Oxygen extraction fraction mapping with multi-parametric quantitative BOLD MRI: Reduced transverse relaxation bias using 3D-GraSE imaging.

Magnetic resonance imaging (MRI)-based quantification of the blood-oxygenation-level-dependent (BOLD) effect allows oxygen extraction fraction (OEF) mapping. The multi-parametric quantitative BOLD (mq-BOLD) technique facilitates relative OEF (rOEF) measurements with whole brain coverage in clinically applicable scan times. Mq-BOLD requires three separate scans of cerebral blood volume and transverse relaxation rates measured by gradient-echo (1/T2∗) and spin-echo (1/T2). Although the current method is of clinical merit in patients with stroke, glioma and internal carotid artery stenosis (ICAS), there are relaxation measurement artefacts that impede the sensitivity of mq-BOLD and artificially elevate reported rOEF values. We posited that T2-related biases caused by slice refocusing imperfections during rapid 2D-GraSE (Gradient and Spin Echo) imaging can be reduced by applying 3D-GraSE imaging sequences, because the latter requires no slice selective pulses. The removal of T2-related biases would decrease overestimated rOEF values measured by mq-BOLD. We characterized effects of T2-related bias in mq-BOLD by comparing the initially employed 2D-GraSE and two proposed 3D-GraSE sequences to multiple single spin-echo reference measurements, both in vitro and in vivo. A phantom and 25 participants, including young and elderly healthy controls as well as ICAS-patients, were scanned. We additionally proposed a procedure to reliably identify and exclude artefact affected voxels. In the phantom, 3D-GraSE derived T2 values had 57% lower deviation from the reference. For in vivo scans, the formerly overestimated rOEF was reduced by -27% (p â€‹< â€‹0.001). We obtained rOEF â€‹= â€‹0.51, which is much closer to literature values from positron emission tomography (PET) measurements. Furthermore, increased sensitivity to a focal rOEF elevation in an ICAS-patient was demonstrated. In summary, the application of 3D-GraSE improves the mq-BOLD-based rOEF quantification while maintaining clinically feasible scan times. Thus, mq-BOLD with non-slice selective T2 imaging is highly promising to improve clinical diagnostics of cerebrovascular diseases such as ICAS.

Reliable estimation of microvascular flow patterns in patients with disrupted blood-brain barrier using dynamic susceptibility contrast MRI.

PURPOSE: To present and quantify the performance of a method to compute tissue hemodynamic parameters from dynamic susceptibility contrast (DSC) MRI data in brain tissue with possible nonintact blood-brain barrier. THEORY AND MATERIALS AND METHODS: We propose a Bayesian scheme to obtain perfusion metrics, including capillary transit-time heterogeneity (CTH), from DSC-MRI data in the presence of contrast agent extravasation. Initial performance assessment is performed through simulations. Next, we assessed possible over- or under correction for tracer extravasation in two patients receiving contrast agent preloading and two patients not receiving preloading. Perfusion metrics for N = 60 patients diagnosed with either grade III (N = 14) or grade IV gliomas (N = 46) were analyzed across tissue types to evaluate the ability to distinguish regions with different hemodynamic patterns. Finally, N = 4 patient cases undergoing anti-angiogenic treatment are evaluated qualitatively for treatment effects. All patient data were acquired at 3.0 Tesla. RESULTS: The simulation studies showed good robustness against low signal-to-noise ratios, exemplified with Pearson correlations of R = 0.833 (mean transit time) and R = 0.738 (CTH) at signal-to-noise ratio = 20. Region-of-interest analysis of the N = 60 glioma patients showed that cerebral blood volume (CBV) significantly separated enhancing core from edema (grade IV: P < 10-8 , grade III: P < 0.05) and enhancing core from normal appearing ipsilateral white matter (NAWM) (grade IV: P < 10-8 , grade III: P < 0.05). The microvascular parameters were particularly good in separating edematous tissue from NAWM tissue in grade IV gliomas (P < 0.001). Finally, CTH separated grade III and grade IV core tissue (P < 0.05). CONCLUSION: We have demonstrated robustness of the proposed Bayesian algorithm against experimental noise and demonstrated complementary value in microvascular parameters to the CBV parameter in separating tissue types in gliomas. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:537-549.

Global intravascular and local hyperoxia contrast phase-based blood oxygenation measurements.

The measurement of venous cerebral blood oxygenation (Yv) has potential applications in the study of patient groups where oxygen extraction and/or metabolism are compromised. It is also useful for fMRI studies to assess the stimulus-induced changes in Yv, particularly since basal Yv partially accounts for inter-subject variation in the haemodynamic response to a stimulus. A range of MRI-based methods of measuring Yv have been developed recently. Here, we use a method based on the change in phase in the MR image arising from the field perturbation caused by deoxygenated haemoglobin in veins. We build on the existing phase based approach (Method I), where Yv is measured in a large vein (such as the superior sagittal sinus) based on the field shift inside the vein with assumptions as to the vein's shape and orientation. We demonstrate two novel modifications which address limitations of this method. The first modification (Method II), maps the actual form of the vein, rather than assume a given shape and orientation. The second modification (Method III) uses the intra and perivascular phase change in response to a known change in Yv on hyperoxia to measure normoxic Yv in smaller veins. Method III can be applied to veins whose shape, size and orientation are not accurately known, thus allowing more localised measures of venous oxygenation. Results demonstrate that the use of an overly fine spatial filter caused an overestimation in Yv for Method I, whilst the measurement of Yv using Method II was less sensitive to this bias, giving Yv = 0.62 ± 0.03. Method III was applied to mapping of Yv in local veins across the brain, yielding a distribution of values with a mode of Yv = 0.661 ± 0.008.

Activation and depression of neural and hemodynamic responses induced by the intracortical microstimulation and visual stimulation in the mouse visual cortex.

Objective. Intracortical microstimulation (ICMS) can be an effective method for restoring sensory perception in contemporary brain-machine interfaces. However, the mechanisms underlying better control of neuronal responses remain poorly understood, as well as the relationship between neuronal activity and other concomitant phenomena occurring around the stimulation site.Approach. Different microstimulation frequencies were investigatedin vivoon Thy1-GCaMP6s mice using widefield and two-photon imaging to evaluate the evoked excitatory neural responses across multiple spatial scales as well as the induced hemodynamic responses. Specifically, we quantified stimulation-induced neuronal activation and depression in the mouse visual cortex and measured hemodynamic oxyhemoglobin and deoxyhemoglobin signals using mesoscopic-scale widefield imaging.Main results. Our calcium imaging findings revealed a preference for lower-frequency stimulation in driving stronger neuronal activation. A depressive response following the neural activation preferred a slightly higher frequency stimulation compared to the activation. Hemodynamic signals exhibited a comparable spatial spread to neural calcium signals. Oxyhemoglobin concentration around the stimulation site remained elevated during the post-activation (depression) period. Somatic and neuropil calcium responses measured by two-photon microscopy showed similar dependence on stimulation parameters, although the magnitudes measured in soma was greater than in neuropil. Furthermore, higher-frequency stimulation induced a more pronounced activation in soma compared to neuropil, while depression was predominantly induced in soma irrespective of stimulation frequencies.Significance. These results suggest that the mechanism underlying depression differs from activation, requiring ample oxygen supply, and affecting neurons. Our findings provide a novel understanding of evoked excitatory neuronal activity induced by ICMS and offer insights into neuro-devices that utilize both activation and depression phenomena to achieve desired neural responses.

Age-related decline in cerebral oxygen consumption in multiple sclerosis.

Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (-15%, p = 0.002) and decreased significantly with age in patients relative to the controls (-1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.

Unveiling metabolic patterns in dementia: Insights from high-resolution quantitative blood-oxygenation-level-dependent MRI.

BACKGROUND: Oxygen extraction fraction (OEF) and deoxyhemoglobin (DoHb) levels reflect variations in cerebral oxygen metabolism in demented patients. PURPOSE: Delineating the metabolic profiles evident throughout different phases of dementia necessitates an integrated analysis of OEF and DoHb levels. This is enabled by leveraging high-resolution quantitative blood oxygenation level dependent (qBOLD) analysis of magnitude images obtained from a multi-echo gradient-echo MRI (mGRE) scan performed on a 3.0 Tesla scanner. METHODS: Achieving superior spatial resolution in qBOLD necessitates the utilization of an mGRE scan with only four echoes, which in turn limits the number of measurements compared to the parameters within the qBOLD model. Consequently, it becomes imperative to discard non-essential parameters to facilitate further analysis. This process entails transforming the qBOLD model into a format suitable for fitting the log-magnitude difference (L-MDif) profiles of the four echo magnitudes present in each brain voxel. In order to bolster spatial specificity, the log-difference qBOLD model undergoes refinement into a representative form, termed as r-qBOLD, particularly when applied to class-averaged L-MDif signals derived through k-means clustering of L-MDif signals from all brain voxels into a predetermined number of clusters. The agreement between parameters estimated using r-qBOLD for different cluster sizes is validated using Bland-Altman analysis, and the model's goodness-of-fit is evaluated using a χ 2 ${\chi ^2}$ -test. Retrospective MRI data of Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented patients without neuropathological disorders, pacemakers, other implants, or psychiatric disorders, who completed a minimum of three visits prior to MRI enrolment, are utilized for the study. RESULTS: Utilizing a cohort comprising 30 demented patients aged 65-83 years in stages 4-6 representing mild, moderate, and severe stages according to the clinical dementia rating (CDR), matched with an age-matched non-demented control group of 18 individuals, we conducted joint observations of OEF and DoHb levels estimated using r-qBOLD. The observations elucidate metabolic signatures in dementia based on OEF and DoHb levels in each voxel. Our principal findings highlight the significance of spatial patterns of metabolic profiles (metabolic patterns) within two distinct regimes: OEF levels exceeding the normal range (S1-regime), and OEF levels below the normal range (S2-regime). The S1-regime, accompanied by low DoHb levels, predominantly manifests in fronto-parietal and perivascular regions with increase in dementia severity. Conversely, the S2-regime, accompanied by low DoHb levels, is observed in medial temporal (MTL) regions. Other regions with abnormal metabolic patterns included the orbitofrontal cortex (OFC), medial-orbital prefrontal cortex (MOPFC), hypothalamus, ventro-medial prefrontal cortex (VMPFC), and retrosplenial cortex (RSP). Dysfunction in the OFC and MOPFC indicated cognitive and emotional impairment, while hypothalamic involvement potentially indicated preclinical dementia. Reduced metabolic activity in the RSP suggested early-stage AD related functional abnormalities. CONCLUSIONS: Integrated analysis of OEF and DoHb levels using r-qBOLD reveals distinct metabolic signatures across dementia phases, highlighting regions susceptible to neuronal loss, vascular involvement, and preclinical indicators.

Blood oxygenation level-dependent (BOLD)-based techniques for the quantification of brain hemodynamic and metabolic properties - theoretical models and experimental approaches.

The quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for the understanding of normal human brain operation, as well as the pathophysiology of neurological disorders. It can also be of great importance for the evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and coworkers of the blood oxygenation level-dependent (BOLD) contrast opened up the possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require the development of theoretical models connecting the MRI signal to brain structure and function, and the design of experimental techniques allowing MR measurements to be made of the salient features of theoretical models. In this review, we discuss several such theoretical models and experimental methods for the quantification of brain hemodynamic and metabolic properties. The review's main focus is on methods for the evaluation of the oxygen extraction fraction (OEF) based on the measurement of the blood oxygenation level. A combination of the measurement of OEF and the cerebral blood flow (CBF) allows an evaluation to be made of the cerebral metabolic rate of oxygen consumption (CMRO2 ). We first consider in detail the magnetic properties of blood - magnetic susceptibility, MR relaxation and theoretical models of the intravascular contribution to the MR signal under different experimental conditions. We then describe a 'through-space' effect - the influence of inhomogeneous magnetic fields, created in the extravascular space by intravascular deoxygenated blood, on the formation of the MR signal. Further, we describe several experimental techniques taking advantage of these theoretical models. Some of these techniques - MR susceptometry and T2 -based quantification of OEF - utilize the intravascular MR signal. Another technique - quantitative BOLD - evaluates OEF by making use of through-space effects. In this review, we target both scientists just entering the MR field and more experienced MR researchers interested in the application of advanced BOLD-based techniques to the study of the brain in health and disease.

Capillary transit time heterogeneity inhibits cerebral oxygen metabolism in patients with reduced cerebrovascular reserve capacity from steno-occlusive disease.

The healthy cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A disruption of this homogeneity may inhibit the extraction of oxygen. A high degree of capillary transit time heterogeneity (CTH) describes that some capillaries have very low blood flows, while others have excessively high blood flows and consequently short transit times. Very short transit times could hinder the oxygen extraction due to insufficient time for diffusion of oxygen into the tissue. CTH could be a consequence of cerebral vessel disease. We examined whether patients with cerebral steno-occlusive vessel disease demonstrate high CTH and if elevation of cerebral blood flow (CBF) by administration of acetazolamide (ACZ) increases the cerebral metabolic rate of oxygen (CMRO2), or if some patients demonstrate reduced CMRO2 related to detrimental CTH. Thirty-four patients and thirty-one healthy controls participated. Global CBF and CMRO2 were acquired using phase-contrast MRI. Regional brain maps of CTH were acquired using dynamic contrast-enhanced MRI. Patients with impaired cerebrovascular reserve capacity demonstrated elevated CTH and a significant reduction of CMRO2 after administration of ACZ, which could be related to high CTH. Impaired oxygen extraction from CTH could be a contributing part of the declining brain health observed in patients with cerebral vessel disease.

Cortical oxygen extraction fraction using quantitative BOLD MRI and cerebral blood flow during vasodilation.

Introduction: We aimed to demonstrate non-invasive measurements of regional oxygen extraction fraction (OEF) from quantitative BOLD MRI modeling at baseline and after pharmacological vasodilation. We hypothesized that OEF decreases in response to vasodilation with acetazolamide (ACZ) in healthy conditions, reflecting compensation in regions with increased cerebral blood flow (CBF), while cerebral metabolic rate of oxygen (CMRO2) remained unchanged. We also aimed to assess the relationship between OEF and perfusion in the default mode network (DMN) regions that have shown associations with vascular risk factors and cerebrovascular reactivity in different neurological conditions. Material and methods: Eight healthy subjects (47 ± 13 years, 6 female) were scanned on a 3 T scanner with a 32-channel head coil before and after administration of 15 mg/kg ACZ as a pharmacological vasodilator. The MR imaging acquisition protocols included: 1) A Gradient Echo Slice Excitation Profile Imaging Asymmetric Spin Echo scan to quantify OEF, deoxygenated blood volume, and reversible transverse relaxation rate (R2 ') and 2) a multi-post labeling delay arterial spin labeling scan to measure CBF. To assess changes in each parameter due to vasodilation, two-way t-tests were performed for all pairs (baseline versus vasodilation) in the DMN brain regions with Bonferroni correction for multiple comparisons. The relationships between CBF versus OEF and CBF versus R2' were analyzed and compared across DMN regions using linear, mixed-effect models. Results: During vasodilation, CBF significantly increased in the medial frontal cortex (P=0.004), posterior cingulate gyrus (pCG) (P=0.004), precuneus cortex (PCun) (P=0.004), and occipital pole (P=0.001). Concurrently, a significant decrease in OEF was observed only in the pCG (8.8%, P=0.003) and PCun (8.7%,P=0.001). CMRO2 showed a trend of increased values after vasodilation, but these differences were not significant after correction for multiple comparisons. Although R2' showed a slightly decreasing trend, no statistically significant changes were found in any regions in response to ACZ. The CBF response to ACZ exhibited a stronger negative correlation with OEF (ß=-0.104±0.027; t=-3.852,P<0.001), than with R2' (ß=-0.016±0.006; t=-2.692,P=0.008). Conclusion: Quantitative BOLD modeling can reliably measure OEF across multiple physiological conditions and captures vascular changes with higher sensitivity than R2' values. The inverse correlation between OEF and CBF across regions in DMN, suggests that these two measurements, in response to ACZ vasodilation, are reliable indicators of tissue health in this healthy cohort.

Hypoxic breathing produces more intense hypoxemia in elderly women than in elderly men.

Background: Brief hypoxic exposures are increasingly applied as interventions for aging-related conditions. To optimize the therapeutic impact of hypoxia, knowledge of the sex-related differences in physiological responses to hypoxia is essential. This study compared hypoxia-induced hypoxemic responses in elderly men and women. Methods: Seven elderly men (70.3 ± 6.0 years old) and nine women (69.4 ± 5.5 years old) breathed 10% O2 for 5 min while arterial (SaO2; transcutaneous photoplethysmography) and cerebral tissue O2 saturation (ScO2; near-infrared spectroscopy), ventilatory frequency, tidal volume, minute-ventilation, and partial pressures of end-tidal O2 (PETO2) and CO2 (mass spectrometry) were continuously monitored. Cerebral tissue oxygen extraction fraction (OEF) equaled (SaO2-ScO2)/SaO2. Results: During 5 min hypoxia SaO2 fell from 97.0 ± 0.8% to 80.6 ± 4.6% in the men and from 96.3 ± 1.4% to 72.6 ± 4.0% in the women. The slope ΔSaO2/min was steeper in the women than the men (-4.71 ± 0.96 vs. -3.24 ± 0.76%/min; p = 0.005). Although SaO2 fell twice as sharply per unit decrease in PETO2 in the women than the men (-1.13 ± 0.11 vs. -0.54 ± 0.06%/mmHg; p = 0.003), minute-ventilation per unit hypoxemia increased less appreciably in the women (-0.092 ± 0.014 vs. -0.160 ± 0.021 L/min/%; p = 0.023). OEF fell with hypoxia duration in the women, but remained stable in the men. Conclusion: During 5 min hypoxic breathing, elderly women experience more intense hypoxemia and reduced chemoreflex sensitivity vs. their male counterparts, which may lower OEF stability in women despite augmented O2 dissociation from hemoglobin during hypoxia. These sex-related differences merit attention when implementing brief hypoxic exposures for therapeutic purposes.

Application of Cluster Analysis of Time Evolution for Magnetic Resonance Imaging -Derived Oxygen Extraction Fraction Mapping: A Promising Strategy for the Genetic Profile Prediction and Grading of Glioma.

Background: The intratumoral heterogeneity of oxygen metabolism and angiogenesis are core hallmarks of glioma, unveiling that genetic aberrations associated with magnetic resonance imaging (MRI) phenotypes may aid in the diagnosis and treatment of glioma. Objective: To explore the predictability of MRI-based oxygen extraction fraction (OEF) mapping using cluster analysis of time evolution (CAT) for genetic profiling and glioma grading. Methods: Ninety-one patients with histopathologically confirmed glioma were examined with CAT for quantitative susceptibility mapping and quantitative blood oxygen level-dependent magnitude-based OEF mapping and dynamic contrast-enhanced (DCE) MRI. Imaging biomarkers, including oxygen metabolism (OEF) and angiogenesis [volume transfer constant, cerebral blood volume (CBV), and cerebral blood flow], were investigated to predict IDH mutation, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, receptor tyrosine kinase (RTK) subgroup, and differentiation of glioblastoma (GBM) vs. lower-grade glioma (LGG). The corresponding DNA sequencing was also obtained. Results were compared with DCE-MRI using receiver operating characteristic (ROC) analysis. Results: IDH1-mutated LGGs exhibited significantly lower OEF and hypoperfusion than IDH wild-type tumors (all p < 0.01). OEF and perfusion metrics showed a tendency toward higher values in MGMT unmethylated GBM, but only OEF retained significance (p = 0.01). Relative prevalence of RTK alterations was associated with increased OEF (p = 0.003) and perfusion values (p < 0.05). ROC analysis suggested OEF achieved best performance for IDH mutation detection [area under the curve (AUC) = 0.828]. None of the investigated parameters enabled prediction of MGMT status except OEF with a moderate AUC of 0.784. Predictive value for RTK subgroup was acceptable by using OEF (AUC = 0.764) and CBV (AUC = 0.754). OEF and perfusion metrics demonstrated excellent performance in glioma grading. Moreover, mutational landscape revealed hypoxia or angiogenesis-relevant gene signatures were associated with specific imaging phenotypes. Conclusion: CAT for MRI-based OEF mapping is a promising technology for oxygen measurement and along with perfusion MRI can predict genetic profiles and tumor grade in a non-invasive and clinically relevant manner. Clinical Impact: Physiological imaging provides an in vivo portrait of genetic alterations in glioma and offers a potential strategy for non-invasively selecting patients for individualized therapies.

Quantitative assessment of cerebral metabolism and hemodynamics in small-for-gestational-age (SGA) newborns.

BACKGROUND: Small-for-gestational-age (SGA) newborns represent approximately 10% of births worldwide and 45% of births in some countries. It has been suggested that SGA might cause learning difficulties and behavioral abnormalities in childhood, yet the neurobiological basis for this is poorly understood. In this study, we employed several advanced imaging techniques-including T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI), and phase-contrast (PC) MRI-to quantify oxygen extraction fraction (OEF), global cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) to elucidate pathophysiological vulnerabilities of SGA neonates. METHODS: A total of 41 newborns were enrolled in this study, consisting of 29 SGA and 12 appropriate-for-gestational-age (AGA) neonates. The SGA group was further divided into subgroups with and without abnormalities on structural MRI, denoted as SGA-a (N=17) and SGA-n (N=12). TRUST and PC MRI were performed to determine OEF, CBF, and CMRO2. Linear regression analyses were performed to examine physiological parameters' dependence on scan age, gender, and group. Similar analyses were conducted for birth weight and brain volume. Receiver operating characteristic (ROC) curves were used to test physiological parameters' ability to different diagnostic groups. RESULTS: Regression analysis revealed that CMRO2 was significantly lower (P=0.04) in the SGA group relative to the AGA group. When further stratifying the SGA participants into SGA-a and SGA-n subgroups, the SGA-a subgroup was found to have the most pronounced physiological deficits, with a lower CMRO2 (P=0.004) and lower CBF (P=0.007) than those in the AGA group. Conversely, CMRO2 (P=0.40) and CBF (P=0.90) in the SGA-n subgroup were not different from those of the AGA group. Accordingly, CBF in the SGA-a group was significantly lower (P=0.01) than that of the SGA-n group and CMRO2 also showed a difference (P=0.09). Additionally, CMRO2 (P=0.002) and CBF (P=0.04) showed an age-related increase during this early developmental period. In analyzing the SGA-a subgroup relative to the remaining neonates, the area under curve (AUC) values were 0.6, 0.6, 0.7, 0.8, and 0.5 for birth weight, OEF, CMRO2, CBF, and brain volume, respectively. In analyzing the SGA-a subgroup relative to the SGA-n subgroup, AUC values were 0.5, 0.6, 0.7, 0.8, and 0.5 for birth weight, OEF, CMRO2, CBF, and brain volume. CONCLUSIONS: Structural damage in SGA-a neonates is associated with cerebral hemodynamic and metabolic deficits. SGA neonates with normal CBF and CMRO2reveal minimal structural abnormalities. Physiological imaging may help identify SGA patients at high risk of developing irreversible brain damage.

Effect of pre-surgery assessments on the prognosis of patients received extracranial-intracranial bypass surgery.

BACKGROUND: Extracranial-intracranial (EC-IC) bypass surgery has been used to improve the conditions of cerebral ischemia symptoms for selected patients resulting from diverse complications such as stroke and atherosclerotic disease. However, several clinical trials showed EC-IC bypass surgery failed to prevent recurrent ischemic stroke in certain patients. OBJECTIVE: Our clinical trial aimed to investigate whether there is a correlation between pre-surgery assessments and prognosis of patients received EC-IC bypass operation. METHODS: We divided all patients into 4 groups according to their compensatory stages of cerebral ischemia. The values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and oxygen extraction fraction (OEF) were obtained by computed tomography perfusion (CTP), single photon emission computed tomography (SPECT), and positron emission tomography (PET) at different time points before and after EC-IC bypass surgery. We assessed the correlations between the compensatory stage with modified Rankin scale (mRS) scores, survival rates, stroke and TIA incidences over the 12 months after surgery. RESULTS: Patients with normal CBF, normal or increased CBV, and normal OEF tended to have a better prognosis after the EI-CI bypass operation than patients with abnormal CBF, CBV and OEF. However, patients with abnormal CBF and CBV, and increased OEF showed elevated mRS, less survival rates, and higher stroke and TIA incidences over the 12 months after surgery, compared to the groups with normal CBF, CBV and OEF. CONCLUSIONS: Our results suggest that a defined compensatory stage of cerebral ischemia might be useful for the prognosis of patients receiving EI-CI bypass surgery.

Increased cortical capillary transit time heterogeneity in Alzheimer's disease: a DSC-MRI perfusion study.

Alzheimer's disease (AD) is characterized by the accumulation of hyperphosphorylated tau and neurotoxic Aß in the brain parenchyma. Hypoxia caused by microvascular changes and disturbed capillary flows could stimulate this build-up of AD-specific proteins in the brain. In this study, we compared cerebral microcirculation in a cohort of AD and mild cognitive impairment (MCI) patients with that of age-matched controls, all without a history of diabetes or of hypertension for more than 2 years, using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Vascular flow disturbances were quantified using a parametric model and mapped to the mid-cortical surface for group-wise statistical analysis. We found widespread hypoperfusion in patients compared with controls and identified areas of increased relative capillary transit time heterogeneity (RTH), consistent with low tissue oxygen tension. Notably, RTH was positively correlated with white matter hyperintensities and positively correlated with symptom severity in the patient cohort. These correlations extended over large parts of the temporal, parietal, and frontal cortices. The results support the hypothesis of disturbed capillary flow patterns in AD and suggest that DSC-MRI may provide imaging biomarkers of impaired cerebral microcirculation in AD.