Bis-hydrophobic 5-(1,2-dithiolan-3-yl)pentanamide budding leads targeting brain sigma-1 receptors.

The temporal signal‐to‐noise ratio (tSNR) of functional magnetic resonance imaging (fMRI) varies across the brain. The ventral anterior temporal cortex and orbitofrontal cortex, for example, are affected by two kinds of magnetic field inhomogeneity. First, these regions are located next to air‐filled sinuses and so are affected by B inhomogeneity that causes signal dropout and geometric distortions (Devlin et al. ; Halai et al. , , ; Jezzard and Clare ). The effects are more severe at higher field strengths, implying that it may be especially difficult to measure task‐related activity in susceptible regions with ultra‐high‐field fMRI (e.g., 7T‐fMRI). Second, at 7T and above, the radiofrequency wavelength is similar to the size of the head, resulting in standing wave effects that cause B
inhomogeneity in the temporal lobes (Gras et al. ; van der Kolk et al. ). This in turn causes spatial variation in flip angle and therefore in image intensity (Uğurbil ; Wu et al. ). B and B
inhomogeneity make it challenging to use fMRI to investigate the roles that these regions may play in a myriad of cognitive processes—including vision (Devereux et al. ), language (Borghesani et al. ), multimodal semantic cognition (Lambon Ralph et al. ), emotion (Fernandez et al. ), social cognition (Binney et al. ; Zahn et al. ), theory of mind (DuPre et al. ) and executive function (Duncan ). However, 7T‐fMRI also has many advantages in regions unaffected by inhomogeneity: 7T‐fMRI offers improved tSNR relative to 3T‐fMRI (Morris et al. ), which can be used to reduce voxel size and enable applications such as laminar fMRI (Koopmans et al. ) or to reduce acquisition times and enable shorter scan times for special populations such as patients with neurodegenerative diseases (Cope et al. ). 7T‐fMRI also benefits from improved spatial specificity relative to 3T‐fMRI because the signal from cortical microvasculature is enhanced while the signal from large veins is reduced (Marques and Norris ). Improving signal homogeneity would allow researchers studying the whole brain (or focusing on regions prone to susceptibility artefacts) to take full advantage of 7T‐fMRI; therefore, in this study we compared three methods of doing so. One possible method for improving image quality is parallel transmit (pTx), which uses multiple transmit elements, controlled independently, to homogenise the flip angle pattern experienced by the tissue (Adriany et al. ; Deniz et al. ; Roemer et al. ; Uğurbil ; Van de Moortele et al. ). In this way, pTx directly counteracts the effect of B
inhomogeneity; however, since the design of spoke pTx pulses incorporates B field maps, pTx is also capable of counteracting B inhomogeneity to an extent (Zhang et al. ). A recent study used pTx to improve image quality in ventral anterior temporal regions for echo‐planar imaging (EPI) 7T fMRI (Ding et al. ). pTx improved tSNR across the brain compared to a standard sequence, particularly in the temporal lobes. However, there was no improvement in functional contrast during a semantic association task that is known to recruit the anterior temporal lobes in 3T‐fMRI studies (Jung et al. ). A second method of recovering signal in these regions is multi‐echo (ME) imaging (Kundu et al. ; Poser et al. ; Posse ), which aims to counteract the effects of B inhomogeneity. T* is known to vary across the brain (Hagberg et al. ); in areas affected by B inhomogeneity, T* is particularly short due to increased intravoxel dephasing. A single echo provides sensitivity to a narrow range of T* values; the echo time (TE) is therefore selected to provide the best compromise of sensitivity to T* across the whole brain. Combining data from multiple echoes increases the range of T* that can be imaged with high fidelity. ME has been shown to improve functional contrast (Poser and Norris ) and spatial specificity (Boyacioğlu et al. ) at 7T and 3T (Fernandez et al. ; Halai et al. ; Kirilina et al. ; Lynch et al. ). Having multiple echoes also facilitates the separation of signal and noise because signals decay in a well‐characterised way across echoes, whereas noise does not. This principle underpins multi‐echo independent components analysis (ME‐ICA), via which ICA components that are TE‐independent, and thus are likely to be noise rather than blood‐oxygen‐level‐dependent (BOLD) signal, can be removed (Dipasquale et al. ; Kundu et al. , , , ). This method may enhance signal detection in areas prone to susceptibility artefacts on top of the advantage offered by ME alone (e.g., Lombardo et al. ). ME sequences have some potential disadvantages. For example, ME can lengthen repetition time (TR). In‐plane acceleration is frequently needed to achieve a sufficiently short first TE, which reduces tSNR (Yun and Shah ). In turn, a short first TE, combined with hardware constraints, often limits the minimum voxel size (Koopmans et al. ). Critically, in many previous studies examining the benefits of ME sequences com