The intravascular contribution to fmri signal change: monte carlo modeling and diffusion-weighted studies in vivo

Understanding the relationship between fMRI signal changes and activated cortex is paramount to successful mapping of neuronal activity. To this end, the relative extravascular and intravascular contribution to fMRI signal change from capillaries (localized), venules (less localized) and macrovessels (remote, draining veins) must be determined. In this work, the authors assessed both the extravascular and intravascular contribution to blood oxygenation level-dependent gradient echo signal change at 1.5 T by using a Monte Carlo model for susceptibility-based contrast in conjunction with a physiological model for neuronal activation-induced changes in oxygenation and vascular volume fraction. The authors compared our Model results with experimental fMRI signal changes with and without velocity sensitization via bipolar gradients to null the intravascular signal. The model and experimental results are in agreement and suggest that the intravascular spins account for the majority of fMRI signal change on T₂^*-weighted images at 1.5 T.     

Chronic brief restraint decreases in vivo binding of benzodiazepine receptor ligand to mouse brain

This study examines the effects of chronic brief restraint on in vivo benzodiazepine (BZD) receptor binding in mouse brain. Three groups of mice were used. Mice in group 1 were neither restrained nor injected (ACUTE control). Mice in group 2 were restrained for 5–6 s by grabbing the back skin and holding the subject upside-down at a 45° angle as if to be injected (CHRONIC SHAM control) for 7 d. Mice in group 3 (CHRONIC SALINE) received daily single intraperitoneal (ip) injections of saline (5 mL/kg) for 7 d. On d 8 BZD receptors were labeled in vivo by administration of 3 μCi [³H]flumazenil (ip). The levels of ligand bound in vivo to cerebral cortex (CX), cerebellum (CB), brain stem (BS), striatum (ST), hippocampus (HP), and hypothalamus (HY) were determined. Results indicated that the level of binding was significantly (p<0.01) lower by 30–50% (depending on the brain region) in saline-injected or sham control groups compared to acute control animals. Furthermore, the values for sham control were similar to the saline-treated group. Our data suggest that exposure to chronic mild restraint produces a decrease in in vivo binding of [³H]flumazenil in mouse brain and supports the hypothesis that chronic mild stress produces a decrease in BZD receptor binding sites.     

Application of Solid-State Nuclear Magnetic Resonance (NMR) to the Study of Skin Hydration

The solid-state nuclear magnetic resonance (NMR) technique of carbon-13 cross-polarization/magic angle spinning (CP/MAS) has been successfully used to obtain high-resolution spectra of whole-thickness, hairy rat skin and to characterize the influence of hydration on the efficiency of cross-polarization and the proton spin-lattice relaxation time in the rotating frame (T1H). Spectra obtained with hydrated samples, which were obtained with 50% more accumulations, had comparable signal-to-noise ratio relative to spectra obtained with dried skin, indicating a disordering effect with the presence of water. The integrated area of spectra of low-shifted peaks rose more rapidly with increasing contact time relative to the high-shifted peaks for both hydrated and dried skin. In addition, the carbonyl intensity of the hydrated skin relative to dried skin reached a maximum at shorter times, reflecting an efficient relaxation mechanism of the protons. The shift of the peak maximum to shorter mixing times quantitatively reflects the interaction of the protons of water with the carbonyl moiety.     

β-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

The use of 15-p-iodophenyl--methyl-pentadecanoic acid (Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioctivity (residue curves) were obtained following bolus injections of both Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, Me-IPPA kinetics were insenstive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significatly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond Me-IPPA-CoA in the oxidative pathway.     

Hypohydration effects on thermoregulation during moderate exercise in the cold

Hyperosmotic hypovolemia impairs vasoconstriction during sedentary cold exposure. The purpose of this study was to determine whether hypohydration alters thermoregulation and cardiovascular responses to exercise in cold air. On four occasions, eight males [35.1 (2.7) years, 175.5 (3.1) cm, 73.3 (2.6) kg, 57.2 (2.6) ml kg^–1 min^–1 maximal oxygen uptake (O_2max), 19.6 (2.4)% fat] walked, in t-shirt, shorts, and shoes, at 50% O_2max, for 60 min in either a 4°C (Cold) or a 25°C (Temperate) environment in both hypohydrated state (HYPO, –4% body mass) and euhydrated state (EU). During exercise–cold stress, rectal temperature (T_re), mean weighted skin temperature, heart rate (HR), cardiac output (CO), and stroke volume (SV) were measured every 20 min. Mean weighted skin temperature values were not different between HYPO and EU but were lower (P<0.05) in Cold versus Temperate trials. T_re was not different (P>0.05) between HYPO–Cold and EU–Cold. CO and SV were not different within hydration states and were not different between Cold and Temperate trials (P<0.05). HR was not different between HYPO–Cold and EU–Cold. These data demonstrate that moderate intensity exercise in the cold while hypohydrated does not alter metabolic heat production, skin temperatures and heat loss, nor does it increase thermoregulatory and cardiovascular strain.     

The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis

The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC). The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (1H-NMR) spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC). We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping) as a fitness test for a supervised system (a genetic algorithm). With this approach, a training set comprised of mass spectra and 1H-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in n-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%.     

The application of molecular techniques to solid tumors

Recent developments in the field of molecular biology including the sequencing of the human genome and related high throughput methodologies are presenting the diagnostic pathologist with new opportunities to expand our understanding of human disease. These techniques enable the comprehensive assessment of molecular alterations with cell populations of interest, including cancer. It will be necessary for the diagnostic pathologist to become familiar with these techniques to effectively translate their potential into the clinical environment.     

Quantitative Characterization of Epicardial Wave Fronts During Regional Ischemia and Elevated Extracellular Potassium Ion Concentration

This study applied zero-delay wave number spectral estimation as a means of quantifying the changes in activation and recovery sequences of propagating plane waves on the epicardial surface of in situ porcine hearts during regional hyperkalemia and ischemia. Unipolar electrograms (104) were recorded from the left ventricular surface of nine hearts using a plaque electrode array with 1 mm spatial sampling intervals. The objectives were (1) to define a set of parameters capable of quantifying the spatial and temporal changes in measured extracellular potentials associated with localized ischemia prior to the onset of conduction block; (2) to elevate regional levels of extracellular potassium ion concentration and quantify potential changes due to this known physiologic manipulation; and (3) to use quantitative parameters to make statistical comparisons in order to distinguish wave fronts during normal, ischemic and hyperkalemic conditions. Results showed that the parameters of wave number and average temporal frequency and the associated power, as determined from the wave number spectrum, provided statistically significant (p < 0.05) quantification of changes in wave front features during normal and ischemic or hyperkalemic conditions. The results were consistent with results obtained from conventional time–space domain methods like isochronal mapping and electrograms, with the advantage of a quantitative result enabling simple comparisons and trend analysis for large numbers of heart beats. © 1998 Biomedical Engineering Society. PAC98: 8759Wc, 8722Fy, 8780+s     

Which treatment for whom for ADHD? Moderators of treatment response in the MTA

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.     

Asthma and the diver

Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with nearly 9 million sport divers in the United States alone. Approximately 7% of the population has been diagnosed with asthma, which is similar to the percentage of divers admitting they have asthma. Numerous concerns exist regarding subjects with asthma who choose to participate in recreational diving. Among these concerns are pulmonary barotrauma, pneumomediastinum, pneumothorax, arterial gas embolism, ear barotrauma, sinus barotrauma, and dental barotrauma. Despite these concerns, a paucity of information exists linking asthma to increased risk of diving complications. However, it has long been the norm to discourage individuals with asthma from participating in recreational scuba diving. This article examines the currently available literature to allow for a more informed decision regarding the possible risks associated with diving and asthma. It examines the underlying physiological principles associated with diving, including Henry’s law and Boyle’s law, to provide a more intimate understanding on physiological changes occurring in the respiratory system under compressive stress. Finally, this article offers a framework for guiding the patient with asthma who is interested in scuba diving. Under the right circumstances, the patient with asthma can safely participate in recreational diving without apparent increased risk of an asthma-related event.