Changes In Cerebral Blood Volume Research Articles

Task-related oxygenation and cerebral blood volume changes estimated from NIRS signals in motor and cognitive tasks

Although functional near-infrared spectroscopy (fNIRS) has an advantage of simultaneously measuring changes in oxy- and deoxy-hemoglobin concentrations (Δ[HbO] and Δ[HbR]), only few analysis approaches exploit this advantage. As an extension of our recently proposed method (task-related component analysis, TRCA), this study proposes a new analysis method that extracts task-related oxygenation and cerebral blood volume (CBV) changes. In the original formulation of TRCA, task-relatedness of a signal is defined as consistent appearance of a same waveform in every task block, thereby constructing task-related components by maximizing inter-block covariance. The new method proposes that, in addition to maximizing inter-block covariance, the covariance between task-related Δ[HbO] and Δ[HbR] is maximized (TRCA+) or minimized (TRCA−) so that oxygenation and CBV changes are maximally contrasted. The proposed method (collectively called TRCA±) was formulated as a matrix eigenvalue problem, which can be solved efficiently with standard numerical methods, and was tested with a synthetic data generated by a balloon model, successfully recovering oxygenation and CBV components. fNIRS data from sensorimotor areas in a finger-tapping task and from prefrontal lobe in a working-memory (WM) task were then analyzed. For both tasks, the time courses and the spatial maps for oxygenation and CBV changes were found to differ consistently, providing certain constraints in the parameters of balloon models. In summary, TRCA can estimate task-related oxygenation and CBV changes simultaneously, thereby extending the applicability of fNIRS.

Abstract W MP9: Early Reperfusion with a Stentriever Device: A First Step to Superior Outcomes in TREVO2

Background: TREVO2 showed better outcomes after thrombectomy with the Trevo stentriever compared to Merci. We studied the impact of early reperfusion up to the first pass to explore the impact of device deployment on subsequent outcomes. Methods: Reperfusion during stentriever deployment and after the first pass in both arms (Merci and Trevo) of TREVO2 was quantified by cerebral blood volume (CBV) delivered to the downstream territory using perfusion angiography (perfAngio) software. Automatic, normalized extraction of CBV distal to anterior circulation occlusions was obtained from AP projections during arterial phase. CBV during deployment, after the first pass and sum of CBV up to the first pass (Σ CBV) were analyzed with respect to angiographic and clinical outcomes. Results: CBV was measured from DSA in 83 (34 Trevo, 49 Merci) occlusions in TREVO2. Clinical variables of this cohort were similar between device arms and with respect to others in the trial. During stentriever deployment, 29/34 cases demonstrated delivery of blood volume to downstream territory, averaging about 10% of the amount delivered after the first pass. Change in CBV from deployment to the first pass in 26/29 cases showed a further increase in 15 and decrease in 11, with re-occlusion in 4. CBV only after the first pass did not differ between Merci and Trevo (p=NS). CBV after first pass (p=0.06) and Σ CBV (p=0.03) both predict successful revascularization and demonstrate a moderate correlation with the time to sustained TICI 2a flow. Logistic regression analysis revealed that Σ CBV is a predictor of good clinical outcome (mRS 0-2) at day 90 (p=0.08) and use of Trevo further impacts outcome. Conclusions: Stentriever deployment achieves delivery of blood volume to the ischemic bed downstream. The amount of CBV delivered up to the first pass influences revascularization and good clinical outcomes.

Evaluation of activity-dependent functional pH and T1ρ response in the visual cortex

Recent experiments suggest that T1 relaxation in the rotating frame (T1ρ) detects localized metabolic changes in the human visual cortex induced by a flashing checkerboard task. Possible sources of the T1ρ signal include pH, glucose, and glutamate concentrations as well as changes in cerebral blood volume. In this study we explored the relationship of the T1ρ signal changes related to cerebral blood volume changes by employing inferior saturation pulses. Our hypothesis was that there would be a contribution of cerebral blood volume to the functional T1ρ signal, but a majority of the signal would correspond to metabolic changes. In addition, the relationship between T1ρ and pH was explored by manipulating the frequency of the flashing checkerboard and imaging with T1ρ, BOLD, and 31P spectroscopy. We hypothesized that T1ρ and pH changes would be sensitive to the stimulation frequency. To test this hypothesis, we used a full-field visual flashing checkerboard and varied the frequency between 1, 4, and 7Hz. Supporting our hypotheses, we found that approximately 73% of the measured signal change corresponds to metabolism in vivo and that increasing stimulation frequency increased responses measured by all three imaging modalities. The activation area detected by T1ρ overlapped to a large degree with that detected by BOLD, although the T1ρ response area was significantly smaller. 31P spectroscopy detected a greater acidosis with the higher stimulation frequencies. These observations suggest that, similar to the BOLD response, the magnitude of the T1ρ and pH response depends on stimulation frequency and is thus likely to be activity-dependent.

Practical Steps for Applying a New Dynamic Model to Near-Infrared Spectroscopy Measurements of Hemodynamic Oscillations and Transient Changes: Implications for Cerebrovascular and Functional Brain Studies

Perturbations in cerebral blood volume (CBV), blood flow (CBF), and metabolic rate of oxygen (CMRO2) lead to associated changes in tissue concentrations of oxy- and deoxy-hemoglobin (ΔO and ΔD), which can be measured by near-infrared spectroscopy (NIRS). A novel hemodynamic model has been introduced to relate physiological perturbations and measured quantities. We seek to use this model to determine functional traces of cbv(t) and cbf(t) - cmro2(t) from time-varying NIRS data, and cerebrovascular physiological parameters from oscillatory NIRS data (lowercase letters denote the relative changes in CBV, CBF, and CMRO2 with respect to baseline). Such a practical implementation of a quantitative hemodynamic model is an important step toward the clinical translation of NIRS. In the time domain, we have simulated O(t) and D(t) traces induced by cerebral activation. In the frequency domain, we have performed a new analysis of frequency-resolved measurements of cerebral hemodynamic oscillations during a paced breathing paradigm. We have demonstrated that cbv(t) and cbf(t) - cmro2(t) can be reliably obtained from O(t) and D(t) using the model, and that the functional NIRS signals are delayed with respect to cbf(t) - cmro2(t) as a result of the blood transit time in the microvasculature. In the frequency domain, we have identified physiological parameters (e.g., blood transit time, cutoff frequency of autoregulation) that can be measured by frequency-resolved measurements of hemodynamic oscillations. The ability to perform noninvasive measurements of cerebrovascular parameters has far-reaching clinical implications. Functional brain studies rely on measurements of CBV, CBF, and CMRO2, whereas the diagnosis and assessment of neurovascular disorders, traumatic brain injury, and stroke would benefit from measurements of local cerebral hemodynamics and autoregulation.

Weighing brain activity with the balance: a contemporary replication of Angelo Mosso’s historical experiment

Sir, Sandrone et al. (2012, 2013) rediscovered, translated, and commented on the manuscripts of Angelo Mosso (1882, 1884), in which Mosso described his ‘human circulation balance’; James (1890) described this as a ‘delicately balanced table which could tip downwards either at the head or the foot if the weight of either end were increased’. Mosso claimed that the balance allowed him to observe changes in cerebral blood volume associated with mental effort and emotional responses, and consequently the balance is regarded as the direct forerunner of modern non-invasive functional neuroimaging techniques. However, Sandrone et al. (2012, 2013) stated that ‘we have no direct evidence that the balance was really able, as stated, to measure changes in cerebral blood flow during acts of cognition … despite its proven ability to measure blood volume changes in various organs (e.g. lungs, feet, hands)’. In our laboratory, we recently constructed a balance similar to Mosso’s, and using modern data collection and analysis methods that were unavailable to Mosso, we investigated whether the balance was sensitive to changes in cerebral blood volume produced by modulating the level of mental activity. The construction and mechanism of our balance is depicted and explained in Fig. 1, and may be compared with Figs 3 and 8 in Sandrone et al. (2013), which show Mosso’s apparatus. The balance is a class 1 lever, in which the moment of a force measured at the fulcrum is proportional to the magnitude of the force and its distance from the fulcrum. With a participant lying on the balance across the fulcrum, if mental activity produces a net shift of blood towards or away from the head then this will produce a slight change in the centre of mass of the participant relative to the fulcrum of the lever, …

COHERENT HEMODYNAMICS SPECTROSCOPY BASED ON A PACED BREATHING PARADIGM — REVISITED

A novel hemodynamic model has been recently introduced, which provides analytical relationships between the changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen ( CMRO 2), and associated changes in the tissue concentrations of oxy- and deoxy-hemoglobin (ΔO and ΔD) measured with near-infrared spectroscopy (NIRS) [S. Fantini, Neuroimage85, 202–221 (2014)]. This novel model can be applied to measurements of the amplitude and phase of induced hemodynamic oscillations as a function of the frequency of oscillation, realizing the novel technique of coherent hemodynamics spectroscopy (CHS) [S. Fantini, Neuroimage85, 202–221 (2014); M. L. Pierro et al., Neuroimage85, 222–233 (2014)]. In a previous work, we have demonstrated an in vivo application of CHS on human subjects during paced breathing [M. L. Pierro et al., Neuroimage85, 222–233 (2014)]. In this work, we present a new analysis of the collected data during paced breathing based on a slightly revised formulation of the hemodynamic model and an efficient fitting procedure. While we have initially treated all 12 model parameters as independent, we have found that, in this new implementation of CHS, the number of independent parameters is eight. In this article, we identify the eight independent model parameters and we show that our previous results are consistent with the new formulation, once the individual parameters of the earlier analysis are combined into the new set of independent parameters.

A note on arterial to venous oxygen saturation as reference for NIRS-determined frontal lobe oxygen saturation in healthy humans

A note on arterial to venous oxygen saturation as reference for NIRS-determined frontal lobe oxygen saturation in healthy humans

Why we feel how we feel: Investigating cerebral blood flow during exercise

University of South Australia, Australia Introduction: The underlying mechanisms of why we feel how we feel during exercise remain unknown and until recently have been methodologically problematic to investigate. Local cerebral blood flow (which reflects activity of the frontal cortex [FC]) can be measured using Near Infrared Spectroscopy (NIRS), and is suitable for use during exercise. The objective of this study is to examine affective responses (i.e. feeling good or feeling bad) and activity in areas of the FC during exercise standardised tometabolic processes (i.e. gas exchange thresholds). Methods: In a fully repeated measures design, participants (n=25, 25.6 years, range21–34) completed an incremental exercise test to volitional exhaustion. Affective responses (using the Feeling Scale; range +5 [very good] to −5 [very bad]) and changes in cerebral oxygenation (O2Hb), deoxygenation (HHb), blood volume (tHb) and haemoglobin difference (HbDiff =O2Hb−HHb), were measured (micromolars; m) from the right (Areas 1–4R) and left (Areas 5–8L) FC (corresponding to Brodmann’s Areas 8,10 and 46) using multi-channel NIRS. Averages were taken at ventilatory threshold (VT), respiratory compensation point (RCP) and exhaustion (END). Results: A one-way Time (Pre-, VT, RCP, END) ANOVA indicated a significant (p<0.05) decline in affect (feeling good to bad) from Pre(M± SD, 2.4±1.1), to VT (1.5±1.0), RCP (−.8±1.7), and END (−2±1.8). A multivariate ANOVA revealed significant (p<0.05) Intensity (3; VT, RCP, END) by Area (8; 1–4R, 5–8L) interactions for O2Hb, tHb and HbDiff. From VT to END, HbDiff increased in Area 6L (+1.7±4.9) compared to Area 1R (−1.3±5.7). From RCP to END, O2Hb declined in Area 1R (−.8±2.2) whereas O2Hb and tHb increased in Area 4R (+1.4±2.5 and +3.2±3.6, respectively). At RCP, Areas 1R (O2Hb, HbDiff) and 6L (HbDiff); and at END, Areas 4R (O2Hb, tHb) and 6L (HbDiff) were associated with feeling bad (range r=−0.44, p<0.02 and −0.61 p<0.01). Discussion: Differential patterns of activity and asymmetry in the FC at exercise intensities above VT are associated with howwe feel during exercise. On-going research is exploring other potential sources of influence i.e. dispositional traits and the effect of intervention strategies on FC activity during exercise to further understand why we feel how we feel.

Changes in regional cerebral and peripheral blood volume during breath-hold diving in humans

Changes in regional cerebral and peripheral blood volume during breath-hold diving in humans

Relationship between early changes in cerebral blood volume and electrocortical activity after hypoxic–ischemic insult in newborn piglets

Background: Early changes in cerebral hemodynamics and depressed electrocortical activity have been reported after a hypoxic–ischemic (HI) insult. However, the relationship between these two parameters is unclear. This study aimed to examine the relationship between changes in cerebral blood volume (CBV) and cerebral Hb oxygen saturation (ScO2) after a HI insult and the low amplitude-integrated electroencephalography (aEEG) duration concomitantly observed. Methods: Sixteen newborn piglets obtained within 24h of birth were used (n=3 controls). Thirteen piglets were subjected to a HI insult of 20-min low-amplitude aEEG (<5μV, LAEEG), after which a low mean arterial blood pressure (<70% of baseline) was maintained for 10min. We measured changes in CBV and ScO2 using near-infrared time-resolved spectroscopy (TRS) and cerebral electrocortical activities using aEEG until 6h after the insult. Results: A positive correlation was observed between the LAEEG duration and CBV increase, but not ScO2, after the insult. Conclusion: These results suggest that a larger increase in CBV reflected a more severe failure in cerebral circulation to maintain cell membrane action potentials, which induced a more extended recovery period of electrocortical activity after the insult. We conclude that an early increase in CBV and longer LAEEG indicate severe brain injury.

Brainstem Structures Are Primarily Affected in an Experimental Model of Severe Scorpion Envenomation

Severe scorpion envenoming (SSE) is more frequent in children and is characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent evidence shows that the central nervous system (CNS) plays a key role in triggering the cascade of symptoms present in SSE. The age-dependent role of the CNS in SSE lethality may be summarized in 3 hypotheses: (1) the shown increased blood brain barrier permeability of infants to the toxins would especially and primarily compromise neurovegetative control areas, (2) the neurons within these areas have high affinity to the toxins, and (3) the neurovascular interaction is such that SSE metabolically compromises proper function of toxin-targeted areas. A pharmacological magnetic resonance imaging paradigm was used to evaluate localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30 min after the injection of TsTX, the most lethal toxin from the venom of the Tityus serrulatus scorpion. The brainstem showed significant rCBV reduction 1 min after TsTX administration, whereas rostral brain areas had delayed increase in rCBV (confirmed by laser Doppler measurements of cortical cerebral blood flow). Moreover, metabolic activity by 14C-2-deoxyglucose autoradiography showed the highest relative increase at the brainstem. To test whether TsTX has high affinity to brainstem neurons, the lateral ventricle was injected with Alexa Fluor 568 TsTX. Although some neurons showed intense fluorescence, the labeling pattern suggests that specific neurons were targeted. Altogether, these results suggest that brainstem areas involved in neurovegetative control are most likely within the primary structures triggering the cascade of symptoms present in SSE.

Slab-selective, BOLD-corrected VASO at 7 Tesla provides measures of cerebral blood volume reactivity with high signal-to-noise ratio

MRI methods sensitive to functional changes in cerebral blood volume (CBV) may map neural activity with better spatial specificity than standard functional MRI (fMRI) methods based on blood oxygen level dependent (BOLD) effect. The purpose of this study was to develop and investigate a vascular space occupancy (VASO) method with high sensitivity to CBV changes for use in human brain at 7 Tesla (T). To apply 7T VASO, several high-field-specific obstacles must be overcome, e.g., low contrast-to-noise ratio (CNR) due to convergence of blood and tissue T1 , increased functional BOLD signal change contamination, and radiofrequency field inhomogeneities. In the present method, CNR was increased by keeping stationary tissue magnetization in a steady-state different from flowing blood, using slice-selective saturation pulses. Interleaved acquisition of BOLD and VASO signals allowed correction for BOLD contamination. During visual stimulation, a relative CBV change of 28% ± 5% was measured, confined to gray matter in the occipital lobe with high sensitivity. By carefully considering all the challenges of high-field VASO and filling behavior of the relevant vasculature, the proposed method can detect and quantify CBV changes with high CNR in human brain at 7T.

Brain activation and neurochemistry

Dopamine (DA) disruption is implicated in the neuropathology of multiple brain disorders (schizophrenia, addiction, attention deficit hyperactivity disorder, Parkinson disease) and it is the main target of antipsychotics, stimulants, and antiparkinson medications. Although with PET and single-photon emission computed tomography one can measure DA signaling in the human brain, the application of these methodologies has been limited by its cost (PET), limited access to radiotracers, and the restrictions imposed by the use of radiation. Thus, alternative imaging modalities that overcome these limitations could expand their utilization in clinical research and would bring us closer to a more accessible biomarker for assessing brain DA activity in the clinical setting. In PNAS, Sander et al. (1) demonstrate a dynamic coupling between DA D2 receptor (D2R) occupancy level, a marker of DA neurotransmission, and the concomitant regional cerebral blood volume (rCBV) changes in the primate brain.

Best oral presentation: Glioblastomas with complete resection: Changes in relative cerebral blood volume in white matter irradiated

Best oral presentation: Glioblastomas with complete resection: Changes in relative cerebral blood volume in white matter irradiated

Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI

This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [(11)C]raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum. Moreover, similar temporal profiles were observed for specific binding estimates and changes in CBV. Injection of graded raclopride mass doses revealed a monotonic coupling between neurovascular responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system with an available PET tracer.

64-Slice spiral CT perfusion combined with vascular imaging of acute ischemic stroke for assessment of infarct core and penumbra

The aim of this study was to determine the value of computed tomography perfusion (CTP) parameters, including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time-to-peak (TP), in a clinical study of patients with stroke. Additionally, we determined which parameter or combination of parameters are reliable in detecting the presence of an infarct and penumbra. CTP was performed within 24 h of the onset of symptoms in 20 patients with possible stroke. Magnetic resonance imaging (MRI) was performed 3-7 days later and the threshold of the CTP was adjusted according to the results to provide CT images that correlated with the MRI; the MRI results were taken as the gold standard. CBV, CBF and TP contrast agent enhancement were calculated using the CT results. The CTP results were compared with the MRI findings. All CTP parameters were reliable in detecting the penumbra (P<0.001). In these parameters, changes of MTT were the most useful. CTP revealed various changes in CBF, CBV, MTT and TP in ischemic areas. CTP parameters were also reliable in detecting the infarct core (P<0.001). We determined that when detecting the penumbra, all CTP parameters are reliable, and when detecting cerebral ischemia, a combination of parameters should be used.

Aging diminishes cerebral blood volume and vasodilation in rats: non‐invasive absolute measurements by Near Infrared Spectroscopy

Brain microvasculature pathology is common in all forms of dementia, but it is unclear whether it precedes or follows neurodegeneration. Since aging is the strongest risk factor for dementia, we hypothesized that it would be accompanied by pathologic microvascular changes that would be discernible by non‐invasive absolute Near Infrared Spectroscopy (NIRS). We measured longitudinal changes in cerebral blood volume (CBV), at rest and in response to hypercapnia, in Wistar‐Kyoto rats, aged 4 months and one year later in middle‐age. Mean absolute CBV dropped with age from 4.42±0.25 to 2.71±0.17 ml/100gr tissue, reflecting a highly significant 37.7±4.3% age‐related decrease. Vasodilation also decreased with age: In middle‐aged rats, hypercapnia caused CBV to increase by only 0.121±0.044ml above resting values, compared to 0.175±0.027ml in young rats. These findings indicate that such microvascular changes may occur as early as middle age. The ability to detect and measure physiological evidence of structural and functional microvascular pathology during life can help to understand the role of microvascular pathology in dementia.

Imaging Patients with Psychosis and a Mouse Model Establishes a Spreading Pattern of Hippocampal Dysfunction and Implicates Glutamate as a Driver

The hippocampus in schizophrenia is characterized by both hypermetabolism and reduced size. It remains unknown whether these abnormalities are mechanistically linked. Here we addressed this question by using MRI tools that can map hippocampal metabolism and structure in patients and mouse models. In at-risk patients, hypermetabolism was found to begin in CA1 and spread to the subiculum after psychosis onset. CA1 hypermetabolism at baseline predicted hippocampal atrophy, which occurred during progression to psychosis, most prominently in similar regions. Next, we used ketamine to model conditions of acute psychosis in mice. Acute ketamine reproduced a similar regional pattern of hypermetabolism, while repeated exposure shifted the hippocampus to a hypermetabolic basal state with concurrent atrophy and pathology in parvalbumin-expressing interneurons. Parallel invivo experiments using the glutamate-reducing drug LY379268 and direct measurements of extracellular glutamate showed that glutamate drives both neuroimaging abnormalities. These findings show that hippocampal hypermetabolism leads to atrophy in psychotic disorder and suggest glutamate as a pathogenic driver.

Non‐invasive quantification of absolute cerebral blood volume during functional activation applicable to the whole human brain

Cerebral blood volume (CBV) changes in many diverse pathologic conditions, and in response to functional challenges along with changes in blood flow, blood oxygenation, and the cerebral metabolic rate of oxygen. The feasibility of a new method for non-invasive quantification of absolute cerebral blood volume that can be applicable to the whole human brain was investigated. Multi-slice data were acquired at 3 T using a novel inversion recovery echo planar imaging (IR-EPI) pulse sequence with varying contrast weightings and an efficient rotating slice acquisition order, at rest and during visual activation. A biophysical model was used to estimate absolute cerebral blood volume at rest and during activation, and oxygenation during activation, on data from 13 normal human subjects. Cerebral blood volume increased by 21.7% from 6.6 ± 0.8 mL/100 mL of brain parenchyma at rest to 8.0 ± 1.3 mL/100 mL of brain parenchyma in the occipital cortex during visual activation, with average blood oxygenation of 84 ± 2.1% during activation, comparing well with literature. The method is feasible, and could foster improved understanding of the fundamental physiological relationship between neuronal activity, hemodynamic changes, and metabolism underlying brain activation; complement existing methods for estimating compartmental changes; and potentially find utility in evaluating vascular health.

Cerebral Blood Volume Affects Blood–Brain Barrier Integrity in an Acute Transient Stroke Model

Insufficient vascular reserve after an ischemic stroke may induce biochemical cascades that subsequently deteriorate the blood-brain barrier (BBB) function. However, the direct relationship between poor cerebral blood volume (CBV) restoration and BBB disruption has not been examined in acute stroke. To quantify BBB integrity at acute stages of transient stroke, in particular for cases in which extravasation of the standard contrast agent (Gd-DTPA) is not observed, we adopted the water exchange index (WEI), a novel magnetic resonance image-derived parameter to estimate the water permeability across the BBB. The apparent diffusion coefficient (ADC) and R2 relaxation rate constant were also measured for outlining the tissue abnormality, while fractional CBV and WEI were quantified for assessing vascular alterations. The significantly decreased ADC and R2 in the ischemic cortices did not correlate with the changes in CBV or WEI. In contrast, a strong negative correlation between the ipsilesional WEI and CBV was found, in which stroke mice were clustered into two groups: (1) high WEI and low CBV and (2) normal WEI and CBV. The low CBV observed for mice with a disrupted BBB, characterized by a high WEI, indicates the importance of CBV restoration for maintaining BBB stability in acute stroke.