T1 relaxation and axon fibre configuration in human white matter.

Understanding the effects of white matter (WM) axon fibre microstructure on T1 relaxation is important for neuroimaging. Here, we have studied the interrelationship between T1 and axon fibre configurations at 3T and 7T. T1 and S0 (=signal intensity at zero TI) were computed from MP2RAGE images acquired with six inversion recovery times. Multishell diffusion MRI images were analysed for fractional anisotropy (FA); MD; V1; the volume fractions for the first (f1), second (f2) and third (f3) fibre configuration; and fibre density cross-section images for the first (fdc1), second (fdc2) and third (fdc3) fibres. T1 values were plotted as a function of FA, f1, f2, f3, fdc1, fdc2 and fdc3 to examine interrelationships between the longitudinal relaxation and the diffusion MRI microstructural measures. T1 values decreased with increasing FA, f1 and f2 in a nonlinear fashion. At low FA values (from 0.2 to 0.4), a steep shortening of T1 was followed by a shallow shortening by 6%-10% at both fields. The steep shortening was associated with decreasing S0 and MD. T1 also decreased with increasing fdc1 values in a nonlinear fashion. Instead, only a small T1 change as a function of either f3 or fdc3 was observed. In WM areas selected by fdc1 only masks, T1 was shorter than in those with fdc2/fdc3. In WM areas with high single fibre populations, as delineated by f1/fdc1 masks, T1 was shorter than in tissue with high complex fibre configurations, as segmented by f2/fdc2 or f3/fdc3 masks. T1 differences between these WM areas are attributable to combined effects by T1 anisotropy and lowered FA. The current data show strong interrelationships between T1, axon fibre configuration and orientation in healthy WM. It is concluded that diffusion MRI microstructural measures are essential in the effort to interpret quantitative T1 images in terms of tissue state in health and disease.

Ethical, legal, and policy challenges in field-based neuroimaging research using emerging portable MRI technologies: guidance for investigators and for oversight.

Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG's consensus recommendations. These recommendations address technology quality control, design and oversight of research, including safety of research participants and others in the scanning environment, engagement of diverse participants, therapeutic misconception, use of artificial intelligence algorithms to acquire and analyze MRI data, data privacy and security, return of results and managing incidental findings, and research participant data access and control.

A Low-Cost, Tabletop LOD-EPR System for Nondestructive Quantification of Iron Oxide Nanoparticles in Tissues.

Iron oxide nanoparticles (IONPs) have wide utility in applications from drug delivery to the rewarming of cryopreserved tissues. Due to the complex behavior of IONPs (e.g., uneven particle distribution and aggregation), further developments and clinical translation can be accelerated by having access to a noninvasive method for tissue IONP quantification. Currently, there is no low-cost method to nondestructively track IONPs in tissues across a wide range of concentrations. This work describes the performance of a low-cost, tabletop, longitudinally detected electron paramagnetic resonance (LOD-EPR) system to address this issue in the field of cryopreservation, which utilizes IONPs for rewarming of rat kidneys. A low-cost LOD-EPR system is realized via simultaneous transmit and receive using MHz continuous-wave transverse excitation with kHz modulation, which is longitudinally detected at the modulation frequency to provide both geometric and frequency isolation. The accuracy of LOD-EPR for IONP quantification is compared with NMR relaxometry. Solution measurements show excellent linearity (R2 > 0.99) versus Fe concentration for both measurements on EMG308 (a commercial nanoparticle), silica-coated EMG308, and PEG-coated EMG308 in water. The LOD-EPR signal intensity and NMR longitudinal relaxation rate constant (R1) of water are affected by particle coating, solution viscosity, and particle aggregation. R1 remains linear but with a reduced slope when in cryoprotective agent (CPA) solution, whereas the LOD-EPR signal is relatively insensitive to this. R1 does not correlate well with Fe concentration in rat kidney sections (R2 = 0.3487), while LOD-EPR does (R2 = 0.8276), with a linear regression closely matching that observed in solution and CPA.

Hypoxia within subcutaneously implanted macroencapsulation devices limits the viability and functionality of densely loaded islets.

Introduction: Subcutaneous macroencapsulation devices circumvent disadvantages of intraportal islet therapy. However, a curative dose of islets within reasonably sized devices requires dense cell packing. We measured internal PO2 of implanted devices, mathematically modeled oxygen availability within devices and tested the predictions with implanted devices containing densely packed human islets. Methods: Partial pressure of oxygen (PO2) within implanted empty devices was measured by noninvasive 19F-MRS. A mathematical model was constructed, predicting internal PO2, viability and functionality of densely packed islets as a function of external PO2. Finally, viability was measured by oxygen consumption rate (OCR) in day 7 explants loaded at various islet densities. Results: In empty devices, PO2 was 12 mmHg or lower, despite successful external vascularization. Devices loaded with human islets implanted for 7 days, then explanted and assessed by OCR confirmed trends proffered by the model but viability was substantially lower than predicted. Co-localization of insulin and caspase-3 immunostaining suggested that apoptosis contributed to loss of beta cells. Discussion: Measured PO2 within empty devices declined during the first few days post-transplant then modestly increased with neovascularization around the device. Viability of islets is inversely related to islet density within devices.