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.

For the first six weeks following total knee arthroplasty (TKA), a patient will attend an outpatient clinic typically seen twice weekly. Here, an exercise regime is performed and improvement assessed using a hand held goniometer that measures the maximum angle of knee flexion, an important metric of progress. Additionally a series of daily exercises is performed at home, recorded in a diary. This protocol has problems. Patients must attend the hospital with assistance since they are not permitted to drive for six weeks following the procedure; appointments are sometimes missed; there are occasionally not enough physiotherapy appointment available; furthermore, it is difficult to be sure that patients are compliant with their exercises at home. The economic and social costs are therefore significant both to the patient and the health service. We describe here an automatic system that performs the monitoring of knee flexion within a domestic environment rather than in a hospital setting. It comprises a master and slave sensor unit that attach using Velcro straps to the thigh and shin above and below the operation wound. The patient performs the prescribed knee exercises whilst wearing the device, during which time it measures and records the angles of knee flexion. The device utilises the Global System for Mobile Communications (GSM) infrastructure to transmit data through the Internet to a secure hospital-based server using an on-board GSM modem. The clinician is then able to view and interpret the information from any computer with internet access and the software. The system does not require the patient to possess a mobile telephone, a computer, or have internet access; the necessary communications technology is completely integrated into the device.

Purpose Contributions of cerebrospinal fluid (CSF) have not been previously taken into account in the quantification of APT CEST effects, and correction for the dilution of CEST effects by CSF may allow for more robust measurement of CEST signals. The objective of this study was to compare the robustness of a partial volume (PV) correction model against a standard (4‐pool) multi‐pool model as far as their ability to quantify CEST effects in healthy, normal, and pathological tissue. Methods MRI data from 12 patients presenting with ischemic stroke, and 6 healthy subjects, were retrospectively analyzed. CEST signals derived from a 4‐pool model and a PV correction model were compared for repeatability and pathological tissue contrast. The effect of PV correction (PVC) was assessed within 3 ranges of tissue PV estimate (PVE): high PVE voxels, low PVE voxels, and the whole slice. Results In voxels with a high tissue PVE, PV correction did not make a significant difference to absolute APTR*. In low PVE voxels, the PVC model exhibited a significantly decreased ischemic core signal. The PVC measures exhibited higher repeatability between healthy subjects (4 pools: 3.4%, PVC: 2.4%) while maintaining a similar ischemic core CNR (0.7) to the 4‐pool model. In whole slice analysis it was found that both models exhibited similar results. Conclusions PV correction yielded a measure of APT effects that was more repeatable than standard 4‐pool analysis while achieving a similar CNR in pathological tissue, suggesting that PV‐corrected analysis was more robust at low values of tissue PVE.

In chemical exchange saturation transfer imaging, saturation effects between −2 to −5 ppm (nuclear Overhauser effects, NOEs) have been shown to exhibit contrast in preclinical stroke models. Our previous work on NOEs in human stroke used an analysis model that combined NOEs and semisolid MT; however their combination might feasibly have reduced sensitivity to changes in NOEs. The aim of this study was to explore the information a 4-pool Bloch-McConnell model provides about the NOE contribution in ischemic stroke, contrasting that with an intentionally approximate 3-pool model. Methods: MRI data from 12 patients presenting with ischemic stroke were retrospectively analyzed, as well as from six animals induced with an ischemic lesion. Two Bloch-McConnell models (4 pools, and a 3-pool approximation)were compared for their ability to distinguish pathological tissue in acute stroke. The association of NOEs with pH was also explored, using pH phantoms that mimic the intracellular environment of naïve mouse brain. Results:The 4-pool measure of NOEs exhibited a different association with tissue outcome compared to 3-pool approximation in the ischemic core and in tissue that underwent delayed infarction. In the ischemic core, the 4-pool measure was elevated in patient white matter (1.20 ± 0.20) and in animals (1.27 ± 0.20). In the naïve brain pH phantoms, significant positive correlation between the NOE and pH was observed. Conclusion:Associations of NOEs with tissue pathology were found using the 4-pool metric that were not observed using the 3-pool approximation. The 4-pool model more adequately captured in vivo changes in NOEs and revealed trends depending on tissue pathology in stroke.