Characterising cerebrovascular reactivity and the pupillary light response-a comparative study.

Introduction: Smooth muscle is integral to multiple autonomic systems, including cerebrovascular dynamics through vascular smooth muscle cells and in ocular muscle dynamics, by regulating pupil size. In the brain, smooth muscle function plays a role in cerebrovascular reactivity (CVR) that describes changes in blood vessel calibre in response to vasoactive stimuli. Similarly, pupil size regulation can be measured using the pupillary light response (PLR), the pupil's reaction to changes in light levels.

The impact of Alzheimer's disease risk factors on the pupillary light response.

Alzheimer's disease (AD) is the leading cause of dementia, and its prevalence is increasing and is expected to continue to increase over the next few decades. Because of this, there is an urgent requirement to determine a way to diagnose the disease, and to target interventions to delay and ideally stop the onset of symptoms, specifically those impacting cognition and daily livelihood. The pupillary light response (PLR) is controlled by the sympathetic and parasympathetic branches of the autonomic nervous system, and impairments to the pupillary light response (PLR) have been related to AD.

Modelling spatiotemporal dynamics of cerebral blood flow using multiple-timepoint arterial spin labelling MRI.

Cerebral blood flow (CBF) is an important physiological parameter that can be quantified non-invasively using arterial spin labelling (ASL) imaging. Although most ASL studies are based on single-timepoint strategies, multi-timepoint approaches (multiple-PLD) in combination with appropriate model fitting strategies may be beneficial not only to improve CBF quantification but also to retrieve other physiological information of interest. In this work, we tested several kinetic models for the fitting of multiple-PLD pCASL data in a group of 10 healthy subjects.

A systematic review of the association between dementia risk factors and cerebrovascular reactivity.

Cumulative evidence suggests that impaired cerebrovascular reactivity (CVR), a regulatory response critical for maintaining neuronal health, is amongst the earliest pathological changes in dementia. However, we know little about how CVR is affected by dementia risk, prior to disease onset. Understanding this relationship would improve our knowledge of disease pathways and help inform preventative interventions.

Estimation of field inhomogeneity map following magnitude-based ambiguity-resolved water-fat separation.

Magnitude-based PDFF (Proton Density Fat Fraction) and R mapping with resolved water-fat ambiguity is extended to calculate field inhomogeneity (field map) using the phase images. The estimation is formulated in matrix form, resolving the field map in a least-squares sense. PDFF and R from magnitude fitting may be updated using the estimated field maps.

Comparison of liver iron concentration calculated from R2* at 1.5 T and 3 T.

Purpose: R2*, a measurement obtained using magnetic resonance imaging (MRI) can be used to estimate liver iron concentration (LIC). 3 T and 1.5 T scanners can be used but conversion of 3 T R2* to LIC is less well validated.

Vascular smooth muscle cell dysfunction in neurodegeneration.

Vascular smooth muscle cells (VSMCs) are the key moderators of cerebrovascular dynamics in response to the brain's oxygen and nutrient demands. Crucially, VSMCs may provide a sensitive biomarker for neurodegenerative pathologies where vasculature is compromised. An increasing body of research suggests that VSMCs have remarkable plasticity and their pathophysiology may play a key role in the complex process of neurodegeneration.

Modeling the Effect of Hyperoxia on the Spin-Lattice Relaxation Rate R1 of Tissues.

Purpose: Inducing hyperoxia in tissues is common practice in several areas of research, including oxygen-enhanced MRI (OE-MRI), which attempts to use the resulting signal changes to detect regions of tumor hypoxia or pulmonary disease. The linear relationship between PO and R1 has been reproduced in phantom solutions and body fluids such as vitreous fluid; however, in tissue and blood experiments, factors such as changes in deoxyhemoglobin levels can also affect the ΔR1.

Theory And Methods: This manuscript proposes a three-compartment model for estimating the hyperoxia-induced changes in R1 of tissues depending on B0, SO , blood volume, hematocrit, oxygen extraction fraction, and changes in blood and tissue PO .

Determination of oxygen relaxivity in oxygen nanobubbles at 3 and 7 Tesla.

Objective: Oxygen-loaded nanobubbles have shown potential for reducing tumour hypoxia and improving treatment outcomes, however, it remains difficult to noninvasively measure the changes in partial pressure of oxygen (PO) in vivo. The linear relationship between PO and longitudinal relaxation rate (R) has been used to noninvasively infer PO in vitreous and cerebrospinal fluid, and therefore, this experiment aimed to investigate whether R is a suitable measurement to study oxygen delivery from such oxygen carriers.

Methods: T mapping was used to measure R in phantoms containing nanobubbles with varied PO to measure the relaxivity of oxygen (r) in the phantoms at 7 and 3 T.

Using Variable Flip Angle (VFA) and Modified Look-Locker Inversion Recovery (MOLLI) T1 mapping in clinical OE-MRI.

Background And Purpose: The imaging technique known as Oxygen-Enhanced MRI is under development as a noninvasive technique for imaging hypoxia in tumours and pulmonary diseases. While promising results have been shown in preclinical experiments, clinical studies have mentioned experiencing difficulties with patient motion, image registration, and the limitations of single-slice images compared to 3D volumes. As clinical studies begin to assess feasibility of using OE-MRI in patients, it is important for researchers to communicate about the practical challenges experienced when using OE-MRI on patients to help the technique advance.

Pancreas MRI Segmentation Into Head, Body, and Tail Enables Regional Quantitative Analysis of Heterogeneous Disease.

Background: Quantitative imaging studies of the pancreas have often targeted the three main anatomical segments, head, body, and tail, using manual region of interest strategies to assess geographic heterogeneity. Existing automated analyses have implemented whole-organ segmentation, providing overall quantification but failing to address spatial heterogeneity.

Purpose: To develop and validate an automated method for pancreas segmentation into head, body, and tail subregions in abdominal MRI.

PyPlr: A versatile, integrated system of hardware and software for researching the human pupillary light reflex.

We introduce PyPlr-a versatile, integrated system of hardware and software to support a broad spectrum of research applications concerning the human pupillary light reflex (PLR). PyPlr is a custom Python library for integrating a research-grade video-based eye-tracker system with a light source and streamlining stimulus design, optimisation and delivery, device synchronisation, and extraction, cleaning, and analysis of pupil data. We additionally describe how full-field, homogenous stimulation of the retina can be realised with a low-cost integrating sphere that serves as an alternative to a more complex Maxwellian view setup.

A simplified empirical model to estimate oxygen relaxivity at different magnetic fields.

The change in longitudinal relaxation rate (R ) produced by oxygen has been used as a means of inferring oxygenation levels in magnetic resonance imaging in numerous applications. The relationship between oxygen partial pressure (pO ) and R is linear and reproducible, and the slope represents the relaxivity of oxygen (r ) in that material. However, there is considerable variability in the values of r reported, and they have been shown to vary by field strength and temperature.

A General Model to Calculate the Spin-Lattice Relaxation Rate (R1) of Blood, Accounting for Hematocrit, Oxygen Saturation, Oxygen Partial Pressure, and Magnetic Field Strength Under Hyperoxic Conditions.

Background: Under normal physiological conditions, the spin-lattice relaxation rate (R1) in blood is influenced by many factors, including hematocrit, field strength, and the paramagnetic effects of deoxyhemoglobin and dissolved oxygen. In addition, techniques such as oxygen-enhanced magnetic resonance imaging (MRI) require high fractions of inspired oxygen to induce hyperoxia, which complicates the R1 signal further. A quantitative model relating total blood oxygen content to R1 could help explain these effects.

Study Protocol: The Heart and Brain Study.

Background: It is well-established that what is good for the heart is good for the brain. Vascular factors such as hypertension, diabetes, and high cholesterol, and genetic factors such as the apolipoprotein E4 allele increase the risk of developing both cardiovascular disease and dementia. However, the mechanisms underlying the heart-brain association remain unclear.

Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non-Small Cell Lung Cancer.

Purpose: Tumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial to determine whether the antimalarial drug atovaquone, a known mitochondrial inhibitor, reduces hypoxia in non-small cell lung cancer (NSCLC).

Patients And Methods: Patients with NSCLC scheduled for surgery were recruited sequentially into two cohorts: cohort 1 received oral atovaquone at the standard clinical dose of 750 mg twice daily, while cohort 2 did not.

Cerebrovascular Reactivity Mapping Without Gas Challenges: A Methodological Guide.

Cerebrovascular reactivity (CVR) is defined as the ability of vessels to alter their caliber in response to vasoactive factors, by means of dilating or constricting, in order to increase or decrease regional cerebral blood flow (CBF). Importantly, CVR may provide a sensitive biomarker for pathologies where vasculature is compromised. Furthermore, the spatiotemporal dynamics of CVR observed in healthy subjects, reflecting regional differences in cerebral vascular tone and response, may also be important in functional MRI studies based on neurovascular coupling mechanisms.

Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma.

Background And Purpose: Oxygen-enhanced magnetic resonance imaging (MRI) and T1-mapping was used to explore its effectiveness as a prognostic imaging biomarker for chemoradiotherapy outcome in anal squamous cell carcinoma.

Materials And Methods: T2-weighted, T1 mapping, and oxygen-enhanced T1 maps were acquired before and after 8-10 fractions of chemoradiotherapy and examined whether the oxygen-enhanced MRI response relates to clinical outcome. Patient response to treatment was assessed 3 months following completion of chemoradiotherapy.

Magnetic resonance imaging of oxygen microbubbles.

Oxygen loaded microbubbles are being investigated as a means of reducing tumour hypoxia in order to improve response to cancer therapy. To optimise this approach, it is desirable to be able to measure changes in tissue oxygenation in real-time during treatment. In this study, the feasibility of using magnetic resonance imaging (MRI) for this purpose was investigated.

Delayed ventilation assessment using fast dynamic hyperpolarised Xenon-129 magnetic resonance imaging.

Objectives: To investigate the use of a fast dynamic hyperpolarised Xe ventilation magnetic resonance imaging (DXeV-MRI) method for detecting and quantifying delayed ventilation in patients with chronic obstructive pulmonary disease (COPD).

Methods: Three male participants (age range 31-43) with healthy lungs and 15 patients (M/F = 12:3, age range = 48-73) with COPD (stages II-IV) underwent spirometry tests, quantitative chest computed tomography (QCT), and DXeV-MRI at 1.5-Tesla.

Multiparametric measurement of cerebral physiology using calibrated fMRI.

The ultimate goal of calibrated fMRI is the quantitative imaging of oxygen metabolism (CMRO), and this has been the focus of numerous methods and approaches. However, one underappreciated aspect of this quest is that in the drive to measure CMRO, many other physiological parameters of interest are often acquired along the way. This can significantly increase the value of the dataset, providing greater information that is clinically relevant, or detail that can disambiguate the cause of signal variations.

Fast dynamic ventilation MRI of hyperpolarized Xe using spiral imaging.

Purpose: To develop and optimize a rapid dynamic hyperpolarized Xe ventilation (DXeV) MRI protocol and investigate the feasibility of capturing pulmonary signal-time curves in human lungs.

Theory And Methods: Spiral k-space trajectories were designed with the number of interleaves N  = 1, 2, 4, and 8 corresponding to voxel sizes of 8 mm, 5 mm, 4 mm, and 2.5 mm, respectively, for field of view = 15 cm.

Rapid cerebrovascular reactivity mapping: Enabling vascular reactivity information to be routinely acquired.

Cerebrovascular reactivity mapping (CVR), using magnetic resonance imaging (MRI) and carbon dioxide as a stimulus, provides useful information on how cerebral blood vessels react under stress. This information has proven to be useful in the study of vascular disorders, dementia and healthy ageing. However, clinical adoption of this form of CVR mapping has been hindered by relatively long scan durations of 7-12 min.