Michael W. Hanson

Mental Stress–Induced Ischemia in the Laboratory and Ambulatory Ischemia During Daily Life Association and Hemodynamic Features

BACKGROUND The purpose of this study was to determine the correspondence of mental stress-induced ischemia in the laboratory with ambulatory ischemia and to assess the relationship between hemodynamic responses to mental stress and the occurrence of ischemia. Although exercise testing is usually used to elicit myocardial ischemia, ischemia during daily life usually occurs at relatively low heart rates and in the absence of strenuous physical exercise. Mental stress has been shown to trigger ischemic events in the laboratory at lower heart rates but at blood pressures comparable to exercise. We therefore compared the extent to which mental stress and exercise testing identify patients who develop ischemia out of hospital. METHODS AND RESULTS One hundred thirty-two patients with documented coronary disease and recent evidence of exercise-induced myocardial ischemia underwent 48-hour ambulatory monitoring and radionuclide ventriculography during exercise and mental stress testing. Patients who displayed mental stress-induced ischemia in the laboratory were more likely to exhibit ischemia during daily life (P < .021). Furthermore, patients who exhibited ischemia during ambulatory monitoring displayed larger diastolic blood pressure (P < .006), heart rate (P < .039), and rate-pressure product responses (P < .018) during mental stress. CONCLUSIONS Among patients with prior positive exercise stress tests, mental stress-induced ischemia, defined by new wall motion abnormalities, predicts daily ischemia independent of exercise-induced ischemia. Exaggerated hemodynamic responses during mental stress testing also identify individuals who are more likely to exhibit myocardial ischemia during daily life and mental stress.

Serial FDG-PET studies in the prediction of survival in patients with primary brain tumors

Objective This study examines the changes in tumor [18F]fluoro-2-deoxyglucose (FDG) uptake on serial FDG-PET studies and the ability of serial FDG-PET studies to predict survival in patients with treated and untreated primary brain tumors. Materials and Methods The study population included 20 patients with primary brain tumors. Changes in FDG uptake over time were visually assessed and correlated with clinical course and survival. Results Although little change in FDG uptake was noted for individual patients, high average FDG uptake (greater than or equal to gray matter) on serial studies was associated with shorter survival. Patients with persistently low FDG uptake (less than gray matter) survived significantly longer than patients with persistently high FDG uptake (p = 0.007). Conclusion Serial evaluation of metabolic activity with PET may provide more accurate prognostic information than a single FDG uptake determination in patients with primary brain tumors.

FDG-PET in the selection of brain lesions for biopsy.

The CT-guided stereotaxic needle biopsy has become a widely used procedure in the diagnostic evaluation of intracranial lesions including tumors. Conventional CT or MR frequently defines the anatomic regions of abnormality, which may be multiple lesions or a single lesion that is heterogeneous in cellular composition owing to the topographic variation of cellular constituency or the combination of active disease, nonspecific inflammation, necrosis, and/or edema. In these cases, selection of the most appropriate site for a successful diagnostic needle biopsy can be difficult. In three patients, we have used [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to determine the site most likely to provide a diagnostic biopsy result. In the first patient, who presented with confusion, multiple biopsies from the temporal lobe, based on MR abnormalities, revealed only reactive gliosis and edema. Repeat biopsy directed by PET revealed an anaplastic astrocytoma. In a second patient, PET allowed us to differentiate radiation effect from active metastatic breast cancer. In the third patient, who presented with a grand mal seizure, biopsy of a CT-defined hypodense region demonstrated lymphocytosis. Metabolism of FDG was normal or increased in areas of Aspergillus encephalitis at autopsy. These preliminary studies suggest a complementary role for FDG-PET and CT or MR in selected patients for defining the intracranial site most likely to yield a positive biopsy result.

Estimation of myocardial blood flow for longitudinal studies with 13N-labeled ammonia and positron emission tomography

BackgroundAlthough several modeling strategies have been developed and validated for quantification of myocardial blood flow (MBF) from 13N-labeled ammonia positron emission tomographic data, a comparison of noise characteristics of the various techniques in serial studies is lacking.Methods and ResultsDynamic 13N-labeled ammonia positron emission tomographic imaging was performed at baseline and after pharmacologic stress in (1) single studies of four dogs with concomitant measurement of microsphere blood flow and (2) initial and follow-up studies of eight normal volunteers. Data were obtained from short-axis images for the blood pool and myocardial regions corresponding to the three arterial vascular territories. Indexes of MBF were obtained by four distinct techniques: (1) University of California, Los Angeles, twocompartment model, (2) Michigan two-compartment model, and (3) a one-compartment model with variable blood volume term. Coronary flow reserve (CFR) was measured as the ratio of stress/rest MBF. The estimated standard deviation of the measurement error for the relative change between studies of rest and stress MBF and CFR was determined for each technique. Estimates of MBF from all techniques showed good correlation with microsphere blood flow (r=0.95 to 0.96) in canine myocardium. In human studies, similar mean estimates of MBF were found with all techniques. Techniques 1 and 3 showed the smallest interstudy variability in MBF and CFR. The estimated standard deviations for these techniques were approximately 20%, 30%, and 27% for rest MBF, stress MBF, and CFR, respectively.ConclusionNoninvasive quantification of MBF and CFR from dynamic 13N-labeled ammonia positron emission tomography is most reproducible with technique 1 or 3. The ability to account for differences in myocardial partial volume gives preference to technique 3. However, substantial interstudy variability in regional MBF remains, suggesting the importance of procedural factors or real temporal fluctuations in MBF.

Correlation of Hippocampal Neuronal Density and FDG-PET in Mesial Temporal Lobe Epilepsy

Summary: Purpose: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) reveals regional hypometabolism in 60–80% of patients with mesial temporal lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the epileptogenic zone. The pathophysiology underlying this widespread change is unknown. This study evaluated the relation between hippocampal neuronal loss and hypometabolism in patients with MTLE.

FDG-PET in pediatric posterior fossa brain tumors

Seventeen pediatric patients with posterior fossa brain tumors were studied with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET). The FDG uptake was ranked by two observers, and the results were correlated with tumor histology. Increased FDG uptake was associated with more malignant and aggressive tumor types. Heterogeneity of FDG uptake was associated with previous therapy, including radiation therapy and chemotherapy. 2-[18F]Fluoro-2-deoxy-D-glucose PET will likely be an important adjunct in the management of pediatric posterior fossa tumors, much as in adult patients with brain tumors.

Depression and increased myocardial ischemic activity in patients with ischemic heart disease.

BACKGROUND Depression is relatively common in patients with ischemic heart disease (IHD) and is associated with increased risk of mortality and morbidity. However, the mechanisms by which depression adversely affects clinical outcomes of patients with IHD are unknown. This study examined the relationship between depression and myocardial ischemia during mental stress testing and during daily living in patients with stable IHD.Methods and results The Center for Epidemiological Studies-Depression scale (CES-D) was administered to 135 patients with IHD to evaluate depressive symptoms. Radionuclide ventriculography was used to evaluate the occurrence of left ventricular wall motion abnormality (WMA) during mental stress and exercise testing. Forty-eight-hour ambulatory electrocardiography was used to assess myocardial ischemia during daily living. The mean CES-D score was 8.2 (SD 7.4, range 0-47) with a median of 7. Logistic regression models using restricted cubic splines revealed a curvilinear relation among CES-D scores and the probability of ischemia. For patients with CES-D scores <or=19 (81.5% of study population), a 5-point increment in the CES-D score was associated with roughly a 2-fold increase in the likelihood of ischemia during mental stress. For patients with CES-D scores >19, the relation among scores and ischemia during mental stress tended to be inversely related, but the portion of the sample is very small. Similar patterns of results were noted for CES-D scores and ischemia during daily life. CONCLUSIONS Patients with mild to moderate depressive symptoms (CES-D scores <or=19) are more likely to exhibit myocardial ischemia during mental stress testing and during daily living. Myocardial ischemia may be one mechanism by which depression increases the risk of mortality and morbidity in patients with IHD. The observed inverse association between higher level of depressive symptoms and ischemic activity needs to be further assessed in large samples.

Neuroimaging in Infantile Autism

Metabolic findings using [18F]fluorodeoxyglucose (FDG) with positron emission tomography (PET) and correlative anatomic findings with computed tomography (CT) or magnetic resonance imaging (MRI) were characterized in 13 children with infantile autism. Four of 13 patients had both an abnormal FDG-PET and an abnormal MRI, whereas seven of 13 patients had both a normal FDG-PET and a normal CT or MRI. Sixteen of a total of 195 brain areas qualitatively examined with FDG-PET had a hypometabolic abnormality on PET. Three of the five abnormal structural imaging studies revealed neuronal migrational anomalies (focal pachygyria). In two of the five patients with anatomic abnormalities, these were noted only after knowledge of the FDG-PET findings. Our experience reveals that anatomic and metabolic abnormalities can be found in children who exhibit autistic behavior. An FDG-PET study may provide evidence of metabolic dysfunction after an initially unremarkable MRI scan because subtle anatomic abnormalities (as those seen with neuronal migrational anomalies) may be found only after knowledge of a regional metabolic abnormality. (J Child Neurol 1994;9:155-161).

Linkages between facial expressions of anger and transient myocardial ischemia in men with coronary artery disease.

The authors examined whether facial expressions of emotion would predict changes in heart function. One hundred fifteen male patients with coronary artery disease underwent the Type A Structured Interview, during which time measures of transient myocardial ischemia (wall motion abnormality and left ventricular ejection fraction) were obtained. Facial behavior exhibited during the ischemia measurement period was videotaped and later coded by using the Facial Action Coding System (P. Ekman & W. V. Friesen, 1978). Those participants who exhibited ischemia showed significantly more anger expressions and nonenjoyment smiles than nonischemics. Cook-Medley Hostility scores did not vary with ischemic status. The findings have implications for understanding how anger and hostility differentially influence coronary heart disease risk.

18‐FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IN CHILDREN AND ADOLESCENTS WITH TRAUMATIC BRAIN INJURY

Twenty‐two previously normal children and adolescents who suffered a severe, non‐penetrating traumatic brain injury had PET during rehabilitation at a median of 1–5 months after the injury. Outcome was assessed at a median of 25 months after brain injury. 16 subjects had CT or MRI within 24 days of PET and 11 subjects had a second PET at the point of outcome (median 28 months after first PET). The PET score (obtained by adding the score of 15 brain regions: normal metabolism = 1; reduced = 0) was significantly associated with the clinical outcome measure. PET earlier than 12 weeks after head trauma correlated with outcome, but later PET did not. PET scores improved significantly between rehabilitation and outcome for the 11 subjects who had two PETs, but improvement was not associated with improvement in clinical condition. PET score did not add to the amount of variance explained in the last regression model for prediction of outcome when the results of contemporaneous CT/MRI and clinical condition were taken into account. The data suggest that routine PET during rehabilitation is no more useful than contemporaneous CT or MRI for prediction of outcome.