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Biomedical subjects

J C Ehrhardt

Publications and source records attributed to J C Ehrhardt.

At least 19 recordsLinked to original sources

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.

Adenocarcinoma

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.

Adenocarcinoma

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.

Adult

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.

Adult

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.

Adenocarcinoma

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.

Adult

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.

Brain Diseases

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.

Adult

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.

Adult

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.

Adult

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.

Brain

Evaluating and validating two methods for estimating brain structure volumes: tessellation and simple pixel counting.

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.

Adult

Cost-effectiveness of high-dose MR contrast studies in the evaluation of brain metastases.

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.

Adult

Subcortical and temporal structures in affective disorder and schizophrenia: a magnetic resonance imaging study.

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.

Adult

T1 and T2 relaxation times in schizophrenia as measured with magnetic resonance imaging.

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.

Adult

Automated identification of left ventricular borders from spin-echo magnetic resonance images. Experimental and clinical feasibility studies.

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.

Animals

MR evaluation of CNS tumors: dose comparison study with gadopentetate dimeglumine and gadoteridol.

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.

Adult