Depth-dependent intracortical myelin organization in the living human brain determined by in vivo ultra-high field magnetic resonance imaging.

BACKGROUND: Intracortical myelin is a key determinant of neuronal synchrony and plasticity that underpin optimal brain function. Magnetic resonance imaging (MRI) facilitates the examination of intracortical myelin but presents with methodological challenges. Here we describe a whole-brain approach for the in vivo investigation of intracortical myelin in the human brain using ultra-high field MRI. METHODS: Twenty-five healthy adults were imaged in a 7 Tesla MRI scanner using diffusion-weighted imaging and a T1-weighted sequence optimized for intracortical myelin contrast. Using an automated pipeline, T1 values were extracted at 20 depth-levels from each of 148 cortical regions. In each cortical region, T1 values were used to infer myelin concentration and to construct a non-linearity index as a measure the spatial distribution of myelin across the cortical ribbon. The relationship of myelin concentration and the non-linearity index with other neuroanatomical properties were investigated. Five patients with multiple sclerosis were also assessed using the same protocol as positive controls. RESULTS: Intracortical T1 values decreased between the outer brain surface and the gray-white matter boundary following a slope that showed a slight leveling between 50% and 75% of cortical depth. Higher-order regions in the prefrontal, cingulate and insular cortices, displayed higher non-linearity indices than sensorimotor regions. Across all regions, there was a positive association between T1 values and non-linearity indices (P < 10-5). Both T1 values (P < 10-5) and non-linearity indices (P < 10-15) were associated with cortical thickness. Higher myelin concentration but only in the deepest cortical levels was associated with increased subcortical fractional anisotropy (P = 0.05). CONCLUSIONS: We demonstrate the usefulness of an automatic, whole-brain method to perform depth-dependent examination of intracortical myelin organization. The extracted metrics, T1 values and the non-linearity index, have characteristic patterns across cortical regions, and are associated with thickness and underlying white matter microstructure.

The quest for high spatial resolution diffusion-weighted imaging of the human brain in vivo.

Diffusion-weighted imaging, a contrast unique to MRI, is used for assessment of tissue microstructure in vivo. However, this exquisite sensitivity to finer scales far above imaging resolution comes at the cost of vulnerability to errors caused by sources of motion other than diffusion motion. Addressing the issue of motion has traditionally limited diffusion-weighted imaging to a few acquisition techniques and, as a consequence, to poorer spatial resolution than other MRI applications. Advances in MRI imaging methodology have allowed diffusion-weighted MRI to push to ever higher spatial resolution. In this review we focus on the pulse sequences and associated techniques under development that have pushed the limits of image quality and spatial resolution in diffusion-weighted MRI.

Reproducibility of myelin content-based human habenula segmentation at 3 Tesla.

In vivo morphological study of the human habenula, a pair of small epithalamic nuclei adjacent to the dorsomedial thalamus, has recently gained significant interest for its role in reward and aversion processing. However, segmenting the habenula from in vivo magnetic resonance imaging (MRI) is challenging due to the habenula's small size and low anatomical contrast. Although manual and semi-automated habenula segmentation methods have been reported, the test-retest reproducibility of the segmented habenula volume and the consistency of the boundaries of habenula segmentation have not been investigated. In this study, we evaluated the intra- and inter-site reproducibility of in vivo human habenula segmentation from 3T MRI (0.7-0.8 mm isotropic resolution) using our previously proposed semi-automated myelin contrast-based method and its fully-automated version, as well as a previously published manual geometry-based method. The habenula segmentation using our semi-automated method showed consistent boundary definition (high Dice coefficient, low mean distance, and moderate Hausdorff distance) and reproducible volume measurement (low coefficient of variation). Furthermore, the habenula boundary in our semi-automated segmentation from 3T MRI agreed well with that in the manual segmentation from 7T MRI (0.5 mm isotropic resolution) of the same subjects. Overall, our proposed semi-automated habenula segmentation showed reliable and reproducible habenula localization, while its fully-automated version offers an efficient way for large sample analysis.

Ultrahigh field single-refocused diffusion weighted imaging using a matched-phase adiabatic spin echo (MASE).

PURPOSE: To improve ultrahigh field diffusion-weighted imaging (DWI) in the presence of inhomogeneous transmit B1 field by designing a novel semi-adiabatic single-refocused DWI technique. METHODS: A 180° slice-selective, adiabatic radiofrequency (RF) pulse of 4 ms duration was designed using the adiabatic Shinnar-Le Roux algorithm. A matched-phase slice-selective 90° RF pulse of 8 ms duration was designed to compensate the nonlinear phase of the adiabatic 180° RF pulse. The resulting RF pulse combination, matched-phase adiabatic spin echo (MASE), was integrated into a single-shot echo planar DWI sequence. The performance of this sequence was compared with single-refocused Stejskal-Tanner (ST), twice-refocused spin echo (TRSE) and twice-refocused adiabatic spin echo (TRASE) in simulations, phantoms, and healthy volunteers at 7 Tesla (T). RESULTS: In regions with inhomogeneous B1 , MASE resulted in increased signal intensity compared with ST (up to 64%). Moderate increase in specific absorption rate (35-39%) was observed for adiabatic RF pulses. MASE resulted in higher signal homogeneity at 7T, leading to improved visualization of measures derived from diffusion-weighted images such as white matter tractography and track density images. CONCLUSION: Efficient adiabatic SLR pulses can be adapted to single-refocused DWI, leading to substantially improved signal uniformity when compared with conventional acquisitions.

Real-time correction of rigid body motion-induced phase errors for diffusion-weighted steady-state free precession imaging.

PURPOSE: Diffusion contrast in diffusion-weighted steady-state free precession magnetic resonance imaging (MRI) is generated through the constructive addition of signal from many coherence pathways. Motion-induced phase causes destructive interference which results in loss of signal magnitude and diffusion contrast. In this work, a three-dimensional (3D) navigator-based real-time correction of the rigid body motion-induced phase errors is developed for diffusion-weighted steady-state free precession MRI. METHODS: The efficacy of the real-time prospective correction method in preserving phase coherence of the steady state is tested in 3D phantom experiments and 3D scans of healthy human subjects. RESULTS: In nearly all experiments, the signal magnitude in images obtained with proposed prospective correction was higher than the signal magnitude in images obtained with no correction. In the human subjects, the mean magnitude signal in the data was up to 30% higher with prospective motion correction than without. Prospective correction never resulted in a decrease in mean signal magnitude in either the data or in the images. CONCLUSIONS: The proposed prospective motion correction method is shown to preserve the phase coherence of the steady state in diffusion-weighted steady-state free precession MRI, thus mitigating signal magnitude losses that would confound the desired diffusion contrast.

Signal-to-noise ratio for hyperpolarized ³He MR imaging of human lungs: a 1.5 T and 3 T comparison.

The signal-to-noise ratio in hyperpolarized noble gas MR imaging is expected to be independent of field strength at frequencies typical of clinical systems (e.g., 1.5 T), where body noise dominates over coil noise. Furthermore, at higher fields (e.g., 3 T), the SNR of lung images may decline due to decreases in T(2) originating from increases in susceptibility-induced field gradients at the air-tissue interface. In this work, the SNR of hyperpolarized (3) He lung imaging at two commonly used clinical field strengths (1.5 T and 3 T) were compared in the same volunteers. Thermally polarized and hyperpolarized (3) He phantoms were used to account for differences in MR imaging system and (3) He polarizer performance, respectively, at the two field strengths. After correcting for T(2) values measured at 1.5 T (16 ± 2 ms) and 3 T (7 ± 1 ms), no significant difference in image SNR between the two field strengths was observed, consistent with theory.

Helium-3 MR q-space imaging with radial acquisition and iterative highly constrained back-projection.

An undersampled diffusion-weighted stack-of-stars acquisition is combined with iterative highly constrained back-projection to perform hyperpolarized helium-3 MR q-space imaging with combined regional correction of radiofrequency- and T1-related signal loss in a single breath-held scan. The technique is tested in computer simulations and phantom experiments and demonstrated in a healthy human volunteer with whole-lung coverage in a 13-sec breath-hold. Measures of lung microstructure at three different lung volumes are evaluated using inhaled gas volumes of 500 mL, 1000 mL, and 1500 mL to demonstrate feasibility. Phantom results demonstrate that the proposed technique is in agreement with theoretical values, as well as with a fully sampled two-dimensional Cartesian acquisition. Results from the volunteer study demonstrate that the root mean squared diffusion distance increased significantly from the 500-mL volume to the 1000-mL volume. This technique represents the first demonstration of a spatially resolved hyperpolarized helium-3 q-space imaging technique and shows promise for microstructural evaluation of lung disease in three dimensions.

Ultrashort TE spectroscopic imaging (UTESI) using complex highly-constrained backprojection with local reconstruction (HYPR LR).

Recently, the highly-constrained backprojection (HYPR) and HYPR with local reconstruction (HYPR LR) methods have been introduced to reconstruct magnitude images from a series of highly undersampled data while preserving high spatial and temporal resolution and high signal-to-noise ratio (SNR) in applications with spatiotemporal correlations. However, these conventional HYPR algorithms are limited to the generation of magnitude images and, therefore, have limitations in their potential applications. In this work, the HYPR LR algorithm has been modified to extend the use of algorithms in the HYPR family to applications that require processing of complex data, such as MR chemical shift imaging (CSI) or spectroscopic imaging. The proposed method processes the magnitude information the same way as in original HYPR LR processing. In addition, it improves the phase images by subtracting the phase map of a synthesized composite image. The feasibility and efficiency of this algorithm has been demonstrated on CSI of cortical bone, Achilles tendon, and a healthy volunteer on a clinical 3T scanner.

Three-dimensional imaging of ventilation dynamics in asthmatics using multiecho projection acquisition with constrained reconstruction.

The purpose of this work is to detect dynamic gas trapping in three dimensions during forced exhalation at isotropic high spatial resolution and high temporal resolution using hyperpolarized helium-3 MRI. Ten subjects underwent hyperpolarized helium-3 MRI and multidetector CT. MRI was performed throughout inspiration, breath-hold, and forced expiration. A multiecho three-dimensional projection acquisition was used to improve data collection efficiency and an iterative constrained reconstruction was implemented to improve signal to noise ratio (SNR) and increase robustness to motion. Two radiologists evaluated the dynamic MRI and breath-held multidetector CT data for gas and air trapping, respectively. Phantom studies showed the proposed technique significantly improved depiction of moving objects compared to view-sharing methods. Gas trapping was detected using MRI in five of the six asthmatic subjects who displayed air trapping with multidetector CT. Locations in disagreement were found to represent small to moderate regions of air trapping. The proposed technique provides whole-lung three-dimensional imaging of respiration dynamics at high spatial and temporal resolution and compares well to the current standard, multidetector CT. While multidetector CT can provide information about static regional air trapping, it is unable to depict dynamics in a setting more comparable to a spirometry maneuver and explore the longitudinal time evolution of the trapped regions.

Iron concentration linked to structural connectivity in the subthalamic nucleus: implications for deep brain stimulation.

OBJECTIVE: The objective of this study was to investigate the relationship between iron and white matter connectivity in the subthalamic nucleus (STN) in patients undergoing deep brain stimulation (DBS) of the STN for treatment of Parkinson's disease. METHODS: Nine Parkinson's disease patients underwent preoperative 3T MRI imaging which included acquisition of T1-weighted anatomical images along with diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM). MR tractography was performed for the seed voxels located within the STN, and the correlations between normalized QSM values and the STN's connectivity to a set of a priori chosen regions of interest were assessed. RESULTS: A strong negative correlation was found between STN connectivity and QSM intensity for the thalamus, premotor, motor, and sensory regions, while a strong positive correlation was found for frontal, putamen, and brain stem areas. CONCLUSIONS: Quantitative susceptibility mapping not only accurately delineates the STN borders but is also able to provide functional information about the STN functional subdivisions. The observed iron-to-connectivity correlation patterns may aid in planning DBS surgery to avoid unwanted side effects associated with DBS.

Reduced field of view echo-planar imaging diffusion tensor MRI for pediatric spinal tumors.

OBJECTIVE: Spine MRI is a diagnostic modality for evaluating pediatric CNS tumors. Applying diffusion-weighted MRI (DWI) or diffusion tensor imaging (DTI) to the spine poses challenges due to intrinsic spinal anatomy that exacerbates various image-related artifacts, such as signal dropouts or pileups, geometrical distortions, and incomplete fat suppression. The zonal oblique multislice (ZOOM)-echo-planar imaging (EPI) technique reduces geometric distortion and image blurring by reducing the field of view (FOV) without signal aliasing into the FOV. The authors hypothesized that the ZOOM-EPI method for spine DTI in concert with conventional spinal MRI is an efficient method for augmenting the evaluation of pediatric spinal tumors. METHODS: Thirty-eight consecutive patients (mean age 8 years) who underwent ZOOM-EPI spine DTI for CNS tumor workup were retrospectively identified. Patients underwent conventional spine MRI and ZOOM-EPI DTI spine MRI. Two blinded radiologists independently reviewed two sets of randomized images: conventional spine MRI without ZOOM-EPI DTI, and conventional spine MRI with ZOOM-EPI DTI. For both image sets, the reviewers scored the findings based on lesion conspicuity and diagnostic confidence using a 5-point Likert scale. The reviewers also recorded presence of tumors. Quantitative apparent diffusion coefficient (ADC) measurements of various spinal tumors were extracted. Tractography was performed in a subset of patients undergoing presurgical evaluation. RESULTS: Sixteen patients demonstrated spinal tumor lesions. The readers were in moderate agreement (kappa = 0.61, 95% CI 0.30-0.91). The mean scores for conventional MRI and combined conventional MRI and DTI were as follows, respectively: 3.0 and 4.0 for lesion conspicuity (p = 0.0039), and 2.8 and 3.9 for diagnostic confidence (p < 0.001). ZOOM-EPI DTI identified new lesions in 3 patients. In 3 patients, tractography used for neurosurgical planning showed characteristic fiber tract projections. The mean weighted ADCs of low- and high-grade tumors were 1201 × 10-6 and 865 × 10-6 mm2/sec (p = 0.002), respectively; the mean minimum weighted ADCs were 823 × 10-6 and 474 × 10-6 mm2/sec (p = 0.0003), respectively. CONCLUSIONS: Diffusion MRI with ZOOM-EPI can improve the detection of spinal lesions while providing quantitative diffusion information that helps distinguish low- from high-grade tumors. By adding a 2-minute DTI scan, quantitative diffusion information and tract profiles can reliably be obtained and serve as a useful adjunct to presurgical planning for pediatric spinal tumors.

The effects of SNR on ADC measurements in diffusion-weighted hyperpolarized He-3 MRI.

The theoretical dependence of the mean and standard deviation of ADC values on signal-to-noise ratio (SNR) was derived and compared to measured values in porous phantoms and the lungs of human subjects using diffusion-weighted hyperpolarized helium-3 MRI. For SNR values below 15, mean ADC values were highly SNR-dependent due to a combination of noise and choice of noise thresholding. Above SNR values of 15 and for mean ADC values within ranges relevant for evaluating lung disease (<0.6 cm2/s), the mean ADC was largely independent of SNR. The standard deviation, by contrast, was highly dependent on SNR over a much larger range, but this dependence was well predicted by theory, suggesting the histogram of ADC values might be corrected for these stochastic processes to more accurately evaluate disease using restricted diffusion measures in the lungs.

A method for u-fiber quantification from 7 T diffusion-weighted MRI data tested in patients with nonlesional focal epilepsy.

In this methods development, we present an ultra-high-field, diffusion-weighted MRI method to quantitatively assess u-fibers and use it to compare u-fiber counts in nonlesional epilepsy patients with controls. Emerging evidence implicates white matter abnormalities in nonlesional epilepsy, including the short-range, cortical-cortical connections, or u-fibers. Eight patients with nonlesional epilepsy and eight demographically matched controls underwent 7 T MRI consisting of a T1-weighted sequence (0.7 mm isotropic resolution) and high-angular-resolved diffusion-weighted MRI (1.05 mm isotropic resolution, 68 directions). MRI data were used to quantify u-fiber counts in known u-fiber populations on the basis of an atlas and fiber tractography. From tractography, connectivity matrices summarizing the u-fiber counts were computed. Quantitative group comparisons were performed on the connectivity matrices. U-fiber counts were found to be lower on average in patients with epilepsy than in healthy controls. The results indicate that the density or the number of u-fibers is reduced in patients with nonlesional epilepsy. Future work will focus on histological validation and determining whether differences in u-fiber counts can be used clinically to noninvasively identify seizure-onset zones.

Case Study of Image-Guided Deep Brain Stimulation: Magnetic Resonance Imaging-Based White Matter Tractography Shows Differences in Responders and Nonresponders.

BACKGROUND: The caudal zona incerta (cZI) is an increasingly popular deep brain stimulation (DBS) target for the treatment of tremor-predominant disease. The dentatorubrothalamic tract (DRTT) is a white matter fiber bundle that traverses the cZI and can be identified using diffusion-weighted magnetic resonance imaging fiber tractography to ascertain its precise course. In this report, we compare 2 patient cases of cZI DBS, a responder and a nonresponder. CASE DESCRIPTION: Patient 1 (responder) is a 65-year-old man with medically refractory Parkinson disease who underwent bilateral DBS lead placement in the cZI. Postoperatively he demonstrated >90% reduction in baseline tremor and was not limited by stimulation side effects. Postoperative imaging showed correct lead placement in the cZI. Tractography revealed a DRTT within the field of stimulation, bilaterally. Patient 2 (nonresponder) is a 61-year-old man with medically refractory Parkinson disease who also underwent bilateral DBS lead placement in the cZI. He initially demonstrated >90% reduction in baseline tremor but developed disabling dystonia of his left leg and significant slurring of his speech in the months after surgery. Postoperative imaging showed bilateral lead placement in the cZI. Right-sided electrode revision was recommended and resulted in relief of tremor and reduced dystonic side effects. Tractography analysis of the original leads revealed a DRTT with an atypical anterior trajectory and a location outside the field of stimulation. Tractography analysis of the revised lead showed a DRTT within the field of stimulation. CONCLUSIONS: Preoperative diffusion-weighted magnetic resonance imaging fiber tractography imaging of the DRTT has the potential to improve and individualize DBS planning.

Multimodal Neuroimaging-Informed Clinical Applications in Neuropsychiatric Disorders.

Recent advances in neuroimaging data acquisition and analysis hold the promise to enhance the ability to make diagnostic and prognostic predictions and perform treatment planning in neuropsychiatric disorders. Prior research using a variety of types of neuroimaging techniques has confirmed that neuropsychiatric disorders are associated with dysfunction in anatomical and functional brain circuits. We first discuss current challenges associated with the identification of reliable neuroimaging markers for diagnosis and prognosis in mood disorders and for neurosurgical treatment planning for deep brain stimulation (DBS). We then present data on the use of neuroimaging for the diagnosis and prognosis of mood disorders and for DBS treatment planning. We demonstrate how multivariate analyses of functional activation and connectivity parameters can be used to differentiate patients with bipolar disorder from those with major depressive disorder and non-affective psychosis. We also present data on connectivity parameters that mediate acute treatment response in affective and non-affective psychosis. We then focus on precision mapping of functional connectivity in native space. We describe the benefits of integrating anatomical fiber reconstruction with brain functional parameters and cortical surface measures to derive anatomically informed connectivity metrics within the morphological context of each individual brain. We discuss how this approach may be particularly promising in psychiatry, given the clinical and etiological heterogeneity of the disorders, and particularly in treatment response prediction and planning. Precision mapping of connectivity is essential for DBS. In DBS, treatment electrodes are inserted into positions near key gray matter nodes within the circuits considered relevant to disease expression. However, targeting white matter tracts that underpin connectivity within these circuits may increase treatment efficacy and tolerability therefore relevant for effective treatment. We demonstrate how this approach can be validated in the treatment of Parkinson's disease by identifying connectivity patterns that can be used as biomarkers for treatment planning and thus refine the traditional approach of DBS planning that uses only gray matter landmarks. Finally, we describe how this approach could be used in planning DBS treatment of psychiatric disorders.

Iterative projection reconstruction of time-resolved images using highly-constrained back-projection (HYPR).

Highly-constrained back-projection (HYPR) is a technique for the reconstruction of sparse, highly-undersampled time-resolved image data. A novel iterative HYPR (I-HYPR) algorithm is presented and validated in computer simulations. The reconstruction method is then applied to cerebral perfusion MRI simulated as a radial acquisition and contrast-enhanced angiography of the head to assess feasibility in accelerating acquisitions requiring high temporal resolution and accurate representation of contrast kinetics. The I-HYPR algorithm is shown to be more robust than standard HYPR in these applications in which the sparsity condition is not met or in which quantitative information is required. Specifically, iterative reconstruction of undersampled perfusion and contrast-enhanced angiography data improved accuracy of the representation of contrast kinetics and increased the temporal separation of arterial and venous contrast kinetics. The I-HYPR reconstruction may have important diagnostic applications in settings requiring high temporal resolution and quantitative signal dynamics. Because I-HYPR allows relaxation of the sparsity requirements for the composite frame, the iterative reconstruction can enable novel acquisition strategies that independently optimize the quality of the composite and temporal resolution of the dynamic frames.

3D hyperpolarized He-3 MRI of ventilation using a multi-echo projection acquisition.

A method is presented for high-resolution 3D imaging of the whole lung using inhaled hyperpolarized (HP) He-3 MR with multiple half-echo radial trajectories that can accelerate imaging through undersampling. A multiple half-echo radial trajectory can be used to reduce the level of artifact for undersampled 3D projection reconstruction (PR) imaging by increasing the amount of data acquired per unit time for HP He-3 lung imaging. The point spread functions (PSFs) for breath-held He-3 MRI using multiple half-echo trajectories were evaluated using simulations to predict the effects of T(2)* and gas diffusion on image quality. Results from PSF simulations were consistent with imaging results in volunteer studies showing improved image quality with increasing number of echoes using up to 8 half-echoes. The 8-half-echo acquisition is shown to accommodate lost breath-holds as short as 6 sec using a retrospective reconstruction at reduced resolution and also to allow reduced breath-hold time compared with an equivalent Cartesian trajectory. Furthermore, preliminary results from a 3D dynamic inhalation-exhalation maneuver are demonstrated using the 8-half-echo trajectory. Results demonstrate the first high-resolution 3D PR imaging of ventilation and respiratory dynamics in humans using HP He-3 MR.

Functional lung imaging using hyperpolarized gas MRI.

The noninvasive assessment of lung function using imaging is increasingly of interest for the study of lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. Hyperpolarized gas MRI (HP MRI) has demonstrated the ability to detect changes in ventilation, perfusion, and lung microstructure that appear to be associated with both normal lung development and disease progression. The physical characteristics of HP gases and their application to MRI are presented with an emphasis on current applications. Clinical investigations using HP MRI to study asthma, COPD, cystic fibrosis, pediatric chronic lung disease, and lung transplant are reviewed. Recent advances in polarization, pulse sequence development for imaging with Xe-129, and prototype low magnetic field systems dedicated to lung imaging are highlighted as areas of future development for this rapidly evolving technology.

Imaging of lung ventilation and respiratory dynamics in a single ventilation cycle using hyperpolarized He-3 MRI.

PURPOSE: To image respiratory dynamics and three-dimensional (3D) ventilation during inhalation, breath-hold, and exhalation for evaluation of obstructive lung disease using a single dose of hyperpolarized (HP) He-3 during MRI. MATERIALS AND METHODS: A single 2D-3D projections inside Z encoding (PRIZE)-2D acquisition was performed that consisted of a rapid 2D radial acquisition phase during inhalation of the HP He-3, a 3D acquisition phase during a breath-hold interval, and finally the same 2D radial acquisition during a forced exhalation maneuver followed by tidal breathing. The 3D PRIZE acquisition was comprised of radial sampling in the coronal plane and Fourier encoding in the patient's anterior-posterior direction. Nine patients with mild/moderate to severe asthma were studied (two individuals were studied twice) using this technique. RESULTS: Breath-hold and dynamic imaging results showed physiological abnormalities and were compared with results from standard spirometry, body plethysmography, and computed tomography (CT). Dynamic images depicted regions of differential gas clearance and trapping observed during and after forced exhalation that were corroborated as regions of air trapping on CT imaging. CONCLUSION: The 2D-3D PRIZE-2D acquisition allowed for 3D depiction of ventilation during a breath-hold, as well as detection of gas trapping. Imaging results were confirmed with spirometry, body plethysmography, and CT.