Measurement of blood-brain barrier water exchange rate using diffusion-prepared and multi-echo arterial spin labelling: Comparison of quantitative values and age dependence.

Water exchange rate (Kw) across the blood-brain barrier (BBB) is an important physiological parameter that may provide new insight into ageing and neurodegenerative disease. Recently, two non-invasive arterial spin labelling (ASL) MRI methods have been developed to measure Kw, but results from the different methods have not been directly compared. Furthermore, the association of Kw with age for each method has not been investigated in a single cohort. Thirty participants (70% female, 63.8 ± 10.4 years) were scanned at 3 T with Diffusion-Prepared ASL (DP-ASL) and Multi-Echo ASL (ME-ASL) using previously implemented acquisition and analysis protocols. Grey matter Kw, cerebral blood flow (CBF) and arterial transit time (ATT) were extracted. CBF values were consistent; approximately 50 ml/min/100 g for both methods, and a strong positive correlation in CBF from both methods across participants (r = 0.82, p < 0.001). ATT was significantly different between methods (on average 147.7 ms lower when measured with DP-ASL compared to ME-ASL) but was positively correlated across participants (r = 0.39, p < 0.05). Significantly different Kw values of 106.6 ± 19.7 min-1 and 306.8 ± 71.7 min-1 were measured using DP-ASL and ME-ASL, respectively, and DP-ASL Kw and ME-ASL Kw were negatively correlated across participants (r = -0.46, p < 0.01). Kw measured using ME-ASL had a significant linear relationship with age (p < 0.05). In conclusion, DP-ASL and ME-ASL provided estimates of Kw with significantly different quantitative values and inconsistent dependence with age. We propose future standardisation of modelling and fitting methods for DP-ASL and ME-ASL, to evaluate the effect on Kw quantification. Also, sensitivity and bias analyses should be performed for both approaches, to assess the effect of varying acquisition and fitting parameters. Lastly, comparison with independent measures of BBB water transport, and with physiological and clinical biomarkers known to be associated with changes in BBB permeability, are essential to validate the ASL methods, and to demonstrate their clinical utility.

Imaging blood-brain barrier dysfunction: A state-of-the-art review from a clinical perspective.

The blood-brain barrier (BBB) consists of specialized cells that tightly regulate the in- and outflow of molecules from the blood to brain parenchyma, protecting the brain's microenvironment. If one of the BBB components starts to fail, its dysfunction can lead to a cascade of neuroinflammatory events leading to neuronal dysfunction and degeneration. Preliminary imaging findings suggest that BBB dysfunction could serve as an early diagnostic and prognostic biomarker for a number of neurological diseases. This review aims to provide clinicians with an overview of the emerging field of BBB imaging in humans by answering three key questions: (1. Disease) In which diseases could BBB imaging be useful? (2. Device) What are currently available imaging methods for evaluating BBB integrity? And (3. Distribution) what is the potential of BBB imaging in different environments, particularly in resource limited settings? We conclude that further advances are needed, such as the validation, standardization and implementation of readily available, low-cost and non-contrast BBB imaging techniques, for BBB imaging to be a useful clinical biomarker in both resource-limited and well-resourced settings.

Multi-day, multi-sensor ambulatory monitoring of gastric electrical activity.

OBJECTIVE: Bioelectrial signals known as slow waves play a key role in coordinating gastric motility. Slow wave dysrhythmias have been associated with a number of functional motility disorders. However, there have been limited human recordings obtained in the consious state or over an extended period of time. This study aimed to evaluate a robust ambulatory recording platform. APPROACH: A commercially available multi-sensor recording system (Shimmer3, ShimmerSensing) was applied to acquire slow wave information from the stomach of six humans and four pigs. First, acute experiments were conducted in pigs to verify the accuracy of the recording module by comparing to a standard widely employed electrophysiological mapping system (ActiveTwo, BioSemi). Then, patients with medically refractory gastroparesis undergoing temporary gastric stimulator implantation were enrolled and gastric slow waves were recorded from mucosally-implanted electrodes for 5 d continuously. Accelerometer data was also collected to exclude data segments containing excessive patient motion artefact. MAIN RESULTS: Slow wave signals and activation times from the Shimmer3 module were closely comparable to a standard electrophysiological mapping system. Slow waves were able to be recorded continuously for 5 d in human subjects. Over the 5 d, slow wave frequency was 2.8 ± 0.6 cpm and amplitude was 0.2 ± 0.3 mV. SIGNIFICANCE: A commercial multi-sensor recording module was validated for recording electrophysiological slow waves for 5 d, including in ambulatory patients. Multiple modules could be used simultaneously in the future to track the spatio-temporal propagation of slow waves. This framework can now allow for patho-electrophysiological studies to be undertaken to allow symptom correlation with dysrhythmic slow wave events.