Thermal stimulus task fMRI in the cervical spinal cord at 7 Tesla.

Although functional magnetic resonance imaging (fMRI) is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0 . Increasing field strength enables higher spatial resolution and improved sensitivity to blood oxygenation level-dependent (BOLD) signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D echo-planar imaging (EPI) protocols, which differ in sensitivity to spatial and temporal B0 inhomogeneity. The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. All protocols used 3 mm slice thickness. For each protocol, the BOLD response to 13 10-s noxious thermal stimuli applied to the right thumb was acquired in a 10-min fMRI run. Image quality, temporal signal to noise ratio (SNR), and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment. PRACTITIONER POINTS: First stimulus task fMRI results in the spinal cord at 7 T. Single-shot 0.75 mm 2D EPI produced the highest mean z-statistic. Multi-shot 0.60 mm 2D EPI provided the best-localized activation and least distortion.

The neuropathology of intimate partner violence.

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd-8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd-9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Impact of autocalibration method on accelerated EPI of the cervical spinal cord at 7 T.

PURPOSE: The spinal cord contains sensorimotor neural circuits of scientific and clinical interest. However, spinal cord functional MRI (fMRI) is significantly more technically demanding than brain fMRI, due primarily to its proximity to the lungs. Accelerated echo-planar imaging (EPI) at 7 T is particularly vulnerable to k-space phase inconsistencies induced by motion or B0 fluctuation, during either autocalibration signal (ACS) or time-series acquisition. For 7 T brain fMRI, sensitivity to motion and B0 fluctuation can be reduced using a re-ordered segmented EPI ACS based on the fast low-angle excitation echo-planar technique (FLEET). However, respiration-induced B0 fluctuations (exceeding 100 Hz at C7) are greater, and fewer k-space lines per slice are required for cervical spinal cord fMRI at 7 T, necessitating a separate evaluation of ACS methods. METHODS: We compared 24-line single-shot EPI with 48-line two-shot segmented EPI, two-shot FLEET, and gradient echo (GRE)-based ACS acquisition methods, performed under various physiological conditions, in terms of temporal signal-to-noise ratio and prevalence of artifacts in generalized autocalibrating partially parallel acquisition (GRAPPA)-accelerated EPI of the cervical spinal cord at 7 T. RESULTS: Segmented EPI and FLEET ACS produce images with nearly identical patterns of severe image artifacts. GRE and single-shot EPI ACS consistently produce images free from significant artifacts, and temporal signal-to-noise ratio is significantly greater for GRE ACS, particularly in lower slices where through-slice dephasing is most severe. CONCLUSIONS: GRE and single-shot EPI-ACS acquisition methods, which are robust to respiration-induced phase errors between k-space segments, produce images with fewer and less severe artifacts than either FLEET or conventionally segmented EPI for accelerated EPI of the cervical spinal cord at 7 T.

Comparison of multicenter MRI protocols for visualizing the spinal cord gray matter.

PURPOSE: Spinal cord gray-matter imaging is valuable for a number of applications, but remains challenging. The purpose of this work was to compare various MRI protocols at 1.5 T, 3 T, and 7 T for visualizing the gray matter. METHODS: In vivo data of the cervical spinal cord were collected from nine different imaging centers. Data processing consisted of automatically segmenting the spinal cord and its gray matter and co-registering back-to-back scans. We computed the SNR using two methods (SNR_single using a single scan and SNR_diff using the difference between back-to-back scans) and the white/gray matter contrast-to-noise ratio per unit time. Synthetic phantom data were generated to evaluate the metrics performance. Experienced radiologists qualitatively scored the images. We ran the same processing on an open-access multicenter data set of the spinal cord MRI (N = 267 participants). RESULTS: Qualitative assessments indicated comparable image quality for 3T and 7T scans. Spatial resolution was higher at higher field strength, and image quality at 1.5 T was found to be moderate to low. The proposed quantitative metrics were found to be robust to underlying changes to the SNR and contrast; however, the SNR_single method lacked accuracy when there were excessive partial-volume effects. CONCLUSION: We propose quality assessment criteria and metrics for gray-matter visualization and apply them to different protocols. The proposed criteria and metrics, the analyzed protocols, and our open-source code can serve as a benchmark for future optimization of spinal cord gray-matter imaging protocols.

Leveraging high-resolution 7-tesla MRI to derive quantitative metrics for the trigeminal nerve and subnuclei of limbic structures in trigeminal neuralgia.

BACKGROUND: Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal sensory pathway and nociception, may play a role in pain processing of TN. The objective of this study was to assess structural alterations in the trigeminal nerve and subregions of the hippocampus, amygdala, and thalamus in TN patients using ultra-high field MRI and examine quantitative differences in these structures compared with healthy controls. METHODS: Thirteen TN patients and 13 matched controls were scanned at 7-Tesla MRI with high resolution, T1-weighted imaging. Nerve cross sectional area (CSA) was measured and an automated algorithm was used to segment hippocampal, amygdaloid, and thalamic subregions. Nerve CSA and limbic structure subnuclei volumes were compared between TN patients and controls. RESULTS: CSA of the posterior cisternal nerve on the symptomatic side was smaller in patients (3.75 mm2) compared with side-matched controls (5.77 mm2, p = 0.006). In TN patients, basal subnucleus amygdala volume (0.347 mm3) was reduced on the symptomatic side compared with controls (0.401 mm3, p = 0.025) and the paralaminar subnucleus volume (0.04 mm3) was also reduced on the symptomatic side compared with controls (0.05 mm3, p = 0.009). The central lateral thalamic subnucleus was larger in TN patients on both the symptomatic side (0.033 mm3) and asymptomatic side (0.035 mm3), compared with the corresponding sides in controls (0.025 mm3 on both sides, p = 0.048 and p = 0.003 respectively). The inferior and lateral pulvinar thalamic subnuclei were both reduced in TN patients on the symptomatic side (0.2 mm3 and 0.17 mm3 respectively) compared to controls (0.23 mm3, p = 0.04 and 0.18 mm3, p = 0.04 respectively). No significant findings were found in the hippocampal subfields analyzed. CONCLUSIONS: These findings, generated through a highly sensitive 7 T MRI protocol, provide compelling support for the theory that TN neurobiology is a complex amalgamation of local structural changes within the trigeminal nerve and structural alterations in subnuclei of limbic structures directly and indirectly involved in nociception and pain processing.

Incorporating non-linear alignment and multi-compartmental modeling for improved human optic nerve diffusion imaging.

In vivo human optic nerve diffusion magnetic resonance imaging (dMRI) is technically challenging with two outstanding issues not yet well addressed: (i) non-linear optic nerve movement, independent of head motion, and (ii) effect from partial-volumed cerebrospinal fluid or interstitial fluid such as in edema. In this work, we developed a non-linear optic nerve registration algorithm for improved volume alignment in axial high resolution optic nerve dMRI. During eyes-closed dMRI data acquisition, optic nerve dMRI measurements by diffusion tensor imaging (DTI) with and without free water elimination (FWE), and by diffusion basis spectrum imaging (DBSI), as well as optic nerve motion, were characterized in healthy adults at various locations along the posterior-to-anterior dimension. Optic nerve DTI results showed consistent trends in microstructural parametric measurements along the posterior-to-anterior direction of the entire intraorbital optic nerve, while the anterior portion of the intraorbital optic nerve exhibited the largest spatial displacement. Multi-compartmental dMRI modeling, such as DTI with FWE or DBSI, was less subject to spatially dependent biases in diffusivity and anisotropy measurements in the optic nerve which corresponded to similar spatial distributions of the estimated fraction of isotropic diffusion components. DBSI results derived from our clinically feasible (∼10 min) optic nerve dMRI protocol in this study are consistent with those from small animal studies, which provides the basis for evaluating the utility of multi-compartmental dMRI modeling in characterizing coexisting pathophysiology in human optic neuropathies.

Formalin tissue fixation biases myelin-sensitive MRI.

PURPOSE: Chemical fixatives such as formalin form cross-links between proteins and affect the relaxation times and diffusion properties of tissue. These fixation-induced changes likely also affect myelin density measurements produced by quantitative magnetization transfer and myelin water imaging. In this work, we evaluate these myelin-sensitive MRI methods for fixation-induced biases. METHODS: We perform quantitative magnetization transfer, myelin water imaging, and deuterium oxide-exchanged zero TE imaging on unfixed human spinal cord tissue at 9.4 Tesla and repeat these measurements after 1 day and 31 days of formalin fixation. RESULTS: The quantitative magnetization-transfer bound pool fraction increased by 30.7% ± 21.1% after 1 day of fixation and by 42.6% ± 33.9% after 31 days of fixation. Myelin water fraction increased by 39.7% ± 15.5% and 37.0% ± 15.9% at these same time points, and mean T2 of the myelin water pool nearly doubled. Reference-normalized deuterium oxide-exchanged zero TE signal intensity increased by 8.17% ± 6.03% after 31 days of fixation but did not change significantly after 1 day of fixation. After fixation, specimen cross-sectional area decreased by approximately 5%; after correction for shrinkage, changes in deuterium oxide-exchanged zero TE intensity were nearly eliminated. CONCLUSION: Bound pool fraction and myelin water fraction are significantly increased by formalin fixation, whereas deuterium oxide-exchanged zero TE intensity is minimally affected. Changes in quantitative magnetization transfer and myelin water imaging may be due in part to delamination and formation of vacuoles in the myelin sheath. Deuterium oxide-exchanged signal intensity may be altered by fixation-induced changes in myelin lipid solid-state 1 H T1 . We urge caution in the comparison of these measurements across subjects or specimens in different states, especially unfixed versus fixed tissue.

Towards quantification of myelin by solid-state MRI of the lipid matrix protons.

PURPOSE: Direct assessment of myelin has the potential to reveal central nervous system abnormalities and serve as a means to follow patients with demyelinating disorders during treatment. Here, we investigated the feasibility of direct imaging and quantification of the myelin proton pool, without the many possible confounds inherent to indirect methods, via long-T2 suppressed 3D ultra-short echo-time (UTE) and zero echo-time (ZTE) MRI in ovine spinal cord. METHODS: ZTE and UTE experiments, with and without inversion-recovery (IR) preparation, were conducted in ovine spinal cords before and after D2O exchange of tissue water, on a 9.4T vertical-bore micro-imaging system, along with some feasibility experiments on a 3T whole-body scanner. Myelin density was quantified relative to reference samples containing various mass fractions of purified myelin lipid, extracted via the sucrose gradient extraction technique, and reconstituted by suspension in water, where they spontaneously self-assemble into an ensemble of multi-lamellar liposomes, analogous to native myelin. RESULTS: MR signal amplitudes from reference samples at 9.4T were linearly correlated with myelin concentration (R2 = 0.98-0.99), enabling their use in quantification of myelin fraction in neural tissues. An adiabatic inversion-recovery preparation was found to effectively suppress long-T2 water signal in white matter, leaving short-T2 myelin protons to be imaged. Estimated myelin lipid fractions in white matter were 19.9%-22.5% in the D2O-exchanged spinal cord, and 18.1%-23.5% in the non-exchanged spinal cord. Numerical simulations based on the myelin spectrum suggest that approximately 4.59% of the total myelin proton magnetization is observable by IR-ZTE at 3T due to T2 decay and the inability to excite the shortest T2* components. Approximately 380 µm of point-spread function blurring is predicted, and ZTE images of the spinal cord acquired at 3T were consistent with this estimate. CONCLUSION: In the present implementation, IR-UTE at 9.4T produced similar estimates of myelin concentration in D2O-exchanged and non-exchanged spinal cord white matter. 3T data suggest that direct myelin imaging is feasible, but remaining challenging on clinical MR systems.

Selective in vivo bone imaging with long-T2 suppressed PETRA MRI.

PURPOSE: To design and evaluate an optimized PETRA (point-wise encoding time reduction with radial acquisition) sequence with long-T2 suppression at 3 Tesla. METHODS: An adiabatic inversion recovery-based scheme was used to null the long-T2 signal. To minimize scan time, the signal was sampled multiple times after each inversion with variable excitation flip angles designed to yield constant short-T2 signal amplitude. The excitation pulses were phase-modulated, allowing for increased flip angle and higher signal-to-noise ratio (SNR). A fast, noniterative image reconstruction algorithm was designed to minimize image artifacts due to nonuniform excitation profile. RESULTS: Phase-modulated pulse excitation, along with the noniterative reconstruction algorithm, allows the use of larger radiofrequency pulse flip angles, resulting in effective suppression of long-T2 protons and improved image SNR without causing image artifacts. Midtibia images representative of collagen-bound water yielded SNR of 15 at 1-mm isotropic resolution in 6.5 minutes with a standard extremity coil. Further, the technology is shown to be suited for generating multi-angle projection images of bone akin to X-ray images displaying subtle anatomic detail. CONCLUSION: Optimized long-T2 suppressed PETRA allows imaging of bone matrix water unencumbered by long-T2 soft tissue and pore water protons, opening up new possibilities for anatomic bone imaging at isotropic resolution and quantification in clinically practical scan times. Magn Reson Med 77:989-997, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

7 Tesla 22-channel wrap-around coil array for cervical spinal cord and brainstem imaging.

PURPOSE: Increased signal-to-noise ratio and blood oxygenation level-dependent sensitivity at 7 Tesla (T) have the potential to enable high-resolution imaging of the human cervical spinal cord and brainstem. We propose a new two-panel radiofrequency coil design for these regions to fully exploit the advantages of ultra-high field. METHODS: A two-panel array, containing four transmit/receive and 18 receive-only elements fully encircling the head and neck, was constructed following simulations demonstrating the B1+ and specific absorption rate (SAR) benefits of two-panel over one-panel arrays. This array was compared with a previously reported posterior-only array and tested for safety using a phantom. Its anatomical, functional, and diffusion MRI performance was demonstrated in vivo. RESULTS: The two-panel array produced more uniform B1+ across the brainstem and cervical spinal cord without compromising SAR, and achieved 70% greater receive sensitivity than the posterior-only array. The two-panel design enabled acceleration of R = 2 × 2 in two dimensions or R = 3 in a single dimension. High quality in vivo anatomical, functional, and diffusion images of the human cervical spinal cord and brainstem were acquired. CONCLUSION: We have designed and constructed a wrap-around coil array with excellent performance for cervical spinal cord and brainstem MRI at 7T, which enables simultaneous human cervical spinal cord and brainstem functional MRI. Magn Reson Med 78:1623-1634, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Solid-State Quantitative (1)H and (31)P MRI of Cortical Bone in Humans.

Magnetic resonance imaging (MRI) plays a pivotal role for assessment of the musculoskeletal system. It is currently the clinical modality of choice for evaluation of soft tissues including cartilage, ligaments, tendons, muscle, and bone marrow. By comparison, the study of calcified tissue by MRI is still in its infancy. In this article, we review the potential of the modality for assessment of cortical bone properties known to be affected in degenerative bone disease, with focus on parameters related to matrix and mineral densities, and porosity, by means of emerging solid-state (1)H and (31)P MRI techniques. In contrast to soft tissues, the MRI signal in calcified tissues has very short lifetime, on the order of 100 µs to a few milliseconds, demanding customized imaging approaches that allow capture of the signal almost immediately after excitation. The technologies described are suited for quantitatively imaging human cortical bone in specimens as well as in vivo in patients on standard clinical imagers, yielding either concentrations in absolute units when measured against a reference standard, or more simply, in the form of surrogate biomarkers. The two major water fractions in cortical bone are those of collagen-bound and pore water occurring at an approximately 3:1 ratio. Collagen-bound water density provides a direct quantitative measure of osteoid density. While at an earlier stage of development, quantification of mineral phosphorus by (31)P MRI yields mineral density and, together with knowledge of matrix density, should allow quantification of the degree of bone mineralization.

Bi-component T2 * analysis of bound and pore bone water fractions fails at high field strengths.

Osteoporosis involves the degradation of the bone's trabecular architecture, cortical thinning and enlargement of cortical pores. Increased cortical porosity is a major cause of the decreased strength of osteoporotic bone. The majority of cortical pores, however, are below the resolution limit of MRI. Recent work has shown that porosity can be evaluated by MRI-based quantification of bone water. Bi-exponential T2 * fitting and adiabatic inversion preparation are the two most common methods purported to distinguish bound and pore water in order to quantify matrix density and porosity. To assess the viability of T2 * bi-component analysis as a method for the quantification of bound and pore water fractions, we applied this method to human cortical bone at 1.5, 3, 7 and 9.4 T, and validated the resulting pool fractions against micro-computed tomography-derived porosity and gravimetrically determined bone densities. We also investigated alternative methods: two-dimensional T1 -T2 * bi-component fitting by incorporation of saturation recovery, one- and two-dimensional fitting of Carr-Purcell-Meiboom-Gill (CPMG) echo amplitudes, and deuterium inversion recovery. The short-T2 * pool fraction was moderately correlated with porosity (R(2) = 0.70) and matrix density (R(2) = 0.63) at 1.5 T, but the strengths of these associations were found to diminish rapidly as the field strength increased, falling below R(2) = 0.5 at 3 T. The addition of the T1 dimension to bi-component analysis only slightly improved the strengths of these correlations. T2 *-based bi-component analysis should therefore be used with caution. The performance of deuterium inversion recovery at 9.4 T was also poor (R(2) = 0.50 vs porosity and R(2) = 0.46 vs matrix density). The CPMG-derived short-T2 fraction at 9.4 T, however, was highly correlated with porosity (R(2) = 0.87) and matrix density (R(2) = 0.88), confirming the utility of this method for independent validation of bone water pools.

Cortical bone water concentration: dependence of MR imaging measures on age and pore volume fraction.

PURPOSE: To quantify bulk bone water to test the hypothesis that bone water concentration (BWC) is negatively correlated with bone mineral density (BMD) and is positively correlated with age, and to propose the suppression ratio (SR) (the ratio of signal amplitude without to that with long-T2 suppression) as a potentially stronger surrogate measure of porosity, which is evaluated ex vivo and in vivo. MATERIALS AND METHODS: Human subject studies were conducted in compliance with institutional review board and HIPAA regulations. Healthy men and women (n = 72; age range, 20-80 years) were examined with a hybrid radial ultrashort echo time magnetic resonance (MR) imaging sequence at 3.0 T, and BWC was determined in the tibial midshaft. In a subset of 40 female subjects, the SR was measured with a similar sequence. Cortical volumetric BMD (vBMD) was measured by means of peripheral quantitative computed tomography (CT). The method was validated against micro-CT-derived porosity in 13 donor human cortical bone specimens. Associations among parameters were evaluated by using standard statistical tools. RESULTS: BWC was positively correlated with age (r = 0.52; 95% confidence interval [CI]: 0.22, 0.73; P = .002) and negatively correlated with vBMD at the same location (r = -0.57; 95% CI: -0.76, -0.29; P < .001). Data were suggestive of stronger associations with SR (r = 0.64, 95% CI: 0.39, 0.81, P < .001 for age; r = -0.67, 95% CI: -0.82, -0.43, P < .001 for vBMD; P < .001 for both), indicating that SR may be a more direct measure of porosity. This interpretation was supported by ex vivo measurements showing SR to be strongly positively correlated with micro-CT porosity (r = 0.88; 95% CI: 0.64, 0.96; P < .001) and with age (r = 0.87; 95% CI: 0.62, 0.96; P < .001). CONCLUSION: The MR imaging-derived SR may serve as a biomarker for cortical bone porosity that is potentially superior to BWC, but corroboration in larger cohorts is indicated.

Bone mineral (31)P and matrix-bound water densities measured by solid-state (31)P and (1)H MRI.

Bone is a composite material consisting of mineral and hydrated collagen fractions. MRI of bone is challenging because of extremely short transverse relaxation times, but solid-state imaging sequences exist that can acquire the short-lived signal from bone tissue. Previous work to quantify bone density via MRI used powerful experimental scanners. This work seeks to establish the feasibility of MRI-based measurement on clinical scanners of bone mineral and collagen-bound water densities, the latter as a surrogate of matrix density, and to examine the associations of these parameters with porosity and donors' age. Mineral and matrix-bound water images of reference phantoms and cortical bone from 16 human donors, aged 27-97 years, were acquired by zero-echo-time 31-phosphorus ((31)P) and 1-hydrogen ((1)H) MRI on whole body 7T and 3T scanners, respectively. Images were corrected for relaxation and RF inhomogeneity to obtain density maps. Cortical porosity was measured by micro-computed tomography (µCT), and apparent mineral density by peripheral quantitative CT (pQCT). MRI-derived densities were compared to X-ray-based measurements by least-squares regression. Mean bone mineral (31)P density was 6.74 ± 1.22 mol/l (corresponding to 1129 ± 204 mg/cc mineral), and mean bound water (1)H density was 31.3 ± 4.2 mol/l (corresponding to 28.3 ± 3.7 %v/v). Both (31)P and bound water (BW) densities were correlated negatively with porosity ((31)P: R(2) = 0.32, p < 0.005; BW: R(2) = 0.63, p < 0.0005) and age ((31)P: R(2) = 0.39, p < 0.05; BW: R(2) = 0.70, p < 0.0001), and positively with pQCT density ((31)P: R(2) = 0.46, p < 0.05; BW: R(2) = 0.50, p < 0.005). In contrast, the bone mineralization ratio (expressed here as the ratio of (31)P density to bound water density), which is proportional to true bone mineralization, was found to be uncorrelated with porosity, age or pQCT density. This work establishes the feasibility of image-based quantification of bone mineral and bound water densities using clinical hardware.

Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design.

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository. METHODS: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes. DISCUSSION: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.

31P NMR relaxation of cortical bone mineral at multiple magnetic field strengths and levels of demineralization.

Recent work has shown that solid-state (1) H and (31) P MRI can provide detailed insight into bone matrix and mineral properties, thereby potentially enabling differentiation of osteoporosis from osteomalacia. However, (31) P MRI of bone mineral is hampered by unfavorable relaxation properties. Hence, accurate knowledge of these properties is critical to optimizing MRI of bone phosphorus. In this work, (31) P MRI signal-to-noise ratio (SNR) was predicted on the basis of T1 and T2 * (effective transverse relaxation time) measured in lamb bone at six field strengths (1.5-11.7 T) and subsequently verified by 3D ultra-short echo-time and zero echo-time imaging. Further, T1 was measured in deuterium-exchanged bone and partially demineralized bone. (31) P T2 * was found to decrease from 220.3 ± 4.3 µs to 98.0 ± 1.4 µs from 1.5 to 11.7 T, and T1 to increase from 12.8 ± 0.5 s to 97.3 ± 6.4 s. Deuteron substitution of exchangeable water showed that 76% of the (31) P longitudinal relaxation rate is due to (1) H-(31) P dipolar interactions. Lastly, hypomineralization was found to decrease T1, which may have implications for (31) P MRI based mineralization density quantification. Despite the steep decrease in the T2 */T1 ratio, SNR should increase with field strength as B0 (0.4) for sample-dominated noise and as B0 (1.1) for coil-dominated noise. This was confirmed by imaging experiments.

Enhancing the brain MRI at ultra-high field systems using a meta-array structure.

BACKGROUND: The main advantage of ultra-high field (UHF) magnetic resonance neuroimaging is theincreased signal-to-noise ratio (SNR) compared with lower field strength imaging. However, the wavelength effect associated with UHF MRI results in radiofrequency (RF) inhomogeneity, compromising whole brain coverage for many commercial coils. Approaches to resolving this issue of transmit field inhomogeneity include the design of parallel transmit systems (PTx), RF pulse design, and applying passive RF shimming such as high dielectric materials. However, these methods have some drawbacks such as unstable material parameters of dielectric pads, high-cost, and complexity of PTx systems. Metasurfaces are artificial structures with a unique platform that can control the propagation of the electromagnetic (EM) waves, and they are very promising for engineering EM device. Implementation of meta-arrays enhancing MRI has been explored previously in several studies. PURPOSE: The aim of this study was to assess the effect of new meta-array technology on enhancing the brain MRI at 7T. A meta-array based on a hybrid structure consisting of an array of broadside-coupled split-ring resonators and high-permittivity materials was designed to work at the Larmor frequency of a 7 Tesla (7T) MRI scanner. When placed behind the head and neck, this construct improves the SNR in the region of the cerebellum,brainstem and the inferior aspect of the temporal lobes. METHODS: Numerical electromagnetic simulations were performed to optimize the meta-array design parameters and determine the RF circuit configuration. The resultant transmit-efficiency and signal sensitivity improvements were experimentally analyzed in phantoms followed by healthy volunteers using a 7T whole-body MRI scanner equipped with a standard one-channel transmit, 32-channel receive head coil. Efficacy was evaluated through acquisition with and without the meta-array using two basic sequences: gradient-recalled-echo (GRE) and turbo-spin-echo (TSE). RESULTS: Experimental phantom analysis confirmed two-fold improvement in the transmit efficiency and 1.4-fold improvement in the signal sensitivity in the target region. In vivo GRE and TSE images with the meta-array in place showed enhanced visualization in inferior regions of the brain, especially of the cerebellum, brainstem, and cervical spinal cord. CONCLUSION: Addition of the meta-array to commonly used MRI coils can enhance SNR to extend the anatomical coverage of the coil and improve overall MRI coil performance. This enhancement in SNR can be leveraged to obtain a higher resolution image over the same time slot or faster acquisition can be achieved with same resolution. Using this technique could improve the performance of existing commercial coils at 7T for whole brain and other applications.

Thermal Stimulus Task fMRI in the Cervical Spinal Cord at 7 Tesla.

PURPOSE: Although functional MRI is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0. Increasing field strength enables higher spatial resolution and improved sensitivity to BOLD signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first stimulus task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D EPI protocols, as they differ in sensitivity to spatial and temporal B0 inhomogeneity. METHODS: The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. For each protocol, the BOLD response to thirteen 10-second noxious thermal stimuli applied to the right thumb was acquired in a 10-minute fMRI run. Image quality, temporal SNR, and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. RESULTS: Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. CONCLUSION: Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment.

A single closed head injury in male adult mice induces chronic, progressive white matter atrophy and increased phospho-tau expressing oligodendrocytes.

Traumatic brain injury (TBI) acutely damages the brain; this injury can evolve into chronic neurodegeneration. While much is known about the chronic effects arising from multiple mild TBIs, far less is known about the long-term effects of a single moderate to severe TBI. We found that a single moderate closed head injury to mice induces diffuse axonal injury within 1-day post-injury (DPI). At 14 DPI, injured animals have atrophy of ipsilesional cortex, thalamus, and corpus callosum, with bilateral atrophy of the dorsal fornix. Atrophy of the ipsilesional corpus callosum is accompanied by decreased fractional anisotropy and increased mean and radial diffusivity that remains unchanged between 14 and 180 DPI. Injured animals show an increased density of phospho-tau immunoreactive (pTau+) cells in the ipsilesional cortex and thalamus, and bilaterally in corpus callosum. Between 14 and 180 DPI, atrophy occurs in the ipsilesional ventral fornix, contralesional corpus callosum, and bilateral internal capsule. Diffusion tensor MRI parameters remain unchanged in white matter regions with delayed atrophy. Between 14 and 180 DPI, pTau+ cell density increases bilaterally in corpus callosum, but decreases in cortex and thalamus. The location of pTau+ cells within the ipsilesional corpus callosum changes between 14 and 180 DPI; density of all cells increases including pTau+ or pTau- cells. >90% of the pTau+ cells are in the oligodendrocyte lineage in both gray and white matter. Density of thioflavin-S+ cells in thalamus increases by 180 DPI. These data suggest a single closed head impact produces multiple forms of chronic neurodegeneration. Gray and white matter regions proximal to the impact site undergo early atrophy. More distal white matter regions undergo chronic, progressive white matter atrophy with an increasing density of oligodendrocytes containing pTau. These data suggest a complex chronic neurodegenerative process arising from a single moderate closed head injury.

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization - An In Vivo Rat Model.

BACKGROUND CONTEXT : Endplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics. PURPOSE : Establish in vivo rat lumbar EP microfracture model with painful phenotype. STUDY DESIGN/SETTING : In vivo rat study to characterize EP-injury model with characterization of IVD degeneration, vertebral bone marrow remodeling, spinal cord sensitization, and pain-related behaviors. METHODS : EP-driven degeneration was induced in 5-month-old male Sprague-Dawley rats L4-5 and L5-6 IVDs through the proximal vertebral body injury with intradiscal injections of TNFα (n=7) or PBS (n=6), compared to Sham (surgery without EP-injury, n=6). The EP-driven model was assessed for IVD height, histological degeneration, pain-like behaviors (hindpaw von Frey and forepaw grip test), lumbar spine MRI and µCT analyses, and spinal cord substance P (SubP). RESULTS : EP injuries induced IVD degeneration with decreased IVD height and MRI T2 values. EP injury with PBS and TNFα both showed MC type1-like changes on T1 and T2-weighted MRI, trabecular bone remodeling on µCT, and damage in cartilage EP adjacent to the injury. EP injuries caused significantly decreased paw withdrawal threshold and reduced grip forces, suggesting increased pain sensitivity and axial spinal discomfort. Spinal cord dorsal horn SubP was significantly increased, indicating spinal cord sensitization. CONCLUSIONS : EP microfracture can induce crosstalk between vertebral bone marrow, IVD and spinal cord with chronic pain-like conditions. CLINICAL SIGNIFICANCE : This rat EP microfracture model of IVD degeneration was validated to induce MC-like changes and pain-like behaviors that we hope will be useful to screen therapies and improve treatment for EP-drive pain.