Voxel Basis Research Articles

Multimodal wavelet embedding representation for data combination (MaWERiC): integrating magnetic resonance imaging and spectroscopy for prostate cancer detection

Recently, both Magnetic Resonance (MR) Imaging (MRI) and Spectroscopy (MRS) have emerged as promising tools for detection of prostate cancer (CaP). However, due to the inherent dimensionality differences in MR imaging and spectral information, quantitative integration of T(2) weighted MRI (T(2)w MRI) and MRS for improved CaP detection has been a major challenge. In this paper, we present a novel computerized decision support system called multimodal wavelet embedding representation for data combination (MaWERiC) that employs, (i) wavelet theory to extract 171 Haar wavelet features from MRS and 54 Gabor features from T(2)w MRI, (ii) dimensionality reduction to individually project wavelet features from MRS and T(2)w MRI into a common reduced Eigen vector space, and (iii), a random forest classifier for automated prostate cancer detection on a per voxel basis from combined 1.5 T in vivo MRI and MRS. A total of 36 1.5 T endorectal in vivo T(2)w MRI and MRS patient studies were evaluated per voxel by MaWERiC using a three-fold cross validation approach over 25 iterations. Ground truth for evaluation of results was obtained by an expert radiologist annotations of prostate cancer on a per voxel basis who compared each MRI section with corresponding ex vivo wholemount histology sections with the disease extent mapped out on histology. Results suggest that MaWERiC based MRS T(2)w meta-classifier (mean AUC, μ = 0.89 ± 0.02) significantly outperformed (i) a T(2)w MRI (using wavelet texture features) classifier (μ = 0.55 ± 0.02), (ii) a MRS (using metabolite ratios) classifier (μ = 0.77 ± 0.03), (iii) a decision fusion classifier obtained by combining individual T(2)w MRI and MRS classifier outputs (μ = 0.85 ± 0.03), and (iv) a data combination method involving a combination of metabolic MRS and MR signal intensity features (μ = 0.66 ± 0.02).

Image registration and analysis for quantitative myocardial perfusion: application to dynamic circular cardiac CT

Large area detector computed tomography systems with fast rotating gantries enable volumetric dynamic cardiac perfusion studies. Prospectively, ECG-triggered acquisitions limit the data acquisition to a predefined cardiac phase and thereby reduce x-ray dose and limit motion artefacts. Even in the case of highly accurate prospective triggering and stable heart rate, spatial misalignment of the cardiac volumes acquired and reconstructed per cardiac cycle may occur due to small motion pattern variations from cycle to cycle. These misalignments reduce the accuracy of the quantitative analysis of myocardial perfusion parameters on a per voxel basis. An image-based solution to this problem is elastic 3D image registration of dynamic volume sequences with variable contrast, as it is introduced in this contribution. After circular cone-beam CT reconstruction of cardiac volumes covering large areas of the myocardial tissue, the complete series is aligned with respect to a chosen reference volume. The results of the registration process and the perfusion analysis with and without registration are evaluated quantitatively in this paper. The spatial alignment leads to improved quantification of myocardial perfusion for three different pig data sets.

Multi-site voxel-based morphometry — Not quite there yet

Voxel-based morphometry (VBM) is a widely applied method in computational neurosciences but it is currently recommended to compare only data collected at a single MRI scanner. Multi-site VBM would be a desirable approach to increase group size and, thus, statistical power. We aimed to assess if multi-site VBM is feasible on similar hardware and compare the magnitude of inter- and intra-scanner differences.18 healthy subjects were scanned in two identical 3T MRI scanners using different head coil designs, twice in scanner A and once in scanner B. 3D T1-weighted images were processed with SPM8 and FSL4.1 and compared as paired t-test (scan versus re-scan) on a voxel basis by means of a general linear model (GLM). Additionally, coefficient-of-difference (coeffD) maps were calculated for respective pairs of gray matter segmentations.We found considerable inter-scanner differences clearly exceeding a commonly used GLM significance threshold of p<0.05 (FWE corrected). The spatial pattern of detected differences was dependent on whether SPM8 or FSL4.1 was used. The inclusion of global correcting factors either aggravated (SPM8) or reduced the GLM detected differences (FSL4.1). The coeffD analysis revealed markedly higher variability within the FSL4.1 stream both for the inter- and the intra-scanner comparison. A lowered bias cutoff (30mm FWHM) in SPM8 improved the comparability for cortical areas. Intra-scanner scan/re-scan differences were generally weaker and did not exceed a p<0.05 (FWE corrected) threshold in the GLM analysis.At 3T profound inter-scanner differences are to be expected that could severely confound an unbalanced VBM analysis. These are like related to the receive bias of the radio-frequency hardware.

Evaluation of a 3D point cloud tetrahedral tomographic reconstruction method

Tomographic reconstruction on an irregular grid may be superior to reconstruction on a regular grid. This is achieved through an appropriate choice of the image space model, the selection of an optimal set of points and the use of any available prior information during the reconstruction process. Accordingly, a number of reconstruction-related parameters must be optimized for best performance. In this work, a 3D point cloud tetrahedral mesh reconstruction method is evaluated for quantitative tasks. A linear image model is employed to obtain the reconstruction system matrix and five point generation strategies are studied. The evaluation is performed using the recovery coefficient, as well as voxel- and template-based estimates of bias and variance measures, computed over specific regions in the reconstructed image. A similar analysis is performed for regular grid reconstructions that use voxel basis functions. The maximum likelihood expectation maximization reconstruction algorithm is used. For the tetrahedral reconstructions, of the five point generation methods that are evaluated, three use image priors. For evaluation purposes, an object consisting of overlapping spheres with varying activity is simulated. The exact parallel projection data of this object are obtained analytically using a parallel projector, and multiple Poisson noise realizations of these exact data are generated and reconstructed using the different point generation strategies. The unconstrained nature of point placement in some of the irregular mesh-based reconstruction strategies has superior activity recovery for small, low-contrast image regions. The results show that, with an appropriately generated set of mesh points, the irregular grid reconstruction methods can out-perform reconstructions on a regular grid for mathematical phantoms, in terms of the performance measures evaluated.

Three‐dimensional microwave imaging of realistic numerical breast phantoms via a multiple‐frequency inverse scattering technique

Breast density measurement has the potential to play an important role in individualized breast cancer risk assessment and prevention decisions. Routine evaluation of breast density will require the availability of a low-cost, nonionizing, three-dimensional (3-D) tomographic imaging modality that exploits a strong properties contrast between dense fibroglandular tissue and less dense adipose tissue. The purpose of this computational study is to investigate the performance of 3-D tomography using low-power microwaves to reconstruct the spatial distribution of breast tissue dielectric properties and to evaluate the modality for application to breast density characterization. State-of-the-art 3-D numerical breast phantoms that are realistic in both structural and dielectric properties are employed. The test phantoms include one sample from each of four classes of mammographic breast density. Since the properties of these phantoms are known exactly, these testbeds serve as a rigorous benchmark for the imaging results. The distorted Born iterative imaging method is applied to simulated array measurements of the numerical phantoms. The forward solver in the imaging algorithm employs the finite-difference time-domain method of solving the time-domain Maxwell's equations, and the dielectric profiles are estimated using an integral equation form of the Helmholtz wave equation. A multiple-frequency, bound-constrained, vector field inverse scattering solution is implemented that enables practical inversion of the large-scale 3-D problem. Knowledge of the frequency-dependent characteristic of breast tissues at microwave frequencies is exploited to obtain a parametric reconstruction of the dispersive dielectric profile of the interior of the breast. Imaging is performed on a high-resolution voxel basis and the solution is bounded by a known range of dielectric properties of the constituent breast tissues. The imaging method is validated using a breast phantom with a single, high-contrast interior scattering target in an otherwise homogeneous interior. The method is then used to image a set of realistic numerical breast phantoms of varied fibroglandular tissue density. Imaging results are presented for each numerical phantom and show robustness of the method relative to tissue density. In each case, the distribution of fibroglandular tissues is well represented in the resulting images. The resolution of the images at the frequencies employed is wider than the feature dimensions of the normal tissue structures, resulting in a smearing of their reconstruction. The results of this study support the utility of 3-D microwave tomography for imaging the distribution of normal tissues in the breast, specifically, dense fibroglandular tissue versus less dense adipose tissue, and suggest that further investigation of its use for volumetric evaluation of breast density is warranted.

Multi-compound polarization by DNP allows simultaneous assessment of multiple enzymatic activities in vivo

Methods for the simultaneous polarization of multiple 13C-enriched metabolites were developed to probe several enzymatic pathways and other physiologic properties in vivo, using a single intravenous bolus. A new method for polarization of 13C sodium bicarbonate suitable for use in patients was developed, and the co-polarization of 13C sodium bicarbonate and [1- 13C] pyruvate in the same sample was achieved, resulting in high solution-state polarizations (15.7% and 17.6%, respectively) and long spin–lattice relaxation times ( T 1) (46.7 s and 47.7 s respectively at 3 T). Consistent with chemical shift anisotropy dominating the T 1 relaxation of carbonyls, T 1 values for 13C bicarbonate and [1- 13C] pyruvate were even longer at 3 T (49.7 s and 67.3 s, respectively). Co-polarized 13C bicarbonate and [1- 13C] pyruvate were injected into normal mice and a murine prostate tumor model at 3 T. Rapid equilibration of injected hyperpolarized 13C sodium bicarbonate with 13C CO 2 allowed calculation of pH on a voxel by voxel basis, and simultaneous assessment of pyruvate metabolism with cellular uptake and conversion of [1- 13C] pyruvate to its metabolic products. Initial studies in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model demonstrated higher levels of hyperpolarized lactate and lower pH within tumor, relative to surrounding benign tissues and to the abdominal viscera of normal controls. There was no significant difference observed in the tumor lactate/pyruvate ratio obtained after the injection of co-polarized 13C bicarbonate and [1- 13C] pyruvate or polarized [1- 13C] pyruvate alone. The technique was extended to polarize four 13C labelled substrates potentially providing information on pH, metabolism, necrosis and perfusion, namely [1- 13C]pyruvic acid, 13C sodium bicarbonate, [1,4- 13C]fumaric acid, and 13C urea with high levels of solution polarization (17.5%, 10.3%, 15.6% and 11.6%, respectively) and spin–lattice relaxation values similar to those recorded for the individual metabolites. These studies demonstrated the feasibility of simultaneously measuring in vivo pH and tumor metabolism using nontoxic, endogenous species, and the potential to extend the multi-polarization approach to include up to four hyperpolarized probes providing multiple metabolic and physiologic measures in a single MR acquisition.

Comparing Image Processing Techniques for Improved 3-Dimensional Ultrasound Imaging

The purpose of this study was to compare volumetric image processing techniques for reducing noise and speckle while retaining tissue structures in 3-dimensional (3D) gray scale ultrasound imaging. Eighty subjects underwent a clinically indicated abdominal or obstetric 3D ultrasound examination (20 hepatic, 20 renal, and 40 obstetric cases). Volume data were processed on a pixel ("2-dimensional [2D] processing") or a voxel ("3D processing") basis using commercially available image enhancement software (ContextVision AB, Linköping, Sweden). Randomized, side-by-side comparisons of the image processing techniques were performed for each subject. An independent and blinded reader scored the volumes for image quality on a 3-point scale from 1 (worst) to 3 (best) and compared the results using a nonparametric Wilcoxson signed rank test. The 40 subjects with abdominal 3D imaging received a mean score (+/- 1 SD) of 1.52 +/- 0.51, 2.45 +/- 0.60, and 2.75 +/- 0.44 for the original, the 2D processed, and the 3D processed volumes, respectively. The differences between the unprocessed and the processed volumes were highly statistically significant (P < .0001), as was the difference between the 2D and 3D processing methods (P = .002). Similar results were obtained for the obstetric data sets (n = 39 due to an acquisition problem) with a mean score of 1.03 +/- 0.16 for the original, 2.33 +/- 0.48 for the 2D processed, and 2.79 +/- 0.47 for the 3D processed volumes (P < .003). A new volumetric ultrasound image enhancement technique has been assessed in abdominal and obstetric applications. Compared to unprocessed volumes and volumes processed with 2D image enhancement software, the new 3D processing technique performed best.

Smoothing that does not blur: Effects of the anisotropic approach for evaluating diffusion tensor imaging data in the clinic

To compare the effects of anisotropic and Gaussian smoothing on the outcomes of diffusion tensor imaging (DTI) voxel-based (VB) analyses in the clinic, in terms of signal-to-noise ratio (SNR) enhancement and directional information and boundary structures preservation. DTI data of 30 Alzheimer's disease (AD) patients and 30 matched control subjects were obtained at 3T. Fractional anisotropy (FA) maps with variable degrees and quality (Gaussian and anisotropic) of smoothing were created and compared with an unsmoothed dataset. The two smoothing approaches were evaluated in terms of SNR improvements, capability to separate differential effects between patients and controls by a standard VB analysis, and level of artifacts introduced by the preprocessing. Gaussian smoothing regionally biased the FA values and introduced a high variability of results in clinical analysis, greatly dependent on the kernel size. On the contrary, anisotropic smoothing proved itself capable of enhancing the SNR of images and maintaining boundary structures, with only moderate dependence of results on smoothing parameters. Our study suggests that anisotropic smoothing is more suitable in DTI studies; however, regardless of technique, a moderate level of smoothing seems to be preferable considering the artifacts introduced by this manipulation.

Fast volumetric spatial-spectral MR imaging of hyperpolarized 13C-labeled compounds using multiple echo 3D bSSFP.

The goal of this work was to develop a fast 3D chemical shift imaging technique for the noninvasive measurement of hyperpolarized (13)C-labeled substrates and metabolic products at low concentration. Multiple echo 3D balanced steady state magnetic resonance imaging (ME-3DbSSFP) was performed in vitro on a syringe containing hyperpolarized [1,3,3-2H3; 1-(13)C]2-hydroxyethylpropionate (HEP) adjacent to a (13)C-enriched acetate phantom, and in vivo on a rat before and after intravenous injection of hyperpolarized HEP at 1.5 T. Chemical shift images of the hyperpolarized HEP were derived from the multiple echo data by Fourier transformation along the echoes on a voxel by voxel basis for each slice of the 3D data set. ME-3DbSSFP imaging was able to provide chemical shift images of hyperpolarized HEP in vitro, and in a rat with isotropic 7-mm spatial resolution, 93 Hz spectral resolution and 16-s temporal resolution for a period greater than 45 s. Multiple echo 3D bSSFP imaging can provide chemical shift images of hyperpolarized (13)C-labeled compounds in vivo with relatively high spatial resolution and moderate spectral resolution. The increased signal-to-noise ratio of this 3D technique will enable the detection of hyperpolarized (13)C-labeled metabolites at lower concentrations as compared to a 2D technique.

Controlling Familywise Error Rate for Matched Subspace Detection in Dynamic FDG PET

Detection of small lesions in fluorodeoxyglucose (FDG) positron emission tomography (PET) is limited by image resolution and low signal to noise ratio. We have previously described a matched subspace detection method that uses the time activity curve to distinguish tumors from background in dynamic FDG PET. Applying this algorithm on a voxel by voxel basis throughout the dynamic image produces a test statistic image or "map" which on thresholding indicates the potential locations of secondary or metastatic tumors. In this paper, we describe a thresholding method that controls familywise error rate (FWER) for the matched subspace detection statistical map. The method involves three steps. First, the PET image is segmented into several homogeneous regions. Then, the statistical map is normalized to a zero mean unit variance Gaussian random field. Finally, the images are thresholded at a fixed FWER by estimating their spatial smoothness and applying a random field theory maximum statistic approach. We evaluate this thresholding method using digital phantoms generated from clinical dynamic images. We also present an application of the proposed approach to clinical PET data from a breast cancer patient with metastatic disease.

Phenomenological modelling of second cancer incidence for radiation treatment planning

It is still an unanswered question whether a relatively low dose of radiation to a large volume or a higher dose to a small volume produces the higher cancer incidence. This is of interest in view of modalities like IMRT or rotation therapy where high conformity to the target volume is achieved at the cost of a large volume of normal tissue exposed to radiation. Knowledge of the shape of the dose response for radiation-induced cancer is essential to answer the question of what risk of second cancer incidence is implied by which treatment modality. This study therefore models the dose response for radiation-induced second cancer after radiation therapy of which the exact mechanisms are still unknown. A second cancer risk estimation tool for treatment planning is presented which has the potential to be used for comparison of different treatment modalities, and risk is estimated on a voxel basis for different organs in two case studies. The presented phenomenological model summarises the impact of microscopic biological processes into effective parameters of mutation and cell sterilisation. In contrast to other models, the effective radiosensitivities of mutated and non-mutated cells are allowed to differ. Based on the number of mutated cells present after irradiation, the model is then linked to macroscopic incidence by summarising model parameters and modifying factors into natural cancer incidence and the dose response in the lower-dose region. It was found that all principal dose-response functions discussed in the literature can be derived from the model. However, from the investigation and due to scarcity of adequate data, rather vague statements about likelihood of dose-response functions can be made than a definite decision for one response. Based on the predicted model parameters, the linear response can probably be rejected using the dynamics described, but both a flattening response and a decrease appear likely, depending strongly on the effective cell sterilisation of the mutated cells. Thus insights could be gained into the impact of parameters describing the effective mutation or cell sterilisation of non-mutated as well as of mutated cells, which constitute precursors of cancer. The biggest drawbacks in the estimation of second cancer incidence remain the low statistical power of clinical studies on radiation induction of cancer and the inability to isolate the effect due to radiation alone – if the latter is possible at all. We conclude that at the present stage of knowledge, further investigations have to be carried out in order to really compare treatment modalities with respect to the second cancer risk they imply.

A dual DTI approach to analyzing white matter in children with dyslexia

Using voxel-based (VBA) and region-of-interest (ROI) diffusion tensor imaging (DTI) analyses, we examined white matter (WM) organization in seven children with dyslexia and six age-matched controls. Both methods demonstrated reduced fractional anisotropy (FA) in the left superior longitudinal fasciculus (SLF) and abnormal orientation in the right SLF in dyslexics. Application of this complementary dual DTI approach to dyslexia, which included novel analyses of fiber orientation, demonstrates its usefulness for analyzing mild and complex WM abnormalities.

Alterations in nicotinic α4β2 receptor binding in vascular dementia using 123I-5IA-85380 SPECT: Comparison with regional cerebral blood flow

To investigate differences in distribution of α4β2 subtypes of nicotinic acetylcholine receptors (nAChRs) using the ligand ¹²³I-5-Iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) and single photon emission computed tomography (SPECT) in subjects with vascular dementia and age-matched controls. ¹²³I-5IA-85380 binding was compared to corresponding regional cerebral blood flow (rCBF) changes in the same subjects. Thirty subjects (14 vascular dementia and 16 controls) underwent ¹²³I-5IA-85380 and rCBF ((99m)Tc-exametazime) SPECT scanning. Image analysis was performed on voxel basis using statistical parametric mapping (SPM2). Compared to controls, reductions in relative ¹²³I-5IA-85380 uptake were identified in dorsal thalamus and right caudate in vascular dementia. Increase in scaled ¹²³I-5IA-85380 uptake in cuneus was also demonstrated in vascular dementia relative to controls. Perfusion deficits in anterior cingulate were apparent in the patient group and did not appear to be associated with ¹²³I-5IA-85380 changes. Reduced ¹²³I-5IA-85380 uptake in vascular dementia was confined to sub-cortical regions, unlike the cortical reductions previously described in Alzheimer's disease. Elevation of normalised ¹²³I-5IA-85380 uptake in cuneus in vascular dementia could be a compensatory response to reduced cholinergic activity in dorsal thalamus.

A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosis

The purpose of this study is to define the topographical distribution of gray matter (GM) and white matter (WM) damage in patients with primary progressive multiple sclerosis (PPMS), using a multiparametric MR-based approach. Using a 3 Tesla scanner, dual-echo, 3D fast-field echo (FFE), and diffusion tensor (DT) MRI scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An optimized voxel-based (VB) analysis was used to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain. In PPMS patients, GM atrophy was found in the thalami and the right insula, while mean diffusivity (MD) changes involved several cortical-subcortical structures in all cerebral lobes and the cerebellum. An overlap between decreased WM fractional anisotropy (FA) and increased WM MD was found in the corpus callosum, the cingulate gyrus, the left short temporal fibers, the right short frontal fibers, the optic radiations, and the middle cerebellar peduncles. Selective MD increase, not associated with FA decrease, was found in the internal capsules, the corticospinal tracts, the superior longitudinal fasciculi, the fronto-occipital fasciculi, and the right cerebral peduncle. A discrepancy was found between regional WM diffusivity changes and focal lesions because several areas had DT MRI abnormalities but did not harbor T2-visible lesions. Our study allowed to detect tissue damage in brain areas associated with motor and cognitive functions, which are known to be impaired in PPMS patients. Combining regional measures derived from different MR modalities may be a valuable tool to improve our understanding of PPMS pathophysiology.

IN VIVO ASSESSMENT OF THALAMOCORTICAL CONNECTIVITY IN SCHIZOPHRENIA USING DTI AND INTEGRATIVE EVIDENCE FROM fMRI

We describe a novel technique for characterizing regional cerebral gray and white matter differences in structural magnetic resonance images by the application of methods derived from functional imaging. The technique involves automatic scalp-editing of images followed by segmentation, smoothing, and spatial normalization to a symmetrical template brain in stereotactic Talairach space. The basic idea is (i) to convert structural magnetic resonance image data into spatially normalized images of gray (or white) matter density, effected by segmenting the images and smoothing, and then (ii) to use Statistical Parametric Mapping to make inferences about the relationship between gray (or white) matter density and symptoms (or other pathophysiological measures) in a regionally specific fashion. Because the whole brain sum of gray (or white) matter indices is treated as a confound, the analysis reduces to a characterization of relative gray (or white) matter density on a voxel by voxel basis. We suggest that this is a powerful approach to voxel-based statistical anatomy. Using the technique, we constructed maps of the regional cerebral gray and white matter density correlates of syndrome scores (distinct psychotic symptoms) in a group of 15 schizophrenic patients. There was a negative correlation between the score for the reality distortion syndrome and regional gray matter density in the left superior temporal lobe (P = 0.01) and regional white matter density in the corpus callosum (P < 0.001). These abnormalities may be associated with functional changes predisposing to auditory hallucinations and delusions. This method permits the detection of structural differences within the entire brain (as opposed to selected regions of interest) and may be of value in the investigation of structural gray and white matter abnormalities in a variety of brain diseases.

Application of distance transformation on parameter optimization of inverse planning in intensity‐modulated radiation therapy

In inverse planning for intensity‐modulated radiation therapy (IMRT), the dose specification and related weighting factor of an objective function for involved organs is usually predefined by a single value and then iteratively optimized, subject to a set of dose—volume constraints. Because the actual dose distribution is essentially non‐uniform and considerably affected by the geometric shape and distribution of the anatomic structures involved, the spatial information regarding those structures should be incorporated such that the predefined parameter distribution is made to approach the clinically expected distribution. Ideally, these parameter distributions should be predefined on a voxel basis in a manual method. However, such an approach is too time‐consuming to be feasible in routine use.In the present study, we developed a computer‐aided method to achieve the goal described above, producing a non‐uniform parameter distribution based on spatial information about the anatomic structures involved. The method consists of two steps: Use distance transformation technique to calculate the distance distribution of the structures.Based on the distance distribution, produce the parameter distribution via a conversion function guided by prior knowledge. We use two simulated cases to examine the effectiveness of the method. The results indicate that application of a non‐uniform parameter distribution produced by distance transformation clearly improves dose‐sparing of critical organs without compromising dose coverage of the planning target.PACS numbers: 87.53.Jw

Atorvastatin Therapy is Associated with Greater and Faster Cerebral Hemodynamic Response

Hypercholesterolemia in midlife increases the risk of subsequent cognitive decline, neurovascular disease, and Alzheimer's disease (AD), and statin use is associated with reduced prevalence of these outcomes. While statins improve vasoreactivity in peripheral arteries and large cerebral arteries, little is known about the effects of statins on cerebral hemodynamic responses and cognition in healthy asymptomatic adults. At the final visit of a 4-month randomized, controlled, double-blind study comparing atorvastatin 40 mg daily to placebo, 16 asymptomatic middle-aged adults (15 had useable data) underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) quantitative cerebral blood flow (qCBF), dynamic susceptibility contrast (DSC) and structural imagings of the brain. Using a memory recognition task requiring discrimination of previously viewed (PV) and novel (NV) human faces, fMRI was used to elicit activation from brain regions known to be vulnerable to changes associated with AD. The BOLD signal amplitude (PV > NV) and latency to each stimulus were tested on a voxel basis between the atorvastatin (n=8) and placebo (n=7) groups. Persons randomized to atorvastatin not only showed significantly greater BOLD amplitude in the right angular gyrus, left superior parietal lobule, right middle temporal and superior sulcus than the placebo group, but also decreased hemodynamic response latencies in the right middle frontal gyrus, left precentral gyrus, left cuneus and right posterior middle frontal gyrus. However, neither the resting cerebral blood flow (CBF) measured with ASL nor the mean transit time (MTT) of cerebral perfusion calculated from DSC showed differences in these regions in either group. The drug related BOLD differences during memory recognition suggest that atorvastatin may have improved cerebral small vessel vasoreactivity, possibly through an effect on endothelial function. Furthermore, these results suggest that the effect of atorvastatin on the task-induced BOLD signal may not be a simple consequence of baseline flow change.

Computer-assisted lateralization of unilateral temporal lobe epilepsy using Z-score parametric F-18 FDG PET images

BackgroundTo evaluate the use of unbiased computer-assisted lateralization of temporal lobe epilepsy (TLE) by z-score parametric PET imaging (ZPET).Methods38 patients with histologically proven unilateral TLE due to pure hippocampal sclerosis, referred for pre-surgical PET evaluation of intractable seizure over a 5-year period, were included. The F-18 FDG images were oriented along temporal long axis and then transformed into ZPET images on a voxel by voxel basis. Multiple regions of interests (21 in total) were placed on cortical, subcortical and cerebellar structures on twenty-eight out of 38 patients with totally seizure-free (class I) outcome. Paired t-tests with Bonferroni correction were used to determine the location of the most asymmetric regions as variables for subsequent discriminant analysis of the entire group of the patients.ResultsThe computer program identified the anterior half of the temporal lobe (p < 0.0005) and thalami (p = 0.021) as the most asymmetric regions in TLE patients with Class I outcome. Discriminant analysis using z-scores from a total of 8 ROIs (in 4 pairs) on these structures correctly lateralized thirty-seven out of 38 (97%) patients (sensitivity = 94%; specificity = 100%). The only false localization came from a patient with equivocal z-scores on the temporal lobes and this patient turned out to have poor outcome.ConclusionThe computer-assisted lateralization of TLE using ZPET provides an accurate, fast and objective way of seizure evaluation.

Voxel-based modeling and quantification of the proximal femur using inter-subject registration of quantitative CT images

We have developed a general framework which employs quantitative computed tomography (QCT) imaging and inter-subject image registration to model the three-dimensional structure of the hip, with the goal of quantifying changes in the spatial distribution of bone as it is affected by aging, drug treatment or mechanical unloading. We have adapted rigid and non-rigid inter-subject registration techniques to transform groups of hip QCT scans into a common reference space and to construct composite proximal femoral models. We have applied this technique to a longitudinal study of 16 astronauts who on average, incurred high losses of hip bone density during spaceflights of 4–6 months on the International Space Station (ISS). We compared the pre-flight and post-flight composite hip models, and observed the gradients of the bone loss distribution. We performed paired t-tests, on a voxel by voxel basis, corrected for multiple comparisons using false discovery rate (FDR), and observed regions inside the proximal femur that showed the most significant bone loss. To validate our registration algorithm, we selected the 16 pre-flight scans and manually marked 4 landmarks for each scan. After registration, the average distance between the mapped landmarks and the corresponding landmarks in the target scan was 2.56 mm. The average error due to manual landmark identification was 1.70 mm.

Estimation of Baseline Dopamine D2 Receptor Occupancy in Striatum and Extrastriatal Regions in Humans with Positron Emission Tomography with [18F] Fallypride

This study examined whether positron emission tomography (PET) studies with [18F] fallypride performed before and after alpha-methyl-para-tyrosine (AMPT) administration can be used to estimate baseline dopamine (DA) D2 receptor occupancy in striatal and extrastriatal regions. Six normal subjects underwent PET with [18 F] fallypride before and after administration of AMPT. The DA D2 receptor binding potentials (bp) were calculated with the reference region method. Percent changes in bp in striatal and extrastriatal regions were calculated with both region-of-interest analysis and on a voxel by voxel basis with parametric images of DA D2 receptor levels. The results of the current study indicate that AMPT treatment significantly increased the bp in the caudate, putamen, ventral striatum, and substantia nigra. A trend level increase was seen in the medial thalamus. This study demonstrates that PET with [18F] fallypride can be used to estimate baseline DA D2 receptor occupancy in striatal and extrastriatal regions.