Pulsed Gradient Spin-echo Sequence Research Articles

Diffusion of Peptides and Small Molecules Encapsulated in Lipidic Cubic Phases by Band-Selective Excitation Short Transient 1H PGSE NMR.

In model membrane systems, such as lipidic cubic phases (LCPs), 1H NMR spectra are dominated by resonances from water and lipid molecules. The measurement of translational diffusion of peptides/molecules encapsulated in LCPs using conventional 1H pulsed-gradient spin-echo (PGSE) NMR is, therefore, immensely difficult due to the dynamic range caused by the intense resonance(s) from the surrounding environment. The present study reports the use of a band-selective short transient PGSE sequence, avoiding the perturbation of both hydration water and lipids, for measuring the diffusion of molecules encapsulated within the lipid bilayer and the aqueous channels of LCPs.

Detection of Treatment Response in Triple-Negative Breast Tumors to Paclitaxel Using MRI Cell Size Imaging.

Breast cancer treatment response evaluation using the response evaluation criteria in solid tumors (RECIST) guidelines, based on tumor volume changes, has limitations, prompting interest in novel imaging markers for accurate therapeutic effect determination. To use MRI-measured cell size as a new imaging biomarker for assessing chemotherapy response in breast cancer. Longitudinal; animal model. Triple-negative human breast cancer cell (MDA-MB-231) pellets (4 groups, n = 7) treated with dimethyl sulfoxide (DMSO) or 10 nM of paclitaxel for 24, 48, and 96 hours, and 29 mice with MDA-MB-231 tumors in right hind limbs treated with paclitaxel (n = 16) or DMSO (n = 13) twice weekly for 3 weeks. Oscillating gradient spin echo and pulsed gradient spin echo sequences at 4.7 T. MDA-MB-231 cells were analyzed using flowcytometry and light microscopy to assess cell cycle phases and cell size distribution. MDA-MB-231 cell pellets were MR imaged. Mice were imaged weekly, with 9, 6, and 14 being sacrificed for histology after MRI at weeks 1, 2, and 3, respectively. Microstructural parameters of tumors/cell pellets were derived by fitting diffusion MRI data to a biophysical model. One-way ANOVA compared cell sizes and MR-derived parameters between treated and control samples. Repeated measures 2-way ANOVA with Bonferroni post-tests compared temporal changes in MR-derived parameters. A P-value <0.05 was considered statistically significant. In vitro experiments showed that the mean MR-derived cell sizes of paclitaxel-treated cells increased significantly with a 24-hours treatment and decreased (P = 0.06) with a 96-hour treatment. For in vivo xenograft experiments, the paclitaxel-treated tumors showed significant decreases in cell size at later weeks. MRI observations were supported by flowcytometry, light microscopy, and histology. MR-derived cell size may characterize the cell shrinkage during treatment-induced apoptosis, and may potentially provide new insights into the assessment of therapeutic response. 2 TECHNICAL EFFICACY STAGE: 4.

Multidimensional encoding of restricted and anisotropic diffusion by double rotation of the qvector.

Diffusion NMR and MRI methods building on the classic pulsed gradient spin-echo sequence are sensitive to many aspects of translational motion, including time and frequency dependence ("restriction"), anisotropy, and flow, leading to ambiguities when interpreting experimental data from complex heterogeneous materials such as living biological tissues. While the oscillating gradient technique specifically targets frequency dependence and permits control of the sensitivity to flow, tensor-valued encoding enables investigations of anisotropy in orientationally disordered materials. Here, we propose a simple scheme derived from the "double-rotation" technique in solid-state NMR to generate a family of modulated gradient waveforms allowing for comprehensive exploration of the 2D frequency-anisotropy space and convenient investigation of both restricted and anisotropic diffusion with a single multidimensional acquisition protocol, thereby combining the desirable characteristics of the oscillating gradient and tensor-valued encoding techniques. The method is demonstrated by measuring multicomponent isotropic Gaussian diffusion in simple liquids, anisotropic Gaussian diffusion in a polydomain lyotropic liquid crystal, and restricted diffusion in a yeast cell sediment.

Impact of tissue properties on time-dependent alterations in apparent diffusion coefficient: a phantom study using oscillating-gradient spin-echo and pulsed-gradient spin-echo sequences

PurposeThe purpose of this study was to investigate whether the changes in apparent diffusion coefficients (ADCs) due to differences in diffusion time reflect tissue properties in actual measurements of phantoms.Materials and methodsVarious n-alkane phantoms and sucrose/collagen phantoms with various collagen densities were set up with and without polyvinyl alcohol (PVA) foam with an average pore diameter of 300 μm. Thus, n-alkanes or sucrose/collagen represented substrate viscosity and the presence of PVA foam represented tissue structure with septum. Diffusion-weighted images with various diffusion times (7.71–60 ms) were acquired using pulsed-gradient spin-echo (PGSE) and oscillating-gradient spin-echo (OGSE) sequences. The ADCs of the phantoms with and without PVA foam were calculated.ResultsThe ADCs of some of the phantoms without PVA decreased with diffusion times decreased. In the n-alkane phantoms, only C8H18 showed significantly different ADCs depending on the use of PVA foam in the OGSE sequence. On the other hand, sucrose/collagen phantoms showed significant differences according to diffusion time. The ADCs of the phantoms decreased as the molecular size of the n-alkanes or collagen density of the sucrose/collagen phantom increased. Compared to phantoms without PVA foam, the ADC of the phantoms with PVA foam decreased as the diffusion time increased.ConclusionChanges in ADCs due to differences in diffusion time reflect tissue properties in actual measurements of phantoms. These changes in ADCs can be used for tissue characterization in vivo.

The relationship between diffusion heterogeneity and microstructural changes in high-grade gliomas using Monte Carlo simulations

PurposeDiffusion-weighted imaging (DWI) may aid accurate tumor grading. Decreased diffusivity and increased diffusion heterogeneity measures have been observed in high-grade gliomas using the non-monoexponential models for DWI. However, DWI measures concerning tissue characteristics in terms of pathophysiological and structural changes are yet to be established. Thus, this study aims to investigate the relationship between the diffusion measurements and microstructural changes in the presence of high-grade gliomas using a three-dimensional Monte Carlo simulation with systematic changes of microstructural parameters. MethodsWater diffusion was simulated in a microenvironment along with changes associated with the presence of high-grade gliomas, including increases in cell density, nuclear volume, extracellular volume (VFex), and extracellular tortuosity (λex), and changes in membrane permeability (Pmem). DWI signals were simulated using a pulsed gradient spin-echo sequence. The sequence parameters, including the maximum gradient strength and diffusion time, were set to be comparable to those of clinical scanners and advanced human MRI systems. The DWI signals were fitted using the gamma distribution and diffusional kurtosis models with b-values up to 6000 and 2500 s/mm2, respectively. ResultsThe diffusivity measures (apparent diffusion coefficients (ADC), Dgamma of the gamma distribution model and Dapp of the diffusional kurtosis model) decreased with increases in cell density and λex, and a decrease in Pmem. These diffusivity measures increased with increases in nuclear volume and VFex. The diffusion heterogeneity measures (σgamma of the gamma distribution model and Kapp of the diffusional kurtosis model) increased with increases in cell density or nuclear volume at the low Pmem, and a decrease in Pmem. Increased σgamma was also associated with an increase in VFex. ConclusionAmong simulated microstructural changes, only increases in cell density at low Pmem or decreases in Pmem corresponded to both the decreased diffusivity and increased diffusion heterogeneity measures. The results suggest that increases in cell density at low Pmem or decreases in Pmem may be associated with the diffusion changes observed in high-grade gliomas.

Diffusion Tensor Imaging of Skeletal Muscle Contraction Using Oscillating Gradient Spin Echo.

Diffusion tensor imaging (DTI) measures water diffusion in skeletal muscle tissue and allows for muscle assessment in a broad range of neuromuscular diseases. However, current DTI measurements, typically performed using pulsed gradient spin echo (PGSE) diffusion encoding, are limited to the assessment of non-contracted musculature, therefore providing limited insight into muscle contraction mechanisms and contraction abnormalities. In this study, we propose the use of an oscillating gradient spin echo (OGSE) diffusion encoding strategy for DTI measurements to mitigate the effect of signal voids in contracted muscle and to obtain reliable diffusivity values. Two OGSE sequences with encoding frequencies of 25 and 50 Hz were tested in the lower leg of five healthy volunteers with relaxed musculature and during active dorsiflexion and plantarflexion, and compared with a conventional PGSE approach. A significant reduction of areas of signal voids using OGSE compared with PGSE was observed in the tibialis anterior for the scans obtained in active dorsiflexion and in the soleus during active plantarflexion. The use of PGSE sequences led to unrealistically elevated axial diffusivity values in the tibialis anterior during dorsiflexion and in the soleus during plantarflexion, while the corresponding values obtained using the OGSE sequences were significantly reduced. Similar findings were seen for radial diffusivity, with significantly higher diffusivity measured in plantarflexion in the soleus muscle using the PGSE sequence. Our preliminary results indicate that DTI with OGSE diffusion encoding is feasible in human musculature and allows to quantitatively assess diffusion properties in actively contracting skeletal muscle. OGSE holds great potential to assess microstructural changes occurring in the skeletal muscle during contraction, and for non-invasive assessment of contraction abnormalities in patients with muscle diseases.

Comparison of PGSE and STEAM DTI acquisitions with varying diffusion times for probing anisotropic structures in human kidneys.

To evaluate the sensitivity of stimulated-echo acquisition mode (STEAM) and pulsed-gradient spin-echo (PGSE) diffusion tensor imaging (DTI) acquisitions with different diffusion times for measuring renal tissue anisotropy. Twelve healthy volunteers underwent an MRI examination at a 3T scanner including STEAM and PGSE DTI with variable diffusion times Δ (20.3, 37 and 125ms). Three volunteers were scanned twice to test the reproducibility for repeated examinations. Diffusion parameters fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in the automatically segmented cortical and medullary regions of interests in both kidneys were calculated and averaged over all subjects for further analysis. Moreover, 5-grade qualitative evaluation of the FA and ADC maps from each sequence was conducted by two experienced radiologists in a consensus. The cortex-medulla difference in the STEAM sequence was significantly higher than that in PGSE with short ∆=20.3ms (P<0.001) and in PGSE with intermediate ∆=37ms (P<0.05) diffusion times. Reproducibility of the FA/ADC measurements was very good and comparable for all acquisition modes investigated. For the FA maps, the PGSE sequence with intermediate diffusion time scored highest in the subjective visual assessment of radiologists. The delineation of anisotropy in renal tissue is depending on the used diffusion time of the DTI sequence. A PGSE acquisition at a diffusion time of about 37ms provides reproducible results with optimal corticomedullary contrast in FA and ADC maps and good image quality.

Magnetic resonance spectroscopy extended by oscillating diffusion gradients: Cell-specific anomalous diffusion as a probe for tissue microstructure in human brain

PurposeTo demonstrate that oscillating gradient spin-echo sequences can be combined with diffusion-weighted magnetic resonance spectroscopy even on clinical MR systems to study human brain at short diffusion times to provide apparent diffusion coefficients (ADCs) sensitive to a narrower cellular length scale than pulsed gradient spin-echo sequences at long diffusion time. MethodsMeasurements were performed on a 3T MR system using a semiLaser sequence with diffusion-weighting realized by oscillating and pulsed gradient modules, encoding diffusion times <10 ms and >50 ms, respectively. Metabolite-cycling was included to measure metabolites and water simultaneously. The sequence was tested in a phantom and in a parieto-occipital cerebral region of interest with mixed gray/white matter content of 6 subjects. The water reference was used for phase, frequency, and eddy-current correction as well as motion compensation. ADCs were estimated by 1D sequential and 2D simultaneous fitting. ResultsMeasurements in the phantom established that both sequences yield equal ADCs, independent of diffusion time, as expected for free diffusion. In contrast, averaged metabolite diffusion in vivo was found to be 1.9 times faster at short (8.3 ms) than at long (155 ms) diffusion times. The difference in ADC was found to be statistically significant for the creatines, cholines, N-acetylaspartate, myo-inositol, and glutamate. The water ADC was measured to be 1.3 times larger at short than at long diffusion time. ConclusionIt is demonstrated that application of oscillating gradients in diffusion-weighted MRS is feasible on clinical MR systems to establish the dependence of ADCs on diffusion times in humans. The initial results largely confirm earlier reports for mice’ and rats’ brain at short and long diffusion times. ADCs representing diffusion at short and ultra-short diffusion times are of interest to probe cellular or subcellular changes in disease. The presented methodology may thus open the door for investigation of pathophysiological changes in cell-specific microstructures in human cohorts.

Time-dependent diffusion MRI to distinguish malignant from benign head and neck tumors.

There is growing interest in the effect of diffusion time on apparent diffusion coefficient (ADC) values in cancers; however, little evidence exists regarding its utility to differentiate malignant from benign head and neck tumors. To investigate the utility of ADC value changes in distinguishing between malignant and benign head and neck tumors using the different diffusion times obtained from oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE) MRI sequences. Prospective. Thirty-one consecutive patients with suspected head and neck tumors and a phantom. 3T MRI with diffusion-weighted imaging (DWI) using OGSE (effective diffusion time: 4.3 msec) and PGSE (effective diffusion time: 82.6 msec) sequences and b-values of 0 and 700 s/mm2 . ADC values using OGSE (ADCOGSE ) and PGSE (ADCPGSE ) and relative ADC value changes between ADCOGSE and ADCPGSE . Wilcoxon test, Mann-Whitney test, and McNemar test. Relative ADC changes for each polyvinylpyrrolidone (PVP) and water in the phantom between OGSE and PGSE sequences were small (relative ADC change within 0.6%). Malignant tumors had significantly smaller ADCOGSE and ADCPGSE values than benign tumors (P < 0.001 and < 0.0001, respectively). Significantly larger relative ADC changes were observed in malignant compared with benign head and neck tumors (P < 0.0001). ADCPGSE values were significantly lower than ADCOGSE values in both malignant and benign head and neck tumors (0.97 vs. 1.28 × 10-3 mm2 /s: P < 0.0001 and 1.93 vs. 1.99 × 10-3 mm2 /s: P = 0.0056, respectively). Relative ADC change and ADCPGSE tended to have higher diagnostic performance than ADCOGSE , with area under the curve (AUC) values of 0.97, 0.96, and 0.89, respectively. ADC values obtained using the PGSE sequence were lower than those obtained with OGSE. This difference was larger for malignant than benign tumors, suggesting differences in tissue structure (diffusion hindrance) or cell permeability, revealed by changes in diffusion time. The results underline the potential importance of reporting diffusion time for interpretation of head and neck diffusion MRI. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:88-95.

Changes in the ADC of diffusion-weighted MRI with the oscillating gradient spin-echo (OGSE) sequence due to differences in substrate viscosities.

Compared with the conventional pulsed gradient spin-echo (PGSE) sequence, diffusion-weighted imaging (DWI) with the oscillating gradient spin-echo (OGSE) sequence can shorten the diffusion time by changing the frequency. The purpose was to investigate whether n-alkanes are suitable as isotropic phantoms for estimating the diffusion coefficient with the OGSE sequence. We investigated changes in the apparent diffusion coefficient (ADC) due to differences in the viscosities of nine n-alkane phantoms with different numbers of carbon atoms from C8H18 to C16H34 using OGSE and PGSE sequences at 21°C. Effective diffusion times of 4.3, 5.1, 6.5, 9.3, 20, 40, and 60ms were used. The T2 relaxation times of each n-alkane phantom were measured using quantitative synthetic magnetic resonance imaging (MRI). Circular regions of interest were placed manually within the alkane phantoms on ADC and T2 maps. In each alkane phantom, changes in mean ADC values were almost constant with changes in diffusion times. Viscosities and ADC values showed inverse proportionality, as expected theoretically. The ADC values of alkanes do not depend on diffusion times. The n-alkanes can be useful phantoms for assessing the accuracy of clinical protocols of DWI with the OGSE sequence.

Abstract A22: A window into 3D culture: A multi-modal imaging compatible bioreactor for developing tumor growth models

Abstract Introduction: We aim to use clinical imaging data to initialize and constrain tumor-specific biophysical models of in situ cell proliferation, motility, and therapy response. Towards this goal, we have developed a 3D in vitro cell culture system that can be non-invasively interrogated by both microscopy and magnetic resonance imaging (MRI). The system supports long-term cell growth and allows for control over microenvironmental factors such as drug delivery and extracellular matrix. Cellular and subcellular level data obtained from confocal microscopy define the cell state and local environment and improve interpretation of the lower resolution, clinically relevant information provided by MRI. Here, we report system design and initial data collection. Apparatus Design: The system consists of the bioreactor body, a reservoir with a filter enabling CO2 equilibration in the incubator, and a peristaltic pump to drive media flow throughout the tubing and bioreactor. The bioreactor body has a cavity for cells embedded in extracellular matrix, a hollow-fiber for delivery of nutrients (FiberCell Systems, Frederick, MD), and is sealed using a gasket and lid with a confocal microscopy window. The removable lid makes the bioreactor reusable after sterilization. Data Collection: As a simplified model of 3D tumor growth, we selected the triple negative breast cancer cell line MDA-MB-231 embedded in 0.4% agarose. MDA-MB-231 cells were labeled with H2B-RFP and FUCCI-GFP to image cell nuclei and entry into the cell cycle, respectively, enabling measurements of cell number and cell division. Fluorescence microscopy images were collected on a Zeiss spinning disk confocal microscope using a 20x objective. Sixty 200 μm z -stacks using the green and red channels can be collected in approximately 90 minutes. The bioreactor is secured into a custom microscope mount using screws, ensuring it is placed in the same location every time. A reference point is marked on the first imaging day, to enable longitudinal alignment at subsequent imaging sessions. The bioreactor was also designed for use on a 9.4 T Agilent Technologies (Palo Alto, CA) MRI scanner equipped with a 38-mm quadrature RF coil, which is conventionally used for small animal studies. Diffusion-weighted (DW) images have been acquired using a standard pulsed gradient spin echo sequence with four b values (67, 200, 400, and 800 s/mm2) and gradients applied simultaneously along three orthogonal directions (x , y , and z ). The apparent diffusion coefficient obtained from the DW-MRI data provides an indirect measure of cell number. Images were acquired at a resolution of 100x100x1000 μm3. Conclusion: Overall, we have designed and fabricated a multi-modal imaging compatible bioreactor that supports long-term 3D cell growth under controlled conditions. We have successfully collected both MRI and confocal microscopy data on the bioreactor system at multiple time points. Currently, we are working towards co-registering these two imaging data types and extending the life of the bioreactor. Our novel multi-modal imaging compatible bioreactor is ideal for iterative biophysical tumor model refinement, providing a bridge to predictive models exclusively populated with non-invasive clinical imaging data. Citation Format: Abigail M. Searfoss, Matthew T. McKenna, Vito Quaranta, Thomas E. Yankeelov, Erin C. Rericha. A window into 3D culture: A multi-modal imaging compatible bioreactor for developing tumor growth models. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A22.

Assessing the accuracy of using oscillating gradient spin echo sequences with AxCaliber to infer micron-sized axon diameters.

Current magnetic resonance imaging (MRI) axon diameter measurements rely on the pulsed gradient spin-echo sequence, which is unable to provide diffusion times short enough to measure small axon diameters. This study combines the AxCaliber axon diameter fitting method with data generated from Monte Carlo simulations of oscillating gradient spin-echo sequences (OGSE) to infer micron-sized axon diameters, in order to determine the feasibility of using MRI to infer smaller axon diameters in brain tissue. Monte Carlo computer simulation data were synthesized from tissue geometries of cylinders of different diameters using a range of gradient frequencies in the cosine OGSE sequence . Data were fitted to the AxCaliber method modified to allow the new pulse sequence. Intra- and extra-axonal water were studied separately and together. The simulations revealed the extra-axonal model to be problematic. Rather than change the model, we found that restricting the range of gradient frequencies such that the measured apparent diffusion coefficient was constant over that range resulted in more accurate fitted diameters. Thus a careful selection of frequency ranges is needed for the AxCaliber method to correctly model extra-axonal water, or adaptations to the method are needed. This restriction helped reduce the necessary gradient strengths for measurements that could be performed with parameters feasible for a Bruker BG6 gradient set. For these experiments, the simulations inferred diameters as small as 0.5μm on square-packed and randomly packed cylinders. The accuracy of the inferred diameters was found to be dependent on the signal-to-noise ratio (SNR), with smaller diameters more affected by noise, although all diameter distributions were distinguishable from one another for all SNRs tested. The results of this study indicate the feasibility of using MRI with OGSE on preclinical scanners to infer small axon diameters.

A two-pool model to describe the IVIM cerebral perfusion

IntraVoxel Incoherent Motion (IVIM) is a magnetic resonance imaging (MRI) technique capable of measuring perfusion-related parameters. In this manuscript, we show that the mono-exponential model commonly used to process IVIM data might be challenged, especially at short diffusion times. Eleven rat datasets were acquired at 7T using a diffusion-weighted pulsed gradient spin echo sequence with b-values ranging from 7 to 2500 s/mm2 at three diffusion times. The IVIM signals, obtained by removing the diffusion component from the raw MR signal, were fitted to the standard mono-exponential model, a bi-exponential model and the Kennan model. The Akaike information criterion used to find the best model to fit the data demonstrates that, at short diffusion times, the bi-exponential IVIM model is most appropriate. The results obtained by comparing the experimental data to a dictionary of numerical simulations of the IVIM signal in microvascular networks support the hypothesis that such a bi-exponential behavior can be explained by considering the contribution of two vascular pools: capillaries and somewhat larger vessels.

Severity of spinal cord injury influences diffusion tensor imaging of the brain.

The purpose of this study was to determine whether DTI changes in the brain induced by a thoracic spinal cord injury are sensitive to varying severity of spinal contusion in rats. A control, mild, moderate, or severe contusion injury was administered over the eighth thoracic vertebral level in 32 Sprague-Dawley rats. At 11 weeks postinjury, ex vivo DTI of the brain was performed on a 9.4T Bruker scanner using a pulsed gradient spin-echo sequence. Mean water diffusion in the internal capsule regions of the brain and pyramid locations of the brainstem were correlated with motor function (r(2) = 0.55). Additionally, there were significant differences between injury severity groups for mean diffusivity and fractional anisotropy at regions associated with the corticospinal tract (P = 0.05). These results indicate that DTI is sensitive to changes in brain tissue as a consequence of thoracic SCI.

PGSE, OGSE, and sensitivity to axon diameter in diffusion MRI: Insight from a simulation study.

PurposeTo identify optimal pulsed gradient spin‐echo (PGSE) and oscillating gradient spin‐echo (OGSE) sequence settings for maximizing sensitivity to axon diameter in idealized and practical conditions.MethodsSimulations on a simple two‐compartment white matter model (with nonpermeable cylinders) are used to investigate a wide space of clinically plausible PGSE and OGSE sequence parameters with trapezoidal diffusion gradient waveforms. Signal sensitivity is measured as a derivative of the signal with respect to axon diameter. Models of parallel and dispersed fibers are investigated separately to represent idealized and practical conditions.ResultsSimulations show that, for the simple case of gradients perfectly perpendicular to straight parallel fibers, PGSE always gives maximum sensitivity. However, in real‐world scenarios where fibers have unknown and dispersed orientation, low‐frequency OGSE provides higher sensitivity. Maximum sensitivity results show that on current clinical scanners (G max = 60 mT/m, signal to noise ratio (SNR) = 20) axon diameters below 6 µm are indistinguishable from zero. Scanners with stronger gradient systems such as the Massachusetts General Hospital (MGH) Connectom scanner (G max = 300 mT/m) can extend this sensitivity limit down to 2–3 µm, probing a much greater proportion of the underlying axon diameter distribution.ConclusionLow‐frequency OGSE provides additional sensitivity to PGSE in practical situations. OGSE is particularly advantageous for systems with high performance gradients. Magn Reson Med 75:688–700, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

In vivo measurement of apparent diffusion coefficients of hyperpolarized 13 C-labeled metabolites

The combination of hyperpolarized MRS with diffusion weighting (dw) allows for determination of the apparent diffusion coefficient (ADC), which is indicative of the intra- or extracellular localization of the metabolite. Here, a slice-selective pulsed-gradient spin echo sequence was implemented to acquire a series of dw spectra from rat muscle in vivo to determine the ADCs of multiple metabolites after a single injection of hyperpolarized [1- ¹³C]pyruvate. An optimal control optimized universal-rotation pulse was used for refocusing to minimize signal loss caused by B1 imperfections. Non-dw spectra were acquired interleaved with the dw spectra and these were used to correct for signal decay during the acquisition as a result of T1 decay, pulse imperfections, flow etc. The data showed that the ADC values for [1- ¹³C]lactate (0.4-0.7 µm² /ms) and [1- ¹³C]alanine (0.4-0.9 µm² /ms) were about a factor of two lower than the ADC of [1- ¹³C]pyruvate (1.1-1.5 µm²/ms). This indicates a more restricted diffusion space for the former two metabolites consistent with lactate and alanine being intracellular. The higher ADC for pyruvate (similar to the proton ADC) reflected that the injected substance was not confined inside the muscle cells but also present extracellular.

An efficient eigenfunction approach to calculate spin-echo signals in heterogeneous porous media

An approximate method for solving the Bloch–Torrey equation by surface integrals is developed. The method presents a fast means for calculating pulsed-gradient spin-echo nuclear magnetic resonance signals in porous systems, and it is especially efficient when the surface-to-volume ratio is low. The number of operations for retrieving echo decays scale as O(k2), where k is the number of surface elements. The theory is numerically validated for pulsed-gradient spin-echo sequences on two-dimensional and three-dimensional examples.

Quantitative Measurement of Brain Perfusion with Intravoxel Incoherent Motion MR Imaging

To evaluate the sensitivity of the perfusion parameters derived from Intravoxel Incoherent Motion (IVIM) MR imaging to hypercapnia-induced vasodilatation and hyperoxygenation-induced vasoconstriction in the human brain. This study was approved by the local ethics committee and informed consent was obtained from all participants. Images were acquired with a standard pulsed-gradient spin-echo sequence (Stejskal-Tanner) in a clinical 3-T system by using 16 b values ranging from 0 to 900 sec/mm(2). Seven healthy volunteers were examined while they inhaled four different gas mixtures known to modify brain perfusion (pure oxygen, ambient air, 5% CO(2) in ambient air, and 8% CO(2) in ambient air). Diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), and blood flow-related parameter (fD*) maps were calculated on the basis of the IVIM biexponential model, and the parametric maps were compared among the four different gas mixtures. Paired, one-tailed Student t tests were performed to assess for statistically significant differences. Signal decay curves were biexponential in the brain parenchyma of all volunteers. When compared with inhaled ambient air, the IVIM perfusion parameters D*, f, and fD* increased as the concentration of inhaled CO(2) was increased (for the entire brain, P = .01 for f, D*, and fD* for CO(2) 5%; P = .02 for f, and P = .01 for D* and fD* for CO(2) 8%), and a trend toward a reduction was observed when participants inhaled pure oxygen (although P > .05). D remained globally stable. The IVIM perfusion parameters were reactive to hyperoxygenation-induced vasoconstriction and hypercapnia-induced vasodilatation. Accordingly, IVIM imaging was found to be a valid and promising method to quantify brain perfusion in humans.

Probing mouse brain microstructure using oscillating gradient diffusion MRI

High resolution diffusion tensor images of the mouse brain were acquired using the pulsed gradient spin echo sequence and the oscillating gradient spin echo sequence. The oscillating gradient spin echo tensor images demonstrated frequency-dependent changes in diffusion measurements, including apparent diffusion coefficient and fractional anisotropy, in major brain structures. Maps of the rate of change in apparent diffusion coefficient with oscillating gradient frequency revealed novel tissue contrast in the mouse hippocampus, cerebellum, and cerebral cortex. The observed frequency-dependent contrasts resembled neuronal soma-specific Nissl staining and nuclei-specific 4',6-diamidino-2-phenylindole (DAPI) staining in the mouse brain, which suggests that the contrasts might be related to key features of cytoarchitecture in the brain. In the mouse cuprizone model, oscillating gradient spin echo-based diffusion MRI revealed significantly higher frequency-dependence of perpendicular diffusivity (λ(⊥) ) in the demyelinated caudal corpus callosum at 4 weeks after cuprizone treatment when compared with control mice and mice at 6 weeks after cuprizone treatment. The elevated frequency-dependence of λ(⊥) coincided with the infiltration of activated microglia/macrophages and disruption of axons during acute demyelination in the caudal corpus callosum. The results demonstrate the potential of oscillating gradient spin echo-based diffusion MRI for providing tissue contrasts complimentary to conventional pulsed gradient spin echo-based diffusion MRI.

Evaluating the accuracy and precision of a two-compartment Kärger model using Monte Carlo simulations

Specific parameters of the neuronal tissue microstructure, such as axonal diameters, membrane permeability and intracellular water fractions are assessable using diffusion MRI. These parameters are commonly estimated using analytical models, which may introduce bias in the estimated parameters due to the approximations made when deriving the models. As an alternative to using analytical models, a database of signal curves generated by fast Monte Carlo simulations can be employed. Simulated diffusion MRI measurements were generated and evaluated using the two-compartment Kärger model as well as the simulation model based on a database containing signal curves from approximately 60 000 simulations performed with different combinations of microstructural parameters. A protocol based on a pulsed gradient spin echo sequence with diffusion times of 30 and 60 ms and with gradient amplitudes obtainable with a clinical MRI scanner was employed for the investigations. When using the analytical model, a major negative bias (up to approximately 25%) in the estimated intracellular volume fraction was observed for short exchange times, while almost no bias was seen for the simulation model. In general, the simulation model improved the accuracy of the estimated parameters as compared to the analytical model, except for the exchange time parameter.