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1. Spatial Gradients of Quantitative MRI as Biomarkers for Early Detection of Osteoarthritis: Data From Human Explants and the Osteoarthritis Initiative

   https://doi.org/10.1002/jmri.28471  

   Wilson, Robert L. ; Emery, Nancy C. ; Pierce, David M. ; Neu, Corey P. ( October 2022 , Journal of Magnetic Resonance Imaging)

   Healthy articular cartilage presents structural gradients defined by distinct zonal patterns through the thickness, which may be disrupted in the pathogenesis of several disorders. Analysis of textural patterns using quantitative MRI data may identify structural gradients of healthy or degenerating tissue that correlate with early osteoarthritis (OA).

   To quantify spatial gradients and patterns in MRI data, and to probe new candidate biomarkers for early severity of OA.

   Retrospective study.

   Fourteen volunteers receiving total knee replacement surgery (eight males/two females/four unknown, average age ± standard deviation: 68.1 ± 9.6 years) and 10 patients from the OA Initiative (OAI) with radiographic OA onset (two males/eight females, average age ± standard deviation: 57.7 ± 9.4 years; initial Kellgren‐Lawrence [KL] grade: 0; final KL grade: 3 over the 10‐year study).

   3.0‐T and 14.1‐T, biomechanics‐based displacement‐encoded imaging, fast spin echo, multi‐slice multi‐echoT2mapping.

   We studied structure and strain in cartilage explants from volunteers receiving total knee replacement, or structure in cartilage of OAI patients with progressive OA. We calculated spatial gradients of quantitative MRI measures (eg, T2) normal to the cartilage surface to enhance zonal variations. We compared gradient values against histologically OA severity, conventional relaxometry, and/or KL grades.

   Multiparametric linear regression for evaluation of the relationship between residuals of the mixed effects models and histologically determined OA severity scoring, with a significance threshold atα = 0.05.

   Gradients of individual relaxometry and biomechanics measures significantly correlated with OA severity, outperforming conventional relaxometry and strain metrics. In human explants, analysis of spatial gradients provided the strongest relationship to OA severity (R² = 0.627). Spatial gradients of T2 from OAI data identified variations in radiographic (KL Grade 2) OA severity in single subjects, while conventional T2 alone did not.

   Spatial gradients of quantitative MRI data may improve the predictive power of noninvasive imaging for early‐stage degeneration.

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2. GdDO3NI Enhanced Magnetic Resonance Imaging Allows Imaging of Hypoxia After Brain Injury

   https://doi.org/10.1002/jmri.27912  

   Moghadas, Babak ; Bharadwaj, Vimala N. ; Tobey, John P. ; Tian, Yanqing ; Stabenfeldt, Sarah E. ; Kodibagkar, Vikram D. ( September 2021 , Journal of Magnetic Resonance Imaging)

   Brain tissue hypoxia is a common consequence of traumatic brain injury (TBI) due to the rupture of blood vessels during impact and it correlates with poor outcome. The current magnetic resonance imaging (MRI) techniques are unable to provide a direct map of tissue hypoxia.

   To investigate whether GdDO3NI, a nitroimidazole‐based T₁MRI contrast agent allows imaging hypoxia in the injured brain after experimental TBI.

   Prospective.

   TBI‐induced mice (controlled cortical impact model) were intravenously injected with either conventional T₁agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n = 5 for each cohort) along with pimonidazole (60 mg/kg) at 1 hour postinjury and imaged for 3 hours following which they were euthanized.

   7 T/T₂‐weighted spin echo and T₁‐weighted gradient echo.

   Injured animals were imaged with T₂‐weighted spin‐echo sequence to estimate the extent of the injury. The mice were then imaged precontrast and postcontrast using a T₁‐weighted gradient‐echo sequence for 3 hours postcontrast. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post‐imaging for immunohistochemical analysis.

   One‐way analysis of variance and two‐samplet‐tests were performed with aP < 0.05 was considered statistically significant.

   GdDO3NI retention in the injury region at 2.5–3 hours post‐injection was significantly higher compared to gadoteridol (mean retention fraction 63.95% ± 27.43% vs. 20.68% ± 7.43% for gadoteridol at 3 hours) while it rapidly cleared out of the muscle region. Pimonidazole staining confirmed the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort showed good agreement with MRI contrast enhancement.

   GdDO3NI was successfully shown to visualize hypoxia in the brain post‐TBI using T₁‐weighted MRI at 2.5–3 hours postcontrast.

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3. Temporally resolved parametric assessment of Z‐magnetization recovery (TOPAZ): Dynamic myocardial T 1 mapping using a cine steady‐state look‐locker approach

   https://doi.org/10.1002/mrm.26887  

   Weingärtner, Sebastian ; Shenoy, Chetan ; Rieger, Benedikt ; Schad, Lothar R. ; Schulz‐Menger, Jeanette ; Akçakaya, Mehmet ( August 2017 , Magnetic Resonance in Medicine)

   To develop and evaluate a cardiac phase‐resolved myocardial T₁mapping sequence.

   The proposed method for temporally resolved parametric assessment of Z‐magnetization recovery (TOPAZ) is based on contiguous fast low‐angle shot imaging readout after magnetization inversion from the pulsed steady state. Thereby, segmented k‐space data are acquired over multiple heartbeats, before reaching steady state. This results in sampling of the inversion‐recovery curve for each heart phase at multiple points separated by an R‐R interval. Joint T₁andestimation is performed for reconstruction of cardiac phase‐resolved T₁andmaps. Sequence parameters are optimized using numerical simulations. Phantom and in vivo imaging are performed to compare the proposed sequence to a spin‐echo reference and saturation pulse prepared heart rate–independent inversion‐recovery (SAPPHIRE) T₁mapping sequence in terms of accuracy and precision.

   In phantom, TOPAZ T₁values with integratedcorrection are in good agreement with spin‐echo T₁values (normalized root mean square error = 4.2%) and consistent across the cardiac cycle (coefficient of variation = 1.4 ± 0.78%) and different heart rates (coefficient of variation = 1.2 ± 1.9%). In vivo imaging shows no significant difference in TOPAZ T₁times between the cardiac phases (analysis of variance:P = 0.14, coefficient of variation = 3.2 ± 0.8%), but underestimation compared with SAPPHIRE (T₁time ± precision: 1431 ± 56 ms versus 1569 ± 65 ms). In vivo precision is comparable to SAPPHIRE T₁mapping until middiastole (P > 0.07), but deteriorates in the later phases.

   The proposed sequence allows cardiac phase‐resolved T₁mapping with integratedassessment at a temporal resolution of 40 ms. Magn Reson Med 79:2087–2100, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    

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4. Measurement of sub‐zero temperatures in MRI using T 1 temperature sensitive soft silicone materials: Applications for MRI‐guided cryosurgery

   https://doi.org/10.1002/mp.15252  

   Hankiewicz, Janusz H. ; Celinski, Zbigniew ; Camley, Robert E. ( October 2021 , Medical Physics)

   One standard method, proton resonance frequency shift, for measuring temperature using magnetic resonance imaging (MRI), in MRI‐guided surgeries, fails completely below the freezing point of water. Because of this, we have developed a new methodology for monitoring temperature with MRI below freezing. The purpose of this paper is to show that a strong temperature dependence of the nuclear relaxation timeT₁in soft silicone polymers can lead to temperature‐dependent changes of MRI intensity acquired withT₁weighting. We propose the use of silicone filaments inserted in tissue for measuring temperature during MRI‐guided cryoablations.

   The temperature dependence ofT₁in bio‐compatible soft silicone polymers was measured using nuclear magnetic resonance spectroscopy and MRI. Phantoms, made of bulk silicone materials and put in an MRI‐compatible thermal container with dry ice, allowed temperature measurements ranging from –60°C to + 20°C.T₁‐weighted gradient echo images of the phantoms were acquired at spatially uniform temperatures and with a gradient in temperature to determine the efficacy of using these materials as temperature indicators in MRI. Ex vivo experiments on silicone rods, 4 mm in diameter, inserted in animal tissue were conducted to assess the practical feasibility of the method.

   Measurements of nuclear relaxation times of protons in soft silicone polymers show a monotonic, nearly linear, change with temperature (R² > 0.98) and have a significant correlation with temperature (Pearson'sr > 0.99,p < 0.01). Similarly, the intensity of the MR images in these materials, taken with a gradient echo sequence, are also temperature dependent. There is again a monotonic change in MRI intensity that correlates well with the measured temperature (Pearson'sr < ‐0.98 andp < 0.01). The MRI experiments show that a temperature change of 3°C can be resolved in a distance of about 2.5 mm. Based on MRI images and external sensor calibrations for a sample with a gradient in temperature, temperature maps with 3°C isotherms are created for a bulk phantom. Experiments demonstrate that these changes in MRI intensity with temperature can also be seen in 4 mm silicone rods embedded in ex vivo animal tissue.

   We have developed a new method for measuring temperature in MRI that potentially could be used during MRI‐guided cryoablation operations, reducing both procedure time and cost, and making these surgeries safer.

    

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5. Non‐invasive imaging of oxygen concentration in a complex in vitro biofilm infection model using 19 F MRI: Persistence of an oxygen sink despite prolonged antibiotic therapy

   https://doi.org/10.1002/mrm.27888  

   Simkins, Jeffrey W. ; Stewart, Philip S. ; Codd, Sarah L. ; Seymour, Joseph D. ( August 2019 , Magnetic Resonance in Medicine)

   Oxygen availability is a critical determinant of microbial biofilm activity and antibiotic susceptibility. However, measuring oxygen gradients in these systems remains difficult, with the standard microelectrode approach being both invasive and limited to single‐point measurement. The goal of the study was to develop a¹⁹F MRI approach for 2D oxygen mapping in biofilm systems and to visualize oxygen consumption behavior in real time during antibiotic therapy.

   Oxygen‐sensing beads were created by encapsulating an emulsion of oxygen‐sensing fluorocarbon into alginate gel.Escherichia colibiofilms were grown in and on the alginate matrix, which was contained inside a packed bed column subjected to nutrient flow, mimicking the complex porous structure of human wound tissue, and subjected to antibiotic challenge.

   The linear relationship between¹⁹F spin‐lattice relaxation rateR₁and local oxygen concentration permitted noninvasive spatial mapping of oxygen distribution in real time over the course of biofilm growth and subsequent antibiotic challenge. This technique was used to visualize persistence of microbial oxygen respiration during continuous gentamicin administration, providing a time series of complete spatial maps detailing the continued bacterial utilization of oxygen during prolonged chemotherapy in an in vitro biofilm model with complex spatial structure.

   Antibiotic exposure temporarily causes oxygen consumption to enter a pseudosteady state wherein oxygen distribution becomes fixed; oxygen sink expansion resumes quickly after antibiotic clearance. This technique may provide valuable information for future investigations of biofilms by permitting the study of complex geometries (typical of in vivo biofilms) and facilitating noninvasive oxygen measurement.

    

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