David Andrew Porter

Nociplastic pain represents a major burden across immune-mediated inflammatory diseases (IMIDs). It is hypothesised, but not yet demonstrated, that peripheral inflammation promotes nociplastic pain by bottom-up sensitisation of the central nervous system (CNS). In rheumatoid arthritis (RA), a prototypic IMID, we used ultra–high field (7T) brain resting-state functional MRI to evaluate whether peripherally targeted anti-inflammatory therapies alter a biomarker of bottom-up CNS sensitisation: inferior parietal lobule (IPL)–insula connectivity. In discovery and replication cohorts, JAK-STAT pathway inhibitors significantly shifted IPL–insula connectivity toward a normalised pattern. This effect was not seen with placebo or anti-TNF therapy. Moreover, after performing an agnostic whole-brain multivariate analysis of functional connectivity change related to JAK-STAT inhibition, the posterior cingulate cortex (PCC) was identified; like the IPL, a major hub of the default mode network (DMN). We then probed the DMN with transcranial magnetic stimulation in an independent RA cohort. Active, but not sham, stimulation altered DMN connectivity and reduced peripheral blood monocyte pSTAT3 function, a surrogate of immune inactivation, suggesting a bi-directional brain–immune circuit. Together, these findings provide the first human experimental evidence that peripheral JAK-STAT pathways contribute to nociplastic pain in IMIDs. One Sentence Summary: Blocking peripheral JAK-STAT signalling reduces both objective and subjective nociplastic pain in rheumatoid arthritis, revealing a localised inflammatory driver behind a traditionally non-inflammatory pain state.

Purpose: To investigate the effects of using different parallel‐transmit (pTx) head coils and specific absorption rate (SAR) supervision strategies on pTx pulse design for ultrahigh‐field MRI using a 3D‐MPRAGE sequence.Methods: The PTx universal pulses (UPs) and fast online‐customized (FOCUS) pulses were designed with pre‐acquired data sets (B₀, B₁⁺ maps, specific absorption rate [SAR] supervision data) from two different 8 transmit/32 receive head coils on two 7T whole‐body MR systems. For one coil, the SAR supervision model consisted of per‐channel RF power limits. In the other coil, SAR estimations were done with both per‐channel RF power limits as well as virtual observation points (VOPs) derived from electromagnetic field (EMF) simulations using three virtual human body models at three different positions. All pulses were made for nonselective excitation and inversion and evaluated on 132 B₀, B₁⁺, and SAR supervision datasets obtained with one coil and 12 from the other. At both sites, 3 subjects were examined using MPRAGE sequences that used UP/FOCUS pulses generated for both coils.Results: For some subjects, the UPs underperformed when simulated on a different coil from which they were derived, whereas FOCUS pulses still showed acceptable performance in that case. FOCUS inversion pulses outperformed adiabatic pulses when scaled to the same local SAR level. For the self‐built coil, the use of VOPs showed reliable overestimation compared with the ground‐truth EMF simulations, predicting about 52% lower local SAR for inversion pulses compared with per‐channel power limits.Conclusion: FOCUS inversion pulses offer a low‐SAR alternative to adiabatic pulses and benefit from using EMF‐based VOPs for SAR estimation.

Purpose: High resolution diffusion‐weighted imaging is limited by susceptibility‐induced distortions and relaxation‐induced blurring. Segmented acquisition techniques can address these limitations at the expense of a prolonged scan time. If segmentation is performed along the readout direction, e.g., in RESOLVE (readout segmentation of long and variable echo‐trains), scan time can be reduced by readout (RO) partial Fourier methods, or simultaneous multi‐slice (SMS) methods. In this paper, we present a new approach to additionally accelerate the image acquisition called variable segment (VASE) RESOLVE.Methods: To avoid discontinuities at the boundaries of the segments, the phase evolution and therefore the effective echo‐spacing needs to be adjusted. To achieve this, we use higher undersampling factors in the outer parts of k‐space. Simultaneously we increase the width of the outer segments resulting in an increase of the echo‐spacing. Because of this variation, we introduce a kind of randomization to the sampling scheme. This enables the use of compressed sensing reconstruction techniques, which results in improved image quality compared to standard parallel imaging methods.Results: The RMS errors for the VASE RESOLVE acquisitions were lower compared to the standard reconstructions. The VASE RESOLVE in vivo images show a higher apparent signal to noise ratio.Conclusion: VASE RESOLVE is a new approach to further decrease the acquisition time of RO segmented acquisitions. Compared to RESOLVE with SMS, VASE RESOLVE additionally reduces the acquisition time by a factor of 2.

Purpose: To introduce a new sequence description format for vendor‐independent MR sequences that include all calculation logic portably. To introduce a new MRI sequence development approach which utilizes flexibly reusable modules.Methods: The proposed sequence description contains a sequence module hierarchy for loop and group logic, which is enhanced by a novel strategy for performing efficient parameter and pulse shape calculation. These calculations are powered by a flow graph structure. By using the flow graph, all calculations are performed with no redundancy and without requiring preprocessing. The generation of this interpretable structure is a separate step that combines MRI techniques while actively considering their context. The driver interface is slim and highly flexible through scripting support. The sequences do not require any vendor‐specific compiling or processing step. A vendor‐independent frontend for sequence configuration can be used. Tests that ensure physical feasibility of the sequence are integrated into the calculation logic.Results: The framework was used to define a set of standard sequences. Resulting images were compared to respective images acquired with sequences provided by the device manufacturer. Images were acquired using a standard commercial MRI system.Conclusions: The approach produces configurable, vendor‐independent sequences, whose configurability enables rapid prototyping. The transparent data structure simplifies the process of sharing reproducible sequences, modules, and techniques.

This article explores several aspects of the early modern poetic tradition as an antidote to presentism in comparative and world literature studies. A passage from Giovanni Battista Pigna’s Renaissance synthesis of Aristotelian and Horatian poetics is used to comment on comparative readings in general. This is followed by close readings of two dream poems by the early modern Italian Giovanni Aurelio Augurello and the modernist Spanish poet Antonio Machado, both of which relate to Renaissance literary traditions in different ways. Two different agonistic poems, one by Pierre-Daniel Huet and one attributed to a Frisian folk hero, are also subject to analysis in order to explore how the process of historical selection reshapes the literary corpus and subjugates certain types of writing to neglect.