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1.  Impact of stepwise hyperventilation on cerebral tissue oxygen saturation in anesthetized patients: a mechanistic study 
While the decrease in blood carbon dioxide (CO2) secondary to hyperventilation is generally accepted to play a major role in the decrease of cerebral tissue oxygen saturation (SctO2), it remains unclear if the associated systemic hemodynamic changes are also accountable.
Twenty-six patients (American Society of Anesthesiologists I–II) undergoing nonneurosurgical procedures were anesthetized with either propofol-remifentanil (n = 13) or sevoflurane (n = 13). During a stable intraoperative period, ventilation was adjusted stepwise from hypoventilation to hyper-ventilation to achieve a progressive change in end-tidal CO2 (ETCO2) from 55 to 25 mmHg. Minute ventilation, SctO2, ETCO2, mean arterial pressure (MAP), and cardiac output (CO) were recorded.
Hyperventilation led to a SctO2 decrease from 78 ± 4% to 69 ± 5% (Δ = −9 ± 4%, P < 0.001) in the propofol-remifentanil group and from 81 ± 5% to 71 ± 7% (Δ = −10 ± 3%, P < 0.001) in the sevoflurane group. The decreases in SctO2 were not statistically different between these two groups (P = 0.5). SctO2 correlated significantly with ETCO2 in both groups (P < 0.001). SctO2 also correlated significantly with MAP (P < 0.001) and CO (P < 0.001) during propofol-remifentanil, but not sevoflurane (P = 0.4 and 0.5), anesthesia.
The main mechanism responsible for the hyperventilation-induced decrease in SctO2 is hypocapnia during both propofol-remifentanil and sevoflurane anesthesia. Hyperventilation-associated increase in MAP and decrease in CO during propofol-remifentanil, but not sevoflurane, anesthesia may also contribute to the decrease in SctO2 but to a much smaller degree.
PMCID: PMC3992996  PMID: 23278596
2.  Quantitative assessment of renal arterial occlusion in a porcine model using spatial frequency domain imaging 
Optics letters  2013;38(18):3566-3569.
We present the results of a feasibility study with spatial frequency domain imaging (SFDI) to produce quantitative measurements of optical property and chromophore concentration maps of three porcine kidneys utilizing a renal occlusion model at the near-infrared wavelengths of 658, 730, and 850 nm. Using SFDI, we examined the dynamics of absolute oxygen saturation (StO2). The mean StO2 for the kidneys varied from approximately 60% before occlusion, to 20% during occlusion, to 55% after reperfusion. We also present, for the first time to the best of our knowledge, reduced scattering coefficient (μs′) maps of the kidney during occlusion. We observed a substantial decrease in the wavelength dependence of scattering (i.e., scattering power) in the three kidneys, with a mean decrease of 18% ± 2.6%, which is indicative of an increase in scatterer size, and is likely due to tissue changes such as edema that follow from occlusion and inflammation.
PMCID: PMC3959861  PMID: 24104815
3.  Impact of phenylephrine administration on cerebral tissue oxygen saturation and blood volume is modulated by carbon dioxide in anaesthetized patients† 
BJA: British Journal of Anaesthesia  2012;108(5):815-822.
Multiple studies have shown that cerebral tissue oxygen saturation () is decreased after phenylephrine treatment. We hypothesized that the negative impact of phenylephrine administration on is affected by arterial blood carbon dioxide partial pressure () because CO2 is a powerful modulator of cerebrovascular tone.
In 14 anaesthetized healthy patients, i.v. phenylephrine bolus was administered to increase the mean arterial pressure ∼20–30% during hypocapnia, normocapnia, and hypercapnia. and cerebral blood volume (CBV) were measured using frequency domain near-infrared spectroscopy, a quantitative technology. Data collection occurred before and after each treatment.
Phenylephrine caused a significant decrease in during hypocapnia [=−3.4 (1.5)%, P<0.001], normocapnia [=−2.4 (1.5)%, P<0.001], and hypercapnia [=−1.4 (1.5)%, P<0.01]. Decreases in were significantly different between hypocapnia, normocapnia, and hypercapnia (P<0.001). Phenylephrine also caused a significant decrease in CBV during hypocapnia (P<0.01), but not during normocapnia or hypercapnia.
The negative impact of phenylephrine treatment on and CBV is intensified during hypocapnia while blunted during hypercapnia.
PMCID: PMC3325051  PMID: 22391890
carbon dioxide; cerebral blood volume; cerebral tissue oxygen saturation; modulation; phenylephrine
4.  Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients 
BJA: British Journal of Anaesthesia  2011;107(2):209-217.
How phenylephrine and ephedrine treatments affect global and regional haemodynamics is of major clinical relevance. Cerebral tissue oxygen saturation ()-guided management may improve postoperative outcome. The physiological variables responsible for changes induced by phenylephrine and ephedrine bolus treatment in anaesthetized patients need to be defined.
A randomized two-treatment cross-over trial was conducted: one bolus dose of phenylephrine (100–200 µg) and one bolus dose of ephedrine (5–20 mg) were given to 29 ASA I–III patients anaesthetized with propofol and remifentanil. , mean arterial pressure (MAP), cardiac output (CO), and other physiological variables were recorded before and after treatments. The associations of changes were analysed using linear-mixed models.
The CO decreased significantly after phenylephrine treatment [▵CO=−2.1 (1.4) litre min−1, P<0.001], but was preserved after ephedrine treatment [▵CO=0.5 (1.4) litre min−1, P>0.05]. The was significantly decreased after phenylephrine treatment [▵=−3.2 (3.0)%, P<0.01] but preserved after ephedrine treatment [▵=0.04 (1.9)%, P>0.05]. CO was identified to have the most significant association with (P<0.001). After taking CO into consideration, the other physiological variables, including MAP, were not significantly associated with (P>0.05).
Associated with changes in CO, decreased after phenylephrine treatment, but remained unchanged after ephedrine treatment. The significant correlation between CO and implies a cause–effect relationship between global and regional haemodynamics.
PMCID: PMC3136202  PMID: 21642644
cardiac output; cerebral tissue oxygen saturation; ephedrine; mean arterial pressure; phenylephrine
5.  Hemodynamic changes in rat leg muscles during tourniquet-induced ischemia-reperfusion injury observed by near-infrared spectroscopy 
Physiological measurement  2009;30(7):529-540.
In this study, we hypothesized that non-invasive continuous wave near-infrared spectroscopy (CWNIRS) can determine the severity or reversibility of muscle damage due to ischemia/reperfusion (I/R), and the results will be highly correlated with those from physical examination and histological analysis. To test this hypothesis, we performed CWNIRS measurements on two groups of male Sprague-Dawley rats (~400 g) that underwent 2 h (n = 6) or 3 h (n = 7) of pneumatic tourniquet application (TKA). Tissue oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] concentration changes were monitored during the 2 h or 3 h of 250 mmHg TKA and for an additional 2 h post-TKA. Rats were euthanized 24 h post-TKA and examined for injury, edema and viability of muscles. Contralateral muscles served as controls for each animal. In both groups, [HbO2] dropped immediately, then gradually decreased further after TKA and then recovered once the tourniquet was released. However, releasing after 2 h of TKA caused [HbO2] to overshoot above the baseline during reperfusion while the 3 h group continued to have lower [HbO2] than baseline. We found a significant correlation between the elapsed time from tourniquet release to the first recovery peak of [HbO2] and the muscle weight ratio between tourniquet and contralateral limb muscles (R = 0.86). Hemodynamic patterns from non-invasive CWNIRS demonstrated significant differences between 2 h and 3 h I/R. The results demonstrate that CWNIRS may be useful as a non-invasive prognostic tool for conditions involving vascular compromise such as extremity compartment syndrome.
PMCID: PMC2868521  PMID: 19436084
ischemia; reperfusion; edema; near-infrared spectroscopy; muscle hemodynamics
6.  In vivo water state measurements in breast cancer using broadband diffuse optical spectroscopy 
Physics in medicine and biology  2008;53(23):6713-6727.
Structural changes in water molecules are related to physiological, anatomical and pathological properties of tissues. Near infrared (NIR) optical absorption methods are sensitive to water, however detailed characterization of water in thick tissues is difficult to achieve because subtle spectral shifts can be obscured by multiple light scattering. In the NIR, a water absorption peak is observed around 975nm. The precise NIR peak shape and position is highly sensitive to water molecular disposition. We introduce a Bound Water Index (BWI) that quantifies shifts observed in tissue water absorption spectra measured by broadband Diffuse Optical Spectroscopy (DOS). DOS quantitatively measures light absorption and scattering spectra and therefore reveals bound-water spectral shifts. BWI as a water state index was validated by comparing broadband DOS to Magnetic Resonance Spectroscopy, diffusion-weighted MRI and conductivity in bound water tissue phantoms. Non-invasive DOS measurements of malignant and normal breast tissues performed in 18 subjects showed a significantly higher fraction of free water in malignant tissues (p<0.0001) compared to normal tissues. BWI of breast cancer tissues inversely correlated with Nottingham-Bloom-Richardson histopathology scores. These results highlight broadband DOS sensitivity to molecular disposition of water, and demonstrate the potential of BWI as a non-invasive in-vivo index that correlates with tissue pathology.
PMCID: PMC2586905  PMID: 18997265
7.  Minimally-invasive debulking of ovarian cancer in the rat pelvis by means of photodynamic therapy using the pegylated photosensitizer PEG-m-THPC 
British Journal of Cancer  1999;81(4):631-637.
Interstitial photodynamic therapy (PDT) using the pegylated photosensitizer PEG-m-THPC was evaluated as a minimally-invasive procedure to selectively debulk unrespectable pelvic ovarian cancer (NuTu-19) in immunocompetent rats. To assess tumour selectivity, PEG-m-THPC at dosages of 0.3, 3.0 and 30 mg kg−1 body weight was administered intravenously to 30 rats 4 weeks following tumour induction. Eight days later laser light at 652 nm and optical doses ranging from 100 to 900 J cm−1 diffuser-length was delivered by an interstitial cylindrical diffusing fibre inserted blindly into the pelvis. Three days following light application, the volume of necrosis was measured and the damage to pelvic organs was assessed histologically on cross sections. For analysis of survival, 20 tumour-bearing rats received PDT using drug doses of 3 or 9 mg kg−1 body weight and an optical dose of 900 J cm−1 diffuser-length, whereas ten untreated tumour-bearing rats served as controls. The histological assessment of PDT induced necrosis showed a non-linear dose–response for both the photosensitizer dose and the optical dose. The lowest drug dose activated with the highest optical dose did not induce more necrosis than seen in tumour-bearing control animals. The same optical dose induced necrosis of 17 mm in diameter using 30 mg kg−1 and 11 mm using 3 mg kg−1 photosensitizer. The optical threshold for induction of significant necrosis was between 100 and 300 J cm−1 diffuser-length for 30 mg kg−1 and between 300 and 500 J cm−1 for 3 mg kg−1 PEG-m-THPC. Significant damage to normal pelvic organs was only seen if 30 mg kg−1 photosensitizer was activated with optical doses of 700 J cm−1 or more. In the survival study, all treated animals survived PDT for at least 2 weeks and the intestinal and urinary tract remained functional. No clinical signs of blood vessel or nerve injury were observed. Mean overall survival of untreated tumour-bearing rats was 25.0 ± 4.5 days compared to 38.4 ± 3.8 days and 40.0 ± 3.6 days for rats treated with 3 mg kg−1 or 9 mg kg−1 PEG-m-THPC mediated PDT respectively (P < 0.05). We conclude that PEG-m-THPC mediated PDT has a favourable therapeutic window and that this minimally-invasive procedure can reduce pelvic cancer bulks effectively and selectively. © 1999 Cancer Research Campaign
PMCID: PMC2362885  PMID: 10574248
interstitial photodynamic therapy; ovarian cancer; PEG-m-THPC; minimally invasive; rat
8.  Non-invasive measurements of breast tissue optical properties using frequency-domain photon migration. 
A multiwavelength, high bandwidth (1 GHz) frequency-domain photon migration (FDPM) instrument has been developed for quantitative, non-invasive measurements of tissue optical and physiological properties. The instrument produces 300 kHz to 1 GHz photon density waves (PDWs) in optically turbid media using a network analyser, an avalanche photodiode detector and four amplitude-modulated diode lasers (674 nm, 811 nm, 849 nm, and 956 nm). The frequency of PDW phase and amplitude is measured and compared to analytically derived model functions in order to calculate absorption, mu a, and reduced scattering, mu s, parameters. The wavelength-dependence of absorption is used to determine tissue haemoglobin concentration (total, oxy- and deoxy- forms), oxygen saturation and water concentration. We present preliminary results of non-invasive FDPM measurements obtained from normal and tumour-containing human breast tissue. Our data clearly demonstrate that physiological changes caused by the presence of small (about 1 cm diameter) palpable lesions can be detected using a handheld FDPM probe.
PMCID: PMC1691955  PMID: 9232853

Results 1-8 (8)