An in vivo study of phosphorus and glucose metabolism in Alzheimer's disease using magnetic resonance spectroscopy and PET.

OBJECTIVES: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls. DESIGN: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism. PATIENTS: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls. RESULTS: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism. CONCLUSIONS: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections.

Inductively coupled wireless RF coil arrays.

As the number of coils increases in multi-channel MRI receiver-coil arrays, RF cables and connectors become increasingly bulky and heavy, degrading patient comfort and slowing workflow. Inductive coupling of signals provides an attractive "wireless" approach, with the potential to reduce coil weight and cost while simplifying patient setup. In this work, multi-channel inductively coupled anterior arrays were developed and characterized for 1.5T imaging. These comprised MR receiver coils inductively (or "wirelessly") linked to secondary or "sniffer" coils whose outputs were transmitted via preamps to the MR system cabinet. The induced currents in the imaging coils were blocked by passive diode circuits during RF transmit. The imaging arrays were totally passive, obviating the need to deliver power to the coils, and providing lightweight, untethered signal reception with easily positioned coils. Single-shot fast spin echo images were acquired from 5 volunteers using a 7-element inductively coupled coil array and a conventionally cabled 7-element coil array of identical geometry, with the inductively-coupled array showing a relative signal-to-noise ratio of 0.86 +/- 0.07. The concept was extended to a larger 9-element coil array to demonstrate the effect of coil element size on signal transfer and RF-transmit blocking.

Chronic toxicity/oncogenicity study of styrene in CD rats by inhalation exposure for 104 weeks.

Groups of 70 male and 70 female Charles River CD (Sprague-Dawley-derived) rats were exposed whole body to styrene vapor at 0, 50, 200, 500, or 1000 ppm 6 h/day 5 days/week for 104 weeks. The rats were observed daily, body weights and food and water consumption were measured periodically, and a battery of hematologic and clinical pathology examinations was conducted at weeks 13, 26, 52, 78, and 104. Nine or 10 rats per sex per group were necropsied after 52 weeks of exposure and the remaining survivors were necropsied after 104 weeks. Control and high-exposure rats received a complete histopathologic examination, while target organs, gross lesions, and all masses were examined in the lower exposure groups. Styrene had no effect on survival in males, but females exposed to 500 or 1000 ppm had a dose-related increase in survival. Levels of styrene in the blood at the end of a 6-h exposure during week 95 were proportional to exposure concentration. Levels of styrene oxide in the blood of rats exposed to 200 ppm or greater styrene were proportional to styrene exposure concentration. There were no changes of toxicologic significance in hematology, clinical chemistry, urinalysis, or organ weights. Males exposed to 500 or 1000 ppm gained less weight than the controls during the first year and maintained the difference during the second year. Females exposed to 200, 500, or 1000 ppm gained less weight during the first year; those exposed to 500 or 1000 ppm continued to gain less during months 13-18. Styrene-related non-neoplastic histopathologic changes were confined to the olfactory epithelium of the nasal mucosa. There was no evidence that styrene exposure caused treatment-related increases of any tumor type in males or females or in the number of tumor-bearing rats in the exposed groups compared to controls. In females, there were treatment-related decreases in pituitary adenomas and mammary adenocarcinomas. Based on an overall evaluation of eight oncogenicity studies, there is clear evidence that styrene does not induce cancer in rats.

Orbital magnetic resonance imaging.

Magnetic resonance images of the eye and orbit performed with surface coils at 1.5 tesla showed anatomic details superior to those of conventional third- and fourth-generation computed tomography.

A review of 1H nuclear magnetic resonance relaxation in pathology: are T1 and T2 diagnostic?

The longitudinal (T1) and transverse (T2) proton (1H) nuclear magnetic resonance (NMR) relaxation times of pathological human and animal tissues in the frequency range 1-100 MHz are archived, reviewed, and analyzed as a function of tissue of origin, NMR frequency, temperature, species, and in vivo versus in vitro status. T1 data from specific disease states of the bone, brain, breast, kidney, liver, muscle, pancreas, and spleen can be characterized by simple dispersions of the form T1 = AvB in the range 1-100 MHz with A and B empirically determined pathology-dependent constants. Pathological tissue T2 values are essentially independent of NMR frequency. Raw relaxation data, best-fit T1 parameters A and B, and the mean T2 values, are tabulated along with standard deviations and sample size to establish the normal range of pathological tissue relaxation times applicable to NMR imaging or in vitro NMR examination. Statistical analysis of relaxation data, assumed independent, reveals that most tumor and edematous tissue T1 values and some breast, liver, and muscle tumor T2 values are significantly elevated (p greater than or equal to 0.95) relative to normal, but do not differ significantly from other tumors and pathologies. Statistically significant abnormalities in the T1 values of some brain, breast, and lung tumors, and most pathological tissue T2 values could not, however, be demonstrated in the presence of large statistical errors. Both T1 and T2 in uninvolved tissue from tumor-bearing animals or organs do not demonstrate statistically significant differences from normal when considered as a group, suggesting no appreciable systemic effects associated with the presence of tumors compared to the statistical uncertainty. Statistical prediction analysis for both T1 and T2 indicates that of all the tissues studied, only liver hepatoma can be reliably distinguished from normal liver based on a single T1 measurement (p greater than or equal to 0.95) given the scatter in the current published data. Indeed, data scatter, not easily attributable to temperature, species, in vivo versus in vitro status, the inclusion of implanted or chemical induced tumors, or the possible existence of multiple component relaxation, is recognized as the major factor inhibiting the diagnostic utility of quantitative NMR relaxation measurements. Malignancy indexes that combine T1 and T2 data as a diagnostic indicator suffer similar problems of uncertainty. The literature review reveals a dearth of information on the temperature and frequency dependence of pathological tissue relaxation and the possible existence of multiple relaxation components.(ABSTRACT TRUNCATED AT 400 WORDS)

Methacholine: a 7-day inhalation toxicity study with primates.

The acute and sub-acute inhalation toxicity of methacholine to cynomolgus monkeys was assessed by exposure of animals to an aerosol of a 2% solution of the material in sterile saline. The acute response was characterized by a decrease in tidal volume, increase in respiratory rate, a fall in dynamic compliance and an increased pulmonary resistance. Onset of the acute response was rapid, reached a peak after 2-3 min of exposure and recovery appeared to be complete after 30 min following termination of an exposure. The sub-acute inhalation toxicity of methacholine was assessed by single daily aerosol exposure of primates to graded doses of the compound for 7 days. Pre- and post-exposure measurements of haematology and blood biochemistry, urinalysis, blood gas analysis and ECG showed no changes which could be attributed to exposure to methacholine. Nor were treatment-related histopathological changes observed in exposed animals. Distinct changes were seen in the mechanical characteristics of the lungs of exposed animals. Pulmonary resistances, measured on the day following final exposure, were increased in all animals exposed to the methacholine aerosol. During 9 weeks following the last of the daily exposures, increased pulmonary resistance values persisted in the animals retained for this period, although there was some indication of a gradual return to pre-exposure resistance values.

Exercise intensity-related responses of beta-endorphin and catecholamines.

Ten men and 10 women exercised on a bicycle ergometer for 20 min at 40, 60, and 80% maximal oxygen uptake (VO2max) to determine the relationship between plasma beta-endorphin, catecholamines, and exercise intensity. Compared to rest, plasma beta-endorphins were not significantly elevated during the 40 and 60% workloads (4.8 +/- 1.0 pmol.l-1 vs 3.8 +/- 0.7 and 6.3 +/- 0.9, respectively). In contrast, the 80% exercise significantly elevated endorphins to 16.1 +/- 4.0 pmol.l-1. Plasma norepinephrine concentrations were 0.30 +/- 0.04 ng.ml-1 at rest and increased with exercise intensity (40% = 0.60 +/- 0.05, 60% = 0.93 +/- 0.07, 80% = 2.00 +/- 0.14, VO2max = 2.55 +/- 0.14 ng.ml-1). Plasma epinephrine followed the same trend (rest = 0.07 +/- 0.01, 40% = 0.33 +/- 0.03, 60% = 0.49 +/- 0.02, 80% = 0.88 +/- 0.07, VO2max = 0.95 +/- 0.06 ng.ml-1). Norepinephrine was found to significantly correlate to endorphins (r = 0.499; P less than 0.02). Conversely, epinephrine was not correlated with beta-endorphin (r = 0.309; P greater than 0.05). The low correlation suggests a weak relationship between beta-endorphin and catecholamine responses during exercise. The results of this investigation suggest that the relationship between beta-endorphin and exercise intensity is curvilinear, with anaerobic activity producing the most significant endorphin response. It was also noted that the beta-endorphin response was not related to gender, but the amine response to exercise was gender-related, being greater for the men.

Coronary artery magnetic resonance imaging: a patient-tailored approach.

Coronary artery magnetic resonance imaging strategies have tended to focus on the use of a single method performed during either breath-holding or free-breathing for all patients. However, significant variations exist among patients in terms of breath-holding ability and respiratory regularity that make the use of a single technique alone not universally successful. Therefore, it is prudent to make available a number of magnetic resonance imaging methods such that an appropriate respiratory motion reduction strategy can be tailored to suit the patient's respiratory pattern and characteristics. A tailored approach that can draw on different image acquisition techniques for coronary artery imaging is presented. A decision tree is proposed to triage patients into imaging regimes with the greatest probability of success, according to the patient's ability to breath-hold or exhibit steady respiration. Methods include volume free-breathing acquisitions using navigator echoes for respiratory monitoring in the 8- to 10-min scan time range, two-dimensional spiral navigators (2- to 3-min scan time), breath-held multislice and vessel-tracking spirals (16- to 20-second scan time), and real-time imaging approaches incorporating adaptive signal averaging. The development of multiple acquisition strategies substantially improves the opportunities to generate high-quality, diagnostic images of the coronary arteries.

Calculated T1 images derived from a partial saturation-inversion recovery pulse sequence with adiabatic fast passage.

Calculated T1 images of the head and abdomen have been obtained using an alternating partial saturation-inversion recovery pulse sequence. Timing parameters were adjusted to yield optimum T1 contrast-to-noise ratio for this sequence for the range of T1 studied. Adiabatic fast passage (AFP) was implemented for the nonselective inverting pulse, to reduce the sensitivity of the measurement to RF and static field inhomogeneity. A nonlinear frequency sweep was used to improve the efficiency of the AFP pulse. The effect on the T1 calculation of slice selection during the pi/2 pulses was also determined and corrected for in the image reconstruction algorithm. The T1's determined by this method show a standard deviation of less than 10%, and good agreement with the literature.

Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141b).

A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.

Practice effects with the NIMH AIDS abbreviated neuropsychological battery.

The degree of practice effects with the Brief NIMH Neuropsychological Battery for HIV Infection and AIDS is reported using a 7-10 day test-retest interval. The patient groups were asymptomatic and symptomatic of HIV while the control group was made up of "at risk" volunteers. Statistically significant practice effects were obtained on the California Verbal Learning Test, the Paced Auditory Serial Addition Task and the Visual Search Test among the infected individuals. The controls subjects demonstrated statistically significant practice effects on all of the neuropsychological tests. The implications of these findings in prospective studies are discussed.

An examination of the life stress-injury relationship among noncontact sport participants.

This study was designed to determine if life stress is predictive of athletic injury among male and female participants in intercollegiate noncontact sports. The Athletic Life Experiences Survey (ALES) was administered to 86 athletes from the sports of baseball, softball, tennis, and track before the start of the season. After the administration of the ALES, injury frequency and severity were recorded for all practices and contests. The results indicated that total life change (TLC) and negative life change (NLC) were significant (p less than .05) predictors of athletic injury frequency. When partitioned by sex and sport, females and track athletes showed significant (p less than .05) predictive relationships, with TLC the significant predictor for females and object loss (OL) for track athletes. No significant predictive models were found for severity of injury. These results suggest that life stress is predictive of the frequency of injury among noncontact sport participants, particularly for track and female athletes.

Neuroendocrine responses of type A individuals to exercise.

Ten Type A and 10 Type B individuals exercised for 20 minutes on a bicycle ergometer at 40%, 60%, and 80% of maximal capacity to determine if differences in neuroendocrine reactivity exist. Pre-exercise plasma concentrations of beta-endorphin and epinephrine were similar for Type As and Type Bs. Pre-exercise plasma levels of norepinephrine tended to be higher for the Type As (p less than 0.07). Post-exercise plasma epinephrine concentrations were similar for As and Bs for all trials. The 40% and 60% trials resulted in no differences in post-exercise norepinephrine and beta-endorphin levels for the Type As and Bs. Conversely, the 80% trials resulted in significantly greater norepinephrine and beta-endorphin concentrations for the Type As (p less than 0.05). Plasma serotonin levels at rest and during exercise were always lower for the Type As (p less than 0.05). These results suggest that our Type As had a greater neuroendocrine response to high-intensity exercise than our Type Bs. The greater reactivity and analgesia may allow the Type A person to suppress feelings of fatigue, thus enduring higher levels of exertion for longer periods of time.

Effects in the rat of inhaling PVC dust at the nuisance dust level (10 mg/m3).

Rats inhaled a paste polymer polyvinyl chloride dust at an aerosol concentration of 10 mg/m3 for 6 hr/day, 5 days/wk for a 15-wk period. A small number of randomly scattered lung lesions were detected at 15 wk; these lesions were also present 15 wk after exposure to polyvinyl chloride had ceased. Few if any biochemical changes were detected at the alveolar surface in lung tissues or other organs of polyvinyl chloride-exposed rats. It is therefore concluded that at "nuisance" dust level this form of polyvinyl chloride polymer exhibits a weak biological reactivity.

Proton Overhauser enhancements in human cardiac phosphorus NMR spectroscopy at 1.5 T.

Narrowband irradiation of water protons with a surface coil yields significant nuclear Overhauser enhancement (nOe) of phosphocreatine (PCr) and some adenosine triphosphate (ATP) moieties in localized and unlocalized phosphorus (31P) NMR spectra from chest and heart muscle. In seven normal subjects at 1.5 T the nOe values were 0.6 +/- 0.3, 0.6 +/- 0.3, 0 +/- 0.3, and 0.3 +/- 0.2 for myocardial PCr, gamma-ATP, alpha-ATP, and beta-ATP, respectively, not significantly different from those in chest muscle. Distortion of the measured PCr/ATP ratios due to differences in the nOe may require accurate correction to realize the full benefit of the effect in studies involving quantitative intergroup comparisons.

Lipid and water suppression by selective 1H homonuclear polarization transfer.

A pulse sequence is presented which uses Polarization Transfer by a Selective Homonuclear Technique (POTSHOT) to retain all resonances, in phase, from a selected coupled spin system while suppressing all other peaks, from both coupled and noncoupled spins. This technique, which is a selective form of Homonuclear Polarization Transfer (HPT), has been used in a 1.5-T whole-body system to generate edited 1H lactate spectra from lactate/oil phantoms and from excised dog hearts.

The relationship between selected psychological traits and fear of success in senior elite level wrestlers.

The present study sought to examine the relationship between selected psychological traits as measured by the Institute for Personality and Ability Testing (IPAT) 16 PF inventory and fear of success as measured by the Fear of Success Scale (FOSS). The subjects were 36 Senior elite wrestlers (age 20-25) who were invited to the Colorado Springs Olympic Training Center to prepare for an up-coming inter-national competition. A stepwise multiple regression analysis revealed that the following 16 PF factors predicted fear of success (p less than .05): IPAT-Q4, IPAT-L, IPAT-E, and IPAT-O. The multiple R was .75 and the R2 was 57.78%. Interpretation of the results suggest that while this sample of Senior elite wrestlers generally exhibit extremely low fear of success scores, athletes who are tense, frustrated, apprehensive, submissive, humble, and trusting tend to be more fearful of the consequences of success than those who are relaxed, unfrustrated, self-assured, assertive, competitive, and suspecting.

31P spectroscopic localization using pinwheel NMR excitation pulses.

Spectroscopic imaging with a one-dimensional phase-encoding gradient and surface-coil reception relies on the restricted range of sensitivity of the surface coil to provide localization in the dimensions transverse to the coil axis and consequently suffers from relatively poor localization in these dimensions. A two-dimensional (2D) cylindrically selective excitation pulse with a large spectral bandwidth is presented here to remedy this problem. The gradient waveforms are derived from multiple spirals in k space which form an overall pinwheel pattern, resulting in a pulse which is much shorter than the equivalent single-spiral trajectory. Nonuniform traversal of the spirals further reduces the pulse width under conditions of gradient slew-rate limitations, yielding overall gains in bandwidth of up to about 30 compared with the equivalent single-spiral trajectory traversed at constant angular rate. The accompanying rf waveform is obtained by weighted 2D Fourier transformation of the desired sensitivity profile. A new weighting factor is introduced into the rf waveform to compensate for nonuniform sampling of k space by the pinwheel near the origin. This factor is independent of the weighting used to account for the rate of traversal of the trajectory and is applicable to 2D pulse design in general. Pulse sequences employing pinwheel excitation in conjunction with either phase-encoding or slice-selective inversion are used to produce multiple-voxel and single-voxel localization in a human heart and a phantom. Pinwheel pulses may be used to advantage on moieties with long spin-lattice relaxation times and short transverse relaxation times and are therefore ideal for applications in phosphorus (31P) NMR.

Rapid, reliable in vivo assays of human phosphate metabolites by nuclear magnetic resonance.

This accurate, reliable, and fast method of assaying absolute concentrations of phosphate metabolites noninvasively in living tissue, including that of humans, combines 31P nuclear magnetic resonance (NMR) spectroscopy and 1H NMR imaging. The images are used to measure the areas of metabolite-bearing tissue in selected sections through the subject, and 31P spectra are acquired from the same section, together with a concentration reference located on the periphery. Metabolite concentrations are calculated from the ratios of areas and integrated signal intensities. Apparatus and protocol are designed to eliminate corrections due to magnetic field nonuniformities and NMR relaxation times. Mean (and SD) concentrations of adenosine triphosphate (ATP), phosphocreatine, and inorganic phosphate (Pi) measured in the brains of 15 normal adult human volunteers with a 1.5-T NMR system were 3.03 (0.49), 5.18 (0.89), and 1.5 (0.7) mmol per liter of wet tissue, respectively. Acquisition times of only a few minutes should facilitate metabolic studies of patients with disorders in limbs and brain, particularly those affecting entire organs.