Acute impact of aerobic exercise on local cutaneous thermal hyperaemia.

Little is known about the acute changes in cutaneous microvascular function that occur in response to exercise, the accumulation of which may provide the basis for beneficial chronic cutaneous vascular adaptations. Therefore, we examined the effects of acute exercise on cutaneous thermal hyperaemia. Twelve healthy, recreationally active participants (11 male, 1 female) performed 30-minute cycling at 50 % (low-intensity exercise, LOW) or 75 % (high-intensity exercise, HIGH) maximum heart rate. Laser Doppler flowmetry (LDF) and rapid local skin heating were used to quantify cutaneous thermal hyperaemia before (PRE), immediately following (IMM) and 1-h (1HR) after exercise. Baseline, axon reflex peak, axon reflex nadir, plateau, maximum skin blood flow responses to rapid local heating (42 °C for 30-min followed by 44 °C for 15-min) at each stage were assessed and indexed as cutaneous vascular conductance [CVC = flux / mean arterial blood pressure (MAP), PU·mm Hg-1], and expressed as a percentage of maximum (%CVCmax). Exercise increased heart rate (HR), MAP and skin blood flow (all P < 0.001), and to a greater extent during HIGH (all P < 0.001). The axon reflex peak and nadir were increased immediately and 1-h after exercise (all comparisons P < 0.01 vs. PRE), which did not differ between intensities (peak: P = 0.34, axon reflex nadir: P = 0.91). The endothelium-dependent plateau response was slightly elevated after exercise (P = 0.06), with no effect of intensity (P = 0.58) nor any interaction effect (P = 0.55). CONCLUSION: Exercise increases cutaneous microvascular axonal responses to local heating for up to 1-h, suggesting an augmented sensory afferent function post-exercise. Acute exercise may only modestly affect endothelial function in cutaneous microcirculation.

The effects of exercise training in the cold on cerebral blood flow and cerebrovascular function in young healthy individuals.

Exercise elicits acute increases in cerebral blood flow velocity (CBFv) and provokes long-term beneficial effects on CBFv, thereby reducing cerebrovascular risk. Acute exposure to a cold stimulus also increases CBFv. We compared the impact of exercise training in cold and thermoneutral environments on CFBv, cerebrovascular function and peripheral endothelial function. Twenty-one (16 males, 22 ± 5 years) individuals were randomly allocated to either a cold (5 °C) or thermoneutral (15 °C) exercise intervention. Exercise consisted of 50-min cycling at 70% heart rate max, three times per week for eight weeks. Transcranial Doppler was used to determine pre and post intervention CBFv, dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVRCO2). Conduit endothelial function, microvascular function and cardiorespiratory fitness were also assessed. Cardiorespiratory fitness improved (2.91 ml.min.kg-1, 95%CI 0.49, 5.3; P = 0.02), regardless of exercise setting. Neither intervention had an impact on CBFv, CVRCO2, FMD or microvascular function (P > 0.05). There was a significant interaction between time and condition for dCA normalised gain with evidence of a decrease by 0.192%cm.s-1.%mmHg-1 (95%CI -0.318, -0.065) following training in the cold and increase (0.129%cm.s-1.%mmHg-1, 95%CI 0.011, 0.248) following training in the thermoneutral environment (P = 0.001). This was also evident for dCA phase with evidence of an increase by 0.072 rad (95%CI -0.007, 0.152) following training in the cold and decrease by 0.065 (95%CI -0.144, 0.014) radians following training in the thermoneutral environment (P = 0.02). Both training interventions improved fitness but CBFv, CVRCO2 and peripheral endothelial function were unaltered. Exercise training in the cold improved dCA whereas thermoneutral negated dCA.

Oxynet: A collective intelligence that detects ventilatory thresholds in cardiopulmonary exercise tests.

The problem of the automatic determination of the first and second ventilatory thresholds (VT1 and VT2) from cardiopulmonary exercise test (CPET) still leads to controversy. The reliability of the gold standard methodology (i.e. expert visual inspection) feeds into the debate and several authors call for more objective automatic methods to be used in the clinical practice. In this study, we present a framework based on a collaborative approach, where a web-application was used to crowd-source a large number (1245) of CPET data of individuals with different aerobic fitness. The resulting database was used to train and test an artificial intelligence (i.e. a convolutional neural network) algorithm. This automatic classifier is currently implemented in another web-application and was used to detect the ventilatory thresholds in the available CPET. A total of 206 CPET were used to evaluate the accuracy of the estimations against the expert opinions. The neural network was able to detect the ventilatory thresholds with an average mean absolute error of 178 (198) mlO2/min (11.1%, r = 0.97) and 144 (149) mlO2/min (6.1%, r = 0.99), for VT1 and VT2 respectively. The performance of the neural network in detecting VT1 deteriorated in case of individuals with poor aerobic fitness. Our results suggest the potential for a collective intelligence system to outperform isolated experts in ventilatory thresholds detection. However, the inclusion of a larger number of VT1 examples certified by a community of experts will be likely needed before the abilities of this collective intelligence can be translated into the clinical use of CPET.

A mechanistic study of the tremor associated with epidural anaesthesia for intrapartum caesarean delivery.

BACKGROUND: It is not known if the tremor associated with an epidural top-up dose for intrapartum caesarean delivery is thermoregulatory shivering. A tremor is only shivering if it has the same frequency profile as cold stress-induced shivering. Thermoregulatory shivering is a response to a reduction in actual body temperature, whereas non-thermoregulatory shivering may be triggered by a reduction in sensed body temperature. This mechanistic study aimed to compare: 1. the frequency profiles of epidural top-up tremor and cold stress-induced shivering; and 2. body temperature (actual and sensed) before epidural top-up and at the onset of tremor. METHODS: Twenty obstetric patients received an epidural top-up for intrapartum caesarean delivery and 20 non-pregnant female volunteers underwent a cold stress. Tremor, surface electromyography, core temperature, skin temperature (seven sites) and temperature sensation votes (a bipolar visual analog score ranging from -50 to +50 mm) were recorded. RESULTS: The mean (SD) primary oscillation (9.9 (1.9) Hz) frequency of epidural top-up tremor did not differ from that of cold stress-induced shivering (9.0 (1.6) Hz; P=0.194), but the mean (SD) burst frequency was slower (6.1 (1.2) × 10-2 Hz vs 6.9 (0.7) × 10-2 Hz, respectively; P=0.046). Before the epidural top-up dose, the mean (SD) core temperature was 37.6 (0.6) °C. Between the epidural top-up dose and the onset of tremor the mean (SD) core temperature did not change (-0.1 (0.1) °C; P=0.126), the mean (SD) skin temperature increased (+0.4 (0.4) °C; P=0.002) and the mean (SD) temperature sensation votes decreased (-12 (16) mm; P=0.012). CONCLUSION: These results suggest that epidural top-up tremor is a form of non-thermoregulatory shivering triggered by a reduction in sensed body temperature.

McSART: an iterative model-based, motion-compensated SART algorithm for CBCT reconstruction.

4D cone beam computed tomography (CBCT) images of the thorax and abdomen can have reduced quality due to the limited number of projections per respiratory bin used in gated image reconstruction. In this work, we present a new algorithm to reconstruct high quality CBCT images by simultaneously reconstructing images and generating an associated respiratory motion model. This is done by updating model parameters to compensate for motion during the iterative image reconstruction process. CBCT image acquisition was simulated using the digital eXternal CArdiac Torso (XCAT) phantom, simulating breathing motion using four patient breathing traces. 4DCBCT images were reconstructed using the simultaneous algebraic reconstruction technique (SART), and compared to the proposed motion-compensated SART (McSART) algorithm. McSART used a motion model that describes tissue position as a function of diaphragm amplitude and velocity. The McSART algorithm alternately updated the motion model and image reconstruction, increasing the number of projections used for image reconstruction with every iteration. The model was able to interpolate and extrapolate deformations according to the magnitude of the surrogate signal. Without noise, the final iteration McSART images had HU errors at 31%, 34%, and 44% of their SART-reconstructed counterparts compared to ground truth XCAT images, with corresponding root-mean-square (RMS) motion model errors of 0.75 mm, 1.08 mm, and 1.17 mm respectively. With added image noise, McSART's HU error was 31% of the SART-reconstructed 4DCBCT error, with a 1.43 mm RMS motion model error. Qualitatively, blurring and streaking artifacts were reduced in all the reconstructed images compared to 3D or SART-reconstructed 4DCBCT. The output of the algorithm was a high quality reference image and a corresponding motion model, that could be used to deform the reference image to any other point in a breathing cycle.

Body temperature, cutaneous heat loss and skin blood flow during epidural anaesthesia for emergency caesarean section.

It is not clear how converting epidural analgesia for labour to epidural anaesthesia for emergency caesarean section affects either cutaneous vasomotor tone or mean body temperature. We hypothesised that topping up a labour epidural blocks active cutaneous vasodilation (cutaneous heat loss and skin blood flow decrease), and that as a result mean body temperature increases. Twenty women in established labour had body temperature, cutaneous heat loss and skin blood flow recorded before and after epidural top-up for emergency caesarean section. Changes over time were analysed with repeated measures ANOVA. Mean (SD) mean body temperature was 36.8 (0.5)°C at epidural top-up and 36.9 (0.6)°C at delivery. Between epidural top-up and delivery, the mean (SD) rate of increase in mean body temperature was 0.5 (0.5) °C.h-1 . Following epidural top-up, chest (p < 0.001) and forearm (p = 0.004) heat loss decreased, but head (p = 0.05), thigh (p = 0.79) and calf (p = 1.00) heat loss did not change. The mean (SD) decrease in heat loss was 15 (19) % (p < 0.001). Neither arm (p = 0.06) nor thigh (p = 0.10) skin blood flow changed following epidural top-up. Despite the lack of change in skin blood flow, the most plausible explanation for the reduction in heat loss and the increase in mean body temperature is blockade of active cutaneous vasodilation. It is possible that a similar mechanism is responsible for the hyperthermia associated with labour epidural analgesia.

A prospective gating method to acquire a diverse set of free-breathing CT images for model-based 4DCT.

Breathing motion modeling requires observation of tissues at sufficiently distinct respiratory states for proper 4D characterization. This work proposes a method to improve sampling of the breathing cycle with limited imaging dose. We designed and tested a prospective free-breathing acquisition protocol with a simulation using datasets from five patients imaged with a model-based 4DCT technique. Each dataset contained 25 free-breathing fast helical CT scans with simultaneous breathing surrogate measurements. Tissue displacements were measured using deformable image registration. A correspondence model related tissue displacement to the surrogate. Model residual was computed by comparing predicted displacements to image registration results. To determine a stopping criteria for the prospective protocol, i.e. when the breathing cycle had been sufficiently sampled, subsets of N scans where 5 ⩽ N ⩽ 9 were used to fit reduced models for each patient. A previously published metric was employed to describe the phase coverage, or 'spread', of the respiratory trajectories of each subset. Minimum phase coverage necessary to achieve mean model residual within 0.5 mm of the full 25-scan model was determined and used as the stopping criteria. Using the patient breathing traces, a prospective acquisition protocol was simulated. In all patients, phase coverage greater than the threshold necessary for model accuracy within 0.5 mm of the 25 scan model was achieved in six or fewer scans. The prospectively selected respiratory trajectories ranked in the (97.5 ± 4.2)th percentile among subsets of the originally sampled scans on average. Simulation results suggest that the proposed prospective method provides an effective means to sample the breathing cycle with limited free-breathing scans. One application of the method is to reduce the imaging dose of a previously published model-based 4DCT protocol to 25% of its original value while achieving mean model residual within 0.5 mm.

MRI-guided radiotherapy for head and neck cancer: initial clinical experience.

PURPOSE: To report a single-institutional experience with the use of magnetic resonance imaging (MRI)-guided radiotherapy for cancers of the head and neck. MATERIALS AND METHODS: Between October 2014 and October 2016, 18 patients with newly diagnosed cancers of the head and neck were prospectively enrolled on an institutional registry trial investigating the feasibility and efficacy of external-beam radiotherapy delivered using on-board MRI. All patients had biopsy-proven evidence of malignancy, measurable disease, and the ability to provide consent. None had previously received any treatment. Median dose was 70 Gy (range 54-70 Gy). MRI scans were obtained as part of an image-guided registration protocol for alignment prior to and during each treatment. Concurrent chemotherapy was administered to 14 patients (78%). Patient-reported outcomes were assessed using the University of Washington quality of life instrument. RESULTS: Seventeen of 18 patients completed the planned intensity-modulated radiotherapy (IMRT) treatment of which 15 (83%) had a complete response and 2 (11%) had a partial response based on initial post-therapy positron emission tomography (PET) at 3 months. The 1-year estimates of progression-free survival, overall survival, and local-regional control were 95, 96, and 95%, respectively. There were no treatment-related fatalities. The incidence of grade 3+ acute toxicity was 44%. The proportion of patients rating their health-related quality of life as "very good" or "outstanding" at 6 months and 1 year after completion of radiation therapy was 60 and 70%, respectively. CONCLUSIONS: MRI-guided radiotherapy achieves clinical outcomes comparable to contemporary series reporting on IMRT for head and neck cancer.

Twenty-four-hour ambulatory blood pressure and heart rate profiles in diagnosing orthostatic hypotension in Parkinson's disease and multiple system atrophy.

BACKGROUND AND PURPOSE: Twenty-four-hour ambulatory blood pressure and heart rate monitoring (24-h ABPM) can provide vital information on circadian blood pressure (BP) profiles, which are commonly abnormal in Parkinson's disease with and without autonomic failure (PD + AF and PD) and multiple system atrophy (MSA). Twenty-four-hour ABPM has not been directly compared between these disorders regarding cardiovascular autonomic function. Our aim was to determine the usefulness of 24-h ABPM with diary compared to head-up tilting (HUT) in diagnosing orthostatic hypotension (OH) in these patients. METHODS: Seventy-four patients (23 MSA, 18 PD + AF, 33 PD) underwent cardiovascular autonomic screening followed by 24-h ABPM with diary. Standing tests were included during 24-h ABPM. The sensitivity and specificity in detecting OH from the 24-h ABPM standing test were compared with HUT. RESULTS: There was no difference in OH during HUT between MSA and PD + AF (P > 0.05). There was a higher proportion of abnormal BP circadian rhythms in MSA and PD + AF compared to PD (P < 0.05) but not between MSA and PD + AF (P > 0.05). Patients were divided into groups with OH (OH+) and without OH (OH-) on HUT. Using the standing test during 24-h ABPM, a systolic BP fall of >20 mmHg showed a sensitivity and specificity of 82% and 100% (area under the curve 0.91, 95% confidence interval 0.84-0.98) in differentiating OH+ from OH-. CONCLUSIONS: Parkinson's disease with autonomic failure and MSA patients had similar circadian BP patterns suggesting that autonomic dysfunction influences abnormal BP circadian patterns similarly in these disorders. The higher sensitivity and specificity in detecting OH using a systolic BP fall of >20 mmHg compared to a diastolic BP fall of >10 mmHg during the standing test supports its usefulness to assess autonomic function in MSA and PD.

Analytical modeling and feasibility study of a multi-GPU cloud-based server (MGCS) framework for non-voxel-based dose calculations.

PURPOSE: In this paper, a multi-GPU cloud-based server (MGCS) framework is presented for dose calculations, exploring the feasibility of remote computing power for parallelization and acceleration of computationally and time intensive radiotherapy tasks in moving toward online adaptive therapies. METHODS: An analytical model was developed to estimate theoretical MGCS performance acceleration and intelligently determine workload distribution. Numerical studies were performed with a computing setup of 14 GPUs distributed over 4 servers interconnected by a 1 Gigabits per second (Gbps) network. Inter-process communication methods were optimized to facilitate resource distribution and minimize data transfers over the server interconnect. RESULTS: The analytically predicted computation time predicted matched experimentally observations within 1-5 %. MGCS performance approached a theoretical limit of acceleration proportional to the number of GPUs utilized when computational tasks far outweighed memory operations. The MGCS implementation reproduced ground-truth dose computations with negligible differences, by distributing the work among several processes and implemented optimization strategies. CONCLUSIONS: The results showed that a cloud-based computation engine was a feasible solution for enabling clinics to make use of fast dose calculations for advanced treatment planning and adaptive radiotherapy. The cloud-based system was able to exceed the performance of a local machine even for optimized calculations, and provided significant acceleration for computationally intensive tasks. Such a framework can provide access to advanced technology and computational methods to many clinics, providing an avenue for standardization across institutions without the requirements of purchasing, maintaining, and continually updating hardware.

Is there an ideal set of prospective scan acquisition phases for fast-helical based 4D-CT?

The article aims to determine if a prospective acquisition algorithm can be used to find the ideal set of free-breathing phases for fast-helical model-based 4D-CT. A retrospective five-patient dataset that consisted of 25 repeated free breathing CT scans per patient was used. The sum of the square root amplitude difference between all the breathing phases was defined as an objective function to determine the optimality of sets of breathing phases. The objective function was intended to determine if a specific set of breathing phases would yield a motion model that could accurately predict the motion in all 25 CT scans. Voxel specific motion models were calculated using all combinations of N scans from 25 breathing trajectories, (3 ⩽ N ⩽ 25), and the minimum number of scans required to absolutely characterize the motion model was analyzed. This analysis suggests that the number of scans could potentially be reduced to as few as five scans. When the objective function was large, the resulting motion model provided an excellent approximation to the motion model created using all 25 scans.

Repeated Warm Water Immersion Induces Similar Cerebrovascular Adaptations to 8 Weeks of Moderate-Intensity Exercise Training in Females.

Exercise training has the potential to enhance cerebrovascular function. Warm water immersion has recently been shown to enhance vascular function including the cerebrovascular response to heating. We suggest that passive heating can be used alternatively to exercise. Our aim was to compare the effects of exercise with warm-water immersion training on cerebrovascular and thermoregulatory function. 18 females (25±5 y) performed 8 weeks of cycling (70% HRmax) or warm water immersion (42°C) for 30 min 3 times per week. Brachial artery flow-mediated dilation (FMD) and peak cardiorespiratory fitness (VO2peak) were measured prior to and following both interventions. A passive heat stress was employed to obtain temperature thresholds (Tb) and sensitivities for sweat rate (SR) and cutaneous vasodilation (CVC). Middle cerebral artery velocity (MCAv) was measured throughout. FMD and VO2peak improved following both interventions (p<0.05). MCAv and cerebrovascular conductance were higher at rest and during passive heating (p<0.001 and <0.001, respectively) following both interventions. SR occurred at a lower Tb following both interventions and SR sensitivity also increased, with a larger increase at the chest (p<0.001) following water immersion. CVC occurred at a lower Tb (p<0.001) following both interventions. Warm water immersion elicits similar cerebrovascular, conduit, and thermoregulatory adaptations compared to a period of moderate-intensity exercise training.

Non-dipping nocturnal blood pressure and psychosis parameters in Parkinson disease.

BACKGROUND: Non-motor symptoms are increasingly recognized in Parkinson disease (PD) and include physical as well as psychological symptoms. A psychological condition that has been well studied in PD is psychosis. Cardiovascular autonomic dysfunction in PD can include a reversed or loss of blood pressure (BP) circadian rhythm, referred to as nocturnal non-dipping. The aim of this study was to determine the relationship between 24 h ambulatory blood pressure measurements (ABPM), i.e., absence or presence of nocturnal dipping, and psychosis scores in PD. METHODS: Twenty-one patiens with PD underwent 24 h ABPM using an autonomic protocol. A decrease in nocturnal mean arterial blood pressure of less than 10% was defined as non-dipping. Patients were interviewed (including the brief psychiatric rating scale; BPRS) for the assessment of psychosis. RESULTS: Eleven patients were dippers and 10 were non-dippers. BPRS scores were higher in non-dippers, who, on average, met the criteria for psychosis (mean non-dipper BPRS: 34.3 ± 7.3 vs mean dipper BPRS: 27.5 ± 5.3; cutoff for "mildly ill" 31). There was a correlation between BPRS scores and non-dipping, indicating that those patients who had a blunted nocturnal fall in BP were more prone to psychotic symptoms (Pearson's Correlation = 0.554, p = 0.009). CONCLUSION: These results suggest that, among PD patients, a non-dipping circadian rhythm is associated with more severe symptoms of psychosis than is a dipping circadian rhythm. This association warrants further investigation.

A GPU based high-resolution multilevel biomechanical head and neck model for validating deformable image registration.

PURPOSE: Validating the usage of deformable image registration (dir) for daily patient positioning is critical for adaptive radiotherapy (RT) applications pertaining to head and neck (HN) radiotherapy. The authors present a methodology for generating biomechanically realistic ground-truth data for validating dir algorithms for HN anatomy by (a) developing a high-resolution deformable biomechanical HN model from a planning CT, (b) simulating deformations for a range of interfraction posture changes and physiological regression, and (c) generating subsequent CT images representing the deformed anatomy. METHODS: The biomechanical model was developed using HN kVCT datasets and the corresponding structure contours. The voxels inside a given 3D contour boundary were clustered using a graphics processing unit (GPU) based algorithm that accounted for inconsistencies and gaps in the boundary to form a volumetric structure. While the bony anatomy was modeled as rigid body, the muscle and soft tissue structures were modeled as mass-spring-damper models with elastic material properties that corresponded to the underlying contoured anatomies. Within a given muscle structure, the voxels were classified using a uniform grid and a normalized mass was assigned to each voxel based on its Hounsfield number. The soft tissue deformation for a given skeletal actuation was performed using an implicit Euler integration with each iteration split into two substeps: one for the muscle structures and the other for the remaining soft tissues. Posture changes were simulated by articulating the skeletal structure and enabling the soft structures to deform accordingly. Physiological changes representing tumor regression were simulated by reducing the target volume and enabling the surrounding soft structures to deform accordingly. Finally, the authors also discuss a new approach to generate kVCT images representing the deformed anatomy that accounts for gaps and antialiasing artifacts that may be caused by the biomechanical deformation process. Accuracy and stability of the model response were validated using ground-truth simulations representing soft tissue behavior under local and global deformations. Numerical accuracy of the HN deformations was analyzed by applying nonrigid skeletal transformations acquired from interfraction kVCT images to the model's skeletal structures and comparing the subsequent soft tissue deformations of the model with the clinical anatomy. RESULTS: The GPU based framework enabled the model deformation to be performed at 60 frames/s, facilitating simulations of posture changes and physiological regressions at interactive speeds. The soft tissue response was accurate with a R(2) value of >0.98 when compared to ground-truth global and local force deformation analysis. The deformation of the HN anatomy by the model agreed with the clinically observed deformations with an average correlation coefficient of 0.956. For a clinically relevant range of posture and physiological changes, the model deformations stabilized with an uncertainty of less than 0.01 mm. CONCLUSIONS: Documenting dose delivery for HN radiotherapy is essential accounting for posture and physiological changes. The biomechanical model discussed in this paper was able to deform in real-time, allowing interactive simulations and visualization of such changes. The model would allow patient specific validations of the dir method and has the potential to be a significant aid in adaptive radiotherapy techniques.

A nonvoxel-based dose convolution/superposition algorithm optimized for scalable GPU architectures.

PURPOSE: Real-time adaptive planning and treatment has been infeasible due in part to its high computational complexity. There have been many recent efforts to utilize graphics processing units (GPUs) to accelerate the computational performance and dose accuracy in radiation therapy. Data structure and memory access patterns are the key GPU factors that determine the computational performance and accuracy. In this paper, the authors present a nonvoxel-based (NVB) approach to maximize computational and memory access efficiency and throughput on the GPU. METHODS: The proposed algorithm employs a ray-tracing mechanism to restructure the 3D data sets computed from the CT anatomy into a nonvoxel-based framework. In a process that takes only a few milliseconds of computing time, the algorithm restructured the data sets by ray-tracing through precalculated CT volumes to realign the coordinate system along the convolution direction, as defined by zenithal and azimuthal angles. During the ray-tracing step, the data were resampled according to radial sampling and parallel ray-spacing parameters making the algorithm independent of the original CT resolution. The nonvoxel-based algorithm presented in this paper also demonstrated a trade-off in computational performance and dose accuracy for different coordinate system configurations. In order to find the best balance between the computed speedup and the accuracy, the authors employed an exhaustive parameter search on all sampling parameters that defined the coordinate system configuration: zenithal, azimuthal, and radial sampling of the convolution algorithm, as well as the parallel ray spacing during ray tracing. The angular sampling parameters were varied between 4 and 48 discrete angles, while both radial sampling and parallel ray spacing were varied from 0.5 to 10 mm. The gamma distribution analysis method (γ) was used to compare the dose distributions using 2% and 2 mm dose difference and distance-to-agreement criteria, respectively. Accuracy was investigated using three distinct phantoms with varied geometries and heterogeneities and on a series of 14 segmented lung CT data sets. Performance gains were calculated using three 256 mm cube homogenous water phantoms, with isotropic voxel dimensions of 1, 2, and 4 mm. RESULTS: The nonvoxel-based GPU algorithm was independent of the data size and provided significant computational gains over the CPU algorithm for large CT data sizes. The parameter search analysis also showed that the ray combination of 8 zenithal and 8 azimuthal angles along with 1 mm radial sampling and 2 mm parallel ray spacing maintained dose accuracy with greater than 99% of voxels passing the γ test. Combining the acceleration obtained from GPU parallelization with the sampling optimization, the authors achieved a total performance improvement factor of >175 000 when compared to our voxel-based ground truth CPU benchmark and a factor of 20 compared with a voxel-based GPU dose convolution method. CONCLUSIONS: The nonvoxel-based convolution method yielded substantial performance improvements over a generic GPU implementation, while maintaining accuracy as compared to a CPU computed ground truth dose distribution. Such an algorithm can be a key contribution toward developing tools for adaptive radiation therapy systems.

Generating lung tumor internal target volumes from 4D-PET maximum intensity projections.

PURPOSE: Positron emission tomography (PET) of lung tumors suffers from breathing-motion induced blurring. Respiratory-correlated PET ameliorates motion blurring and enables visualization of lung tumor functional uptake throughout the breathing cycle but has achieved limited clinical use in radiotherapy planning. In this work, the authors propose a process for generating a gated PET maximum intensity projection (MIP), a breathing-phase projection of the 4D image set comprising gated PET images, as a technique to quantitatively and efficiently incorporate respiratory-correlated PET information into radiotherapy treatment planning. METHODS: 4D-CT and respiratory-gated PET using [(18)F]fluorodeoxyglucose (FDG) were acquired of three patients with a total of four small (4-18 cc), clearly defined lower-lobe lung tumors. Internal target volumes (ITVs) for the lung tumors were generated by threshold-based segmentation of PET-MIP images and ungated PET images (ITV(PET-MIP) and ITV(3D-PET), respectively), and by manual contouring of CT-MIP and end-exhale and end-inhale phases of 4D-CT (ITV(CT-MIP)) by a radiation oncologist. Because of the sensitivity of tumor segmentation to threshold value, several different thresholds were tested for ITV generation, including 40%, 30%, and 20% of maximum standardized uptake value (SUV(max)) for FDG as well as absolute SUV thresholds of 2.5 and 3.0. The normalized overlap and relative volumes of ITV(PET-MIP) and ITV(3D-PET) with respect to ITV(CT-MIP) were compared. The images were also visually compared. ITV(CT-MIP) was considered a gold standard for these tumors with CT-visible morphology. RESULTS: The mean and standard deviation normalized overlap and relative volumes between ITV(PET-MIP) and ITV(CT-MIP) were 0.68 ± 0.07 and 1.07 ± 0.42, respectively, averaged over all four tumors and all five threshold values. The mean and standard deviation normalized overlap and relative volumes of ITV(3D-PET) and ITV(CT-MIP) were 0.47 ± 0.12 and 0.69 ± 0.56, respectively. CONCLUSIONS: PET-MIP images better match CT-MIP images for this sample of four small CT-visible tumors as compared to ungated PET images, based on the metrics of volumetric overlap and relative volumes as well as visual interpretation. The PET-MIP is a way to incorporate 4D-PET imaging into the process of lung tumor contouring that is time-efficient for the radiation oncologist and involves minimal effort to implement in treatment planning software, because it requires only a single PET image beyond contouring on CT alone.

Botulinum toxin abolishes sweating via impaired sweat gland responsiveness to exogenous acetylcholine.

BACKGROUND: Botulinum toxin A (BTX) disrupts neurotransmitter release from cholinergic nerves. The effective duration of impaired sweat secretion with BTX is longer relative to that of impaired muscle contraction, suggesting different mechanisms in these tissues. OBJECTIVES: The aim of this study was to test the hypothesis that BTX is capable of altering sweating by reducing the responsiveness of the sweat gland to acetylcholine. METHODS: BTX was injected into the dorsal forearm skin of healthy subjects at least 3 days before subsequent assessment. On the day of the experiment, intradermal microdialysis probes were placed within the BTX-treated area and in an adjacent untreated area. Incremental doses of acetylcholine were administered through the microdialysis membranes while the sweat rate (protocol 1; n = 8) or a combination of sweat rate and skin blood flow (protocol 2; n = 8) were assessed. RESULTS: A relative absence of sweating was observed at the BTX site for both protocols (protocol 1: 0.05 +/- 0.09 mg cm(-2) min(-1); protocol 2: 0.03 +/- 0.04 mg cm(-2) min(-1), both at the highest dose of acetylcholine), while the sweat rate increased appropriately at the control sites (protocol 1: 0.90 +/- 0.46 mg cm(-2) min(-1); protocol 2: 1.07 +/- 0.67 mg cm(-2) min(-1)). Cutaneous vascular conductance increased to a similar level at both the BTX and control sites. CONCLUSIONS: These results demonstrate that BTX is capable of inhibiting sweat secretion by reducing the responsiveness of the sweat gland to acetylcholine, while not altering acetylcholine-mediated cutaneous vasodilatation.

Dosimetric variances anticipated from breathing- induced tumor motion during tomotherapy treatment delivery.

In their classic paper, Yu et al (1998 Phys. Med. Biol. 43 91) investigated the interplay between tumor motion caused by breathing and dynamically collimated, intensity-modulated radiation delivery. The paper's analytic model assumed an idealized, sinusoidal pattern of motion. In this work, we investigate the effect of tumor motion based on patients' breathing patterns for typical tomotherapy treatments with field widths of 1.0 and 2.5 cm. The measured breathing patterns of 52 lung- and upper-abdominal-cancer patients were used to model a one-dimensional motion. A convolution of the measured beam-dose profiles with the motion model was used to compute the dose-distribution errors, and the positive and negative dose errors were recorded for each simulation. The dose errors increased with increasing motion magnitude, until the motion was similar in magnitude to the field width. For the 1.0 cm and 2.5 cm field widths, the maximum dose-error magnitude exceeded 10% in some simulations, even with breathing-motion magnitudes as small as 5 mm and 10 mm, respectively. Dose errors also increased slightly with increasing couch speed. We propose that the errors were due to subtle drifts in the amplitude and frequency of breathing motion, as well as changes in baseline (exhalation) position, causing both over- and under-dosing of the target. The results of this study highlight potential breathing-motion-induced dose delivery errors in tomotherapy. However, for conventionally fractionated treatments, the dose delivery errors may not be co-located and may average out over many fractions, although this may not be true for hypofractionated treatments.

Contact-dependent growth inhibition causes reversible metabolic downregulation in Escherichia coli.

Contact-dependent growth inhibition (CDI) is a mechanism identified in Escherichia coli by which bacteria expressing two-partner secretion proteins encoded by cdiA and cdiB bind to BamA in the outer membranes of target cells and inhibit their growth. A third gene in the cluster, cdiI, encodes a small protein that is necessary and sufficient to confer immunity to CDI, thereby preventing cells expressing the cdiBA genes from inhibiting their own growth. In this study, the cdiI gene was placed under araBAD promoter control to modulate levels of the immunity protein and thereby induce CDI by removal of arabinose. This CDI autoinhibition system was used for metabolic analyses of a single population of E. coli cells undergoing CDI. Contact-inhibited cells showed altered cell morphology, including the presence of filaments. Notably, CDI was reversible, as evidenced by resumption of cell growth and normal cellular morphology following induction of the CdiI immunity protein. Recovery of cells from CDI also required an energy source. Cells undergoing CDI showed a significant, reversible downregulation of metabolic parameters, including aerobic respiration, proton motive force (Deltap), and steady-state ATP levels. It is unclear whether the decrease in respiration and/or Deltap is directly involved in growth inhibition, but a role for ATP in the CDI mechanism was ruled out using an atp mutant. Consistent with the observed decrease in Deltap, the phage shock response was induced in cells undergoing CDI but not in recovering cells, based on analysis of levels of pspA mRNA.

MicroRT-small animal conformal irradiator.

A novel small animal conformal radiation therapy system has been designed and prototyped: MicroRT. The microRT system integrates multimodality imaging, radiation treatment planning, and conformal radiation therapy that utilizes a clinical 192Ir isotope high dose rate source as the radiation source (teletherapy). A multiparameter dose calculation algorithm based on Monte Carlo dose distribution simulations is used to efficiently and accurately calculate doses for treatment planning purposes. A series of precisely machined tungsten collimators mounted onto a cylindrical collimator assembly is used to provide the radiation beam portals. The current design allows a source-to-target distance range of 1-8 cm at four beam angles: 0 degrees (beam oriented down), 90 degrees, 180 degrees, and 270 degrees. The animal is anesthetized and placed in an immobilization device with built-in fiducial markers and scanned using a computed tomography, magnetic resonance, or positron emission tomography scanner prior to irradiation. Treatment plans using up to four beam orientations are created utilizing a custom treatment planning system-microRTP. A three-axis computer-controlled stage that supports and accurately positions the animals is programmed to place the animal relative to the radiation beams according to the microRTP plan. The microRT system positioning accuracy was found to be submillimeter. The radiation source is guided through one of four catheter channels and placed in line with the tungsten collimators to deliver the conformal radiation treatment. The microRT hardware specifications, the accuracy of the treatment planning and positioning systems, and some typical procedures for radiobiological experiments that can be performed with the microRT device are presented.