A novel method of combining blood oxygenation and blood flow sensitive magnetic resonance imaging techniques to measure the cerebral blood flow and oxygen metabolism responses to an unknown neural stimulus.

Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged

Turbo-FLASH based arterial spin labeled perfusion MRI at 7 T.

Motivations of arterial spin labeling (ASL) at ultrahigh magnetic fields include prolonged blood T1 and greater signal-to-noise ratio (SNR). However, increased B0 and B1 inhomogeneities and increased specific absorption ratio (SAR) challenge practical ASL implementations. In this study, Turbo-FLASH (Fast Low Angle Shot) based pulsed and pseudo-continuous ASL sequences were performed at 7T, by taking advantage of the relatively low SAR and short TE of Turbo-FLASH that minimizes susceptibility artifacts. Consistent with theoretical predictions, the experimental data showed that Turbo-FLASH based ASL yielded approximately 4 times SNR gain at 7T compared to 3T. High quality perfusion images were obtained with an in-plane spatial resolution of 0.85×1.7 mm(2). A further functional MRI study of motor cortex activation precisely located the primary motor cortex to the precentral gyrus, with the same high spatial resolution. Finally, functional connectivity between left and right motor cortices as well as supplemental motor area were demonstrated using resting state perfusion images. Turbo-FLASH based ASL is a promising approach for perfusion imaging at 7T, which could provide novel approaches to high spatiotemporal resolution fMRI and to investigate the functional connectivity of brain networks at ultrahigh field

B 0 field inhomogeneity considerations in pseudo‐continuous arterial spin labeling (pCASL): effects on tagging efficiency and correction strategy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89456/1/nbm1675.pd

Changes in arterial cerebral blood volume during lower body negative pressure measured with MRI

Cerebral Autoregulation (CA), defined as the ability of the cerebral vasculature to maintain stable levels of blood flow despite changes in systemic blood pressure, is a critical factor in neurophysiological health. Magnetic resonance imaging (MRI) is a powerful technique for investigating cerebrovascular function, offering high spatial resolution and wide fields of view (FOV), yet it is relatively underutilized as a tool for assessment of CA. The aim of this study was to demonstrate the potential of using MRI to measure changes in cerebrovascular resistance in response to lower body negative pressure (LBNP). A Pulsed Arterial Spin Labeling (PASL) approach with short inversion times (TI) was used to estimate cerebral arterial blood volume (CBVa) in eight healthy subjects at baseline and -40mmHg LBNP. We estimated group mean CBVa values of 3.13±1.00 and 2.70±0.38 for baseline and lbnp respectively, which were the result of a differential change in CBVa during -40 mmHg LBNP that was dependent on baseline CBVa. These data suggest that the PASL CBVa estimates are sensitive to the complex cerebrovascular response that occurs during the moderate orthostatic challenge delivered by LBNP, which we speculatively propose may involve differential changes in vascular tone within different segments of the arterial vasculature. These novel data provide invaluable insight into the mechanisms that regulate perfusion of the brain, and establishes the use of MRI as a tool for studying CA in more detail

The effects of hemodynamic lag on functional connectivity and behavior after stroke

Stroke disrupts the brain's vascular supply, not only within but also outside areas of infarction. We investigated temporal delays (lag) in resting state functional magnetic resonance imaging signals in 130 stroke patients scanned two weeks, three months and 12 months post stroke onset. Thirty controls were scanned twice at an interval of three months. Hemodynamic lag was determined using cross-correlation with the global gray matter signal. Behavioral performance in multiple domains was assessed in all patients. Regional cerebral blood flow and carotid patency were assessed in subsets of the cohort using arterial spin labeling and carotid Doppler ultrasonography. Significant hemodynamic lag was observed in 30% of stroke patients sub-acutely. Approximately 10% of patients showed lag at one-year post-stroke. Hemodynamic lag corresponded to gross aberrancy in functional connectivity measures, performance deficits in multiple domains and local and global perfusion deficits. Correcting for lag partially normalized abnormalities in measured functional connectivity. Yet post-stroke FC-behavior relationships in the motor and attention systems persisted even after hemodynamic delays were corrected. Resting state fMRI can reliably identify areas of hemodynamic delay following stroke. Our data reveal that hemodynamic delay is common sub-acutely, alters functional connectivity, and may be of clinical importance

Supporting measurements or more averages? How to quantify cerebral blood flow most reliably in 5 minutes by arterial spin labeling

Purpose To determine whether sacrificing part of the scan time of pseudo-continuous arterial spin labeling (PCASL) for measurement of the labeling efficiency and blood T1 is beneficial in terms of CBF quantification reliability. Methods In a simulation framework, 5-minute scan protocols with different scan time divisions between PCASL data acquisition and supporting measurements were evaluated in terms of CBF estimation variability across both noise and ground truth parameter realizations taken from the general population distribution. The entire simulation experiment was repeated for a single-post-labeling delay (PLD), multi-PLD, and free-lunch time-encoded (te-FL) PCASL acquisition strategy. Furthermore, a real data study was designed for preliminary validation. Results For the considered population statistics, measuring the labeling efficiency and the blood T1 proved beneficial in terms of CBF estimation variability for any distribution of the 5-minute scan time compared to only acquiring ASL data. Compared to single-PLD PCASL without support measurements as recommended in the consensus statement, a 26%, 33%, and 42% reduction in relative CBF estimation variability was found for optimal combinations of supporting measurements with single-PLD, free-lunch, and multi-PLD PCASL data acquisition, respectively. The benefit of taking the individual variation of blood T1 into account was also demonstrated in the real data experiment. Conclusions Spending time to measure the labeling efficiency and the blood T1 instead of acquiring more averages of the PCASL data proves to be advisable for robust CBF quantification in the general population

Opioids depress cortical centers responsible for the volitional control of respiration

Respiratory depression limits provision of safe opioid analgesia and is the main cause of death in drug addicts. Although opioids are known to inhibit brainstem respiratory activity, their effects on cortical areas that mediate respiration are less well understood. Here, functional magnetic resonance imaging was used to examine how brainstem and cortical activity related to a short breath hold is modulated by the opioid remifentanil. We hypothesized that remifentanil would differentially depress brain areas that mediate sensory-affective components of respiration over those that mediate volitional motor control. Quantitative measures of cerebral blood flow were used to control for hypercapnia-induced changes in blood oxygen level-dependent (BOLD) signal. Awareness of respiration, reflected by an urge-to-breathe score, was profoundly reduced with remifentanil. Urge to breathe was associated with activity in the bilateral insula, frontal operculum, and secondary somatosensory cortex. Localized remifentanil-induced decreases in breath hold-related activity were observed in the left anterior insula and operculum. We also observed remifentanil-induced decreases in the BOLD response to breath holding in the left dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, and periaqueductal gray, brain areas that mediate task performance. Activity in areas mediating motor control (putamen, motor cortex) and sensory-motor integration (supramarginal gyrus) were unaffected by remifentanil. Breath hold-related activity was observed in the medulla. These findings highlight the importance of higher cortical centers in providing contextual awareness of respiration that leads to appropriate modulation of respiratory control. Opioids have profound effects on the cortical centers that control breathing, which potentiates their actions in the brainstem

Practical considerations for territorial perfusion mapping in the cerebral circulation using super-selective pseudo-continuous arterial spin labeling

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151967/1/mrm27936.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151967/2/mrm27936_am.pd

Multidelay ASL of the pediatric brain

Arterial spin labeling (ASL) is a powerful noncontrast MRI technique for evaluation of cerebral blood flow (CBF). A key parameter in single-delay ASL is the choice of postlabel delay (PLD), which refers to the timing between the labeling of arterial free water and measurement of flow into the brain. Multidelay ASL (MDASL) utilizes several PLDs to improve the accuracy of CBF calculations using arterial transit time (ATT) correction. This approach is particularly helpful in situations where ATT is unknown, including young subjects and slow-flow conditions. In this article, we discuss the technical considerations for MDASL, including labeling techniques, quantitative metrics, and technical artefacts. We then provide a practical summary of key clinical applications with real-life imaging examples in the pediatric brain, including stroke, vasculopathy, hypoxic-ischemic injury, epilepsy, migraine, tumor, infection, and metabolic disease