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Fulltext Quantitative CEST imaging of amide proton transfer in acute ischaemic stroke

Msayib Y, Harston GWJ, Tee YK, Sheerin F, Blockley NP, Okell TW, et al.

Neuroimage Clin, 2019;23:101833.
PMID: 31063943 DOI: 10.1016/j.nicl.2019.101833

BACKGROUND: Amide proton transfer (APT) imaging may help identify the ischaemic penumbra in stroke patients, the classical definition of which is a region of tissue around the ischaemic core that is hypoperfused and metabolically stressed. Given the potential of APT imaging to complement existing imaging techniques to provide clinically-relevant information, there is a need to develop analysis techniques that deliver a robust and repeatable APT metric. The challenge to accurate quantification of an APT metric has been the heterogeneous in-vivo environment of human tissue, which exhibits several confounding magnetisation transfer effects including spectrally-asymmetric nuclear Overhauser effects (NOEs). The recent literature has introduced various model-free and model-based approaches to analysis that seek to overcome these limitations.
OBJECTIVES: The objective of this work was to compare quantification techniques for CEST imaging that specifically separate APT and NOE effects for application in the clinical setting. Towards this end a methodological comparison of different CEST quantification techniques was undertaken in healthy subjects, and around clinical endpoints in a cohort of acute stroke patients.
METHODS: MRI data from 12 patients presenting with ischaemic stroke were retrospectively analysed. Six APT quantification techniques, comprising model-based and model-free techniques, were compared for repeatability and ability for APT to distinguish pathological tissue in acute stroke.
RESULTS: Robustness analysis of six quantification techniques indicated that the multi-pool model-based technique had the smallest contrast between grey and white matter (2%), whereas model-free techniques exhibited the highest contrast (>30%). Model-based techniques also exhibited the lowest spatial variability, of which 4-pool APTR∗ was by far the most uniform (10% coefficient of variation, CoV), followed by 3-pool analysis (20%). Four-pool analysis yielded the highest ischaemic core contrast-to-noise ratio (0.74). Four-pool modelling of APT effects was more repeatable (3.2% CoV) than 3-pool modelling (4.6% CoV), but this appears to come at the cost of reduced contrast between infarct growth tissue and normal tissue.
CONCLUSION: The multi-pool measures performed best across the analyses of repeatability, spatial variability, contrast-to-noise ratio, and grey matter-white matter contrast, and might therefore be more suitable for use in clinical imaging of acute stroke. Addition of a fourth pool that separates NOEs and semisolid effects appeared to be more biophysically accurate and provided better separation of the APT signal compared to the 3-pool equivalent, but this improvement appeared be accompanied by reduced contrast between infarct growth tissue and normal tissue.
Fulltext Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging

Harston GW, Tee YK, Blockley N, Okell TW, Thandeswaran S, Shaya G, et al.

Brain, 2015 Jan;138(Pt 1):36-42.
PMID: 25564491 DOI: 10.1093/brain/awu374

The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke.
Fulltext Aerobic exercise increases brain vessel lumen size and blood flow in young adults with elevated blood pressure. Secondary analysis of the TEPHRA randomized clinical trial

Lapidaire W, Forkert ND, Williamson W, Huckstep O, Tan CM, Alsharqi M, et al.

Neuroimage Clin, 2023;37:103337.
PMID: 36709637 DOI: 10.1016/j.nicl.2023.103337

IMPORTANCE: Cerebrovascular changes are already evident in young adults with hypertension and exercise is recommended to reduce cardiovascular risk. To what extent exercise benefits the cerebrovasculature at an early stage of the disease remains unclear.
OBJECTIVE: To investigate whether structured aerobic exercise increases brain vessel lumen diameter or cerebral blood flow (CBF) and whether lumen diameter is associated with CBF.
DESIGN: Open, parallel, two-arm superiority randomized controlled (1:1) trial in the TEPHRA study on an intention-to-treat basis. The MRI sub-study was an optional part of the protocol. The outcome assessors remained blinded until the data lock.
SETTING: Single-centre trial in Oxford, UK.
PARTICIPANTS: Participants were physically inactive (<150 min/week moderate to vigorous physical activity), 18 to 35 years old, 24-hour ambulatory blood pressure 115/75 mmHg-159/99 mmHg, body mass index below 35 kg/m2 and never been on prescribed hypertension medications. Out of 203 randomized participants, 135 participated in the MRI sub-study. Randomisation was stratified for sex, age (<24, 24-29, 30-35 years) and gestational age at birth (<32, 32-37, >37 weeks).
INTERVENTION: Study participants were randomised to a 16 week aerobic exercise intervention targeting 3×60 min sessions per week at 60 to 80 % peak heart rate.
MAIN OUTCOMES AND MEASURES: cerebral blood flow (CBF) maps from ASL MRI scans, internal carotid artery (ICA), middle cerebral artery (MCA) M1 and M2 segments, anterior cerebral artery (ACA), basilar artery (BA), and posterior cerebral artery (PCA) diameters extracted from TOF MRI scans.
RESULTS: Of the 135 randomized participants (median age 28 years, 58 % women) who had high quality baseline MRI data available, 93 participants also had high quality follow-up data available. The exercise group showed an increase in ICA (0.1 cm, 95 % CI 0.01 to 0.18, p =.03) and MCA M1 (0.05 cm, 95 % CI 0.01 to 0.10, p =.03) vessel diameter compared to the control group. Differences in the MCA M2 (0.03 cm, 95 % CI 0.0 to 0.06, p =.08), ACA (0.04 cm, 95 % CI 0.0 to 0.08, p =.06), BA (0.02 cm, 95 % CI -0.04 to 0.09, p =.48), and PCA (0.03 cm, 95 % CI -0.01 to 0.06, p =.17) diameters or CBF were not statistically significant. The increase in ICA vessel diameter in the exercise group was associated with local increases in CBF.
CONCLUSIONS AND RELEVANCE: Aerobic exercise induces positive cerebrovascular remodelling in young people with early hypertension, independent of blood pressure. The long-term benefit of these changes requires further study.
TRIAL REGISTRATION: Clinicaltrials.gov NCT02723552, 30 March 2016.

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