Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative BOLD MRI with Intraoperative and Histologic Validation.

Purpose To validate ferumoxytol-based quantitative blood oxygenation level-dependent (BOLD) MRI for mapping oxygenation of human infiltrative astrocytomas by using intraoperative measurement of tissue oxygen tension and histologic staining. Materials and Methods Fifteen patients with infiltrative astrocytomas were recruited into this prospective multicenter study between July 2014 and December 2016. Prior to treatment, participants underwent preoperative quantitative BOLD MRI with ferumoxytol to generate tissue oxygen saturation (StO2) maps. Two intratumoral sites were identified, one with low StO2 and one with high StO2. Neuronavigation was used to locate sites intraoperatively for insertion of oxygen-sensing probes to measure local tissue oxygen tension (PtO2). Biopsies from both sites were taken and stained for markers of hypoxia (hypoxia-inducible factor 1α, carbonic anhydrase IX) and neoangiogenesis (vascular endothelial growth factor, endoglin [CD105]). Spearman correlation and nonparametric sign-rank tests were used to analyze data. Results Ten patients with median age of 58.5 years (interquartile range, 25 years; four men and six women) completed the study. Because there is no linear relationship between StO2 and PtO2, the ratios of low to high StO2 versus low to high PtO2 in each patient were compared and a significant correlation was found (r = 0.73; P = .01). Pathologic analyses revealed differences between carbonic anhydrase IX (P = .03) for sites of low StO2 versus high StO2. CD105 displayed a similar trend but was not significant (P = .09). Conclusion Ferumoxytol-based quantitative blood oxygenation level-dependent MRI can potentially be used as a noninvasive surrogate for oxygenation mapping in infiltrative astrocytomas. This technique can potentially be integrated in treatment planning for aggressive targeting of hypoxic areas in tumors.

Simultaneous Multislice Resting-State Functional Magnetic Resonance Imaging at 3 Tesla: Slice-Acceleration-Related Biases in Physiological Effects.

Simultaneous multislice echo-planar imaging (SMS-EPI) can enhance the spatiotemporal resolution of resting-state functional MRI (rs-fMRI) by encoding and simultaneously imaging "groups" of slices. However, phenomena, including respiration, cardiac pulsatility, respiration volume per time (RVT), and cardiac rate variation (CRV), referred to as "physiological processes," impact SMS-EPI rs-fMRI in a manner that is yet to be well characterized. In particular, physiological noise may incur aliasing and introduce spurious signals from one slice into another within the "slice group" in rs-fMRI data, resulting in a deleterious effect on resting-state functional connectivity MRI (rs-fcMRI) maps. In the present work, we aimed to quantitatively compare the effects of physiological noise on regular EPI and SMS-EPI in terms of rs-fMRI data and resulting functional connectivity measurements. We compare SMS-EPI and regular EPI data acquired from 11 healthy young adults with matching parameters. The physiological noise characteristics were compared between the two data sets through different combinations of physiological regression steps. We observed that the physiological noise characteristics differed between SMS-EPI and regular EPI, with cardiac pulsatility contributing more to noise in regular EPI data but low-frequency heart rate variability contributing more to SMS-EPI. In addition, a significant slice-group bias was observed in the functional connectivity density maps derived from SMS-EPI data. We conclude that making appropriate corrections for physiological noise is likely more important for SMS-EPI than for regular EPI acquisitions.

A robust method for suppressing motion-induced coil sensitivity variations during prospective correction of head motion in fMRI.

Prospective motion correction is a promising candidate solution to suppress the effects of head motion during fMRI, ideally allowing the imaging plane to remain fixed with respect to the moving head. Residual signal artifacts may remain, however, because head motion in relation to a fixed multi-channel receiver coil (with non-uniform sensitivity maps) can potentially introduce unwanted signal variations comparable to the weak fMRI BOLD signal (~1%-4% at 1.5-3.0T). The present work aimed to investigate the magnitude of these residual artifacts, and characterize the regime over which prospective motion correction benefits from adjusting sensitivity maps to reflect relative positional change between the head and the coil. Numerical simulations were used to inform human fMRI experiments. The simulations indicated that for axial imaging within a commonly used 12-channel head coil, 5° of head rotation in-plane produced artifact signal changes of ~3%. Subsequently, six young adults were imaged with and without overt head motions of approximately this extent, with and without prospective motion correction using the Prospective Acquisition CorrEction (PACE) method, and with and without sensitivity map adjustments. Sensitivity map adjustments combined with PACE strongly protected against the artifacts of interest, as indicated by comparing three metrics of data quality (number of activated voxels, Dice coefficient of activation overlap, temporal standard deviation of baseline fMRI timeseries data) across the different experimental conditions. It is concluded that head motion in relation to a fixed multi-channel coil can adversely affect fMRI with prospective motion correction, and that sensitivity map adjustment can mitigate this effect at 3.0T.

Suppressing Respiration Effects when Geometric Distortion Is Corrected Dynamically by Phase Labeling for Additional Coordinate Encoding (PLACE) during Functional MRI.

Echo planar imaging (EPI) suffers from geometric distortions caused by magnetic field inhomogeneities, which can be time-varying as a result of small amounts of head motion that occur over seconds and minutes during fMRI experiments, also known as "dynamic geometric distortion". Phase Labeling for Additional Coordinate Encoding (PLACE) is a promising technique for geometric distortion correction without reduced temporal resolution and in principle can be used to correct for motion-induced dynamic geometric distortion. PLACE requires at least two EPI images of the same anatomy that are ideally acquired with no variation in the magnetic field inhomogeneities. However, head motion and lung ventilation during the respiratory cycle can cause changes in magnetic field inhomogeneities within the EPI pair used for PLACE. In this work, we exploited dynamic off-resonance in k-space (DORK) and averaging to correct the within EPI pair magnetic field inhomogeneities; and hence proposed a combined technique (DORK+PLACE+averaging) to mitigate dynamic geometric distortion in EPI-based fMRI while preserving the temporal resolution. The performance of the combined DORK, PLACE and averaging technique was characterized through several imaging experiments involving test phantoms and six healthy adult volunteers. Phantom data illustrate reduced temporal standard deviation of fMRI signal intensities after use of combined dynamic PLACE, DORK and averaging compared to the standard processing and static geometric distortion correction. The combined technique also substantially improved the temporal standard deviation and activation maps obtained from human fMRI data in comparison to the results obtained by standard processing and static geometric distortion correction, highlighting the utility of the approach.