BOLD Temporal Dynamics of Rat Superior Colliculus and Lateral Geniculate Nucleus following Short Duration Visual Stimulation

Background: The superior colliculus (SC) and lateral geniculate nucleus (LGN) are important subcortical structures for vision. Much of our understanding of vision was obtained using invasive and small field of view (FOV) techniques. In this study, we use non-invasive, large FOV blood oxygenation level-dependent (BOLD) fMRI to measure the SC and LGN's response temporal dynamics following short duration (1 s) visual stimulation. Methodology/Principal Findings: Experiments are performed at 7 tesla on Sprague Dawley rats stimulated in one eye with flashing light. Gradient-echo and spin-echo sequences are used to provide complementary information. An anatomical image is acquired from one rat after injection of monocrystalline iron oxide nanoparticles (MION), a blood vessel contrast agent. BOLD responses are concentrated in the contralateral SC and LGN. The SC BOLD signal measured with gradient-echo rises to 50% of maximum amplitude (PEAK) 0.2±0.2 s before the LGN signal (p<0.05). The LGN signal returns to 50% of PEAK 1.4±1.2 s before the SC signal (p<0.05). These results indicate the SC signal rises faster than the LGN signal but settles slower. Spin-echo results support these findings. The post-MION image shows the SC and LGN lie beneath large blood vessels. This subcortical vasculature is similar to that in the cortex, which also lies beneath large vessels. The LGN lies closer to the large vessels than much of the SC. Conclusions/Significance: The differences in response timing between SC and LGN are very similar to those between deep and shallow cortical layers following electrical stimulation, which are related to depth-dependent blood vessel dilation rates. This combined with the similarities in vasculature between subcortex and cortex suggest the SC and LGN timing differences are also related to depth-dependent dilation rates. This study shows for the first time that BOLD responses in the rat SC and LGN following short duration visual stimulation are temporally different. © 2011 Lau et al

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Sources of distortion in functional MRI data.

Functional magnetic resonance image (fMRI) experiments rely on the ability to detect subtle signal changes in magnetic resonance image time series. Any areas of signal change that correlate with the neurological stimulus can then be identified and compared with a corresponding high-resolution anatomical scan. This report reviews some of the several artefacts that are frequently present in fMRI data, degrading their quality and hence their interpretation. In particular, the effects of magnetic field inhomogeneities are described, both on echo planar imaging (EPI) data and on spiral imaging data. The modulation of these distortions as the subject moves in the magnet is described. The effects of gradient coil nonlinearities and EPI ghost correction schemes are also discussed

Rapid T(1) mapping using multislice echo planar imaging.

Determination of neurological pathology in white matter disease can be made in a semiquantitative way from T(1)- or T(2)-weighted images. A higher level of quantification based on measured T(1) or T(2) values has been either limited to specific regions of interest or to low-resolution maps. Higher-resolution T(1) maps have proved difficult to obtain due to the excessively long scan times required using conventional techniques. In this study, clinically acceptable images are obtained by using single-shot echo planar imaging (EPI) with an acquisition scheme that maximizes signal-to-noise while minimizing the scan time. Magn Reson Med 45:630-634, 2001

Investigations on the efficiency of cardiac-gated methods for the acquisition of diffusion-weighted images.

Diffusion-weighted images are inherently very sensitive to motion. Pulsatile motion of the brain can give rise to artifactual signal attenuation leading to over-estimation of the apparent diffusion coefficients, even with snapshot echo planar imaging. Such miscalculations can result in erroneous estimates of the principal diffusion directions. Cardiac gating can be performed to confine acquisition to the quiet portion of the cycle. Although effective, this approach leads to significantly longer acquisition times. On the other hand, it has been demonstrated that pulsatile motion is not significant in regions above the corpus callosum. To reduce acquisition times and improve the efficiency of whole brain cardiac-gated acquisitions, the upper slices of the brain can be imaged during systole, reserving diastole for those slices most affected by pulsatile motion. The merits and disadvantages of this optimized approach are investigated here, in comparison to a more standard gating method and to the non-gated approach

Quantitative perfusion measurements using pulsed arterial spin labeling: effects of large region-of-interest analysis.

PURPOSE: To study arterial spin labeling (ASL) MRI techniques and to investigate various problematic issues that still hinder the accurate and robust quantitative analysis of ASL data. MATERIALS AND METHODS: A pulsed-ASL (PASL) sequence was implemented on a 3-T imaging system and a protocol was developed for the measurement of perfusion based on fitting to a standard kinetic model. Both numerical simulations and multi-inversion time MRI data were analyzed. The effect of fitting a kinetic curve to a large region of interest (ROI) with a distribution of arterial transit times was compared to a pixel-by-pixel (PBP) method. RESULTS: It was found that a significant underestimation of perfusion of approximately 17+/-6% (P&lt;0.001) occurs in gray matter, when comparing an ROI with a PBP analysis over a group of 12 healthy subjects. CONCLUSION: Analysis of ASL data based on a large ROI may suffer from inaccuracies arising from a distribution of transit times, implying that averaging of ASL kinetic data over such regions should therefore be avoided. When possible, a PBP fit should be performed

Compensating for B(1) inhomogeneity using active transmit power modulation.

The effect of poor B(1) homogeneity on MRI images not only affects the appearance of the images, but produces difficulty in automated segmentation and in certain quantification methods. While improved RF coil design is the first line in reducing such artifact, compensation methods can significantly improve the quality of images. Existing methods of compensation typically apply a filter during the image reconstruction. Here a method is presented that compensates for part of the inhomogeneity by actively modulating the RF transmit power as a function of slice position. The method is demonstrated both quantitatively on a phantom and qualitatively on a human brain

A comparison of structurally and functionally defined human primary visual cortex

Early visual areas can be defined using fMRI on the basis of their retinotopic organisation. Recently, very high-resolution images of the human brain in vivo have identified areas of myelination within the grey matter, corresponding to the striate cortex (Barbier et al. 2002; Clare et al. 2002). This myelination has traditionally been understood to correspond to the human primary visual cortex (V1). To test this correspondence, we compared the location of visually identified striate in high resolution images with the location of functionally defined V1. For imaging the myeloarchitecture, a magnetisation prepared 3D FLASH sequence was used as described in Clare et al. (2002). The resulting images had a resolution of 0.3×0.3×1.5 mm. Functional MRI was performed at a lower resolution of 3×3×1.5 mm using single shot EPI at the same 16 slice locations as the structural scan. Retinotopy data were collected using expanding ring and rotating wedge stimuli. The data were transformed onto a segmented (mrGray) and flattened (mrFlatMesh) T1-weighted scan (1×1×1mm). V1 was defined by locating the upper and lower field V1/V2 borders from the rotating wedge phase map. From the high-resolution myeloarchitecture images, striate cortex was conservatively determined as those regions where a stripe was identified within the grey matter. These observer drawn maps of striate cortex were then transformed into flattened space to allow comparison with the functional data. A good level of correspondence was found between the striate cortex determined in the structural MRI and V1 determined by fMRI. While the striate cortex was not identified as a continuous band, it is hoped that more striate will be revealed by using multiple slice orientations in the same subjects. In the future these very high-resolution structural images will offer the opportunity to combine the study of myeloarchitecture with functional architecture in the living human cortex