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Purpose: MitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD). Methods: Simulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume (↑LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated. Results: MitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3±7.1 kPa (p<0.0001) in AL and 14.8±1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1±2.2 mm (p<0.0001) and increased Err in the sub-valvular lateral LV myocardium at ED by 0.09±0.04 (p<0.0001)). Furthermore, MitraClip in ↑LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9±14.4 kPa (p = 0.0268) and in PL by 22.5±23.7 kPa (p = 0.0101). Conclusions: MitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement. [ABSTRACT FROM AUTHOR]

Objectives: An extended-wavelength diffuse reflectance spectroscopy (EWDRS) technique was evaluated for its ability to differentiate between and classify different skin and tissue types in an in vivo pig model. Materials and methods: EWDRS recordings (450–1550 nm) were made on skin with different degrees of pigmentation as well as on the pig snout and tongue. The recordings were used to train a support vector machine to identify and classify the different skin and tissue types. Results: The resulting EWDRS curves for each skin and tissue type had a unique profile. The support vector machine was able to classify each skin and tissue type with an overall accuracy of 98.2%. The sensitivity and specificity were between 96.4 and 100.0% for all skin and tissue types. Conclusion: EWDRS can be used in vivo to differentiate between different skin and tissue types with good accuracy. Further development of the technique may potentially lead to a novel diagnostic tool for e.g. non-invasive tumor margin delineation. [ABSTRACT FROM AUTHOR]

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies. [ABSTRACT FROM AUTHOR]

Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical load in myofibrillar function, we compared the skinned fiber force between denervated (DEN) and dexamethasone-treated (DEX) rat skeletal muscles with or without neuromuscular electrical stimulation (ES) training. DEN and DEX were induced by cutting the sciatic nerve and daily injection of dexamethasone (5 mg/kg/day) for 7 days, respectively. For ES training, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. In situ maximum torque was markedly depressed in the DEN muscles compared to the DEX muscles (-74% vs. -10%), whereas there was not much difference in the degree of atrophy in gastrocnemius muscles between DEN and DEX groups (-24% vs. -17%). Similar results were obtained in the skinned fiber preparation, with a greater reduction in maximum Ca2+-activated force in the DEN than in the DEX group (-53% vs. -16%). Moreover, there was a parallel decline in myosin heavy chain (MyHC) and actin content per muscle volume in DEN muscles, but not in DEX muscles, which was associated with upregulation of NADPH oxidase (NOX) 2, neuronal nitric oxide synthase (nNOS), and endothelial NOS expression, translocation of nNOS from the membrane to the cytosol, and augmentation of mRNA levels of muscle RING finger protein 1 (MuRF-1) and atrogin-1. Importantly, mechanical load evoked by ES protects against DEN- and DEX-induced myofibrillar dysfunction and these molecular alterations. Our findings provide novel insights regarding the difference in intrinsic contractile properties between DEN and DEX and suggest an important role of mechanical load in preserving myofibrillar function in skeletal muscle. [ABSTRACT FROM AUTHOR]

Purpose: The effects of gravity on bevacizumab or the recommended head position after intraocular bevacizumab injection have not been reported. To evaluate the effect of gravity on bevacizumab in vitro, we added bevacizumab to the upper part of a test tube filled with balanced salt solution (BSS) and examined its distribution over time. Materials and methods: Sixty-four test tubes were divided equally into two groups; group 1 (32, collected from upper part of the tube) and group 2 (32, collected from lower part of the tube). Each test tube was filled with 5 mL BSS before bevacizumab (1.25 mg/0.05 mL) was added, and then stored at 36°C. Bevacizumab concentration in 8 test tubes from each group was measured at 12, 24, 48, and 168 h using an enzyme-linked immunosorbent analysis (ELISA) kit. Mann–Whitney and Jonckheere–Terpstra tests were used for statistical analysis. Results: Bevacizumab concentration was significantly higher in Group 2 than in Group 1 at 12, 24, 48, and 168 h (12, 24, 48, and 168 h; P < 0.01 each; Mann–Whitney test). The mean change in bevacizumab concentration over time tended to increase in Group 1 (P < 0.01; Jonckheere–Terpstra test), but tended to decrease in Group 2 (P < 0.01; Jonckheere–Terpstra test). Conclusions: The significant differences in concentration between the upper and lower parts even after a considerable amount of storage time showed that bevacizumab did not dissolve immediately and diffused evenly throughout the solution. It appeared that more bevacizumab settled in the lower part of the tube than in the upper part because of gravitational force. However, the concentration difference between the upper and lower parts decreased as bevacizumab gradually diffused over time, indicating that the difference in concentration due to gravity was more significant at the beginning of bevacizumab injection. [ABSTRACT FROM AUTHOR]

The transport and distribution of charged molecules in polyelectrolyte solutions are of both fundamental and practical importance. A practical example, which is the specific subject addressed in the present paper, is the transport and distribution of charged species into cartilage. The charged species could be a contrast agent or a drug molecule involved in diagnosis or treatment of the widespread degenerative disease osteoarthritis, which leads to degradation of articular cartilage. Associated scientific issues include the rate of transport and the equilibrium concentrations of the charged species in the cartilage and the synovial fluid. To address these questions, we present results from magnetic resonance micro-imaging experiments on a model system of articular cartilage. The experiments yield temporally and spatially resolved data on the transport of a negatively charged contrast agent (charge = -2), used in medical examinations of cartilage, into a polyelectrolyte solution, which is designed to capture the electrostatic interactions in cartilage. Also presented is a theoretical analysis of the transport where the relevant differential equations are solved using finite element techniques as well as treated with approximate analytical expressions. In the analysis, non-ideal effects are included in the treatment of the mobile species in the system. This is made possible by using results from previous Monte Carlo simulations. The results demonstrate the importance of taking non-idealities into account when data from measurements of transport of charged solutes in a system with fixed charges from biological polyelectrolytes are analyzed. [ABSTRACT FROM AUTHOR]

Electrical impedance myography (EIM) is a technique for the assessment of muscle health and composition and has been shown to be sensitive to a variety of muscle pathologies including neurogenic atrophy and connective tissue deposition. However, it has been minimally studied in pure inflammation. In this study, we sought to assess EIM sensitivity to experimental inflammation induced by the localized intramuscular injection of λ-carrageenan. A total of 91 mice underwent 1–1000 kHz EIM measurements of gastrocnemius using a needle array, followed by injection of either 0.3% λ-carrageenan in phosphate-buffered saline (PBS) or PBS alone. Animals were then remeasured with EIM at 4, 24, 48, or 72 hours and euthanized and quantitative assessment of muscle histology was performed. Parallel alterations in both 5 and 50 kHz EIM values were identified at 4 and 24 hours, including reductions in phase, reactance, and resistance. In PBS-treated animals these values normalized by 48 hours, whereas substantial reductions in phase and reactance in 5 kHz EIM values persisted at 48 and 72 hours (i.e., values of phase 72 hours post-injection were 6.51 ± 0.40 degrees for λ-carrageenan versus 8.44 ± 0.35 degrees for PBS p<0.001, n = 11 per group). The degree of basophilic area observed in muscle sections by histology correlated to the degree of phase change at these two time points (Rspearman = -0.51, p = 0.0029). Changes in low frequency EIM parameters are sensitive to the presence of inflammatory infiltrates, and have the potential of serving as a simple means of quantifying the presence and extent of muscle inflammation without the need for biopsy. [ABSTRACT FROM AUTHOR]

Collapse of the lateral cerebral ventricles after ventriculo-peritoneal drainage is a fatal complication in dogs with internal hydrocephalus. It occurs due to excessive outflow of cerebrospinal fluid into the peritoneal cavity (overshunting). In most shunt systems, one-way valves with different pressure settings regulate flow into the distal catheter to avoid overshunting. The rationale for the choice of an appropriate opening pressure is a setting at the upper limit of normal intracranial pressure in dogs. However, physiological intraventricular pressure in normal dogs vary between 5 and 12 mm Hg. Furthermore, we hypothesise that intraventricular pressure in hydrocephalic dogs might differ from pressure in normal dogs and we also consider that normotensive hydrocephalus exists in dogs, as in humans. In order to evaluate intraventricular pressure in hydrocephalic dogs, twenty-three client owned dogs with newly diagnosed communicating internal hydrocephalus were examined before implantation of a ventriculo-peritoneal shunt using a single use piezo-resistive strain-gauge sensor (MicroSensor ICP probe). Ventricular volume and brain volume were measured before surgery, based on magnetic resonance images. Total ventricular volume was calculated and expressed in relation to the total volume of the brain, including the cerebrum, cerebellum, and brainstem (ventricle-brain index). Multiple logistic regression analysis was performed to assess the influence of the covariates “age”, “gender”, “duration of clinical signs”, “body weight”, and “ventricle-brain index” on intraventricular pressure. The mean cerebrospinal fluid pressure in the hydrocephalic dogs was 8.8 mm Hg (standard deviation 4.22), ranging from 3–18 mm Hg. The covariates “age”, (P = 0.782), “gender” (P = 0.162), “body weight”, (P = 0.065), or ventricle-brain index (P = 0.27)” were not correlated with intraventricular pressure. The duration of clinical signs before surgery, however, was correlated with intraventricular pressure (P< 0.0001). Dogs with internal hydrocephalus do not necessarily have increased intraventricular pressure. Normotensive communicating hydrocephalus exists in dogs. [ABSTRACT FROM AUTHOR]

Purpose: Diffusion magnetic resonance imaging and tractography has an important role in the visualization of brain white matter and assessment of tissue microstructure. There is a lack of correspondence between diffusion metrics of live tissue, ex vivo tissue, and histological findings. The objective of this study is to elucidate this connection by determining the specific diffusion alterations between live and ex vivo brain tissue. This may have an important role in the incorporation of diffusion imaging in ex vivo studies as a complement to histological sectioning as well as investigations of novel neurosurgical techniques. Methods: This study presents a method of high angular resolution diffusion imaging and tractography of intact and non-fixed ex vivo piglet brains. Most studies involving ex vivo brain specimens have been formalin-fixed or excised from their original biological environment, processes both of which are known to affect diffusion parameters. Thus, non-fixed ex vivo tissue is used. A region-of-interest based analysis of diffusion tensor metrics are compared to in vivo subjects in a selection of major white matter bundles in order to assess the translatability of ex vivo diffusion measurements. Results: Tractography was successfully achieved in both in vivo and ex vivo groups. No significant differences were found in tract connectivity, average streamline length, or apparent fiber density. Significantly decreased diffusivity (mean, axial, and radial; p<0.0005) in the non-fixed ex vivo group and unaltered fractional anisotropy (p>0.059) between groups were observed. Conclusion: This study validates the extrapolation of non-fixed fractional anisotropy measurements to live tissue and the potential use of ex vivo tissue for methodological development. [ABSTRACT FROM AUTHOR]

Purpose: To investigate cerebral microstructural alterations in patients treated with calcineurin inhibitors (CNI) after orthotopic liver transplantation (OLT) using quantitative magnetic resonance imaging (qMRI) and a cross-sectional study design. Methods: Cerebral qMRI was performed in 85 patients in a median 10 years after OLT compared to 31 healthy controls. Patients were treated with different dosages of CNI or with a CNI-free immunosuppression (CNI-free: n = 19; CNI-low: n = 36; CNI-standard: n = 30). T2-, T2*- and T2’- relaxation times, as well as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain gray and white matter by using the regions of interest method. Results: In comparison to controls, patients revealed significantly increased T2, T2*, T2’, ADC and reduced FA, predominantly in the frontal white matter, indicating microstructural brain alterations represented by increased free water (increased T2), reduced neuronal metabolism (increased T2’) and a lower degree of spatial organization of the nervous fibers (reduced FA). CNI-low and CNI-free patients showed more alterations than CNI-standard patients. Analysis of their history revealed impairment of kidney function while under standard CNI dose suggesting that these patients may be more vulnerable to toxic CNI side-effects. Conclusion: Our findings suggest that the individual sensitivity to toxic side effects should be considered when choosing an appropriate immunosuppressive regimen in patients after liver transplantation. [ABSTRACT FROM AUTHOR]

Inverse dynamics problems are usually solved in the analysis of human gait to obtain reaction forces and moments at the joints. However, these actions are not the actual forces and moments supported by the joint structure, because they do not consider the forces of the muscles acting across the joint. Therefore, to analyse bone-on bone forces it is necessary to estimate those muscle forces. Usually, this problem is addressed by means of optimization algorithms. One of the parameters required to solve this problem is the musculotendon geometry. These data are usually taken from cadavers or MRI data from several subjects, different from the analysed subject. Then, the model is scaled to the subject morphology. This procedure constitutes a source of error. The goals of this work were two. First, to perform a sensitivity analysis of the influence of muscle insertion locations on the muscle forces acting on the hip joint and on the hip joint bone-on-bone forces. Second, to compare the hip joint bone-on-bone forces during gait cycle obtained through muscle insertion locations taken from a musculoskeletal model template and a scaling procedure to those obtained from a subject-specific model using an MRI of the subject. The problem was solved using OpenSim. Results showed that anatomical variability should be analysed from two perspectives. One the one hand, throughout the gait cycle, in a global way. On the other hand, at a characteristic instant of the gait cycle. Variations of ±1 cm in the position of the attachment points of certain muscles caused variations of up to 14.21% in averaged deviation of the muscle forces and 58.96% in the peak force in the modified muscle and variations up to 57.23% in the averaged deviation of the muscle force and up to 117.23% in the peak force in the rest of muscles. Then, the influence of that variability on muscle activity patterns and hip bone-on-bone forces could be described more precisely. A biomechanical analysis of a subject-specific musculoskeletal model was carried out. Using MRI data, variations up to 5 cm in the location of the insertion points were introduced. These modifications showed significant differences between the baseline model and the customized model: within the range [-12%, 10%] for muscle forces and around 35% of body weight for hip bone-on-bone forces. [ABSTRACT FROM AUTHOR]

The bovine dry period is a non-lactating period between consecutive lactations characterized by mammary gland involution and redevelopment phases to replace senescent mammary epithelial cells with active cells primed for the next lactation. Dairy cows exposed to heat stress during the dry period experience milk yield reductions between 3–7.5 kg/d in the next lactation, partially attributed to processes associated with mammary cell growth and turnover during the dry period. However, the carry-over impact of dry period heat stress on mammary morphology during lactation has yet to be determined. In the current study, we hypothesized that exposure to heat stress during the dry period would alter alveolar microstructure and cellular turnover (i.e. proliferation and apoptosis) during lactation. Cows were either subjected to heat stress (HT, access to shade; n = 12) or cooling (CL, access to shade, fans, and soakers; n = 12) for a 46 d dry period. Upon calving, all cows were treated similarly with access to cooling for their entire lactation. Six cows per treatment were randomly selected for mammary gland biopsies at 14, 42, and 84 days in milk. Tissues were sectioned and stained for histological analysis. During lactation, HT cows produced 4 kg less colostrum and 3.7 kg less milk compared with CL cows. Lactating mammary gland microstructure was impacted after exposure to dry period heat stress; HT cows had fewer alveoli and a higher proportion of connective tissue in the mammary gland relative to CL cows, however alveolar area was similar between treatments. Rates of mammary epithelial cell proliferation and apoptosis were similar between treatment groups. This suggests that heat stress exposure during the dry period leads to reductions in milk yield that could be caused, in part, by a reduction in alveoli number in the lactating mammary gland but not to dynamic alterations in cellular turnover once lactation is established. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) has become a valuable imaging modality in ophthalmology, especially for the diagnosis and treatment planning of patients with uveal melanoma, the most common primary intra-ocular tumor. We aim to develop and evaluate the value of silent Zero Echo Time (ZTE) MRI to image patients with ocular tumors at 7Tesla. Therefore, ZTE and different types of magnetization-prepared ZTE (FLAIR, SPIR, T2 and Saturation recovery), have been developed. After an initial validation with 7 healthy subjects, nine patients with an eye tumor have been evaluated. The ZTE scans were compared to their Cartesian equivalent in terms of contrast, motion-sensitivity, diagnostic quality and patient comfort. All volunteers and especially the patients reported a more comfortable experience during the ZTE scans, which had at least a 10 dB lower sound pressure. The image contrast in the native ZTE was poor, but in the different magnetization-prepared ZTE, the eye lens, cornea and retina were clearly discriminated. Overall the T2-prepared scan yielded the best contrast, especially between tumor and healthy tissue, and proved to be robust against eye motion. Although the intrinsic 3D nature of the ZTE-technique provides an accurate analysis of the tumor morphology, the quality of the ZTE-images is lower than their Cartesian equivalent. In conclusion, the quality of magnetization-prepared ZTE images is sufficient to assess the 3D tumor morphology, but insufficient for more detailed evaluations. As such this technique can be an option for patients who cannot comply with the sound-levels of Cartesian scans, but for other patients the conventional Cartesian scans offer a better image quality. [ABSTRACT FROM AUTHOR]

The incidence of heatstroke has been increasing. Heatstroke has been shown to affect physiological barrier functions. However, there are few studies of the effect of heat stress on the blood-brain barrier (BBB) function. In this study, we investigated the influence of heat stress on brain microvascular endothelial cells in vivo and in vitro. Heatstroke model mice administered Texas Red-dextran showed leakage outside the brain vessel walls. In addition, trans-endothelial electrical resistance (TEER) value was significantly reduced in induced pluripotent stem (iPS) cell-derived brain microvascular endothelial cells under heat stress by reducing claudin-5 expression. In addition, our results showed that the expression level of P-glycoprotein (P-gp) was increased in iPS cell-derived brain microvascular endothelial cells under heat stress. Furthermore, serum from heatstroke model mice could impair the BBB integrity of iPS cell-derived brain microvascular endothelial cells. These results suggest that BBB integrity was affected by heat stress in vivo and in vitro and provide important insights into the development of new therapeutic strategies for heatstroke patients. [ABSTRACT FROM AUTHOR]

In the United States, breast cancer is one of the most common and the second leading cause of cancer-related death in women. Treatment modalities for mammary tumor are surgical removal of the tumor tissue followed by either chemotherapy or radiotherapy or both. Radiation therapy is a whole body irradiation regimen that suppresses the immune system leaving hosts susceptible to infection or secondary tumors. Boron neutron capture therapy (BNCT) in that regard is more selective, the cells that are mostly affected are those that are loaded with 109 or more 10B atoms. Previously, we have described that liposomal encapsulation of boron-rich compounds such as TAC and MAC deliver a high payload to the tumor tissue when injected intravenously. Here we report that liposome-mediated boron delivery to the tumor is inversely proportional to the size of the murine mammary (EMT-6) tumors. The plausible reason for the inverse ratio of boron and EMT-6 tumor size is the necrosis in these tumors, which is more prominent in the large tumors. The large tumors also have receding blood vessels contributing further to poor boron delivery to these tumors. We next report that the presence of boron in blood is essential for the effects of BNCT on EMT-6 tumor inhibition as direct injection of boron-rich liposomes did not provide any added advantage in inhibition of EMT-6 tumor in BALB/c mice following irradiation despite having a significantly higher amount of boron in the tumor tissue. BNCT reaction in PBMCs resulted in the modification of these cells to anti-tumor phenotype. In this study, we report the immunomodulatory effects of BNCT when boron-rich compounds are delivered systemically. [ABSTRACT FROM AUTHOR]

This study presents a modelling framework in which information on muscle fiber direction and orientation during contraction is derived from diffusion tensor imaging (DTI) and incorporated in a computational model of the surface electromyographic (EMG) signal. The proposed model makes use of the principle of reciprocity to simultaneously calculate the electric potentials produced at the recording electrode by charges distributed along an arbitrary number of muscle fibers within the muscle, allowing for a computationally efficient evaluation of extracellular motor unit action potentials. The approach is applied to the complex architecture of the first dorsal interosseous (FDI) muscle of the hand to simulate EMG during index finger flexion and abduction. Using diffusion tensor imaging methods, the results show how muscle fiber orientation and curvature in this intrinsic hand muscle change during flexion and abduction. Incorporation of anatomically accurate muscle architecture and other hand tissue morphologies enable the model to capture variations in extracellular action potential waveform shape across the motor unit population and to predict experimentally observed differences in EMG signal features when switching from index finger abduction to flexion. The simulation results illustrate how structural and electrical properties of the tissues comprising the volume conductor, in combination with fiber direction and curvature, shape the detected action potentials. Using the model, the relative contribution of motor units of different sizes located throughout the muscle under both conditions is examined, yielding a prediction of the detection profile of the surface EMG electrode array over the muscle cross-section. [ABSTRACT FROM AUTHOR]

It remains unclear what is the real safe limit of torque magnitude during Bilateral Apical Vertebral Derotation (BAVD) in thoracic curve correction. Up to author’s knowledge there is no study except this one, to reproduce in–vivo real measurements and intraoperative conditions during BAVD maneuver. The objective of this study was to evaluate the torsional strength of the instrumented thoracic spine under axial rotation moment as well as to define safety limits under BAVD corrective maneuver in scoliosis surgery. 10 fresh, full-length, young and intact human cadavers were tested. After proper assembly of the apparatus, the torque was applied through its apical part, simulating thoracic curve derotation. During each experiment the torque magnitude and angular range of derotation were evaluated. For more accurate analysis after every experiment the examined section of the spine was resected from the cadaver and evaluated morphologically and with a CT scan. The average torque to failure during BAVD simulation was 73,3 ± 5,49Nm. The average angle of BAVD to failure was 44,5 ± 8,16°. The majority of failures were in apical area. There was no significant difference between the fracture occurrence of left or right side of lateral wall of the pedicle. There was no spinal canal breach and/or medial wall failure in any specimen. The safety limits of thoracic spine and efficacy of BAVD for axial plane correction in the treatment of Adolescent Idiopathic Scoliosis (AIS) were established. It provided qualitative and quantitative information essential for the spinal derotation under safe loading limits. [ABSTRACT FROM AUTHOR]

The impact of a rider’s and saddle’s mass on saddle thermal pattern distribution was evaluated using infrared thermography (IRT). Eighteen racehorses were ridden by four riders with their own saddle. Images of the saddle panels were captured at each of six thermographic examinations. On each image, six regions of interest (ROIs) were marked on the saddle panels. The mean temperature for each ROI was extracted. To evaluate the influence of load on saddle fit, 4 indicators were used: ΔTmax (difference between the mean temperature of the warmest and coolest ROI); standard deviation of the mean temperature of the six ROIs; right/left; bridging/rocking and front/back thermal pattern indicator. Incorrect saddle fit was found in 25 measurements (23.1%) with ΔTmax greater than 2°C. The relationships between rider and saddle fit as well as saddle fit and horse were significant (p<0.001). An average ΔTmax in rider A was significantly higher than in other riders (p<0.001). The right/left thermal pattern differed significantly from the optimal value for riders A and B; while the bridging/rocking thermal pattern differed significantly from this value for riders A, C and D (p<0.05). Front saddle thermal pattern was most frequent for rider A (41.5%), whereas back saddle thermal pattern was most frequent for rider C (85.7%). Measurement of the mean temperature in 6 ROIs on saddle panels after training was helpful in assessing the influence of rider and saddle mass on saddle fit. IRT offered a non-invasive, rapid and simple method for assessing load on thermal pattern distribution in race saddles. [ABSTRACT FROM AUTHOR]

Metal implants not only deteriorate image quality, but also increase radiation exposure. The purpose of this study was to evaluate the effect of metal hip prosthesis on absorbed radiation dose and assess the efficacy of organ dose modulation (ODM) and metal artifact reduction (MAR) protocols on dose reduction. An anthropomorphic phantom was scanned with and without bilateral metal hip prostheses, and surface and deep level radiation doses were measured at the abdomen and pelvis. Finally, the absorbed radiation doses at pelvic and abdominal cavities in the reference, ODM, and two MAR scans (Gemstone spectral imaging, GE) were compared. The Mann Whitney-U test and Kruskal-Wallis test were performed to compare the volume CT dose index (CTDIvol) and mean absorbed radiation doses. Unilateral and bilateral metal hip prostheses increased CTDIVOL by 14.4% and 30.5%, respectively. MAR protocols decreased absorbed radiation doses in the pelvis. MAR showed the most significant dose reduction in the deep pelvic cavity followed by ODM. However, MAR protocols increased absorbed radiation doses in the upper abdomen. ODM significantly reduced absorbed radiation in the pelvis and abdomen. In conclusion, metal hip implants increased radiation doses in abdominopelvic CT scans. MAR and ODM techniques reduced absorbed radiation dose in abdominopelvic CT scans with metal hip prostheses. [ABSTRACT FROM AUTHOR]

Background: Impaired myocardial deformation has been sporadically described in cardiac asymptomatic systemic sclerosis (SSc). We aimed to study myocardial deformation indices in cardiac asymptomatic SSc patients using cardiac magnetic resonance feature tracking (CMR-FT) and correlate these findings to the phenotypic and autoimmune background. Methods: Fifty-four cardiac asymptomatic SSc patients (44 females, 56±13 years), with normal routine cardiac assessment and CMR evaluation, including cine and late gadolinium enhancement (LGE) images, were included. SSc patients were compared to 21 sex- and age- matched healthy controls (17 females; 54±19 years). For CMR-FT analysis, a mid-ventricular slice for LV peak systolic radial and circumferential strain and a 4-chamber view for LV/RV peak systolic longitudinal strain were used. Results: Twenty-four patients had diffuse cutaneous SSc and 30 limited cutaneous SSc. Thirteen patients had digital ulcers. Median disease duration was 3.6 years. LV ejection fraction was higher in SSc patients compared to controls (62±6% vs. 59±5%, p = 0.01). Four patients had no LGE examination; in the remaining patients LGE was absent in 74%, while 18% had RV insertion fibrosis and 8% evidence of subendocardial infarction. LV longitudinal strain differed in those with insertion fibrosis (-18.0%) and infarction (-16.7%) compared to no fibrosis (-20.3%, p = 0.04). Patients with SSc had lower RV longitudinal strain and strain rate compared to controls (p<0.001 and p = 0.01, respectively). All other strain and strain rate measurements were non-significant between patients and controls. Conclusions: In cardiac asymptomatic SSc patients with normal routine functional indices, CMR-FT identifies subclinical presence of insertion fibrosis and/or myocardial infarction by impaired LV longitudinal strain. RV derived longitudinal indices were impaired in the patient group. CMR FT indices did not correlate to the patients’ phenotypic and autoimmune features. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging studies typically use standard anatomical atlases for identification and analyses of (patho-)physiological effects on specific brain areas; these atlases often fail to incorporate neuroanatomical alterations that may occur with both age and disease. The present study utilizes Parkinson’s disease and age-specific anatomical atlases of the subthalamic nucleus for diffusion tractography, assessing tracts that run between the subthalamic nucleus and a-priori defined cortical areas known to be affected by Parkinson’s disease. The results show that the strength of white matter fiber tracts appear to remain structurally unaffected by disease. Contrary to that, Fractional Anisotropy values were shown to decrease in Parkinson’s disease patients for connections between the subthalamic nucleus and the pars opercularis of the inferior frontal gyrus, anterior cingulate cortex, the dorsolateral prefrontal cortex and the pre-supplementary motor, collectively involved in preparatory motor control, decision making and task monitoring. While the biological underpinnings of fractional anisotropy alterations remain elusive, they may nonetheless be used as an index of Parkinson’s disease. Moreover, we find that failing to account for structural changes occurring in the subthalamic nucleus with age and disease reduce the accuracy and influence the results of tractography, highlighting the importance of using appropriate atlases for tractography. [ABSTRACT FROM AUTHOR]

Purpose: Pharmacokinetic models facilitate assessment of properties of the micro-vascularization based on DCE-MRI data. However, accurate pharmacokinetic modeling in the liver is challenging since it has two vascular inputs and it is subject to large deformation and displacement due to respiration. Methods: We propose an improved pharmacokinetic model for the liver that (1) analytically models the arrival-time of the contrast agent for both inputs separately; (2) implicitly compensates for signal fluctuations that can be modeled by varying applied flip-angle e.g. due to B1-inhomogeneity. Orton’s AIF model is used to analytically represent the vascular input functions. The inputs are independently embedded into the Sourbron model. B1-inhomogeneity-driven variations of flip-angles are accounted for to justify the voxel’s displacement with respect to a pre-contrast image. Results: The new model was shown to yield lower root mean square error (RMSE) after fitting the model to all but a minority of voxels compared to Sourbron’s approach. Furthermore, it outperformed this existing model in the majority of voxels according to three model-selection criteria. Conclusion: Our work primarily targeted to improve pharmacokinetic modeling for DCE-MRI of the liver. However, other types of pharmacokinetic models may also benefit from our approaches, since the techniques are generally applicable. [ABSTRACT FROM AUTHOR]

Reflective or translucent materials are a challenge to digitize in 3D. Results are better with a matt coating although objects from museum collections are often too fragile or too valuable to be treated in this way. It is therefore essential that alternative solutions are found. This study analyzed spectral photogrammetry as a possible solution. Spectral photogrammetry is an emerging technique which uses images at different wavelengths to create 3D models. Tooth enamel is a challenging material to digitize. Six sets of teeth were photographed at different wavelengths. The results showed that the quality of the models enamels parts improved when taken with ultraviolet wavelengths whilst models were less accurate when photogrammetry was performed with the red and infrared spectrum. This can be explained by the optical properties of enamel. This study demonstrates that knowing the optical properties of a material beforehand could help future photogrammetric digitization of challenging materials. [ABSTRACT FROM AUTHOR]

Background: Auscultation is one of the first examinations that a patient is subjected to in a GP’s office, especially in relation to diseases of the respiratory system. However it is a highly subjective process and depends on the physician’s ability to interpret the sounds as determined by his/her psychoacoustical characteristics. Here, we present a cross-sectional assessment of the skills of physicians of different specializations and medical students in the classification of respiratory sounds in children. Methods and findings: 185 participants representing different medical specializations took part in the experiment. The experiment comprised 24 respiratory system auscultation sounds. The participants were tasked with listening to, and matching the sounds with provided descriptions of specific sound classes. The results revealed difficulties in both the recognition and description of respiratory sounds. The pulmonologist group was found to perform significantly better than other groups in terms of number of correct answers. We also found that performance significantly improved when similar sound classes were grouped together into wider, more general classes. Conclusions: These results confirm that ambiguous identification and interpretation of sounds in auscultation is a generic issue which should not be neglected as it can potentially lead to inaccurate diagnosis and mistreatment. Our results lend further support to the already widespread acknowledgment of the need to standardize the nomenclature of auscultation sounds (according to European Respiratory Society, International Lung Sounds Association and American Thoracic Society). In particular, our findings point towards important educational challenges in both theory (nomenclature) and practice (training). [ABSTRACT FROM AUTHOR]

Substantial controversy exists as to which part of brain activity is genuinely attributable to pain-related percepts and which activity is due to general aspects of sensory stimulation, such as its salience, or the accompanying arousal. The challenge posed by this question rests largely in the fact that pain per se exhibits highly intense but unspecific characteristics. These therefore should be matched by potential control conditions. Here, we used a unique combination of functional magnetic resonance imaging (fMRI) and behavioral and autonomic measures to address this longstanding debate in pain research. Subjects rated perceived intensity in a sequence alternating between heat and sound stimuli. Neuronal activity was monitored using fMRI. Either modality was presented in 6 different intensities, 3 of which lay above the pain threshold (for heat) or the unpleasantness threshold (for sound). We performed our analysis on 26 volunteers in which psychophysiological responses (as per skin conductance responses [SCRs]) did not differ between the 2 stimulus modalities. Having thus ascertained a comparable amount of stimulation-related but unspecific activation, we analyzed stimulus-response functions (SRFs) after painful stimulation and contrasted them with those of the matched acoustic control condition. Furthermore, analysis of fMRI data was performed on the brain surface to circumvent blurring issues stemming from the close proximity of several regions of interest located in heavily folded cortical areas. We focused our analyses on insular and peri-insular regions that are strongly involved in processing of painful stimuli. We employed an axiomatic approach to determine areas showing higher activation in painful compared to nonpainful heat and, at the same time, showing a steeper SRF for painful heat compared to unpleasant sound. Intriguingly, an area in the posterior parietal operculum emerged, whose response showed a pain preference after satisfying all axiomatic constraints. This result has important implications for the interpretation of functional imaging findings in pain research, because it clearly demonstrates that there are areas where activity following painful stimulation is not due to general attributes or results of sensory stimulation, such as salience or arousal. Conversely, several areas did not conform to the formulated axioms to rule out general factors as explanations. [ABSTRACT FROM AUTHOR]

In Ebstein’s anomaly, maximal expansion in the atrialized right ventricle (RV) occurs during early diastole, whereas that of the functional RV occurs in late diastole, resulting in diastolic dyssynchronous expansion (DSE). We quantitatively assessed DSE and identified preoperative factors correlated with persistent DSE after surgery. Seventeen patients diagnosed with Ebstein’s anomaly in whom transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) images available were retrospectively analyzed for quantitative DSE assessment and 10 patients who underwent surgery and postoperative TTE available were additionally analyzed for postoperative DSE. Severity of DSE was assessed by the time difference of maximal expansion between the atrialized and functional RV divided by the cardiac cycle length × 100 (“DSE index”). Relations between DSE and, clinical, electrophysiologic parameters and the severity of tricuspid valve (TV) tethering (the RV length / tethering height during diastole: “Tethering index”) were assessed. In total patients, median DSE index and tethering index were 30.3 and 2.1 respectively, and the DSE index was correlated with tethering index (rs = 0.664, P = 0.004). In 10 patients who underwent surgery, this association remained after surgery and at 2-year follow up. Tethering index ≥2.5 separated patients with and without persistent DSE. In conclusion, DSE exists in Ebstein’s anomaly. DSE index is related to the tethering index and DSE persists postoperatively if tethering index ≥ 2.5. As the persistent DSE might possibly impede the optimal recovery of RV function after surgery, severity of TV tethering should take into account in considering surgery. [ABSTRACT FROM AUTHOR]

Introduction: In the equine racehorse industry, reduced athletic performance due to joint injury and lameness has been extensively reviewed. Intra-articular injections of glucocorticoids are routinely used to relieve pain and inflammation associated with osteoarthritis. Intra-articular injections of pharmaceutical agents require practice for precise needle placement and to minimize complications. Training on simulators or models is a viable alternative for developing these technical skills. The purpose of this study was to compare the qualitative ultrasonographic characteristics of three-dimensional (3D) printed models of equine cervical articular process joints to that of a dissected equine cervical spine (gold standard). Methods: A randomized complete block design study was conducted in which a total of thirteen cervical articular process joint models were printed using several materials, printers, and printing technologies. Ultrasound video clips with the models immersed in water were recorded. Two board certified veterinary radiologists and three veterinary radiology residents reviewed the videos and responded to a survey assessing and comparing the ultrasonographic characteristics of the 3D printed models to those of the gold standard. Results: Six 3D printed models had ultrasonographic characteristics similar to the gold standard. These six models were (material, printer, printing technology): nylon PA 12, EOS Formiga P100, selective laser sintering (P = 0.99); Onyx nylon with chopped carbon fiber, Markforged Onyx Two, fused deposition modeling (P = 0.48); polycarbonate, Ultimaker 3, fused deposition modeling (P = 0.28); gypsum, ProJet CJP 660 Pro, ColorJet Printing (P = 0.28); polylactic acid, Prusa I3, fused deposition modeling (P = 0.23); and high temperature V1 resin, Form 2, stereolithography (P = 0.22). Conclusion: When assessed in water, it is possible to replicate the qualitative ultrasonographic characteristics of bone using three dimensional printed models made by combining different materials, printing technologies, and printers. However, not all models share similar qualitative ultrasonographic characteristics with bone. We suggest that the aforementioned six models be used as proxy for simulating bones or joints for use with ultrasound. In order to replicate the resistance and acoustic window provided by soft tissues, further work testing the ability of these models to withstand embedding in material such as ballistic gelatin is required. [ABSTRACT FROM AUTHOR]

Background: Quantifying reproducibility of native T1 and T2 mapping over a long period (> 1 year) is necessary to assess whether changes in T1 and T2 over repeated sessions in a longitudinal study are associated with variability due to underlying tissue composition or technical confounders. Objectives: To carry out a single-center phantom study to 1) investigate measurement reproducibility of slice-interleaved T1 (STONE) and T2 mapping over 20 months, 2) quantify sources of variability, and 3) compare reproducibility and measurements against reference spin-echo measurements. Methods: MR imaging was performed on a 1.5 Tesla Philips Achieva scanner every 2–3 weeks over 20 months using the T1MES phantom. In each session, slice-interleaved T1 and T2 mapping was repeated 3 times for 5 slices, and maps were reconstructed using both 2-parameter and 3-parameter fit models. Reproducibility between sessions, and repeatability between repetitions and slices were evaluated using coefficients of variation (CV). Different sources of variability were quantified using variance decomposition analysis. The slice-interleaved measurement was compared to the spin-echo reference and MOLLI. Results: Slice-interleaved T1 had excellent reproducibility and repeatability with a CV < 2%. The main sources of T1 variability were temperature in 2-parameter maps, and slice in 3-parameter maps. Superior between-session reproducibility to the spin-echo T1 was shown in 2-parameter maps, and similar reproducibility in 3-parameter maps. Superior reproducibility to MOLLI T1 was also shown. Similar measurements to the spin-echo T1 were observed with linear regression slopes of 0.94–0.99, but slight underestimation. Slice-interleaved T2 showed good reproducibility and repeatability with a CV < 7%. The main source of T2 variability was slice location/orientation. Between-session reproducibility was lower than the spin-echo T2 reference and showed good measurement agreement with linear regression slopes of 0.78–1.06. Conclusions: Slice-interleaved T1 and T2 mapping sequences yield excellent long-term reproducibility over 20 months. [ABSTRACT FROM AUTHOR]

Background: Clinical tuberculosis diagnosis and empiric treatment have traditionally been common among patients with negative bacteriologic test results. Increasing availability of rapid molecular diagnostic tests, including Xpert MTB/RIF and the new Xpert Ultra cartridge, may alter the role of empiric treatment. Methods: We prospectively enrolled outpatients age > = 15 who were evaluated for pulmonary tuberculosis at three health facilities in Kampala, Uganda. Using sputum mycobacterial culture, interviews, and clinical record abstraction, we estimated the accuracy of clinical diagnosis relative to Xpert and sputum culture and assessed the contribution of clinical diagnosis to case detection. Results: Over a period of 9 months, 99 patients were diagnosed with pulmonary tuberculosis and subsequently completed sputum culture; they were matched to 196 patients receiving negative tuberculosis evaluations in the same facilities. Xpert was included in the evaluation of 291 (99%) patients. Compared to culture, Xpert had a sensitivity of 92% (95% confidence interval 83–97%) and specificity of 95% (92–98%). Twenty patients with negative Xpert were clinically diagnosed with tuberculosis and subsequently had their culture status determined; two (10%) were culture-positive. Considering all treated patients regardless of Xpert and culture data completeness, and considering treatment initiations before a positive Xpert (N = 4) to be empiric, 26/101 (26%) tuberculosis treatment courses were started empirically. Compared to sputum smear- or Xpert-positive patients with positive cultures, empirically-treated, Xpert-negative patients with negative cultures had higher prevalence of HIV (67% versus 37%), shorter duration of cough (median 4 versus 8 weeks), and lower inflammatory markers (median CRP 7 versus 101 mg/L). Conclusion: Judged against sputum culture in a routine care setting of high HIV prevalence, the accuracy of Xpert was high. Clinical judgment identified a small number of additional culture-positive cases, but with poor specificity. Although clinicians should continue to prescribe tuberculosis treatment for Xpert-negative patients whose clinical presentations strongly suggest pulmonary tuberculosis, they should also carefully consider alternative diagnoses. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effects of walking speed and slope on foot pressure changes in young healthy adults. Methods: Twenty young healthy adults (mean age 22.4 years, SD 1.2 years; 10 male and 10 female) participated in the study. Dynamic pedobarographic data during treadmill walking were obtained for combinations of three different walking speeds (3.2 km/hr, 4.3 km/hr, and 5.4 km/hr) and 5 different slopes (downhill 8 degrees, downhill 4 degrees, ground walking (0 degree), uphill 4 degrees, and uphill 8 degrees). Pedobarographic data such as the peak pressure and pressure–time integral were measured on five plantar segments: medial forefoot (MFF), lateral forefoot (LFF), medial midfoot (MMF), lateral midfoot (LMF), and heel. Maximum ankle dorsiflexion was also recorded using the Plug in Gait marker set. Results: All participants maintained heel-toe gait in all walking conditions. The peak pressure on the MFF during downhill slope walking was lower than that during ground and uphill walking, whereas the peak pressure on the MFF during uphill slope walking was similar to that during ground walking at each walking speed. The peak pressures on the heel were similar for different walking slopes at each walking speed. The peak pressures on the MFF and heel increased with an increase in walking speed. The pressure-time integral of the MFF did not show significant changes at different walking speeds and slopes. The pressure-time integral of the heel increased with an increase in walking slope and decrease in walking speed. Conclusions: Different walking speeds and slopes affected the pedobarographic characteristics of young healthy adults. Downhill walking with slower speed appeared to be beneficial to reduce or optimize MFF pressures, while downhill walking at a comfortable speed would be helpful to reduce or optimize heel pressures. The findings of this study have clinical implications in recommending activities to patients with foot pressure-related symptoms and disorders. [ABSTRACT FROM AUTHOR]

Purpose: This study compares the plan quality of magnetic-resonance image (MRI)-based intensity modulated radiation therapy (IMRT) using a linac (MR-linac-IMRT), MRI-based IMRT using tri-Co-60 sources (MR-Co-60-IMRT), and volumetric modulated arc therapy (VMAT) for spine stereotactic ablative radiotherapy (SABR). Methods: Twenty patients with thoracic spine metastasis were retrospectively selected for this study. For each patient, the MR-linac-IMRT, MR-Co-60-IMRT, and VMAT plans were generated using an identical CT image set and structures, except for the spinal cord and spinal cord planning organ-at-risk volume (PRV). Those two structures were contoured based on CT image sets for VMAT planning while those were contoured based on MR image sets for MR-linac-IMRT and MR-Co-60-IMRT planning. The initial prescription doses were 18 Gy in a single fraction for every plan in this study. If the tolerance level of the spinal cord was not met, the prescription doses were reduced to meet the tolerance level of the spinal cord. Dose-volumetric parameters of each plan were analyzed. Results: The average spinal cord volumes contoured based on the CT and MR images were 3.8±1.6 cm3 and 1.1±1.0 cm3, respectively (p<0.001). For four patients, the prescription doses of VMAT plans were reduced to 16 Gy to satisfy the spinal cord tolerance level. For thirteen patients, the prescription doses of MR-Co-60-IMRT plans were reduced to be less than 16 Gy to meet the spinal cord tolerance level. However, for every MR-linac-IMRT plan, the initial prescription doses of 18 Gy could be delivered to the target volume while satisfying the spinal cord tolerance. The average values of D10%, V10Gy, and V14Gy of the spinal cord PRV consistently indicated that the doses to the spinal cord PRV in the MR-linac-IMRT plans were the lowest among three types of plans in this study (all with p≤0.003). Conclusion: MR-linac-IMRT appears promising for spine SABR. [ABSTRACT FROM AUTHOR]

Purpose: To develop a 7T simultaneous multi-slice (SMS) 2D gradient-echo sequence for susceptibility contrast imaging, and to compare its quality to 3D imaging. Methods: A frequency modulated and phase cycled RF pulse was designed to simultaneously excite multiple slices in multi-echo 2D gradient-echo imaging. The imaging parameters were chosen to generate images with susceptibility contrast, including T2*-weighted magnitude/phase images, susceptibility-weighted images and quantitative susceptibility/R2* maps. To compare their image quality with 3D gradient-echo imaging, both 2D and 3D imaging were performed on 11 healthy volunteers and 4 patients with multiple sclerosis (MS). The signal to noise ratio (SNR) in gray and white matter and their contrast to noise ratio (CNR) was simulated for the 2D and 3D magnitude images using parameters from the imaging. The experimental SNRs and CNRs were measured in gray/white matter and deep gray matter structures on magnitude, phase, R2* and QSM images from volunteers and the visibility of MS lesions on these images from patients was visually rated. All SNRs and CNRs were compared between the 2D and 3D imaging using a paired t-test. Results: Although the 3D magnitude images still had significantly higher SNRs (by 13.0~17.6%), the 2D magnitude and QSM images generated significantly higher gray/white matter or globus pallidus/putamen contrast (by 13.3~87.5%) and significantly higher MS lesion contrast (by 5.9~17.3%). Conclusion: 2D SMS gradient-echo imaging can serve as an alternative to often used 3D imaging to obtain susceptibility-contrast-weighted images, with an advantage of providing better image contrast and MS lesion sensitivity. [ABSTRACT FROM AUTHOR]

Evidence using well-established imaging techniques, such as functional magnetic resonance imaging and electrocorticography, suggest that speech-specific cortical responses can be functionally localised by contrasting speech responses with an auditory baseline stimulus, such as time-reversed (TR) speech or signal-correlated noise (SCN). Furthermore, these studies suggest that SCN is a more effective baseline than TR speech. Functional near-infrared spectroscopy (fNIRS) is a relatively novel, optically-based imaging technique with features that make it ideal for investigating speech and language function in paediatric populations. However, it is not known which baseline is best at isolating speech activation when imaging using fNIRS. We presented normal speech, TR speech and SCN in an event-related format to 25 normally-hearing children aged 6–12 years. Brain activity was measured across frontal and temporal brain areas in both cerebral hemispheres whilst children passively listened to the auditory stimuli. In all three conditions, significant activation was observed bilaterally in channels targeting superior temporal regions when stimuli were contrasted against silence. Unlike previous findings in infants, we found no significant activation in the region of interest over superior temporal cortex in school-age children when normal speech was contrasted against either TR speech or SCN. Although no statistically significant lateralisation effects were observed in the region of interest, a left-sided channel targeting posterior temporal regions showed significant activity in response to normal speech only, and was investigated further. Significantly greater activation was observed in this left posterior channel compared to the corresponding channel on the right side under the normal speech vs SCN contrast only. Our findings suggest that neither TR speech nor SCN are suitable auditory baselines for functionally isolating speech-specific processing in an experimental set up involving fNIRS with 6–12 year old children. [ABSTRACT FROM AUTHOR]

Objective: To investigate the accuracy and precision of ultrasound shear wave elasticity measurements as a function of target elasticity and acquisition depth. Materials and methods: Using five ultrasound systems (VTQ, VTIQ, EPIQ 5, Aixplorer, and Aplio 500), two operators independently measured shear wave elasticities in two phantoms containing five different target elasticities (8±3, 14±4, 25±6, 45±8, and 80±12 kPa) at depths of 15, 30, 35, and 60 mm. Accuracy was assessed by evaluating measurement errors and the proportions of outliers, while factors affecting accuracy were assessed using logistic regression analysis. Measurement errors were defined as differences between the measured values and 1) the margins of the target elasticity, and 2) the median values of the target elasticity. Outliers were defined as measured values outside the margins of the target elasticity. Precision was assessed by calculating the reproducibility of measurements using the within-subject coefficient of variation (wCV). Results: Mean measurement errors and the proportions of outliers were higher for high than for low target elasticities (p<0.001), but did not differ in relation to acquisition depth, either within an elastography system or across the different systems. Logistic regression analysis showed that target elasticity (p<0.001) significantly affected accuracy, whereas acquisition depth (p>0.05) did not. The wCV for the 80±12 kPa target (31.33%) was significantly higher than that for lower elasticity targets (6.96–10.43 kPa; p<0.001). The wCV did not differ across acquisition depths. The individual elastography systems showed consistent results. Conclusions: Targets with high elasticity showed lower accuracy and lower precision than targets with low elasticity, while acquisition depth did not show consistent patterns in either accuracy or precision. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is one of the most common genetic disorders among the White population. The disease has a progressive course and leads to a reduction in the quality of life and of life expectancy. Standard diagnostic procedures used in the monitoring of CF patients include methods which expose patients to ionizing radiation. With increasing life expectancy in CF the cumulative dose of ionising radiation increases, prompting clinicians’ search for safer imaging studies. Despite its safety and availability lung ultrasound (LUS) is not routinely used in the diagnostic evaluation of CF patients. The aim of the study was to evaluate the diagnostic value of LUS in children with CF compared to a chest X-ray, and to assess the diagnostic value of the recently developed LUS score—CF-USS (Cystic Fibrosis Ultrasound Score). LUS was performed in 48 CF children and adolescents aged from 5 to 18 years (24 girls and 24 boys). LUS consisted of the assessment of the pleura, lung sliding, A-line and B-line artefacts, "lung rockets", alveolar consolidations, air bronchogram and pleural effusion. Chest radiography was performed in all patients and analyzed according to the modified Chrispin-Norman score. LUS was analyzed according to CF-USS. The correlation between the CF-USS and the modified Chrispin-Norman scores was moderate (R = 0.52, p = 0.0002) and strong in control studies. In 75% of patients undergoing LUS, small areas of subpleural consolidations were observed, which were not visible on x-rays. At the same time, LUS was not sensitive enough to visualize bronchial pathology, which plays an important role in assessing the progression of the disease. Conclusions: LUS constitutes an invaluable tool for the diagnosis of subpleural consolidations. CF-USS results correlate with the conventional x-ray modified Chrispin–Norman score. LUS should be considered a supplementary radiographic examination in the monitoring of CF patients, and CF-USS may provide clinicians with valuable information concerning the progression of the disease. [ABSTRACT FROM AUTHOR]

Objective: Meningitis after microsurgery for vestibular schwannoma (VS) is a severe complication that results in high morbidity. However, few studies have focused on meningitis after VS surgery. The purpose of this study was to identify the risk factors for meningitis after VS surgery. Methods: We performed a retrospective analysis of all VS patients who underwent microsurgery and survived for at least 7 days after surgery, between 1 June 2015 and 30 November 2018 at West China Hospital of Sichuan University. Univariate and multivariate analyses were performed to identify the risk factors for postoperative meningitis (POM). Results: We enrolled 410 patients, 27 of whom had POM. Through univariate analysis, the factors of hydrocephalus (p = 0.018), Koos grade IV (p = 0.04), operative duration > 3 hours (p = 0.03) and intraoperative bleeding volume ≥400 ml (p = 0. 02) were significantly correlated with POM. The multivariate analysis showed that Koos grade IV (p = 0.04; OR = 3.19; 95% CI 1.032–3.190), operation duration > 3 hours (p = 0.03; OR = 7.927; 95% CI 1.043–60.265), and intraoperative bleeding volume ≥ 400 ml (p = 0.02; OR = 2.551; 95% CI 1.112–5.850) were the independent influencing factors of POM. Conclusions: Koos grade IV, operation duration > 3 hours, and intraoperative blood loss ≥ 400 ml were identified as independent risk factors for POM after microsurgery for VS. POM also caused a prolonged hospital stay. [ABSTRACT FROM AUTHOR]

Introduction: Tissue Phase Mapping (TPM) MRI can accurately measure regional myocardial velocities and strain. The lengthy data acquisition, however, renders TPM prone to errors due to variations in physiological parameters, and reduces data yield and experimental throughput. The purpose of the present study is to examine the quality of functional measures (velocity and strain) obtained by highly undersampled TPM data using compressed sensing reconstruction in infarcted and non-infarcted rat hearts. Methods: Three fully sampled left-ventricular short-axis TPM slices were acquired from 5 non-infarcted rat hearts and 12 infarcted rat hearts in vivo. The datasets were used to generate retrospectively (simulated) undersampled TPM datasets, with undersampling factors of 2, 4, 8 and 16. Myocardial velocities and circumferential strain were calculated from all datasets. The error introduced from undersampling was then measured and compared to the fully sampled data in order to validate the method. Finally, prospectively undersampled data were acquired and compared to the fully sampled datasets. Results: Bland Altman analysis of the retrospectively undersampled and fully sampled data revealed narrow limits of agreement and little bias (global radial velocity: median bias = -0.01 cm/s, 95% limits of agreement = [-0.16, 0.20] cm/s, global circumferential strain: median bias = -0.01%strain, 95% limits of agreement = [-0.43, 0.51] %strain, all for 4x undersampled data at the mid-ventricular level). The prospectively undersampled TPM datasets successfully demonstrated the feasibility of method implementation. Conclusion: Through compressed sensing reconstruction, highly undersampled TPM data can be used to accurately measure the velocity and strain of the infarcted and non-infarcted rat myocardium in vivo, thereby increasing experimental throughput and simultaneously reducing error introduced by physiological variations over time. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to investigate the effectiveness of monitoring relevant variations during treatments for electronic portal imaging device (EPID)-based 3D in vivo verification performed using planning CTs. Methods: Experiments on two simple phantoms (uniform and nonuniform phantoms) and a thoracic phantom were analyzed in this study, and six relevant variations including the machine output, planning target volume (PTV) deformation, multileaf collimator (MLC) and Phantom shift (set-up errors), and gantry and couch angle shifts were evaluated. 3D gamma and dose-volume histogram (DVH) methods were used to evaluate the detection sensitivity of the EPID-based 3D in vivo dosimetry and the dose accuracy of the EPID reconstruction, respectively, as affected by the variations, and the results were validated by determining the consistency with TPS simulated results. Results: The results of the simple phantoms showed that the gamma failure rates and DVH trend of EPID reconstructions were consistent with the results of TPS simulations for machine output and MLC shifts and inconsistent for phantom shift, gantry/couch angle shift and PTV deformation variations. The results of the thoracic phantom showed that CBCT-guided EPID reconstruction sensitively detected 3-mm Phantom shift in thoracic phantom and its gamma failure rates and DVH trend were consistent with the results of TPS simulations. Conclusion: The variations, such as machine output and MLC shift, that are phantom unrelated and cause changes in the beam of the linear accelerator can be sensitively detected by EPID-based 3D in vivo dosimetry and do not affect the accuracy of the EPID reconstruction dose. Planning CT will limit the detection sensitivity and the accuracy of the reconstruction dose of the EPID-based 3D in vivo dosimetry for phantom-related variations (such as Phantom shift and gantry/couch angle shift). EPID reconstruction combined with IGRT technology is a more effective method to monitor phantom shift variations. [ABSTRACT FROM AUTHOR]

Innovative protein engineering and chemical conjugation technologies have yielded an impressive number of drug candidates in clinical development including >80 antibody drug conjugates, >60 bispecific antibodies, >35 Fc-fusion proteins and >10 immuno-cytokines. Despite these innovations, technological advances are needed to address unmet medical needs with new pharmacological mechanisms. Age-related eye diseases are among the most common causes of blindness and poor vision in the world. Many such diseases affect the back of the eye, where the inaccessibility of the site of action necessitates therapeutic delivery via intravitreal (IVT) injection. Treatments administered via this route typically have vitreal half-lives <10 days in humans, requiring frequent administration. Since IVT injection is burdensome to patients, there exists a strong need to develop therapeutics with prolonged residence time in the eye. We report here a strategy to increase retention of a therapeutic fragment antibody (Fab) in the eye, using an anti-complement factor D Fab previously optimized for ocular delivery. Polyethylene glycol structures, varying in length, geometry and degree of branching, were coupled to the Fab via maleimide-activated termini. A screening strategy was developed to allow for key determinants of ocular half-life to be measured in vitro. After compound selection, a scalable process was established to enable tolerability and pharmacokinetic studies in cynomolgus monkeys, demonstrating an increase in vitreal half-life with no associated adverse events. Further, we show that the technique for compound selection, analytical characterization, and scalable production is general for a range of antibody fragments. The application of the technology has broad impact in across many therapeutic areas with the first major advancement in the treatment of an important ocular disease. [ABSTRACT FROM AUTHOR]

Since the outset of body image reconstruction for diagnosis purposes, ultrasound has been used to investigate structural changes located in tendons. Ultrasound has clinical applications in the intensive care unit, but its utility for tendon imaging remains unknown. Thus, we aimed to determine intra- and inter-rater reproducibility of measures obtained by images generated through morphological tendon sonographic analysis recorded from critically ill patients. We designed a cross-sectional study to assess thickness, cross-sectional area, and echogenicity of patellar and quadriceps tendons in a convenience sample formed with 20 critically ill patients. Two independent raters (experienced and novice) recorded repeated measures, checking for agreement (Kappa statistics) and reliability (Intraclass coefficient Correlation-ICC and Bland-Altman). The quality of images acquired by the two independent raters substantially agreed (k = 0.571–1.000), regardless of the region on the patellar tendon or the studied tendon (patellar or quadriceps). Regardless of how much experience the rater had, their repeated records (intra-rater reliability) always demonstrated almost complete correlation, ICC ranging from 0.89 to 0.98 for both tendons in all outcomes. At the same way, the statistically significant inter-rater ICC ranging from 0.87 to 0.97. Both repeated measures by the raters (intra-rater) and the repeated single and double measures between the raters (inter-rater) presented a minimum measurement error constituting a predominant pattern of random variability. We conclude that ultrasound imaging acquisition performed by independent raters for tendon thickness, CSA, and echogenicity monitoring of critically ill patients are acceptable and are not influenced by rater experience. [ABSTRACT FROM AUTHOR]

Conventional ultrasound (US) is the first-line imaging method for abdominal pathologies, but its diagnostic accuracy is operator-dependent, and data storage is usually limited to two-dimensional images. A novel tomographic US system (Curefab CS, Munich, Germany) processes imaging data combined with three-dimensional spatial information using a magnetic field tracking. This enables standardized image presentation in axial planes and a review of the entire examination. The applicability and diagnostic performance of this tomographic US approach was analyzed in an abdominal setting using conventional US as reference. Tomographic US data were successfully compiled in all subjects of a training cohort (20 healthy volunteers) and in 50 patients with abdominal lesions. Image quality (35% and 79% for training and patient cohort respectively) and completeness of organ visualization (45% and 44%) were frequently impaired in tomographic US compared to conventional US. Conventional and tomographic US showed good agreement for measurement of organ sizes in the training cohort (right liver lobe and both kidneys with a median deviation of 5%). In the patient cohort, tomographic US identified 57 of 74 hepatic or renal lesions detected by conventional ultrasound (sensitivity 77%). In conclusion, this study illustrates the diagnostic potential of abdominal tomographic US, but current significant limitations of the tomographic ultrasound device demand further technical improvements before this and comparable approaches can be implemented in clinical practice. [ABSTRACT FROM AUTHOR]

Interstitial cystitis and/or bladder pain syndrome (IC/BPS) are characterized by discomfort, abdominal pain, and pelvic pain, and they are often associated with chronic diseases. Pathological conditions related to IC/BPS can occur due to a defect in the integrity of the bladder lining. This defect has been ascribed to damage to the glycosaminoglycan (GAG) layer of the urinary epithelium. In addition, the incipient cascade of inflammation events might prompt extracellular matrix degradation. Several medical devices based on GAG instillation were proposed to re-establish epithelial integrity by GAGs binding to proteoglycans or interacting with structural urothelium. However, to date, only in vitro studies have investigated the GAG, hyaluronic acid (HA). In the present study, TNFα treatment was used to mimic IC/BPS-induced damage in bladder cells in an in vitro model. Highly purified fermentative HA and pharmaceutical grade bovine chondroitin sulfate (CSb), alone or in combination, were evaluated for the ability to counteract bladder cell damage. We evaluated NF-κB with western blots, and we analyzed interleukin 6 and 8 expression at the transcriptional and protein levels with quantitative RT-PCR, western blotting, and ELISA. We also evaluated the expression of an antibacterial peptide, human β-defensin-2. We confirmed our results in a 3D bladder epithelium model. Our results demonstrated that inflammatory status was reduced in the presence of HA, CSb, and the combination of both (HA/CSb 1.6%/2% w/v). This result suggested that these GAGs might be suitable for treating IC/BPS. All the assayed biomarkers showed that HA/CSb treatment modulated cells towards a more physiological status. Finally, we compared two commercial products suggested for the IC/BPS treatments and found that the product with more Ca++, showed enhanced anti-inflammatory activity and provided superior mucoadhesivity. [ABSTRACT FROM AUTHOR]

Early detection of asymptomatic carotid stenosis may help identifying individuals at risk of stroke. We explore a new method based on laser Doppler vibrometry (LDV) which could allow the non-contact detection of stenosis from neck skin vibrations due to stenosis-induced flow disturbances. Experimental fluid dynamical tests were performed with water on a severely stenosed patient-specific carotid bifurcation model. Measurements were taken under various physiological flow regimes both in a compliant and stiff-walled version of the model, at 1 to 4 diameters downstream from the stenosis. An inter-arterial pressure catheter was positioned as reference. Increasing flow led to corresponding increase in power spectral density (PSD) of pressure and LDV recordings in the 0–500 Hz range. The stiff model lead to higher PSD. PSD of the LDV signal was less dependent on the downstream measurement location than pressure. The strength of the association between PSD and flow level, model material and measuring location was highest in the 0–50 Hz range, however useful information was found up to 200 Hz. This proof-of-concept suggests that LDV has the potential to detect stenosis-induced disturbed flow. Further computational and clinical validation studies are ongoing to assess the sensitivity and specificity of the technique for clinical screening. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the effect of a mentally demanding response inhibitory task on time trial performance in sub-elite under 23 cyclists. Methods: Ten under 23 road cyclists completed two separate testing sessions during which they performed two different cognitive tasks before completing a 30-min time trial on the cycle ergometer. In the experimental condition, 30 min of a standard cognitive task (Stroop task) was used to elicit mental fatigue; in the control condition, a non-demanding activity was carried out. Subjective workload and mood were measured before and after the treatments, and motivation was recorded before the time-trial. During the time trial, power, cadence, heart rate, and rate of perceived exertion were assessed. Blood lactate concentrations and heart rate variability (using the root mean square of the successive differences) were measured before and after the time trial. Results: The Stroop task was rated more mentally (P < 0.001) and temporally (P < 0.001) demanding, effortful (P < 0.001), and frustrating (P = 0.001) than the control task; fatigue (P = 0.002) and vigor (P = 0.018) after the cognitive tasks were respectively higher and lower than in the control task. Mean power output (P = 0.007) and cadence (P = 0.043) were negatively affected by the Stroop task, while heart rate (P = 0.349), rating of perceived exertion (P = 0.710), blood lactate concentration (P = 0.850), and root mean square of the successive differences (P = 0.355) did not differ between the two conditions. Conclusion: A mentally demanding activity reduced the subsequent physical performance in sub-elite under 23 cyclists. Thus, avoiding cognitive efforts before training and races could improve performance of high-level athletes. [ABSTRACT FROM AUTHOR]

The benefit of revascularization of chronic total occlusion (CTO) in percutaneous coronary intervention (PCI) is controversial. On the other hand, left ventricular (LV) global longitudinal strain (GLS) is a more sensitive marker of LV myocardial ischemia and LV function than LV ejection fraction (EF). The purpose of this study was to investigate the impact of revascularization of CTO on LV function using LV GLS. A total of 70 consecutive patients (65.1±8.9 years, 59 males, LVEF 51.0±12.0%) with CTO who had a positive functional ischemia and underwent PCI, were included in this study. Echocardiography was performed before and 9 months after the procedure with conventional assessment including LV end-diastolic and end-systolic volume (LVEDV, LVESV), LVEF, and with 2DSTE analysis of GLS. Successful PCI was obtained in 60 patients (86%). There were no stent thromboses during follow-up. GLS showed a significant improvement 9 months after successful PCI (pre-PCI -12.4±4.1% vs. post-PCI -14.5±4.1%, P< 0.01), whereas in failed PCI group that did not change significantly (pre-PCI -13.2±4.2% vs. post-PCI -14.0±4.7%, P = 0.64). LVEF, LVEDV and LVESV did not change significantly during follow-up in both successful and failed groups. Successful PCI for CTO improved LV function, assessed by LV GLS. [ABSTRACT FROM AUTHOR]

Wall shear stress (WSS), the frictional force exerted on endothelial cells by blood flow, is hypothesised to influence atherosclerotic plaque growth and composition. We developed a methodology for image registration of MR and histology images of advanced human carotid plaques and corresponding WSS data, obtained by MRI and computational fluid dynamics. The image registration method requires four types of input images, in vivo MRI, ex vivo MRI, photographs of transversally sectioned plaque tissue and histology images. These images are transformed to a shared 3D image domain by applying a combination of rigid and non-rigid registration algorithms. Transformation matrices obtained from registration of these images are used to transform subject-specific WSS data to the shared 3D image domain as well. WSS values originating from the 3D WSS map are visualised in 2D on the corresponding lumen locations in the histological sections and divided into eight radial segments. In each radial segment, the correlation between WSS values and plaque composition based on histological parameters can be assessed. The registration method was successfully applied to two carotid endarterectomy specimens. The resulting matched contours from the imaging modalities had Hausdorff distances between 0.57 and 0.70 mm, which is in the order of magnitude of the in vivo MRI resolution. We simulated the effect of a mismatch in the rigid registration of imaging modalities on WSS results by relocating the WSS data with respect to the stack of histology images. A 0.6 mm relocation altered the mean WSS values projected on radial bins on average by 0.59 Pa, compared to the output of original registration. This mismatch of one image slice did not change the correlation between WSS and plaque thickness. In conclusion, we created a method to investigate correlations between WSS and plaque composition. [ABSTRACT FROM AUTHOR]

Purpose: To test the accuracy, validity, reliability and sensitivity of an alternative method for the measure of TMS-assessed voluntary activation (VATMS) in the knee extensors. Methods: Ten healthy males (24 ± 5 years) completed a neuromuscular assessment protocol before and after a fatiguing isometric exercise: two sets of five contractions (50%, 62.5%, 75%, 87.5%, 100% Maximal Voluntary Contraction; MVC) with superimposed TMS-evoked twitches for calculation of VATMS using either the first 5 stimulations (1x5C) or all 10 (2x5C). This was performed on two separate occasions (between-day reliability). Accuracy and validity were compared with a routinely used protocol [i.e. 50%, 75%, and 100% of MVC (1x3C) performed three times (3x3C)]. Results: 95% confidence interval for estimated resting twitch, a key determinant of VATMS, was similar between 1x5C, 2x5C, and 3x3C but improved by six-fold when compared to 1x3C (P<0.05). In a fresh state, potentiated twitch force was unchanged following 1x5C but decreased following 2x5C (P<0.05). A recovery was found post-exercise but was smaller for 1x5C compared to 2x5C (P<0.05), with no difference between the latter two (P>0.05). Absolute reliability was strong enough for both 1x5C and 2x5C to depict a true detectable change in the sample's VATMS following the fatiguing exercise (TEM < 3% at rest, <9% post-exercise) but 2x5C was marginally more sensitive to individual's changes from baseline. Conclusion: Both 1x5C and 2x5C provide reliable measures of VATMS. However, 1x5C may hold stronger internal validity. Both protocols allow detection of 'true' changes in sample's means but not individual scores following a fatiguing isometric exercise. [ABSTRACT FROM AUTHOR]

Lung tissue causes significant small-angle X-ray scattering, which can be visualized with grating-based X-ray dark-field imaging. Structural lung diseases alter alveolar microstructure, which often causes a dark-field signal decrease. The imaging method provides benefits for diagnosis of such diseases in small-animal models, and was successfully used on porcine and human lungs in a fringe-scanning setup. Micro- and macroscopic changes occur in the lung during breathing, but their individual effects on the dark-field signal are unknown. However, this information is important for quantitative medical evaluation of dark-field thorax radiographs. To estimate the effect of these changes on the dark-field signal during a clinical examination, we acquired in vivo dark-field chest radiographs of two pigs at three ventilation pressures. Pigs were used due to the high degree of similarity between porcine and human lungs. To analyze lung expansion separately, we acquired CT scans of both pigs at comparable posture and ventilation pressures. Segmentation, masking, and forward-projection of the CT datasets yielded maps of lung thickness and logarithmic lung attenuation signal in registration with the dark-field radiographs. Upon correlating this data, we discovered approximately linear relationships between the logarithmic dark-field signal and both projected quantities for all scans. Increasing ventilation pressure strongly decreased dark-field extinction coefficients, whereas the ratio of lung dark-field and attenuation signal changed only slightly. Furthermore, we investigated ratios of dark-field and attenuation noise levels at realistic signal levels via calculations and phantom measurements. Dark-field contrast-to-noise ratio (CNR) per lung height was 5 to 10% of the same quantity in attenuation. We conclude that better CNR performance in the dark-field modality is typically due to greater anatomical noise in the conventional radiograph. Given the high physiological similarity of human and porcine lungs, the presented thickness-normalized, ventilation-dependent values allow estimation of dark-field activity of human lungs of variable size and inspiration, which facilitates the design of suitable clinical imaging setups. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate the feasibility of intraosseous (i.o.) contrast media injection (CMI) for emergency computed tomography (CT) of severe trauma and the associated image quality compared to intravenous (i.v.) CMI. Materials and methods: The authors retrospectively analysed objective (contrast-to-noise ratio (CNR)) and subjective (4-point Likert scale) image quality of CTs after i.o. (n = 4, mean age (y) 57.0±11.0) versus i.v. (n = 20, mean age (y) 58.8±4.4) CMI. All patients underwent a native head CT scan, a cerebral CT angiography (CTA) and CTA of the supra-aortic vasculature as well as a chest and abdominal CT scan in the venous phase; one patient with an i.o. access additionally received a CTA of the lower limbs. Electronic patient records have been reviewed to determine i.o. access related complications. Results: Both groups were consistent in age, heart rate, scan parameters including the flow rate of the contrast agent, resulting in comparable radiation dose levels. The image noise and CNR had no significant difference between the two groups. Scoring the delineation of the main vessels after i.o. CMI showed no significant difference to the i.v. group. There were no CT or i.o. access related complications observed. Conclusion: The i.o. access is a safe and suitable alternative for emergency CMI in CT. Using established protocols good to very good image quality can be achieved, comparable to i.v. CMI. We show for the first time, that i.o. CMI is also feasible for CTA imaging of the head and neck region as well as of pelvic and leg vessels. [ABSTRACT FROM AUTHOR]

To meet the need for Parkinson’s disease biomarkers and evidence for amount and distribution of pathological changes, MRI diffusion tensor imaging (DTI) has been explored in a number of previous studies. However, conflicting results warrant further investigations. As tissue microstructure, particularly of the grey matter, is heterogeneous, a more precise diffusion model may benefit tissue characterization. The purpose of this study was to analyze the diffusion-based imaging technique restriction spectrum imaging (RSI) and DTI, and their ability to detect microstructural changes within brain regions associated with motor function in Parkinson’s disease. Diffusion weighted (DW) MR images of a total of 100 individuals, (46 Parkinson’s disease patients and 54 healthy controls) were collected using b-values of 0–4000s/mm2. Output diffusion-based maps were estimated based on the RSI-model combining the full set of DW-images (Cellular Index (CI), Neurite Density (ND)) and DTI-model combining b = 0 and b = 1000 s/mm2 (fractional anisotropy (FA), Axial-, Mean- and Radial diffusivity (AD, MD, RD)). All parametric maps were analyzed in a voxel-wise group analysis, with focus on typical brain regions associated with Parkinson’s disease pathology. CI, ND and DTI diffusivity metrics (AD, MD, RD) demonstrated the ability to differentiate between groups, with strongest performance within the thalamus, prone to pathology in Parkinson’s disease. Our results indicate that RSI may improve the predictive power of diffusion-based MRI, and provide additional information when combined with the standard diffusivity measurements. In the absence of major atrophy, diffusion techniques may reveal microstructural pathology. Our results suggest that protocols for MRI diffusion imaging may be adapted to more sensitive detection of pathology at different sites of the central nervous system. [ABSTRACT FROM AUTHOR]