Jonathan L. Williams

The UF family of reference hybrid phantoms for computational radiation dosimetry

Computational human phantoms are computer models used to obtain dose distributions within the human body exposed to internal or external radiation sources. In addition, they are increasingly used to develop detector efficiencies for in vivo whole-body counters. Two classes of computational human phantoms have been widely utilized for dosimetry calculation: stylized and voxel phantoms that describe human anatomy through mathematical surface equations and 3D voxel matrices, respectively. Stylized phantoms are flexible in that changes to organ position and shape are possible given avoidance of region overlap, while voxel phantoms are typically fixed to a given patient anatomy, yet can be proportionally scaled to match individuals of larger or smaller stature, but of equivalent organ anatomy. Voxel phantoms provide much better anatomical realism as compared to stylized phantoms which are intrinsically limited by mathematical surface equations. To address the drawbacks of these phantoms, hybrid phantoms based on non-uniform rational B-spline (NURBS) surfaces have been introduced wherein anthropomorphic flexibility and anatomic realism are both preserved. Researchers at the University of Florida have introduced a series of hybrid phantoms representing the ICRP Publication 89 reference newborn, 15 year, and adult male and female. In this study, six additional phantoms are added to the UF family of hybrid phantoms-those of the reference 1 year, 5 year and 10 year child. Head and torso CT images of patients whose ages were close to the targeted ages were obtained under approved protocols. Major organs and tissues were segmented from these images using an image processing software, 3D-DOCTOR. NURBS and polygon mesh surfaces were then used to model individual organs and tissues after importing the segmented organ models to the 3D NURBS modeling software, Rhinoceros. The phantoms were matched to four reference datasets: (1) standard anthropometric data, (2) reference organ masses from ICRP Publication 89, (3) reference elemental compositions provided in ICRP 89 as well as ICRU Report 46, and (4) reference data on the alimentary tract organs given in ICRP Publications 89 and 100. Various adjustments and refinements to the organ systems of the previously described newborn, 15 year and adult phantoms are also presented. The UF series of hybrid phantoms retain the non-uniform scalability of stylized phantoms while maintaining the anatomical realism of patient-specific voxel phantoms with respect to organ shape, depth and inter-organ distance. While the final versions of these phantoms are in a voxelized format for radiation transport simulation, their primary format is given as NURBS and polygon mesh surfaces, thus permitting one to sculpt non-reference phantoms using the reference phantoms as an anatomic template.

Hybrid computational phantoms of the male and female newborn patient : NURBS-based whole-body models

Anthropomorphic computational phantoms are computer models of the human body for use in the evaluation of dose distributions resulting from either internal or external radiation sources. Currently, two classes of computational phantoms have been developed and widely utilized for organ dose assessment: (1) stylized phantoms and (2) voxel phantoms which describe the human anatomy via mathematical surface equations or 3D voxel matrices, respectively. Although stylized phantoms based on mathematical equations can be very flexible in regard to making changes in organ position and geometrical shape, they are limited in their ability to fully capture the anatomic complexities of human internal anatomy. In turn, voxel phantoms have been developed through image-based segmentation and correspondingly provide much better anatomical realism in comparison to simpler stylized phantoms. However, they themselves are limited in defining organs presented in low contrast within either magnetic resonance or computed tomography images-the two major sources in voxel phantom construction. By definition, voxel phantoms are typically constructed via segmentation of transaxial images, and thus while fine anatomic features are seen in this viewing plane, slice-to-slice discontinuities become apparent in viewing the anatomy of voxel phantoms in the sagittal or coronal planes. This study introduces the concept of a hybrid computational newborn phantom that takes full advantage of the best features of both its stylized and voxel counterparts: flexibility in phantom alterations and anatomic realism. Non-uniform rational B-spline (NURBS) surfaces, a mathematical modeling tool traditionally applied to graphical animation studies, was adopted to replace the limited mathematical surface equations of stylized phantoms. A previously developed whole-body voxel phantom of the newborn female was utilized as a realistic anatomical framework for hybrid phantom construction. The construction of a hybrid phantom is performed in three steps: polygonization of the voxel phantom, organ modeling via NURBS surfaces and phantom voxelization. Two 3D graphic tools, 3D-DOCTOR and Rhinoceros, were utilized to polygonize the newborn voxel phantom and generate NURBS surfaces, while an in-house MATLAB code was used to voxelize the resulting NURBS model into a final computational phantom ready for use in Monte Carlo radiation transport calculations. A total of 126 anatomical organ and tissue models, including 38 skeletal sites and 31 cartilage sites, were described within the hybrid phantom using either NURBS or polygon surfaces. A male hybrid newborn phantom was constructed following the development of the female phantom through the replacement of female-specific organs with male-specific organs. The outer body contour and internal anatomy of the NURBS-based phantoms were adjusted to match anthropometric and reference newborn data reported by the International Commission on Radiological Protection in their Publication 89. The voxelization process was designed to accurately convert NURBS models to a voxel phantom with minimum volumetric change. A sensitivity study was additionally performed to better understand how the meshing tolerance and voxel resolution would affect volumetric changes between the hybrid-NURBS and hybrid-voxel phantoms. The male and female hybrid-NURBS phantoms were constructed in a manner so that all internal organs approached their ICRP reference masses to within 1%, with the exception of the skin (-6.5% relative error) and brain (-15.4% relative error). Both hybrid-voxel phantoms were constructed with an isotropic voxel resolution of 0.663 mm--equivalent to the ICRP 89 reference thickness of the newborn skin (dermis and epidermis). Hybrid-NURBS phantoms used to create their voxel counterpart retain the non-uniform scalability of stylized phantoms, while maintaining the anatomic realism of segmented voxel phantoms with respect to organ shape, depth and inter-organ positioning.

Influence of tidal volume on the distribution of gas between the lungs and stomach in the nonintubated patient receiving positive-pressure ventilation.

Abstract Objectives: When ventilating a nonintubated patient in cardiac arrest, the European Resuscitation Council has recently recommended a decrease in the tidal volume from 0.8 to 1.2 L to 0.5 L, partly in an effort to decrease peak flow rate, and therefore, to minimize stomach inflation. The purpose of the present study was to examine the validity of the European Resuscitation Councils recommendation in terms of gas distribution between lungs and stomach in a bench model that simulates ventilation of a nonintubated patient with a self‐inflatable bag representing tidal volumes of 0.5 and 0.75 L. Design: A bench model of a patient with a nonintubated airway was used consisting of face mask, manikin head, training lung (lung compliance, 50 mL/cm H2 O; airway resistance, 5 cm H2 O/L/sec), adjustable lower esophageal sphincter pressure (LESP) and simulated stomach. Setting: University hospital laboratory. Subjects: Thirty healthcare professionals. Interventions: Healthcare professionals performed 1‐min bag‐mask ventilation at each LESP level of 5, 10, and 15 cm H2 O at a rate of 12 breaths/min, using an adult and pediatric self‐inflating bag, respectively. Volunteers were blinded to the LESP, which was randomly varied. Measurements and Main Results: Both types of self‐inflating bags induced stomach inflation, with higher stomach and lower lung tidal volumes when the LESP was decreased. Lung tidal volume with the pediatric bag was significantly (p < .05) lower at all LESP levels when compared with the adult bag, and ranged between 240 mL at an LESP of 15 cm H2 O and 120 mL at an LESP of 5 cm H2 O. Stomach tidal volume with the adult bag ranged between 250 mL at an LESP of 15 cm H2 O and increased to 550 mL at an LESP of 5 cm H2 O. Stomach tidal volume with the pediatric bag was significantly lower (p < .05) at all LESP levels when compared with the adult bag and ranged between 70 mL at an LESP of 15 cm H2 O and 300 mL at an LESP of 5 cm H2 O. Conclusions: Our data support the recommendation of the European Resuscitation Council to decrease tidal volumes to 0.5 L when ventilating a cardiac arrest victim with an unprotected airway. A small tidal volume may be a better trade‐off in the basic life support phase, as this may provide reasonable ventilation while avoiding massive stomach inflation. (Crit Care Med 1998; 26:364‐368) When ventilating a nonintubated cardiac arrest patient, the European Resuscitation Council has recently recommended a decrease in the tidal volume from 0.8 to 1.2 L [1] to 0.5 L [2], partly in an effort to decrease peak flow rate, and therefore, to minimize stomach inflation. Ventilation volume has an effect on pH, CO2 elimination, and oxygenation when pulmonary blood flow is extremely low, such as during cardiopulmonary resuscitation (CPR) or shock [3]. The Airway and Ventilation Management Working Group of the European Resuscitation Council [2] stated that ventilating a nonintubated cardiac arrest patient with a smaller tidal volume may be a better trade‐off in order to provide reasonable ventilation, while avoiding massive stomach inflation that may result in life‐threatening pulmonary complications. The gas distribution between lungs and stomach during positive‐pressure ventilation in a nonintubated airway depends on patient characteristics (lower esophageal sphincter pressure [LESP], airway resistance, and respiratory system compliance) and performance variables of the rescuer applying positive‐pressure ventilation (tidal volume, peak flow rate, and upper airway pressure). Thus, assessing the above‐mentioned recommendation in a clinical study is difficult to perform due to many confounding variables that are difficult to control and to evaluate when emergently managing therapy during CPR. As an example of the usefulness of laboratory models of ventilation, the American Heart Association [1] recommended increasing inspiratory time when ventilating a nonintubated cardiac arrest patient [1,4]. For example, such a model has the advantage that each variable of respiratory mechanics can be controlled and adjusted to investigate a certain hypothesis. We [4,5] previously studied the effect of tidal volume and peak flow rate on gas distribution between lungs and stomach during mechanical positive‐pressure ventilation, using a modification of the earlier described bench model of an unprotected airway. Although a mechanical ventilator is a valuable tool to study gas distribution in an unprotected airway, a self‐inflatable bag is the device usually used by the emergency medical service and in the hospital during the initial care of a cardiac arrest victim. Thus, the purpose of the present study was to examine the validity of the European Resuscitation Council recommendation [2] in terms of gas distribution between lungs and stomach in a bench model that simulates positive‐pressure ventilation of a nonintubated patient with self‐inflatable bags representing tidal volumes of 0.5 L and 0.75 L. Since observations in an animal model [6] showed that the LESP decreases rapidly after an untreated cardiac arrest, we further evaluated the effect of a decreased LESP on gas distribution between lungs and stomach in this model.

Respiratory system compliance decreases after cardiopulmonary resuscitation and stomach inflation: impact of large and small tidal volumes on calculated peak airway pressure

The purpose of the present study was to evaluate respiratory system compliance after cardiopulmonary resuscitation (CPR) and subsequent stomach inflation. Further, we calculated peak airway pressure according to the different tidal volume recommendations of the European Resuscitation Council (7.5 ml/kg) and the American Heart Association (15 ml/kg) for ventilation of an unintubated cardiac arrest victim. After 4 min of ventricular fibrillation, and 6 min of CPR, return of spontaneous circulation (ROSC) after defibrillation occurred in seven pigs. Respiratory system compliance was measured at prearrest, after ROSC, and after 2 and 4 l of stomach inflation in the postresuscitation phase; peak airway pressure was subsequently calculated. Before cardiac arrest the mean (+/- S.D.) respiratory system compliance was 30 +/- 3 ml/cm H2O, and decreased significantly (P < 0.05) after ROSC to 24 +/- 5 ml/cm H2O, and further declined significantly to 18 +/- 4 ml/cm H2O after 2 l, and to 13 +/- 3 ml/cm H2O after 4 l of stomach inflation. At prearrest, the mean +/- S.D. calculated peak airway pressure according to European versus American guidelines was 9 +/- 1 versus 18 +/- 3 cm H2O, after ROSC 12 +/- 2 versus 23 +/- 4 cm H2O, and 15 +/- 2 versus 30 +/- 5 cm H2O after 2 l, and 22 +/- 6 versus 44 +/- 12 cm H2O after 4 l of stomach inflation. In conclusion, respiratory system compliance decreased significantly after CPR and subsequent induction of stomach inflation in an animal model with a wide open airway. This may have a significant impact on peak airway pressure and distribution of gas during ventilation of an unintubated patient with cardiac arrest.

Hybrid computational phantoms of the 15-year male and female adolescent: Applications to CT organ dosimetry for patients of variable morphometry

Currently, two classes of the computational phantoms have been developed for dosimetry calculation: (1) stylized (or mathematical) and (2) voxel (or tomographic) phantoms describing human anatomy through mathematical surface equations and three-dimensional labeled voxel matrices, respectively. Mathematical surface equations in stylized phantoms provide flexibility in phantom design and alteration, but the resulting anatomical description is, in many cases, not very realistic. Voxel phantoms display far better anatomical realism, but they are limited in terms of their ability to alter organ shape, position, and depth, as well as body posture. A new class of computational phantoms--called hybrid phantoms-takes advantage of the best features of stylized and voxel phantoms-flexibility and anatomical realism, respectively. In the current study, hybrid computational phantoms representing reference 15-year male and female body anatomy and anthropometry are presented. For the male phantom, organ contours were extracted from the University of Florida (UF) 14-year series B male voxel phantom, while for the female phantom, original computed tomography (CT) data from two 14-year female patients were used. Polygon mesh models for the major organs and tissues were reconstructed for nonuniform rational B-spline (NURBS) surface modeling. The resulting NURBS/polygon mesh models representing body contour and internal anatomy were matched to anthropometric data and reference organ mass data provided by the Centers for Disease Control and Prevention (CDC) and the International Commission on Radiation Protection (ICRP), respectively. Finally, two hybrid 15-year male and female phantoms were completed where a total of eight anthropometric data categories were matched to standard values within 4% and organ masses matched to ICRP data within 1% with the exception of total skin. To highlight the flexibility of the hybrid phantoms, 10th and 90th weight percentile 15-year male and female phantoms were further developed from the 50th percentile phantoms through adjustments in the body contour to match the total body masses given in CDC pediatric growth curves. The resulting six NURBS phantoms, male and female phantoms representing their 10th, 50th, and 90th weight percentiles, were used to investigate the influence of body fat distributions on internal organ doses following CT imaging. The phantoms were exposed to multislice chest and abdomen helical CT scans, and in-field organ absorbed doses were calculated. The results demonstrated that the use of traditional stylized phantoms yielded organ dose estimates that deviate from those given by the UF reference hybrid phantoms by up to a factor of 2. The study also showed that use of reference, or 50th percentile, phantoms to assess organ doses in underweight 15-year-old children would not lead to significant organ dose errors (typically less than 10%). However, more significant errors were noted (up to approximately 30%) when reference phantoms are used to represent overweight children in CT imaging dosimetry. These errors are expected to only further increase as one considers CT organ doses in overweight and obese individuals of the adult patient population, thus emphasizing the advantages of patient-sculptable phantom technology.

The UF series of tomographic computational phantoms of pediatric patients

Two classes of anthropomorphic computational phantoms exist for use in Monte Carlo radiation transport simulations: tomographic voxel phantoms based upon three-dimensional (3D) medical images, and stylized mathematical phantoms based upon 3D surface equations for internal organ definition. Tomographic phantoms have shown distinct advantages over the stylized phantoms regarding their similarity to real human anatomy. However, while a number of adult tomographic phantoms have been developed since the early 1990s, very few pediatric tomographic phantoms are presently available to support dosimetry in pediatric diagnostic and therapy examinations. As part of a larger effort to construct a series of tomographic phantoms of pediatric patients, five phantoms of different ages (9-month male, 4-year female, 8-year female, 11-year male, and 14-year male) have been constructed from computed tomography (CT) image data of live patients using an IDL-based image segmentation tool. Lungs, bones, and adipose tissue were automatically segmented through use of window leveling of the original CT numbers. Additional organs were segmented either semiautomatically or manually with the aid of both anatomical knowledge and available image-processing techniques. Layers of skin were created by adding voxels along the exterior contour of the bodies. The phantoms were created from fused images taken from head and chest-abdomen-pelvis CT exams of the same individuals (9-month and 4-year phantoms) or of two different individuals of the same sex and similar age (8-year, 11-year, and 14-year phantoms). For each model, the resolution and slice positions of the image sets were adjusted based upon their anatomical coverage and then fused to a single head-torso image set. The resolutions of the phantoms for the 9-month, 4-year, 8-year, 11-year, and 14-year are 0.43 x 0.43 x 3.0 mm, 0.45 x 0.45 x 5.0 mm, 0.58 x 0.58 x 6.0 mm, 0.47 X 0.47 x 6.00 mm, and 0.625 x 0.625 x 6.0 mm, respectively. While organ masses can be matched to reference values in both stylized and tomographic phantoms, side-by-side comparisons of organ doses in both phantom classes indicate that organ shape and positioning are equally important parameters to consider in accurate determinations of organ absorbed dose from external photon irradiation. Preliminary studies of external photon irradiation of the 11-year phantom indicate significant departures of organ dose coefficients from that predicted by the existing stylized phantom series. Notable differences between pediatric stylized and tomographic phantoms include anterior-posterior (AP) and right lateral (RLAT) irradiation of the stomach wall, left lateral (LLAT) and right lateral (RLAT) irradiation of the thyroid, and AP and posterior-anterior (PA) irradiation of the urinary bladder.

Whole-body voxel phantoms of paediatric patients--UF Series B.

Following the previous development of the head and torso voxel phantoms of paediatric patients for use in medical radiation protection (UF Series A), a set of whole-body voxel phantoms of paediatric patients (9-month male, 4-year female, 8-year female, 11-year male and 14-year male) has been developed through the attachment of arms and legs from segmented CT images of a healthy Korean adult (UF Series B). Even though partial-body phantoms (head-torso) may be used in a variety of medical dose reconstruction studies where the extremities are out-of-field or receive only very low levels of scatter radiation, whole-body phantoms play important roles in general radiation protection and in nuclear medicine dosimetry. Inclusion of the arms and legs is critical for dosimetry studies of paediatric patients due to the presence of active bone marrow within the extremities of children. While the UF Series A phantoms preserved the body dimensions and organ masses as seen in the original patients who were scanned, comprehensive adjustments were made for the Series B phantoms to better match International Commission on Radiological Protection (ICRP) age-interpolated reference body masses, body heights, sitting heights and internal organ masses. The CT images of arms and legs of a Korean adult were digitally rescaled and attached to each phantom of the UF series. After completion, the resolutions of the phantoms for the 9-month, 4-year, 8-year, 11-year and 14-year were set at 0.86 mm x 0.86 mm x 3.0 mm, 0.90 mm x 0.90 mm x 5.0 mm, 1.16 mm x 1.16 mm x 6.0 mm, 0.94 mm x 0.94 mm x 6.00 mm and 1.18 mm x 1.18 mm x 6.72 mm, respectively.

Successful treatment of neonatal aortic thrombosis with tissue plasminogen activator

The widespread use of invasive vascular catheters in neonates has increased thrombotic complications and the need for specific thrombolytic therapy. First-generation thrombolytic drugs, including streptokinase and urokinase, lack clot specificity, fail to lyse formed clots effectively, and cause systemic proteolysis. The resulting hemorrhage has limited their use in neonatal thrombotic disease. The introduction of more clot-selective second-generatio n thrombolytic agents, including tissue plasminogen activator, may make thrombolytic therapy acceptably safe for neonates. We have used t-PA for successful thrombolysis of a life-threatening arterial clot in a very premature infant. CASE REPORT

Response-Dependent and Reduced Treatment in Lower Risk Hodgkin Lymphoma in Children and Adolescents, Results of P9426: A Report from the Children’s Oncology Group

Hodgkin lymphoma is highly curable but associated with significant late effects. Reduction of total treatment would be anticipated to reduce late effects. This aim of this study was to demonstrate that a reduction in treatment was possible without compromising survival outcomes.

Treatment of stage I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomycin, vincristine and etoposide (DBVE) and radiation: A Pediatric Oncology Group (POG) study

The objectives of this study were to evaluate the feasibility of reducing therapy, while maintaining treatment efficacy, in the context of a cooperative group clinical trial that allowed for clinical staging in early stage Hodgkin disease (HD).