Partial volume correction for quantitative CEST imaging of acute ischemic stroke.

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.

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

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.

Measuring venous blood volume changes during activation using hyperoxia.

This study describes a novel method for measuring relative changes in venous cerebral blood volume (CBVv) using hyperoxia as a contrast agent. This method exploits the extravascular BOLD effect and its dependency on both task-related activation induced changes in venous blood oxygenation and changes due to breathing an oxygen enriched gas mixture. Changes in CBVv on activation can be estimated by comparing the change in transverse relaxation rate, R2*, due to hyperoxia in both baseline and activation states. Furthermore these measurements can be converted into a measure of the percentage change in CBVv. Experiments were performed to measure changes in a CBVv-weighted signal in response to a simple motor task. Both positive and negative changes in CBVv-weighted signal were detected in the positively activated BOLD region.

Perturbation of the BOLD response by a contrast agent and interpretation through a modified balloon model.

This study used an infusion of a paramagnetic contrast agent to perturb intravascular blood susceptibility and investigate its effect on the BOLD hemodynamic response. A three compartment BOLD signal model combined with a modified balloon model was developed to interpret the MR signal. This model incorporated arterial blood volume in order to simulate signal changes resulting from the contrast agent. The BOLD signal model was fitted to the experimental data to test the hypothesis that arterial blood volume changes during activation. It was found that allowing arterial blood volume to change, rather than assuming this change is negligible as often assumed in the literature, provides a better fit to the experimental data, particularly during the BOLD overshoot. The post-stimulus undershoot was fitted well, regardless of whether the arterial blood volume was allowed to change, by assuming that this feature is due to delayed venous compliance. However the resultant elevation in post-stimulus blood volume decays with an extremely long time constant, taking more than 55 s to recover to baseline following a 4.8 s stimulus. The post-stimulus signal changes measured here could alternatively be described by a post-stimulus elevation in metabolism. An alternative model of oxygen extraction, in place of the Oxygen Limitation model, would be required to test this hypothesis.

Field strength dependence of R1 and R2* relaxivities of human whole blood to ProHance, Vasovist, and deoxyhemoglobin.

This study has measured the longitudinal and transverse (T2* relaxivity curves for ProHance (Gadoteridol), Vasovist (Gadofosveset) and deoxyhemoglobin at 1.5, 3.0, and 7.0 Tesla. The plots of R(1) versus both contrast agent and deoxyhemoglobin concentration were linear. The plots of R2* versus deoxyhemoglobin concentration showed a quadratic dependence. R2* versus contrast agent concentration showed a parabolic dependence with a minimum occurring at contrast agent concentrations of approximately 1.5 mM, corresponding to an accessible concentration in vivo. Monte Carlo simulations were performed to support the hypothesis that the minimum results from the susceptibility of the red blood cells being matched to the susceptibility of the plasma. Relaxivity values (s(-1)mM(-1)) for R2* and R1 for all agents and all three field strengths are given.