Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data.

BOLD fMRI signal has been used in conjunction with vasodilatory stimulation as a marker of cerebrovascular reactivity (CVR): the relative change in cerebral blood flow (CBF) arising from a unit change in the vasodilatory stimulus. Using numerical simulations, we demonstrate that the variability in the relative BOLD signal change induced by vasodilation is strongly influenced by the variability in deoxyhemoglobin-containing cerebral blood volume (CBV), as this source of variability is likely to be more prominent than that of CVR. It may, therefore, be more appropriate to describe the relative BOLD signal change induced by an isometabolic vasodilation as a proxy of deoxygenated CBV (CBVdHb) rather than CVR. With this in mind, a new method was implemented to map a marker of CBVdHb, termed BOLD-CBV, based on the normalization of voxel-wise BOLD signal variation by an estimate of the intravascular venous BOLD signal from voxels filled with venous blood. The intravascular venous BOLD signal variation, recorded during repeated breath-holding, was extracted from the superior sagittal sinus in a cohort of 27 healthy volunteers and used as a regressor across the whole brain, yielding maps of BOLD-CBV. In the same cohort, we demonstrated the potential use of BOLD-CBV for the normalization of stimulus-evoked BOLD fMRI by comparing group-level BOLD fMRI responses to a visuomotor learning task with and without the inclusion of voxel-wise vascular covariates of BOLD-CBV and the BOLD signal change per mmHg variation in end-tidal carbon dioxide (BOLD-CVR). The empirical measure of BOLD-CBV accounted for more between-subject variability in the motor task-induced BOLD responses than BOLD-CVR estimated from end-tidal carbon dioxide recordings. The new method can potentially increase the power of group fMRI studies by including a measure of vascular characteristics and has the strong practical advantage of not requiring experimental measurement of end-tidal carbon dioxide, unlike traditional methods to estimate BOLD-CVR. It also more closely represents a specific physiological characteristic of brain vasculature than BOLD-CVR, namely blood volume.

Sleep-stage-dependent alterations in cerebral oxygen metabolism quantified by magnetic resonance.

A key function of sleep is to provide a regular period of reduced brain metabolism, which is critical for maintenance of healthy brain function. The purpose of this work was to quantify the sleep-stage-dependent changes in brain energetics in terms of cerebral metabolic rate of oxygen (CMRO2 ) as a function of sleep stage using quantitative magnetic resonance imaging (MRI) with concurrent electroencephalography (EEG) during sleep in the scanner. Twenty-two young and older subjects with regular sleep hygiene and Pittsburgh Sleep Quality Index (PSQI) in the normal range were recruited for the study. Cerebral blood flow (CBF) and venous oxygen saturation (SvO2 ) were obtained simultaneously at 3 Tesla field strength and 2.7-s temporal resolution during an 80-min time series using OxFlow, an in-house developed imaging sequence. The method yields whole-brain CMRO2 in absolute physiologic units via Fick's Principle. Nineteen subjects yielded evaluable data free of subject motion artifacts. Among these subjects, 10 achieved slow-wave (N3) sleep, 16 achieved N2 sleep, and 19 achieved N1 sleep while undergoing the MRI protocol during scanning. Mean CMRO2 was 98 ± 7(µmol min-1 )/100 g awake, declining progressively toward deepest sleep stage: 94 ± 10.8 (N1), 91 ± 11.4 (N2), and 76 ± 9.0 µmol min-1 /100 g (N3), with each level differing significantly from the wake state. The technology described is able to quantify cerebral oxygen metabolism in absolute physiologic units along with non-REM sleep stage, indicating brain oxygen consumption to be closely associated with depth of sleep, with deeper sleep stages exhibiting progressively lower CMRO2 levels.

Pathophysiology of multiple sclerosis damage and repair: Linking cerebral hypoperfusion to the development of irreversible tissue loss in multiple sclerosis using magnetic resonance imaging.

BACKGROUND AND PURPOSE: Reduced cerebral perfusion has been observed in multiple sclerosis (MS) and may contribute to tissue loss both acutely and chronically. Here, we test the hypothesis that hypoperfusion occurs in MS and relates to the presence of irreversible tissue damage. METHODS: In 91 patients with relapsing MS and 26 healthy controls (HC), gray matter (GM) cerebral blood flow (CBF) was assessed using pulsed arterial spin labeling. GM volume, T1 hypointense and T2 hyperintense lesion volumes (T1LV and T2LV, respectively), and the proportion of T2-hyperintense lesion volume that appears hypointense on T1-weighted magnetic resonance imaging (T1LV/T2LV) were quantified. GM CBF and GM volume were evaluated globally, as well as regionally, using an atlas-based approach. RESULTS: Global GM CBF was lower in patients (56.9 ± 12.3 mL/100 g/min) than in HC (67.7 ± 10.0 mL/100 g/min; p < 0.001), a difference that was widespread across brain regions. Although total GM volume was comparable between groups, significant reductions were observed in a subset of subcortical structures. GM CBF negatively correlated with T1LV (r = -0.43, p = 0.0002) and T1LV/T2LV (r = -0.37, p = 0.0004), but not with T2LV. CONCLUSIONS: GM hypoperfusion occurs in MS and is associated with irreversible white matter damage, thus suggesting that cerebral hypoperfusion may actively contribute and possibly precede neurodegeneration by hampering tissue repair abilities in MS.

Evaluation of Vascular Reactivity of Maternal Vascular Adaptations of Pregnancy With Quantitative MRI: Pilot Study.

BACKGROUND: Abnormal maternal vascular function during pregnancy stemming from systemic endothelial dysfunction (EDF) has a central role in the pathophysiology of preeclampsia (PE). PURPOSE: To utilize quantitative MRI to investigate changes in physiological measures of vascular reactivity during normal pregnancy, and to explore EDF associated with preeclampsia. STUDY TYPE: Prospective. POPULATION: Healthy pregnant (HP) (n = 14, mean GA = 26 ± 7 weeks) and nonpregnant women (NP; n = 14); newly postpartum (PP <48 hours) women with severe PE (PP-PE; n = 4) and normotensive pregnancy (PP-HP; n = 5). FIELD STRENGTH/SEQUENCE: 1.5T/3T. RF spoiled multiecho gradient-recalled echo, 1D phase-contrast MRI, time-of-flight. ASSESSMENT: The micro- and macrovascular function (vasodilatory capacity of arterioles and conduit arteries, respectively) of the femoral vascular bed was evaluated with MRI-based venous oximetry, arterial velocimetry, and luminal flow-mediated dilation quantification, during cuff-induced reactive hyperemia. Aortic arch pulse-wave velocity (aPWV) was quantified to assess arterial stiffness using an ungated 1D technique. STATISTICAL TESTS: Two-tailed unpaired t-tests were performed to address our two, primary a priori comparisons, HP vs. NP, and PP-PE vs. PP-HP. Given the pilot nature of this study, adjustments for multiple comparisons were not performed. RESULTS: In HP, microvascular function was attenuated compared to NP by a significant increase in the washout time (10 ± 2 vs. 8 ± 2 sec; P < 0.05) and reduced upslope (2.1 ± 0.5 vs. 3.2 ± 0.8%HbO2 /s; P < 0.05), time of forward flow (28 ± 5 vs. 33 ± 6 sec, P < 0.05), and hyperemic index (11 ± 3 vs. 16 ± 4 cm/s2 ; P < 0.05), but luminal flow-mediated dilatation (FMDL )was comparable between HP and NP. PP-PE exhibited significant vascular dysfunction compared to PP-HP, as evidenced by differences in upslope (2.2 ± 0.6 vs. 1.3 ± 0.2%HbO2 /s, P < 0.05), overshoot (16 ± 5 vs. 7 ± 3%HbO2 , P < 0.05), time of forward flow (28 ± 6 vs. 15 ± 7 s, P < 0.05), and aPWV (7 ± 1 vs. 8 ± 1 m/s, P < 0.05). DATA CONCLUSION: Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.

Superior sagittal sinus flow as a proxy for tracking global cerebral blood flow dynamics during wakefulness and sleep.

Sleep, a state of reduced consciousness, affects brain oxygen metabolism and lowers cerebral metabolic rate of oxygen (CMRO2). Previously, we quantified CMRO2 during sleep via Fick's Principle, with a single-band MRI sequence measuring both hemoglobin O2 saturation (SvO2) and superior sagittal sinus (SSS) blood flow, which was upscaled to obtain total cerebral blood flow (tCBF). The procedure involves a brief initial calibration scan to determine the upscaling factor (fc), assumed state-invariant. Here, we used a dual-band sequence to simultaneously provide SvO2 in SSS and tCBF in the neck every 16 seconds, allowing quantification of fc dynamically. Ten healthy subjects were scanned by MRI with simultaneous EEG for 80 minutes, yielding 300 temporal image frames per subject. Four volunteers achieved slow-wave sleep (SWS), as evidenced by increased δ-wave activity (per American Academy of Sleep Medicine criteria). SWS was maintained for 13.5 ± 7.0 minutes, with CMRO2 28.6 ± 5.5% lower than pre-sleep wakefulness. Importantly, there was negligible bias between tCBF obtained by upscaling SSS-blood flow, and tCBF measured directly in the inflowing arteries of the neck (intra-class correlation 0.95 ± 0.04, averaged across all subjects), showing that the single-band approach is a valid substitute for quantifying tCBF, simplifying image data collection and analysis without sacrificing accuracy.

Performance of Diffusion Kurtosis Imaging Versus Diffusion Tensor Imaging in Discriminating Between Benign Tissue, Low and High Gleason Grade Prostate Cancer.

RATIONALE AND OBJECTIVES: To investigate the performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in discriminating benign tissue, low- and high-grade prostate adenocarcinoma (PCa). MATERIALS AND METHODS: Forty-eight patients with biopsy-proven PCa of different Gleason grade (GG), who provided written informed consent, were enrolled. All subjects underwent 3T DWI examinations by using b values 0, 500, 1000, 1500, 2000, and 2500 s/mm2 and six gradient directions. Mean diffusivity, fractional anisotropy (FA), apparent kurtosis (K), apparent kurtosis-derived diffusivity (D), and proxy fractional kurtosis anisotropy (KFA) maps were obtained. Regions of interest were selected in PCa, in the contralateral benign zone, and in the peritumoral area. Histogram analysis was performed by measuring mean, 10th, 25th, and 90th (p90) percentile of the whole-lesion volume. Kruskal-Wallis test with Bonferroni correction was used to assess significant differences between different regions of interest. The correlation between diffusion metrics and GG and between DKI and DTI parameters was evaluated with Pearson's test. ROC curve analysis was carried out to analyze the ability of histogram variables to differentiate low- and high-GG PCa. RESULTS: All metrics significantly discriminated PCa from benign and from peritumoral tissue (except for K, KFAp90, and FA). Kp90 showed the highest correlation with GG and the best diagnostic ability (area under the curve = 0.84) in discriminating low- from high-risk PCa. CONCLUSION: Compared to DTI, DKI provides complementary and additional information about prostate cancer tissue, resulting more sensitive to PCa-derived modifications and more accurate in discriminating low- and high-risk PCa.

Changes of statistical structural fluctuations unveils an early compacted degraded stage of PNS myelin.

Degradation of the myelin sheath is a common pathology underlying demyelinating neurological diseases from Multiple Sclerosis to Leukodistrophies. Although large malformations of myelin ultrastructure in the advanced stages of Wallerian degradation is known, its subtle structural variations at early stages of demyelination remains poorly characterized. This is partly due to the lack of suitable and non-invasive experimental probes possessing sufficient resolution to detect the degradation. Here we report the feasibility of the application of an innovative non-invasive local structure experimental approach for imaging the changes of statistical structural fluctuations in the first stage of myelin degeneration. Scanning micro X-ray diffraction, using advances in synchrotron x-ray beam focusing, fast data collection, paired with spatial statistical analysis, has been used to unveil temporal changes in the myelin structure of dissected nerves following extraction of the Xenopus laevis sciatic nerve. The early myelin degeneration is a specific ordered compacted phase preceding the swollen myelin phase of Wallerian degradation. Our demonstration of the feasibility of the statistical analysis of SµXRD measurements using biological tissue paves the way for further structural investigations of degradation and death of neurons and other cells and tissues in diverse pathological states where nanoscale structural changes may be uncovered.