Associations between Total Cerebral Blood Flow and Age Related Changes of the Brain

Background and Purpose

Although total cerebral blood flow (tCBF) is known to be related to age, less is known regarding the associations between tCBF and the morphologic changes of the brain accompanying cerebral aging. The purpose of this study was to investigate whether total cerebral blood flow (tCBF) is related to white matter hyperintensity (WMH) volume and/or cerebral atrophy. Furthermore, we investigate whether tCBF should be expressed in mL/min, as was done in all previous MR studies, or in mL/100 mL/min, which yielded good results in precious SPECT, PET and perfusion MRI studies investigating regional cerebral blood flow.

Materials and Methods

Patients were included from the nested MRI sub-study of the PROSPER study. Dual fast spin echo and FLAIR images were obtained in all patients. In addition, single slice phase contrast MR angiography was used for flow measurements in the internal carotids and vertebral arteries. tCBF was expressed in both mL/min and mL/100 mL/min.

Results

We found a significant correlation between tCBF in mL/min and both age (r = −.124; p = p≤.001) and parenchymal volume (r = 0.430; p≤.001). We found no association between tCBF in mL/min and %-atrophy (r = −.077; p = .103) or total WMH volume (r = −.069; p = .148). When tCBF was expressed in mL/100 mL/min the correlation between tCBF and age was no longer found (r = −.001; p = .985). Multivariate regression analyses corrected for age showed a significant correlation between tCBF in mL/100 mL/min and WMH volume (r = −.106; p = .044). No significant association between tCBF in mL/100 mL/min and %-atrophy was found.

Conclusion

From this study we conclude that, when evaluating tCBF alterations due to various pathologies, tCBF should in mL/100 mL/min instead of mL/min. Furthermore, changes or differences in WMH volume should be accounted for.     

Increased Force Variability in Chronic Stroke: Contributions of Force Modulation below 1 Hz

Increased force variability constitutes a hallmark of arm disabilities following stroke. Force variability is related to the modulation of force below 1 Hz in healthy young and older adults. However, whether the increased force variability observed post stroke is related to the modulation of force below 1 Hz remains unknown. Thus, the purpose of this study was to compare force modulation below 1 Hz in chronic stroke and age-matched healthy individuals. Both stroke and control individuals (N = 26) performed an isometric grip task to submaximal force levels. Coefficient of variation quantified force variability, and power spectrum density of force quantified force modulation below 1 Hz with a high resolution (0.07 Hz). Analyses indicated that force variability was greater for the stroke group compared with to healthy controls and for the paretic hand compared with the non-paretic hand. Force modulation below 1 Hz differentiated the stroke individuals and healthy controls, as well as the paretic and non-paretic hands. Specifically, stroke individuals (paretic hand) exhibited greater power ∼0.2 Hz (0.07–0.35 Hz) and lesser power ∼0.6 Hz (0.49–0.77 Hz) compared to healthy controls (non-dominant hand). Similarly, the paretic hand exhibited greater power ∼0.2 Hz, and lesser power ∼0.6 Hz than the non-paretic hand. Moreover, variability of force was strongly predicted from the modulation of specific frequencies below 1 Hz (R ² = 0.80). Together, these findings indicate that the modulation of force below 1 Hz provides significant insight into changes in motor control after stroke.     

A New Model-Free Index of Dynamic Cerebral Blood Flow Autoregulation

The classic dynamic autoregulatory index (ARI), proposed by Aaslid and Tiecks, is one of the most widely used methods to assess the efficiency of dynamic cerebral autoregulation. Although this index is often used in clinical research and is also included in some commercial equipment, it exhibits considerable intra-subject variability, and has the tendency to produce false positive results in clinical applications. An alternative index of dynamic cerebral autoregulation is proposed, which overcomes most of the limitations of the classic method and also has the advantage of being model-free. This new index uses two parameters that are obtained directly from the response signal of the cerebral blood flow velocity to a transient decrease in arterial blood pressure provoked by the sudden release of bilateral thigh cuffs, and a third parameter measuring the difference in slope of this response and the change in arterial blood pressure achieved. With the values of these parameters, a corresponding classic autoregulatory index value could be calculated by using a linear regression model built from theoretical curves generated with the Aaslid-Tiecks model. In 16 healthy subjects who underwent repeated thigh-cuff manoeuvres, the model-free approach exhibited significantly lower intra-subject variability, as measured by the unbiased coefficient of variation, than the classic autoregulatory index (p = 0.032) and the Rate of Return (p<0.001), another measure of cerebral autoregulation used for this type of systemic pressure stimulus, from 39.23%±41.91% and 55.31%±31.27%, respectively, to 15.98%±7.75%.     

Impaired Cerebral Autoregulation Is Associated with Brain Atrophy and Worse Functional Status in Chronic Ischemic Stroke

Dynamic cerebral autoregulation (dCA) is impaired following stroke. However, the relationship between dCA, brain atrophy, and functional outcomes following stroke remains unclear. In this study, we aimed to determine whether impairment of dCA is associated with atrophy in specific regions or globally, thereby affecting daily functions in stroke patients.We performed a retrospective analysis of 33 subjects with chronic infarctions in the middle cerebral artery territory, and 109 age-matched non-stroke subjects. dCA was assessed via the phase relationship between arterial blood pressure and cerebral blood flow velocity. Brain tissue volumes were quantified from MRI. Functional status was assessed by gait speed, instrumental activities of daily living (IADL), modified Rankin Scale, and NIH Stroke Score.Compared to the non-stroke group, stroke subjects showed degraded dCA bilaterally, and showed gray matter atrophy in the frontal, parietal and temporal lobes ipsilateral to infarct. In stroke subjects, better dCA was associated with less temporal lobe gray matter atrophy on the infracted side ( = 0.029), faster gait speed ( = 0.018) and lower IADL score (0.002). Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions.     

Low-Level Carotid Baroreceptor Stimulation Suppresses Ventricular Arrhythmias during Acute Ischemia

Background

The autonomic imbalance during acute ischemia is involved in the occurrence of life-threatening arrhythmias.

Objective

To investigate the effect of autonomic nervous system (ANS) modulation by low-level carotid baroreceptor stimulation (LL-CBS) on ventricular ischemia arrhythmias.

Methods

Anesthetized dogs were received either sham treatment (SHAM group, n = 10) or LL-CBS treatment (LL-CBS group, n = 10). The voltage lowering the blood pressure was used as the threshold for setting LL-CBS at 80% below the threshold. Treatment started 1 hour before left anterior descending coronary (LAD) occlusion, and continued until the end of experience. Ventricular effective refractory periods (ERP), monophasic action potential duration at 90% (APD₉₀), ventricular arrhythmias, indices of heart rate variability, left stellate ganglion nerve activity (LSGNA) and infarct sizes were measured and analyzed.

Results

Ventricular ischemia resulted in an acute reduction of blood pressure, which was not significantly affected by LL-CBS. After 1 hour of LL-CBS, there was a progressive and significant increase in ERP, increase in APD₉₀, and decrease in LSGNA vs the SHAM group (all P<0.05). LL-CBS apparently reduced premature ventricular contractions (PVC, 264±165 in the SHAM group vs 60±37 in the LL-CBS group; P<0.01) during LAD occlusion. Number of episodes of ventricular fibrillation (VF) was 8 in the Control group versus 3 in the LL-CBS group (80% versus 30%, P<0.05). LL-CBS obviously increased high frequency (HF) component (P<0.05) and decreased low frequency/high frequency ratio (P<0.05) compared with the SHAM group. Ischemic size was not affected by LL-CBS between the two groups.

Conclusions

LL-CBS reduced the occurrences of ventricular arrhythmias during acute ischemia without affecting blood pressure. The procedure was associated with changes of electrophysiological characteristics, nerve activity and heart rate variability. Therefore, LL-CBS may protect from ventricular arrhythmias during acute ischemic events by modulating ANS.     

Regional Differences in Dynamic Cerebral Autoregulation in the Healthy Brain Assessed by Magnetic Resonance Imaging

A novel method is described for mapping dynamic cerebral blood flow autoregulation to assess autoregulatory efficiency throughout the brain, using magnetic resonance imaging (MRI). Global abnormalities in autoregulation occur in clinical conditions, including stroke and head injury, and are of prognostic significance. However, there is limited information about regional variations. A gradient-echo echo-planar pulse sequence was used to scan the brains of healthy subjects at a rate of 1 scan/second during a transient decrease in arterial blood pressure provoked by a sudden release of pressure in bilateral inflated thigh cuffs. The signal decrease and subsequent recovery were analyzed to provide an index of autoregulatory efficiency (MRARI). MRI time-series were successfully acquired and analyzed in eleven subjects. Autoregulatory efficiency was not uniform throughout the brain: white matter exhibited faster recovery than gray (MRARI = 0.702 vs. 0.672, p = 0.009) and the cerebral cortex exhibited faster recovery than the cerebellum (MRARI = 0.669 vs. 0.645, p = 0.016). However, there was no evidence for differences between different cortical regions. Differences in autoregulatory efficiency between white matter, gray matter and the cerebellum may be a result of differences in vessel density and vasodilation. The techniques described may have practical importance in detecting regional changes in autoregulation consequent to disease.     

Association of CVD Candidate Gene Polymorphisms with Ischemic Stroke and Cerebral Hemorrhage in Chinese Individuals

Background

Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.

Methods

There were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model.

Results

After adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant.

Conclusions

The NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population.     

Multi Frequency Phase Fluorimetry (MFPF) for Oxygen Partial Pressure Measurement: Ex Vivo Validation by Polarographic Clark-Type Electrode

Background

Measurement of partial pressure of oxygen (P_O2) at high temporal resolution remains a technological challenge. This study introduces a novel P_O2 sensing technology based on Multi-Frequency Phase Fluorimetry (MFPF). The aim was to validate MFPF against polarographic Clark-type electrode (CTE) P_O2 measurements.

Methodology/Principal Findings

MFPF technology was first investigated in N = 8 anaesthetised pigs at F_IO2 of 0.21, 0.4, 0.6, 0.8 and 1.0. At each F_IO2 level, blood samples were withdrawn and P_O2 was measured in vitro with MFPF using two FOXY-AL300 probes immediately followed by CTE measurement. Secondly, MFPF-P_O2 readings were compared to CTE in an artificial circulatory setup (human packed red blood cells, haematocrit of 30%). The impacts of temperature (20, 30, 40°C) and blood flow (0.8, 1.6, 2.4, 3.2, 4.0 L min⁻¹) on MFPF-P_O2 measurements were assessed. MFPF response time in the gas- and blood-phase was determined. Porcine MFPF-P_O2 ranged from 63 to 749 mmHg; the corresponding CTE samples from 43 to 712 mmHg. Linear regression: CTE = 15.59+1.18*MFPF (R² = 0.93; P<0.0001). Bland Altman analysis: mean_diff 69.2 mmHg, range_diff -50.1/215.6 mmHg, 1.96-SD limits -56.3/194.8 mmHg. In artificial circulatory setup, MFPF-P_O2 ranged from 20 to 567 mmHg and CTE samples from 11 to 575 mmHg. Linear regression: CTE = −8.73+1.05*MFPF (R² = 0.99; P<0.0001). Bland-Altman analysis: mean_diff 6.6 mmHg, range_diff -9.7/20.5 mmHg, 1.96-SD limits -12.7/25.8 mmHg. Differences between MFPF and CTE-P_O2 due to variations of temperature were less than 6 mmHg (range 0–140 mmHg) and less than 35 mmHg (range 140–750 mmHg); differences due to variations in blood flow were less than 15 mmHg (all P-values>0.05). MFPF response-time (monoexponential) was 1.48±0.26 s for the gas-phase and 1.51±0.20 s for the blood-phase.

Conclusions/Significance

MFPF-derived P_O2 readings were reproducible and showed excellent correlation and good agreement with Clark-type electrode-based P_O2 measurements. There was no relevant impact of temperature and blood flow upon MFPF-P_O2 measurements. The response time of the MFPF FOXY-AL300 probe was adequate for real-time sensing in the blood phase.     

Resistance Training Improves Hemodynamic Function,Collagen Deposition and Inflammatory Profiles: Experimental Model of Heart Failure

The role of resistance training on collagen deposition, the inflammatory profile and muscle weakness in heart failure remains unclear. Therefore, this study evaluated the influence of a resistance training program on hemodynamic function, maximum strength gain, collagen deposition and inflammatory profile in chronic heart failure rats. Thirty-two male Wistar rats submitted to myocardial infarction by coronary artery ligation or sham surgery were assigned into four groups: sedentary sham (S-Sham, n = 8); trained sham (T-Sham, n = 8); sedentary chronic heart failure (S-CHF, n = 8) and trained chronic heart failure (T-CHF, n = 8). The maximum strength capacity was evaluated by the one maximum repetition test. Trained groups were submitted to an 8-week resistance training program (4 days/week, 4 sets of 10–12 repetitions/session, at 65% to 75% of one maximum repetition). After 8 weeks of the resistance training program, the T-CHF group showed lower left ventricular end diastolic pressure (P<0.001), higher left ventricular systolic pressure (P<0.05), higher systolic blood pressure (P<0.05), an improvement in the maximal positive derivative of ventricular pressure (P<0.05) and maximal negative derivative of ventricular pressure (P<0.05) when compared to the S-CHF group; no differences were observed when compared to Sham groups. In addition, resistance training was able to reduce myocardial hypertrophy (P<0.05), left ventricular total collagen volume fraction (P<0.01), IL-6 (P<0.05), and TNF-α/IL-10 ratio (P<0.05), as well as increasing IL-10 (P<0.05) in chronic heart failure rats when compared to the S-CHF group. Eight weeks of resistance training promotes an improvement of cardiac function, strength gain, collagen deposition and inflammatory profile in chronic heart failure rats.     

Regular Cocaine Use Is Associated with Increased Systolic Blood Pressure,Aortic Stiffness and Left Ventricular Mass in Young Otherwise Healthy Individuals

Background

The cardiovascular impact of cocaine use in otherwise healthy individuals who consider themselves ‘social’ users is not well established.

Methods/Results

Twenty regular cocaine users and 20 control subjects were recruited by word-of-mouth. Cardiovascular magnetic resonance was performed to assess cardiac and vascular structure and function. Cocaine users had higher systolic blood pressure compared to non-users (134±11 vs 126±11 mmHg, p = 0.036), a finding independent of age, body surface area, smoking and alcohol consumption. Cocaine use was associated with increased arterial stiffness - reflected by reduced aortic compliance (1.3±0.2 vs 1.7±0.5 cm²×10⁻².mmHg⁻¹, p = 0.004), decreased distensibility (3.8±0.9 vs 5.1±1.4 mmHg⁻¹.10⁻³, p = 0.001), increased stiffness index (2.6±0.6 vs 2.1±0.6, p = 0.005), and higher pulse wave velocity (5.1±0.6 vs 4.4±0.6 m.s⁻¹, p = 0.001). This change in aortic stiffness was independent of vessel wall thickness. Left ventricular mass was 18% higher in cocaine users (124±25 vs 105±16 g, p = 0.01), a finding that was independent of body surface area, and left atrial diameter was larger in the user group than controls (3.8±0.6 vs 3.5±0.3 cm, p = 0.04). The increased left ventricular mass, systolic blood pressure and vascular stiffness measures were all associated with duration and/or frequency of cocaine use. No late gadolinium enhancement or segmental wall motion abnormalities were seen in any of the subjects.

Conclusions

Compared with the non-user control cohort, cocaine users had increased aortic stiffness and systolic blood pressure, associated with greater left ventricular mass. These measures are all well known risk factors for premature cardiovascular events, highlighting the dangers of cocaine use, even in a ‘social’ setting, and have important public health implications.     

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, ¹⁸F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of ¹⁸F-DPA-714 was increased in ALS patients during the “time of diagnosis” phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.     

Cognitive Modulation of Psychophysical,Respiratory and Autonomic Responses to Cold Pressor Test

In healthy subjects with high hypnotisability (highs) under hypnosis, subjectively effective suggestions for analgesia abolish the increases in blood pressure associated with cold pressor test (cpt) by reducing the peripheral vascular resistance. The aim of the present study was to investigate the effects of the suggestions of analgesia on the responses to cpt in healthy highs (n = 22) and in low hypnotisable participants (lows, n = 22) out of hypnosis. Cpt was administered without (CPT) and with suggestions for analgesia (CPT+AN). Psychophysical (pain intensity, pain threshold, cpt duration (time of immersion) and pain tolerance, defined as the difference between cpt duration and pain threshold), respiratory (amplitude and frequency) and autonomic variables (tonic skin conductance, mean RR interval (RR = 1/heart rate), blood pressure, skin blood flow) were studied. The suggestions for analgesia increased cpt duration and RR in both groups, but decreased pain intensity and enhanced pain threshold only in highs; in both groups they did not modulate systolic blood pressure, tonic skin conductance and skin blood flow; thus, increased parasympathetic activity appears responsible for the heart rate reduction induced by suggestions in both groups. In conclusion, our findings show that suggestions modulate pain experience differentially in highs and lows, and are partially effective also in lows. We hypothesize that the mechanisms responsible for the efficacy of suggestions in healthy lows may be involved also in their efficacy in chronic pain patients with low hypnotisability.     

Marine Mammal Strandings and Environmental Changes: A 15-Year Study in the St. Lawrence Ecosystem

Understanding the effects of climatic variability on marine mammals is challenging due to the complexity of ecological interactions. We used general linear models to analyze a 15-year database documenting marine mammal strandings (1994–2008; n = 1,193) and nine environmental parameters known to affect marine mammal survival, from regional (sea ice) to continental scales (North Atlantic Oscillation, NAO). Stranding events were more frequent during summer and fall than other seasons, and have increased since 1994. Poor ice conditions observed during the same period may have affected marine mammals either directly, by modulating the availability of habitat for feeding and breeding activities, or indirectly, through changes in water conditions and marine productivity (krill abundance). For most species (75%, n = 6 species), a low volume of ice was correlated with increasing frequency of stranding events (e.g. R² _adj = 0.59, hooded seal, Cystophora cristata). This likely led to an increase in seal mortality during the breeding period, but also to increase habitat availability for seasonal migratory cetaceans using ice-free areas during winter. We also detected a high frequency of stranding events for mysticete species (minke whale, Balaenoptera acutorostrata) and resident species (beluga, Delphinapterus leucas), correlated with low krill abundance since 1994. Positive NAO indices were positively correlated with high frequencies of stranding events for resident and seasonal migratory cetaceans, as well as rare species (R² _adj = 0.53, 0.81 and 0.34, respectively). This contrasts with seal mass stranding numbers, which were negatively correlated with a positive NAO index. In addition, an unusual multiple species mortality event (n = 114, 62% of total annual mortality) in 2008 was caused by a harmful algal bloom. Our findings provide an empirical baseline in understanding marine mammal survival when faced with climatic variability. This is a promising step in integrating stranding records to monitor the consequences of environmental changes in marine ecosystems over long time scales.     

First Autonomous Bio-Optical Profiling Float in the Gulf of Mexico Reveals Dynamic Biogeochemistry in Deep Waters

Profiling floats equipped with bio-optical sensors well complement ship-based and satellite ocean color measurements by providing highly-resolved time-series data on the vertical structure of biogeochemical processes in oceanic waters. This is the first study to employ an autonomous profiling (APEX) float in the Gulf of Mexico for measuring spatiotemporal variability in bio-optics and hydrography. During the 17-month deployment (July 2011 to December 2012), the float mission collected profiles of temperature, salinity, chlorophyll fluorescence, particulate backscattering (b_bp), and colored dissolved organic matter (CDOM) fluorescence from the ocean surface to a depth of 1,500 m. Biogeochemical variability was characterized by distinct depth trends and local “hot spots”, including impacts from mesoscale processes associated with each of the water masses sampled, from ambient deep waters over the Florida Plain, into the Loop Current, up the Florida Canyon, and eventually into the Florida Straits. A deep chlorophyll maximum (DCM) occurred between 30 and 120 m, with the DCM depth significantly related to the unique density layer ρ = 1023.6 (R² = 0.62). Particulate backscattering, b_bp, demonstrated multiple peaks throughout the water column, including from phytoplankton, deep scattering layers, and resuspension. The bio-optical relationship developed between b_bp and chlorophyll (R² = 0.49) was compared to a global relationship and could significantly improve regional ocean-color algorithms. Photooxidation and autochthonous production contributed to CDOM distributions in the upper water column, whereas in deep water, CDOM behaved as a semi-conservative tracer of water masses, demonstrating a tight relationship with density (R² = 0.87). In the wake of the Deepwater Horizon oil spill, this research lends support to the use of autonomous drifting profilers as a powerful tool for consideration in the design of an expanded and integrated observing network for the Gulf of Mexico.     

Longitudinal Hemodynamic Measurements in Swine Heart Failure Using a Fully Implantable Telemetry System

Chronic monitoring of heart rate, blood pressure, and flow in conscious free-roaming large animals can offer considerable opportunity to understand the progression of cardiovascular diseases and can test new diagnostics and therapeutics. The objective of this study was to demonstrate the feasibility of chronic, simultaneous measurement of several hemodynamic parameters (left ventricular pressure, systemic pressure, blood flow velocity, and heart rate) using a totally implantable multichannel telemetry system in swine heart failure models. Two solid-state blood pressure sensors were inserted in the left ventricle and the descending aorta for pressure measurements. Two Doppler probes were placed around the left anterior descending (LAD) and the brachiocephalic arteries for blood flow velocity measurements. Electrocardiographic (ECG) electrodes were attached to the surface of the left ventricle to monitor heart rate. The telemeter body was implanted in the right side of the abdomen under the skin for approximately 4 to 6 weeks. The animals were subjected to various heart failure models, including volume overload (A-V fistula, n = 3), pressure overload (aortic banding, n = 2) and dilated cardiomyopathy (pacing-induced tachycardia, n = 3). Longitudinal changes in hemodynamics were monitored during the progression of the disease. In the pacing-induced tachycardia animals, the systemic blood pressure progressively decreased within the first 2 weeks and returned to baseline levels thereafter. In the aortic banding animals, the pressure progressively increased during the development of the disease. The pressure in the A-V fistula animals only showed a small increase during the first week and remained stable thereafter. The results demonstrated the ability of this telemetry system of long-term, simultaneous monitoring of blood flow, pressure and heart rate in heart failure models, which may offer significant utility for understanding cardiovascular disease progression and treatment.     

Artificial Polychromatic Light Affects Growth and Physiology in Chicks

Despite the overwhelming use of artificial light on captive animals, its effect on those animals has rarely been studied experimentally. Housing animals in controlled light conditions is useful for assessing the effects of light. The chicken is one of the best-studied animals in artificial light experiments, and here, we evaluate the effect of polychromatic light with various green and blue components on the growth and physiology in chicks. The results indicate that green-blue dual light has two side-effects on chick body mass, depending on the various green to blue ratios. Green-blue dual light with depleted and medium blue component decreased body mass, whereas enriched blue component promoted body mass in chicks compared with monochromatic green- or blue spectra-treated chicks. Moreover, progressive changes in the green to blue ratios of green-blue dual light could give rise to consistent progressive changes in body mass, as suggested by polychromatic light with higher blue component resulting in higher body mass. Correlation analysis confirmed that food intake was positively correlated with final body mass in chicks (R² = 0.7664, P = 0.0001), suggesting that increased food intake contributed to the increased body mass in chicks exposed to higher blue component. We also found that chicks exposed to higher blue component exhibited higher blood glucose levels. Furthermore, the glucose level was positively related to the final body mass (R² = 0.6406, P = 0.0001) and food intake (R² = 0.784, P = 0.0001). These results demonstrate that spectral composition plays a crucial role in affecting growth and physiology in chicks. Moreover, consistent changes in spectral components might cause the synchronous response of growth and physiology.     

Extra-Hippocampal Subcortical Limbic Involvement Predicts Episodic Recall Performance in Multiple Sclerosis

Background

Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging.

Methodology/Principal Findings

34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, P<.0005) and mammillary body volumes (age-adjusted means 0.114 ml vs. 0.126 ml, P<.023). Multivariate regression analysis identified fornix FA and mammillary bodies as predictor of visual recall (R² = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R² = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency.

Conclusions/Significance

These findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.     

Force Control Is Related to Low-Frequency Oscillations in Force and Surface EMG

Force variability during constant force tasks is directly related to oscillations below 0.5 Hz in force. However, it is unknown whether such oscillations exist in muscle activity. The purpose of this paper, therefore, was to determine whether oscillations below 0.5 Hz in force are evident in the activation of muscle. Fourteen young adults (21.07±2.76 years, 7 women) performed constant isometric force tasks at 5% and 30% MVC by abducting the left index finger. We recorded the force output from the index finger and surface EMG from the first dorsal interosseous (FDI) muscle and quantified the following outcomes: 1) variability of force using the SD of force; 2) power spectrum of force below 2 Hz; 3) EMG bursts; 4) power spectrum of EMG bursts below 2 Hz; and 5) power spectrum of the interference EMG from 10–300 Hz. The SD of force increased significantly from 5 to 30% MVC and this increase was significantly related to the increase in force oscillations below 0.5 Hz (R ² = 0.82). For both force levels, the power spectrum for force and EMG burst was similar and contained most of the power from 0–0.5 Hz. Force and EMG burst oscillations below 0.5 Hz were highly coherent (coherence = 0.68). The increase in force oscillations below 0.5 Hz from 5 to 30% MVC was related to an increase in EMG burst oscillations below 0.5 Hz (R ² = 0.51). Finally, there was a strong association between the increase in EMG burst oscillations below 0.5 Hz and the interference EMG from 35–60 Hz (R ² = 0.95). In conclusion, this finding demonstrates that bursting of the EMG signal contains low-frequency oscillations below 0.5 Hz, which are associated with oscillations in force below 0.5 Hz.     

A randomised, controlled crossover comparison of the C-MAC videolaryngoscope with direct laryngoscopy in 150 patients during routine induction of anaesthesia

Background

The insertion of Ventricular Assist Devices is a common strategy for cardiovascular support in patients with refractory cardiogenic shock. This study sought to determine the impact of ventricular assist devices on the dynamic relationship between arterial blood pressure and cerebral blood flow velocity.

Methods

A sample of 5 patients supported with a pulsatile ventricular assist device was compared with 5 control patients. Controls were matched for age, co-morbidities, current diagnosis and cardiac output state, to cases. Beat-to-beat recordings of mean arterial pressure and cerebral blood flow velocity, using transcranial Doppler were obtained. Transfer function analysis was performed on the lowpass filtered pressure and flow signals, to assess gain, phase and coherence of the relationship between mean arterial blood pressure and cerebral blood flow velocity. These parameters were derived from the very low frequency (0.02-0.07 Hz), low frequency (0.07-0.2 Hz) and high frequency (0.2-0.35 Hz).

Results

No significant difference was found in gain and phase values between the two groups, but the low frequency coherence was significantly higher in cases compared with controls (mean ± SD: 0.65 ± 0.16 vs 0.38 ± 0.19, P = 0.04). The two cases with highest coherence (~0.8) also had much higher spectral power in mean arterial blood pressure.

Conclusions

Pulsatile ventricular assist devices affect the coherence but not the gain or phase of the cerebral pressure-flow relationship in the low frequency range; thus whether there was any significant disruption of cerebral autoregulation mechanism was not exactly clear. The augmentation of input pressure fluctuations might contribute in part to the higher coherence observed.     

Population-Based Input Function Modeling for [18F]FMPEP-d 2, an Inverse Agonist Radioligand for Cannabinoid CB1 Receptors: Validation in Clinical Studies

Background

Population-based input function (PBIF) may be a valid alternative to full blood sampling for quantitative PET imaging. PBIF is typically validated by comparing its quantification results with those obtained via arterial sampling. However, for PBIF to be employed in actual clinical research studies, its ability to faithfully capture the whole spectrum of results must be assessed. The present study validated a PBIF for [¹⁸F]FMPEP-d ₂, a cannabinoid CB₁ receptor radioligand, in healthy volunteers, and also attempted to utilize PBIF to replicate three previously published clinical studies in which the input function was acquired with arterial sampling.

Methods

The PBIF was first created and validated with data from 42 healthy volunteers. This PBIF was used to assess the retest variability of [¹⁸F]FMPEP-d ₂, and then to quantify CB₁ receptors in alcoholic patients (n = 18) and chronic daily cannabis smokers (n = 29). Both groups were scanned at baseline and after 2–4 weeks of monitored drug abstinence.

Results

PBIF yielded accurate results in the 42 healthy subjects (average Logan-distribution volume (V _T) was 13.3±3.8 mL/cm³ for full sampling and 13.2±3.8 mL/cm³ for PBIF; R² = 0.8765, p<0.0001) and test-retest results were comparable to those obtained with full sampling (variability: 16%; intraclass correlation coefficient: 0.89). PBIF accurately replicated the alcoholism study, showing a widespread ∼20% reduction of CB₁ receptors in alcoholic subjects, without significant change after abstinence. However, a small PBIF-V _T bias of −9% was unexpectedly observed in cannabis smokers. This bias led to substantial errors, including a V _T decrease in regions that had shown no downregulation in the full input function. Simulated data showed that the original findings could only have been replicated with a PBIF bias between −6% and +4%.

Conclusions

Despite being initially well validated in healthy subjects, PBIF may misrepresent clinical protocol results and be a source of variability between different studies and institutions.