Ultra-high field (7T) functional magnetic resonance imaging in amyotrophic lateral sclerosis: a pilot study

Barry, Robert; Babu, Suma; Anteraper, Sheeba Arnold; Triantafyllou, Christina; Keil, Boris; Rowe, Olivia; Rangaprakash, D.; Paganoni, Sabrina; Lawson, Robert; Dheel, Christina; Cernasov, Paul; Rosen, Bruce R.; Ratai, Eva‐Maria; Atassi, Nazem

doi:10.1016/j.nicl.2021.102648

Cited by 13 publications

(11 citation statements)

References 121 publications

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“…Radiologically, the BCNSB appears intact in ALS patients on standard imaging techniques, in contrast to multiple sclerosis and other CNS inflammatory conditions whereby BCNSB disruption is typically demonstrated by gadolinium extravasation on MRI. While early clinical ALS studies using novel 7T MRI scanners have largely explored the CNS anatomy and connectivity (Verstraete et al, 2010b ; Cosottini et al, 2016 ; Barry et al, 2021 ), BCNSB leakage has not been extensively investigated with this technique. Of note, indirect measures of BBB integrity such as microbleeds in ALS were not increased as measured by 7T MRI (Verstraete et al, 2010a ).…”

Section: Resultsmentioning

confidence: 99%

Breached Barriers: A Scoping Review of Blood-Central Nervous System Barrier Pathology in Amyotrophic Lateral Sclerosis

Mirian

Moszczynski

Soleimani

et al. 2022

Front. Cell. Neurosci.

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IntroductionRecent studies have implicated changes in the blood-central nervous system barriers (BCNSB) in amyotrophic lateral sclerosis (ALS). The objective of this scoping review is to synthesize the current evidence for BCNSB structure and functional abnormalities in ALS studies and propose how BCNSB pathology may impact therapeutic development.MethodsA literature search was conducted using Ovid Medline, EMBASE, and Web of Science, from inception to November 2021 and limited to entries in English language. Simplified search strategy included the terms ALS/motor neuron disease and [BCNSB or blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB)]. Henceforth, BCNSB is used as a term that is inclusive of the BBB and BSCB. Four independent reviewers conducted a title and abstract screening, hand-searched the reference lists of review papers, and performed a full text review of eligible studies. Included studies were original peer-reviewed full text publications, evaluating the structure and function of the BCNSB in preclinical models of ALS, clinical ALS, or postmortem human ALS tissue. There was no restriction on study design. The four reviewers independently extracted the data.ResultsThe search retrieved 2,221 non-duplicated articles and 48 original studies were included in the synthesis. There was evidence that the integrity of the BCNSB is disrupted throughout the course of the disease in rodent models, beginning prior to symptom onset and detectable neurodegeneration. Increased permeability, pharmacoresistance with upregulated efflux transporters, and morphological changes in the supporting cells of the BCNSB, including pericytes, astrocytes, and endothelial cells were observed in animal models. BCNSB abnormalities were also demonstrated in postmortem studies of ALS patients. Therapeutic interventions targeting BCNSB dysfunction were associated with improved motor neuron survival in animal models of ALS.ConclusionBCNSB structural and functional abnormalities are likely implicated in ALS pathophysiology and may occur upstream to neurodegeneration. Promising therapeutic strategies targeting BCNSB dysfunction have been tested in animals and can be translated into ALS clinical trials.

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Section: Resultsmentioning

confidence: 99%

Breached Barriers: A Scoping Review of Blood-Central Nervous System Barrier Pathology in Amyotrophic Lateral Sclerosis

Mirian

Moszczynski

Soleimani

et al. 2022

Front. Cell. Neurosci.

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“…3 TRs = 10.5 s; ~0.1 Hz), it is sufficient to track the change of resting-state signals, the peaks of which are usually detected within a frequency of 0.03-0.04 Hz (Zuo et al, 2010, Xue et al, 2014, Yuen et al, 2019, Bajaj et al, 2014) in the gray matter. Furthermore, it has been reported that conventional resting-state analyses are not significantly altered by TR (Huotari et al, 2019), and methods employing relatively slow sampling have succeeded in tracking laminar dynamics (e.g., 3960ms (Sharoh et al, 2019), 5000ms (Barry et al, 2021), 8300ms (Huber et al, 2020)). Despite the advantages of TR-external EPIK over conventional EPI, the GE nature of the technique makes it susceptible to vein-derived contamination, just as any other GE-EPI sequence.…”

Section: Discussionmentioning

confidence: 99%

Cortical depth-dependent human fMRI of resting-state networks using EPIK

Pais-Roldán

Yun

Palomero-Gallagher

et al. 2020

Preprint

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Recent laminar-fMRI studies have provided substantial understanding of the evoked cortical responses in multiple sub-systems; in contrast, the laminar component of resting-state networks remains largely unknown. Here, we used EPIK, which offers unprecedented coverage at sub-millimetre resolution, to investigate cortical resting-state dynamics with depth specificity. After verifying laminar activation profiles in response to a task, we investigated whole-brain laminar dynamics. During rest, signal oscillations were stronger in the superficial layers of the cortical ribbon, and functional connectivity analysis indicated that most resting-state cortical connections occurring at rest involve supra-granular layers. Coherence assessed in a lateral motor network suggested a modified distribution of layer-specific responses during task performance compared to resting-state. Whole-brain evaluation of laminar-fMRI encompasses unprecedented computational challenges; nonetheless, it enables a new dimension of the human cerebral cortex to be investigated from a global view, which may be key in the characterization of neurological disorders from a novel perspective.Significance statementResting-state networks sustain conscious awareness and diverse cognitive processing in the absence of tasks. In contrast to cortical areas, the cortical depth-specific signals across different networks have been poorly investigated, mainly due to the small brain coverage enforced in high-resolution imaging methods. Here, we demonstrate the different involvement of the cortical layers in the maintenance of the resting-state dynamics at near whole-brain level, using an optimized fMRI sequence. Given the cytoarchitectonics of the human neocortex, and based on our results, the cortical thickness constitutes an important dimension to characterize the resting-state oscillations in the healthy brain and its functional study may facilitate the identification of novel targets in neurological diseases.

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“…However, since rs‐fMRI focuses on low‐frequency fluctuations (<0.1 Hz), conventional data analyses require a TR of 5 s to cope with the Nyquist sampling of the upper limit (Berman et al, 2021 ). Accordingly, the use of a long TR for rs‐fMRI has also been demonstrated in previous publications: TR of 3960, 5000 and 5856 ms (Barry et al, 2021 ; Berman et al, 2021 ; Sharoh et al, 2019 ). Depending on the method selected from the literature, it may be possible to achieve an increased spatial resolution or larger slice coverage by a protocol adjustment.…”

Section: Discussionmentioning

confidence: 53%

“…Accordingly, the use of a long TR for rs-fMRI has also been demonstrated in previous publications: TR of 3960, 5000 and 5856 ms (Barry et al, 2021;Berman et al, 2021;Sharoh et al, 2019). Depending on the method selected from the literature, it may be possible to achieve an increased spatial resolution or larger slice coverage by a protocol adjustment.…”

Section: Rsn Results For An Isovoxel Protocolmentioning

confidence: 81%

Mapping of whole‐cerebrum resting‐state networks using ultra‐high resolution acquisition protocols

Yun

Pais‐Roldán

Palomero‐Gallagher

et al. 2022

Human Brain Mapping

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Resting‐state functional magnetic resonance imaging (fMRI) has been used in numerous studies to map networks in the brain that employ spatially disparate regions. However, attempts to map networks with high spatial resolution have been hampered by conflicting technical demands and associated problems. Results from recent fMRI studies have shown that spatial resolution remains around 0.7 × 0.7 × 0.7 mm 3 , with only partial brain coverage. Therefore, this work aims to present a novel fMRI technique that was developed based on echo‐planar‐imaging with keyhole (EPIK) combined with repetition‐time‐external (TR‐external) EPI phase correction. Each technique has been previously shown to be effective in enhancing the spatial resolution of fMRI, and in this work, the combination of the two techniques into TR‐external EPIK provided a nominal spatial resolution of 0.51 × 0.51 × 1.00 mm 3 (0.26 mm 3 voxel) with whole‐cerebrum coverage. Here, the feasibility of using half‐millimetre in‐plane TR‐external EPIK for resting‐state fMRI was validated using 13 healthy subjects and the corresponding reproducible mapping of resting‐state networks was demonstrated. Furthermore, TR‐external EPIK enabled the identification of various resting‐state networks distributed throughout the brain from a single fMRI session, with mapping fidelity onto the grey matter at 7T. The high‐resolution functional image further revealed mesoscale anatomical structures, such as small cerebral vessels and the internal granular layer of the cortex within the postcentral gyrus.

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Ultra-high field (7T) functional magnetic resonance imaging in amyotrophic lateral sclerosis: a pilot study

Abstract: Highlights Participants with ALS exhibited impaired function between the cortex and cerebellum. The cerebellum is associated with complex motor and cognitive processing tasks. These findings add to the growing number of ALS reports implicating the cerebellum.

Cited by 13 publications

References 121 publications

Breached Barriers: A Scoping Review of Blood-Central Nervous System Barrier Pathology in Amyotrophic Lateral Sclerosis

Breached Barriers: A Scoping Review of Blood-Central Nervous System Barrier Pathology in Amyotrophic Lateral Sclerosis

Cortical depth-dependent human fMRI of resting-state networks using EPIK

Mapping of whole‐cerebrum resting‐state networks using ultra‐high resolution acquisition protocols

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