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Biomedical subjects

S R Dager

Publications and source records attributed to S R Dager.

At least 37 records · Page 2Linked to original sources
PubMed1998

Functional MR spectroscopy of the brain.

Functional MR spectroscopy is a technique for measuring brain activation that is based on metabolic changes in MR spectroscopy-detectable metabolites. This article covers functional MR spectroscopy applications in visual stimulation, auditory stimulation, language activation, cerebral metabolic rate, water MR spectroscopy, and in psychiatric disorders. Functional MR spectroscopy offers the ability to measure changes in the brain during neuronal activation that may be a more direct measure of cellular activation than functional magnetic resonance imaging. MR spectroscopy-detectable chemicals that are currently of greatest interest for measuring brain activation are also discussed.

Acoustic Stimulation↗
PubMed1997

Single-voxel 1H-MRS investigation of brain metabolic changes during lactate-induced panic.

Intravenous sodium lactate infusion is a robust laboratory technique for eliciting panic in susceptible individuals. The objective for this study was to replicate previous work which found differential brain lactate rises among lactate-sensitive panic subjects relative to control subjects using single-voxel 1H-magnetic resonance spectroscopy (MRS). Single-voxel 1H-MRS was used to measure brain lactate changes in the insular cortex region among 13 panic disorder subjects and 10 healthy control subjects during the infusion. One panic subject prematurely terminated the study due to a panic response during lactate infusion. Data from two additional control subjects and one panic subject were lost due to technical problems. Four panic subjects were reinfused with lactate while panic-free under treatment with fluoxetine (20 mg/day). At the time of initial infusion, all subjects were medication-free for at least 1 month. Ten panic subjects, but no control subjects, panicked during lactate infusion. In comparison to control subjects, panic subjects demonstrated significantly greater and prolonged brain lactate rises in the insular cortex region. Three of four medicated panic subjects experienced blockage of panic symptoms during lactate reinfusion but all exhibited persistent excesses in brain lactate rise. Consistent with our prior observations, greater and prolonged lactate rises in the insular brain region occur during and following lactate infusion among panic subjects compared to control subjects. This differential brain metabolic response did not appear to normalize when a small subset of panic patients were reinfused following resolution of panic symptoms during treatment over 3-4 months with fluoxetine.

Adult↗
PubMed1997

In vivo measurement of regional brain metabolic response to hyperventilation using magnetic resonance: proton echo planar spectroscopic imaging (PEPSI).

A new rapid spectroscopic imaging technique with improved sensitivity and lipid suppression, referred to as Proton Echo Planar Spectroscopic Imaging (PEPSI), has been developed to measure the 2-dimensional distribution of brain lactate increases during hyperventilation on a conventional clinical scanner equipped with a head surface coil phased array. PEPSI images (nominal voxel size: 1.125 cm3) in five healthy subjects from an axial section approximately 20 mm inferior to the intercommissural line were obtained during an 8.5-min baseline period of normocapnia and during the final 8.5 min of a 10-min period of capnometry-controlled hyperventilation (end-tidal PCO2 of 20 mmHg). The lactate/N-acetyl aspartate signal increased significantly from baseline during hyperventilation for the insular cortex, temporal cortex, and occipital regions of both the right and left hemisphere, but not in the basal ganglia. Regional or hemispheric right-to-left differences were not found. The study extends previous work using single-voxel MR spectroscopy to dynamically study hyperventilation effects on brain metabolism.

Adult↗
PubMed1997

19F magnetic resonance spectroscopy investigation in vivo of acute and steady-state brain fluvoxamine levels in obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to investigate the pharmacokinetics of fluvoxamine in the human brain by using fluorine-19 magnetic resonance spectroscopy (19F MRS) and to assess the relationships among fluvoxamine brain levels, fluvoxamine plasma levels, and clinical efficacy. METHOD: Eight subjects with DSM-IV obsessive-compulsive disorder were entered into a prospective, open-label treatment trial of fluvoxamine. 19F MRS measurements of whole brain drug and metabolite concentrations and spin-lattice (T1) relaxation times were performed serially in seven subjects for up to 5 months. A psychiatric determination of clinical response and a blood sample for plasma fluvoxamine measurement were obtained at each 19F MRS session. RESULTS: The subjects achieved steady-state brain concentrations of fluvoxamine within 30 days after consistent daily dosing, as determined by stabilization of brain fluvoxamine concentrations. The mean brain-to-plasma ratio at steady state was 24 to 1. Brain fluvoxamine T1 values from 140 to 230 msec were observed. All but one subject experienced substantial improvement in symptoms. The one nonresponder exhibited several-fold higher plasma and brain fluvoxamine levels. CONCLUSIONS: Brain fluvoxamine levels were substantially higher than plasma levels. Steady-state brain levels correlated to plasma levels but not to dose. Systematic assessment of treatment response in relation to brain or plasma fluvoxamine level was not feasible because of the marked and rapid clinical response during open-label treatment. These data suggest that fluvoxamine attains brain steady-state levels substantially faster than fluoxetine, with corresponding clinical implications.

Adolescent↗
PubMed1997

Regional dynamic signal changes during controlled hyperventilation assessed with blood oxygen level-dependent functional MR imaging.

PURPOSE: To quantitate the amplitude changes and temporal dynamics of regional functional MR imaging signals during voluntary hyperventilation using blood oxygen level-dependent contrast echo-planar imaging. METHODS: Seven male subjects were studied during voluntary hyperventilation (PetCO2 = 20 mm Hg) regulated by capnometry. Measurements were made on multisection echo-planar MR images obtained with parameters of 1000/66 (repetition time/echo time), flip angle of 30 degrees, and voxel size of 3 x 3 x 5 mm3. Sensitivity of the functional MR imaging signal to changes in PetCO2, time delays in relation to PetCO2 changes, and time constants of functional MR imaging signal changes were assessed on a region-by-region basis. RESULTS: Within 20 seconds of starting hyperventilation, rapid and substantial decreases in the functional MR imaging signal (by as much as 10%) were measured in areas of gray matter, which were significantly greater than the modest changes observed in white matter. Regional-specific effects in areas of the frontal, occipital, and parietooccipital cortex were stronger than in subcortical regions or in the cerebellum. Signal decreases measured with functional MR imaging were significantly delayed with respect to the reduction in PetCO2. Apparent differences between regional time constants did not reach statistical significance. CONCLUSION: Regional and gray-white matter differences in functional MR imaging signal changes during controlled hyperventilation may reflect differences in metabolic activity, vascular regulation, and/or capillary density. When measuring brain activation with functional MR imaging, arterial PCO2 differences due to unregulated respiration may confound interpretation of activation-related functional MR imaging signal changes.

Adult↗
PubMed1995

Application of a novel fiber-optic biosensor in situ to investigate the metabolic effect of lactate infusion.

Recently developed biosensor technology, which allows near real-time measurement in situ of gas tension (pCO2 and pO2) and of pH, was applied to arterial blood, cerebrospinal fluid (CSF), and brain parenchyma during intravenous lactate infusion in monkeys. Comparison of simultaneous biosensor measurements and discrete arterial blood sampling for traditional blood gas analyses indicated a high level of correlation for pCO2, pO2, and pH. Arterial pO2 and pH values were significantly higher and pCO2 significantly lower than corresponding CSF and brain parenchyma values at baseline, during and following lactate infusion. There was a divergence between arterial and brain parenchyma pH and pO2 measurements. Lactate infusion was associated with progressive arterial pH rises, consistent with the production of a metabolic alkalosis. Cerebrospinal fluid pCO2 remained unchanged during and following lactate infusion. Brain parenchyma exhibited a complex pattern of response characterized by a trend for pO2 and pH to decrease during lactate infusion, which reversed following completion of the infusion. These observations are suggestive of a transient hypoxia from decreased cerebral blood flow and/or reduced oxyhemoglobin dissociation during lactate infusion, but verification of these results is required.

Animals↗
PubMed1995

Proton magnetic resonance spectroscopy investigation of hyperventilation in subjects with panic disorder and comparison subjects.

OBJECTIVE: The purpose of this study was to investigate differential effects of hyperventilation on brain lactate in patients with panic disorder and comparison subjects as a possible mechanism for explaining previous observations of an excess rise in brain lactate among panic disorder subjects during lactate infusion. METHOD: Seven treatment-responsive patients with panic disorder and seven healthy comparison subjects were studied with proton magnetic resonance spectroscopy to measure brain lactate during controlled, voluntary hyperventilation over a period of 20 minutes. Hyperventilation was regulated with the use of capnometry to maintain end-tidal PCO2 at approximately 20 mm Hg during the period of hyperventilation. Blood lactate was measured prior to and at the end of hyperventilation. RESULTS: At baseline the two groups had similar brain lactate levels. Panic disorder subjects exhibited significantly greater rises in brain lactate than comparison subjects in response to the same level of hyperventilation. Blood lactate levels before and after 20 minutes of hyperventilation were not significantly different between groups. CONCLUSIONS: Controlled hyperventilation increases brain lactate and does so disproportionately in subjects with panic disorder. This increase in brain lactate may result from decreased cerebral blood flow due to hypocapnia, and individuals with panic disorder may have greater sensitivity to this regulatory mechanism.

Adult↗
PubMed1994

Preliminary application of magnetic resonance spectroscopy to investigate lactate-induced panic.

OBJECTIVE: To characterize changes associated with lactate-induced panic, proton magnetic resonance spectroscopy (MRS) was used to measure brain lactate during intravenous infusion of 0.5-M sodium lactate in panic disorder patients and comparison subjects. METHOD: Eight panic disorder subjects, five medicated and three unmedicated, and eight healthy comparison subjects were studied at baseline, during lactate infusion (5 meq/kg over 20 minutes), and after infusion. Localized proton MRS was used to acquire averaged spectra every 5 minutes from a 27-ml sampling volume in the insular cortex and adjacent regions. Brain lactate levels, quantitatively estimated in relationship to N-acetyl aspartate, were compared to blood lactate levels. RESULTS: The procedure was generally well tolerated; one panic subject requested early termination before lactate infusion. Significant rises in brain lactate levels occurred for all subjects during infusion. The panic patients who responded to lactate (N = 3) had significantly higher brain lactate levels before, during, and after infusion than did the comparison subjects (N = 8) and medicated patients who were lactate nonresponders (N = 4). After infusion the panic patients with lactate-induced panic exhibited a striking dissociation between decreasing blood lactate and further increases in brain lactate levels. CONCLUSIONS: These preliminary observations indicate that brain lactate increases during a standard lactate infusion. Lactate-induced panic is associated with greater increases than in comparison subjects and with prolonged elevations in brain lactate that are decoupled from falling blood lactate levels after completion of lactate infusion. Further investigation is necessary to clarify the mechanism(s) responsible for these findings and establish whether a causal relationship to the occurrence of lactate-induced panic exists.

Adult↗
PubMed1993

Dawn simulation treatment of winter depression: a controlled study.

OBJECTIVE: This study sought to determine whether dawn simulation was superior to a shorter dimmer "placebo" dawn signal in treating winter depression. METHOD: In a randomized, parallel design, 22 patients with winter depression were treated with either 1 week of a 2-hour dawn simulation peaking at 250 lux or 1 week of a 30-minute dawn simulation peaking at 0.2 lux. The subjects were told that they would receive either a "gradual" dawn or a "rapid" dawn reaching an intensity that would be dimmer than standard bright light treatment. At the end of both the baseline week and the treatment week, subjects were assessed in a blind manner with the Hamilton Rating Scale for Depression. Analysis of covariance was used to compare the two dawn treatments. RESULTS: The 2-hour, 250-lux dawn simulation resulted in Hamilton depression scale scores that were significantly lower than scores after the 30-minute, 0.2-lux dawn simulation. CONCLUSIONS: This study indicates that dawn simulation is an effective treatment for winter depression.

Adult↗
PubMed1992

MRS detection of whole brain lactate rise during 1 M sodium lactate infusion in rats.

Proton magnetic resonance spectroscopy (1H MRS) performed in vivo on nine Sprague Dawley rats detected a threefold increase in whole brain lactate during intravenous 1 mol/L sodium lactate infusion. Significant increases in whole brain lactate were detected within 5 min after starting lactate infusion, progressively rose to a maximum level estimated at 3.2 +/- 1.5 mmol/L (all values +/- SD) immediately postinfusion, then decreased towards baseline levels during the next hr. Venous lactate concentration, increasing from 2.3 +/- 2.4 mmol/L to 43.0 +/- 8.0 mmol/L during the infusion, exhibited a steeper rise and then decreased more rapidly in comparison to changes in whole brain lactate. These data suggest MRS can be used in vivo to study acute changes in brain lactate associated with increasing blood lactate concentrations.

Animals↗
PubMed1992

Localized magnetic resonance spectroscopy measurement of brain lactate during intravenous lactate infusion in healthy volunteers.

Proton magnetic resonance spectroscopy (1H MRS) localized to the left temporal-parietal region in 8 healthy volunteers detected a 2.1-fold +/- 0.7-fold increase (all values +/-SD) in brain lactate during intravenous infusion of 0.5 molar (M) sodium lactate (5 meq/kg over 20 minutes). Significant increases in brain lactate occurred within 5-10 minutes after starting lactate infusion, progressively rose during the infusion, then decreased towards baseline levels during 30 minutes post-infusion. Venous lactate concentration increased from 0.8 +/- 0.2 mM to 10.9 +/- 4.1 mM or 13.6-fold during the infusion. Flow phantom findings in vitro suggest attenuation of 1H MRS blood lactate signal from arteries and veins as a result of flow velocity effects. Correlations between paired blood and brain lactate measurements at each sampling time indicate a non-linear relationship between compartments during lactate infusion.

Adult↗
PubMed1992

Applications of magnetic resonance spectroscopy to the investigation of neuropsychiatric disorders.

Magnetic resonance spectroscopy (MRS) can noninvasively characterize tissue composition and metabolism in vivo without the need for radioactive isotope administration. For the neuropsychiatrist interested in the functional basis of disease, MRS offers an investigative tool capable of studying a wide variety of neuropsychiatric disorders. This report provides an overview of how MRS works, current and potential clinical applications for specific psychiatric populations, and limitations of the technology.

Brain Chemistry↗
PubMed1991

Lactate vulnerability after alprazolam versus placebo treatment of panic disorder.

Thirty-six patients with panic disorder underwent sodium lactate infusion before and after 8 weeks of treatment with alprazolam or placebo. With reinfusion, those patients panic-free with chronic alprazolam treatment displayed significantly decreased reactivity to lactate, as measured by subjective symptom ratings, duration of infusion before developing peak lactate-induced symptoms, and the proportion of patients experiencing lactate-induced anxiety or panic. Patients panic-free on placebo, as well as nonresponders to alprazolam treatment, displayed some, although less striking, decreases in reactivity to lactate with reinfusion. As a group, patients clinically unchanged with placebo treatment showed no systematic change in lactate response with reinfusion. Although the small numbers of patients in each treatment outcome group prohibit drawing definitive conclusions, these findings suggest that decreases in lactate-induced panic after successful alprazolam treatment of panic may result from a combination of changes in clinical state and direct effects of the medication.

Adult↗
PubMed1991

Morning or evening bright light treatment of winter depression? The significance of hypersomnia.

In a randomized crossover design 19 patients with winter depression were treated with 7 days of bright morning light (6:00 to 8:00 AM) and 7 days of evening light (7:00 to 9:00 PM). Bright light in the morning reduced the Hamilton Depression Rating Scale score from 22.3 to 5.5; bright light in the evening decreased the Hamilton score from 21.0 to 12.2. Improvement in the depression as measured by the Hamilton Depression Rating scores was greater with morning light compared with evening lights. Hypersomnia was associated (p less than 0.05) with a superior response to morning light.

Adult↗
PubMed1991

Chronicity of depressive episode in relation to antidepressant-placebo response.

Pooled data from three 6-week placebo-controlled, double-blind, phase III clinical trials, designed to assess the efficacy of newer antidepressants, were retrospectively analyzed to study the relationship between chronicity of presenting depressive episode and response to placebo, imipramine, and adinazolam. One hundred forty-six depressed outpatients met criteria for inclusion into this study; 80 received placebo treatment, 27 imipramine and 39 adinazolam treatment. Consistent with our hypothesis the response to placebo was low in subjects who were depressed for 1 year or longer (22.6%) as compared to a higher response rate (44.9%) among those who were not as chronically depressed. The response to imipramine and adinazolam was not related to the duration of presenting depressive episode. The implications of these findings are discussed.

Adult↗