Changes In Cerebral Blood Volume Research Articles

Imaging the response to deep brain stimulation in rodent using functional ultrasound

In this study, we explored the feasibility of using functional ultrasound (fUS) imaging to visualize cerebral activation associated with thalamic deep brain stimulation (DBS), in rodents. The ventrolateral (VL) thalamus was stimulated using electrical pulses of low and high frequencies of 10 and 100 Hz, respectively, and multiple voltages (1–7 V) and pulse widths (50–1500 μs). The fUS imaging demonstrated DBS-evoked activation of cerebral cortex based on changes of cerebral blood volume, specifically at the primary motor cortex (PMC). Low frequency stimulation (LFS) demonstrated significantly higher PMC activation compared to higher frequency stimulation (HFS), at intensities (5–7 V). Whereas, at lower intensities (1–3 V), only HFS demonstrated visible PMC activation. Further, LFS-evoked cerebral activation was was primarily located at the PMC. Our data presents the functionality and feasibility of fUS imaging as an investigational tool to identify brain areas associated with DBS. This preliminary study is an important stepping stone towards conducting real-time functional ultrasound imaging of DBS in awake and behaving animal models, which is of significant interest to the community for studying motor-related disorders.

Mathematical Modelling in Hydrocephalus.

Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral blood flow (CBF) dynamics in the pathogenesis of hydrocephalus and suggest the role of mathematical modeling in studying these complex interactions. This narrative review discusses mathematical models of CSF and CBF dynamics, including Marmarou's compartmental model of CSF spaces and a model of cardiac changes in cerebral arterial blood volume. The diagnostic utility of CSF compensatory parameters is described along with current information on secondary model-based indices of cerebral hemodynamics in hydrocephalus. Compensatory parameters derived from the model of CSF circulation have long been used in the diagnosis and management of hydrocephalus patients. However, recent studies using mathematical models of cerebral circulation also show alterations in CBF dynamics, and model-based indices of cerebral hemodynamics, which can be calculated non-invasively using transracranial Doppler ultrasonography, can be used as a complementary source of information about the state of the cerebrospinal space.

Spectral Cerebral Blood Volume Accounting for Noninvasive Estimation of Changes in Cerebral Perfusion Pressure in Patients with Traumatic Brain Injury.

We present the application of a new method for non-invasive cerebral perfusion pressure estimation (spectral nCPP or nCPPs) accounting for changes in transcranial Doppler-derived pulsatile cerebral blood volume. Primarily, we analysed cases in which CPP was changing (delta [∆],magnitude of changes]): (1) rise during vasopressor-induced augmentation of ABP (N=16); and (2) spontaneous changes in intracranial pressure (ICP) during plateau waves (N=14). Secondarily, we assessed nCPPs in a larger cohort in which CPP presented a wider range of values. The average correlation in the time domain between CPP and nCPPs for patients undergoing an induced rise in arterial blood pressure (ABP) was 0.95±0.07. For the greater traumatic brain injury (TBI) cohort, this correlation was 0.63±0.37. ∆ correlations between mean values of CPP and nCPPs were 0.73 (p=0.002) and 0.78 (p<0.001) respectively for induced rise in ABP and ICP plateau wave cohorts. The area under the curve (AUC) for ∆CPP was of 0.71 with a 95% confidence interval of 0.54-0.88. To detect low CPP, AUC was 0.817 with a 95% confidence interval of 0.79-0.85. nCPPs can reliably identify changes in direct CPP across time and the magnitude of these changes in absolute values. The ability to detect changes in CPP is reasonable but stronger for detecting low CPP, ≤70mmHg.

Differential Changes in Arteriolar Cerebral Blood Volume between Parkinson's Disease Patients with Normal and Impaired Cognition and Mild Cognitive Impairment (MCI) Patients without Movement Disorder - An Exploratory Study.

Cognitive impairment amongst Parkinson’s disease (PD) patients is highly prevalent and associated with an increased risk of dementia. There is growing evidence that altered cerebrovascular functions contribute to cognitive impairment. Few studies have compared cerebrovascular changes in PD patients with normal and impaired cognition and those with mild-cognitive-impairment (MCI) without movement disorder. Here, we investigated arteriolar-cerebral-blood-volume (CBVa), an index reflecting the homeostasis of the most actively regulated segment in the microvasculature, using advanced MRI in various brain regions in PD and MCI patients and matched controls. Our goal is to find brain regions with altered CBVa that are specific to PD with normal and impaired cognition, and MCI-without-movement-disorder, respectively. In PD patients with normal cognition (n=10), CBVa was significantly decreased in the substantia nigra, caudate and putamen when compared to controls. In PD patients with impaired cognition (n=6), CBVa showed a decreasing trend in the substantia nigra, caudate and putamen, but was significantly increased in the presupplementary motor area and intracalcarine gyrus compared to controls. In MCI-patients-without-movement-disorder (n=18), CBVa was significantly increased in the caudate, putamen, hippocampus and lingual gyrus compared to controls. These findings provide important information for efforts towards developing biomarkers for the evaluation of potential risk of PD dementia (PDD) in PD patients. The current study is limited in sample size and therefore is exploratory in nature. The data from this pilot study will serve as the basis for power analysis for subsequent studies to further investigate and validate the current findings.

NIMG-19. USING FUNCTIONAL ULTRASOUND (FUS) TO MAP BRAIN FUNCTIONALITY AND TUMOR VASCULATURE WITH MICROMETER-MILLISECOND PRECISION

Abstract OBJECTIVE In the early 20th century, Dr. Cushing first demonstrated the use of electrical stimulation mapping (ESM) to define motor and sensory cortices during neurosurgical procedures. Essentially, little has changed in what guides a neurosurgeon’s intra-operative decision-making since. Inherent limitations of ESM such as limited depth penetration and risk of seizure elicitation, warrant the development of new image-guided resection tools. Here, we present functional Ultrasound (fUS)-imaging as a new, high-resolution tool to guide intra-operative decision-making during awake tumor removal. METHODS fUS relies on high-frame-rate ultrasound, which offers images at thousands of frames-per-second. As such, fUS is sensitive to very small motions caused by vascular dynamics (µDoppler), allowing measurements of changes in cerebral blood volume (CBV). This facilitates the possibility to 1) detect functional response, as CBV-changes reflect changes in metabolism of activated neurons through neurovascular coupling and 2) visualize high-resolution vascular morphology of tumor and healthy tissue. During conventional awake craniotomy surgery, n= 10 patients were asked to perform 60s functional tasks to elicit cortical responses. Simultaneously, a conventional 5 MHz ultrasound probe connected to an experimental acquisition system, was placed over ESM-defined functional areas. After image acquisition, correlation analyses with the corresponding tasks revealed functional and non-functional areas. In addition, 3D vascular maps were reconstructed from subsequent 2D-Power Doppler Images (PDIs). RESULTS fUS was able to detect functional areas as activated using conventional motor tasks, as well as complex language-related tasks. In addition, both 2D-PDIs and 3D-reconstructions revealed the ability of fUS to detect unique high-resolution onco-vascular characteristics in high- and low-grade malignancies. In all cases, images were acquired with micrometer-millisecond (300 µm, 1.5-2.0 msec) precision at imaging depths &amp;gt; 5 cm. CONCLUSIONS Applying fUS-imaging successfully in this awake craniotomy series serves as a clear demonstration of the technique’s revolutionary potential for maximizing safe tumor removal.

Assessing Dynamic Cerebral Autoregulation in Patients with Sickle Cell Disease Using Near-Infrared Spectroscopy and Paced Breathing

Introduction. Sickle cell disease (SCD) is caused by hemoglobin S polymerization leading to vaso-occlusion, small vessel disease, and reduced tissue oxygen saturation. Noninvasive assessments and screening of small vessel disease and decreased oxygen saturation in select organs, like the brain, are poorly developed. Cerebral autoregulation, a mechanism that ensures cerebral blood flow (CBF) remains constant with changes in mean arterial pressure, is impaired with and is a marker of small vessel disease. Frequency-domain near-infrared spectroscopy (FD-NIRS) can be used as a noninvasive technique to measure cerebral autoregulation by recording cerebral microvascular changes in hemoglobin concentration that are related to cerebral blood flow. Transfer function analysis is a method to noninvasively quantify the relationship between measured physiologic signals, and can be used to estimate cerebral autoregulation. In this study, we hypothesized patients with SCD have impaired cerebral autoregulation and reduced tissue oxygen saturation, which we evaluated via FD-NIRS with transfer function analysis, as compared to healthy controls. Methods. All patients provided informed consent under an IRB protocol approved by the University of Pittsburgh and Carnegie Mellon University. Patients with SCD (n = 11) and healthy, race-matched controls (n =14) were enrolled. All participants sat upright in a chair with probes of a commercial multi-distance FD-NIRS apparatus applied to their forehead in a dark room (Fig. 1A). We used paced breathing to dynamically induce controlled changes in the microvascular tone at 0.1, 0.125, and 0.1667 Hz, spanning normal to more challenging breathing rates, with a visual metronome guiding each paced breathing session (Fig.1.B). To validate each breathing pace, we recorded the participants' respiratory rate via a belt placed around their chest, and their mean arterial pressure through a finger and arm cuff attached to a beat-to-beat finger plethysmographer (Fig.1.A). We used the modified Beer-Lambert law to calculate changes in oxy-hemoglobin (O), deoxy-hemoglobin (D), and total hemoglobin (T) concentrations. Data was bandpass-filtered around the paced breathing frequencies, and the Hilbert transform was applied to calculate the amplitude ratios, |D|/|O|, and phase latency, Arg(D)−Arg(O). The tissue oxygen saturation of hemoglobin, StO2 (mean ±SD), was computed based on an average baseline of two minutes. Results. Arg(D)−Arg(O) and |D|/|O| are shown for controls and patients at all paced breathing frequencies (Fig.1C-D) from the largest source-detector distance. A non-zero phase lag between D and O within both groups indicates influences of cerebral blood volume (CBV) and CBF changes. The phase differences of D and O are therefore related to cerebral autoregulation. We found a greater phase difference (mean range: -320° to -340°) in patients with SCD compared to controls (mean range: -200° to -240°), indicating the presence of vascular obstruction and impaired cerebral autoregulation. Higher amplitude ratios |D|/|O| may indicate slower blood transmit times. We found that patients with SCD had increased amplitude ratios for hemodynamic oscillations at lower paced breathing frequencies compared to healthy controls (Fig. 1D). Finally, we found a significantly reduced cerebral tissue oxygen saturation in patients with SCD (63.1 % ± 7.8 %) in comparison with controls (65.9 % ± 4.9 %, p&amp;lt;0.05, Fig.1E). Discussion. We provide preliminary evidence that FD-NIRS can be used to assess cerebral autoregulation in SCD. Our results confirm and extend those of a prior study by Reinhard et al, 2003, by using the phase latency, Arg(D)−Arg(O), and the amplitude ratios, |D|/|O|, to assess autoregulation. In addition, we detected a noticeable reduction in oxygen saturation in patients with SCD as compared to healthy controls. Further studies may extend our findings to additional frequencies in a larger sample size to more comprehensively assess the impact of mean arterial pressure on autoregulation. Noninvasive measurement of cerebral autoregulation and brain oxygenation in SCD by FD-NIRS may represent a novel biomarker of cerebral vasculopathy in SCD and may help monitor changes in cerebral oxygenation, particularly during treatment with drugs that modulate the hemoglobin oxygen affinity, such as the recently FDA-approved voxelotor. Figure 1 Disclosures No relevant conflicts of interest to declare.

Enhancing classification accuracy of fNIRS-BCI using features acquired from vector-based phase analysis

Objective. In this paper, a novel methodology for feature extraction to enhance classification accuracy of functional near-infrared spectroscopy (fNIRS)-based two-class and three-class brain–computer interface (BCI) is presented. Approach. Novel features are extracted using vector-based phase analysis method. Changes in oxygenated and de-oxygenated ) haemoglobin are used to calculate four novel features: change in cerebral blood volume (), change in cerebral oxygen exchange (), vector magnitude (|L|) and angle (k). is the sum and is difference of and , whereas |L| is magnitude and k is angle of vector. fNIRS signals of seven healthy subjects, corresponding to left-hand index finger tapping (LFT), right-hand index finger tapping (RFT) and rest are acquired from motor cortex using multi-channel continuous-wave imaging system. After removing physiological and instrumental noises from the acquired signals, the four novel features are calculated. For validation, conventional temporal, spatial and spatiotemporal features; mean, peak, slope, variance, kurtosis and skewness are also calculated using and. All possible two-feature and three-feature combinations of the novel and conventional features are then used to classify two-class (LFT vs RFT) and three-class (LFT vs RFT vs rest) fNIRS-BCI using linear discriminant analysis. Main results. Results demonstrate that combination of four novel features yields significantly higher average classification accuracies of 98.7 ± 1.0% and 85.4 ± 1.4% as compared to 68.7 ± 6.9% and 53.6 ± 10.6% using conventional features for two-class and three-class problem, respectively. Validation of proposed method on an open access database containing RFT, LFT and dominant side foot tapping tasks for 30 subjects also shows improvement in average classification accuracies for two-class and three-class fNIRS-BCIs. Significance. This study provides a step forward in improving the classification accuracies of state-of-the-art fNIRS-BCIs by showing significant improvement in classification accuracies of two-class and three-class fNIRS-BCIs using novel features extracted by vector-based phase analysis.

Impaired response of cerebral oxygen metabolism to visual stimulation in Huntington’s disease

Huntington’s disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) in the brain in response to functional stimulation in premanifest and early manifest HD patients. A recently developed 3-D-TRiple-acquisition-after-Inversion-Preparation magnetic resonance imaging (MRI) approach was used to measure dynamic responses in CBV, CBF, and CMRO2 during visual stimulation in one single MRI scan. Experiments were conducted in 23 HD patients and 16 healthy controls. Decreased occipital cortex CMRO2 responses were observed in premanifest and early manifest HD patients compared to controls (P < 0.001), correlating with the CAG-Age Product scores in these patients (R2 = 0.4, P = 0.001). The results suggest the potential value of this reduced CMRO2 response during visual stimulation as a biomarker for HD and may illuminate the role of metabolic alterations in the pathophysiology of HD.

Functional ultrasound imaging to study brain dynamics: Application of pharmaco-fUS to atomoxetine

Functional ultrasound (fUS) is a new tool enabling the imaging of brain activity through the regional monitoring of cerebral blood volume (CBV) dynamics. This innovative technique has not yet demonstrated its full potential in pharmacological applications and drug development. In the current proof-of-concept study, the impact of atomoxetine (ATX), a potent norepinephrine reuptake inhibitor and non-stimulant treatment marketed in attention-deficit/hyperactivity-disorder, was evaluated in anesthetized rat using pharmacological functional ultrasound (pharmaco-fUS) at increasing doses (0.3, 1 and 3 mg/kg). Using regions of interest (acute changes of CBV and functional connectivity) or pixel-based (general linear modeling and independent component analysis) analysis, we here demonstrated that ATX consistently displayed a hemodynamic effect in the visual cortex, the dentate gyrus and thalamus, especially visual areas such as lateral posterior thalamic nuclei and lateral geniculate nuclei (LGN). The time profile of ATX effects was dose-dependent, with fastest CBV increases at the highest dose, and longer CBV increases at the intermediate dose. Standardizing the use of pharmaco-fUS could improve our understanding of the mechanism of action of drugs active in the brain and might constitute a new step to move forward in drug development for neurological disorders.

Changes in prefrontal cerebral oxygenation and microvascular blood volume in hypoxia and possible association with acute mountain sickness.

What is the central question of this study? The role of the cerebral haemodynamic response to either normobaric or hypobaric hypoxia in people susceptible to acute mountain sickness (AMS) is still under debate. Prefrontal cortex near-infrared spectroscopy-derived parameters were monitored in normobaric hypoxia at rest and during moderate-intensity exercise in AMS-prone and non-AMS individuals. What is the main finding and its importance? The AMS-prone individuals did not increase microvascular blood volume and showed lower prefrontal cerebral oxygenation in normobaric hypoxia both at rest and during exercise compared with non-AMS subjects, suggesting that these changes might underpin later development of AMS at altitude. The aim of this study was to evaluate changes in prefrontal cerebral oxygenation and microvascular blood volume during exercise in normobaric hypoxia and to investigate possible associations with the occurrence of acute mountain sickness (AMS) at altitude. Twenty-two healthy individuals (age, 26±4years; peak oxygen uptake, 42±4mlkg-1 min-1 ) were tested in two different conditions: normoxia (NORM) and normobaric hypoxia (fraction of inspired O2 =0.13; HYPO). Data were collected at rest and during submaximal constant-speed exercise. The peripheral oxyhaemoglobin saturation was measured by finger pulse oximeter. Changes in prefrontal cerebral oxygenation (ΔHbO2 ), deoxygenation (ΔHHb) and microvascular blood volume (ΔHbtot ) were obtained by near-infrared spectroscopy. Within 2weeks after laboratory testing, subjects rapidly ascended to 3647m a.s.l., and AMS was evaluated using the Lake Louise scale. Eight subjects were AMS+ , whereas 14 were AMS- . During NORM, near-infrared spectroscopy variables did not change from baseline values both at rest and during exercise, with similar results in AMS+ and AMS- subjects. During HYPO, ΔHHb increased to a similar extent in both groups, both at rest and during exercise. The ΔHbO2 was significantly less in AMS+ compared with AMS- subjects, both at rest [-3.23±5.90 versus 1.44±2.14μm, P=0.04, effect size (ES)=1.1, respectively] and during exercise (-6.56±5.51versus 0.37±4.36μm,P<0.01,ES=1.2, respectively). Total haemoglobin did not change from baseline, both at rest (-1.67±9.53μm) and during exercise (-0.96±9.12μm) in AMS+ subjects, which was significantly different from the AMS- group (5.49±3.99μm, P=0.03, ES=1.0 and 8.17±7.34μm, P=0.02, ES=1.0, respectively). Individuals prone to AMS seem to be unable to increase microvascular blood volume and to maintain oxygenation at the cerebral level during exercise in acute normobaric hypoxia, suggesting that these changes might underpin later development of AMS.

Modeling of vascular space occupancy and BOLD functional MRI from first principles using real microvascular angiograms.

The vascular space occupancy (VASO) is a functional MRI technique for probing cerebral blood volume changes noninvasively, including during neuronal activation in humans. An important consideration when implementing VASO is the BOLD effect in the signal. Assessing the physical origin of this BOLD contamination and the capabilities of correction methods could improve the quantification of cerebral blood volume changes with VASO. Given the heterogeneity of cerebral microvascular architecture, the vascular geometry within an MRI voxel can influence both BOLD and VASO signals. To investigate this effect, 3D high-resolution images of mouse cerebral vasculature measured with two-photon microscopy were used to model BOLD and VASO signals from first principles using Monte Carlo diffusion of water protons. Quantitative plots of VASO together with intravascular and extravascular BOLD signals as a function of TE at B0 fields 1.5 T to 14 T were obtained. The BOLD contamination of the VASO response was on the order of 50% for gradient echo and 5% for spin echo at 7 T and TE = 6 ms and significantly increased with TE and B0 . Two currently used correction schemes were shown to account for most of this contamination and recover accurate relative signal changes, with optimal correction obtained using TEs as short as possible. These results may provide useful information for optimizing sequence parameters in VASO and BOLD functional MRI, leading the way to a wider application of these techniques in healthy and diseased brain.

Value of dynamic contrast perfusion MRI to predict early response to bevacizumab in newly diagnosed glioblastoma: results from ACRIN 6686 multicenter trial.

In Radiation Therapy Oncology Group (RTOG) 0825, a phase III trial of standard therapy with bevacizumab or without (placebo) in newly diagnosed glioblastoma, 44 patients underwent dynamic contrast enhanced (DCE) and/or dynamic susceptibility contrast (DSC) MRI in the American College of Radiology Imaging Network (ACRIN) trial 6686. The association between early changes in relative cerebral blood volume (rCBV) and volume transfer constant (Ktrans) with overall survival (OS) was evaluated. MRI was performed at postop baseline (S0), immediately before (S1), 1 day after (S2), and 7 weeks after (S3) bevacizumab or placebo initiation. Mean normalized and standardized rCBV (nRCBV, sRCBV) and Ktrans were measured within contrast-enhancing lesion. Wilcoxon rank sum tests compared parameter changes from S1-S2 and S1-S3. Association with OS and progression-free survival (PFS) were determined using Kaplan-Meier and log-rank tests. Treatment response for groups stratified by pretreatment nRCBV (S0, S1) was explored. The intraclass correlation coefficient and repeatability coefficient for the placebo arm (S1-S2) were used to assess repeatability. Evaluable were 27-36 datasets per time point. Significant differences between treatment arms were found for changes in nRCBV and sRCBV from S1-S2 and S1-S3, and in Ktrans for S1-S3. Improved PFS (P = 0.05) but not OS (P = 0.46) was observed. High pretreatment rCBV predicted improved OS for bevacizumab-treated patients. Based on the intraclass correlation coefficient, sRCBV (0.92) was more repeatable than nRCBV (0.71) and Ktrans (0.75), consistent with repeatability coefficient values. Bevacizumab significantly changes rCBV but not Ktrans as early as 1 day posttreatment in newly diagnosed glioblastoma unrelated to outcomes. Improvements in clinical trial design to maximize rCBV benefit are indicated.

Transfer functions linking neural calcium to single voxel functional ultrasound signal

Functional ultrasound imaging (fUS) is an emerging technique that detects changes of cerebral blood volume triggered by brain activation. Here, we investigate the extent to which fUS faithfully reports local neuronal activation by combining fUS and two-photon microscopy (2PM) in a co-registered single voxel brain volume. Using a machine-learning approach, we compute and validate transfer functions between dendritic calcium signals of specific neurons and vascular signals measured at both microscopic (2PM) and mesoscopic (fUS) levels. We find that transfer functions are robust across a wide range of stimulation paradigms and animals, and reveal a second vascular component of neurovascular coupling upon very strong stimulation. We propose that transfer functions can be considered as reliable quantitative reporters to follow neurovascular coupling dynamics.

Neurochemical underpinning of hemodynamic response to neuropsychiatric drugs: A meta- and cluster analysis of preclinical studies

Functional magnetic resonance imaging (fMRI) is an extensively used method for the investigation of normal and pathological brain function. In particular, fMRI has been used to characterize spatiotemporal hemodynamic response to pharmacological challenges as a non-invasive readout of neuronal activity. However, the mechanisms underlying regional signal changes are yet unclear. In this study, we use a meta-analytic approach to converge data from microdialysis experiments with relative cerebral blood volume (rCBV) changes following acute administration of neuropsychiatric drugs in adult male rats. At whole-brain level, the functional response patterns show very weak correlation with neurochemical alterations, while for numerous brain areas a strong positive correlation with noradrenaline release exists. At a local scale of individual brain regions, the rCBV response to neurotransmitters is anatomically heterogeneous and, importantly, based on a complex interplay of different neurotransmitters that often exert opposing effects, thus providing a mechanism for regulating and fine tuning hemodynamic responses in specific regions.

Cerebral venous volume changes and pressure autoregulation in critically ill infants.

ObjectiveTo determine whether ventilator-related fluctuations in cerebral blood volume (CBV) are associated with cerebral pressure passivity.Study designIn a prospective study of newborns undergoing positive-pressure ventilation, we calculated coherence between continuous mean arterial pressure (MAP) and cerebral near-infrared spectroscopy hemoglobin difference (HbD). Significant HbD–MAP coherence indicated cerebral pressure passivity. CBV changes were measured as the spectral power of total hemoglobin (SHbT) at the ventilator frequency. A regression model tested whether SHbT predicts cerebral pressure passivity and/or death/brain injury, controlling for birth gestational age and other factors.ResultsWe studied 68 subjects with prematurity (n = 19), congenital heart disease (n = 11), and hypoxic–ischemic encephalopathy (n = 38). SHbT, sedative use, and pCO2 were positively associated, and circulating hemoglobin negatively associated, with cerebral pressure passivity (p < 0.001), which was positively associated with brain injury (p < 0.001).ConclusionIn sick newborns, ventilator-related CBV fluctuations may predispose to cerebral pressure passivity, which may predispose to an adverse neonatal outcome.

Prediction of survival and progression in glioblastoma patients using temporal perfusion changes during radiochemotherapy

BackgroundThe aim of this study was to investigate changes in structural magnetic resonance imaging (MRI) according to the RANO criteria and perfusion- and permeability related metrics derived from dynamic contrast-enhanced MRI (DCE) and dynamic susceptibility contrast MRI (DSC) during radiochemotherapy for prediction of progression and survival in glioblastoma. MethodsTwenty-three glioblastoma patients underwent biweekly structural and perfusion MRI before, during, and two weeks after a six weeks course of radiochemotherapy. Temporal trends of tumor volume and the perfusion-derived parameters cerebral blood volume (CBV) and blood flow (CBF) from DSC and DCE, in addition to contrast agent capillary transfer constant (Ktrans) from DCE, were assessed. The patients were separated in two groups by median survival and differences between the two groups explored. Clinical- and MRI metrics were investigated using univariate and multivariate survival analysis and a predictive survival index was generated. ResultsMedian survival was 19.2 months. A significant decrease in contrast-enhancing tumor size and CBV and CBF in both DCE- and DSC-derived parameters was seen during and two weeks past radiochemotherapy (p < 0.05). A 10%/30% increase in Ktrans/CBF two weeks after finishing radiochemotherapy resulted in significant shorter survival (13.9/16.8 vs. 31.5/33.1 months; p < 0.05). Multivariate analysis revealed an index using change in Ktrans and relative CBV from DSC significantly corresponding with survival time in months (r2 = 0.843; p < 0.001). ConclusionsSignificant temporal changes are evident during radiochemotherapy in tumor size (after two weeks) and perfusion-weighted MRI-derived parameters (after four weeks) in glioblastoma patients. While DCE-based metrics showed most promise for early survival prediction, a multiparametric combination of both DCE- and DSC-derived metrics gave additional information.

Development of Rat-Scale Magnetic Particle Spectroscopy for Functional Magnetic Particle Imaging

Magnetic particle imaging (MPI) is a fast and sensitive technique for imaging of magnetic nanoparticle (MNP) concentrations. MPI directly measures and maps the particle concentration over a measured spatial position. Functional MPI (fMPI) is a specific application of MPI that aims to detect the change of cerebral blood volume (CBV) through imaging. Assuming that the concentration of MNPs in the CBV is uniform, the resultant concentration of MNPs can indicate the CBV changes. Magnetic particle spectroscopy (MPS) is basically a zero-dimensional MPI scanner which can be used to conduct spectroscopic studies and fMPI. In this letter, we suggest an MPS for fMPI with a bore size of 50 mm compatible with rat head dimensions. The system utilizes 0.015 T magnetic field at a frequency of 29.5 kHz and uses an integrated method to measure the small iron component of magnetic particles. Based on the integrated output signal, the MPS consisting of an excitation coil and a gradiometer coil with three parts—a receive coil, a cancellation coil, and a calibration coil—can detect down to 25 ng of Fe. The suggested MPS has demonstrated the achievement of sensitivity that is feasible for fMPI.

Functional connectivity analysis based on optical imaging of cerebral blood volume changes

Functional connectivity analysis based on optical imaging of cerebral blood volume changes

A Simulation Model for Interaction between Cyclic Variation of Brain Tissue Temperature and Intracranial Pressure

The brain responds with high sensitivity in case of cerebral damage. Brain temperature (BT), cerebral blood flow (CBF), cerebral blood volume (CBV) and intracranial pressure (ICP) are essential parameters for brain revival in case of cerebral damage. For this reason, the coordinated learning of BT, CBF and ICP is required for improving the remedial impacts. Thus, in this exploration, a simulation model has been developed for association between brain tissue temperature (BTT), CBF, CBV and ICP to improve the apprehensions of the ICP. It includes the cardiac output, partial pressures of oxygen and carbon dioxide in cerebral artery and vein, temperature variations of brain tissue, cerebral metabolic process and pressure-volume relationship for cranial cavity. The model simulates the interaction between arterial blood pressure, BTT, produced amount of CO2 from brain tissue, changes in CBV and changes in ICP. The results show that the ICP and CBV will increase with an increase in brain tissue temperature. This model elaborates the physiology of BTT and ICP with less complexity.

Neurovascular coupling preserved in a chronic mouse model of Alzheimer’s disease: Methodology is critical

Impaired neurovascular coupling has been suggested as an early pathogenic factor in Alzheimer’s disease (AD), which could serve as an early biomarker of cerebral pathology. We have established an anaesthetic regime to allow repeated measurements of neurovascular function over three months in the J20 mouse model of AD (J20-AD) and wild-type (WT) controls. Animals were 9–12 months old at the start of the experiment. Mice were chronically prepared with a cranial window through which 2-Dimensional optical imaging spectroscopy (2D-OIS) was used to generate functional maps of the cerebral blood volume and saturation changes evoked by whisker stimulation and vascular reactivity challenges. Unexpectedly, the hemodynamic responses were largely preserved in the J20-AD group. This result failed to confirm previous investigations using the J20-AD model. However, a final acute electrophysiology and 2D-OIS experiment was performed to measure both neural and hemodynamic responses concurrently. In this experiment, previously reported deficits in neurovascular coupling in the J20-AD model were observed. This suggests that J20-AD mice may be more susceptible to the physiologically stressing conditions of an acute experimental procedure compared to WT animals. These results therefore highlight the importance of experimental procedure when determining the characteristics of animal models of human disease.