Optical biopsy and imaging using optical coherence tomography.

Optical coherence tomography is a new imaging technique that can perform high-resolution, micrometre-scale, cross-sectional imaging in biological systems. The technology has been developed, and reduced to, preliminary clinical practice in ophthalmology. The challenging problem that OCT may address is the development of 'optical biopsy' techniques. These techniques can provide diagnostic imaging of tissue morphology without the need for excision of specimens. Many investigations remain to identify optimal areas for clinical application, and additional engineering must be done to integrate vertically the technology and to reduce it to clinical practice. Nevertheless, preliminary studies indicate the feasibility of developing this technology for a wide range of clinical and research diagnostic imaging applications. The ability to non-excisionally evaluate tissue morphology using a catheter or an endoscope could have a significant impact on the diagnosis and management of a wide range of diseases.

The molecular landscape of ASPM mutations in primary microcephaly.

BACKGROUND: Autosomal recessive primary microcephaly (MCPH) is a model disease to study human neurogenesis. In affected individuals the brain grows at a reduced rate during fetal life resulting in a small but structurally normal brain and mental retardation. The condition is genetically heterogeneous with mutations in ASPM being most commonly reported. METHODS AND RESULTS: We have examined this further by studying three cohorts of microcephalic children to extend both the phenotype and the mutation spectrum. Firstly, in 99 consecutively ascertained consanguineous families with a strict diagnosis of MCPH, 41 (41%) were homozygous at the MCPH5 locus and all but two families had mutations. Thus, 39% of consanguineous MCPH families had homozygous ASPM mutations. Secondly, in 27 non-consanguineous, predominantly Caucasian families with a strict diagnosis of MCPH, 11 (40%) had ASPM mutations. Thirdly, in 45 families with a less restricted phenotype including microcephaly and mental retardation, but regardless of other neurological features, only 3 (7%) had an ASPM mutation. This report contains 27 novel mutations and almost doubles the number of MCPH associated ASPM mutations known to 57. All but one of the mutations lead to the use of a premature termination codon, 23 were nonsense mutations, 28 deletions or insertions, 5 splicing, and 1 was a translocation. Seventeen of the 57 mutations were recurrent. There were no definitive missense mutations found nor was there any mutation/phenotype correlation. ASPM mutations were found in all ethnic groups studied. CONCLUSION: This study confirms that mutations in ASPM are the most common cause of MCPH, that ASPM mutations are restricted to individuals with an MCPH phenotype, and that ASPM testing in primary microcephaly is clinically useful.

Optical coherence tomography.

A technique called optical coherence tomography (OCT) has been developed for noninvasive cross-sectional imaging in biological systems. OCT uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures in a way that is analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and lateral spatial resolutions of a few micrometers and can detect reflected signals as small as approximately 10(-10) of the incident optical power. Tomographic imaging is demonstrated in vitro in the peripapillary area of the retina and in the coronary artery, two clinically relevant examples that are representative of transparent and turbid media, respectively.

Overexpression of sarcoplasmic reticulum Ca(2+)-ATPase improves cardiac contractile function in hypothyroid mice.

OBJECTIVE: Prolonged cardiac contraction and relaxation in hypothyroidism are in part related to diminished expression of the gene coding for the calcium pump of the sarcoplasmic reticulum (SERCA2a). Therefore, we examined whether or not transgenic SERCA2a gene expression in mice may compensate for the cardiac effects of hypothyroidism. METHODS: SERCA2a mRNA and protein were analyzed from hearts of euthyroid and hypothyroid mice of wild-type or SERCA2a transgene status. Contractile function was studied in isolated left ventricular papillary muscles. RESULTS: We found significant decreases of SERCA2a mRNA and protein levels in hearts of hypothyroid wild-type mice in comparison with euthyroid wild-type mice (controls). Papillary muscles from hypothyroid wild-type mice showed significant increases in time to peak contraction and relaxation times compared with controls. In contrast, SERCA2a mRNA and protein levels were significantly higher in hypothyroid SERCA2a transgenic mice than in hypothyroid wild-type mice. The transgene led to a functional improvement by compensating for the prolonged contraction and relaxation of papillary muscles. CONCLUSIONS: Our murine model of hypothyroidism revealed decreases in SERCA2a gene expression accompanied by prolonged contraction and relaxation of papillary muscles, and an improvement of the contractile phenotype due to compensated SERCA2a gene expression in SERCA2a transgenic mice.

Altered cardiac phenotype in transgenic mice carrying the delta337 threonine thyroid hormone receptor beta mutant derived from the S family.

The heart has been recognized as a major target of thyroid hormone action. Our study investigates both the regulation of cardiac-specific genes and contractile behavior of the heart in the presence of a mutant thyroid hormone receptor beta1 (T3Rbeta1-delta337T) derived from the S kindred. The mutant receptor was originally identified in a patient with generalized resistance to thyroid hormone. Cardiac expression of the mutant receptor was achieved by a transgenic approach in mice. As the genes for myosin heavy chains (MHC alpha and MHC beta) and the cardiac sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2) are known to be regulated by T3, their cardiac expression was analyzed. The messenger RNA levels for MHC alpha and SERCA2 were markedly down-regulated, MHC beta messenger RNA was up-regulated. Although T3 levels were normal in these animals, this pattern of cardiac gene expression mimics a hypothyroid phenotype. Cardiac muscle contraction was significantly prolonged in papillary muscles from transgenic mice. The electrocardiogram of transgenic mice showed a substantial prolongation of the QRS interval. Changes in cardiac gene expression, cardiac muscle contractility, and electrocardiogram are compatible with a hypothyroid cardiac phenotype despite normal T3 levels, indicating a dominant negative effect of the T3Rbeta mutant.

Imaging of coronary artery microstructure (in vitro) with optical coherence tomography.

OCT achieves high-resolution and image differentiation of vascular tissues to a degree that has not been previously possible with any method except excisional biopsy. Thus, OCT represents a promising new diagnostic technology for intracoronary imaging, which could permit the in vivo evaluation of critical vascular pathology.

Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography.

OBJECTIVE: To demonstrate a new diagnostic technique, optical coherence tomography, for high-resolution cross-sectional imaging of structures in the anterior segment of the human eye in vivo. Optical coherence tomography is a new, noninvasive, noncontact optical imaging modality that has spatial resolution superior to that of conventional clinical ultrasonography (< 20 microns) and high sensitivity (dynamic range, > 90 dB). DESIGN: Survey of intraocular structure and dimension measurements. SETTING: Laboratory. PATIENTS: Convenience sample. MAIN OUTCOME MEASURES: Correlation with range of accepted normal intraocular structure profiles and dimensions. RESULTS: Direct in vivo measurements with micrometer-scale resolution were performed of corneal thickness and surface profile (including visualization of the corneal epithelium), anterior chamber depth and angle, and iris thickness and surface profile. Dense nuclear cataracts were successfully imaged through their full thickness in a cold cataract model in calf eyes in vitro. CONCLUSIONS: Optical coherence tomography has potential as a diagnostic tool for applications in noncontact biometry, anterior chamber angle assessment, identification and monitoring of intraocular masses and tumors, and elucidation of abnormalities of the cornea, iris, and crystalline lens.

Quantitative assessment of macular edema with optical coherence tomography.

OBJECTIVE: To evaluate optical coherence tomography, a new technique for high-resolution cross-sectional imaging of the retina, for quantitative assessment of retinal thickness in patients with macular edema. DESIGN: Survey examination with optical coherence tomography of patients with macular edema. SETTING: Referral eye center. PATIENTS: Forty-nine patients with the clinical diagnosis of diabetes or diabetic retinopathy and 25 patients with macular edema secondary to retinal vein occlusion, uveitis, epiretinal membrane formation, or cataract extraction. MAIN OUTCOME MEASURES: Correlation of optical coherence tomograms with slit-lamp biomicroscopy, fluorescein angiography, and visual acuity. RESULTS: Optical coherence tomograms of cystoid macular edema closely corresponded to known histopathologic characteristics. Quantitative measurement of retinal thickness is possible because of the well-defined boundaries in optical reflectivity at the inner and outer margins of the neurosensory retina. Serial optical coherence tomographic examinations allowed tracking of both the longitudinal progression of macular thickening and the resolution of macular edema after laser photocoagulation. In patients with diabetic retinopathy, measurements of central macular thickness with optical coherence tomography correlated with visual acuity, and optical coherence tomography was more sensitive than slit-lamp biomicroscopy to small changes in retinal thickness. CONCLUSIONS: Optical coherence tomography appears useful for objectively monitoring retinal thickness with high resolution in patients with macular edema. It may eventually prove to be a sensitive diagnostic test for the early detection of macular thickening in patients with diabetic retinopathy.

Optical coherence tomography of the human retina.

OBJECTIVE: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. DESIGN: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. SETTING: Research laboratory. PARTICIPANTS: Convenience sample of normal human subjects. MAIN OUTCOME MEASURES: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. RESULTS: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10-microns depth resolution. CONCLUSION: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography.

PURPOSE: Quantitative assessment of nerve fiber layer (NFL) thickness in normal and glaucomatous eyes, and correlation with conventional measurements of the optic nerve structure and function. METHODS: We studied 59 eyes of 33 subjects by conventional ophthalmologic physical examination, Humphrey 24-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography. RESULTS: Nerve fiber layer thickness as measured by optical coherence tomography demonstrated a high degree of correlation with functional status of the optic nerve, as measured by visual field examination (P = .0001). Neither cupping of the optic nerve nor neuroretinal rim area were as strongly associated with visual field loss as was NFL thickness (P = .17 and P = .21, respectively). Cupping correlated with NFL thickness only when the cup was small (cup-to-diameter ratio, 0.1 to 0.3) or large (cup-to-diameter ratio, 0.8 to 1.0) (P = .006); there was no correlation between cupping and NFL thickness otherwise. Nerve fiber layer, especially in the inferior quadrant, was significantly thinner in glaucomatous eyes than in normal eyes (P = .04). Finally, we found a decrease in NFL thickness with aging, even when controlling for factors associated with the diagnosis of glaucoma (P = .03). CONCLUSIONS: Nerve fiber layer thickness can be measured using optical coherence tomography. These measurements provide good structural and functional correlation with known parameters.

Assessing atherosclerotic plaque morphology: comparison of optical coherence tomography and high frequency intravascular ultrasound.

BACKGROUND: OCT can image plaque microstructure at a level of resolution not previously demonstrated with other imaging techniques because it uses infrared light rather than acoustic waves. OBJECTIVES: To compare optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of in vitro atherosclerotic plaques. METHODS: Segments of abdominal aorta were obtained immediately before postmortem examination. Images of 20 sites from five patients were acquired with OCT (operating at an optical wavelength of 1300 nm which was delivered to the sample through an optical fibre) and a 30 MHz ultrasonic transducer. After imaging, the microstructure of the tissue was assessed by routine histological processing. RESULTS: OCT yielded superior structural information in all plaques examined. The mean (SEM) axial resolution of OCT and IVUS imaging was 16 (1) and 110 (7), respectively, as determined by the point spread function from a mirror. Furthermore, the dynamic range of OCT was 109 dB compared with 43 dB for IVUS imaging. CONCLUSIONS: OCT represents a promising new technology for intracoronary imaging because of its high resolution, broad dynamic range, and ability to be delivered through intravascular catheters.

Optical coherence tomography of central serous chorioretinopathy.

PURPOSE: To assess the potential of a new imaging technique, optical coherence tomography, for the diagnosis and monitoring of central serous chorioretinopathy. Optical coherence tomography is a novel noninvasive, noncontact imaging modality that produces high longitudinal resolution, cross-sectional tomographs of ocular tissue. METHODS: Optical coherence tomography is analogous to ultrasound, except that it uses light rather than sound to obtain higher image resolution in the retina. Cross-sectional tomographs of optical reflectivity within the retina are produced with longitudinal resolution of 10 microns. Optical coherence tomography was used to examine 16 patients at a referral eye center whose initial examination disclosed the clinical diagnosis of central serous chorioretinopathy. The optical coherence tomography results were correlated with slit-lamp biomicroscopy, fundus photography, and fluorescein angiography. RESULTS: The cross-sectional view produced by optical coherence tomography was effective in objectively quantifying the amount of serous retinal detachment in the disease. Optical coherence tomography disclosed detachments that were undetected by slit-lamp biomicroscopy. Longitudinal measurements with optical coherence tomography were successfully able to track the resolution of subretinal fluid accumulation. CONCLUSION: Optical coherence tomography is potentially useful as a new, noninvasive diagnostic technique for quantitative examination of patients with central serous chorioretinopathy and objectively monitoring the clinical course of the serous retinal detachment in this disease.

Argon laser retinal lesions evaluated in vivo by optical coherence tomography.

PURPOSE: To assess the in vivo evolution of argon laser retinal lesions by correlating the cross-sectional structure from sequential optical coherence tomography with histopathologic sectioning. METHODS: Argon laser lesions were created in the retinas of Macaca mulatta and evaluated by cross-section optical coherence tomography, which was compared at selected time points with corresponding histopathology. RESULTS: Argon laser lesions induced an optical coherence tomography pattern of early outer retinal relative high reflectivity with subsequent surrounding relative low reflectivity that correlated well with histopathologic findings. The in vivo optical coherence tomography images of macular laser lesions clearly demonstrated differences in pathologic response by retinal layer over time. CONCLUSION: The novel sequential imaging of rapidly evolving macular lesions with optical coherence tomography provides new insight into the patterns of acute tissue response by cross-sectional layer. This sequential imaging technique will aid in our understanding of the rapid evolution of retinal pathology and response to treatment in the research and clinical setting.

Alzheimer's residents' cognitive and functional measures: special and traditional care unit comparison.

The aim of this field experiment was to compare the effects of a special care unit (SCU) on residents with Alzheimer's disease (AD) who lived on the SCU and on traditional (integrated) nursing home units. Twenty-two subjects, 13 on the SCU and 9 on traditional integrated units were compared. Repeated measures ANOVA was used to assess differences between the two groups and within the groups over two bimonthly pretests and two bimonthly posttests. No significant differences on cognitive or functional abilities scores were evident for the groups and no significant differences were found over time. However, consistent with the prediction of the Progressively Lower Stress Threshold Model, the SCU subjects' function was better than subjects on traditional units when measured by socially accessible behaviors.

Outcome indicators for direct and indirect caregiving.

Informal caregiving and outcomes for caregiving are an important part of health care and of particular importance in nursing. The purpose of this research is to report the results of a survey mailed to nursing experts for validation of the outcome labels Caregiver Role Performance: Direct Care and Caregiver Role Performance: Indirect Care and their accompanying indicators. Experts were asked to rate how important the identified indicators were for assessing those two outcomes. In addition, the respondents were asked to what extent nursing interventions influence the achievement of each identified indicator for Caregiver Role Performance: Direct Care and Caregiver Role Performance: Indirect Care. In general, the validity of the concept analysis work by the caregiver focus group was supported. Ten indicators for Caregiver Performance: Direct Care were retained, 1 was dropped that was considered most appropriate for indirect care, and 3 new indicators were added to reflect the nurse experts surveyed. For Caregiver Performance: Indirect Care, all of the indicators were retained.

Peer review.

All research agencies and prestigious journals insist they are rewarding excellence, that they have a merit-based system, and that their system serves their mission well--all part of the ideology of the infallibility of peer review. There have been, and continue to be, criticism about the peer review system and several alternatives to peer review have been posed. A discussion of peer review is intended to allow the reader to evaluate approaches to the peer review system.

The integrated health professions education program seminar.

Powerful dynamics of change require practitioners from all disciplines to be prepared to work in interdisciplinary teams, competently access health and information technologies, and understand the multiple functions required for adequate healthcare provision. The University of Iowa's Integrated Health Professions Program is a state-funded effort designed to provide students with a common educational experience to enable them to work collaboratively in underserved or rural settings. Students take part in a series of team-building seminars including technology-based instruction and activities in conjunction with visits to community clinical sites. The authors discuss the experiential, collaborative, and cooperative forms of learning that take place during the seminar series.

Reliability and validity of a new preadmission acuity tool for long-term care.

The purpose of this project was to develop a new tool designed to assess the acuity of applicants to long-term facilities. Using a known groups method, residents of long-term care facilities were categorized as independent (n = 68), assist (n = 71), and dependent (n = 65) and assessed using the Preadmission Acuity Inquiry Tool (PAI) to generate the data base for examining its psychometric properties. The progression of the mean scores from independent to assist to dependent demonstrates the ability of the tool to differentiate across varying levels of functional independence. Using discriminant analysis, the degree of accuracy in predicting group membership for the independent group was 88%, for the dependent group 75%, and for the assist group 17% with the overall agreement between PAI scores and a priori classifications at 60%. Kappa coefficients for interrater reliability ranged from .54 to 1.0 with a mean of .90. The Cronbach's alpha coefficient was .81. The PAI has demonstrated sufficient reliability and validity to warrant further refinement and testing. This new instrument may enable health care professionals to provide the appropriate level of care in a cost-effective manner.

Review process for nursing journals: making the best of any review system.

Within nursing, different review practices exist in the operation of nursing's professional journals. This article describes each of the three major review practices and provides you with some tips on how to work with these approaches as an author or editor.

Who owns the rights to a teaching tool?

Copyright issues are not always clear, especially when multiple authors and roles are involved. The following question and response analyzes one such situation involving the rights to a teaching tool developed by a faculty member.