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Simple Summary: Brain cells require a continuous and adequate supply of oxygen for optimal functioning; however, this balance is disrupted in the presence of brain tumors. The rapid growth of these tumors exceeds the capacity of the existing blood vessels, leading to areas of hypoxia. This condition contributes to accelerated tumor growth and diminishes the effectiveness of treatments. Utilizing MRI to non-invasively map hypoxia in the brain enables doctors to tailor treatment plans more effectively and to understand the tumor's level of aggressiveness. In this study, we investigated the efficacy of a new MRI method, streamlined quantitative blood-oxygen-level-dependent (sqBOLD) MRI, in mapping hypoxia across different brain tumor types. Moreover, we utilize MRI to examine the vascular features of the tumors, aiming to elucidate the dynamics of oxygen delivery. In addition, this study includes microscopic evaluations of tumor biopsies, providing valuable insights into the hypoxic environments within the tumors. Cerebral hypoxia significantly impacts the progression of brain tumors and their resistance to radiotherapy. This study employed streamlined quantitative blood-oxygen-level-dependent (sqBOLD) MRI to assess the oxygen extraction fraction (OEF)—a measure of how much oxygen is being extracted from vessels, with higher OEF values indicating hypoxia. Simultaneously, we utilized vessel size imaging (VSI) to evaluate microvascular dimensions and blood volume. A cohort of ten patients, divided between those with glioma and those with brain metastases, underwent a 3 Tesla MRI scan. We generated OEF, cerebral blood volume (CBV), and vessel size maps, which guided 3–4 targeted biopsies per patient. Subsequent histological analyses of these biopsies used hypoxia-inducible factor 1-alpha (HIF-1α) for hypoxia and CD31 for microvasculature assessment, followed by a correlation analysis between MRI and histological data. The results showed that while the sqBOLD model was generally applicable to brain tumors, it demonstrated discrepancies in some metastatic tumors, highlighting the need for model adjustments in these cases. The OEF, CBV, and vessel size maps provided insights into the tumor's hypoxic condition, showing intertumoral and intratumoral heterogeneity. A significant relationship between MRI-derived measurements and histological data was only evident in the vessel size measurements (r = 0.68, p < 0.001). [ABSTRACT FROM AUTHOR]

Purpose: To alleviate the spatial encoding limitations of single‐shot echo‐planar imaging (EPI) by developing multi‐shot segmented EPI for ultra‐high‐resolution functional MRI (fMRI) with reduced ghosting artifacts from subject motion and respiration. Theory and Methods: Segmented EPI can reduce readout duration and reduce acceleration factors, however, the time elapsed between segment acquisitions (on the order of seconds) can result in intermittent ghosting, limiting its use for fMRI. Here, "FLEET" segment ordering, where segments are looped over before slices, was combined with a variable flip angle progression (VFA‐FLEET) to improve inter‐segment fidelity and maximize signal for fMRI. Scaling a sinc pulse's flip angle for each segment (VFA‐FLEET‐Sinc) produced inconsistent slice profiles and ghosting, therefore, a recursive Shinnar‐Le Roux (SLR) radiofrequency (RF) pulse design was developed (VFA‐FLEET‐SLR) to generate unique pulses for every segment that together produce consistent slice profiles and signals. Results: The temporal stability of VFA‐FLEET‐SLR was compared against conventional‐segmented EPI and VFA‐FLEET‐Sinc at 3T and 7T. VFA‐FLEET‐SLR showed reductions in both intermittent and stable ghosting compared to conventional‐segmented and VFA‐FLEET‐Sinc, resulting in improved image quality with a minor trade‐off in temporal SNR. Combining VFA‐FLEET‐SLR with acceleration, we achieved a 0.6‐mm isotropic acquisition at 7T, without zoomed imaging or partial Fourier, demonstrating reliable detection of blood oxygenation level‐dependent (BOLD) responses to a visual stimulus. To counteract the increased repetition time from segmentation, simultaneous multi‐slice VFA‐FLEET‐SLR was demonstrated using RF‐encoded controlled aliasing. Conclusions: VFA‐FLEET with a recursive RF pulse design supports acquisitions with low levels of artifact and spatial blur, enabling fMRI at previously inaccessible spatial resolutions with a "full‐brain" field of view. [ABSTRACT FROM AUTHOR]

Purpose: To derive an expression for the transverse signal time course from systems in the motional narrowing regime, such as water diffusing in blood. This was validated in silico and experimentally with ex vivo blood samples. Methods: A closed‐form solution (CFS) for transverse signal decay under any train of refocusing pulses was derived using the weak field approximation. The CFS was validated via simulations of water molecules diffusing in the presence of spherical perturbers, with a range of sizes and under various pulse sequences. The CFS was compared with more conventional fits assuming monoexponential decay, including chemical exchange, using ex vivo blood Carr‐Purcell‐Meiboom‐Gill data. Results: From simulations, the CFS was shown to be valid in the motional narrowing regime and partially into the intermediate dephasing regime, with increased accuracy with increasing Carr‐Purcell‐Meiboom‐Gill refocusing rate. In theoretical calculations of the CFS, fitting for the transverse relaxation rate (R2) gave excellent agreement with the weak field approximation expression for R2 for Carr‐Purcell‐Meiboom‐Gill sequences, but diverged for free induction decay. These same results were confirmed in the ex vivo analysis. Conclusion: Transverse signal decay in the motional narrowing regime can be accurately described analytically. This theory has applications in areas such as tissue iron imaging, relaxometry of blood, and contrast agent imaging. Magn Reson Med 80:341–350, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Cerebral cortex thinning and cerebral blood flow (CBF) reduction are typically observed during normal healthy aging. However, imaging-based age prediction models have primarily used morphological features of the brain. Complementary physiological CBF information might result in an improvement in age estimation. In this study, T1-weighted structural magnetic resonance imaging and arterial spin labeling CBF images were acquired in 146 healthy participants across the adult life span. Sixty-eight cerebral cortex regions were segmented, and the cortical thickness and mean CBF were computed for each region. Linear regression with age was computed for each region and data type, and laterality and correlation matrices were computed. Sixteen predictive models were trained with the cortical thickness and CBF data alone as well as a combination of both data types. The age explained more variance in the cortical thickness data (average R 2  of 0.21) than in the CBF data (average R 2  of 0.09). All 16 models performed significantly better when combining both measurement types and using feature selection, and thus, we conclude that the inclusion of CBF data marginally improves age estimation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Quantitative BOLD (qBOLD) is a technique for mapping oxygen extraction fraction (OEF) and deoxygenated blood volume (DBV) in the human brain. Recent measurements using an asymmetric spin echo (ASE) based qBOLD approach produced estimates of DBV which were systematically higher than measurements from other techniques. In this study, we investigate two hypotheses for the origin of this DBV overestimation using simulations and consider the implications for experimental measurements. Investigations were performed by combining Monte Carlo simulations of extravascular signal with an analytical model of the intravascular signal. HYPOTHESIS 1: DBV overestimation is due to the presence of intravascular signal which is not accounted for in the analysis model. Intravascular signal was found to have a weak effect on qBOLD parameter estimates. HYPOTHESIS 2: DBV overestimation is due to the effects of diffusion which are not accounted for in the analysis model. The effect of diffusion on the extravascular signal was found to result in a vessel radius dependent variation in qBOLD parameter estimates. In particular, DBV overestimation peaks for vessels with radii from 20 to 30 μm and is OEF dependent. This results in the systematic underestimation of OEF. IMPLICATIONS: The impact on experimental qBOLD measurements was investigated by simulating a more physiologically realistic distribution of vessel sizes with a small number of discrete radii. Overestimation of DBV consistent with previous experiments was observed, which was also found to be OEF dependent. This results in the progressive underestimation of the measured OEF. Furthermore, the relationship between the measured OEF and the true OEF was found to be dependent on echo time and spin echo displacement time. The results of this study demonstrate the limitations of current ASE based qBOLD measurements and provide a foundation for the optimisation of future acquisition approaches., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The primary goal of this study was to estimate the value of β , the exponent in the power law relating changes of the transverse relaxation rate and intra-extravascular local magnetic susceptibility differences as Δ R 2 ∗ ∝ ( Δ χ ) β . The secondary objective was to evaluate any differences that might exist in the value of β obtained using a deoxyhemoglobin-weighted Δ χ distribution versus a constant Δ χ distribution assumed in earlier computations. The third objective was to estimate the value of β that is relevant for methods based on susceptibility contrast agents with a concentration of Δ χ higher than that used for BOLD fMRI calculations., Methods: Our recently developed model of real microvascular anatomical networks is used to extend the original simplified Monte-Carlo simulations to compute β from the first principles., Results: Our results show that β = 1 for most BOLD fMRI measurements of real vascular networks, as opposed to earlier predictions of β = 1 .5 using uniform Δ χ distributions. For perfusion or fMRI methods based on contrast agents, which generate larger values for Δ χ , β = 1 for B 0 ≤ 9.4 T, whereas at 14 T β can drop below 1 and the variation across subjects is large, indicating that a lower concentration of contrast agent with a lower value of Δ χ is desired for experiments at high B 0 ., Conclusion: These results improve our understanding of the relationship between R 2 * and the underlying microvascular properties. The findings will help to infer the cerebral metabolic rate of oxygen and cerebral blood volume from BOLD and perfusion MRI, respectively., (© 2019 International Society for Magnetic Resonance in Medicine.)

A new method is proposed for obtaining cerebral perfusion measurements whereby blood oxygen level dependent (BOLD) MRI is used to dynamically monitor hyperoxia-induced changes in the concentration of deoxygenated hemoglobin in the cerebral vasculature. The data is processed using kinetic modeling to yield perfusion metrics, namely: cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Ten healthy human subjects were continuously imaged with BOLD sequence while a hyperoxic (70% O 2 ) state was interspersed with baseline periods of normoxia. The BOLD time courses were fit with exponential uptake and decay curves and a biophysical model of the BOLD signal was used to estimate oxygen concentration functions. The arterial input function was derived from end-tidal oxygen measurements, and a deconvolution operation between the tissue and arterial concentration functions was used to yield CBF. The venous component of the CBV was calculated from the ratio of the integrals of the estimated tissue and arterial concentration functions. Mean gray and white matter measurements were found to be: 61.6 ± 13.7 and 24.9 ± 4.0 ml 100 g -1  min -1 for CBF; 1.83 ± 0.32 and 1.10 ± 0.19 ml 100 g -1 for venous CBV; and 2.94 ± 0.52 and 3.73 ± 0.60 s for MTT, respectively. We conclude that it is possible to derive CBF, CBV and MTT metrics within expected physiological ranges via analysis of dynamic BOLD fMRI acquired during a period of hyperoxia., (Copyright © 2018. Published by Elsevier Inc.)

Calibrated functional magnetic resonance imaging (fMRI) is a method to independently measure the metabolic and hemodynamic contributions to the blood oxygenation level dependent (BOLD) signal. This technique typically requires the use of a respiratory challenge, such as hypercapnia or hyperoxia, to estimate the calibration constant, M. There has been a recent push to eliminate the gas challenge from the calibration procedure using asymmetric spin echo (ASE) based techniques. This study uses simulations to better understand spin echo (SE) and ASE signals, analytical modelling to characterize the signal evolution, and in vivo imaging to validate the modelling. Using simulations, it is shown how ASE imaging generally underestimates M and how this depends on several parameters of the acquisition, including echo time and ASE offset, as well as the vessel size. This underestimation is the result of imperfect SE refocusing due to diffusion of water through the extravascular environment surrounding the microvasculature. By empirically characterizing this SE attenuation as an exponential decay that increases with echo time, we have proposed a quadratic ASE biophysical signal model. This model allows for the characterization and compensation of the SE attenuation if SE and ASE signals are acquired at multiple echo times. This was tested in healthy subjects and was found to significantly increase the estimates of M across grey matter. These findings show promise for improved gas-free calibration and can be extended to other relaxation-based imaging studies of brain physiology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To determine the contribution of paramagnetic dissolved oxygen in blood plasma to blood-oxygenation-level-dependent (BOLD) signal changes in hyperoxic calibrated BOLD studies., Methods: Bovine blood plasma samples were prepared with partial pressures of oxygen (pO 2 ) ranging from 110 to 600 mmHg. R 1 , R 2 , and R 2 * of the plasma with dissolved oxygen were measured using quantitative MRI sequences at 3 Tesla. Simulations were performed to predict the relative effects of dissolved oxygen and deoxyhemoglobin changes in hyperoxia calibrated BOLD., Results: The relaxivities of dissolved oxygen in plasma were found to be r 1, O2 =1.97 ± 0.09 ×10 -4 s -1 mmHg -1 , r 2, O2 =2.3 ± 0.7 ×10 -4 s -1 mmHg -1 , and r 2, O2 * = 2.3 ± 0.7 ×10 -4 s -1 mmHg -1 . Simulations predict that neither the transverse nor longitudinal relaxation rates of dissolved oxygen contribute significantly to the BOLD signal during hyperoxia., Conclusion: During hyperoxia, the increases in R 2 and R 2 * of blood from dissolved oxygen in plasma are considerably less than the decreases in R 2 and R 2 * from venous deoxyhemoglobin. R 1 effects due to dissolved oxygen are also predicted to be negligible. As a result, dissolved oxygen in arteries should not contribute significantly to the hyperoxic calibrated BOLD signal. Magn Reson Med 76:1905-1911, 2016. © 2015 International Society for Magnetic Resonance in Medicine., (© 2015 International Society for Magnetic Resonance in Medicine.)

Purpose: It has been predicted that, during hyperoxia, excess O2 dissolved in arterial blood will significantly alter the blood's magnetic susceptibility. This would confound the interpretation of the hyperoxia-induced blood oxygenation level-dependent signal as arising solely from changes in deoxyhemoglobin. This study, therefore, aimed to determine how dissolved O2 affects the susceptibility of blood., Theory and Methods: We present a comprehensive model for the effect of dissolved O2 on the susceptibility of blood and compare it with another recently published model, referred to here as the ideal gas model (IGM). For validation, distilled water and samples of bovine plasma were oxygenated over a range of hyperoxic O2 concentrations and their susceptibilities were determined using multiecho gradient echo phase imaging., Results: In distilled water and plasma, the measured changes in susceptibility were very linear, with identical slopes of 0.062 ppb/mm Hg of O2. This change was dramatically less than previously predicted using the IGM and was close to that predicted by our model. The primary source of error in the IGM is the overestimation of the volume fraction occupied by dissolved O2., Conclusion: Under most physiological conditions, the susceptibility of dissolved O2 can be disregarded in MRI studies employing hyperoxia., (© 2015 Wiley Periodicals, Inc.)