Publications by authors named "Kristin P O'Grady"

While typical qualitative T1-weighted magnetic resonance images reflect scanner and protocol differences, quantitative T1 mapping aims to measure T1 independent of these effects. Changes in T1 in the brain reflect structural changes in brain tissue. Magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) is an acquisition protocol that allows for efficient T1 mapping with a much lower scan time per slab compared to multi-TI inversion recovery (IR) protocols.

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Background And Purpose: Conclusions from prior literature regarding the impact of sex, age, and height on spinal cord (SC) MRI morphometrics are conflicting, while the effect of body weight on SC morphometrics has been found to be nonsignificant. The purpose of this case-control study is to assess the associations between cervical SC MRI morphometric parameters and age, sex, height, and weight to establish their potential role as confounding variables in a clinical study of people with multiple sclerosis (MS) compared to a cohort of healthy volunteers.

Methods: Sixty-nine healthy volunteers and 31 people with MS underwent cervical SC MRI at 3 Tesla field strength.

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  • Clinical research typically requires careful study designs that account for variables like sex and age, but often overlooks body size factors like height and weight in neuroimaging studies.
  • This study analyzed data from 267 healthy adults to explore how body height and weight relate to various brain and spinal cord MRI metrics, finding significant correlations, especially with brain gray matter volume and cervical spinal cord area.
  • The results suggest that body size is an important biological variable that should be included in clinical neuroimaging study designs to enhance accuracy in understanding brain and spinal cord structures.
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  • Diffusion MRI of the spinal cord faces challenges due to geometric distortions and motion artifacts, which can lead to issues with image alignment and quality.
  • This study examines two key techniques: susceptibility corrections for better geometric alignment and cardiac triggering to reduce motion artifacts during imaging.
  • Results indicate that while susceptibility corrections improve alignment with high-contrast cerebrospinal fluid images, they do not necessarily enhance spinal cord geometry or matter contrast; however, skipping cardiac triggering does not compromise image quality and allows for quicker scans.
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Background: Imaging investigation of cerebrospinal fluid (CSF) in multiple sclerosis (MS) is understudied. Development of noninvasive methods to detect pathological CSF changes would have a profound effect on MS diagnosis and would offer insight into MS pathophysiology and mechanisms of neurological impairment.

Objective: We propose magnetization transfer (MT) MRI as a tool to detect macromolecular changes in spinal CSF.

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Background And Purpose: Paramagnetic rims and the central vein sign (CVS) are proposed imaging markers of multiple sclerosis (MS) lesions. Using 7 tesla magnetic resonance imaging, we aimed to: (1) characterize the appearance of paramagnetic rim lesions (PRLs); (2) assess whether PRLs and the CVS are associated with higher levels of MS pathology; and (3) compare the characteristics between subjects with and without PRLs in early MS.

Methods: Prospective study of 32 treatment-naïve subjects around the time of diagnosis who were assessed for the presence of PRLs and the CVS.

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  • Susceptibility-weighted imaging (SWI) has primarily been used in brain studies, particularly for conditions like multiple sclerosis (MS), but there's limited research on its application in the spinal cord.
  • This study includes a comparison of the cervical spinal cord in 9 MS patients and 12 healthy controls using high-field SWI techniques, revealing significant vascular differences and unique lesion characteristics in the MS group.
  • Results demonstrated better visibility of blood vessels and distinct changes associated with MS pathology, suggesting that SWI could enhance our understanding of spinal cord disease processes in MS patients.
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Functional MRI (fMRI) of the spinal cord is an expanding area of research with potential to investigate neuronal activity in the central nervous system. We aimed to characterize the functional connectivity features of the human lumbar spinal cord using resting-state fMRI (rs-fMRI) at 3T, using region-based and data-driven analysis approaches. A 3D multi-shot gradient echo resting-state blood oxygenation level dependent-sensitive rs-fMRI protocol was implemented in 26 healthy participants.

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Quantitative diffusion MRI (dMRI) is a promising technique for evaluating the spinal cord in health and disease. However, low signal-to-noise ratio (SNR) can impede interpretation and quantification of these images. The purpose of this study is to evaluate several dMRI denoising approaches on their ability to improve the quality, reliability, and accuracy of quantitative diffusion MRI of the spinal cord.

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Spinal cord magnetic resonance imaging (MRI) has a central role in multiple sclerosis (MS) clinical practice for diagnosis and disease monitoring. Advanced MRI sequences capable of visualizing and quantifying tissue macro- and microstructure and reflecting different pathological disease processes have been used in MS research; however, the spinal cord remains under-explored, partly due to technical obstacles inherent to imaging this structure. We propose that the study of the spinal cord merits equal ambition in overcoming technical challenges, and that there is much information to be exploited to make valuable contributions to our understanding of MS.

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Several recent multi-compartment diffusion MRI investigations and modeling strategies have utilized the orientationally-averaged, or spherical mean, diffusion-weighted signal to study tissue microstructure of the central nervous system. Most experimental designs sample a large number of diffusion weighted directions in order to calculate the spherical mean signal, however, sampling a subset of these directions may increase scanning efficiency and enable either a decrease in scan time or the ability to sample more diffusion weightings. Here, we aim to determine the minimum number of gradient directions needed for a robust measurement of the spherical mean signal.

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  • * The study involved 26 RRMS patients and assessed tissue integrity using diffusion tensor imaging (DTI), revealing lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the normal white matter of RRMS patients compared to controls.
  • * Higher FC in the dorsal sensory network was significantly linked to various markers of tissue damage, suggesting that increased connectivity may be a compensatory response to maintain sensory function despite structural damage in RRMS patients.
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Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS).

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  • Vascular endothelial cells react to changes in their environment, such as how stiff the substrate is, impacting barrier functions in conditions like atherosclerosis, but the effects on blood-brain barrier (BBB) cells are less understood.
  • This study used hydrogel substrates of different stiffness to examine how induced pluripotent stem cell-derived brain microvascular endothelial-like cells (BMEC-like) behave, assessing changes through imaging and functional tests like transendothelial electrical resistance (TEER).
  • Results showed that softer substrates enhance TEER longevity and alter the formation of actin stress fibers, indicating that stiffness affects passive barrier function in BBB cells, which could improve understanding of BBB issues in neurodegenerative diseases.
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  • A new standardized quantitative MRI protocol for spinal cord imaging, called the spine generic protocol, has been developed to be used with 3T MRI systems from major manufacturers like GE, Philips, and Siemens.
  • The protocol includes specific imaging techniques for evaluating spinal cord macrostructure and microstructure, such as T1 and T2-weighted imaging to determine cross-sectional areas and diffusion-weighted imaging for white matter assessment.
  • An open-access document detailing the protocol is available online, providing a useful resource for researchers and clinicians aiming to enhance spinal cord imaging in neuroimaging practices.
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  • - The paper by Cohen-Adad et al. introduces a standardized MRI protocol for evaluating spinal cord integrity, tested across 19 and 42 centers for single and multi-subject datasets respectively, involving a total of 260 participants.
  • - The datasets are openly available online, allowing researchers to access valuable data for analysis using tools like the Spinal Cord Toolbox, which produces normative values and statistics on variability across sites and manufacturers.
  • - The protocol demonstrated high reproducibility with less than 5% variation across different sites and manufacturers, aiming to enhance the accessibility and reliability of quantitative MRI assessments in spinal research.
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Cognitive impairment (CI) is a major manifestation of multiple sclerosis (MS) and is responsible for extensively hindering patient quality of life. Cortical gray matter (cGM) damage is a significant contributor to CI, but is poorly characterized by conventional MRI let alone with quantitative MRI, such as quantitative magnetization transfer (qMT). Here we employed high-resolution qMT at 7T via the selective inversion recovery (SIR) method, which provides tissue-specific indices of tissue macromolecular content, such as the pool size ratio (PSR) and the rate of MT exchange (kmf).

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Multi-compartment tissue modeling using diffusion magnetic resonance imaging has proven valuable in the brain, offering novel indices sensitive to the tissue microstructural environment in vivo on clinical MRI scanners. However, application, characterization, and validation of these models in the spinal cord remain relatively under-studied. In this study, we apply a diffusion "signal" model (diffusion tensor imaging, DTI) and two commonly implemented "microstructural" models (neurite orientation dispersion and density imaging, NODDI; spherical mean technique, SMT) in the human cervical spinal cord of twenty-one healthy controls.

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The inherent antioxidant function of poly(propylene sulfide) (PPS) microspheres (MS) was dissected for different reactive oxygen species (ROS), and therapeutic benefits of PPS-MS were explored in models of diabetic peripheral arterial disease (PAD) and mechanically induced post-traumatic osteoarthritis (PTOA). PPS-MS (∼1 m diameter) significantly scavenged hydrogen peroxide (HO), hypochlorite, and peroxynitrite but not superoxide in vitro in cell-free and cell-based assays. Elevated ROS levels (specifically HO) were confirmed in both a mouse model of diabetic PAD and in a mouse model of PTOA, with greater than 5- and 2-fold increases in HO, respectively.

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Background: Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T- and T-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM.

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