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Irene Margaret Vavasour^1,2, Kyle Vavasour³, Adam Dvorak⁴, Tigris Joseph^2,4, Robert Carruthers⁵, Shannon Kolind^1,2,4,5, Alice Schabas⁵, Ana-Luiza Sayao⁵, Virginia Devonshire⁵, Roger Tam^1,6, GR Wayne Moore^2,5,7, Anthony Traboulsee⁵, David Li^1,5, and Cornelia Laule^1,2,4,7
1Radiology, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada, ³University of British Columbia, Vancouver, BC, Canada, ⁴Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ⁵Medicine, University of British Columbia, Vancouver, BC, Canada, ⁶School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada, ⁷Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Keywords: Multiple Sclerosis, Multiple Sclerosis, diffusely abnormal white matter, T2 relaxation

Diffusely abnormal white matter (DAWM) is seen on 25-50% of conventional brain MRI scans from all stages of multiple sclerosis (MS). From 8 advanced MRI metrics, geometric mean T₂ of the intra/extracellular water (IET₂) best separated MS participants with and without DAWM. Comparing IET₂ to controls using z-scores, regions with an intermediate increase in IET₂ (z-scores between 1-2) may identify DAWM voxels.

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Yawen Sun¹, Hongjiang Wei², and Yan Zhou^1
1Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, ²School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

Keywords: Dementia, Diffusion/other diffusion imaging techniques, Free water mapping

This study was to evaluate the neuroinflammation-related characteristics of the deep gray matter using free-water mapping in small vessel disease over 1-2 years.  Our results support the presence of elevated free water at the preclinical stage of small vessel disease, which remains persistent during the early course of the illness. The free water values changes might be the biomarkers for the mechanism of cognitive decline in the evolution of small vessel disease.

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Ali Rezaei^1,2, Stefanie A Tremblay^1,2, Dalia Sabra^1,2,3,4, Safa Sanami^1,2, Brittany Intzandt⁵, Julia Huck¹, Zacharie Potvin-Jutras^1,2, Christine Gagnon², Amelie Mainville-Berthiaume⁶, Lindsay N Wright^1,2, Dajana Vuckovic⁷, Josep Iglesies-Grau^2,8, Thomas Vincent², Mathieu Gayda², Anil Nigam², Louis Bherer^2,8,9, and Claudine J Gauthier^1,2
1Physics Department, Concordia University, Montreal, QC, Canada, ²Centre Epic and Research Center, Montreal Heart Institute, Montreal, QC, Canada, ³Department of Biomedical Science, Faculty of Medicine, Université de Montreal, Montreal, QC, Canada, ⁴PERFORM Centre, Concordia University, Montreal, QC, Canada, ⁵BrainLab, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada, ⁶Department of Psychology, Concordia University, Montreal, QC, Canada, ⁷Department of Chemistry and Biochemistry, Concordia University, Montreal, QC, Canada, ⁸Department of Medicine, Université de Montreal, Montreal, QC, Canada, ⁹Research Center, Institut Universitaire de Gériatrie de Montréal, Montreal, QC, Canada

Keywords: Blood vessels, Oxygenation

Here we investigated the effect of coronary artery disease (CAD) on the brain oxygen extraction fraction (OEF) using quantitative susceptibility mapping (QSM). Our results, in a pilot dataset, show that OEF was significantly higher in CAD patients than in healthy controls in the caudate nucleus. This may be the result of declining cerebrovascular health in CAD patients in this region. However, since the caudate nucleus is iron-rich, this difference may also be interpreted as iron deposition as CAD has a known neuroinflammatory effect. Future work will investigate the impact of CAD on other metabolic and vascular components of brain health.

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Nhat Hoang¹, Henry Wang², Sahin Bogachan³, Muhammad Waqas Khan⁴, Abrar Faiyaz⁵, Meera Singh³, Jinjiang Pang⁶, Shumin Wang⁶, Li Chen⁷, Chun Yuan⁷, Jianhui Zhong¹, Hongmei Yang⁸, Md Nasir Uddin³, and Giovanni Schifitto^3
1Physics, University of Rochester, Rochester, NY, United States, ²Radiology, University of Rochester, Rochester, NY, United States, ³Neurology, University of Rochester, Rochester, NY, United States, ⁴Neurology-Stroke Division, University of Rochester, Rochester, NY, United States, ⁵Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, United States, ⁶Cardiology Research, University of Rochester, Rochester, NY, United States, ⁷Department of Electrical and Computer Engineering, University of Washington, Seattle, WA, United States, ⁸Biostatistics, University of Rochester, Rochester, NY, United States

Keywords: Neuroinflammation, Vessels, MRA, CSVD, HIV

HIV infected individuals (HIV+) are subjected to high risks of neurological complications, including cerebrovascular disease. Quantification of vascular features may provide a tool to investigate pathomechanisms and monitor cerebrovascular disease progression. In this study we used intracranial artery feature extraction (iCafe) to compare HIV+ with age matched controls. 

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Mario Ocampo-Pineda^1,2,3, Alessandro Cagol^1,2,3, Muhamed Barakovic^1,2,3, Po-Jui Lu^1,2,3, Jannis Müller^1,2,3, Sabine Schaedelin⁴, Pascal Benkert⁴, Matthias Weigel^1,2,3,5, Lester Melie-Garcia^1,2,3, Jens Kuhle^2,3, Ludwig Kappos^1,2,3, and Cristina Granziera^1,2,3
1Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland, ²Department of Neurology, University Hospital Basel, Basel, Switzerland, ³Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland, ⁴Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland, ⁵Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland

Keywords: White Matter, Diffusion Tensor Imaging

Progression independent of relapse activity (PIRA) has been described in patients with multiple sclerosis (MS) even in the earliest disease stages. Patients with PIRA show increased atrophy rates in multiple brain regions compared to stable patients. Here, we investigated whether patients with PIRA exhibit loss of integrity in WM tracts compared to stable patients. We studied 62 RRMS patients, 27 PIRA and 35 stable patients using a clinical DW-MRI protocol. Our results showed that PIRA patients present smaller FA values in areas of corpus callosum and along corticosprinal tract. These differences suggest neurodegeneration in major WM tracts of PIRA patients.

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Kyla Ann Gaudet¹, Laleh Eskandarian¹, Melanie Li², Susie Y Huang¹, and Katharina Eikermann-Haerter^3
1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States, ²Department of Neurology, New York University Grossman School of Medicine, New York, NY, United States, ³Division of Neuroradiology, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States

Keywords: Gray Matter, Neuroinflammation

Migraine is one of the most common neurological disorders. Thirty percent of migraine patients develop transient neurological symptoms, the so-called migraine aura. Migraineurs, particularly those with aura, show an increased incidence of white matter lesions (WML). To improve our understanding of WML in migraineurs, we utilized Soma and Neurite Density Image (SANDI) as an advanced diffusion magnetic resonance imaging signal model to assess in-vivo microstructure of gray matter and white matter. We found evidence for occult changes in microstructural gray and white matter integrity that point to a common underlying mechanism driving cellular inflammation and neuronal injury in migraine.

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Michael Lan¹, Valentin Stepanov¹, Jenny Chen¹, Benjamin Ades-Aron¹, Dmitry S. Novikov¹, and Els Fieremans^1
1Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States

Keywords: Multiple Sclerosis, Diffusion/other diffusion imaging techniques

Diabetes mellitus (DM) has been potentially associated with multiple sclerosis (MS), but has not been definitively shown to worsen its severity. Our study used diffusion kurtosis imaging (DKI) analyzed with tract-based spatial statistics to identify significant differences in DKI metrics in addition to measuring lesion volume in MS and Control patients with and without DM. We observed significantly increased diffusion and axial kurtosis and increased periventricular lesion volume in MS patients with DM compared to those without DM, indicating worsening inflammation and demyelination, suggesting that DM may serve as an exacerbating factor for worsening MS prognosis.

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Thanh D. Nguyen¹, Liangdong Zhou¹, Yeona Kang², Emily Demmon¹, Michael Sakirsky¹, Elizabeth M. Sweeney³, Yi Wang¹, Yi Li¹, and Susan A. Gauthier^1
1Weill Cornell Medicine, New York, NY, United States, ²Howard University, Washington, DC, United States, ³University of Pennsylvania, Philadelphia, PA, United States

Keywords: Multiple Sclerosis, Neurofluids

We applied FAST-T2 multi-component T2 relaxometry to 200 MS patients and 66 healthy controls and found that the thalamic cerebrospinal fluid fraction (CSFF) increases with age and follows a different trajectory in MS. In 13 MS patients, we also found a strong correlation between CSFF and [¹¹C]PK11195 uptake on PET in the thalamus and putamen, suggesting a connection between glymphatic dysfunction and microglial inflammation in the MS brain.

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Jack TE Elkas¹, Frederico Pieruccini-Faria², Manuel Montero-Odasso², and Robert Bartha^3
1Neuroscience Department, Western University, London, ON, Canada, ²Gait and Brain Lab, Parkwood Institute and Lawson Health Research Institute, London, ON, Canada, ³Department of Medical Biophysics and Robarts Research Institute, Schulich School of Medicine and Dentistry, London, ON, Canada

Keywords: Dementia, Spectroscopy, Neuroinflammation, Dementia, Aging, Brain, Degenerative, Dementia, Neurodegeneration

The dual-task cost on walking speed (DTC) can predict the progression of dementia in people with mild cognitive impairment (MCI). In MCI, levels of choline in the primary motor cortex, an MRS metabolite associated with inflammation, has been negatively correlated with dual-task speed. However, it is unknown whether DTC can predict choline changes in MCI. 65 MCI patients were assessed for DTC speed and absolute choline concentration in the motor cortex before and after 6 months. DTC at baseline was positively correlated with changes in choline after 6 months, suggesting that gait impairment may precede neuroinflammation in MCI.

Qingrui Li¹, Xiarong Gong², Qiu Bi², Yunzhu Wu³, and Kunhua Wu^2
1Kunming University of Science and Technology, Kunming, China, ²the Affiliated Hospital of Kunming University of Science and Technology, Kunming, China, ³MR Scientific Marketing, Siemens Healthineers, Shanghai, China

Keywords: Neuroinflammation, Diffusion Tensor Imaging, encephalitis

In this study, diffusion tensor imaging (DTI) analysis based on Tract-based spatial statistics (TBSS) was used to investigate the microstructural changes of white matter (WM) in viral encephalitis (VE) and autoimmune encephalitis (AE). The study found that WM injury degree in patients with VE and AE was different. The DTI parameters can separate AE, VE and healthy control group. The study results indicate that DTI could serve the function of early diagnosing and distinguishing AE from VE, and provide imaging evidence for the pathophysiological changes of WM in AE and VE patients.

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Giacomo Boffa¹, Simona Schiavi¹, Francesco Tazza¹, Caterina Lapucci², Gian Franco Piredda^3,4,5, Domenico Zacà⁶, Luca Roccatagliata⁷, Tom Hilbert^3,4,5, Tobias Kober^3,5,8, Matilde Inglese¹, and Mauro Costagli^1,9
1Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy, ²Laboratory of Experimental Neurosciences, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, ³Advanced Clinical Imaging Technology, Siemens Healthineers International AG, Lausanne, Switzerland, ⁴Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ⁵LTS5, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁶Siemens Healthcare, Milan, Italy, ⁷Department of Neuroradiology, Health Sciences, University of Genoa, Genoa, Italy, ⁸Lausanne University Hospital and University of Lausanne, Department of Radiology, Luasanne, Switzerland, ⁹IRCCS Stella Maris, Pisa, Italy

Keywords: Multiple Sclerosis, Multi-Contrast

Quantitative MRI has the potential to disentangle the heterogeneity of multiple sclerosis (MS) lesions in vivo, which can be decisive for treatment and monitoring. In this study, we distinguished different types of MS lesions based on quantitative susceptibility mapping (QSM) and characterized them using T1 relaxometry, diffusion imaging and myelin mapping. We identified four types of lesions (hypo/isointense, homogeneous hyperintense, inhomogeneous hyperintense and paramagnetic rim), which were characterized by increasing degrees of axonal and myelin disruption. Paramagnetic rim lesions were closer to the ventricular CSF, corroborating the presence of a noxious activity of CSF in MS pathology.

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Samantha Noteboom¹, Jelle J. Vellema¹, Martijn D. Steenwijk¹, Helga E. de Vries², Frederik Barkhof^3,4, Joep Killestein⁵, Eva M. M. Strijbis⁵, and Menno M. Schoonheim^1
1MS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, Netherlands, ²Department of Molecular Cell Biology and Immunology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, Netherlands, ³MS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, Netherlands, ⁴Institutes of Neurology and Healthcare Engineering, UCL London, London, United Kingdom, ⁵MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, Netherlands

Keywords: Multiple Sclerosis, Neuroinflammation

Enlargement of the choroid plexus (ChP) has been recently suggested in multiple sclerosis (MS), but relations with clinical and MRI outcome measures remain unclear. In this study, we compared automated segmentation approaches to assess ChP volume on 3D-T1 to manual outlines. Next, ChP volume was assessed in 327 patients with MS and 78 healthy controls. Gaussian Mixture Modelling (GMM)-based segmentation showed best agreement with manual segmentations in MS and controls. Enlargement of ChP was observed in MS compared to controls, and was associated with worse physical disability and cognitive impairment and more severe brain, cortical and thalamic atrophy. 

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Emani Hunter¹, Lesley Foley², Yifan Zhao¹, Howard Aizenstein^1,3, Minjie Wu^1,3, and Bistra Iordanova^1
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ²Animal Imaging Center, University of Pittsburgh, Pittsburgh, PA, United States, ³Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States

Keywords: Alzheimer's Disease, Relaxometry, Diffusion Tensor Imaging

Cerebral microbleeds are morphologic changes contributing to the progression of Alzheimer’s Disease and vascular dementias. However, the effects of microbleeds on brain connectivity across age and sex remain to be understood. In this study, we performed T2* mapping, that was registered to a DTI space to measure diffusion changes in microbleed locations. R2* and diffusion tensor indices demonstrate an inverse relationship, where diffusion is low and R2* rates are high. Our results suggest that microbleeds decrease water diffusion in the brain possibly due to increased neuroinflammation and hemosiderin accumulation, shedding light on abnormal tissue structure in Alzheimer’s disease subjects.

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Juin W. Zhou¹, Chuan Huang^1,2, Kritikos Minos³, Sean A.P. Clouston³, Megan K. Horton⁴, Roman Kotov⁵, Roberto G. Lucchini^6,7, Evelyn J. Bromet⁵, and Benjamin J. Luft^8,9
1Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States, ²Radiology, Renaissance School of Medicine, Stony Brook, NY, United States, ³Family, Population, and Preventative Medicine, Renaissance School of Medicine, Stony Brook, NY, United States, ⁴Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ⁵Psychiatry, Renaissance School of Medicine, Stony Brook, NY, United States, ⁶Environmental Health Sciences, Florida International University, Miami, FL, United States, ⁷Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy, ⁸Medicine, Renaissance School of Medicine, Stony Brook, NY, United States, ⁹Stony Brook WTC Wellness Program, Renaissance School of Medicine, Stony Brook, NY, United States

Keywords: Neurodegeneration, Psychiatric Disorders

World Trade Center (WTC) responders are at mid-life, with 23% presenting with chronic post-traumatic stress disorder (PTSD). Epidemiologic studies suggest that chronic PTSD is associated with psychomotor slowing and physical functional limitations consistent with intracortical neuroinflammation. Prior neuroimaging has suggested that chronic PTSD is associated with glial activation and reduced cortical complexity, as well as neurodegeneration in the hippocampus and anterior cingulate, suggestive of PTSD-induced cortical neuropathology. Hypothesizing that these results might reduce intercortical density, we evaluated intercortical demyelination in WTC responders with chronic PTSD. We used gray-white contrast purported to measure cortical demyelination and, by extension, interneuronal health.

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Safiya Aafreen¹, Wenshen Wang^2,3, Jiadi Xu^2,3, Peter CM van Zijl^2,3, Aline Thomas², Jeff WM Bulte^1,2,3,4, and Guanshu Liu^2,3
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States, ²Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States, ⁴Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Keywords: Contrast Agent, Molecular Imaging, Blood-Brain Barrier; Multiple Sclerosis

Prevailing imaging methods primarily focus on detecting blood-brain barrier (BBB) dysfunction utilising tracers of small molecular weight. Robust imaging methods suitable for assessing BBB permeability in the macro-molecular size range are still lacking. Our study aimed to develop and optimize a dextran-based MRI approach for detecting size-dependent BBB permeability. Demonstrated in an EAE MS mouse model, we established a dextran-based CEST MRI protocol for measuring the intracerebral distribution of non-labeled dextrans, validated the results using immunohistochemistry, and compared the CEST MRI results with conventional Gd-enhanced MRI.

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Alessandro Cagol^1,2,3, Mario Ocampo-Pineda^1,2,3, Lester Melie-Garcia^1,2,3, Po-Jui Lu^1,2,3, Muhamed Barakovic^1,2,3, Matthias Weigel^1,2,3,4, Xinjie Chen^1,2,3, Antoine Lutti⁵, Thanh D. Nguyen⁶, Yi Wang⁶, Jens Kuhle^2,3, Ludwig Kappos^1,2,3, and Cristina Granziera^1,2,3
1Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ²Department of Neurology, University Hospital Basel, Basel, Switzerland, ³Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland, ⁴Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland, ⁵Laboratory for Research in Neuroimaging, Department of Clinical Neuroscience, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ⁶Department of Radiology, Weill Cornell Medical College, New York, NY, United States

Keywords: Multiple Sclerosis, Quantitative Imaging

We explored the value of multiple longitudinal quantitative MRI (qMRI) measures in detecting microstructural changes occurring in normal-appearing tissue of patients with multiple sclerosis (PwMS). While no differences in qMRI longitudinal changes were measured between PwMS and healthy controls, progressive PwMS showed accelerated T1-relaxometry increase in normal-appearing tissue with respect to both healthy controls and relapsing-remitting PwMS, reflecting increased micro/macrostructural damage. In PwMS the rates of qMRI changes during follow-up were associated with the severity of clinical disability, with higher neurological impairment being associated with qMRI changes reflecting accelerated micro/macrostructural damage, demyelination, and axon/dendrite loss.

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Min-Hui Cui¹, Roman Fleysher¹, Lidiane Torres², Kamalakar Ambadipudi¹, and Craig A. Branch^1
1Radiology/Gruss MRRC, Albert Einstein College of Medicine, Bronx, NY, United States, ²Cell Biology, Albert Einstein College of Medicine, Bronx, NY, United States

Keywords: White Matter, Transplantation, white matter, spectroscopy, irradiation, animal

Adult cells from transplanted bone marrow can generate new neurons in central nervous system (CNS) in rodent and human. Here we report for the first time in live mouse that white matter integrity in lethally irradiated mouse transplanted with adult mouse bone marrow  (BMTX) is preserved, reflected in increased fractional anisotropy (FA) of corpus callosum post BMTX. Stable concentration of N-acetyl-aspartate (NAA) and increased FA after BMTX suggests that donor cells along with irradiation may stimulate new neuronal proliferation. Nevertheless, decreased myo-inositol concentration may reflect its cell volume regulation function as seen in morphometric adjustments in BMTX brains.

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Hannah Goldman¹, Katherine Le², Orlando Aristizabal¹, Matias Aristizabal¹, Mia Weissman¹, Victor Torres², and Youssef Zaim Wadghiri^1
1Radiology, NYU Langone Health, New York, NY, United States, ²Microbiology, NYU Grossman School of Medicine, New York, NY, United States

Keywords: Infectious disease, Preclinical

Staphylococcus aureus is of particular concern due to the deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains. There is not currently a vaccine as translation from preclinical models to humans has been unsuccessful. Acquiring reproducible and comparable spinal images that offer non-invasive visualization of the extent and impact of the infection are important for successful intervention or vaccine development. 3D-printed, MRI-compatible cradles enable reproducible positioning and analysis for both in vivo and ex vivo MR spinal imaging in mouse models while allowing for nondestructive analysis of the potential additional benefits to visualization associated with ex vivo MEMRI.