Around 0.4% of pregnant women in England have chronic HBV infection and need services to prevent vertical transmission. In this national audit, sociodemographic, clinical and laboratory information was requested from all maternity units in England for HBsAg positive women initiating antenatal care in 2014. We describe these women's characteristics and indicators of access to/uptake of healthcare. of 2542 pregnancies in 2538 women, median maternal age was 31 [IQR 27, 35] years, 94% (1986/2109) were non-UK born (25% (228/923) having arrived into the UK

Evidence suggests children HIV-exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV-exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother-to-Child HIV Transmission Programme after Option B+ implementation (2014-2018). Anthropometry was measured at enrolment (age 1-6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) z-scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi-variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82-6.17]), which was modified by co-trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi-faceted health risks, alongside maternal ART prescription, and follow-up of mother-child pairs.

BACKGROUND: the UK National Screening Committee currently recommends against antenatal screening for Hepatitis C virus (HCV) infection in England due to lack of HCV prevalence data and treatment licensed for use in pregnancy. We aimed to produce regional and national estimates of the number and proportion of livebirths to HCV seropositive women in England in 2013 and 2018. METHODS: a logistic regression model fitted in the Bayesian framework estimated probabilities of HCV seropositivity among 24,599 mothers delivering in the North Thames area of England in 2012 adjusted by maternal age and region of birth. These probabilities were applied to the underlying population structures of women delivering livebirths in England in 2013 and 2018 to estimate the number of livebirths to HCV seropositive women in these years nationally and by region. The Bayesian approach allowed the uncertainty associated with all estimates to be properly quantified. RESULTS: Nationally, the estimated number of livebirths to women seropositive for HCV for England was 464 (95% credible interval [CI] 300-692) in 2013 and 481 (95%CI 310-716) in 2018, or 70.0 (95%CI 45.0-104.1) per 100,000 and 76.9 (95%CI 49.5-114.4) per 100,000 in these years respectively. Regions with the highest estimated number of livebirths to HCV seropositive women in 2013 and 2018 included London with 118.5 and 124.4 and the South East with 67.0 and 74.0 per 100,000 livebirths. CONCLUSION: Few previous studies have investigated HCV among pregnant women in England. These findings complement and supplement existing research by providing national and regional estimates for the number of livebirths to HCV seropositive women in England. Bayesian modelling allows future national and regional estimates to be produced and the associated uncertainty to be properly quantified.

Zika virus (ZIKV) is a vector-borne flavivirus with a known teratogenic effect, yet the full spectrum has not been delineated. Studies on endemic areas tried to characterize the clinical outcomes of ZIKV intrauterine exposure. We aimed to describe early neurodevelopmental outcomes on prenatally ZIKV-exposed children in a non-endemic ZIKV area. This is a prospective observational cohort study conducted from May 2016 to December 2021 at Hospital Universitari Vall d'Hebron in Barcelona, Catalonia, Spain. We monitored for up to 24 months 152 children extracted from a pregnant women cohort with suspected ZIKV infection; eleven women (11/150; 7.3%) fulfilled the criteria for a confirmed ZIKV infection. Among the 152 children included, we describe two cases of congenital ZIKV syndrome (CZS) born from women with a confirmed ZIKV infection. Additionally, we describe five cases of other potentially ZIKV-related outcomes (OPZROs), all with normal birth cranial circumference and born to women with probable ZIKV infection. The low exposed prevalence of adverse outcomes in asymptomatic children at birth in a non-endemic area suggests that close follow-up should be addressed by primary care pediatricians instead of pediatric specialists. Further studies are needed to assess the effects of ZIKV intrauterine exposure beyond two years of life.

Objective:Poor vascular health is associated with reduced bone strength and increased risk of fragility fracture. However, direct measurement of intraosseous vascular health is difficult due to the density and mineral content of bone. We investigated the feasibility of using a commercially available continuous wave near infrared spectroscopy (NIRS) system for the investigation of vascular haemodynamics in human bonein vivo.Approach:An arterial occlusion (AO) protocol was developed for obtaining haemodynamic measurements of the proximal tibia and lateral calf, including assessment of the protocol’s intra operator reproducibility. For 36 participants, intraosseous haemodynamics derived by NIRS were compared to alternative tests of bone health based on dual x-ray absorptiometry (DXA) testing and MRI.Main Results:Near infrared spectroscopy markers of haemodynamics of the proximal tibia demonstrated acceptable reproducibility, comparable with reproducibility assessments of alternative modalities measuring intraosseous haemodynamics, and the use of NIRS for measuring muscle. Novel associations have been demonstrated between haemodynamic markers of bone measured with NIRS and body composition and bone mineral density (BMD) measurements obtained with both DXA and MRI.Significance:Near infrared spectroscopy provides inexpensive, non-invasive, safe, and real time data on changes in oxygenated and deoxygenated haemoglobin concentration in bone at the proximal tibia. This study has demonstrated the potential for NIRS to contribute to research investigating the pathophysiological role of vascular dysfunction within bone tissue, but also the limitations and need for further development of NIRS technology.

The benefit of enhanced shear stress to the vascular endothelium has been well-documented in conduit arteries but is less understood in skin microcirculation. The aim of this study was to provide physiological evidence of the vascular changes in skin microcirculation induced by intermittent pneumatic compression (IPC) of 1 s cuff inflation (130 mmHg) every 20 s to the palm of the hand for 30 min. The oxygenation and hemodynamics of dorsal mid-phalangeal finger skin microcirculation were assessed by laser Doppler fluximetry and reflectance spectroscopy before, during, and after IPC in 15 young (18-39 years old) and 39 older (40-80 years old) controls and 32 older subjects with type 2 diabetes mellitus. Each individual cuff inflation induced: 1) brief surge in flux immediately after cuff deflation followed by 2) transitory reduction in blood oxygen for ∼4 s, and 3) a second increase in perfusion and oxygenation of the microcirculation peaking ∼11 s after cuff deflation in all subject groups. With no significant change in blood volume observed by reflectance spectroscopy, despite the increased shear stress at the observed site, this second peak in flux and blood oxygen suggests a delayed vasoactive response upstream inducing increased arterial influx in the microcirculation that was higher in older controls and subjects with diabetes compared to young controls (P < 0.001, P < 0.001, respectively) and achieving maximum capillary recruitment in all subject groups. Transitory hypoxic stimuli with conducted vasodilation may be a mechanism through which IPC enhances capillary perfusion in skin microcirculation independent of age and type 2 diabetes mellitus.NEW & NOTEWORTHY This study demonstrates that hand intermittent pneumatic compression evokes transitory hypoxic stimuli in distal finger skin microcirculation inducing vasodilation of arterial inflow vessels, enhanced perfusion, and maximum capillary recruitment in young and older subjects and older subjects with type 2 diabetes mellitus. Enhanced shear stress in the microcirculation did not appear to induce local skin vasodilation.

Non-melanoma skin cancer (NMSC) can be treated clinically using Photodynamic Therapy (PDT), a nurse-led treatment method which is an attractive alternative to invasive removal methods, which are currently common practice. PDT is significantly cheaper, easier for the patient and notably does not result in cosmetic damage. The treatment works by first applying a topical exogenous photosensitiser (PS) which is then selectively uptaken by malignant cells. The PS in the presence of molecular oxygen produces reactive oxygen species (ROS), which cause local cytotoxic damage, when exposed to light of an appropriate wavelength. Targeted removal of the lesion is achieved as the damaging ROS are localised to malignant cells, leaving healthy tissue relatively unharmed.
However, the efficacy of PDT is limited to thin (< 2mm) lesions. Penetration of activating light is limited by the optical properties of biological tissue, which are strongly scattering at the visible wavelengths typically used during PDT. Availability of molecular oxygen also may become a limiting factor during treatment, and the concentration of PpIX (the PS molecule) is not assumed to be uniformly distributed throughout the skin. The PpIX molecule itself forms part of a cell’s natural synthesis cycle, and so is naturally converted into Heam (the end product) when Iron (the other component) is available. Chelating agents (such as CP94) may also be topically applied to remove free iron from the local volume, suppressing the final step of Haem synthesis and allowing PpIX levels to accumulate.

Practical investigations into PDT are common, and the fundamental aspects of the reaction mechanism are well understood. Whilst clinical studies will always remain the final and most important stage of investigation, they are limited in terms of how many can be conducted, and what may ethically attempted in the first place. Measurement and analysis in a practical setting is also limited by the nature of reality making measurements in practice is usually an invasive procedure in and of itself. The end result is that detailed analysis of a system (beyond a limited number of scalar measurements) is not practically possible. Alternatively, numerical methods allow us to form the well understood details of the system the reaction mechanisms and the way in which species travel throughout the system and structure them into a model which we can continuously measure (with omnipotence) as it evolves through simulated time. After calibration, simulations (the product of the numerical method and the model) allow us to run experiments beyond those that can be conducted practically. The detailed output of these simulations may then be used to investigate the inner dynamics of the system, which in turn lead to better informed treatment plans in future practice.

This thesis concerns the development of a novel library of code (completely documented) which provides the framework for several simulations and tools, which themselves are capable of simulating the entire PDT system in a fully three-dimensional skin model. The PDT mechanism is a complex processes which requires modelling of chemical interactions and diffusion, as well as light scattering in turbid media. The three of these mechanisms require different simulation methodologies, and must all interact fluidly with one another and the underlying input model. These simulations should also scalable, capable of running a complete model within an hour on a clinic laptop, up to HPC workstations with high-core CPUs and substantially more memory which can produce highly-resolved data for detailed analysis. Altogether these tools can be used to create a complete virtual laboratory, which simulates the PDT treatment process in its entirety, supporting the investigation into how PDT may be improved in general practice. Parameterisation of the model is straightforward and simple to update as empirical values are refined. Furthermore, if a patients particular presentation can be measured to a high enough level of fidelity then a model can be parameterised specifically for their unique case opening the door to informed personalised medicine.
Source code and parameterisations are presented alongside the written document of the thesis, and can be downloaded here. Details of what’s happening will be discussed in context during the later chapters, but for the impatient running the Bash script in the /input folder will first download the dependencies (NetCDF, HDF5 and the Rust compiler), and then proceed to produce all data afresh under the /output directory.

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in short: first we will explore the pathology and histology of NMSC, and the benefits PDT offers as a method of treatment and how it operates on a biological, chemical and physical level. Secondly, the theory behind each of the numerical methods utilised is described and explored such that a future researcher could derive even better software without viewing any of the presented code. Thirdly, the implementation of these numerical methods within the general arctk library is then discussed, before being composed into the numerical software tools which are actually used to realise a set of novel results. The fourth chapter explicitly walks through how each of the tools may be parameterised and combined into a complete pipeline which models the standard PDT protocol for a selection of tumours of different penetrating depths. Chapter five subsequently applies these tools in a photo-thermal (PTT) setting, investigating how surface tumours may be treated using gold nanorods (GNRs) to locally modify the absorption optical properties of a lesion such that exposure to thermal photons induces hyperthermal cell death. Chapter six investigates how the standard PDT method may be improved to allow treatment of thicker lesions, how the light source may be modified spectrally to increase efficacy at depth, how fibre optics may be introduced to increase light fluence at depth, and how chelating agents may be used to increase the threshold concentration of PpIX within the skin, resulting in increased ROS generation at depth. Finally chapter seven will discuss some of the other ways that the arctk library is currently being used in research with Jeynes’ investigations into PTT, Moran using Raman spectroscopy to develop a non-invasive method of breast cancer detection, and Morell using the MCRT tool to determine the impact of artificial light on ecology. We will then conclude with some remarks on how machine learning, in particular Gaussian processes, may be used to better chart the parameter space which simulations allow us to explore in the first place.
To the best of our knowledge, no prior work has captured the skin model geometry and the evolution of constituent chemical species to the same level of detail as presented within this work. The numerical methods detailed allow for a robust and extensive investigation of the problem, and the software implementation enables results to be computed within relatively short timescales, something which has also not been previously achieved. The results of these simulations provide significant contributions to the state of medical physics as they allow us to quantify the impacts of an altered treatment method, in an accurate

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and repeatable manner.

KEY POINTS: the vasodilatory response to reactive hyperaemia is impaired with advancing age, but it is unclear whether this is because of an altered wall shear rate (WSR) stimulus or an altered flow-mediated dilatation (FMD) response. Using new technology that allows detailed WSR measurement, we assessed the WSR-FMD response in healthy older people. Our data show that older people have a markedly altered and diminished WSR response to reactive hyperaemia compared to young people, but reduced WSR alone does not fully explain reduced FMD. In young people, WSR appears to be coupled to FMD but, by age ∼65 years, the arterial vasodilatory response has begun to uncouple from the WSR stimulus. These findings point to the importance and utility of comprehensively characterizing the WSR-FMD response when using reactive hyperaemia to assess vascular function, as well as giving new insight into the age-related alteration in vascular function. ABSTRACT: the vasodilatory response to reactive hyperaemia is impaired with age, but it is unknown whether this is because of an altered wall shear rate (WSR) stimulus or an altered flow-mediated dilatation (FMD) response to the WSR stimulus. Inherent difficulties in measuring blood flow velocity close to the arterial wall have prevented detailed assessment of the WSR-FMD response. Using an enhanced multigate spectral Doppler ultrasound system (ultrasound advanced open platform), we aimed to produce new data on the WSR-FMD relationship in healthy older adults. Sixty healthy people, comprising 28 young (27.5 ± 5.5 years) and 32 older (64.9 ± 3.7 years) individuals, underwent FMD assessment. Raw data were post-processed using custom-designed software to obtain WSR and diameter parameters. The data revealed that older people have a much altered and diminished WSR response to reactive hyperaemia compared to younger people [e.g. WSR peak: 622 (571-673) vs. 443 (396-491) 1/s in young and older respectively; P 

Wall shear rate (WSR) is an important stimulus for the brachial artery flow-mediated dilation (FMD) response. However, WSR estimation near the arterial wall by conventional Doppler is inherently difficult. To overcome this limitation, we utilized multigate Doppler to accurately determine the WSR stimulus near the vessel wall simultaneously with the FMD response using an integrated FMD system [Ultrasound Advanced Open Platform (ULA-OP)]. Using the system, we aimed to perform a detailed analysis of WSR-FMD response and establish novel WSR parameters in a healthy young population. Data from 33 young healthy individuals (27.5 ± 4.9 yr, 19 females) were analyzed. FMD was assessed with reactive hyperemia using ULA-OP. All acquired raw data were postprocessed using custom-designed software to obtain WSR and diameter parameters. The acquired velocity data revealed that nonparabolic flow profiles within the cardiac cycle and under different flow states, with heterogeneity between participants. We also identified seven WSR magnitude and four WSR time-course parameters. Among them, WSR area under the curve until its return to baseline was the strongest predictor of the absolute ( R2 = 0.25) and percent ( R2 = 0.31) diameter changes in response to reactive hyperemia. For the first time, we identified mono- and biphasic WSR stimulus patterns within our cohort that produced different magnitudes of FMD response [absolute diameter change: 0.24 ± 0.10 mm (monophasic) vs. 0.17 ± 0.09 mm (biphasic), P < 0.05]. We concluded that accurate and detailed measurement of the WSR stimulus is important to comprehensively understand the FMD response and that this advance in current FMD technology could be important to better understand vascular physiology and pathology. NEW & NOTEWORTHY an estimation of wall shear rate (WSR) near the arterial wall by conventional Doppler ultrasound is inherently difficult. Using a recently developed integrated flow-mediated dilation ultrasound system, we were able to accurately estimate WSR near the wall and identified a number of novel WSR variables that may prove to be useful in the measurement of endothelial function, an important biomarker of vascular physiology and disease.

AIMS: Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular risk and diabetes independent of obesity. We investigated whether adipose tissue dysfunction is exacerbated due to increased tissue hypoxia. METHODS: Adipose tissue (AT) oxygenation was measured with a Clarke-type electrode (pATO2) in 16 men with OSAS before and after 4 months of continuous positive airway pressure therapy (CPAP) and in BMI-matched controls. Oxygenation was simultaneously monitored in arterial blood by pulse oximetry (SaO2); mixed blood in AT microcirculation by reflectance spectroscopy (SATO2) along with blood flow. Markers of hypoxia, adipo- and angiogenesis, inflammation and fibrosis were analysed in AT and serum. RESULTS: OSAS subjects were more insulin resistant. Despite lower arterial SaO2 (95.4±1.3% vs. 97.1±1.6%, P=0.013) in subjects with OSAS, there was no difference in the oxygen content of AT microcirculation (61.6±18.4 vs. 72.2±7.0%, P=0.07) or pATO2 (49.2±7.5 vs. 50.4±14.7mmHg, P=0.83) between groups. Resting AT blood flow was higher in OSAS compared to controls (108.5±22.7 vs. 78.9±24.9au, P

Background: Mildly elevated lactate levels (i.e. 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. Methods: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. Results: in 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). Conclusions: in a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. Trial registration: ClinicalTrials.gov, NCT01179243. Registered on August 3, 2010.

Oxygen extraction (OE) by all cells is dependent on an adequate supply of oxygen in proximal blood vessels and the cell's need and ability to uptake that oxygen. Here the role of blood flow in regulating OE in skin and skeletal muscle was investigated in lean and obese men. OE was derived by two optical reflectance spectroscopy techniques: 1) from the rate of fall in mean blood saturation during a 4 min below knee arterial occlusion, and thus no blood flow, in calf skin and skeletal muscle and 2) in perfused, unperturbed skin, using the spontaneous falls in mean blood saturation induced by vasomotion in calf and forearm skin of 24 subjects, 12 lean and 12 obese. OE in perfused skin was significantly higher in lean compared with obese subjects in forearm (Mann-Whitney, P < 0.004) and calf (P < 0.001) and did not correlate with OE in unperfused skin (ρ = -0.01, P = 0.48). With arterial occlusion and thus no blood flow, skin OE in lean and obese subjects no longer differed (P = 0.23, not significant). In contrast in skeletal muscle with arterial occlusion and no blood flow, the difference in OE between lean and obese subjects occurred, with obese subjects exhibiting significantly higher OE (P < 0.012). The classic model of metabolic blood flow regulation to support oxygen extraction is evident in perfused skin; OE is perturbed without blood flow and reduced in obesity. In resting skeletal muscle other mechanism(s), independent of blood flow, are implicated in oxygen extraction.

OBJECTIVE: We have previously described a distinct abnormality in the cutaneous microcirculation that is characterized by an abnormal reperfusion response following an ischemic stimulus. We investigated the physiological significance of this abnormality; by measuring microvascular perfusion and blood oxygen saturation in groups stratified by three distinct reperfusion responses. METHODS: Cutaneous microvascular reperfusion after four minutes of arterial occlusion above the ankle was measured on the foot using laser Doppler fluximetry and optical reflectance spectroscopy in almost 400 adults. Individuals were stratified into three groups according to the microvascular reperfusion response: normal and two abnormal patterns (DEP and NDEP). RESULTS: Our main findings were that abnormal microvascular reperfusion responses (DEP and NDEP) had a higher baseline oxygen saturation (p = 0.005), a lower plateau in oxygen saturation (p < 0.0001 and

Objectives: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. Design: Multicenter observational point prevalence study. Setting: the Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. Patients: a heterogeneous ICU population consisting of 501 patients. Interventions: None. Measurements and Main Results: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. Conclusions: in a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.

Methyl aminolevulinate photodynamic therapy (MAL-PDT) (a topical treatment used for a number of precancerous skin conditions) utilizes the combined interaction of a photosensitizer (protoporphyrin IX (PpIX)), light of the appropriate wavelength, and molecular oxygen to produce singlet oxygen and other reactive oxygen species which induce cell death. During treatment, localized oxygen depletion occurs and is thought to contribute to decreased efficacy. The aim of this study was to investigate whether an oxygen pressure injection (OPI) device had an effect on localized oxygen saturation levels and/or PpIX fluorescence of skin lesions during MAL-PDT. This study employed an OPI device to apply oxygen under pressure to the skin lesions of patients undergoing standard MAL-PDT. Optical reflectance spectrometry and fluorescence imaging were used to noninvasively monitor the localized oxygen saturation and PpIX fluorescence of the treatment area, respectively. No significant changes in oxygen saturation were observed when these data were combined for the group with OPI and compared to the group that received standard MAL-PDT without OPI. Additionally, no significant difference in PpIX photobleaching or clinical outcome at 3 months between the groups of patients was observed, although the group that received standard MAL-PDT demonstrated a significant increase (p < 0.05) in PpIX fluorescence initially and both groups produced a significant decrease (p < 0.05) after light irradiation. In conclusion, with this sample size, this OPI device was not found to be an effective method with which to improve tissue oxygenation during MAL-PDT. Further investigation is therefore required to find a more effective method of MAL-PDT enhancement. © 2012 Springer-Verlag London Ltd.

Methyl aminolevulinate photodynamic therapy (MAL-PDT) (a topical treatment used for a number of precancerous skin conditions) utilizes the combined interaction of a photosensitizer (protoporphyrin IX (PpIX)), light of the appropriate wavelength, and molecular oxygen to produce singlet oxygen and other reactive oxygen species which induce cell death. During treatment, localized oxygen depletion occurs and is thought to contribute to decreased efficacy. The aim of this study was to investigate whether an oxygen pressure injection (OPI) device had an effect on localized oxygen saturation levels and/or PpIX fluorescence of skin lesions during MAL-PDT. This study employed an OPI device to apply oxygen under pressure to the skin lesions of patients undergoing standard MAL-PDT. Optical reflectance spectrometry and fluorescence imaging were used to noninvasively monitor the localized oxygen saturation and PpIX fluorescence of the treatment area, respectively. No significant changes in oxygen saturation were observed when these data were combined for the group with OPI and compared to the group that received standard MAL-PDT without OPI. Additionally, no significant difference in PpIX photobleaching or clinical outcome at 3 months between the groups of patients was observed, although the group that received standard MAL-PDT demonstrated a significant increase (p

Vasomotion is defined as a spontaneous local oscillation in vascular tone whose function is unclear but may have a beneficial effect on tissue oxygenation. Optical reflectance spectroscopy and laser Doppler fluximetry provide unique insights into the possible mechanisms of vasomotion in the cutaneous microcirculation through the simultaneous measurement of changes in concentration of oxyhemoglobin ([HbO(2)]), deoxyhemoglobin ([Hb]), and mean blood saturation (S(mb)O(2)) along with blood volume and flux. The effect of vasomotion at frequencies 29.3°C (X(2) = 6.19, P < 0.02). A consistent minimum threshold in S(mb)O(2) (mean: 39.4%, range: 24.0-50.6%) was seen to precede a sudden transient surge in flux, inducing a fast rise in S(mb)O(2). The integral increase in flux correlated with the integral increase in [HbO(2)] (Pearson's correlation r(2) = 0.50, P < 0.001) and with little change in blood volume suggests vasodilation upstream, responding to a low S(mb)O(2) downstream. This transient surge in flux was followed by a sustained period where blood volume and flux remained relatively constant and a steady decrease in [HbO(2)] and equal and opposite increase in [Hb] was considered to provide a measure of oxygen extraction. A measure of this oxygen extraction has been approximated by the mean half-life of the decay in S(mb)O(2) during this period. A comparison of the mean half-life in the 8 normal subjects [body mass index (BMI) 29.5 kg/m(2)) of 18.8 s was statistically significant (Mann Whitney, P < 0.004). The S(mb)O(2) fluctuated spontaneously in this saw tooth manner by an average of 9.0% (range 4.0-16.2%) from mean S(mb)O(2) values ranging from 30 to 52%. These observations support the hypothesis that red blood cells may act as sensors of local tissue hypoxia, through the oxygenation status of the hemoglobin, and initiate improved local perfusion to the tissue through hypoxic vasodilation.

A noninvasive method of measuring hemoglobin flow through an organ by near-infrared spectroscopy (NIRS) is described that allows blood flow to be calculated. The method is derived from the Fick principle and uses a small change in arterial oxyhemoglobin concentration (brought about by a change in the fractional inspired O2 concentration) as an intravascular tracer. Changes in deoxyhemoglobin and oxyhemoglobin concentrations are quantified by monitoring variations in the absorption of near-infrared light in the organ, thus providing a measure of tracer accumulation. The tracer input function is calculated from the change in arterial O2 saturation, measured by pulse oximetry. The method was used to determine hemoglobin flow in the forearms of six healthy young adults on 10 occasions. Forearm hemoglobin flow ranged from 22.5 to 82.6 mumol.l-1.min-1. Calculated forearm blood flow ranged from 1.01 to 4.01 ml.100 g-1.min-1. For comparison, forearm blood flow was measured by venous occlusion plethysmography, and the relation between flow calculated by NIRS (y) and plethysmography (x) was y = 0.93x + 0.30 (r2 = 0.95). The mean difference between the methods was 0.14 ml.100 g-1.min-1. The technique may be widely applicable.

Near infrared spectroscopy was used to investigate the effects of intravenously administered indomethacin (0.1-0.2 mg/kg) on cerebral haemodynamics and oxygen delivery in 13 very preterm infants treated for patent ductus arteriosus. 7 infants received indomethacin by rapid injection (30 s) and 6 by slow infusion (20-30 min). In all the infants cerebral blood flow, oxygen delivery, blood volume, and the reactivity of blood volume to changes in arterial carbon dioxide tension fell sharply after indomethacin. There were no differences in the effects of rapid and slow infusion. These falls in cerebral oxygen delivery and the disruption of cerebrovascular control might compromise cellular oxygen availability, particularly in regions of the brain where the arterial supply is precarious. Care should be taken to ensure that oxygen delivery is optimum before the administration of indomethacin to preterm infants.

Current methods for measuring cerebral blood volume (CBV) in newborn infants are unsatisfactory. A new method is described in which the effect of a small change (5-10%) in arterial oxygen saturation (SaO2) on cerebral oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] concentration is observed by near-infrared (NIR) spectroscopy. Previous experiments in which the NIR absorption characteristics of HbO2 and Hb and the pathlength of NIR light through the brain were defined allowed changes in [HbO2] and [Hb] to be quantified from the Beer-Lambert law. It is shown here that CBV can then be derived from the expression CBV = (delta[HbO2] - delta[Hb])/(2. delta SaO2.H.R.), where H is the large vessel total hemoglobin concentration and R to the cerebral-to-large vessel hematocrit ratio. Observations on 12 newborn infants with normal brains, born at 25-40 wk of gestation and aged 10-240 h, gave a mean value for CBV of 2.22 +/- 0.40 (SD) ml/100 g, whereas mean CBV was significantly higher 3.00 +/- 1.04 ml/100 g in 10 infants with brain injury born at 24 to 42 wk of gestation and aged 4-168 h (P less than 0.05).

The results of near infrared spectroscopy in eight patients with osteoradionecrosis of the mandible are presented. These suggest that sites of osteoradionecrosis may be marked by decreased amounts of deoxygenated haemoglobin. The advantages and potential of near infrared spectroscopy are discussed but the technique requires further refinement.

A new method of quantifying cerebral blood flow which allows repeated cotside measurements is described. 31 observations were made on nine ill, mostly very preterm, infants. Cerebral blood flow was usually about 18 ml.100 g-1.min-1, but ranged from 7 ml.100g-1.min-1 (after the administration of indomethacin to a very preterm infant) to 33 ml.100 g-1.min-1 in a birth-asphyxiated post-term infant.

Event-related potentials particularly the P3 component have been noted to be abnormal in illnesses affecting cognitive processes, such as dementia. The relationship between the P3 latency and objective tests of mental function in patients with Alzheimer's disease and vascular dementia has been studied. A significant correlation was demonstrated between P3 latency and automated psychometric tests in patients with Alzheimer's disease.