Influence of parking on train station choice under uncertainty for park-and-ride users

This paper presents a station choice model for park and ride (PnR) users based on uncertain parking attributes, such as parking search time (PST). In order to take into account uncertainty in PnR users’ choice process, a mixed logit model was developed within the framework of the discrete choice theory, the utility function in the model was established using a mean-variance approach under the cumulative prospect theory framework proposed Tversky and Kahneman [1]. A stated preference survey was designed for studying PnR users’ preference of stations, which was influenced by parking conditions at a train station. The experimental design was optimized using the D-optimality criterion. Our results show that the number that parking bays left in PnR facilities at given access time, parking cost including parking fees and fines and the variation of PST are important factors affecting PnR users’ station choice. PnR users were risk averse toward the variation of PST, which means that a PnR user is willing to choose a station with less uncertain or variation of PS

Signatures of Exposure to Childhood Trauma in Young Adults in the Structure and Neurochemistry of the Superior Temporal Gyrus

Background: Childhood trauma (CT) has been linked to increased risk for mental illness in adulthood. Although work in experimental animals has shown that early life stressors can affect inhibitory and excitatory neurotransmission in adult rodents, with possible excitotoxic effects on local grey matter volumes (GMV), the neurobiological mechanisms that mediate this relationship in humans remain poorly understood. Aim: To examine glutamate and gamma-aminobutyric acid (GABA) metabolite concentrations and potential excitotoxic effects on GMV, in adults who experienced CT. Methods: Fifty-six young adults (Mage = 20.41) were assigned to High CT (n = 29) and Low CT (n = 27) groups (by using the CT questionnaire) and underwent magnetic resonance spectroscopy (1H-MRS) to measure temporal lobe metabolite concentrations and volumetric imaging to measure GMV. Results: Glutamate concentrations did not differ between groups; however, relative to the Low CT group, participants in the High CT group had reduced GABA concentrations in the left superior temporal gyrus (STG) voxel. Furthermore, logistic regression showed that participants with low left STG GABA concentrations and low left STG volumes were significantly more likely to be in the high CT group. Conclusions: This study provides the first evidence that both low GABA concentrations and its interaction with GMV in the left STG are associated with high levels of CT and suggest that altered inhibitory neurotransmission/metabolism may be linked to a lower GMV in the left STG in adults who experienced CT. Future studies are warranted to establish if utilizing these measures can stratify clinical high-risk and predict future clinical outcomes in high CT individuals

Monitoring the Growth of an Orthotopic Tumour Xenograft Model: Multi-Modal Imaging Assessment with Benchtop MRI (1T), High-Field MRI (9.4T), Ultrasound and Bioluminescence

BACKGROUND: Research using orthotopic and transgenic models of cancer requires imaging methods to non-invasively quantify tumour burden. As the choice of appropriate imaging modality is wide-ranging, this study aimed to compare low-field (1T) magnetic resonance imaging (MRI), a novel and relatively low-cost system, against established preclinical techniques: bioluminescence imaging (BLI), ultrasound imaging (US), and high-field (9.4T) MRI. METHODS: A model of colorectal metastasis to the liver was established in eight mice, which were imaged with each modality over four weeks post-implantation. Tumour burden was assessed from manually segmented regions. RESULTS: All four imaging systems provided sufficient contrast to detect tumours in all of the mice after two weeks. No significant difference was detected between tumour doubling times estimated by low-field MRI, ultrasound imaging or high-field MRI. A strong correlation was measured between high-field MRI estimates of tumour burden and all the other modalities (p < 0.001, Pearson). CONCLUSION: These results suggest that both low-field MRI and ultrasound imaging are accurate modalities for characterising the growth of preclinical tumour models

Insular and occipital changes in visual snow syndrome: a BOLD fMRI and MRS study.

OBJECTIVE To investigate the pathophysiology of visual snow (VS), through a combined functional neuroimaging and magnetic resonance spectroscopy (1 H-MRS) approach. METHODS We applied a functional MRI block-design protocol studying the responses to a visual stimulation mimicking VS, in combination with 1 H-MRS over the right lingual gyrus, in 24 patients with VS compared to an equal number of age- and gender-matched healthy controls. RESULTS We found reduced BOLD responses to the visual stimulus with respect to baseline in VS patients compared to controls, in the left (k = 291; P = 0.025; peak MNI coordinate [-34 12 -6]) and right (k = 100; P = 0.003; peak MNI coordinate [44 14 -2]) anterior insula. Our spectroscopy analysis revealed a significant increase in lactate concentrations in patients with respect to controls (0.66 ± 0.9 mmol/L vs. 0.07 ± 0.2 mmol/L; P < 0.001) in the right lingual gyrus. In this area, there was a significant negative correlation between lactate concentrations and BOLD responses to visual stimulation (P = 0.004; r = -0.42), which was dependent on belonging to the patient group. INTERPRETATION As shown by our BOLD analysis, VS is characterized by a difference in bilateral insular responses to a visual stimulus mimicking VS itself, which could be due to disruptions within the salience network. Our results also suggest that patients with VS have a localized disturbance in extrastriate anaerobic metabolism, which may in turn cause a decreased metabolic reserve for the regular processing of visual stimuli

Stem cell delivery to kidney via minimally invasive ultrasound-guided renal artery injection in mice

Cell-based therapies are promising treatments for various kidney diseases. However, the major hurdle in initiating therapeutic responses is the inefficiency of injection routes to deliver cells to the kidney parenchyma. Systemic injection, such as intravenous injection only delivers a small proportion of cells to the kidney. Whereas direct delivery, such as renal artery injection requires surgical procedures. A minimally invasive renal artery injection was therefore developed to enhance cell delivery to kidney. In this study, luciferase expressing human adipocyte derived stem cells (ADSC) were labelled with gold nanorods (GNR) and injected into the renal artery using ultrasound guidance. The ADSCs were tracked using bioluminescence and photoacoustic imaging serially over 7 days. Imaging confirmed that the majority of signal was within the kidney, indicative of successful injection and that the cells remained viable for 3 days. Histology showed co-localization of GNRs with ADSC staining throughout the kidney with no indication of injury caused by injection. These findings demonstrate that ultrasound-guided renal artery injection is feasible in mice and can successfully deliver a large proportion of cells which are retained within the kidney for 3 days. Therefore, the techniques developed here will be useful for optimising cell therapy in kidney diseases

Investigating changes in blood-cerebrospinal fluid barrier function in a rat model of chronic hypertension using non-invasive magnetic resonance imaging

Chronic hypertension is a major risk factor for the development of neurodegenerative disease, yet the etiology of hypertension-driven neurodegeneration remains poorly understood. Forming a unique interface between the systemic circulation and the brain, the blood-cerebrospinal fluid barrier (BCSFB) at the choroid plexus (CP) has been proposed as a key site of vulnerability to hypertension that may initiate downstream neurodegenerative processes. However, our ability to understand BCSFB’s role in pathological processes has, to date, been restricted by a lack of non-invasive functional measurement techniques. In this work, we apply a novel Blood-Cerebrospinal Fluid Barrier Arterial Spin Labeling (BCSFB-ASL) Magnetic resonance imaging (MRI) approach with the aim of detecting possible derangement of BCSFB function in the Spontaneous Hypertensive Rat (SHR) model using a non-invasive, translational technique. SHRs displayed a 36% reduction in BCSFB-mediated labeled arterial water delivery into ventricular cerebrospinal fluid (CSF), relative to normotensive controls, indicative of down-regulated choroid plexus function. This was concomitant with additional changes in brain fluid biomarkers, namely ventriculomegaly and changes in CSF composition, as measured by T1 lengthening. However, cortical cerebral blood flow (CBF) measurements, an imaging biomarker of cerebrovascular health, revealed no measurable change between the groups. Here, we provide the first demonstration of BCSFB-ASL in the rat brain, enabling non-invasive assessment of BCSFB function in healthy and hypertensive rats. Our data highlights the potential for BCSFB-ASL to serve as a sensitive early biomarker for hypertension-driven neurodegeneration, in addition to investigating the mechanisms relating hypertension to neurodegenerative outcomes

Non-invasive MRI biomarkers for the early assessment of iron overload in a humanized mouse model of β-thalassemia

β-thalassemia (βT) is a genetic blood disorder causing profound and life threatening anemia. Current clinical management of βT is a lifelong dependence on regular blood transfusions, a consequence of which is systemic iron overload leading to acute heart failure. Recent developments in gene and chelation therapy give hope of better prognosis for patients, but successful translation to clinical practice is hindered by the lack of thorough preclinical testing using representative animal models and clinically relevant quantitative biomarkers. Here we demonstrate a quantitative and non-invasive preclinical Magnetic Resonance Imaging (MRI) platform for the assessment of βT in the γβ(0)/γβ(A) humanized mouse model of βT. Changes in the quantitative MRI relaxation times as well as severe splenomegaly were observed in the heart, liver and spleen in βT. These data showed high sensitivity to iron overload and a strong relationship between quantitative MRI relaxation times and hepatic iron content. Importantly these changes preceded the onset of iron overload cardiomyopathy, providing an early biomarker of disease progression. This work demonstrates that multiparametric MRI is a powerful tool for the assessment of preclinical βT, providing sensitive and quantitative monitoring of tissue iron sequestration and cardiac dysfunction- parameters essential for the preclinical development of new therapeutics

Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction

Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but are challenging to obtain. Here, manganese, a calcium analogue and clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an imaging biomarker of myocardial viability in the first hours after experimental MI. Safe Mn dosing is confirmed by measuring in vitro beating rates, calcium transients, and action potentials in cardiomyocytes, and in vivo heart rates and cardiac contractility in mice. Quantitative T1 mapping-manganese-enhanced MRI (MEMRI) reveals elevated and increasing Mn uptake in viable myocardium remote from the infarct, suggesting MEMRI offers a quantitative biomarker of cardiac inotropy. MEMRI evaluation of infarct size at 1 h, 1 and 14 days after MI quantifies myocardial viability earlier than the current gold-standard technique, late-gadolinium-enhanced MRI. These data, coupled with the re-emergence of clinical Mn -based contrast agents open the possibility of using MEMRI for direct evaluation of myocardial viability early after ischemic onset in patients