Accurate measures of changes in regional lung air volumes from chest x-rays of small animals.

Objective. To develop a robust technique for calculating regional volume changes within the lung from x-ray radiograph sequences captured during ventilation, without the use of computed tomography (CT).Approach. This technique is based on the change in transmitted x-ray intensity that occurs for each lung region as air displaces the attenuating lung tissue.Main results. Lung air volumes calculated from x-ray intensity changes showed a strong correlation (R2= 0.98) against the true volumes, measured from high-resolution CT. This correlation enables us to accurately convert projected intensity data into relative changes in lung air volume. We have applied this technique to measure changes in regional lung volumes from x-ray image sequences of mechanically ventilated, recently-deceased newborn rabbits, without the use of CT.Significance. This method is suitable for biomedical research studies,enabling quantitative regional measurement of relative lung air volumes at high temporal resolution, and shows great potential for future clinical application.

Tomographic phase and attenuation extraction for a sample composed of unknown materials using x-ray propagation-based phase-contrast imaging.

Propagation-based phase-contrast x-ray imaging (PB-PCXI) generates image contrast by utilizing sample-imposed phase-shifts. This has proven useful when imaging weakly attenuating samples, as conventional attenuation-based imaging does not always provide adequate contrast. We present a PB-PCXI algorithm capable of extracting the x-ray attenuation  ß and refraction  δ, components of the complex refractive index of distinct materials within an unknown sample. The method involves curve fitting an error-function-based model to a phase-retrieved interface in a PB-PCXI tomographic reconstruction, which is obtained when Paganin-type phase retrieval is applied with incorrect values of δ and ß. The fit parameters can then be used to calculate true δ and ß values for composite materials. This approach requires no a priori sample information, making it broadly applicable. Our PB-PCXI reconstruction is single-distance, requiring only one exposure per tomographic angle, which is important for radiosensitive samples. We apply this approach to a breast-tissue sample, recovering the refraction component  Î´, with 0.6-2.4% accuracy compared with theoretical values.

Dynamic In Vivo Chest X-ray Dark-Field Imaging in Mice.

X-ray grating interferometry is a powerful emerging tool in biomedical imaging, providing access to three complementary image modalities. In addition to the conventional attenuation modality, interferometry provides a phase modality, which visualizes soft tissue structures, and a dark-field modality, which relates to the number and size of sub-resolution scattering objects. A particularly strong dark-field signal originates from the alveoli or air sacs in the lung. Dark-field lung radiographs in animal models have already shown increased sensitivity in diagnosing lung diseases, such as lung cancer or emphysema, compared to conventional X-ray chest radiography. However, to date, X-ray dark-field lung imaging has either averaged information over several breaths or has been captured during a breath hold. In this paper, we demonstrate the first time-resolved dark-field imaging of a breath cycle in a mechanically ventilated mouse, in vivo, which was obtained using a grating interferometer. We achieved a time resolution of 0.1 s, visualizing the changes in the dark-field, phase, and attenuation images during inhalation and exhalation. These measurements show that the dark-field signal depends on the air volume and, hence, the alveolar dimensions of the lung. Conducting this type of scan with animal disease models would help to locate the optimum breath point for single-image diagnostic dark-field imaging and could indicate if the changes in the dark-field signal during breath provide a diagnostically useful complementary measure.

Phase contrast x-ray velocimetry of small animal lungs: optimising imaging rates.

Chronic lung diseases affect a vast portion of the world's population. One of the key difficulties in accurately diagnosing and treating chronic lung disease is our inability to measure dynamic motion of the lungs in vivo. Phase contrast x-ray imaging (PCXI) allows us to image the lungs in high resolution by exploiting the difference in refractive indices between tissue and air. Combining PCXI with x-ray velocimetry (XV) allows us to track the local motion of the lungs, improving our ability to locate small regions of disease under natural ventilation conditions. Via simulation, we investigate the optimal imaging speed and sequence to capture lung motion in vivo in small animals using XV on both synchrotron and laboratory x-ray sources, balancing the noise inherent in a short exposure with motion blur that results from a long exposure.

Assessment of the use of a diffuser in propagation-based x-ray phase contrast imaging.

A rotating random-phase-screen diffuser is sometimes employed on synchrotron x-ray imaging beamlines to ameliorate field-of-view inhomogeneities due to electron-beam instabilities and beamline optics phase artifacts. The ideal result is a broader, more uniformly illuminated beam intensity for cleaner coherent x-ray images. The spinning diffuser may be modeled as an ensemble of transversely random thin phase screens, with the resulting set of intensity maps over the detector plane being incoherently averaged over the ensemble. Whilst the coherence width associated with the source is unaffected by the diffuser, the magnitude of the complex degree of second-order coherence may be significantly reduced [K. S. Morgan, S. C. Irvine, Y. Suzuki, K. Uesugi, A. Takeuchi, D. M. Paganin, and K. K. W. Siu, Opt. Commun. 283, 216 (2010)]. Through use of a computational model and experimental data obtained on x-ray beamline BL20XU at SPring-8, Japan, we investigate the effects of such a diffuser on the quality of Fresnel diffraction fringes in propagation-based x-ray phase contrast imaging. We show that careful choice of diffuser characteristics such as thickness and fiber size, together with appropriate placement of the diffuser, can result in the ideal scenario of negligible reduction in fringe contrast whilst the desired diffusing properties are retained.

The projection approximation and edge contrast for x-ray propagation-based phase contrast imaging of a cylindrical edge.

We examine the projection approximation in the context of propagation-based phase contrast imaging using hard x-rays. Specifically, we consider the case of a cylinder or a rounded edge, as a simple model for the edges of many biological samples. The Argand-plane signature of a propagation-based phase contrast fringe from the edge of a cylinder is studied, and the evolution of this signature with propagation. This, along with experimental images obtained using a synchrotron source, reveals how propagation within the scattering volume is not fully described in the projection approximation's ray-based approach. This means that phase contrast fringes are underestimated by the projection approximation at a short object-to-detector propagation distance, namely a distance comparable to the free-space propagation within the volume. This failure of the projection approximation may become non-negligible in the detailed study of small anatomical features deep within a large body. Nevertheless, the projection approximation matches the exact solution for a larger propagation distance typical of those used in biomedical phase contrast imaging.

Phase contrast X-ray imaging for the non-invasive detection of airway surfaces and lumen characteristics in mouse models of airway disease.

We seek to establish non-invasive imaging able to detect and measure aspects of the biology and physiology of surface fluids present on airways, in order to develop novel outcome measures able to validate the success of proposed genetic or pharmaceutical therapies for cystic fibrosis (CF) airway disease. Reduction of the thin airway surface liquid (ASL) is thought to be a central pathophysiological process in CF, causing reduced mucociliary clearance that supports ongoing infection and destruction of lung and airways. Current outcome measures in animal models, or humans, are insensitive to the small changes in ASL depth that ought to accompany successful airway therapies. Using phase contrast X-ray imaging (PCXI), we have directly examined the airway surfaces in the nasal airways and tracheas of anaesthetised mice, currently to a resolution of approximately 2 microm. We have also achieved high resolution three-dimensional (3D) imaging of the small airways in mice using phase-contrast enhanced computed tomography (PC-CT) to elucidate the structure-function relationships produced by airway disease. As the resolution of these techniques improves they may permit non-invasive monitoring of changes in ASL depth with therapeutic intervention, and the use of 3D airway and imaging in monitoring of lung health and disease. Phase contrast imaging of airway surfaces has promise for diagnostic and monitoring options in animal models of CF, and the potential for future human airway imaging methodologies is also apparent.

Off-axis photorefractive eye screening in children.

PURPOSE: To determine the utility of mass photoscreening for detecting visual anomalies in young, school-age children. SETTING: Seventy elementary schools in Alabama, Florida, Georgia, North Carolina, and Virginia, USA. METHODS: An off-axis photorefractive technique was used to screen 14,591 children in kindergarten, first, and fourth grades in 70 schools in 5 southeastern states in the United States. RESULTS: A total of 14,075 (96.5%) of the screenings yielded analyzable photographs. Overall, 647 (4.6%) children had significant ocular findings; significant was defined as hyperopia 2.50 diopters (D) or more, myopia 1.00 D or more, anisometropia 1.00 D or more, astigmatism 2.00 D or more, media opacity 1.0 mm or more in diameter, or 5 degrees or more or 10.00 prism diopters or more of ocular misalignment. Another 950 (6.7%) had possibly significant findings, defined as the sign being present but in an amount less than that considered significant. The most common refractive error was myopia (4.5%), followed by anisometropia (3.1%), hyperopia (2.9%), and astigmatism (1.0%). Alignment problems were found in 1.7% and media opacities in 0.1%. Among the 1.0% with other ocular anomalies were cases of anisocoria greater than 2.0 mm or irregular pupils, ptosis greater than 2.0 mm, and subconjunctival hemorrhages. In all, 202 children had significant anomalies thought to predispose to amblyopia, including 196 with significant anisometropia and 6 with significant lens opacities. At a screening cost of $5 per child for the whole study, the cost of identifying these children with potentially blinding eye disease was $361 each. CONCLUSION: Mass photoscreening may be used to detect amblyogenic conditions in children early enough to prevent blindness with timely and appropriate treatment.

Pediatric cataract and lens implantation.

Cataracts in children present a greater management challenge, compared with cataracts in adults, because of the wider variety of causes and the vulnerability of the developing visual system. The fundamental principles--early diagnosis and treatment for visually significant cataracts--have not changed. Amblyopia remains a major problem in children with unilateral and asymmetrical cataracts. The use of vitrectomy instrumentation in the removal of infantile cataracts has become relatively standard; however, the tendency now is to leave a rim of posterior capsule sufficient to allow secondary placement of a posterior chamber intraocular lens at a later date. Intraocular lens implantation is being aggressively pursued in children and, with modern microsurgical techniques, may be desirable in children as young as 2 years of age or younger in special circumstances. Contact lenses continue to be ideal for the infant and growing child to provide flexibility as the refraction changes.

Relationship between frequent episodes of peritonitis and altered immune status.

A 60-year-old Native American diabetic female patient had a history of nine episodes of peritonitis (both relapsing and persistent) during the year that she was treated with continuous ambulatory peritoneal dialysis (CAPD). At the start of CAPD the patient had an inverted CD4 to CD8 ratio that decreased from 0.97 to 0.50 in 1 year. This finding was due to a decrease in CD4+ cells and an increase in CD8+ cells that were also positive for CD57 (Leu-7) and HLA-DR (Ia) antigen, suggesting a state of activation. The serology indicated a cytomegalovirus immunoglobulin G titer of 1:2,048. The patient also had significantly increased natural killer cells. These alterations suggest the presence of a chronic viral infection that may have caused the patient to be immunosuppressed, thereby predisposing her to repeated episodes of peritonitis.

Cataract surgery and intraocular lens implantation in children.

As in the past, the current literature on childhood cataracts demonstrates the need for early diagnosis, surgical treatment that is quite different from adult cataract surgery, and prompt and adequate optical correction, as well as long-term and conscientious amblyopia therapy in cases of uniocular cataract. The choice of optical correction continues to generate controversy. Contact lenses, intraocular lenses, and epikeratophakia all have their advocates. Although contact lenses are still the most common option, interest in using intraocular lenses in children has grown. Over the past year, however, two disturbing reports of complications due to intraocular lens implants were published. Treatment of childhood cataracts remains more challenging than treatment of cataracts in adults, and indications for particular approaches to optical rehabilitation in the pediatric population continue to evolve.

The acuity card procedure: longitudinal assessments.

Traditional methods of visual assessment in preverbal pediatric patients rely on refined but subjective measurement techniques. A standard ophthalmologic examination includes evaluation of a child's fixation patterns, with performance ranked on the basis of ability to fix and follow an object (F & F) or maintain central, steady fixation (CSM). In the hands of a skilled clinician, these evaluations are important for diagnosis and treatment. Documentation of quantitative changes in visual abilities of preverbal patients, however, has only recently become feasible. We began using the acuity card procedure in our pediatric clinical practice more than 3 years ago. This assessment, a modified version of the standard Forced-Choice Preferential Looking paradigm (FPL), provides quantitative evaluation of visual functioning in preverbal patients. The total number of patients assessed on one or more occasions exceeds 900. Of this group, we followed 83 patients with at least four acuity card evaluations on separate visits. Thirty of these patients, all with different diseases, have been evaluated with acuity cards on six or more visits. We found the information provided by the acuity card assessments extremely helpful in quantifying the developmental and therapeutic changes in vision, previously monitored only qualitatively.

Keratometry in children.

Corneal curvature was evaluated in 70 children by central keratometric measurements. The mean keratometric reading in each age group was seen to decline systematically from birth to about 54 months of age. The mean in the newborn-to-6-month-old group was 47.59 D; in the 12-18-month-old group it had decreased to 45.56 D. The cornea appears to stabilize at about 54 months, with an average reading of 42.69 D. Evaluation of 11 eyes diagnosed as having persistent hyperplastic primary vitreous revealed that eyes with this diagnosis generally have steeper corneas than normal eyes at any given age.

The correction of unilateral aphakia in children treated for orbital rhabdomyosarcoma.

The survival rate of children with localized orbital rhabdomyosarcoma is now greater than 90% 3 years after diagnosis as a result of advances in radiation and chemotherapy. Ninety percent of these children develop cataracts within 1 to 4 years after the completion of radiotherapy. The correction of aphakia in these children is complicated by the concurrent keratoconjunctivitis and dryness associated with radiotherapy. Three patients with a diagnosis of orbital rhabdomyosarcoma underwent treatment for uniocular cataract. Two of the patients were unable to use extended wear contact lenses. Both underwent epikeratophakia with poor results. One patient who had clinically significant ocular drying prior to cataract extraction underwent successful implantation of an intraocular lens as a primary procedure, with excellent visual results. Clinicians should be aware of the difficulties associated with contact lens wear and epikeratophakia tissue lenses in children who have had high doses of radiation for orbital rhabdomyosarcoma. Such patients are probably best served by primary intraocular lens implantation or by preservation of the posterior capsule at the time of cataract extraction to allow secondary lens implantation if contact lens wear is unsuccessful.

Update on epikeratophakia in children.

Epikeratophakia continues to be an extremely attractive option for younger children with unilateral aphakia who are noncompliant users of contact lenses but who are young enough to benefit from amblyopia therapy. The epikeratophakia procedure is much safer than IOL implantation. The epikeratophakia tissue lens is especially useful for children with traumatic aphakia and corneal lacerations because the lens can strengthen and smooth the cornea as well as correct the aphakia. This allows much quicker rehabilitation than could be accomplished with contact lenses. The epikeratophakia procedure may be combined with a cataract extraction and should be in those children with acquired cataracts who demonstrate contact lens noncompliance in an office trial of contact lens insertion before operation. Epikeratophakia should be used with caution in neonates and young infants because of the rapid growth of the eye. Extended-wear contact lenses are a safer option for these children, and epikeratophakia can be performed as a secondary procedure if and when problems with contact lens compliance arise. Surface ocular problems such as uncontrolled dry eyes or severe blepharitis will continue to be incompatible with the survival of epikeratophakia tissue lenses. Children who are treated with high doses of radiation for orbital tumors such as rhabdomyosarcomas invariably develop radiation cataracts, which can occur before the onset of radiation keratitis. These children do not do well with epikeratophakia tissue lenses. Likewise, children with severe metabolic disturbances who are not healthy or gaining weight have a diminished chance of graft healing, as do children with poor vision in whom oculodigital autostimulation produces persistent epithelial defects, which prevent survival of the tissue lens.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined cataract extraction and epikeratophakia in children.

Nineteen children between the ages of 2 1/2 and 6 1/2 years who had cataracts not associated with trauma and who were judged to be poor candidates for contact lens wear underwent combined cataract extraction and epikeratophakia, followed by intensive amblyopia therapy. Follow-up ranged from 6 months to 7 years. In these monocularly aphakic children, three (16%) of the original 19 procedures failed and the tissue lenses were removed; two of these were repeated successfully. The success rate for the surgery was 86% (18/21) and 95% (18/19) for the patients. Postoperative visual acuity of 20/50 or better was achieved in six (33%) of the 18 patients with successful surgery. Another 11 (61%) achieved between 20/60 and 20/200. Postoperative astigmatism ranged between 0 and 4 diopters, with an average of 1.7 diopters. The results demonstrate that epikeratophakia can be successfully combined with cataract extraction in children with visually significant non-traumatic cataracts and that the majority of such children demonstrate an improvement in visual acuity.

Teller acuity cards versus clinical judgment in the diagnosis of amblyopia with strabismus.

Teller acuity card testing, which is a form of the preferential-looking procedure, is a popular way of assessing visual acuity in preverbal patients. The authors suspected that the clinical judgment of a pediatric ophthalmologist is superior to the Teller acuity cards in diagnosing amblyopia when strabismus is present. Acuity card and fixation preference measurements on each eye were compared at the same clinical visit in a group of 108 strabismic patients. The authors found that the acuity cards could be used to detect amblyopia. However, the pediatric ophthalmologist was more sensitive in diagnosing amblyopia than the Teller acuity cards in the presence of strabismus.

Lensectomy in an infant with cri du chat syndrome and cataracts.

We report an 11-month-old infant with cri du chat syndrome and cataracts. The chromosomal abnormality was transmitted via a balanced 5/11 translocation from a phenotypically normal mother. The child underwent bilateral cataract extraction and was fitted with extended wear contact lenses. Congenital cataracts may be associated with cri du chat syndrome.

The nationwide study of epikeratophakia for aphakia in older children.

A nationwide study of epikeratophakia for aphakia in older children was conducted from March 1984 to March 1986. Sixty-three patients, 8 to 18 years of age, underwent this procedure in 65 eyes. Twenty-eight patients had congenital cataracts and 35 had traumatic cataracts. Fifty-one of the 65 eyes were aphakic at the time of surgery (secondary procedures). All surgeries were successful; no tissue lenses were lost or removed. Postoperatively, 73% of the patients were within 3 diopters (D) of emmetropia. The patients with congenital cataracts gained an average of one Snellen line of best-corrected visual acuity; patients with traumatic cataracts lost an average of one Snellen line of best-corrected visual acuity. In older pediatric patients, epikeratophakia appears to be a safe and effective procedure for the correction of aphakia.