 5 (delta SNR = 5) is determined for a T1 weighted pulse sequence and several hypothetical tumor/normal tissue pairs. The impact of various contrast agent characteristics including initial tumor/normal tissue relaxation values, differential uptake of contrast agent, and in vivo relaxivity are considered. Isointense tumor/normal tissue with longer initial relaxation times are shown to be more affected by the presence of contrast agent. In addition those with initially longer relaxation times have less rigorous requirements for tumor specificity. Typically, a normal tissue/tumor uptake ratio of 1:2 increases the concentration required for delta SNR = 5 by a factor of two compared to that of exclusive uptake in tumor. For the T1 weighted pulse sequence employed, the concentration required for delta SNR = 5 is shown to be linear with the inverse of in vivo relaxivity for the hypothetical tissues considered. The isointense model is also extended to predict the field dependence of tumor-specific contrast enhancement by Mn(III)TPPS4.     

Combination of BOLD-fMRI and VEP recordings for spin-echo MRI detection of primary magnetic effects caused by neuronal currents

In the present paper, for the first time, the feasibility to detect primary magnetic field changes caused by neuronal activity in vivo by spin-echo (SE) magnetic resonance imaging (MRI) is investigated. The detection of effects more directly linked to brain activity than secondary hemodynamic–metabolic changes would enable the study of brain function with improved specificity. However, the detection of neuronal currents by MRI is hampered by such accompanying hemodynamic changes. Therefore, SE image acquisition, rather than gradient-echo (GE) image acquisition, was preferred in the present work since the detection of primary neuronal and not blood oxygenation level-dependent (BOLD)-related effects may be facilitated by this approach. First of all, a precise spatiotemporal synchronization of image acquisition with the neuronal event had to be performed to avoid refocusing of the dephasing phenomenon during the course of the SE sequence. At this aim, we propose the combined use of visual evoked potential (VEP) recordings and BOLD-fMRI measurements prior to SE MRI scanning. Moreover, we exemplify by theory and experimentation how the control of artefactual signal changes due to BOLD and movement effects may be further improved by the experimental design. Finally, results from a pilot study using the proposed combination of VEP recordings and MRI techniques are reported, suggesting the feasibility of this method.     

Inhomogeneity-free heteronuclear iMQC

Intermolecular dipolar interactions between proton and carbon spins can be used to indirectly detect carbon spectra with high sensitivity. In this communication, we present a modified sequence that, in addition to the high sensitivity of heteronuclear intermolecular multiple quantum coherence (iMQC) experiments, retains the line narrowing capability characteristic of homonuclear zero-quantum coherences. We demonstrate that this sequence can be used to obtain high resolution (13)C spectra in the presence of magnetic field inhomogeneities, both for thermal and hyperpolarized samples, and discuss applications to water-hyperpolarized carbon imaging.     

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.     

A comparison of three SPRITE techniques for the quantitative 3D imaging of the 23Na spin density on a 4T whole-body machine

Sodium density maps acquired with three SPRITE-based methods have been compared in terms of the resulting quantitative information as well as image quality and acquisition times. Consideration of factors relevant for the clinical implementation of SPRITE shows that the Conical-SPRITE variant is preferred because of a 20-fold reduction in acquisition time, slightly improved image quality, and no loss of quantitative information. The acquisition of a 3D data set (32x32x16; FOV=256x256x160 mm) for the quantitative determination of sodium density is demonstrated. In vivo Conical-SPRITE 23Na images of the brain of a healthy volunteer were acquired in 30 min with a resolution of 7.5x7.5x7.5 mm and a signal-to-noise ratio of 23 in cerebrospinal fluid and 17 in brain tissue.