James C. Ehrhardt

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.

A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia

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.

Correlation between echocardiographically demonstrated segmental dyskinesis and regional myocardial perfusion.

In order to evaluate the relationship between regional myocardial perfusion and segmental dyskinesis, 22 open chest dogs were studied using ultrasound to register cardiac wall motion and radioactive labeled microspheres to determine myocardial perfusion. In six dogs, motion and perfusion were correlated at two levels of partial circumflex coronary artery occlusion followed by complete occlusion. A good correlation between declining myocardial perfusion of all the ischemic segments and development of aneurysmal bulging (during isometric contraction) was seen: r = -0.80. A similar correlation between myocardial perfusion and endocardial wall velocity (during systolic ejection) was observed: r = 0.92. In nine dogs, the effect of 45 minutes of complete coronary occlusion followed by 30 minutes of reperfusion was evaluated with respect to perfusion and motion. After coronary reperfusion myocardial perfusion of the ischemic area returned to control levels (from 32.6 ± 3.5 to 130.3 ± 13.3 ml/100 g/min), but aneurysmal bulging during isometric contraction persisted. Endocardial wall velocity during systolic ejection showed a variable response to reperfusion, achieving values ranging from 32% to 162% of the preocclusion levels. In seven dogs the ultrasound beam was reflected off nonischemic myocardium adjacent to areas of ischemia resulting from coronary occlusion. Despite preservation of normal myocardial perfusion in these nonischemic areas wall motion abnormalities were evident: endocardial wall velocity declined from 25.8 ± 5.8 to 14.0 ± 4.9 mm/sec (P < 0.01), and aneurysmal bulging developed in three animals. These changes may be due to transient undetected ischemia in the segments struck by the ultrasound beam, or to passive alteration of the motion of the normally perfused areas by the severe dyskinesis of the adjacent ischemic myocardium.

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.

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 subjects MRI. Sex differences were detected in several global volume measures.

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.

Regulation of total and regional spinal cord blood flow.

SUMMARY Studies of the regulation of total spinal cord blood flow have been limited by methodology. Total flow has been difficult to measure and flow to the gray and white matter within the cord has not been previously assessed. We have used labeled microspheres to measure blood flow in the spinal cord. Our purpose was to examine the effects of several physiological stimuli on the regulation of blood flow to different regions of the spinal cord (cervical, thoracic, and lumbosacral) and to different tissue in the cord (gray and white matter). The four types of stimuli examined were: chemical stimulation (alterations in systemic blood gases); autoregulation (increases in systemic pressure); neurogenic stimulation (activation of chemo- and baroreceptor reflexes); and metabolic stimulation (activation of spinal cord neurons). Studies were performed in dogs, sheep, and lambs; cerebral flow and spinal cord flow were measured simultaneously. Mean blood flow to the cervical and lumbosacral cord segments was 40% higher than flow to the thoracic cord. Under control conditions gray and white matter flows to the lumbosacral cord of sheep were 110 ± 15 (mean ± SE) and 25 ± 6 ml/min per 100 g, respectively. Chemical stimulation markedly altered spinal cord blood flow (hypoxia and hypercapnia increased flow; hypocapnia decreased flow), and distribution of flow to gray and white matter was unchanged. Autoregulation maintained total and regional spinal cord flow constant during increases in systemic pressure. Neurogenic stimulation did not alter the tone of spinal cord blood vessels. Metabolic stimulation selectively increased blood flow to gray matter of the stimulated region. Regulation of total and regional spinal cord blood flow generally parallels that of the brain; chemical, autoregulatory, and metabolic factors are important determinants in the control of spinal cord blood flow.

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.

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.

Limitations of thallium-201 myocardial perfusion scintigrams.

SUMMARY The reliability of myocardial perfusion scintigrams with thallium-201 (201TI) for detecting areas of hypoperfusion was assessed in 16 closed-chest dogs. Variable areas of ischemia were produced either by occluding or stenosing the left anterior descending coronary artery. Cardiac scintigrams taken in four projections were compared with regional myocardial perfusion maps. Segmental concentrations and segmental perfusions were quantitated by counting the emissions from 201TI and the microspheres in each of 96 segments of the left ventricle. In addition, studies with a phantom were performed. The results indicate: 1) The emissions from 201TI and from microspheres correlated well in ischemic segments (r = 0.93 ± SE 0.02). 2) Seven of twelve ischemic hearts had definitely abnormal scintigrams and in each of these the hypoperfused zone was greater than 4.9 grams and perfusion was decreased by more than 45%. 3) In the phantom, abnormal scintigrams could be detected in the presence of lesser deficits than in the dogs. The limitation of the thallium perfusion scintigrams will be the inconsistent detection of small perfusion deficits.