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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., (Copyright 2000 Wiley-Liss, Inc.)

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., (Copyright 2000 Academic Press.)

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.

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.

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.

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.

OBJECTIVE: To develop a technique for the evaluation of tumor perfusion prior to and during chemo- and radiation therapy.METHODS: Using the [(15)O]water autoradiographic technique and positron emission tomography (PET), perfusion in solid cervical tumors was investigated in a series of women prior to and during radiation therapy for cervical cancer. A 60-second summed image was used with the arterial blood curve to create a parametric image. The parametric images were registered to sagittal magnetic resonance (MR) images. Regions drawn on the MR images encompassing the tumor were transferred to the corresponding co-registered PET images.RESULTS: All tumors were easily visualized by both imaging modalities and tissue heterogeneity could be evaluated. Mean pre- and during therapy flow values averaged 41.5 +/- 11.9 and 48.2 +/- 7.2 mL/min/100 g tumor, respectively.CONCLUSIONS: Perfusion status of solid tumors, an assumed predictor of response potential, can be assessed using PET and the [(15)O]water technique.

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.

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.

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.

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 (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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Developments in imaging technology have made three-dimensional visualization of internal brain structures possible with excellent resolution. Since improved visualization implies improved measurement, these advances hold promise to more accurately measure the volumes of internal structures. As new technologies and techniques emerge, evaluating the relative benefits of measurement methods becomes necessary. We compared and evaluated two methods of estimating volumes from images of brain structures. One method counted pixels within a region of interest, while the other method tessellated the surface between tracings on adjacent slices. Our study assessed both measurement error for true phantom volumes and method disparity for in vivo structures in a randomly selected sample of subjects (n = 100). For our comparisons, we focused on the temporal lobe, ventricular system, and hippocampus. Bias, independence of measurement errors and maximal discrimination of individual differences are properties that are relevant to validating and evaluating measurements of cerebral structure. Pixel counting proved to be the more robust of the two methods, being less sensitive to nuisance-interactions between size of object, shape, and slice thickness. Clinical and research applications of imaging techniques may have distinctive but overlapping needs when evaluating and validating new developments in imaging.

Purpose: To investigate the cost-effectiveness of high-dose MR contrast studies in the management of brain metastases., Methods: During the phase III clinical trial of high-dose contrast studies (0.3 mmol/kg), 11 of 27 patients were judged by the reviewers to have potential treatment changes based on the additional information provided by the high-dose studies. We retrospectively evaluated how many of these 27 patients had actual treatment changes because of the results of the high-dose study. Using the fee schedule at our institution, the cost-effectiveness was analyzed based on the cost savings from treatment changes and the additional expense of implementing the high-dose studies., Results: A total of 3 craniotomies ($22,800 each) and 2 aggressive courses of radiation therapy ($1122 each) were avoided in 4 patients because of the additional lesions detected by the high-dose studies. This resulted in a treatment cost savings of $70,644. The extra expense for implementing the high-dose study is $9126 for a single injection in all 27 patients, $9295 for 2 separate injections completed in 1 visit in the 11 patients, and $11,154 for 2 separate injections completed in 2 separate visits. The cost savings in management (diagnosis and treatment) therefore ranged from $59,490 to $61,518 for all patients and from $2203 to $2278 per patient., Conclusion: Based on our limited data, the high-dose study seems to impact positively on the cost-effectiveness in the management of brain metastases. However, because our study had limitations, our results need to be confirmed with a larger patient population and a more standardized treatment approach and fee schedule.

An amputee (traumatic) experienced increased phantom limb pain when exposed to the magnetic fields of two magnetic resonance imagers. With a visual analog scale used to measure pain, electric stimulation studies demonstrated that the residual limb was unusually sensitive to subthreshold (for muscle twitch) levels of current. The painful symptoms produced mimicked those experienced in the presence of the imagers.

Volumetric measurements of subcortical and temporal structures were done on a sample of 54 schizophrenic patients, who were compared with 48 bipolar patients and 47 normal controls. We observed the male schizophrenic patients to have significant enlargement in the putamen and lesser enlargement in the caudate. We found the right temporal lobe to be larger than the left across all diagnostic groups, although bipolar females failed to have this asymmetry. We did not replicate the finding of decreased hippocampal, amygdala, or temporal lobe volume in our schizophrenic patients. Nor did we find significant differences between our bipolar patients and controls in the structures measured, with the exception of the right hippocampus. Our findings are consistent with a developmental defect in pruning of subcortical brain regions or with a compensatory synaptic increase secondary to decreased input from other brain regions such as the prefrontal cortex or anterior temporal lobe structures. Coupled with the lack of temporal lobe asymmetry in bipolar females, these findings suggest that different types of gender-specific neurodevelopmental abnormalities may occur in affective versus schizophrenic psychosis, which may reflect the effects of hormonal influences on brain development in predisposed individuals.

Purpose: To assess the effectiveness and safety of higher doses of gadoteridol in the MR evaluation of patients with brain metastases., Materials and Methods: Thirty-one patients with a clinical suspicion of brain metastases were studied prospectively with gadoteridol, a new, nonionic, low-osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg and an additional dose of 0.2 mmol/kg 30 minutes later. Images were obtained before, immediately after, and 10 and 20 minutes after the initial dose. Images also were acquired immediately after the additional dose of gadoteridol., Results: No adverse effects were attributed to the injection of gadoteridol. Four patients' examinations were excluded from analysis because of machine malfunction (two patients) and excessive motion artifact (two patients). Four patients had no detectable metastases. After the additional dose of gadoteridol, there was a marked qualitative improvement in lesion conspicuity and detection. The conspicuity of 80 of 81 lesions was increased in the high-dose studies, and 46 new lesions were detected in 19 of 27 patients. Quantitative image analysis demonstrated a significant increase in normalized mean lesion contrast between the initial-dose and high-dose studies (35 lesions identified in 13 patients, P less than .0001). The additional information gained by high-dose examinations contributed to a potential modification of the treatment in 10 of 27 patients. High-dose examinations increased flow-related artifact in the posterior fossa in 12 of 27 patients., Conclusion: Based on our preliminary results, high-dose gadolinium-enhanced MR examinations may have advantages over 0.1 mmol/kg examinations in detecting early and/or small metastases. This may be significant in the management of patients with cerebral metastases.

Metallic implants or prostheses can be potentially hazardous during magnetic resonance (MR) imaging because of movement or dislodgment of the foreign object. Magnetic eye implants have been reported to exhibit strong movement when placed in water and exposed to a field of 1.5 T. The authors report a case of orbital implant extrusion possibly caused by the movement of a magnetic orbital implant during MR imaging at 0.5 T.

T1 and T2 relaxation times were measured in ten brain regions on the right and left side in a sample of 27 schizophrenic patients and 37 normal controls. The schizophrenic patients showed a prolongation of T2 relaxation time, and to a lesser extent of T1 relaxation time, which was more predominantly localized in the right hemisphere and in gray matter structures. These results may indicate that metabolic, physiological, or neurochemical brain function in schizophrenia is related in some way to a change in tissue fluid in neuronal cell bodies or interstitial gray matter.

The goal of this study was to determine the accuracy, the reproducibility, and some of the tissue determinants of image-based myocardial T2 measurements. Image-based T2 calculations for the free walls of the right ventricle (RV) and left ventricle (LV), in vitro T2 determination (at 0.47 T), and water, fat, and collagen content analyses were performed in ex vivo hog hearts. T2 values of the RV and LV free walls were also determined from spin-echo images of 14 healthy human subjects. Preliminary reproducibility studies were performed with 10 sets of images acquired from a single subject. For both in vitro and image-based T2 values of hog hearts, RV T2 was significantly longer than LV T2. Water content was the only tissue factor to significantly correlate with in vitro and image-based T2 values. For the 14 human subjects studied, image-based T2 values calculated from the first- and third-echo images demonstrated a significant difference between LV and RV. The difference was not significant when the first- and second-echo images were used. Image-based T2 measurements of a single subject showed a coefficient of variation of 6.8% for the LV and 9.1% for the RV. The authors conclude that image-based T2 measurements of normal myocardium can be made with sufficient precision to identify differences of the magnitude of those found between RV and LV T2 values. Image-based T2 values of myocardium may provide useful data to aid in patient treatment.

In phase II and III trials of gadoteridol (Gd-HP-D03A), a new nonionic, low-osmolar contrast agent, 40 patients with intracranial neoplasms underwent magnetic resonance (MR) imaging with experimental doses of 0.05-0.3 mmol/kg. Fifteen patients also underwent contrast studies with the standard dose (0.1 mmol/kg) of gadopentetate dimeglumine. Both gadopentetate dimeglumine and gadoteridol appear to have a similar effect when given in equal doses (0.1 mmol/kg, n = 5). Lesion enhancement and delineation were better at higher experimental doses (0.2 or 0.3 mmol/kg, n = 7) and worse at a lower experimental dose (0.05 mmol/kg, n = 3). Quantitative analysis of 10 lesions examined with identical imaging protocols revealed a directly proportional relationship (r = .975) between lesion contrast ratio and dose over a range of 0.05-0.3 mmol/kg. Phantom experiments support the clinical results. Improved enhancement, detection, and delineation of central nervous system (CNS) neoplasms resulting from increased injected doses of gadoteridol have the potential to be clinically significant and may justify the possibly higher cost of increased contrast material dosage. Lower doses may not be adequate for the evaluation of most CNS tumors.

Gated cardiac magnetic resonance imaging (MRI) permits detailed evaluation of cardiac anatomy, including the calculation of left ventricular volume and mass. Current methods of deriving this information, however, require manual tracing of boundaries in several images; such manual methods are tedious, time consuming, and subjective. The purpose of this study is to apply a new computerized method to automatically identify endocardial and epicardial borders in MRIs. The authors obtained serial, short-axis, spin-echo MRIs of 13 excised animal hearts. Also obtained were selected short-axis, spin-echo ventricular images of 11 normal human volunteers. A method of automated edge detection based on graph-searching principles was applied to the ex vivo and in vivo images. Endocardial and epicardial areas were used to compute left ventricular mass and were compared with the anatomic left ventricular mass for the images of excised hearts. The endocardial and epicardial areas calculated from computer-derived borders were compared with areas from observer tracing. There was very close correspondence between computer-derived and observer tracings for excised hearts (r = 0.97 for endocardium, r = 0.99 for epicardium) and in vivo scans (r = 0.92 for endocardium, r = 0.90 for epicardium). There also was a close correspondence between computer-generated and actual left ventricular mass in the excised hearts (r = 0.99). These data suggest the feasibility of automated edge detection in MRIs. Although further validation is needed, this method may prove useful in clinical MRI.

Structural brain abnormalities were examined in a sample of 48 patients with bipolar affective disorder who were compared with 54 schizophrenic patients and 47 normal controls. As in our previous work using computed tomographic scanning, lateral ventricular enlargement was due to a diagnostic effect. In this study, the effect was more prominent in the schizophrenic men, while a trend was seen in the bipolar men. Women in both groups did not differ significantly from normal subjects. This finding is possibly consistent with the fact that men have a higher frequency of birth anomalies such as hydrocephalus. Since one cause of such birth anomalies might be periventricular hemorrhage or infarction, we also evaluated all scans for the presence of small focal regions of signal hyperintensity. A significant increase in the number of focal signal hyperintensities was noted in the bipolar patients, in comparison with normal subjects, but not in the schizophrenics. The bipolar patients with focal signal hyperintensities had a trend toward larger ventricular size than those without. The pathophysiological significance of these findings is unclear.

Magnetic resonance imaging was used to evaluate neuroanatomical and neuropathologic abnormalities in a consecutive series of 140 patients with schizophrenia for comparison with normal controls. Partial agenesis of the corpus callosum, a rare neurodevelopmental abnormality, was found in two patients, one of whom also had a callosal lipoma. Evidence is presented suggesting that this finding represents an increased prevalence of partial agenesis in schizophrenia. The corpus callosum develops embryologically in intimate relationship to the hippocampal formation, fornix, septum pellucidum, and cingulate gyrus. In individuals with callosal agenesis, abnormalities also occur in the development of these limbic structures. Recent neuropathologic studies have suggested the occurrence of abnormal neurogenesis in the hippocampal formation and in the cingulate gyrus in schizophrenic patients. An increased prevalence of callosal agenesis and its related limbic abnormalities would further support investigation into neurodevelopmental abnormalities of these anatomical regions in schizophrenia.

The two-compartment radioassay for microbial kinetics based on continuous measurement of the 14CO2 released by bacterial metabolism of 14C-labeled substrate offers a valuable approach to testing the potency of antimicrobial drugs. By using a previously validated radioassay with gram-positive and gram-negative bacteria, a group of protein synthesis inhibitors was evaluated for their effect on microbial growth kinetics. All tested drugs induced changes in both the slopes and intercepts of the growth curves. An exponential growth model was applied to quantify the drug effect on the processes of bacterial 14CO2 liberation and cell generation. The response was measured in terms of a generation rate constant. A linear dependence of the generation rate constant on the dose of spectinomycin was observed with Escherichia coli. Sigmoidal-shaped curves were found in the assays of chloramphenicol and tetracycline. The implications of dose-response curves are discussed on the basis of the receptor site concept for drug action. The assay sensitivities for chloramphenicol and tetracycline were similar to those obtained by the cell counting method, but the sensitivity of the radioassay was at least 10 times greater for spectinomycin.

Fast Fourier algorithms are presented for image reconstruction from nonrectangularly sampled data. Since standard display devices require image matrices with rectangular pixels, these algorithms accept nonrectangularly sampled input and calculate output points on a rectangular array. Images are reconstructed with no loss of resolution on a 256x256 square pixel format from 224x256 hexagonally sampled raw data points with no interpolation. The images demonstrate aliasing in a hexagonal pattern around the primary image. This technique can be used to reduce scan time, data throughput, and data-storage requirements while maintaining resolution or to improve resolution while maintaining scan time.

In a second large series of schizophrenic patients studied with magnetic resonance imaging at the University of Iowa, Iowa City, earlier findings of decreased frontal, cerebral, and cranial size were not replicated. In this second series, control subjects were selected to be educationally equivalent to the schizophrenic patients, a modification in design that may partially account for the failure to replicate. By means of coronal images, ventricular volume was compared in patients and controls and found to differ to a highly significant degree, with the frontal horns being possibly slightly more enlarged than the rest of the ventricular system. A prominent sex effect was also observed, with most of the increased ventricular size occurring in the male patients. Within the male patients, the thalamus was also observed to be significantly smaller, a finding that could be consistent with periventricular injury. Patients with prominent negative symptoms had significantly larger ventricular size than did those with the mixed or positive subtypes. Because of its superior resolution, magnetic resonance imaging appears to offer a more sensitive index of ventricular enlargement than that provided by computed tomography.

Two previous postmortem studies reported an increased thickness of the corpus callosum in schizophrenic patients compared to psychiatric controls. We report an in vivo study of the corpus callosum in schizophrenic patients (n = 38) and healthy controls (n = 41) using magnetic resonance (MR) brain imaging. A significant increase in mean callosal thickness was found in the middle and anterior, but not the posterior, parts of the callosal body. However, when the patients and controls were compared by gender and handedness, schizophrenic men were found not to differ from control men in callosal thickness, regardless of handedness, whereas schizophrenic women were found to have a highly significant increase in callosal middle and anterior thickness compared to control women. The data suggest that increased callosal thickness in schizophrenia is gender related, a factor that is not considered by postmortem studies. The implications of increased callosal dimensions in female schizophrenics are discussed.

New methods are proposed and described to examine the quality of gamma camera collimators in two special performance categories, namely, uniformity in regional efficiency and regional variations in channel tilt. These two performances are critical areas for SPECT imaging. Results obtained from experimental and commercial collimators illustrate the variability seen for these performance characteristics in currently available collimators.

The quantitative relationship between abnormalities seen on technetium-99m pyrophosphate (99mTc-PYP) infarct scintigrams and the size of the myocardial infarction is unclear. We evaluated two possible determinants of 99mTc-PYP accumulation: myocardial perfusion measured with 7-10 mu microspheres and the extent of necrosis determined histologically. Hemodynamics and myocardial perfusion to small segments of the left ventricle were measured prior to, 5-10 min, and 44-48 hours following sudden occlusion of the left anterior descending coronary artery in ten awake dogs. 99mTc-PYP was injected i.v. following the third injection of microspheres and the animals were killed 2 hours later. The important findings were as follows: 1) there is a close relationship between the extent of myocardial necrosis observed and the perfusion of segments 5-10 min following coronary occlusion; and 2) that segmental myocardial perfusion is an important determinant of 99mTc-PYP accumulation by myocardial segments which contain areas of necrosis. Although the present data preclude statistical analysis of the relationship between the level of necrosis in a segment and the accumulation of 99mTc-PYP by that segment, the two do not appear to be related, a finding which would discourage use of intensity of 99mTc-PYP images for infarct size. The distribution of an abnormality on the scintigram may provide an estimate of infarct size. However, the geometry of the infarct and the resolving power of the scanning equipment will significantly limit this in many clinical situations.

When an abrupt, fixed increase in afterload induces hypertrophy, the myocardium exhibits normal pump function in vivo, depressed muscle function in vitro, and paradoxically increased oxygen consumption. Such abnormalities may be either a transient response to a reversible myocardial injury or instead may be a persistent characteristic of hypertrophy contributing to eventual heart failure. To distinguish between these alternatives, we developed a model of chronic progressive pressure overload. Kittens had either a sham operation or pulmonary banding for 25 (group I) or 60 (group II) weeks. Banding produced a gradually increasing pressure overload with growth, maximum at 16 weeks after operation. The ratio of right ventricular to body weight increase from 0.54 +/- 0.03 to 0.82 +/0.04 g/kg (P less than 0.01) in group I and from 0.50 +/- 0.03 to 0.72 +/- 0.03 (P less than 0.01) in group II. In vivo right ventricular pump function (cardiac output and ejection fraction) was normal in both groups. In vitro contractile function and metabolism were measured in papillary muscles from the same right ventricles. Both experimental groups showed marked contractile abnormalities: preloaded shortening velocity was reduced from 0.80 +/- 0.05 to 0.53 +/- 0.05 muscle length/sec (P less than 0.01) in group I and from 0.84 +/- 0.04 to 0.60 +/- 0.06 (P less than ).01) in group II. Maximum isometric active tension was reduced from 60 +/- 7 to 35 +/- 5 mN/mm2 (P less than 0.01) in group I and from 56 +/- 5 to 27 +/- 4 (P less than 0.01) in group II. Metabolism was normal in both experimental groups. Thus, under conditions relevant to the study of clinical cardiac hypertrophy that are unlikely to cause acute injury, hypertrophy produces persistently abnormal intrinsic contractile function

Alterations of left ventricular mass occur in a variety of congenital and acquired heart diseases. In vivo determination of left ventricular mass, using several different techniques, has been previously reported. Problems inherent in some previous methods include the use of ionizing radiation, complicated geometric assumptions and invasive techniques. We tested the ability of gated nuclear magnetic resonance imaging to determine in vivo left ventricular mass in animals. By studying both dogs (n = 9) and cats (n = 2) of various sizes, a broad range of left ventricular mass (7 to 133 g) was examined. With a 0.5 tesla superconducting nuclear magnetic resonance imaging system the left ventricle was imaged in the transaxial plane and multiple adjacent 10 mm thick slices were obtained. Endocardial and epicardial edges were manually traced in each computer-displayed image. The wall area of each image was determined by computer and the areas were summed and multiplied by the slice thickness and the specific gravity of muscle, providing calculated left ventricular mass. Calculated left ventricular mass was compared with actual postmortem left ventricular mass using linear regression analysis. An excellent relation between calculated and actual mass was found (r = 0.95; SEE = 13.1 g; regression equation: magnetic resonance mass = 0.95 X actual mass + 14.8 g). Intraobserver and interobserver reproducibility were also excellent (r = 0.99). Thus, gated nuclear magnetic resonance imaging can accurately determine in vivo left ventricular mass in anesthetized animals.

Imaging characteristics of 43 commercial gamma-ray collimators for rectillinear scanners are measured. The modulation transfer functions, plane sensitivity, full width at half maximum, depth-of-field, and focal length for each collimator are reported. The products of all five companies examined appear to represent the current state of the art.