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.

Changes of brain parenchyma free water fraction reflect tissue damage and impaired processing speed in multiple sclerosis.

Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm2, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.

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.

Acute e-cig inhalation impacts vascular health: a study in smoking naïve subjects.

This study was designed to investigate the acute effects of nonnicotinized e-cigarette (e-cig) aerosol inhalation in nonsmokers both in terms of blood-based markers of inflammation and oxidative stress and evaluate their association with hemodynamic-metabolic MRI parameters quantifying peripheral vascular reactivity, cerebrovascular reactivity, and aortic stiffness. Thirty-one healthy nonsmokers were subjected to two blood draws and two identical MRI protocols, each one before and after a standardized e-cig vaping session. After vaping, the serum levels of C-reactive protein, soluble intercellular adhesion molecule, and the danger signal machinery high-mobility group box 1 (HMGB1) and its downstream effector and the NLR family pyrin domain containing 3 (NLRP3) inflammasome (as monitored by its adaptor protein ASC) increased significantly relative to the respective baseline (prevaping) values. Moreover, nitric oxide metabolites and reactive oxygen species production decreased and increased, respectively. These observations were paralleled by impaired peripheral vascular reactivity (with reduced flow-mediated dilation and attenuated hyperemic response after a cuff-occlusion test) and metabolic alterations expressed by decreased venous oxygen saturation, postvaping. The current results suggest propagation of inflammation signaling via activation of the danger signaling axis (HMGB1-NLRP3). The findings indicate that a single episode of vaping has adverse impacts on vascular inflammation and function.NEW & NOTWORTHY Endothelial cell signaling and blood biomarkers were found to correlate with functional vascular changes in a single episode e-cigarettes inhalation in healthy adults. This is indicative of the potential of e-cigarettes (even when inhaled acutely) to lead of vascular dysfunction.

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.

Radiologic, Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions.

Proposed as a safer alternative to smoking, the use of electronic cigarettes has not proven to be innocuous. With numerous deaths, there is an increasing degree of public interest in understanding the symptoms, imaging appearances, causes of, and treatment of electronic cigarette or vaping product use-associated lung injury (EVALI). Patients with EVALI typically have a nonspecific clinical presentation characterized by a combination of respiratory, gastrointestinal, and constitutional symptoms. EVALI is a diagnosis of exclusion; the patient must elicit a history of recent vaping within 90 days, other etiologies must be eliminated, and chest imaging findings must be abnormal. Chest CT findings in EVALI most commonly show a pattern of acute lung injury on the spectrum of organizing pneumonia and diffuse alveolar damage. The pathologic pattern found depends on when in the evolution of the disease process the biopsy sample is taken. Other less common forms of lung injury, including acute eosinophilic pneumonia and diffuse alveolar hemorrhage, have also been reported. Radiologists and pathologists help play an important role in the evaluation of patients suspected of having EVALI. Accurate and rapid identification may decrease morbidity and mortality by allowing for aggressive clinical management and glucocorticoid administration, which have been shown to decrease the severity of lung injury in some patients. In this review, the authors summarize the current state of the art for the imaging and pathologic findings of this disorder and outline a few of the major questions that remain to be answered.

Age-related microstructural and physiological changes in normal brain measured by MRI γ-metrics derived from anomalous diffusion signal representation.

Nowadays, increasing longevity associated with declining cerebral nervous system functions, suggests the need for continued development of new imaging contrast mechanisms to support the differential diagnosis of age-related decline. In our previous papers, we developed a new imaging contrast metrics derived from anomalous diffusion signal representation and obtained from diffusion-weighted (DW) data collected by varying diffusion gradient strengths. Recently, we highlighted that the new metrics, named γ-metrics, depended on the local inhomogeneity due to differences in magnetic susceptibility between tissues and diffusion compartments in young healthy subjects, thus providing information about myelin orientation and iron content within cerebral regions. The major structural modifications occurring in brain aging are myelinated fibers damage in nerve fibers and iron accumulation in gray matter nuclei. Therefore, we investigated the potential of γ-metrics in relation to other conventional diffusion metrics such as DTI, DKI and NODDI in detecting age-related structural changes in white matter (WM) and subcortical gray matter (scGM). DW-images were acquired in 32 healthy subjects, adults and elderly (age range 20-77 years) using 3.0T and 12 b-values up to 5000 s/mm2. Association between diffusion metrics and subjects' age was assessed using linear regression. A decline in mean γ (Mγ) in the scGM and a complementary increase in radial γ (γ⊥) in frontal WM, genu of corpus callosum and anterior corona radiata with advancing age were found. We suggested that the increase in γ⊥ might reflect declined myelin density, and Mγ decrease might mirror iron accumulation. An increase in D// and a decrease in the orientation dispersion index (ODI) were associated with axonal loss in the pyramidal tracts, while their inverted trends within the thalamus were thought to be linked to reduced architectural complexity of nerve fibers. γ-metrics together with conventional diffusion-metrics can more comprehensively characterize the complex mechanisms underlining age-related changes than conventional diffusion techniques alone.

Acute exposure to e-cigarettes causes inflammation and pulmonary endothelial oxidative stress in nonsmoking, healthy young subjects.

The effects of e-cigarette (e-cig) aerosol inhalation by nonsmokers have not been examined to date. The present study was designed to evaluate the acute response to aerosol inhalation of non-nicotinized e-cigarettes in terms of oxidative stress and indices of endothelial activation in human pulmonary microvascular endothelial cells (HPMVEC). Ten smoking-naïve healthy subjects (mean age ± SD = 28.7 ± 5.5 yr) were subjected to an e-cig challenge, following which their serum was monitored for markers of inflammation [C-reactive protein (CRP) and soluble intercellular adhesion molecule (sICAM)] and nitric oxide metabolites (NOx). The oxidative stress and inflammation burden of the circulating serum on the vascular network was also assessed by measuring reactive oxygen species (ROS) production and induction of ICAM-1 expression on HPMVEC. Our results show that serum indices of oxidative stress and inflammation increased significantly (P < 0.05 as compared with baseline), reaching a peak at approximately 1-2 h post-e-cig aerosol inhalation and returning to baseline levels at 6 h. The circulatory burden of the serum (ICAM-1 and ROS) increased significantly at 2 h and returned to baseline values 6 h post-e-cig challenge. ROS production by HPMVEC was found to occur via activation of the NADPH oxidase 2 (NOX2) pathways. These findings suggest that even in the absence of nicotine, acute e-cig aerosol inhalation leads to a transient increase in oxidative stress and inflammation. This can adversely affect the vascular endothelial network by promoting oxidative stress and immune cell adhesion. Thus e-cig inhalation has the potential to drive the onset of vascular pathologies.

Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI.

Background Previous studies showed that nicotinized electronic cigarettes (hereafter, e-cigarettes) elicit systemic oxidative stress and inflammation. However, the effect of the aerosol alone on endothelial function is not fully understood. Purpose To quantify surrogate markers of endothelial function in nonsmokers after inhalation of aerosol from nicotine-free e-cigarettes. Materials and Methods In this prospective study (from May to September 2018), nonsmokers underwent 3.0-T MRI before and after inhaling nicotine-free e-cigarette aerosol. Peripheral vascular reactivity to cuff-induced ischemia was quantified by temporally resolving blood flow velocity and oxygenation (SvO2) in superficial femoral artery and vein, respectively, along with artery luminal flow-mediated dilation. Precuff occlusion, resistivity index, baseline blood flow velocity, and SvO2 were evaluated. During reactive hyperemia, blood flow velocity yielded peak velocity, time to peak, and acceleration rate (hyperemic index); SvO2 yielded washout time of oxygen-depleted blood, rate of resaturation, and maximum SvO2 increase (overshoot). Cerebrovascular reactivity was assessed in the superior sagittal sinus, evaluating the breath-hold index. Central arterial stiffness was measured via aortic pulse wave velocity. Differences before versus after e-cigarette vaping were tested with Hotelling T2 test. Results Thirty-one healthy never-smokers (mean age, 24.3 years ± 4.3; 14 women) were evaluated. After e-cigarette vaping, resistivity index was higher (0.03 of 1.30 [2.3%]; P < .05), luminal flow-mediated dilation severely blunted (-3.2% of 9.4% [-34%]; P < .001), along with reduced peak velocity (-9.9 of 56.6 cm/sec [-17.5%]; P < .001), hyperemic index (-3.9 of 15.1 cm/sec2 [-25.8%]; P < .001), and delayed time to peak (2.1 of 7.1 sec [29.6%]; P = .005); baseline SvO2 was lower (-13 of 65 %HbO2 [-20%]; P < .001) and overshoot higher (10 of 19 %HbO2 [52.6%]; P < .001); and aortic pulse wave velocity marginally increased (0.19 of 6.05 m/sec [3%]; P = .05). Remaining parameters did not change after aerosol inhalation. Conclusion Inhaling nicotine-free electronic cigarette aerosol transiently impacted endothelial function in healthy nonsmokers. Further studies are needed to address the potentially adverse long-term effects on vascular health. © RSNA, 2019 Online supplemental material is available for this article.

Acquisition Parameters Influence Diffusion Metrics Effectiveness in Probing Prostate Tumor and Age-Related Microstructure.

This study aimed to investigate the Diffusion-Tensor-Imaging (DTI) potential in the detection of microstructural changes in prostate cancer (PCa) in relation to the diffusion weight (b-value) and the associated diffusion length lD. Thirty-two patients (age range = 50-87 years) with biopsy-proven PCa underwent Diffusion-Weighted-Imaging (DWI) at 3T, using single non-zero b-value or groups of b-values up to b = 2500 s/mm2. The DTI maps (mean-diffusivity, MD; fractional-anisotropy, FA; axial and radial diffusivity, D// and D┴), visual quality, and the association between DTI-metrics and Gleason Score (GS) and DTI-metrics and age were discussed in relation to diffusion compartments probed by water molecules at different b-values. DTI-metrics differentiated benign from PCa tissue (p ≤ 0.0005), with the best discriminative power versus GS at b-values ≥ 1500 s/mm2, and for b-values range 0-2000 s/mm2, when the lD is comparable to the size of the epithelial compartment. The strongest linear correlations between MD, D//, D┴, and GS were found at b = 2000 s/mm2 and for the range 0-2000 s/mm2. A positive correlation between DTI parameters and age was found in benign tissue. In conclusion, the use of the b-value range 0-2000 s/mm2 and b-value = 2000 s/mm2 improves the contrast and discriminative power of DTI with respect to PCa. The sensitivity of DTI parameters to age-related microstructural changes is worth consideration.

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.

Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation.

Cerebrovascular reactivity (CVR) reflects the capacity of the brain's vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain's blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVRGM and CVRWM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVRGM (p = 0.04) and CVRWM (p = 0.02) compared to HC. In patients, a lower pre-treatment CVRGM was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVRGM (p = 0.02) and CVRWM (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = - 0.58, p = 0.005; WM: r = - 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = - 0.48, p = 0.02, WM: r = - 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring.

Cerebral metabolic rate of oxygen during transition from wakefulness to sleep measured with high temporal resolution OxFlow MRI with concurrent EEG.

During slow-wave sleep, synaptic transmissions are reduced with a concomitant reduction in brain energy consumption. We used 3 Tesla MRI to noninvasively quantify changes in the cerebral metabolic rate of O2 (CMRO2) during wakefulness and sleep, leveraging the 'OxFlow' method, which provides venous O2 saturation (SvO2) along with cerebral blood flow (CBF). Twelve healthy subjects (31.3 ± 5.6 years, eight males) underwent 45-60 min of continuous scanning during wakefulness and sleep, yielding one image set every 3.4 s. Concurrent electroencephalography (EEG) data were available in eight subjects. Mean values of the metabolic parameters measured during wakefulness were stable, with coefficients of variation below 7% (average values: CMRO2 = 118 ± 12 µmol O2/min/100 g, SvO2 = 67.0 ± 3.7% HbO2, CBF = 50.6 ±4.3 ml/min/100 g). During sleep, on average, CMRO2 decreased 21% (range: 14%-32%; average nadir = 98 ± 16 µmol O2/min/100 g), while EEG slow-wave activity, expressed in terms of δ-power, increased commensurately. Following sleep onset, CMRO2 was found to correlate negatively with relative δ-power (r = -0.6 to -0.8, P < 0.005), and positively with heart rate (r = 0.5 to 0.8, P < 0.0005). The data demonstrate that OxFlow MRI can noninvasively measure dynamic changes in cerebral metabolism associated with sleep, which should open new opportunities to study sleep physiology in health and disease.

Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology.

Neural tissue is a hierarchical multiscale system with intracellular and extracellular diffusion compartments at different length scales. The normal diffusion of bulk water in tissues is not able to detect the specific features of a complex system, providing nonlocal, diffusion measurement averaged on a 10-20 µm length scale. Being able to probe tissues with sub-micrometric diffusion length and quantify new local parameters, transient anomalous diffusion (tAD) would dramatically increase the diagnostic potential of diffusion MRI (DMRI) in detecting collective and sub-micro architectural changes of human tissues due to pathological damage. In DMRI, the use of tAD parameters quantified using specific DMRI acquisition protocols and their interpretation has often aroused skepticism. Although the derived formulas may accurately fit experimental diffusion-weighted data, the relationships between the postulated dynamical feature and the underlying geometrical structure remains elusive, or at most only suggestive. This work aimed to elucidate and validate the image contrast and information that can be obtained using the tAD model in white matter (WM) through a direct comparison between different diffusion metrics and histology. Towards this goal, we compared tAD metrics extracted from pure subdiffusion (α-imaging) and super-pseudodiffusion (γ-imaging) in excised mouse spinal cord WM, together with T2 and T2* relaxometry, conventional (normal diffusion-based) diffusion tensor imaging (DTI) and q-space imaging (QSI), with morphologic measures obtained by optical microscopy, to determine which structural and topological characteristics of myelinated axons influenced tAD contrast. Axon diameter (AxDiam), the standard deviation of diameters (SD ax.diam ), axonal density (AxDens) and effective local density (ELD) were extracted from optical images in several WM tracts. Among all the diffusion parameters obtained at 9.4 T, γ-metrics confirmed a strong dependence on magnetic in-homogeneities quantified by R2* = 1/T2* and showed the strongest associations with AxDiam and ELD. On the other hand, α-metrics showed strong associations with SD ax.diam and was significantly related to AxDens, suggesting its ability to quantify local heterogeneity degree in neural tissue. These results elucidate the biophysical mechanism underpinning tAD parameters and show the clinical potential of tAD-imaging, considering that both physiologic and pathologic neurodegeneration translate into alterations of WM morphometry and topology.

New Insights From MRI and Cell Biology Into the Acute Vascular-Metabolic Implications of Electronic Cigarette Vaping.

The popularity of electronic cigarettes (e-cigs) has grown at a startling rate since their introduction to the United States market in 2007, with sales expected to outpace tobacco products within a decade. Spurring this trend has been the notion that e-cigs are a safer alternative to tobacco-based cigarettes. However, the long-term health impacts of e-cigs are not yet known. Quantitative magnetic resonance imaging (MRI) approaches, developed in the authors' laboratory, provide conclusive evidence of acute deleterious effects of e-cig aerosol inhalation in the absence of nicotine in tobacco-naïve subjects. Among the pathophysiologic effects observed are transient impairment of endothelial function, vascular reactivity, and oxygen metabolism. The culprits of this response are currently not fully understood but are likely due to an immune reaction caused by the aerosol containing thermal breakdown products of the e-liquid, including radicals and organic aldehydes, with particle concentrations similar to those emitted by conventional cigarettes. The acute effects observed following a single vaping episode persist for 1-3 h before subsiding to baseline and are paralleled by build-up of biological markers. Sparse data exist on long-term effects of vaping, and it is likely that repeated regular exposure to e-cig aerosol during vaping will lead to chronic conditions since there would be no return to baseline conditions as in the case of an isolated vaping episode. This brief review aims to highlight the potential of pairing MRI, with its extraordinary sensitivity to structure, physiology and metabolism at the holistic level, with biologic investigations targeting serum and cellular markers of inflammation and oxidative stress. Such a multi-modal framework should allow interpretation of the impact of e-cigarette vaping on vascular health at the organ level in the context of the underlying biological alterations. Applications of this approach to the study of other lifestyle-initiated pathologies including hypertension, hypercholesterolemia, and metabolic syndrome are indicated.

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.

Multiscale distribution of oxygen puddles in 1/8 doped YBa2Cu3O6.67.

Despite intensive research a physical explanation of high Tc superconductors remains elusive. One reason for this is that these materials have generally a very complex structure making useless theoretical models for a homogeneous system. Little is known on the control of the critical temperature by the space disposition of defects because of lack of suitable experimental probes. X-ray diffraction and neutron scattering experiments used to investigate y oxygen dopants in YBa2Cu3O6+y lack of spatial resolution. Here we report the spatial imaging of dopants distribution inhomogeneity in YBa2Cu3O6.67 using scanning nano X-ray diffraction. By changing the X-ray beam size from 1 micron to 300 nm of diameter, the lattice inhomogeneity increases. The ordered oxygen puddles size distribution vary between 6-8 nm using 1 × 1 µm(2) beam, while it is between 5-12 nm with a fat tail using the 300 × 300 nm(2) beam. The increased inhomogeneity at the nanoscale points toward a network of superconducting puddles made of ordered oxygen interstitials.