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1. 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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2. Improved detection of fMRI activation in the cerebellum at 7T with dielectric pads extending the imaging region of a commercial head coil

   https://doi.org/10.1002/jmri.25936  

   Vaidya, Manushka V. ; Lazar, Mariana ; Deniz, Cem M. ; Haemer, Gillian G. ; Chen, Gang ; Bruno, Mary ; Sodickson, Daniel K. ; Lattanzi, Riccardo ; Collins, Christopher M. ( January 2018 , Journal of Magnetic Resonance Imaging)

   There is growing interest in detecting cerebro‐cerebellar circuits, which requires adequate blood oxygenation level dependent contrast and signal‐to‐noise ratio (SNR) throughout the brain. Although 7T scanners offer increased SNR, coverage of commercial head coils is currently limited to the cerebrum.

   To improve cerebellar functional MRI (fMRI) at 7T with high permittivity material (HPM) pads extending the sensitivity of a commercial coil.

   Simulations were used to determine HPM pad configuration and assess radiofrequency (RF) safety. In vivo experiments were performed to evaluate RF field distributions and SNR and assess improvements of cerebellar fMRI.

   Eight healthy volunteers enrolled in a prospective motor fMRI study with and without HPM.

   Gradient echo (GRE) echo planar imaging for fMRI, turbo FLASH for flip angle mapping, GRE sequence for SNR maps, and T₁‐weighted MPRAGE were acquired with and without HPM pads at 7T.

   Field maps, SNR maps, and anatomical images were evaluated for coverage. Simulation results were used to assess SAR levels of the experiment. Activation data from fMRI experiments were compared with and without HPM pads.

   fMRI data were analyzed using FEAT FSL for each subject followed by group level analysis using paired t‐test of acquisitions with and without HPM.

   Simulations showed 52% improvement in transmit efficiency in cerebellum with HPM and SAR levels well below recommended limits. Experiments showed 27% improvement in SNR in cerebellum and improvement in coverage on T₁‐weighted images. fMRI showed greater cerebellar activation in individual subjects with the HPM pad present (Z > = 4), especially in inferior slices of cerebellum, with 59% average increase in number of activated voxels in the cerebellum. Group‐level analysis showed improved functional activation (Z > = 2.3) in cerebellar regions with HPM pads without loss of measured activation elsewhere.

   HPM pads can improve cerebellar fMRI at 7T with a commonly‐used head coil without compromising RF safety.

   Level of Evidence: 2

   Technical Efficacy: Stage 1

   J. MAGN. RESON. IMAGING 2018;48:431–440.

    

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3. Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors

   https://doi.org/10.1002/smll.201903422  

   Shen, Zheyu ; Fan, Wenpei ; Yang, Zhen ; Liu, Yijing ; Bregadze, Vladimir I. ; Mandal, Swadhin K. ; Yung, Bryant C. ; Lin, Lisen ; Liu, Ting ; Tang, Wei ; et al ( August 2019 , Small)

   Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non‐specificity, and lowr₁) that limit their applications. Herein, a wet‐chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES‐GON‐PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerfulT₁‐weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r₁= 70.2 ± 1.8 mM⁻¹s⁻¹, andr₂/r₁= 1.02 ± 0.03, at 1.5 T). Ther₁is much higher and ther₂/r₁is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES‐GON‐PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES‐GON‐PAA@RGD2) forT₁‐weighted MRI of tumors that overexpress RGD receptors (i.e., integrinα_vβ₃). The maximum signal enhancement (ΔSNR) forT₁‐weighted MRI of tumors reaches up to 372 ± 56% at 2 h post‐injection of ES‐GON‐PAA@RGD2, which is much higher than commercial Gd‐chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES‐GON‐PAA@RGD2 with remarkable relaxivities is a promising and powerfulT₁‐weighted MRI contrast agent.

    

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4. Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury

   https://doi.org/10.1002/adhm.202300782  

   Diaz, Miranda D. ; Kandell, Rebecca M. ; Wu, Jason R. ; Chen, Alexander ; Christman, Karen L. ; Kwon, Ester J. ( July 2023 , Advanced Healthcare Materials)

   Traumatic brain injury (TBI) affects millions of people each year and, in many cases, results in long‐term disabilities. Once a TBI has occurred, there is a significant breakdown of the blood−brain barrier resulting in increased vascular permeability and progression of the injury. In this study, the use of an infusible extracellular matrix‐derived biomaterial (iECM) for its ability to reduce vascular permeability and modulate gene expression in the injured brain is investigated. First, the pharmacokinetics of iECM administration in a mouse model of TBI is characterized, and the robust accumulation of iECM at the site of injury is demonstrated. Next, it is shown that iECM administration after injury can reduce the extravasation of molecules into the brain, and in vitro, iECM increases trans‐endothelial electrical resistance across a monolayer of TNFα‐stimulated endothelial cells. In gene expression analysis of brain tissue, iECM induces changes that are indicative of downregulation of the proinflammatory response 1‐day post‐injury/treatment and neuroprotection at 5 days post‐injury/treatment. Therefore, iECM shows potential as a treatment for TBI.

    

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5. Effective connectivity in the default mode network after paediatric traumatic brain injury

   https://doi.org/10.1111/ejn.15546  

   Vaughn, Kelly A. ; DeMaster, Dana ; Kook, Jeong Hwan ; Vannucci, Marina ; Ewing‐Cobbs, Linda ( December 2021 , European Journal of Neuroscience)

   Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi‐subject vector autoregressive modelling (BVAR‐connect), which used white matter integrity as priors to evaluate effective connectivity—the time‐dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions—within the default mode network (DMN). In a prospective longitudinal study, children ages 8–15 years with mild to severe TBI underwent diffusion tensor imaging and resting state fMRI 7 weeks after injury; post‐concussion and anxiety symptoms were assessed 7 months after injury. The goals of this study were to (1) characterize differences in positive effective connectivity of resting‐state DMN circuitry between healthy controls and children with TBI, (2) determine if severity of TBI was associated with differences in DMN connectivity and (3) evaluate whether patterns of DMN effective connectivity predicted persistent post‐concussion symptoms and anxiety. Healthy controls had unique positive connectivity that mostly emerged from the inferior temporal lobes. In contrast, children with TBI had unique effective connectivity among orbitofrontal and parietal regions. These positive orbitofrontal‐parietal DMN effective connectivity patterns also differed by TBI severity and were associated with persisting behavioural outcomes. Effective connectivity may be a sensitive neuroimaging marker of TBI severity as well as a predictor of chronic post‐concussion symptoms and anxiety.

    

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