Noninvasive determination of the optical properties of adult brain: near-infrared spectroscopy approach

The basic parameters for physiological measurements provided by near-infrared spectroscopy are the local absorption and scattering coefficients. For the adult human head, they have been difficult to measure noninvasively because of the layered structure of the head. The results of measurements of absorption and reduced scattering coefficients through the forehead on 30 adult volunteers using a multidistance frequency domain method are reported. The optode separation distance ranged from 10 to 80 mm and measurements were recorded at 758 and 830 nm. The measured absorption and reduced scattering coefficients of the forehead were used to evaluate the hemoglobin content in the scalp and brain as well as cerebral oxygen saturation. We found that cerebral oxygenation was relatively narrowly distributed within the subject group (the standard deviation was about 3% for scalp and 6% for brain, respectively), whereas hemoglobin concentrations had a relatively broader distribution. We found that as the optode distance increased, the absorption coefficients increased and the scattering coefficients decreased, retrieving the optical values of scalp and brain for shorter and longer optode distances, respectively. We present the transition curves of the absorption and reduced scattering coefficients as functions of the optode distance. In order to verify the values for each layer, a comparison between the experimental data and a prediction based on the two-layer model of the adult head was carried out. The thicknesses of scalp and skull for the two-layer model were obtained by magnetic resonance imaging of a subject's head. The optical parameters obtained from the two-layer model agreed very well with those measured by the multidistance method

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Optimization of the signal-to-noise ratio of frequency-domain instrumentation for near-infrared spectro-imaging of the human brain.

Frequency-domain near-infrared spectro-imaging offers significant advantages over the continuous-wave method in human brain applications. However, the drawback of existing instruments is a low signal-to-noise ratio for measured phase and modulation depth changes caused by cerebral activation. In this paper we show that in the case of the geometry specific for the activated area in the human brain, the SNR can be significantly improved by increasing the modulation frequency. We present the results of two studies: one performed experimentally using a subnanosecond pulsed light source and a spherical absorbing inhomogeneity immersed in a highly scattering solution, and the other performed numerically using Monte Carlo simulations of light transport in an MRI based digital phantom of the adult human head. We show that changes caused by the absorbing inhomogeneity in both phase and modulation depth increase with frequency and reach maximum values at frequencies between 400 and 1400 MHz, depending on the particular source-detector distance. We also show that for the human head geometry an increase of the modulation frequency from 100 to 500 MHz can increase the phase SNR 2-3 times, and the modulation depth SNR up to 10 times

The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal.

To study the behavior of cerebral physiological parameters and to further the understanding of the functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) effect, multisource frequency-domain near-infrared and BOLD fMRI signals were recorded simultaneously during motor functional activation in humans. From the near-infrared data information was obtained on the changes in cerebral blood volume and oxygenation. To relate our observations to changes in cerebral blood flow the well-known "balloon" model was employed. Our data showed that the deoxyhemoglobin concentration is the major factor determining the time course of the BOLD signal. The increase in cerebral blood oxygenation during functional activation is due to an increase in the velocity of blood flow, and occurs without significant swelling of the blood vessels