Voxel Analysis Research Articles

Locally increased P-glycoprotein function in major depression: a PET study with [11C]verapamil as a probe for P-glycoprotein function in the blood–brain barrier

The aetiology of depressive disorder remains unknown, although genetic susceptibility and exposure to neurotoxins are currently being discussed as possible contributors to this disorder. In normal circumstances, the brain is protected against bloodborne toxic influences by the blood-brain barrier, which includes the molecular efflux pump P-glycoprotein (P-gp) in the vessel wall of brain capillaries. We hypothesized that P-gp function in the blood-brain barrier is changed in patients with major depression. Positron emission tomography was used to measure brain uptake of [11C]verapamil, which is normally expelled from the brain by P-gp. Cerebral volume of distribution (V(T)) of [11C]verapamil was used as a measure of P-gp function. Both region-of-interest (ROI) analysis and voxel analysis using statistical parametric mapping (SPM2) were performed to assess regional brain P-gp function. We found that patients with a major depressive episode, using antidepressants, compared to healthy controls showed a significant decrease of [11C]verapamil uptake in different areas throughout the brain, in particular in frontal and temporal regions. The decreased [11C]verapamil uptake correlates with an increased function of the P-gp protein and may be related to chronic use of psychotropic drugs. Our results may explain why treatment-resistant depression can develop.

Measuring Noncalcified Coronary Atherosclerotic Plaque Using Voxel Analysis with MDCT Angiography: A Pilot Clinical Study

The purpose of our study was to evaluate a new method using voxel analysis for quantifying noncalcified plaque in coronary arteries using MDCT angiography (MDCTA) compared with luminal stenosis by catheter coronary arteriography. Forty-one normal and eight abnormal arterial cross sections with noncalcified plaque selected from 40 patients undergoing MDCTA were analyzed for percentage of stenosis and plaque volume using a voxel analysis technique. Using voxel analysis, the normal arterial wall thickness was determined to be 0.8 +/- 0.4 mm. Attenuation values (in Hounsfield units) for normal segments ranged between 30 and 175 H and for abnormal (plaque-containing) segments ranged from -49 to 139 H (p < 0.05). Plaque volume measurements varied from 0.90 to 156 mm(3) with good interobserver correlation (R(2) = 0.9671). Percentage of stenosis correlated with quantitative coronary arteriography measurement (R(2) = 0.55). Voxel analysis underestimated the percentage of stenosis (Pearson's correlation coefficient, 1.2; p = 0.03). The study shows that the voxel analysis technique appears to be an accurate and reproducible method to measure arterial wall thickness, noncalcified plaque, and degree of arterial stenosis using density values measured in Hounsfield units. The technique may be useful on further correlative studies.

Measuring Noncalcified Coronary Atherosclerotic Plaque Using Voxel Analysis with MDCT Angiography: Phantom Validation

This purpose of this study was to evaluate the accuracy and reproducibility of a voxel analysis technique for measuring noncalcified plaque in the coronary arteries. Polyethylene phantoms representing noncalcified plaque were scanned in both MDCT and micro-CT scanners and inter- and intrareader variability of volume calculation was performed. Volume measurements by both MDCT and micro-CT were comparable to the true volume as measured by micrometry (< 3%, p = 0.05). There appears to be no significant difference (< 3%) between MDCT and micro-CT measurements.

Blood–brain barrier P-glycoprotein function is not impaired in early Parkinson's disease

The cause of Parkinson's disease (PD) is unknown. Genetic susceptibility and exposure to environmental toxins contribute to specific neuronal loss in PD. Decreased blood–brain barrier (BBB) P-glycoprotein (P-gp) efflux function has been proposed as a possible causative link between toxin exposure and PD neurodegeneration. In the present study BBB P-gp function was investigated in vivo in 10 early stage PD patients and 8 healthy control subjects using ( R)-[ 11C]-verapamil and PET. Cerebral volume of distribution ( V d) of verapamil was used as measure of P-gp function. Both region of interest (ROI) analysis and voxel analysis using statistical parametric mapping (SPM) were performed to assess regional brain P-gp function. In addition, MDR1 genetic polymorphism was assessed. In the present study, a larger variation in V d of ( R)-[ 11C]-verapamil was seen in the PD group as compared to the control group. However, decreased BBB P-gp function in early stage PD patients could not be confirmed.

Soft Tissue Tendon Graft Fixation in Serially Dilated or Extraction-Drilled Tibial Tunnels

Background Tibial tunnel preparation may contribute to improved soft tissue graft fixation. Hypothesis Step dilation produces greater tunnel wall bone volume than does extraction drilling and increases fixation strength. Bioabsorbable interference screw divergence decreases fixation strength, regardless of tunnel preparation method. Study Design Controlled laboratory study. Methods Twenty porcine tibias were divided into 2 groups of 10 with matching mean apparent bone mineral density. One group received 9-mm-diameter extraction-drilled tunnels, and the other group received 7-mm-diameter extraction-drilled tunnels followed by step dilation to 9 mm. High-resolution quantitative computerized tomography scans and voxel analysis techniques determined tunnel wall bone volume fraction. Screws secured 8.5-mm-diameter porcine grafts in the tunnels. Repeat scans were used to determine screw divergence. Cyclic loading was performed in a servohydraulic device before load to failure testing. Results The step dilation group had greater tunnel wall bone volume/total volume than did the extraction drilled group; however, a significant increase in fixation strength was not detected. Specimens with screw divergence angles less than 15° had superior fixation and insertion torques compared with specimens with angles 15° or more. Screw divergence correlated more strongly with fixation strength than did mean apparent bone mineral density or screw insertion torque. Conclusion Step dilation increased tunnel wall bone volume/total volume, but fixation strength did not improve. Screw divergence ≥15° decreases graft-bone tunnel fixation whether or not step dilation is performed. Clinical Relevance Screw alignment plays a greater role in anterior cruciate ligament graft fixation than does extraction drilling or step dilation tunnel preparation methods in healthy bone.

1902 重合メッシュ法によるボクセル解析の熱構造連成問題への適用(OS19.大規模連成解析と関連話題(1))

1902 重合メッシュ法によるボクセル解析の熱構造連成問題への適用(OS19.大規模連成解析と関連話題(1))

Spinning Disk Confocal Microscopy of Live, Intraerythrocytic Malarial Parasites. 1. Quantification of Hemozoin Development for Drug Sensitive versus Resistant Malaria

We have customized a Nipkow spinning disk confocal microscope (SDCM) to acquire three-dimensional (3D) versus time data for live, intraerythrocytic malarial parasites. Since live parasites wiggle within red blood cells, conventional laser scanning confocal microscopy produces blurred 3D images after reconstruction of z stack data. In contrast, since SDCM data sets at high x, y, and z resolution can be acquired in hundreds of milliseconds, key aspects of live parasite cellular biochemistry can be much better resolved on physiologically meaningful times scales. In this paper, we present the first 3D DIC transmittance "z stack" images of live malarial parasites and use those to quantify hemozoin (Hz) produced within the living parasite digestive vacuole, under physiologic conditions. Using live synchronized cultures and voxel analysis of sharpened DIC z stacks, we present the first quantitative in vivo analysis of the rate of Hz growth for chloroquine sensitive (CQS) versus resistant (CQR) malarial parasites. We present data for laboratory strains, as well as pfcrt transfectants expressing a CQR conferring mutant pfcrt gene. We also analyze the rate of Hz growth in the presence and absence of physiologically relevant doses of chloroquine (CQ) and verapamil (VPL) and thereby present the first in vivo quantification of key predictions from the well-known Fitch hypothesis for CQ pharmacology. In the following paper [Gligorijevic, B., et al. (2006) Biochemistry 45, pp 12411-12423], we acquire fluorescent images of live parasite DV via SDCM and use those to quantify DV volume for CQS versus CQR parasites.

Comparison of the diagnostic performance of FDG-PET and VBM-MRI in very mild Alzheimer’s disease

The aim of this study was to compare the diagnostic performance of( 18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM) on magnetic resonance imaging (MRI) in the same group of patients with very mild Alzheimer's disease (AD). Thirty patients with very mild AD (age 67.0+/-5.8 years; MMSE score 25.5+/-1.2, range 24-28), 32 patients with mild AD (age 67.0+/-4.5 years, MMSE score 22.1+/-0.8, range 21-23) and 60 age- and sex-matched normal volunteers underwent both FDG-PET and three-dimensional spoiled gradient echo MRI. Statistical parametric mapping was used to conduct voxel by voxel analysis and Z score mapping. First, the region of interest (ROI) maps of significant reductions in glucose metabolism and grey matter density in the mild AD patients were defined. Secondly, analysis of receiver operating characteristic (ROC) curves for Z scores in the ROI maps discriminating very mild AD patients and normal controls was performed. In mild AD patients, FDG-PET indicated significant reductions in glucose metabolism in the bilateral posterior cingulate gyri and the right parietotemporal area, while VBM analysis showed a significant decrease in grey matter volume density in the bilateral amygdala/hippocampus complex, compared with the normal control group. ROC analysis showed that in very mild AD patients the accuracy of FDG-PET diagnosis was 89% and that of VBM-MRI diagnosis was 83%. The accuracy of the combination of FDG-PET and VBM-MRI diagnosis was 94%. In very mild AD, both FDG-PET and VBM-MRI had high accuracy for diagnosis, but FDG-PET showed slightly higher accuracy than VBM-MRI. Combination of the two techniques will yield a higher diagnostic accuracy in very mild AD by making full use of functional and morphological images.

Heterogeneity in the angiogenic response of a BT474 human breast cancer to a novel vascular endothelial growth factor‐receptor tyrosine kinase inhibitor: Assessment by voxel analysis of dynamic contrast‐enhanced MRI

To investigate the heterogeneity in the angiogenic response of a human breast cancer xenograft to a novel vascular endothelial growth factor (VEGF)-receptor tyrosine kinase inhibitor, AG-013736, using dynamic contrast-enhanced MR imaging (DCE-MRI). Changes in pharmacokinetic parameters in a seven-day interval were compared between AG-treated and control groups, using Gd-DTPA and albumin-(Gd-DTPA)30. A voxel-by-voxel analysis was performed to produce parametric spatial pharmacokinetic parametric maps and histograms. Histogram segmentation was used to quantify the heterogeneity in tumor response to therapy, and compared with conventional descriptive measures of distribution in terms of their capacity to separate control from AG-treated tumors. The albumin-(Gd-DTPA)30 endothelial transfer constant, Kps, showed changes with AG-013736 treatment and tumor growth. The changes were highly heterogeneous for individual segments of the histogram with different Kps values, and the overall patterns in which the frequency distribution changed differed significantly between the two groups. A change in the number of voxels with Kps ranging from 0.03 to 0.14 mL/min/(100 mL tissue) was the most sensitive variable for separating control from AG-treated tumors (P = 0.0008). Parametric maps of the kinetic parameters also showed spatial heterogeneity in tumor response to treatment. The Kps maps depicted rapid development of central necrosis as a result of AG-013736 treatment. Maps of v(p) demonstrated a marked increase at peripheral regions of necrotic areas. Similar trends were noted in the Gd-DTPA rate constant Ktrans distribution. This study demonstrates the value of histogram analysis of maps of pharmacokinetic parameters for assessing heterogeneity in tumor response to antiangiogenic therapy. Changes in the number of voxels within certain segments of the Kps histogram were the most sensitive variable for separating control from AG-treated tumors.

Longitudinal Diffusion Changes in Cerebral Hemispheres after MCA Infarcts

Diffusion tensor imaging can be used in vivo to assess the longitudinal and regional microstructural changes occurring after middle cerebral artery (MCA) infarcts in humans. Nine patients were investigated 1 week (D7), 1 (M1), 3 (M3), and 6 months (M6) after the occurrence of an isolated MCA infarction. First, an overall analysis was performed using histograms of mean diffusivity (MD) and fractional anisotropy (FA) in each hemisphere. Thereafter, the regional pattern of diffusion changes was investigated voxel by voxel with statistical parametric mapping 99. In the hemisphere ipsilateral to the infarction, histogram analysis revealed a significant decrease in FA between D7 and M6 associated with a progressive increase in MD from D7 to M3. Remote from the MCA territory, the voxel by voxel analyses detected a significant increase in MD within the thalamus at M3 and M6 and a reduction in FA along the pyramidal tract at M6. In the contralateral hemisphere, between D7 and M6, a significant hemispheric atrophy was observed in association with a global reduction in anisotropy, in the absence of distinctive regional diffusion changes. These results suggest that micro- and macrostructural tissue modifications can be detected with diffusion tensor imaging in regions remote from the ischemic area in both hemispheres.

APOE and modulation of Alzheimer's and frontotemporal dementia

To investigate the difference in the morphologic expression of frontotemporal dementia (FTD) and Alzheimer's disease (AD) in patients carrying and not carrying the ϵ4 allele of APOE, MR images of 26 controls, 18 AD patients (11 carrying the ϵ4 allele, seven non-carriers), and eight FTD (two carriers, six non-carriers) were compared using voxel by voxel analysis. Greater atrophy was found in the disease-specific regions of the ϵ4 carriers vs the non-carriers at P<0.05 corrected: medial temporal atrophy was greater in the AD carrying the ϵ4 allele, right ventral striatal atrophy in the FTD carrying the allele. The non-carriers did not have atrophic regions compared to the carriers. The ϵ4 allele of the APOE might modulate the expression of degenerative dementias by enhancing the specific effects of neurodegenerative diseases on the brain.

Analysis of Fracture Mechanism Using Adaptive Finite Cover Method

In this paper, the multi-level finite cover method is extended to adaptive analysis and applied to the fracture analysis. Finite cover method (FCM) employs the concept of mathematical cover from Manifold method, and applied to the voxel analysis. FCM-CLSA enables the multi-level distribution of voxel. For the indicator of sub-division of voxel, a-posteriori error estimation and accuracy of geometric representation is considered. For the representation of crack propagation the removal of te voxel at the area where fracture occurred is proposed and by this approach it was shown that the representation of crack propagation can be carried out much easier than the traditional approach in which geometrical reprenentation of crack is needed, while keeping the necessary accuracy by keeping the size of voxel small enough where fracture occurs. 2 dimensional example of avalanche is shown to demonstrate the capability of the approach.

Development of Design Support Tool Using 3D Topology Optimization with Multilevel Voxel Analysis

Development of Design Support Tool Using 3D Topology Optimization with Multilevel Voxel Analysis

Increased ventral striatal monoaminergic innervation in Tourette syndrome

Excessive striatal dopaminergic innervation is suggested to underlie Tourette syndrome (TS). Prior imaging and postmortem studies yield conflicting data. The authors used PET with the type 2 vesicular monoamine transporter ligand [(11)C]dihydrotetrabenazine (DTBZ) to quantify striatal monoaminergic innervation in patients with TS (n = 19) and control subjects (n = 27). Compartmental modeling was used to determine blood to brain ligand transport (K(1)) and tissue to plasma distribution volume (a measure of ligand binding) during continuous infusion of DTBZ. TS data were compared with control data using predefined regions of interest and on a voxel by voxel basis. There were no significant differences in ligand binding or ligand transport between patients with TS and control subjects in the dorsal striatum. With voxel by voxel analysis, there was increased DTBZ binding in the right ventral striatum. Previously reported differences between patients with TS and control subjects in dorsal striatal dopamine terminal markers may reflect medication-induced regulation of terminal marker expression or be the result of intrinsic differences in striatal dopaminergic synaptic function. Increased right ventral striatal DTBZ binding suggests that abnormal ventral striatal dopaminergic innervation may underlie tics.

Hydrogen-1 MR Spectroscopy of the Peritumoral Zone in Patients with Cerebral Glioma: Assessment of the Value of the Method

Rationale and Objectives The determination of tumor boundaries, especially in high-grade glioma, is critically important for the proper planning of treatment, but the standard diagnostic imaging methods do not enable precise delimitation of the extent of tumor cell infiltration into the surrounding tissue. The objective of this study was to assess the usefulness of hydrogen-1 (H-1) magnetic resonance (MR) spectroscopy for determining the extent of gliomatous infiltrate in the “uncertain zone”—the peritumoral area that appears unchanged on standard diagnostic MR images. Materials and Methods The study group consisted of 64 patients with cerebral glioma scheduled for tumor resection and subsequent radiation therapy. All patients were examined prior to resection with MR imaging and MR spectroscopy. MR spectra were obtained from examination of the solid part of the tumor and from two peritumoral volumes of interest located approximately along the axis of surgical access to the tumor. MR spectra obtained from a group of 32 healthy volunteers were used as control data. Results Analysis of the consequent voxels in the peritumoral zone revealed statistically significant differences in lipid/creatine and lactate/creatine metabolite ratios between patient subgroups with recurrent malignant lesions and without recurrent lesions. Significant differences also were found between the patient group and the control group in most metabolite ratios assessed. Conclusion H-1 MR spectroscopic demonstration of metabolic changes in the peritumoral zone can guide treatment for cerebral glioma, enabling the physician to identify patients who have a high risk of recurrence.

Volumetrijska analiza sive mase, bele mase i prostora cerebrospinalne tecnosti u shizofreniji

Schizophrenia is characterized by diffuse brain abnormalities, some of them involving volumes of three intracranial compartments: gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Novel methods, such as Statistical Parametrical Mapping, provide an automated means of comparing structural features across high quality MRI scans and the measurement based on the principles of voxel based morphometry. For the purposes of the present study, we selected sex balanced group of young adults with recent onset illness to assess the effects of the illness on the volumes of compartments and also to minimize the effects of chronicity, medication, sex and aging. Sixty-four subjects were selected from a larger sample (inclusion criteria: age range 18-31). Thirty-one had DSM IV diagnosis of schizophrenia or schizoaffective disorder, 33 were controls. T1 weighted MRI images were acquired on two scanners (1.5T both): a) fast gradient echo sequence, FLASH, 40 msec repetition time, 5 ms echo time, 40 degree flip angle and b) turbo gradient echo, 12 msec repetition time, 4 msec echo time, 20 degree flip angle, 1 excitation). The resulting data set consisted of: a) 128 consecutive slices with 1.17 mm thickness and 256 x 256 pixels per slice and b) 160 consecutive slices of 1 mm thickness and 256 x 256 pixels per slice. All 64 images were processed by ANALZYE, and normalized and segmented by SPM99. Following the automatic segmentation of the images into the three intracranial compartments, volumetry was performed based on the principles of voxel analysis. Results were expressed relative to whole brain volume, and MANOVA analyses were performed to correct the confounding effects of MRI acquisition center differences and age difference between diagnostic groups. Young adults with recent onset schizophrenia had 6% reduction in GM volume and 14% increase in the volume of CSF, after all confounders were included into analyses (MANCOVA: p = 0.006 and 0.0002, respectively). No significant changes in WM volume were evident. In comparison to a few similar studies published recently, all results yielded similar scores regarding effects of recent onset illness and young adult population, thus confirming the reliability of the procedure. In conclusion, global neuropil reduction was discussed as a consequence of the cortical neurodevelopmental disgenesis. It was suggested that neuropil reduction i.e. synaptic and dendritic changes were to induce functional abnormalities and the expression of schizophrenia.

VOXEL ANALYSIS OF GROUNDWATER FLOW FOR UNDERGROUND REPOSITORY PLANNING

VOXEL ANALYSIS OF GROUNDWATER FLOW FOR UNDERGROUND REPOSITORY PLANNING

Feature-space clustering for fMRI meta-analysis.

Clustering functional magnetic resonance imaging (fMRI) time series has emerged in recent years as a possible alternative to parametric modeling approaches. Most of the work so far has been concerned with clustering raw time series. In this contribution we investigate the applicability of a clustering method applied to features extracted from the data. This approach is extremely versatile and encompasses previously published results [Goutte et al., 1999] as special cases. A typical application is in data reduction: as the increase in temporal resolution of fMRI experiments routinely yields fMRI sequences containing several hundreds of images, it is sometimes necessary to invoke feature extraction to reduce the dimensionality of the data space. A second interesting application is in the meta-analysis of fMRI experiment, where features are obtained from a possibly large number of single-voxel analyses. In particular this allows the checking of the differences and agreements between different methods of analysis. Both approaches are illustrated on a fMRI data set involving visual stimulation, and we show that the feature space clustering approach yields nontrivial results and, in particular, shows interesting differences between individual voxel analysis performed with traditional methods.

Reduction of frontal neocortical grey matter associated with affective aggression in patients with temporal lobe epilepsy: an objective voxel by voxel analysis of automatically segmented MRI

BACKGROUNDInterictal episodes of aggression are often reported in patients with epilepsy. Some have characteristics of what has been referred to as episodic dyscontrol or intermittent explosive disorder (IED). Although structural...

Detecting Anatomical Changes Using Logistic Regression of Structure Masks

Introduction Neuroscientists are often interested in determining whether external covariates are related to changes in brain shape. There are three main ways currently being used to determine anatomical changes in human brains: 1) deformation fields produced from nonlinear warping techniques [1-3]; 2) surface extraction techniques [4,6,7,10] and 3) voxel analysis of structure masks [9]. Using results from random field theory, we show how logistic regression of structure masks can be used to detect anatomical changes.