Lynn Keenliside

Three-dimensional photoacoustic imaging by sparse-array detection and iterative image reconstruction

Photoacoustic imaging (PAI) has the potential to acquire 3-D optical images at high speed. Attempts at 3-D photoacoustic imaging have used a dense 2-D array of ultrasound detectors or have densely scanned a single detector on a 2-D surface. The former approach is costly and complicated to realize, while the latter is inherently slow. We present a different approach based on a sparse 2-D array of detector elements and an iterative reconstruction algorithm. This approach has the potential for fast image acquisition, since no mechanical scanning is required, and for simple and compact construction due to the smaller number of detector elements. We obtained spatial sensitivity maps of the sparse array and used them to optimize the image reconstruction algorithm. We then validated the method on phantoms containing 3-D distributions of optically absorbing point sources. Reconstruction of the point sources from the time-domain signals resulted in images with good contrast and accurate localization (< or =1 mm error). Image acquisition time was 1 s. The results suggest that 3-D PAI with a sparse array of detector elements is a viable approach. Furthermore, the rapid acquisition speed indicates the possibility of high frame rate 3-D PAI.

Light alters nociceptive effects of magnetic field shielding in mice: intensity and wavelength considerations

Previous experiments with mice have shown that repeated 1 hour daily exposure to an ambient magnetic field-shielded environment induces analgesia (antinociception). The exposures were carried out in the dark (less than 2.0×1016 photons s−1 m−2) during the mid-light phase of the diurnal cycle. However, if the mice were exposed in the presence of visible light (2.0×1018 photons s−1 m−2, 400–750 nm), then the analgesic effects of shielding were eliminated. Here, we show that this effect of light is intensity and wavelength dependent. Introduction of red light (peak at 635 nm) had little or no effect, presumably because mice do not have photoreceptors sensitive to red light above 600 nm in their eyes. By contrast, introduction of ultraviolet light (peak at 405 nm) abolished the effect, presumably because mice do have ultraviolet A receptors. Blue light exposures (peak at 465 nm) of different intensities demonstrate that the effect has an intensity threshold of approximately 12% of the blue light in the housing facility, corresponding to 5×1016 photons s−1 m−2 (integral). This intensity is similar to that associated with photoreceptor-based magnetoreception in birds and in mice stimulates photopic/cone vision. Could the detection mechanism that senses ambient magnetic fields in mice be similar to that in bird navigation?

The detection threshold for extremely low frequency magnetic fields may be below 1000 nT-Hz in mice.

Previous experiments with mice have shown that a repeated 1 h daily exposure to an ambient magnetic field shielded environment induces analgesia (anti-nociception). This shielding reduces ambient static and extremely low frequency magnetic fields (ELF-MF) by approximately 100 times for frequencies below 120 Hz. To determine the threshold of ELF-MF amplitude that would attenuate or abolish this effect, 30 and 120 Hz magnetic fields were introduced into the shielded environment at peak amplitudes of 25, 50, 100 and 500 nT. At 30 Hz, peak amplitudes of 50, 100, and 500 nT attenuated this effect in proportion to the amplitude magnitude. At 120 Hz, significant attenuation was observed at all amplitudes. Exposures at 10, 60, 100, and 240 Hz with peak amplitudes of 500, 300, 500, and 300 nT, respectively, also attenuated the induced analgesia. No exposure abolished this effect except perhaps at 120 Hz, 500 nT. If the peak amplitude frequency product was kept constant at 6000 nT-Hz for frequencies of 12.5, 25, 50, and 100 Hz, the extent of attenuation was constant, indicating that the detection mechanism is dependent on the nT-Hz product. A plot of effect versus the induced current metric nT-Hz suggests a threshold of ELF-MF detection in mice at or below 1000 nT-Hz.

Magnetoreception in laboratory mice: sensitivity to extremely low-frequency fields exceeds 33 nT at 30 Hz

Magnetoreception in the animal kingdom has focused primarily on behavioural responses to the static geomagnetic field and the slow changes in its magnitude and direction as animals navigate/migrate. There has been relatively little attention given to the possibility that weak extremely low-frequency magnetic fields (wELFMF) may affect animal behaviour. Previously, we showed that changes in nociception under an ambient magnetic field-shielded environment may be a good alternative biological endpoint to orientation measurements for investigations into magnetoreception. Here we show that nociception in mice is altered by a 30 Hz field with a peak amplitude more than 1000 times weaker than the static component of the geomagnetic field. When mice are exposed to an ambient magnetic field-shielded environment 1 h a day for five consecutive days, a strong analgesic (i.e. antinociception) response is induced by day 5. Introduction of a static field with an average magnitude of 44 µT (spatial variability of ±3 µT) marginally affects this response, whereas introduction of a 30 Hz time-varying field as weak as 33 nT has a strong effect, reducing the analgesic effect by 60 per cent. Such sensitivity is surprisingly high. Any purported detection mechanisms being considered will need to explain effects at such wELFMF.

Micronuclei in the blood and bone marrow cells of mice exposed to specific complex time-varying pulsed magnetic fields

For 8 weeks, adult CD-1 male mice were continuously exposed to complex time-varying pulsed magnetic fields (PMF) generated in the horizontal direction by a set of square Helmholtz coils. The PMF were <1000 Hz and delivered at a peak flux density of 1 mT. Sham-exposed mice were kept in a similar exposure system without a PMF. Positive control animals exposed to 1 Gy gamma radiation were also included in the study. Blood samples were collected before (time 0) and at 2, 4, 6, and 8 weeks. All mice were euthanized at the end of 8 weeks and their bone marrow was collected. From each blood and bone marrow sample, smears were prepared on microscope slides, fixed in absolute methanol, air-dried, and stained with acridine orange. All slides were coded and examined using a fluorescence microscope. The extent of genotoxicity and cytotoxicity was assessed from the incidence of micronuclei (MN) and percent polychromatic erythrocytes (PCE) in the blood and bone marrow, respectively. The data indicated that both indices in PMF-exposed mice were not significantly different from those observed in sham-exposed animals. In contrast, positive control mice exhibited significantly increased MN, and decreased percentages of PCE in both tissues. Thus, the overall data suggested that 8 weeks of continuous exposure to PMF did not induce significantly increased genotoxicity and cytotoxicity in experimental mice. Further investigations are underway using other genotoxicity assays (comet assay, gamma-H2AX foci, and chromosomal aberrations) to assess genotoxicity following PMF exposure.

Adaptive shut‐down of EEG activity predicts critical acidemia in the near‐term ovine fetus

In fetal sheep, the electrocorticogram (ECOG) recorded directly from the cortex during repetitive heart rate (FHR) decelerations induced by umbilical cord occlusions (UCO) predictably correlates with worsening hypoxic‐acidemia. In human fetal monitoring during labor, the equivalent electroencephalogram (EEG) can be recorded noninvasively from the scalp. We tested the hypothesis that combined fetal EEG – FHR monitoring allows for early detection of worsening hypoxic‐acidemia similar to that shown for ECOG‐FHR monitoring. Near‐term fetal sheep (n = 9) were chronically instrumented with arterial and venous catheters, ECG, ECOG, and EEG electrodes and umbilical cord occluder, followed by 4 days of recovery. Repetitive UCOs of 1 min duration and increasing strength (with regard to the degree of reduction in umbilical blood flow) were induced each 2.5 min until pH dropped to <7.00. Repetitive UCOs led to marked acidosis (arterial pH 7.35 ± 0.01 to 7.00 ± 0.03). At pH of 7.22 ± 0.03 (range 7.32–7.07), and 45 ± 9 min (range 1 h 33 min–20 min) prior to attaining pH < 7.00, both ECOG and EEG amplitudes began to decrease ~fourfold during each FHR deceleration in a synchronized manner. Confirming our hypothesis, these findings support fetal EEG as a useful adjunct to FHR monitoring during human labor for early detection of incipient fetal acidemia.

Rapid and selective brain cooling method using vortex tube: A feasibility study☆☆☆

Vortex tubes are simple mechanical devices to produce cold air from a stream of compressed air without any moving parts. The primary focus of the current study is to investigate the feasibility and efficiency of nasopharyngeal brain cooling method using a vortex tube. Experiments were conducted on 5 juvenile pigs. Nasopharygeal brain cooling was achieved by directing cooled air via a catheter in each nostril into the nasal cavities. A vortex tube was used to generate cold air using various sources of compressed air: (I) hospital medical air outlet (n = 1); (II) medical air cylinders (n = 3); and (III) scuba (diving) cylinders (n = 1). By using compressed air from a hospital medical air outlet at fixed inlet pressure of 50 PSI, maximum brain-rectal temperature gradient of -2°C was reached about 45-60 minutes by setting the flow rate of 25 L/min and temperature of -7°C at the cold air outlet. Similarly, by using medical air cylinders at fill-pressure of 2265 PSI and down regulate the inlet pressure to the vortex tube to 50 PSI, brain temperature could be reduced more rapidly by blowing -22°C ± 2°C air at a flow rate of 50 L/min; brain-body temperature gradient of -8°C was obtained about 30 minutes. Furthermore, we examined scuba cylinders as a portable source of compressed gas supply to the vortex tube. Likewise, by setting up the vortex tube to have an inlet pressure of 25 PSI and 50 L/min and -3°C at the cold air outlet, brain temperature decreased 4.5°C within 10-20 min.

Selective Cooling of the Brain in Newborn Piglets and Rabbits Using a Novel Nasopharyngeal Method

Mild hypothermia has become an effective neuroprotective strategy following head trauma, cardiac arrest and neonatal asphyxia. However, cooling the whole body below 33-34°C can induce severe complications; therefore, selective brain cooling (SBC) could minimize adverse effects by maintaining core body temperature at normal values over an extended period of time. Recently, we developed a novel method of SBC and demonstrated its safety and efficacy in a piglet model. the method was based on spraying room temperature or cold air into the nostrils at different flow rates. Pigs possess a carotid rete (a set of small parallel arteries) which is surrounded by the cavernous sinus; together these serve as an effective heat exchanger for the brain. However, in mammals in which the carotid rete is missing such as rabbits and humans, some suggest that there is no effective heat exchange in the cavernous sinus and, consequently, SBC is not efficient in these species. OBJECTIVE To evaluate the effectiveness of this approach on rabbits and compare it with previous finding on newborn piglets.

Brain Cooling With Ventilation of Cold Air Over Respiratory Tract in Newborn Piglets: An Experimental and Numerical Study

We investigate thermal effects of pulmonary cooling which was induced by cold air through an endotracheal tube via a ventilator on newborn piglets. A mathematical model was initially employed to compare the thermal impact of two different gas mixtures, O₂-medical air (1:2) and O₂-Xe (1:2), across the respiratory tract and within the brain. Following mathematical simulations, we examined the theoretical predictions with O₂-medical air condition on nine anesthetized piglets which were randomized to two treatment groups: 1) control group (n = 4) and 2) pulmonary cooling group (n = 5). Numerical and experimental results using O₂-medical air mixture show that brain temperature fell from 38.5 °C and 38.3 °C ± 0.3 °C to 35.7 °C ± 0.9 °C and 36.5 °C ± 0.6 °C during 3 h cooling which corresponded to a mean cooling rate of 0.9 °C/h ± 0.2 °C/h and 0.6 °C/h ± 0.1 °C/h, respectively. According to the numerical results, decreasing the metabolic rate and increasing air velocity are helpful to maximize the cooling effect. We demonstrated that pulmonary cooling by cooling of inhalation gases immediately before they enter the trachea can slowly reduce brain and core body temperature of newborn piglets. Numerical simulations show no significant differences between two different inhaled conditions, i.e., O₂-medical air (1:2) and O₂-Xe (1:2) with respect to cooling rate.