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MR Imaging the spinal cord of non-human primates (NHP), such as squirrel monkey, is important since the injuries in NHP resemble those that afflict human spinal cords. Our previous studies have reported a multi-parametric MRI protocol, including functional MRI, diffusion tensor imaging, quantitative magnetization transfer and chemical exchange saturation transfer, which allows non-invasive detection and monitoring of injury-associated structural, functional and molecular changes over time. High signal-to-noise ratio (SNR) is critical for obtaining high-resolution images and robust estimates of MRI parameters. In this work, we describe our construction and use of a single channel coil designed to maximize the SNR for imaging the squirrel monkey cervical spinal cord in a 21 cm bore magnet at 9.4 T. We first numerically optimized the coil dimension of a single loop coil and then evaluated the benefits of a quadrature design. We then built an optimized coil based on the simulation results and compared its SNR performance with a non-optimized single coil in both phantoms and in vivo.
Copyright © 2020 Elsevier Inc. All rights reserved.

Imaging mass spectrometry is a powerful technology that combines the molecular measurements of mass spectrometry with the spatial information inherent to microscopy. This unique combination of capabilities is ideally suited for the analysis of metabolites and lipids from single cells. This chapter describes a methodology for the sample preparation and analysis of single cells using high performance MALDI FTICR MS. Using this approach, we are able to generate profiles of lipid and metabolite expression from single cells that characterize cellular heterogeneity. This approach also enables the detection of variations in the expression profiles of lipids and metabolites induced by chemical stimulation of the cells. These results demonstrate that MALDI IMS provides an insightful view of lipid and metabolite expression useful in the characterization of a number of biological systems at the single cell level.

Cells of any organism are consistently exposed to changes over time in their environment. The kinetics by which these changes occur are critical for the cellular response and fate decision. It is therefore important to control the temporal changes of extracellular stimuli precisely to understand biological mechanisms in a quantitative manner. Most current cell culture and biochemical studies focus on instant changes in the environment and therefore neglect the importance of kinetic environments. To address these shortcomings, we developed two experimental methodologies to precisely control the environment of single cells. These methodologies are compatible with standard biochemistry, molecular, cell and quantitative biology assays. We demonstrate applicability by obtaining time series and time point measurements in both live and fixed cells. We demonstrate the feasibility of the methodology in yeast and mammalian cell culture in combination with widely used assays such as flow cytometry, time-lapse microscopy and single-molecule RNA Fluorescent in-situ Hybridization (smFISH). Our experimental methodologies are easy to implement in most laboratory settings and allows the study of kinetic environments in a wide range of assays and different cell culture conditions.

PURPOSE - Transcranial focused ultrasound (FUS) is increasingly being explored to modulate neuronal activity. To target neuromodulation, researchers often localize the FUS beam onto the brain region(s) of interest using spatially tracked tools overlaid on pre-acquired images. Here, we quantify the accuracy of optically tracked image-guided FUS with magnetic resonance imaging (MRI) thermometry, evaluate sources of error and demonstrate feasibility of these procedures to target the macaque somatosensory region.
METHODS - We developed an optically tracked FUS system capable of projecting the transducer focus onto a pre-acquired MRI volume. To measure the target registration error (TRE), we aimed the transducer focus at a desired target in a phantom under image guidance, heated the target while imaging with MR thermometry and then calculated the TRE as the difference between the targeted and heated locations. Multiple targets were measured using either an unbiased or bias-corrected calibration. We then targeted the macaque S1 brain region, where displacement induced by the acoustic radiation force was measured using MR acoustic radiation force imaging (MR-ARFI).
RESULTS - All calibration methods enabled registration with TRE on the order of 3 mm. Unbiased calibration resulted in an average TRE of 3.26 mm (min-max: 2.80-4.53 mm), which was not significantly changed by prospective bias correction (TRE of 3.05 mm; 2.06-3.81 mm, p = 0.55). Restricting motion between the transducer and target and increasing the distance between tracked markers reduced the TRE to 2.43 mm (min-max: 0.79-3.88 mm). MR-ARFI images showed qualitatively similar shape and extent as projected beam profiles in a living non-human primate.
CONCLUSIONS - Our study describes methods for image guidance of FUS neuromodulation and quantifies errors associated with this method in a large animal. The workflow is efficient enough for in vivo use, and we demonstrate transcranial MR-ARFI in vivo in macaques for the first time.

BACKGROUND - Misidentifying parathyroid glands (PGs) during thyroidectomies or parathyroidectomies could significantly increase postoperative morbidity. Imaging systems based on near infrared autofluorescence (NIRAF) detection can localize PGs with high accuracy. These devices, however, depict NIRAF images on remote display monitors, where images lack spatial context and comparability with actual surgical field of view. In this study, we designed an overlay tissue imaging system (OTIS) that detects tissue NIRAF and back-projects the collected signal as a visible image directly onto the surgical field of view instead of a display monitor, and tested its ability for enhancing parathyroid visualization.
STUDY DESIGN - The OTIS was first calibrated with a fluorescent ink grid and initially tested with parathyroid, thyroid, and lymph node tissues ex vivo. For in vivo measurements, the surgeon's opinion on tissue of interest was first ascertained. After the surgeon looked away, the OTIS back-projected visible green light directly onto the tissue of interest, only if the device detected relatively high NIRAF as observed in PGs. System accuracy was determined by correlating NIRAF projection with surgeon's visual confirmation for in situ PGs or histopathology report for excised PGs.
RESULTS - The OTIS yielded 100% accuracy when tested ex vivo with parathyroid, thyroid, and lymph node specimens. Subsequently, the device was evaluated in 30 patients who underwent thyroidectomy and/or parathyroidectomy. Ninety-seven percent of exposed tissue of interest was visualized correctly as PGs by the OTIS, without requiring display monitors or contrast agents.
CONCLUSIONS - Although OTIS holds novel potential for enhancing label-free parathyroid visualization directly within the surgical field of view, additional device optimization is required for eventual clinical use.
Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

LEVEL OF EVIDENCE - 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.
© 2019 International Society for Magnetic Resonance in Medicine.

Matrix assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful technology used to investigate the spatial distributions of thousands of molecules throughout a tissue section from a single experiment. As proteins represent an important group of functional molecules in tissue and cells, the imaging of proteins has been an important point of focus in the development of IMS technologies and methods. Protein identification is crucial for the biological contextualization of molecular imaging data. However, gas-phase fragmentation efficiency of MALDI generated proteins presents significant challenges, making protein identification directly from tissue difficult. This review highlights methods and technologies specifically related to protein identification that have been developed to overcome these challenges in MALDI IMS experiments.
Copyright © 2018 Elsevier Ltd. All rights reserved.

OBJECTIVES/HYPOTHESIS - Intubation is an essential component of intensive care, yet it does have potential complications. Posterior glottic stenosis (PGS) is among the most severe sequela. Risk factors are poorly understood. One hypothesis is that large endotracheal tubes (ETTs) in smaller airways may increase risk. Because tracheal diameter is proportional to height, we designed a case-control study to evaluate the association between intensive care unit (ICU)-patient height (proxy for tracheal diameter) and their risk of postintubation PGS.
STUDY DESIGN - Retrospective case-control study METHODS: Among patients who underwent intubation in an ICU at a single tertiary care medical center between 2001 and 2015, a convenience sample of all patients with confirmed PGS (cases) were enrolled. Cases were matched 1:1 by age, sex, and race with intubated non-PGS controls chosen from the same population of ventilated patients. Data on height, weight, comorbidities, size of ETT, and duration of intubation were abstracted from the medical record. Multivariate models were used to test the association between patient height and risk of PGS development.
RESULTS - In all, 106 PGS cases (mean age 48.9 years, 50.7% female, 79.2% Caucasian) were identified; 77 met inclusion criteria. Compared to matched controls, cases were significantly shorter (mean 166 cm vs. 173 cm, P = .001). Height and PGS showed an inverse relationship in multivariate models. Specifically, odds of PGS decreased 9% (95% confidence interval: 0.01%-16%) for each centimeter increase in height.
CONCLUSIONS - Shorter height is independently associated with increased odds of having PGS. Further work should consider whether height should be incorporated into ETT selection algorithms.
LEVEL OF EVIDENCE - 3b Laryngoscope, 128:2811-2814, 2018.
© 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Preterm birth (PTB) is the leading cause of neonatal death, however, accurate prediction methods do not exist. Detection of early changes in the cervix, an organ that biochemically remodels to deliver the fetus, has potential to predict PTB risk. Researchers have employed light-based methods to monitor biochemical changes in the cervix during pregnancy, however, these approaches required patients to undergo a speculum examination which many patients find uncomfortable and is not standard practice during prenatal care. Herein, a visually guided optical probe is presented that measures the cervix via introduction by bimanual examination, a procedure that is commonly performed during prenatal visits and labor for tactile monitoring of the cervix. The device incorporates a Raman spectroscopy probe for biochemical monitoring and a camera for visualizing measurement location to ensure it is void of cervical mucus and blood. This probe was tested in 15 patients receiving obstetric and gynecological care, and results acquired with and without a speculum revealed similar spectra, demonstrating that the visually guided probe conserved data quality. Additionally, the majority of patients reported reduced discomfort from the device. In summary, the visual guidance probe successfully measured the cervix while integrating with standard prenatal care, reducing a barrier in clinical translation.
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Arrays of radiofrequency coils are widely used in magnetic resonance imaging to achieve high signal-to-noise ratios and flexible volume coverage, to accelerate scans using parallel reception, and to mitigate field non-uniformity using parallel transmission. However, conventional coil arrays require complex decoupling technologies to reduce electromagnetic coupling between coil elements, which would otherwise amplify noise and limit transmitted power. Here we report a novel self-decoupled RF coil design with a simple structure that requires only an intentional redistribution of electrical impedances around the length of the coil loop. We show that self-decoupled coils achieve high inter-coil isolation between adjacent and non-adjacent elements of loop arrays and mixed arrays of loops and dipoles. Self-decoupled coils are also robust to coil separation, making them attractive for size-adjustable and flexible coil arrays.