Biomedical subjects

Colin Studholme

Publications and source records attributed to Colin Studholme.

11 recordsLinked to original sources

PubMed2006

Deformation-based morphometry of brain changes in alcohol dependence and abstinence.

Brain atrophy associated with chronic alcohol consumption is partially reversible after cessation of drinking. Recovering alcoholics (RA, 45+/-8 years) were studied with MRI within 1 week of entering treatment, with follow-up at 8 months. Light drinkers (LD) were studied with MRI twice 1 year apart. For each participant, deformation maps of baseline structure and longitudinal size changes between baseline and follow-up scans were created using nonlinear registration techniques. ANCOVA assessed group differences and regression methods examined relationships between deformation maps and measures of drinking severity or baseline atrophy. At baseline, RA showed significant atrophy in the frontal and temporal lobes. Longitudinally, abstainers recovered tissue volumes significantly faster than LD in parietal and frontal lobes. When comparing abstainers to relapsers, additional regions with significantly greater recovery in abstainers were temporal lobes, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulate, insula, and subcortical white matter. Gray matter volume at baseline predicted volume recovery during abstinence better than white matter. Drinking severity was not significantly related to brain structural changes assessed with this method. Longitudinally, deformation-based morphometry confirmed tissue recovery in RAs who maintain long-term sobriety. Abstinence-associated tissue volume gains are significant in focal parts of the fronto-ponto-cerebellar circuit that is adversely affected by heavy drinking.

Adult↗

PubMed2006

Non-treatment-seeking heavy drinkers: effects of chronic cigarette smoking on brain structure.

We previously reported [Cardenas, V.A., Studholme, C., Meyerhoff, D.J., Song, E., Weiner, M.W., 2005. Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes. Psychiatry Res. 138, 115-130] that non-treatment-seeking, active heavy drinkers (HD) demonstrated smaller regional neocortical gray matter volumes compared to light drinking controls; however, the potential effects of chronic cigarette smoking on regional brain volumes were not addressed. The goal of this retrospective analysis was to determine if chronic smoking affected brain structure in the non-treatment-seeking heavy drinking sample from our earlier report (i.e., Cardenas et al., 2005). Regional volumetric comparisons were made among age-matched smoking HD (n=17), non-smoking HD (n=16), and non-smoking light drinkers (nsLD; n=20) from our original sample. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance imaging. Smoking HD demonstrated smaller volumes than nsLD in the frontal, parietal, temporal GM, and for total neocortical GM. Smoking HD also demonstrated smaller temporal and total GM volumes than non-smoking HD. Non-smoking HD and nsLD did not differ significantly on GM volumes. Further, the three groups did not differ on lobar WM, subcortical structures or regional CSF volumes. These retrospective analyses indicate neocortical GM volume reductions in non-treatment-seeking smoking HD, but not in non-smoking HD, which are consistent with our studies in recently detoxified treatment-seeking alcohol-dependent samples.

Adult↗

PubMed2006

Longitudinal stability of MRI for mapping brain change using tensor-based morphometry.

Measures of brain change can be computed from sequential MRI scans, providing valuable information on disease progression, e.g., for patient monitoring and drug trials. Tensor-based morphometry (TBM) creates maps of these brain changes, visualizing the 3D profile and rates of tissue growth or atrophy, but its sensitivity depends on the contrast and geometric stability of the images. As part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), 17 normal elderly subjects were scanned twice (at a 2-week interval) with several 3D 1.5 T MRI pulse sequences: high and low flip angle SPGR/FLASH (from which Synthetic T1 images were generated), MP-RAGE, IR-SPGR (N = 10) and MEDIC (N = 7) scans. For each subject and scan type, a 3D deformation map aligned baseline and follow-up scans, computed with a nonlinear, inverse-consistent elastic registration algorithm. Voxelwise statistics, in ICBM stereotaxic space, visualized the profile of mean absolute change and its cross-subject variance; these maps were then compared using permutation testing. Image stability depended on: (1) the pulse sequence; (2) the transmit/receive coil type (birdcage versus phased array); (3) spatial distortion corrections (using MEDIC sequence information); (4) B1-field intensity inhomogeneity correction (using N3). SPGR/FLASH images acquired using a birdcage coil had least overall deviation. N3 correction reduced coil type and pulse sequence differences and improved scan reproducibility, except for Synthetic T1 images (which were intrinsically corrected for B1-inhomogeneity). No strong evidence favored B0 correction. Although SPGR/FLASH images showed least deviation here, pulse sequence selection for the ADNI project was based on multiple additional image analyses, to be reported elsewhere.

Aged↗

PubMed2006

Registration-based approach for reconstruction of high-resolution in utero fetal MR brain images.

RATIONALE AND OBJECTIVES: This paper describes a novel approach to forming high-resolution MR images of the human fetal brain. It addresses the key problem of fetal motion by proposing a registration-refined compounding of multiple sets of orthogonal fast two-dimensional MRI slices, which are currently acquired for clinical studies, into a single high-resolution MRI volume. MATERIALS AND METHODS: A robust multiresolution slice alignment is applied iteratively to the data to correct motion of the fetus that occurs between two-dimensional acquisitions. This is combined with an intensity correction step and a super-resolution reconstruction step, to form a single high isotropic resolution volume of the fetal brain. RESULTS: Experimental validation on synthetic image data with known motion types and underlying anatomy, together with retrospective application to sets of clinical acquisitions, are included. CONCLUSION: Results indicate that this method promises a unique route to acquiring high-resolution MRI of the fetal brain in vivo allowing comparable quality to that of neonatal MRI. Such data provide a highly valuable window into the process of normal and abnormal brain development, which is directly applicable in a clinical setting.

Algorithms↗

PubMed2006

Deformation-based mapping of volume change from serial brain MRI in the presence of local tissue contrast change.

This paper is motivated by the analysis of serial structural magnetic resonance imaging (MRI) data of the brain to map patterns of local tissue volume loss or gain over time, using registration-based deformation tensor morphometry. Specifically, we address the important confound of local tissue contrast changes which can be induced by neurodegenerative or neurodevelopmental processes. These not only modify apparent tissue volume, but also modify tissue integrity and its resulting MRI contrast parameters. In order to address this confound we derive an approach to the voxel-wise optimization of regional mutual information (RMI) and use this to drive a viscous fluid deformation model between images in a symmetric registration process. A quantitative evaluation of the method when compared to earlier approaches is included using both synthetic data and clinical imaging data. Results show a significant reduction in errors when tissue contrast changes locally between acquisitions. Finally, examples of applying the technique to map different patterns of atrophy rate in different neurodegenerative conditions is included.

Algorithms↗

PubMed2005

Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes.

The goals of this study were to measure if chronic active heavy drinking is associated with brain volume loss in non-treatment seeking men and women, and to assess the effect of positive family history of problem drinking on brain structure in heavy drinkers. Automated image processing was used to analyze high-resolution T1-weighted magnetic resonance images from 49 active heavy drinkers and 49 age- and sex-matched light drinkers, yielding gray matter, white matter and cerebrospinal fluid (CSF) volumes within the frontal, temporal, parietal and occipital lobes. Regional brain volume measures were compared as a function of group, sex and their interaction. Within heavy drinkers, volumes were correlated with measures of alcohol consumption and compared as a function of family history of problem drinking. Deformation morphometry explored localized patterns of atrophy associated with heavy drinking or severity of drinking. We found significant gray matter volume losses, but no white matter losses, in active heavy drinkers compared with light drinkers. Women had greater gray matter and smaller white matter and CSF volumes as a percentage of intracranial vault than men. Within heavy drinkers, smaller gray matter volumes were associated with higher current levels of drinking and older age, while a positive family history of problem drinking was associated with smaller CSF volumes. Community-dwelling heavy drinkers who are not in alcoholism treatment have dose-related gray matter volume losses, and family history of problem drinking ameliorates some structural consequences of heavy drinking.

Adult↗

PubMed2005

Using automated morphometry to detect associations between ERP latency and structural brain MRI in normal adults.

Despite the clinical significance of event-related potential (ERP) latency abnormalities, little attention has focused on the anatomic substrate of latency variability. Volume conduction models do not identify the anatomy responsible for delayed neural transmission between neural sources. To explore the anatomic substrate of ERP latency variability in normal adults using automated measures derived from magnetic resonance imaging (MRI), ERPs were recorded in the visual three-stimulus oddball task in 59 healthy participants. Latencies of the P3a and P3b components were measured at the vertex. Measures of local anatomic size in the brain were estimated from structural MRI, using tissue segmentation and deformation morphometry. A general linear model was fitted relating latency to measures of local anatomic size, covarying for intracranial vault volume. Longer P3b latencies were related to contractions in thalamus extending superiorly into the corpus callosum, white matter (WM) anterior to the central sulcus on the left and right, left temporal WM, the right anterior limb of the internal capsule extending into the lenticular nucleus, and larger cerebrospinal fluid volumes. There was no evidence for a relationship between gray matter (GM) volumes and P3b latency. Longer P3a latencies were related to contractions in left temporal WM, and left parietal GM and WM near the interhemispheric fissure. P3b latency variability is related chiefly to WM, thalamus, and lenticular nucleus, whereas P3a latency variability is not related as strongly to anatomy. These results imply that the WM connectivity between generators influences P3b latency more than the generators themselves do.

Adult↗

PubMed2004

Positive and negative network correlations in temporal lobe epilepsy.

Temporal lobe seizures are accompanied by complex behavioral phenomena including loss of consciousness, dystonic movements and neuroendocrine changes. These phenomena may arise from extended neural networks beyond the temporal lobe. To investigate this, we imaged cerebral blood flow (CBF) changes during human temporal lobe seizures with single photon emission computed tomography (SPECT) while performing continuous video/EEG monitoring. We found that temporal lobe seizures associated with loss of consciousness produced CBF increases in the temporal lobe, followed by increases in bilateral midline subcortical structures. These changes were accompanied by marked bilateral CBF decreases in the frontal and parietal association cortex. In contrast, temporal lobe seizures in which consciousness was spared were not accompanied by these widespread CBF changes. The CBF decreases in frontal and parietal association cortex were strongly correlated with increases in midline structures such as the mediodorsal thalamus. These results suggest that impaired consciousness in temporal lobe seizures may result from focal abnormal activity in temporal and subcortical networks linked to widespread impaired function of the association cortex.

Adolescent↗

PubMed2004

A technique to re-establish dose distributions for previously treated brain cancer patients in external beam radiotherapy.

Tumor recurrences or new tumors may develop after irradiation of local lesion(s) in the brain, and additional radiotherapy treatments are often needed for previously treated patients. It is critical to re-establish the dose distributions delivered during the previous treatment in the current patient geometry, so that the previous dose distributions can be accurately taken into consideration in the design of the current treatment plan. The difficulty in re-establishing the previous treatment dose distributions in the current patient geometry arises from the fact that the patient position at the time of reirradiation is different from that at the previous treatment session. Simple re-entry of the previous isocenter coordinates, gantry, and couch and collimator angles into the new treatment plan would result in incorrect beam orientations relative to the new patient anatomy, and therefore incorrect display of the previous dose distributions on the current patient anatomy. To address this issue, a method has been developed so that the previous dose distributions can be accurately re-established in the framework of the current brain treatment. The method involves 3 matrix transformations: (1) transformation of beams from machine coordinate system to patient coordinate system in the previous treatment; (2) transformation of beams from patient coordinate system in the previous treatment to patient coordinate system in the current treatment; and (3) transformation of beams from patient coordinate system in the current treatment to machine coordinate system. The transformation matrices used in the second transformation are determined by registration using a mutual information-based algorithm with which the old and new computed tomography (CT) scan sets are registered automatically without human interpretation. A series of transformation matrices are derived to calculate the isocenter coordinates, the gantry, couch, and collimator angles of the beams for the previous treatment in the current patient geometry, and the previous dose distributions are re-established on the current CT images. The method has been proven to be successful and robust.

Algorithms↗

PubMed2003

Selective frontal, parietal, and temporal networks in generalized seizures.

Are "generalized" seizures truly generalized? Generalized tonic-clonic seizures are classified as either secondarily generalized with local onset or primarily generalized, without known focal onset. In both types of generalized seizures widespread regions of the nervous system engage in abnormally synchronous and high-frequency neuronal firing. However, emerging evidence suggests that all neurons are not homogeneously involved; specific nodes within the network may be crucial for the propagation and behavioral manifestations of generalized tonic-clonic seizures. Study of human tonic-clonic seizures has been limited by problems with patient movement and variable seizure types. To circumvent these problems, we imaged generalized tonic-clonic seizures during electroconvulsive therapy, in which seizure type and timing are well controlled. (99m)Tc-hexamethylpropylene amine oxime injections during seizures provide a "snapshot" of cerebral blood flow that can be imaged by single photon emission computed tomography (SPECT) after seizure termination. Here we show that focal regions of frontal and parietal association cortex show the greatest relative signal increases. Involvement of the higher-order association cortex may explain the profound impairment of consciousness seen in generalized seizures. In addition, focal involvement of the dominant temporal lobe was associated with impaired retrograde verbal memory. Similar focal increases were also seen in imaging of spontaneous secondarily generalized tonic-clonic seizures. Relative sparing of many brain regions during both spontaneous and induced seizures suggests that specific networks may be more important than others in so-called generalized seizures.

Adult↗

PubMed2002

Comparison of statistical parametric mapping and SPECT difference imaging in patients with temporal lobe epilepsy.

PURPOSE: Statistical parametric mapping (SPM) is an image-analysis tool that assesses the statistical significance of cerebral blood flow (CBF) changes on a voxel-by-voxel basis, thereby removing the subjectivity inherent in conventional region-of-interest (ROI) analysis. Our platform of single-photon emission computed tomography (SPECT) ictal-interictal difference imaging in clinical epilepsy has been validated for localizing seizure onset. We extend the tools of SPM by further applying statistical measures for the significance of perfusion changes in individual patients to localize epileptogenic foci in patients with defined temporal lobe epilepsy by using paired scans in this preliminary study. METHODS: Twelve patients with pairs of periictal and interictal SPECT scans were analyzed in this comparison study between SPECT difference imaging and SPM difference analysis by using a reference database of paired normal healthy images. These 12 patients possessed seizure foci localized to the mesial temporal lobe as confirmed by surgical outcome and by hippocampal sclerosis on pathology. SPM was used to identify clusters of increased or decreased CBF in each patient in contrast to our control group. RESULTS: The regions having the most significant increased or decreased CBF by SPM analysis were in agreement with regions identified by conventional difference imaging and visual analysis by viewers blinded to the results of the SPM analysis. Differentiated further by time of radiopharmaceutical injection, six of seven patients injected within 100 s of seizure onset displayed hyperperfusion changes localized to the corresponding epileptogenic temporal lobe by both techniques. Among patients receiving injections after 100 s, both techniques showed primarily regions of hypoperfusion, which again were similar between these two methods. CONCLUSIONS: The results provide strong evidence supporting SPM difference analysis in assessing regions of significant CBF change from baseline in concordance with our current clinically used technique of SPECT ictal--interictal difference imaging in epilepsy patients. Difference analysis using SPM could serve as a useful diagnostic tool in the evaluation of seizure focus in temporal lobe epilepsy.

Adolescent↗