Design, Development and Temporal Evaluation of an MRI-Compatible In-Vitro Circulation Model Using a Compliant AAA Phantom

Biomechanical characterization of abdominal aortic aneurysms (AAA) has become commonplace in rupture risk assessment studies. However, its translation to the clinic has been greatly limited due to the complexity associated with its tools and their implementation. The unattainability of patient-specific tissue properties leads to the use of generalized population-averaged material models in finite element analyses, which adds a degree of uncertainty to the wall mechanics quantification. In addition, computational fluid dynamics modeling of AAA typically lacks the patient-specific inflow and outflow boundary conditions that should be obtained by non-standard of care clinical imaging. An alternative approach for analyzing AAA flow and sac volume changes is to conduct in vitro experiments in a controlled laboratory environment. We designed, built, and characterized quantitatively a benchtop flow-loop using a deformable AAA silicone phantom representative of a patient-specific geometry. The impedance modules, which are essential components of the flow-loop, were fine-tuned to ensure typical intra-sac pressure conditions. The phantom was imaged with a magnetic resonance imaging (MRI) scanner to acquire time-resolved images of the moving wall and the velocity field inside the sac. Temporal AAA sac volume changes lead to a corresponding variation in compliance throughout the cardiac cycle. The primary outcome of this work was the design optimization of the impedance elements, the quantitative characterization of the resistive and capacitive attributes of a compliant AAA phantom, and the exemplary use of MRI for flow visualization and quantification of the deformed AAA geometry

ECG-triggered non-enhanced MR angiography of peripheral arteries in comparison to DSA in patients with peripheral artery occlusive disease

Object: The purpose of this study was to evaluate peripheral non-enhanced-MRA (NE-MRA) acquired with a 3D Turbo Spin Echo sequence with electrocardiographt (ECG) triggering in comparison to Digital Subtraction Angiography (DSA) as the gold standard in symptomatic peripheral artery occlusive disease (PAOD) patients. Materials and methods: This IRB approved prospective study included 23 PAOD patients from whom three patients had to be excluded. The remaining 20 subjects were included in the analysis (15 male; mean age 62.4±15.3years). The patients first underwent DSA followed by NE-MRA on a 1.5-T whole body scanner within 24h after the DSA study. A NATIVE (Non-contrast Angiography of the Arteries and Veins) SPACE (Sampling Perfection with Application Optimized Contrast by using different flip angle Evolution) sequence at four levels (pelvis, upper leg, knee region and lower leg) was acquired. For evaluation purposes, subtracted standardized MIP (maximum intensity projection) images were generated from the NE-MRA data sets. Qualitative assessment of NE-MRA images in reference to the corresponding DSA images, as well as blinded stenosis grading of preselected segments in NE-MRA images were performed by two experienced readers. Image quality in 95 corresponding arterial segments was rated from 1 (good) to 4 (inadequate) directly comparing the NE-MRA with the corresponding DSA segment as the gold standard. Blinded stenosis grading consisted of 66 preselected stenoses rated from 1 (90%) in NE-MRA which were compared to the grade in the corresponding DSA. Results: The mean image quality of NE-MRA in comparison to DSA was 2.7±1.1 (reader 1) and 3.0±1.0 (reader 2). The kappa value indicating interobserver agreement was 0.34; readers 1 and 2 rated the image quality as good in 21% and 3%, sufficient in 19% and 41%, limited in 29% and 14% and inadequate in 31% and 42%, respectively. Stenosis graduation revealed significantly higher grades in NE-MRA (reader 1: 3.0±0.7, p<0.001 and reader 2: 3.1+0.8, p<0.001) compared to DSA (mean value DSA 2.7±0.8). The kappa value indicating interobserver agreement concerning stenosis grading was 0.59. Conclusion: NE-MRA revealed a relatively high number of inadequate quality segments. This is in line with recently published comparable studies of the similar SPACE NE-MRA techniques. Further advance of NE-MRA techniques remains desirable for patients with PAO

Gold-silver alloy nanoshells: a new candidate for nanotherapeutics and diagnostics

We have developed novel gold-silver alloy nanoshells as magnetic resonance imaging (MRI) dual T1 (positive) and T2 (negative) contrast agents as an alternative to typical gadolinium (Gd)-based contrast agents. Specifically, we have doped iron oxide nanoparticles with Gd ions and sequestered the ions within the core by coating the nanoparticles with an alloy of gold and silver. Thus, these nanoparticles are very innovative and have the potential to overcome toxicities related to renal clearance of contrast agents such as nephrogenic systemic fibrosis. The morphology of the attained nanoparticles was characterized by XRD which demonstrated the successful incorporation of Gd(III) ions into the structure of the magnetite, with no major alterations of the spinel structure, as well as the growth of the gold-silver alloy shells. This was supported by TEM, ICP-AES, and SEM/EDS data. The nanoshells showed a saturation magnetization of 38 emu/g because of the presence of Gd ions within the crystalline structure with r1 and r2 values of 0.0119 and 0.9229 mL mg-1 s-1, respectively (Au:Ag alloy = 1:1). T1- and T2-weighted images of the nanoshells showed that these agents can both increase the surrounding water proton signals in the T1-weighted image and reduce the signal in T2-weighted images. The as-synthesized nanoparticles exhibited strong absorption in the range of 600-800 nm, their optical properties being strongly dependent upon the thickness of the gold-silver alloy shell. Thus, these nanoshells have the potential to be utilized for tumor cell ablation because of their absorption as well as an imaging agent

Lower locus coeruleus integrity in older COVID-19 survivors: initial findings from an international 7T MRI consortium

Background: The SARS-CoV-2 coronavirus has been associated with structural brain changes, consistent with its neurological manifestations. Recent studies showed a specific predilection for brainstem glial activation and hypometabolism, possibly indicating involvement of the locus coeruleus. The locus coeruleus (LC) modulates many cognitive functions and behaviors and its norepinephrine projections regulate both immune responses and vascular reactivity. We aimed to examine differences in LC integrity between COVID-19 survivors and controls. Method: Participants are enrolled across 3 US and 1 UK sites using harmonized cognitive and 7T MR-imaging protocols. Here, we analyzed data from 18 participants enrolled at Houston Methodist (12 COVID-19 survivors, 6 controls; Figure 1). COVID-19 survivors were required to have had a positive antigen test and an illness syndrome consistent with COVID-19. Healthy controls were required to have no significant pre-existing medical, neurologic, or psychiatric illness and no illness requiring hospitalization in the last 2 years. LC imaging was performed using a dedicated 7T MT-TFL sequence (0.4 x 0.4 x0.5mm). A site-specific normalized template was constructed using ANTs/FSL. The entire average LC integrity as well as voxel-wise integrity values were compared between COVID-19 survivors and controls using a robust linear regression (age-controlled and threshold free cluster enhancement corrected). LC integrity was correlated with age, sex, ethnicity and cognition using Spearman’s rank correlation. Result: Average LC integrity was not correlated with age, sex, or Hispanic ethnicity (p\u3e0.3). COVID-19 survivors did not differ from Controls when examining the entire LC (p=0.54). Voxel-wise analyses revealed a small cluster (19 voxels) in the middle portion of the left LC where COVID-19 survivors exhibited lower LC integrity than controls (p=0.005; Figure 2). Integrity of this cluster was not related to age or Hispanic ethnicity (p=0.9). LC integrity did not correlate with cognitive performance within the COVID-19 survivors (Trail Making Test B: p=0.43; Craft Story delayed recall p=0.47; MoCA p=0.84). Conclusion: Consistent with previous animal and human studies, our initial findings provide evidence for neuroinvasive potential of SARS-CoV-2 localized in the middle LC. In the future, we aim to expand our sample and link these observations to the neurocognitive sequelae of COVID-19

Clinical implications of skeletal muscle blood-oxygenation-level-dependent (BOLD) MRI

Blood-oxygenation-level-dependent (BOLD) contrast in magnetic resonance (MR) imaging of skeletal muscle mainly depends on changes of oxygen saturation in the microcirculation. In recent years, an increasing number of studies have evaluated the clinical relevance of skeletal muscle BOLD MR imaging in vascular diseases, such as peripheral arterial occlusive disease, diabetes mellitus, and chronic compartment syndrome. BOLD imaging combines the advantages of MR imaging, i.e., high spatial resolution, no exposure to ionizing radiation, with functional information of local microvascular perfusion. Due to intrinsic contrast provoked via changes in hemoglobin oxygen saturation, it is a safe and easy applicable procedure on standard whole-body MR devices. Therefore, BOLD MR imaging of skeletal muscle is a potential new diagnostic tool in the clinical evaluation of vascular, inflammatory, and muscular pathologies. Our review focuses on the current evidence concerning the use of BOLD MR imaging of skeletal muscle under pathological conditions and highlights ways for future clinical and scientific application

Preliminary neurocognitive finding from a multi-site study investing long-term neurological impact of COVID-19 using ultra-high field 7 Tesla MRI-based neuroimaging

Background: Globally, over six hundred million cases of SARS-CoV-2 have been confirmed. As the number of individuals in recovery rises, examining long-term neurological effects, including cognitive impairment and cerebral microstructural and microvascular changes, has become paramount., We present preliminary cognitive findings from an ongoing multi-site study investigating the long-term neurological impacts of COVID-19 using 7 Tesla MRI-based neuroimaging. Methods: Across 3 US and 1 UK sites, we identified adult (\u3e=18) COVID-19 survivors (CS) and healthy controls (HC) without significant pre-existing medical, neurological, or psychiatric illness. Using the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS-3) battery and Norms Calculator, 12 cognitive scores were adjusted for age, sex, and education and classified as either unimpaired or mild (\u3c9th percentile), moderate (\u3c2nd percentile), or severely impaired (\u3c1st percentile). The observed frequency of impairment across the two groups is reported along with proportional differences (PD) and confidence intervals (CI). Illness severity and time since infection were evaluated as potential associates of cognitive impairment. Results: Over a period of 11 months, we enrolled 108 participants. At the time of reporting, 80 (46.3% female; mean age: 60.3 ± 8.6; 61 CS, 19 HC) had completed cognitive assessments. Of the participants for whom we ascertained time since symptom onset and illness severity (n=51 and 43, respectively), 31.4% had their index COVID-19 infection within the past year, and 60.5% had a severe to critical infection (Table 1). Table 2 reports observed frequency of impairment for each metric. Aggregating all 12 cognitive metrics, we found 45 (73.8%) of CS had at least one impairment [vs HC: 10 (52.6%)]. A significantly greater proportion of CS had at least one moderate to severe or severe impairment (Figure 1). CS also had significantly higher frequencies of presenting with two or more mild to severe impairments [PD 0.33 (0.13, 0.54)]. Illness severity and time since infection were not significantly associated with cognitive impairment. Conclusion: Our preliminary results are consistent with potentially sustained COVID-associated cognitive impairment in a subset of participants. Enrollment in the multi-site cohort is ongoing, and updated results will be presented along with ultra-high field MRI-based neuroimaging correlates

Investigating white matter hyperintensities in a multicenter COVID-19 study using 7T MRI

Background: Emerging evidence indicates that COVID-19 can negatively impact patient’s brain health (Douaud et al., 2022) (Cecchetti et al., 2022). Common clinical symptoms include brain fog, headaches, difficulty concentrating, and loss of sense of smell or taste. Some studies suggest that SARS-CoV-2 infection can damage the blood brain barrier either directly or through immune-inflammatory mechanisms (Zhang, et al. 2021). White matter hyperintensities (WMH) are imaging biomarkers of brain vascular or inflammatory injury. We investigated the association between severity of COVID-19 infection and burden of white matter hyperintensity volumes within a diverse multi-nation, multi-racial cohort using 7 Tesla (7T) MRI that can detect more subtle injury than conventional 1.5 or 3T MRI. Method: Participants were recruited at 4 sites: Pittsburgh, San Antonio and Houston, USA, and Nottingham, UK. To date, we have scanned and included the following participants in our analysis (Table 1). Detailed cognitive, neurological, mood and functional assessments and high-resolution MRI scans were collected. Subsequent WMH segmentation was performed using our in-house built deep learning based model (Figure 1). All segmentations were visually inspected and manually corrected before statistical analysis. Normalized WMH is calculated as a ratio of the WMH volume and the intracranial volume (WMH/ICV). Imaging data for an additional 36 age-matched controls were retrieved from the 7 Tesla Bioengineering Research Program (7TBRP) imaging bank at Pittsburgh. Result: Figure 1 shows the WMH segmentation outputs from our deep learning based model on images acquired at the 3 sites. Our Linear regression models along with our non-parametric Kruskal-Wallis test result suggests that compared to mild COVID cases and healthy control, COVID infected individuals that were ICU admitted show elevated WMH burden (Figure 2). Conclusion: Our results demonstrate that white matter hyperintensity volumes were higher among patients who had severe acute COVID infection that required ICU admission, compared to healthy age-matched controls. In contrast, no difference in white matter burden was observed in patients with mild COVID infection compared to healthy controls. Additional data (both cross-sectional and longitudinal), including more sensitive MRI measures is being collected to define the full spectrum of brain injury associated with sequelae of COVID infection