Diffusion Tensor Phenomapping of the Healthy and Pressure-Overloaded Human Heart.

Current techniques to image the microstructure of the heart with diffusion tensor MRI (DTI) are highly under-resolved. We present a technique to improve the spatial resolution of cardiac DTI by almost 10-fold and leverage this to measure local gradients in cardiomyocyte alignment or helix angle (HA). We further introduce a phenomapping approach based on voxel-wise hierarchical clustering of these gradients to identify distinct microstructural microenvironments in the heart. Initial development was performed in healthy volunteers (n=8). Thereader, subjects with severe but well-compensated aortic stenosis (AS, n=10) were compared to age-matched controls (CTL, n=10). Radial HA gradient was significantly reduced in AS (8.0±0.8°/mm vs. 10.2±1.8°/mm, p=0.001) but the other HA gradients did not change significantly. Four distinct microstructural clusters could be idenJfied in both the CTL and AS subjects and did not differ significantly in their properties or distribution. Despite marked hypertrophy, our data suggest that the myocardium in well-compensated AS can maintain its microstructural coherence. The described phenomapping approach can be used to characterize microstructural plasticity and perturbation in any organ system and disease.

Eddy current-induced artifact correction in high b-value ex vivo human brain diffusion MRI with dynamic field monitoring.

PURPOSE: To investigate whether spatiotemporal magnetic field monitoring can correct pronounced eddy current-induced artifacts incurred by strong diffusion-sensitizing gradients up to 300 mT/m used in high b-value diffusion-weighted (DW) EPI. METHODS: A dynamic field camera equipped with 16 1 H NMR field probes was first used to characterize field perturbations caused by residual eddy currents from diffusion gradients waveforms in a 3D multi-shot EPI sequence on a 3T Connectom scanner for different gradient strengths (up to 300 mT/m), diffusion directions, and shots. The efficacy of dynamic field monitoring-based image reconstruction was demonstrated on high-gradient strength, submillimeter resolution whole-brain ex vivo diffusion MRI. A 3D multi-shot image reconstruction framework was developed that incorporated the nonlinear phase evolution measured with the dynamic field camera. RESULTS: Phase perturbations in the readout induced by residual eddy currents from strong diffusion gradients are highly nonlinear in space and time, vary among diffusion directions, and interfere significantly with the image encoding gradients, changing the k-space trajectory. During the readout, phase modulations between odd and even EPI echoes become non-static and diffusion encoding direction-dependent. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting reduction approaches such as navigator- and structured low-rank-based methods or MUSE followed by image-based distortion correction with the FSL tool "eddy." CONCLUSION: Strong eddy current artifacts characteristic of high-gradient strength DW-EPI can be well corrected with dynamic field monitoring-based image reconstruction.

Metal artifact reduction around cervical spine implant using diffusion tensor imaging at 3T: A phantom study.

PURPOSE: Diffusion MRI continues to play a key role in non-invasively assessing spinal cord integrity and pre-operative injury evaluation. However, post-operative Diffusion Tensor Imaging (DTI) acquisition of patients with metal implants results in severe geometric distortion. We propose and demonstrate a method to alleviate the technical challenges facing the acquisition of DTI on post-operative cases and longitudinal evaluation of therapeutics. MATERIAL AND METHODS: The described technique is based on the combination of the reduced Field-Of-View (rFOV) strategy and the phase segmented EPI, termed rFOV-PS-EPI. A custom-built phantom based on a cervical spine model with metal implants was used to collect DTI data at 3 Tesla scanner using: rFOV-PS-EPI, reduced Field-Of-View single-shot EPI (rFOV-SS-EPI), and conventional full FOV techniques including SS-EPI, PS-EPI, and readout-segmented EPI (RS-EPI). Geometric distortion, SNR, and signal void were assessed to evaluate images and compare the sequences. A two-sample t-test was performed with p-value of 0.05 or less to indicate statistical significance. RESULTS: The reduced FOV techniques showed better capability to reduce distortions compared to the Full FOV techniques. The rFOV-PS-EPI method provided DTI images of the phantom at the level of the hardware whereas the conventional rFOV-SS-EPI is useful only when the metal is approximately 20 mm away. In addition, compared to the rFOV-SS-EPI technique, the suggested approach produced smaller signal voids area as well as significantly reduced geometric distortion in Circularity (p < 0.005) and Eccentricity (p < 0.005) measurements. No statistically significant differences were found for these geometric distortion measurements between the rFOV-PS-EPI DTI sequence and conventional structural T2 images (p > 0.05). CONCLUSION: The combination of rFOV and a phase-segmented acquisition approach is effective for reducing metal-induced distortions in DTI scan on spinal cord with metal hardware at 3 T.

Metal Artifact Reduction Around Cervical Spine Implant Using Diffusion Tensor Imaging at 3T: A Phantom Study.

Diffusion MRI continues to play a key role in non-invasively assessing spinal cord integrity and pre-operative injury evaluation. However, post-operative Diffusion Tensor Imaging (DTI) acquisition of a patient with a metal implant results in severe geometric image distortion. A method has been proposed here to alleviate the technical challenges facing the acquisition of DTI in post-operative cases and to evaluate longitudinal therapeutics. The described technique is based on the combination of the reduced Field-Of-View (rFOV) strategy and the phase segmented acquisition scheme (rFOV-PS-EPI) for significantly mitigating metal-induced distortions. A custom-built phantom based on spine model with metal implant was used to collect high-resolution DTI data at 3 Tesla scanner using a home-grown diffusion MRI pulse sequence, rFOV-PS-EPI, single-shot (rFOV-SS-EPI), and the conventional full FOV techniques including SS-EPI, PS-EPI, and the readout-segmented (RS-EPI). This newly developed method provides high-resolution images with significant reduced metal-induced artifacts. In contrast to the other techniques, the rFOV-PS-EPI allows DTI measurement at the level of the metal hardware whereas the current rFOV-SS-EPI is useful when the metal is approximately 20 mm away. The developed approach enables high-resolution DTI in patients with metal implant.

Eddy current-induced artifacts correction in high gradient strength diffusion MRI with dynamic field monitoring: demonstration in ex vivo human brain imaging.

Purpose: To demonstrate the advantages of spatiotemporal magnetic field monitoring to correct eddy current-induced artifacts (ghosting and geometric distortions) in high gradient strength diffusion MRI (dMRI). Methods: A dynamic field camera with 16 NMR field probes was used to characterize eddy current fields induced from diffusion gradients for different gradients strengths (up to 300 mT/m), diffusion directions, and shots in a 3D multi-shot EPI sequence on a 3T Connectom scanner. The efficacy of dynamic field monitoring-based image reconstruction was demonstrated on high-resolution whole brain ex vivo dMRI. A 3D multi-shot image reconstruction framework was informed with the actual nonlinear phase evolution measured with the dynamic field camera, thereby accounting for high-order eddy currents fields on top of the image encoding gradients in the image formation model. Results: Eddy current fields from diffusion gradients at high gradient strength in a 3T Connectom scanner are highly nonlinear in space and time, inducing high-order spatial phase modulations between odd/even echoes and shots that are not static during the readout. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting approaches such as navigator- and structured low-rank-based methods or MUSE, followed by image-based distortion correction with eddy. Improved dMRI analysis is demonstrated with diffusion tensor imaging and high-angular resolution diffusion imaging. Conclusion: Strong eddy current artifacts characteristic of high gradient strength dMRI can be well corrected with dynamic field monitoring-based image reconstruction, unlike the two-step approach consisting of ghosting correction followed by geometric distortion reduction with eddy.

A nanoparticle probe for the imaging of autophagic flux in live mice via magnetic resonance and near-infrared fluorescence.

Autophagy-the lysosomal degradation of cytoplasmic components via their sequestration into double-membraned autophagosomes-has not been detected non-invasively. Here we show that the flux of autophagosomes can be measured via magnetic resonance imaging or serial near-infrared fluorescence imaging of intravenously injected iron oxide nanoparticles decorated with cathepsin-cleavable arginine-rich peptides functionalized with the near-infrared fluorochrome Cy5.5 (the peptides facilitate the uptake of the nanoparticles by early autophagosomes, and are then cleaved by cathepsins in lysosomes). In the heart tissue of live mice, the nanoparticles enabled quantitative measurements of changes in autophagic flux, upregulated genetically, by ischaemia-reperfusion injury or via starvation, or inhibited via the administration of a chemotherapeutic or the antibiotic bafilomycin. In mice receiving doxorubicin, pre-starvation improved cardiac function and overall survival, suggesting that bursts of increased autophagic flux may have cardioprotective effects during chemotherapy. Autophagy-detecting nanoparticle probes may facilitate the further understanding of the roles of autophagy in disease.

Manifold-based respiratory phase estimation enables motion and distortion correction of free-breathing cardiac diffusion tensor MRI.

PURPOSE: For in vivo cardiac DTI, breathing motion and B0 field inhomogeneities produce misalignment and geometric distortion in diffusion-weighted (DW) images acquired with conventional single-shot EPI. We propose using a dimensionality reduction method to retrospectively estimate the respiratory phase of DW images and facilitate both distortion correction (DisCo) and motion compensation. METHODS: Free-breathing electrocardiogram-triggered whole left-ventricular cardiac DTI using a second-order motion-compensated spin echo EPI sequence and alternating directionality of phase encoding blips was performed on 11 healthy volunteers. The respiratory phase of each DW image was estimated after projecting the DW images into a 2D space with Laplacian eigenmaps. DisCo and motion compensation were applied to the respiratory sorted DW images. The results were compared against conventional breath-held T2 half-Fourier single shot turbo spin echo. Cardiac DTI parameters including fractional anisotropy, mean diffusivity, and helix angle transmurality were compared with and without DisCo. RESULTS: The left-ventricular geometries after DisCo and motion compensation resulted in significantly improved alignment of DW images with T2 reference. DisCo reduced the distance between the left-ventricular contours by 13.2% ± 19.2%, P < .05 (2.0 ± 0.4 for DisCo and 2.4 ± 0.5 mm for uncorrected). DisCo DTI parameter maps yielded no significant differences (mean diffusivity: 1.55 ± 0.13 × 10-3 mm2 /s and 1.53 ± 0.13 × 10-3 mm2 /s, P = .09; fractional anisotropy: 0.375 ± 0.041 and 0.379 ± 0.045, P = .11; helix angle transmurality: 1.00% ± 0.10°/% and 0.99% ± 0.12°/%, P = .44), although the orientation of individual tensors differed. CONCLUSION: Retrospective respiratory phase estimation with LE-based DisCo and motion compensation in free-breathing cardiac DTI resulting in significantly reduced geometric distortion and improved alignment within and across slices.

Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance.

OBJECTIVES: The authors present a novel technique to detect and characterize LAA thrombus in humans using combined positron emission tomography (PET)/cardiac magnetic resonance (CMR) of a fibrin-binding radiotracer, [64Cu]FBP8. BACKGROUND: The detection of thrombus in the left atrial appendage (LAA) is vital in the prevention of stroke and is currently performed using transesophageal echocardiography (TEE). METHODS: The metabolism and pharmacokinetics of [64Cu]FBP8 were studied in 8 healthy volunteers. Patients with atrial fibrillation and recent TEEs of the LAA (positive n = 12, negative n = 12) were injected with [64Cu]FBP8 and imaged with PET/CMR, including mapping the longitudinal magnetic relaxation time (T1) in the LAA. RESULTS: [64Cu]FBP8 was stable to metabolism and was rapidly eliminated. The maximum standardized uptake value (SUVMax) in the LAA was significantly higher in the TEE-positive than TEE-negative subjects (median of 4.0 [interquartile range (IQR): 3.0-6.0] vs 2.3 [IQR: 2.1-2.5]; P < 0.001), with an area under the receiver-operating characteristic curve of 0.97. An SUVMax threshold of 2.6 provided a sensitivity of 100% and specificity of 84%. The minimum T1 (T1Min) in the LAA was 970 ms (IQR: 780-1,080 ms) vs 1,380 ms (IQR: 1,120-1,620 ms) (TEE positive vs TEE negative; P < 0.05), with some overlap between the groups. Logistic regression using SUVMax and T1Min allowed all TEE-positive and TEE-negative subjects to be classified with 100% accuracy. CONCLUSIONS: PET/CMR of [64Cu]FBP8 is able to detect acute as well as older platelet-poor thrombi with excellent accuracy. Furthermore, the integrated PET/CMR approach provides useful information on the biological properties of thrombus such as fibrin and methemoglobin content. (Imaging of LAA Thrombosis; NCT03830320).

Connectome 2.0: Developing the next-generation ultra-high gradient strength human MRI scanner for bridging studies of the micro-, meso- and macro-connectome.

The first phase of the Human Connectome Project pioneered advances in MRI technology for mapping the macroscopic structural connections of the living human brain through the engineering of a whole-body human MRI scanner equipped with maximum gradient strength of 300 mT/m, the highest ever achieved for human imaging. While this instrument has made important contributions to the understanding of macroscale connectional topology, it has also demonstrated the potential of dedicated high-gradient performance scanners to provide unparalleled in vivo assessment of neural tissue microstructure. Building on the initial groundwork laid by the original Connectome scanner, we have now embarked on an international, multi-site effort to build the next-generation human 3T Connectome scanner (Connectome 2.0) optimized for the study of neural tissue microstructure and connectional anatomy across multiple length scales. In order to maximize the resolution of this in vivo microscope for studies of the living human brain, we will push the diffusion resolution limit to unprecedented levels by (1) nearly doubling the current maximum gradient strength from 300 mT/m to 500 mT/m and tripling the maximum slew rate from 200 T/m/s to 600 T/m/s through the design of a one-of-a-kind head gradient coil optimized to minimize peripheral nerve stimulation; (2) developing high-sensitivity multi-channel radiofrequency receive coils for in vivo and ex vivo human brain imaging; (3) incorporating dynamic field monitoring to minimize image distortions and artifacts; (4) developing new pulse sequences to integrate the strongest diffusion encoding and highest spatial resolution ever achieved in the living human brain; and (5) calibrating the measurements obtained from this next-generation instrument through systematic validation of diffusion microstructural metrics in high-fidelity phantoms and ex vivo brain tissue at progressively finer scales with accompanying diffusion simulations in histology-based micro-geometries. We envision creating the ultimate diffusion MRI instrument capable of capturing the complex multi-scale organization of the living human brain - from the microscopic scale needed to probe cellular geometry, heterogeneity and plasticity, to the mesoscopic scale for quantifying the distinctions in cortical structure and connectivity that define cyto- and myeloarchitectonic boundaries, to improvements in estimates of macroscopic connectivity.

Accelerated in Vivo Cardiac Diffusion-Tensor MRI Using Residual Deep Learning-based Denoising in Participants with Obesity.

PURPOSE: To develop and assess a residual deep learning algorithm to accelerate in vivo cardiac diffusion-tensor MRI (DT-MRI) by reducing the number of averages while preserving image quality and DT-MRI parameters. MATERIALS AND METHODS: In this prospective study, a denoising convolutional neural network (DnCNN) for DT-MRI was developed; a total of 26 participants, including 20 without obesity (body mass index [BMI] < 30 kg/m2; mean age, 28 years ± 3 [standard deviation]; 11 women) and six with obesity (BMI ≥ 30 kg/m2; mean age, 48 years ± 11; five women), were recruited from June 19, 2019, to July 29, 2020. DT-MRI data were constructed at four averages (4Av), two averages (2Av), and one average (1Av) without and with the application of the DnCNN (4AvDnCNN, 2AvDnCNN, 1AvDnCNN). All data were compared against the reference DT-MRI data constructed at eight averages (8Av). Image quality, characterized by using the signal-to-noise ratio (SNR) and structural similarity index (SSIM), and the DT-MRI parameters of mean diffusivity (MD), fractional anisotropy (FA), and helix angle transmurality (HAT) were quantified. RESULTS: No differences were found in image quality or DT-MRI parameters between the accelerated 4AvDnCNN DT-MRI and the reference 8Av DT-MRI data for the SNR (29.1 ± 2.7 vs 30.5 ± 2.9), SSIM (0.97 ± 0.01), MD (1.3 µm2/msec ± 0.1 vs 1.31 µm2/msec ± 0.11), FA (0.32 ± 0.05 vs 0.30 ± 0.04), or HAT (1.10°/% ± 0.13 vs 1.11°/% ± 0.09). The relationship of a higher MD and lower FA and HAT in individuals with obesity compared with individuals without obesity in reference 8Av DT-MRI measurements was retained in 4AvDnCNN and 2AvDnCNN DT-MRI measurements but was not retained in 4Av or 2Av DT-MRI measurements. CONCLUSION: Cardiac DT-MRI can be performed at an at least twofold-accelerated rate by using DnCNN to preserve image quality and DT-MRI parameter quantification.Keywords: Adults, Cardiac, Obesity, Technology Assessment, MR-Diffusion Tensor Imaging, Heart, Tissue CharacterizationSupplemental material is available for this article.© RSNA, 2021.

A 48-channel receive array coil for mesoscopic diffusion-weighted MRI of ex vivo human brain on the 3 T connectome scanner.

In vivo diffusion-weighted magnetic resonance imaging is limited in signal-to-noise-ratio (SNR) and acquisition time, which constrains spatial resolution to the macroscale regime. Ex vivo imaging, which allows for arbitrarily long scan times, is critical for exploring human brain structure in the mesoscale regime without loss of SNR. Standard head array coils designed for patients are sub-optimal for imaging ex vivo whole brain specimens. The goal of this work was to design and construct a 48-channel ex vivo whole brain array coil for high-resolution and high b-value diffusion-weighted imaging on a 3T Connectome scanner. The coil was validated with bench measurements and characterized by imaging metrics on an agar brain phantom and an ex vivo human brain sample. The two-segment coil former was constructed for a close fit to a whole human brain, with small receive elements distributed over the entire brain. Imaging tests including SNR and G-factor maps were compared to a 64-channel head coil designed for in vivo use. There was a 2.9-fold increase in SNR in the peripheral cortex and a 1.3-fold gain in the center when compared to the 64-channel head coil. The 48-channel ex vivo whole brain coil also decreases noise amplification in highly parallel imaging, allowing acceleration factors of approximately one unit higher for a given noise amplification level. The acquired diffusion-weighted images in a whole ex vivo brain specimen demonstrate the applicability and advantage of the developed coil for high-resolution and high b-value diffusion-weighted ex vivo brain MRI studies.

Optimized 64-channel array configurations for accelerated simultaneous multislice acquisitions in 3T cardiac MRI.

PURPOSE: Three 64-channel cardiac coils with different detector array configurations were designed and constructed to evaluate acceleration capabilities in simultaneous multislice (SMS) imaging for 3T cardiac MRI. METHODS: Three 64-channel coil array configurations obtained from a simulation-guided design approach were constructed and systematically evaluated regarding their encoding capabilities for accelerated SMS cardiac acquisitions at 3T. Array configuration AUni-sized consists of uniformly distributed equally sized loops in an overlapped arrangement, BGapped uses a gapped array design with symmetrically distributed equally sized loops, and CDense has non-uniform loop density and size, where smaller elements were centered over the heart and larger elements were placed surrounding the target region. To isolate the anatomic variation from differences in the coil configurations, all three array coils were built with identical semi-adjustable housing segments. The arrays' performance was compared using bench-level measurements and imaging performance tests, including signal-to-noise ratio (SNR) maps, array element noise correlation, and SMS acceleration capabilities. Additionally, all cardiac array coils were evaluated on a healthy volunteer. RESULTS: The array configuration CDense with the non-uniformly distributed loop density showed the best overall cardiac imaging performance in both SNR and SMS encoding power, when compared to the other constructed arrays. The diffusion weighted cardiac acquisitions on a healthy volunteer support the favorable accelerated SNR performance of this array configuration. CONCLUSION: Our results indicate that optimized highly parallel cardiac arrays, such as the 64-channel coil with a non-uniform loop size and density improve highly accelerated SMS cardiac MRI in comparison to symmetrically distributed loop array designs.

Free-breathing diffusion tensor MRI of the whole left ventricle using second-order motion compensation and multitasking respiratory motion correction.

PURPOSE: We aimed to develop a novel free-breathing cardiac diffusion tensor MRI (DT-MRI) approach, M2-MT-MOCO, capable of whole left ventricular coverage that leverages second-order motion compensation (M2) diffusion encoding and multitasking (MT) framework to efficiently correct for respiratory motion (MOCO). METHODS: Imaging was performed in 16 healthy volunteers and 3 heart failure patients with symptomatic dyspnea. The healthy volunteers were scanned to compare the accuracy of interleaved multislice coverage of the entire left ventricle with a single-slice acquisition and the accuracy of the free-breathing conventional MOCO and MT-MOCO approaches with reference breath-hold DT-MRI. Mean diffusivity (MD), fractional anisotropy (FA), helix angle transmurality (HAT), and intrascan repeatability were quantified and compared. RESULTS: In all subjects, free-breathing M2-MT-MOCO DT-MRI yielded DWI of the entire left ventricle without bulk motion-induced signal loss. No significant differences were seen in the global values of MD, FA, and HAT in the multislice and single-slice acquisitions. Furthermore, global quantification of MD, FA, and HAT were also not significantly different between the MT-MOCO and breath-hold, whereas conventional MOCO yielded significant differences in MD, FA, and HAT with MT-MOCO and FA with breath-hold. In heart failure patients, M2-MT-MOCO DT-MRI was feasible yielding higher MD, lower FA, and lower HAT compared with healthy volunteers. Substantial agreement was found between repeated scans across all subjects for MT-MOCO. CONCLUSION: M2-MT-MOCO enables free-breathing DT-MRI of the entire left ventricle in 10 min, while preserving quantification of myocardial microstructure compared to breath-held and single-slice acquisitions and is feasible in heart failure patients.

High-gradient diffusion MRI reveals distinct estimates of axon diameter index within different white matter tracts in the in vivo human brain.

Axon diameter and density are important microstructural metrics that offer valuable insight into the structural organization of white matter throughout the human brain. We report the systematic acquisition and analysis of a comprehensive diffusion MRI data set acquired with 300 mT/m maximum gradient strength in a cohort of 20 healthy human subjects that yields distinct and consistent patterns of axon diameter index in white matter tracts of arbitrary orientation. We use a straightforward, previously validated approach to estimating indices of axon diameter and volume fraction that involves interpolating the diffusion signal perpendicular to the principal fiber orientation and fitting a three-compartment model of intra-axonal, extra-axonal and free water diffusion. The resultant maps confirm the presence of larger diameter indices in the body of corpus callosum compared to the genu and splenium, as previously reported, and show larger axon diameter index in the corticospinal tracts compared to adjacent white matter tracts such as the cingulum. An anterior-to-posterior gradient in axon diameter index is also observed, with smaller diameter indices in the frontal lobes and larger diameter indices in the parieto-occipital white matter. These observations are consistent with known trends from prior histologic studies in humans and non-human primates. Rather than serving as fully quantitative measures of axon diameter and density, our results may be considered as axon diameter- and volume fraction-weighted images that appear to be modulated by the underlying microstructure and may capture broad trends in axonal size and packing density, acknowledging that the precise origin of such modulation requires further investigation that will be facilitated by the availability of high gradient strengths for in vivo human imaging.

Association of orthostatic hypertension with mortality in the Systolic Hypertension in the Elderly Program.

We examined the association of orthostatic hypertension with all-cause mortality in the active treatment and placebo randomized groups of the Systolic Hypertension in the Elderly Program (SHEP). SHEP was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the effect of chlorthalidone-based antihypertensive treatment on the rate of occurrence of stroke among older persons with isolated systolic hypertension (ISH). Men and women aged 60 years and above with ISH defined by a systolic blood pressure (SBP) of 160 mm Hg or higher and diastolic blood pressure lower than 90 mm Hg were randomized to chlorthalidone-based stepped care therapy or matching placebo. Among 4736 SHEP participants, 4073 had a normal orthostatic response, 203 had orthostatic hypertension, and 438 had orthostatic hypotension. Compared with normal response, orthostatic hypertension was associated with higher all-cause mortality at 4.5 and 17 years in analyses adjusted for age, gender, treatment, SBP, and pulse pressure (PP, HR 1.87, 95% CI 1.30-2.69, p = 0.0007; HR 1.40, 95% CI 1.17-1.68, p = 0.0003, respectively). These associations remained significant after additional adjustment for risk factors and comorbidities (HR 1.43, 95% CI 0.99-0.08, p = 0.0566 at 4.5 years, and HR 1.27, 95% CI 1.06-1.53, p = 0.0096 at 17 years). The increased risk of all-cause mortality associated with orthostatic hypertension was observed in both the active and placebo groups without significant interaction between randomization group and the effect on mortality. Orthostatic hypertension is associated with future mortality risk, is easily detected, and can be used in refining cardiovascular risk assessment.

Age-related alterations in axonal microstructure in the corpus callosum measured by high-gradient diffusion MRI.

Cerebral white matter exhibits age-related degenerative changes during the course of normal aging, including decreases in axon density and alterations in axonal structure. Noninvasive approaches to measure these microstructural alterations throughout the lifespan would be invaluable for understanding the substrate and regional variability of age-related white matter degeneration. Recent advances in diffusion magnetic resonance imaging (MRI) have leveraged high gradient strengths to increase sensitivity toward axonal size and density in the living human brain. Here, we examined the relationship between age and indices of axon diameter and packing density using high-gradient strength diffusion MRI in 36 healthy adults (aged 22-72) in well-defined central white matter tracts in the brain. A recently validated method for inferring the effective axonal compartment size and packing density from diffusion MRI measurements acquired with 300 mT/m maximum gradient strength was applied to the in vivo human brain to obtain indices of axon diameter and density in the corpus callosum, its sub-regions, and adjacent anterior and posterior fibers in the forceps minor and forceps major. The relationships between the axonal metrics, corpus callosum area and regional gray matter volume were also explored. Results revealed a significant increase in axon diameter index with advancing age in the whole corpus callosum. Similar analyses in sub-regions of the corpus callosum showed that age-related alterations in axon diameter index and axon density were most pronounced in the genu of the corpus callosum and relatively absent in the splenium, in keeping with findings from previous histological studies. The significance of these correlations was mirrored in the forceps minor and forceps major, consistent with previously reported decreases in FA in the forceps minor but not in the forceps major with age. Alterations in the axonal imaging metrics paralleled decreases in corpus callosum area and regional gray matter volume with age. Among older adults, results from cognitive testing suggested an association between larger effective compartment size in the corpus callosum, particularly within the genu of the corpus callosum, and lower scores on the Montreal Cognitive Assessment, largely driven by deficits in short-term memory. The current study suggests that high-gradient diffusion MRI may be sensitive to the axonal substrate of age-related white matter degeneration reflected in traditional DTI metrics and provides further evidence for regionally selective alterations in white matter microstructure with advancing age.

A comprehensive diffusion MRI dataset acquired on the MGH Connectome scanner in a biomimetic brain phantom.

We provide a comprehensive diffusion MRI dataset acquired with a novel biomimetic phantom mimicking human white matter. The fiber substrates in the diffusion phantom were constructed from hollow textile axons ("taxons") with an inner diameter of 11.8±1.2 µm and outer diameter of 33.5±2.3 µm. Data were acquired on the 3 T CONNECTOM MRI scanner with multiple diffusion times and multiple q-values per diffusion time, which is a dedicated acquisition for validation of microstructural imaging methods, such as compartment size and volume fraction mapping. Minimal preprocessing was performed to correct for susceptibility and eddy current distortions. Data were deposited in the XNAT Central database (project ID: dMRI_Phant_MGH).

Myocardial Scar Delineation Using Diffusion Tensor Magnetic Resonance Tractography.

BACKGROUND: Late gadolinium enhancement (LGE) is the current standard for myocardial scar delineation. In this study, we introduce the tractographic propagation angle (PA), a metric of myofiber curvature (degrees/unit distance) derived from diffusion tensor imaging (DTI), and compare its use to LGE and invasive scar assessment by endocardial voltage mapping. METHODS AND RESULTS: DTI was performed on 7 healthy human volunteers, 5 patients with myocardial infarction, 6 normal mice, and 7 mice with myocardial infarction. LGE to delineate the infarct and border zones was performed with a 2-dimensional inversion recovery gradient-echo sequence. Ex vivo DTI was performed on 5 normal human and 5 normal sheep hearts. Endocardial electroanatomic mapping and subsequent ex vivo DTI was performed on 5 infarcted sheep hearts. PA in the normal human hearts varied smoothly and was generally <4. The mean PA in the infarct zone was significantly elevated (10.34±1.02 versus 4.05±0.45, P<0.05). Regions with a PA ≤4 consistently had a bipolar voltage ≥1.5 mV, whereas those with PA values between 4 and 10 had voltages between 0.5 and 1.5 mV. A PA threshold >4 was the most accurate DTI-derived measure of infarct size and demonstrated the greatest correlation with LGE (r=0.95). CONCLUSIONS: We found a strong correlation between infarct size by PA and LGE in both mice and humans. There was also an inverse relationship between PA values and endocardial voltage. The use of PA may enable myocardial scar delineation and characterization of arrhythmogenic substrate without the need for exogenous contrast agents.

Validation of diffusion MRI estimates of compartment size and volume fraction in a biomimetic brain phantom using a human MRI scanner with 300 mT/m maximum gradient strength.

Diffusion microstructural imaging techniques have attracted great interest in the last decade due to their ability to quantify axon diameter and volume fraction in healthy and diseased human white matter. The estimates of compartment size and volume fraction continue to be debated, in part due to the lack of a gold standard for validation and quality control. In this work, we validate diffusion MRI estimates of compartment size and volume fraction using a novel textile axon ("taxon") phantom constructed from hollow polypropylene yarns with distinct intra- and extra-taxonal compartments to mimic white matter in the brain. We acquired a comprehensive set of diffusion MRI measurements in the phantom using multiple gradient directions, diffusion times and gradient strengths on a human MRI scanner equipped with maximum gradient strength (Gmax) of 300 mT/m. We obtained estimates of compartment size and restricted volume fraction through a straightforward extension of the AxCaliber/ActiveAx frameworks that enables estimation of mean compartment size in fiber bundles of arbitrary orientation. The voxel-wise taxon diameter estimates of 12.2 ±â€¯0.9 µm were close to the manufactured inner diameter of 11.8 ±â€¯1.2 µm with Gmax = 300 mT/m. The estimated restricted volume fraction demonstrated an expected decrease along the length of the fiber bundles in accordance with the known construction of the phantom. When Gmax was restricted to 80 mT/m, the taxon diameter was overestimated, and the estimates for taxon diameter and packing density showed greater uncertainty compared to data with Gmax = 300 mT/m. In conclusion, the compartment size and volume fraction estimates resulting from diffusion measurements on a human scanner were validated against ground truth in a phantom mimicking human white matter, providing confidence that this method can yield accurate estimates of parameters in simplified but realistic microstructural environments. Our work also demonstrates the importance of a biologically analogous phantom that can be applied to validate a variety of diffusion microstructural imaging methods in human scanners and be used for standardization of diffusion MRI protocols for neuroimaging research.

Diffusion MRI in the heart.

Diffusion MRI provides unique information on the structure, organization, and integrity of the myocardium without the need for exogenous contrast agents. Diffusion MRI in the heart, however, has proven technically challenging because of the intrinsic non-rigid deformation during the cardiac cycle, displacement of the myocardium due to respiratory motion, signal inhomogeneity within the thorax, and short transverse relaxation times. Recently developed accelerated diffusion-weighted MR acquisition sequences combined with advanced post-processing techniques have improved the accuracy and efficiency of diffusion MRI in the myocardium. In this review, we describe the solutions and approaches that have been developed to enable diffusion MRI of the heart in vivo, including a dual-gated stimulated echo approach, a velocity- (M1 ) or an acceleration- (M2 ) compensated pulsed gradient spin echo approach, and the use of principal component analysis filtering. The structure of the myocardium and the application of these techniques in ischemic heart disease are also briefly reviewed. The advent of clinical MR systems with stronger gradients will likely facilitate the translation of cardiac diffusion MRI into clinical use. The addition of diffusion MRI to the well-established set of cardiovascular imaging techniques should lead to new and complementary approaches for the diagnosis and evaluation of patients with heart disease. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.