Publications

2004
Topgaard D, Pines A. Self-diffusion measurements with chemical shift resolution in inhomogeneous magnetic fields. J Magn Reson. 2004;168 (1) :31-5.Abstract
A methodology for chemical shift resolved molecular self-diffusion measurements in time-independent static and radiofrequency field gradients is demonstrated. Diffusion encoding is provided by a stimulated echo sequence with additional z-storage that allows for a change of diffusion time without affecting the relaxation weighting. The signal is acquired stroboscopically between the pulses of a train of adiabatic double passages that induces a z-rotation counteracting the phase spread resulting from precession in the inhomogeneous static field, as demonstrated in recent approaches to the goal of high-resolution "ex situ" NMR. Simulations of the pulse sequence show that the acquired signal results from the desired coherence pathway. Successful demonstrations of the experiment were performed on a mixture of water and isopropanol.
Zou KH, Warfield SK, Bharatha A, Tempany CMC, Kaus MR, Haker SJ, Wells WM, Jolesz FA, Kikinis R. Statistical validation of image segmentation quality based on a spatial overlap index. Acad Radiol. 2004;11 (2) :178-89.Abstract
RATIONALE AND OBJECTIVES: To examine a statistical validation method based on the spatial overlap between two sets of segmentations of the same anatomy. MATERIALS AND METHODS: The Dice similarity coefficient (DSC) was used as a statistical validation metric to evaluate the performance of both the reproducibility of manual segmentations and the spatial overlap accuracy of automated probabilistic fractional segmentation of MR images, illustrated on two clinical examples. Example 1: 10 consecutive cases of prostate brachytherapy patients underwent both preoperative 1.5T and intraoperative 0.5T MR imaging. For each case, 5 repeated manual segmentations of the prostate peripheral zone were performed separately on preoperative and on intraoperative images. Example 2: A semi-automated probabilistic fractional segmentation algorithm was applied to MR imaging of 9 cases with 3 types of brain tumors. DSC values were computed and logit-transformed values were compared in the mean with the analysis of variance (ANOVA). RESULTS: Example 1: The mean DSCs of 0.883 (range, 0.876-0.893) with 1.5T preoperative MRI and 0.838 (range, 0.819-0.852) with 0.5T intraoperative MRI (P < .001) were within and at the margin of the range of good reproducibility, respectively. Example 2: Wide ranges of DSC were observed in brain tumor segmentations: Meningiomas (0.519-0.893), astrocytomas (0.487-0.972), and other mixed gliomas (0.490-0.899). CONCLUSION: The DSC value is a simple and useful summary measure of spatial overlap, which can be applied to studies of reproducibility and accuracy in image segmentation. We observed generally satisfactory but variable validation results in two clinical applications. This metric may be adapted for similar validation tasks.
Zou KH, Wells WM, Kikinis R, Warfield SK. Three validation metrics for automated probabilistic image segmentation of brain tumours. Stat Med. 2004;23 (8) :1259-82.Abstract
The validity of brain tumour segmentation is an important issue in image processing because it has a direct impact on surgical planning. We examined the segmentation accuracy based on three two-sample validation metrics against the estimated composite latent gold standard, which was derived from several experts' manual segmentations by an EM algorithm. The distribution functions of the tumour and control pixel data were parametrically assumed to be a mixture of two beta distributions with different shape parameters. We estimated the corresponding receiver operating characteristic curve, Dice similarity coefficient, and mutual information, over all possible decision thresholds. Based on each validation metric, an optimal threshold was then computed via maximization. We illustrated these methods on MR imaging data from nine brain tumour cases of three different tumour types, each consisting of a large number of pixels. The automated segmentation yielded satisfactory accuracy with varied optimal thresholds. The performances of these validation metrics were also investigated via Monte Carlo simulation. Extensions of incorporating spatial correlation structures using a Markov random field model were considered.
Mocanu D, Kettenbach J, Sweeney MO, Kikinis R, Kenknight BH, Eisenberg SR. A comparison of biventricular and conventional transvenous defibrillation: a computational study using patient derived models. Pacing Clin Electrophysiol. 2004;27 (5) :586-93.Abstract
Conventional transvenous defibrillation is performed with an ICD using a dual current pathway. The defibrillation energy is delivered from the RV electrode to the superior vena cava (SVC) electrode and the metallic case (CAN) of the ICD. Biventricular defibrillation uses an additional electrode placed in the LV free wall with sequential shocks to create an additional current vector. Clinical studies of biventricular defibrillation have reported a 45% reduction in mean defibrillation threshold (DFT) energy. The aim of the study was to use computational methods to examine the biventricular defibrillation fields together with their corresponding DFTs in a variety of patient derived models and to compare them to simulations of conventional defibrillation. A library of thoracic models derived from nine patients was used to solve for electric field distributions. The defibrillation waveform consisted of a LV --> SVC + CAN monophasic shock followed by a biphasic shock delivered via the RV --> SVC + CAN electrodes. When the initial voltage of the two shocks is the same, the simulations show that the biventricular configuration reduces the mean DFT by 46% (3.5 +/- 1.3 vs 5.5 +/- 2.7 J, P = 0.005). When the leading edge of the biphasic shock is equal to the trailing edge of the monophasic shock, there is no statistically significant difference in the mean DFT (4.9 +/- 1.9 vs 5.5 +/- 2.7 J, P > 0.05) with the DFT decreasing in some patients and increasing in others. These results suggest that patient-specific computational models may be able to identify those patients who would most benefit from a biventricular configuration.
Friman O, Borga M, Lundberg P, Knutsson H. Detection and detrending in fMRI data analysis. Neuroimage. 2004;22 (2) :645-55.Abstract
This article addresses the impact that colored noise, temporal filtering, and temporal detrending have on the fMRI analysis situation. Specifically, it is shown why the detection of event-related designs benefit more from pre-whitening than blocked designs in a colored noise structure. Both theoretical and empirical results are provided. Furthermore, a novel exploratory method for producing drift models that efficiently capture trends and drifts in the fMRI data is introduced. A comparison to currently employed detrending approaches is presented. It is shown that the novel exploratory model is able to remove a major part of the slowly varying drifts that are abundant in fMRI data. The value of such a model lies in its ability to remove drift components that otherwise would have contributed to a colored noise structure in the voxel time series.
Bonnet F, Visseaux M, Barbier-Baudry D, Vigier E, Kubicki MM. Genuine heteroleptic complexes of early rare-earth metals: synthesis, X-ray structure, and their use for stereospecific isoprene polymerization catalysis. Chemistry. 2004;10 (10) :2428-34.Abstract
Genuine heteroleptic neodymium and samarium complexes of formula [Cp*'Ln[(p-tol)NN](BH4)] (Cp*' = C5Me4(nPr), (p-tol)NN = (p-tol)NC(Me)CHC(Me)N(p-tol), Ln = Sm: 1a, Ln = Nd: 1b) have been synthesized for the first time. These unprecedented homologues of early lanthanocenes are prepared by a metathetic reaction between their monocyclopentadienylbisborohydrido precursors with the corresponding potassium diketiminate. Both complexes were obtained in good yields and were characterized by 1H NMR spectroscopy and elemental analysis. Complex 1 a has an non-solvated dimeric structure, as indicated by its crystallographic data. The chloroneodymium analogue [Cp*'Nd[(p-tol)NN](Cl)] (2b) was only obtained as a part of a mixture. Analysis of crystals of 2b by X-ray diffraction revealed a molecular structure very similar to that of 1a. Preliminary isoprene polymerization experiments were carried out with 1 b in the presence of an alkylmagnesium coactivator. The resulting bimetallic Nd/Mg system behaves as an efficient and highly stereospecific catalyst with the synthesis of trans-1,4-polyisoprene with more than 98% regularity. The control of the polymer structure is related to the steric hindrance around the lanthanide atom.
Park H-J, Levitt J, Shenton ME, Salisbury DF, Kubicki M, Kikinis R, Jolesz FA, McCarley RW. An MRI study of spatial probability brain map differences between first-episode schizophrenia and normal controls. Neuroimage. 2004;22 (3) :1231-46.Abstract
We created a spatial probability atlas of schizophrenia to provide information about the neuroanatomic variability of brain regions of patients with the disorder. Probability maps of 16 regions of interest (ROIs) were constructed by taking manually parcellated ROIs from subjects' magnetic resonance images (MRIs) and linearly transforming them into Talairach space using the Montreal Neurological Institute (MNI) template. ROIs included temporal, parietal, and prefrontal cortex subregions, with a principal focus on temporal lobe structures. Subject Ns ranged from 11 to 28 for the different ROIs. Our global measure of the spatial distribution of the transformed ROI was the sum of voxels with 50% overlap among subjects. The superior temporal gyrus (STG) and fusiform gyrus (FG) had lower values for schizophrenic subjects than for normal controls, suggestive of greater spatial variability for these ROIs in schizophrenic subjects. For the computation of statistical significance of group differences in portions of the ROI, we used voxel-wise comparisons and Fisher's exact test. First-episode schizophrenic patients compared with controls showed lower probability (P < 0.05) at dorso-posterior areas of planum temporale and Heschl's gyrus, lateral and anterior regions in the left hippocampus (HIPP), and dorsolateral regions of fusiform gyrus. Importantly, most ROIs of schizophrenic subjects showed a significantly lower spatial overlap than controls, even after nonlinear spatial normalization, suggesting a greater heterogeneity in the spatial distribution of ROIs. There is consequently a need for caution in neuroimaging studies where data from schizophrenic subjects are normalized to a particular stereotaxic coordinate system based on healthy controls. Apparent group differences in activation may simply reflect a greater heterogeneity of spatial distribution in schizophrenia.
Ellsmere J, Stoll J, Wells W, Kikinis R, Vosburgh K, Kane R, Brooks D, Rattner D. A new visualization technique for laparoscopic ultrasonography. Surgery. 2004;136 (1) :84-92.Abstract
BACKGROUND: Using laparoscopic ultrasonography (LUS) is challenging for both novice and experienced ultrasonographers. The major difficulty surgeons experience is understanding the orientation of the ultrasonography image. The purpose of this study was to assess whether providing surgeons with orientation information improves their ability to interpret LUS images. METHODS: We performed a LUS examination on a 25-kg pig and simultaneously digitized video from the laparoscopic camera, the LUS, and a novel orientation system. From the video recordings, 12 different clips of intra-abdominal anatomy were prepared. Twenty surgeons (18 staff, 2 fellows) volunteered to participate in an experimental crossover study. Test subjects reviewed the LUS clips along with the laparoscopic video images and the orientation display. Controls reviewed the LUS clips with only the laparoscopic video images. Diagnostic accuracy was compared by using the odds ratio. RESULTS: For all vessels, the orientation display improved the odds ratio for correctly identifying structures from 3.7 to 8.9 (P=.02). For arteries, the orientation display improved the odds ratio from 2.4 to 9.6 (P=.01). For veins, the orientation display improved the odds ratio from 4.4 to 13.6 (P=.04). CONCLUSIONS: Providing orientation information significantly improves a surgeon's ability to interpret LUS images.
Malmborg C, Topgaard D, Söderman O. NMR diffusometry and the short gradient pulse limit approximation. J Magn Reson. 2004;169 (1) :85-91.Abstract
In NMR diffusometry, one often uses the short gradient pulse (SGP) limit approximation in the interpretation of data from systems with restricted diffusion. The SGP limit approximation means that the gradient pulse length, delta, is so short that the spins do not diffuse during the pulse duration, but this condition is rarely met. If the length scale of the pores corresponds to the molecular mean square displacement during the gradient pulse, the measured echo intensities become a function of the gradient pulse length. Here, we have studied highly concentrated emulsions to show how the length of the gradient pulse influences NMR diffusion experiments. We have focused on molecules confined to one pore and molecules that can migrate through the porous system. For the former the echo decays give smaller pores than the actual case and for the latter we show large changes in echo decay depending on the gradient pulse length, everything else being equal.
Salisbury DF, Griggs CB, Shenton ME, McCarley RW. The NoGo P300 'anteriorization' effect and response inhibition. Clin Neurophysiol. 2004;115 (7) :1550-8.Abstract
OBJECTIVE: The P300 event-related potential shows anterior P300 increases on NoGo tasks (target stimulus=withhold response) relative to Go tasks (target stimulus=commit response). This 'NoGo anteriorization' has been hypothesized to reflect response inhibition. However, silent-count tasks show similar P300 anteriorization. The P300 anteriorization on silent-count tasks relative to Go tasks cannot reflect inhibition-related processes, and questions the degree to which anteriorization observed on NoGo trials can be ascribed to response inhibition. Comparison of anteriorization between the silent-count and NoGo tasks is thus essential. P300 topography on NoGo and silent-count tasks has not been previously compared. METHODS: P300 on Go, NoGo, and silent-count auditory oddball tasks were compared. If the NoGo P300 anteriorization reflects response inhibitory processes, the NoGo P300 should be larger anteriorly than the Go P300 (overt responses) and the silent-count P300s (covert responses). If anteriorization primarily reflects negative voltage Go task motor activity that reduces the normal frontal P300 amplitude, then the Go task P300 should be smaller than both the NoGo and silent-count P300s, which should not differ from one another. RESULTS: The Go task elicited a bilaterally reduced frontal P300 and asymmetrical frontal P300 relative to both the NoGo and silent-count tasks. The NoGo task P300 and silent-count task P300 showed similar amplitude and topography. P300 and slow wave on the NoGo task were not asymmetrical. CONCLUSIONS: The increased frontal P300 in NoGo tasks cannot be attributed solely to a positive-going inhibitory process, but likely reflects negative voltage response execution processes on Go trials. However, the alternative explanation that memory-related processes increase the silent-count P300 anteriorly to the same degree as NoGo inhibitory processes cannot be ruled out.
Bonnet F, Visseaux M, Barbier-Baudry D, Hafid A, Vigier E, Kubicki MM. Organometallic early lanthanide clusters: syntheses and X-ray structures of new monocyclopentadienyl complexes. Inorg Chem. 2004;43 (12) :3682-90.Abstract
The reaction of Ln(BH(4))(3)(THF)(3) or LnCl(3)(THF)(3) with 1 equiv of KCp*' ligand (Cp' = C(5)Me(4)n-Pr) afforded the new monocyclopentadienyl complexes Cp*'LnX(2)(THF)(n) (X = BH(4), Ln = Sm, n = 1, 1a, Ln = Nd, n = 2, 1b; X = Cl, Ln = Sm, n = 1, 3a) and [Cp*'LnX(2)](n') (X = BH(4), n' = 6, Ln = Sm, 2a, Ln = Nd, 2b; X = Cl, Ln = Nd, 4b). All these compounds were characterized by elemental analysis and (1)H NMR. Crystals of mixed borohydrido/chloro-bridged [Cp*'(6)Ln(6)(BH(4))(12-x))Cl(x)(THF)(n')] (x = 10, n' = 4, Ln = Sm, 2a', Ln = Nd, 2b'; x = 5, n = 2, Ln = Sm, 2a' ') were also isolated. Compounds 2a, 2b, 2a', 2b', and 2a'' were structurally characterized; they all exhibit a hexameric structure in the solid state containing the [Cp*(3)Ln(3)X(5)(THF)] building block. The easy clustering of THF adducts first isolated is illustrative of the well-known bridging ability of the BH(4) group. Hexameric 2a was found to be unstable in the presence of THF vapors; this may be correlated to the opening of unsymmetrical borohydride bridges observed in the molecular structure.
Mocanu D, Kettenbach J, Sweeney MO, Kikinis R, Kenknight BH, Eisenberg SR. Patient-specific computational analysis of transvenous defibrillation: a comparison to clinical metrics in humans. Ann Biomed Eng. 2004;32 (6) :775-83.Abstract
The goal of this study is to assess the predictive capacity of computational models of transvenous defibrillation by comparing the results of patient-specific simulations to clinical defibrillation thresholds (DFT). Nine patient-specific models of the thorax and in situ electrodes were created from segmented CT images taken after implantation of the cardioverter-defibrillator. The defibrillation field distribution was computed using the finite volume method. The DFTs were extracted from the calculated field distribution using the 95% critical mass criterion. The comparison between simulated and clinical DFT energy resulted in a rms difference of 12.4 J and a 0.05 correlation coefficient (cc). The model-predicted DFTs were well matched to the clinical values in four patients (rms = 1.5 J; cc = 0.84). For the remaining five patients the rms difference was 18.4 J with a cc = 0.85. These results suggest that computational models based soley on the critical mass criterion and a single value of the inexcitability threshold are not able to consistently predict DFTs for individual patients. However, inspection of the weak potential gradient field in all nine patients revealed a relationship between the degree of dispersion of the weak field and the clinical DFT, which may help identify high DFT patients.
Niznikiewicz MA, Friedman M, Shenton ME, Voglmaier M, Nestor PG, Frumin M, Seidman L, Sutton J, McCarley RW. Processing sentence context in women with schizotypal personality disorder: an ERP study. Psychophysiology. 2004;41 (3) :367-71.Abstract
Accumulating evidence suggests that schizophrenic patients do not use context efficiently. Also, studies suggest similarities in clinical and cognitive profiles between schizophrenic and schizotypal personality disorder (SPD) individuals, and epidemiological studies point to a genetic link between the two disorders. This study examined electrophysiological correlates of processing sentence context in a group of SPD women in a classical N400 sentence paradigm. The study assessed if the dysfunction in context use found previously in schizophrenia and male SPD also exists in female SPD. We tested 17 SPD and 16 matched normal control women. The results suggest the presence of abnormality in context use in female SPD similar to that previously reported for male schizophrenic and SPD individuals, but of lesser degree of severity. In SPD women, relative to their comparison group, a more negative N400 was found only to auditory congruent sentences.
Kasai K, McCarley RW, Salisbury DF, Onitsuka T, Demeo S, Yurgelun-Todd D, Kikinis R, Jolesz FA, Shenton ME. Cavum septi pellucidi in first-episode schizophrenia and first-episode affective psychosis: an MRI study. Schizophr Res. 2004;71 (1) :65-76.Abstract
A high prevalence of abnormal cavum septi pellucidi (CSP) in schizophrenia may reflect neurodevelopmental abnormalities in midline structures of the brain. The relationship, however, between abnormal CSP and clinical symptoms, and with abnormalities in other limbic structures remains unclear, as does the question of whether a similar abnormality is present in affective psychosis. Seventy-four patients at their first hospitalization, 33 with schizophrenia and 41 with affective (mainly manic) psychosis, and 56 healthy control subjects underwent high-spatial-resolution magnetic resonance imaging (MRI). CSP on six slices or more on 0.9375-mm resampled coronal images was categorized as abnormal. The prevalence of abnormal CSP in both schizophrenic patients (26.1%) and affective psychosis patients (18.2%) was significantly higher than was observed in control subjects (8.2%). In schizophrenic patients only, larger CSP was significantly associated with more severe thinking disturbance and smaller left parahippocampal gyrus gray matter volumes. While the relationships between CSP ratings and clinical symptoms did not significantly differ between the two psychosis groups as assessed by the comparison of regression slopes, the association with limbic volumes appeared to be specific to schizophrenic patients. These results suggest that psychosis associated with schizophrenia and affective disorder share, at least to some extent, neurodevelopmental abnormalities involving midline structures and associated psychopathological consequences. However, the association between abnormal CSP and limbic systems may be more specific to schizophrenia.
Dickey CC, Salisbury DF, Nagy AI, Hirayasu Y, Lee CU, McCarley RW, Shenton ME. Follow-up MRI study of prefrontal volumes in first-episode psychotic patients. Schizophr Res. 2004;71 (2-3) :349-51.
Onitsuka T, Shenton ME, Salisbury DF, Dickey CC, Kasai K, Toner SK, Frumin M, Kikinis R, Jolesz FA, McCarley RW. Middle and inferior temporal gyrus gray matter volume abnormalities in chronic schizophrenia: an MRI study. Am J Psychiatry. 2004;161 (9) :1603-11.Abstract
OBJECTIVE: The middle temporal gyrus and inferior temporal gyrus subserve language and semantic memory processing, visual perception, and multimodal sensory integration. Functional deficits in these cognitive processes have been well documented in patients with schizophrenia. However, there have been few in vivo structural magnetic resonance imaging (MRI) studies of the middle temporal gyrus and inferior temporal gyrus in schizophrenia. METHOD: Middle temporal gyrus and inferior temporal gyrus gray matter volumes were measured in 23 male patients diagnosed with chronic schizophrenia and 28 healthy male subjects by using high-spatial-resolution MRI. For comparison, superior temporal gyrus and fusiform gyrus gray matter volumes were also measured. Correlations between these four regions and clinical symptoms were also investigated. RESULTS: Relative to healthy subjects, the patients with chronic schizophrenia showed gray matter volume reductions in the left middle temporal gyrus (13% difference) and bilateral inferior temporal gyrus (10% difference in both hemispheres). In addition, the patients showed gray matter volume reductions in the left superior temporal gyrus (13% difference) and bilateral fusiform gyrus (10% difference in both hemispheres). More severe hallucinations were significantly correlated with smaller left hemisphere volumes in the superior temporal gyrus and middle temporal gyrus. CONCLUSIONS: These results suggest that patients with schizophrenia evince reduced gray matter volume in the left middle temporal gyrus and bilateral reductions in the inferior temporal gyrus. In conjunction with findings of left superior temporal gyrus reduction and bilateral fusiform gyrus reductions, these data suggest that schizophrenia may be characterized by left hemisphere-selective dorsal pathophysiology and bilateral ventral pathophysiology in temporal lobe gray matter.
Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, McCarley RW. Neural synchrony indexes disordered perception and cognition in schizophrenia. Proc Natl Acad Sci U S A. 2004;101 (49) :17288-93.Abstract
Current views of schizophrenia suggest that it results from abnormalities in neural circuitry, but empirical evidence in the millisecond range of neural activity has been difficult to obtain. In pursuit of relevant evidence, we previously demonstrated that schizophrenia is associated with abnormal patterns of stimulus-evoked phaselocking of the electroencephalogram in the gamma band (30-100 Hz). These patterns may reflect impairments in neural assemblies, which have been proposed to use gamma-band oscillations as a mechanism for synchronization. Here, we report the unique finding that, in both healthy controls and schizophrenia patients, visual Gestalt stimuli elicit a gamma-band oscillation that is phase-locked to reaction time and hence may reflect processes leading to conscious perception of the stimuli. However, the frequency of this oscillation is lower in schizophrenics than in healthy individuals. This finding suggests that, although synchronization must occur for perception of the Gestalt, it occurs at a lower frequency because of a reduced capability of neural networks to support high-frequency synchronization in the brain of schizophrenics. Furthermore, the degree of phase locking of this oscillation is correlated with visual hallucinations, thought disorder, and disorganization in the schizophrenia patients. These data provide support for linking dysfunctional neural circuitry and the core symptoms of schizophrenia.
Nestor PG, Kubicki M, Gurrera RJ, Niznikiewicz M, Frumin M, McCarley RW, Shenton ME. Neuropsychological correlates of diffusion tensor imaging in schizophrenia. Neuropsychology. 2004;18 (4) :629-37.Abstract
Patients with schizophrenia (n = 41) and healthy comparison participants (n = 46) completed neuropsychological measures of intelligence, memory, and executive function. A subset of each group also completed magnetic resonance diffusion tensor imaging (DTI) studies (fractional anisotropy and cross-sectional area) of the uncinate fasciculus (UF) and cingulate bundle (CB). Patients with schizophrenia showed reduced levels of functioning across all neuropsychological measures. In addition, selective neuropsychological-DTI relationships emerged. Among patients but not controls, lower levels of declarative-episodic verbal memory correlated with reduced left UF, whereas executive function errors related to performance monitoring correlated with reduced left CB. The data suggested abnormal DTI patterns linking declarative-episodic verbal memory deficits to the left UF and executive function deficits to the left CB among patients with schizophrenia.
Pichon E, Tannenbaum A, Kikinis R. A statistically based flow for image segmentation. Med Image Anal. 2004;8 (3) :267-74.Abstract
In this paper we present a new algorithm for 3D medical image segmentation. The algorithm is versatile, fast, relatively simple to implement, and semi-automatic. It is based on minimizing a global energy defined from a learned non-parametric estimation of the statistics of the region to be segmented. Implementation details are discussed and source code is freely available as part of the 3D Slicer project. In addition, a new unified set of validation metrics is proposed. Results on artificial and real MRI images show that the algorithm performs well on large brain structures both in terms of accuracy and robustness to noise.
McArdle JJ, Hamgami F, Jones K, Jolesz F, Kikinis R, Spiro A, Albert MS. Structural modeling of dynamic changes in memory and brain structure using longitudinal data from the normative aging study. J Gerontol B Psychol Sci Soc Sci. 2004;59 (6) :P294-304.Abstract
This is an application of new longitudinal structural equation modeling techniques to time-dependent associations of memory and brain structure measurements. There were 225 participants aged 30-80 years at baseline who were measured again after a 7-year interval on both the lateral ventricular size and Wechsler memory score. Multiple regression analyses show nonlinear associations with age but no relationships among longitudinal changes. Mixed-effects latent growth curve analyses and analyses based on latent difference scores indicate that longitudinal changes in both variables are reasonably well described by an exponential or dual change model. Bivariate dynamic structural equation modeling analyses indicate age-lagged changes operate in a coupled-over-time fashion, with the brain measure (lateral ventricular size) as a leading indicator in time of memory (Wechsler memory score) declines.

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