Adrienne N. Dula

Multiexponential T2, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord.

Quantitative MRI measures of multiexponential T2 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 T2 relaxation characteristics varied substantially with variation of microanatomy, while the magnetization transfer characteristics remained close to constant. The most‐often‐cited multiexponential T2 relaxation metric, myelin water fraction, varied by almost a factor of 2 between two regions with myelin volume fractions that differed by only ≈ 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 T2 values and is, presumably, a greater factor in white matter regions where axons are small and myelin is thin. In contrast to the multiexponential T2 relaxation observations, magnetization transfer metrics were relatively constant across white matter tracts and concluded to be relatively insensitive to intercompartmental water exchange. Magn Reson Med 63:902–909, 2010.

Amide proton transfer imaging of the breast at 3 T: Establishing reproducibility and possible feasibility assessing chemotherapy response

Chemical exchange saturation transfer imaging can generate contrast that is sensitive to amide protons associated with proteins and peptides (termed amide proton transfer, APT). In breast cancer, APT contrast may report on underlying changes in microstructural tissue composition. However, to date, there have been no developments or applications of APT chemical exchange saturation transfer to breast cancer. As a result, the aims of this study were to (i) experimentally explore optimal scan parameters for breast chemical exchange saturation transfer near the amide resonance at 3 T, (ii) establish the reliability of APT imaging of healthy fibroglandular tissue, and (iii) demonstrate preliminary results on APT changes in locally advanced breast cancer observed during the course of neoadjuvant chemotherapy. Chemical exchange saturation transfer measurements were experimentally optimized on cross‐linked bovine serum albumin phantoms, and the reliability of APT imaging was assessed in 10 women with no history of breast disease. The mean difference between test–retest APT values was not significantly different from zero, and the individual difference values were not dependent on the average APT value. The 95% confidence interval limits were ±0.70% (α = 0.05), and the repeatability was 1.91. APT measurements were also performed in three women before and after one cycle of chemotherapy. Following therapy, APT increased in the one patient with progressive disease and decreased in the two patients with a partial or complete response. Together, these results suggest that APT imaging may report on treatment response in these patients. Magn Reson Med, 2013.

Development of chemical exchange saturation transfer at 7T

Chemical exchange saturation transfer (CEST) MRI is a molecular imaging method that has previously been successful at reporting variations in tissue protein and glycogen contents and pH. We have implemented amide proton transfer (APT), a specific form of chemical exchange saturation transfer imaging, at high field (7T) and used it to study healthy human subjects and patients with multiple sclerosis. The effects of static field inhomogeneities were mitigated using a water saturation shift referencing method to center each z‐spectrum on a voxel‐by‐voxel basis. Contrary to results obtained at lower fields, APT imaging at 7T revealed significant contrast between white and gray matters, with a higher APT signal apparent within the white matter. Preliminary studies of multiple sclerosis showed that the APT asymmetry varied with the type of lesion examined. An increase in APT asymmetry relative to healthy tissue was found in some lesions. These results indicate the potential utility of APT at high field as a noninvasive biomarker of white matter pathology, providing complementary information to other MRI methods in current clinical use. Magn Reson Med, 2011.

Effect of intercompartmental water exchange on the apparent myelin water fraction in multiexponential T2 measurements of rat spinal cord

The myelin water fraction has been used as a quantitative measure of the amount of myelin present in tissue. However, recent work has suggested that intercompartmental exchange of water between myelin and nonmyelin compartments may cause the myelin water fraction to underestimate the true myelin content of tissue. In this work, multiexponential T2 experiments were performed in vivo within the rat spinal cord, and a wide variation of the myelin water fraction (10–35%) was measured within four rat spinal cord tracts with similar myelin content. A numerical simulation based upon segmented histology images was used to quantitatively account for T2 variations between tracts. The model predicts that a difference in exchange between the four spinal cord tracts, mediated by a difference in the average axon radius and myelin thickness, is sufficient to account for the variation in myelin water fraction measured in vivo. Magn Reson Med, 2012.

Amide proton transfer imaging of the human breast at 7T: Development and reproducibility

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. Copyright

Resting state functional connectivity in the human spinal cord

Functional magnetic resonance imaging using blood oxygenation level dependent (BOLD) contrast is well established as one of the most powerful methods for mapping human brain function. Numerous studies have measured how low-frequency BOLD signal fluctuations from the brain are correlated between voxels in a resting state, and have exploited these signals to infer functional connectivity within specific neural circuits. However, to date there have been no previous substantiated reports of resting state correlations in the spinal cord. In a cohort of healthy volunteers, we observed robust functional connectivity between left and right ventral (motor) horns, and between left and right dorsal (sensory) horns. Our results demonstrate that low-frequency BOLD fluctuations are inherent in the spinal cord as well as the brain, and by analogy to cortical circuits, we hypothesize that these correlations may offer insight into the execution and maintenance of sensory and motor functions both locally and within the cerebrum. DOI: http://dx.doi.org/10.7554/eLife.02812.001

Optimal echo spacing for multi-echo imaging measurements of Bi-exponential T2 relaxation.

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.

Quantitative magnetization transfer imaging in human brain at 3 T via selective inversion recovery.

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 kmf. 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 kmf 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. Magn Reson Med, 2011.

The microstructural correlates of T1 in white matter.

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.

Assessment of MRI Issues at 7 T for 28 Implants and Other Objects

OBJECTIVE Metallic implants are currently a contraindication for volunteer subjects and patients referred for 7-T examinations because of concerns related to magnetic field interactions and MRI-related heating. Artifacts may also be problematic. Therefore, the purpose of this investigation was to evaluate these MRI issues for 28 implants and other objects in association with a 7-T MR system. MATERIALS AND METHODS Tests were performed at 7 T using standardized procedures to evaluate magnetic field interactions (translational attraction and torque) for all 28 items. MRI-related heating and artifacts were assessed using spin-echo and gradient-echo pulse sequences, respectively, for two aneurysm clips located within a transmit-receive head radiofrequency coil. RESULTS Eight of the 28 items showed magnetic field interactions at levels that could pose risks to human subjects. The two aneurysm clips exhibited heating, but the temperature rise did not exceed 1°C. Artifacts were dependent on the material and dimensions of each aneurysm clip. CONCLUSION These findings show that certain implants and objects may be acceptable for human subjects undergoing MRI examinations at 7 T, whereas others may involve possible risks. This information has important implications for individuals referred for MRI examinations at 7 T.