Confocal Optical Coherence Tomography Research Articles

Virtual Bronchoscopy

SummaryVirtual bronchoscopy is evolving rapidly, and is becoming accepted into standard clinical practice. Virtual bronchoscopy is a term, which encompasses not only multi‐row detector X‐ray computerized tomography‐derived images, but also other computer graphics and computer vision‐derived value‐added digital imagery. Other imaging data sources used to create three‐dimensional image renderings of the bronchial tree include magnetic resonance imaging, positron emission tomography, the digital colour image taken at real bronchoscopy as part of macro‐optical imaging, and various emerging micro‐optical imaging modalities, such as catheter‐based confocal microscopy and optical coherence tomography. Software solutions now exist for providing simple renderings of the bronchial tree through which a fly‐through of the airway lumen along the centreline of the airway can be added (the fly‐through mimics the view that a real flexible bronchoscope affords the operator). The images so produced are visually accurate and with currently available software also analytically correct. More advanced virtual bronchoscopic applications, including image‐based pathfinding to mediastinal and peripheral lung structures, are also in development, and are finding their way into clinical studies. Exciting and synergistic data sets composed of image data from multiple image sources are also being constructed. One emerging issue is to enhance the understanding and reporting on these data sets, which are often complex, and which are full of useful as well as redundant information. The new discipline of eidomics will inform the non‐specialist end user, and act to predict important outcomes. These increasingly powerful tools will continue to advance the use of imaging in technology‐supported personalized medicine, to compliment the information from genomics.

Boundary conditions in photoacoustic tomography and image reconstruction

Recently, the field of photoacoustic tomography has experienced considerable growth. Although several commercially available pure optical imaging modalities, including confocal microscopy, two-photon microscopy, and optical coherence tomography, have been highly successful, none of these technologies can penetrate beyond approximately 1 mm into scattering biological tissues because all of them are based on ballistic and quasiballistic photons. Consequently, heretofore there has been a void in high-resolution optical imaging beyond this depth limit. Photoacoustic tomography has filled this void by combining high ultrasonic resolution and strong optical contrast in a single modality. However, it has been assumed in reconstruction of photoacoustic tomography until now that ultrasound propagates in a boundary-free infinite medium. We present the boundary conditions that must be considered in certain imaging configurations; the associated inverse solutions for image reconstruction are provided and validated by numerical simulation and experiment. Partial planar, cylindrical, and spherical detection configurations with a planar boundary are covered, where the boundary can be either hard or soft. Analogously to the method of images of sources, which is commonly used in forward problems, the ultrasonic detectors are imaged about the boundary to satisfy the boundary condition in the inverse problem.

Intense Pulsed Light Therapy for Superficial Pigmented Lesions Evaluated by Reflectance-Mode Confocal Microscopy and Optical Coherence Tomography

Intense pulsed light (IPL) therapy is reported to be effective for pigment removal from pigmented lesions. However, the dynamic mechanism of pigment removal by IPL therapy is not completely understood. We investigated the mechanism of IPL therapy for the removal of pigmented skin lesions through non-invasive observation of the epidermis. Subjects with solar lentigines on the face were treated with three sessions of IPL therapy. The solar lentigines were observed on consecutive days after the treatments using reflectance-mode confocal microscopy (RCM) and optical coherence tomography (OCT). In addition, desquamated microcrusts that formed after the treatment were investigated by transmission electron microscopy (TEM). The images of RCM and OCT showed that the melanosomes in the epidermal basal layer rapidly migrated to the skin surface. The TEM images of the extruded microcrusts revealed numerous melanosomes together with cell debris. It was also found that the IPL irradiated melanocytes in the lesions seemed to be left intact and resumed their high activity after treatment. We conclude that IPL therapy effectively removed the dense melanosomes in the epidermal-basal layer. However, additional application of suppressive drugs such as hydroquinone or Q-switched laser irradiation is necessary to suppress the remaining active melanocytes.

Chromoendoscopy: A new vision for colonoscopic surveillance in IBD

Chromoendoscopy: A new vision for colonoscopic surveillance in IBD

Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging

Although optical absorption is strongly associated with the physiological status of biological tissue, existing high-resolution optical imaging modalities, including confocal microscopy, two-photon microscopy and optical coherence tomography, do not sense optical absorption directly. Furthermore, optical scattering prevents these methods from imaging deeper than approximately 1 mm below the tissue surface. Here we report functional photoacoustic microscopy (fPAM), which provides multiwavelength imaging of optical absorption and permits high spatial resolution beyond this depth limit with a ratio of maximum imaging depth to depth resolution greater than 100. Reflection mode, rather than orthogonal or transmission mode, is adopted because it is applicable to more anatomical sites than the others. fPAM is demonstrated with in vivo imaging of angiogenesis, melanoma, hemoglobin oxygen saturation (sO2) of single vessels in animals and total hemoglobin concentration in humans.

Topographic Angiography and Optical Coherence Tomography: A Correlation of Imaging Characteristics

Topographic angiography (TAG) using confocal scanning laser angiography and optical coherence tomography (OCT) are new imaging modalities that have been introduced during recent years. OCT and TAG imaging were compared to specify the characteristics of each imaging modality. TAG using fluorescein angiography (FA) provides a three-dimensional profile of the vascular structures based on the analysis of a set of 32 confocal images over a depth of 4 mm. OCT provides cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex (RPE-CC). The authors compared and evaluated both modalities in 10 patients with predominantly classic choroidal neovascularization (CNV), 10 patients with serous pigment epithelial detachment (PED), and 10 patients with geographic RPE atrophy, all secondary to age-related macular degeneration (ARMD). In patients with classic CNV, TAG detected neovascular structures and delineated their configuration. In PEDs pooling of extravascular fluid is demonstrated, and in geographic RPE atrophy TAG showed reduced choroidal perfusion. Classic CNV was demonstrated by OCT as a hyperreflective band at the level of the RPE-CC, and PED showed a dome-shaped RPE detachment. In geographic RPE atrophy, OCT imaged loss of the RPE band and had an increased depth resolution. TAG and OCT are useful imaging modalities in the evaluation of ARMD cases. TAG visualizes the vascular configuration and dynamic perfusion and leakage changes. OCT is able to document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. Both modalities may provide further valuable insight into ARMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.

Evaluation of the Influence of Tilt of Optic Disc on the Measurement of Optic Disc Variables Obtained by Optical Coherence Tomography and Confocal Scanning Laser Ophthalmoscopy

To evaluate the relationship between optic disc variables measured by confocal scanning laser ophthalmoscopy (CSLO) and optical coherence tomography (OCT). Fifty-one eyes in 27 non-glaucomatous patients were scanned using a CSLO-TopSStrade mark and an OCT-OCT 3000trade mark. The relationship between the following four optic disc variables-disc area (DA), cup area (CA), neuroretinal rim area (NRRA), and cup-disc area ratio (CDAR)-measured by CSLO and OCT were evaluated, and the relationship between these measurements and optic disc tilt was assessed. Horizontal (HD) and vertical diameters (VD) of the optic disc were measured from disc photographs, and by CSLO and OCT, and ratios (HD/VD) were then compared. There was a good correlation in DA, CA, and CDAR except NRRA between OCT and CSLO measurements. In eyes with a tilt >/=4 degrees, DA and NRRA were measured larger, and CDAR and CA were measured smaller by OCT than by CSLO. However, in the eyes with a tilt of <4 degrees, no significant differences in measurement of disc variables were observed for the two measurement systems. HD/VD measured from disc photographs was well correlated with those determined by CSLO (r = 0.741, P < 0.0001), however, it correlated poorly with those measured by OCT in whole study eyes (r = 0.410, P = 0.008) and in eyes tilted by >/=4 degrees, respectively (P = 0.280). Although CSLO and OCT measurements of the optic disc are highly correlated, discrepancy becomes prominent in eyes with a disc tilted >/=4 degrees. Therefore, analysis of the optic nerve head by OCT must be cautiously interpreted in eyes with a highly tilted disc.

Optical MEMS for Minimally Invasive Therapy

Several optical MEMS devices have been developed for minimally invasive diagnosis and therapy. Micro MEMS scanners have been developed for new endoscopes which enable high resolution inspection in the human body using a confocal microscopicsystem or optical coherence tomography. For realizing precis elaser treatment in the human body, a two-dimensional laser scanning micro tool has been also developed. Fiber-optic sensors have been developed for mechanical sensing, for example, local pressure or forces in the human body. Micro-mechanical sensing structures are fabricated using the MEMS process and installed at the tip of the optical fiber. This paper reviews optical MEMS devices developed for minimally invasive diagnosis and therapy.

Two Mutations in the TGFBI (BIGH3) Gene Associated with Lattice Corneal Dystrophy in an Extensively Studied Family

To determine the genetic basis for lattice corneal dystrophy (LCD) in an extensively studied family. Ten affected family members were examined clinically, and three individuals were studied with in vivo confocal microscopy and optical coherence tomography (OCT). Corneal tissues from eight affected family members were examined histopathologically. The status of the transforming growth factor beta-induced gene (TGFBI) gene was determined in each consenting family member (six affected, seven nonaffected) by amplifying, sequencing, and analyzing exons 4 and 12 of TGFBI for mutations. All exons from the entire coding region of TGFBI of one affected person were analyzed for mutations. Slit lamp biomicroscopy disclosed the clinical features of LCD in both eyes of affected individuals. In vivo confocal microscopy confirmed the presence of deposits as bright lesions within the corneal stroma. OCT revealed increased reflectivity within the corneal stroma. The corneal stroma in persons undergoing penetrating keratoplasty contained amyloid. Affected members of the family were found to have two heterozygous single-nucleotide mutations in exon 12 of the TGFBI gene (C1637A and C1652A) leading to predicted amino acid substitutions in the encoded TGFbeta-induced protein (A546D and P551Q). Mutations were not detected in exon 4. In addition, an inconsequential single-nucleotide polymorphism T1620C (F540F) was found in some affected and nonaffected family members. Two mutations in the TGFBI gene (A546D and P551Q) cosegregated with LCD in an extensively studied family that lacked the R124C mutation that frequently accompanies this form of corneal amyloidosis.

Optical imaging of the cervix.

Recent advances in fiber optics, sources and detectors, imaging, and computer-controlled instrumentation have stimulated a period of unprecedented growth in the development of photonics technologies for a wide variety of diagnostic and therapeutic clinical applications. These include the application of quantitative optical spectroscopy and imaging for the detection of precancerous lesions in the uterine cervix, a topic of interest at the Second International Conference on Cervical Cancer, which was held April 11-14, 2002. Investigators have applied the Littenberg method of emerging technology assessment to new optical methods used to detect cervical neoplasia. Currently, such technologies as fluorescence spectroscopy (the combination of fluorescence and diffuse reflectance spectroscopy), tri-modal spectroscopy, and light-scattering spectroscopy that probe the spectral characteristics of tissue are being investigated. Optical technologies that create images of subcellular structure without biopsy subsequent to pathology that currently are under investigation include in vivo confocal imaging and optical coherence tomography. Numerous small studies have demonstrated the potential of these optical technologies. What remains to be elucidated are the fundamental biophysical origins of variations in remitted optical signals between normal and dysplastic tissue. Large multicenter randomized controlled trials are needed to confirm the detection and imaging capabilities of optical technology. Furthermore, the development of contrast agents that could boost detection with these technologies is needed, and basic biologic characterization of signals should be pursued. Applying the Littenberg assessment will help ensure that superior, not simply alternative, technologies are implemented.

Endoscopic microscopy.

In vivo endoscopic optical microscopy provides a tool to assess tissue architecture and morphology with contrast and resolution similar to that provided by standard histopathology – without need for physical tissue removal. In this article, we focus on optical imaging technologies that have the potential to dramatically improve the detection, prevention, and therapy of epithelial cancers. Epithelial pre-cancers and cancers are associated with a variety of morphologic, architectural, and molecular changes, which currently can be assessed only through invasive, painful biopsy. Optical imaging is ideally suited to detecting cancer-related alterations because it can detect biochemical and morphologic alterations with sub-cellular resolution throughout the entire epithelial thickness. Optical techniques can be implemented non-invasively, in real time, and at low cost to survey the tissue surface at risk. Our manuscript focuses primarily on modalities that currently are the most developed: reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). However, recent advances in fluorescence-based endoscopic microscopy also are reviewed briefly. We discuss the basic principles of these emerging technologies and their current and potential applications in early cancer detection. We also present research activities focused on development of exogenous contrast agents that can enhance the morphological features important for cancer detection and that have the potential to allow vital molecular imaging of cancer-related biomarkers. In conclusion, we discuss future improvements to the technology needed to develop robust clinical devices.

Confocal enhanced optical coherence tomography for nondestructive evaluation of paints and coatings

We investigate confocal enhanced optical coherence tomography as a nondestructive evaluation tool for imaging with improved image contrast and depth resolution through a highly scattering paint layer. The depth responses provided by confocal microscopy, optical coherence tomography, and confocal enhanced optical coherence tomography for imaging through paint are investigated. We demonstrate that a new combination of confocal microscopy and optical coherence tomography provides significantly improved resolution and contrast for coherence gated imaging of substrate structures under the paint.

Heidelberg retina tomography and optical coherence tomography in normal, ocular-hypertensive, and glaucomatous eyes

Purpose To evaluate optic disc and retinal nerve fiber layer (RNFL) appearance in normal, ocular-hypertensive, and glaucomatous eyes undergoing confocal scanning laser ophthalmoscopy and optical coherence tomography (OCT). Design Prospective, cross-sectional study. Participants Seventy-eight eyes of 78 consecutive normal (n = 17), ocular-hypertensive (n = 23), and glaucomatous subjects (n = 38) were enrolled. Methods Each patient underwent complete ophthalmic examination, achromatic automated perimetry, confocal scanning laser ophthalmoscopy (Heidelberg Retinal Tomography [HRT]), and OCT. Topographic HRT parameters (disc area, cup-disc ratio, rim area, rim volume, cup shape measure, mean RNFL thickness, and cross-sectional area) and mean OCT-generated RNFL thickness were evaluated in each group. Main outcome measures OCT and HRT assessment of optic disc and RNFL anatomy. Results OCT RNFL thickness showed no difference between normal and ocular-hypertensive eyes ( P = 0.15) but was significantly less in glaucomatous eyes ( P < 0.001). HRT measurements of rim area, cup-disc ratio, cup shape measure, RNFL thickness, and RNFL cross-sectional area were significantly less in glaucomatous eyes (all P < 0.005) and were correlated with mean OCT RNFL thickness (all P < 0.02). RNFL thickness using OCT or HRT was highly correlated with visual field mean defect during achromatic perimetry ( P < 0.0001). Conclusion Both HRT and OCT can differentiate glaucomatous from nonglaucomatous eyes. RNFL thickness measurements using OCT correspond to disc topographic parameters using HRT.

Choosing treatment for metastatic breast cancer

The membrane-associated palmitoylated protein 5 (MPP5 or PALS1) is thought to organize intracellular PALS1-CRB-MUPP1 protein scaffolds in the retina that are involved in maintenance of photoreceptor–Müller glia cell adhesion. In humans, the Crumbs homolog 1 (<i>CRB1</i>) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype–phenotype correlation for <i>CRB1</i> mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, especially PALS1, we generated and analyzed conditional knockdown mice for <i>Pals1</i>. Small irregularly shaped spots were detected throughout the PALS1 deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. The electroretinography a- and b-wave was severely attenuated in the aged mutant retinas, suggesting progressive degeneration of photoreceptors. The histological analysis showed abnormal retinal pigment epithelium structure, ectopic photoreceptor nuclei in the subretinal space, an irregular outer limiting membrane, half rosettes of photoreceptors in the outer plexiform layer, and a thinner photoreceptor synaptic layer suggesting improper photoreceptor cell layering during retinal development. The PALS1 deficient retinas showed reduced levels of Crumbs complex proteins adjacent to adherens junctions, upregulation of glial fibrillary acidic protein indicative of gliosis, and persisting programmed cell death after retinal maturation. The phenotype suggests important functions of PALS1 in the retinal pigment epithelium in addition to the neural retina.