In JoVE (1)

Other Publications (48)

Articles by Daniel F. Gochberg in JoVE

 JoVE Medicine

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

1Institute of Imaging Science, Vanderbilt University, 2Department of Radiology and Radiological Sciences, Vanderbilt University, 3Department of Biomedical Engineering, Vanderbilt University, 4Department of Molecular Physiology and Biophysics, Vanderbilt University, 5Department of Physical Medicine and Rehabilitation, Vanderbilt University, 6Department of Physics and Astronomy, Vanderbilt University

JoVE 52352

Other articles by Daniel F. Gochberg on PubMed

Quantitative Imaging of Magnetization Transfer Using an Inversion Recovery Sequence

Magnetic Resonance in Medicine. Mar, 2003  |  Pubmed ID: 12594753

A new imaging method has been developed for quantitatively measuring magnetization transfer (MT). It uses a simple inversion recovery sequence, although one with very short (milliseconds) inversion times, and thus can be implemented on clinical imaging systems with little modification to existing pulse sequences. The sequence requires an inversion pulse with a length much longer than T(2m) (typically 10 micros) and much shorter than T(2f) (typically tens of ms) and 1/k(mf) (typically tens of ms), where T(2m) and T(2f) are the transverse relaxation times of the immobile macromolecular and free water protons, respectively, and k(mf) is the rate of MT between these populations. The resultant NMR signal is sensitive to MT when this inversion pulse affects the mobile and immobile proton pools to different degrees and by appropriate analysis of the signals obtained for different inversion times, quantitative information can be derived on the macromolecular content and exchange rates within the sample. The method has been used in conjunction with echo planar imaging to produce maps of the spatial distribution of the macromolecular content and MT rate in cross-linked bovine serum albumin. Comparisons between this method and other quantitative MT techniques are discussed.

A Quantitative Study of Magnetization Transfer in MAGIC Gels

Physics in Medicine and Biology. Nov, 2003  |  Pubmed ID: 14653567

Magnetization transfer (MT) has been measured quantitatively as a function of radiation dose in MAGIC polymer gels. The MT rates between the free and immobile macromolecular proton pools (kmr and kfm), and the ratio of the sizes of these coupled proton pools (Pm/Pf), were measured by analysing the response to an inversion recovery sequence. While pm/pf increases linearly with dose, the fast MT rate kmf also increases with dose, unlike previous measurements in BANG gels. This dependence of kmf on dose suggests there are additional factors that modify spin exchange in MAGIC gels as irradiation occurs.

Simultaneous Measurement of D and T2 Using the Distant Dipolar Field

Journal of Magnetic Resonance (San Diego, Calif. : 1997). Jan, 2006  |  Pubmed ID: 16243551

The presence of long-range dipolar fields in liquids is known to introduce a non-linear term in the Bloch-Torrey equations which is responsible for many interesting effects in nuclear magnetic resonance as well as in magnetic resonance imaging. We show here, for the first time, that the diffusion coefficient D and the spin-spin relaxation time T2 can be obtained simultaneously from the time evolution profile of the long-range dipolar field refocused signal. In a COSY Revamped by Z-asymmetric Echo Detection sequence, the analytical first-order approximation solution of the Bloch-Torrey equations modified to include the effect of the distant dipolar field is used to demonstrate the technique in an experiment using doped water.

Quantitative Magnetization Transfer Imaging Via Selective Inversion Recovery with Short Repetition Times

Magnetic Resonance in Medicine. Feb, 2007  |  Pubmed ID: 17260381

Quantitative magnetization transfer imaging (qMTI) methods are able to estimate fundamental sample parameters, such as the relative size of the solid-like macromolecular proton pool and the spin exchange rate between this pool and the directly measured free water protons. One such method is selective inversion recovery (SIR), in which the free water protons are selectively inverted and the signal is fit to a biexponential function of the inversion time (TI). SIR uses only low-power pulses and requires no separate RF (B1) or static field (B0) field maps, and the analysis is largely independent of the macromolecular pool lineshape. These are all advantages over steady-state off-resonance saturation qMTI methods. However, up to now, SIR has been implemented only with repetition times TR>T1. This paper describes a modification of SIR with smaller TR values and a greater signal-to-noise ratio (SNR) efficiency.

Assessing Signal Enhancement in Distant Dipolar Field-based Sequences

Journal of Magnetic Resonance (San Diego, Calif. : 1997). Nov, 2007  |  Pubmed ID: 17869560

The possibility of improving the signal-to-noise efficiency of NMR signal refocused by long-range dipolar interactions has been discussed recently [R.T. Branca, G. Galiana, W.S. Warren, Signal enhancement in CRAZED experiments, J. Magn. Reson. 187 (2007) 38-43]. For systems where T(1)>T(2), by including an extra radio-frequency pulse in a standard CRAZED sequence, it is possible to increase the available signal by exploiting its sensitivity to T(1) relaxation. Here, we use analytical calculations to investigate the source of this improved signal and determine the maximum enhancement provided by the method.

Magnetization Transfer Proportion: a Simplified Measure of Dose Response for Polymer Gel Dosimetry

Physics in Medicine and Biology. Dec, 2008  |  Pubmed ID: 19033644

The response to radiation of polymer gel dosimeters has most often been described by measuring the nuclear magnetic resonance transverse relaxation rate as a function of dose. This approach is highly dependent upon the choice of experimental parameters, such as the echo spacing time for Carr-Purcell-Meiboom-Gill-type pulse sequences, and is difficult to optimize in imaging applications where a range of doses are applied to a single gel, as is typical for practical uses of polymer gel dosimetry. Moreover, errors in computing dose can arise when there are substantial variations in the radiofrequency (B1) field or resonant frequency, as may occur for large samples. Here we consider the advantages of using magnetization transfer imaging as an alternative approach and propose the use of a simplified quantity, the magnetization transfer proportion (MTP), to assess doses. This measure can be estimated through two simple acquisitions and is more robust in the presence of some sources of system imperfections. It also has a dependence upon experimental parameters that is independent of dose, allowing simultaneous optimization at all dose levels. The MTP is shown to be less susceptible to B1 errors than are CPMG measurements of R2. The dose response can be optimized through appropriate choices of the power and offset frequency of the pulses used in magnetization transfer imaging.

Optimal Echo Spacing for Multi-echo Imaging Measurements of Bi-exponential T2 Relaxation

Journal of Magnetic Resonance (San Diego, Calif. : 1997). Feb, 2009  |  Pubmed ID: 19028432

Calculations, analytical solutions, and simulations were used to investigate the trade-off of echo spacing and receiver bandwidth for the characterization of bi-exponential transverse relaxation using a multi-echo imaging pulse sequence. The Cramer-Rao lower bound of the standard deviation of the four parameters of a two-pool model was computed for a wide range of component T(2) values and echo spacing. The results demonstrate that optimal echo spacing (TE(opt)) is not generally the minimal available given other pulse sequence constraints. The TE(opt) increases with increasing value of the short T(2) time constant and decreases as the ratio of the long and short time constant decreases. A simple model of TE(opt) as a function of the two T(2) time constants and four empirically derived scalars is presented.

Transverse Relaxation and Magnetization Transfer in Skeletal Muscle: Effect of PH

Magnetic Resonance in Medicine. Mar, 2009  |  Pubmed ID: 19097244

Exercise increases the intracellular T(2) (T(2,i)) of contracting muscles. The mechanism(s) for the T(2,i) increase have not been fully described, and may include increased intracellular free water and acidification. These changes may alter chemical exchange processes between intracellular free water and proteins. In this study, the hypotheses were tested that (a) pH changes T(2,i) by affecting the rate of magnetization transfer (MT) between free intracellular water and intracellular proteins, and (b) the magnitude of the T(2,i) effect depends on acquisition mode (localized or nonlocalized) and echo spacing. Frog gastrocnemius muscles were excised and their intracellular pH was either kept at physiological pH (7.0) or modified to model exercising muscle (pH 6.5). The intracellular transverse relaxation rate (R(2,i) = 1/T(2,i)) always decreased in the acidic muscles, but the changes were greater when measured using more rapid refocusing rates. The MT rate from the macromolecular proton pool to the free water proton pool, its reverse rate, and the spin-lattice relaxation rate of water decreased in acidic muscles. It is concluded that intracellular acidification alters the R(2,i) of muscle water in a refocusing rate-dependent manner, and that the R(2,i) changes are correlated with changes in the MT rate between macromolecules and free intracellular water.

The MT Pool Size Ratio and the DTI Radial Diffusivity May Reflect the Myelination in Shiverer and Control Mice

NMR in Biomedicine. Jun, 2009  |  Pubmed ID: 19123230

A quantitative magnetization transfer (qMT) technique was employed to quantify the ratio of the sizes of the bound and free water proton pools in ex vivo mouse brains. The goal was to determine the pool size ratio sensitivity to myelin. Fixed brains from both shiverer mice and control littermates were imaged. The pool size ratio in the corpus callosum of shiverer mice was substantially lower than that in the control mice, while there was no distinguishable difference in the pool size ratio in the gray matter. These results correlate with diffusion tensor imaging (DTI) derived radial diffusivity which previously was shown to reflect myelin integrity in this animal model. Histological study reveals the presence of myelin in control mice white matter and the absence of myelin in shiverer mice white matter, supporting the qMT and DTI results. Our findings support the view that qMT may be used for estimating myelin integrity.

Quantitative Magnetization Transfer Measured Pool-size Ratio Reflects Optic Nerve Myelin Content in Ex Vivo Mice

Magnetic Resonance in Medicine. Feb, 2009  |  Pubmed ID: 19165898

Optic nerves from mice that have undergone retinal ischemia were examined using a newly implemented quantitative magnetization transfer (qMT) technique. Previously published results indicate that the optic nerve from retinal ischemia mice suffered significant axon degeneration without detectable myelin injury at 3 days after reperfusion. At this time point, we acquired ex vivo qMT parameters from both shiverer mice (which have nearly no myelin) and control mice that have undergone retinal ischemia, and these qMT measures were compared with diffusion tensor imaging (DTI) results. Our findings suggests that the qMT estimated ratio of the pool sizes of the macromolecular and free water protons reflected the different myelin contents in the optic nerves between the shiverer and control mice. This pool size ratio was specific to myelin content only and was not significantly affected by the presence of axon injury in mouse optic nerve 3 days after retinal ischemia.

Nuclear Magnetic Resonance Signal Dynamics of Liquids in the Presence of Distant Dipolar Fields, Revisited

The Journal of Chemical Physics. May, 2009  |  Pubmed ID: 19425789

The description of the nuclear magnetic resonance magnetization dynamics in the presence of long-range dipolar interactions, which is based upon approximate solutions of Bloch-Torrey equations including the effect of a distant dipolar field, has been revisited. New experiments show that approximate analytic solutions have a broader regime of validity as well as dependencies on pulse-sequence parameters that seem to have been overlooked. In order to explain these experimental results, we developed a new method consisting of calculating the magnetization via an iterative formalism where both diffusion and distant dipolar field contributions are treated as integral operators incorporated into the Bloch-Torrey equations. The solution can be organized as a perturbative series, whereby access to higher order terms allows one to set better boundaries on validity regimes for analytic first-order approximations. Finally, the method legitimizes the use of simple analytic first-order approximations under less demanding experimental conditions, it predicts new pulse-sequence parameter dependencies for the range of validity, and clarifies weak points in previous calculations.

Multiexponential T2, Magnetization Transfer, and Quantitative Histology in White Matter Tracts of Rat Spinal Cord

Magnetic Resonance in Medicine. Apr, 2010  |  Pubmed ID: 20373391

Quantitative MRI measures of multiexponential T(2) relaxation and magnetization transfer were acquired from six samples of excised and fixed rat spinal cord and compared with quantitative histology. MRI and histology data were analyzed from six white matter tracts, each of which possessed unique microanatomic characteristics (axon diameter and myelin thickness, in particular) but a relatively constant volume fraction of myelin. The results indicated that multiexponential T(2) relaxation characteristics varied substantially with variation of microanatomy, while the magnetization transfer characteristics remained close to constant. The most-often-cited multiexponential T(2) relaxation metric, myelin water fraction, varied by almost a factor of 2 between two regions with myelin volume fractions that differed by only approximately 12%. Based on the quantitative histology, the proposed explanation for this variation was intercompartmental water exchange, which caused the underestimation of myelin water fraction and T(2) values and is, presumably, a greater factor in white matter regions where axons are small and myelin is thin. In contrast to the multiexponential T(2) relaxation observations, magnetization transfer metrics were relatively constant across white matter tracts and concluded to be relatively insensitive to intercompartmental water exchange.

Optimized Inversion Recovery Sequences for Quantitative T1 and Magnetization Transfer Imaging

Magnetic Resonance in Medicine. Aug, 2010  |  Pubmed ID: 20665793

Inversion recovery sequences that vary the inversion time (t(i)) have been employed to determine T(1) and, more recently, quantitative magnetization transfer parameters. Specifically, in previous work, the inversion recovery pulse sequences varied t(i) only while maintaining a constant delay (t(d)) between repetitions. T(1) values were determined by fitting to a single exponential function, and quantitative magnetization transfer parameters were then determined by fitting to a biexponential function with an approximate solution. In the current study, new protocols are employed, which vary both t(i) and t(d) and fit the data with minimal approximations. Cramer-Rao lower bounds are calculated to search for acquisition schemes that will maximize the precision efficiencies of T(1) and quantitative magnetization transfer parameters. This approach is supported by Monte Carlo simulations. The optimal T(1) schemes are verified by measurements on MnCl(2) samples. The optimal quantitative magnetization transfer schemes are confirmed by measurements on a series of cross-linked bovine serum albumin phantoms of varying concentrations. The effects of varying the number of sampling data points are also explored, and a rapid acquisition scheme is demonstrated in vivo. These new optimized quantitative imaging methods provide an improved means for determining T(1) and magnetization transfer parameter values compared to previous inversion recovery based methods.

RF Coil Considerations for Short-T2 MRI

Magnetic Resonance in Medicine. Dec, 2010  |  Pubmed ID: 20665825

With continuing hardware and pulse sequence advancements, modern MRI is gaining sensitivity to signals from short-T(2) (1)H species under practical experimental conditions. However, conventional MRI coils are typically not designed for this type of application, as they often contain proton-rich construction materials that may contribute confounding (1)H background signal during short-T(2) measurements. An example of this is shown herein. Separately, a loop-gap style coil was used to compare different coil construction materials and configurations with respect to observed (1)H background signal sizes in a small animal imaging system. Background signal sources were spatially identified and quantified in a number of different coil configurations. It was found that the type and placement of structural coil materials around the loop-gap resonator, as well as the coil's shielding configuration, are critical determinants of the coil's background signal size. Although this study employed a loop-gap resonator design, these findings are directly relevant to standard volume coils commonly used for MRI.

Characterization of 1H NMR Signal in Human Cortical Bone for Magnetic Resonance Imaging

Magnetic Resonance in Medicine. Sep, 2010  |  Pubmed ID: 20806375

Recent advancements in MRI have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular-scale sensitivities unavailable to conventional X-ray-based diagnostics. In human cortical bone, MRI is sensitive to populations of protons ((1)H) partitioned among water and protein sources, which may be differentiated according to intrinsic NMR properties such as chemical shift and transverse and longitudinal relaxation rates. Herein, these NMR properties were assessed in human cortical bone donors from a broad age range, and four distinct (1)H populations were consistently identified and attributed to five microanatomical sources. These findings show that modern human cortical bone MRI contrast will be dominated by collagen-bound water, which can also be exploited to study human cortical bone collagen via magnetization transfer.

P130Cas Src-binding and Substrate Domains Have Distinct Roles in Sustaining Focal Adhesion Disassembly and Promoting Cell Migration

PloS One. Oct, 2010  |  Pubmed ID: 20976150

The docking protein p130Cas is a prominent Src substrate found in focal adhesions (FAs) and is implicated in regulating critical aspects of cell motility including FA disassembly and protrusion of the leading edge plasma membrane. To better understand how p130Cas acts to promote these events we examined requirements for established p130Cas signaling motifs including the SH3-binding site of the Src binding domain (SBD) and the tyrosine phosphorylation sites within the substrate domain (SD). Expression of wild type p130Cas in Cas -/- mouse embryo fibroblasts resulted in enhanced cell migration associated with increased leading-edge actin flux, increased rates of FA assembly/disassembly, and uninterrupted FA turnover. Variants lacking either the SD phosphorylation sites or the SBD SH3-binding motif were able to partially restore the migration response, while only a variant lacking both signaling functions was fully defective. Notably, the migration defects associated with p130Cas signaling-deficient variants correlated with longer FA lifetimes resulting from aborted FA disassembly attempts. However the SD mutational variant was fully defective in increasing actin assembly at the protruding leading edge and FA assembly/disassembly rates, indicating that SD phosphorylation is the sole p130Cas signaling function in regulating these processes. Our results provide the first quantitative evidence supporting roles for p130Cas SD tyrosine phosphorylation in promoting both leading edge actin flux and FA turnover during cell migration, while further revealing that the p130Cas SBD has a function in cell migration and sustained FA disassembly that is distinct from its known role of promoting SD tyrosine phosphorylation.

Non-invasive Predictors of Human Cortical Bone Mechanical Properties: T(2)-discriminated H NMR Compared with High Resolution X-ray

PloS One. Jan, 2011  |  Pubmed ID: 21283693

Recent advancements in magnetic resonance imaging (MRI) have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular-scale sensitivities unavailable to conventional X-ray-based diagnostics. To this end, (1)H nuclear magnetic resonance (NMR) and high-resolution X-ray signals from human cortical bone samples were correlated with mechanical properties of bone. Results showed that (1)H NMR signals were better predictors of yield stress, peak stress, and pre-yield toughness than were the X-ray derived signals. These (1)H NMR signals can, in principle, be extracted from clinical MRI, thus offering the potential for improved clinical assessment of fracture risk.

Optimizing Pulsed-chemical Exchange Saturation Transfer Imaging Sequences

Magnetic Resonance in Medicine. Oct, 2011  |  Pubmed ID: 21432903

Chemical exchange saturation transfer (CEST) provides a new imaging contrast mechanism sensitive to labile proton exchange. Pulsed-CEST imaging is better suited to the hardware constraints on clinical imaging systems when compared with traditional continuous wave-CEST imaging methods. However, designing optimum pulsed-CEST imaging sequences entails complicated and time-consuming numerical integrations. In this work, a simplified and computationally efficient technique is provided to optimize the pulsed-CEST imaging sequence. An analysis was performed of the optimal average irradiation power and the optimal irradiation flip angle as a function of the acquisition parameters and sample properties in both a two-pool model and a three-pool model of endogenous amine exchange. Key simulated and experimental results based on a creatine/agar tissue phantom show that (1) the average irradiation power is a more meaningful sequence metric than is the average irradiation field amplitude, (2) the optimal average powers for continuous wave and pulsed-CEST imaging are approximately equal to each other for a relevant range of solute frequency offsets, exchange rates, and concentrations, (3) an irradiation flip angle of 180° is optimal or near optimal, independent of the other acquisition parameters and the sample properties, and (4) higher duty cycles yield higher CEST contrast.

Quantitative Magnetization Transfer Imaging in Human Brain at 3 T Via Selective Inversion Recovery

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Nov, 2011  |  Pubmed ID: 21608030

Quantitative magnetization transfer imaging yields indices describing the interactions between free water protons and immobile, macromolecular protons-including the macromolecular to free pool size ratio (PSR) and the rate of magnetization transfer between pools k(mf) . This study describes the first implementation of the selective inversion recovery quantitative magnetization transfer method on a clinical 3.0-T scanner in human brain in vivo. Selective inversion recovery data were acquired at 16 different inversion times in nine healthy subjects and two patients with relapsing remitting multiple sclerosis. Data were collected using a fast spin-echo readout and reduced repetition time, resulting in an acquisition time of 4 min for a single slice. In healthy subjects, excellent intersubject and intrasubject reproducibilities (assessed via repeated measures) were demonstrated. Furthermore, PSR values in white (mean ± SD = 11.4 ± 1.2%) and gray matter (7.5 ± 0.7%) were consistent with previously reported values, while k(mf) values were approximately 2-fold slower in both white (11 ± 2 s(-1) ) and gray matter (15 ± 6 s(-1) ). In relapsing remitting multiple sclerosis patients, quantitative magnetization transfer indices were sensitive to pathological changes in lesions and in normal appearing white matter.

Exchange-mediated Contrast Agents for Spin-lock Imaging

Magnetic Resonance in Medicine. May, 2012  |  Pubmed ID: 21954094

Measurements of relaxation rates in the rotating frame with spin-locking techniques are sensitive to substances with exchanging protons with appropriate chemical shifts. The authors develop a novel approach to exchange-rate selective imaging based on measured T(1ρ) dispersion with applied locking field strength, and demonstrate the method on samples containing the X-ray contrast agent Iohexol with and without cross-linked bovine serum albumin. T(1ρ) dispersion of water in the phantoms was measured with a Varian 9.4-T magnet by an on-resonance spin-locking pulse with fast spin-echo readout, and the results used to estimate exchange rates. The Iohexol phantom alone gave a fitted exchange rate of ~1 kHz, bovine serum albumin alone was ~11 kHz, and in combination gave rates in between. By using these estimated rates, we demonstrate how a novel spin-locking imaging method may be used to enhance contrast due to the presence of a contrast agent whose protons have specific exchange rates.

Multi-angle Ratiometric Approach to Measure Chemical Exchange in Amide Proton Transfer Imaging

Magnetic Resonance in Medicine. Sep, 2012  |  Pubmed ID: 22161770

Amide proton transfer imaging, a specific form of chemical exchange saturation transfer imaging, has previously been applied to studies of acute ischemic acidosis, stroke, and cancer. However, interpreting the resulting contrast is complicated by its dependence on the exchange rate between amides and water, the amide concentration, amide and water relaxation, and macromolecular magnetization transfer. Hence, conventional chemical exchange saturation transfer contrast is not specific to changes such as reductions in pH due to tissue acidosis. In this article, a multi-angle ratiometric approach based on several pulsed-chemical exchange saturation transfer scans at different irradiation flip angles is proposed to specifically reflect exchange rates only. This separation of exchange effects in pulsed-chemical exchange saturation transfer experiments is based on isolating rotation vs. saturation contributions, and such methods form a new subclass of chemical exchange rotation transfer (CERT) experiments. Simulations and measurements of creatine/agar phantoms indicate that a newly proposed imaging metric isolates the effects of exchange rate changes, independent of other sample parameters.

Clinically Compatible MRI Strategies for Discriminating Bound and Pore Water in Cortical Bone

Magnetic Resonance in Medicine. Dec, 2012  |  Pubmed ID: 22294340

Advances in modern magnetic resonance imaging (MRI) pulse sequences have enabled clinically practical cortical bone imaging. Human cortical bone is known to contain a distribution of T(1) and T(2) components attributed to bound and pore water, although clinical imaging approaches have yet to discriminate bound from pore water based on their relaxation properties. Herein, two clinically compatible MRI strategies are proposed for selectively imaging either bound or pore water by utilizing differences in their T(1)s and T(2)s. The strategies are validated in a population of ex vivo human cortical bones, and estimates obtained for bound and pore water are compared to bone mechanical properties. Results show that the two MRI strategies provide good estimates of bound and pore water that correlate to bone mechanical properties. As such, the strategies for bound and pore water discrimination shown herein should provide diagnostically useful tools for assessing bone fracture risk, once applied to clinical MRI.

A New Method for Detecting Exchanging Amide Protons Using Chemical Exchange Rotation Transfer

Magnetic Resonance in Medicine. Mar, 2013  |  Pubmed ID: 22505325

In this study, we introduce a new method for amide proton transfer imaging based on chemical exchange rotation transfer. It avoids several artifacts that plague conventional chemical exchange saturation transfer approaches by creating label and reference scans based on varying the irradiation pulse rotation angle (π and 2π radians) instead of the frequency offset (3.5 and -3.5 ppm). Specifically, conventional analysis is sensitive to confounding contributions from magnetic field (B(0)) inhomogeneities and, more problematically, inherently asymmetric macromolecular resonances. In addition, the lipid resonance at -3.5 ppm complicates the interpretation of the reference scan and decreases the resulting contrast. Finally, partial overlap of the amide signal by nearby amines and hydroxyls obscure the results. By avoiding these issues, our new method is a promising approach for imaging endogenous protein and peptide content and mapping pH.

Quantitative Magnetization Transfer Imaging of Human Brain at 7 T

NeuroImage. Jan, 2013  |  Pubmed ID: 22940589

Quantitative magnetization transfer (qMT) imaging yields indices describing the interactions between free water protons and immobile macromolecular protons. These indices include the macromolecular to free pool size ratio (PSR), which has been shown to be correlated with myelin content in white matter. Because of the long scan times required for whole-brain imaging (≈20-30 min), qMT studies of the human brain have not found widespread application. Herein, we investigated whether the increased signal-to-noise ratio available at 7.0 T could be used to reduce qMT scan times. More specifically, we developed a selective inversion recovery (SIR) qMT imaging protocol with a i) novel transmit radiofrequency (B(1)(+)) and static field (B(0)) insensitive inversion pulse, ii) turbo field-echo readout, and iii) reduced TR. In vivo qMT data were obtained in the brains of healthy volunteers at 7.0 T using the resulting protocol (scan time≈40 s/slice, resolution=2 × 2 × 3 mm(3)). Reliability was also assessed in repeated acquisitions. The results of this study demonstrate that SIR qMT imaging can be reliably performed within the radiofrequency power restrictions present at 7.0 T, even in the presence of large B(1)(+) and B(0) inhomogeneities. Consistent with qMT studies at lower field strengths, the observed PSR values were higher in white matter (mean±SD=17.6 ± 1.3%) relative to gray matter (10.3 ± 1.6%) at 7.0 T. In addition, regional variations in PSR were observed in white matter. Together, these results suggest that qMT measurements are feasible at 7.0 T and may eventually allow for the high-resolution assessment of changes in composition throughout the normal and diseased human brain in vivo.

The Radial Diffusivity and Magnetization Transfer Pool Size Ratio Are Sensitive Markers for Demyelination in a Rat Model of Type III Multiple Sclerosis (MS) Lesions

NeuroImage. Jul, 2013  |  Pubmed ID: 23481461

Determining biophysical sensitivity and specificity of quantitative magnetic resonance imaging is essential to develop effective imaging metrics of neurodegeneration. Among these metrics, apparent pool size ratio (PSR) from quantitative magnetization transfer (qMT) imaging and radial diffusivity (RD) from diffusion tensor imaging (DTI) are both known to relate to histological measure of myelin density and integrity. However their relative sensitivities towards quantitative myelin detection are unknown. In this study, we correlated high-resolution quantitative magnetic resonance imaging measures of subvoxel tissue structures with corresponding quantitative myelin histology in a lipopolysaccharide (LPS) mediated animal model of MS. Specifically, we acquired quantitative magnetization transfer (qMT) and diffusion tensor imaging (DTI) metrics (on the same tissue sample) in an animal model system of type III oligodendrogliopathy which lacked prominent lymphocytic infiltration, a system that had not been previously examined with quantitative MRI. We find that the qMT measured apparent pool size ratio (PSR) showed the strongest correlation with a histological measure of myelin content. DTI measured RD showed the next strongest correlation, and other DTI and relaxation parameters (such as the longitudinal relaxation rate (R1f) or fractional anisotropy (FA)) showed considerably weaker correlations with myelin content.

Amide Proton Transfer Imaging of the Human Breast at 7T: Development and Reproducibility

NMR in Biomedicine. Oct, 2013  |  Pubmed ID: 23559550

Chemical exchange saturation transfer (CEST) can offer information about protons associated with mobile proteins through the amide proton transfer (APT) effect, which has been shown to discriminate tumor from healthy tissue and, more recently, has been suggested as a prognosticator of response to therapy. Despite this promise, APT effects are small (only a few percent of the total signal), and APT imaging is often prone to artifacts resulting from system instability. Here we present a procedure that enables the detection of APT effects in the human breast at 7T while mitigating these issues. Adequate signal-to-noise ratio (SNR) was achieved via an optimized quadrature RF breast coil and 3D acquisitions. To reduce the influence of fat, effective fat suppression schemes were developed that did not degrade SNR. To reduce the levels of ghosting artifacts, dummy scans have been integrated into the scanning protocol. Compared with results obtained at 3T, the standard deviation of the measured APT effect was reduced by a factor of four at 7T, allowing for the detection of APT effects with a standard deviation of 1% in the human breast at 7T. Together, these results demonstrate that the APT effect can be reliably detected in the healthy human breast with a high level of precision at 7T.

In-vivo Multi-exponential T2, Magnetization Transfer and Quantitative Histology in a Rat Model of Intramyelinic Edema

NeuroImage. Clinical. 2013  |  Pubmed ID: 24179832

Two MRI methods, multi-exponential analysis of transverse relaxation (MET2) and quantitative magnetization transfer (qMT), were used along with quantitative evaluation of histology in a study of intra-myelinic edema in rat spinal white matter. The results showed a strong linear correlation between a distinct long-T2 signal from MET2 analysis and the edema water volume fraction as measured by histology, although this analysis overestimated the edema water content by ≈ 100% relative to quantitative histological measurements. This overestimation was reasoned to result from the effects of inter-compartmental water exchange on observed transverse relaxation. Commonly studied MRI markers for myelin, the myelin water fraction (from MET2 analysis) and the macromolecular pool size ratio (from qMT analysis) produced results that could not be explained purely by changes in myelin content. The results demonstrate the potential for MET2 analysis as well as the limits of putative myelin markers for characterizing white matter abnormalities involving intra-myelinic edema.

Validation of Quantitative Bound- and Pore-water Imaging in Cortical Bone

Magnetic Resonance in Medicine. Jun, 2014  |  Pubmed ID: 23878027

To implement and validate a previously proposed ultra-short echo time method for measuring collagen-bound- and pore-water concentrations in bone based on their T2 differences.

Exchange-mediated Contrast in CEST and Spin-lock Imaging

Magnetic Resonance Imaging. Jan, 2014  |  Pubmed ID: 24239335

Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1ρ) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples.

Imaging Amide Proton Transfer and Nuclear Overhauser Enhancement Using Chemical Exchange Rotation Transfer (CERT)

Magnetic Resonance in Medicine. Aug, 2014  |  Pubmed ID: 24302497

This study investigates amide proton transfer (APT) and nuclear overhauser enhancement (NOE) in phantoms and 9L tumors in rat brains at 9.4 Tesla, using a recently developed method that can isolate different contributions to exchange.

Quantitative Magnetization Transfer Imaging of Rodent Glioma Using Selective Inversion Recovery

NMR in Biomedicine. Mar, 2014  |  Pubmed ID: 24338993

Magnetization transfer (MT) provides an indirect means to detect noninvasively variations in macromolecular contents in biological tissues, but, so far, there have been only a few quantitative MT (qMT) studies reported in cancer, all of which used off-resonance pulsed saturation methods. This article describes the first implementation of a different qMT approach, selective inversion recovery (SIR), for the characterization of tumor in vivo using a rodent glioma model. The SIR method is an on-resonance method capable of fitting qMT parameters and T1 relaxation time simultaneously without mapping B0 and B1 , which is very suitable for high-field qMT measurements because of the lower saturation absorption rate. The results show that the average pool size ratio (PSR, the macromolecular pool versus the free water pool) in rat 9 L glioma (5.7%) is significantly lower than that in normal rat gray matter (9.2%) and white matter (17.4%), which suggests that PSR is potentially a sensitive imaging biomarker for the assessment of brain tumor. Despite being less robust, the estimated MT exchange rates also show clear differences from normal tissues (19.7 Hz for tumors versus 14.8 and 10.2 Hz for gray and white mater, respectively). In addition, the influence of confounding effects, e.g. B1 inhomogeneity, on qMT parameter estimates is investigated with numerical simulations. These findings not only help to better understand the changes in the macromolecular contents of tumors, but are also important for the interpretation of other imaging contrasts, such as chemical exchange saturation transfer of tumors.

Inverse Z-spectrum Analysis for Spillover-, MT-, and T1 -corrected Steady-state Pulsed CEST-MRI--application to PH-weighted MRI of Acute Stroke

NMR in Biomedicine. Mar, 2014  |  Pubmed ID: 24395553

Endogenous chemical exchange saturation transfer (CEST) effects are always diluted by competing effects, such as direct water proton saturation (spillover) and semi-solid macromolecular magnetization transfer (MT). This leads to unwanted T2 and MT signal contributions that lessen the CEST signal specificity to the underlying biochemical exchange processes. A spillover correction is of special interest for clinical static field strengths and protons resonating near the water peak. This is the case for all endogenous CEST agents, such as amide proton transfer, -OH-CEST of glycosaminoglycans, glucose or myo-inositol, and amine exchange of creatine or glutamate. All CEST effects also appear to be scaled by the T1 relaxation time of water, as they are mediated by the water pool. This forms the motivation for simple metrics that correct the CEST signal. Based on eigenspace theory, we propose a novel magnetization transfer ratio (MTRRex ), employing the inverse Z-spectrum, which eliminates spillover and semi-solid MT effects. This metric can be simply related to Rex , the exchange-dependent relaxation rate in the rotating frame, and ka , the inherent exchange rate. Furthermore, it can be scaled by the duty cycle, allowing for simple translation to clinical protocols. For verification, the amine proton exchange of creatine in solutions with different agar concentrations was studied experimentally at a clinical field strength of 3 T, where spillover effects are large. We demonstrate that spillover can be properly corrected and that quantitative evaluation of pH and creatine concentration is possible. This proves that MTRRex is a quantitative and biophysically specific CEST-MRI metric. Applied to acute stroke induced in rat brain, the corrected CEST signal shows significantly higher contrast between the stroke area and normal tissue, as well as less B1 dependence, than conventional approaches.

On the Origins of Chemical Exchange Saturation Transfer (CEST) Contrast in Tumors at 9.4 T

NMR in Biomedicine. Apr, 2014  |  Pubmed ID: 24474497

Chemical exchange saturation transfer (CEST) provides an indirect means to detect exchangeable protons within tissues through their effects on the water signal. Previous studies have suggested that amide proton transfer (APT) imaging, a specific form of CEST, detects endogenous amide protons with a resonance frequency offset 3.5 ppm downfield from water, and thus may be sensitive to variations in mobile proteins/peptides in tumors. However, as CEST measurements are influenced by various confounding effects, such as spillover saturation, magnetization transfer (MT) and MT asymmetry, the mechanism or degree of increased APT signal in tumors is not certain. In addition to APT, nuclear Overhauser enhancement (NOE) effects upfield from water may also provide distinct information on tissue composition. In the current study, APT, NOE and several other MR parameters were measured and compared comprehensively in order to elucidate the origins of APT and NOE contrasts in tumors at 9.4 T. In addition to conventional CEST methods, a new intrinsic inverse metric was applied to correct for relaxation and other effects. After corrections for spillover, MT and T1 effects, corrected APT in tumors was found not to be significantly different from that in normal tissues, but corrected NOE effects in tumors showed significant decreases compared with those in normal tissues. Biochemical measurements verified that there was no significant enhancement of protein contents in the tumors studied, consistent with the corrected APT measurements and previous literature, whereas quantitative MT data showed decreases in the fractions of immobile macromolecules in tumors. Our results may assist in the better understanding of the contrast depicted by CEST imaging in tumors, and in the development of improved APT and NOE measurements for cancer imaging.

Multi-parametric MRI Characterization of Inflammation in Murine Skeletal Muscle

NMR in Biomedicine. Jun, 2014  |  Pubmed ID: 24777935

Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi-parametric, quantitative, non-invasive imaging approaches may be able to resolve these individual pathological components. The goal of this study was to use multi-parametric MRI to investigate inflammation as an isolated pathological feature. Proton relaxation, diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT-MRI), and dynamic contrast enhanced (DCE-MRI) parameters were calculated from data acquired in a single imaging session conducted 6-8 hours following the injection of λ-carrageenan, a local inflammatory agent. T2 increased in the inflamed muscle and transitioned to bi-exponential behavior. In diffusion measurements, all three eigenvalues and the apparent diffusion coefficient increased, but λ3 had the largest relative change. Analysis of the qMT data revealed that the T1 of the free pool and the observed T1 both increased in the inflamed tissue, while the ratio of exchanging spins in the solid pool to those in the free water pool (the pool size ratio) significantly decreased. DCE-MRI data also supported observations of an increase in extracellular volume. These findings enriched the understanding of the relation between multiple quantitative MRI parameters and an isolated inflammatory pathology, and may potentially be employed for other single or complex myopathy models.

Multi-parametric MRI Characterization of Healthy Human Thigh Muscles at 3.0 T - Relaxation, Magnetization Transfer, Fat/water, and Diffusion Tensor Imaging

NMR in Biomedicine. Sep, 2014  |  Pubmed ID: 25066274

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo-pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin-echo T2 imaging (with and without fat signal suppression, FS), selective inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re-imaged an average of 35 days later. Pre-testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between-day intra-class correlations were observed in all quantitative indices except for the macromolecular-to-free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two-way analysis of variance revealed no significant between-day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland-Altman plots, and low repeatability coefficients were obtained for all parameters. Among-muscle differences in the quantitative MRI indices and inter-class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T1 , T2 , fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters.

Imaging of Amide Proton Transfer and Nuclear Overhauser Enhancement in Ischemic Stroke with Corrections for Competing Effects

NMR in Biomedicine. Feb, 2015  |  Pubmed ID: 25483870

Chemical exchange saturation transfer (CEST) potentially provides the ability to detect small solute pools through indirect measurements of attenuated water signals. However, CEST effects may be diluted by various competing effects, such as non-specific magnetization transfer (MT) and asymmetric MT effects, water longitudinal relaxation (T1 ) and direct water saturation (radiofrequency spillover). In the current study, CEST images were acquired in rats following ischemic stroke and analyzed by comparing the reciprocals of the CEST signals at three different saturation offsets. This combined approach corrects the above competing effects and provides a more robust signal metric sensitive specifically to the proton exchange rate constant. The corrected amide proton transfer (APT) data show greater differences between the ischemic and contralateral (non-ischemic) hemispheres. By contrast, corrected nuclear Overhauser enhancements (NOEs) around -3.5 ppm from water change over time in both hemispheres, indicating whole-brain changes that have not been reported previously. This study may help us to better understand the contrast mechanisms of APT and NOE imaging in ischemic stroke, and may also establish a framework for future stroke measurements using CEST imaging with spillover, MT and T1 corrections.

A Combined Analytical Solution for Chemical Exchange Saturation Transfer and Semi-solid Magnetization Transfer

NMR in Biomedicine. Feb, 2015  |  Pubmed ID: 25504828

Off-resonant RF irradiation in tissue indirectly lowers the water signal by saturation transfer processes: on the one hand, there are selective chemical exchange saturation transfer (CEST) effects originating from exchanging endogenous protons resonating a few parts per million from water; on the other hand, there is the broad semi-solid magnetization transfer (MT) originating from immobile protons associated with the tissue matrix with kilohertz linewidths. Recently it was shown that endogenous CEST contrasts can be strongly affected by the MT background, so corrections are needed to derive accurate estimates of CEST effects. Herein we show that a full analytical solution of the underlying Bloch-McConnell equations for both MT and CEST provides insights into their interaction and suggests a simple means to isolate their effects. The presented analytical solution, based on the eigenspace solution of the Bloch-McConnell equations, extends previous treatments by allowing arbitrary lineshapes for the semi-solid MT effects and simultaneously describing multiple CEST pools in the presence of a large MT pool for arbitrary irradiation. The structure of the model indicates that semi-solid MT and CEST effects basically add up inversely in determining the steady-state Z-spectrum, as previously shown for direct saturation and CEST effects. Implications for existing previous CEST analyses in the presence of a semi-solid MT are studied and discussed. It turns out that, to accurately quantify CEST contrast, a good reference Z-value, the observed longitudinal relaxation rate of water, and the semi-solid MT pool size fraction must all be known.

Detection of Microcalcifications by Characteristic Magnetic Susceptibility Effects Using MR Phase Image Cross-correlation Analysis

Medical Physics. Mar, 2015  |  Pubmed ID: 25735297

To develop and evaluate a new method for detecting calcium deposits using their characteristic magnetic susceptibility effects on magnetic resonance (MR) images at high fields and demonstrate its potential in practice for detecting breast microcalcifications.

A Rapid Approach for Quantitative Magnetization Transfer Imaging in Thigh Muscles Using the Pulsed Saturation Method

Magnetic Resonance Imaging. Apr, 2015  |  Pubmed ID: 25839394

Quantitative magnetization transfer (qMT) imaging in skeletal muscle may be confounded by intramuscular adipose components, low signal-to-noise ratios (SNRs), and voluntary and involuntary motion artifacts. Collectively, these issues could create bias and error in parameter fitting. In this study, technical considerations related to these factors were systematically investigated, and solutions were proposed. First, numerical simulations indicate that the presence of an additional fat component significantly underestimates the pool size ratio (F). Therefore, fat-signal suppression (or water-selective excitation) is recommended for qMT imaging of skeletal muscle. Second, to minimize the effect of motion and muscle contraction artifacts in datasets collected with a conventional 14-point sampling scheme, a rapid two-parameter model was adapted from previous studies in the brain and spinal cord. The consecutive pair of sampling points with highest accuracy and precision for estimating F was determined with numerical simulations. Its performance with respect to SNR and incorrect parameter assumptions was systematically evaluated. QMT data fitting was performed in healthy control subjects and polymyositis patients, using both the two- and five-parameter models. The experimental results were consistent with the predictions from the numerical simulations. These data support the use of the two-parameter modeling approach for qMT imaging of skeletal muscle as a means to reduce total imaging time and/or permit additional signal averaging.

The Microstructural Correlates of T1 in White Matter

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Apr, 2015  |  Pubmed ID: 25920491

Several studies have shown strong correlations between myelin content and T1 within the brain, and have even suggested that T1 can be used to estimate myelin content. However, other micro-anatomical features such as compartment size are known to affect longitudinal relaxation rates, similar to compartment size effects in porous media.

In Vivo Quantitative MR Imaging of Bound and Pore Water in Cortical Bone

Radiology. Oct, 2015  |  Pubmed ID: 26020434

To translate and evaluate an in vivo magnetic resonance (MR) imaging protocol for quantitative mapping of collagen-bound and pore water concentrations in cortical bone that involves relaxation-selective ultrashort echo time (UTE) methods.

R1 Correction in Amide Proton Transfer Imaging: Indication of the Influence of Transcytolemmal Water Exchange on CEST Measurements

NMR in Biomedicine. Dec, 2015  |  Pubmed ID: 26466161

Amide proton transfer (APT) imaging may potentially detect mobile proteins/peptides non-invasively in vivo, but its specificity may be reduced by contamination from other confounding effects such as asymmetry of non-specific magnetization transfer (MT) effects and spin-lattice relaxation with rate R1 (=1/T1). Previously reported spillover, MT and R1 correction methods were based on a two-pool model, in which the existence of multiple water compartments with heterogeneous relaxation properties in real tissues was ignored. Such simple models may not adequately represent real tissues, and thus such corrections may be unreliable. The current study investigated the effectiveness and accuracy of correcting for R1 in APT imaging via simulations and in vivo experiments using tumor-bearing rats subjected to serial injections of Gd-DTPA that produced different tissue R1 values in regions of blood-brain-barrier breakdown. The results suggest that conventional measurements of APT contrast (such as APT* and MTRasym ) may be significantly contaminated by R1 variations, while the R1 -corrected metric AREX* was found to be relatively unaffected by R1 changes over a broad range (0.4-1 Hz). Our results confirm the importance of correcting for spin-lattice relaxation effects in quantitative APT imaging, and demonstrate the reliability of using the observed tissue R1 for corrections to obtain more specific and accurate measurements of APT contrast in vivo. The results also indicate that, due to relatively fast transcytolemmal water exchange, the influence of intra- and extracellular water compartments on CEST measurements with seconds long saturation time may be ignored in tumors.

In Vivo Quantitative MR Imaging of Bound and Pore Water in Cortical Bone

Radiology. Dec, 2015  |  Pubmed ID: 26599934

Influence of Water Compartmentation and Heterogeneous Relaxation on Quantitative Magnetization Transfer Imaging in Rodent Brain Tumors

Magnetic Resonance in Medicine. Aug, 2016  |  Pubmed ID: 26375875

The goal of this study was to investigate the influence of water compartmentation and heterogeneous relaxation properties on quantitative magnetization transfer (qMT) imaging in tissues, and in particular whether a two-pool model is sufficient to describe qMT data in brain tumors.

Evaluation of Diffusion Kurtosis Imaging in Ex Vivo Hypomyelinated Mouse Brains

NeuroImage. Jan, 2016  |  Pubmed ID: 26400013

Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and DKI-derived white matter tract integrity metrics (WMTI) were experimentally evaluated ex vivo through comparisons to histological measurements and established magnetic resonance imaging (MRI) measures of myelin in two knockout mouse models with varying degrees of hypomyelination. DKI metrics of mean and radial kurtosis were found to be better indicators of myelin content than conventional DTI metrics. The biophysical WMTI model based on the DKI framework reported on axon water fraction with good accuracy in cases with near normal axon density, but did not provide additional specificity to myelination. Overall, DKI provided additional information regarding white matter microstructure compared with DTI, making it an attractive method for future assessments of white matter development and pathology.

MRI-derived Bound and Pore Water Concentrations As Predictors of Fracture Resistance

Bone. Jun, 2016  |  Pubmed ID: 26993059

Accurately predicting fracture risk in the clinic is challenging because the determinants are multi-factorial. A common approach to fracture risk assessment is to combine X-ray-based imaging methods such as dual-energy X-ray absorptiometry (DXA) with an online Fracture Risk Assessment Tool (FRAX) that includes additional risk factors such as age, family history, and prior fracture incidents. This approach still does not adequately diagnose many individuals at risk, especially those with certain diseases like type 2 diabetes. As such, this study investigated bound water and pore water concentrations (Cbw and Cpw) from ultra-short echo time (UTE) magnetic resonance imaging (MRI) as new predictors of fracture risk. Ex vivo cadaveric arms were imaged with UTE MRI as well as with DXA and high-resolution micro-computed tomography (μCT), and imaging measures were compared to both whole-bone structural and material properties as determined by three-point bending tests of the distal-third radius. While DXA-derived areal bone mineral density (aBMD) and μCT-derived volumetric BMD correlated well with structural strength, they moderately correlated with the estimate material strength with gender being a significant covariate for aBMD. MRI-derived measures of Cbw and Cpw had a similar predictive ability of material strength as aBMD but did so independently of gender. In addition, Cbw was the only imaging parameter to significantly correlate with toughness, the energy dissipated during fracture. Notably, the strength of the correlations with the material properties of bone tended to be higher when a larger endosteal region was used to determine Cbw and Cpw. These results indicate that MRI measures of Cbw and Cpw have the ability to probe bone material properties independent of bone structure or subject gender. In particular, toughness is a property of fracture resistance that is not explained by X-ray based methods. Thus, these MRI-derived measures of Cbw and Cpw in cortical bone have the potential to be useful in clinical populations for evaluating fracture risk, especially involving diseases that affect material properties of the bone beyond its strength.

A New NOE-mediated MT Signal at Around -1.6ppm for Detecting Ischemic Stroke in Rat Brain

Magnetic Resonance Imaging. Oct, 2016  |  Pubmed ID: 27211260

In the present work, we reported a new nuclear Overhauser enhancement (NOE)-mediated magnetization transfer (MT) signal at around -1.6ppm (NOE(-1.6)) in rat brain and investigated its application in the detection of acute ischemic stroke in rodent model. Using continuous wave (CW) MT sequence, the NOE(-1.6) is reliably detected in rat brain. The amplitude of this new NOE signal in rat brain was quantified using a 5-pool Lorentzian Z-spectral fitting method. Amplitudes of amide, amine, NOE at -3.5ppm (NOE(-3.5)), as well as NOE(-1.6) were mapped using this fitting method in rat brain. Several other conventional imaging parameters (R1, R2, apparent diffusion coefficient (ADC), and semi-solid pool size ratio (PSR)) were also measured. Our results show that NOE(-1.6), R1, R2, ADC, and APT signals from stroke lesion have significant changes at 0.5-1h after stroke. Compared with several other imaging parameters, NOE(-1.6) shows the strongest contrast differences between stroke and contralateral normal tissues and stays consistent over time until 2h after onset of stroke. Our results demonstrate that this new NOE(-1.6) signal in rat brain is a new potential contrast for assessment of acute stroke in vivo and might provide broad applications in the detection of other abnormal tissues.

MR Imaging of a Novel NOE-mediated Magnetization Transfer with Water in Rat Brain at 9.4 T

Magnetic Resonance in Medicine. Sep, 2016  |  Pubmed ID: 27604612

To detect, map, and quantify a novel nuclear Overhauser enhancement (NOE)-mediated magnetization transfer (MT) with water at approximately -1.6 ppm [NOE(-1.6)] in rat brain using MRI.

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