Magnetization transfer of water T(2) relaxation components in human brain: implications for T(2)-based segmentation of spectroscopic volumes

Biexponential T(2) relaxation of the localized water signal can be used for segmentation of spectroscopic volumes. To assess the specificity of the components an iterative relaxation measurement of the localized water signal (STEAM, 12 echo times, geometric spacing from 30 ms to 2000 ms) was combined with magnetization transfer (MT) saturation (40 single lobe pulses, 12 ms duration, 1440 degrees nominal flip angle, 1 kHz offset, repeated every 30 ms). Voxels including CSF were examined in parietal cortex and periventricular parietal white matter (10 each), as well as 13 voxels in central white matter and 16 T(1)-hypointense non-enhancing multiple sclerosis lesions without CSF inclusion. Biexponential models (excluding myelin water) were fitted to the relaxation data. In periventricular VOIs the component of long T(2) (1736 +/- 168 ms) that is attributed to CSF was not affected by MT. In cortical VOIs this component had markedly shorter T(2)'s (961 +/- 239 ms) and showed both attenuation and prolongation with MT, indicating contributions from tissue. MS lesions and central WM showed a second tissue component of intermediate T(2) (160-410 ms). In white matter similar MT attenuation indicated strong exchange between the two tissue components, prohibiting segmentation. In MS lesions, however, markedly less MT of the intermediate component was found, which is consistent with decreased cellularity and exchange in a region that is large compared to diffusion motion.     

Diffusion-weighted EPI with magnetization transfer contrast

Capabilities of diffusion-weighted (DW) and magnetization transfer (MT) imaging are well established for tissue characterization in various pathologies individually. However, the effect of suppression of macromolecules on applying MT pulse on signals associated with DW imaging and resulting change in the apparent diffusion coefficient (ADC) of water molecules has not been demonstrated previously. In the present study, we have performed DW echo planar imaging (EPI) with and without MT preparation pulse to see the effect of macromolecular signal suppression on ADC. A total of 10 normal volunteers and 20 patients with different intracranial cystic lesions [abscesses (n=10), cystic tumors (n=5), arachnoid cysts (n=5)] were subjected to DW imaging (b=0 and 1000 s/mm(2)) with and without MT saturation pulse. Analysis of region of interest (ROI) from different areas of white matter in normal volunteers and in the wall and cavity of cystic lesions in patients was carried out for calculating the ADC values. We found a significant increase (P<.05) in the ADC values in brain parenchyma and cavity of those intracranial cystic lesions having considerable amount of proteins after the application of MT preparation pulse except for arachnoid cysts. This is due to the size of the macromolecules present in the normal and abnormal tissue. Our studies suggest that this technique is likely to give a novel image contrast and may be of value in improving the tissue specificity in pathologies associated with variable macromolecular size.     

o-Semiquinonato and o-iminosemiquinonato rhodium complexes. EPR study of the reactions in coordination sphere of rhodium

Chemical exchange saturation transfer (CEST) processes in aqueous systems are quantified by evaluation of z-spectra, which are obtained by acquisition of the water proton signal after selective RF presaturation at different frequencies. When saturation experiments are performed in vivo, three effects are contributing: CEST, direct water saturation (spillover), and magnetization transfer (MT) mediated by protons bound to macromolecules and bulk water molecules. To analyze the combined saturation a new analytical model is introduced which is based on the weak-saturation-pulse (WSP) approximation. The model combines three single WSP approaches to a general model function. Simulations demonstrated the benefits and constraints of the model, in particular the capability of the model to reproduce the ideal proton transfer rate (PTR) and the conventional MT rate for moderate spillover effects (up to 50% direct saturation at CEST-resonant irradiation). The method offers access to PTR from z-spectra data without further knowledge of the system, but requires precise measurements with dense saturation frequency sampling of z-spectra. PTR is related to physical parameters such as concentration, transfer rates and thereby pH or temperature of tissue, using either exogenous contrast agents (PARACEST, DIACEST) or endogenous agents such as amide protons and -OH protons of small metabolites.     

Quantitative and qualitative assessment of articular cartilage in the goat knee with magnetization transfer imaging

We investigated the role of collagen in the magnetization transfer (MT) effect in contrast to other macromolecules. By means of phantoms made of collagen, chondroitin sulfate (CS) and albumin, MR parameters have been optimized in order to reduce the acquisition time and improve the sensitivity, as well as to minimize the contributions from CS and albumin to the MT induced signal attenuation. The same method was used to study cartilage ex vivo (bovine articular and nasal cartilage plugs) and in vivo (goat knee femoral chondyle). In phantom samples, the MT signal attenuation depended on the collagen concentration while contributions from the other macromolecules were found to be minimal. In average, analysis of MT images revealed a 25%, 35% and 30% signal attenuation in 10% w/v type I collagen gels, cartilage plugs, and cartilage from the weight-bearing areas of the goat knee, respectively. Biochemical data revealed that treatment of cartilage plugs with bacterial collagenase led to collagen depletion and correspondingly to a decrease of the MT response. In contrast, trypsin-induced proteoglycan loss in cartilage plugs did not alter the MT effect. A significant correlation was observed between the collagen content in these plugs and their respective MT ratios and the rate constant k for the exchange process bound versus free water. Finally, data obtained from in vivo MT measurement of the goat knee demonstrated that intra-articular injection of papain might not only cause degradation of proteoglycans but also a change in collagen integrity in a dose-dependent manner. We conclude that in vivo measurement of MT ratios gives quantitative and qualitative information on the collagen status and may be applied for the routine evaluation of normal and abnormal articular cartilage.     

Quantitative interpretation of magnetization transfer in spoiled gradient echo MRI sequences

A method for analyzing general pulsed magnetization transfer (MT) experiments in which off-resonance saturation pulses are interleaved with on-resonance excitation pulses is presented. We apply this method to develop a steady-state signal equation for MT-weighted spoiled gradient echo sequences and consider approximations that facilitate its rapid computation. Using this equation, we assess various experimental designs for quantitatively imaging the fractional size of the restricted pool, cross-relaxation rate, and T(1) and T(2) relaxation times of the two pools in a binary spin bath system. From experiments on agar gel, this method is shown to reliably and accurately estimate the exchange and relaxation properties of a material in an imaging context, suggesting the feasibility of using this technique in vivo.     

Increasing the speed of relaxometry-based compartmental analysis experiments in STEAM spectroscopy

In this work we present a method for improving the speed of spin-spin relaxation time (T2) measurements for compartmental analysis in stimulated echo localized magnetic resonance spectroscopy without reducing the sampling density. The technique uses a progressive repetition time (TR) to compensate for echo time (TE) dependent variations in saturation effects that would otherwise modulate the received signal at short TRs. The method was validated in T2 studies on 10 young healthy subjects in spectroscopic voxels localized along either the right or left Sylvian fissure (2 x 2 x 1.5 cm3, 10 ms mixing time (TM), 2048 data points, 819.2 ms acquisition time). The TR was automatically adjusted so that TR-TM-TE/2 was kept constant as the TE was incremented. Compared to long TR T2 experiments, the progressive TR technique consistently replicated the T2 relaxation times and reference signals of the tissue water compartment while reducing the data acquisition time by more than 50%. The percent error was on average less than 2% for estimates of T2 and S(0) for the tissue water, an indication that the progressive TR technique is a useful method for determining the tissue water signal for internal referencing.     

Multi-component T1 relaxation and magnetisation transfer in peripheral nerve

We report here a study of longitudinal relaxation (T₁) and magnetisation transfer (MT) in peripheral nerve. Amphibian sciatic nerve was maintained in vitro and studied at a magnetic field strength of 3 T. A CPMG pulse sequence was modified to include either a saturation pulse to measure T₁ relaxation or an off-resonance RF irradiation pulse to measure MT. The resulting transverse relaxation (T₂) spectra yielded four components corresponding to three nerve compartments, taken to result from myelinic, axonal, and inter-axonal water, and a fourth corresponding to the buffer solution water in which the nerve sample was bathed. Each nerve component was analysed for T₁ relaxation and MT. All three nerve T₂ components exhibited unique T₁ relaxation and MT characteristics, providing further support for the assignment of the components to unique physical compartments of water. Numerical investigation of T_1sat measurements of each of the three nerve T₂ components indicates that while the two shorter-lived exhibit similar steady-state magnetisation transfer ratios (MTRs), their respective MT properties are quite different. Simulations demonstrate that mobile water exchange between these two components is not necessary to explain their similar steady-state MTR. In the context of the assignment of these two components to signal from myelinic and axonal water, this is to say that these two microanatomical regions of nerve may exhibit similar steady-state MTR characteristics despite possessing widely different MT exchange rates. Therefore, interpreting changes in MTR solely to reflect a change in degree of myelination could lead to erroneous conclusions.     

Effects of fat saturation on short T2 quantification

Ultrashort TE (UTE) sequences have the capability to image tissues with very short T2s that typically appear as low signal in clinical sequences. UTE sequences can also be used in multi-echo acquisitions which allow assessment of the T2s of these tissues. Here we study the accuracy of such T2 measurements when combined with fat saturation (FS).     

Analysis of longitudinal relaxation rate constants from magnetization transfer MR images of human tissues at 0.1 T.

The human calf muscle was examined by using the magnetization transfer MR imaging technique. The time-dependent saturation transfer (TDST) method was applied at low magnetic field 0.1 T in order to measure the mobile water relaxation time T1w, the magnetization transfer rate Rwm from water to solid macromolecules, and the magnetization transfer contrast (MTC) of the human tissue. The magnetization transfer contrast of 0.67 was attained. The transfer rate Rwm was 4.5 sec-1 (+/- 0.3 sec-1) for the anterior tibial muscle and 5.0 sec-1 (+/- 0.4 sec-1) for the gastrocnemius muscles. The values of Rwm are considerably larger than the values of corresponding relaxation rates measured at high fields. The relaxation rate measurements of human tissues in vivo was shown to be possible at 0.1 T even within the framework of normal routine MR imaging. Magnetization transfer MR imaging is a very promising and practical method in order to assess the relaxation processes in heterogeneous human tissues in vivo, and it can improve the tissue characterization possibilities of MR imaging techniques.     

Constrained modeling for spectroscopic measurement of bi-exponential spin-lattice relaxation of water in vivo

The (1)H NMR water signal from spectroscopic voxels localized in gray matter contains contributions from tissue and cerebral spinal fluid (CSF). A typically weak CSF signal at short echo times makes separating the tissue and CSF spin-lattice relaxation times (T(1)) difficult, often yielding poor precision in a bi-exponential relaxation model. Simulations show that reducing the variables in the T(1) model by using known signal intensity values significantly improves the precision of the T(1) measurement. The method was validated on studies on eight healthy subjects (four males and four females, mean age 21 +/- 2 years) through a total of twenty-four spectroscopic relaxation studies. Each study included both T(1) and spin-spin relaxation (T(2)) experiments. All volumes were localized along the Sylvian fissure using a stimulated echo localization technique with a mixing time of 10 ms. The T(2) experiment consisted of 16 stimulated echo acquisitions ranging from a minimum echo time (TE) of 20 ms to a maximum of 1000 ms, with a repetition time of 12 s. All T(1) experiments consisted of 16 stimulated echo acquisition, using a homospoil saturation recovery technique with a minimum recovery time of 50 ms and a maximum 12 s. The results of the T(2) measurements provided the signal intensity values used in the bi-exponential T(1) model. The mean T(1) values when the signal intensities were constrained by the T(2) results were 1055.4 ms +/- 7.4% for tissue and 5393.5 ms +/- 59% for CSF. When the signal intensities remained free variables in the model, the mean T(1) values were 1085 ms +/- 19.4% and 5038.8 ms +/- 113.0% for tissue and CSF, respectively. The resulting improvement in precision allows the water tissue T(1) value to be included in the spectroscopic characterization of brain tissue.     

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.     

Magnetization transfer and T2 quantitation in normal appearing cortical gray matter and white matter adjacent to focal abnormality in patients with traumatic brain injury

Traumatic brain injury (TBI) is one of the commonest causes of morbidity and mortality in the developed countries with posttraumatic epilepsy and functional disability being its major sequelae. The purpose of this study was to test the hypothesis whether the normal appearing adjacent gray and white matter regions on T2 and T1 weighted magnetization transfer (MT) weighted images show any abnormality on quantitative imaging in patients with TBI. A total of 51 patients with TBI and 10 normal subjects were included in this study. There were significant differences in T2 and MT ratio values of T2 weighted and T1 weighted MT normal appearing gray matter regions adjacent to focal image abnormality compared to normal gray matter regions in the normal individuals as corresponding contralateral regions of the TBI patient's group (p < 0.05). However the adjoining normal appearing white matter quantitative values did not show any significant change compared to the corresponding contralateral normal white matter values. We conclude that quantitative T2 and MT ratio values provide additional abnormality in patients with TBI that is not discernable on conventional T2 weighted and T1 weighted MT imaging especially in gray matter. This additional information may be of value in overall management of these patients with TBI.     

Water content profiles with a 1D centric SPRITE acquisition

The purpose of this work is to develop a rapid MRI method amenable to profiling with minimal or no T(1) relaxation weighting. The behavior of a signal during a centric SPRITE acquisition is analyzed. It is shown that the technique can be made immune to a broad range of T(1) changes. In a properly executed measurement, only T(2)* and proton density parameters define the image intensity. A T(2)* mapping technique can be easily applied, separating T(2)* and proton density contributions to the image. A drying soil sample with low initial water content is experimentally studied as a demonstration of the technique. A characteristic baseline artifact is easily removed from the profiles by a simple operation.     

人脑GABA磁共振波谱测量中大分子影响的研究

J差分谱编辑技术已广泛用于人脑g-氨基丁酸(γ-amino butyric acid,GABA)的检测,利用MEGA-PRESS序列可以有效编辑GABA在δ_H 3.02处的信号.由于相近的化学位移和J耦合作用,大分子(macromolecule,MM)在δ_H 3.00的信号也同时被编辑,因此测量得到的GABA信号中包含一部分MM信号(GABA+MM,简称GABA+).对称谱编辑技术可以有效抑制大分子,但该方法对编辑脉冲的频率选择性要求较高,因此对称谱编辑技术中编辑脉冲持续时间一般较长.该研究将MEGA-PRESS序列中编辑脉冲持续时间由14 ms增加到20 ms,回波时间(echo time,TE)由68 ms增加到80 ms,分别测量GABA+与对称谱编辑技术抑制大分子后的GABA(简称GABA).结果发现,在较长编辑脉冲作用时间和较长TE条件下,GABA比GABA+含量低27%;长编辑脉冲持续时间可以有效提高编辑脉冲的频率选择性,更好地实现对称谱编辑技术抑制大分子,有助于分析人脑GABA含量测定中大分子信号干扰的影响.纯GABA含量测量,有助于更准确地分析GABA在人脑中的代谢过程,以及GABA含量与各种疾病和功能认知反应之间的相关性.     

Quantitative magnetization transfer by trains of radio frequency pulses in human brain: extension of a free evolution model to continuous-wave-like conditions

A theoretical model of free evolution between repeated magnetic transfer (MT) pulses was extended to continuous-wave (CW)-like conditions showing that only the repetitive "direct" saturation of bulk water changes the transient and stationary behavior. The influence of the pulse repetition period (PR) on progressive saturation was studied in cortical gray matter (GM) and central white matter (WM) under conditions of short periods of free evolution and strong macromolecular saturation. Interpulse delays of 3 ms were achieved in vivo on a 1.5-T MR system with bell-shaped MT pulses of 12-ms duration and nominal flip angles of up to 1440 degrees and single-shot readout by a stimulated echo acquisition mode localization sequence. The frequency offset was chosen between 1 and 3 kHz to avoid excessive direct saturation. The stationary MT ratio (MTR) followed an inverse linear PR dependence, showing a consistent partial saturation of about 90% at zero PR for both WM and GM. Comparison to a relaxation-matched liquid indicated the presence of MT, but not necessarily of direct saturation. The transient behavior indicated considerable direct saturation, but this could also be explained by MT. These inconsistencies showed that the intervals of time evolution in our experiments were too long to be modeled by CW-like conditions. Free evolution takes place during the whole PR rather than during the interpulse delay only. Quantification using the rates of free evolution theory yielded the saturations and rate constants necessary to explain the observed behavior. The theory of rapid CW-like pulsing provides an upper limit for the rate of progressive saturation. This limit is approached at PR below an estimated value of 5 ms. The phenomenological PR dependence of the steady-state MTR may indicate that MT exceeded the direct saturation. Unlike to an idealized CW experiment, the extrapolated value at zero PR is subject to direct effects and not a physically meaningful constant.     

On neglecting chemical exchange effects when correcting in vivo (31)P MRS data for partial saturation

Signal acquisition in most MRS experiments requires a correction for partial saturation that is commonly based on a single exponential model for T(1) that ignores effects of chemical exchange. We evaluated the errors in (31)P MRS measurements introduced by this approximation in two-, three-, and four-site chemical exchange models under a range of flip-angles and pulse sequence repetition times (T(R)) that provide near-optimum signal-to-noise ratio (SNR). In two-site exchange, such as the creatine-kinase reaction involving phosphocreatine (PCr) and gamma-ATP in human skeletal and cardiac muscle, errors in saturation factors were determined for the progressive saturation method and the dual-angle method of measuring T(1). The analysis shows that these errors are negligible for the progressive saturation method if the observed T(1) is derived from a three-parameter fit of the data. When T(1) is measured with the dual-angle method, errors in saturation factors are less than 5% for all conceivable values of the chemical exchange rate and flip-angles that deliver useful SNR per unit time over the range T(1)/5 < or = T(R) < or = 2T(1). Errors are also less than 5% for three- and four-site exchange when T(R) > or = T(1)(*)/2, the so-called "intrinsic" T(1)'s of the metabolites. The effect of changing metabolite concentrations and chemical exchange rates on observed T(1)'s and saturation corrections was also examined with a three-site chemical exchange model involving ATP, PCr, and inorganic phosphate in skeletal muscle undergoing up to 95% PCr depletion. Although the observed T(1)'s were dependent on metabolite concentrations, errors in saturation corrections for T(R) = 2 s could be kept within 5% for all exchanging metabolites using a simple interpolation of two dual-angle T(1) measurements performed at the start and end of the experiment. Thus, the single-exponential model appears to be reasonably accurate for correcting (31)P MRS data for partial saturation in the presence of chemical exchange. Even in systems where metabolite concentrations change, accurate saturation corrections are possible without much loss in SNR.     

A multi-inversion-recovery magnetic resonance fingerprinting for multi-compartment water mapping

PurposeThis study aimed at introducing short-T1/T2 compartment to MR fingerprinting (MRF) at 3 T. Water that is bound to myelin macromolecules have significantly shorter T1 and T2 than free water and can be distinguished from free water by multi-compartment analysis.MethodsWe developed a new multi-inversion-recovery (mIR) water mapping-MRF based on an unbalanced steady-state coherent sequence (FISP). mIR pulses with an interval of 400 or 500 repetition times (TRs) were inserted into the conventional FISP MRF sequence. Data from our proposed mIR MRF was used to quantify different compartments, including myelin water, gray matter free water, and white matter free water, of brain water by virtue of the iterative non-negative least square (NNLS) with reweighting. Three healthy volunteers were scanned with mIR MRF on a clinical 3 T MRI.ResultsUsing an extended phase graph simulation, we found that our proposed mIR scheme with four IR pulses allowed differentiation between short and long T1/T2 components. For in vivo experiments, we achieved the quantification of myelin water, gray matter water, and white matter water at an image resolution of 1.17 × 1.17 × 5 mm³/pixel. As compared to the conventional MRF technique with single IR, our proposed mIR improved the detection of myelin water content. In addition, mIR MRF using spiral-in/out trajectory provided a higher signal level compared with that with spiral-out trajectory. Myelin water quantification using mIR MRF with 4 IR and 5 IR pulses were qualitatively similar. Meanwhile, 5 IR MRF showed fewer artifacts in myelin water detection.ConclusionWe developed a new mIR MRF sequence for the rapid quantification of brain water compartments.     

A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST)

It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent saturation transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a chemical exchange site on the agent via saturation transfer. The ideal chemical exchange site would have a large chemical shift from water. This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5, 6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.     

Nondestructive detection of internal bruise and spraing disease symptoms in potatoes using magnetic resonance imaging

Magnetic resonance imaging (MRI) was applied to detect nonvisible internal bruise and spraing symptoms and to get insight on the chemical and anatomical causes of such defects. Cultivar Saturna with internal bruise and cultivar Estima with spraing symptoms were investigated by comparison of different MR images as proton density-, T(1)- and T(2)-weighted images and T(2) maps. In all these types of MR images, it was possible to identify internal bruise and spraing spots in the potatoes, where these phenomena were present. When combining the information in the MR images, the interior of the internal bruise was characterised as being very dry (low signal in the proton-weighted image) with a small amount of highly mobile water in the shell around the bruise (high signal in T(2)-weighted image and high relaxation time in T(2) map). The spraing spots were more diffuse; however, the dry interior and highly mobile water around the spraing dots were somewhat similar to the appearance of internal bruise but resembled more the appearance of human tumour tissue than bruise disorders in, for example, fruits. In conclusion, this study demonstrated that MRI can detect nonvisible internal bruise and spraing symptoms in potatoes, which has not been published before. MRI may, therefore, be an appropriate method for detecting and for studying developmental changes of such disorders and related disorders during postharvest storage in future experiments.     

Characterization of the calcaneal fat pad in diabetic and non-diabetic patients using magnetic resonance imaging.

It is well known that diabetic patients have a high incidence of foot ulceration. The purpose of this study was to determine whether magnetic resonance (MR) imaging can detect changes in the composition of the calcaneal fat pad in diabetic feet. MR data were collected in vitro from amputated specimens (eight from diabetic patients and eight from non-diabetic patients) as well as in vivo from age-matched diabetic and control subjects (four subjects each group.) Three types of images were acquired: spin lattice (T1), spin-spin (T2), and magnetization transfer (MT). The in vitro results showed statistically significant differences in the T1, T2, and MT parameters between the two disease groups. The same trends were shown in the study of live subjects but the differences were not statistically significant. The differences are believed to arise from changes in the composition of the tissues as a result of the progression of diabetes.