Patient Perception of Cough in Interstitial Lung Disease; Impact of Cough Hypersensitivity.

INTRODUCTION: Cough is common in interstitial lung disease (ILD) and is associated with disease progression, yet its mechanisms are understudied. We investigated cough hypersensitivity features and impact in ILD. METHODS: Participants with ILD and cough (n = 195) completed a multiple choice and free text questionnaire on cough sensations/triggers and impacts. RESULTS: The majority of participants were male (54%), aged > 65 (64%), with idiopathic pulmonary fibrosis (IPF, 75%). Common cough triggers were body position (74%), physical activity (72%), and talking (62%). Common laryngeal sensations were globus (43%), and itch/tickle (42%). Cough impacted everyday life in 55%, and all activities in 31%, causing exhaustion (59%), social embarrassment (70%), urinary incontinence (46% females), and syncope/pre-syncope (12%). The total number of cough-provoking sensations/triggers correlated with impacts; ρ = 0.73, p < 0.001. CONCLUSION: Cough hypersensitivity symptoms are prevalent in ILD and detrimentally affect quality of life. Further studies investigating mechanisms of cough hypersensitivity and targeted pharmacotherapy are warranted.

Anatomic findings associated with epispadias in boys: Implications for surgical management and urinary continence.

INTRODUCTION: Pre-operative physical examination of male epispadias allows for classification of epispadias level as glanular (GE), penile (PE) or penopubic (PPE), and for delineation of anatomic anomalies. The incidence of associated extragenital abnormalities, such as vesicoureteral reflux (VUR), bladder neck (BN) abnormality and abnormal pubic diastasis (PD), and their impact on urinary continence has not yet been systematically studied. OBJECTIVE: The goal of this study was to evaluate whether the more proximal level of epispadias correlated with associated extragenital anatomic anomalies seen on initial imaging or endoscopic evaluation, and whether these pre-operative findings contributed to subsequent surgical management and impacted on achieving urinary continence. It was hypothesized that the more severe forms of epispadias may be associated with a higher frequency of associated anomalies. STUDY DESIGN: The study was an IRB-approved, retrospective case study of all male patients treated initially for isolated epispadias at the current institution between 1994 and 2011. Data collection was achieved by chart and radiology review evaluating PD, BN appearance, presence of VUR, surgical treatment, and urinary continence. RESULTS: A total of 26 patients were identified and divided into three groups based on appearance at physical examination: four glanular (GE), eight penile (PE), and 14 penopubic (PPE); 17 patients had an abnormal BN. Reflux was noted in nine of 20 patients who had a voiding cystourethrogram (VCUG), two of which had an episode of pyelonephritis. Of the 22 patients past the age of toilet training, 17 were continent (64% (9/14) penopubic, 63% (5/8) penile, and 75% (3/4) glanular). DISCUSSION: Anatomic classification for male epispadias did not provide sufficient information regarding extragenital findings. This study provided new information regarding PD, BN appearance, presence of reflux, and ultimate urinary continence. Pubic diastasis and BN abnormalities were more frequently seen in more severe forms of epispadias, whereas VUR seemed more prevalent in less severe forms. A template for pre-operative evaluation was outlined. Limitations of the study were its retrospective design and relatively small cohort of patients, which reflected the rarity of the condition. CONCLUSION: Based on the information generated, additional anatomic information was generated regarding boys with epispadias. This information will help guide the evaluation and the management of these patients in the future.

Robotic-assisted laparoscopic bladder augmentation in the pediatric patient.

INTRODUCTION: Bladder augmentation is a common surgical intervention for neuropathic bladder dysfunction, and has conventionally been an open procedure. We present a robotic ileocystoplasty to demonstrate the feasibility of an entirely intracorporeal approach in a pediatric patient. METHODS: The patient was a 6 year old (18.5 kg) boy with a neurogenic bladder secondary to lumbar myelomeningocele. Urodynamics revealed a small capacity and poorly compliant bladder and he was incontinent between frequent catheterizations. A robotic augmentation cystoplasty was performed. RESULTS: At one-month postoperatively, a cystogram revealed no urine leak, and the suprapubic tube was removed. The patient resumed CIC every 3 h during the day and once overnight until postoperative urodynamic studies confirmed safe dynamics, after which the CIC interval was lengthened. CONCLUSION: Robotic bladder augmentation is safe and feasible in a select pediatric population. The entire procedure including preparation of the bowel segment can be completed intracorporeally, even in smaller children.

Sacral agenesis and neurogenic bladder: Long-term outcomes of bladder and kidney function.

BACKGROUND: Sacral agenesis (SA) is a rare congenital condition that refers to the absence of part or all of two or more lower sacral vertebral bodies. It can be associated with neurogenic bladder dysfunction that does not necessarily correlate with the level of spinal or skeletal defect. Patients with SA should undergo urodynamic studies (UDS) to guide lower urinary tract (LUT) management. OBJECTIVE: This review aimed to update the present institutional experience since 1981 of this rare patient population with detailed, long-term follow-up of bladder and kidney function. STUDY DESIGN: A single institution, retrospective, IRB-approved review was performed on patients born after January 1, 1981 with an isolated diagnosis of sacral agenesis without spina bifida, and followed with urologic involvement at Boston Children's Hospital. Records were reviewed for demographics, radiologic imaging, UDS including cystometrogram (CMG) and electromyography (EMG), surgery, and blood chemistries. Comparisons were made between groups of patients based on age at diagnosis, with specific focus on renal function and stability of neurogenic bladder lesion. RESULTS: Forty-three patients were identified: 23 female and 20 male. Thirty-seven children (86%) had a known age of diagnosis. Nineteen were diagnosed before 2 months old, including five who were diagnosed prenatally, 11 were diagnosed between 2 and 18 months, and seven were diagnosed after 18 months. All 43 had UDS, with 24 (55.8%) studied at the time of diagnosis (Summary Table). Twenty had serial full UDS, with 30% demonstrating neurourologic instability. None developed end-stage renal disease (ESRD) or required spinal cord detethering. DISCUSSION: Many children with SA appeared to be diagnosed prenatally or early in life; SA was mostly identified during evaluation of associated anomalies. Though UDS aid in urologic management, testing was not routinely utilized at the time of diagnosis. CONCLUSIONS: This review of long-term follow-up in SA patients showed stable LUT and renal function, with minimal risk of progression to ESRD.

Automatic selection of non-coplanar beam directions for three-dimensional conformal radiotherapy.

An algorithm is described, based on ray-tracing and the beam's-eye-view, that exhaustively searches all permitted beam directions. The evaluation of the search is based on a general cost function that can be adapted to the clinical objectives by means of parameters and weighting factors. The approach takes into account the constraints of the linear accelerator by discarding beam directions that are not permitted. A sensitivity analysis was carried out to determine appropriate parameters for different sized organs, and a prostate case was used to benchmark the approach. The algorithm was also applied to two clinical cases (brain and sinus) to test the benefits of the approach compared with manual angle selection. The time to perform a beam direction search was approximately 2 min for the coplanar and 12 min for the non-coplanar beam space. The angles obtained for the prostate case compared well with reports in the literature. For the brain case, the mean dose to the right and left optic nerves was reduced by 12% and 50%, respectively, whilst the target dose uniformity was improved. For the sinus case, the mean doses to the right and left parotid glands were reduced by 54% and 46%, respectively, to the right and left optic nerves by 37% and 62%, respectively, and to the optic chiasm by 39%, whilst the target dose uniformity was also improved. For the clinical cases the plans based on optimized beam directions were simpler and resulted in better sparing of critical structures compared with plans based on manual angle selection. The approach provides a practical alternative to elaborate and time consuming beam angle optimization schemes and is suitable for routine clinical usage.

Competitive Market Analysis of Transplant Centers and Discrepancy of Wait-Listing of Recipients for Kidney Transplantation.

BACKGROUND: There are over 250 kidney transplant programs in the USA. OBJECTIVE: To determine if highly competitive regions, defined as regions with a higher number of transplant centers, will approve and wait-list more end-stage renal disease (ESRD) candidates for transplant despite consistent incidence and prevalence of ESRD nationwide. METHODS: ESRD Network and OPTN data completed in 2011 were obtained from all transplant centers including listing data, market saturation, market share, organs transplanted, and ESRD prevalence. Herfindahl-Hirschman Index (HHI) was used to measure the size of firms in relation to the industry to determine the amount of competition. RESULTS: States were separated into 3 groups (HHI<1000 considered competitive; HHI 1000-1800 considered moderate competition; and HHI>1800 considered highly concentrated). The percentage of ESRD patients listed in competitive, moderate, and highly concentrated regions were 19.73%, 17.02%, and 13.75%, respectively. The ESRD listing difference between competitive versus highly concentrated was significant (p<0.05). CONCLUSION: When there is strong competition without a dominant center as defined by the HHI, the entire state tends to list more patients for transplant to drive up their own center's market share. Our analysis of the available national data suggests a discrepancy in access for ESRD patient to transplantation due to transplant center competition.

Leaf sequencing with secondary beam blocking under leaf positioning constraints for continuously modulated radiotherapy beams.

The creation of arbitrary photon fluence patterns for intensity modulated radiotherapy is addressed. The proposed method is intended for a class of multileaf collimators with a requirement for minimum leaf separation. Unlike the solution of Convery and Webb in which discrete beam intensity modulation was assumed, the present method deals with continuous modulation or that consisting of infinitely small bixels. The method begins with the time-optimal solution of Spirou-Stein-Svensson disregarding the minimum gap requirement. Subsequently, the gaps are restored by mobilizing the secondary beam blocking devices to prevent overexposure resulting from the leaf separation process. The secondary beam blocking is provided by means of two orthogonal backup diaphragms that are computer controlled. The results indicate that the method can be used to accurately deliver the desired modulation while satisfying the leaf positioning constraints. Furthermore, an example is presented which illustrates the efficacy of using the horizontal backup diaphragms (moving in perpendicular direction of the leaves) in addition to the vertical backup diaphragms (moving in the parallel direction of the leaves) to generate zero fluence regions.

Dynamic and omni wedge implementation on an Elekta SL linac.

The concommitant use of a multileaf collimator (MLC) and a wedge can result in conflicts in the optimal collimator angle if both MLC and wedge are fixed relative to one another. This is particularly true of linacs in which a single wedge orientation is provided. In this paper, a solution is provided that makes use of two orthogonal universal wedges (omni wedge). Although this technique can be applied regardless of the means by which the wedged fields are implemented, the measurements reported in this paper were performed using a fixed, internal mechanical wedge coupled with a dynamic wedge, formed by the motion of one of the backup jaws. An implementation of a dynamic wedge for the Elekta SL series of linear accelerators is presented. Results of measurements of the dosimetric characteristics of both the particular implementation of the dynamic wedge and of the omni field are presented. For the dynamic wedge, measurements were made of the wedge factor and dose profile as a function of field size and depth. In addition, the effects of variables, such as dynamic delivery technique and direction of diaphragm motion, on the dynamic wedge profiles were studied and discussed. For the omni wedge, measurements were made of the degree to which the mathematical formalism for describing an omni wedge matches the measured isodose distributions. Comparisons between mechanical wedge dose distributions and the omni wedge were also made.

Verification of dynamic intensity-modulated beam deliveries in canine subjects.

Our objective in this work was to assess the precision and degree of accuracy with which intensity modulated radiation therapy (IMRT) can deliver highly localized dose distributions to tumors near critical structures using the dynamic sliding window technique. Measurements of dose distribution were performed both in vivo and in vitro using a combination of dosimeters [thermoluminescent dosimeters (TLD's), films, and diodes]. In vivo measurements were performed in two groups of purpose-bred dogs: one receiving four-field three-dimensional (3D) conformal treatment and the other receiving IMRT. The algorithms used in the inverse planning process included the Macro Pencil Beam (MPB) model and Projections onto Convex Sets (POCS). Single beam measurements were performed in phantoms to verify the accuracy of monitor unit settings required for delivering the desired doses. The composite doses from the delivery of the seven beam intensity modulated plans were measured in phantoms and cadavers, Biological end points (spinal cord toxicity and neurologic deficits due to irradiation) were evaluated at the end of one year to determine the spatial accuracy of the IMRT treatments over a fractionated course in live subjects. Results in single beam measurements were used at first to improve the dose calculation and translation algorithms. Results of the measurements for the delivery of all seven beams in phantoms confirmed that the system was capable of accurate spatial and dosimetric IMRT delivery. The in vivo results showed dramatic differences between control and IMRT-treated dogs, with the IMRT group showing no adverse effects and the control animals showing severe spinal cord injuries due to irradiation. The measurements presented in this paper have helped to verify the successful and accurate delivery of IMRT in a clinically related model using the University of Washington Medical Center (UWMC) system.

Optimization of intensity modulated beams with volume constraints using two methods: cost function minimization and projections onto convex sets.

For accurate prediction of normal tissue tolerance, it is important that the volumetric information of dose distribution be considered. However, in dosimetric optimization of intensity modulated beams, the dose-volume factor is usually neglected. In this paper we describe two methods of volume-dependent optimization for intensity modulated beams such as those generated by computer-controlled multileaf collimators. The first method uses a volume sensitive penalty function in which fast simulated annealing is used for cost function minimization (CFM). The second technique is based on the theory of projections onto convex sets (POCS) in which the dose-volume constraint is replaced by a limit on integral dose. The ability of the methods to respect the dose-volume relationship was demonstrated by using a prostate example involving partial volume constraints to the bladder and the rectum. The volume sensitive penalty function used in the CFM method can be easily adopted by existing optimization programs. The convex projection method can find solutions in much shorter time with minimal user interaction.

Reduction of computational dimensionality in inverse radiotherapy planning using sparse matrix operations.

For dynamic multileaf collimator-based intensity modulated radiotherapy in which small beam elements are used to generate continuous modulation, the sheer size of the dose calculation matrix could pose serious computational challenges. In order to circumvent this problem, the dose calculation matrix was reduced to a sparse matrix by truncating the weakly contributing entries below a certain cutoff to zero. Subsequently, the sparse matrix was compressed and matrix indexing vectors were generated to facilitate matrix-vector and matrix-matrix operations used in inverse planning. The application of sparsity permitted the reduction of overall memory requirement by an order of magnitude. In addition, the effect of disregarding the small scatter components on the quality of optimization was investigated by repeating the inverse planning using the dense dose calculation matrix. Comparison of dense and sparse matrix-based plans revealed an insignificant difference in optimization outcome, thus demonstrating the feasibility and usefulness of the sparse method in inverse planning. Furthermore, two additional methods of memory minimization are suggested, namely hexagonal dose sampling and limited normal tissue sampling.

Hardware-sensitive optimization for intensity modulated radiotherapy.

The multileaf collimator (MLC) hardware constraints are usually neglected in the process of intensity-modulated beam optimization. Consequently, it is not always possible to deliver planned beam modulation using dynamic MLC. Beam optimization is significantly diminished if the results must be approximated due to limitations imposed by the delivery device. To overcome this problem, an inverse beam optimization method which incorporates the hardware constraints has been developed. The hardware constraints, including the leaf velocity, the dose rate and the minimum required gap between opposing and adjacent leaves, were considered. An iterative search for feasible modulation was conducted alternately in the dosimetric space and the MLC position-time space. The optimization algorithm was designed for a unidirectional leaf trajectory and a constant dose rate. A scheme to reduce tongue-and-groove underdosage during optimization was also implemented. Comparisons were made between the solutions produced by this method and conventional optimization disregarding the hardware restrictions. The beam profiles generated by the conventional method were modified to satisfy the hardware specifications. The results indicate that inclusion of MLC constraints during optimization can improve the degree of conformity that is deliverable.

Automated detection of BB pixel clusters in digital fluoroscopic images.

Small ball bearings (BBs) are often used to characterize and correct for geometric distortion of x-ray image intensifiers. For quantitative applications the number of BBs required for accurate distortion correction is prohibitively large for manual detection. A method to automatically determine the BB coordinates is described. The technique consists of image segmentation, pixel coalescing and centroid calculation. The dependence of calculated BB coordinates on segmentation threshold was also evaluated and found to be within the uncertainty of measurement.

The FE-lspd model for electron beam dosimetry.

The FE-lspd model is a two-component electron beam model that distinguishes between electrons that can be described by small-angle transport theory and electrons that are too widely scattered for small-angle transport theory to be applicable. The two components are called the primary beam and the laterally scattered primary distribution (lspd). The primary beam component incorporates a simple version of the Fermi-Eyges model and dominates dose calculations at therapeutic depths. The lspd component corrects erros in the lateral spreading of the primary beam component, thereby improving the accuracy by which the FE-lspd model calculates dose distribution in blocked fields. Comparisons were made between dose profiles and central-axis depth dose distributions in small fields calculated by the FE-lspd, Fermi-Eyges and EGS4 Monte Carlo models for a 10 MeV beam in a homogeneous water phantom. The maximum difference between the dose calculated using the FE-lspd model and EGS4 Monte Carlo is about 6% at a field diameter of about 1 cm, and less than 2% for field sizes greater than 3 cm diameter. The maximum difference between the Fermi-Eyges and Monte Carlo calculations is about 18% at a field diameter of about 2.5 cm. A comparison was made with the central-axis depth dose distribution measured in water for a 3 cm diameter field in a 10 MeV clinical electron beam. The errors in the dose distribution were found to be less than 2% using the FE-lspd model but almost 18% using the Fermi-Eyges model. A comparison was also made with pencil beam profiles calculated using the second-order Fermi-Eyges transport model.

Conformal radiotherapy computation by the method of alternating projections onto convex sets.

Synthesis of beam profiles for a given dose prescription is a central problem in radiotherapy. Care must be taken in the beam design to expose the tumour volume at a high level, to avoid significant irradiation of critical organs, and to minimize exposure of all other tissue. Use of the synthesis procedure known as alternating projections onto convex sets (POCS) is shown to be a viable approach to beam design. POCS is a powerful tool for signal and image restoration and synthesis. Convex sets of signals obeying desired constraint sets are first specified. Then, by repeated projections onto these sets, convergence is to a signal obeying all desired constraints if the constraint sets have a finite intersection. In this paper we apply the method of POCS to conformal radiotherapy dose computation. The performance of the method is shown through three representative examples.

Cone-beam CT for radiotherapy applications.

Clinical implementation of cone-beam tomography has been hampered by the lack of two-dimensional electronic x-ray detectors that can encompass the full width of the body. We encountered the undersized detector problem in our development of a cone-beam CT system for radiotherapy applications. In order to mitigate the problem, we developed an algorithm which permits an increased reconstruction volume to be imaged using a detector of a given size. We describe the algorithm and report on its implementation using a radiotherapy simulator configured with a digital fluorography unit.

A spherical dose model for radiosurgery plan optimization.

Conventional 3D dose calculations for stereotactic radiosurgery involve integration of individual static beams comprising a set of arcs. For iterative optimization of multiple isocentre treatment, which requires repetitive dose calculations at a large number of sample points, the conventional method is too slow. To overcome this problem spherically symmetric dose distributions are assumed. The authors describe a spherical dose model derived from a parametrized convolution of the collimator width and a dose spread kernel. The method is fast and easy to implement requiring just a single empirically derived value. Furthermore, the model is differentiable with respect to the parameters to be optimized. This property is useful when the optimization strategies rely on gradient information.

Feldkamp and circle-and-line cone-beam reconstruction for 3D micro-CT of vascular networks.

Detailed morphometric knowledge of the microvascular network is needed for studies relating structure to haemodynamic function in organs like the lung. Clinical volumetric CT is limited to millimetre-order spatial resolution. Since evidence suggests that small arterioles (50 to 300 micrometres) dominate pulmonary haemodynamics, we built a micro-CT scanner, capable of imaging excised lungs in 3D with 100 microm resolution, for basic physiology research. The scanner incorporates a micro-focal (3 microm) x-ray source, an xyz theta stage and a CCD-coupled image intensifier detector. We imaged phantoms and contrast-enhanced rat lungs, reconstructing the data with either the Feldkamp or the circle-and-line cone-beam reconstruction algorithm. We present reconstructions using 180 views over 360 degrees for the circular trajectory, augmented with views from a linear scan for the circle-and-line algorithm. Especially for platelike features perpendicular to the rotation axis and remote from the midplane, the circle-and-line algorithm produces superior reconstructions compared with Feldkamp's algorithm. We conclude that the use of nonplanar source trajectories to perform micro-CT on contrast-enhanced, excised lungs can provide data useful for morphometric analysis of vascular trees, currently down to the 130 microm level.

Use of intensity modulation for missing tissue compensation of pediatric spinal fields.

Irradiation of the cranio-spinal axis is often one of the treatment modalities of certain childhood cancers, e.g., medulloblastoma. In order to achieve a uniform dose to the spinal cord, missing tissue compensators are required. In the past, our practice was to fabricate compensators out of strips of lead. We report on the use of intensity modulated fields to achieve the desired compensation. Seven cases of pediatric cancer whose treatment involved irradiation of the cranio-spinal axis had compensators designed using a beam intensity modulation method rather than making mechanical compensators. The compensators only adjusted for missing tissue along the spinal axis. Comparisons between calculated and measured doses were made at depth in phantoms and on the surface of the patient. The intensity modulated fields were delivered using a step-and-shoot delivery on an Elekta SL20 accelerator equipped with multileaf collimator. The intensity-modulated compensators provided more flexibility in design than the physical compensator method. Finer intensity steps were achievable, more accurate dose distributions were able to be calculated, and adjustments during treatment, e.g., junction changes, were more easily implemented. Convolution/superposition dose calculations were within +/-3% of measurements. Intensity modulated fields are a practical and more efficient method of delivering uniform doses to the spine in pediatric cancer treatments. They provide many advantages over mechanical compensators with regard to time and flexibility.

Cone-beam CT from width-truncated projections.

In this paper we report cone-beam CT techniques that permit reconstruction from width-truncated projections. These techniques are variants of Feldkamp's filtered backprojection algorithm and assume quasi-redundancy of ray integrals. Two methods are derived and compared. The first method involves the use of preconvolution weighting of the truncated data. The second technique performs post-convolution weighting preceded by non-zero estimation of the missing information. The algorithms were tested using the three-dimensional Shepp-Logan head phantom. The results indicate that given an appropriate amount of overscan, satisfactory reconstruction can be achieved. These techniques can be used to solve the problem of undersized detectors.