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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. This systematic review investigates 59 studies examining how CVR (measured by magnetic resonance imaging) is affected by modifiable, non-modifiable, and clinical risk factors for dementia. We report that non-modifiable risk (older age and apolipoprotein ε4), some modifiable factors (diabetes, traumatic brain injury, hypertension) and some clinical factors (stroke, carotid artery occlusion, stenosis) were consistently associated with reduced CVR. We also note a lack of conclusive evidence on how other behavioural factors such as physical inactivity, obesity, or depression, affect CVR. This review explores the biological mechanisms underpinning these brain-behaviour associations, highlights evident gaps in the literature, and identifies the risk factors that could be managed to preserve CVR in an effort to prevent dementia.

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.To develop and validate an automated method for pancreas segmentation into head, body, and tail subregions in abdominal MRI.Retrospective.One hundred and fifty nominally healthy subjects from UK Biobank (100 subjects for method development and 50 subjects for validation). A separate 390 UK Biobank triples of subjects including type 2 diabetes mellitus (T2DM) subjects and matched nondiabetics.A 1.5 T, three-dimensional two-point Dixon sequence (for segmentation and volume assessment) and a two-dimensional axial multiecho gradient-recalled echo sequence.Pancreas segments were annotated by four raters on the validation cohort. Intrarater agreement and interrater agreement were reported using Dice overlap (Dice similarity coefficient [DSC]). A segmentation method based on template registration was developed and evaluated against annotations. Results on regional pancreatic fat assessment are also presented, by intersecting the three-dimensional parts segmentation with one available proton density fat fraction (PDFF) image.Wilcoxon signed rank test and Mann-Whitney U-test for comparisons. DSC and volume differences for evaluation. A P value lt; 0.05 was considered statistically significant.Good intrarater (DSC mean, head: 0.982, body: 0.940, tail: 0.961) agreement and interrater (DSC mean, head: 0.968, body: 0.905, tail: 0.943) agreement were observed. No differences (DSC, head: P = 0.4358, body: P = 0.0992, tail: P = 0.1080) were observed between the manual annotations and our method's segmentations (DSC mean, head: 0.965, body: 0.893, tail: 0.934). Pancreatic body PDFF was different between T2DM and nondiabetics matched by body mass index.The developed segmentation's performance was no different from manual annotations. Application on type 2 diabetes subjects showed potential for assessing pancreatic disease heterogeneity.4 TECHNICAL EFFICACY STAGE: 3.

The change in longitudinal relaxation rate (R1 ) 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 (pO2 ) and R1 is linear and reproducible, and the slope represents the relaxivity of oxygen (r1Ox ) in that material. However, there is considerable variability in the values of r1Ox reported, and they have been shown to vary by field strength and temperature. Therefore, we have compiled 28 reported empirical values of the relaxivity of oxygen as a resource for researchers. Furthermore, we provide an empirical model for estimating the relaxivity of oxygen in water, saline, plasma, and vitreous fluids, accounting for magnetic field strength and temperature. The model agrees well (R2 = 0.93) with the data gathered from the literature for fields ranging from 0.011 to 8.45 T and temperatures of 21-40 °C. This provides a useful resource for researchers seeking to quantify pO2 in simple fluids in their studies, such as water and saline phantoms, or bodily fluids such as vitreous fluids, cerebrospinal fluids, and amniotic fluids.

Aims The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a prognostic marker of treatment response would enable early individualisation of treatment. We aimed to quantify the changes in mean apparent diffusion coefficient (ΔADC_mean) between a DW-MRI at diagnosis and on fraction 8–10 of chemoradiotherapy (CRT) as a biomarker for cellularity, and correlate these with anal squamous cell carcinoma recurrence. Materials and methods This prospective study recruited patients with localised anal cancer between October 2014 and November 2017. DW-MRI was carried out at diagnosis and after fraction 8–10 of radical CRT. A region of interest was delineated for all primary tumours and any lymph nodes >2 cm on high-resolution T 2-weighted images and propagated to the ADC map. Routine clinical follow-up was collected from Nation Health Service electronic systems. Results Twenty-three of 29 recruited patients underwent paired DW-MRI scans. Twenty-six regions of interest were delineated among the 23 evaluable patients. The median (range) tumour volume was 13.6 cm^3 (2.8–84.9 cm^3). Ten of 23 patients had lesions with ΔADC_mean ≤ 20%. With a median follow-up of 41.2 months, four patients either failed to have a complete response to CRT or subsequently relapsed. Three of four patients with disease relapse had lesions demonstrating ΔADC_mean Conclusions We demonstrated a potential correlation between patients with ΔADC_mean

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. Purpose:To propose and assess a general model to estimate the R1 of blood, accounting for hematocrit, SO2, PO2, and B0 under both normal physiological and hyperoxic conditions. Study Type:Mathematical modeling. Population:One hundred and twenty-six published values of R1 from phantoms and animal models. Field Strength/Sequence:5–8.45 T. Assessment:We propose a two-compartment nonlinear model to calculate R1 as a function of hematocrit, PO2, and B0. The Akaike Information Criterion (AIC) was used to select the best-performing model with the fewest parameters. A previous model of R1 as a function of hematocrit, SO2, and B0 has been proposed by Hales et al, and our work builds upon this work to make the model applicable under hyperoxic conditions (SO2> 0.99). Models were assessed using the AIC, mean squared error (MSE), coefficient of determination (R2), and Bland–Altman analysis. The effect of volume fraction constants WRBC and Wplasmawas assessed by the SD of resulting R1. The range of the model was determined by the maximum and minimum B0, hematocrit, SO2, and PO2of the literature data points. Statistical Tests:Bland–Altman, AIC, MSE, coefficient of determination (R2), SD. Results:The model estimates agreed well with the literature values of R1 of blood (R2=0.93, MSE=0.0013 s−2), and its performance was consistent across the range of parameters: B0=1.5–8.45 T, SO2=0.40–1, PO2=30–700 mmHg. Data Conclusion:Using the results from this model, we have quantified and explained the contradictory decrease in R1 reported in oxygen-enhanced MRI and oxygen-delivery experiments. Level of Evidence:3 Technical Efficacy:Stage 1

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. Users can integrate their own light source, but we provide full native software support for a high-end, commercial research-grade 10-primary light engine that offers advanced control over the temporal and spectral properties of light stimuli as well as spectral calibration utilities. Here, we describe the hardware and software in detail and demonstrate its capabilities with two example applications: 1) pupillometer-style measurement and parametrisation of the PLR to flashes of white light, and 2) comparing the post-illumination pupil response (PIPR) to flashes of long and short-wavelength light. The system holds promise for researchers who would favour a flexible approach to studying the PLR and the ability to employ a wide range of temporally and spectrally varying stimuli, including simple narrowband stimuli.

Multiparametric MRI of the pancreas can potentially benefit from the fusion of multiple acquisitions. However, its small, irregular structure often results in poor organ alignment between acquisitions, potentially leading to inaccurate quantification. Recent studies using UK Biobank data have proposed using pancreas segmentation from a 3D volumetric scan to extract a region of interest in 2D quantitative maps. A limitation of these studies is that potential misalignment between the volumetric and single-slice scans has not been considered. In this paper, we report a slice-to-volume registration (SVR) method with multimodal similarity that aligns the UK Biobank pancreatic 3D acquisitions with the 2D acquisitions, leading to more accurate downstream quantification of an individual’s pancreas T1. We validate the SVR method on a challenging UK Biobank subset of N = 50, using both direct and indirect performance metrics.

The UK Biobank imaging sub-study enables large-scale measurement of pancreas volume, an important biomarker in metabolic disease, including diabetes. Previous methods utilised a pancreas-specific (PS) 3D MRI UK Biobank acquisition to automatically measure pancreas volume. This may lead to a clinically significant underestimation of volume, due to partial coverage of the pancreas in these acquisitions. To address this, we propose a pipeline for the accurate measurement of pancreas volume using stitched whole-body (WB) 3D MRI UK Biobank acquisitions and deep learning-based segmentation. We implement and compare the performance of six different U-Net-like model architectures, leveraging attention layers, recurrent layers, and residual blocks. Furthermore, we investigate pancreas volumetry in 42,313 subjects, separated by sex, and present novel results concerning the change in pancreas volume throughout the course of a day (diurnal variation). To the best of our knowledge, this is the largest pancreas volumetry study to date and the first to propose a pipeline using the whole-body UK Biobank MRI acquisitions to measure pancreas volume.

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. Primary imaging endpoint was change in tumor hypoxic volume (HV) measured by hypoxia PET-CT. Intercohort comparison of hypoxia gene expression signatures using RNA sequencing from resected tumors was performed. Results: Thirty patients were evaluable for hypoxia PET-CT analysis, 15 per cohort. Median treatment duration was 12 days. Eleven (73.3%) atovaquone-treated patients had meaningful HV reduction, with median change −28% [95% confidence interval (CI), −58.2 to −4.4]. In contrast, median change in untreated patients was +15.5% (95% CI, −6.5 to 35.5). Linear regression estimated the expected mean HV was 55% (95% CI, 24%–74%) lower in cohort 1 compared with cohort 2 (P = 0.004), adjusting for cohort, tumor volume, and baseline HV. A key pharmacodynamics endpoint was reduction in hypoxia-regulated genes, which were significantly downregulated in atovaquone-treated tumors. Data from multiple additional measures of tumor hypoxia and perfusion are presented. No atovaquone-related adverse events were reported. Conclusions: This is the first clinical evidence that targeting tumor mitochondrial metabolism can reduce hypoxia and produce relevant antitumor effects at the mRNA level. Repurposing atovaquone for this purpose may improve treatment outcomes for NSCLC.

Objectives To investigate the use of a fast dynamic hyperpolarised 129Xe 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. Regional delayed ventilation was captured by measuring the temporal signal change in each lung region of interest (ROI) in comparison to that in the trachea. In addition to its qualitative assessment through visual inspection by a clinical radiologist, delayed ventilation was quantitatively captured by calculating a covariance measurement of the lung ROI and trachea signals, and quantified using both the time delay, and the difference between the integrated areas covered by the signal-time curves of the two signals. Results Regional temporal ventilation, consistent with the expected physiological changes across a free breathing cycle, was demonstrated with DXeV-MRI in all patients. Delayed ventilation was observed in 13 of the 15 COPD patients and involved variable lung ROIs. This was in contrast to the control group, where no delayed ventilation was demonstrated (p = 0.0173). Conclusions DXeV-MRI offers a non-invasive way of detecting and quantifying delayed ventilation in patients with COPD, and provides physiological information on regional pulmonary function during a full breathing cycle. Key Points • Dynamic xenon MRI allows for the non-invasive detection and measurement of delayed ventilation in COPD patients. • Dynamic xenon MRI during a free breathing cycle can provide unique information about pulmonary physiology and pulmonary disease pathophysiology. • With further validation, dynamic xenon MRI could offer a non-invasive way of measuring collateral ventilation which can then be used to guide lung volume reduction therapy (LVRT) for certain COPD patients. Electronic supplementary material The online version of this article (10.1007/s00330-019-06415-1) contains supplementary material, which is available to authorized users.

Clinical pain is difficult to study using standard Blood Oxygenation Level Dependent (BOLD) magnetic resonance imaging because it is often ongoing and, if evoked, it is associated with stimulus-correlated motion. Arterial spin labelling (ASL) offers an attractive alternative. This study used arm repositioning to evoke clinically-relevant musculoskeletal pain in patients with shoulder impingement syndrome. Fifty-five patients were scanned using a multi post-labelling delay pseudo-continuous ASL (pCASL) sequence, first with both arms along the body and then with the affected arm raised into a painful position. Twenty healthy volunteers were scanned as a control group. Arm repositioning resulted in increased perfusion in brain regions involved in sensory processing and movement integration, such as the contralateral primary motor and primary somatosensory cortex, mid- and posterior cingulate cortex, and, bilaterally, in the insular cortex/operculum, putamen, thalamus, midbrain and cerebellum. Perfusion in the thalamus, midbrain and cerebellum was larger in the patient group. Results of a post hoc analysis suggested that the observed perfusion changes were related to pain rather than arm repositioning. This study showed that ASL can be useful in research on clinical ongoing musculoskeletal pain but the technique is not sensitive enough to detect small differences in perfusion.

The ultimate goal of calibrated fMRI is the quantitative imaging of oxygen metabolism (CMRO2), 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 CMRO2, 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. This can also be somewhat of a double-edged sword: calibrated fMRI experiments combine multiple parameters into a physiological model that requires multiple steps, thereby providing more opportunity for error propagation and increasing the noise and error of the final derived values. As with all measurements, there is a trade-off between imaging time, spatial resolution, coverage, and accuracy. In this review, we provide a brief overview of the benefits and pitfalls of extracting multiparametric measurements of cerebral physiology through calibrated fMRI experiments.

PurposeIntravoxel incoherent motion (IVIM) has been proposed as a means of non-invasive MRI measurement of perfusion parameters such as blood flow and blood volume. Its main competitor in the brain is arterial spin labelling (ASL). In theory, IVIM should not suffer from some of the same limitations as ASL such as poor signal in white matter, and assumptions about arterial arrival times that may be violated in the presence of pathology.MethodsIn this study we aimed to test IVIM as a viable alternative to ASL for quantitative imaging of perfusion parameters in the brain. First, a direct comparison was performed between IVIM and multi-post label delay pseudo-continuous ASL; second, IVIM images were acquired with and without nulling cerebrospinal fluid; and finally, ultra-high resolution IVIM was performed to minimise partial voluming.ResultsIn all three tests, IVIM failed to disprove the null hypothesis, strongly suggesting that, at least within the brain, the technique does not measure perfusion parameters as proposed.ConclusionFurthermore, the results obtained suggest that the contrast visible in IVIM-derived images is primarily sensitive to cerebrospinal fluid, and not the microvascular blood compartment.

Background Anal Squamous Cell Carcinoma (ASCC) is radically treated by chemoradiotherapy (CRT). The use of DW-MRI as a predictive marker of outcome would enable early individualisation of treatment. We aimed to quantify the changes in mean apparent-diffusion-coefficient (ADCMean) between a DW-MRI at diagnosis and on fraction 8-10 of CRT as a biomarker for cellularity, and correlate these with outcome. Methods This prospective study recruited patients with ASCC between October 2014 and November 2017. DW-MRI was performed at diagnosis and after fraction 8-10 of radical CRT. A region of interest (ROI) was delineated for all primary tumours and any lymph nodes >2 cm on high-resolution T2 –weighted images and propagated to the ADC map. A pre-defined cut-off for percentage change in ADCMean (ΔADC) was set at Results Twenty-three of 29 recruited patients underwent paired DW-MRI scans. The median (range) tumour volume was 13.6 cm3 (2.8 cm3 to 84.9 cm3). The median ΔADCMean between scans was 20.7% (95% CI: 12.7%, 34.1%). Nine of 23 (43%) patients had a change of ADCMean Conclusions In a subset of patients, Clinical trial identification NCT02145416. Legal entity responsible for the study University of Oxford. Funding CRUK EPSRC Cancer Imaging Centre in Oxford, the CRUK Oxford Centre and the NIHR.M Hawkins is supported by Medical Research Council grant MC_UU_00001/2. Disclosure R. Muirhead: Honoraria (self), Fee for lecture: Boehringer Ingelheim. V. Goh: Research grant / Funding (self): Siemens. All other authors have declared no conflicts of interest.

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 to 12 minutes. By replacing the conventional block presentation of carbon dioxide enriched air with a sinusoidally modulated stimulus, the aim of this study was to investigate whether more clinically acceptable scan durations are possible. Firstly, the conventional block protocol was compared with a sinusoidal protocol of the same duration of 7 minutes. Estimates of the magnitude of the CVR signal (CVR magnitude) and the relative timing of the CVR response (CVR phase) were found to be in good agreement between the stimulus protocols. Secondly, data from the sinusoidal protocol was reanalysed using decreasing amounts of data in the range 1 to 6 minutes. The CVR magnitude was found to tolerate this reduction in scan duration better than CVR phase. However, these analyses indicate that scan durations in the range of 3 to 5 minutes produce robust data.

Vessel size imaging (VSI) is a magnetic resonance imaging (MRI) technique that aims to provide quantitative measurements of tissue microvasculature. An emerging variation of this technique uses the blood oxygenation level-dependent (BOLD) effect as the source of the imaging contrast. Gas challenges have the advantage over contrast injection techniques in that they are noninvasive and easily repeatable because of the fast washout of the contrast. However, initial results from BOLD-VSI studies are somewhat contradictory, with substantially different estimates of the mean vessel radius. Owing to BOLD-VSI being an emerging technique, there is not yet a standard processing methodology, and different techniques have been used to calculate the mean vessel radius and reject uncertain estimates. In addition, the acquisition methodology and signal modeling vary from group to group. Owing to these differences, it is difficult to determine the source of this variation. Here we use computer modeling to assess the impact of noise on the accuracy and precision of different BOLD-VSI calculations. Our results show both potential overestimates and underestimates of the mean vessel radius, which is confirmed with a validation study at 3T.

Investigations into the blood oxygenation level-dependent (BOLD) functional MRI signal have used respiratory challenges with the aim of probing cerebrovascular physiology. Such challenges have altered the inspired partial pressures of either carbon dioxide or oxygen, typically to a fixed and constant level (fixed inspired challenge (FIC)). The resulting end-tidal gas partial pressures then depend on the subject's metabolism and ventilatory responses. In contrast, dynamic end-tidal forcing (DEF) rapidly and independently sets end-tidal oxygen and carbon dioxide to desired levels by altering the inspired gas partial pressures on a breath-by-breath basis using computer-controlled feedback. This study implements DEF in the MRI environment to map BOLD signal reactivity to CO2. We performed BOLD (T2*) contrast FMRI in four healthy male volunteers, while using DEF to provide a cyclic normocapnichypercapnic challenge, with each cycle lasting 4 mins (PetCO2 mean±s.d., from 40.9 ± 1.8 to 46.4 ± 1.6 mm Hg). This was compared with a traditional fixed-inspired (FiCO2 = 5%) hypercapnic challenge (PetCO2 mean±s.d., from 38.2 ± 2.1 to 45.6 ± 1.4 mm Hg). Dynamic end-tidal forcing achieved the desired target PetCO2 for each subject while maintaining PetCO2 constant. As a result of CO2-induced increases in ventilation, the FIC showed a greater cyclic fluctuation in PetCO2. These were associated with spatially widespread fluctuations in BOLD signal that were eliminated largely by the control of PetCO2 during DEF. The DEF system can provide flexible, convenient, and physiologically well-controlled respiratory challenges in the MRI environment for mapping dynamic responses of the cerebrovasculature.

A system of new integral equations is presented. They are derived from Maxwell's equations and describe radio-frequency (RF) current densities on a two-dimensional flat plate. The equations are generalisations of Pocklington's integral equation showing phase-retardation in two dimensions. These singular equations are solved, numerically, for the case of one-dimensional geometry. The solutions are shown to display effects which correspond to damped resonance when the wavelength of the current matches aspects of the geometry of the conductor.

Combined blood oxygenation level-dependent (BOLD) and arterial spin labeling (ASL) functional MRI (fMRI) was performed for simultaneous investigation of neurovascular coupling in the primary visual cortex (PVC), primary motor cortex (PMC), and supplementary motor area (SMA). The hypercapnia-calibrated method was employed to estimate the fractional change in cerebral metabolic rate of oxygen consumption (CMR(O2)) using both a group-average and a per-subject calibration. The group-averaged calibration showed significantly different CMR(O2)-CBF coupling ratios in the three regions (PVC: 0.34 +/- 0.03; PMC: 0.24 +/- 0.03; and SMA: 0.40 +/- 0.02). Part of this difference emerges from the calculated values of the hypercapnic calibration constant M in each region (M(PVC) = 6.6 +/- 3.4, M(PMC) = 4.3 +/- 3.5, and M(SMA) = 7.2 +/- 4.1), while a relatively minor part comes from the spread and shape of the sensorimotor BOLD-CBF responses. The averages of the per-subject calibrated CMR(O2)-CBF slopes were 0.40 +/- 0.04 (PVC), 0.31 +/- 0.03 (PMC), and 0.44 +/- 0.03 (SMA). These results are 10-30% higher than group-calibrated values, and are potentially more useful for quantifying individual differences in focal functional responses. The group-average calibrated motor coupling value is increased to 0.28 +/- 0.03 when stimulus-correlated increases in end-tidal CO(2) are included. Our results support the existence of regional differences in neurovascular coupling, and argue for the importance of achieving optimal accuracy in hypercapnia calibrations to resolve method-dependent variations in published results.

We offer a new method for characterizing the magnitude and dynamics of the vascular response to changes in arterial gas tensions using non-invasive blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) and paradigms appropriate for clinical settings. A novel respiratory task, "Cued Deep Breathing" (CDB), consisting of two consecutive cycles of cued breaths, has been developed to cause transient hypocapnia, and consequently a strong, short-lived BOLD signal decrease. Data from CDB hypocapnia paradigms and traditional breath-holding hypercapnia paradigms were analyzed on a voxel-wise basis to map regional heterogeneity in magnitude and timing parameters. The tasks caused comparable absolute BOLD percent signal changes (approximately 0.5-3.0% in gray matter) and both datasets suggested consistent regional heterogeneity in the response timing: parts of the basal ganglia, particularly the putamen, and bilateral areas of medial cortex reached their maximum signal change several seconds earlier than remaining cortical gray matter voxels. This phenomenon and a slightly delayed response in posterior cortical regions were present in group-maps of ten healthy subjects. An auxiliary experiment in different subjects measured end-tidal CO2 changes associated with the new CDB task and quantitatively compared the resulting reactivity maps with those acquired using a traditional hypercapnia challenge of 4% CO2 gas inspiration. The CDB task caused average end-tidal CO2 decreases between 6.0+/-1.1 and 10.5+/-2.6 mm Hg, with levels returning to baseline after approximately three breaths, giving evidence that the task indeed causes transient mild hypocapnia. Similarity between resulting reactivity maps suggest CDB offers an alternative method for mapping cerebrovascular reactivity.

This article will consider how physiological monitoring can be used both as an intrinsic part of an experiment, or for removing unwanted physiological signals from the FMRI time series. As functional MRI is used for a wide variety of applications beyond the identification of regions involved in a task, different sources of noise in the time series become important. The use of arterial spin labelling sequences, either in isolation or combined with BOLD imaging, means that temporal noise must be dealt with differently. Moreover, when these are combined with global cerebrovascular stimuli, such as respiratory challenges, the standard analysis tools must be employed with great care so as not to detrimentally distort the data. Acquiring and analysing physiological data is sometimes more art than science, and this article attempts to provide some insight into common techniques as well as advice on identifying and correcting some of the problems that may be encountered.

Cerebrovascular reactivity to vasodilatory hypercapnic and vasoconstrictive hypocapnic challenges is known to be altered in several hemodynamic disorders, which is often attributable to changes in smooth muscle-mediated vascular compliance. Recently, attenuated reactivity to hypercapnia but enhanced reactivity to hypocapnia was observed in patients with chronic stroke. We hypothesize that the latter observation could be explained by a change in the basal vascular tone. In particular, reduced cerebral perfusion pressure, as is prevalent in these patients, may cause vasodilation through autoregulatory mechanisms, and this compensatory baseline condition may alter reactivity to vasoconstrictive hypocapnic challenges. To test this hypothesis, a predilated vascular condition was created in young, healthy subjects ( n = 11; age = 23 to 36 years) using inhalation of 4% CO2. Using blood oxygenation level-dependent functional magnetic resonance imaging at 3 T, breath holding and cued deep breathing respiratory challenges were administered to assess hypercapnia and hypocapnia reactivity, respectively. During the predilated condition, vasoconstrictive reactivity to hypocapnia was significantly (21.1%, P = 0.016) enhanced throughout the gray matter, whereas there was no significant change (6.4%, P = 0.459) in hypercapnic vasodilatory reactivity. This suggests that baseline vasodilation may explain the enhanced hypocapnia reactivity observed in some stroke patients, and that hypocapnia challenges may help identify the level of vascular compliance in patients with reduced cerebral perfusion pressure.

MRI may be used to measure fractional changes in cerebral oxygen metabolism via a metabolic model. One step commonly used in this measurement is calibration with image data acquired during hypercapnia, which is a state of increased CO2 content of the blood. In this study some commonly used hypercapnia-inducing stimuli were compared to assess their suitability for the calibration step. The following stimuli were investigated: (a) inspiration of a mixture of 4% CO2, 21% O2 and balance N2; (b) 30-s breath holding; and (c) inspiration of a mixture of 4% CO2 and 96% O2 (i.e., carbogen). Measurements of BOLD and cerebral blood flow made on nine subjects during the different hypercapnia-inducing stimuli showed that each stimulus leads to a different calibration of the model. We argue that of the aforementioned stimuli, inspiration of 4% CO2, 21% O2 and balance N2 should be preferred for the calibration as the other stimuli produce responses that violate assumptions of the metabolic model.

Oxygen plays a fundamental role in functional magnetic resonance imaging (FMRI). Blood oxygenation level-dependent (BOLD) imaging is the foundation stone of all FMRI and is still the essential workhorse of the vast majority of FMRI procedures. Hemoglobin may provide the magnetic properties that allow the technique to work, but it is oxygen that allows the contrast to effectively be switched on or off, and it is oxygen that we are interested in tracking in order to observe the oxygen metabolism changes. In general the changes in venous oxygen saturation are observed in order to infer changes in the correlated mechanisms, which can include changes in cerebral blood flow, metabolism, and the fraction of inspired oxygen. By independently manipulating the fraction of inspired oxygen it is possible to alter the amount of dissolved oxygen in the plasma, the venous saturation, or even the blood flow. The effects that these changes have on the observed MRI signal can be either a help or a hindrance depending on how well the changes induced are understood. The administration of supplemental inspired oxygen is in a unique position to provide a flexible, noninvasive, inexpensive, patient-friendly addition to the MRI toolkit to enable investigations to look beyond statistics and regions of interest, and actually produce calibrated, targeted measurements of blood flow, metabolism or pathology.

Recent work has suggested that diffusion-weighted functional magnetic resonance imaging (FMRI) with strong diffusion weighting (high b value) detects neuronal swelling that is directly related to neuronal firing. This would constitute a much more direct measure of brain activity than current methods and represent a major advance in neuroimaging. However, it has not been firmly established that the observed signal changes do not reflect residual vascular effects, which are known to exist at low b value. This study measures the vascular component of diffusion FMRI directly by using hypercapnia, which induces blood flow changes in the absence of a change in neuronal firing. Hypercapnia elicits a similar diffusion FMRI response to a visual stimulus including a rise in percent signal change with increasing b value, which was reported for visual activation. Analysis of the response timing found no evidence for an early response at high b value, which has been reported as evidence for a nonhemodynamic response. These results suggest that a large component of the diffusion FMRI signal at high b value is vascular rather than neuronal.

Purpose To develop a new method of measuring quantitative regional cerebral blood volume (CBV) using epochs of hyperoxia as an intravenous contrast agent with T2*-weighted MRI. Materials and Methods Images were acquired from six subjects (four male, two female, mean age 29 ± 3.7 years) using a sequence combining pulsed arterial spin labeling interleaved with a gradient echo echo-planar imaging (EPI) blood oxygenation level-dependent (BOLD) sequence at 3T. The hyperoxia paradigm lasted 28 minutes consisting of 4 minutes of normoxia, two 6-minute blocks of hyperoxia separated by 6 minutes of normoxia. During the hyperoxic blocks the subjects were delivered a fractional oxygen concentration of 0.5. Results The mean CBV was calculated to be 3.77 ± 1.05 mL/100 g globally, 3.93 ± 0.90 mL/100 g in gray matter (GM), and 2.52 ± 0.78 mL/100 g in white matter (WM). The mean GM/WM ratio was thus found to be 1.56. These values are comparable to those obtained in other studies. Conclusion The hyperoxia technique for measuring CBV may be particularly useful for patient groups where an injected bolus of contrast agent is contraindicated. As more functional studies are employing epochs of inspired gases for calibration purposes, this method is easily incorporated into existing paradigms to produce a noninvasive, repeatable, easily tolerated, and quantitative measurement of regional CBV. J. Magn. Reson. Imaging 2007;26:894–899. © 2007 Wiley-Liss, Inc.

This paper describes a new method of measuring some magnetic properties of steel under applied biaxial stresses in the x-y plane when the steel is magnetized in the z direction (called "z magnetization"). Results are compared with two other sets of experimental data. The conclusions are that z magnetization is prone to several sources of error of significant amounts, whichever technique is used, and that these errors must be reduced if the small changes in magnetic properties predicted by the theory are to be reliably verified.

A hypothesis is presented to explain the mechanism by which externally applied stresses can affect the magnetic properties of ferromagnetic materials. Experiments have revealed coincident points in the second and fourth quadrants on stressed hysteresis loops of mild steel. The results are presented along with an explanation of this effect. An atomic level theory of the origins of the magnetomechanical effect is introduced whereby spin-spin and spin-orbit coupling interact with magnetic moments to alter the magnetocrystalline anisotropy and exchange energies. © 2002 Elsevier Science B.V. All rights reserved.

Purpose The calculation of the calibration parameter M, which represents the maximum theoretically possible blood oxygen level dependent (BOLD) signal increase, is an essential intermediate step in any calibrated fMRI experiment. To better compare M values obtained across different studies, it is common to scale M values from their original BOLD echo time (TE) to a different echo time according to the theory that M is directly proportional to TE. To the best of our knowledge, this relationship has never been directly tested. Theory and Methods A pseudocontinuous arterial spin labeling sequence with five readouts (TE ranging from 20 to 78 ms) was implemented to test the relationship between M and TE, both with and without the application of flow crushing gradients. Results Both M and the BOLD signal were found to be linear functions of TE, but with a nonzero intercept. This intercept was reduced when crusher gradients were added, suggesting that the deviation from theory is a result of nonnegligible intravascular signal. Conclusion The linear scaling method introduces some error when comparing M values acquired with different BOLD echo times. However, this error is small compared with other considerations, and would generally not preclude the continued use of this scaling method. Magn Reson Med 75:556–561, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Functional magnetic resonance imaging measures signal increases arising from a variety of interrelated effects and physiological sources. Recently there has been some success in disentangling this signal in order to quantify baseline physiological parameters, including the resting oxygen extraction fraction (OEF), cerebral blood volume (CBV) and mean vessel size. However, due to the complicated nature of the signal, each of these methods relies on certain physiological assumptions to derive a solution. In this work we present a framework for the simultaneous, voxelwise measurement of these three parameters. The proposed method removes the assumption of a fixed vessel size from the quantification of OEF and CBV, while simultaneously removing the need for an assumed OEF in the calculation of vessel size. The new framework is explored through simulations and validated with a pilot study in healthy volunteers. The MRI protocol uses a combined hyperoxia and hypercapnia paradigm with a modified spin labelling sequence collecting multi-slice gradient echo and spin echo data.

Measurement of cerebrovascular reactivity (CVR) can give valuable information about existing pathology and the risk of adverse events, such as stroke. A common method of obtaining regional CVR values is by measuring the blood flow response to carbon dioxide (CO2)-enriched air using arterial spin labeling (ASL) or blood oxygen level-dependent (BOLD) imaging. Recently, several studies have used carbogen gas (containing only CO2 and oxygen) as an alternative stimulus. A direct comparison was performed between CVR values acquired by ASL and BOLD imaging using stimuli of (1) 5% CO2 in air and (2) 5% CO2 in oxygen (carbogen-5). Although BOLD and ASL CVR values are shown to be correlated for CO2 in air (mean response 0.11 ± 0.03% BOLD, 4.46 ± 1.80% ASL, n = 16 hemispheres), this correlation disappears during a carbogen stimulus (0.36 ± 0.06% BOLD, 4.97 ± 1.30% ASL). It is concluded that BOLD imaging should generally not be used in conjunction with a carbogen stimulus when measuring CVR, and that care must be taken when interpreting CVR as measured by ASL, as values obtained from different stimuli (CO2 in air versus carbogen) are not directly comparable.

Functional magnetic resonance imaging typically measures signal increases arising from changes in the transverse relaxation rate over small regions of the brain and associates these with local changes in cerebral blood flow, blood volume and oxygen metabolism. Recent developments in pulse sequences and image analysis methods have improved the specificity of the measurements by focussing on changes in blood flow or changes in blood volume alone. However, FMRI is still unable to match the physiological information obtainable from positron emission tomography (PET), which is capable of quantitative measurements of blood flow and volume, and can indirectly measure resting metabolism. The disadvantages of PET are its cost, its availability, its poor spatial resolution and its use of ionising radiation. The MRI techniques introduced here address some of these limitations and provide physiological data comparable with PET measurements. We present an 18-minute MRI protocol that produces multi-slice whole-brain coverage and yields quantitative images of resting cerebral blood flow, cerebral blood volume, oxygen extraction fraction, CMRO(2), arterial arrival time and cerebrovascular reactivity of the human brain in the absence of any specific functional task. The technique uses a combined hyperoxia and hypercapnia paradigm with a modified arterial spin labelling sequence.