Long-term deficits of preterm birth: evidence for arousal and attentional disturbances.

OBJECTIVE: Quantitative measures of pre-attentional, attentional and frontal lobe processes were compared to evaluate quantitative measures of these deficits in Ex-Preterm vs. Ex-Term adolescents. METHODS: We compared 43 Ex-Preterm with 26 Ex-Term adolescents using the P50 auditory potential, the Psychomotor Vigilance Task (PVT), a reaction time (RT) test, and Near Infrared Spectroscopy (NIRS). RESULTS: The mean amplitude (+/-SE) of the P50 amplitude was similar in the Ex-Preterm (1.8+/-1.4 microV) vs. Ex-Term adolescents (1.8+/-0.6 microV, df = 68, F = 0.05, p = 0.8), but the Ex-Preterm group showed a trimodal distribution in amplitude (High, 3.3+/-0.4 microV, df=42.25, F=19.2, p < 0.01; Medium, 1.7+/-0.1 microV, df = 39, F = 0.41, p = 0.53; Low, 0.7+/-0.1 microV, df = 40, F = 49.5, p < 0.01) suggested by statistically significant variance between populations (Kolmogorov-Kuiper test, df = 42.25, F = 5.4, p < 0.01). Mean RT was longer in Ex-Preterm (250+/-8 ms) vs. Ex-Term subjects (200+/-5 ms, df = 68, F = 18.8, p < 0.001). PVT lapses were increased in Ex-Preterm subjects, and varied inversely with P50 amplitude (Overall Mean 17+/-5 lapses, df = 67, F = 5.34, p < 0.05; Low P50 amplitude, 25+/-10, df = 40, F = 8.8, p < 0.01; Medium, 21+/-11, df = 38, F = 5.37, p < 0.05; High, 6+/-2, df = 39, F = 6.78, p < 0.01) vs. Ex-Term subjects (2+/-0.4 lapses, p < 0.01). NIRS levels did not differ statistically, but tended to correlate with P50 amplitude in the Ex-Preterm group. CONCLUSIONS: These findings suggest differential pre-attentional, attentional and frontal lobe dysfunction in Ex-Preterm adolescents. SIGNIFICANCE: These measures could provide a means to objectively assess differential dysregulation of arousal and attention in Ex-Preterm adolescents, allowing optimization of therapeutic designs.     

Accuracy of intraoperative registration during electromagnetic neuronavigation in intracranial procedures performed in children

BACKGROUND AND PURPOSE: The aim of the study was to evaluate registration accuracy in an electromagnetic navigation system applied to image-guided intracranial procedures in children. MATERIAL AND METHODS: In a group of 34 children aged from 2 weeks to 17 years, 38 procedures were performed using electromagnetic navigation, including 24 neuroendoscopic procedures, 10 craniotomies, and 4 shunting or drainage procedures. Thirty-three registrations based on 7 to 10 anatomical landmarks were digitised, and three-dimensional models of patients' heads were constructed using magnetic resonance images (MRI) (23 cases) or computed tomography scans (CT) (10 cases) and used for further analysis. Registration error calculated by the system was used as a measure of registration accuracy. RESULTS: Registration error in the study group ranged from 0.7 mm to 4.4 mm (median 2.1 mm, mean 2.24 +/- 0.7 mm). It was shown that registration accuracy increased with patients' age. Differences between mean registration errors in procedures based on MRI or CT studies were not significant. There was no correlation between the number of landmarks registered and registration accuracy. CONCLUSIONS: Electromagnetic neuronavigation, which does not require firm head fixation, can be used in the youngest age group. Nevertheless, registration accuracy is lower in newborns and infants. Neither imaging modality (MRI or CT) used for creation of a three-dimensional model of the patient's head nor registration of more than 6 landmarks have an impact on registration accuracy.     

Automatic alignment of EEG/MEG and MRI data sets.

OBJECTIVEs: We developed a new technique of fully automatic alignment of brain data acquired with scalp sensors (e.g. electroencephalography/evoked potential (EP) electrodes, magnetoencephalography sensors) with a magnetic resonance imaging (MRI) volume of the head. METHODS: The method uses geometrical features (two sets of head points: digitized from the subject and extracted from MRI) to guide the alignment. It combines matching on 3 dimensional (3D) geometrical moments that perform the initial alignment, and 3D distance-based alignment that provides the final tuning. To reduce errors of the initial guessed computation resulting from digitization of the head surface points we introduced weights to compute geometrical moments, and a procedure to remove outliers to eliminate incorrectly digitized points. RESULTS: The method was tested on simulated (Monte Carlo trials) and on real data sets. The simulations demonstrated that for the number of test points within the range of 0.1-1% of the total number of head surface points and for the digitization error in the range of -2-2 mm the average map error was between 0.7 and 2.1 mm. The average distance error was less than 1 mm. Tests on real data gave the average distance error between 2.1 and 2.5 mm. CONCLUSIONS: The developed technique is fast, robust and comfortable for the patient and for medical personnel. It registers scalp sensor positions with MRI head volume with accuracy that is satisfactory for localization of biological processes examined with a commonly used number of scalp sensors (32, 64, or 128).     

Real-time refinement of subthalamic nucleus targeting using Bayesian decision-making on the root mean square measure.

The subthalamic nucleus (STN) is a major target for treatment of advanced Parkinson's disease patients undergoing deep brain stimulation surgery. Microelectrode recording (MER) is used in many cases to identify the target nucleus. A real-time procedure for identifying the entry and exit points of the STN would improve the outcome of this targeting procedure. We used the normalized root mean square (NRMS) of a short (5 seconds) MER sampled signal and the estimated anatomical distance to target (EDT) as the basis for this procedure. Electrode tip location was defined intraoperatively by an expert neurophysiologist to be before, within, or after the STN. Data from 46 trajectories of 27 patients were used to calculate the Bayesian posterior probability of being in each of these locations, given RMS-EDT pair values. We tested our predictions on each trajectory using a bootstrapping technique, with the rest of the trajectories serving as a training set and found the error in predicting the STN entry to be (mean +/- SD) 0.18 +/- 0.84, and 0.50 +/- 0.59 mm for STN exit point, which yields a 0.30 +/- 0.28 mm deviation from the expert's target center. The simplicity and computational ease of RMS calculation, its spike sorting-independent nature and tolerance to electrode parameters of this Bayesian predictor, can lead directly to the development of a fully automated intraoperative physiological procedure for the refinement of imaging estimates of STN borders.     

MRI investigation of temporal lobe structures in bipolar patients

Previous anatomical MRI studies have suggested abnormalities in amygdala volumes in bipolar disorder, whereas hippocampus, temporal lobe (TL), and superior temporal gyri (STG) measures have been reported to be normal. This study further investigated the existence of anatomical abnormalities in these brain structures in bipolar subjects, to attempt to replicate previously reported findings. Twenty-four DSM-IV bipolar patients (mean age+/-S.D.=35+/-10 years) and 36 healthy controls (mean age+/-S.D.=37+/-10 years) were studied. 3D SPGR images were obtained with a 1.5T-GE Signa magnet (TR=25 ms, TE=5 ms, FOV=24 cm, slice-thickness=1.5 mm, matrix-size=256 x 192). Volumetric measurements of TL, hippocampus, amygdala, and STG were performed blindly, with a semi-automated software. Bipolar patients had significantly larger left amygdala volumes compared with controls (mean volumes+/-S.D.=2.57+/-0.69 vs. 2.17+/-0.58 ml, respectively; ANCOVA, age, gender, ICV as covariates; F=4.42, df=1/55, P=0.04). The volumes of the other temporal lobe structures did not differ significantly between the two groups (ANCOVA, age, gender, and ICV as covariates, P>0.05). Our findings of enlarged left amygdala in bipolar patients are in agreement with prior MRI studies, suggesting that abnormalities in this brain structure may be implicated in pathophysiology of the illness. Longitudinal studies in high-risk offspring and first-episode patients will be needed to examine whether such abnormalities precede the appearance of symptoms, or whether they may appear subsequently as a result of illness course.     

Comparison of spatial normalization procedures and their impact on functional maps

The alignment accuracy and impact on functional maps of four spatial normalization procedures have been compared using a set of high resolution brain MRIs and functional PET volumes acquired in 20 subjects. Simple affine (AFF), fifth order polynomial warp (WRP), discrete cosine basis functions (SPM), and a movement model based on full multi grid (FMG) approaches were applied on the same dataset for warping individual volumes onto the Human Brain Atlas (HBA) template. Intersubject averaged structural volumes and tissue probability maps were compared across normalization methods and to the standard brain. Thanks to the large number of degrees of freedom of the technique, FMG was found to provide enhanced alignment accuracy as compared to the other three methods, both for the grey and white matter tissues; WRP and SPM exhibited very similar performances whereas AFF had the lowest registration accuracy. SPM, however, was found to perform better than the other methods for the intra-cerebral cerebrospinal fluid (mainly in the ventricular compartments). Limited differences in terms of activation morphology and detection sensitivity were found between low resolution functional maps (FWHM approximately 10 mm) spatially normalized with the four methods, which overlapped in 42.8% of the total activation volume. These findings suggest that the functional variability is much larger than the anatomical one and that precise alignment of anatomical features has low influence on the resulting intersubject functional maps. When increasing the spatial resolution to approximately 6 mm, however, differences in localization of activated areas appear as a consequence of the different spatial normalization procedure used, restricting the overlap of the normalized activated volumes to only 6.2%.     

The role of electrode size on the incidence of spreading depression and on cortical cerebral blood flow as measured by H2 clearance.

Cerebral blood flow was measured by the H2 clearance method 30 and 60 min after the implantation of 300, 250, 125, or 50 microns diameter platinum-iridium electrodes 2 mm deep into the right parietal cortex of normothermic, normocarbic halothane-anesthetized rats. Another group of animals had 50 microns electrodes inserted 1 mm. In all animals, the presence or absence of a wave of spreading depression (SD) was noted at the time of implantation, with recordings made with glass micropipettes. H2 flow values were compared with those measured in gray matter from the same anatomical region (but from different rats), using [3H]nicotine. The incidence of SD ranged from 60% following insertion of 300 microns electrodes to 0% with 50 microns electrodes. H2 clearance flows also varied with electrode size, from 77 +/- 21 ml 100 g-1 min-1 (mean +/- standard deviation) with 300 microns electrodes to 110 +/- 31 and 111 +/- 16 ml 100 g-1 min-1 with 125 and 50 microns electrodes, respectively (insertion depth of 2 mm). A CBF value of 155 +/- 60 ml 100 g-1 min-1 was obtained with 50 micron electrodes inserted only 1 mm. Cortical gray matter blood flow measured with [3H]nicotine was 154 +/- 35 ml 100 g-1 min-1. When the role of SD in subsequent flow measurements was examined, there was a gradual increase in CBF between 30 and 60 min after electrode insertion in those animals with SD, while no such change was seen in rats without SD.(ABSTRACT TRUNCATED AT 250 WORDS)     

AHP reductions in rabbit hippocampal neurons during conditioning correlate with acquisition of the learned response

Young adult male albino rabbits were conditioned using a free field auditory conditioned stimulus (CS) and periorbital shock unconditioned stimulus (US) in a short delay eye blink paradigm. All rabbits received two 80-trial training sessions. Intracellular recordings were made from hippocampal CA1 pyramidal neurons within brain slices prepared 24 h following the second training session. All 46 CA1 neurons included in the analysis had stable penetration, at least 70 mV impulse amplitudes and at least 40 M omega input resistance. Recording and initial data analysis were done 'blind' regarding behavioral training performance of the rabbit from which the slices were prepared. The animals were separated into a High (86 +/- 6% CRs, n = 12), and Low (12 +/- 4% CRs, n = 10) Acquisition group based on the number of blink CRs shown on the second training day (P less than 0.001). CA1 pyramidal neurons from the High Acquisition group (n = 20) showed a significant reduction in the afterhypolarization (AHP) response following 4 impulses elicited by intracellular current injection as compared to neurons from the Low Acquisition group (n = 26). The mean maximal AHP amplitudes after 4 spikes were -2.9 +/- 0.34 mV and -4.0 +/- 0.31 mV, respectively, in the High and Low Acquisition groups (P less than 0.01). The size of the AHP examined at 100 ms intervals during the first 1.7 s after the current pulse proved to be reduced in the High group both when evaluated for all points (F = 5.88, df = 1.44, P less than 0.02) and for each of the individual time points (at least P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Automated alignment of perioperative MRI scans: A technical note and application in pediatric epilepsy surgery

Conventional image registration utilizing brain voxel information may be erroneous in a neurosurgical setting due to pathology and surgery‐related anatomical distortions. We report a novel application of an automated image registration procedure based on skull segmentation for magnetic resonance imaging (MRI) scans acquired before, during and after surgery (i.e., perioperative). The procedure was implemented to assist analysis of intraoperative brain shift in 11 pediatric epilepsy surgery cases, each of whom had up to five consecutive perioperative MRI scans. The procedure consisted of the following steps: (1) Skull segmentation using tissue classification tools. (2) Estimation of rigid body transformation between image pairs using registration driven by the skull segmentation. (3) Composition of transformations to provide transformations between each scan and a common space. The procedure was validated using locations of three types of reference structural landmarks: the skull pin sites, the eye positions, and the scalp skin surface, detected using the peak intensity gradient. The mean target registration error (TRE) scores by skull pin sites and scalp skin rendering were around 1 mm and <1 mm, respectively. Validation by eye position demonstrated >1 mm TRE scores, suggesting it is not a reliable reference landmark in surgical scenarios. Comparable registration accuracy was achieved between opened and closed skull scan pairs and closed and closed skull scan pairs. Our procedure offers a reliable registration framework for processing intrasubject time series perioperative MRI data, with potential of improving intraoperative MRI‐based image guidance in neurosurgical practice. Hum Brain Mapp 37:3530–3543, 2016. © 2016 Wiley Periodicals, Inc.     

Simultaneous measurements of cerebral oxygenation changes during brain activation by near-infrared spectroscopy and functional magnetic resonance imaging in healthy young and elderly subjects

Near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) both allow non-invasive monitoring of cerebral cortical oxygenation responses to various stimuli. To compare these methods in elderly subjects and to determine the effect of age on cortical oxygenation responses, we determined motor-task-related changes in deoxyhemoglobin concentration ([HHb]) over the left motor cortex in six healthy young subjects (age 35 +/- 9 years, mean +/- SD) and five healthy elderly subjects (age 73 +/- 3 years) by NIRS and blood-oxygen-level-dependent (BOLD) fMRI simultaneously. The motor-task consisted of seven cycles of 20-sec periods of contralateral finger-tapping at a rate as fast as possible alternated with 40-sec periods of rest. Time-locked averages over the seven cycles were used for further analysis. Task-related decreases in [HHb] over the motor cortex were measured by NIRS, with maximum changes of -0.83 +/- 0.38 mumol/L (P < 0.01) for the young and -0.32 +/- 0.17 mumol/L (P < 0.05) for the elderly subjects. The BOLD-fMRI signal increased over the cortex volume under investigation with NIRS, with maximum changes of 2.11 +/- 0.72% (P < 0.01) for the young and 1.75 +/- 0.71% (P < 0.01) for the elderly subjects. NIRS and BOLD-fMRI measurements showed good correlation in the young (r = -0.70, r(2) = 0.48, P < 0.001) and elderly subjects (r = -0.82, r(2) = 0.67, P < 0.001). Additionally, NIRS measurements demonstrated age-dependent decreases in task-related cerebral oxygenation responses (P < 0.05), whereas fMRI measurements demonstrated smaller areas of cortical activation in the elderly subjects (P < 0.05). These findings demonstrate that NIRS and fMRI similarly assess cortical oxygenation changes in young subjects and also in elderly subjects. In addition, cortical oxygenation responses to brain activation alter with aging.     

Anatomical standardization of small animal brain FDG-PET images using synthetic functional template: experimental comparison with anatomical template

Anatomical standardization (also called spatial normalization) of positron emission tomography (PET) small animal brain images is required to make statistical comparisons across individuals. Frequently, PET images are co-registered to an individual MR or CT image of the same subject in order to transform the functional images to an anatomical space. In the present work, we evaluate the normalization of synthetic PET (synPET) images to a synthetic PET template. To provide absolute error in terms of pixel misregistration, we created a synthetic PET image from the individual MR image through segmentation of the brain into gray and white matter which produced functional and anatomical images in the same space. When comparing spatial normalization of synPET images to a synPET template with the gold standard (MR images to an MR template), a mean translation error of 0.24mm (±0.20) and a maximal mean rotational error of 0.85° (±0.91) were found. Significant decrease in misregistration error was measured when achieving spatial normalization of functional images to a functional template instead of an anatomical template. This accuracy strengthens the use of standardization methods where individual PET images are registered to a customized PET template in order to statistically assess physiological changes in rat brains.     

Frontal activation during a verbal-fluency task as measured by near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) is an optical method which allows non-invasive in vivo measurements of concentration changes of oxygenated hemoglobin (O(2)Hb) and deoxygenated hemoglobin (HHb) in brain tissue. The present study investigated the blood oxygenation changes that were associated with the execution of the Verbal-Fluency Test (VFT) in left and right prefrontal brain areas of 14 healthy subjects by means of NIRS. During the VFT, subjects were required to pronounce as many nouns as possible beginning with the letters "A," "F," and "S." Compared to a baseline resting condition, we found a significant increase of O2Hb (left hemisphere: baseline, 1.2+/-1.1microm; VFT(letterS), 3.56+/-2.02microm; right hemisphere: baseline, 1.26+/-1.08microm; VFT(letterS), 3.67+/-2.03microm) and a significant decrease of HHb (left hemisphere: baseline, -0.21+/-0.59microm; VFT(letterS), -0.67+/-0.60microm; right hemisphere: baseline, -0.29+/-0.53microm; VFT(letterS), -0.68+/-0.44microm) during the execution of the VFT over both hemispheres. No lateralization effects were observed. The results confirm that NIRS is suitable for the measurement of blood oxygenation changes in frontal brain areas that are associated with cognitive tasks.     

Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans.

Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78%+/-4%; mean+/-s.d.) was halfway between the arterial (98%+/-1%) and jugular venous oxygenation (SvO2; 61%+/-6%). Both NIRS devices monitored SCap (P<0.001) within approximately 5% as SvO2 increased from 39%+/-5% to 79%+/-7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29+/-8 to 65+/-15 cm/sec. When SCap fell below approximately 70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P<0.001) and brain lactate release increased concomitantly (P<0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r>0.74; P<0.05). These results show that NIRS is an adequate cerebral capillary-oxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.     

Normal pituitary volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study

The volume of the pituitary gland in adults with bipolar disorder has previously been reported to be smaller than that of healthy controls. Such abnormalities would be consistent with the HPA dysfunction reported in this illness. We conducted a study of children and adolescents with bipolar disorder to determine whether size abnormalities in the pituitary gland are already present early in illness course. Magnetic resonance imaging (MRI) morphometric analysis of the pituitary gland was carried out in 16 DSM-IV children and adolescents with bipolar disorder (mean age+/-sd=15.5+/-3.4 years) and 21 healthy controls (mean age+/-sd=16.9+/-3.8 years). Subjects underwent a 1.5 T MRI, with 3-D Spoiled Gradient Recalled (SPGR) acquisition. There was no statistically significant difference between pituitary gland volumes of bipolar patients compared to healthy controls (ANCOVA, age, gender, and ICV as covariates; F=1.77, df=1,32, P=.19). There was a statistically significant direct relationship between age and pituitary gland volume in both groups (r=.59, df=17, P=.007 for healthy controls; r=.61, df=12, P=.008 for bipolar patients). No evidence of size abnormalities in the pituitary gland was found in child and adolescent bipolar patients, contrary to reports involving adult bipolar patients. This suggests that anatomical abnormalities in this structure may develop later in illness course as a result of continued HPA dysfunction.     

Multi-modal MRI in normal pressure hydrocephalus identifies pre-operative haemodynamic and diffusion coefficient changes in normal appearing white matter correlating with surgical outcome

Magnetic resonance techniques were used to investigate haemodynamic abnormalities and their consequences in normal pressure hydrocephalus (NPH) and to assess changes in these parameters following surgery. Eleven patients with NPH were studied pre- and post-operatively using perfusion and diffusion weighted imaging and compared with ten age-matched controls. Pre-operative periventricular relative cerebral blood volume (rCBV) was reduced in patients (0.76+/-0.11) compared with control (1.16+/-0.16, P<0.01). There was no difference between outcome groups and no change in haemodynamic parameters following surgery. The periventricular apparent diffusion coefficient (ADC) was elevated in the poor outcome group (1.67+/-0.3 x 10(-3) mm(2) s(-1)) compared with both controls (1.04+/-0.4 x 10(-3) mm(2) s(-1), P<0.05) and the good outcome group (0.99+/-0.3 x 10(-3) mm(2) s(-1), P<0.05) despite appearing normal on conventional imaging. In white matter hyperintensities (WMH), rCBV was reduced (0.70+/-0.12 vs. 1.00+/-0.10, P<0.01), and the ADC was increased (1.98+/-0.6 vs. 1.04+/-0.4 x 10(-3) mm(2) s(-1), P<0.05) compared with the same anatomical location in controls. As low rCBV and high ADC is characteristic of chronic infarction, the findings in WMH regions suggest they are irreversibly damaged. Normal appearing periventricular tissue rCBV was reduced, implying that significant haemodynamic consequences contribute to symptoms in NPH. The elevated pre-operative ADC of the same region, was correlated with poor outcome, and may, therefore, be useful in selecting patients for surgery.     

Rise of blood pressure with periodic limb movements in sleep and wakefulness.

OBJECTIVE: To measure changes in blood pressure and pulse rate associated with periodic limb movements in sleep (PLMS) in patients with restless legs syndrome (RLS). METHODS: We measured autonomic activation as indicated by a rise in blood pressure and pulse rate during periodic limb movements in sleep (PLMS) in 8 patients (6 women average age 57.6+/-16.5 yr and 2 men average age 34+/-28 yr) with RLS. The patients had overnight polysomnographic (PSG) recordings with continuous monitoring of blood pressure (BP) and heart rate (HR). The patients were asked to perform voluntary movements mimicking PLMS (Fake PLMS) which served as controls for PLMS during PSG. We analyzed 601 movements: 145 periodic limb movements in wakefulness (PLMW), 173 periodic limb movements in sleep with cortical arousal (PLMSA), 168 periodic limb movements in sleep without cortical arousal (PLMSNA) and 115 respiratory related limb movements (RRLM). RESULTS: There was a statistically significant rise in systolic blood pressure (SBP), diastolic blood pressure (DBP) after PLMW (SBP 11.7+/-7.6 mm Hg), PLMSA (SBP 16.7+/-9.4 mm Hg), PLMSNA (SBP 11.2+/-8.7 mm Hg) and RRLM (SBP 18.9+/-14.9 mm Hg) which exceeded that seen with Fake PLMS (SBP 3.2+/-3.1 mm Hg) in wakefulness. There were comparable increases in heart rate that did not quite reach statistical significance. CONCLUSIONS: There is a rise in SBP, DBP and HR with PLMW, PLMSNA, PLMSA and RRLM as compared to Fake PLMS. SIGNIFICANCE: One possibility is that the concomitant rise in the blood pressure and heart rate after periodic limb movements indicating autonomic activation may have long-term adverse cardiovascular consequences. This remains to be determined in future experiments.     

Cerebral hemodynamics measured with simultaneous PET and near-infrared spectroscopy in humans

Near-infrared spectroscopy (NIRS) enables continuous non-invasive quantification of blood and tissue oxygenation, and may be useful for quantification of cerebral blood volume (CBV) changes. In this study, changes in cerebral oxy- and deoxyhemoglobin were compared to corresponding changes in CBF and CBV as measured by positron emission tomography (PET). Furthermore, the results were compared using a physiological model of cerebral oxygenation. In five healthy volunteers changes in CBF were induced in a randomized order by hyperventilation or inhalation of 6% CO(2). Arterial content of O(2) and CO(2) was measured several times during each scanning. Changes in deoxyhemoglobin (deltaHb), oxyhemoglobin (deltaHbO(2)) and total hemoglobin (deltaHb(tot)) were continuously recorded with NIRS equipment. CBF and CBV was also determined in MRI-coregistered PET-slices in regions determined by the placement of the two optodes, as localized from the transmission scan. The PET-measurements showed an average CBV of 5.5+/-0.74 ml 100 g(-1) in normoventilation, with an increase of 29% during hypercapnia, whereas no significant changes were seen during hyperventilation. CBF was 51+/-10 in normoventilation, increased by 37% during 6% CO(2) and decreased by 25% during hyperventilation. NIRS showed significant increases in oxygenation during hypercapnia, and a trend towards decreases during hyperventilation. Changes in CBV measured with both techniques were significantly correlated to CO(2) levels. However, deltaCBV(NIRS) was much smaller than deltaCBV(PET), and measured NIRS parameters smaller than those predicted from the model. It is concluded that while qualitatively correct, NIRS measurements of CBV should be used with caution when quantitative results are needed.     

Application of PET-MRI registration techniques to cat brain imaging

In positron emission tomography (PET) studies of diseased animals, it is very useful to have accurate anatomical information as a reference. In human studies, anatomical information is usually obtained from magnetic resonance imaging (MRI) of the subject with retrospective registration of the subject's PET image to the MRI. A number of PET-MRI registration techniques are used for this purpose. However, the utility of these methods has not been tested for animals image registration. This paper studies the feasibility of applying two currently used human brain PET-MRI registration techniques to cat brain images. METHODS: Three cats were anesthetized with isoflurane gas, and PET images were acquired with H(2)(15)O, benzodiazepine receptor ligand 11C-flumazemil (FMZ), dopamine receptor ligand 11C-nemonapride (NEM) and fluorodeoxy glucose (18F-FDG). The four PET scans were acquired consecutively within the same day while the cat remained fixed in the scanner. We also obtained T1-weighted and T2-weighted MRI of the cats in a 4.7 T unit. The PET images were registered to MRI using two human brain registration techniques: a semi-automatic method (SAM), which is a two-step method based on the extraction of the midsagittal plane, and an automatic method (AMIR) method that minimizes PET pixel variance within spatially connected segments determined by MRI. RESULTS: T2-weighted MRI provided better structural information than T1 MRI. FMZ did, while FDG or H(2)O PET images did not, provide a structural outline of the brain. The FMZ PET image was registered to MRI satisfactorily using SAM. The striatum visualized in nemonapride PET image re-sliced with the same parameters matched the striatum identified in T2-weighted MRI. Registration by AMIR was successful by inspection for FMZ, FDG or H(2)O PET images in only one of the three cats. The registration error of SAM was estimated to be less than 2 mm or 2 degrees. CONCLUSION: A satisfactory registration of FMZ-PET to T2-weighted MRI of the cat brain was obtained by a two-step manual registration technique. This will enhance the usefulness of PET in the field of cerebral pathophysiology.     

The VADO approach in psychiatric rehabilitation: a randomized controlled trial

OBJECTIVE: This study investigated whether a specific structured planning and evaluation approach called VADO (in English, Skills Assessment and Definition of Goals) resulted in improved personal and social functioning among patients with chronic schizophrenia. METHODS: A total of 85 patients with chronic schizophrenia who were under a stable medication regimen were randomly allocated to the VADO-based intervention or to routine care; 78 completed the program. Interventions were carried out in nine Italian day treatment or residential rehabilitation facilities. Assessment at the beginning of the study and at the one-year follow-up included the Personal and Social Performance scale (PSP) and Brief Psychiatric Rating Scale Version 4.0 (BPRS). Clinically significant improvement was defined as an increase of at least 10 points on the PSP or a decrease of at least 20 percent on the BPRS total score. RESULTS: At baseline, average PSP scores in the experimental group and in the control group were 33.9+/-8.1 and 34.0+/-11.2, respectively (possible scores range from 1 to 100, with higher scores indicating better functioning). At six months, the score improved markedly in the experimental group (40.8+/-10.9) and minimal change was observed in the control group (35.3+/-11.6); the difference between groups was significant (difference of 6.9 points compared with 1.3 points; t=2.21, df=81, p<.05). At 12 months, the same trend was observed (difference of 12.0 points compared with 3.5 points), and the difference between groups was both statistically and clinically significant (t=2.99, df=75, p<.01). CONCLUSIONS: A statistically and clinically significant improvement in functioning was observed among patients treated with the VADO approach.     

Surface based electrode localization and standardized regions of interest for intracranial EEG

Intracranial recordings captured from subdural electrodes in patients with drug resistant epilepsy offer clinicians and researchers a powerful tool for examining neural activity in the human brain with high spatial and temporal precision. There are two major challenges, however, to interpreting these signals both within and across individuals. Anatomical distortions following implantation make accurately identifying the electrode locations difficult. In addition, because each implant involves a unique configuration, comparing neural activity across individuals in a standardized manner has been limited to broad anatomical regions such as cortical lobes or gyri. We address these challenges here by introducing a semi‐automated method for localizing subdural electrode contacts to the unique surface anatomy of each individual, and by using a surface‐based grid of regions of interest (ROIs) to aggregate electrode data from similar anatomical locations across individuals. Our localization algorithm, which uses only a postoperative CT and preoperative MRI, builds upon previous spring‐based optimization approaches by introducing manually identified anchor points directly on the brain surface to constrain the final electrode locations. This algorithm yields an accuracy of 2 mm. Our surface‐based ROI approach involves choosing a flexible number of ROIs with different spatial resolutions. ROIs are registered across individuals to represent identical anatomical locations while accounting for the unique curvature of each brain surface. This ROI based approach therefore enables group level statistical testing from spatially precise anatomical regions.