Diffusion tractography of the fornix in schizophrenia.

BACKGROUND: White matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia. METHODS: DTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and fractional anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition. RESULTS: Analysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (p=0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: p=0.048; right side p=0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r=0.554, p=0.026), combined verbal memory (r=0.647, p=0.007), combined recall (r=0.516, p=0.041), and combined recognition (r=0.710, p=0.002) for the control group. No such statistically significant correlations were found in the patient group. CONCLUSIONS: Our findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease.

Automatic and efficient MRI-US segmentations for improving intraoperative image fusion in image-guided neurosurgery.

Knowledge of the exact tumor location and structures at risk in its vicinity are crucial for neurosurgical interventions. Neuronavigation systems support navigation within the patient's brain, based on preoperative MRI (preMRI). However, increasing tissue deformation during the course of tumor resection reduces navigation accuracy based on preMRI. Intraoperative ultrasound (iUS) is therefore used as real-time intraoperative imaging. Registration of preMRI and iUS remains a challenge due to different or varying contrasts in iUS and preMRI. Here, we present an automatic and efficient segmentation of B-mode US images to support the registration process. The falx cerebri and the tentorium cerebelli were identified as examples for central cerebral structures and their segmentations can serve as guiding frame for multi-modal image registration. Segmentations of the falx and tentorium were performed with an average Dice coefficient of 0.74 and an average Hausdorff distance of 12.2 mm. The subsequent registration incorporates these segmentations and increases accuracy, robustness and speed of the overall registration process compared to purely intensity-based registration. For validation an expert manually located corresponding landmarks. Our approach reduces the initial mean Target Registration Error from 16.9 mm to 3.8 mm using our intensity-based registration and to 2.2 mm with our combined segmentation and registration approach. The intensity-based registration reduced the maximum initial TRE from 19.4 mm to 5.6 mm, with the approach incorporating segmentations this is reduced to 3.0 mm. Mean volumetric intensity-based registration of preMRI and iUS took 40.5 s, including segmentations 12.0 s.

Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum.

BACKGROUND: A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions. METHODS: DTI and structural MRI scans were obtained from 32 chronic schizophrenic subjects and 42 controls. Corpus callosum cross sectional area and its probabilistic subdivisions were determined automatically from structural MRI scans using a model based deformable contour segmentation. These subdivisions employ a previously generated probabilistic subdivision atlas, based on fiber tractography and anatomical lobe subdivision. The structural scan was then co-registered with the DTI scan and the anatomical corpus callosum subdivisions were propagated to the associated FA map. RESULTS: Results revealed decreased FA within parts of the corpus interconnecting frontal regions in schizophrenia compared with controls, but no significant changes for callosal fibers interconnecting parietal and temporo-occipital brain regions. In addition, integrity of the anterior corpus was statistically significantly correlated with negative as well as positive symptoms, while posterior measures correlated with positive symptoms only. CONCLUSIONS: This study provides quantitative evidence for a reduction of interhemispheric brain connectivity in schizophrenia, involving corpus callosum, and further points to frontal connections as possibly disrupted in schizophrenia.

Robot-assisted needle placement in open MRI: system architecture, integration and validation.

In prostate cancer treatment, there is a move toward targeted interventions for biopsy and therapy, which has precipitated the need for precise image-guided methods for needle placement. This paper describes an integrated system for planning and performing percutaneous procedures with robotic assistance under MRI guidance. A graphical planning interface allows the physician to specify the set of desired needle trajectories, based on anatomical structures and lesions observed in the patient's registered pre-operative and pre-procedural MR images, immediately prior to the intervention in an open-bore MRI scanner. All image-space coordinates are automatically computed, and are used to position a needle guide by means of an MRI-compatible robotic manipulator, thus avoiding the limitations of the traditional fixed needle template. Automatic alignment of real-time intra-operative images aids visualization of the needle as it is manually inserted through the guide. Results from in-scanner phantom experiments are provided.

Patient specific simulation and navigation of ventriculoscopic interventions.

In this paper a comprehensive framework for pre-operative planning, procedural skill training, and intraoperative navigation is presented. The goal of this system is to integrate surgical simulation with surgical planning in order to improve the individual treatment of patients. Various surgical approaches and new, more complex procedures can be assessed using a safe and objective platform that will allow the physicians to explore and discuss possible risks and benefits prior to the intervention. A simulation environment extends the pre-operative planning in a natural way, as it allows for direct evaluation of the surgical approach envisioned for each case. In addition, by providing intraoperative navigation based on this simulation, surgeons can carry out the previously optimized plan with higher precision and greater confidence.

Needle artifact localization in 3T MR images.

This work explores an image-based approach for localizing needles during MRI-guided interventions, for the purpose of tracking and navigation. Susceptibility artifacts for several needles of varying thickness were imaged, in phantoms, using a 3 tesla MRI system, under a variety of conditions. The relationship between the true needle positions and the locations of artifacts within the images, determined both by manual and automatic segmentation methods, have been quantified and are presented here.

Robot-assisted needle placement in open-MRI: system architecture, integration and validation.

This work describes an integrated system for planning and performing percutaneous procedures-such as prostate biopsy-with robotic assistance under MRI-guidance. The physician interacts with a planning interface in order to specify the set of desired needle trajectories, based on anatomical structures and lesions observed in the patient's MR images. All image-space coordinates are automatically computed, and used to position a needle guide by means of an MRI-compatible robotic manipulator, thus avoiding the limitations of the traditional fixed needle template. Direct control of real-time imaging aids visualization of the needle as it is manually inserted through the guide. Results from in-scanner phantom experiments are provided.

Prefrontal cortex and schizophrenia. A quantitative magnetic resonance imaging study.

OBJECTIVE: To measure prefrontal cortical volume in a group of schizophrenic subjects who presented with mainly positive symptoms and who were previously shown to have volume reductions in left temporal lobe structures. METHOD: Fourteen men with chronic schizophrenia and 15 male control subjects were matched for age, IQ, handedness, and parental socioeconomic status. Magnetic resonance images were obtained by means of a 1.5-T magnet, and contiguous 1.5-mm slices of the entire brain were obtained. RESULTS: No significant differences were found between schizophrenic and control subjects in mean values for prefrontal white or gray matter on either the right or the left side. However, within the schizophrenic group, there was evidence of a relationship between the volumes of left prefrontal gray matter and left temporal lobe structures that was not present in the control group. CONCLUSIONS: At least in this group of schizophrenic subjects with mainly positive symptoms, temporal lobe abnormalities can exist in conjunction with no gross volumetric abnormalities of the prefrontal cortex.

Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia.

Abnormalities in the auditory P300 event-related potential are one of the most robust findings in schizophrenia. To investigate the brain source(s) of this major functional abnormality, we combined P300 recordings with the use of a new generation of magnetic resonance imaging (MRI) technology to examine specific temporal lobe gray matter regions of interest in schizophrenics and normal controls. In schizophrenics, gray matter volume reductions in the left posterior superior temporal gyrus (STG), which includes Heschl's gyrus and the planum temporale, were highly and specifically associated with both P300 amplitude reduction and left < right topographic asymmetry. In contrast, left hippocampus and parahippocampal gyrus gray matter volume reductions, although present in schizophrenics, were not associated with any P300 abnormalities. There were also no statistically significant correlations between P300 amplitude at any of the central or left-sided electrode sites or any of the MRI-defined volumes of gray matter regions of interest in the right temporal lobe, superior frontal gyrus, or cingulate gyrus; additional work will thus be required to determine the role of these regions, if any, in P300 generation, along with the role of other brain areas not examined in the present study. These initial data appear most compatible with a model that postulates a major role for bilateral STG sources in P300 generation: The strongly asymmetric STG volume reduction (left < < right STG volume) found in many schizophrenic subjects produces asymmetric P300 amplitudes (left < < right) at lateral electrode sites, where the influence of the abnormal region is most easily detected.

Left planum temporale volume reduction in schizophrenia.

BACKGROUND: The planum temporale, located on the posterior and superior surface of the temporal lobe, is a brain region thought to be a biological substrate of language and possibly implicated in the pathophysiology of schizophrenia. To investigate further the role of planum temporale abnormalities in schizophrenia, we measured gray matter volume underlying the planum temporale from high spatial resolution magnetic resonance imaging techniques. METHODS: Sixteen male patients with chronic schizophrenia and 16 control subjects were matched for age, sex, handedness, and parental socioeconomic status. Magnetic resonance imaging images were obtained from a 1.5-T magnet. RESULTS: Gray matter volume was significantly reduced in the left planum temporale (28.2%) in schizophrenic patients compared with normal controls. Schizophrenic patients showed a reversal of the left greater than right planum temporale asymmetry found in normal controls. Heschl's gyrus (primary auditory cortex) showed no differences between the left and right sides in either group. Of note, the Suspiciousness/Persecution subscale score of the Positive and Negative Syndrome Scale was associated with reduced left planum temporale volume in schizophrenic patients. CONCLUSIONS: Patients with schizophrenia have reduced left planum temporale gray matter and a reversal of planum temporale asymmetry, which may underlie an impairment in language processing and symptoms of suspiciousness or persecution characteristic of schizophrenia.

Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients.

BACKGROUND: Magnetic resonance imaging studies in schizophrenia have revealed abnormalities in temporal lobe structures, including the superior temporal gyrus. More specifically, abnormalities have been reported in the posterior superior temporal gyrus, which includes the Heschl gyrus and planum temporale, the latter being an important substrate for language. However, the specificity of the Heschl gyrus and planum temporale structural abnormalities to schizophrenia vs affective psychosis, and the possible confounding roles of chronic morbidity and neuroleptic treatment, remain unclear. METHODS: Magnetic resonance images were acquired using a 1.5-T magnet from 20 first-episode (at first hospitalization) patients with schizophrenia (mean age, 27.3 years), 24 first-episode patients with manic psychosis (mean age, 23.6 years), and 22 controls (mean age, 24.5 years). There was no significant difference in age for the 3 groups. All brain images were uniformly aligned and then reformatted and resampled to yield isotropic voxels. RESULTS: Gray matter volume of the left planum temporale differed among the 3 groups. The patients with schizophrenia had significantly smaller left planum temporale volume than controls (20.0%) and patients with mania (20.0%). Heschl gyrus gray matter volume (left and right) was also reduced in patients with schizophrenia compared with controls (13.1%) and patients with bipolar mania (16.8%). CONCLUSIONS: Compared with controls and patients with bipolar manic psychosis, patients with first-episode schizophrenia showed left planum temporale gray matter volume reduction and bilateral Heschl gyrus gray matter volume reduction. These findings are similar to those reported in patients with chronic schizophrenia and suggest that such abnormalities are present at first episode and are specific to schizophrenia.

Increased rate of P300 latency prolongation with age in schizophrenia. Electrophysiological evidence for a neurodegenerative process.

BACKGROUND: The latency of the P300 event-related potential is prolonged in disorders associated with neural damage and degeneration and also becomes prolonged in the course of neural changes that accompany aging. We tested whether the rate of P300 latency increase with age was greater in male schizophrenic patients than in normal subjects because a steeper slope in schizophrenia would suggest a progressive neurodegenerative process. We also evaluated a subset of these subjects for changes in brain volumes as determined by magnetic resonance imaging. METHOD: The P300 component was elicited during an auditory "oddball" paradigm and was recorded from 47 male patients with chronic schizophrenia whose mean age at onset was 22.4 years and from 47 age-, handedness-, and gender-matched control subjects. The relation of P300 latency and amplitude to age within each group was evaluated using correlation and regression analyses. Brain volumes determined via magnetic resonance imaging were evaluated by quantitative volumetric analyses of images acquired with three-dimensional Fourier transform and double echo-spin echo-pulse sequences. RESULTS: The slope of P300 latency on age was steeper for schizophrenic patients than for normal control subjects at midline frontal and central electrode sites. The slope of N100 latency did not differ, implying that the P300 differences were not likely to be due to peripheral hearing loss or damage affecting the initial stages of neural processing. Posterior superior temporal gyrus gray matter volume determined via magnetic resonance imaging significantly diminished with age on the left side in patients with schizophrenia but not on the right side or in controls; these slopes were not, however, statistically significantly different from each other. CONCLUSIONS: These findings provide preliminary evidence that male patients with chronic schizophrenia experience a neurodegenerative process that becomes evident in adulthood and is reflected by the rate of change of P300 latency with age. Whether this process is due to the primary effects of schizophrenia or is secondary to factors associated with schizophrenia's chronic course and treatment remains a question for future investigation.

Development and testing of a cross-sectional area measurement tool for evaluating vein size.

This paper describes a software system for measuring cross-sectional area in reconstructed elliptical tubular structures. A measurement tool was developed using the freely available, cross-platform, open-source three-dimensional (3-D) Slicer environment. The software is easy to operate and allows the user to make multiple measurements on the fly. Results can be displayed to the screen, output to the system printer, and written to a user-specified data file for later analysis in commercial spreadsheet software. Measuring a known cross-sectional area tested the software. Phantoms of known physical dimensions were imaged using both CT and MR. The measured cross-sectional areas reported by the software were compared to each other, and the cross-sectional areas calculated from the known physical dimensions of the phantoms. The measurement errors were negligible. The results of this study indicate that the cross-sectional area measurement tool described provides reliable measurements and is an inexpensive and versatile alternative to high-end 3-D modeling software.

Volumetric evaluation of the thalamus in schizophrenic male patients using magnetic resonance imaging.

BACKGROUND: The thalamus, an important subcortical brain region connecting limbic and prefrontal cortices, has a significant role in sensory and cortical processing. Although inconsistently, previous studies have demonstrated neuroanatomical abnormalities in the thalamus of schizophrenic patients. METHODS: This structural magnetic resonance imaging study, based on segmentation of contiguous coronal 1.5-mm images, compared thalamic brain volumes of 15 chronic, male schizophrenic patients with 15 normal controls matched on age, sex, handedness, and parental socioeconomic status. RESULTS: There were no significant differences between patients and controls in thalamic volumes, right or left, adjusted for total brain volume; however, there were significantly different correlations of thalamic volumes with prefrontal white matter and lateral ventricles among patients, but not among controls. Thalamic volumes among patients were also significantly correlated with bizarre behavior, hallucinations, and thought disorder. CONCLUSIONS: Findings suggest that connectivity between thalamic nuclei and prefrontal cortical areas are abnormal in chronic male schizophrenic patients. In addition, ventricular enlargement may be, in part, due to subtle reduction in thalamic volume and/or in volume of thalamocortical and corticothalamic fibers secondary to thalamic abnormalities. Finally, correlations with positive symptomatology underscore the role of the thalamus in gating or filtering of sensory information and coordination of cortical processing.

The auditory N2 component in schizophrenia: relationship to MRI temporal lobe gray matter and to other ERP abnormalities.

The N2 component of the auditory event-related potential (ERP) indexes cognitive processes involved in the categorization of deviant stimuli. Although N2 amplitude and latency abnormalities have been reported in schizophrenia, their relationship to MRI structural changes, clinical status, and P3 abnormalities has not been defined. We therefore studied the auditory N2 and P3 components elicited by an oddball paradigm in 15 right-handed male subjects with schizophrenia and 14 control subjects who had quantitative MRI measures of temporal lobe gray-matter structures. To provide a methodological comparison, we measured the auditory N2 from both the target ERP (N2t) and the target-minus-frequent ERP difference (N2d) waveforms. Both N2t and N2d amplitude were bilaterally reduced in schizophrenics, with N2d showing a more pronounced reduction. Within the schizophrenic group, N2 amplitude reduction was associated with reduction in gray-matter volume of the left superior temporal gyrus (STG) and of medial temporal lobe structures bilaterally, and clinically, with greater chronicity. P3 amplitude, in contrast, correlated only with left posterior STG volume, and was more prominently associated with delusions and thought disorder. These findings suggest that the N2 and P3 components, though occurring sequentially in the ERP, tap separable anatomic and behavioral abnormalities in schizophrenia.

Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder.

This study used quantitative volumetric magnetic resonance imaging techniques to explore the neuroanatomic correlates of chronic, combat-related posttraumatic stress disorder (PTSD) in seven Vietnam veterans with PTSD compared with seven nonPTSD combat veterans and eight normal nonveterans. Both left and right hippocampi were significantly smaller in the PTSD subjects compared to the Combat Control and Normal subjects, even after adjusting for age, whole brain volume, and lifetime alcohol consumption. There were no statistically significant group differences in intracranial cavity, whole brain, ventricles, ventricle:brain ratio, or amygdala. Subarachnoidal cerebrospinal fluid was increased in both veteran groups. Our finding of decreased hippocampal volume in PTSD subjects is consistent with results of other investigations which utilized only trauma-unexposed control groups. Hippocampal volume was directly correlated with combat exposure, which suggests that traumatic stress may damage the hippocampus. Alternatively, smaller hippocampi volume may be a pre-existing risk factor for combat exposure and/or the development of PTSD upon combat exposure.

Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter.

BACKGROUND: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. METHODS: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. RESULTS: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. CONCLUSIONS: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.

Neuropsychological correlates of MRI temporal lobe abnormalities in schizophrenia.

OBJECTIVE: The authors evaluated the neuropsychological correlates of temporal lobe abnormalities in schizophrenic patients. METHOD: Fifteen schizophrenic patients underwent assessment of memory, by the Wechsler Memory Scale--Revised, and abstraction/categorization, by the similarities subtest of the Wechsler Adult Intelligence Scale--Revised and the Wisconsin Card Sorting Test. Neuropsychological tests of motor and constructional functions were used as control tasks. The patients also underwent magnetic resonance imaging (MRI) studies in which new neuroimaging techniques were used to derive measurements of volume and three-dimensional surface renderings of temporal lobe structures. RESULTS: Spearman rank-order correlations indicated significant associations between poor scores on tests of verbal memory, abstraction, and categorization and reduced volume in temporal lobe structures, including the parahippocampal gyrus and posterior superior temporal gyrus (left and right). By contrast, performance on tests of visual memory and on control tasks was not correlated with MRI temporal lobe abnormalities. CONCLUSIONS: These findings suggest a significant but modest relation between reduced volume in specific temporal lobe regions and neuropsychological deficits in abstraction, categorization, and verbal memory, all of which may reflect a dysfunctional semantic system in schizophrenia.

Quantitative volumetric MRI study of the cerebellum and vermis in schizophrenia: clinical and cognitive correlates.

OBJECTIVE: Recent evidence suggests that the cerebellum may play a role in higher cognitive functions and, therefore, may play an important role in schizophrenia. METHOD: The authors used magnetic resonance imaging to measure cerebellum and vermis volume in 15 patients with schizophrenia and 15 normal comparison subjects. RESULTS: They found that 1) vermis volume was greater in patients with schizophrenia than in normal subjects, 2) greater vermis white matter volume in the patients with schizophrenia significantly correlated with severity of positive symptoms and thought disorder and with impairment in verbal logical memory, and 3) patients with schizophrenia showed a trend for more cerebellar hemispheric volume asymmetry (left greater than right). CONCLUSIONS: These data suggest that an abnormality in the vermis may contribute to the pathophysiology of schizophrenia.