MRI size assessment of cerebral microvasculature using diffusion-time-dependent stimulated-echo acquisition: A feasibility study in rodent.

In this study, a stimulated-echo (STE) method was employed to robustify the cerebral vessel size estimation near air-tissue, bone-tissue interfaces, and large vessels. The proposed solution is to replace the relaxation rate change from gradient-echo (GRE) with that from STE with long diffusion time after the injection of an intravascular contrast agent, superparamagnetic iron oxide nanoparticles. The corresponding diffusion length of STE is shorter than the length over which the unwanted macroscopic field inhomogeneities but is still longer than the correlation length of the fields induced by small vessels. Therefore, the unwanted field inhomogeneities are refocused, while preserving microscopic susceptibility contrast from cerebral vessels. The mean vessel diameter (dimensionless) derived from the diffusion-time-varying STE method was compared to the mean vessel diameter obtained by a conventional spin-echo (SE) and GRE combination based on Monte-Carlo proton diffusion simulations and in vivo rat experiments at 7 â€‹T. The in vivo mean vessel diameter from the MRI experiments was directly compared to available reference mouse brain vasculature obtained by a knife-edge scanning microscope (KESM), which is considered to be the gold standard. Monte-Carlo simulation revealed that SE and GRE-based MR relaxation rate changes (ΔR2 and ΔR2∗, respectively) can be enhanced using single STE-based MR relaxation rate change (ΔRSTE) by regulating diffusion time, especially for small vessels. The in vivo mean vessel diameter from the STE method demonstrated a closer agreement with that from the KESM compared to the combined SE and GRE method, especially in the olfactory bulb and cortex. This study demonstrates that STE relaxation rate changes can be used as consistent measures for assessing small cerebral microvasculature, where macroscopic field inhomogeneity is severe and signal contamination from adjacent large vessels is significant.

Autoregulation assessment by direct visualisation of pial arterial blood flow in the piglet brain.

Impairment of cerebrovascular autoregulation (CAR) is common after brain injury, although the pathophysiology remains elusive. The mechanisms of vascular dysregulation, their impact on brain function, and potential therapeutic implications are still incompletely understood. Clinical assessment of CAR remains challenging. Observational studies suggest that CAR impairment is associated with worse outcomes, and that optimization of cerebral blood flow (CBF) by individual arterial blood pressure (ABP) targets could potentially improve outcome. We present a porcine closed cranial window model that measures the hemodynamic response of pial arterioles, the main site of CBF control, based on changes in their diameter and red blood cell velocity. This quantitative direct CAR assessment is compared to laser Doppler flow (LDF). CAR breakpoints are determined by segmented regression analysis and validated using LDF and brain tissue oxygen pressure. Using a standardized cortical impact, CAR impairment in traumatic brain injury can be studied using our method of combining pial arteriolar diameter and RBC velocity to quantify RBC flux in a large animal model. The model has numerous potential applications to investigate CAR physiology and pathophysiology of CAR impairment after brain injury, the impact of therapeutic interventions, drugs, and other confounders, or to develop personalized ABP management strategies.

Dependence of the MR signal on the magnetic susceptibility of blood studied with models based on real microvascular networks.

PURPOSE: The primary goal of this study was to estimate the value of ß , the exponent in the power law relating changes of the transverse relaxation rate and intra-extravascular local magnetic susceptibility differences as ΔR2∗∝(Δχ)ß . The secondary objective was to evaluate any differences that might exist in the value of ß obtained using a deoxyhemoglobin-weighted Δχ distribution versus a constant Δχ distribution assumed in earlier computations. The third objective was to estimate the value of ß that is relevant for methods based on susceptibility contrast agents with a concentration of Δχ higher than that used for BOLD fMRI calculations. METHODS: Our recently developed model of real microvascular anatomical networks is used to extend the original simplified Monte-Carlo simulations to compute ß from the first principles. RESULTS: Our results show that ß=1 for most BOLD fMRI measurements of real vascular networks, as opposed to earlier predictions of ß=1 .5 using uniform Δχ distributions. For perfusion or fMRI methods based on contrast agents, which generate larger values for Δχ , ß=1 for B0≤ 9.4 T, whereas at 14 T ß can drop below 1 and the variation across subjects is large, indicating that a lower concentration of contrast agent with a lower value of Δχ is desired for experiments at high B0 . CONCLUSION: These results improve our understanding of the relationship between R2* and the underlying microvascular properties. The findings will help to infer the cerebral metabolic rate of oxygen and cerebral blood volume from BOLD and perfusion MRI, respectively.

Assessment of cerebral blood flow in neonates and infants: A phase-contrast MRI study.

Abnormal cerebral blood flow (CBF) is implicated in several neonatal and infant diseases. However, measurement of CBF in this population remains difficult and has not been used in routine clinical MRI. Arterial spin labeling (ASL) methods suffer from both low SNR and poor quantification when applied to very young children. Furthermore, rapid change in brain physiology in this age range makes it difficult to choose sequence parameters such as labeling pulse flip angle and post labeling delay. Phase-contrast (PC) MRI is another approach to measure flow. It provides fast and reliable global CBF assessment, and has great promises in pediatric applications. In this study, we aimed to apply PC-MRI technique for CBF quantification in neonates and infants up to 18 months of age. We first compared several implementations of time-of-flight (TOF) MR angiogram for the visualization of brain's feeding arteries, which provides anatomical information for the positioning of PC-MRI scans. We then measured flow velocity and CBF of the internal carotid artery (ICA) and vertebral artery (VA) in 21 subjects (age 34-114 gestational weeks, 3 females, 18 males), using six encoding velocities (Venc) in each vessel. In ICA, peak arterial flow velocity was 10.2 cm/s at birth and increased to 56.0 cm/s at 18 months old. These values were 4.5-36.3 cm/s, respectively, for VA. CBF after accounting for brain volume revealed a significant (p < 0.001) age-related increase from 13.1 to 84.7 ml/100  g/min within the first 18 months after birth. Based on the peak flow velocity, we provided age-specific recommendations for Venc selection in PC-MRI when one only has time for one scan. The present study used a multi-Venc scheme to determine flow velocities in major feeding arteries of infant brain and may lay a foundation for accurate measurement of whole-brain CBF in this population.

Induced Dynamic Intracranial Pressure and Cerebrovascular Reactivity Assessment of Cerebrovascular Autoregulation After Traumatic Brain Injury with High Intracranial Pressure in Rats.

OBJECTIVE: In previous work we showed that high intracranial pressure (ICP) in the rat brain induces a transition from capillary (CAP) to pathological microvascular shunt (MVS) flow, resulting in brain hypoxia, edema, and blood-brain barrier (BBB) damage. This transition was correlated with a loss of cerebral blood flow (CBF) autoregulation undetected by static autoregulatory curves but identified by induced dynamic ICP (iPRx) and cerebrovascular (iCVRx) reactivity. We hypothesized that loss of CBF autoregulation as correlated with MVS flow would be identified by iPRx and iCVRx in traumatic brain injury (TBI) with elevated ICP. METHODS: TBI was induced by lateral fluid percussion (LFP) using a gas-driven device in rats. Using in vivo two-photon laser scanning microscopy, cortical microcirculation, tissue oxygenation (NADH autofluoresence), and BBB permeability (fluorescein dye extravasation) were measured before and for 4 h after TBI. Laser Doppler cortical flux, rectal and brain temperature, ICP and mean arterial pressure (MAP), blood gases, and electrolytes were monitored. Every 30 min, a transient 10 mmHg rise in MAP was induced by i.v. bolus of dopamine. iPRx = ΔICP/ΔMAP and iCVRx = ΔCBF/ΔMAP. RESULTS: We demonstrated that iPRx and iCVRx correctly identified more severe loss of CBF autoregulation correlated with a transition of blood flow to MVS after TBI with high ICP compared to TBI without an increase in ICP. CONCLUSIONS: In TBI with high ICP, high-velocity MVS flow is responsible for the loss of CBF autoregulation identified by iPRx and iCVRx.

Protocol for intraoperative assessment of the human cerebrovascular glycocalyx.

INTRODUCTION: Adequate functioning of the blood-brain barrier (BBB) is important for brain homoeostasis and normal neuronal function. Disruption of the BBB has been described in several neurological diseases. Recent reports suggest that an increased permeability of the BBB also contributes to increased seizure susceptibility in patients with epilepsy. The endothelial glycocalyx is coating the luminal side of the endothelium and can be considered as the first barrier of the BBB. We hypothesise that an altered glycocalyx thickness plays a role in the aetiology of temporal lobe epilepsy (TLE), the most common type of epilepsy. Here, we propose a protocol that allows intraoperative assessment of the cerebrovascular glycocalyx thickness in patients with TLE and assess whether its thickness is decreased in patients with TLE when compared with controls. METHODS AND ANALYSIS: This protocol is designed as a prospective observational case-control study in patients who undergo resective brain surgery as treatment for TLE. Control subjects are patients without a history of epileptic seizures, who undergo a craniotomy or burr hole surgery for other indications. Intraoperative glycocalyx thickness measurements of sublingual, cortical and hippocampal microcirculation are performed by video microscopy using sidestream dark-field imaging. Demographic details, seizure characteristics, epilepsy risk factors, intraoperative haemodynamic parameters and histopathological evaluation are additionally recorded. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the local medical ethical committee (ID: NL51594.068.14) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Informed consent is obtained before study enrolment and only coded data will be stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NTR5568.

Quantitative Assessment of Cerebral Basement Membranes Using Electron Microscopy.

In this chapter we describe in detail the tissue processing techniques we employ for the study of cerebral tissue by transmission electron microscopy (TEM). In particular, we explain a technique that enables quantification of changes in cerebral basement membranes at the ultrastructural level. This is significant, as age related pathological conditions affecting the brain are often accompanied by ultrastructural changes in the cerebral vasculature.Briefly, experimental mice are fixed by perfusion and their brains removed. Brains are then vibratomed into 100 µm slices with regions of interest microdissected and processed for TEM following a protocol optimized for the preservation of cerebral tissue. Changes in the thickness of cerebral basement membranes are then quantified using novel software. Some prior knowledge of general TEM specimen preparation and sectioning will be useful when performing this protocol.

Microdialysis Assessment of Cerebral Perfusion during Cardiac Arrest, Extracorporeal Life Support and Cardiopulmonary Resuscitation in Rats - A Pilot Trial.

Cerebral metabolic alterations during cardiac arrest, cardiopulmonary resuscitation (CPR) and extracorporeal cardiopulmonary life support (ECLS) are poorly explored. Markers are needed for a more personalized resuscitation and post-resuscitation care. Aim of this study was to investigate early metabolic changes in the hippocampal CA1 region during ventricular fibrillation cardiac arrest (VF-CA) and ECLS versus conventional CPR. Male Sprague-Dawley rats (350g) underwent 8min untreated VF-CA followed by ECLS (n = 8; bloodflow 100ml/kg), mechanical CPR (n = 18; 200/min) until return of spontaneous circulation (ROSC). Shams (n = 2) were included. Glucose, glutamate and lactate/pyruvate ratio were compared between treatment groups and animals with and without ROSC. Ten animals (39%) achieved ROSC (ECLS 5/8 vs. CPR 5/18; OR 4,3;CI:0.7-25;p = 0.189). During VF-CA central nervous glucose decreased (0.32±0.1mmol/l to 0.04±0.01mmol/l; p<0.001) and showed a significant rise (0.53±0.1;p<0.001) after resuscitation. Lactate/pyruvate (L/P) ratio showed a 5fold increase (31 to 164; p<0.001; maximum 8min post ROSC). Glutamate showed a 3.5-fold increase to (2.06±1.5 to 7.12±5.1µmol/L; p<0.001) after CA. All parameters normalized after ROSC with no significant differences between ECLS and CPR. Metabolic changes during ischemia and resuscitation can be displayed by cerebral microdialysis in our VF-CA CPR and ECLS rat model. We found similar microdialysate concentrations and patterns of normalization in both resuscitation methods used. Institutional Protocol Number: GZ0064.11/3b/2011.

Dynamic light scattering Monte Carlo: a method for simulating time-varying dynamics for ordered motion in heterogeneous media.

Few methods exist that can accurately handle dynamic light scattering in the regime between single and highly multiple scattering. We demonstrate dynamic light scattering Monte Carlo (DLS-MC), a numerical method by which the electric field autocorrelation function may be calculated for arbitrary geometries if the optical properties and particle motion are known or assumed. DLS-MC requires no assumptions regarding the number of scattering events, the final form of the autocorrelation function, or the degree of correlation between scattering events. Furthermore, the method is capable of rapidly determining the effect of particle motion changes on the autocorrelation function in heterogeneous samples. We experimentally validated the method and demonstrated that the simulations match both the expected form and the experimental results. We also demonstrate the perturbation capabilities of the method by calculating the autocorrelation function of flow in a representation of mouse microvasculature and determining the sensitivity to flow changes as a function of depth.

Spatio-temporal assessment of the neuroprotective effects of neuregulin-1 on ischemic stroke lesions using MRI.

The neuroprotective effects of neuregulin-1 (NRG-1) on stroke lesions were assessed longitudinally in rats with middle cerebral artery occlusion (MCAo) using MRI. Sprague-Dawley rats (n=16, 250±20g) underwent permanent MCAo surgery with cerebral blood flow (CBF) monitored by laser doppler flowmetry at ipsilateral side of bregma for 20min post-occlusion. A single 50µl bolus dose of NRG-1 or vehicle was administered into the left internal carotid artery immediately prior to MCAo. The expansion of the ischemic lesion into the cortex was attenuated by NRG-1 over a 48-hour (h) time span as measured by diffusion weighted imaging (DWI). The final infarct volumes of NRG-1 treated rats were significantly smaller than those of the vehicle treated rats at 48h (264.8±192.1 vs. 533.4±175.5mm(3), p<0.05). The NRG-1 treated rats were further subdivided into 2 subgroups according to their CBF reduction during stroke surgery: mild ischemia (<70% CBF reduction) or severe ischemia (>70% CBF reduction). In particular, ischemic infarction was not usually observed in the cortex of NRG-1 treated rats with mild ischemia at 3 and 48h post-occlusion. Histological results validated the imaging findings and demonstrated that NRG-1 treated rats had fewer injured neurons in peri-infarct areas 48h post-ischemia. In summary, the neuroprotective effect of NRG-1 in the pMCAo stroke model was demonstrated by prevention of ischemic lesion expansion, reduced infarct volume and protection of neurons from ischemic damage.

Assessment of neurovascular dynamics during transient ischemic attack by the novel integration of micro-electrocorticography electrode array with functional photoacoustic microscopy.

This study developed a novel system combining a 16-channel micro-electrocorticography (µECoG) electrode array and functional photoacoustic microscopy (fPAM) to examine changes in neurovascular functions following transient ischemic attack (TIA) in rats. To mimic the pathophysiology of TIA, a modified photothrombotic ischemic model was developed by using 3 min illumination of 5 mW continuous-wave (CW) green laser light focusing on a distal branch of the middle cerebral artery (MCA). Cerebral blood volume (CBV), hemoglobin oxygen saturation (SO2), somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were measured pre- and post-ischemia over a focal cortical region (i.e., 1.5×1.5 mm(2)). Unexpectedly, the SO2, peak-to-peak amplitude (PPA) of SSEPs and ADR recovered and achieved levels greater than the baseline values at the 4th hour post-ischemia induction without any intervention, whereas the CBV value only partially recovered. In other words, transient ischemia led to increased neural activity when the relative CBV was reduced, which may further compromise neural integrity or lead to subsequent vascular disease. This novel µECoG-fPAM system complements currently available imaging techniques and represents a promising technology for studying neurovascular coupling in animal models.

Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer's disease and vascular dementia.

Perfusion is reduced in the cerebral neocortex in Alzheimer's disease. We have explored some of the mechanisms, by measurement of perfusion-sensitive and disease-related proteins in post-mortem tissue from Alzheimer's disease, vascular dementia and age-matched control brains. To distinguish physiological from pathological reduction in perfusion (i.e. reduction exceeding the decline in metabolic demand), we measured the concentration of vascular endothelial growth factor (VEGF), a protein induced under conditions of tissue hypoxia through the actions of hypoxia-inducible factors, and the myelin associated glycoprotein to proteolipid protein 1 (MAG:PLP1) ratio, which declines in chronically hypoperfused brain tissue. To evaluate possible mechanisms of hypoperfusion, we also measured the levels of amyloid-ß40, amyloid-ß42, von Willebrand factor (VWF; a measure of microvascular density) and the potent vasoconstrictor endothelin 1 (EDN1); we assayed the activity of angiotensin I converting enzyme (ACE), which catalyses the production of another potent vasoconstrictor, angiotensin II; and we scored the severity of arteriolosclerotic small vessel disease and cerebral amyloid angiopathy, and determined the Braak tangle stage. VEGF was markedly increased in frontal and parahippocampal cortex in Alzheimer's disease but only slightly and not significantly in vascular dementia. In frontal cortex the MAG:PLP1 ratio was significantly reduced in Alzheimer's disease and even more so in vascular dementia. VEGF but not MAG:PLP1 increased with Alzheimer's disease severity, as measured by Braak tangle stage, and correlated with amyloid-ß42 and amyloid-ß42: amyloid-ß40 but not amyloid-ß40. Although MAG:PLP1 tended to be lowest in cortex from patients with severe small vessel disease or cerebral amyloid angiopathy, neither VEGF nor MAG:PLP1 correlated significantly with the severity of structural vascular pathology (small vessel disease, cerebral amyloid angiopathy or VWF). However, MAG:PLP1 showed a significant negative correlation with the level of EDN1, which we previously showed to be elevated in the cerebral cortex Alzheimer's disease. These finding are in contrast with the previously demonstrated reduction in EDN1, and positive correlation with MAG:PLP1, in the hypoperfused white matter in Alzheimer's disease. The decline in MAG:PLP1 strongly suggests pathological hypoperfusion of the frontal cortex in Alzheimer's disease. Although severe small vessel disease or cerebral amyloid angiopathy may contribute in some cases, abnormal vascular contractility mediated by EDN1 is likely to be a more important overall contributor. Both amyloid-ß accumulation and hypoperfusion are likely to cause the upregulation of VEGF.

Cytotoxic and vasogenic cerebral oedema in traumatic brain injury: assessment with FLAIR and DWI imaging.

PRIMARY OBJECTIVE: Cerebral oedema is a common complication of traumatic brain injury (TBI). The use of Fluid-Attenuated Inversion Recovery (FLAIR) imaging in combination with Diffusion Weighted Imaging (DWI) has the potential to distinguish between cytotoxic and vasogenic oedema. This study hypothesized a significant relationship between cytotoxic lesion volume and outcome. RESEARCH DESIGN: This observational study reports on a convenience sample where MRI was obtained for clinical purposes. METHODS AND PROCEDURES: Clinical post-TBI FLAIR and DWI images were analysed. For this study, lesions were defined as primarily cytotoxic oedema if the ratio of FLAIR to DWI lesion volume was comparable, defined as a ratio <2. If the ratio of FLAIR to DWI lesion volume was ≥2, oedema was considered predominantly of vasogenic origin. MAIN OUTCOMES AND RESULTS: The sample consisted primarily of males with TBIs whose injury severity ranged from complicated mild to severe. Analysis revealed that both oedema types are common after TBI and both are associated with functional deficits 6 months after injury. CONCLUSIONS: Acute MRI may be useful to assess pathology at the tissue after traumatic brain injury. Clinical trials targeting cytotoxic and vasogenic mechanisms of oedema formation may benefit from using DWI and FLAIR MRI as a means to differentiate the predominant oedema type after TBI.

Chronic assessment of cerebral hemodynamics during rat forepaw electrical stimulation using functional ultrasound imaging.

Functional ultrasound imaging is a method recently developed to assess brain activity via hemodynamics in rodents. Doppler ultrasound signals allow the measurement of cerebral blood volume (CBV) and red blood cells' (RBCs') velocity in small vessels. However, this technique originally requires performing a large craniotomy that limits its use to acute experiments only. Moreover, a detailed description of the hemodynamic changes that underlie functional ultrasound imaging has not been described but is essential for a better interpretation of neuroimaging data. To overcome the limitation of the craniotomy, we developed a dedicated thinned skull surgery for chronic imaging. This procedure did not induce brain inflammation nor neuronal death as confirmed by immunostaining. We successfully acquired both high-resolution images of the microvasculature and functional movies of the brain hemodynamics on the same animal at 0, 2, and 7 days without loss of quality. Then, we investigated the spatiotemporal evolution of the CBV hemodynamic response function (HRF) in response to sensory-evoked electrical stimulus (1 mA) ranging from 1 (200 µs) to 25 pulses (5s). Our results indicate that CBV HRF parameters such as the peak amplitude, the time to peak, the full width at half-maximum and the spatial extent of the activated area increase with stimulus duration. Functional ultrasound imaging was sensitive enough to detect hemodynamic responses evoked by only a single pulse stimulus. We also observed that the RBC velocity during activation could be separated in two distinct speed ranges with the fastest velocities located in the upper part of the cortex and slower velocities in deeper layers. For the first time, functional ultrasound imaging demonstrates its potential to image brain activity chronically in small animals and offers new insights into the spatiotemporal evolution of cerebral hemodynamics.

Xenon-enhanced CT assessment of cerebral blood flow in stroke-in-progress patients with unilateral internal carotid artery or middle cerebral artery stenosis.

Carotid or cerebral artery stenosis resulting in low perfusion is a major cause of ischemic stroke. Understanding the unique hemodynamic features in each patient undergoing a stroke-in-progress (SIP) and the correlation between progression and cerebral blood flow (CBF) status would help in the diagnosis and treatment of individual patients. We used xenon-enhanced CT (Xe-CT) to examine cerebral perfusion in patients with or without SIP (30 patients/group), recruited from October 2009 to October 2010. Only SIP patients with unilateral stenosis in the internal or middle cerebral artery were recruited. The occurrence of watershed infarction was higher in the SIP group than in the non-SIP group (P <0.05). In the SIP group, larger hypoperfused areas were found around the lesions than in the non-SIP group. In the SIP group, the CBF values in the ipsilateral areas were significantly lower than those in corresponding regions on the contralateral side. CBF values in the contralateral hemisphere were significantly lower in the SIP group than in the non-SIP group. In SIP patients, infarctions were surrounded by larger hypoperfused areas than in non-SIP patients. These larger hypoperfused areas may result in pathological damage to the brain that is responsible for the progression of stroke.

Assessment of cortical hemodynamics by multichannel near-infrared spectroscopy in steno-occlusive disease of the middle cerebral artery.

BACKGROUND AND PURPOSE: In a pilot study we evaluated near-infrared spectroscopy as to its potential benefit in monitoring patients with steno-occlusive disease of a major cerebral artery for alterations in cortical hemodynamics. METHODS: Cortical maps of time-to-peak (TTP) in 10 patients unilaterally affected by severe stenosis or occlusion of the middle cerebral artery were acquired by multichannel near-infrared spectroscopy after bolus application of indocyanine green. Hemodynamic manifestations were assessed by comparison between affected and unaffected hemisphere and evaluated for common constituents by principal component analysis. In one patient, TTP values were compared with those obtained by dynamic susceptibility contrast imaging. RESULTS: TTP was increased on the affected hemisphere in 9 patients. Mean difference in TTP between hemispheres was 0.44 second (P<0.05) as compared with a mean lateral difference of 0.12 second found in a control group of 10 individuals. In group analysis a significant rise in TTP was found in the distribution of the affected middle cerebral artery, whereas principal component analysis suggests augmentation of hemodynamic effects toward the border zones as a dominant pattern. A linear correlation of 0.61 between TTP values determined by dynamic susceptibility contrast MRI and near-infrared spectroscopy was found to be statistically significant (P<0.001). CONCLUSIONS: Multichannel near-infrared spectroscopy might facilitate detection of disease-related hemodynamic changes as yet only accessible by tomographic imaging modalities. Being indicative for hypoperfusion and collateral flow increased values of TTP, as found to a varying extent in the present patient group, might be of clinical relevance.

Assessment of cerebral blood flow findings using 99mTc-ECD single-photon emission computed tomography in patients diagnosed with major depressive disorder.

BACKGROUND: Single-photon emission computed tomography (SPECT) is used as an ancillary diagnostic tool in clinical psychiatry. A variety of SPECT studies has been conducted on the findings and the factors that affect the findings, and there is a possibility that age has an effect on cerebral blood flow. We used SPECT to verify the cerebral blood flow findings of patients with major depressive disorder (MDD) considering the effect of age on the findings. METHODS: We conducted a retrospective survey of inpatients who fulfilled the DSM-IV diagnostic criteria for MDD and who had undergone imaging by technetium-99m ethyl cysteinate dimer ((99m)Tc-ECD) SPECT (N=98, 37 males). After excluding organic factors and comorbidities, we established a depression group (N=61, 24 males) and conducted an inter-group comparison with a normal control group by using SPM software considering the effect of age. RESULTS: The depression group showed the reduction of cerebral blood flow in the prefrontal area bilaterally, predominantly on the left, including the orbitofrontal cortex, anterior portion of the gyrus cinguli, and dorsolateral prefrontal area, in the left temporal lobe, and in the occipital lobe bilaterally, predominantly on the left. The findings were common to all age groups and that age-specific pattern was not detected. LIMITATIONS: The facts that this was a retrospective study and small sample size in each age group were limitations of this research. Although it also seems important to evaluate the impact of medication on cerebral blood flow and conduct an evaluation according to the subtype of depression, but we couldn't in this study. In the future it will be necessary to accumulate additional cases and conduct additional studies, including a prospective survey. CONCLUSION: The results of this study may suggest the existence of a common biological background in patients with MDD that is unaffected by age.

DL-3-n-Butylphthalide, an anti-oxidant agent, prevents neurological deficits and cerebral injury following stroke per functional analysis, magnetic resonance imaging and histological assessment.

DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.

Quantitative assessment of diffuse optical tomography sensitivity to the cerebral cortex using a whole-head probe.

We quantify the variability in diffuse optical tomography (DOT) sensitivity over the cortical surface in eight young adult subjects. We use the 10/5 electroencephalography system as a basis for our whole-head optical high-density probe design. The contrast-to-noise ratio (CNR) is calculated along with the percentage of the cortex that is above a CNR = 0 dB threshold. We also quantify the effect of including vasculature on the forward model and list our assumptions that allow us to estimate light penetration depth in the head. We show that using the 10/5 system for the optical probe design allows for the measurement of 37% of the cortical surface on average, with a mean CNR in the visible region of 5.5 dB. Certain anatomical regions, such as the lateral occipital cortex, had a very high percentage above the CNR threshold, while other regions such as the cingulate cortex were not measurable. Vasculature blocked optical sensitivity over 1% of the cortex. Cortical coverage was positively correlated with intracranial volume and relative cerebrospinal fluid volume, and negatively correlated with relative scalp volume and skull volume. These contributions allow experimenters to understand how anatomical variation in a subject population may impact DOT or functional near-infrared spectroscopy measurements.

Multichannel fNIRS assessment of overt and covert confrontation naming.

Confrontation naming tasks assess cognitive processes involved in the main stage of word production. However, in fMRI, the occurrence of movement artifacts necessitates the use of covert paradigms, which has limited clinical applications. Thus, we explored the feasibility of adopting multichannel functional near-infrared spectroscopy (fNIRS) to assess language function during covert and overt naming tasks. Thirty right-handed, healthy adult volunteers underwent both naming tasks and cortical hemodynamics measurement using fNIRS. The overt naming task recruited the classical left-hemisphere language areas (left inferior frontal, superior and middle temporal, precentral, and postcentral gyri) exemplified by an increase in the oxy-Hb signal. Activations were bilateral in the middle and superior temporal gyri. However, the covert naming task recruited activation only in the left-middle temporal gyrus. The activation patterns reflected a major part of the functional network for overt word production, suggesting the clinical importance of fNIRS in the diagnosis of aphasic patients.