Toward forward-looking OCT needle tip vision of the spinal neuroforamen: animal studies

Neurologic complications have been reported with spinal transforaminal injections. Causes include intraneural injection, plus embolization occlusion of the radicular artery with subsequent spinal cord infarction. 1 Optical coherence tomography (OCT) is a non-invasive imaging modality, which is used to image tissue microstructure with very high resolution (less than 20 microns) in real-time. With a view toward needle tip OCT visualization of the spinal neuroforamen, we conducted animal studies to explore OCT imaging of paraspinal neurovascular structures. With institutional animal care committee approval, we performed ex-vivo and in situ OCT studies in a euthanized dog, pig, and rabbit. Image data was gathered on spinal nerve roots, dura, and brachial plexus. Two systems were used: frequency domain OCT imaging system developed at California Institute of Technology, and time domain Imalux NIRIS system with a 2.7 mm diameter probe. In a euthanized pig, excised dura was punctured with a 17-gauge Tuohy needle. FDOCT dural images of the puncture showed a subsurface cone-shaped defect. In a rabbit in situ study, puncture of the dura with a 26-gauge needle is imaged as a discontinuity. FDOCT imaging of both small artery and large arteries will be presented, along with H&E and OCT images of the brachial plexus

Multiscale neural modeling of resting-state fMRI reveals executive-limbic malfunction as a core mechanism in major depressive disorder

Major depressive disorder (MDD) represents a grand challenge to human health and society, but the underlying pathophysiological mechanisms remain elusive. Previous neuroimaging studies have suggested that MDD is associated with abnormal interactions and dynamics in two major neural systems including the default mode - salience (DMN-SAL) network and the executive - limbic (EXE-LIM) network, but it is not clear which network plays a central role and which network plays a subordinate role in MDD pathophysiology. To address this question, we refined a newly developed Multiscale Neural Model Inversion (MNMI) framework and applied it to test whether MDD is more affected by impaired circuit interactions in the DMN-SAL network or the EXE-LIM network. The model estimates the directed connection strengths between different neural populations both within and between brain regions based on resting-state fMRI data collected from normal healthy subjects and patients with MDD. Results show that MDD is primarily characterized by abnormal circuit interactions in the EXE-LIM network rather than the DMN-SAL network. Specifically, we observe reduced frontoparietal effective connectivity that potentially contributes to hypoactivity in the dorsolateral prefrontal cortex (dlPFC), and decreased intrinsic inhibition combined with increased excitation from the superior parietal cortex (SPC) that potentially lead to amygdala hyperactivity, together resulting in activation imbalance in the PFC-amygdala circuit that pervades in MDD. Moreover, the model reveals reduced PFC-to-hippocampus excitation but decreased SPC-to-thalamus inhibition in MDD population that potentially lead to hypoactivity in the hippocampus and hyperactivity in the thalamus, consistent with previous experimental data. Overall, our findings provide strong support for the long-standing limbic-cortical dysregulation model in major depression but also offer novel insights into the multiscale pathophysiology of this debilitating disease

Toward forward-looking OCT needle tip vision of the spinal neuroforamen: animal studies

Neurologic complications have been reported with spinal transforaminal injections. Causes include intraneural injection, plus embolization occlusion of the radicular artery with subsequent spinal cord infarction. 1 Optical coherence tomography (OCT) is a non-invasive imaging modality, which is used to image tissue microstructure with very high resolution (less than 20 microns) in real-time. With a view toward needle tip OCT visualization of the spinal neuroforamen, we conducted animal studies to explore OCT imaging of paraspinal neurovascular structures. With institutional animal care committee approval, we performed ex-vivo and in situ OCT studies in a euthanized dog, pig, and rabbit. Image data was gathered on spinal nerve roots, dura, and brachial plexus. Two systems were used: frequency domain OCT imaging system developed at California Institute of Technology, and time domain Imalux NIRIS system with a 2.7 mm diameter probe. In a euthanized pig, excised dura was punctured with a 17-gauge Tuohy needle. FDOCT dural images of the puncture showed a subsurface cone-shaped defect. In a rabbit in situ study, puncture of the dura with a 26-gauge needle is imaged as a discontinuity. FDOCT imaging of both small artery and large arteries will be presented, along with H&E and OCT images of the brachial plexus

Novel analytics for rapid adventitious agent detection in cell and gene therapy manufacturing

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Intermolecular Nonreductive Alkylation of Enamides via Radical−Polar Crossover

A carbon−carbon bond construction method is disclosed which involves radical addition of α-haloesters or iodoacetonitrile to enamides. Despite the presence of tri-n-butylstannane, nonreductive addition was predominant; H-atom transfer from tin hydride was not observed. Rapid iodine atom transfer to (or electron transfer from) the radical adduct, resulting in an iminium ion intermediate and radical chain propagation, is consistent with the observed reactivity