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Biomedical subjects

D Cardwell

Publications and source records attributed to D Cardwell.

9 recordsLinked to original sources

Effects of gender and region on proton MRS of normal human brain.

Localized, in vivo 1H magnetic resonance spectroscopy has been performed in a number of brain regions of neuropsychiatric interest in male and female control subjects to determine if gender and region affect the measured metabolite ratios. In contrast to some previous reports, no significant differences were seen in any region for any metabolite ratio between males and females. As expected, significant variations with brain region were seen for metabolite ratios for the total group of subjects.

Adult↗

Regional proton magnetic resonance spectroscopy in schizophrenia and exploration of drug effect.

Schizophrenia is a disorder with an unclear pathophysiology, despite numerous attempts to elucidate its etiology. We have employed proton magnetic resonance spectroscopy in vivo to explore the neurochemistry of several brain regions (left frontal and temporal cortices, left basal ganglia, and left and right thalamus) in patients with schizophrenia and in normal control subjects. We have also examined patients in different medication states. A trend toward a decreased level of inositol/creatine was found in the left temporal lobe of patients with schizophrenia, as was a trend toward a reduced level of N-acetylaspartate/creatine in the left thalamus of patients. In schizophrenic patients treated with atypical antipsychotics, decreased levels of choline were found in the left basal ganglia, while increased levels of N-acetylaspartate were found in the left frontal cortex. These results suggest altered metabolism in patients with schizophrenia, and imply that further study is needed to clarify the effects of the more recently available antipsychotics.

Adult↗

In vivo proton magnetic resonance spectroscopy of the medial temporal lobes of subjects with combat-related posttraumatic stress disorder.

Recent findings using volumetric MRI techniques have revealed that patients with combat-related and noncombat-related posttraumatic stress disorder (PTSD) have reductions in right hippocampal volume. Twenty-one veterans with PTSD and eight age-matched control veterans were studied using proton magnetic resonance spectroscopy to test the hypothesis that the N-acetyl-L-aspartic acid/creatine (NAA/Cr) ratio would be decreased in the right medial temporal lobe structures of patients with PTSD compared to controls. Patients with PTSD displayed significantly lower NAA/Cr ratio for the right medial temporal lobe relative to the left (P < or = 0.011). Patients with PTSD also had lower NAA/Cr in right medial temporal lobe (P < or = 0.013) and lower choline/Cr in left medial temporal lobe (P < or = 0.030) compared to control subjects. Because NAA is regarded as an indicator of neuronal density, this finding suggests that the neuronal density of right-sided medial temporal structures in patients with combat-related PTSD may be decreased.

Adult↗

In vivo 19F spin relaxation and localized spectroscopy of fluoxetine in human brain.

Fluorine-19 NMR spectroscopy was used to monitor the anti-depressant drug fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a signal from the head 2 to 4 times stronger than for surface coils. It was used to measure the in vivo 19F spin-lattice relaxation time (T1) of fluoxetine for five patients by the inversion-recovery technique. The individual T1s varied from 149 to 386 ms, which was attributed in part to interindividual differences based on the reproducibility of a phantom T1. The individual T1 correlated weakly with approximate brain concentration. A lower limit of 3 to 4 ms was found for the spin-spin relaxation time from line width measurements. Low resolution 4-dimensional spectroscopic imaging confirmed that the single in vivo 19F resonance for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for 19 weeks was comparable with that seen for patients in vivo. The in vivo signal arose about equally from fluoxetine and the active metabolite norfluoxetine, as demonstrated by the in vitro 19F NMR spectrum of the lipophilic extract of a small section of brain. In vitro quantitation of frozen samples from three brain regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6 micrograms/ml, which is higher than typically determined in vivo, and suggests that the fluorinated drugs may not be 100% visible in vivo.

Adolescent↗

In vivo 7Li nuclear magnetic resonance study of lithium pharmacokinetics and chemical shift imaging in psychiatric patients.

New data are presented on the application of 7Li in vivo nuclear magnetic resonance (NMR) spectroscopy to human studies. The technique was used to monitor the between-dose pharmacokinetics of lithium (Li) in brain for three patients on Li therapy. Brain Li concentrations were at their highest from 0 to 2 hours after the peak occurred in serum concentration. Elimination from brain tissue took longer than elimination from muscle, and no signal could be detected from brain at 10 days after termination of therapy. A birdcage radiofrequency coil for 7Li was constructed and used to measure the 7Li spin-lattice relaxation time of 4.6 seconds in vivo in human head, and to acquire preliminary spectroscopic images of a phantom and human brain.

Blood-Brain Barrier↗

In vivo 7Li NMR imaging and localized spectroscopy of rat brain.

Lithium-7 in vivo NMR spectroscopy and imaging techniques have been developed at 4.7 T for rat head. The pharmacokinetics of lithium (Li) uptake in rat head has been measured using STEAM localized spectroscopy for the whole brain, which showed relatively rapid uptake of Li and a steady level of Li from about 5 to 20 h. Localized spectroscopy on brain sections revealed no differences in Li concentration among the front, middle, and rear of the brain. The spin-lattice relaxation time showed a single exponential decay for the head. The spin-spin relaxation time for head showed a biexponential behavior. Using a 1H-7Li double coil assembly, 7Li images were generated for rat head, as was the corresponding 1H image for anatomic localization. The 7Li image (7-mm slice thickness, 4-mm in-plane resolution) recorded after the last dose in a multiple ip dose protocol shows the Li distribution in the head and neck. Based on 7Li images, the Li level in muscle was about twice that in the brain. Variations of 7Li intensity level across the brain were typically small.

Animals↗

In vivo NMR spectroscopy of lithium-7 in humans.

The pharmacokinetics of lithium uptake was measured by 7Li NMR spectroscopy at 24.83 MHz in vivo in the brain and muscle of a normal subject and a patient suffering from bipolar affective disorder, using a modified General Electric Signa clinical magnetic resonance imaging system. Comparison was made to standard phantoms to estimate Li concentrations. The levels of Li in brain and muscle were similar, were typically less than the level in serum, and generally tracked the level in serum. The Li level at steady state in the brain of a patient suffering from schizoaffective disorder was measured over a 7-month period. Substantial variation was seen, which showed some correlation with serum level. Serum level peaked about 2 h after a single 300-mg dose at steady state, and muscle level, immediately thereafter. Brain level peaked considerably later at 4 h. Localized in vivo 7Li NMR spectroscopy was demonstrated by acquisition of a 125-cm3 DRESS slice from the occipital region in less than 7 min.

Adult↗