Louis Collins

Enhancement of MR images using registration for signal averaging

Purpose: With the advent of noninvasive neuroimaging, a plethora of digital human neuroanatomical atlases has been developed. The accuracy of these atlases is constrained by the resolution and signal-gathering powers of available imaging equipment. In an attempt to circumvent these limitations and to produce a high resolution in vivo human neuroanatomy, we investigated the usefulness of intrasubject registration for post hoc MR signal averaging. Method: Twenty-seven high resolution (7 x 0.78 and 20 x 1.0 mm 3 ) Tl-weighted volumes were acquired from a single subject. along with 12 double echo T2/proton density-weighted volumes. These volumes were automatically registered to a common stereotaxic space in which they were subsampled and intensity averaged. The resulting images were examined for anatomical quality and usefulness for other analytical techniques. Results: The quality of the resulting image from the combination of as few as five Tl volumes was visibly enhanced. The signal-to-noise ratio was expected to increase as the root of the number of contributing scans to 5.2, n = 27. The improvement in the n = 27 average was great enough that fine anatomical details, such as thalamic subnuclei and the gray bridges between the caudate and putamen, became crisply defined. The gray/white matter boundaries were also enhanced. as was the visibility of any finer structure that was surrounded by tissue of varying Tl intensity. The T2 and proton density average images were also of higher quality than single scans, but the improvement was not as dramatic as that of the Tl volumes. Conclusion: Overall, the enhanced signal in the averaged images resulted in higher quality anatomical images, and the data lent themselves to several postprocessing techniques. The high quality of the enhanced images permits novel uses of the data and extends the possibilities for in vivo human neuroanatomy.

Anatomical mapping of functional activation in stereotactic coordinate space

Numerous applications have been reported for the stereotactic mapping of focal changes in cerebral blood flow during sensory and cognitive activation as measured with positron emission tomography (PET) subtraction images. Since these images lack significant anatomical information, analysis of these kinds of data has been restricted to an automated search for peaks in the PET subtraction dataset and localization of the peak coordinates within a standardized stereotactic atlas. This method is designed to identify isolated foci with dimensions smaller than the image resolution. Details of activation patterns that may extend over finite distances, following the underlying anatomical structures, will not be apparent. We describe the combined mapping into stereotactic coordinate space of magnetic resonance imaging (MRI) and PET information from each of a set of subjects such that the major features of the activation pattern, particularly extended tracts of increased blood flow, can be immediately assessed within their true anatomical context as opposed to that presumed using a standard atlas alone. Near areas of high anatomical variability, e.g., central sulcus, or of sharp curvature, e.g., frontal and temporal poles, this information can be essential to the localization of a focus to the correct gyrus or for the rejection of extracerebral peaks. It also allows for the removal from further analysis of data from cognitively-normal subjects with abnormal anatomy such as enlarged ventricles. In patients with neuropathology, e.g., Alzheimers disease, arteriovenous malformation, stroke, or neoplasm, the use of correlated MRI is mandatory for correct localization of functional activation.

MRI-PET Correlation in Three Dimensions Using a Volume-of-Interest (VOI) Atlas

Quantitative interpretation of functional images (PET or SPECT) is hampered by poor spatial resolution, low counting statistics, and, for many tracers, low contrast between different brain structures of interest. Furthermore, normal tracer distributions can be severely disrupted by such gross pathologies as stroke, tumor, and dementia. Hence, the complementary anatomical information provided by CT or MRI is essential for accurate and reproducible regional analysis of functional data. We have developed methods for the simultaneous three-dimensional display and analysis of image volumes from MRI and PET. A general algorithm for defining the affine transformation between two equivalent point ensembles has been adapted for the purpose of registering MRI and PET image volumes by means of a simple fiducial arrangement. In addition, we have extended previous MRI-based computerized atlas methodology to three dimensions. The native atlas planes were spaced at 2 mm intervals, sufficient axial sampling to permit the generation of oblique planar sections through the atlas space. This will allow for an infinite number of angulations and axial offsets in two-dimensional region-of-interest (ROI) templates, all derived from the same master three-dimensional volume-of-interest (VOI) atlas and therefore maintaining topographical consistency throughout. These ROI templates may be selected to match the image orientation for conventional two-dimensional segmentation and data extraction.

Stress regulation in the central nervous system: evidence from structural and functional neuroimaging studies in human populations - 2008 Curt Richter Award Winner

The metabolic effects of stress are known to have significant health effects in both humans and animals. Most of these effects are mediated by the major stress hormonal axis in the body, the hypothalamic-pituitary-adrenal (HPA) axis. Within the central nervous system (CNS), the hippocampus, the amygdala and the prefrontal cortex as part of the limbic system are believed to play important roles in the regulation of the HPA axis. With the advent of structural and functional neuroimaging techniques, the role of different CNS structures in the regulation of the HPA axis can be investigated more directly. In the current paper, we summarize the findings obtained in our laboratory in the context of stress and HPA axis regulation. Our laboratory has developed and contributed to the development of manual and automated segmentation protocols from structural magnetic resonance imaging (MRI) scans for assessment of hippocampus, amygdala, medial temporal lobe and frontal lobe structures. Employing these protocols, we could show significant age-related changes in HC volumes, which were different between men and women, with pre-menopausal women showing smaller age-related volume decline compared to men. We could recently extent these findings by showing how estrogen therapy after menopause leads to higher volumes in the HC. Investigating possible neurotoxicity effects of steroids, we showed effects of long-term steroid exposure on HC volumes, and investigated variability of HC volumes in relation to HPA axis regulation in young and elderly populations. Here, we were able to follow-up from non-imaging studies showing that subjects low in self-esteem have higher cortisol stress responses, and the HC emerged as the critical link between these variables. Recently, we have made two more important discoveries with regard to HC volume: we could show that HC volume is as variable in young as it is in older adults, in subjects ranging in age from 18 to 80 years. Also, we have linked birth weight and maternal care to HC volumes in young adults, demonstrating the effects of variations in maternal care on the integrity of the CNS. Besides structural assessments, there is increasing interest in functional techniques to investigate possible links between CNS activity and HPA axis regulation. These two approaches complement each other; some aspects of HPA axis regulation might be linked to the integrity of a specific CNS structure, while other aspects might be linked to the function of a specific structure with no involvement of CNS morphology. Thus, we have developed a mental arithmetic stress task that can be employed in functional neuroimaging studies, and have used it in a number of functional neuroimaging studies. Employing positron emission tomography (PET), we were able to demonstrate that stress causes dopamine release if subjects reported low maternal care early in life. Finally, employing the task in functional magnetic resonance imaging (fMRI), we could show how exposure to stress and activation of the HPA axis are associated with decreased activity in major portions of the limbic system, a result that allows to speculate on the effects of stress on cognitive and emotional regulation in the brain. Taken together, the use of neuroimaging techniques in Psychoneuroendocrinology opens exciting new possibilities for the investigation of stress effects in the central nervous system.

Changes in Cortical Thickness During the Course of Illness in Schizophrenia

CONTEXT Whether cortical thickness changes in schizophrenia over time are more pronounced relative to the changes that can be attributed to normal aging has not been studied. OBJECTIVE To compare patients with schizophrenia and healthy control participants on cortical thickness change. DESIGN A 5-year longitudinal study comparing schizophrenic patients and healthy controls using 2 magnetic resonance images of the brain. SETTING Patients were recruited from the Department of Psychiatry at the University Medical Centre Utrecht and from other psychiatric hospitals in the Netherlands. Healthy controls were recruited via advertisement in newspapers and notice boards. PARTICIPANTS Ninety-six schizophrenic patients and 113 healthy controls aged 16 to 56 years. MAIN OUTCOME MEASURES Cortical thickness and change in cortical thickness on a vertex-by-vertex basis across the cortical mantle, measures of functional and symptomatic outcome, and cumulative intake of antipsychotics during the scan interval. RESULTS At baseline, the schizophrenic patients had thinner left orbitofrontal and right parahippocampal and superior temporal cortices and a thicker superior parietal lobule and occipital pole compared with the controls. Mean cortical thickness did not differ between the groups. Over time, excessive cortical thinning was found in widespread areas on the cortical mantle, most pronounced bilaterally in the temporal cortex and in the left frontal area. Poor outcome in patients was associated with more pronounced cortical thinning. Higher cumulative intake of typical antipsychotics during the scan interval was associated with more pronounced cortical thinning, whereas higher cumulative intake of atypical antipsychotic medication was associated with less pronounced cortical thinning. CONCLUSIONS In schizophrenia, the cortex shows excessive thinning over time in widespread areas of the brain, most pronounced in the frontal and temporal areas, and progresses across the entire course of the illness. The excessive thinning of the cortex appears related to outcome and medication intake.

A new improved version of the realistic digital brain phantom.

Image analysis methods must be tested and evaluated within a controlled environment. Simulations can be an extremely helpful tool for validation because ground truth is known. We created the digital brain phantom that is at the heart of our publicly available database of realistic simulated magnetic resonance image (MRI) volumes known as BrainWeb. Even though the digital phantom had l mm(3) isotropic voxel size and a small number of tissue classes, the BrainWeb database has been used in more than one hundred peer-reviewed publications validating different image processing methods. In this paper, we describe the next step in the natural evolution of BrainWeb: the creation of digital brain phantom II that includes three major improvements over the original phantom. First, the realism of the phantom, and the resulting simulations, was improved by modeling more tissue classes to include blood vessels, bone marrow and dura mater classes. In addition. a more realistic skull class was created. The latter is particularly useful for SPECT, PET and CT simulations for which bone attenuation has an important effect. Second, the phantom was improved by an eight-fold reduction in voxel volume to 0.125 mm(3). Third, the method used to create the new phantom was modified not only to take into account the segmentation of these new structures, but also to take advantage of many more automated procedures now available. The overall process has reduced subjectivity and manual intervention when compared to the original phantom, and the process may be easily applied to create phantoms from other subjects. MRI simulations are shown to illustrate the difference between the previous and the new improved digital brain phantom II. Example PET and SPECT simulations are also presented.

Automated atlas integration and interactive three-dimensional visualization tools for planning and guidance in functional neurosurgery

Many critical functionally distinct subcortical structures are not distinguishable on anatomical magnetic resonance imaging (MRI) scans. In order to provide the neurosurgeon with this missing information, a deformable volumetric atlas of the basal ganglia and thalamus has been created from the Schaltenbrand and Wahren atlas of cryogenic slices. The volumetric atlas can be automatically deformed to an individual patients MRI. To facilitate the clinical use of the atlas, a visualization platform has been developed for preoperative and intraoperative use which permits manipulation of the merged atlas and MRI data sets in two- and three-dimensional views. The platform includes graphical tools which allow the visualization of projections of a leukotome and other surgical tools with respect to the atlas data, as well as preregistered images from any other imaging modality. In addition, a graphical interface has been designed to create custom virtual lesions using computer models of neurosurgical tools for intraoperative planning. To date this system has been employed as an adjunct to over 30 functional neurosurgical cases including surgery for movement disorders.

Multivariate analysis of MRI data for Alzheimer's disease, mild cognitive impairment and healthy controls.

We have used multivariate data analysis, more specifically orthogonal partial least squares to latent structures (OPLS) analysis, to discriminate between Alzheimers disease (AD), mild cognitive impairment (MCI) and elderly control subjects combining both regional and global magnetic resonance imaging (MRI) volumetric measures. In this study, 117 AD patients, 122 MCI patients and 112 control subjects (from the AddNeuroMed study) were included. High-resolution sagittal 3D MP-RAGE datasets were acquired from each subject. Automated regional segmentation and manual outlining of the hippocampus were performed for each image. Altogether this yielded volumes of 24 different anatomically defined structures which were used for OPLS analysis. 17 randomly selected AD patients, 12 randomly selected control subjects and the 22 MCI subjects who converted to AD at 1-year follow up were excluded from the initial OPLS analysis to provide a small external test set for model validation. Comparing AD with controls we found a sensitivity of 87% and a specificity of 90% using hippocampal measures alone. Combining both global and regional measures resulted in a sensitivity of 90% and a specificity of 94%. This increase in sensitivity and specificity resulted in an increase of the positive likelihood ratio from 9 to 15. From the external test set, the model predicted 82% of the AD patients and 83% of the control subjects correctly. Finally, 73% of the MCI subjects which converted to AD at 1 year follow-up were shown to resemble AD patients more closely than controls. This method shows potential for distinguishing between different patient groups. Combining the different MRI measures together resulted in a significantly better classification than using them separately. OPLS also shows potential for predicting conversion from MCI to AD.

Anatomical-Functional Correlative Analysis Of The Human Brain Using Three Dimensional Imaging Systems

Quantitative interpretation of functional images (PET or SPECT) is hampered by poor spatial resolution, low counting statistics and, for many tracers, low contrast between different brain structures of interest. Further, normal tracer distributions can be severely distorted by such gross pathologies as stroke, tumor and dementia. Hence, the complementary anatomical information provided by CT or MRI is essential for accurate and reproducible regional analysis of functional data. We have developed methods for the three-dimensional integration and simultaneous display of image volumes from MRI and PET. PET data was collected from an older Therascan 3-slice scanner with 12 mm resolution and a 15-slice Scanditronix PC-2048 system having 5-6 mm resolution in each dimension. MRI data was obtained from a Philips 1.5 Tesla Gyroscan scanner. The image volumes were loaded into a PIXAR 3-D image computer for simultaneous display. A general algorithm for finding the optimal transformation between two ensembles of equivalent points was implemented and investigated through simulation studies. Using a locally-developed 3-D image/graphics analysis package, equivalent points in the two image volumes were identified, either manually or via an adjustable computerized volume-of-interest (VOI) atlas. The MRI data were then re-sampled along planes parallel to the PET planes and the two volumes overlaid using opacity-weighted composition. Arbitrary oblique planes through the two volumes were obtained in interactive sessions.

Cannabis use and progressive cortical thickness loss in areas rich in CB1 receptors during the first five years of schizophrenia.

Cerebral grey matter volume reductions are progressive in schizophrenia, with larger grey matter volume decreases associated with cannabis use. It is unknown whether this grey matter loss is globally distributed over the entire brain or more pronounced in specific cortical brain regions. Fifty-one patients with recent-onset schizophrenia and 31 matched healthy subjects were included. For all subjects, magnetic resonance imaging scans were obtained at inclusion and at 5-year follow-up. Nineteen patients (ab-)used cannabis but no other illicit drugs; 32 patients and the healthy comparison subjects did not use any drugs during the 5-year follow-up. At follow-up, clinical outcome was measured. To evaluate the local differences in cortical thickness change over five years between the two groups regression analysis was carried out over the cortical surface. At inclusion cortical thickness did not differ between patients and controls and between cannabis-using and non-using patients. Over the follow-up period we found excessive thinning of the right supplementary motor cortex, inferior frontal cortex, superior temporal gyrus, angular gyrus, occipital and parietal lobe in patients relative to controls after controlling for cannabis use. Patients who used cannabis showed additional thinning in the left dorsolateral prefrontal cortex (DLPFC), left anterior cingulate cortex (ACC) and left occipital lobe as compared to those patients that did not use cannabis during the scan interval. First-episode schizophrenia patients who use cannabis show a more pronounced cortical thinning than non-using patients in areas known for their high density of CB1 receptors, such as the ACC and the DLPFC.