Pixel analysis of MR perfusion imaging in predicting radiation therapy outcome in cervical cancer.

The purpose of this study was to assess heterogeneity of tumor microcirculation determined by dynamic contrast-enhanced magnetic resonance (MR) imaging and its prognostic value for tumor radiosensitivity and long-term tumor control using pixel-by-pixel analysis of the dynamic contrast enhancement. Sixteen patients with advanced cervical cancer were examined with dynamic contrast-enhanced MR imaging at the time of radiation therapy. Pixel-by-pixel statistical analysis of the ratio of post- to precontrast relative signal intensity (RSI) values in the tumor region was performed to generate pixel RSI distributions of dynamic enhancement patterns. Histogram parameters were correlated with subsequent tumor control based on long-term cancer follow-up (median follow-up 4.6 years; range 3.8-5.2 years). The RSI distribution histograms showed a wide spectrum of heterogeneity in the dynamic enhancement pattern within the tumor. The quantity of low-enhancement regions (10th percentile RSI < 2.5) significantly predicted subsequent tumor recurrence (88% vs. 0%, P = 0.0004). Discriminant analysis based on both 10th percentile RSI and pixel number (reflective of tumor size) further improved the prediction rate (100% correct prediction of subsequent tumor control vs. recurrence). These preliminary results suggest that quantification of the extent of poor vascularity regions within the tumor may be useful in predicting long-term tumor control and treatment outcome in cervical cancer. J. Magn. Reson. Imaging 2000;12:1027-1033.

Cerebellar hypoactivity in frequent marijuana users.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using PET, regional cerebral blood flow was compared in frequent marijuana users and comparable, non-using controls after at least 26 h of monitored abstention by all subjects. Marijuana users showed substantially lower brain blood flow than controls in a large region of posterior cerebellum, indicating altered brain function in frequent marijuana users. A cerebellar locus of some chronic and acute effects of marijuana is plausible, e.g. the cerebellum has been linked to an internal timing system, and alterations of time sense are common following marijuana smoking.

Visualization of subthalamic nuclei with cortex attenuated inversion recovery MR imaging.

There is a significant amount of interest in studying the thalamus because of its central location in the brain and its role as a gatekeeper to higher centers of cognition. Imaging and measuring of the individual subnuclei of the thalamus has proven extremely difficult in MR because of the contrast-to-noise (CNR) of the MR sequences used. This report describes a novel MR pulse sequence known as cortex attenuated inversion recovery (CAIR), which increases the CNR in images and allows the individual subnuclei of the thalamus to be visualized by selectively nulling the gray matter in the brain using an inversion recovery sequence with an inversion time of 700 ms at 1.5 T.

Effects of frequent marijuana use on brain tissue volume and composition.

To investigate CNS effects of frequent marijuana use, brain tissue volume and composition were measured using magnetic resonance imaging (MRI) in 18 current, frequent, young adult marijuana users and 13 comparable, non-using controls. Automated image analysis techniques were used to measure global and regional brain volumes, including, for most regions, separate measures of gray and white matter. The marijuana users showed no evidence of cerebral atrophy or global or regional changes in tissue volumes. Volumes of ventricular CSF were not higher in marijuana users than controls, but were, in fact, lower. There were no clinically significant abnormalities in any subject's MRI. Sex differences were detected in several global volume measures.

Measurement of brain structures with artificial neural networks: two- and three-dimensional applications.

PURPOSE: To evaluate the ability of an artificial neural network (ANN) to identify brain structures. This ANN was applied to postprocessed magnetic resonance (MR) images to segment various brain structures in both two- and three-dimensional applications. MATERIALS AND METHODS: An ANN was designed that learned from experience to define the corpus callosum, whole brain, caudate, and putamen. Manual segmentation was used as a training set for the ANN. The ANN was trained on two-thirds of the manually segmented images and was tested on the remaining one-third. The reliability of the ANN was compared against manual segmentations by two technicians. RESULTS: The ANN was able to identify the brain structures as readily and as well as did the two technicians. Reliability of the ANN compared with the technicians was 0.96 for the corpus callosum, 0.95 for the whole brain, 0.86 (right) and 0.93 (left) for the caudate, and 0.71 (right) and 0.88 (left) for the putamen. CONCLUSION: The ANN was able to identify the structures used in this study as well as did the two technicians. The ANN could do this much more rapidly and without rater drift. Several other cortical and subcortical structures could also be readily identified with this method.

Pediatric extracranial applications of MR angiography.

Extracranial magnetic resonance angiography (MRA) was performed in 20 children to evaluate for various arterial and venous conditions. Time-of-flight and phase-contrast angiograms were constructed using a maximal-intensity-projection algorithm. The accuracy of MRA was comparable to Doppler ultrasound (n = 12) and conventional angiography (n = 3). MRA could provide an excellent mapping of patent (including collaterals) versus thrombosed vessels at sites not evaluated or inaccessible by sonography. Limitations included assessment of small and/or tortuous vessels, severely stenotic lesions, and very slow flow.

Prediction of tumor control in patients with cervical cancer: analysis of combined volume and dynamic enhancement pattern by MR imaging.

OBJECTIVE: Quantitative analysis of either tumor volume or dynamic enhancement pattern using MR imaging has been reported as useful in the prediction of response to radiation therapy in cancer of the cervix. Because data for both analyses can be obtained in a single MR examination, the purpose of this study was to evaluate whether combining both analyses can further improve the efficacy of using MR imaging to predict tumor control after radiation therapy. MATERIALS AND METHODS: Twenty patients with bulky carcinomas of the cervix, stages bulky IB (n = 2), IIB (n = 6), IIIA (n = 1), IIIB (n = 9), IVA (n = 1), and recurrent (n = 1), were studied. Initial tumor volumes were calculated by outlining the area of tumor in each slice on T2-weighted images and multiplying by the slice profile. Two dynamic contrast-enhanced MR studies were obtained in each patient immediately before the start of radiation therapy and after 20-22 Gy in 2 weeks of radiation therapy. Dynamic enhancement imaging was performed at 3-sec intervals in the sagittal plane for 120 sec after rapid (9 ml/sec) i.v. injection of MR contrast agent (0.1 mmol/kg of gadoteridol) using a power injector. Time and signal intensity curves reflecting the relative signal intensity of contrast enhancement in the tumor region were generated, and the relative signal intensity of the tumor region during the early plateau phase was calculated. Median follow-up was 25 months (range, 11-35 months). RESULTS: The combined analysis did not improve the prediction rate of local recurrence in small-sized tumors, which responded well to radiation therapy regardless of their dynamic enhancement pattern. However, the combined analysis did improve the prediction rate of local recurrence in intermediate- and large-sized tumors (75% and 80%, respectively) over assessment by either volume analysis (33% and 60%, respectively) or dynamic enhancement pattern analysis (64% and 64%, respectively). The combined analysis was most useful in intermediate-sized tumors (40-99 cm3; 33% recurrence), significantly improving differentiation between high-risk (80% recurrence) and low-risk 10% recurrence) patients (p = .010). CONCLUSION: Our preliminary results suggest that the combined data of both tumor morphologic (volume) and microcirculatory (dynamic enhancement pattern) parameters allow more accurate prediction of local failure in patients with advanced cervical cancer than does each individual parameter alone. Combined data appear to have the greatest potential in patients with intermediate-sized tumors, who constitute most patients (60%) and remain a challenge for outcome prediction and management.

Comparison of inversion recovery asymmetrical spin-echo EPI and gradient-echo EPI for brain motor activation study.

An inversion recovery asymmetric spin-echo (IR-ASE) echo-planar imaging (EPI) sequence has been developed for functional studies of the brain. This technique uses an 180 degrees inversion pulse with a long inversion time (TI) to suppress the pulsatile cerebrospinal fluid and an asymmetric spin-echo readout to obtain activation signals from brain capillaries. Because gradient-echo sequences are most sensitive to large vessels, motor cortex activation studies using a gradient-echo technique also were conducted for comparison with the IR-ASE method. The results suggest that the IR-ASE pulse sequence may be a useful complement to the gradient-echo technique for the study of neuronal activity of the human brain.

Tumor size evaluated by pelvic examination compared with 3-D quantitative analysis in the prediction of outcome for cervical cancer.

PURPOSE: Tumor size estimated by pelvic examination (PE) is an important prognostic factor in cervical cancer treated with radiation therapy (RT). Recent histologic correlation studies also showed that magnetic resonance (MR) imaging provides highly accurate measurements of the actual tumor volume. The purpose of this study was to: (a) compare the accuracy of PE and MR in predicting outcome, and (b) correlate tumor measurements by PE versus MR. METHODS AND MATERIALS: Tumor measurements were performed prospectively in 43 patients with advanced cervical cancer. MR and PE were performed at the same time intervals: (a) at the start of RT, (b) after 20-24 Gy/2-2.5 weeks, (c) after 40-50 Gy/4-5 weeks, and (d) at follow-up (1-2 months after RT completion). PE measured tumor diameters in anteroposterior, lateral, and craniocaudal direction, and PE-derived tumor size was computed as maximum diameter, average diameter, and ellipsoid volume. MR-derived tumor size was calculated by summation of the tumor areas in each section and multiplication by the section thickness. Tumor regression during RT was calculated for each method as percentage of initial volume. The measurements were correlated with local failure and disease-free survival. Median follow-up was 29 months (range: 9-56 months). RESULTS: Prediction of local control: Overall, tumor regression rate (rapid versus slow) was more precise than the initial tumor size in the prediction of outcome. MR provided a more accurate and earlier prediction of local control (at 2-2.5 weeks, and at 4-5 weeks of RT) than PE (only at follow-up). Based on the initial tumor size, MR was also better than PE in predicting disease-free survival and local control, particularly in large (> or = 100 cm3) tumors. Size correlation: Tumor size (maximum diameter, average diameter, volume) by PE and MR did not correlate well (r = 0.51, 0.61, and 0.58, respectively). When using MR measurements as a reference, PE tended to overestimate intermediate-size (40-99 cm3) tumors. CONCLUSION: This preliminary study suggests that increased precision of tumor volume measurement leads to more accurate and earlier prediction of outcome in cervical cancer. MR tumor volumetry may be useful as an adjunct to PE in selected cases, and holds the potential to impact therapeutic decision-making.

A method to determine activation thresholds in fMRI paradigms.

Determining meaningful activation thresholds in functional magnetic resonance imaging (fMRI) paradigms is complicated by several factors. These include the time-series nature of the data, the influence of physiological rhythms (e.g. respiration) and vacillations introduced by the experimental design (e.g. cueing). We present an empirical threshold for each subject and each fMRI experiment that takes these factors into account. The method requires an additional fMRI data set as similar to the experimental paradigm as possible without dichotomously varying the experimental task of interest. A letter fluency task was used to illustrate this method. This technique differs from classical methods since the Pearson correlation probability values tabulated from statistical theory are not used. Rather each subject defines his or her own set of threshold probability values for correlations. It is against these empirical thresholds, not Pearson's, that an experimental fMRI correlation is assessed.

Cavum septi pellucidi in normals and patients with schizophrenia as detected by magnetic resonance imaging.

Cavum septi pellucidi (CSP) is a cavity between the two leaflets of the septum pellucidum. CSP is a developmental anomaly, yet the pathologic implications, if any, of an abnormally large CSP remain unclear. The reported incidence of CSP among normal populations varies greatly from 0.15% to 85%. Several studies have suggested that there is a higher incidence of CSP in patients with schizophrenia. We conducted a thin-slice magnetic resonance imaging study to evaluate the prevalence of CSP in a sample of 75 controls and 55 patients. There was a high incidence of small CSP among both groups: 58.8% in the controls and 58.2% in the patients, suggesting that a small cavum could be considered a normal variant; however, the patient group had significantly higher incidence of large CSP (20.7%) compared to the normal group (3%). The patients with large CSP were all male.

Peripheral nerve stimulation in a whole-body echo-planar imaging system.

Echo-planar techniques in MRI use a rapidly oscillating frequency-encoding gradient with the potential to produce peripheral nerve stimulation. To evaluate the incidence, type, and location of stimulation in a commercial whole-body scanner, we studied two groups: (a) 173 consecutive individuals scanned by echo-planar imaging for other purposes and (b) seven subjects who were scanned with an extensive set of 36 echo-planar sequences (with prompting after each scan to report any peripheral nerve stimulation) to test the effects of various parameters. Although only 5% of group A reported symptoms of peripheral nerve stimulation, all in group B experienced some type of stimulation, dependent primarily on direction of the oscillating gradient and location of the body within the gradient coil. Maximum stimulation typically occurred 30 to 40 cm from isocenter in the region of maximum dB/dt. Generally, y gradients produced truncal stimulation, and x gradients produced stimulation in the head. When hands were clasped over the abdomen, a tingling in the hands occasionally was felt. Patients should be instructed to keep their hands apart.

Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay.

PURPOSE: This study investigated sequential changes in tumor blood supply using magnetic resonance (MR) perfusion imaging and assessed their significance in the prediction of outcome of patients with advanced cervical cancer. The purpose of this project was to devise a simple, noninvasive method to predict early signs of treatment failure in advanced cervical cancer treated with conventional radiation therapy. METHODS AND MATERIALS: Sixty-eight MR perfusion studies were performed prospectively in 17 patients with squamous carcinomas (14) and adenocarcinomas (3) of the cervix, Stages bulky IB (1), IIB (5), IIIA (1), IIIB (8), and IVA (1), and recurrent (1). Four sequential studies were obtained in each patient: immediately before radiation therapy (pretherapy), after a dose of 20-22 Gy/ approximately 2 weeks (early therapy), after a dose of 40-45 Gy/ approximately 4-5 weeks (midtherapy), and 4-6 weeks after completion of therapy (follow-up). Perfusion imaging of the tumor was obtained at 3-s intervals in the sagittal plane. A bolus of 0.1 mmol/kg of MR contrast material (gadoteridol) was injected intravenously 30 s after beginning image acquisition at a rate of 9 ml/s using a power injector. Time/signal-intensity curves to reflect the onset, slope, and relative signal intensity (rSI) of contrast enhancement in the tumor region were generated. Median follow-up was 8 months (range 3-18 months). RESULTS: Tumors with a higher tissue perfusion (rSI > or = 2.8) in the pretherapy and early therapy (20-22 Gy) studies had a lower incidence of local recurrence than those with a rSI of < 2.8, but this was not statistically significant (13% vs. 67%; p = 0.05). An increase in tumor perfusion early during therapy (20-22 Gy), particularly to an rSI of > or = 2.8, was the strongest predictor of local recurrence (0% vs. 78%; p = 0.002). However, pelvic examination during early therapy (20-22 Gy) commonly showed no appreciable tumor regression. The slope of the time/signal-intensity curve obtained before and during radiation therapy also correlated with local recurrence. Follow-up perfusion studies did not provide information to predict recurrence. CONCLUSION: These preliminary results suggest that two simple MR perfusion studies before and early in therapy can offer important information on treatment outcome within the first 2 weeks of radiation therapy before response is evident by clinical examination. High tumor perfusion before therapy and increasing or persistent high perfusion early during the course of therapy appear to be favorable signs. High perfusion suggests a high blood and oxygen supply to the tumor. The increase in tumor perfusion seen in some patients early during radiation therapy suggests improved oxygenation of previously hypoxic cells following early cell kill. Radiation therapy is more effective in eradicating these tumors, resulting in improved local control. Our technique may be helpful in identifying early-while more aggressive therapy can still be implemented-those patients who respond poorly to conventional radiation therapy.

Usefulness of tumor volumetry by magnetic resonance imaging in assessing response to radiation therapy in carcinoma of the uterine cervix.

PURPOSE: Clinical evaluation of tumor size in cervical cancer is often difficult, and clinical signs of radiation therapy failure may not be present until well after completion of treatment. The purpose of this study is to investigate early indicators of treatment response using magnetic resonance (MR) imaging for quantitative assessment of tumor volume and tumor regression rate before, during, and after radiation therapy. METHODS AND MATERIALS: Thirty-four patients with cervical cancer Stages IB [5], IIB [8], IIIA [1], IIIB [14], IVA [3], IVB [1], and recurrent [2] were studied prospectively with four serial MR examinations obtained at the start of radiation therapy, at 2-2.5 weeks (20-24 Gy), at 4-5 weeks (40-50 Gy), and 1-2 months after treatment completion. Tumor volume was assessed by three-dimensional volumetric measurements using T2-weighted images of each MR examination. The volume regression rate was generated based on the four sequential MR studies. These findings were correlated with local control, metastasis rate, and disease-free survival. Median follow-up was 18 months (range: 9-43 months). RESULTS: The tumor regression rate after a dose of 40-50 Gy correlated significantly with treatment outcome. The actuarial 2-year disease-free survival was 88.4% in patients with tumors regressing to < 20% of the initial volume compared with 45.4% in those with > or = 20% residual (p = 0.007). The incidence of local recurrence was 9.5% (2 out of 21) and 76.9% (10 out of 13), respectively (p < 0.001). Analysis by initial tumor volume showed that this observation was valid in patients with initial volumes between 40 and 100 cm3. Analysis by FIGO stage confirmed this observation in all patients except those with Stage IB. CONCLUSION: Sequential tumor volumetry using MR imaging appears to be a sensitive measure of the responsiveness of cervical cancer to irradiation. Treatment response can be assessed as early as during the course of radiation therapy by measurement of initial tumor volume and regression rate at 40-50 Gy. In patients with large (> 40 cm3) and advanced (Stage > or = IIIA) tumors, this technique may be helpful in supplementing the clinical examination for response assessment. The identification of patients at high risk for treatment failure may ultimately lead to improved clinical outcome.

Echo-planar FLAIR imaging in evaluation of intracranial lesions.

Fluid-attenuated inversion-recovery (FLAIR) imaging is a magnetic resonance imaging technique that improves lesion detection in the brain. This technique suppresses signal from free water in cerebrospinal fluid and maintains the hyperintense lesion contrast of T2-weighted spin-echo imaging. Unfortunately, conventional FLAIR imaging requires a long acquisition time and provides a limited number of sections. A combination of echo-planar imaging and FLAIR imaging offers the image contrast effects of FLAIR imaging and the speed of echo-planar imaging. Clinically, the echo-planar FLAIR technique is most helpful in detecting subtle, early lesions that do not enhance, such as early infarct, demyelinating disease, early infection, and trauma. The increased magnetic susceptibility effect associated with the echo-planar technique can be clinically useful in detecting subtle hemorrhage and cavernous angioma. Echo-planar FLAIR imaging is a practical and efficient means of screening the entire brain in a short time.

Automatic atlas-based volume estimation of human brain regions from MR images.

OBJECTIVE: MRI offers many opportunities for noninvasive in vivo measurement of structure-function relationships in the human brain. Although automated methods are now available for whole-brain measurements, an efficient and valid automatic method for volume estimation of subregions such as the frontal or temporal lobes is still needed. MATERIALS AND METHODS: We adapted the Talairach atlas to the study of brain subregions. We supplemented the atlas with additional boxes to include the cerebellum. We assigned all the boxes to 1 of 12 regions of interest (ROIs) (frontal, parietal, temporal, and occipital lobes, cerebellum, and subcortical regions on right and left sides of the brain). Using T1-weighted MR scans collected with an SPGR sequence (slice thickness = 1.5 mm), we manually traced these ROIs and produced volume estimates. We then transformed the scans into Talairach space and compared the volumes produced by the two methods ("traced" versus "automatic"). The traced measurements were considered to be the "gold standard" against which the automatic measurements were compared. RESULTS: The automatic method was found to produce measurements that were nearly identical to the traced method. We compared absolute measurements of volume produced by the two methods, as well as the sensitivity and specificity of the automatic method. We also compared the measurements of cerebral blood flow obtained through [15O]H2O PET studies in a sample of nine subjects. Absolute measurements of volume produced by the two methods were very similar, and the sensitivity and specificity of the automatic method were found to be high for all regions. The flow values were also found to be very similar by both methods. CONCLUSION: The automatic atlas-based method for measuring the volume of brain subregions produces results that are similar to manual techniques. The method is rapid, efficient, unbiased, and not subject to the problems of rater drift or potentially poor interrater reliability that plague manual methods. Consequently, this method may be very useful for the study of structure-function relationships in the human brain.

Brain morphology in first-episode schizophrenia.

OBJECTIVE: Neuroimaging studies have provided robust evidence that schizophrenia is associated with structural brain abnormalities. However, the underlying pathophysiology of these changes is still unknown. By evaluating brain morphology early in the course of illness, confounding effects of treatment and duration of illness are minimized. The goal of this study was to evaluate brain structure in patients early in the course of schizophrenia who had received no or minimal neuroleptics. METHOD: Magnetic resonance imaging was used to evaluate 12 male and 12 female patients experiencing their first episode of schizophrenia (mean duration of psychotic episode = 14 weeks) and 12 male and 12 female normal volunteers equivalent in age, height, and parents' socioeconomic status. A totally automated method was used to analyze scans, yielding volumes of brain tissue and CSF, divided into lobes. RESULTS: The patient group had significantly more total CSF than the comparison subjects. This was accounted for by higher levels of intersulcal CSF as well as ventricular CSF. There were no differences in total volume of brain tissue between the two groups, but patients had a significant regionally specific decrement in frontal lobe tissue compared with the normal subjects. CONCLUSIONS: These findings indicate that structural brain abnormalities are present very early in schizophrenia and may not be due to factors such as treatment or chronicity of illness. Rather, since the abnormalities are present near the onset of the illness, a neurodevelopmental mechanism may be suggested.

Effects of diagnosis, laterality, and gender on brain morphology in schizophrenia.

OBJECTIVE: Structural neuroimaging and neuropathological studies have demonstrated a variety of aspects of brain morphology that appear to distinguish schizophrenic patients from comparison subjects (diagnostic effects), a predominance of left-sided pathology (laterality effects), and a greater likelihood of brain abnormality among males (gender effects). However, findings have been inconsistent across studies, perhaps reflecting limited power due to small study group sizes. The goal of this study was to examine diagnostic, laterality, and gender effects of brain morphology as assessed by magnetic resonance imaging in a large, carefully evaluated group of schizophrenic and comparison subjects. METHOD: One hundred two patients with schizophrenia (DSM-III-R) (70 men and 32 women) and 87 normal comparison subjects, chosen to be equivalent to the patients in terms of familial socioeconomic background, underwent magnetic resonance imaging with a 1.5-tesla scanner. All regions of interest were outlined manually by an experienced technician on all slices in which they were visualized. Region of interest volumes were compared across groups, and age, sex, and stature were controlled. RESULTS: Schizophrenic patients were found to have larger lateral and third ventricles and smaller thalamic, hippocampal, and superior temporal volumes than comparison subjects. No significant differences were demonstrated for intracranial, cerebral, cerebellar, temporal lobe, caudate nuclei, or temporal horn volumes. There were no significant Laterality by Diagnosis effects and no significant Gender by Diagnosis effects for any of the regions of interest. CONCLUSIONS: Many, but not all, of the hypotheses informed by earlier studies regarding diagnostic effects were confirmed, while hypotheses regarding gender and laterality interactions with diagnosis were not supported.

Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging.

OBJECTIVE: To determine general and regional indices of structural brain abnormality in schizophrenia. DESIGN: Case-control comparison study. SUBJECTS: Fifty-two patients diagnosed as having schizophrenia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, were compared with 90 healthy volunteers recruited from the community. MEASUREMENTS: Structural brain images were acquired using magnetic resonance; measurements were obtained using three-dimensional visualization of volume-rendered brains and an automated atlas-based dissection of specific regions. General measures included the volume of total brain tissue, total cerebrospinal fluid (CSF), and CSF within the ventricular system. Regional measures included the volume of tissue and CSF in the frontal, temporal, parietal, and occipital lobes and the cerebellum. RESULTS: Compared with the controls, the patients had a smaller average volume of total brain tissue and a greater average volume of total and ventricular CSF. A specific relative decrease in brain tissue was found only in the frontal lobes, although the volume of CSF was greater in patients than in controls in all brain regions. CONCLUSION: In addition to the generalized brain abnormalities observed in schizophrenia, a regional abnormality may be present in frontal regions. Since the frontal lobes integrate multimodality information and perform a variety of "higher" cognitive and emotional functions that are impaired in schizophrenia, the frontal abnormality noted is consistent with the clinical presentation of the illness. Impaired frontal function and a disruption in its complex circuitry (including thalamocortical projections) may explain why patients with schizophrenia often have significant deficits in formulating concepts and organizing their thinking and behavior.

Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging.

Schizophrenia is a complex illness characterized by multiple types of symptoms involving many aspects of cognition and emotion. Most efforts to identify its underlying neural substrates have focused on a strategy that relates a single symptom to a single brain region. An alternative hypothesis, that the variety of symptoms could be explained by a lesion in midline neural circuits mediating attention and information processing, is explored. Magnetic resonance images from patients and controls were transformed with a "bounding box" to produce an "average schizophrenic brain" and an "average normal brain." After image subtraction of the two averages, the areas of difference were displayed as an effect size map. Specific regional abnormalities were observed in the thalamus and adjacent white matter. An abnormality in the thalamus and related circuitry explains the diverse symptoms of schizophrenia parsimoniously because they could all result from a defect in filtering or gating sensory input, which is one of the primary functions of the thalamus in the human brain.