Revealing how maltodextrin-containing droplets dry using optical coherence tomography.

Properties of powders produced from drying solute-containing droplets arise from the dynamic redistribution of solute during drying. While insights on the dynamic redistribution are instrumental for the rational design of powders and for the optimized operation of equipment such as spray dryers, experimental techniques that allow measuring the spatio-temporal concentration of solute in drying droplets are scarce. In this work, we explore and demonstrate the use of optical coherence tomography (OCT) to measure the spatio-temporal concentration of solute in drying droplets and the development of a solidifying shell at the liquid-air interface, using aqueous droplets of maltodextrin as a model system. This work provides a solid foundation for the use of OCT to quantify the dynamic redistribution of solute and link it to the development of the morphology of the produced particles and agglomerates.

Fatigue, not self-rated motor symptom severity, affects quality of life in functional motor disorders.

While fatigue is found to be an impairing symptom in functional motor disorders (FMD) in clinical practice, scientific evidence is lacking. We investigated fatigue severity and subtypes in FMD compared to organic neurological disease. Furthermore, the role of fatigue within FMD and its impact on quality of life and self-rated health were investigated. Data from 181 patients participating in the self-help on the internet for functional motor disorders, randomised Trial were included. Data from 217 neurological controls with neuromuscular disorders (NMD) originated from a historical cohort. Fatigue was measured using the checklist individual strength (CIS). Motor symptom severity, depression and anxiety were correlated to fatigue. For multivariable regression analyses, physical functioning and pain were additionally taken into account. Severe fatigue was, respectively, present in 78 and 53% of FMD and NMD patients (p < 0.001). FMD patients scored higher than NMD patients on all fatigue subdomains (p < 0.001). In the FMD group, fatigue subdomains were correlated to depression, anxiety and partly to motor symptom severity. Quality of life was negatively associated with fatigue [OR 0.93 (0.90-0.96), p < 0.001] and depression [OR 0.87 (0.81-0.93), p < 0.001], but not self-rated motor symptom severity. Self-rated health was negatively associated with fatigue [OR 0.92 (0.88-0.96), p < 0.001] and pain [OR 0.98 (0.97-0.99), p < 0.001]. Fatigue was found to be a prevalent problem in FMD, more so than in organic neurological disease. It significantly affected quality of life and self-rated health, while other factors such as motor symptom severity did not. Fatigue should be taken into account in clinical practice and treatment trials.

Transmission optical coherence tomography based measurement of optical material properties.

We present transmission optical coherence tomography (transmission OCT) as a versatile tool to measure optical material properties of turbid media. The transmission OCT signal is described in detail and it is demonstrated how the group refractive index (n(g)), group velocity dispersion (GVD) and optical attenuation can be determined from this signal. We experimentally validate the refractive index properties of glasses, liquids and glucose water solutions in terms of n(g) and GVD. Measurements of scattering coefficients are determined using transmission OCT for suspensions of silica particles. Quantitative agreement is obtained with a dependent scattering model, both for the average as well as the wavenumber resolved optical attenuation coefficient. Good agreement is observed between our measurements and literature values.

Dependent and multiple scattering in transmission and backscattering optical coherence tomography.

We use transmission and backscattering optical coherence tomography (OCT) to distinguish and quantify dependent and multiple scattering effects in turbid media. With transmission OCT the dependent scattering coefficients for a range of monodisperse silica particle suspensions are determined. An excellent agreement is observed between the measured dependent scattering coefficients and calculations based on Mie calculations, the Percus-Yevick radial distribution function, and coherent light scattering theory. Backscattering OCT measurements are fitted using the extended Huygens-Fresnel (EHF) model with the dependent scattering coefficients obtained from the transmission OCT measurements as input parameters. Good agreement between the EHF model and the backscattering OCT measurements is observed. For large particles, the rms scattering angle θrms obtained from the EHF fit is in fair agreement with θrms calculated from the transmission OCT data.

Integrated-optics-based swept-source optical coherence tomography.

We designed, fabricated, and characterized an integrated-optics-based swept-source optical coherence tomography (SS-OCT) system in TriPleX technology. An external 1300 nm swept source is coupled to the chip, which contains waveguide structures for interferometric depth ranging and balanced detection. The complete OCT chip has a footprint of 0.4 cm × 1.8 cm. Light from the chip is focused onto the sample using an aspheric lens; the lateral resolution is 21±1 µm. OCT measurements, performed with a moveable mirror, demonstrate a sensitivity of -80 dB and imaging up to the maximum depth of 5.09 mm. Corrected for dispersion, the measured OCT axial resolution of 12.7±0.5 µm is in good agreement with the bandwidth limited resolution. Finally, we demonstrate cross-sectional OCT imaging of a multilayered tissue phantom over the whole depth range with the integrated-optics-based SS-OCT system.

Multiple scattering effects in Doppler optical coherence tomography of flowing blood.

We investigate the effect of multiple scattering on the optical coherence tomography (OCT) signal and the Doppler OCT signal of flowing blood. Doppler OCT measurements at 1300 nm are performed on flowing diluted porcine blood with hematocrit ranging between 0% and 15%. Measured blood hematocrit and mean red blood cell volume are used to calculate, using the discrete dipole approximation model, the (single) scattering coefficient and scattering anisotropy of blood. Monte Carlo simulations, based on the calculated scattering coefficients and scattering anisotropies, are compared to Doppler OCT measurements for hematocrit smaller than 10%. Good quantitative agreement between Doppler OCT measurements and Monte Carlo simulations is observed. Our measurements, calculations and simulations explain the relatively low attenuation coefficients and well preserved flow profiles measured with Doppler OCT for flowing blood. Monte Carlo simulations demonstrate the effect of the scattering anisotropy of the medium on the strength of multiple scattering effects in Doppler OCT signals. With increasing scattering anisotropy the OCT attenuation decreases; the distortion of the flow profile is strongest at intermediate scattering anisotropies (≈0.6).

Determination of the scattering anisotropy with optical coherence tomography.

In this work we demonstrate measurements with optical coherence tomography (OCT) of the scattering phase function in the backward direction and the scattering anisotropy parameter g. Measurements of the OCT attenuation coefficient and the backscattering amplitude are performed on calibrated polystyrene microspheres with a time-domain OCT system. From these measurements the phase function in the backward direction is determined. The measurements are described by the single scattering model and match Mie calculations very well. Measurements on Intralipid demonstrate the ability to determine the g of polydisperse samples and, for Intralipid, g = 0.35 ± 0.03 is measured, which is well in agreement with g from literature. These measurements are validated using the Intralipid particle size distribution determined from TEM measurements. Measurements of g and the scattering phase function in the backward direction can be used to monitor changes in backscattering, which can indicate morphological changes of the sample or act as contrast enhancement mechanism.

Multiple and dependent scattering effects in Doppler optical coherence tomography.

Doppler optical coherence tomography (OCT) is a technique to image tissue morphology and to measure flow in turbid media. In its most basic form, it is based on single (Mie) scattering. However, for highly scattering and dense media multiple and concentration dependent scattering can occur. For Intralipid solutions with varying scattering strength, the effect of multiple and dependent scattering on the OCT signal attenuation and Doppler flow is investigated. We observe a non-linear increase in the OCT signal attenuation rate and an increasingly more distorted Doppler OCT flow profile with increasing Intralipid concentration. The Doppler OCT attenuation and flow measurements are compared to Monte Carlo simulations and good agreement is observed. Based on this comparison, we determine that the single scattering attenuation coefficient micros is 15% higher than the measured OCT signal attenuation rate. This effect and the distortion of the measured flow profile are caused by multiple scattering. The non-linear behavior of the single scattering attenuation coefficient with Intralipid concentration is attributed to concentration dependent scattering.

Path-length-resolved diffusive particle dynamics in spectral-domain optical coherence tomography.

We describe a new method to measure the decorrelation rate of the optical coherence tomography (OCT) magnitude simultaneously in space and time. We measure the decorrelation rate of the OCT magnitude in a Fourier-domain OCT system for a large range of translational diffusion coefficients by varying the sphere diameter. The described method uses the sensitivity advantage of Fourier-domain OCT over time-domain OCT to increase the particle diffusion imaging speed by a factor of 200. By coherent gating, we reduce the contribution of multiple scattering to the detected signal, allowing a quantitative study of diffusive particle dynamics in high concentration samples. We demonstrate that this technique is well suited to image diffusive particle dynamics in samples with a complex geometry as we measure the morphology and diffusive particle dynamics simultaneously with both high spatial and high temporal resolution.

Quantitative comparison of the OCT imaging depth at 1300 nm and 1600 nm.

One of the present challenges in optical coherence tomography (OCT) is the visualization of deeper structural morphology in biological tissues. Owing to a reduced scattering, a larger imaging depth can be achieved by using longer wavelengths. In this work, we analyze the OCT imaging depth at wavelengths around 1300 nm and 1600 nm by comparing the scattering coefficient and OCT imaging depth for a range of Intralipid concentrations at constant water content. We observe an enhanced OCT imaging depth for 1600 nm compared to 1300 nm for Intralipid concentrations larger than 4 vol.%. For higher Intralipid concentrations, the imaging depth enhancement reaches 30%. The ratio of scattering coefficients at the two wavelengths is constant over a large range of scattering coefficients and corresponds to a scattering power of 2.8 ± 0.1. Based on our results we expect for biological tissues an increase of the OCT imaging depth at 1600 nm compared to 1300 nm for samples with high scattering power and low water content.

Purcell-factor-enhanced scattering from Si nanocrystals in an optical microcavity.

Scattering processes in an optical microcavity are investigated for the case of silicon nanocrystals embedded in an ultra-high-Q toroid microcavity. Using a novel measurement technique based on the observable mode splitting, we demonstrate that light scattering is highly preferential: more than 99.8% of the photon flux is scattered into the original doubly degenerate cavity modes. The large capture efficiency is shown to result from the Purcell enhancement of the optical density of states over the free space value, an effect that is more typically associated with spontaneous emission. The experimentally determined Purcell factor has a lower bound of 171.

Effects of training and albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy.

BACKGROUND: We recently reported a randomised controlled trial on the efficacy of strength training and the beta2-adrenergic agonist albuterol in patients with facioscapulohumeral muscular dystrophy (FSHD). Strength training and albuterol appeared safe interventions with limited positive effect on muscle strength and volume. We concurrently explored the prevalence and the characteristics of pain and fatigue in the participating FSHD patients, because these are probably underreported but clinically relevant symptoms in this disorder. Next, we studied the effects of albuterol and strength training on pain, experienced fatigue, health-related functional status and psychological distress. METHODS: Sixty-five patients were randomised to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks, albuterol (sustained-release, 8 mg bid) was added in a randomised, double-blind, placebo-controlled design. Outcomes comprised self-reported pain, experienced fatigue, functional status and psychological distress obtained with validated questionnaires at 52 weeks. RESULTS: Eighty percent of patients reported chronic persistent or periodic, multifocal pains. Thirty-four percent of the participants were severely fatigued. Strength training and albuterol failed to have a significant effect on all outcomes. CONCLUSIONS: Pain and fatigue are important features in FSHD. Strength training and albuterol do not have a positive or negative effect on pain, experienced fatigue, functional status and psychological distress.

Psychiatric disorders appear equally in patients with myotonic dystrophy, facioscapulohumeral dystrophy, and hereditary motor and sensory neuropathy type I.

OBJECTIVES: To study the presence of psychiatric comorbidity assessed by the use of a structured clinical interview and self-reported questionnaires in a large sample of patients with adult-onset myotonic dystrophy (DM), facioscapulohumeral muscular dystrophy (FSHD), and hereditary motor and sensory neuropathy type I (HMSN-I), and to assess whether psychiatric comorbidity is related to fatigue severity and/or muscle strength. METHODS: In a cohort of 217 patients with a neuromuscular disorder (79 DM, 65 FSHD and 73 HMSN-I patients) overall psychiatric comorbidity was studied cross-sectionally with the structured clinical interview for DSM-IV axis I disorders. Self-reported psychopathology, fatigue severity and muscle strength were assessed with the Beck Depression Inventory, Symptom Checklist-90, General Health Questionnaire-12, Checklist Individual Strength and muscle strength [Medical Research Council (MRC)-scale]. RESULTS: In all three neuromuscular disorders (DM, FSHD and HMSN), 10-12% of the patients met DSM IV clinical criteria for current psychiatric disorders. Lifetime psychiatric disorders were found in 32% of patients in all three patient groups. The most common psychiatric disorders were depression and phobias. A comparison of patients with and without current psychiatric disorder showed that fatigue severity and muscle strength (MRC) were not related to psychiatric comorbidity. CONCLUSION: Psychiatric disorders appear equally in patients with DM, FSHD and HMSN-I and are not related to fatigue or muscle strength in these patients.

Experienced and physiological fatigue in neuromuscular disorders.

OBJECTIVE: Fatigue has been described as a typical symptom of neurological diseases. It might be caused both by changes at the peripheral and at the central level. This study measured the level of experienced fatigue and physiological correlates of fatigue in three genetically defined neuromuscular disorders. METHODS: Sixty-five facioscapulohumeral dystrophy (FSHD), 79 classical myotonic dystrophy (DM), 73 hereditary motor and sensory neuropathy type I (HMSN) patients and 24 age-matched healthy controls made a 2-min sustained maximal voluntary contraction of the biceps brachii muscle. Experienced fatigue at the current moment was assessed with the abbreviated fatigue questionnaire just before the physiological measurement. Peripheral fatigue was quantified by comparing the amplitudes of an initial and a final stimulated force response during rest. Muscle fibre conduction velocity was determined from a 5-channel surface EMG recording in order to show peripheral changes during the contraction. Central aspects of fatigue were measured using superimposed electrical endplate stimulation. RESULTS: Patients showed an increased level of experienced fatigue. Total physiological and peripheral fatigue were smaller in patients compared to controls, and central fatigue was normal. The most interesting result of this study was the presence of a large central activation failure (CAF) in all groups of neuromuscular patients; they showed CAF values of 36-41% already directly at the start of sustained contraction, whereas the control group showed only 12%. CAF slightly correlated with the level of experienced fatigue just before the test. CONCLUSIONS: The cause of the large CAF in patients is unclear. Reduced concentration, motivation or effort can lead to lower central activation. In neuromuscular patients especially fear of physical activity or fear to damage the muscle or nerve tissue may contribute. Besides, also physiological feedback mechanisms or changes at the motocortical level may be a cause of reduced central activation. SIGNIFICANCE: For the clinician it is important to know that experienced fatigue is part of the clinical spectrum of neuromuscular patients. Besides, the weakness in these patients is aggravated by reduced central activation. Potentially, both problems could be subject of an intervention.

Central adaptations during repetitive contractions assessed by the readiness potential.

Physiological fatigue, a loss of maximal force producing capacity, may originate both from changes at the peripheral and at the central level. The readiness potential (RP) provides a measure to study adaptations to physiological fatigue at the motor cortex. We have studied the RP in the course of repetitive contractions at a high force level. Fourteen female healthy subjects made repetitive force grip contractions at 70% of their maximal voluntary contraction (MVC) for 30 min. Contractions were self-paced and inter-squeeze interval was about 7 s. During the repetitive contractions, the area under the curve of the RP almost doubled at electrode Cz and increased fourfold at electrodes C3' and C4'. The onset of negativity moved forward from 1.5 to 1.9 s before force onset at Cz and from 1.0 to 1.6 s and 1.7 s before force onset at C3' and C4', respectively. EMG amplitude and median frequency did not change significantly and MVC after the fatiguing exercise was 93% of MVC before, indicating relatively little physiological fatigue. The increase of the RP during the repetitive contractions is clearly in excess of the almost absent signs of peripheral fatigue. Because the increase of the RP does not lead to an increased force production, we propose that it is a central adaptation counteracting the decrease of cortical efficiency during repetitive contractions.

Experienced fatigue in facioscapulohumeral dystrophy, myotonic dystrophy, and HMSN-I.

OBJECTIVE: To assess the prevalence of severe fatigue and its relation to functional impairment in daily life in patients with relatively common types of neuromuscular disorders. METHODS: 598 patients with a neuromuscular disease were studied (139 with facioscapulohumeral dystrophy, 322 with adult onset myotonic dystrophy, and 137 with hereditary motor and sensory neuropathy type I). Fatigue severity was assessed with Checklist Individual Strength (CIS-fatigue). Functional impairments in daily life were measured with the short form 36 item health questionnaire (SF-36). RESULTS: The three different neuromuscular patient groups were of similar age and sex. Severe experienced fatigue was reported by 61-74% of the patients. Severely fatigued patients had more problems with physical functioning, social functioning, mental health, bodily pain, and general health perception. There were some differences between the three disorders in the effects of fatigue. CONCLUSIONS: Severe fatigue is reported by the majority of patients with relatively common types of neuromuscular disorders. Because experienced fatigue severity is associated with the severity of various functional impairments in daily life, it is a clinically and socially relevant problem in this group of patients.

Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome.

OBJECTIVE: We have investigated whether central activation failure (CAF) is increased during local muscle fatigue in chronic fatigue syndrome (CFS). METHODS: Fourteen female CFS patients and 14 age-matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle. Before, during, and after sustained MVC, electrical endplate stimulation was applied. Force and 5 channel surface EMG (sEMG) were registered. RESULTS: Although force responses upon stimulation during rest did not differ between patients and controls, MVC was significantly lower in patients. Already at the beginning of sustained MVC, CFS patients showed significantly larger CAF than controls (36.5+/-17.0% and 12.9+/-13.3%, respectively). For all individual patients mean CAF over the first 45 s was higher than 30%, while it was below 30% for all controls. Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction. CONCLUSIONS: Central activation is diminished in CFS patients. Possible causes include changed perception, impaired concentration, reduced effort and physiologically defined changes, e.g. in the corticospinal excitability or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue. SIGNIFICANCE: CFS patients show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined.

[Fatigue in neuromuscular disease]. / Moeheid bij neuromusculaire aandoeningen.

Chronic fatigue is a symptom of diseases such as cancer, multiple sclerosis, Parkinson's and cerebrovascular disease. Fatigue can also be present in people with no demonstrable somatic disease. If certain criteria are met, chronic-fatigue syndrome may be diagnosed in these cases. Fatigue is a multi-dimensional concept with physiological and psychological dimensions. The 'Short Fatigue Questionnaire' consisting of 4 questions is a tool to measure fatigue with a high degree of reliability and validity. Within the group of neuromuscular disorders, fatigue has been reported by patients with post-polio syndrome, myasthenia gravis, and Guillain-Barré syndrome. The percentage of neuromuscular patients suffering from severe fatigue (64%) is comparable with that of patients with multiple sclerosis, a disease in which fatigue is an acknowledged symptom. Now that reliable psychological and clinical neurophysiological techniques are available, a multidisciplinary approach to fatigue in patients with well-defined neuromuscular disorders may contribute towards the elucidation of the pathophysiological mechanisms of chronic fatigue, with the ultimate goal being to develop methods of treatment for fatigue in neuromuscular patients.

Preoperative prediction of severe postoperative pain.

We developed and validated a prediction rule for the occurrence of early postoperative severe pain in surgical inpatients, using predictors that can be easily documented in a preoperative setting. A cohort of surgical inpatients (n=1416) undergoing various procedures except cardiac surgery and intracranial neurosurgery in a University Hospital were studied. Preoperatively the following predictors were collected: age, gender, type of scheduled surgery, expected incision size, blood pressure, heart rate, Quetelet index, the presence and severity of preoperative pain, health-related quality of life the (SF-36), Spielberger's State-Trait Anxiety Inventory (STAI) and the Amsterdam Preoperative Anxiety and Information Scale (APAIS). The outcome was the presence of severe postoperative pain (defined as Numeric Rating Scale > or =8) within the first hour postoperatively. Multivariate logistic regression in combination with bootstrapping techniques (as a method for internal validation) was used to derive a stable prediction model. Independent predictors of severe postoperative pain were younger age, female gender, level of preoperative pain, incision size and type of surgery. The area under the receiver operator characteristic (ROC) curve was 0.71 (95% CI: 0.68-0.74). Adding APAIS scores (measures of preoperative anxiety and need for information), but not STAI, provided a slightly better model (ROC area 0.73). The reliability of this extended model was good (Hosmer and Lemeshow test p-value 0.78). We have demonstrated that severe postoperative pain early after awakening from general anesthesia can be predicted with a scoring rule, using a small set of variables that can be easily obtained from all patients at the preoperative visit. Before this internally validated preoperative prediction rule can be applied in clinical practice to support anticipatory pain management, external validation in other clinical settings is necessary.